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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(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant 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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Single-domain antibodies as therapeutics for solid tumor treatment

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2854-2868页

作者： Mingkai Wang Tianlei Ying Yanling Wu MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology School of Basic Medical SciencesDepartment of Pulmonary and Critical Care MedicineDepartment of Liver Surgery and TransplantationZhongshan HospitalFudan UniversityShanghai 200032China Shanghai Engineering Research Center for Synthetic Immunology Shanghai 200032China

Single-domain antibodies(sdAbs),initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs,have emerged as a promising alternative to conventional therapeutic *** sdAbs have many superior physicochemical and pharmacological properties,including small size,good solubility and thermostability,easier accessible epitopes,and strong tissue ***,the inherent challenges associated with the animal origin of sdAbs limit their clinical *** recent years,various innovative humanization technologies,including complementarity-determining region(CDR)grafting or complete engineering of fully human sdAbs,have been developed to mitigate potential immunogenicity issues and enhance their *** review provides a comprehensive exploration of sdAbs,emphasizing their distinctive features and the progress in humanization *** addition,we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment,such as sdAbedrug conjugates,multispecific sdAbs,sdAb-based delivery systems,and sdAb-based cell therapy.

关键词： Single-domain antibody Nanobody Humanization Fully human singledomain antibody Solid tumor

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Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma

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Cancer Communications 2024年第2期44卷 226-250页

作者： Weiren Liu Huqiang Wang Qianfu Zhao Chenyang Tao Weifeng Qu Yushan Hou Run Huang Zimei Sun Guiqi Zhu Xifei Jiang Yuan Fang Jun Gao Xiaoling Wu Zhixiang Yang Rongyu Ping Jiafeng Chen Rui Yang Tianhao Chu Jian Zhou Jia Fan Zheng Tang Dong Yang Yinghong Shi Department of liver surgery and transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationShanghaiP.R.China Research Unit of liver cancer Recurrence and Metastasis Chinese Academy of Medical SciencesBeijingP.R.China State Key Laboratory of Medical Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingP.R.China

Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic *** metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely ***,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat ***:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome *** on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was *** and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic *** proliferation analysis,5-ethynyl-2’-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA ***:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were *** metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic *** S2 subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)*** the S2 subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)***:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing

关键词： diacylglycerol kinaseα intrahepatic cholangiocarcinoma MAPK signaling metabolic classifi-cation multiomics analysis phosphatidic acid metabolism

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Human leukocyte antigen compatibility and incidence of donorspecific antibodies in pediatric liver transplant recipients

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World Journal of Gastroenterology 2024年第33期30卷 3837-3845页

作者： Melina U Melere Flavia H Feier Jorge Neumann Antônio N Kalil Juliana de M Montagner Luiza S Nader Carolina S da Silva Marco Aurélio F Junior Gabriela P Coral Guilherme P Bobsin Cristina T Ferreira Department of Hepatology and liver transplantation Santa Casa de Porto AlegrePorto Alegre 90050170Rio Grande do SulBrazil Department of Hepato-biliary-pancreatic surgery and liver transplantation Irmandade Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90020-090Rio Grande do SulBrazil Postgraduation program in Medicine:Hepatology Federal University of Health Sciences of Porto AlegrePorto Alegre 90050-170Rio Grande do SulBrazil Laboratory of transplantation Immunology Irmandade Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90020-090Rio Grande do SulBrazil

BACKGROUND Antibody-mediated rejection following liver transplantation(LT)has been increasingly recognized,particularly with respect to the emergence of de novo donor-specific antibodies(DSAs)and their impact on graft *** substantial evidence for adult populations exists,research focusing on pediatric LT outcomes remains *** To investigate the prevalence of human leukocyte antigen(HLA)mismatches and DSA and evaluate their association with rejection episodes after pediatric *** A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre,Brazil,between December 2013 and December *** patients who survived for>30 days after LT with at least one DSA analysis were *** classes I and II and cross-matches were *** presence of de novo DSA(dnDSA)was evaluated at least 3 months after LT using the Luminex®single antigen bead method,with a positive reaction threshold set at 1000 *** episodes were confirmed by liver *** Overall,67 transplanted children were analyzed;61 received grafts from living donors,85%of whom were related to ***-transplant DSA(class I or II)was detected in 28.3%of patients,and dnDSA was detected in 48.4%.The median time to DSA detection after LT was 19.7[interquartile range(IQR):4.3-35.6]*** rejection occurred in 13 patients at follow-up,with C4d positivity observed in 5/13 liver *** median time to rejection was 7.8(IQR:5.7-12.8)*** presence of dnDSA was significantly associated with rejection(36%vs 3%,Ptransplantation protocols for pediatric LT *** implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recip

