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World Journal of Hepatology 2024年第4期16卷 537-549页

作者： Jing-Jing Li Jia-Xi Mao Han-Xiang Zhong Yuan-Yu Zhao Fei Teng Xin-Yi Lu Li-Ye Zhu Yang Gao Hong Fu Wen-Yuan Guo Department of liver Surgery and organ transplantation Shanghai Changzheng HospitalNaval Medical UniversityShanghai 200003China

The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and *** and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage ***,recent studies have shown that lymphatic endothelial cells(LECs)and blood endothelial cells(BECs)also play multifaceted roles in the tumor microenvironment beyond their structural functions,particularly in hepatocellular carcinoma(HCC).This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC,including their involvement in angiogenesis,immune modulation,lymphangiogenesis,and *** providing a detailed account of the complex interplay between LECs,BECs,and tumor cells,this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.

关键词： Lymphatic endothelial cells Blood endothelial cells Hepatocellular carcinoma Tumor microenvironment

Clinical application of COVID-19 vaccine in liver transplant recipients

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 339-343页

作者： Feng-Chao Liu Man Xie Wei Rao Division of Hepatology Liver Disease CenterThe Affiliated Hospital of Qingdao UniversityQingdao 266000China organ transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266000China Institute of organ Donation and transplantation of Qingdao University Qingdao 266000China Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdao 266000China

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related ***,COVID-19 vaccination has been recommended to be administered as early as possible in *** sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in ***:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of *** the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained ***,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver ***:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

关键词： liver transplant COVID-19 SARS-CoV-2 Vaccine Antibody response

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(Porgan allocation.

关键词： Sex liver transplantation hepatocellular carcinoma outcome recipient donor

liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 123-128页

作者： Prashant Bhangui Institute of liver transplantation and Regenerative Medicine Medanta–The MedicitySector 38GurgaonDelhi NCR 122001India

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for *** recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in *** review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic *** therapies have helped make curative resection or LT a reality in selected *** review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy *** patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

关键词： Hepatocellular carcinoma Portal vein tumour thrombosis Downstaging therapies Living donor liver transplantation and resection Outcomes

Machine learning in liver surgery:Benefits and pitfalls

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World Journal of Clinical Cases 2024年第12期12卷 2134-2137页

作者： Rafael Calleja Manuel Durán María Dolores Ayllón Ruben Ciria Javier Briceño Hepatobiliary Surgery and liver transplantation unit Hospital Universitario Reina SofíaMaimonides Biomedical Research Institute of CordobaCórdoba 14004Spain

The application of machine learning(ML)algorithms in various fields of hepatology is an issue of ***,we must be cautious with the *** this letter,based on a published ML prediction model for acute kidney injury after liver surgery,we discuss some limitations of ML models and how they may be addressed in the *** the future faces significant challenges,it also holds a great potential.

关键词： Machine learning liver surgery Artificial intelligence Random forest Prediction model

Differentiation and immunosuppressive function of CD19^(+)CD24^(hi)CD27^(+) regulatory B cells are regulated through the miR-29a-3p/NFAT5 pathway

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 472-480页

作者： Jin-Yang Li Tian-Shuo Feng Ji Gao Xin-Xiang Yang Xiang-Cheng Li Zhen-Hua Deng Yong-Xiang Xia Zheng-Shan Wu Hepatobiliary Center the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Key Laboratory of liver transplantation Chinese Academy of Medical SciencesNanjing 210029China NHC Key Laboratory of Living Donor liver transplantation Nanjing Medical UniversityNanjing 210029China

Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.

