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Evaluation of hepatitis B viral replication and proteomic analysis of HepG2.2.15 cell line after knockdown of HBx

hepatobiliary & pancreatic Diseases International 2011年第3期10卷 295-302页

作者： Hai-Yang Xie,Jun Cheng,Chun-Yang Xing,Jin-Jin Wang,Rong Su,Xu-Yong Wei,Lin Zhou and Shu-Sen Zheng Author Affiliations: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,first affiliated hospital,zhejiang university school of medicine,hangzhou 310003,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 First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Hepatitis B virus (HBV) is one of the major pathogens of human liver *** have shown that HBV X protein (HBx) plays an important role in promoting viral gene expression and *** this study we performed a global proteomic profiling to identify the downstream functional proteins of HBx,thereby detecting the mechanisms of action of HBx on virion ***:HBx in the HepG2.2.15 cell line was knocked down by the transfection of small interfering RNA (siRNA).The replication level of HBV was evaluated by microparticle enzyme immunoassay analysis of HBsAg and HBeAg in the culture supernatant,and real-time quantitative PCR analysis of HBV ***-dimensional electrophoresis combined with MALDI-TOF/TOF was performed to analyze the changes in protein expression profile after treatment with HBx ***:Knockdown of HBx disturbed HBV replication in *** target siRNA significantly inhibited the expression of HBsAg,HBeAg and the replication of HBV *** significantly changed proteins (7 upregulated and 5 downregulated) were successfully identified by MALDI-TOF/TOF using proteomics differential expression analysis after the knockdown of *** these identified proteins,HSP70 was validated by Western ***:The results of the study indicated the positive effect of HBx on HBV replication,and a group of downstream target proteins of HBx may be responsible for this effect.

关键词： hepatitis B virus HBx replication proteomics

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Kupffer cells contribute to concanavalin A-induced hepatic injury through a Th1 but not Th17 type response-dependent pathway in mice

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hepatobiliary & pancreatic Diseases International 2011年第2期10卷 171-178页

作者： Lin Chen,Xiao-Jun Xie,Yu-Fu Ye,Lin Zhou,Hai-Yang Xie,Qin-Fen Xie, Jiong Tian and Shu-Sen Zhengzhejiang university school of medicine,hangzhou 310003,chinaKey Laboratory of Combined Multi-organ Transplantation,Ministry of Public Health department of hepatobiliary and pancreatic surgery department of Nephrology,first affiliated hospital,zhejiang university school of medicine,hangzhou 310003,china [a] zhejiang university school of medicine Hangzhou 310003 China [b] Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health department of hepatobiliary and pancreatic surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China [c] department of Nephrology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Increasing evidence suggests that a close interaction of Kupffer cells with T cells plays a central role in concanavalin A-induced hepatic injury in mice,but the underlying mechanisms remain *** present study aimed to determine the relative roles of Th1 and Th17 type responses in concanavalin A-induced hepatic injury in mice, and to investigate whether or not Kupffer cells contribute to hepatic injury via a Th1 or Th17 type response-dependent pathway. METHODS:Immune-mediated hepatic injury was induced in C57BL/6 mice by intravenous injection of concanavalin A. Kupffer cells were inactivated by pretreatment with gadolinium chloride 24 hours before the concanavalin A *** interferon-gamma(IFN-γ)and interleukin-17(IL-17)pathways were blocked by specific neutralizing *** injury was assessed using serum transferase activity and pathological *** of inflammatory cytokines within the liver was detected by real-time polymerase chain reaction and immunohistochemistry. RESULTS:Neutralization of IFN-γsignificantly attenuated concanavalin A-induced hepatic ***,neutralization of IL-17 failed to suppress the *** of Kupffer cells by gadolinium chloride pretreatment protected against concanavalin A-induced injury and significantly reduced hepatic cytokine levels including TNF-α,IL-6 and IFN-γbut not ***:Our findings suggest that Kupffer cells contribute to concanavalin A-induced hepatic injury via a Th1 type response-dependent pathway and production of inflammatory cytokines including TNF-α,IL-6 and IFN-γ.

