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Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao Jie Jiang Wei Wu Jiaqi Shi Yanfang Wang Yuejun Yao Tao Sheng Feng Liu Wei Liu Peng Zhao Feifei Lv Jie Sun Hongjun Li Zhen Gu National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu Laboratory Zhejiang University Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology Zhejiang University School of Medicine Department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University Department of Laboratory Medicine The First Affiliated Hospital Zhejiang University School of Medicine Department of hepatobiliary and Pancreatic surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua institute of Zhejiang University MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University Department of General surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy

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Comprehensive prognostic and immune analysis of sterol Oacyltransferase 1 in patients with hepatocellular carcinoma

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World Journal of Hepatology 2024年第3期16卷 439-451页

作者： Chang-Jiao Gan Yue Zheng Bin Yang Li-Min Cao Development Research Department National Medical Products Administration Institute of Executive DevelopmentBeijing 100071China School of Medicine Nankai University Affiliated Third Center HospitalTianjin 300070China Tianjin institute of hepatobiliary Disease The Third Central Hospital of TianjinTianjin 300170China Department of Science and Technology Tianjin Third Central HospitalTianjin 300170China

BACKGROUND Sterol O-acyltransferase 1(SOAT1)is an important target in the diagnosis and treatment of liver ***,the prognostic value of SOAT1 in patients with hepatocellular carcinoma(HCC)is still not *** To investigate the correlation of SOAT1 expression with HCC,using RNA-seq and gene expression data of The Cancer Genome Atlas(TCGA)-liver hepatocellular carcinoma(LIHC)and *** The correlation between SOAT1 expression and HCC was *** hazard regression models were conducted to investigate the prognostic value of SOAT1 in *** survival and disease-specific survival were explored based on TCGA-LIHC *** processes and functional pathways mediated by SOAT1 were characterized by gene ontology(GO)analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of differentially expressed *** addition,the protein-protein interaction network and co-expression analyses of SOAT1 in HCC were performed to better understand the regulatory mechanisms of SOAT1 in this *** SOAT1 and SOAT2 were highly expressed in unpaired samples,while only SOAT1 was highly expressed in paired *** area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748,while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was *** with higher SOAT1 expression had lower survival *** from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway,the IL-18 signaling pathway,the calcium signaling pathway,secreted factors,the Wnt signaling pathway,the Jak/STAT signaling pathway,the MAPK family signaling pathway,and cell–cell communication were involved in such ***1 expression was positively associated with the abundance of macrophages,Th2 cells,T helper cells,CD56bright natural killer cells,and Th1 cells,and negatively

关键词： Sterol O-acyltransferase 1 Hepatocellular carcinoma Prognostic Immune

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Hepatocellular carcinoma:An analysis of the expression status of stress granules and their prognostic value

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2571-2591页

作者： Qing-Shuai Ren Qiu Sun Shu-Qin Cheng Li-Ming Du Ping-Xuan Guo Department of Cardiovascular surgery North China University of Science and Technology Affiliated HospitalTangshan 063000Hebei ProvinceChina Department of hepatobiliary Kailuan General HospitalTangshan 063000Hebei ProvinceChina Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjin 300000China Department of Traditional Chinese Medicine Kailuan General HospitalTangshan 063000Hebei ProvinceChina Department of Anesthesiology Kailuan General HospitalNorth China University of Science and TechnologyTangshan 063000Hebei ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is *** To analyze the impacts of stress granule(SG)genes on overall survival(OS),survival time,and prognosis in *** The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC),GSE25097,and GSE36376 datasets were utilized to obtain genetic and clinical *** hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach,and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression,*** prognostic model’s receiver operating characteristic(ROC)curve was produced and plotted utilizing the time ROC software *** models were constructed to predict the outcomes at 1,3,and 5-year OS prognostications with good prediction *** We identified seven SG genes(DDX1,DKC1,BICC1,HNRNPUL1,CNOT6,DYRK3,CCDC124)having a prognostic significance and developed a risk score *** findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group(P<0.001).The nomogram model’s findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC *** Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle,RNA editing,and other biological *** Based on the impact of SG genes on HCC prognosis,in the future,it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.

