Co-reporter:Baohong Wang;Deying Chen;Yu Chen;Zhenhua Hu;Min Cao;Qing Xie;Jiali Xu;Yanfei Chen;Shusen Zheng
Journal of Proteome Research February 3, 2012 Volume 11(Issue 2) pp:1217-1227
Publication Date(Web):2017-2-22
DOI:10.1021/pr2009252
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and usually develops in patients with liver cirrhosis (LC). Biomarkers that discriminate HCC from LC are important but are limited. In the present study, an ultraperformance liquid chromatography–mass spectrometry (UPLC–MS)-based metabonomics approach was used to characterize serum profiles from HCC (n = 82), LC (n = 48), and healthy subjects (n = 90), and the accuracy of UPLC–MS profiles and alpha-fetoprotein (AFP) levels were compared for their use in HCC diagnosis. By multivariate data and receiver operating characteristic curves analysis, metabolic profiles were capable of discriminating not only patients from the controls but also HCC from LC with 100% sensitivity and specificity. Thirteen potential biomarkers were identified and suggested that there were significant disturbances of key metabolic pathways, such as organic acids, phospholipids, fatty acids, bile acids, and gut flora metabolism, in HCC patients. Canavaninosuccinate was first identified as a metabolite that exhibited a significant decrease in LC and an increase in HCC. In addition, glycochenodeoxycholic acid was suggested to be an important indicator for HCC diagnosis and disease prognosis. UPLC–MS signatures, alone or in combination with AFP levels, could be an efficient and convenient tool for early diagnosis and screening of HCC in high-risk populations.Keywords: hepatocellular carcinoma (HCC); liquid chromatography−mass spectrometry (LC−MS); liver cirrhosis (LC); metabonomics; serum;
Co-reporter:Shao-rui Hao;Shi-chao Geng;Lin-xiao Fan
Journal of Zhejiang University-SCIENCE B 2017 Volume 18( Issue 5) pp:393-401
Publication Date(Web):10 May 2017
DOI:10.1631/jzus.B1600273
Jaundice is a common and complex clinical symptom potentially occurring in hepatology, general surgery, pediatrics, infectious diseases, gynecology, and obstetrics, and it is fairly difficult to distinguish the cause of jaundice in clinical practice, especially for general practitioners in less developed regions. With collaboration between physicians and artificial intelligence engineers, a comprehensive knowledge base relevant to jaundice was created based on demographic information, symptoms, physical signs, laboratory tests, imaging diagnosis, medical histories, and risk factors. Then a diagnostic modeling and reasoning system using the dynamic uncertain causality graph was proposed. A modularized modeling scheme was presented to reduce the complexity of model construction, providing multiple perspectives and arbitrary granularity for disease causality representations. A “chaining” inference algorithm and weighted logic operation mechanism were employed to guarantee the exactness and efficiency of diagnostic reasoning under situations of incomplete and uncertain information. Moreover, the causal interactions among diseases and symptoms intuitively demonstrated the reasoning process in a graphical manner. Verification was performed using 203 randomly pooled clinical cases, and the accuracy was 99.01% and 84.73%, respectively, with or without laboratory tests in the model. The solutions were more explicable and convincing than common methods such as Bayesian Networks, further increasing the objectivity of clinical decision-making. The promising results indicated that our model could be potentially used in intelligent diagnosis and help decrease public health expenditure.黄疸待查是一个常见而复杂的临床问题, 涉及到 内、外、妇、儿等多个学科。目前我国医学专家 存在数量相对不足, 分布不均匀等情况, 导致了 区域性和部门性医疗服务水平不足。本研究旨在 建立一个客观的黄疸待查智能诊断系统, 以提高 医学诊断的正确性, 提升基层医院及急诊的诊断 水平, 同时减少病人的花费。本研究采用了国际先进的动态不确定性因果图 (DUCG)模型, 建立了黄疸待查相关疾病的知 识库, 通过203 例临床病例的测试, 其准确率达 99.01%。文章以图形化的方式给出了疾病的诊断 过程, 方便医师理解和学习。本研究采用了DUCG 模型进行疾病诊断, 首先根 据DUCG 模型的定义和黄疸诊断思路建立了包 含27 种黄疸相关疾病(表4)的知识库(图2), 其中包括了疾病的危险因素、临床症状和体征、客观检查检验结果等。然后与根据DUCG 算法 (公式1–4)编写的推理软件相结合形成诊断系 统, 对203 例临床黄疸患者进行智能诊断, 准确 率达99.01%。最后对一例丙型病毒性肝炎患者 的具体诊断过程进行了拆解阐述, 体现了DUCG 模型适用于复杂逻辑关系、计算效率高、不依赖 推理概率和结果易于理解等优点。DUCG 模型成功实现了对黄疸待查相关疾病的智 能诊断, 准确率高, 实用性好。该方法具有在其 他医学领域推广应用的价值。
Co-reporter:Ermei Chen, Juan Lu, Deying Chen, Danhua Zhu, Yini Wang, Yimin Zhang, Ning Zhou, Jie Wang, Jianzhou Li, Lanjuan Li
Biomedicine & Pharmacotherapy 2017 Volume 93(Volume 93) pp:
Publication Date(Web):1 September 2017
DOI:10.1016/j.biopha.2017.06.049
Metabolomics facilitates investigation of the mechanisms of disease and screening for biomarkers. Here, a gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics approach was employed to identify plasma biomarkers of acute liver failure (ALF) in pigs. Blood was collected from pigs at 12 h intervals during ALF. Hepatic injury was quantified by determining liver function and histopathology. Based on a multivariate data matrix and pattern recognition, two upregulated metabolites, namely, amino acids and conjugated bile acids, and two downregulated metabolites, lysophosphatidylcholines (LPCs) and phosphatidylcholines (PCs), were identified. All of these metabolites showed a strong relationship with the extent of liver injury. Amino acids were biomarkers of the severity of liver impairment, conjugated bile acids were predictive of early stage liver damage, and LPCs and PCs were related to the prognosis of liver injury. In conclusion, our results demonstrated the occurrence of marked metabolic disturbances during ALF and that integrated metabolomics analysis facilitates identification of biomarkers of disease.
Co-reporter:Jie Wang;Panpan Cen;Jiajia Chen;Linxiao Fan;Jun Li
Stem Cell Research & Therapy 2017 Volume 8( Issue 1) pp:137
Publication Date(Web):06 June 2017
DOI:10.1186/s13287-017-0576-4
Liver failure is a severe clinical syndrome with a poor prognosis. Mesenchymal stem cell (MSC) transplantation has emerged as a new intervention in treating liver failure. It is conventionally recognized that MSCs exert their therapeutic effect mainly through transdifferentiation. Recently, published articles have shown that MSCs work in liver failure by secreting trophic and immunomodulatory factors as well as extracellular vesicles (EVs) before transdifferentiation. In particular,MSC-derived EVs have shown similar curative effects as MSCs. Here we review the role of MSCs as well as their derived factors and EVs in liver failure and discuss the use of MSC-derived EVs instead of intact MSCs in treating liver failure.
Co-reporter:Baohong Wang, Mingfei Yao, Longxian Lv, Zongxin Ling, Lanjuan Li
Engineering 2017 Volume 3, Issue 1(Volume 3, Issue 1) pp:
Publication Date(Web):1 February 2017
DOI:10.1016/J.ENG.2017.01.008
Trillions of microbes have evolved with and continue to live on and within human beings. A variety of environmental factors can affect intestinal microbial imbalance, which has a close relationship with human health and disease. Here, we focus on the interactions between the human microbiota and the host in order to provide an overview of the microbial role in basic biological processes and in the development and progression of major human diseases such as infectious diseases, liver diseases, gastrointestinal cancers, metabolic diseases, respiratory diseases, mental or psychological diseases, and autoimmune diseases. We also review important advances in techniques associated with microbial research, such as DNA sequencing, metabonomics, and proteomics combined with computation-based bioinformatics. Current research on the human microbiota has become much more sophisticated and more comprehensive. Therefore, we propose that research should focus on the host-microbe interaction and on cause-effect mechanisms, which could pave the way to an understanding of the role of gut microbiota in health and disease, and provide new therapeutic targets and treatment approaches in clinical practice.
Co-reporter:Shigui Yang, Jie Wu, Cheng Ding, Yuanxia Cui, ... Lanjuan Li
The Lancet Infectious Diseases 2017 Volume 17, Issue 7(Volume 17, Issue 7) pp:
Publication Date(Web):1 July 2017
DOI:10.1016/S1473-3099(17)30227-X
BackgroundThe model of infectious disease prevention and control changed significantly in China after the outbreak in 2003 of severe acute respiratory syndrome (SARS), but trends and epidemiological features of infectious diseases are rarely studied. In this study, we aimed to assess specific incidence and mortality trends of 45 notifiable infectious diseases from 2004 to 2013 in China and to investigate the overall effectiveness of current prevention and control strategies.MethodsIncidence and mortality data for 45 notifiable infectious diseases were extracted from a WChinese public health science data centre from 2004 to 2013, which covers 31 provinces in mainland China. We estimated the annual percentage change in incidence of each infectious disease using joinpoint regression.FindingsBetween January, 2004, and December, 2013, 54 984 661 cases of 45 infectious diseases were reported (average yearly incidence 417·98 per 100 000). The infectious diseases with the highest yearly incidence were hand, foot, and mouth disease (114·48 per 100 000), hepatitis B (81·57 per 100 000), and tuberculosis (80·33 per 100 000). 132 681 deaths were reported among the 54 984 661 cases (average yearly mortality 1·01 deaths per 100 000; average case fatality 2·4 per 1000). Overall yearly incidence of infectious disease was higher among males than females and was highest among children younger than 10 years. Overall yearly mortality was higher among males than females older than 20 years and highest among individuals older than 80 years. Average yearly incidence rose from 300·54 per 100 000 in 2004 to 483·63 per 100 000 in 2013 (annual percentage change 5·9%); hydatid disease (echinococcosis), hepatitis C, and syphilis showed the fastest growth. The overall increasing trend changed after 2009, and the annual percentage change in incidence of infectious disease in 2009–13 (2·3%) was significantly lower than in 2004–08 (6·2%).InterpretationAlthough the overall incidence of infectious diseases was increasing from 2004, the rate levelled off after 2009. Effective prevention and control strategies are needed for diseases with the highest incidence—including hand, foot, and mouth disease, hepatitis B, and tuberculosis—and those with the fastest rates of increase (including hydatid disease, hepatitis C, and syphilis).FundingChinese Ministry of Science and Technology, National Natural Science Foundation (China).
Co-reporter:Mingfei Yao, Jiong Wu, Bo Li, Hang Xiao, David Julian McClements, Lanjuan Li
Food Hydrocolloids 2017 Volume 72(Volume 72) pp:
Publication Date(Web):1 November 2017
DOI:10.1016/j.foodhyd.2017.05.033
•Encapsulating Lactobacillus salivarious Li01 into biopolymer microgels greatly enhanced their survival rates when exposed to long-term storage, heat and simulated gastrointestinal conditions.•Alginate/gelatin-microgels were more effective at protecting the probiotics than alginate-microgels, which was attributed to differences in the physicochemical and structural properties of their interiors.•Alginate/gelatin microgels are a promising vehicle for protecting and delivering Lactobacillus salivarious Li01 to the gut microflora.Probiotics are used in food products, dietary supplements and pharmaceutical products because they may provide health-promoting effects in humans. To be efficacious, probiotics need to be viable at sufficient abundance within the large intestine. However, many commercial products containing probiotics suffer from a substantial loss of bacterial viability during shelf storage and during gastrointestinal transit. In this study, a probiotic (Lactobacillus salivarious Li01) was incorporated into either alginate or alginate-gelatin microgels. The morphology of the microgels was characterized by scanning electron microscopy, which indicated that they had a spherical shape and that almost all of the bacterial cells were encapsulated inside them. Probiotic viability was determined under aerobic conditions, heat treatment, and simulated gastrointestinal conditions. Encapsulation significantly enhanced the viability of the probiotic during aerobic storage. The microgels maintained their structures under simulated gastric conditions, but either eroded or swelled under simulated small intestine conditions. The alginate-gelatin microgels were the most effective at protecting the bacteria under simulated gastrointestinal conditions when compared to the alginate microgels and non-encapsulated bacteria. In conclusion, alginate-gelatin microgels have great potential for the protection and delivery of probiotics in food, supplement, and pharmaceutical products.Download high-res image (209KB)Download full-size image
Co-reporter:Xiaotian Dong, Xiaoru Su, Jiong Yu, Jingqi Liu, Xiaowei Shi, Qiaoling Pan, Jinfeng Yang, Jiajia Chen, Lanjuan Li, Hongcui Cao
Journal of Molecular Graphics and Modelling 2017 Volume 71() pp:116-123
Publication Date(Web):January 2017
DOI:10.1016/j.jmgm.2016.11.011
•Constructed a three-dimensional structural model of the HIF2α-pVHL complex.•Discerned how HIF2α can be recognized and captured by pVHL in the process of its degradation.•Revealed structural defects responsible for weakening the interaction of HIF2a mutants with pVHL.BackgroundHypoxia-inducible factor 2 alpha (HIF2α), prolyl hydroxylase domain protein 2 (PHD2), and the von Hippel Lindau tumor suppressor protein (pVHL) are three principal proteins in the oxygen-sensing pathway. Under normoxic conditions, a conserved proline in HIF2α is hydroxylated by PHD2 in an oxygen-dependent manner, and then pVHL binds and promotes the degradation of HIF2α. However, the crystal structure of the HIF2α-pVHL complex has not yet been established, and this has limited research on the interaction between HIF and pVHL. Here, we constructed a structural model of a 23-residue HIF2α peptide (528–550)-pVHL-ElonginB-ElonginC complex by using homology modeling and molecular dynamics simulations. We also applied these methods to HIF2α mutants (HYP531PRO, F540L, A530 V, A530T, and G537R) to reveal structural defects that explain how these mutations weaken the interaction with pVHL.MethodsHomology modeling and molecular dynamics simulations were used to construct a three-dimensional (3D) structural model of the HIF2α-VHL complex. Subsequently, MolProbity, an active validation tool, was used to analyze the reliability of the model. Molecular mechanics energies combined with the generalized Born and surface area continuum solvation (MM-GBSA) and solvated interaction energy (SIE) methods were used to calculate the binding free energy between HIF2a and pVHL, and the stability of the simulation system was evaluated by using root mean square deviation (RMSD) analysis. We also determined the secondary structure of the system by using the definition of secondary structure of proteins (DSSP) algorithm. Finally, we investigated the structural significance of specific point mutations known to have clinical implications.ResultsWe established a reliable structural model of the HIF2α-pVHL complex, which is similar to the crystal structure of HIF1α in 1LQB. Furthermore, we compared the structural model of the HIF2α-pVHL complex and the HIF2α (HYP531P, F540L, A530V, A530T, and G537R)-pVHL mutants on the basis of RMSD, DSSP, binding free energy, and hydrogen bonding. The experimental data indicate that the stability of the structural model of the HIF2α-pVHL complex is higher than that of the mutants, consistently with clinical observations.ConclusionsThe structural model of the HIF2α-pVHL complex presented in this study enhances understanding of how HIF2α is captured by pVHL. Moreover, the important contact amino acids that we identified may be useful in the development of drugs to treat HIF2a-related diseases.
