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C–C motif chemokine ligand 16 inhibits the progression of liver cirrhosis via inactivating hepatic stellate cells

hepatobiliary & pancreatic Diseases International 2020年第5期19卷 440-448页

作者： Jian-Yong Zhuo Di Lu Zu-Yuan Lin Bei-Ni Cen Xu-Yong Wei Hai-Yang Xie Shu-Sen Zheng Xiao Xu department of hepatobiliary and pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China NHC Key Laboratory of Combined Multi-organ transplantation Key Laboratory of the Diagnosis and Treatment of Organ TransplantationCAMSHangzhou 310003China department of hepatobiliary and pancreatic surgery Shulan(Hangzhou)HospitalHangzhou 310003China

Background:liver cirrhosis results from many forms of chronic damage,characterized by accumulation of extracellular *** present study aimed to explore a potential non-invasive biomarker and its mechanism in the progression of liver ***:Gene Expression Omnibus(GEO)dataset(GSE15654,n=216)was analyzed to screen genes associated with progression of liver cirrhosis.A total of 181 plasma samples,including healthy control(HC,n=20),chronic hepatitis B(CHB,n=77)and HBV-related liver cirrhosis(LC,n=84),were enrolled for *** vitro and in vivo experiments were employed for the mechanistic ***:GEO dataset analysis showed that relatively low mRNA-expression of C–C motif chemokine ligand 16(CCL16)was associated with elevated Child-Pugh score(P=0.034)and worse prognosis(P=0.025).Plasma CCL16 level decreased in a stepwise pattern,with a median concentration of 10.29,6.57 and 4.47 ng/mL in the HC,CHB and LC groups,respectively(Pliver cell line(LO2)reduced the extracellular matrix associated proteins(Col1 and Col4)in human hepatic stellate cell line(LX-2).In vivo,the pathological feature of cirrhosis was alleviated by the hepatocytespecific expression of ***:CCL16 could be a feasible plasma marker to predict the occurrence and progression of liver ***16 might impact liver cirrhosis through inactivating hepatic stellate cells.

关键词： C-C motif chemokine ligand 16 liver cirrhosis Hepatitis B virus infection

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A score model for predicting post-liver transplantation survival in HBV cirrhosis-related hepatocellular carcinoma recipients: a single center 5-year experience

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hepatobiliary & pancreatic Diseases International 2015年第1期14卷 43-49页

作者： Li-Ying Wang Shu-Sen Zheng Xiao Xu Wei-Lin Wang Jian Wu Min Zhang Yan Shen Sheng Yan Hai-Yang Xie Xin-Hua Chen Tian-An Jiang Fen Chen 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 Health

BACKGROUND： The prognostic prediction of liver transplantation（LT） guides the donor organ allocation. However, there is currently no satisfactory model to predict the recipients’ outcome, especially for the patients with HBV cirrhosis-related hepatocellular carcinoma（HCC）. The present study was to develop a quantitative assessment model for predicting the post-LT survival in HBV-related HCC ***： Two hundred and thirty-eight LT recipients at the liver Transplant Center, First Affiliated Hospital, Zhejiang University School of Medicine between 2008 and 2013 were included in this study. Their post-LT prognosis was recorded and multiple risk factors were analyzed using univariate and multivariate analyses in Cox ***： The score model was as follows： 0.114×（Child-Pugh score）-0.002×（positive HBV DNA detection time）＋0.647×（number of tumor nodules）＋0.055×（max diameter of tumor nodules）＋0.231×ln AFP＋0.437×（tumor differentiation grade）.The receiver operating characteristic curve analysis showed that the area under the curve of the scoring model for predicting the post-LT survival was 0.887. The cut-off value was 1.27, which was associated with a sensitivity of 72.5% and a specificity of 90.7%, ***： The quantitative score model for predicting post-LT survival proved to be sensitive and specific.

关键词： HBV cirrhosis hepatocellular carcinoma liver transplantation Hangzhou criteria post-LT survival

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Key factors and potential drug combinations of nonalcoholic steatohepatitis:Bioinformatic analysis and experimental validation-based study

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hepatobiliary & pancreatic Diseases International 2021年第5期20卷 433-451页

作者： Guang-Han Fan Rong-Li Wei Xu-Yong Wei Chen-Zhi Zhang Zhe-Tuo Qi Hai-Yang Xie Shu-Sen Zheng Xiao Xu department of hepatobiliary and pancreatic surgery Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China department of hepatobiliary and pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China NHC Key Laboratory of Combined Multi-organ transplantation Hangzhou 310003China department of hepatobiliary and pancreatic surgery Shulan(Hangzhou)HospitalHangzhou 310000China

