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Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

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Cancer Biology & Medicine 2024年第4期21卷 347-362页

作者： Jian Chen Zhe Yang Fengqiang Gao Zhisheng Zhou Junli Chen Di Lu Kai Wang Meihua Sui Zhengxin Wang Wenzhi Guo Guoyue Lyu Haizhi Qi Jinzhen Cai Jiayin Yang Shusen Zheng Xiao Xu zhejiang University School of Medicine Hangzhou 310030China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310030China Department of Hepatobiliary and Pancreatic Surgery Shulan Hospital of HangzhouHangzhou 310006China National Center for Healthcare Quality Management in Liver Transplant Hangzhou 310003China Department of General Surgery Huashan HospitalFudan UniversityShanghai 200040China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Hepatobiliary and Pancreatic Surgery The First Hospital of Jilin UniversityChangchun 130021China Department of Liver Transplantation Second Xiangya HospitalCentral South UniversityChangsha 410008China Department of Organ Transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of Liver Surgery and Liver Transplantation Center West China HospitalSichuan UniversityChengdu 610044China NHC Key Laboratory of Combined Multi-organ Transplantation Hangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be *** study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with ***:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were *** associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further ***:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male *** analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(Pplant pattern was associated with the poorest post-LT *** from male donors may provide the most benefit to female *** results indicate that sex should be considered as a critical factor in organ allocation.

关键词： Sex liver transplantation hepatocellular carcinoma outcome recipient donor

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Coastal hypoxia response to the coupling of catastrophic flood,extreme marine heatwave and typhoon:a case study off the Changjiang River Estuary in summer 2020

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Acta Oceanologica Sinica 2024年第6期43卷 107-118页

作者： Xiao Ma Qicheng Meng Dewang Li Yuanli Zhu Xiaobo Ni Dingyong Zeng Di Tian Ting Huang Zhihao Jiang Haiyan Jin Feng Zhou State Key Laboratory of Satellite Ocean Environment Dynamics Second Institute of OceanographyMinistry of Natural ResourcesHangzhou 310012China Observation and research Station of Yangtze River Delta Marine Ecosystems Ministry of Natural ResourcesZhoushan 316022China Key Laboratory of Marine Ecosystem Dynamics Second Institute of OceanographyMinistry of Natural ResourcesHangzhou 310012China School of Oceanography Shanghai Jiao Tong UniversityShanghai 200240China College of Oceanography Zhejiang UniversityZhoushan 316021China

Massive bodies of low-oxygen bottom waters are found in coastal areas worldwide,which are detrimental to coastal *** summer 2020,the response of coastal hypoxia to extreme weather events,including a catastrophic flooding,an extreme marine heatwave,and Typhoon Bavi,is investigated based on multiple satellite,four cruises,and mooring *** extensive fan-shaped hypoxia zone presents significant northward extension during July-September 2020,and is estimated as large as 13 000 km^(2) with rather low oxygen minimum(0.42 mg/L) during its peak in 28-30 *** severe hypoxia is attributed to the persistent strong stratification,which is indicated by flood-induced larger amount of riverine freshwater input and subsequent marine heatwave off the Changjiang River ***,the Typhoon Bavi has limited effect on the marine heatwave and coastal hypoxia in summer 2020.

关键词： coastal hypoxia Changjiang River Estuary extreme weather events seasonal evolution

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Biomimetic natural biomaterials for tissue engineering and regenerative medicine:new biosynthesis methods,recent advances,and emerging applications

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Military Medical research 2024年第1期11卷 50-79页

作者： Shuai Liu Jiang-Ming Yu Yan-Chang Gan Xiao-Zhong Qiu Zhe-Chen Gao Huan Wang Shi-Xuan Chen Yuan Xiong Guo-Hui Liu Si-En Lin Alec McCarthy Johnson V.John Dai-Xu Wei Hong-Hao Hou Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering the Fifth Affiliated HospitalSchool of Basic Medical ScienceSouthern Medical UniversityGuangzhou 510900China Department of Orthopedics Tongren HospitalShanghai Jiao Tong UniversityShanghai 200336China The Eighth Affiliated Hospital Sun Yat-Sen UniversityShenzhen 518033GuangdongChina Engineering research Center of Clinical Functional Materials and Diagnosis&Treatment Devices of zhejiang province Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325011ZhejiangChina Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Orthopaedics and Traumatology Faculty of Medicinethe Chinese University of Hong KongHong Kong SAR 999077China Department of Functional Materials Terasaki Institute for Biomedical InnovationLos AngelesCA 90064USA Mary&Dick Holland Regenerative Medicine Program College of MedicineUniversity of Nebraska Medical CenterOmahaNE 68130USA Zigong Affiliated Hospital of Southwest Medical University Zigong Psychiatric Research CenterZigong Institute of Brain ScienceZigong 643002SichuanChina Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of EducationSchool of MedicineDepartment of Life Sciences and MedicineNorthwest UniversityXi’an 710127China

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative *** contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative *** paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future *** highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ***,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE ***,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

