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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 146-153页

作者： Philip C.Muller Matthias Pfister Dilmurodjon Eshmuminov Kuno Lehmann department of Surgery and transplantation University Hospital ZurichRämistrasse 100Zurich CH-8091Switzerland

Background:liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in *** comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is *** goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of *** sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March ***:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed *** liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free *** highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are *** factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic *** on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to *** benefits of LT were lost in patients beyond the Milan ***:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to *** evidence suggests even stricter selection criteria with regard to tumor biology.

关键词： liver transplantation Neuroendocrine liver metastases liver resection Selection criteria Tumor biology

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liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 139-145页

作者： Wellington Andraus Francisco Tustumi Alexandre Chagas Santana Rafael Soares Nunes Pinheiro Daniel Reis Waisberg Liliana Ducatti Lopes Rubens Macedo Arantes Vinicius Rocha Santos Rodrigo Bronze de Martino Luiz Augusto Carneiro D’Albuquerque department of Gastroenterology Transplantation UnitUniversidade de São PauloSão PauloBrazil

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal *** is no consensus regard-ing the best treatment for patients with unresectable *** present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical *** sources:The search was conducted in PubMed,Embase,Cochrane,and *** related references were searched *** criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver *** reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the ***:Most of the current literature is based on observational retrospective studies with low grades of *** resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable *** candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic *** a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for *** of these criteria should be individually *** transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary ***:phCCC is a complex condition with high *** therapies,including hepatec-tomy and liv

关键词： liver transplantation Cholangiocarcinoma liver neoplasms

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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

Chinese expert consensus on the application of immune checkpoint inhibitors in liver transplantation for hepatocellular carcinoma

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中华医学杂志(英文版) 2024年第18期137卷 2024 Aug 15页

作者： Wang Zhengxin Yang Jiayin Li Guangming liver transplantation Center General Surgery Department Huashan Hospital Affiliated to Fudan University Organ Transplantation Institute of Fudan University Shanghai China Organ transplantation Center West China Hospital Sichuan University Chengdu Sichuan China liver transplantation Center General Surgery Department of Beijing Youan Hospital Capital Medical University Beijing China

RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway

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Journal of Clinical and Translational Hepatology 2024年第4期12卷 357-370页

作者： Yongsheng Tang Zenan Yuan Xu Lu Yingqiu Song Shuguang Zhu Chunhui Qiu Qi zhang Binsheng Fu Changchang Jia Hua Li department of Hepatic Surgery Liver Transplantation CenterThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina department of Gastrointestinal Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina department of Cell-Gene Therapy Translational Medicine Research Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Background and Aims:Hepatic ischemia-reperfusion injury(HIRI)is a prevalent complication of liver transplantation,partial hepatectomy,and severe infection,necessitating the development of more effective clinical *** activity–modifying protein 1(RAMP1),a member of the G protein–coupled receptor adapter family,has been implicated in numerous physiological and pathological *** study aimed to investigate the pathogenesis of RAMP1 in ***:We established a 70%liver ischemia-reperfusion model in RAMP1 knockout(KO)and wild-type *** and blood samples were collected after 0,6,and 24 h of hypoxia/*** histological and serological analyses were performed to evaluate liver *** also conducted in-vitro and in-vivo experiments to explore the molecular mechanism underlying RAMP1 ***:liver injury was exacerbated in RAMP1-KO mice compared with the sham group,as evidenced by increased cell death and elevated serum transaminase and inflammation *** was promoted in RAMP1-KO mice via the induction of hepatocyte apoptosis and inhibition of *** absence of RAMP1 led to increased activation of the extracellular signal–regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)pathway and yes-associated protein(YAP)phosphorylation,ultimately promoting ***772984,an ERK/MAPK phosphorylation inhibitor,and PY-60,a YAP phosphorylation inhibitor,reduced apoptosis in in-vitro and in-vivo ***:Our findings suggest that RAMP1 protects against HIRI by inhibiting ERK and YAP phosphorylation signal transduction,highlighting its potential as a therapeutic target for HIRI and providing a new avenue for intervention.