Background:Nonalcoholic fatty liver disease and its advanced stage,nonalcoholic steatohepatitis(NASH),are the major cause of hepatocellular carcinoma(HCC)and other end-stage liver ***,the potential mechanism and therapeutic strategies have not been *** study aimed to identify potential roles of mi RNA/m RNA axis in the pathogenesis and drug combinations in the treatment of ***:Microarray GSE59045 and GSE48452 were downloaded from the Gene Expression Omnibus and analyzed using *** we obtained differentially expressed genes(DE-genes).DAVID database was used for Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment pathway ***-protein interaction(PPI)networks were used for the identification of hub *** found upstream regulators of hub genes using mi RTar *** expression and correlation of key mi RNA and its targets were detected by q *** Pair Seeker was employed to predict drug combinations against *** expression of mi RNA and hub genes in HCC was identified in the Cancer Genome Atlas database and Human Protein Atlas ***:Ninety-four DE-genes were *** and KEGG analysis showed that these predicted genes were linked to lipid *** genes were identified as hub genes in PPI networks,and they were highly expressed in cells with vigorous lipid ***-mi R-335-5 p was the upstream regulator of 9 genes in the 11 hub genes,and it was identified as a key mi *** hub genes were highly expressed in NASH models,while hsa-mi R-335-5 p was lowly *** correlation of mi RNA-m RNA was established by q *** verification indicated that hsa-mi R-335-5 p had inhibitory effect on the development of ***,drug combinations were predicted and the expression of mi RNA and hub genes in HCC was ***:In the study,potential mi RNA-m RNA pathways related to NASH were *** these pathways may be novel s

关键词： Nonalcoholic steatohepatitis Hepatocellular carcinoma microRNA Bioinformatic analysis Drug combination

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The circFASN/miR-33a pathway participates in tacrolimusinduced dysregulation of hepatic triglyceride homeostasis

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2132-2141页

作者： Chenzhi Zhang Kangchen Chen Rongli Wei Guanghan Fan Xuechun Cai Li Xu Beini Cen Jianguo Wang Haiyang Xie Shusen Zheng Xiao Xu Division of hepatobiliary and pancreatic surgery Department of SurgeryFirst Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China Key Lab of Combined Multi-Organ transplantation Ministry of Public HealthHangzhou 310000China department of hepatobiliary and pancreatic surgery Shulan(Hangzhou)HospitalHangzhou 310000China

Dyslipidemia exhibits a high incidence after liver transplantation,in which tacrolimus,a widely used immunosuppressant,plays a fundamental *** and related circRNAs represent a class of noncoding RNAs that have been recognized as important regulators of genes associated with lipid ***,their transcriptional activities and functional mechanisms in tacrolimus-related dyslipidemia remain *** this study,we observed that tacrolimus could induce triglyceride accumulation in hepatocytes by stimulating sterol response element-binding proteins(SREBPs)and *** in silico and experimental analyses identified miR-33a as a direct target of *** could downregulate circFASN and result in elevated miR-33a in vivo and in *** of circFASN or silencing of miR-33a decreased the promoting effects of tacrolimus on triglyceride ***,the incidence of dyslipidemia in liver transplant recipients with elevated serum miR-33a after liver transplantation was higher than that in patients without elevated serum miR-33a(46.3%vs.18.8%p=0.012,n=73).Our results showed that the circFASN/miR-33a regulatory system plays a distinct role in tacrolimus-induced disruption of lipid ***-33a is likely a risk factor for tacrolimus-related dyslipidemia,providing a potential therapeutic target to combat tacrolimus-induced dyslipidemia after liver transplantation.

关键词： tacrolimus homeostasis elevated

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Is laparoscopic radical cholecystectomy an effective and safe approach for advanced gallbladder cancer?

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hepatobiliary & pancreatic Diseases International 2020年第3期19卷 203-204页

作者： Li-Ming Jin Yu-Hua Zhang Cheng-Wu Zhang Wei-Ding Wu Jia Wu Chang-Wei Dou Fang-Qiang Wei Zhi-Fei Wang Zhi-Ming Hu Shu-Sen Zheng Division of hepatobiliary pancreatic surgery First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Division of hepatobiliary and pancreatic surgery Zhejiang Provincial People’s HospitalAffiliated People’s Hospital of Hangzhou Medical CollegeHangzhou 310014China department of hepatobiliary and pancreatic surgery Department of Liver TransplantationShulan(Hangzhou)HospitalZhejiang Shuren University School of MedicineHangzhou 310022China

Although laparoscopy has been widely used in the surgical field and is even considered the first-line to diagnose various diseases,laparoscopic radical cholecystectomy(LRC)for gallbladder cancer(GBC)has always been relatively *** lymphadenectomy,complicated liver resection,specific biological behavior of GBC cells,and chimney and aerosol effects from the pneumoperitoneum are the previously misunderstood areas in laparoscopic surgery[1].Initially,laparoscopic approach was used for intra-abdominal GBC exploration to determine the presence of peritoneal metastasis,intraoperative staging,and palliative *** the advancement of laparoscopic surgery,laparoscopic liver resection,laparoscopic pancreaticoduodenectomy,and laparoscopic radical gastrectomy have been routinely performed in several medical *** et al.[2]recently demonstrated that laparoscopic technique is feasible for ***,the feasibility of LRC depends on the following factors.