关键词： Regulatory B cells miR-29a-3p NFAT5 liver transplantation

Diagnosis and therapy of tacrolimus toxicity in a liver transplant recipient during COVID-19 treatment

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 326-330页

作者： Feng Zhu Yi-Ming Wang Ming Ni Yuan Liang Jie-Hui Huang Xue-Hao Wang Feng Cheng Ling Lu Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical UniversityKey Laboratory of Liver TransplantationChinese Academy of Medical SciencesNHC Key Laboratory of Liver TransplantationResearch Unit of Liver Transplantation and Transplant ImmunologyChinese Academy of Medical SciencesNanjing 210000China Department of Respiratory and Critical Care Medicine Wuxi Fifth People’s HospitalWuxi 214000China Jiangsu Key Laboratory of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 210000China

To the Editor:SARS-CoV-2,the pathogen responsible for the pandemic of coronavirus disease 2019(COVID-19),has had profound impacts on human health,and its antagonist Paxlovid is a commonly used treatment option[1].However,treatment selection for immunosuppressed patients,such as liver recipients,remains uncertain due to potential drug interactions and the risk of immunosuppressant dosage adjustment,which can cause liver injury[2].

关键词： dosage treatment antagonist

Combined hepatocellular cholangiocarcinoma: A clinicopathological update

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World Journal of Hepatology 2024年第5期16卷 766-775页

作者： Mukul Vij Fadl H Veerankutty Ashwin Rammohan Mohamed Rela Department of Pathology Institute of Liver Disease and TransplantationChennai 600044India Comprehensive liver Care Institute VPS LakeshoreCochin 682040India Institute of liver Disease and transplantation Dr.Rela Institute and Medical CentreChennai 600044India

Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling *** diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists *** diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored *** a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare *** this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.

关键词： Combined hepatocellular-cholangiocarcinoma Immunotherapy Nestin Hepatocellular carcinoma Cholangiocarcinoma liver cancer Biomarker Immune checkpoint inhibitors Pathology Genomic landscape

Hippo(YAP)-autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling

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Chinese Medical Journal 2024年第6期137卷 657-668页

作者： Shuguang Zhu Xiaowen Wang Haoqi Chen Wenfeng Zhu Xuejiao Li Ruiwen Cui Xiaomeng Yi Xiaolong Chen Hua Li Genshu Wang Department of Hepatic Surgery Liver TransplantationThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Hepatology lab The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of General Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of organ transplantation The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Renal transplantation Guangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China Department of Surgical Intensive Care unit The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Hepatic Surgery Liver TransplantationGuangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China

Background:Hepatic ischemia-reperfusion injury(HIRI)remains a common complication during liver transplantation(LT)in *** a key downstream effector of the Hippo pathway,Yes-associated protein(YAP)has been reported to be involved in various physiological and pathological ***,it remains elusive whether and how YAP may control autophagy activation during ***:Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy *** an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of ***:Autophagy was activated in the post-perfusion liver grafts during LT in patients,and the expression of YAP positively correlated with the autophagic level of ***-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI(P<0.05).YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models(P<0.05).Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with *** addition,inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species(P<0.05).Moreover,the regulation of autophagy by YAP during HIRI was mediated by AP1(c-Jun)N-terminal kinase(JNK)signaling through binding to the transcriptional enhanced associate domain(TEAD).Conclusions:YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of *** Hippo(YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

关键词： YAP-signaling proteins Autophagy c-Jun N-terminal kinase Ischemia-reperfusion injury liver transplantation

Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

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World Journal of Gastroenterology 2024年第14期30卷 1958-1962页

作者： Jian-Xin Tang Dong Zhao Department of liver Surgery and organ transplantation Center Shenzhen Third People’s HospitalThe Second Affiliated Hospital of Southern University of Science and TechnologyNational Clinical Research Center for Infectious DiseaseShenzhen 518000Guangdong ProvinceChina

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 *** overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in *** addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly *** often leads to the development of end-stage liver and kidney ***,organ transplantation has emerged as an important part of active treatment for HIV infected ***,the curative effect is not *** infection has been considered a contraindication for organ *** the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively *** prolonged survival,the failure of important organs has become the main cause of death among HIV ***,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive *** study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land *** date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have *** analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary co

关键词： liver transplantation Human immunodeficiency virus Infection Hepatitis B virus End-stage liver disease China'Mainland