关键词： Stress granule genes Hepatocellular carcinoma Gastrointestinal neoplasms Bioinformatics prognosis Prognostic value

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人类肝移植图谱揭示了一种与早期移植物功能不全发生相关的致病免疫生态位（英文）

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Engineering 2024年第5期 193-208页

作者：邵鑫王峥汪恺陆晓燕张萍郭蓉芳廖杰杨鹏挥郑树森徐骁范骁辉 Pharmaceutical Informatics institute College of Pharmaceutical Sciences Zhejiang University National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River Delta Zhejiang University Zhejiang University School of Medicine NHC Key Laboratory of Combined Multi-organ Transplantation Department of hepatobiliary and Pancreatic surgery Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College Zhejiang Shuren University Engineering Research Center of Innovative Anticancer Drugs Ministry of Education

Liver transplantation（LT） is the standard therapy for individuals afflicted with end-stage liver *** notable advancements in LT technology, the incidence of early allograft dysfunction（EAD）remains a critical concern, exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients. Unfortunately, the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD. Herein, we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients, with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages. Comparison of the 75 231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells, granzyme B+（GZMB+） granzyme K+（GZMK+） natural killer cells, and S100 calcium binding protein A12+（S100A12+） neutrophils. Moreover, we verified this immune niche and its association with EAD occurrence in two independent cohorts. Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level, thus, offering valuable insights into EAD onset.

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Co-alteration of Myc and RTK-RAS pathways defines a liver-metastatic propensity and immune-cold subgroup of pancreatic adenocarcinoma

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Genes & Diseases 2024年第3期11卷 47-50页

作者： Yuyuan Zhang Ziyang Zu Hui Xu Siyuan Weng Yuqing Ren Quan Cheng Peng Luo Jian Zhang Zaoqu Liu Xinwei Han Department of Interventional Radiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Interventional institute of Zhengzhou University ZhengzhouHenan450052China Interventional Treatment and Clinical Research Center of Henan Province ZhengzhouHenan 450052China Department of hepatobiliary and Pancreatic surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Oncology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong 510280China

Co-altered pathways refer to the phenomenon where multiple biological pathways exhibit aberrant changes simultaneously within the same tumor *** phenomenon can facilitate a better understanding of the mechanism and evolution of tumors and serve as a biological marker for diagnosing,classifying,and treating tumors.1 However,the nature of alteration occurrence and the impact on pancreatic adenocarcinoma(PAAD)remain *** SELECT algorithm was originally designed to systematically assess the evolutionary dependencies and their impact between altered genes in cancer for anticipating drug resistance and proposing alternative ***,to better characterize the etiology of PAAD and develop an improved risk assessment strategy,2 by utilizing SELECT,we identified a co-altered pathway subgroup of PAAD that demonstrated an elevated risk for unfavorable prognosis,a propensity for liver metastasis,and an immunologically cold microenvironment.

关键词： adenocarcinoma elevated alteration

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Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus:State of art and future perspectives

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hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 221-227页

作者： Paschalis Gavriilidis Timothy M Pawlik Daniel Azoulay Department of surgery Colchester General HospitalTurner RoadColchester CO45JLUK Department of surgery The Ohio State Wexner Medical CenterJames Comprehensive Cancer CenterColumbusOHUSA Department of Hepato-Biliary and Liver Transplantation surgery Paul Brousse University HospitalParis-Saclay UniversityVillejuif 94800France

Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage *** vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if *** sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic ***:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic *** elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical *** review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of ***:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.

