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The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

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Hepatobiliary & Pancreatic diseases International 2024年第1期23卷 71-76页

作者： Alessandro Fugazza Matteo Colombo Michel Kahaleh V.Raman Muthusamy Bick Benjamin Wim Laleman Carmelo Barbera Carlo Fabbri Jose Nieto Abed Al-Lehibi Mohan Ramchandani Amy Tyberg Haroon Shahid Avik Sarkar Dean Ehrlich Stuart Shermand Cecilia Binda Marco Spadaccini Andrea Iannone Kareem Khalaf Nageshwar Reddy Andrea Anderloni Alessandro Repici Division of Gastroenterology and digestive Endoscopy Humanitas Research Hospital-IRCCSVia Manzoni 5620089RozzanoMilanoItaly Gastroenterology Rutgers Robert Wood JohnsonNew BrunswickNew JerseyUSA Vatche and Tamar Manoukian Division of digestive diseases University of CaliforniaLos Angeles School of Medicine at UCLALos AngelesCaliforniaUSA Division of digestive and Liver Disorders Indiana University School of MedicineIndianapolisINUSA department of Gastroenterology and Hepatology University Hospitals LeuvenKU Leuven3000 LeuvenBelgium U.O.C.di Gastroenterologia ed Endoscopia Digestiva Ospedale Giuseppe MazziniASL TeramoItaly Gastroenterology and digestive Endoscopy Unit Forlì-Cesena HospitalsAUSL RomagnaForlì-CesenaItaly Borland Groover Clinic JacksonvilleFloridaUSA department of Gastroenterology and Hepatology King Fahad Medical CityRiyadhSaudi Arabia Asian institute of Gastroenterology HyderabadIndia Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy department of Biomedical Sciences Humanitas UniversityVia Rita Levi Montalcini 420090Pieve EmanueleMilanItaly

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 ***: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

关键词： Single-operator cholangioscopy Single-use duodenoscope Endoscopic retrograde cholangiopancreatography Indeterminate biliary stricture Difficult biliary stones

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

A novel mouse model of PEDF-associated serious liver inflammation,hepatic tumorigenesis and cardiovascular injury mimics human nonalcoholic steatohepatitis

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Genes & diseases 2024年第1期11卷 11-14页

作者： Xinghui Li Haiping Wang Yandi Wu Li Zou Shijie Dengg Xintu Fu Tongsheng Huang Conghui Shen Teng Wu Weibin Cai Guangdong Engineering&Technology Research Center for disease-Model Animals Laboratory Animal CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China department of Biochemistry Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China School of Pharmacy Guangdong Pharmaceutical UniversityGuangzhouGuangdong 510006China Guangdong Provincial Key Laboratory of digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107China

There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic metabolic disorders,hepatic steatosis,intense liver inflammation and fibrosis,liver tumorigenesis,and cardiovascularcomplications.i,2"Pigment"epitheliumderived factor(PEDF)is a lipid metabolism regulator with high expression in the liver,and its reduced expression in the liver is closely related to the development of nonalcoholic fatty liver disease(NAFLD).

关键词： inflammation PEDF hepatic

STING-mediated IL-6 Inhibits OATP1B1 Expression via the TCF4 Signaling Pathway in Cholestasis

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Journal of Clinical and Translational Hepatology 2024年第8期12卷 701-712页

作者： Yan Guo Hongjia Zhang Nan Zhao Ying Peng Dongya Shen Yubin Chen Xiaoxun Zhang Can-E Tang Jin Chai department of Endocrinology Xiangya HospitalCentral South UniversityChangshaHunanChina department of Gastroenterology Institute of Digestive Diseases of PLACholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver DiseaseThe First Affiliated Hospital(Southwest Hospital)to Third Military Medical University(Army Medical University)ChongqingChina department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangshaHunanChina department of Cardiac Surgery Xiangya HospitalCentral South UniversityChangshaHunanChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina

