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Association of polymorphisms in non-classic MHC genes with susceptibility to autoimmune hepatitis

Hepatobiliary & Pancreatic diseases International 2012年第2期11卷 125-131页

作者： Jie Tang,Cheng Zhou,Zhi-Jun Zhang and Shu-Sen Zheng hangzhou,china key laboratory of Combined Multi-organ Trans- plantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery , and state key laboratory for diagnosis and treatment of infectious disease, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china key laboratory of Combined Multi-organ Transplantation Ministry of Public Health Department of Hepatobiliary and Pancreatic Surgery Hangzhou China state key laboratory for diagnosis and treatment of infectious disease First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Autoimmune hepatitis is a chronic,generally progressive inflammatory disorder of the liver,of which the cause is *** was demonstrated that genetic factors are involved in its *** studies showed that human leukocyte antigen in the major histocompatibility complex(MHC) is associated with susceptibility to autoimmune *** genome scanning studies suggest that genes outside the MHC also play a critical role in autoimmune *** article focuses on our current understanding of the polymorphisms of these genes and their roles in the pathogenesis of autoimmune *** SOURCES:Studies were identified by searching MEDLINE and PubMed for articles using the keywords autoimmune hepatitis,polymorphism,CTLA-4,Fas,TNF-α TGF-β1,TBX21 and VDR up to May *** papers were identified by a manual search of the references from key ***:According to the case-control studies on genetic polymorphisms,at least six genes(CTLA-4,Fas,TNF-α TGF-β1,TBX21 and VDR) are involved in autoimmune hepatitis besides *** far,there has been no agreement about gene susceptibility and the actual clinical significance of these genes is still ***:Studies on gene polymorphisms outside the MHC and knowledge of genetic predispositions for autoimmune hepatitis may not only elucidate pathogenic mechanisms,but also provide new targets for therapy in the future.

关键词： autoimmune hepatitis polymorphism gene expression

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Effects of suppressing glucose transporter-1 by an antisense oligodeoxynucleotide on the growth of human hepatocellular carcinoma cells

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Hepatobiliary & Pancreatic diseases International 2011年第1期10卷 72-77页

作者： Tian-Qi Liu,Jun Fan,Lin Zhou and Shu-Sen Zheng key laboratory of Combined Multi-organ Trans-plantation,Ministry of Public Health key laboratory of Organ Trans-plantation,zhejiang Province and Division of Hepatobiliary and Pancreatic Surgery,Department of Surgery state key laboratory for diagnosis and treatment of infectious disease,first affiliated hospital,zhejiang university school of medicine,hangzhou 310003,china Department of Hepatobiliary Surgery,the People’s hospital of Guangxi Zhuang Autonomous Region, Nanning 530021,china key laboratory of Combined Multi-organ Transplantation Ministry of Public Health key laboratory of Organ Transplantation Zhejiang Province and Division of Hepatobiliary and Pancreatic Surgery Department of Surgery Zhejiang University School of Medicine Hangzhou 310003 China Department of Hepatobiliary Surgery the People's Hospital of Guangxi Zhuang Autonomous Region Nanning 530021 China state key laboratory for diagnosis and treatment of infectious disease First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:The glucose transporter-1(Glut-1),a key ratelimiting factor in the transport and metabolism of glucose in cancer cells,is over-expressed in many human cancer cells and this overexpression is correlated with poor biological behavior. The increased levels of Glut-1 expression in hepatocellular carcinoma(HCC)cells functionally affect *** study was undertaken to investigate effects of suppressing Glut-1 by an antisense oligodeoxynucleotide(AS-ODN)on the growth of human hepatocellular carcinoma(HepG-2)cells. METHODS:We used AS-ODN targeting against the Glut-1 gene in a HepG-2 cell *** were four experimental groups: empty pcDNA3.1 vector(mock transfection),pcDNA3.1-anti-Glut(+),pcDNA3.1-Glut(+),and non-transfected HepG-2 cells. The Glut-1 mRNA expression was detected by RT-PCR and the Glut-1 protein expression by Western blotting after cell culture, and the glucose uptake was detected after glucose stimulation in each group. RESULTS:Compared with non-transfected HepG-2 or Glut-1 pcDNA3.1,a down-regulation of Glut-1 mRNA in HepG-2 cells transfected with anti-Glut-1 pcDNA3.1 was noted(P<0.05).Glut-1 protein in HepG-2 cells transfected with Glut-1 AS-ODN was decreased compared with non-transfected HepG-2,Glut-1 pcDNA3.1,or empty vectors. Glucose uptake by the HepG-2 cells transfected with AS-ODN was decreased at 1 hour after glucose ***:The application of Glut-1 AS-ODN can down-regulate the expression of Glut-1 at mRNA and protein,and inhibit glucose uptake partially in HepG-2 *** Glut-1 gene maybe a potential therapeutic target for HCC.

