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Evaluating the efficacy of immunotherapy in gastric cancer:Insights from immune checkpoint inhibitors

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World Journal of Gastroenterology 2024年第32期30卷 3726-3729页

作者： Yu-Nuo Yang Li-Sheng Wang Yan-Qi Dang Guang Ji institute of digestive Diseases Longhua HospitalChina-Canada Center of Research for Digestive DiseasesShanghai University of Traditional Chinese MedicineShanghai 200032China department of Biochemistry University of OttawaOttawa K1H 8M5ONCanada

The emergence of immunotherapy,particularly immune checkpoint inhibitors(ICIs),represents a groundbreaking approach to treating gastric cancer(GC).However,the prognosis of GC patients receiving ICI treatment is influenced by various *** manuscript identified sarcopenia and myosteatosis as independent prognostic factors impacting the outcomes of GC patients treated with ***,this study introduced a visual predictive model to estimate the prognosis of GC *** confirmed by further studies,this observation could provide valuable insights to propel the advancement of personalized clinical medicine and the integration of precision medicine practices.

关键词： Gastric cancer Immune checkpoint inhibitors Sarcopenia Myosteatosis Prediction model

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

Human pangenome:far-reaching implications in precision medicine

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Frontiers of Medicine 2024年第2期18卷 403-409页

作者： Yingyan Yu Hongzhuan Chen department of General Surgery of Ruijin Hospital Shanghai Institute of Digestive Surgeryand Shanghai Key Laboratory for Gastric NeoplasmsShanghai Jiao Tong University School of MedicineShanghai200025China Shuguang Lab for Future Health Shanghai Frontier Science Center of TCM Chemical BiologyShanghai University of Traditional Chinese MedicineShanghai201203China

*** May 11,2023,the internationally renowned journal Nature announced that a first draft of the human pangenome reference has been constructed[1].This research was carried out by the Human Pangenome Reference Consortium(HPRC).One month later,on June 14,2023,a pangenome reference of 36 Chinese populations was published on journal Nature[2],which was performed by Chinese Pangenome Consortium(CPC).As the scientists pointed out that since the Human Genome Project(HGP)published the human reference genome,it provided a reference blueprint for genomic ***,the limitations of the human reference genome have gradually emerged,and it is difficult to reflect the genome diversity of the"human"species.

关键词： Human journal limitations

Oxidative stress-initiated one-carbon metabolism drives the generation of interleukin-10-producing B cells to resolve pneumonia

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Cellular & Molecular Immunology 2024年第1期21卷 19-32页

作者： Ying Fu Baichao Yu Qi Wang Zhou Lu Hushan Zhang Dan Zhang Feifei Luo Ronghua Liu Luman Wang Yiwei Chu department of Immunology School of Basic Medical SciencesShanghai Key Laboratory of Medical Epigenetics and MetabolismInstitutes of Biomedical SciencesFudan UniversityShanghaiChina Zhongshan Hospital institute of Clinical Science Zhongshan HospitalShanghaiChina Zhaotong Health Vocational College ZhaotongYunnanChina department of digestive Diseases Huashan HospitalFudan UniversityShanghaiChina shanghai Fifth People’s Hospital Fudan UniversityShanghaiChina

The metabolic reprogramming underlying the generation of regulatory B cells during infectious diseases remains *** a Pseudomonas aeruginosa-induced pneumonia model,we reported that IL-10-producing B cells(IL-10+B cells)play a key role in spontaneously resolving infection-mediated *** cytosolic reactive oxygen species(ROS)during inflammation were shown to drive IL-10+B-cell generation by remodeling one-carbon *** of the enzyme serine hydroxymethyltransferase 1(Shmt1)led to inadequate one-carbon metabolism and decreased IL-10+B-cell ***,increased one-carbon flux elevated the levels of the methyl donor S-adenosylmethionine(SAM),altering histone H3 lysine 4 methylation(H3K4me)at the Il10 gene to promote chromatin accessibility and upregulate Il10 expression in B ***,the one-carbon metabolism-associated compound ethacrynic acid(EA)was screened and found to potentially treat infectious pneumonia by boosting IL-10+B-cell ***,these findings reveal that ROS serve as modulators to resolve inflammation by reprogramming one-carbon metabolism pathways in B cells.

