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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

Survival factors after resection of small hepatocellular carcinoma

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Hepatobiliary & Pancreatic diseases International 2005年第3期4卷 379-384页

作者： departments of Surgical Oncology (Wu FS, Zhao WH, Ma ZM, Teng LS and Wang M) and General Surgery ( Liang TB and Zheng SS) , first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china department of Surgical Oncology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China. qiouhang@***

Early resection of hepatocellular carcinoma is a key measure to prolong the survival of patients. This study was designed to summarize our experience in surgical resection of small hepatocellular carcinoma (HCC), and to analyze the factors influencing the postoperative survival of patients. METHODS:The clinicopathologic data of 105 patients with small HCC after resection from 1986 through 2003 were analyzed ; the patients had been followed up for more than half a year (median 33 months). Nine clinicopathologic factors, preoperative α-fetoprotein (AFP) level, liver cirrhosis, Child-Pugh score, tumor size (>2cm vs.≤2 cm) and number (single vs. multiple), capsule formation, portal vein tumor thrombi (PVTT), Edmondson tumor grade and surgical method, were analyzed by the log-rank test and the Cox proportional harzards model analysis. RESULTS:The cumulative 1-,3- and 5-year survival rates after the operation were 86.5%, 70.3% and 55.2%, respectively, and the 1-, 3- and 5-year disease-free survival rates were 78%, 58. 9% and 45. 6%, respectively. One patient died from esophagogastric varices hemorrhage in 2 weeks after reoperation. Thirty-six patients had intrahepatic recurrence or metastasis postoperatively and 34 patients died. The Kaplan-Meier method and the Cox proportional harzards model analysis indicated that poor Child-Pugh score, tumor more than 2 cm in diameter, PVTT and multiple lesions (including satellitic lesions) were adverse factors affecting postoperative survival. The Cox proportional harzards model analysis indicated that tumor size, PVTT and multiple lesions were the factors influencing postoperative disease-free survival. CONCLUSIONS:Limited hepatectomy with a margin more than 1 cm is an appropriate surgical approach. Adverse preoperative Child-Pugh score and postoperative intrahepatic recurrences are the main factors leading to the death of patients with small HCC.

关键词： carcinoma, hepatocellular small hepatocellular carcinoma hepatectomy prognosis

Do the lungs contribute to propofol elimination in patients during orthotopic liver transplantation without veno-venous bypass?

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Hepatobiliary & Pancreatic diseases International 2006年第4期5卷 511-514页

作者： Yi-Zhong Chen, Sheng-Mei Zhu, Hui-Liang He, Jian-Hong Xu, Su-Qin Huang and Qing-Lian Chen department of Anesthesiology, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china department of Anesthesiology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.

BACKGROUND: The clearance of propofol is very rapid, and its transformation takes place mainly in the liver. Some reports indicated extrahepatic clearance of the drug and that the lungs are the likely place where the process occurs. This study was undertaken to compare the plasma concentrations of propofol both in the pulmonary and radial arteries after constant infusion during the dissection, anhepatic and reperfusion phases of orthotopic liver transplantation (OLT) without veno-venous bypass, attempting to investigate extrahepatic clearance and to determine whether the human lungs take part in the elimination of propofol. METHODS: Fifteen patients undergoing OLT without veno-venous bypass were enrolled in the study, and propofol was infused via a forearm vein at a rate of 2 mg· kg-1·h-1. Blood samples were simultaneously collected from pulmonary and radial arteries at the end of the first hepatic portal dissection (T0), at the clamping of the portal vein (T1), 30, and 60 minutes after the beginning of the anhepatic phase (T2, T3), and 30, 60, and 120 minutes after the unclamping of the new liver (T4, T5, T6). Plasma propofol concentrations were measured using a reversed- phase, high-performance liquid chromatographic method with fluorescence detection. RESULTS: The concentrations of plasma propofol in the pulmonary and radial arteries at T2 and T3 rose significantly compared with T0 and T1 (P<0.01) respectively. After reperfusion, the drug concentrations at T4, T5 and T6 decreased significantly compared with T2, T3 (P<0.01)respectively. There were no significant differences in plasma propofol concentrations between the pulmonary and radial arteries at any time points. CONCLUSIONS: Propofol is eliminated mainly by the liver, and also by extrahepatic organs. The lungs seem to be not a major site contributing to the extrahepatic metabolism of propofol in humans.