关键词： Hepatic ischemia-reperfusion injury(HIRI) Receptor activity-modifying protein 1(RAMP1) YES-Associated Protein(YAP) Extracellular signalregulated kinase(ERK)

Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

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World Journal of Gastroenterology 2024年第7期30卷 759-769页

作者： Maja Cigrovski Berkovic Alessandro Coppola Vibor Sesa Anna Mrzljak Quirino Lai department for Sport and Exercise Medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia department of Surgery Sapienza University of RomeRome 00185Italy department of Gastroenterology and Hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia department of Medicine School of MedicineZagreb 10000Croatia General Surgery and Organ transplantation Unit Department of SurgerySapienza University of RomeRome 00018Italy

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor ***,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is *** this perspective,metformin is emerging as a molecule of *** studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR *** systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with *** To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of *** A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free *** A total of 13 studies(5674 patients)were included in this *** of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of *** T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS

关键词： Pancreatic neuroendocrine tumors Type 2 diabetes mellitus Prognosis Treatment Metformin

liver transplantation for primary sclerosing cholangitis-morbidities including disease recurrence

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 143-146页

作者： Nobuhisa Akamatsu Artificial Organ and transplantation Surgery Division Department of SurgeryUniversity of TokyoTokyoJapan

Primary sclerosing cholangitis(PSC)is one of the major diseases indicated for liver transplantation(LTx).There are some important points to be considered when discussing LTx for PSC,which makes it a unique etiology among liver transplant *** often coexists with inflammatory bowel disease(IBD),mainly ulcerative colitis(UC),and patients with PSC are prone to develop colorectal cancer and cholangiocarcinoma both before and after LTx.

关键词： liver transplantation(LTx) primary sclerosing cholangitis(PSC) recurrent disease

Integrated bulk and single-cell transcriptome data identify clinically relevant cell populations in clear cell renal cell carcinoma

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Genes & Diseases 2024年第1期11卷 42-45页

作者： Pingbao Zhang Pu Zhang Jun Gao Xiaosong Li Chengcheng Wei Weihui Liu QingLiu He Yuan Zhang department of Urology Zhongshan HospitalFudan UniversityShanghai 200032China department of Urology Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China department of liver Surgery and transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghai 200032China Clinical Molecular Medicine Testing Center The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Urology The Second Affiliated Hospital of Fujian Medical UniversityQuanzhouFujian 362000China department of Nephrology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China

Renal cell carcinoma,which consists of three main histological subtypes,namely,clear cell renal cell carcinoma(ccRCC),papillary RCC(pRCC),and chromophobe RCC(chRCC),accounts for most kidney cancer *** accounts for approximately 85%of all RcC cases,1 and it is a malignant tumor with multiple molecular features and a poor *** have shown that ccRCC is one of the most immune and vaso-invasive cancer types.2 Considering that ccRCC is not sensitive to either radiotherapy or chemotherapy,targeted therapies.

关键词： chemotherapy cancer cases

Inhaled nitric oxide as a salvage therapy for refractory hypoxemia in the post-transplantation period of hepatopulmonary syndrome:An explorative report of three cases

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liver Research 2024年第3期8卷 188-192页

作者： Haijin Lyu Xiaomeng Yi Yunshan Zou Pinglan Lu Lijuan Li Jianrong Liu Senbiao Chen Xuxia Wei Yang Yang Huimin Yi Surgical Intensive Care Unit The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Provincial Key Laboratory of liver Disease Research GuangzhouGuangdongChina department of Hepatic Surgery and liver transplantation Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

liver transplantation(LT)is the only effective treatment for hepatopulmonary syndrome(HPS).Moreover,perioperative refractory hypoxemia(pRH)is a prevalent life-threatening condition and has extremely limited treatment ***,we report three patients with HPS who experienced pRH after LT and were consecutively treated with different salvage therapies,ephedrine inhalation,intravenous use of methylene blue with nitric oxide(NO)inhalation,and NO inhalation *** results showed that unresolved severe hypoxia may induce fatal morbidity such as early biliary leakage and acute kidney *** initiation of NO inhalation,rather than ephedrine,can significantly improve oxygenation in patients with pRH and may help prevent hypoxia-related ***,based on the response to these exploratory salvage treatments,we further demonstrate the unique ventilation-perfusion mismatch pathophysiology in specific lung regions during pRH in *** propose that early inhalation of NO is an important treatment option to rescue severe hypoxia in patients with HPS during the perioperative period of LT.

关键词： Hepatopulmonary syndrome liver transplantation Hypoxia Nitric oxide(NO) Vasodilators Ventilation-perfusion mismatch

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

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