关键词： laparoscopic gallbladder routine

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Exosome is involved in liver graft protection after remote ischemia reperfusion conditioning

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国际肝胆胰疾病杂志:英文版 2023年第5期22卷 498-503页

作者： Jian-Hui Li Jun-Jun Jia Ning He Xue-Lian Zhou Yin-Biao Qiao Hai-Yang Xie Lin Zhou Shu-Sen Zheng department of hepatobiliary and pancreatic surgery Department of Liver TransplantationShulan(Hangzhou)HospitalZhejiang Shuren University School of MedicineHangzhou 310022China NHC Key Laboratory of Combined Multi-organ transplantation Hangzhou 310022China Division of hepatobiliary pancreatic surgery First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Endocrinology Children’s HospitalZhejiang University School of MedicineHangzhou 310052China

Background:Remote ischemic perconditioning(RIPerC)has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury(IRI).This study investigated the role of exosomes in RIPerC of liver grafts in ***:Twenty-five rats(including 10 donors)were randomly divided into five groups(n=5 each group):five rats were used as sham-operated controls(Sham),ten rats were for orthotopic liver transplantation(OLT,5 donors and 5 recipients)and ten rats were for OLT+RIPerC(5 donors and 5 recipients).liver architecture and function were ***:Compared to the OLT group,the OLT+RIPerC group exhibited significantly improved liver graft histopathology and liver function(P<0.05).Furthermore,the number of exosomes and the level of P-Akt were increased in the OLT+RIPerC ***:RIPerC effectively improves graft architecture and function,and this protective effect may be related to the increased number of *** upregulation of P-Akt may be involved in underlying mechanisms.

关键词： Exosome P-Akt Ischemia-reperfusion injury Remote ischemic perconditioning

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Surgical vs percutaneous radiofrequency ablation for hepatocellular carcinoma in dangerous locations

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World Journal of Gastroenterology 2011年第1期17卷 123-129页

作者： Ji-Wei Huang Roberto Hernandez-Alejandro Kristopher P Croome Lu-Nan Yan Hong Wu Zhe-Yu Chen Pankaj Prasoon Yong Zeng department of Hepato-Biliary-pancreatic surgery Division of Liver Transplantation West China Hospital Sichuan University Chengdu 610041 Sichuan Province China department of surgery University of Western Ontario Hepatobiliary and Liver Transplant Surgery London Health Sciences Centre London Ontario N6A 4S2 Canada

AIM:To compare the long-term outcome of percutaneous vs surgical radiofrequency ablation(RFA) for hepatocellular carcinoma(HCC) in dangerous ***:One hundred and sixty-two patients with HCC in dangerous locations treated with percutaneous or surgical RFA were enrolled in this *** patients were divided into percutaneous RFA group and surgical RFA *** the patients were regularly followed up for a long time,their curative rate,hospital stay time,postoperative complications and 5-year local tumor progression were compared and ***:No significant difference was observed in curative rate between the two groups(91.3% vs 96.8%,P = 0.841).The hospital stay time was longer and more analgesics were required while the incidence of bile duct injury and RFA-related hemorrhage was lower in surgical RFA group than in percutaneous RFA group(P < 0.05).The local progression rate of HCC in dangerous locations was significantly lower in surgical RFA group than in percutaneous RFA group(P = 0.05).The relative risk of local tumor progression was 14.315 in percutaneous RFA ***:The incidence of severe postoperative complications and local tumor progression is lower after surgical RFA than after percutaneous RFA.

关键词： Hepatocellular carcinoma Radiofrequency ablation liver cirrhosis Recurrence Local therapy

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liver protection strategies in liver transplantation

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hepatobiliary & pancreatic Diseases International 2015年第1期14卷 34-42页

作者： Jun-Jun Jia Jian-Hui Li Li Jiang Bin-Yi Lin Li Wang Rong Su Lin Zhou Shu-Sen Zheng Key Laboratory of Combined Multi-organ transplantation Ministry of Health department of hepatobiliary and pancreatic surgery First Affiliated Hospital Zhejiang University School of Medicine