关键词： Human leukocyte antigens Donor-specific antibodies liver transplantation Pediatric Rejection

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FGF21-mediated autophagy:Remodeling the homeostasis in response to stress in liver diseases

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Genes & Diseases 2024年第3期11卷 264-274页

作者： Wei Shen Modan Yang Hao Chen Chiy He Huigang Li Xinyu Yang Jianyong Zhuo Zuyuan Lin Zhihang Hu Di Lu Xiao Xu Zhejiang University School of Medicine HangzhouZhejiang 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 MedicineHangzhouZhejiang 310006China The Institute for Organ Repair and Regenerative Medicine of Hangzhou HangzhouZhejiang 310006China Institute of Organ transplantation Zhejiang UniversityHangzhouZhejiang 310003China National Center for Healthcare Quality Management in liver Transplant HangzhouZhejiang 310003China

liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum *** exact interplay between stress and liver diseases remains *** plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver *** the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain *** recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much ***21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to ***,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal *** review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.

关键词： Autophagy Fibroblast growth factor 21 liver diseases mTOR Stress

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De Novo Dissecting the Three‑Dimensional Facial Morphology of 2379 Han Chinese Individuals

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Phenomics 2024年第1期4卷 1-12页

作者： Hui Qiao Jingze Tan Shaoqing Wen Menghan Zhang Shuhua Xu Li Jin State Key Laboratory of Genetic Engineering Center for Evolutionary BiologyCollaborative Innovation Center for Genetics and DevelopmentSchool of Life SciencesFudan UniversityShanghai 200438China Ministry of Education Key Laboratory of Contemporary Anthropology Human Phenome InstituteZhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Institute of Archaeological Science Fudan UniversityShanghai 200433China Institute of Modern Languages and Linguistics Fudan UniversityShanghai 200433China Department of liver surgery and transplantation liver Cancer Institute Zhongshan HospitalFudan UniversityShanghai 200032China

Phenotypic diversity,especially that of facial morphology,has not been fully investigated in the Han Chinese,which is the largest ethnic group in the *** this study,we systematically analyzed a total of 14,838 facial traits representing 15 categories with both a large-scale three-dimensional(3D)manual landmarking database and computer-aided facial segmented phenotyping in 2379 Han Chinese *** results illustrate that homogeneous and heterogeneous facial morphological traits exist among Han Chinese populations across the three geographical regions:Zhengzhou,Taizhou,and *** identifed 1560 shared features from extracted phenotypes,which characterized well the basic facial morphology of the Han *** particular,heterogeneous phenotypes showing population structures corresponded to geographical *** greatest facial variation among these geographical populations was the angle of glabella,left subalare,and right cheilion(p=3.4×10^(−161)).Interestingly,we found that Han Chinese populations could be classifed into northern Han,central Han,and southern Han at the phenotypic level,and the facial morphological variation pattern of central Han Chinese was between the typical diferentiation of northern and southern Han *** result was highly consistent with the results revealed by the genetic *** fndings provide new insights into the analysis of multidimensional phenotypes as well as a valuable resource for further facial phenotype-genotype association studies in Han Chinese and East Asian populations.