Co-reporter:Guoping Sheng, Ying Chen, Lijie Han, Yong Huang, Xiaoli Liu, Lanjuan Li, Zhengwei Mao
Acta Biomaterialia 2016 Volume 43() pp:251-261
Publication Date(Web):1 October 2016
DOI:10.1016/j.actbio.2016.07.012
Abstract
Although indocyanine green (ICG) has promising applications in photothermal therapy (PPT) because of its low toxicity and high efficiency in inducing heat and singlet oxygen formation in response to near-infrared light with a wavelength of approximately 800 nm, its clinical application has been restricted because of its rapid body clearance and poor water stability. Therefore, cell membrane capsules (CMCs) derived from mammalian cells were used to encapsulate negatively charged ICG by temporarily permeating the plasma membrane and resealing using positively charged doxorubicin hydrochloride (DOX). The resulting CMCs@DOX/ICG exhibited a spherical shape, with a diameter of approximately 800 nm. The DOX and ICG encapsulation was confirmed by the UV–vis spectrum; a very small amount of DOX (0.8 μg) and a very high amount of ICG (∼110 μg) were encapsulated in 200 μg CMCs. Encapsulation in the CMCs leads to sustained release of ICG, especially in the presence of positively charged DOX. The temperature enhancement and generation of ROS by ICG encapsulated in CMCs were confirmed upon laser irradiation in vitro, leading to cell death. CMCs@DOX/ICG also can significantly enhance the retention of ICG in a tumor after intratumoral injection in vivo. As a result, combination treatment with CMCs@DOX/ICG and laser irradiation demonstrated much better anticancer efficacy than that of free DOX/ICG and CMCs@ICG. The encapsulation of ICG into CMCs, especially with the assistance of DOX, significantly slows down the body clearance of ICG, with a retained PPT effect against tumors, an important step forward in the practical application of ICG in cancer therapy.
Statement of Significance
In this study, cell membrane capsules (CMCs) derived from mammalian cells were used to encapsulate negatively charged indocyanine green (ICG) by temporarily permeating the plasma membrane and resealing, in the presence of positively charged doxorubicin hydrochloride (DOX). The resulting CMCs@DOX/ICG exhibited a spherical shape, with a diameter of approximately 800 nm. Encapsulation in the CMCs leads to sustained release of ICG and thus slower clearance inside body, especially in the presence of positively charged DOX. The system provides a better photothermal effect against tumors, an important step forward in the practical application of ICG in cancer therapy.
Co-reporter:Zeyu Sun, Xiaoli Liu, Jing Jiang, Haijun Huang, Jie Wang, Daxian Wu, and Lanjuan Li
Analytical Chemistry 2016 Volume 88(Issue 17) pp:8518
Publication Date(Web):July 29, 2016
DOI:10.1021/acs.analchem.6b01333
We describe a cheap, robust, fast, high-throughput, and flexible proteomic sample processing method based on a regular 96-well plate by acetone precipitation under low centrifuge speed (96PACS), which enables predigestion processing of 96 samples within 2 h. Tested on a complex Huh-7 total lysate, 96PACS produced comparable proteome coverage and even showed better reproducibility than FASP. Quantitative performance of 96PACS was further tested using data-independent acquisition and parallel reaction monitoring quantitation in a set of 6 benchmark samples consisting of 6 serial dilutions of BSA spiked in complex E. coli proteome background. The protocol was also successfully modified for automation and was validated in a comparative label-free proteomic study to develop serum markers for early detection of liver fibrosis and necroinflammation in patients chronically infected with hepatitis B virus.
Co-reporter:Xiaoling Su, Nan Wang, Deying Chen, Yunong Li, Yingfeng Lu, Tao Huan, Wei Xu, Liang Li, Lanjuan Li
Analytica Chimica Acta 2016 Volume 903() pp:100-109
Publication Date(Web):15 January 2016
DOI:10.1016/j.aca.2015.11.027
•A method of parallel analysis of urine and fecal metabolomes is developed.•Dansylation isotope labeling LC-MS is used for amine/phenol submetabolome quantification.•Detection of 3089 metabolites in urine and 3012 metabolites in feces for a total of 5372 metabolites.•Parallel profiling of urine and feces increases the metabolomic coverage.Human urine and feces can be non-invasively collected for metabolomics-based disease biomarker discovery research. Because urinary and fecal metabolomes are thought to be different, analysis of both biospecimens may generate a more comprehensive metabolomic profile that can be better related to the health state of an individual. Herein we describe a method of using differential chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) for parallel metabolomic profiling of urine and feces. Dansylation labeling was used to quantify the amine/phenol submetabolome changes among different samples based on 12C-labeling of individual samples and 13C-labeling of a pooled urine or pooled feces and subsequent analysis of the 13C-/12C-labeled mixture by LC-MS. The pooled urine and pooled feces are further differentially labeled, mixed and then analyzed by LC-MS in order to relate the metabolite concentrations of the common metabolites found in both biospecimens. This method offers a means of direct comparison of urinary and fecal submetabolomes. We evaluated the analytical performance and demonstrated the utility of this method in the analysis of urine and feces collected daily from three healthy individuals for 7 days. On average, 2534 ± 113 (n = 126) peak pairs or metabolites could be detected from a urine sample, while 2507 ± 77 (n = 63) peak pairs were detected from a fecal sample. In total, 5372 unique peak pairs were detected from all the samples combined; 3089 and 3012 pairs were found in urine and feces, respectively. These results reveal that the urine and fecal metabolomes are very different, thereby justifying the consideration of using both biospecimens to increase the probability of finding specific biomarkers of diseases. Furthermore, the CIL LC-MS method described can be used to perform parallel quantitative analysis of urine and feces, resulting in more complete coverage of the human metabolome.
Co-reporter:C Hu, H Cao, X Pan, J Li, J He, Q Pan, J Xin, X Yu, J Li, Y Wang, D Zhu and L Li
Cell Death & Disease 2016 7(3) pp:e2141
Publication Date(Web):2016-03-01
DOI:10.1038/cddis.2016.1
Current evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and transdifferentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type is unknown. Placental-derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. No studies have comprehensively analyzed the transition in morphology, surface antigens, metabolism and multilineage potency of differentiated PDMSCs after their dedifferentiation. In this study, we showed that after withdrawing extrinsic factors, adipogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The mitochondrial network during differentiation and dedifferentiation may serve as a marker of absent or acquired pluripotency in various stem cell models. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. The cell adhesion molecules (CAMs) signaling pathway and extracellular matrix (ECM) components modulate cell behavior and enable the cells to proliferate or differentiate during the differentiation, dedifferentiation and redifferentiation processes in our study. These observations indicate that the dedifferentiated PDMSCs are distinguishable from the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies. Furthermore, whether PDMSCs differentiated into other lineages can be dedifferentiated to a primitive cell population needs to be investigated.
Co-reporter:Jiezuan Yang, Guoping Sheng, Dangsheng Xiao, Haiyan Shi, Wei Wu, Haifeng Lu, Hongcui Cao and Lanjuan Li
Cellular & Molecular Immunology 2016 13(5) pp:678-687
Publication Date(Web):February 22, 2016
DOI:10.1038/cmi.2015.100
The frequency and T-cell receptor beta-chain variable (TCRBV) patterns of peripheral CD4+CD25+ regulatory T-cells (Tregs) are ambiguously altered in chronic hepatitis B (CHB) patients following tenofovir disoproxil fumarate (TDF) treatment. Moreover, the clinical significance of these parameters in relation to hepatitis B e antigen (HBeAg) seroconversion (SC) is largely unknown. In this study, the circulation of Tregs in HBeAg-positive CHB patients was determined by flow cytometry, and the molecular profiles of frequent TCRBV patterns of Tregs were analyzed using a gene melting spectral pattern. The parameters, such as Treg frequency, the number of skewed TCRBV patterns, hepatitis B virus (HBV) DNA levels, and alanine aminotransferase (ALT) levels, were analyzed by comparing their associations in seroconverting and non-seroconverting patients following TDF treatment. The Treg frequency was significantly correlated with the ALT level in seroconverting but not in non-seroconverting patients. Similarly, skewed TCRBV patterns were remarkably associated with HBV DNA levels in the SC group. Six TCRBV families (BV3, BV11, BV12, BV14, BV20, and BV24) were more prevalent than other TCRBV members in seroconverting patients pretreated with TDF, while BV12, BV15, and BV22 were predominant in non-seroconverting patients during TDF treatment. Taken together, the preferential TCRBV patterns may be associated with immune responses related to SC. The dynamic frequency and skewed TCRBV patterns of peripheral Tregs could contribute to predicting SC in CHB patients. Moreover, the conserved TCRBV complementarity-determining region (CDR3) motif may be targeted to develop personalized immunotherapy for CHB patients.
Co-reporter:Xianzhong Jiang;Kunkai Su;Jingjing Tao;Rongli Fan;Yi Xu;Haijun Han
Amino Acids 2016 Volume 48( Issue 11) pp:2589-2598
Publication Date(Web):2016 November
DOI:10.1007/s00726-016-2283-3
Genome-wide association study indicates that STAT4 is a plausible candidate for an association study with HBV-related liver diseases. We aimed to examine the roles of STAT4 polymorphisms on HBV-related liver diseases in a Chinese Han population. We selected 13 SNPs in STAT4 based on the HapMap database to investigate their associations in 3,033 participants. SNP rs7574865 was significantly associated with HBV infection [odds ratio (OR) 1.15; 95 % confidence interval (CI) 1.00, 1.31; P = 0.046] and clearance (OR 1.17; 95 % CI 1.02, 1.33; P = 0.028). Further, haplotype-based association analysis indicated that the haplotype CTCTT, formed by SNPs rs8179673, rs7574865, rs4274624, rs11889341, and rs10168266, was significantly associated with HBV infection (OR 0.87; 95 % CI 0.76, 0.99; P = 0.022) and clearance (OR 0.86; 95 % CI 0.75, 0.99; P = 0.018). Bioinformatics analysis of these SNPs predicted that they participate in transcriptional regulation. Taken together, our findings demonstrate that variants in STAT4 play a critical role in HBV infection and clearance in the Chinese Han population.
Co-reporter:Chen Yunzhi;Lu Huijuan;Linda Shapiro
Journal of Biological Research-Thessaloniki 2016 Volume 23( Issue 1 Supplement) pp:
Publication Date(Web):2016 May
DOI:10.1186/s40709-016-0044-9
Ontology development, as an increasingly practical vehicle applied in various fields, plays a significant role in knowledge management. This paper, focusing on constructing and querying a hepatitis ontology, aims to provide a framework for ontology-based medical services. The paper is devoted to the algorithm of query expansion for the hepatitis ontology, including synonym expansion, hypernym/hyponym expansion and expansion of similar words. It applies semantic similarity calculation to judge the similarity of retrieval terms.The paper proposes a new prototype system. The accuracy of query expansion is improved in both precision@40 and AP@40, which indicates that query expansion improves the accuracy of the query after using the method proposed in this paper.The paper has adopted semantic similarity computing to improve retrieval performance. Experiments show that search precision of query expansion is higher based on domain concept relationship.
Co-reporter:Juan Lu;Yanhong Zhang;Danhua Zhu;Jie Wang;Chao Ye
Biotechnology Letters 2016 Volume 38( Issue 6) pp:909-917
Publication Date(Web):2016 June
DOI:10.1007/s10529-016-2063-x
To determine the optimal storage solution containing suitable protective agents for the preservation of microencapsulated hepatocytes at 4 °C as well as the optimum incubation time after hypothermic preservation.L15 was the optimum solution for both maintaining microcapsule integrity and cell viability. Furthermore, 5 %(v/v) PEG (20 or 35 kDa) added to Leibovitz-15 medium was optimal for microencapsulated C3A cells, enhancing cell viability and liver-specific functions, including albumin and urea synthesis as well as CYP1A2 and CYP3A4 activities. The transcription levels of several CYP450-related genes were also dramatically increased in cells incubated in the optimal solution. Pre-incubation for 2 h was the optimal time for restoring favorable levels of CYP1A2 and CYP3A4 activities in microencapsulated C3A cells for short term, 2 day storage.Leibovitz-15 medium supplemented with 5 % (v/v) PEG is a promising cold solution for microencapsulated hepatocytes at 4 °C, with an incubation of 2 h at 37 °C after hypothermic preservation being the best incubation duration for further cell application.
Co-reporter:Beiwen Zheng;Xiawei Jiang;Zemin Xu;Yunhui Fang
Extremophiles 2016 Volume 20( Issue 1) pp:37-44
Publication Date(Web):2016 January
DOI:10.1007/s00792-015-0795-5
In this study, a novel metallo-β-lactamases fold hydrolase PH-1 was identified from Pelagibacterium halotolerans B2T. This novel member of the family Hyphomicrobiaceae was isolated from the East China Sea. In silico analysis demonstrated that PH-1 and its relative homologues cluster in a unique branch and constitute a new subgroup among MBLs. PH-1 was cloned and overexpressed in Escherichia coli BL21 in a soluble form. SDS-PAGE, MALDI-TOF/TOF–MS, and size-exclusion chromatography analysis demonstrated that the PH-1 was a monomer with molecular weight of about 29 kDa. Substrate specificity study showed PH-1 preferred penicillin type β-lactams and exhibited maximum activity toward penicillin-G. Additionally, our experiments also revealed that PH-1 was a halotolerant enzyme since it is active under 4 M NaCl. The enzyme activity of PH-1 was negatively affected by 1 mM Mn2+ and EDTA. These observations lay a foundation for further study of MBLs from marine bacterium.
Co-reporter:Hainv Gao;Hangping Yao;Shigui Yang
Frontiers of Medicine 2016 Volume 10( Issue 4) pp:377-382
Publication Date(Web):2016 December
DOI:10.1007/s11684-016-0466-7
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic pathogen. In 2012, the infectious outbreak caused by MERS-CoV in Saudi Arabia has spread to more than 1600 patients in 26 countries, resulting in over 600 deaths.Without a travel history, few clinical and radiological features can reliably differentiate MERS from SARS. But in real world, comparing with SARS, MERS presents more vaguely defined epidemiology, more severe symptoms, and higher case fatality rate. In this review, we summarize the recent findings in the field of MERS-CoV, especially its molecular virology, interspecies mechanisms, clinical features, antiviral therapies, and the further investigation into this disease. As a newly emerging virus, many questions are not fully answered, including the exact mode of transmission chain, geographical distribution, and animal origins. Furthermore, a new protocol needs to be launched to rapidly evaluate the effects of unproven antiviral drugs and vaccine to fasten the clinical application of new drugs.
Co-reporter:Wei Xu, Deying Chen, Nan Wang, Ting Zhang, Ruokun Zhou, Tao Huan, Yingfeng Lu, Xiaoling Su, Qing Xie, Liang Li, and Lanjuan Li
Analytical Chemistry 2015 Volume 87(Issue 2) pp:829
Publication Date(Web):December 8, 2014
DOI:10.1021/ac503619q
Human fecal samples contain endogenous human metabolites, gut microbiota metabolites, and other compounds. Profiling the fecal metabolome can produce metabolic information that may be used not only for disease biomarker discovery, but also for providing an insight about the relationship of the gut microbiome and human health. In this work, we report a chemical isotope labeling liquid chromatography–mass spectrometry (LC–MS) method for comprehensive and quantitative analysis of the amine- and phenol-containing metabolites in fecal samples. Differential 13C2/12C2-dansyl labeling of the amines and phenols was used to improve LC separation efficiency and MS detection sensitivity. Water, methanol, and acetonitrile were examined as an extraction solvent, and a sequential water–acetonitrile extraction method was found to be optimal. A step-gradient LC–UV setup and a fast LC–MS method were evaluated for measuring the total concentration of dansyl labeled metabolites that could be used for normalizing the sample amounts of individual samples for quantitative metabolomics. Knowing the total concentration was also useful for optimizing the sample injection amount into LC–MS to maximize the number of metabolites detectable while avoiding sample overloading. For the first time, dansylation isotope labeling LC–MS was performed in a simple time-of-flight mass spectrometer, instead of high-end equipment, demonstrating the feasibility of using a low-cost instrument for chemical isotope labeling metabolomics. The developed method was applied for profiling the amine/phenol submetabolome of fecal samples collected from three families. An average of 1785 peak pairs or putative metabolites were found from a 30 min LC–MS run. From 243 LC–MS runs of all the fecal samples, a total of 6200 peak pairs were detected. Among them, 67 could be positively identified based on the mass and retention time match to a dansyl standard library, while 581 and 3197 peak pairs could be putatively identified based on mass match using MyCompoundID against a Human Metabolome Database and an Evidence-based Metabolome Library, respectively. This represents the most comprehensive profile of the amine/phenol submetabolome ever detected in human fecal samples. The quantitative metabolome profiles of individual samples were shown to be useful to separate different groups of samples, illustrating the possibility of using this method for fecal metabolomics studies.
