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Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang Xu Zhu Zequn Lu Yimin Cai Bin Li Ying Zhu Xiangpan Li Yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao Department of Epidemiology and biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China Department of Cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China Department of gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China Department of gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China Department of Epidemiology and biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly ***,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics *** a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in *** the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in *** subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras ***,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 ***,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC *** summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

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Intestinal malrotation complicated with gastric cancer: A case report

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World Journal of Clinical Cases 2024年第1期12卷 210-216页

作者： Xiang-Hao Jia Shuai Kong Xin-Xin Gao Bi-Cong Cong Chun-Ning Zheng School of Clinical Medicine Weifang Medical UniversityWeifang 261053Shandong ProvinceChina Department of gastrointestinal Surgery Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250000Shandong ProvinceChina

BACKGROUND Intestinal malrotation is a congenital defect of embryonic development caused by various teratogenic *** this condition,the intestinal tube,along with the superior mesenteric artery serving as the axis for the counterclockwise movement,is incomplete or abnormally rotated due to incomplete attachment of the mesentery and abnormal intestinal tube *** a case is usually asymp-tomatic and thus difficult to ***,similar variant malformations are only found during an operation required for other abdominal *** SUMMARY An elderly male patient was admitted to the hospital due to gastric *** abdominal computed tomography(CT)scan with contrast revealed that the ascending and descending colon were parallel on the right side of the abdominal cavity,while the sigmoid colon extended into the right iliac fossa,allowing the diagnosis of congenital midgut *** thorough preoperative preparation,the patient underwent laparoscopic radical gastrectomy to treat his gastric ***,an exploration of the abdominal cavity uncovered the absence of the transverse *** distal colon at the hepatic flexure,along with the ascending colon,extended into the right iliac fossa,where it continued as the sigmoid *** planned,the laparoscopic radical gastrectomy was perform-ed,and the patient was discharged from the hospital 7 d after the *** Asymptomatic intestinal malrotation is best detected by CT,requiring no treatment but possibly interfering with the treatment of other diseases.

关键词： Intestinal malrotation Congenital malformation Gastric cancer Abdominal

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Pylorus-preserving gastrectomy for early gastric cancer

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World Journal of gastrointestinal Oncology 2024年第3期16卷 653-658页

作者： Ke-Kang Sun Yong-You Wu Department of gastrointestinal Surgery The Affiliated Kunshan Hospital to Jiangsu UniversitySuzhou 215300Jiangsu ProvinceChina Department of gastrointestinal Surgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215008Jiangsu ProvinceChina

Pylorus-preserving gastrectomy(PPG)has been widely accepted as a function-preserving gastrectomy for middle-third early gastric cancer(EGC)with a distal tumor border at least 4 cm proximal to the *** procedure essentially preserves the function of the pyloric sphincter,which requires to preserve the upper third of the stomach and a pyloric cuff at least 2.5 *** suprapyloric and infrapyloric vessels are usually preserved,as are the hepatic and pyloric branches of the vagus *** with distal gastrectomy,PPG has significant advantages in preventing dumping syndrome,body weight loss and bile reflux *** postoperative complications after PPG have reached an acceptable *** can be considered a safe,effective,and superior choice in EGC,and is expected to be extensively performed in the future.

关键词： Gastric cancer Pylorus-preserving gastrectomy Oncological safety Gastric stasis

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Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1711-1725页

作者： Yingting Wu Jiaqi Xin Xinyu Li Ting Yang Yi Liu Yongsheng Zhao Wen Xie Mengxi Jiang Department of Pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Department of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Advanced Innovation center for Human Brain Protection Capital Medical UniversityBeijing 100069China

Drug repurposing offers an efficient approach to therapeutic *** this study,our bioinformatic analysis first predicted an association between obesity and lansoprazole(LPZ),a commonly prescribed drug for gastrointestinal *** went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity,insulin resistance,and hepatic stea-tosis in *** with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes,and induced cold tolerance in cold-exposed mice,suggesting the activity of LPZ in promoting adipose thermogenesis and energy ***,LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1(PHOSPHOI)and produces metabolic benefits in a PHOS-PHO1-dependent *** results suggested that LPZ may stimulate adipose thermogenesis by inhi-biting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid(2-AG-LPA)to 2-arachidonoylglycerol(2-AG)and reduce the activity of the thermogenic-suppressive cannabinoid recep-tor *** summary,we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome,and identified a potential metabolic basis by which LPZ improves energy metabolism.

