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Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects

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Science China(Life Sciences) 2024年第10期67卷 2132-2148页

作者： Mengting Wang Liping Wang Yanxin Huang Zhibin Qiao Shanru Yi Weina Zhang Jing Wang Guang Yang Xinyu Cui Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Jiayu Chen Clinical and translational research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Shanghai Tenth People’s Hospital School of MedicineTongji UniversityShanghai 200072China Frontier Science Center for Stem Cell research Tongji UniversityShanghai 200092China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China Shanghai Institute of Stem Cell research and Clinical translation Shanghai 200120China

The TET family is well known for active DNA demethylation and plays important roles in regulating transcription,the epigenome and ***,previous studies using knockdown(KD)or knockout(KO)models to investigate the function of TET have faced challenges in distinguishing its enzymatic and nonenzymatic roles,as well as compensatory effects among TET family members,which has made the understanding of the enzymatic role of TET not accurate *** solve this problem,we successfully generated mice catalytically inactive for specific Tet members(Tetm/m).We observed that,compared with the reported KO mice,mutant mice exhibited distinct developmental defects,including growth retardation,sex imbalance,infertility,and perinatal ***,Tetm/mmouse embryonic stem cells(mESCs)were successfully established but entered an impaired developmental program,demonstrating extended pluripotency and defects in ectodermal differentiation caused by abnormal DNA ***,Tet3,traditionally considered less critical for m ESCs due to its lower expression level,had a significant impact on the global hydroxymethylation,gene expression,and differentiation potential of ***,there were common regulatory regions between Tet1 and Tet3 in pluripotency *** summary,our study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.

关键词： Tet hydroxymethylase activity mESCs DNA demethylation 5hmC

Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

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Chinese Journal of Cancer research 2024年第1期36卷 90-102页

作者： Jianwei Zhang Hanxiao Chen Junli Zhang Sha Wang Yanfang Guan Wenguang Gu Jie Li Xiaotian Zhang Jian Li Xicheng Wang Zhihao Lu Jun Zhou Zhi Peng Yu Sun Yang Shao Lin Shen Minglei Zhuo Ming Lu Key Laboratory of Carcinogenesis and translational research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Department of Radiation Therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518172China Key Laboratory of Carcinogenesis and translational research(Ministry of Education/Beijing) Department I of Thoracic OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Medical Department Nanjing Geneseeq Technology Inc.Nanjing 210061China Geneplus-Beijing Beijing 102200China 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 PathologyPeking University Cancer Hospital&InstituteBeijing 100142China

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its ***: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable ***: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive *** the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

关键词： Neuroendocrine carcinoma gastroenteropancreatic lung genetic alterations molecular markers

research progress on the development of hepatocyte growth factor/c-Met signaling pathway in gastric cancer:A review

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World Journal of gastrointestinal Oncology 2024年第8期16卷 3397-3409页

作者： Wu-Jie Wei Ya-Li Hong Yi Deng Guan-Liang Wang Jiang-Tao Qiu Fang Pan Department of Oncology People's Hospital of Chongqing HechuanChongqing 401520China Department of Cardiovascular People's Hospital of Chongqing HechuanChongqing 401520China Intensive Care unit People's Hospital of Chongqing HechuanChongqing 401520China Department of gastrointestinal Surgery Beijing Tsinghua Changgung HospitalBeijing 100084China

Hepatocyte growth factor(HGF)and its receptor,c-Met,play important roles in the occurrence,development,and treatment of gastric cancer(GC).This review explored the function of the HGF/c-Met signaling pathway in GC and its potential targeted therapeutic *** one of the most common malignant tumors worldwide,GC has a complex pathogenesis and limited therapeutic ***,a thorough understanding of the molecular mechanism of GC is very important for the development of new therapeutic *** HGF/c-Met signaling pathway plays an important role in the proliferation,migration,and invasion of GC cells and has become a new therapeutic *** review summarizes the current research progress on the role of HGF/c-Met in GC and discusses targeted therapeutic strategies targeting this signaling pathway,providing new ideas and directions for the treatment of GC.