Background and Aims Organic anion-transporting polypeptides(OATPs)play a crucial role in the transport of bile acids and *** our previous study,interleukin 6(IL-6)reduced OATP1B3 levels in cholestatic ***,it remains unclear whether IL-6 inhibits OATP1B1 expression in cholestatic *** study aimed to investigate whether IL-6 can inhibit OATP1B1 expression and explore the underlying *** The effect of stimulator of interferon genes(STING)signaling on inflammatory factors was investigated in a cholestatic mouse model using RT-qPCR and enzyme-linked immunosorbent *** assess the impact of inflammatory factors on OATP1B1 expression in hepatocellular carcinoma,we analyzed OATP1B1 expression by RT-qPCR and Western Blot after treating PLC/PRF/5 cells with TNF-α,IL-1β,and *** elucidate the mechanism by which IL-6 inhibits OATP1B1 expression,we examined the expression of the OATP1B1 regulator TCF4 in PLC/PRF/5 and HepG2 cells using RT-qPCR and Western *** interaction mechanism betweenβ-catenin/TCF4 and OATP1B1 was investigated by knocking downβ-catenin/TCF4 through siRNA *** The STING inhibitor decreased inflammatory factor levels in the cholestatic mouse model,with IL-6 exhibiting the most potent inhibitory effect on ***-6 downregulatedβ-catenin/TCF4,leading to decreased OATP1B1 ***-downβ-catenin/TCF4 counteracted theβ-catenin/TCF4-mediated repression of *** STING-mediated IL-6 up-regulation may inhibit OATP1B1,leading to reduced transport of bile acids and bilirubin by *** may contribute to altered pharmacokinetics in patients with diseases associated with increased IL-6 production.

关键词： Inflammation Bile acid Bilirubin Cholestasis STING IL-6 β-catenin TCF4

Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer(NECTAR):a multi-center phase 2 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1721-1729页

作者： Zhengyang Yang Jiale Gao Jianyong Zheng Jiagang Han Ang Li Gang Liu Yi Sun Jie Zhang Guangyong Chen Rui Xu Xiao Zhang Yishan Liu Zhigang Bai Wei Deng Wei He Hongwei Yao Zhongtao Zhang department of General Surgery Beijing Friendship HospitalCapital Medical UniversityState Key Lab of Digestive HealthNational Clinical Research Center for Digestive DiseasesBeijingChina department of Gastrointestinal Surgery The First Affiliated Hospital of Air Force Medical UniversityXi'anChina department of General Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina department of General Surgery Beijing Xuanwu HospitalCapital Medical UniversityBeijingChina department of General Surgery Tianjin Medical University General HospitalTianjinChina department of Anorectal Tianjin People's HospitalTianjinChina department of Radiology Beijing Friendship Hospital Capital Medical UniversityBeijingChina department of Pathology Beijing Friendship HospitalCapital Medical UniversityBeijingChina department of Thoracic Surgery/institute of Thoracic Oncology West China HospitalSichuan UniversityChengduChina

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer(LARC)patients with microsatellite stable(MsS)/mismatch repair-proficient(pMMR)tumors is an attractive,but debatable *** phase 2,multicenter,prospective,single-arm study enrolled patients from 6 centers from June 2021 to November *** advanced rectal cancer(LARC,cT_(3-4a)N_(0)M_(0) and cT_(1-4a)N_(1-2)M_(0))patients aged≥18 years with the distance from distal border of tumor to anal verge≤10 cm(identified by Magnetic Resonance Imaging)were qualifed for *** patients received long-course radiotherapy(50 Gy/25 fractions,2 Gy/fraction,5 days/week)and three 21-day cycles capecitabine(850-1000 mg/m2,bid,po,day1-14)and three 21-day cycles tislelizumab(200 mg,***,day8)as *** mesorectal excision(TME)was 6-12 weeks after the end of radiotherapy to achieve radical resection.A total of 50 patients were enrolled in this *** pathological complete response rate was 40.0%[20/50,95%confidence interval(CI):27.61-53.82%],while 15(30.0%,95%CI:19.1-43.75%),9(18.0%,95%CI:9.77-30.8%),2(4.0%,95%CI:1.10-13.46%)patients respectively achieved grade 1,2,and 3 tumor ***-related adverse events(TRAEs)occurred in 28(56.0%)LARC patients,including 26(52.0%)with grade I-II and 2(4.0%)with grade II(1 with grade 3 immune-related colitis and 1 with grade 3 rash).PD-1 blockade plus long-course chemoradiotherapy(CRT)showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients.A larger randomized controlled study is desired to further validate the above findings.