关键词： Kupffer cells interferon-gamma interleukin-17 concanavalin A hepatic injury hepatitis

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Novel H1N1 influenza A virus infection in a patient with acute rejection after liver transplantation

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hepatobiliary & pancreatic Diseases International 2010年第6期9卷 658-660页

作者： Jiang-Juan He,Sheng Yan,Min Zhang,Wei-Lin Wang and Shu-Sen Zheng division of hepatobiliary and pancreatic surgery, first affiliated hospital,zhejiang university school of medicine,hangzhou 310003,china division of hepatobiliary and pancreatic surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.

BACKGROUND:The 2009 H1N1 influenza A virus was first identified in April 2009 and rapidly evolved into a pandemic. Recipients of solid-organ transplants have a higher risk for severe infection because of *** are limited reports of 2009 H1N1 influenza in liver transplant recipients,especially in china. METHODS:We present a case of a 48-year-old male liver transplant recipient with 2009 H1N1 influenza A *** received therapy for acute rejection after transplantation and was confirmed with H1N1 virus infection. RESULTS:The patient was started on oseltamivir(75 mg, orally twice daily)and had a benign hospital course,with defervescence and resolution of symptoms within 72 hours. The follow-up chest radiograph after discharge was normal. CONCLUSIONS:The 2009 H1N1 influenza in this hospitalized transplant recipient was relatively mild,and prolonged viral shedding was not *** can be a valid measure in immunocompromised individuals.

关键词： H1N1 influenza A virus liver transplantation acute rejection

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Liver transplantation in china: problems and their solutions

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hepatobiliary & pancreatic Diseases International 2004年第2期3卷 170-174页

作者： Jian Wu and Shu-Sen Zheng hangzhou, china department of hepatobiliary surgery, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003 , Chi- na department of hepatobiliary surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.

BACKGROUND: The past decade has witnessed the rapid development of liver transplantation in china. The 1-year survival of liver transplant patients comes to 80% in many leading medical centers and the number of liver transplanta- tion is increasing. However, liver transplantation in china is facing several challenges including recipient with hepato- cellular carcinoma (HCC), recurrence of HCC and hepati- tis B, long-term postoperative care, the bridge to liver transplantation, and shortage of liver donor. This review was to understand the status of and problems in liver trans- plantation in china. DATA RESOURCES: An English-language literature search using MEDLINE (1990-2003) on liver transplantation and other related reports and review articles in Chinese from major transplant centers in china. RESULTS: HCC is one of the main indications for liver transplantation in china but different centers adopted dif- ferent criteria for selection of patients. Hepatitis B virus re- infection is a vital problem after liver transplantation in HBV-related patients. More and more attention was fo- cused on long-term postoperative care and donor shortage. Artificial liver support system has been applied in patients waiting for a graft in many centers. CONCLUSIONS: HCC remains to be one of the main indi- cations for liver transplantation in china; combined hepati- tis B immune globulin and lamivudine is considered effec- tive to prevent hepatitis B virus reinfection. Apart from long-term postoperative care for the improvement of the survival rate, early steroid withdrawal is feasible in liver transplantation. Living donor liver transplantation, split liv- er transplantation, and marginal donor transplantation can deal with donor shortage to some extent. Artificial liver as- sist system serves as a bridge to liver transplantation.

关键词： liver transplantation hepatocellular carcinoma hepatitis B virus donor shortage artificial liver support system, postoperative care

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Liver transplantation in Crigler-Najjar syndrome type I disease

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hepatobiliary & pancreatic Diseases International 2012年第5期11卷 545-548页

作者： Zhen-Hua Tu, De-Sheng Shang, Jin-Cai Jiang, Wu Zhang, Min Zhang, Wei-Lin Wang, Hai-Yan Lou,Shu-Sen Zheng division of hepatobiliary and pancreatic surgery, department of surgery, first affiliated hospital, zhejiang university school of medicine, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health & Key Laboratory of Organ Transplantation of zhejiang Province department of Radiology,first affiliated hospital,zhejiang university school of medicine, hangzhou 310003, china [a] division of hepatobiliary and pancreatic surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Key Laboratory of Combined Multi-Organ Transplantation Ministry of Public Health & Key Laboratory of Organ Transplantation of Zhejiang Province Hangzhou 310003 Hangzhou China [b] department of Radiology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 Hangzhou China

BACKGROUND: Crigler-Najjar syndrome type I (CNS I) is a very rare autosomal recessive inherited disease that liver transplantation can properly deal with. METHODS: We present one case of an 18-month-old child with CNS I diagnosed by clinical findings and genetic detecting LTx was performed 5 days after kernicterus broke out and neurological symptoms were successfully reversed. RESULT: Magnetic resonance imaging and magnetic resonance spectroscopy showed encouraging results that brain pathology had a trend to return to normal in 1-year follow-up, combined with electroencephalogram and motor development estimate studies. CONCLUSIONS: Liver transplantation can cure CNS I with reversible neurological symptoms to some extent in time Magnetic resonance spectroscopy may be a future option of predicting brain conditions and selecting suitable patients with CNS I for transplantation.