关键词： Hepatectomy Liver surgery Liver neoplasms Portal vein tumor thrombus

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Multi-omics joint analysis revealed the metabolic profile of retroperitoneal liposarcoma

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Frontiers of Medicine 2024年第2期18卷 375-393页

作者： Fu’an Xie Yujia Niu Lanlan Lian Yue Wang Aobo Zhuang Guangting Yan Yantao Ren Xiaobing Chen Mengmeng Xiao Xi Li Zhe Xi Gen Zhang Dongmei Qin Kunrong Yang Zhigang Zheng Quan Zhang Xiaogang Xia Peng Li Lingwei Gu Ting Wu Chenghua Luo Shu-Hai Lin Wengang Li Cancer Research Center Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361102China State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen361102China Xiamen University Research Center of Retroperitoneal Tumor Committee of Oncology Society of Chinese Medical Association Xiamen UniversityXiamen361102China Department of Laboratory Medicine Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361102China Department of Retroperitoneal Tumor surgery Peking University International HospitalBeijing102206China School of Public Health Harvard UniversityBostonMA02115USA Laboratory of Biochemistry and Molecular Biology Research Department of Clinical LaboratoryFujian Medical University Cancer HospitalFuzhou350014China surgery Department Affiliated Fuzhou First Hospital of Fujian Medical UniversityFuzhou350009China National institute for Data Science in Health and Medicine Xiamen UniversityXiamen361102China Department of hepatobiliary surgery Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361102China

Retroperitoneal liposarcoma(RLPS)is the main subtype of retroperitoneal soft sarcoma(RSTS)and has a poor prognosis and few treatment options,except for *** proteomic and metabolic profiles of RLPS have remained *** aim of our study was to reveal the metabolic profile of ***,we performed proteomic analysis(n=10),metabolomic analysis(n=51),and lipidomic analysis(n=50)of retroperitoneal dedifferentiated liposarcoma(RDDLPS)and retroperitoneal well-differentiated liposarcoma(RWDLPS)tissue and paired adjacent adipose tissue obtained during *** analysis mainly revealed that glycolysis,purine metabolism,pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue,whereas the tricarboxylic acid(TCA)cycle,lipid absorption and synthesis,fatty acid degradation and biosynthesis,as well as glycine,serine,and threonine metabolism were *** particular importance,the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway(PPP)inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor *** study not only describes the metabolic profiles of RDDLPS and RWDLPS,but also offers potential therapeutic targets and strategies for RLPS.

关键词： RLPS proteomics metabolomics lipidomics metabolism

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Nomogram based on liver stiffness and spleen area with ultrasound for posthepatectomy liver failure:A multicenter study

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World Journal of Gastroenterology 2024年第27期30卷 3314-3325页

作者： Guang-Wen Cheng Yan Fang Li-Yun Xue Xiao-Hui Qiao Xue-Qi Li Yan Zhang Jia Guo Xiao-Yan Xie Hong Ding Department of Ultrasound Huashan HospitalFudan UniversityShanghai 200040China Department of Ultrasound Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Medical Ultrasonics Institute of Diagnostic and Interventional UltrasoundSun Yat-sen University First Affiliated HospitalGuangzhou 510080Guangdong ProvinceChina institute of Ultrasound in Medicine and Engineering Shanghai Cancer CenterShanghai 200040China Department of Ultrasound Eastern Hepatobiliary Surgical HospitalSecond Military Medical UniversityShanghai 200433China Department of Ultrasound National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghai 200040China

BACKGROUND Liver stiffness(LS)measurement with two-dimensional shear wave elastography(2D-SWE)correlates with the degree of liver fibrosis and thus indirectly reflects liver function *** size of the spleen increases due to tissue proliferation,fibrosis,and portal vein congestion,which can indirectly reflect the situation of liver fibrosis/*** was reported that the size of the spleen was related to posthepatectomy liver failure(PHLF).So far,there has been no study combining 2D-SWE measurements of LS with spleen size to predict *** prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area(SPA)for the prediction of PHLF in hepatocellular carcinoma(HCC)patients and to develop a risk prediction *** To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction *** This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March *** 1 wk before partial hepatectomy,ultrasound examination was performed to measure LS and SPA,and blood was drawn to evaluate the patient’s liver function and other *** absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a *** performance was validated *** diagnostic performance of the nomogram was evaluated with receiver operating charac-teristic curve compared with the conventional models,including the model for end-stage liver disease(MELD)score and the albumin-bilirubin(ALBI)*** A total of 562 HCC patients undergoing hepatectomy(500 in the training cohort and 62 in the validation cohort)were enrolled in this *** independent predictors of PHLF were LS,SPA,range of resection,blood loss,international normalized ratio,and total *** diagnostic performanc