关键词： Lansoprazole Proton pump inhibitors Adipose thermogenesis Energy expenditure Metabolic syndrome PHOSPHO1 inhibitor Cannabinoid receptor signaling Drug repurposing

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Hepatocellular carcinoma presenting as an extrahepatic mass:A case report and review of literature

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World Journal of gastrointestinal Oncology 2024年第5期16卷 2241-2252页

作者： Wei Kelly Wu Krutika Patel Chandrasekhar Padmanabhan Kamran Idrees Department of Surgery Vanderbilt University Medical CenterNashvilleTN 37232United States Department of Pathology Microbiology and ImmunologyVanderbilt University Medical CenterNashvilleTN 37232United States Division of Surgical Oncology and Endocrine Surgery Department of SurgeryVanderbilt University Medical CenterNashvilleTN 37232United States

BACKGROUND Hepatocellular carcinoma(HCC)is a primary liver tumor generally diagnosed based on radiographic *** disease is typically associated with increased tumor diameter,multifocality,and vascular *** report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography(CT).We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic *** SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval,mixed cystic-solid *** CT evaluations demonstrated steatosis,but no cirrhosis or liver *** ultrasound demonstrated a normal-appearing pancreas,biliary tree,and *** needle aspiration yielded atypical *** differential diagnosis included duodenal or pancreatic cyst,lymphoproliferative cyst,stromal or mesenchymal lesions,nodal involvement from gastrointestinal or hematologic malignancy,or duodenal gastrointestinal stromal *** review by a multidisciplinary tumor board,the patient underwent open surgical resection of a 5.2 cm×5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated *** resonance imaging(MRI)subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement,fatty sparing,and intrinsic T1 *** fetoprotein was 23.3 ng/*** patient was diagnosed with HCC with portocaval nodal ***:We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic *** identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions,and 30 cases of extrahepatic HCC found to be primary,ectopic *** Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of

关键词： Extrahepatic Metastasis Portocaval Lymph node Case report

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Dynamics of glutamine synthetase expression in hepatic ischemiareperfusion injury: Implications for therapeutic interventions

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World Journal of Hepatology 2024年第8期16卷 1177-1184页

作者： Zhi-Hao Huang Meng-Qi Dong Feng-Yong Liu Wei-Jie Zhou State Key Laboratory of Organ Failure Research Department of General SurgeryGuangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal TumorNanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of Interventional Radiology Senior Department of OncologyFifth Medical Center of PLA General HospitalBeijing 100853China

BACKGROUND hepatic ischemia-reperfusion injury(IRI)poses a great challenge in liver surgery and transplantation because of oxidative stress and inflammatory *** changes in glutamine synthetase(GS)expression during hepatic IRI remain *** To investigate the dynamic expression of GS during hepatic *** Following hepatic ischemia for 1 h and reperfusion,liver tissue samples were collected at 0.5,6,and 24 hours postreperfusion for fixation,embedding,*** and eosin staining and GS staining were *** GS expression rapidly decreases in hepatocytes around the central vein after IRI,reaching its lowest point at 6 hours postreperfusion,and then gradually *** GS is highly sensitive to IRI,highlighting its potential role as an indicator of liver injury states and a target for therapeutic intervention.

关键词： hepatic ischemia-reperfusion Glutamine synthetase Central vein Liver Injury repair

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Simplified liver imaging reporting and data system for the diagnosis of hepatocellular carcinoma on gadoxetic acid-enhanced magnetic resonance imaging

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World Journal of gastrointestinal Oncology 2024年第6期16卷 2439-2448页

作者： Rong Lyu Wei-Juan Hu Di Wang Jiao Wang Yu-Bing Ye Ke-Feng Jia Department of Radiology Tianjin Third Central HospitalTianjin Key Laboratory of Extracorporeal Life Support for Critical DiseasesArtificial Cell Engineering Technology Research CenterTianjin 300170China