关键词： hepatocellular carcinoma HepG-2 cell glucose transporter-1 therapeutic target

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Advances in cell sources of hepatocytes for bioartificial liver

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Hepatobiliary & Pancreatic diseases International 2012年第6期11卷 594-605页

作者： Xiao-Ping Pan , Lan-Juan Li state key laboratory for diagnosis and treatment of infectious diseases, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china state key laboratory for diagnosis and treatment of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND: Orthotopic 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 SOURCES: A 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. RESULTS: Methods 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 alginate encapsulated 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. CONCLUSIONS: Aside from genetically modified liver cell lines and immortalized human hepatocytes, other functionalhepatocytes 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 fa

关键词： bioartificial liver liver failure hepatocyte liver cell source stem cell differentiation immortalization

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key challenges to the development of extracorporeal bioartificial liver support systems

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Hepatobiliary & Pancreatic diseases International 2012年第3期11卷 243-249页

作者： Li-Fu Zhao, Xiao-Ping Pan and Lan-Juan Li state key laboratory for diagnosis and treatment of infectious diseases, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china state key laboratory for diagnosis and treatment of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND: For 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 SOURCE: We carried out a PubMed search of Englishlanguage articles relevant to extracorporeal BAL support systems and liver failure. RESULTS: Extracorporeal BALs face a series of challenges. first, an appropriate cell source for BAL is not readily available. Second, existing bioreactors do not provide in vivolike 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. CONCLUSIONS: Extracorporeal 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.

关键词： bioartificial liver liver failure cell source bioreactor

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Hepatitis C virus infection and biological falsepositive syphilis test:a single-center experience

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Hepatobiliary & Pancreatic diseases International 2011年第4期10卷 399-402页

作者： Wei-Fang Zhu,Shui-Ying Lei and Lan-Juan Li state key laboratory for diagnosis and treatment of infectious diseases key laboratory of infectious diseases,zhejiang Province Department of infectious diseases,first affiliated hospital,zhejiang university school of medicine,hangzhou 310003,china state key laboratory for diagnosis and treatment of infectious diseases key laboratory of infectious diseases Zhejiang Province Department of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Rapid 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) *** 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 ***:A total of 2656 patients with positive anti-HCV and 5600 healthy control subjects were enrolled in this *** C serology was determined by a second generation ELISA test for HCV *** serology was determined by the RPR *** subjects with reactive RPR positive underwent the TPHA *** and laboratory data were collected by trained ***:Among 2656 patients,111 (4.2%) had a reactive RPR *** 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 *** (17.5%) controls with HCV(-)/RPR(+) had a non-reactive TPHA *** represented 1.1% of all HCV-positive and 0.3% of all HCV-negative subjects (P0.05).CONCLUSIONS:The data of this study demonstrate that HCV infection is associated with a false-positive RPR *** this study BFPs were significantly more common in HCV positive patients compared to HCV-negative *** abnormality can be considered as a predictor for *** BFPs must be considered in assessing the frequency of syphilis in a

关键词： hepatitis C virus biological false-positive syphilis

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Prevalence of hepatitis B and C in HIV-infected patients:a meta-analysis

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Hepatobiliary & Pancreatic diseases International 2011年第2期10卷 122-127页

