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Gut Microbiota Modulation:A Viable Strategy to Address Medical Needs in Hepatocellular Carcinoma and Liver Transplantation

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Engineering 2023年第10期29卷 59-72页

作者： Ze Xiang Jian Wu Jiarui Li Shusen Zheng xuyong wei Xiao Xu Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s HospitalSchool of MedicineZhejiang UniversityHangzhou 310006China School of Medicine Zhejiang UniversityHangzhou 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Affiliated Hangzhou First People’s HospitalSchool of MedicineZhejiang UniversityHangzhou 310006China Department of Clinical Laboratory The Affiliated Suzhou Hospital of Nanjing Medical University&Suzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215008China Shulan(Hangzhou)Hospital Zhejiang Shuren University School of MedicineHangzhou 310022China National Health Commission(NHC)Key Laboratory of Combined Multi-organ Transplantation the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China

Hepatocellular carcinoma(HCC)is the most common malignancy of the liver,posing a significant threat to public *** liver transplantation(LT)is an effective treatment for HCC,ischemia–reperfusion(I/R)injury,transplant rejection,and complications after LT can greatly reduce its *** recent years,transplant oncology has come into being,a comprehensive discipline formed by the intersection and integration of surgery,oncology,immunology,and other related *** microbiota,an emerging field of research,also plays a crucial *** the microbiome–gut–liver axis,the gut microbiota has an impact on the onset and progression of HCC as well as *** review summarizes the mechanisms by which the gut microbiota affects HCC and its bidirectional interactions with chronic liver disease that can develop into HCC as well as the diagnostic and prognostic value of the gut microbiota in *** addition,gut microbiota alterations after LT were reviewed,and the relationship between the gut microbiota and liver I/R injury,the efficacy of immunosuppressive drugs used,and complications after LT were *** the era of LT oncology,the role of the gut microbiota in HCC and LT should be emphasized,which can provide new insights into the management of HCC and LT via gut microbiota modulation.

关键词： Gut microbiota Hepatocellular carcinoma(HCC) Liver transplantation(LT) Clinical value Mediating mechanism

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Genetic engineering drives the breakthrough of pig models in liver disease research

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Liver Research 2024年第3期8卷 131-140页

作者： Chenhao Xu Xixi Fang Xiao Xu xuyong wei Zhejiang University School of Medicine HangzhouZhejiangChina Department of Hepatobiliary and Pancreatic Surgery Hangzhou First People’s HospitalHangzhouZhejiangChina Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province HangzhouZhejiangChina Hangzhou Normal University HangzhouZhejiangChina School of Clinical Medicine Hangzhou Medical CollegeHangzhouZhejiangChina NHC Key Laboratory of Combined Multi-organ Transplantation HangzhouZhejiangChina Institute of Translational Medicine Zhejiang UniversityHangzhouZhejiangChina

Compared with the widely used rodents,pigs are anatomically,physiologically,and genetically more similar to humans,making them high-quality models for the study of liver ***,we review the latest research progress on pigs as a model of human liver disease,including methods for establishing them and their advantages in studying cystic fibrosis liver disease,acute liver failure,liver regeneration,non-alcoholic fatty liver disease,liver tumors,and *** also emphasize the importance of genetic engineering techniques,mainly the CRISPR/Cas9 system,which has greatly enhanced the utility of porcine models as a tool for substantially advancing liver disease *** engineering is expected to propel the pig as one of the irreplaceable animal models for future biomedical research.

关键词： Animal model Liver disease Genetic engineering CRISPR/Cas9 Xenogeneic liver transplantation Pig

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ZIP4 inhibits Ephrin-B1 ubiquitination,activating Wnt5A/JNK/ZEB1 to promote liver cancer metastasis

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Genes & Diseases 2024年第6期11卷 1-4页

作者： Haijun Guo Renyi Su Xinfeng Lu Hui Zhang xuyong wei Xiao Xu Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China Zhejiang University School of Medicine HangzhouZhejiang 310058China The Fourth School of Clinical Medicine Zhejiang Chinese Medicine UniversityHangzhouZhejiang 310053China School of Clinical Medicine Hangzhou Medical CollegeHangzhouZhejiang 310014China

Hepatocellular carcinoma(HCC),a highly malignant tumor,faces a major challenge with its high post-hepatectomy recurrence impacting patient *** and preventive strategies remain to be ***-/lrt-like protein 4(ZIP4,also called SLC39A4/solute carrier family 39 member 4)belongs to the zinc transporter ZiP superfamily of which the members play an important role in maintaining zinc steady state,and its high expression in various tumors is associated with the prognosis of cancer patients.