BACKGROUND The liver imaging reporting and data system(LI-RADS)diagnostic table has 15 cells and is too *** diagnostic performance of LI-RADS for hepatocellular carcinoma(HCC)is not satisfactory on gadoxetic acid-enhanced magnetic resonance imaging(EOB-MRI).AIM To evaluate the ability of the simplified LI-RADS(sLI-RADS)to diagnose HCC on *** A total of 331 patients with 356 hepatic observations were retrospectively *** diagnostic performance of sLI-RADS A-D using a single threshold was evaluated and compared with LI-RADS v2018 to determine the optimal *** algorithms of sLI-RADS A-D are as follows:The single threshold for sLI-RADS A and B was 10 mm,that is,classified observations≥10mm using an algorithm of 10-19 mm observations(sLI-RADS A)and≥20 mm observations(sLI-RADS B)in the diagnosis table of LI-RADS v2018,respectively,while the classification algorithm remained unchanged for observations0.999).With HBP hypointensity as an MF,the sensitivity of F-sLI-RADS was greater than that of LI-RADS v2018(93.0%vs 87.0%,P<0.001)and sLI-RADS D(93.0%vs 89.8%,P=0.016),without a lower specificity(86.5%vs 90.1%,P=0.062;86.5%vs 89.4%,P=0.125).Compared with that of LI-RADS v2018,the time to classif

关键词： Hepatocellular carcinoma Magnetic resonance imaging Liver Diagnosis Contrast agent

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Current research status of transarterial therapies for hepatocellular carcinoma

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World Journal of gastrointestinal Oncology 2024年第9期16卷 3752-3760页

作者： Mao-Ting Zhou Peng Zhang Qi Mao Xiao-Qin Wei Lin Yang Xiao-Ming Zhang Department of Radiology Interventional Medical CenterScience and Technology Innovation CenterThe Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina School of medical Imaging North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina

With continuous advancements in interventional radiology,considerable progress has been made in transarterial therapies for hepatocellular carcinoma(HCC)in recent years,and an increasing number of research papers on transarterial therapies for HCC have been *** this editorial,we comment on the article by Ma et al published in the recent issue of the World Journal of gastrointestinal Oncology:“Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC”.We focus specifically on the current research status and future directions of transarterial *** the future,more studies are needed to determine the optimal transarterial local treatment for *** the emergence of checkpoint immunotherapy modalities,it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.

关键词： Hepatocellular carcinoma Transarterial therapies Transarterial chemoembolization hepatic artery infusion chemotherapy Transarterial embolization Transarterial radioembolization

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A nonenzymatic electrochemical sensor for the detection of hydrogen peroxide in vitro and in vivo fibrosis models

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Chinese Chemical Letters 2024年第3期35卷 394-398页

作者： Hongyao Liu Yan Yu Taixiong Xue Cailing Gan Yuting Xie Doudou Wang Peilin Li Zhiyong Qian Tinghong Ye Department of Gastroenterology and Hepatology Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer and Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Department of biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Fibrosis occurs due to the excessive deposition of extracellular matrix caused by cell *** various types of tissue injury,the dysregulation of the internal response can eventually lead to the destruction of organ structure and *** is increasing evidence that oxidative stress,which is characterized by excessive production of hydrogen peroxide(H_(2)O_(2)),is an important cause of ***,we synthesized a biosensitive and efficient electrochemical H_(2)O_(2)sensor based on PtNi nanoparticle-doped N-reduced graphene oxide(PtNi-N-rGO)to detect H_(2)O_(2)released from transforming growth factorβ1(TGFβ1)-induced *** addition,the sensor could easily detect changes in H_(2)O_(2)in the lung and bronchoalveolar lavage fluid(BALF)of mice with pulmonary ***,the sensor could also detect H_(2)O_(2)in activated hepatic stellate cells and the liver of carbon tetrachloride(CCl_(4))-induced liver ***,the alterations in H_(2)O_(2)detected by the sensor were consistent with nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)protein expression and the staining results of pathological *** together,these results highlight the use of H_(2)O_(2)sensors for the rapid detection of fibrosis and facilitate the rapid evaluation of antifibrotic drug candidates.

关键词： Fibrosis H_(2)O_(2) Electrochemical sensor NOX4 Nintedanib

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Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer:A retrospective study

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Chinese Journal of Cancer Research 2024年第1期36卷 78-89页

作者： Changsong Qi Xiaoyi Chong Ting Zhou Mingyang Ma Jifang Gong Miao Zhang Jian Li Jun Xiao Xiaohui Peng Zhen Liu Zonghai Li Lin Shen Xiaotian Zhang State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China CARsgen Therapeutics Co. LtdShanghai 200231China CARsgen Life Sciences Co. LtdShanghai 200131China

Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in ***: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression ***: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of *** death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of ***18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(Pinvestigation.

关键词： Gastric cancer claudin18.2 CT041 PD-L1 immunotherapy

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