关键词： Crigler-Najjar liver transplantation inborn error of metabolism magnetic resonance imaging hyperbilirubinemia

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Technical aspects of biliary reconstruction in adult living donor liver transplantation

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hepatobiliary & pancreatic Diseases International 2011年第2期10卷 136-142页

作者： Xiao-Ning Feng, Chao-Feng Ding, Mei-Yuan Xing, Min-Xia Cai and Shu-Sen Zhengdivision of hepatobiliary and pancreatic surgery, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china division of hepatobiliary and pancreatic surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND: The last decade has witnessed great progress in living donor liver transplantation worldwide. However, biliary complications are more common in partial liver transplantation than in whole liver transplantation. This is due to an impaired blood supply of the hilar bile duct during organ procurement and recipient surgery, commonly encountered anatomical variations, a relatively small graft duct, and complicated surgical techniques used in biliary reconstruction. DATA SOURCES: MEDLINE and PubMed were searched for articles on 'living donor liver transplantation', 'biliary complication', 'anatomical variation', 'biliary reconstruction', 'stenting' and related topics. RESULT: In this review, biliary complications were analyzed with respect to anatomical variation, surgical techniques in biliary reconstruction, and protection of the arterial plexus of the hilar bile duct. CONCLUSION: Transecting the donor bile duct at the right place to secure a larger bile duct stump, anastomosing techniques, and stenting methods as well as preserving the blood supply to the bile duct are all important in reducing biliary complications.

关键词： living donor liver transplantation biliary complications biliary reconstruction biliary drainage biliary anatomy

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Inhibitory effect of cyclosporine A on hepatitis B virus replication in vitro and its possible mechanisms

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hepatobiliary & pancreatic Diseases International 2005年第1期4卷 18-22页

作者： Wei-Liang Xia, Yan Shen and Shu-Sen Zheng hangzhou, china department of hepatobiliary surgery, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china department of hepatobiliary surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.

BACKGROUND: Hepatitis B related end-stage liver disease is recently acknowledged as one of the main indications for orthotopic liver transplantation (OLT). However, the high recurrence rate of hepatitis B virus infection following transplantation is regarded as a major factor affecting the long-term survival of transplant recipients especially in Chi- na. Cyclosporine A (CsA), which is routinely used to pre- vent the allograft rejection, is reported to have the inhibito- ry activity on hepatitis B virus (HBV) replication in vitro. In this paper, we review the inhibitory effect and its possi- ble mechanisms of CsA on HBV replication in vitro. DATA RESOURCES: An English-language literature search was conducted using MEDLINE (1990-2004) on cyclospo- rine A, hepatitis B virus, mitochondria, calcium and other related reports and review articles. RESULTS: Hepatitis B x protein (HBx) is essential to HBV replication. The cytosolic calcium signaling mediated by mitochondria and the Src kinase pathway were involved during HBx activation of HBV replication. CsA inhibits the HBV replication in vitro by its binding to mitochondrial cy- clophilin D, then blocking the mitochondria-mediated cy- tosolic calcium signaling. The derivates of CsA also have the HBV replication inhibitory effect in vitro. CONCLUSIONS; By interacting with mitochondria, pre- venting the release of intramitochondrial calcium, and then blocking the cytosolic calcium signaling, CsA inhibits the HBV replication in vitro. The derivates of CsA also have this activity.

关键词： hepatitis B virus cyclosporine A calcium

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Current status and perspective of liver preservation solutions

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hepatobiliary & pancreatic Diseases International 2006年第4期5卷 490-494页

作者： Xiao-Ning Feng, Xiao Xu and Shu-Sen Zheng department of hepatobiliary surgery, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china department of hepatobiliary surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.