关键词： Biomimic Scaffold Biosynthesis Natural biomaterial Tissue engineering

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TNFR2 is a potent prognostic biomarker for post-transplant lung metastasis in patients with hepatocellular carcinoma

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Chinese Journal of Cancer research 2023年第1期35卷 66-80页

作者： Huigang Li Zuyuan Lin Jianyong Zhuo Modan Yang Wei Shen Zhihang Hu Yichen Ding Hao Chen Chiyu He Xinyu Yang Siyi Dong Xuyong Wei Beicheng Sun Shusen Zheng Ren Lang Di Lu Xiao Xu zhejiang University School of Medicine Hangzhou 310058China 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 MedicineHangzhou 310006China The Institute for Organ Repair and Regenerative Medicine of Hangzhou Hangzhou 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China National Center for Healthcare Quality Management in Liver Transplant Hangzhou 310003China Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou 311112China NHC Key Laboratory of Combined Multi-organ Transplantation Hangzhou 31003China Department of Hepatobiliary Surgery Beijing Chaoyang Hospital Affiliated to Capital Medical UniversityBeijing 100020China

Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great ***:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling *** enrolled 241 HCC patients who underwent liver transplantation from three *** microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung ***:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of *** expression of TNF was degraded in comparison to that in para-tumor tissues(Pey receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(Pplant lung metastasis(hazard ratio:1.146;Pplant lung metastasis,and a novel nomogram was established *** nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan ***:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantatio

关键词： Lung metastasis hepatocellular carcinoma liver transplantation nomogram

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Recent advances in immunotherapy for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2021年第6期20卷 511-520页

作者： Abid Ali Khan Zhi-Kun Liu Xiao Xu Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Lab of Combined Multi-Organ Transplantation Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesMinistry of Public HealthHangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China

Background:Treatment of hepatocellular carcinoma(HCC)is challenging as most patients are diagnosed at advanced stage with underlying chronic liver *** systemic chemotherapy has failed in HCC,and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains *** sources:Literature search was conducted in Pub Med for relevant articles published before January *** search aimed to identify recent developments in immune-based treatment approaches for *** of clinical trials was obtained from https://***/.Results:Two immune checkpoint inhibitors(ICIs),nivolumab and pembrolizumab were approved as monotherapies,which has revolutionized HCC ***,combination ICIs have also got accelerated FDA approval ***-based therapies have challenged targeted drugs owing to their safety,tolerability,and survival *** addition to the significant success in ICIs,other immunotherapeutic strategies such as cancer vaccine,chimeric antigen receptor T-cells,natural killer cells,cytokines,and combination therapy,have also shown promising outcomes in clinical *** diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ***:Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent ***,challenges such as low response rate and acquired resistance in previously respondent patients still *** research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.

关键词： Hepatocellular carcinoma Immunotherapy Immune checkpoint inhibitor Adoptive cellular therapy Immune evasion Combination therapy Predictive biomarkers

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A double-edged sword:The HBV-induced non-coding RNAs alterations in hepatocellular carcinoma

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BIOCELL 2023年第1期47卷 27-32页

作者： TIANXING LIU HONGYAN DIAO Department of Cell and Systems Biology University of TorontoTorontoOntarioM5S1A1Canada State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310003China

Non-coding RNAs are speculated to exert important regulatory functions at the level of gene expression,oncogenesis,and many other *** B virus(HBV)infection is a leading cause of hepatocellular carcinoma(HCC),and some studies have shown that the expression of non-coding RNAs has an assignable effect on the development of HBV-induced *** this context,the functions and molecular mechanisms of the HBVinduced non-coding RNA expression in the development of hepatoma have attracted increasing *** review covers the progress in the exploration of the relationship between HBV-induced hepatoma and non-coding RNA expression,cataloging the recent reports about the roles of non-coding RNAs in HBV-induced hepatoma into five classes,including(1)modulation of metabolism in hepatic cancer,(2)aggravation of inflammation and hepatic fibrosis,(3)alteration of the tumor immune microenvironment,(4)non-coding RNA N6-methyladenosine modification,and a seemingly opposite process,(5)the suppression of the progression of HBV-related *** evidence supports non-coding RNAs as promising novel targets for the early diagnosis and treatments for HCC.

关键词： Non-coding RNA Hepatitis B virus Hepatocellular cancer

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When immunotherapy meets liver transplantation for hepatocellular carcinoma: A bumpy but promising road

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Chinese Journal of Cancer research 2023年第2期35卷 92-107页

作者： Yufeng Gu Shengjun Xu Zhengxin Wang Jiayin Yang Shusen Zheng Qiang Wei Zhikun Liu Xiao Xu The Fourth School of Clinical Medicine Zhejiang Chinese Medical UniversityHangzhou 310053China Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China Key Laboratory of Integrated Oncology and Intelligent Medicine of zhejiang province Hangzhou 310006China Department of General Surgery Huashan HospitalFudan UniversityShanghai 200040China Department of Liver Surgery Liver Transplantation CenterWest China Hospital of Sichuan UniversityChengdu 610044China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou 311112China Westlake Laboratory of Life Sciences and Biomedicine Hangzhou 310024China