Co-reporter:Zaifa Pan;Xiaoya Huang;Yuan Zhong;Lili Wang;Danhua Zhu
Journal of Separation Science 2015 Volume 38( Issue 9) pp:1499-1506
Publication Date(Web):
DOI:10.1002/jssc.201401497
The determination of α-ketoacid concentration is demanded to evaluate the absorption and metabolic behavior of compound α-ketoacid tablets taken by chronic kidney disease patients. To eliminate the interference of endogenous substance of urine and enrich the analytes, a three-phase hollow-fiber liquid-phase microextraction combined with ion-pair high-performance liquid chromatography method was established for the determination of d,l-α-hydroxymethionine calcium, d,l-α-ketoisoleucine calcium, α-ketovaline calcium, α-ketoleucine calcium, and α-ketophenylalanine calcium of compound α-ketoacid tablets in human urine samples. The extraction parameters, such as organic solvent, pH of donor phase and acceptor phase, stirring rate, and extraction time were optimized. Under the optimal conditions, the obtained enrichment factors were up to 11-, 110-, 198-, 202-, and 50-fold, respectively. The calibration curves for these analytes were linear over the range of 0.1–10 mg/L for α-ketovaline calcium, d,l-α-ketoisoleucine calcium, and α-ketoleucine calcium, 0.5–10 mg/L for d,l-α-hydroxymethionine calcium, and α-ketophenylalanine calcium with r > 0.99. The relative standard deviations (n = 5) were less than 6.27% and the LODs were 100.7, 10.0, 5.8, 7.8, and 8.6 μg/L (based on S/N = 3), respectively. Good recoveries from spiked urine samples (92–118%) were obtained. The proposed method demonstrated excellent sample clean-up and analytes enrichment to determine the five components in human urine.
Co-reporter:Jingjing Tao;Kunkai Su;Chengbo Yu;Xiaoli Liu;Wei Wu;Wei Xu
Amino Acids 2015 Volume 47( Issue 12) pp:2623-2634
Publication Date(Web):2015 December
DOI:10.1007/s00726-015-2054-6
Recent genome-wide association studies have revealed the HLA region on chromosome 6p21 as a susceptibility locus for hepatitis B virus (HBV) infection, a finding subsequently replicated in independent samples. However, only limited single nucleotide polymorphisms (SNPs) were analyzed in most of these studies, and it remains to be determined which SNPs contribute to the detected association. After genotyping 140 SNPs within this genomic region in a total of 1657 HBV-positive patients and 1456 HBV-negative controls, we conducted a series of genetic epidemiological and bioinformatics analysis, including individual SNP-based association analysis, haplotype-based association analysis, and conditional analysis. We identified 76 SNPs and 5 LD blocks in HLA-DP/DQ clusters that are significantly associated with HBV infection, with the smallest P value being 3.88 × 10−18 for rs9277535 in HLA-DPB1. With conditional analysis, we further revealed that the genes contributing to the effects of variants in HLA-DP/DQ on infection are independent of each other, and the LD block 5 in the 3′-UTR region of HLA-DPB1 had a predominant effect in the association of HLA-DP with HBV infection. We also found that the SNPs in the 3′-UTR region of HLA-DPB1 were significant between the subgroups of inactive HBV carrier, chronic hepatitis B, or hepatic cirrhosis from the case group and the spontaneous HBV-clearance subgroup from the control group. Finally, we did further association analysis of SNPs in this region with different subgroups from the case group, which revealed no association of these SNPs with the progression of HBV-related diseases. In sum, we showed, for the first time, that the HLA-DP/DQ clusters contribute independently to HBV infection, and the 3′-UTR region of HLA-DPB1 represents an important functional region involved in HBV infection.
Co-reporter:Chenxia Hu
Protein & Cell 2015 Volume 6( Issue 8) pp:562-574
Publication Date(Web):2015 August
DOI:10.1007/s13238-015-0180-2
Various liver diseases result in terminal hepatic failure, and liver transplantation, cell transplantation and artificial liver support systems are emerging as effective therapies for severe hepatic disease. However, all of these treatments are limited by organ or cell resources, so developing a sufficient number of functional hepatocytes for liver regeneration is a priority. Liver regeneration is a complex process regulated by growth factors (GFs), cytokines, transcription factors (TFs), hormones, oxidative stress products, metabolic networks, and microRNA. It is well-known that the function of isolated primary hepatocytes is hard to maintain; when cultured in vitro, these cells readily undergo dedifferentiation, causing them to lose hepatocyte function. For this reason, most studies focus on inducing stem cells, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), hepatic progenitor cells (HPCs), and mesenchymal stem cells (MSCs), to differentiate into hepatocyte-like cells (HLCs) in vitro. In this review, we mainly focus on the nature of the liver regeneration process and discuss how to maintain and enhance in vitro hepatic function of isolated primary hepatocytes or stem cell-derived HLCs for liver regeneration. In this way, hepatocytes or HLCs may be applied for clinical use for the treatment of terminal liver diseases and may prolong the survival time of patients in the near future.
Co-reporter:Jiezuan Yang, Jiajia Chen, Jianqin He, Yirui Xie, Yixing Zhu, Hongcui Cao and Lanjuan Li
Cellular & Molecular Immunology 2014 11(4) pp:343-354
Publication Date(Web):April 21, 2014
DOI:10.1038/cmi.2014.22
The profile of T-cell receptor beta-chain variable (TRBV) genes usually skews in subjects with virus infection or cancer. The gene melting spectral pattern (GMSP) can be used to determine the profile of the TRBV gene family. To explore the portrait of the TRBV family in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection (AHI), peripheral blood mononuclear cells (PBMCs) were separated and further sorted into CD4+ and CD8+ T-cell subsets. The molecular features of the TRBV complementary determining region 3 (CDR3) motifs were determined using GMSP analysis. When a GMSP profile showed a single peak, the monoclonally expanded TRBV gene was cloned and sequenced. Skewed expansions of multiple TRBV genes were observed among the CD4+ and CD8+ T-cell subsets and the PBMCs. The frequency of monoclonally expanded TRBV genes in the CD8+ T-cell subset was significantly higher than that of the CD4+ T-cell subset and the PBMCs. Compared to other members of the TRBV gene family, TRBV11, BV15 and BV20 were predominantly expressed in the repertoire of peripheral blood lymphocytes in recovered AHI subjects. The relatively conserved amino acid motifs of TRBV5.1 and BV20 CDR3 were also detected in the CD4+ and CD8+ T-cell subsets. These results demonstrate the presence of multiple biased TRBV families in recovered AHI subjects. TRBV11, BV15 and BV20, especially from the CD8+ T-cell subset, may be relevant to the pathogenesis of subjects with AHI. The preferentially selected TRBV5.1 and BV20 with the relatively conserved CDR3 motif may be potential targets for personalized treatments of chronic HBV infection.
Co-reporter:LanJuan Li
Science China Life Sciences 2014 Volume 57( Issue 5) pp:551-552
Publication Date(Web):2014 May
DOI:10.1007/s11427-014-4626-1
Co-reporter:Haibo Wu;Nanping Wu;Xiaorong Peng;Changzhong Jin;Xiangyun Lu
Virus Genes 2014 Volume 49( Issue 1) pp:80-88
Publication Date(Web):2014 August
DOI:10.1007/s11262-014-1065-9
In 2013, 15 avian
influenza viruses (AIVs), H3N2 (n = 7), H3N3 (n = 3), H3N6 (n = 3), and H3N8 (n = 2), were isolated from domestic ducks in Zhejiang Province in China. These strains were characterized by whole genome sequencing with subsequent phylogenetic analysis and genetic comparison. Phylogenetic analysis of all eight viral genes showed that these strains clustered in the AIV Eurasian lineage. Analysis of the neuraminidase (NA) gene indicates that a re-assortment event between H3 and H9N2 AIV occurred in these ducks. The molecular markers analyzed over the genome of all viruses indicated that these strains were low-pathogenic AIVs. Although there was no evidence of re-assortment in subtype H3 AIVs among the avian species’ and mammalian hosts in this study, continued surveillance is needed considering the important role of domestic ducks in AIV re-assortment.
Co-reporter:Hongcui Cao;Jing Ma;Jinfeng Yang;Xiaoru Su;Deying Chen;Jiong Yu
Metabolomics 2014 Volume 10( Issue 4) pp:651-662
Publication Date(Web):2014 August
DOI:10.1007/s11306-013-0603-0
Metabonomics has become a highly sensitive and powerful tool for screening of biomarkers and elucidation of biochemical processes. Recently, we reported beneficial therapeutic effect of human placenta mesenchymal stem cells (hPMSCs) transplantation on d-galactosamine (GalN)-induced liver injury in Chinese miniature pigs. However, the underlying mechanism remains largely unclear. Here, UPLC/TOF/MS-based metabonomics approach was employed to analyze serum from GalN-treated pigs with the goal of identifying potential biomarkers for acute liver injury. Our results showed that obvious metabolic disturbance occurred during acute liver failure (ALF), which can be ameliorated by the hPMSCs transplantation. The metabolic profiles of the hPMSCs transplantation group returned back to the original state 5 weeks after the hPMSCs transplantation. In addition, the result obtained from metabolic trajectory analysis correlated well with those from biochemical analysis and histological examination. Serum levels of several metabolites including glycoursodeoxycholic acid, glycochenodeoxycholic acid, aromatic amino acids, phosphatidylcholine, lysophosphatidylcholine and sphingomyelin, were significantly modified during the process of ALF and cell treatment. Taken together, our study has gained new insight into the molecular mechanism on how hPMSCs administration facilitates the recovery of ALF, and provided strong support for treating liver diseases with stem cell-based therapies.
Co-reporter:Zongxin Ling;Xia Liu;Yuezhu Wang;Charlie Xiang
Microbial Ecology 2013 Volume 65( Issue 2) pp:487-495
Publication Date(Web):2013 February
DOI:10.1007/s00248-012-0123-x
Describing the biogeography of bacterial communities within the human body is critical for establishing healthy baselines from which to detect differences associated with diseases. Little is known, however, about the baseline of normal salivary microbiota from healthy Chinese children and adults. With parallel barcoded 454 pyrosequencing, the bacterial diversity and richness of saliva were thoroughly investigated from ten healthy Chinese children and adults. The overall taxonomic distribution of our metagenomic data demonstrated that the diversity of salivary microbiota from children was more complex than adults, while the composition and richness of salivary microbiota were similar in children and adults, especially for predominant bacteria. A large number of bacterial phylotypes were shared by healthy children and adults, indicating the existence of a core salivary microbiome. In children and adults, the vast majority of sequences in salivary microbiota belonged to Streptococcus, Prevotella, Neisseria, Haemophilus, Porphyromonas, Gemella, Rothia, Granulicatella, Fusobacterium, Actinomyces, Veillonella, and Aggregatibacter, which constituted the major components of normal salivary microbiota. With the exception of Actinomyces, the other seven non-predominant bacteria including Moraxella, Leptotrichia, Peptostreptococcus, Eubacterium, and members of Neisseriaceae, Flavobacteriaceae, and SR1 showed significant differences between children and adults (p < 0.05). We first established the framework of normal salivary microbiota from healthy Chinese children and adults. Our data represent a critical step for determining the diversity of healthy microbiota in Chinese children and adults, and our data established a platform for additional large-scale studies focusing on the interactions between health and diseases in the future.
Co-reporter:Jun Li, Jiaojiao Xin, Shaorui Hao, Liyuan Zhang, Longyan Jiang, Deying Chen, Qing Xie, Wei Xu, Hongcui Cao, and Lanjuan Li
Journal of Proteome Research 2012 Volume 11(Issue 6) pp:3414-3422
Publication Date(Web):2017-2-22
DOI:10.1021/pr3002639
Our recent study first demonstrated that human bone marrow mesenchymal stem cell (hBMSC) transplantation could prevent death from fulminant hepatic failure (FHF) in pigs. To further clarify the metabolic mechanism of hBMSC transplantation in FHF, the plasma collected from FHF pigs that received transplantation of hBMSCs was examined using metabolic analysis to identify the key molecular markers that regulate recovery. The results showed that obvious metabolic disturbance occurred during FHF, whereas the hBMSC transplantation group showed less severe liver injury. The metabolic trajectory returns to its original state at week 3 following the hBMSC transplantation. In total, the concentration of 26 metabolites, including conjugated bile acids, phosphatidylcholines, lysophosphatidylcholines, fatty acids, amino acid and sphingomyelin, are significantly different between the FHF group and the hBMSC transplantation group. Moreover, the time course of changes in the metabolites corresponded with that of the biochemical and histological analyses. Real-time PCR further confirmed that the gene expression of phospholipase A1, lecithin-cholesterol acyltransferase and lysophosphatidylcholine acyltransferase 1 decreased significantly, whereas that of phospholipase A2 remained stable, which explains the decrease of the phosphatidylcholines and lysophosphatidylcholines. These novel results have revealed a metabolic mechanism for the hBMSC transplantation in FHF, which could lead to the future development of treatment strategies for stem cell therapies.
Co-reporter:Shuchao Wu, Wei Xu, Qamar Subhani, Bingcheng Yang, Deying Chen, Yan Zhu, Lanjuan Li
Talanta 2012 Volume 101() pp:541-545
Publication Date(Web):15 November 2012
DOI:10.1016/j.talanta.2012.09.039
This paper describes the determination of carbamazepine (CBZ) in human plasma using ion chromatography combined with online electrochemical derivatization and fluorescence detection. Separation of CBZ with anion exchange column was demonstrated to be feasible using either basic (10 mM NaOH) or acidic (0.1 M H3PO4) reagent with a small amount of acetonitrile (ACN) added as eluent. Electrochemical derivatization of CBZ into a strongly fluorescent product, which could be carried out only under the acidic condition, was investigated via the previously reported electrolytic cell (EC), as well as two modes of acidification. The linear range of CBZ for human plasma was between 10–2000 μg L−1 under the optimized experimental conditions. The limit of detection (LOD, S/N=3) was 1.3 μg L−1 and the relative standard deviation (RSD, n=7) was 2.6%. Better sensitivity and selectivity of the present method were demonstrated in comparison with ion chromatography with ultraviolet detection (IC-UV). The spiked recoveries of CBZ in 2 human plasma samples were 78.5 and 114%, respectively.Highlights► Determination of carbamazepine by ion chromatography – online electrochemical derivatization – fluorescence detection. ► Elution of carbamazepine can be performed using either basic or acidic eluent. ► Better sensitivity and selectivity were obtained compared with IC-UV.
Co-reporter:Jing-jing Ren;Xue-wei Dai;Zheng-gang Jiang
Journal of Zhejiang University-SCIENCE B 2012 Volume 13( Issue 11) pp:948-954
Publication Date(Web):2012 November
DOI:10.1631/jzus.B1200179
To evaluate the immunological effects of three types of domestic 10-μg/dose hepatitis B vaccines in adults compared with a foreign vaccine, and to provide scientific evidence in support of adult hepatitis B vaccination.Adults from five counties (Deqing, Changxing, Nanxun, Wuxing, Anji) in Huzhou City, Shaoxing County and Tongxiang County, Zhejiang Province, China were selected. Blood samples were taken to assess serum HBsAg, anti-HBs, and anti-HBc using a chemiluminescence immunoassay. Adults, aged 16 to 49 years and who were anti-HBs negative at baseline, received hepatitis B immunizations at 0, 1, and 6 months. Anti-HBs levels were assessed one month after the third and final vaccination.A total of 1 872 adults were immunized and the average positive rate was 89.5%. Four types of hepatitis B vaccine were used, including three from Chinese companies (Shenzhen Kangtai, Dalian High-Tech, and North China Pharmaceutical) and one from a UK company (GlaxoSmithKline). Their seroconversion rates were 81.67%, 95.05%, 89.64%, and 86.81%, respectively. There was a significant difference between the anti-HBs positive conversion rates of the four types (P<0.005) but the seroconversion rates among the different vaccines were not significantly different (χ2=2.123, P=0.145). The average anti-HBs geometric mean titers (GMTs) of non-immune adults immunized with each of the four vaccines were 177.28, 473.23, 246.13, and 332.20 mIU/ml, respectively. There were no statistically significant differences in the GMTs between the three types of domestic vaccine and the foreign vaccine (t=−1.575, P=0.116).Domestic recombinant hepatitis B vaccines can achieve immunization effects comparable to those of a foreign vaccine.