作者： Jia-Jia Chen, Cheng-Bo Yu, Wei-Bo Du and Lan-Juan Listate key laboratory for diagnosis and treatment of infectious diseases, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china state key laboratory for diagnosis and treatment of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND: Hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share similar routes of transmission by sexual intercourse or drug use by parenteral injection, so coinfection is common. This study aimed to determine the prevalence of coinfection with either HCV or HBV in patients infected with HIV. DATA SOURCES: A meta-analysis was performed to quantify HBV coinfection with HCV in HIV patients. Published studies in the English and Chinese language medical literature involving cohorts of HIV patients concomitantly infected with HBV and/or HCV were collected from the PubMed database, ISI Web of Science, the Cochrane library clinical trials registry, CNKI (china National Knowledge Infrastructure) and Google Scholar, for relevant articles before November 2009. The search was conducted with the following key words:hepatitis C, HCV, hepatitis B, HBV, human immunodeficiency virus, HIV, and coinfection. Data were extracted from relevant studies by two investigators. RevMan 5.0 software was used to perform the meta-analysis. RESULTS: We identified 22 studies involving 17 664 patients. Substantial differences in the HCV rate compared to the HBV rate in HIV patients were found in the overall analysis [odds ratio (OR)=3.00; 95% confidence interval (CI) 1.90-4.73]. A subgroup analysis showed similar results in a European group, but not in Asian or African groups. However, a meta-analysis between HIV+HBV+HCV+ and HIV+HBV+HCV-patients showed no significant difference (OR=0.91; 95% CI 0.57-1.45). Although subgroup analysis still lacked essential differences, different regions seemed to have different patterns. CONCLUSIONS: HCV-HIV coinfection is more frequent than HBV-HIV coinfection overall. However, HCV infection does not affect the prevalence of HBV infection in HIV-positive patients.

关键词： hepatitis B virus hepatitis C virus human immunodeficiency virus coinfection meta-analysis

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Correlation of the occurrence of YMDD mutations with HBV genotypes,HBV-DNA levels,and HBeAg status in Chinese patients with chronic hepatitis B during lamivudine treatment

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Hepatobiliary & Pancreatic diseases International 2012年第2期11卷 172-176页

作者： Feng Wu,Min-Jin Wu,Xiao-Lin Zhuge,Shao-Ming Zhu and Biao Zhu Department of Chinese Pharmacy, Department of laboratory medicine , state key laboratory for diagnosis and treatment of infectious diseases , first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china Department of Chinese Pharmacy First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China Department of laboratory medicine First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China state key laboratory for diagnosis and treatment of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Continuous lamivudine therapy is associated with high rates of YMDD mutations,which are the main causes of drug *** current study explores the association of the emergence of YMDD mutations with pretherapy HBV genotype,HBV-DNA levels,HBeAg status,and serum alanine aminotransferase(ALT) levels in Chinese patients receiving lamivudine therapy for chronic hepatitis ***:A total of 319 chronic hepatitis B patients who received lamivudine therapy for more than a year were enrolled in this *** mutations,HBV genotype,HBV-DNA levels,HBeAg status,and ALT levels were determined prior to their lamivudine treatment and every three months for a year of this ***:Among the 319 patients,137(42.95%) were infected with genotype B and 182(57.05%) with genotype *** to 94 patients(29.47%) developed YMDD mutations within one year of lamivudine ***,50 patients with HBV genotype B and 44 patients with genotype C developed YMDD mutations(36.50% vs 24.18%,P<0.05).Logistic regression analysis showed that pretherapy HBV genotype,HBV-DNA levels,and HBeAg status are independent factors for the emergence of YMDD mutations(HBV genotype:OR=2.159,95% CI 1.291-3.609,P=0.003;HBV-DNA:OR=1.653,95% CI 1.231-2.218,P=0.001;HBeAg:OR=2.021,95% CI 1.201-3.399,P=0.008).CONCLUSIONS:HBV genotype,HBV-DNA levels,and HBeAg status at baseline are the independent factors associated with the emergence of YMDD mutations among Chinese patients receiving lamivudine therapy for chronic hepatitis *** findings are helpful to the development of therapeutic strategies for these patients.

