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Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 300-309页

作者： Qing Huang Jia-Wen Liu Hai-Bin Dong Zheng-Jie Wei Jin-Zhe Liu Yu-Tang Ren Xuan Jiang Bo Jiang department of gastroenterology Beijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102218China

Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains *** has been reported that pyroptosis worsens *** present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic ***:Thirty-six male Sprague Dawley(SD)rats were divided into six different *** rats were randomly divided into the SAP and control *** monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP *** SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or *** collected blood and tissue samples from pancreas,gut and MAT for ***:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological *** cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and *** SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological *** expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP *** injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in *** upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological *** administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of ***:In SAP,MAT B lymphocytes aggravated local

关键词： Acute pancreatitis Mesenteric adipose tissue B lymphocyte Intestinal barrier Pyroptosis

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Visceral adipose tissue predicts severity and prognosis of acute pancreatitis in obese patients

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 458-462页

作者： Yuan Tian Qing Huang Yu-Tang Ren Xuan Jiang Bo Jiang department of gastroenterology Beijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102218China

Acute pancreatitis is a common systemic inflammatory disease, manifested by a spectrum of severity, ranging from mild in the majority of patients to severe acute pancreatitis. Patients with severe acute pancreatitis suffer from severe local and systemic complications and organ failure, leading to a poor prognosis. The early recognition of the severe condition is important to improve prognosis. Obesity has risen in tandem with an increase in the severity of acute pancreatitis in recent years. Studies have revealed that adipose tissue, particularly visceral adipose tissue is associated with the prognosis of acute pancreatitis. This review discussed the role of visceral adipose tissue in obese patients with acute pancreatitis and explored the possible mechanism involved.

关键词： Visceral adipose tissue Obesity Acute pancreatitis

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Microvascular structural changes in esophageal squamous cell carcinoma pathology according to intrapapillary capillary loop types under magnifying endoscopy

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3471-3480页

作者： Wei-Yang Shu Yan-Yan Shi Jiu-Tian Huang Ling-Mei Meng He-Jun Zhang Rong-Li Cui Yuan Li Shi-Gang Ding department of gastroenterology Peking University Third HospitalBeijing 100191China Research Center of clinical Epidemiology Peking University Third HospitalBeijing 10019China department of gastroenterology Pathology Laboratory Peking University Third HospitalBeijing 100191China department of gastroenterology Peking University International HospitalBeijing 102206China

BACKGROUND The intrapapillary capillary loop(IPCL)characteristics,visualized using magnifying endoscopy,are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma(ESCC).Japan Esophageal Society(JES)classification is the most widely used *** structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor:tortuosity,dilatation,irregular caliber,and different ***,the pathological characteristics of IPCLs have not been thoroughly investigated,especially the microvascular structures corresponding to the deepest parts of the lesions'*** To investigate differences in pathological microvascular structures of ESCC,which correspond to the deepest parts of the lesions'*** Patients with ESCC and precancerous lesions diagnosed at Peking university Third hospital were enrolled between January 2019 and April *** first underwent magnified endoscopic examination,followed by endoscopic submucosal dissection or surgical *** images were scanned using a threedimensional slice scanner,and the pathological structural differences in different types,according to the JES classification,were analyzed using nonparametric tests and *** The 35 lesions were divided into four groups according to the JES classification:A,B1,B2,and *** analyses revealed significant differences(aP0.05).However,significant differences in the short calibers,long calibers,and area of IPCL were observed between types B1 and B3(aP0.05).CONCLUSION Pathological structures of IPCLs in the deepest infiltrating regions differ among va

关键词： Esophageal squamous cell carcinoma Intrapapillary capillary loop The Japan Esophageal Society classification Magnifying endoscopy Pathological characteristics

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Protein lipidation in health and disease:molecular basis,physiological function and pathological implication

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1423-1465页

作者： Yuan Yuan Peiyuan Li jianghui Li Qiu Zhao Ying Chang Xingxing He department of gastroenterology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina department of gastroenterology Zhongnan Hospital of Wuhan UniversityWuhanChina Hubei clinical Center and Key Laboratory of Intestinal and Colorectal Diseases WuhanChina