关键词： Phenotypes Three-dimensional facial imaging Facial morphology Han Chinese

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Development and validation of a nomogram based on perioperative risk factors for the prediction of early thrombotic complications following pediatric liver transplantation

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中华医学杂志(英文版) 2024年第16期137卷 2024 May 30页

作者： You Qiang Qu Enze Zeng Kaining Liu Jianrong Yang Qing Tang Hui Feng Xiao Yao Jia Huang Xinru Zhang Tong Fu Binsheng Li Hua Zhao Hui Zheng Jun Yi Shuhong Yang Yang Department of Hepatic surgery and liver transplantation Center of the Third Affiliated Hospital of Sun Yat-sen University Organ Transplantation Research Center of Guangdong Province Guangdong Province Engineering Laboratory for Transplantation Medicine Guangzhou Guangdong China Guangdong Key Laboratory of liver Disease Research Key Laboratory of Liver Disease Biotherapy and Translational Medicine of Guangdong Higher Education Institutes The Third Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong China Department of Ultrasound The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou Guangdong China Surgical ICU of the Third Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong China

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Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 83-90页

作者： Zhikun LIU Yichao WU Abid Ali KHAN Lun LU Jianguo WANG Jun CHEN Ningyang JIA Shusen ZHENG 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 Zhejiang University School of Medicine Hangzhou310058China Department of Radiology Easter Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai200438China Department of Hepatobiliary and Pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou310003China NHC Key Laboratory of Combined Multi-organ transplantation Hangzhou310003China Department of Hepatobiliary and Pancreatic surgery Shulan(Hangzhou)HospitalHangzhou310022China

Hepatocellular carcinoma(HCC)is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide(Forner et al.,2018;He et al.,2023).Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle(SM)mass that may be age-related or the result of malnutrition in cancer patients(Cruz-Jentoft and Sayer,2019).Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival(Voron et al.,2015;van Vugt et al.,2016).

关键词： cancer patients

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Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 463-471页

作者： Yu Nie Jin-Bo Huang Shu-Jiao He Hua-Di Chen Jun-Jun Jia Jing-Jing Li Xiao-Shun He Qiang Zhao General surgery Center Department of Hepatobiliary Surgery IIResearch Center for Artificial Organ and Tissue EngineeringGuangzhou Clinical Research and Transformation Center for Artificial LiverInstitute of Regenerative MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510515China Organ Transplant Center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology Guangzhou 510080China Guangdong Provincial International Cooperation Base of Science and Technology Guangzhou 510080China Division of Hepatobiliary Pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use

关键词： Primary non-function Early allograft failure Risk predicting model liver transplantation

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Routine use of a transanastomotic stent is unnecessary for hepatojejunostomy in liver transplantation

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Chinese Medical Journal 2012年第14期125卷 2411-2416页

作者： WANG Gen-shu YANG Yang JIANG Nan FU Bin-sheng LI Hua LI Shi-hui JIN Hai YANG Jian-xu ZHANG Jian CHEN Gui-hua liver transplantation Center Department of Hepatic surgery

Background The use of transanastomotic stents for Roux-en-Y hepatojejunostomy （RYHJ） in liver transplantation （LT） remains controversial. The aim of this retrospective study was to assess the role of transanastomotic stent for RYHJ in LT. Methods RYHJ for biliary reconstruction in LT was performed in 52 patients. Twenty-five patients had bile duct reconstruction by RYHJ with transanastomotic stents （S group）, while 27 patients underwent the same procedure without transanastomotic stents （non-S group）. The two groups were compared in terms of post-LT biliary complications and survival. Results The incidences of bile leakage, anastomotic stricture, non-anastomotic stricture, biliary sludge/lithiasis and biliary infection were 12% （3/25）, 9.5% （2/21）, 23.5% （4/17）, 11.8% （2/17）, and 24% （6/25）, respectively in the S group, and 0, 0, 20.0% （5/25）, 10.0% （2/20）, and 16.7% （4/24）, respectively in the non-S group. One and three year survival rates were 48.0% （12/25） and 34.0% （8/23）, respectively, in the S group and 57.7% （15/26） and 38.9% （7/18）, respectively, in the non-S group. There was no significant difference between the two groups in terms of the incidence of various biliary complications and survival （P 〉0.05）. Conclusion The routine use of transanastomotic stents is not necessary for RYHJ for biliary reconstruction in LT.

关键词： hepatojejunostomy liver transplantation, stent

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