Liver transplantation(LT)is a highly curative therapy for patients with hepatocellular carcinoma(HCC).However,due to the shortage of donor livers and rapid progression of HCC,a majority of patients are dropped out from the ***,immunotherapy has shown great promise in the treatment of advanced ***,the use of immunotherapy is limited in LT mainly due to the potentially increasing risk of graft *** of the main challenges for researchers is the protection of donor graft from an immunotherapy-boosted immune response mounted by the ***,the safety,availability,and costs of immunotherapy are other challenges that need to be ***,we reviewed the literature involving patients who received immunotherapy prior to transplant to avoid waitlist dropouts and following transplantation to prevent the progression of tumor recurrence and ***,the incidence of rejection was 25.0%pre-transplant and 18.5%*** on the review of these clinical studies,we can conclude that conducting clinical trials on the safety and efficacy of currently available immunotherapy drugs and identifying novel immunotherapy targets through extensive research may be promising for patients who do not meet the selection criteria for LT and who experience post-transplant *** date,the clinical experience on the use of immunotherapy before or after LT comes from individual case *** some of the reported results are promising,they are not sufficient to support the standardized use of immunotherapy in clinical practice.

关键词： Liver transplantation hepatocellular carcinoma immunotherapy immune checkpoint inhibitors adoptive cell therapy

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Efficacy and safety of anlotinib as an adjuvant therapy in hepatocellular carcinoma patients with a high risk of postoperative recurrence

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中国癌症研究:英文版 2023年第4期35卷 399-407页

作者： Jianguo Wang Xiaonan Xiang Zhixiong Shi Hui Zhang Quanbao Zhang Zhikun Liu Guangjie Zhao Chuanxing Wu Qiang Wei Lin Zhong Zhengxin Wang Guoyue Lv Shusen Zheng Xiao Xu Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006China Key Laboratory of Integrated Oncology and Intelligent Medicine of zhejiang province Hangzhou 310006China Department of General Surgery Huashan HospitalFudan UniversityShanghai 200040China Department of Hepatobiliary and Pancreatic Surgery the First Bethune Hospital of Jilin UniversityChangchun 130021China Department of Hepatobiliary and Pancreatic Surgery Shanghai General HospitalShanghai 200080China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalZhejiang Shuren University School of MedicineHangzhou 310022China

Objective:Hepatocellular carcinoma(HCC)has a high rate of postoperative recurrence and lacks an effective treatment to prevent *** study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence ***:For this multicenter,retrospective study,we recruited 63 HCC patients who received either anlotinib(n=27)or transcatheter arterial chemoembolization(TACE)(n=36)from six research centers in China between March 2019 and October *** primary endpoint was disease-free survival(DFS)and the secondary endpoints were overall survival(OS)and ***:In this study,the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups,*** was no significant difference in the median DFS between the anlotinib[26.8 months,95%confidence interval(95%CI):6.8-NE]and TACE groups(20.6 months,95%CI:8.4-NE).The 12-month OS rates in the anlotinib and TACE groups were 96.3%and 97.2%,*** the anlotinib group,19 of 27patients(70.4%)experienced treatment-emergent adverse events,with the most common events(≥10%)being hypertension(22.2%)and decreased platelet count(22.2%).Conclusions:The results indicate that anlotinib,as a new,orally administered tyrosine kinase inhibitor,has the same efficacy as TACE,and side effects can be well controlled.

关键词： Hepatocellular carcinoma adjuvant therapy anlotinib transcatheter arterial chemoembolization

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The critical role of therapeutic plasma exchange in ABO-incompatible liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2022年第6期21卷 538-542页

作者： Cheng-Zuo Han Qiang Wei Meng-Fan Yang Li Zhuang 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 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China National Center for Healthcare Quality Management in Liver Transplant Hangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou 310022China

Background:The shortage of donor liver restricts liver transplantation(LT).Nowadays,donor liver with ABO blood group incompatibility between donor and recipient has become an option to expand the source of donor *** it is now possible to perform ABO-incompatible(ABO-I)LT,antibody-mediated rejection(AMR)has been recognized as the primary cause of desperate outcomes after ABO-I ***-A/B antibody is the trigger of immune response to ABO-I LT graft *** plasma ex-change(TPE)can quickly reduce the titer of plasma antibodies and effectively inhibit humoral *** sources:We searched PubMed and CNKI databases using search terms“therapeutic plasma ex-change”,“ABO-incompatible liver transplantation”,“ABO-I LT”,“liver transplantation”,“LT”,“antibody-mediated rejection”,and“AMR”.Additional publications were identified by a manual search of references from key *** relevant publications published before September 30,2020 were included in this ***:Different centers have made different attempts on whether to use TPE,when to use TPE and how often to use ***,the control standard of lectin revision level is always controversial,the target titer varies significantly from center to center,and the standard target titer has not yet been *** has several schemes to reduce antibody titers,but there is a lack of clinical trials that provide standardized ***:TPE is essential for ABO-I ***,further research and clinical trials should be conducted to determine the best regimen for TPE to remove ABO antibodies and prevent AMR.

关键词： Plasma exchange ABO blood group system Blood group incompatibility Liver transplantation Graft rejection

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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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