关键词： Shear-wave elastography Spleen Hepatectomy Posthepatectomy liver failure Hepatocellular carcinoma

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受自体材料启发的药物递送系统

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Science China Materials 2024年第8期67卷 2427-2446页

作者：冯慧珩程伊安柳扶摇顾臻李洪军 State Key Laboratory of Advanced Drug Delivery and Release Systems and Liangzhu LaboratoryCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Jinhua institute of Zhejiang University Jinhua 321299China Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of General surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310016China MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China Department of hepatobiliary and Pancreatic surgery the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China

随着个性化医疗理念的深入研究,基于自体来源材料的药物递送系统受到越来越多的关注并快速发展.自体来源材料具有保留其体内天然生理学特性和优良的生物相容性等特点,这为其在材料功能化和药物递送方面开辟了广泛的研究空间,也为疾病治... 详细信息

随着个性化医疗理念的深入研究,基于自体来源材料的药物递送系统受到越来越多的关注并快速发展.自体来源材料具有保留其体内天然生理学特性和优良的生物相容性等特点,这为其在材料功能化和药物递送方面开辟了广泛的研究空间,也为疾病治疗提供了坚实的基础.借助这些优势,受自体来源材料启发的药物递送系统有望在疾病治疗方面实现减毒增效.本文对基于人源蛋白、细胞材料及细胞外基质支架的药物递送系统的最新研究进行了全面回顾,重点关注了这类药物递送系统的载药策略和应用场景,深入分析了它们在疾病治疗中的优势和限制.此外,本文还探讨了受自体来源材料启发的药物递送系统在临床转化过程中面临的潜在机遇和挑战.

关键词：生理学特性药物递送疾病治疗减毒增效个性化医疗生物相容性功能化

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Unveiling hidden outcomes in malignant gastric outlet obstruction research–insights from a"Pancreas 2000"review

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World Journal of Gastrointestinal Endoscopy 2024年第8期16卷 451-461页

作者： Filipe Vilas-Boas Giacomo Emanuele Maria Rizzo Charles De Ponthaud Stuart Robinson Sebastien Gaujoux Gabriele Capurso Giuseppe Vanella Bahadır Bozkırlı Department of Gastroenterology São João University HospitalPorto 4200Portugal Endoscopy Service Department of Diagnostic and Therapeutic ServicesScientific Institute for ResearchHospitalization and Healthcare-The Mediterranean Institute for Transplantation and Highly Specialized TherapiesPalermo 90127SiciliaItaly Department of Digestive Hepato-Biliary and Pancreatic Surgery and Liver TransplantationAP-HP Pitié-SalpêtriereSorbonne UniversitéParis 75013Île-de-FranceFrance Department of hepatobiliary Pancreatic and Transplant SurgeryFreeman HospitalNewcastle NE77DNNewcastle upon TyneUnited Kingdom Division of Pancreato-Biliary Endoscopy and Endosonography Pancreas Translational and Clinical Research CenterIRCCS San Raffaele Scientific InstituteVita-Salute San Raffaele UniversityMilano 20132Italy Department of General surgery HPB-UnitAcıbadem Maslak HospitalIstanbul 34398Türkiye

Malignant gastric outlet obstruction(mGOO)is a major condition affecting patients with periampullary tumors,including pancreatic *** current treatment options include surgical gastroenterostomy,endoscopic stenting and more recently EUS-guided *** studies comparing the outcomes of the three procedures focus on technical success,clinical success and ***“occult”outcomes relevant to the patient’s viewpoints and perspective may ultimately impact on cancer-related and overall survival,such as body mass composition,nutritional biomarkers,chemotherapy tolerance and patient-reported quality of *** aim of this review is to provide an overview of potential key outcomes that should be explored in future comparative research around mGOO treatment options.

关键词： Malignant gastric outlet obstruction Endoscopic ultrasound-guided gastroenterostomy Patient-reported outcomes Body composition Nutrition Quality of life

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