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Integrative analysis of the transcriptome and metabolome reveals the importance of hepatokine FGF21 in liver aging

Genes & Diseases 2024年第5期11卷 407-427页

作者： Wenchao Wang Junjie Qian Mingge Shang Yiting Qiao Jiacheng Huang Xinxin Gao Zhou Ye Xinyu Tong Kangdi Xu Xiang Li Zhengtao Liu Lin Zhou Shusen Zheng Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryFirst Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310003China NHC Key Laboratory of Combined Multi-organ transplantation HangzhouZhejiang 310003China Key Laboratory of the Diagnosis and Treatment of Organ transplantation Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic CancerChinese Academy of Medical Sciences(2019RU019)HangzhouZhejiang 310003China Key Laboratory of Organ transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesHangzhouZhejiang 310003China Shulan International Medical College Zhejiang Shuren UniversityHangzhouZhejiang 310015China Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College HangzhouZhejiang 310000China

Aging is a contributor to liver ***,the concept of liver aging has become prominent and has attracted considerable interest,but its underlying mechanism remains poorly *** our study,the internal mechanism of liver aging was explored via multi-omics analysis and molecular experiments to support future targeted *** aged rat liver model was established with D-galactose,and two other senescent hepatocyte models were established by treating HepG2 cells with D-galactose and *** then performed transcriptomic and metabolomic assays of the aged liver model and transcriptome analyses of the senescent hepatocyte *** livers,genes related to peroxisomes,fatty acid elongation,and fatty acid degradation exhibited down-regulated expression with aging,and the hepatokine Fgf21 expression was positively correlated with the down-regulation of these *** senescent hepatocytes,similar to the results found in aged livers,FGF21 expression was also ***,the expressions of cell cycle-related genes were significantly down-regulated,and the down-regulated gene E2F8 was the key cell cycle-regulating transcription *** then validated that FGF21 overexpression can protect against liver aging and that FGF21 can attenuate the declines in the antioxidant and regenerative capacities in the aging *** successfully validated the results from cellular and animal experiments using human liver and blood *** study indicated that FGF21 is an important target for inhibiting liver aging and suggested that pharmacological prevention of the reduction in FGF21 expression due to aging may be used to treat liver aging-related diseases.

关键词： Antioxidant capability FGF21 liver aging liver regeneration Multiomics analysis

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Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 25-34页

作者： Hai-Li Bao Chuan-Zhi Chen Chang-Zhen Ren Ke-Yan Sun Hao Liu Shao-Hua Song Zhi-Ren Fu department of Organ transplantation Shanghai Changzheng HospitalNavy Military Medical UniversityShanghai 200003China department of Surgical Oncology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Cardiology Shanghai Changzheng HospitalNaval Military Medical UniversityShanghai 200003China department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various ***,little is known about its effect on hepatic ischemia-reperfusion(I/R)*** study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying ***:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R *** alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver *** severity related to the inflammatory response and reactive oxygen species(ROS)production was also ***,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in ***:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and *** oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin *** addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in *** blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling ***:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.

关键词： Hepatic ischemia-reperfusion injury Polydatin Macrophage Polarization Inflammation

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Pancreatic neuroendocrine tumors:Are tumors smaller than 2 cm truly indolent?

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1756-1762页

作者： Sergio Hoyos Pablo Posada-Moreno Natalia Guzman-Arango Romario Chanci-Drago Jaime Chavez Alvaro Andrés-Duarte Santiago Salazar-Ochoa Hepatobilary and liver Transplant Unit Hospital Pablo Tobon Uribe and Gastrohepathology Group Universidad de AntioquiaMedellin 050034AntioquiaColombia department of General Surgery Universidad Pontificia BolivarianaMedellín 050034AntioquiaColombia

BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic *** can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related *** diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for ***,it is unclear whether managing these small tumors expectantly is truly *** To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm orsmaller than 2 cm in diameter and those larger than 2 cm in *** recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 *** survival was additionally comparable between the two tumor *** Tumor size does not dictate prognosis;lymph node and lymphovascular involvement a