Co-reporter:XiaoPing Pan;JianZhou Li;WeiBo Du;XiaoPeng Yu;ChunXia Zhu
Biotechnology Letters 2012 Volume 34( Issue 12) pp:2183-2190
Publication Date(Web):2012 December
DOI:10.1007/s10529-012-1025-1
An immortalized human hepatocyte cell line, HepLi5, was established via transfection of Simian virus 40 large T antigen (SV40 LT) into primary human hepatocytes. The morphologic and functional characteristics of HepLi5 cells were evaluated. The expression of SV40 LT in HepLi5 cells was detected by reverse transcription-PCR (RT-PCR) and western blotting. mRNA expression of liver-enriched genes, including glutamine synthetase, albumin, and cytochrome P450 was detected via RT-PCR in HepLi5 cells. Activity of CYP1A2, one of the drug-metabolizing P450 enzymes, was detected. Subcutaneous injection of HepLi5 cells into nude mice did not induce tumors within 3 months. Short Tandem Repeat results confirmed the authenticity of the cell line. Clinical-grade quantities of HepLi5 cells could be harvested using large-scale culture in roller bottles after which their cellular function was significantly enhanced. Therefore, the immortalized HepLi5 cells are a suitable cell source for applications in bioartificial livers.
Co-reporter:Min Xu;Baohong Wang;Yiqi Fu;Yanfei Chen;Fengling Yang;Haifeng Lu
Microbial Ecology 2012 Volume 63( Issue 2) pp:304-313
Publication Date(Web):2012 February
DOI:10.1007/s00248-011-9925-5
The beneficial effects of Bifidobacteria on health have been widely accepted. Patients with chronic liver disease have varying degrees of intestinal microflora imbalance with a decrease of total Bifidobacterial counts. Since different properties have been attributed to different Bifidobacterium species and there is no information available for the detailed changes in the genus Bifidobacterium in patients with chronic liver disease heretofore, it is meaningful to investigate the structure of this bacterium at the species level in these patients. The aim of this study was to characterize the composition of intestinal Bifidobacterium in patients with hepatitis B virus-induced chronic liver disease. Nested-PCR-based denaturing gradient gel electrophoresis (PCR-DGGE), clone library, and real-time quantitative PCR were performed on the fecal samples of 16 patients with chronic hepatitis B (CHB patients), 16 patients with hepatitis B virus-related cirrhosis (HBV cirrhotics), and 15 healthy subjects (Controls). Though there was no significant difference in the diversity among the three groups (P = 0.196), Bifidobacterium dentium seems to be specifically enhanced in patients as the PCR-DGGE profiles showed, which was further validated by clone library and real-time quantitative PCR. In contrast to the B. dentium, Bifidobacteriumcatenulatum/Bifidobacterium pseudocatenulatum were detected less frequently in the predominant profile and by quantitative PCR in HBV cirrhotics than in the controls, and the level of this species was also significantly different between these two groups (P = 0.023). Although having no quantitative difference among the three groups, Bifidobacterium longum was less commonly detected in HBV cirrhotics than in CHB patients and Controls by quantitative PCR (P = 0.011). Thus, the composition of intestinal Bifidobacterium was deeply altered in CHB and HBV cirrhotic patients with a shift from beneficial species to opportunistic pathogens. The results provide further insights into the dysbiosis of the intestinal microbiota in patients with hepatitis B virus-induced chronic liver disease and might potentially serve as guidance for the probiotics interventions of these diseases.
Co-reporter:Yuefang Hu;Wei Xu;Jianping Li
Luminescence 2012 Volume 27( Issue 1) pp:63-68
Publication Date(Web):
DOI:10.1002/bio.1326
ABSTRACT
A rapid, sensitive and simple electrochemiluminescence method for the determination of 5-hydroxytryptamine (5-HT) using capillary electrophoresis was proposed. The experimental parameters, including the detection potential, the concentration of Ru(bpy)32+, the concentration and pH of phosphate buffer for separation and detection, the injection voltage and time and the separation voltage on the determination of 5-HT, were optimized. Under the optimized conditions, the linear concentration range for 5-HT was 3.5 × 10-9–5.1 × 10-3 mol/L, with a detection limit of 5 × 10-10 mol/L. The relative standard deviations (RSDs) of the ECL intensity and the migration times for six continuous injections of 1.0 µmol/L 5-HT were 2.48% and 1.3%, respectively. The method was successfully applied to 5-HT assay in samples of human serum in 5 min and the extraction recoveries with spiked serum samples were over 94.4%. Copyright © 2011 John Wiley & Sons, Ltd.
Co-reporter:Pengcheng Zhou;Jianzhou Li;Li Shao;Guoliang Lv;Lifu Zhao;Haijun Huang
Metabolomics 2012 Volume 8( Issue 5) pp:869-879
Publication Date(Web):2012 October
DOI:10.1007/s11306-011-0381-5
Fulminant hepatic failure (FHF) is still an intractable disease associated with serious metabolic disorder. Investigating the dynamic changes of serum metabolites during the development of FHF would facilitate revealing the pathogenesis and also promote its treatment. Therefore, this study characterized the dynamic metabonome of serum from FHF Pigs using ultra performance liquid chromatography–mass spectrometry. Based on multiple statistical analysis of the resulting dataset, three types of up-regulated and one type of down-regulated patterns were delineated. Each pattern demonstrated distinct trends at different stages during the whole process of FHF, implying the differential clinical significance of them. Specifically, aromatic amino acids (Pattern 1) and lysophosphatidylcholines (LPCs) (Pattern 4) might be good markers for evaluating the severity of FHF, while some conjugated bile acids, long chain acylcarnitines (Pattern 2) and Glycocholic acid (Pattern 3) could indicate liver injury in the early stage. Inspired from the PCA plot that the pathogenetic condition of FHF aggravated with sampling time, a linear discriminant analysis (LDA) model based on phenylalanine and LPC 18:1 were further constructed for evaluating the severity of FHF. The leave-one-out cross-validation accuracy of 91.67% for the training set and the prediction accuracy of 92.31% for the external validation set confirmed its excellent performance. In conclusion, findings obtained from the present study, including four types of Dynamic Patterns of serum metabolites during FHF development and an LDA model for evaluating the severity of FHF, will be of great help to the research and management of FHF in the future.
Co-reporter:Yu Chen;Zhiliang Xu;Hongwei Kong;Nan Chen;Jing Chen;Lina Zhou
Metabolomics 2012 Volume 8( Issue 5) pp:845-853
Publication Date(Web):2012 October
DOI:10.1007/s11306-011-0379-z
To improve the grading and staging of liver cirrhosis among patients with HBV infection noninvasively, a high-performance liquid chromatography with mass spectrometry metabolomics method was used to investigate the potential metabolic biomarkers in the serum of patients with different degrees of hepatic cirrhosis. The results demonstrate that lysophosphatidyl choline (LPC) from positive electrospray ionization (ESI) mode, and fatty acids and bile acids from negative ESI mode play important roles in distinguishing decompensated from compensated cirrhosis. A total of 21 differential metabolites were found from the two groups of patients. LPCs, fatty acids, and taurocholic acid (TCA) 3-sulfate decreased in patients with decompensated cirrhosis, whereas other bile acids increased significantly. The levels of TCA 3-sulfate, LPC 16:0, and LPC 18:0 were significantly correlated with the stages of the decompensated cirrhosis, and they may serve as potential biomarkers for the stage assessment of liver cirrhosis in patients with HBV infections.
Co-reporter:Hongcui Cao, Haijun Huang, Wei Xu, Deying Chen, Jiong Yu, Jun Li, Lanjuan Li
Analytica Chimica Acta 2011 Volume 691(1–2) pp:68-75
Publication Date(Web):8 April 2011
DOI:10.1016/j.aca.2011.02.038
Fecal metabolome of healthy humans and patients suffering from liver cirrhosis and hepatocellular carcinoma (HCC) were studied using ultra performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF MS). Metabolic features detected by the method were then statistically treated using partial least squares to latent structure-discriminant analysis (PLS-DA) models to discriminate between healthy and diseased states. PLS-DA was also used to discriminate between cirrhosis and HCC stressed fecal metabolomes and to identify potential biomarkers for cirrhosis and HCC that are expressed at significantly different amounts in fecal metabolomes.Score plots of pattern recognition analysis distinguished liver cirrhosis and HCC patients from healthy humans. Based on the variable of importance in the project (VIP) values and S-plots, six metabolites were considered as potential biomarkers with a strong increase in lysophosphatidylcholines and a dramatic decrease in bile acids and bile pigments in patients with liver cirrhosis and HCC in comparison with healthy humans. Results demonstrate the potential of UPLC-MS as an efficient and convenient method that can be applied to screen fecal samples and aid in the early diagnosis of cirrhosis and hepatocellular carcinoma.
Co-reporter:Kaijin Xu, Yuanyuan Liu, Shaomin Liu, Aoyang Liu, Pengyun Liu, Lihong Liu, Lanjuan Li
Ceramics International 2011 Volume 37(Issue 7) pp:2109-2115
Publication Date(Web):September 2011
DOI:10.1016/j.ceramint.2011.02.023
Abstract
The aim of this study was to incorporate silver nanoparticles into yttria-stabilized zirconia (YSZ) ceramic for eliminating microorganism adhesion on dental restoration graft. Y2O3 (3% mol) partially stabilized ZrO2 powder with particle size around 80 nm was employed to fabricate tetragonal phase dominated YSZ ceramic block. Silver nanoparticles were efficiently loaded at pH 9.5 by NaBH4 reducing of AgNO3. The biocompatibility of silver incorporated YSZ was evaluated by MTT assay. Antimicrobial activities were quantitatively determined by optical density measurement and qualitatively analysed by scanning electro microscope. Inductively coupled plasma-mass spectrometry (ICP-MS) revealed that YSZ block containing 0.0047 wt% nanosilver, which is safe to mammalian cell, can inhibit the growth of Escherichia coli, Streptococcus mitis and Candida albicans. The pristine YSZ disc had no effect on bacterial growth. This study suggests that silver nanoparticles incorporated into YSZ blocks possess a broad spectrum antimicrobial effect and may help prevent biofilm formation on their surfaces to improve implant survival rate.
Co-reporter:Shaorui Hao;Jiaojiao Xin;Jiangshan Lian;Qing Xie;Deying Chen
Metabolomics 2011 Volume 7( Issue 3) pp:400-412
Publication Date(Web):2011 September
DOI:10.1007/s11306-010-0260-5
Liver failure induced by hepatitis B virus (HBV) is a severe disease with a high mortality rate. Liver support treatment is a powerful method for treating liver failure and is a bridge to liver transplantation. Patients with similar liver function indices, however, have different outcomes following treatment, and no satisfying prediction parameters exist. In this study, we used ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) to investigate plasma metabolites in groups of acute-on-chronic liver failure patients with different prognosis. An orthogonal partial least squares (OPLS) model, with satisfactory explanatory and predictive ability (R2Y = 0.943, Q2 = 0.913) was established using SIMCA-P + 12.0. The model was based on samples collected just before the first artificial treatment for comparable model efficacy. The concordance statistics of our model was 0.968 (95% CI [0.951, 0.985]) which is superior to that of the MELD (the Model for End-stage Liver Diseases) score (0.737, 95% CI [0.578, 0.896]). Three groups of markers were identified: lysophosphatidylcholine, primary fatty acid amides and conjugated bile acids. Lysophosphatidylcholine and conjugated bile acids were protection factors for survival and primary fatty acid amides were risk factors. The cut-off point for the predictive value of our model was greater than or equal to 0.196, at which the model showed the best discrimination between the recovery and non-recovery groups, with a sensitivity of 95% and a specificity of 87%. This metabolomic model, based on plasma UPLC-MS profiles, provides not only excellent discrimination and prognostic ability for HBV-induced acute-on-chronic liver failure but also early and precise warning of possible liver transplantation.
Co-reporter:Lan-Juan Li
Frontiers of Medicine 2010 Volume 4( Issue 2) pp:139-146
Publication Date(Web):2010 June
DOI:10.1007/s11684-010-0033-6
Hand, foot and mouth disease (HFMD) is an acute viral illness that primarily affects infants and young children, and often occurs in clusters or outbreaks. The major causative agents of HFMD are coxsackievirus A16 (CVA16), human enterovirus 71 (HEV71) and coxsackievirus A10 (CVA10), of the genus Enterovirus in the family Picornaviridae. HFMD caused by EV71 is associated with severe neurological complications and death. Since the late 1990s, several major epidemics of EV71 HFMD have swept through the Asia-Pacific region, associated with a rapid fulminant course, severe neurological complications, and a large number of fatalities. Until now, little has been known about the genetics and transmission trends of the fast-mutation virus, and there is no effective and specific antiviral therapy or vaccine for HFMD. It is time to step up efforts to understand the molecular epidemics and pathogenesis so that we can develop effective management strategies and surveillance programs.
Co-reporter:Huaying Wang, Kaijin Xu, Lihong Liu, Jeremy P.K. Tan, Yunbo Chen, Yongtao Li, Weimin Fan, Zeqing Wei, Jifang Sheng, Yi-Yan Yang, Lanjuan Li
Biomaterials 2010 31(10) pp: 2874-2881
Publication Date(Web):
DOI:10.1016/j.biomaterials.2009.12.042
Co-reporter:Lanjuan Li, Huaying Wang, Zhan Yuin Ong, Kaijin Xu, Pui Lai Rachel Ee, Shusen Zheng, James L. Hedrick, Yi-Yan Yang
Nano Today 2010 Volume 5(Issue 4) pp:296-312
Publication Date(Web):August 2010
DOI:10.1016/j.nantod.2010.06.007
Liver diseases, particularly hepatitis B virus infections, liver cirrhosis and hepatocellular carcinoma continue to pose a significant health challenge worldwide due to the dire lack of curative treatment options besides liver resection and transplantation. Nanoparticle therapeutics, comprising of drugs, nucleic acids or proteins in association with a carrier, have emerged as safe and efficient systems in the treatment of the respective liver diseases. This review describes targeting strategies employed in relation to liver anatomy and disease etiologies, summarizes recent advances in the field and discusses the challenges and future perspectives for the effective treatment of liver diseases using polymer- and lipid-based nanoparticle therapeutics.
Co-reporter:Qian Yang;Fei Liu;Xiao Ping Pan;GuoLiang Lv;AnYe Zhang
Hepatology International 2010 Volume 4( Issue 4) pp:757-761
Publication Date(Web):2010 December
DOI:10.1007/s12072-010-9210-6
Bioartificial liver assist devices (BLADs) are expected to bridge liver failure patients to liver transplantation, but porcine endogenous retroviruses (PERVs) still pose a potential risk in pig-to-human xenotransplantation and thereby limit the use of bioartificial liver therapy. In our lab, fluidized-bed BLADs based on microencapsulated primary porcine hepatocytes have been successfully used to treat liver failure pigs. We detected the risk of PERVs transmission of microencapsulated primary porcine hepatocytes—the key component of fluidized-bed BLADs, to evaluate the biosafety of this device for further clinical applications.Microencapsulated primary porcine hepatocytes (cell diameter = 300 μm) were cultured in Dulbecco’s modified Eagles medium (DMEM). Microencapsulated cell culture supernatants were collected at 6, 12, 24 and 72 h. HEK-293 were cocultured with these supernatants, and the cocultured cells were harvested every 7 days. RT-PCR was used to detect PERVs transmission. RT-qPCR was used to get the number of virus copies. PK-15 was used as the positive control whereas HepG2 was used as the negative control.PERV was detected in all supernatants, and the viral load of the supernatants increased with time. Moreover, cocultured 293 cells were positive for PERV-specific sequences.The kind of fluidized-bed BLADs based on microencapsulated primary porcine hepatocytes have risk of PERVs transmission. Further extensive pre-clinical study focused on biosafety is warranted.