Posttranslational modifications increase the complexity and functional diversity of proteins in response to complex external stimuli and internal *** these,protein lipidations which refer to lipid attachment to proteins are prominent,which primarily encompassing five types including S-palmitoylation,N-myristoylation,S-prenylation,glycosylphosphatidylinositol(GPl)anchor and *** attachment to proteins plays an essential role in the regulation of protein trafficking,localisation,stability,conformation,interactions and signal transduction by enhancing *** evidence from genetic,structural,and biomedical studies has consistently shown that protein lipidation is pivotal in the regulation of broad physiological functions and is inextricably linked to a variety of *** of dedicated research have driven the development of a wide range of drugs targeting protein lipidation,and several agents have been developed and tested in preclinical and clinical studies,some of which,such as asciminib and lonafarnib are FDA-approved for therapeutic use,indicating that targeting protein lipidations represents a promising therapeutic ***,we comprehensively review the known regulatory enzymes and catalytic mechanisms of various protein lipidation types,outline the impact of protein lipidations on physiology and disease,and highlight potential therapeutic targets and clinical research progress,aiming to provide a comprehensive reference for future protein lipidation research.

关键词： Lipid ation primarily

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Knockdown of RCN1 contributes to the apoptosis of colorectal cancer via regulating IP3R1

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BIOCELL 2024年第5期48卷 835-845页

作者： XUAN SHI YUFEN WANG CHENYU LI WANGSHU FU XINYUE ZHANG AIXIA GONG department of gastroenterology The First Affiliated Hospital of Dalian Medical UniversityDalianChina department of gastroenterology The First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina The First clinical College Dalian Medical UniversityDalianChina

Background:The incidence of colorectal cancer(CRC)has been increasing in recent ***,the discovery of factors that can assist in alleviating CRC is urgently ***:To identify a potential factor involved in the development of CRC,we screened the upregulated genes in tumor tissues through four datasets from an online *** expression of reticulocalbin 1(RCN1),a Ca2+-binding protein,was upregulated in the four *** on loss-offunction experiments,the effect of RCN1 on cell viability was assessed by Cell Counting Kit-8(CCK-8)*** regulatory effect of RCN1 on apoptosis was evaluated through Annexin V-fluorescein 5-isothiocyanate(FITC)/propidium iodide(PI)staining assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)assay in RKO and SW480 *** of endoplasmic reticulum(ER)stress signaling pathways was confirmed by estimating the phosphorylation and expression of PRKR-like ER kinase(PERK),inositol-requiring kinase-1(IRE1),transcription factor 6(ACT6),and CCAAT/enhancer-binding protein-homologous protein(CHOP).The intracellular Ca2+homeostasis regulated by RCN1 was determined through the detection of Ca2+concentration and mitochondrial membrane potential(MMP)***,whether inositol 1,4,5-trisphosphate receptor type 1(IP3R1)was involved in the regulation of RCN1 in CRC was verified through the depletion of IP3R1 in RKO ***:Knockdown of RCN1 reduced cell viability and facilitated apoptosis in RKO and SW480 *** of PERK and IRE1,activation of ATF6,and upregulation of CHOP were induced by the absence of RCN1,suggesting that the unfolded protein response(UPR)was activated in CRC *** concentration of Ca2+in mitochondria was increased after RCN1 depletion,followed by reduction in the MMP and release of cytochrome c from mitochondria to the cytoplasm in RKO and SW480 ***,it was demonstrated that IP3R1 mediates the effect of RCN1 on apoptosis i

关键词： Reticulocalbin 1 Unfolded protein response IP3R1 Colorectal cancer

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TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-β1/Smad3 Signaling Pathway

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Current Medical Science 2024年第3期44卷 519-528页

作者： Jia SONG Dong-lei SUN Chen-yang LI Yu-xin LUO Qian LIU Yue YAO Hong ZHANG Ting-ting YANG Mei SONG Xin-li BAI Xiao-lan ZHANG department of gastroenterology The Second Hospital of Hebei Medical UniversityHebei Key Laboratory of GastroenterologyHebei Institute of GastroenterologyHebei Clinical Research Center for Digestive DiseasesShijiazhuang050000China department of Pediatrics The Second Hospital of Hebei Medical UniversityShijiazhuang050000China