关键词： Neuroendocrine tumor Pancreatic neoplasm Pancreas Pancreatic neuroendocrine neoplasm Pancreatic neuroendocrine tumors

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Comparison of different preoperative objective nutritional indices for evaluating 30-d mortality and complications after liver transplantation

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 143-154页

作者： Chuan Li Hong-Xia Chen Yan-Hua Lai department of transplantation People’s Hospital of Guangxi Zhuang Autonomous RegionNanning 530021Guangxi Zhuang Autonomous RegionChina department of Clinical Pharmacy People’s Hospital of Guangxi Zhuang Autonomous RegionNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND The nutritional status is closely related to the prognosis of liver transplant re-cipients,but few studies have reported the role of preoperative objective nutri-tional indices in predicting liver transplant *** To compare the predictive value of various preoperative objective nutritional indicators for determining 30-d mortality and complications following liver transplantation(LT).METHODS A retrospective analysis was conducted on 162 recipients who underwent LT at our institution from December 2019 to June *** This study identified several independent risk factors associated with 30-d mor-tality,including blood loss,the prognostic nutritional index(PNI),the nutritional risk index(NRI),and the control nutritional *** 30-d mortality rate was 8.6%.Blood loss,the NRI,and the PNI were found to be independent risk factors for the occurrence of severe postoperative *** NRI achieved the highest prediction values for 30-d mortality[area under the curve(AUC)=0.861,Pliver Disease scores and prothrombin time(P<0.05).Furthermore,the group with a low NRI exhibited significantly greater incidences of intraabdominal bleeding,primary graft nonfunction,and *** The NRI has good predictive value for 30-d mortality and severe complications following *** NRI could be an effective tool for transplant surgeons to evaluate perioperative nutritional risk and develop relevant nutritional therapy.

关键词： liver transplantation Nutritional indicator Complications Prognosis Nutrition assessment

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Recent advances in the diagnosis of drug-induced liver injury

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World Journal of Hepatology 2024年第2期16卷 186-192页

作者： Taqwa Ahmed Jawad Ahmad department of Medicine Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States department of Recanati-Miller transplantation Institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States

Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital *** DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other *** addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver *** scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these *** review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.

关键词： Drug induced liver injury liver biopsy Diagnosis RUCAM RECAM

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The Dallas Donation after Circulatory Death transplantation Summit:expanding donation after circulatory death procedures through process improvement,broader utilization,and innovation

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Hepatobiliary Surgery and Nutrition 2024年第5期13卷 824-836,I0009页

作者： Michele Finotti Anji Wall Anthony D’Alessandro Gary Schwartz Chris Sonnenday David Goldberg Ashish Shah Peter Friend Jeff P.Orlowski Greg McKenna Steve Newton Brad Adams William C.Chapman Amit Mathur Marwan Abouljoud Tim Pruett Amelia Hessheimer James F.Trotter Sumeet K.Asrani Giuliano Testa Simmons Transplant Institute Baylor University Medical CenterDallasTXUSA Hepatobiliary and General Surgery Unit Regional Hospital TrevisoDISCOGUniversity of PaduaPaduaItaly Division of transplantation Department of SurgeryUniversity of Wisconsin School of Medicine and Public HealthMadisonWIUSA department of Thoracic Surgery and Lung transplantation Baylor University Medical CenterCenter for Advanced Heart and Lung DiseaseDallasTXUSA department of Surgery University of MichiganAnn ArborMIUSA Division of Digestive Health and liver Diseases Department of MedicineUniversity of Miami Miller School of MedicineMiamiFLUSA department of Cardio-Thoracic Surgery Vanderbilt University Medical CenterNashvilleTNUSA Nuffield department of Surgical Sciences University of OxfordOxfordUK LifeShare Transplant Donor Services of Oklahoma Oklahoma CityOKUSA Administration Baylor University Medical CenterDallasTXUSA Southwest Transplant Alliance DallasTXUSA department of Surgery/transplantation Washington UniversitySt.LouisMOUSA Division of Transplant Surgery Department of SurgeryMayo Clinic ArizonaAlix School of MedicinePhoenixAZUSA Divisions of Transplant and Hepatobiliary Surgery Henry Ford HospitalDetroitMIUSA department of Surgery University of MinnesotaMinneapolisMNUSA General and Digestive Surgery Hospital Universitario La PazIdiPAZMadridSpain