Co-reporter:Hongcui Cao;Jiong Yu;Wei Xu;Xiaofei Jia;Jinfeng Yang;Qiaoling Pan
Proteome Science 2009 Volume 7( Issue 1) pp:
Publication Date(Web):2009 December
DOI:10.1186/1477-5956-7-48
Although 70% (or 2/3) partial hepatectomy (PH) is the most studied model for liver regeneration, the hepatic protein expression profile associated with lower volume liver resection (such as 50% PH) has not yet been reported. Therefore, the aim of this study was to determine the global protein expression profile of the regenerating mouse liver following 50% PH by differential proteomics, and thereby gaining some insights into the hepatic regeneration mechanism(s) under this milder but clinically more relevant condition.Proteins from sham-operated mouse livers and livers regenerating for 24 h after 50% PH were separated by SDS-PAGE and analyzed by nanoUPLC-Q-Tof mass spectrometry. Compared to sham-operated group, there were totally 87 differentially expressed proteins (with 50 up-regulated and 37 down-regulated ones) identified in the regenerating mouse livers, most of which have not been previously related to liver regeneration. Remarkably, over 25 differentially expressed proteins were located at mitochondria. Several of the mitochondria-resident proteins which play important roles in citric acid cycle, oxidative phosphorylation and ATP production were found to be down-regulated, consistent with the recently-proposed model in which the reduction of ATP content in the remnant liver gives rise to early stress signals that contribute to the onset of liver regeneration. Pathway analysis revealed a central role of c-Myc in the regulation of liver regeneration.Our study provides novel evidence for mitochondria as a pivotal organelle that is connected to liver regeneration, and lays the foundation for further studies on key factors and pathways involved in liver regeneration following 50% PH, a condition frequently used for partial liver transplantation and conservative liver resection.
Co-reporter:Min Li;Menghui Zhang;Baohong Wang;Mattias Rantalainen;Shengyue Wang;Xiaoyan Pang;Meiling Zhang;Jian Shen;Yan Zhang;Haokui Zhou;Hua Wei;Jian Zuo;Yu Chen;Haifeng Lu;Mingming Su;Chaoni Xiao;Yunping Qiu;Wei Jia;Shengli Yang;Leon M. Smith;Elaine Holmes;Huiru Tang;Guoping Zhao;Jeremy K. Nicholson;Liping Zhao
PNAS 2008 Volume 105 (Issue 6 ) pp:2117-2122
Publication Date(Web):2008-02-12
DOI:10.1073/pnas.0712038105
Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (microbiome) and individual variations
in the microbiome influence host health, may be implicated in disease etiology, and affect drug metabolism, toxicity, and
efficacy. However, the molecular basis of these microbe–host interactions and the roles of individual bacterial species are
obscure. We now demonstrate a“transgenomic” approach to link gut microbiome and metabolic phenotype (metabotype) variation.
We have used a combination of spectroscopic, microbiomic, and multivariate statistical tools to analyze fecal and urinary
samples from seven Chinese individuals (sampled twice) and to model the microbial–host metabolic connectivities. At the species
level, we found structural differences in the Chinese family gut microbiomes and those reported for American volunteers, which
is consistent with population microbial cometabolic differences reported in epidemiological studies. We also introduce the
concept of functional metagenomics, defined as “the characterization of key functional members of the microbiome that most
influence host metabolism and hence health.” For example, Faecalibacterium prausnitzii population variation is associated with modulation of eight urinary metabolites of diverse structure, indicating that this
species is a highly functionally active member of the microbiome, influencing numerous host pathways. Other species were identified
showing different and varied metabolic interactions. Our approach for understanding the dynamic basis of host–microbiome symbiosis
provides a foundation for the development of functional metagenomics as a probe of systemic effects of drugs and diet that
are of relevance to personal and public health care solutions.
Co-reporter:ChunChao Zhang;Feng Zhu;JianFeng Wei
Science China Life Sciences 2007 Volume 50( Issue 3) pp:312-319
Publication Date(Web):2007 June
DOI:10.1007/s11427-007-0038-9
In order to understand the allograft rejection in orthotopic liver transplantation (OLT), an allograft rejection rat model was established and studied by proteomic approach. The protein expression profiles of liver tissues were acquired by fluorescence two-dimensional difference gel electrophoresis (2D DIGE) that incorporated a pooled internal standard and reverse fluorescent labeling method. The expression levels of 27 protein spots showed significant changes in acute rejection rats. Among these spots, 19 were identified with peptide mass fingerprinting using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) after tryptic in-gel digestion. The results of the present paper could be helpful for our better understanding of allograft rejection in organ transplantation.
Co-reporter:
Science 1918 Vol 48(1249) pp:572-573
Publication Date(Web):06 Dec 1918
DOI:10.1126/science.48.1249.572
Co-reporter:Jiezuan Yang, Kaijin Xu, Jianfang Zheng, Li Wei, Jun Fan, Lanjuan Li
Tuberculosis (September 2013) Volume 93(Issue 5) pp:529-537
Publication Date(Web):1 September 2013
DOI:10.1016/j.tube.2013.05.007
Mycobacterium tuberculosis (MTB)-specific antigens, ESAT-6 or CFP-10 play a key role in diagnosis and control MTB infection. T cell receptor (TCR) reflects the status and function of T cells. However, the features of the TCR beta variable (TCRBV) repertoire used against ESAT-6 and CFP-10 from MTB subjects have not been well described. The molecular profiles of TCRBV complementarity-determining region 3 (CDR3) in PBMCs with or without ESAT-6 or CFP-10 stimulation were assayed using a gene melting spectral pattern (GMSP) assay developed in our previous study. The average number of skewed TCRBV family in PBMCs stimulated with ESAT-6 or CFP-10 was significantly higher than that in unstimulated PBMCs. TCRBV3, BV5.1, BV12, BV13.1, BV13.2, BV20 and BV24 were used more frequently than other TCRBV members in PBMCs from MTB subjects, and TCRBV3, BV5.1 in stimulated PBMCs have a preference in the usage of variable (V) and joining (J) segments and CDR3. The results indicate that the T cell immune response in MTB subjects involves a few of specific T cells. The preferred usage of certain V and J segments and CDR3s of TCRBV3 or BV5.1 may be related to ESAT-6 or CFP-10 respectively, which would help clinical differential diagnosis and treatment of MTB-infected subjects.
Co-reporter:Yonghong Xiao, Jin Wang, Ping Shen, Beiwen Zheng, Yingdong Zheng, Lanjuan Li
International Journal of Antimicrobial Agents (October 2016) Volume 48(Issue 4) pp:409-414
Publication Date(Web):1 October 2016
DOI:10.1016/j.ijantimicag.2016.06.017
•Inappropriate antibiotic use is a serious problem in primary medical institutions in China.•Prescribers preferred to use new and broad-spectrum antibiotics.•The Essential Medicine Policy (EMP) was implemented in 2009 after initiation of a new round of healthcare reform in China.•Enforcing the EMP could reduce the cost of medical services.•The EMP did not have an impact on promoting rational antibiotic use.The objective of this study was to understand the impact of implementation of the Essential Medicine Policy (EMP) on the rational use of antibiotics in primary medical institutions in China. A retrospective survey was conducted in 39 primary medical institutions to compare the efficacy of EMP in rational antibiotic use. All institutions completed the survey 1 year before and 1 year after implementation of the EMP. In particular, antibiotic use and its rationality were closely examined. The institutions mainly dealt with common diseases, especially non-infectious chronic diseases. Antibiotic usage was very inappropriate both before and after EMP implementation. Before and after EMP implementation, respectively, the median outpatient cost was US$6.34 and US$5.05, 52.50% (2005/3819) and 53.41% (1865/3492) of the outpatient prescriptions contained antibiotics, and 76.23% (1132/1485) and 78.83% (1106/1403) of inpatients were administered antibiotics. In addition, 98.38% (425/432) and 97.52% (512/525) of surgical inpatients were administered antibiotics, respectively, and 80.76% (638/790) and 75.19% (503/669) of patients with a cold were prescribed antibiotics, respectively. The most commonly used antibiotics were broad-spectrum and injectable agents, including cephalosporins, fluoroquinolones and penicillins. This profile showed little change following implementation of the EMP. In conclusion, inappropriate antibiotic use is a serious problem in primary medical institutions in China. Whilst enforcing the EMP reduced the cost of medical services, it had little effect on promoting the rational use of antibiotics.
Co-reporter:Yonghong Xiao, Jin Wang, Ping Shen, Beiwen Zheng, Yingdong Zheng, Lanjuan Li
International Journal of Antimicrobial Agents (October 2016) Volume 48(Issue 4) pp:409-414
Publication Date(Web):1 October 2016
DOI:10.1016/j.ijantimicag.2016.06.017
•Inappropriate antibiotic use is a serious problem in primary medical institutions in China.•Prescribers preferred to use new and broad-spectrum antibiotics.•The Essential Medicine Policy (EMP) was implemented in 2009 after initiation of a new round of healthcare reform in China.•Enforcing the EMP could reduce the cost of medical services.•The EMP did not have an impact on promoting rational antibiotic use.The objective of this study was to understand the impact of implementation of the Essential Medicine Policy (EMP) on the rational use of antibiotics in primary medical institutions in China. A retrospective survey was conducted in 39 primary medical institutions to compare the efficacy of EMP in rational antibiotic use. All institutions completed the survey 1 year before and 1 year after implementation of the EMP. In particular, antibiotic use and its rationality were closely examined. The institutions mainly dealt with common diseases, especially non-infectious chronic diseases. Antibiotic usage was very inappropriate both before and after EMP implementation. Before and after EMP implementation, respectively, the median outpatient cost was US$6.34 and US$5.05, 52.50% (2005/3819) and 53.41% (1865/3492) of the outpatient prescriptions contained antibiotics, and 76.23% (1132/1485) and 78.83% (1106/1403) of inpatients were administered antibiotics. In addition, 98.38% (425/432) and 97.52% (512/525) of surgical inpatients were administered antibiotics, respectively, and 80.76% (638/790) and 75.19% (503/669) of patients with a cold were prescribed antibiotics, respectively. The most commonly used antibiotics were broad-spectrum and injectable agents, including cephalosporins, fluoroquinolones and penicillins. This profile showed little change following implementation of the EMP. In conclusion, inappropriate antibiotic use is a serious problem in primary medical institutions in China. Whilst enforcing the EMP reduced the cost of medical services, it had little effect on promoting the rational use of antibiotics.
Co-reporter:Jing-Jing Ren, Ying Liu, Wen Ren, Yan Qiu, ... Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (October 2014) Volume 13(Issue 5) pp:495-500
Publication Date(Web):1 October 2014
DOI:10.1016/S1499-3872(14)60313-1
BackgroundHepatitis B virus (HBV) infection may impose an economic burden to patients or their families. The prevention and control of HBV could effectively reduce the burden. However, the management of HBV-related patients has not been well controlled in China. With the development of general practitioner (GP) system in this country, GPs may greatly improve the management of the patients with HBV infection. However, the role of GPs in controlling HBV infection has been rarely studied.Data SourcesA literature search of PubMed, CNKI, Wanfang data and VIP was performed with the following key words: “general practitioner”, “family physician”, “community management”, “community health care workers”, “family practice”, “hepatitis B virus”, “HBV”, “HBV vaccination”, “HBV prevention”, “HBV management”, “HBV treatment”, “antiviral therapy” and “chronic hepatitis B (CHB)”. The information about the GPs-involved prevention, diagnosis and treatment of CHB was reviewed.ResultsThe reports on the role of GPs in the prevention, diagnosis and treatment of HBV infection are few. But the experiences from Western countries demonstrated that GPs could play a significant role in the management of patients with CHB. The importance of GPs is obvious although there are some difficulties in China. GPs and health officials at different levels should work together in the management of patients with CHB.ConclusionsThe involvement of GPs in the management of patients with HBV infection is effective in China. But GPs' knowledge and skills for the control of HBV infection have to be improved currently. GPs' involvement will enforce the management of CHB in China in the near future.
Co-reporter:Jianfeng Shen, Bin Ju, Tao Jiang, Jingjing Ren, Miao Zheng, Chengwei Yao, Lanjuan Li
Neurocomputing (November 2011) Volume 74(Issue 18) pp:3785-3792
Publication Date(Web):1 November 2011
DOI:10.1016/j.neucom.2011.07.012
Image classification is an important task in computer vision and machine learning. However, it is known that manually labeling images is time-consuming and expensive, but the unlabeled images are easily available. Active learning is a mechanism which tries to determine which unlabeled data points would be the most informative (i.e., improve the classifier the most) if they are labeled and used as training samples. In this paper, we introduce the idea of column subset selection, which aims to select the most representation columns from a data matrix, into active learning and propose a novel active learning algorithm, column subset selection for active learning (CSSactive). CSSactive selects the most representative images to label, then the other images are reconstructed by these labeled images. The goal of CSSactive is to minimize the reconstruction error. Besides, most of the previous active learning approaches are based on linear model, and hence they only consider linear functions. Therefore, they fail to discover the intrinsic geometry in images when the image space is highly nonlinear. Therefore, we provide a kernel-based column subset selection for active learning (KCSSactive) algorithm which performs the active learning in Reproducing Kernel Hilbert Space (RKHS) instead of the original image space to address this problem. Experimental results on Yale, AT&T and COIL20 data sets demonstrate the effectiveness of our proposed approaches.
Co-reporter:Shi-Gui Yang, Hong-Jun Dong, Fu-Rong Li, Shu-Yun Xie, ... Lan-Juan Li
Journal of Infection (November 2007) Volume 55(Issue 5) pp:419-424
Publication Date(Web):1 November 2007
DOI:10.1016/j.jinf.2007.07.011
BackgroundScarlet fever is caused by group A beta-hemolytic streptococci (GAS). The clinical syndrome has receded in recent years, but occasionally explosive outbreaks do occur likely due to the emergence of GAS with virulence factors peculiar to this syndrome.MethodsFollowing the notification of an unexpectedly large number of scarlet fever cases amongst adults associated with a school in Ningbo, China, in June 2006, the epidemiological and clinical features of the outbreak were investigated. Logistic regression was conducted to investigate the risk factors of the outbreak and its transmission route.ResultsForty five individuals suffered scarlet fever with an attack rate of 4.98% (45/904). There was a single peak in the epidemic curve, with the majority of the cases occurring during the first two days of the outbreak. The median age of cases was 35.5 years (range 17–65). Most patients had fever (43/45), sore throat (40/45), scarlatinoid rash (39/45) and strawberry-like tongue (30/45). In laboratory detection, 45 cases’ throat swabs samples were collected and GAS were isolated from 8 throat swabs samples. All of the cases, except for 2, had eaten the Plain Boiled Chicken (PBC) for lunch on June 6th, and teaching staff and students who had not eaten the PBC were not affected by the epidemic. Logistic regression analysis indicated that PBC was a key risk factor (OR = 21.0, P < 0.05). The chef of the school refectory was responsible for washing, braising, cutting, and distributing the PBC, and was identified as the likely source.ConclusionsWe describe an outbreak of scarlet fever caused by GAS- contaminated food.
Co-reporter:G. Cui, H. Diao, Y. Wei, J. Chen, ... L. Li
Revista Portuguesa de Pneumologia (English Edition) (May–June 2015) Volume 21(Issue 3) pp:157-162
Publication Date(Web):1 May 2015
DOI:10.1016/j.rppnen.2014.11.003
IntroductionH7N9 infection has raised serious concerns worldwide. Pregnant women were considered to be at a high risk of influenza infection. Normal pregnancy was dependent on T helper (Th) 2 deviation. However, whether pregnancy influences the immune status of influenza H7N9 patients has not been reported.Case reportHere, we reported a case of pregnant woman in the first trimester with H7N9 infection compared with the two non-pregnant female H7N9 patients for clinical features and relevant immunological changes. We found that there were no differences in plasma levels of Th1 and Th2 cytokines between the pregnant and non-pregnant patients, and there was no Th2 deviation in the acute phase. However, the Th2 deviation was recurrent along with the clearance of infection in the H7N9 pregnant patient.ConclusionThese cases highlighted that the pregnant patient infected with H7N9 could induce an effective Th1 immune response equal to that of non-pregnant patients with H7N9 virus infection, although the pregnancy itself could lead to a Th2 deviation. These data suggested that pregnant patients could acquire a similar antiviral response for H7N9 infection versus non-pregnant patients.