关键词： rectal cancer phase

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

Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2697-2715页

作者： Ze Dai Kai-Li Deng Xiao-Mei Wang Dong-Xue Yang Chun-Lan Tang Yu-Ping Zhou department of Gastroenterology The First Affiliated Hospital of Ningbo UniversityNingbo 315020Zhejiang ProvinceChina Health Science Center Ningbo UniversityNingbo 315211Zhejiang ProvinceChina School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina institute of digestive disease of Ningbo University Ningbo UniversityNingbo 315020Zhejiang ProvinceChina Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology Ningbo Key LaboratoryNingbo 315020Zhejiang ProvinceChina

BACKGROUND Colorectal cancer(CRC)has a high incidence and *** studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis,progression,and metastasis of *** To investigate the effect of indole-3-acetaldehyde(IAAD)on *** The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines(HCT116 and DLD-1).Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity *** apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium *** was investigated using the transwell *** blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor(AhR)downstream *** PharmMapper,SEA,and SWISS databases were used to screen for potential target proteins of IAAD,and the core proteins were identified through the String *** IAAD reduced tumorigenesis in a syngeneic mouse *** CRC cell lines HCT116 and DLD1,IAAD exhibited cytotoxicity starting at 24 h of treatment,while it reduced Ki67 expression in the *** results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells,which may be related to the activation of *** can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 *** low concentrations(<12.5μmol/L),IAAD only exhibited cytotoxic effects without promoting cell *** addition,predictions based on online databases,protein-protein interaction analysis,and molecular docking showed that IAAD can bind to matrix metalloproteinase-9(MMP9),angiotensin converting enzyme(ACE),poly(ADP-ribose)polymerase-1(PARP1),matrix metalloproteinase-2(MMP2),and myeloperoxidase(MPO).CONCLUSION Indole-3-aldehyde can induce cell apoptosis and inhibit cell prol

关键词： Indole-3-acetaldehyde Colorectal cancer Tryptophan metabolism Apoptosis Epithelial-mesenchymal transition

Modifiable risk factors for esophageal cancer in endoscopic screening population:A modeling study

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Chinese Medical Journal 2024年第3期137卷 350-352页

作者： Qian Zhang Fan Wang Hao Feng Jie Xing Shengtao Zhu Hao Zhang Yang Li Wenqiang Wei Shutian Zhang department of Gastroenterology Beijing Friendship HospitalCapital Medical UniversityNational Clinical Research Center for Digestive DiseaseBeijing Digestive Disease CenterBeijing Key Laboratory for Precancerous Lesion of Digestive DiseaseBeijing 100050China Center for Applied Statistics and School of Statistics Renmin University of ChinaBeijing 100872China Statistical Consulting Center Renmin University of ChinaBeijing 100872China National Cancer Center National Clinical Research Center for CancerCancer InstituteChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China department of Gastroenterology Jizhong Energy Fengfeng Group HospitalHandanHebei 056000China RSS and China-Re Life Joint Lab on Public Health and Risk Management Renmin University of ChinaBeijing 100872China

To the Editor:Esophageal cancer,one of the most common cancer types in China,with an estimated 346,633 new cases and 323,600 deaths in 2022,is becoming an increasingly serious clinical and public health problem.^([1])The successful promotion of the self-management strategy has indicated that lifestyle modifications can be valuable in the primary prevention of cancer *** a healthy lifestyle has become a novel strategy for primary prevention and risk reduction in high-risk *** epidemiological studies have identified several lifestyle-related risk factors for esophageal cancer,including smoking and diet.^([2])Each factor can typically explain a modest proportion of cancer ***,when combined,these known risk factors may substantially affect the risk of esophageal ***,some risk factors for esophageal cancer are non-modifiable,including age,low socioeconomic status,and family *** and how these non-modifiable risk factors affect primary cancer prevention by intervening with modifiable risk factors remain unclear.

关键词： esophageal prevention promotion

Benefit-Risk Assessment of Chinese Medicine Injections for Primary Liver Cancer Based on Multi-criteria Decision Analysis

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Chinese Journal of Integrative Medicine 2024年第6期30卷 559-564页

作者： ZHANG Rong-rong SHAO Ming-yi FU Yu ZHAO Rui-xia WANG Jing-wen FANG Yu-xuan The First Clinical Medical College of Henan University of Traditional Chinese Medicine Zhengzhou450046China Personal department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Scientific Research department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China digestive department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China

ObjectiveTo evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical *** controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation *** total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (−0.86, 17.75), 5 (−5.01, 11.09), and 6 (−1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, *** on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

关键词： multi-criteria decision analysis benefit-risk assessment Chinese medicine injections primary livercancer