Despite a significant increase in utilization over the past decade,the number of donation after circulatory death(DCD)organs that are procured and transplanted in the United States(US)remains well below its *** is still room for expansion,as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in *** convened a multidisciplinary transplantation summit to examine various aspects of DCD,with faculty members from around the world with clinical and academic interest in DCD donation and transplantation,including abdominal and cardiothoracic surgeons,organ procurement organization directors,hepatologists,and *** conference focused on identifying barriers to DCD organ utilization and strategies to overcome these *** divide the barriers to DCD utilization into three mains categories:(Ⅰ)policy and process variation;(II)logistical and transportation challenges;and(Ⅲ)higher risk perceptions related to DCD *** each barrier,we proposed a variety of solutions,providing an overview of the status of DCD donation in the US and suggestions on how to increase the use of *** is a specific focus on ex situ machine perfusion,normothermic regional perfusion,and other opportunities to expand DCD utilization without negatively impacting recipient outcomes.

关键词： Donation after circulatory death donation(DCD donation) marginal graft donor pool machine perfusion(MP)

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Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model

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Chinese Medical Journal 2024年第12期137卷 1453-1464页

作者： Xia Qiu Hedong Zhang Zhouqi Tang Yuxi Fan Wenjia Yuan Chen Feng Chao Chen Pengcheng Cui Yan Cui Zhongquan Qi Tengfang Li Yuexing Zhu Liming Xie Fenghua Peng Tuo Deng Xin Jiang Longkai Peng Helong Dai Medical College Guangxi UniversityNanningGuangxi 530004China department of Kidney transplantation Center of Organ TransplantationThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China National Clinical Research Center for Metabolic Diseases and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China department of Organ transplantation The Fifth Clinical Medical College of Henan University of Chinese Medicine(Zhengzhou People’s Hospital)ZhengzhouHenan 450000China

Background:Homoharringtonine(HHT)is an effective anti-inflammatory,anti-viral,and anti-tumor protein synthesis inhibitor that has been applied ***,we explored the therapeutic effects of HHT in a mouse heart transplant ***:Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver,kidney,and hematology.A mouse heart transplantation model was constructed,and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan-Meier analysis,immunostaining,and bulk RNA sequencing *** HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells(Tregs)***:HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex *** of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days(P<0.001)without non-immune *** allografts had long-term survival after continuous HHT treatment for 28 *** significantly reduced lymphocyte infiltration in the graft,and interferon-γ-secreting CD4^(+)and CD8^(+)T cells in the spleen(P<0.01).HHT significantly increased the number of peripheral Tregs(about 20%,P<0.001)and serum interleukin(IL)-10 *** downregulated the expression of T cell receptor(TCR)signaling pathway-related genes(CD4,H2-Eb1,TRAT1,and CD74)and upregulated the expression of IL-10 and transforming growth factor(TGF)-βpathway-related genes and Treg signature genes(CTLA4,Foxp3,CD74,and ICOS).HHT increased CD4^(+)Foxp3^(+)cells and Foxp3 expression ex vivo,and it enhanced the inhibitory function of inducible ***:HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels,thereby promoting mouse heart allograft *** findings may have therapeutic implications for organ tr

关键词： Heart transplantation Homoharringtonine Immunosuppressive agents T-lymphocytes,Regulatory Graft acceptance

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Cold ischemia time in liver transplantation:An overview

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World Journal of Hepatology 2024年第6期16卷 883-890页

作者： Manuela Cesaretti Alessandro Izzo Roberta Anna Pellegrino Alessandro Galli Orestes Mavrothalassitis department of HPB and liver transplantation Brotzu HospitalCagliari 09122Italy department of Nanophysic Istituto Italiano di TecnologiaGenova 16163Italy department of Critical Care Medicine and Anesthesia ASST Papa Giovanni XXIIIBergamo 24100Italy department of Anesthesia and Perioperative Care University of California San FranciscoSan FranciscoCA 94143United States

The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time(CIT).This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time,transit time,and recipient surgery time,and is one of the most important donor-related risk factors which may influence the graft and recipient’s ***,the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation *** review details the CIT definition and analyzes its different *** also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.