关键词： ZEB1 metastasis cancer

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Visual analysis of mesenchymal stem cell research in liver disease based on bibliometrics

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iLIVER 2022年第4期1卷 283-291页

作者： Chengzuo Han Rui Wang Nan Xu xuyong wei Qiang wei Xiao Xu Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou310006China Westlake Laboratory of Life Sciences and Biomedicine Hangzhou310024China

The research of mesenchymal stem cells(MSCs)in the field of liver diseases has received more and more *** paper introduces the current situation,hot spots,and development trends in this ***-hensive searches were conducted using Web of Science Core Collection from January 1,2000 to December 13,2021 with the following keywords:TS(topic)¼(liver*OR hepatic*OR hepatocyte)AND TS(topic)¼(Mesen-chymal stem cell*).VOSviewer(version 1.6.16)and CiteSpace V are used as bibliometric tools to analyze and visualize the knowledge graph.A total of 4452 papers were included in this study,and the number of research papers on MSCs in the field of liver diseases increased from January 2000 to December ***-four countries and regions have published articles on research in this field,among which China and the United States are the main two countries of *** on the keyword burst detection,we find that the research in this field has shifted from basic research to clinical application,from medical research to interdisciplinary *** engineering and regenerative medicine are the frontier fields of MSCs research in liver ***,multi-author cooperation,and multi-disciplinary intersection are the research trends in this *** body,obesity,and tissue engineering are the hotspots in this field.

关键词： Mesenchymal stem cells Liver disease Bibliometrics Visualization

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Fibroblast growth factor 21(FGF21) attenuates tacrolimus-induced hepatic lipid accumulation through transcription factor EB(TFEB)-regulated lipophagy

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第6期24卷 485-495页

作者： Zhensheng ZHANG Li XU Xun QIU Xinyu YANG Zhengxing LIAN xuyong wei Di LU Xiao XU Zhejiang University School of Medicine Hangzhou 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Hangzhou 310006China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China NHC Key Laboratory of Combined Multi-organ Transplantation Hangzhou 310003China Westlake Laboratory of Life Sciences and Biomedicine Hangzhou 310024China

Tacrolimus(TAC),also called FK506,is one of the classical immunosuppressants to prevent allograft rejection after liver ***,it has been proved to be associated with post-transplant *** mechanism behind this is unknown,and it is urgent to explore preventive strategies for hyperlipemia after ***,we established a hyperlipemia mouse model to investigate the mechanism,by injecting TAC intraperitoneally for eight *** TAC treatment,the mice developed hyperlipemia(manifested as elevated triglyceride(TG)and low-density lipoprotein cholesterol(LDL-c),as well as decreased high-density lipoprotein cholesterol(HDL-c)).Accumulation of lipid droplets was observed in the *** addition to lipid accumulation,TAC induced inhibition of the autophagy-lysosome pathway(microtubule-associated protein 1light chain 3β(LC3B)II/I and LC3B II/actin ratios,transcription factor EB(TFEB),protein 62(P62),and lysosomal-associated membrane protein 1(LAMP1))and downregulation of fibroblast growth factor 21(FGF21)in *** of FGF21may reverse TAC-induced TG *** this mouse model,the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome *** conclude that TAC downregulates FGF21and thus exacerbates lipid accumulation by impairing the autophagy-lysosome *** FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.

关键词： Autophagy Fibroblast growth factor 21(FGF21) Lipid Lipophagy Lysosome Tacrolimus Transcription factor EB(TFEB)

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Clinical challenges and research perspectives in liver transplant oncology

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中华医学杂志(英文版) 2024年第22期137卷 2024 Oct 25页

作者： Xu Shengjun Shu Wenzhi He Xinyu Ling Sunbin wei xuyong Xu Xiao NHFPC Key Laboratory of Combined Multi-Organ Transplantation Institute of Organ Transplantation Zhejiang University Hangzhou Zhejiang China Center of Hepatobiliary Pancreatic Disease Beijing Tsinghua Changgung Hospital School of Clinical Medicine Tsinghua University Beijing China The Fourth School of Clinical Medicine Zhejiang Chinese Medical University Hangzhou Zhejiang China School of Clinical Medicine Hangzhou Medical College Hangzhou Zhejiang China Institute of Translational Medicine Zhejiang University Hangzhou Zhejiang China

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Extrahepatic organs in the development of non-alcoholic fatty liver disease in liver transplant patients