关键词： IL-10-producing B cell Reactive oxygen species One-carbon metabolism H3K4me Pneumonia

Identification of marker genes associated with N6-methyladenosine and autophagy in ulcerative colitis

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World Journal of Clinical Cases 2024年第10期12卷 1750-1765页

作者： Xiao-Yan Liu Dan Qiao Ya-Li Zhang Zi-Xuan Liu You-Lan Chen Ren-Ye Que Hong-Yan Cao Yan-Cheng Dai department of Gastroenterology Shanghai Traditional Chinese Medicine-Integrated HospitalShanghai University of Traditional Chinese MedicineShanghai 200082China institute of digestive Diseases Long Hua Hospital Shanghai University of Traditional Chinese MedicineShanghai 200032China department of Gastroenterology Shu Guang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China

BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be *** To elucidate the autophagy-related genes of m6A with a diagnostic value for *** The correlation between m6A-related genes and autophagy-related genes(ARGs)was ***,gene set enrichment analysis(GSEA)was performed on the characteristic ***,the expression levels of four characteristic genes were verified in dextran sulfate sodium(DSS)-induced colitis in *** GSEA indicated that BAG3,P4HB and TP53INP2 were involved in the inflammatory response and TNF-αsignalling via nuclear factor ***,polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control *** This study identified four m6A-ARGs that predict the occurrence of UC,thus providing a scientific reference for further studies on the pathogenesis of UC.

关键词： Ulcerative colitis m6A Autophagy Characteristic genes Immune infiltration

Lactobacillus plantarum AR113 attenuates liver injury in D-galactose-induced aging mice via the inhibition of oxidative stress and endoplasmic reticulum stress

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Food Science and Human Wellness 2024年第2期13卷 885-897页

作者： Yongjun Xia Yujie Gong Xiangna Lin Yijin Yang Xin Song Guangqiang Wang Zhiqiang Xiong Yangyang Qian Zhuan Liao Hui Zhang Lianzhong Ai School of Health Science and Engineering Shanghai Engineering Research Center of Food MicrobiologyUniversity of Shanghai for Science and TechnologyShanghai 200093China College of Life Sciences Linyi UniversityLinyi 276000China department of Gastroenterol. Digestive Endoscopy CenterChanghai HospitalShanghai 200082China

Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is *** major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging *** result showed that pretreatment with *** AR113 significantly relieving H_(2)O_(2)induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme *** D-galactose induced aging mice,*** AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione(GSH)synthesis and activating the Nrf2/Keap1 signaling pathway in mice,and increasing the expression of regulated phaseⅡdetoxification enzymes and antioxidant *** analysis shown that gavage of *** AR113 could significantly reduce the expression of G protein-coupled receptor 78(GPR78)and C/EBP homologous protein(CHOP)proteins,and promote the restoration of endoplasmic reticulum(ER)homeostasis,thereby activating cell anti-apoptotic *** results were also confirmed in H_(2)O_(2)-treated HepG2 *** indicated that *** AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative *** AR113 have good application potential in anti-aging and alleviating metabolic disorders.