Co-reporter:Tiansheng Xie, Zongxing Yang, Shigui Yang, Nanping Wu, Lanjuan Li
International Journal of Infectious Diseases (May 2014) Volume 22() pp:1-3
Publication Date(Web):1 May 2014
DOI:10.1016/j.ijid.2013.11.013
Data on the topic of novel avian influenza A (H7N9) were collected based on the web analysis tool ‘Baidu Index’, a major Chinese search engine. We found a positive correlation between the volume of H7N9-related ‘cyber user awareness’ and the epidemic situation during the H7N9 outbreak in China (r = 0.98, p < 0.01, cumulative; r = 0.43, p = 0.018, daily) except in the early stage; the ranks of H7N9-related topics changed at different epidemic stages. This study may improve our understanding of the role of web-based media in infectious disease surveillance in China.
Co-reporter:Wenrui Wu, Ding Shi, Daiqiong Fang, Feifei Guo, Jing Guo, Fengming Huang, Yanfei Chen, Longxian Lv, Lanjuan Li
International Journal of Infectious Diseases (March 2016) Volume 44() pp:31-36
Publication Date(Web):1 March 2016
DOI:10.1016/j.ijid.2016.01.009
•Compared with H1N1 virus, H7N9 virus can induce high expression of C-reactive protein (CRP).•H7N9 patients with high levels of CRP had poor outcomes.•MIP-1β, MCP-1, IP-10, and IL-6 plasma levels were positively related to CRP levels.•The plasma IL-17A level had a negative correlation with CRP.•CRP may be an indicator to assess cytokine storms and identify high-risk cases.ObjectivesThe avian influenza H7N9 virus can cause cytokine overproduction and result in severe pneumonia and acute respiratory distress syndrome. Many studies have focused on hypercytokinemia during avian influenza infection. This study examined the association between C-reactive protein (CRP) and cytokines.MethodsThe plasma cytokine and chemokine profiles of 57 H7N9 patients were investigated using a multiplex immunoassay. The CRP levels of patients with H7N9 and patients with H1N1 were also compared. Further, the association between cytokines and CRP in H7N9 infections was explored.ResultsCompared with H1N1 virus, it was found that H7N9 virus induced higher expression of CRP, leading to cytokine storms. Several cytokines, including MIP-1β, MCP-1, IP-10, and IL-6, were observed to have significantly positive relationships with CRP levels, whereas IL-17A was negatively associated with CRP levels.ConclusionsThese findings suggest that CRP may be used as an early indicator to identify high-risk patients, to assess disease progression, and to determine the development of hypercytokinemia.
Co-reporter:Y. Chen, X. Chen, F. Yu, M. Wu, R. Wang, S. Zheng, D. Han, Q. Yang, H. Kong, F. Zhou, J. Zhu, H. Yao, W. Zhou, L. Li
Clinical Microbiology and Infection (March 2016) Volume 22(Issue 3) pp:258.e9-258.e16
Publication Date(Web):1 March 2016
DOI:10.1016/j.cmi.2015.11.003
Vibrio parahaemolyticus is a leading cause of food-borne diarrhoea in coastal countries. Although V. parahaemolyticus cases have been reported since 1950, they have been poorly documented. From July 2009 to June 2013, we collected 6951 faecal specimens for pathogen detection; V. parahaemolyticus strains were isolated from 563 specimens (8.1%). We then analysed the characteristics of the 501 V. parahaemolyticus strains that were isolated as the sole pathogen. Twenty-one serotypes were identified among these strains; O3:K6 was the most common serotype (65.1%), followed by O4:K8, O4:K68 and O1:K36. One strain of the O4:K18 serotype was isolated from clinical patients for the first time. Pandemic O3:K6 clones were predominant and accounted for 69.1% of all of the pandemic strains. This is the first report of one strain expressing the O3:K8 serotype with a pandemic genotype. The presence of the haemolysin gene tdh (93.0%) was the key characteristic of the virulent strains; however, a few strains carried the trh gene. We also confirmed the presence of the type III secretion system 2 (T3SS2) genes in all of the pathogenic strains. Subsequent multilocus sequence typing split the isolates into 16 sequence types (STs), with ST3 and ST88 as the most prevalent in southeastern China. Most isolates were sensitive to common antimicrobial agents, apart from ampicillin. However, the resistance rate to ampicillin has apparently increased in this area. In conclusion, our results indicate that pandemic O3:K6 V. parahaemolyticus isolates are predominant in southeastern China, and additional surveillance should be conducted to facilitate control of the transmission of this pathogen.
Co-reporter:Yonghong Xiao, Lanjuan Li
The Lancet Infectious Diseases (March 2013) Volume 13(Issue 3) pp:189-191
Publication Date(Web):1 March 2013
DOI:10.1016/S1473-3099(13)70011-2
Co-reporter:Jia-Jia Chen, Jian-Rong Huang, Qian Yang, Xiao-Wei Xu, ... Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (June 2016) Volume 15(Issue 3) pp:275-281
Publication Date(Web):1 June 2016
DOI:10.1016/S1499-3872(16)60084-X
BackgroundPlasma exchange (PE)-centered artificial liver support system reduced the high mortality rate of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages.MethodsFrom December 2009 to December 2011, we evaluated 250 patients at different stages of HBV-ACLF from 10 major medical centers in China. All the laboratory parameters were collected at admission, before and after PE.ResultsAmong the 250 patients who underwent 661 rounds of PE, one-month survival rate was 61.6%; 141 (56.4%) showed improvement after PE. Variables such as age (P=0.000), levels of total bilirubin (TB, P=0.000), direct bilirubin (P=0.000), total triglycerides (P=0.000), low-density lipoprotein (P=0.022), Na+ (P=0.014), Cl− (P=0.038), creatinine (Cr, P=0.007), fibrinogen (P=0.000), prothrombin time (PT, P=0.000), white blood cell (P=0.000), platelet (P=0.003) and MELD (P=0.000) were significantly related to prognosis. Multivariate logistic regression analysis showed that age, disease stage, TB, Cr and PT levels were independent risk factors of mortality among HBV-ACLF patients.ConclusionsPE can improve the clinical outcome of patients with HBV-ACLF. Levels of TB, Cr and PT, age and disease stage help to predict prognosis.
Co-reporter:Baohong Wang, Lanjuan Li
Trends in Microbiology (June 2015) Volume 23(Issue 6) pp:328-329
Publication Date(Web):1 June 2015
DOI:10.1016/j.tim.2015.04.001
Until recently, the reason for age-dependent immune clearance of hepatitis B virus remained elusive. A new study has revealed that establishment of the commensal gut microbiota could modulate the liver immunity phenotype in a hydrodynamic transfection mouse model, suggesting that natural gut–liver interactions can help achieve rapid viral clearance.
Co-reporter:Yonghong Xiao, Zeqing Wei, Ping Shen, Jinru Ji, ... Lanjuan Li
Microbes and Infection (June 2015) Volume 17(Issue 6) pp:417-425
Publication Date(Web):1 June 2015
DOI:10.1016/j.micinf.2015.02.001
The purpose of this study was to survey antibacterial resistance in outpatients of Chinese county hospitals. A total of 31 county hospitals were selected and samples continuously collected from August 2010 to August 2011. Drug sensitivity testing was conducted in a central laboratory. A total of 2946 unique isolates were collected, including 634 strains of Escherichia coli, 606 Klebsiella pneumoniae, 476 Staphylococcus aureus, 308 Streptococcus pneumoniae, and 160 Haemophilus influenzae. Extended-spectrum β-lactamases were detected in E. coli (42.3% strains), K. pneumoniae (31.7%), and Proteus mirabilis (39.0%). Ciprofloxacin-resistance was detected in 51.0% of E. coli strains. Salmonella spp. and Shigella spp. were sensitive to most antibacterial agents. Less than 8.0% of Pseudomonas aeruginosa isolates were resistant to carbapenem. For S. aureus strains, 15.3% were resistant to methicillin, and some strains of S. pneumoniae showed resistance to penicillin (1.6%), ceftriaxone (13.0%), and erythromycin (96.4%). β-lactamase was produced by 96.5% of Moraxella catarrhalis strains, and 36.2% of H. influenzae isolates were resistant to ampicillin. Azithromycin-resistant H. influenzae, imipenem-resistant but meropenem-sensitive Proteus, and ceftriaxone- and carbapenem non-sensitive M. catarrhalis were recorded. In conclusion, cephalosporin- and quinolone-resistant strains of E. coli and Klebsiella pneumonia and macrolide-resistant Gram-positive cocci were relatively prominent in county hospitals. The antibacterial resistance profiles of isolates from different geographical locations varied significantly, with proportions in county hospitals lower than those in their tertiary counterparts in the central cities, although the difference is diminishing.
Co-reporter:Y. Chen, C. Yu, G. Lv, H. Cao, ... L. Li
Transplantation Proceedings (June 2014) Volume 46(Issue 5) pp:1649-1657
Publication Date(Web):1 June 2014
DOI:10.1016/j.transproceed.2014.03.002
IntroductionThe efficacy of any bioartificial liver device requires both rapid production and proper bioactivity of the cells for the bioreactor. The goal of this study was to observe the effect of spinner speed and cell density on the proliferation of microencapsulated immortalized human hepatocytes (HepLL) and human hepatoma (HepG2) cells.Materials and MethodsAlginate-chitosan microcapsulated HepG2 and HepLL cells were randomly divided into 2 groups, and each group was further divided into 8 subgroups according to embedded cell density and spinner speed. The growth, metabolism, and functions of the encapsulated cells in each group were evaluated.ResultsIn each group, the cell number, ammonium removal, albumin synthesis, and diazepam clearance increased significantly with the spinner speed, whereas embedded cell density had no impact. Albumin synthesis, removal of ammonium, and diazepam clearance were significantly higher in the microencapsulated HepLL groups than in HepG2 cells at any time point, without any significant difference in cell numbers.ConclusionsSpinner culture significantly promoted microencapsulated HepLL and HepG2 cell bioactivity. Wrapped cells had optimal function on day 10 in rolling culture groups. These data show that HepLL cells would be a promising candidate for cell-based liver support therapy.
Co-reporter:Hongyan Diao, Jianqin He, Qishi Zheng, Jianing Chen, ... Lanjuan Li
Immunology Letters (July 2014) Volume 160(Issue 1) pp:65-71
Publication Date(Web):1 July 2014
DOI:10.1016/j.imlet.2014.03.013
•NKT-like cell frequency positively correlates with HBV DNA in patients with CHB.•NKT-like cell frequency decreases in patients who respond to telbivudine.•NKT-like cell frequency positively correlates with serum IL-17 in CHB patients.•NKT-like cells may be a immunologic marker of the efficacy of anti-HBV therapy.•NKT-like cells may be an important source of IL-17 in patients with CHB.Natural killer T-like (NKT-like) cells are a source of different pro-inflammatory cytokines and therefore may be involved in inflammatory processes. However, little is known about NKT-like cells during antiviral therapy. In this study, we observed significantly higher numbers of CD3+CD56+ cells in patients with chronic hepatitis B (CHB) than healthy controls. Importantly, CD3+CD56+ NKT-like cells markedly decreased during telbivudine treatment in patients with CHB, and a positive correlation between NKT-like cell frequency and the serum HBV DNA level was observed during early antiviral therapy. Interestingly, NKT-like cell frequency significantly reduced in well-responders at week 12 of telbivudine therapy compared to baseline, but did not significantly change in non-responders after treatment. Previous studies have shown that interleukin (IL)-17 plays a role in the pathogenesis of CHB. Serum IL-17 levels reduced significantly during early antiviral therapy, however, interferon (IFN)-γ, IL-6 and tumor necrosis factor (TNF)-α levels did not change significantly. A positive correlation was observed between the NKT-like cell frequency and serum IL-17 level in CHB patients, and NKT-like cells isolated from patients with CHB secreted substantial amounts of IL-17 in vitro. These results suggest that the NKT-like cell frequency may be one of useful immunologic marker for evaluating the efficacy of anti-HBV therapy, and that NKT-like cells are also an important source of IL-17 (in addition to conventional T cells) in patients with CHB.
Co-reporter:Yu Chen, Xuefen Li, Bo Ye, Xianzhi Yang, Wei Wu, Baode Chen, Xiaoping Pan, Hongcui Cao, Lanjuan Li
Antiviral Research (July 2011) Volume 91(Issue 1) pp:23-31
Publication Date(Web):July 2011
DOI:10.1016/j.antiviral.2011.04.008
Co-reporter:Beiwen Zheng, Saiping Jiang, Zemin Xu, Yonghong Xiao, Lanjuan Li
The Brazilian Journal of Infectious Diseases (January–February 2015) Volume 19(Issue 1) pp:85-89
Publication Date(Web):1 January 2015
DOI:10.1016/j.bjid.2014.07.006
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasingly causing infective endocarditis over the past decade. Here we report a healthy man who developed a severe acute infective endocarditis with systemic embolism caused by CA-MRSA. The strain was recovered from repeated blood cultures and was characterized using molecular detection and genotyping. The S. aureus isolate was typed as ST630 SCCmecV with spa-type t4549, agrI/IV and was PVL-negative. This is the only case report, to our knowledge, of CA-MRSA infective endocarditis in China. This case highlights the emergence and geographical spread of life-threatening CA-MRSA infection within China.
Co-reporter:Jingjing Wu, Yini Wang, Lanjuan Li
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (January 2017) Volume 1863(Issue 1) pp:292-297
Publication Date(Web):January 2017
DOI:10.1016/j.bbadis.2016.10.024
Co-reporter:Zongxin Ling, Xia Liu, Yiwen Cheng, Lanjuan Li
Journal of Allergy and Clinical Immunology (February 2016) Volume 137(Issue 2) pp:
Publication Date(Web):1 February 2016
DOI:10.1016/j.jaci.2015.09.043
Co-reporter:Guang-yong Ye, Na Li, Yun-Bo Chen, Tao Lv, Ping Shen, Si-Lan Gu, Yun-hui Fang, Lan-Juan Li
Anaerobe (February 2016) Volume 37() pp:54-57
Publication Date(Web):February 2016
DOI:10.1016/j.anaerobe.2015.11.010
Co-reporter:Meifang Yang, Hainv Gao, Jiajia Chen, Xiaowei Xu, Lingling Tang, Yida Yang, Weifeng Liang, Liang Yu, Jifang Sheng, Lanjuan Li
Diagnostic Microbiology and Infectious Disease (February 2016) Volume 84(Issue 2) pp:165-169
Publication Date(Web):1 February 2016
DOI:10.1016/j.diagmicrobio.2015.10.018
•H7N9-infected patients with bacterial coinfection exhibit more severe disease.•S. aureus was the most prevalent pathogen.•Procalcitonin is an accurate marker for diagnosing bacterial coinfection in H7N9 patients.Patients contracting avian influenza A (H7N9) often develop severe disease. However, information on the contribution of bacterial coinfection to the severity of H7N9 is limited. We retrospectively studied 83 patients with confirmed H7N9 infection from April 2013 to February 2014. The severity of patients with bacterial coinfection and markers for early diagnosis of bacterial coinfection in H7N9 were analyzed. We found Staphylococcus aureus was the most prevalent pathogen. Higher Acute Physiology and Chronic Health Evaluation II score, shock, renal replacement treatment, mechanical ventilation, and extracorporeal membrane oxygenation treatment were more frequently observed in patients with bacterial coinfection. Procalcitonin is more sensitive than C-reactive protein in determining bacterial coinfection in H7N9 patients. In conclusion, H7N9 infection patients with bacterial coinfection had a more severe condition. Elevated procalcitonin is an accurate marker for diagnosing bacterial coinfection in H7N9 patients, thus enabling earlier antibiotic therapy.