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Hepatobiliary Surgery and Nutrition 2022年第3期11卷 400-411页

作者： Renyi Su xuyong wei Qiang wei Di Lu Zuyuan Lin Shuo Wang Chuxiao Shao Xiao Xu Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouChina NHC Key Laboratory of Combined Multi-Organ Transplantation HangzhouChina Department of Hepatobiliary and Pancreatic Surgery Shu Lan HospitalShu Lan International Medical College of Zhejiang Shuren UniversityHangzhouChina Department of Hepatobiliary and Pancreatic Surgery Affiliated Lishui HospitalZhejiang University School of MedicineLishuiChina

Background and Objective:Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients who undergo liver transplantation(LT).Whereas there is huge data on NAFLD,little is known about NAFLD in *** this review,we aim to explore extrahepatic organs and their potential mechanisms in the development of NAFLD in LT patients and discuss current limitations in preclinical and clinical scenarios with suggestions for future ***:The following keywords,such as NAFLD,NASH,liver transplant,therapy,pathogenesis and biomarkers,were set for literature *** articles which were published articles in English till 25th June 2020 in PubMed database were included,and there is no limit for the study design *** Content and Findings:Following LT,there are significant shifts in the microbiota and farnesoid X receptor may be a potential therapeutic target for NAFLD in LT *** roles of probiotics and diet on NALFD remain inconclusive in LT ***,the adipokines and cytokines disorder and local insulin resistance of adipose tissue may contribute to NAFLD *** surgeries are promising in controlling de novo and recurrent NAFLD with significant reduction in abdominal adipose tissue,despite the optimal timing is inconclusive in LT ***,circumstantial evidence indicates that miRNA-33a may function as a mediator bridging sarcopenia and NAFLD of post-LT.β-Hydroxy-β-Methyl-Butyrate treatment could improve muscle status in graft recipients and shows protective potential for NAFLD in LT ***:Gut,adipose tissue and muscle are intricately intertwined in promoting NAFLD in LT *** animal studies are needed to deepen our understanding of mechanisms in multi-organ *** quality clinical trials are warrant for making guidelines and developing management strategies on NAFLD after LT.

关键词： Non-alcoholic fatty liver disease(NAFLD) liver transplant sarcopenia lipid gut

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Molecular phenotypes reveal heterogeneous engraftments of patient-derived hepatocellular carcinoma xenografts

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Chinese Journal of Cancer Research 2021年第4期33卷 470-479页

作者： Jianyong Zhuo Di Lu Jianguo Wang Zhengxing Lian Jiali Zhang Huihui Li Beini Cen xuyong wei Qiang wei Haiyang Xie Xiao Xu Department of Hepatobiliary and Pancreatic Surgery The Center for Integrated Oncology and Precision MedicineAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China National Health Commission Key Laboratory of Combined Multi-organ Transplantation Institute of Organ TransplantationZhejiang UniversityHangzhou 310003China

Objective:Patient-derived xenograft(PDX)models provide a promising preclinical platform for hepatocellular carcinoma(HCC).However,the molecular features associated with successful engraftment of PDX models have not been ***:HCC tumor samples from 76 patients were implanted in immunodeficient *** molecular expression was evaluated by *** and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square *** independent prediction parameters were identified by logistic regression ***:The engraftment rate for PDX models from patients with HCC was 39.47%(30/76).Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment *** with poor differentiation and vascular invasion were related to engraftment *** positive expression of CK19,CD133,glypican-3(GPC3),and Ki67 in tumor samples was associated with engraftment *** regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX *** with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates,with 71.9%in GPC3^(+)/Ki67^(+)tumors,30.8%in GPC3^(-)/Ki67^(+)tumors,15.0%in GPC3^(+)/Ki67^(-)tumors,and 0 in GPC3^(-)/Ki67^(-)***:Successful engraftment of HCC PDXs was significantly related to molecular *** with the GPC3+/Ki67+phenotype were the most likely to successfully establish HCC PDXs.