关键词： Targeted therapy Hepatocyte growth factor c-Met Gastric cancer Prognosis assessment Review

Preoperative blood markers and intra-abdominal infection after colorectal cancer resection

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World Journal of gastrointestinal Surgery 2024年第2期16卷 451-462页

作者： Chang-Qing Liu Zhong-Bei Yu Jin-Xian Gan Tian-Ming Mei Department of gastrointestinal Anorectal Surgery Suzhou Hospital Affiliated to Anhui Medical UniversitySuzhou 234000Anhui ProvinceChina

BACKGROUND Colorectal cancer(CRC)has one of the highest morbidity and mortality rates among digestive tract ***-abdominal infection(IAI)is a common postoperative complication that affects the clinical outcomes of patients with CRC and hinders their rehabilitation ***,the factors influencing abdominal infection after CRC surgery remain unclear;further,prediction models are rarely used to analyze preoperative laboratory indicators and postoperative *** To explore the predictive value of preoperative blood markers for IAI after radical resection of *** The data of 80 patients who underwent radical resection of CRC in the Anorectal Surgery Department of Suzhou Hospital affiliated with Anhui Medical University were *** patients were categorized into IAI(n=15)and non-IAI groups(n=65)based on whether IAI *** factors were compared;general data and laboratory indices of both groups were *** relationship between the indicators was ***,a nomogram prediction model was developed and evaluated;its utility and clinical applic-ability were *** The risk factors for IAI after radical resection of CRC were neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),and carcinoembryonic antigen(CEA)*** was correlated with PLR and SII(r=0.604,0.925,and 0.305,respectively),while PLR was correlated with SII(r=0.787).The nomogram prediction model demonstrated an area under the curve of 0.968[95%confidence interval(CI):0.948-0.988]in the training set(n=60)and 0.926(95%CI:0.906-0.980)in the validation set(n=20).The average absolute errors of the calibration curves for the training and validation sets were 0.032 and 0.048,respectively,indicating a good model *** decision curve analysis curves demonstrated high net income above the 5%threshold,indicating the clinical practicality of the *** The nomogram model constructed

关键词： Radical resection of colorectal cancer Inflammatory factors Intra-abdominal infection Predictive model Blood markers

Clinical efficacy and pathological outcomes of transanal endoscopic intersphincteric resection for low rectal cancer

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World Journal of gastrointestinal Oncology 2024年第3期16卷 933-944页

作者： Zhi-Wen Xu Jing-Tao Zhu Hao-Yu Bai Xue-Jun Yu Qing-Qi Hong Jun You Department of gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361000Fujian ProvinceChina

BACKGROUND Transanal endoscopic intersphincteric resection(ISR)surgery currently lacks sufficient clinical research and *** To investigate the clinical effectiveness of transanal endoscopic ISR,in order to promote the clinical application and development of this *** This study utilized a retrospective case series *** and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were *** patients underwent transanal endoscopic ISR as the surgical *** conducted this study to determine the perioperative recovery status,postoperative complications,and pathological specimen charac-teristics of this group of *** This study included 45 eligible patients,with no perioperative *** overall incidence of early complications was 22.22%,with a rate of 4.44%for Clavien-Dindo grade≥III *** patients(4.4%)developed anastomotic leakage after surgery,including one case of grade A and one case of grade *** pathological examination confirmed negative circumferential resection margins and distal resection margins in all *** mean distance between the tumor lower margin and distal resection margin was found to be 2.30±0.62 *** transanal endoscopic ISR procedure consistently yielded high quality pathological *** Transanal endoscopic ISR is safe,feasible,and provides a clear anatomical *** is associated with a low incidence of postoperative complications and favorable pathological outcomes,making it worth further research and application.

关键词： Intersphincteric resection Transanal Rectal cancer Complications Endoscopic

Gut microbiota and female health

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World Journal of Gastroenterology 2024年第12期30卷 1655-1662页

作者： Meng-Yao Wang Li-Xuan Sang Si-Yu Sun Department of Gastroenterology Shengjing Hospital of China Medical UniversityShenyang 110022Liaoning ProvinceChina Department of Gastroenterology Endoscopic CenterEngineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic TechniquesShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina

The gut microbiota is recognized as an endocrine organ with the capacity to influence distant organs and associated biological *** advan-cements underscore the critical role of gut microbial homeostasis in female health;with dysbiosis potentially leading to diseases among women such as polycystic ovarian syndrome,endometriosis,breast cancer,cervical cancer,and ovarian cancer *** this,there has been limited discussion on the underlying *** editorial explores the three potential mechanisms through which gut microbiota dysbiosis may impact the development of diseases among women,namely,the immune system,the gut microbiota-estrogen axis,and the metabolite *** focused on approaches for treating diseases in women by addressing gut microbiota imbalances through probiotics,prebiotics supple-mentation,and fecal microbiota transplantation(FMT).Future studies should focus on determining the molecular mechanisms underlying associations between dysbiosis of gut microbiota and female diseases to realize precision medicine,with FMT emerging as a promising intervention.