Co-reporter:Xiao-Xin Wu, Hai-Nv Gao, Hai-Bo Wu, Xiu-Ming Peng, Hui-Lin Ou, Lan-Juan Li
International Journal of Infectious Diseases (December 2015) Volume 41() pp:3-5
Publication Date(Web):1 December 2015
DOI:10.1016/j.ijid.2015.10.009
•The mortality rate for avian-origin influenza A (H7N9) infections remains high (52%).•We successfully used convalescent plasma to treat an H7N9 infection in a 45-year-old man.•We are the first to use oseltamivir and convalescent plasma to treat H7N9 in China.In January 2015, there was an outbreak of avian-origin influenza A (H7N9) virus in Zhejiang Province, China. A 45-year-old man was admitted to the First Affiliated Hospital of Zhejiang University with a high fever that had lasted 7 days, chills, and a cough with yellow sputum. Laboratory testing confirmed infection with the H7N9 virus, likely obtained from contact with poultry at a local live poultry market. A large dense shadow was apparent in the patient's left lung at the time of admission. Treatment with oseltamivir (75 mg twice daily) did not improve the patient's condition. The decision was made to try using convalescent plasma to treat the infection. Convalescent plasma was administered 3 days after the patient was admitted to the hospital and led to a marked improvement. To our knowledge, this is the first report of the successful use of convalescent plasma to treat a case of H7N9 infection in China. These results suggest that the combination of convalescent plasma and antiviral drugs may be effective for the treatment of avian-origin H7N9 infection.
Co-reporter:Hai Nv Gao, Hang Ping Yao, Wei Feng Liang, Xiao Xin Wu, Hai Bo Wu, Nan Ping Wu, Shi Gui Yang, Qiong Zhang, Kun Kai Su, Jing Guo, Shu Fa Zheng, Yi Xin Zhu, Hong Lin Chen, Kwok-yung Yuen, Lan Juan Li
International Journal of Infectious Diseases (December 2014) Volume 29() pp:254-258
Publication Date(Web):1 December 2014
DOI:10.1016/j.ijid.2014.10.029
•We provided detailed clinical data, epidemiological information of two family cluster patients emerged in Zhejiang, China.•Genome sequencing and analyses of phylogenetic trees demonstrated that limited human-to-human transmission of the virus probable occurred in the family cluster cases.•We noted PB2 E627K substitution that was not existed in the isolates of the first wave, as well as two new mutations in the NA gene and six in PB2 gene.•We observed the reduced sensitivity of the new isolates to oseltamivir.ObjectivesIn the winter of 2013, people were facing the risk of human-to-human transmission of the re-emerging influenza A(H7N9) virus. We report herein information on the clinical features of two patients from the same family infected with this virus, the genomic sequences of the viruses harbored, and antiviral drug sensitivity.MethodsClinical and epidemiological data of two patients from the same family were collected and analyzed. Sequencing was done for the viruses isolated from these two patients and one epidemiologically related chicken, and the sequences of the eight gene segments of the viruses were analyzed phylogenetically. The sensitivity of the viruses to antiviral drug treatment was determined by neuraminidase inhibitor susceptibility test.ResultsThe two patients from one family cluster shared the same symptoms but had different outcomes, and had a strong epidemiological link. Three strains, two from these two patients and one from the chicken, were isolated. Genome sequencing and analyses of phylogenetic trees demonstrated that the two viruses were almost identical. We noted the presence of the PB2 E627K amino acid substitution that was not present in isolates from the first wave, as well as two new mutations in the NA gene and six in the PB2 gene. Drug sensitivity testing showed that the new isolates were resistant to oseltamivir but sensitive to peramivir.ConclusionsThe two patients from one family cluster were probable human-to-human transmission cases. The new isolates were sensitive to peramivir but showed reduced sensitivity to oseltamivir.
Co-reporter:Xiao-Ping Pan, Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (December 2012) Volume 11(Issue 6) pp:594-605
Publication Date(Web):1 December 2012
DOI:10.1016/S1499-3872(12)60230-6
BackgroundOrthotopic liver transplantation (OLT) is the most effective therapy for liver failure. However, OLT is severely limited by the shortage of liver donors. Bioartificial liver (BAL) shows great potential as an alternative therapy for liver failure. In recent years, progress has been made in BAL regarding genetically engineered cell lines, immortalized human hepatocytes, methods for preserving the phenotype of primary human hepatocytes, and other functional hepatocytes derived from stem cells.Data SourcesA systematic search of PubMed and ISI Web of Science was performed to identify relevant studies in English language literature using the key words such as liver failure, bioartificial liver, hepatocyte, stem cells, differentiation, and immortalization. More than 200 articles related to the cell sources of hepatocyte in BAL were systematically reviewed.ResultsMethods for preserving the phenotype of primary human hepatocytes have been successfully developed. Many genetically engineered cell lines and immortalized human hepatocytes have also been established. Among these cell lines, the incorporation of BAL with GS-HepG2 cells or alginateencapsulated HepG2 cells could prolong the survival time and improve pathophysiological parameters in an animal model of liver failure. The cBAL111 cells were evaluated using the AMC-BAL bioreactor, which could eliminate ammonia and lidocaine, and produce albumin. Importantly, BAL loading with HepLi-4 cells could significantly improve the blood biochemical parameters, and prolong the survival time in pigs with liver failure. Other functional hepatocytes differentiated from stem cells, such as human liver progenitor cells, have been successfully achieved.ConclusionsAside from genetically modified liver cell lines and immortalized human hepatocytes, other functional hepatocytes derived from stem cells show great potential as cell sources for BAL. BAL with safe and effective liver cells may be achieved for clinical liver failure in the near future.
Co-reporter:Ning Zhou, Jianzhou Li, Yimin Zhang, Juan Lu, ... Lanjuan Li
Journal of Hepatology (August 2015) Volume 63(Issue 2) pp:378-387
Publication Date(Web):1 August 2015
DOI:10.1016/j.jhep.2015.03.018
Background & AimsExtracorporeal blood purification systems for supportive therapy of liver failure are widely used. We developed a novel blood purification system, named Li’s artificial liver system (Li-ALS), which couples low-volume plasma exchange (low-volume PE) with plasma filtration adsorption (PFA). This study aims to evaluate the efficacy of our novel system in pigs with acute liver failure (ALF).MethodsThirty-two pigs were infused with D-galactosamine (1.3 g/kg) to induce ALF. All animals were equally and randomly divided into four groups: the ALF control group received intensive care, the PFA group underwent five hour plasma recycling filtration and adsorption purification, the low-volume PE group received one hour low-volume PE, and the Li-ALS group underwent one hour low-volume PE, followed by five hour PFA. Intervention was initiated 36 hours after drug administration. The efficacy of each treatment was assessed by survival time and improvement in hematological, biochemical, and immunohistological parameters.ResultsPigs in the Li-ALS group survived longer than those in the other groups (p <0.001, ALF control: 60 ± 2 h; PFA group: 74 ± 2 h; low-volume PE group: 75 ± 2 h; and Li-ALS group: 90 ± 3 h). Liver enzyme, bilirubin, bile acid and blood ammonia levels were decreased significantly after Li-ALS treatment, and increases in inflammatory cytokines were ameliorated. A higher hepatocyte regeneration index was also observed in the Li-ALS group.ConclusionOur novel Li-ALS could expedite liver regeneration and improve survival time; hence, it could be promising for treating ALF.Download high-res image (142KB)Download full-size image
Co-reporter:Hai-jun Huang, An-ye Zhang, Hong-cui Cao, Hai-feng Lu, ... Lan-Juan Li
Digestive and Liver Disease (August 2013) Volume 45(Issue 8) pp:677-682
Publication Date(Web):1 August 2013
DOI:10.1016/j.dld.2013.01.001
BackgroundThe study of faeces offers a unique opportunity to observe cooperation between the microbiome and the metabolism of mammalian hosts, an essential element in the study of the human metabolome. In the present study, a global metabolomics approach was used to identify metabolites differentially excreted in the faeces of cirrhotic patients compared to controls.MethodsSeventeen cirrhotic patients and 24 healthy individuals were recruited. Faecal metabolites were detected through non-targeted reversed-phase ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry.ResultsA total of 9215 peaks were detected. Using unequal variance t-tests, 2393 peaks were observed with P ≤ 0.05, approximately 74.0% of which were due to decreased faecal metabolite concentrations in liver cirrhosis vs. healthy controls. Integrating multivariate data analyses, we identified six major groups of metabolites. Relative levels of identified metabolites were as follows: strong increase in lysophosphatidylcholines, aromatic amino acids, fatty acids, and acylcarnitines, and a dramatic decrease in bile acids and bile pigments.ConclusionWith severe hepatic injury in patients with liver cirrhosis, malabsorption occurs along with disorders of fatty acid metabolism, potentially due to changes in gut microflora.
Co-reporter:Qiang Wang, Yiping Liu, Daizhi An, Hongyan Diao, Wei Xu, Xiang He, Rubao Sun, Li Wei, Lanjuan Li
Virus Research (August 2012) Volume 167(Issue 2) pp:302-309
Publication Date(Web):1 August 2012
DOI:10.1016/j.virusres.2012.05.014
Eukaryotic initiation factors (eIFs) are required for encoding polyprotein of hepatitis C virus (HCV) which is mediated by an internal ribosome-entry site (IRES). Iron overload, a common finding among HCV patients, may be correlated with HCV pathology, but the underlying molecular mechanisms are poorly understood. In this study, we investigated the possible relationship among iron status, eIFs and HCV IRES-mediated translation in vitro. Using bicistronic reporter gene constructs carrying HCV IRES sequence, we found that the levels of intracellular iron were positively associated with the HCV IRES-dependent translation initiation in Huh-7 cells. RT-PCR method showed that iron treatment specifically increased the levels of eIF3A mRNA and La mRNA, whereas iron chelation reduced them. Western blots also confirmed that iron-dependent changes in eIF3A mRNA and La mRNA affected the expression of their proteins. Moreover, antisense phosphorothioate oligodeoxynucleotides to eIF3A and La successfully suppressed the levels of eIF3A and La protein and significantly reduced iron-dependent HCV translation. Taken together, our results suggest that iron promotes the translation initiation of HCV by stimulating the expression of eIF3A and La proteins. Inhibition of eIF3A and La proteins substantially repressed iron-dependent HCV translation, a beneficial effect that may have significant clinical implications.Highlights► Iron is positively associated with the HCV IRES-dependent translation. ► Iron enhances the expression of eIF3A and La proteins. ► Inhibition of eIF3A and La substantially repress iron-dependent HCV translation.
Co-reporter:Yu Chen, Zhenjing Chen, Renyong Guo, Nan Chen, Haifeng Lu, Shuai Huang, Jie Wang, Lanjuan Li
Diagnostic Microbiology and Infectious Disease (August 2011) Volume 70(Issue 4) pp:492-498
Publication Date(Web):1 August 2011
DOI:10.1016/j.diagmicrobio.2010.04.005
This study aims to compare the diversity of intestinal fungal microbiota in patients with different degrees of chronic hepatitis B virus (HBV) infection. Culture-independent and culture-dependent methods were performed on 38 patients with hepatitis B cirrhosis, 35 patients with chronic hepatitis B, 33 HBV carriers, and 55 healthy volunteers. An overall fungal biodiversity of 37 different operational taxonomic units was found in the clone libraries; only Candida spp. and Saccharomyces cerevisiae were obtained by the culture-dependent analysis. There was a higher richness of fungal species in patients with hepatitis B cirrhosis than in patients with chronic hepatitis B, and the latter was higher than that in HBV carriers and healthy volunteers. There was little difference in enteric fungal diversity between HBV carriers and healthy volunteers. The results indicate that the diversity of enteric fungi was positively correlated with the disease progression of patients with different degrees of chronic HBV infection.
Co-reporter:Wei-Fang Zhu, Shui-Ying Lei, Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (August 2011) Volume 10(Issue 4) pp:399-402
Publication Date(Web):1 August 2011
DOI:10.1016/S1499-3872(11)60067-2
BackgroundRapid plasma regain positive and/or treponema pallidum hemagglutination negative [RPR(+)/TPHA(−)] results were designated as biologic false-positive (BFP). There are limited data about BFP reactions against syphilis in patients with hepatitis C virus (HCV) infection. This study aimed to determine the prevalence of BFP reactions for syphilis in patients with HCV infection in a large sample and assess the relationship between BFP reactions and HCV infection.MethodsA total of 2656 patients with positive anti-HCV and 5600 healthy control subjects were enrolled in this study. Hepatitis C serology was determined by a second generation ELISA test for HCV antibody. Syphilis serology was determined by the RPR test. Those subjects with reactive RPR positive underwent the TPHA test. Demographics and laboratory data were collected by trained clinicians.ResultsAmong 2656 patients, 111 (4.2%) had a reactive RPR test. Of the 111 patients who were subjected to reactive RPR test, 30 (27.0%) showed HCV(+)/RPR(+). Of 5600 healthy controls, 80 (1.4%) had a reactive RPR test. Fourteen (17.5%) controls with HCV(−)/RPR(+) had a non-reactive TPHA test. These represented 1.1% of all HCV-positive and 0.3% of all HCV-negative subjects (P<0.001). A significantly increased prevalence shown by false-positive tests for syphilis was observed in elderly HCV-seropositive patients. BFP-HCV positive group had a higher prevalence of eosinophilia. The eosinophil abnormality was compared between the patients and controls (66.7% vs 21.4%, P= 0.0043). No significant results were observed in antinuclear antibodies, antiphospholipid and complement (C3, C4) (P>0.05).ConclusionsThe data of this study demonstrate that HCV infection is associated with a false-positive RPR test. In this study BFPs were significantly more common in HCV positive patients compared to HCV-negative ones. Eosinophil abnormality can be considered as a predictor for BFP. Excessive BFPs must be considered in assessing the frequency of syphilis in a HCV-positive population and the importance of the treponemal specific serologic test should be emphasized for a diagnosis of syphilis in such population.
Co-reporter:Xiao-Ping Pan, Yi-Ni Wang, Xiao-Peng Yu, Chun-Xia Zhu, ... Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (April 2016) Volume 15(Issue 2) pp:173-179
Publication Date(Web):1 April 2016
DOI:10.1016/S1499-3872(16)60074-7
BackgroundDifferentiation of liver progenitor cells (LPCs) to functional hepatocytes holds great potential to develop new strategies for hepatocyte transplantation and the screening of drug-induced cytotoxicity. However, reports on the efficient and convenient hepatic differentiation of LPCs to hepatocytes are few. The present study aims to investigate the possibility of generating functional hepatocytes from LPCs in an indirect co-culture system.MethodsMouse LPCs were co-cultured in Transwell plates with an immortalized human hepatic stellate cell line (HSC-Li) we previously established. The morphology, expression of hepatic markers, and functions of mouse LPC-derived cells were monitored and compared with those of conventionally cultured LPCs.ResultsCo-culturing with HSC-Li cells induced differentiation of mouse LPCs into functional hepatocyte-like cells. The differentiated cells were morphologically transformed into hepatocyte-like cells 3 days after co-culture initiation. In addition, the differentiated cells expressed liver-specific genes and possessed hepatic functions, including glycogen storage, low-density lipoprotein uptake, albumin secretion, urea synthesis, and cytochrome P450 1A2 enzymatic activity.ConclusionsOur method, which employs indirect co-culture with HSC-Li cells, can efficiently induce the differentiation of LPCs into functional hepatocytes. This finding suggests that this co-culture system can be a useful method for the efficient generation of functional hepatocytes from LPCs.