关键词： Cold ischemia time liver transplantation Organ donation Donation after cardiac death Warm ischemia time Machine perfusion

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Prognostic value of ultrasound in early arterial complications post liver transplant

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 13-20页

作者： Ning-Bo Zhao Yi Chen Rui Xia Jian-Bo Tang Dong Zhao department of Ultrasound National Clinical Research Centre for Infectious DiseaseShenzhen Third People's HospitalThe Second Affiliated Hospital of Southern University of Science and TechnologyNational Clinical Research Center for Infectious DiseaseShenzhen 518112Guangdong ProvinceChina department of Thyroid and Hernia Surgery The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510000Guangdong ProvinceChina department of Biomedical Engineering Southern University of Science and TechnologyShenzhen 51800Guangdong ProvinceChina 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 518112Guangdong ProvinceChina

liver transplantation is the primary therapeutic intervention for end-stage liver ***,vascular complications,particularly those involving the hepatic artery,pose significant risks to *** clinical manifestations associated with early arterial complications following liver transplantation are often *** timely intervention,these complications can result in graft fai-lure or patient ***,early diagnosis and the formulation of an op-timal treatment plan are *** examination remains the pre-dominant imaging modality for detecting complications post liver *** article comprehensively reviews common causes and clinical present-ations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these ***,ultrasound offers the advantages of convenience,safety,effect-iveness,and *** enables real-time,dynamic,and precise evalua-tion,making it the preferred diagnostic method for post-liver transplantation *** liver transplantation stands as the primary therapeutic approach for end-stage liver *** advancements in surgical techniques and the application of novel immunosuppressive agents contribute to ongoing improvements in the success rate and overall survival in patients undergoing liver transplantation *** these advan-cements,vascular complications,particularly those involving the hepatic artery,pose significant risks to *** the early stages following liver transplantation(within the first 30 d),proper hepatic artery function is crucial for hepatic arterial blood *** later stages,collateral circulation,including arteries such as the phrenic artery,right gastric artery,and gastroduodenal artery,becomes important for maintaining hepatic blood *** is now understood that the establishment of effective collat

关键词： liver transplantation Vascular complication Arterial complication Ultrasound

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Progress in the diagnosis and treatment of graft fibrosis after liver transplantation

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Portal Hypertension & Cirrhosis 2024年第1期3卷 22-30页

作者： Youwei Zhao Lijun Wang Man Xie Wei Rao department of Gastroenterology Medical College of Qingdao UniversityQingdaoShandongChina department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdaoShandongChina Division of Hepatology Liver Disease CenterThe Affiliated Hospital of Qingdao UniversityQingdaoShandongChina department of Organ transplantation Center The Affiliated Hospital of Qingdao UniversityQingdaoShandongChina

liver transplantation(LT)is considered one of the best treatments for patients with end-stage liver ***,some patients with no significant clinical manifestations or abnormal laboratory tests still experience graft fibrosis during postoperative follow-up,which is often recognized by graft *** fibrosis can lead to graft dysfunction,thereby reducing the survival time of the recipient and even requiring ***,noninvasive methods are widely applied in the assessment of hepatic and allograft *** both noninvasive diagnostic models based on laboratory examination indicators and elastography technology that can quantify liver stiffness have some value in the evaluation of fibrosis,the diagnostic accuracy and characteristics of these various methods vary and cannot replace liver biopsy *** recent years,some liver-protective drugs and proprietary Chinese traditional medicines have been proven to delay or reverse chronic liver ***,their efficacy and safety for LT recipients need to be further *** article reviews the diagnosis and treatment of graft fibrosis after LT to provide a reference for improving the overall survival rate of LT recipients.

关键词： diagnosis fibrosis liver transplantation therapeutics

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