BACKGROUND： liver transplantation is the therapy of choice for patients with end-stage liver diseases. However, the gap between the low availability of organs and high demand is continuously increasing. Innovative strategies for organ protection are necessary to expand donor pool and to achieve better outcomes for liver transplantation. The present review analyzed and compared various strategies of liver *** SOURCES： Databases such as PubM ed, Embase and Ovid were searched for the literature related to donor liver protection strategies using following key words：＂ischemia reperfusion injury＂, ＂graft preservation＂, ＂liver transplantation＂, ＂machine perfusion＂ and ＂conditioning＂. Of the 146 studies identified,only those with cutting edge strategies were ***： A variety of therapeutic approaches were proposed to alleviate graft ischemia/reperfusion injury, which included static cold storage, machine perfusion （hypothermic, normothermic and subnormothermic）, manual conditioning （pre,post and remote）, and pharmacological conditioning. Evidences from animal experiments and clinical trials suggested that all these strategies could potentially protect liver graft; however, their clinical applications are limited partially due to their own ***： There are a plenty of methods suggested to decrease the degree of donor liver transplantation-related injury. However, none of these approaches is perfect in clinical practice. More translational researches （molecular and clinical studies） are needed to improve the techniques in liver graft protection.

关键词： ischemia reperfusion injury liver transplantation organ protection conditioning

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Mitofusin-2 mediated mitochondrial Ca2+ uptake 1/2 induced liver injury in rat remote ischemic perconditioning liver transplantation and alpha mouse liver-12 hypoxia cell line models

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World Journal of Gastroenterology 2017年第38期23卷 6995-7008页

作者： Ruo-Peng Liang Jun-Jun Jia Jian-Hui Li Ning He Yan-Fei Zhou Li Jiang Tao Bai Hai-Yang Xie Lin Zhou Yu-Ling Sun department of hepatobiliary and pancreatic surgery The First Affiliated Hospital of Zhengzhou University Institute of hepatobiliary and pancreatic Diseases Zhengzhou University Key Lab of Combined Multi-Organ transplantation Ministry of Public Health Division of hepatobiliary and pancreatic surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases

AIM To investigate the protective mechanism of mitofusin-2 (Mfn2) in rat remote ischemic perconditioning (RIC) models and revalidate it in alpha mouse liver-12 (AML-12) hypoxia cell lines. METHODS Sprague-Dawley rats were divided into three groups (n = 6 each): sham, orthotopic liver transplantation and RIC. After operation, blood samples were collected to test alanine aminotransferase and aspartate aminotransferase. The liver lobes were harvested for histopathological examination, western blotting (WB) and quantitative real-time (qRT)-PCR. AML-12 cell lines were then subjected to normal culture, anoxic incubator tank culture (hypoxia) and anoxic incubator tank culture with Mfn2 knockdown (hypoxia + Si), and data of qRT-PCR, WB, mitochondrial membrane potential (Delta psi m), apoptosis, endoplasmic reticulum Ca2+ concentrations and mitochondrial Ca2+ concentrations were collected. RESULTS Both sham and normal culture groups showed no injury during the experiment. The RIC group showed amelioration of liver function compared with the orthotopic liver transplantation group (P liver injury in rat RIC models and AML-12 hypoxia cell lines by regulating the MICUs pathway.

关键词： Remote ischemic per-conditioning Ischemia-reperfusion injury Ca2+ Mitofusin-2 Mitochondrial Ca2+ uniporter

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Derivation and validation of a preoperative prognostic model for resectable pancreatic ductal adenocarcinoma

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hepatobiliary & pancreatic Diseases International 2023年第2期22卷 160-168页

作者： Shuai Xu Xiu-Ping Zhang Guo-Dong Zhao Wen-Bo Zou Zhi-Ming Zhao Qu Liu Ming-Gen Hu Rong Liu Faculty of Hepato-Biliary-pancreatic surgery The First Medical CenterChinese PLA General HospitalBeijing 100853China department of liver transplantation and hepatobiliary surgery Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China

Background: The prognosis of patients with pancreatic ductal adenocarcinoma(PDAC) remains poor even after radical pancreaticoduodenectomy(PD). The study aimed to develop and validate a novel preoperative prognostic model to accurately predict the long-term survival of patients with ***: Patients with PDAC of pancreatic head from Chinese PLA General Hospital were included. The preoperative PDAC model with contour plots was developed using a non-linear model in the training cohort and then tested in the validation ***: Of 421 patients who met the inclusion criteria, 280 were in the training cohort and 141 in the validation cohort. Contour plots for preoperative PDAC model were established to visually predict the survival probabilities of these patients, based on preoperative carbohydrate antigen 19-9, preoperative fibrinogen to albumin ratio and pain symptoms. This model stratified patients into low-and high-risk groups with distinctly different long-term survival in the training cohort [median overall survival(OS)32.1 vs. 17.5 months;median recurrence-free survival(RFS) 19.3 vs. 10.0 months, both P pancreatic head. Besides, the model can screen high-risk patients with poor prognosis, which may provide references for personal treatment strategies in the future.

关键词： pancreatic ductal adenocarcinoma pancreaticoduodenectomy Contour plot Overall survival Recurrence-free survival

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