关键词： propofol extrahepatic metabolism orthotopic liver transplantation without veno-venous bypass

Roles of sulfonylurea receptor 1 and multidrug resistance protein 1 in modulating insulin secretion in human insulinoma

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Hepatobiliary & Pancreatic diseases International 2011年第1期10卷 88-94页

作者： Cheng-Jiang Li,Hua-Li Zhou,Jun Li,Hong-Tian Yao,Rong Su and Wen-Peng Li department of Endocrinology(Li CJ,Zhou HL and Li WP),department of Pathology,and Key Laboratory of Multi-organ Transplantation of Ministry of Public Health,first affiliated hospital,zhejiang university school of medicine,hangzhou 310003,china department of Endocrinology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China department of Pathology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China Key Laboratory of Multi-organ Transplantation of Ministry of Public Health First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Sulfonylurea receptor 1(SUR1)and multidrug resistance protein 1(MRP1)are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion. METHODS:Fasting glucose,insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma *** content,SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence. RESULTS:Insulinoma patients presented the typical demons-trations of Whipple’s *** glucose of each insulinoma patient was lower than 2.8 mmol/L,and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high *** and immunofluorescence staining showed that SUR1 increased,but MRP1 decreased in insulinoma compared with the adjacent islets. CONCLUSIONS:The hypersecretion of insulin in insulinomas might be,at least partially,due to the enrichment of SUR1. In contrast,MRP1,which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.

关键词： sulfonylurea receptor 1 multidrug resistance protein 1 ATP-binding cassette transporters insulinoma insulin secretion

Evaluation of hepatitis B virus replication and proteomic analysis of HepG2.2.15 cell line after cyclosporine A treatment

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Acta Pharmacologica Sinica 2007年第7期28卷 975-984页

作者： Hai-yang XIE,Wei-liang XIA,Chun-chao ZHANG,Li-ming WU,Hao-feng JI,Yu CHENG,Shu-sen ZHENG~2department of Hepatobiliary Pancreatic Surgery,Key Laboratory of Multiple Organ Transplantation,Ministry of Public Health,Key Labo-ratory of Organ Transplantation zhejiang Province,first affiliated hospital,school of medicine,zhejiang university,hangzhou 310003,china department of Hepatobiliary Pancreatic Surgery Key Laboratory of Multiple Organ Transplantation Ministry of Public Health Key Laboratory of Organ Transplantation Zhejiang Province First Affiliated Hospital School of Medicine Zhejiang University Hangzhou China

Aim:The effect of cyclosporine A (CsA) on hepatitis B virus (HBV) replicationwas investigated,and proteomics expression differentiation after CsA treatmentwas studied in order to provide clues to explore the effect of CsA on ***:Methyl thiazolyl tetrazolium (MTT) assay was used toevaluate the cytotoxicity of *** HBV replication level in the HBV genomicDNA transfected HepG2.2.15 cell line was determined by an ELISA analysis ofhepatitis B surface antigens (HBsAg) and Hepatitis B e antigens (HBeAg) inculture supernatant,while the intracellular HBV DNA replication level was ana-lyzed by slot blot ***-dimensional electrophoresis was used toinvestigate the alteration of protein expression in HepG2.2.15 after CsA treatmentin *** differentially-expressed proteins were identified by Matrix-assistedlaser desorption/ionization-time of flight mass spectrometry combined with anonline database ***:CsA was able to inhibit the expression of HBsAg,HBeAg,and HBV DNA replication in vitro in a dose-dependent *** analysis indicated that the expression of 17 proteins changed signifi-cantly in the CsA treatment group compared to the control *** of the 17proteins were identified,including the overexpression of eukaryotic translationinitiation factors (eIF) 3k,otubain 1,14.3.3 protein,eIF2-α,eIF5A,and thetyrosine 3/tryptophan 5-mono-oxygenase activation protein in CsA-treatedHepG2.2.15 *** downregulation of the ferritin light subunit,erythrocytecytosolic protein of 51 kDa (ECP-51),stathmin 1/oncoprotein,adeninephosphoribosyl-transferase,and the position of a tumor protein,translationally-controlled 1,was shifted,suggesting it had undergone ***:Our study identified the inhibitory effect of CsA onHBV replication,and found that a group of proteins may be responsible for thisinhibitory effect.