Co-reporter:Kunkai Su, Qi Wang, Luoyang Qi, Dasong Hua, Jingjing Tao, Connor J. Mangan, Yijia Lou, Lanjuan Li
Toxicology Letters (6 September 2016) Volume 258() pp:101-107
Publication Date(Web):6 September 2016
DOI:10.1016/j.toxlet.2016.06.010
•Cysteinyl-leukotrienes accumulated during Concanavalin A-induced mouse liver injury.•5-LO upregulation triggered the autoimmune reaction after Concanavalin A challenge.•Seven upregulated and two downregulated miRs were found related to hepatotoxicity of Concanavalin A.•MiR-674-5p negatively regulated 5-LO in hepatic cells with IL-6 or TNF-α presence.Autoimmune hepatitis is characterized, in part, by the pathways involving cysteinyl-leukotriene metabolites of arachidonic acid, the dynamics of which remain unclear. Here, we explored post-transcriptional regulation in the 5-lipoxygenase (5-LO) pathway of arachidonic acid in a Concanavalin A (Con A) induced mouse model. We found that Con A administration lead to 5-LO overexpression and cysteinyl-leukotriene release in early hepatic injury, which was attenuated by cyclosporin A pretreatment. Subsequent microarray and qRT-PCR analysis further showed that microRNA-674-5p (miR-674-5p) displayed a significant decrease in expression in Con A-damaged liver. Noting that miR-674-5p harbors a potential binding region for 5-LO, we further transfected hepatic cell lines with overexpressing miR-674-5p mimic and discovered a negative regulating effect of miR-674-5p on 5-LO expression in the presence of IL-6 or TNF-α. These findings suggest that miR-674-5p might be a negative regulator in 5-LO mediated autoimmune liver injury, representing a compelling avenue towards future therapeutic interventions.
Co-reporter:Long-Xian Lv, Ren Yan, Hai-Yan Shi, Ding Shi, Dai-Qiong Fang, Hui-Yong Jiang, Wen-Rui Wu, Fei-Fei Guo, Xia-Wei Jiang, Si-Lan Gu, Yun-Bo Chen, Jian Yao, Lan-Juan Li
Journal of Proteomics (6 January 2017) Volume 150() pp:
Publication Date(Web):6 January 2017
DOI:10.1016/j.jprot.2016.08.021
•An integrated transcriptomic and proteomic investigation of bile response mechanism was first performed conducted in L. salivarius by using strain LI01.•L. salivarius LI01 is a non-BSH-producing strain. Its bile resistance was is mainly based on a highly remodeled cell envelopes and reinforced bile efflux systems.•Bile-induced alterations in regulatory systems, cell surface, general stress response and central metabolism processes were observed and also to contributed to the bile resistance of LI01.•Bile-induced potential alterations of LI 01 such as the uptake of aromatic amino acids may be helpful forin liver protection.Lactobacillus salivarius LI01, isolated from healthy humans, has demonstrated probiotic properties in the prevention and treatment of liver failure. Tolerance to bile stress is crucial to allow lactobacilli to survive in the gastrointestinal tract and exert their benefits. In this work, we used a Digital Gene Expression transcriptomic and iTRAQ LC-MS/MS proteomic approach to examine the characteristics of LI01 in response to bile stress. Using culture medium with or without 0.15% ox bile, 591 differentially transcribed genes and 347 differentially expressed proteins were detected in LI01. Overall, we found the bile resistance of LI01 to be based on a highly remodeled cell envelope and a reinforced bile efflux system rather than on the activity of bile salt hydrolases. Additionally, some differentially expressed genes related to regulatory systems, the general stress response and central metabolism processes, also play roles in stress sensing, bile-induced damage prevention and energy efficiency. Moreover, bile salts appear to enhance proteolysis and amino acid uptake (especially aromatic amino acids) by LI01, which may support the liver protection properties of this strain. Altogether, this study establishes a model of global response mechanism to bile stress in L. salivarius LI01.Biological significanceL. salivarius strain LI01 exhibits not only antibacterial and antifungal properties but also exerts a good health-promoting effect in acute liver failure. As a potential probiotic strain, the bile-tolerance trait of strain LI01 is important, though this has not yet been explored. In this study, an analysis based on DGE and iTRAQ was performed to investigate the gene expression in strain LI01 under bile stress at the mRNA and protein levels, respectively. To our knowledge, this work also represents the first combined transcriptomic and proteomic analysis of the bile stress response mechanism in L. salivarius.
Co-reporter:Huilin Ou, Hangping Yao, Wei Yao, Nanping Wu, ... Lanjuan Li
Vaccine (29 April 2016) Volume 34(Issue 20) pp:2362-2370
Publication Date(Web):29 April 2016
DOI:10.1016/j.vaccine.2016.03.037
•This split vaccine is the first one using A/Zhejiang/1/2013 strain.•The MF59 adjuvant was compared with alum paired with this split vaccine.•We evaluated the cytokine changes especially after the wide type H7N9 virus incubation.•This preclinical experiment was carried out in a relatively comprehensive and systematic manner.The H7N9 influenza virus caused significant mortality and morbidity in humans during an outbreak in China in 2013. A recombinant H7N9 influenza seed with hemagglutinin (HA) and neuraminidase (NA) gene segments from A/Zhejiang/DTID-ZJU01/2013(H7N9) and six internal protein gene segments from A/Puerto Rico/8/34(H1N1; PR8) were generated using reverse genetics. We sought to determine the immunogenic, protective properties, and mechanisms of a split avian influenza A/H7N9 vaccine mixed with MF59 adjuvant in comparison to vaccines that included other adjuvant. BALB/c mice were vaccinated with two doses of different amounts and combinations of this novel A/ZJU01/PR8/2013 split vaccine with adjuvant. Mice were subsequently challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) by intranasal inoculation. We verified that MF59 enhanced the HI, MN, and IgG antibody titers to influenza antigens. Compared with alum, MF59 could more potentially induce humoral immune responses and Th2 cytokine production after virus infection, while both MF59 and alum can slightly increase NK cell activity. This split H7N9 influenza vaccine with MF59 adjuvant could effectively induce antibody production and protect mice from H7N9 virus challenge. We have selected this vaccine for manufacture and future clinical studies to protect humans from H7N9 virus infection.
Co-reporter:Yi-Min Zhang, Wei Yu, Ning Zhou, Jian-Zhou Li, ... Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (15 June 2015) Volume 14(Issue 3) pp:287-292
Publication Date(Web):15 June 2015
DOI:10.1016/S1499-3872(15)60379-4
BackgroundLinezolid is an effective antibiotic reagent for Gram-positive bacterial infection; its most common side effect is thrombocytopenia. However, the incidence of thrombocytopenia in patients with acute-on-chronic liver failure (ACLF) who underwent linezolid therapy was unclear. The present study was to evaluate the incidence of thrombocytopenia in ACLF and non-ACLF patients treated with linezolid and the risk factors of thrombocytopenia in these patients.MethodsThirty-five patients with ACLF who had been subjected to intravenous administration of 600 mg linezolid every 12 hours for more than 7 days were categorized as a ACLF treatment (ACLF-T) group, 72 patients without ACLF treated with the same dosage of linezolid were recruited as a non-ACLF treatment (NACLF-T) group, and 70 patients with ACLF without linezolid treatment served as an ACLF control (ACLF-C) group. The incidences of thrombocytopenia in different groups were compared at day 14. Risk factors were investigated using logistic regression analysis.ResultsThe incidence of thrombocytopenia at day 14 was significantly higher in the ACLF-T group than in the ACLF-C group (20/35 vs 24/70, P=0.025) and in the NACLF-T group (20/35 vs 9/72, P<0.001). Multivariate analysis showed that the ratio of platelet count (day 7/day 0) <1 (OR=10.021; P=0.012) and the baseline platelet count (OR=0.985; P=0.036) were independent risk factors of thrombocytopenia at day 14 of linezolid therapy.ConclusionsThe benefits of linezolid treatment should outweigh the risk of thrombocytopenia in patients with ACLF. Moreover, it is necessary to closely monitor the platelet count during linezolid therapy especially in the patients with decreased platelet count at day 7 of linezolid therapy.
Co-reporter:Li-Fu Zhao, Xiao-Ping Pan, Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (15 June 2012) Volume 11(Issue 3) pp:243-249
Publication Date(Web):15 June 2012
DOI:10.1016/S1499-3872(12)60155-6
BackgroundFor nearly three decades, extracorporeal bioartificial liver (BAL) support systems have been anticipated as promising tools for the treatment of liver failure. However, these systems are still far from clinical application. This review aimed to analyze the key challenges to the development of BALs.Data SourcesWe carried out a PubMed search of English-language articles relevant to extracorporeal BAL support systems and liver failure.ResultsExtracorporeal BALs face a series of challenges. First, an appropriate cell source for BAL is not readily available. Second, existing bioreactors do not provide in vivo-like oxygenation and bile secretion. Third, emergency needs cannot be met by current BALs. Finally, the effectiveness of BALs, either in animals or in patients, has been difficult to document.ConclusionsExtracorporeal BAL support systems are mainly challenged by incompetent cell sources and flawed bioreactors. To advance this technology, future research is needed to provide more insights into interpreting the conditions for hepatocyte differentiation and liver microstructure formation.
Co-reporter:Jianfeng Shen, Jiajun Bu, Bin Ju, Tao Jiang, Hao Wu, Lanjuan Li
Neurocomputing (15 June 2012) Volume 87() pp:19-25
Publication Date(Web):15 June 2012
DOI:10.1016/j.neucom.2012.01.029
Gaussian mixture model (GMM) has been widely used for data analysis in various domains including text documents, face images and genes. GMM can be viewed as a simple linear superposition of Gaussian components, each of which represents a data cluster. Recent models, namely Laplacian regularized GMM (LapGMM) and locally consistent GMM (LCGMM) have been proposed to preserve the local manifold structure of the data for modeling Gaussian mixtures, and show superior performance than the original GMM. However, these two models ignore the global manifold structure without consideration of the widely separated points. In this paper, we introduce refined Gaussian mixture model (RGMM), which explicitly places separated points far apart from each other as well as brings nearby points closer together according to the probability distributions of Gaussians, in the hope of fully discovering the discriminating power of manifold learning for estimating Gaussian mixtures. We use EM algorithm to optimize the maximum likelihood function of RGMM. Experimental results on three real-world data sets demonstrate the effectiveness of RGMM in data clustering.
Co-reporter:Zhong-Wen Wu, Zong-Xin Ling, Hai-Feng Lu, Jian Zuo, ... Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (15 February 2012) Volume 11(Issue 1) pp:40-50
Publication Date(Web):15 February 2012
DOI:10.1016/S1499-3872(11)60124-0
BackgroundLiver transplantation is one of the most effective therapeutic options for patients with end-stage liver diseases, and gut microbiota is actively involved in potential infections in pretransplant and posttransplant patients. However, the diversity of gut microbiota and its relationship with the immune parameter of liver transplantation recipients are not well understood.MethodsWe collected fresh feces and blood samples from 190 participants in China from November 2004 to May 2008, including 28 healthy volunteers, 51 cirrhotic patients and 111 liver-transplanted patients. Six interesting gut bacteria, plasma endotoxin, serum cytokines (i.e., tumor necrosis factor alpha and interleukin-6) and fecal secretory IgA (SIgA) were investigated by real-time quantitative PCR, chromogenic limulus amoebocyte assay, sandwich-type enzyme-linked immunosorbent assay and radioimmunoassay, respectively.ResultsAll Eubacteria, Bifidobacterium spp., Faecalibacterium prausnitzii and Lactobacillus spp. were significantly lower in the liver transplantation recipients while Enterobacteriaceae and Enterococcus spp. were significantly higher (P<0.05). Except for Enterococcus spp., other bacteria showed a tendency to restore to normal level along with the time after liver transplantation. Plasma endotoxin, interleukin-6 and fecal SIgA in cirrhotic patients increased significantly, but not in liver transplantation recipients. Plasma endotoxin and interleukin-6 were negatively correlated with all Eubacteria and the Bacteroides-Prevotella group, while tumor necrosis factor alpha was not significantly correlated with these six gut bacteria in cirrhotic patients.ConclusionsOur study demonstrates that abundant gut bacteria were altered significantly in both cirrhotic and liver transplantation patients, while plasma endotoxin and interleukin-6 increased remarkably in cirrhotic patients, showing significant correlations with gut microbiota. Interestingly, our data show a tendency for these gut bacteria to restore to normal levels in liver transplantation recipients.
Co-reporter:Shui-Ying Lei, Yan-Ping Dong, Pan-Zhi Wang, Shou-Chu Qian, ... Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (15 February 2012) Volume 11(Issue 1) pp:10-11
Publication Date(Web):15 February 2012
DOI:10.1016/S1499-3872(11)60118-5
Co-reporter:Yong-Tao Li, Cheng-Bo Yu, Dong Yan, Jian-Rong Huang, Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (15 August 2016) Volume 15(Issue 4) pp:399-405
Publication Date(Web):15 August 2016
DOI:10.1016/S1499-3872(16)60113-3
BackgroundAcute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model.MethodsOral supplementation with Salmonella enterica serovar enteritidis (S. enteritidis) was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury.ResultsThe levels of liver damage and endotoxin were significantly increased in the Salmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury (P>0.01); The peyer's patch CD3+ T cell counts were increased significantly when the Salmonella infection with severe injury group was compared with the normal group (P>0.05). S. enteritidis pretreatment enhanced intestinal barrier impairment and bacterial translocation.ConclusionsOral S. enteritidis administration exacerbates acute liver injury, especially when injury was severe. Major factors of the exacerbation include inflammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.
Co-reporter:Jin-Feng Yang, Hong-Cui Cao, Qiao-Ling Pan, Jiong Yu, ... Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (15 April 2015) Volume 14(Issue 2) pp:186-193
Publication Date(Web):15 April 2015
DOI:10.1016/S1499-3872(15)60354-X
BackgroundCell therapy has been promising for various diseases. We investigated whether transplantation of human umbilical cord mesenchymal stem cells (hUCMSCs) has any therapeutic effects on D-galactosamine/lipopolysaccharide (GalN/LPS)-induced fulminant hepatic failure in mice.MethodshUCMSCs isolated from human umbilical cord were cultured and transplanted via the tail vein into severe combined immune deficiency mice with GalN/LPS-induced fulminant hepatic failure. After transplantation, the localization and differentiation of hUCMSCs in the injured livers were investigated by immunohistochemical and genetic analyses. The recovery of the injured livers was evaluated histologically. The survival rate of experimental animals was analyzed by the Kaplan-Meier method and log-rank test.ResultshUCMSCs expressed high levels of CD29, CD73, CD13, CD105 and CD90, but did not express CD31, CD79b, CD133, CD34, and CD45. Cultured hUCMSCs displayed adipogenic and osteogenic differentiation potential. Hematoxylin and eosin staining revealed that transplantation of hUCMSCs reduced hepatic necrosis and promoted liver regeneration. Transplantation of hUCMSCs prolonged the survival rate of mice with fulminant hepatic failure. Polymerase chain reaction for human alu sequences showed the presence of human cells in mouse livers. Positive staining for human albumin, human alpha-fetoprotein and human cytokeratin 18 suggested the formation of hUCMSCs-derived hepatocyte-like cells in vivo.ConclusionshUCMSC was a potential candidate for stem cell based therapies. After transplantation, hUCMSCs partially repaired hepatic damage induced by GalN/LPS in mice. hUCMSCs engrafted into the injured liver and differentiated into hepatocyte-like cells.
Co-reporter:Cheng-Bo Yu, Jia-Jia Chen, Wei-Bo Du, Ping Chen, ... Lan-Juan Li
Hepatobiliary & Pancreatic Diseases International (15 April 2014) Volume 13(Issue 2) pp:179-183
Publication Date(Web):15 April 2014
DOI:10.1016/S1499-3872(14)60028-X
BackgroundAcute fatty liver of pregnancy (AFLP) in the third trimester or early postpartum period can lead to fatal liver damage. Its traditional therapy is not very effective in facilitating hepatic recovery. The safety and effect of plasma exchange (PE) in combination with continuous renal replacement therapy (CRRT) (PE+CRRT) for AFLP still needs evaluation.MethodsFive AFLP patients with hepatic encephalopathy and renal failure were subjected to PE+CRRT in our department from 2007 to 2012. Their symptoms, physical signs and results were observed, and all relevant laboratory tests were compared before and after PE+CRRT.ResultsAll the 5 patients were well tolerated to the therapy. Four of them responded to the treatment and showed improvement in clinical symptoms/signs and laboratory results, and they were cured and discharged home after the treatment. One patient succeeded in bridging to transplantation for slowing down hepatic failure and its complications process after 2 treatment sessions. Intensive care unit stay and hospital stay were 9.4 (range 5–18) and 25.0 days (range 11–42), respectively.ConclusionPE+CRRT is safe and effective and should be used immediately at the onset of hepatic encephalopathy and/or renal failure in patients with AFLP.
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