Objective Intestinal fibrosis is a refractory complication of inflammatory bowel disease(IBD).Tumor necrosis factor ligand-related molecule-1A(TL1A)is important for IBD-related intestinal fibrosis in a dextran sodium sulfate(DSS)-induced experimental colitis *** study aimed to explore the effects of TL1A on human colonic *** A trinitrobenzene sulfonic acid(TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic(Tg)or wild-type(WT)mice was established to determine the effect and mechanism of TL1A on intestinal *** human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell(PBMC)*** proliferation and activation of CCD-18Co cells were detected by BrdU assays,flow cytometry,immunocytochemistry and Western *** metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction(RT-qPCR).Results The level of collagen metabolism in the TNBS+ethyl alcohol(EtOH)/Tg group was greater than that in the TNBS+EtOH/WT *** growth factor-β1(TGF-β1)and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT *** proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A,and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4%at 24 ***1A promoted cell activation and increased the levels of COL1A2,COL3A1,and TIMP-1 in CCD-18Co *** of CCD-18Co cells with TL1A increased the expression of TGF-β1 and *** TL1A promotes TGF-β1-mediated intestinal fibroblast activation,proliferation,and collagen deposition and is likely related to an increase in the TGF-β1/Smad3 signaling pathway.

关键词： tumor necrosis factor ligand-related molecule-1A fibrosis inflammatory bowel disease myofibroblasts transforming growth factor-β1

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Development and validation of a novel criterion of histologic healing in ulcerative colitis defined by inflammatory cell enumeration in lamina propria mucosa:A multicenter retrospective cohort in China

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Chinese Medical Journal 2024年第11期137卷 1316-1323页

作者： Han Gao Kangsheng Peng Yadi Shi Shenshen Zhu Ruicong Sun Chunjin Xu Ping Liu Zhi Pang Lanxiang Zhu Weichang Chen Baisui Feng Huili Wu Guangxi Zhou Mingsong Li Junxiang Li Baijing Ding Zhanju Liu Center for IBD Research and department of gastroenterology Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200085China clinical Medicine Sanquan College of Xinxiang Medical UniversityXinxiangHenan 453003China department of gastroenterology The First People’s Hospital of Shangqiu City Affiliated to Xinxiang Medical UniversityShangqiuHenan 476100China department of gastroenterology Wuhu First People’s HospitalWuhuAnhui 241000China department of gastroenterology Suzhou Municipal Hospital Affiliated to Nanjing Medical UniversitySuzhouJiangsu 215008China department of gastroenterology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 251006China department of gastroenterology The Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450014China department of gastroenterology Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhouHenan 450000China department of gastroenterology The Affiliated Hospital of Jining Medical CollegeJiningShandong 272004China department of gastroenterology The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510140China department of gastroenterology Dongfang Hospital of Beijing University of Chinese MedicineBeijing 100078China

Background:Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis(UC).Here,we developed a novel diagnostic criterion for assessing histological healing in UC ***:We conducted a retrospective cohort study in UC patients,whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s hospital of Tongji university from January 2017 to May *** identified an inflammatory cell enumeration index(ICEI)for assessing histological healing based on the proportions of eosinophils,CD177^(+)neutrophils,and CD40L^(+)T cells in the colonic lamina propria under high power field(HPF),and the outcomes(risks of symptomatic relapses)of achieving histological remission *** histological inflammation using Kaplan-Meier *** reliability and inter-reader reliability were evaluated by each *** relationships to the changes in the Nancy index and the Geboes score were also assessed for *** ICEI was further validated in a new cohort of UC patients from other nine university ***:We developed an ICEI for clinical diagnosis of histological healing,i.e.,Y=1.701X_(1)+0.758X_(2)+1.347X_(3)-7.745(X_(1),X_(2),and X_(3)represent the proportions of CD177^(+)neutrophils,eosinophils,and CD40L^(+)T cells,respectively,in the colonic lamina propria under HPF).The receiver operating characteristics curve(ROC)analysis revealed that Y<-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve(AUC)was 0.942(95%confidence interval[CI]:0.905-0.979)with a sensitivity of 92.5%and a specificity of 83.6%(P<0.001).The intraclass correlation coefficient(ICC)for the intrareader reliability was 0.855(95%CI:0.781-0.909),and ICEI had good inter-reader reliability of 0.832(95%CI:0.748-0.894).During an 18-month follow-up,patients with histological healing had a substantially better outcome com