关键词： hepatitis B virus cyclosporine A replication proteomics

Endoscopic management of biliary complications after orthotopic liver transplantation

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Hepatobiliary & Pancreatic diseases International 2006年第1期5卷 39-42页

作者： Yun-Sheng Qin, Zhao-Shen Li, Zhen-Xing Sun, Ren-Pei Wu, Na Wang and Yin-Zhen Yao department of Hepatobiliary Surgery, first affiliated hospital, zhejiang university, school of medicine, hangzhou 310003, china department of Gastroenterology, Changhai hospital, Second Military Medical university, Shanghai 200433, china department of Hepatobiliary Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China.

BACKGROUND: Biliary complications are a serious problem in patients after liver transplantation and often require reoperation. This study was conducted to summarize the endoscopic diagnosis and management of biliary complications after orthotopic liver transplantation (OLT). METHODS: From December 2000 to November 2003, twelve endoscopic retrograde cholangiopancreatographies(ERCPs) were performed in 7 patients after OLT at Digestive Endoscopic Center of Changhai hospital in Shanghai, china. The therapeutic maneuvers included endoscopic sphincterotomy (EST), biliary stent placement, balloon and basket extraction, irrigation, and nasobiliary tube placement. A retrospective study was made to determine the types of biliary tract complications after OLT. The success of ERCP and therapeutic maneuvers was also evaluated. RESULTS: Biliary tract complications including biliary stricture, biliary leak, biliary sludge, and stump leak of the cyst duct were treated respectively by endoscopic sphincterotomy with sludge extraction, stricture dilation or endoscopic retrograde biliary drainage. Two of the 3 patients with proximal common bile duct stricture were successfully treated with ERCP and stent placement. Four patients with anastomotic stricture and/without bile leak were treated successfully by dilation and stent placement or endoscopic nosobiliary drainage. No severe ERCP-related complications occurred. CONCLUSIONS: ERCP is an effective and accurate approach for the diagnosis of biliary tract complications after OLT, and placement of a stent is a safe initial treatment for biliary complications after liver transplantation.

关键词： liver transplantation biliary tract complications endoscopic retrograde cholangiopancreatography

Protective effects of heat shock protein70 induced by geranyl-geranylacetone in atrophic gastritis in rats

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Acta Pharmacologica Sinica 2007年第7期28卷 1001-1006页

作者： Wei-li LIU~2,Shu-jie CHEN~2,Yan CHEN~(2,3),Lei-min SUN~2,Wei ZHANG~2,Ya-min ZENG~2,Tian-hua ZHOU~(2,4),Jian-min SI~(2,5)~2 department of Gastroenterology and zhejiang Key laboratory of Traditional Chinese medicine(TCM),Sir Run Run Shaw hospital,zhejianguniversity school of medicine,hangzhou 310012,china ~3 department of Gastroenterology,Second affiliated hospital and ~4 Center forDisease Modeling,zhejiang university College of medicine,hangzhou 310058,china department of Gastroenterology and zhejiang Key laboratory of Traditional Chinese medicine (TCM) Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China department of Gastroenterology Second Affiliated Hospital Zhejiang University College of Medicine Hangzhou China Center for Disease Modeling Zhejiang University College of Medicine Hangzhou China