关键词： Hepatocellular carcinoma patient-derived xenografts heterogeneous establishment molecular phenotype

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Stratified Analysis of Survival Benefit for ABO-incompatible Deceased-donor Liver Transplantation:Multicenter Propensity Score-matched Study

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 827-838页

作者： Mengfan Yang xuyong wei Abdul Rehman Khan Qiang wei Rui Wang Binhua Pan Kun Wang Zhisheng Zhou Di Lu Beini Cen Shuijun Zhang Wenzhi Guo Shusen Zheng Yang Yang Xiao Xu Department of Organ Transplantation Qilu Hospital of Shandong UniversityJinanShandongChina Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province HangzhouZhejiangChina Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouZhejiangChina Zhejiang University School of Medicine HangzhouZhejiangChina National Center for Healthcare Quality Management in Liver Transplant HangzhouZhejiangChina Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityHenanChina Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhouZhejiangChina Department of Hepatobiliary and Pancreatic Surgery The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdongChina

Background and Aims:Liver transplantation(LT)using ABO-incompatible(ABOi)grafts can extend the donor pool to a certain extent and hence reduce the waiting time for ***,concerns of the impending prognosis associated with this option,especially for patients with liver failure and higher model for end-stage liver disease(MELD)scores,who tend to be more fragile during the waiting period before ***:Recipients undergoing LT for acute-onchronic liver failure or acute liver failure were retrospectively enrolled at four *** survival was compared and a Cox regression analysis was *** score matching was performed for further *** were stratified by MELD score and cold ischemia time(CIT)to determine the subgroups with survival ***:Two hundred ten recipients who underwent ABOi LT and 1,829 who underwent ABO compatible(ABOc)LT were *** 5-year overall survival rate was significantly inferior in the ABOi group compared with the ABOc group after matching(50.6%vs.75.7%,p0.05).Comparison of the survival rates revealed no statistically significant difference for patients with MELD scores≥40(p>0.05).For patients with MELD scores of 31-39,the overall survival rate was significantly inferior in the ABOi group compared with the ABOc group(p<0.001);however,the rate was increased when the liver graft CIT was<8 ***:For recipients with MELD scores≤30,ABOi LT had a prognosis comparable to that of ABOc LT and can be regarded as a feasible *** recipients with MELD scores≥40,ABOi should be adopted with caution in emergency *** recipients with MELD scores of 31-39,the ABOi LT prognosis was ***,those patients benefited from receiving ABOi grafts with a CIT of<8 h.

关键词： Liver transplantation ABO-incompatible Model for end-stage liver disease score Cold ischemia time Propensity score matching

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Zinc finger protein 296 promotes hepatocellular carcinoma progression via intervening interaction between macrophages and B cells

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Chinese Journal of Cancer Research 2024年第5期36卷 517-529页

作者： Nan Xu Xiaonan Xiang Huan Chen Yiyuan Chen Shuai Wang Haijun Guo xuyong wei Jun Chen Xiao Xu Qiang wei Zhejiang University School of Medicine Hangzhou 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhou 310006China Department of Colorectal Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China School of Clinical Medicine Hangzhou Medical CollegeHangzhou 310053China Institute of Translational Medicine Zhejiang University School of MedicineHangzhou 310029China

Objective:Hepatocellular carcinoma(HCC)is a prevalent malignancy with poor *** cell types in the tumor microenvironment participate in the tumorigenesis and progression of *** study aimed to analyze the immune microenvironment of HCC and its relationship with clinical ***:We analyzed HCC RNA-seq for cell type identification and prognosis by estimating relative subsets of RNA transcripts using *** interaction between B cells and macrophages in HCC was analyzed using a Hepa1-6 orthotopic transplantation mouse model and flow *** effect of Zinc finger protein 296(ZNF296)on the interaction of B cells and macrophages was verified using human HCC tissues analyzed through western blot,quantitative real-time polymerase chain reaction(qPCR),and multiplex immunofluorescence.A comparative analysis of immune cells associated with HCC prognosis was performed using RNA-seq data from The Cancer Genome Atlas(TCGA),bulk multimodal data,and single-cell transcriptomic data from existing HCC single-cell transcriptomic data employing the Single Cell Inferred Site Specific Omics Resource for Tumor Microenvironments(SCISSOR).Results:Liver hepatocellular carcinoma(LIHC)RNA-seq analysis of TCGA showed that high eosinophil infiltration promoted HCC *** proportion of B cells correlated with that of macrophages(r=−0.24)and affected the infiltration and programmed death ligand 1(PD-L1)expression of macrophages in ***296 may participate in the interaction between B cells and macrophages to accelerate the HCC progression by regulating PAFAH1B3 and ***,ZNF296 expression positively correlated with LAG3(r=0.27)and CTLA4(r=0.31)expression *** the immune cell phenotypes related to survival and death identified by SCISSOR analysis,T cells correlated with an excellent prognosis of *** normal function of liver and dendritic cells was also associated with a good prognosis in ***:This study analyzed the

关键词： Hepatocellular carcinoma immune cells prognosis Zinc finger protein 296

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