关键词： Lactiplantibacillus plantarun AR113 HepG2 D-galactose Oxidative stress ER stress

Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1690-1705页

作者： Yan Fu Keyu Shen Hao Wang Shun Wang Xufeng Wang Le Zhu Yan Zheng Tiantian Zou Hongfei Ci Qiongzhu Dong Lun-Xiu Qin Hepatobiliary Surgery Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan University200040 ShanghaiChina Center of Interventional Radiology and Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast University87 Dingjiaqiao Road210009 NanjingChina institutes of Biomedical Sciences Fudan University200032 ShanghaiChina Key Laboratory of Whole-period Monitoring and Precise Intervention of digestive Cancer Shanghai Municipal Health CommissionMinhang HospitalFudan UniversityShanghaiChina

Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor *** cells could exhibit a"neural addiction"property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated *** the dysregulated nervous systems might represent a novel strategy for cancer ***,whether intrahepatic cholangiocarcinoma(ICC)could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely *** staining and Enzyme-linked immunosorbent assay suggested that IcC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes IcC metastasis by inducing epithelial-mesenchymal transition(EMT).Acetylcholine promoted iCC metastasis through interacting with its receptor,alpha 5 nicotine acetylcholine receptor subunits(CHRNA5).Furthermore,acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca^(2+)-mediated activation of Ca/calmodulin-dependent protein kinases(CAMKll).In addition,acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor(BDNF),which formed a feedforward acetylcholine-BDNF axis to promote ICC ***93,a small-molecule inhibitor of CAMKIll,significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC *** all,Acetylcholine/CHRNA5 axis increased the expression ofβ-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKIl/GSK3βsignaling,and the CAMKIl inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.

关键词： GSK3β metastasis Alpha

A toolbox for genetic manipulation in intestinal Clostridium symbiosum

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Synthetic and Systems Biotechnology 2024年第1期9卷 43-54页

作者： Pengjie Yang Jinzhong Tian Lu Zhang Hui Zhang Gaohua Yang Yimeng Ren Jingyuan Fang Yang Gu Weihong Jiang CAS-Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai200032China University of Chinese Academy of Sciences Beijing100049China Xianghu Laboratory Hangzhou311231China NHC Key Laboratory of digestive Diseases Division of Gastroenterology and HepatologyShanghai Institute of Digestive DiseaseRenji HospitalSchool of MedicineShanghai Jiao Tong University145 Middle Shandong RoadShanghai200001China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen518120China The Wallenberg Laboratory Department of Molecular and Clinical MedicineSahlgrenska AcademyUniversity of GothenburgBruna Straket 16Gothenburg41345Sweden

Gut microbes are closely related with human health,but remain much to *** symbiosum is a conditionally pathogenic human gut bacterium and regarded as a potential biomarker for early diagnosis of intestinal ***,the absence of an efficient toolbox that allows diverse genetic manipulations of this bacterium limits its in-depth ***,we obtained the complete genome sequence of *** ATCC 14940,a representative strain of *** this basis,we further developed a series of genetic manipulation methods for this ***,following the identification of a functional replicon pBP1 in *** ATCC 14940,a highly efficient conjugative DNA transfer method was established,enabling the rapid introduction of exogenous plasmids into ***,we constructed a dual-plasmid CRISPR/Cas12a system for genome editing in this bacterium,reaching over 60% repression for most of the chosen genes as well as efficient deletion(>90%)of three target ***,this toolbox was used for the identification of crucial functional genes,involving growth,synthesis of important metabolites,and virulence of *** ATCC *** work has effectively established and optimized genome editing methods in intestinal ***,thereby providing strong support for further basic and application research in this bacterium.

关键词： Gut Clostridium symbiosum Toolbox Gene overexpression Gene deletion Gene regulation

Cellular strategies to induce immune tolerance after liver transplantation:Clinical perspectives

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World Journal of Gastroenterology 2024年第13期30卷 1791-1800页

作者： Ai-Wei Zhou Jing Jin Yuan Liu department of Liver Surgery Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China department of Nursing Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China department of Liver Transplantation Shanghai Immune Therapy InstituteShanghai 200127China

Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative ***,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more *** tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain *** approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced *** first two means require no specific intervention but withdrawing immunosuppressant gradually during *** clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after *** the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT *** strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune *** safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical ***,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.

关键词： Cellular therapy Induced tolerance Liver transplantation Regulatory T cells Regulatory dendritic cells