Aim:To investigate the effect of geranylgeranylacetone (GGA) on the progres-sion of atrophic gastritis in rats and its potential ***:Atrophicgastritis was induced in Sprague-Dawley rats with 0.1% ammonia solution,60%ethanol,and 20 mmol/L deoxycholic acid for 24 *** by theinduction of atrophic gastritis,200 mg/kg GGA was administered by oral gavagefor 8 weeks (weeks 17-24).The histological changes in gastric mucosa werequantitated by the index of inflammation,the gastric mucosal thickness,and theamount of glands of 1 mm horizontal length in *** heat shockprotein (HSP)70 levels and distribution were determined by immunoblotting andimmunohistochemistry in gastric ***:GGA alleviated the pathologi-cal progression of atrophic gastritis with inflammation relief (inflammation index:1.40 in the GGA group and 1.65 in the atrophic gastritis group) and glandularrestoration (mucosal thickness and quantity of glands:194.3 μm and 38.7 mm inthe GGA group;123.3 μm and 32.7 mm in the atrophic gastritis group;P<0.05).GGA significantly induced HSP70 synthesis (P<0.05).Moreover,quercetin,aninhibitor of HSP70 expression,aggravated the infiltration of inflammatory cellsand glandular loss in the ***:GGA prevented the progression ofatrophic gastritis in rats via the induction of HSP70 expression.

关键词： geranylgeranylacetone heat shock protein70 atrophic gastritis quercetin

Cloning of UGT1A9 cDNA from liver tissues and its expression in CHL cells

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World Journal of Gastroenterology 2001年第6期7卷 841-845页

作者： Xin Li~(1,2) Ying-Nian Yu~1 Ge-Jian Zhu~1 Yu-Li Qian~1 1 department of Pathophysiology,school of medicine,zhejiang university,hangzhou,china2 College of Pharmcy,zhejiang university,hangzhou,china department of Pathophysiology School of Medicine Zhejiang University Hangzhou China.

AIM: To clone the cDNA of UGT1A9 from a Chinese human liver and establish the Chinese hamster lung (CHL) cell line expressing human UGT1A9. METHODS: cDNA of UGT1 A9 was transcripted from mRNA by reverse transcriptase-ploymerase chain reaction, and was cloned into the pGEM-T vector which was amplified in the host bacteric *** DH5(alpha). The inserted fragment, verified by DNA sequencing, was subcloned into the Hind III /Not I site of a mammalian expression vector pREP9 to construct the plasmid termed pREP9-UGT1A9. CHL cells were transfected with the resultant recombinants, pREP9-UGT1A9, and selected by G418 (400 mg x L(-1)) for one month. The surviving clone (CHL-UGT1A9) was harvested as a pool and sub-cultured in medium containing G418 to obtain samples forUGT1A9 assays. The enzyme activity of CHL-UGT1A9 towards propranolol in S9 protein of the cell was determined by HPLC. RESULTS: The sequence of the cDNA segment cloned, which was 1666 bp in length, was identical to that released by Gene Bank (GenBank accession number: AF056188) in coding region. The recombinant constructed, pREP9-UGT1A9, contains the entire coding region, along with 18 bp of the 5' and 55 bp of the 3' untranslated region of theUGT1A9 cDNA, respectively. The cell lines established expressed the protein of UGT1A9, and the enzyme activity towards propranolol in S9 protein was found to be 101+/- 24 pmol x min(-1) x mg(-1) protein (n=3), but was not detectable in parental CHL cells. CONCLUSION: The cDNA of UGT1A9 was successfully cloned from a Chinese human liver and transfected into CHL cells. The CHL-UGT1 A9 cell lines established efficiently expressed the protein ofUGT1A9 for the further enzyme study of drug glucuronidation.

关键词： Cloning, Molecular Gene Expression Animals Cell Line Cricetinae Cricetulus DNA, Complementary Glucuronosyltransferase Humans Liver Molecular Sequence Data Research Support, Non-U.S. Gov't

Variations and reconstruction of the hepatic artery in liver transplantation

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Hepatobiliary & Pancreatic diseases International 2006年第2期5卷 170-172页

作者： Xiao Xu and Shu-Sen Zheng department of Hepatobiliary and Pancreatic Surgery, first affiliated hospital, zhejiang university school of medicine, hangzhou 310003, china

Any surgical refinement and innovation is certain to improve the long-term survival of recipients following liver transplantation. In the past de- cade, the shortage or donor organs has prompted us to use partial liver graft in split liver transplantation and living donor liver transplantation. As an anatomic problem in a successful transplantation, which actually is beyond the category of anatomy, the variations and reconstruction of hepatic vasculatures have drawn much attention of surgeons.

关键词： HAV