BACKGROUND: A safe and effective preservation solution is a precondition for liver transplantation, which is accepted as the radical treatment for patients with end- stage liver disease. The increasing use of marginal donors and non-heart beating donors as well as the establishment of a national organ allocation network call for better preservation. New preservation solutions like histidine- tryptophan-ketoglutarate (HTK) solution and Celsior solution have been introduced to liver preservation, and protective gene intervention and other modifications have also been investigated. In this article, we review recent advances in liver preservation solutions. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1990-2005) on liver preservation solution, biliary complication, protective gene and other related subjects. RESULTS: Although the high viscosity of the university of Wisconsin (UW) solution proved harmful to the hepatic microcirculation, three solutions showed equivalent preservation effects. When the cold ischemia time was short, there were no significant differences among the three solutions in the incidence of biliary complications. So far, modifications of preservation solutions have achieved great success. Several types of protective genes like A20, Bcl-2, Bcl-XL and HO-1 were reported to have definite liver protective effects. The addition of other substrates like TNF-α antibody, tacrolimus (FK506) and fructose-1, 6-bisphosphate (FBP) can also improve the preservation effect. However, addition of insulin to UW solution is harmful to the graft. CONCLUSIONS: In centers with highly-developed transplantation techniques, HTK and Celsior solutions are acceptable in liver preservation. Protective genemodification and addition of substrates like TNF-α antibody, FK506 and FBP are prominent approaches to improve liver preservation.

关键词： liver preservation solution biliary complication protective gene microcirculation

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A modified rat model for hepatocellular carcinoma

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hepatobiliary & pancreatic Diseases International 2004年第4期3卷 585-587页

作者： Fu-Chun Yang, Shu-Sen Zheng and Tian-An Jiang hangzhou, china department of hepatobiliary pancreatic surgery and Liver Transplantation Center, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china department of hepatobiliary pancreatic surgery and Liver Transplantation Center First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.

BACKGROUND: Rat hepatocellular carcinoma ( HCC ) model which has a high analogy to clinical liver cancer is of great value in understanding the pathogenesis and evolution of liver cancer, in searching effective anti-cancer treat- ments ( drug, hepatectomy and liver transplantation ), and designing cancer prevention strategies. In this study we es- tablished a modified rat model of hepatocellular carcinoma to enhance rats' physique and surgical endurance. METHODS: Wistar rats were fed with diethylnitrosamine (DENA) by three methods for evaluation of general condi- tions for 130 days: Doppler ultrasonographic measurement, laparotomy and histopathological examination. RESULTS: No rat died in control group ( group A) and modified DENA-induction-HCC group ( group C), but 6 deaths in classical DENA-induction-HCC group (group B) (survival rate 80%). All survived rats in groups B and C de- veloped diffusive hepatocellular carcinoma and liver cirrho- sis. General appearance of rats in the group C was better than that in the group B. CONCLUSION: With good general conditions for surgery, the modified rat model for hepatocellular carcinoma has a high carcinogenic rate and a high survival rate.

关键词： hepatocellular carcinoma model rat diethylnitrosamine

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Primary liver cancer in the elderly: report of 125 cases

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hepatobiliary & pancreatic Diseases International 2003年第1期2卷 59-61页

作者： Ying-Sheng Wu Ting-Bo Liang Shu-Sen Zheng the department of hepatobiliary & Pancreas surgery, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china department of hepatobiliary & Pancreas surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China. walkaloner200@***

OBJECTIVES: To understand the characteristics of primary, liver camcer (PLC) in the elderly and summarize the experience in treatment of such patients. METHODS: The clinical data of PLC in the elderly group (≥60 years, 125 patients) and the young group (≤59 years, 295 patients) were analyzed retrospectively. RESULTS: In the elderly group, 64 patients were found HBsAg positive, 39 patients small PLC, 24 large PLC, 15 tumor emboli in the portal vein, 86 AFP positive, and 34 hepatectomy performed. In the young group, 205 patients were found HBsAg positive, 79 patients small PLC, 97 large PLC, 96 tumor emboli in the portal vein, 200 AFP positive, and 126 hepatectomy performed. The median survival was 44 and 25 months respectively, and no significant difference was observed in the mortality between the two groups (P>0.05). CONCLUSIONS: Hepatectomy is a choice of treatment for PLC in the elderly based on their liver function. AFP and B-ultrasonography are important methods for the diagnosis of PLC in the elderly.

关键词： primary liver cancer hepatectomy elderly

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