关键词： YMDD mutations lamivudine therapy chronic hepatitis B HBV genotype

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Changes of gut bacteria and immune parameters in liver transplant recipients

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Hepatobiliary & Pancreatic diseases International 2012年第1期11卷 40-50页

作者： Zhong-Wen Wu, Zong-Xin Ling, Hai-Feng Lu, Jian Zuo, Ji-Fang Sheng, Shu-Sen Zheng and Lan-Juan Li state key laboratory for diagnosis and treatment of infectious diseases, Department of infectious diseases key Lab of Combined Multiorgan Transplantation, Ministry of Public Health, key Lab of Organ Transplantation and Department of Hepatobiliary and Pancreatic Surgery , first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china state key laboratory for diagnosis and treatment of infectious diseases Department of Infectious Diseases Zhejiang University School of Medicine Hangzhou 310003 Hangzhou China key Lab of Combined Multi-organ Transplantation Ministry of Public Health Key Lab of Organ Transplantation and Department of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 Hangzhou China

BACKGROUND: Liver 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. METHODS: We 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. RESULTS: All 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 ***: Our 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 fo

关键词： gut bacteria interleukin-6 tumor necrosis factor alpha fecal secretory IgA liver transplantation

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The study of of miR-let-7g/i inducing apoptosis in hepatoma cell

The study of of miR-let-7g/i inducing apoptosis in hepatoma ...

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第二十一次全国中西医结合肝病学术会议

作者： Lingjiao Wu 1,Qiangfeng Wang 2,Xiuming Zhu 2,Jiang Han 2,Fusheng Wu 2 1 state key laboratory for diagnosis and treatment for infectious diseases,The first affiliated hospital, zhejiang university school of medicine,hangzhou,china 2 Department of Oncological Surgery,The first affiliated hospital,zhejiang university school of medicine hangzhou,china

Background Since the initial discovery of miR-let-7 in Caenorhabditis elegans,special attention has been focused on understanding the biogenesis and cellular function of noncoding regulatory miR-let-7. Methods The expression level of miR-let-7g/i in hepatoma cells were quantified by real-time ***-let-7g/i Agomir was transfected into hepatocellular carcinoma cell to overexpression miR-let-7g/*** MTS、EdU retention assay and flowcytometry analysis were used to detect the effect of over-expression miR-let-7g/i on BEL-7402 cell proliferation,the activity of DNA replication and *** the expression of associated protein of the mitochondrial apoptotic pathway after the up regulation of miR-let-7g/i were analyzed by western blot. Results The expression level of miR-let-7g/i was significantly decreased in HCC cell lines compared to L-02 *** vitro experiment,over-expression of miR-let-7g/i significantly inhibited the proliferation,suppressed DNA replication and promoted the apoptosis of BEL-7402,compared to the negative control group cells,as well as associated proteins of the mitochondrial apoptotic pathway of Bcl-xL,Bak and Bax. Conclusion(s) The expression level of miR-let-7g/i was significantly down-regulated in HCC cell *** expression of miR-let-7g/i could inhibit DNA replication,and then decrease the proliferation and promote the apoptosis of BEL-7402 by affect the expression of Bcl-xL,Bak and Bax.

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人工肝血液净化系统治疗细胞因子风暴综合征专家共识

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中华临床感染病杂志 2024年第1期17卷 14-22页

作者：中华医学会感染病学分会肝衰竭与人工肝学组传染病重症诊治全国重点实验室国家传染病医学中心李兰娟不详浙江大学医学院附属第一医院传染病重症诊治全国重点实验室国家感染性疾病临床医学研究中心感染性疾病协同创新中心杭州310003

细胞因子风暴综合征(cytokine storm syndrome,CSS)是一种由感染、肿瘤和自身免疫性疾病等病因引起的免疫反应失控的临床综合征。患者主要表现为血浆中细胞因子水平明显升高,并出现发热、全身多个系统或脏器发生炎症反应及功能损害,甚... 详细信息

细胞因子风暴综合征(cytokine storm syndrome,CSS)是一种由感染、肿瘤和自身免疫性疾病等病因引起的免疫反应失控的临床综合征。患者主要表现为血浆中细胞因子水平明显升高,并出现发热、全身多个系统或脏器发生炎症反应及功能损害,甚至衰竭而死亡。人工肝血液净化系统治疗能清除炎症因子,减轻炎症反应对机体的损伤,其在重症H7N9、重型/危重型新型冠状病毒感染患者临床救治中具有重要应用价值。专家组在《人工肝血液净化系统应用于重型、危重型新型冠状病毒肺炎治疗的专家共识》基础上,结合现有临床应用经验及国内外研究进展,针对人工肝血液净化系统治疗CSS患者的基本原理、治疗适应证、相对禁忌证、治疗模式选择、监测指标及疗效评价等进行总结,制订了本专家共识,供临床医护人员参考。

关键词：人工肝血液净化细胞因子风暴共识

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