关键词： Ulcerative colitis Histological healing Inflammatory cell enumeration index Prognosis

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Identification of differentially expressed mRNAs as novel predictive biomarkers for gastric cancer diagnosis and prognosis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1947-1964页

作者： Jian-Wei Zhou Yi-Bing Zhang Zhi-Yang Huang Yu-Ping Yuan Jie Jin department of gastroenterology Wenzhou Central HospitalDingli Clinical College of Wenzhou Medical UniversityThe Second Affiliated Hospital of Shanghai UniversityWenzhou 325000Zhejiang ProvinceChina

BACKGROUND Gastric cancer(GC)has a high mortality rate *** significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains *** To identify important candidate genes related to the development of GC and iden-tify potential pathogenic mechanisms through comprehensive bioinformatics *** The Gene Expression Omnibus database was used to obtain the GSE183136 dataset,which includes a total of 135 GC *** limma package in R software was employed to identify differentially expressed genes(DEGs).Thereafter,enrichment analyses of Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were performed for the gene modules using the clusterProfile package in R *** protein-protein interaction(PPI)networks of target genes were constructed using STRING and visualized by Cytoscape *** common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn *** expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier ***,real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase(GPT)in GC and normal immortalized cell *** addition,cell viability,cell cycle distribution,migration and invasion were evaluated by cell counting kit-8,flow cytometry and transwell ***,we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central hospital,Dingli clinical College of Wenzhou Medical university,The Second Affiliated hospital of Shanghai university between January 2017 to December *** tumor and adjacent normal samples were collected from the patients to determine the

关键词： Gastric cancer Differentially expressed genes Bioinformatics Hub genes Prognosis

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A BBS4 mutation causes autosomal dominant polycystic liver disease

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Genes & Diseases 2024年第1期11卷 72-75页

作者： Yalu Cui Wenping Xu Jinpei Liu Shuqing Liu Wei Huang Yihai Shi Xin Zhang Cuihua Lu Weifen Xie department of gastroenterology Changzheng HospitalNaval Medical UniversityShanghai 200003China department of gastroenterology Gongli Hospital of Shanghai Pudong New AreaShanghai 200135China department of gastroenterology Affiliated Hospital of Nantong UniversityNantong UniversityNantongJiangsu 226001China

Autosomal dominant polycystic liver disease(ADPLD)refers to a condition characterized by the presence of numerous cholangiocytes-lined and fluid-filled cysts in the liver and the absence of polycystic kidney disease.1 Although patients with ADPLD may be asymptomatic,some patients suffer from abdominal pain,gastroesophageal reflux,and nausea,because of hepatomegaly.

关键词： liver polycystic patients

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Early detection of multiple endocrine neoplasia type 1: A case report

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World Journal of gastroenterology 2024年第26期30卷 3247-3252页

作者： Jie-Hao Yuan Su Luo Ding-Guo Zhang Li-Sheng Wang department of gastroenterology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan University)Shenzhen 518020Guangdong ProvinceChina

BACKGROUND Multiple endocrine neoplasias(MENs)are a group of hereditary diseases invol-ving multiple endocrine glands,and their prevalence is *** type 1(MEN1)has diverse clinical manifestations,mainly involving the parathyroid glands,gastrointestinal tract,pancreas and pituitary gland,making it easy to miss the clinical *** SUMMARY We present the case of a patient in whom MEN1 was detected early.A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the *** tests at admission revealed hypercalcemia and hypophosphatemia,and emission computed tomography of the parathyroid glands revealed a hy-perfunctioning parathyroid *** findings suggested a duodenal bulge and *** endoscopy revealed a hypoechoic lesion in the duodenal *** blood tests revealed elevated levels of serum *** was performed,and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal *** time from onset to the definitive diagnosis of MEN1 was only approximately 1 *** For patients who present with gastrointestinal symptoms accompanied by hyper-calcemia and hypophosphatemia,clinicians need to be alert to the possibility of MEN1.

关键词： Multiple endocrine neoplasia type 1 Gastrointestinal symptoms Hypercal-cemia Early detection Case report

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