关键词： Gut microbiota Female health Estrogen Polycystic ovarian syndrome Endometriosis

A Multimodal Critical Discourse Analysis of Lingnan Cultural Promotional Videos on Social Media

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Journal of Contemporary Educational research 2024年第4期8卷 59-68页

作者： Lu Jiang School of translation Studies Jinan UniversityZhuhai 519070Guangdong ProvinceChina

In recent years,more and more directors of culture and tourism have taken part in the promotion of local cultural tourism by cross-dressing,talent shows,and pushing their limits on self-media *** study investigates short videos of Lingnan culture promoted by directors general and deputy directors general of the Culture,Radio,Television,Tourism,and Sports Bureau of counties and cities in Guangdong Province on social media by the method of multimodal critical discourse *** analysis of 33 videos shows that Lingnan culture is a domineering and confident culture,historical culture,graceful and elegant culture,and vibrant and active *** and confident culture is embedded in the utterances and behaviors of the directors general or deputy directors general in the *** culture is realized through the conversation with historical figures through time *** and elegant culture is constructed in the depiction of sceneries and the depiction of characters’*** and active culture is represented in the depiction of the characters’actional process and analytical process.

关键词： Lingnan culture Multimodal critical discourse analysis Promotional videos TikTok WeChat

Identification and Validation of SLC9A2 as A Potential Tumor Suppressor in Colorectal Cancer:Integrating Bioinformatics Analysis with Experimental Confirmation

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Current Medical Science 2024年第3期44卷 529-544页

作者： Yan-min LIU Tie-cheng YANG Xiao-chang FANG Li-jie YANG Li-wen SHI Hua-qiao WANG Ting-ting DOU Lin SHU Tian-Liang CHEN Jun HU Xiao-ming YU Xuan-fei LI Department of Gastroenterology the Central Hospital of WuhanKey Laboratory for Molecular Diagnosis of Hubei ProvinceTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430014China Department of gastrointestinal Surgery Zhongnan Hospital of Wuhan UniversityWuhan430071China Clinical Medical research Center of Peritoneal Cancer of Wuhan Wuhan430071China Hubei Provincial Clinical research Center for Cancer Hubei Key Laboratory of Tumor Biological Behavi Wuhan430071China Department of General Surgery Taihe HospitalHubei University of MedicineShiyan442000China Department of gastrointestinal Surgery Huangshi Central HospitalAffiliated Hospital of Hubei Polytechnic UniversityWuhan435001China

Objective To uncover the mechanisms underlying the development of colorectal cancer(CRC),we applied bioinformatic analyses to identify key genes and experimentally validated their possible roles in CRC onset and *** We performed Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis on differentially expressed genes(DEGs),constructed a protein-protein interaction(PPI)network to find the top 10 hub genes,and analyzed their expression in colon adenocarcinoma(COAD)and rectum adenocarcinoma(READ).We also studied the correlation between these genes and immune cell infiltration and prognosis and validated the expression of SLC9A2 in CRC tissues and cell lines using qRT-PCR and Western *** experiments were conducted in vitro to investigate the effects of SLC9A2 on tumor growth and *** We found 130 DEGs,with 45 up-regulated and 85 down-regulated in *** analysis indicated that these DEGs were primarily enriched in functions related to the regulation of cellular pH,zymogen granules,and transmembrane transporter *** pathway analysis revealed that the DEGs played pivotal roles in pancreatic secretion,rheumatoid arthritis,and the IL-17 signaling *** identified 10 hub genes:CXCL1,SLC26A3,CXCL2,MMP7,MMP1,SLC9A2,SLC4A4,CLCA1,CLCA4,and *** enrichment analysis showed that these hub genes were predominantly involved in the positive regulation of *** expression analysis revealed that CXCL1,CXCL2,MMP1,and MMP7 were highly expressed in CRC,whereas CLCA1,CLCA4,SLC4A4,SLC9A2,SLC26A3,and ZG16 were expressed at lower *** analysis revealed that 5 key genes were significantly associated with the prognosis of *** mRNA and protein expression levels of SLC9A2 were markedly reduced in CRC tissues and cell ***,SLC9A2 overexpression in SW480 cells led to a notable inhibition of cell proliferation,migration,and *** blotting analysis revealed tha

关键词： SLC9A2 colorectal cancer bioinformatic analysis biomarkers immune infiltrate

Muscle strength and non-alcoholic fatty liver disease/metabolicassociated fatty liver disease

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World Journal of Gastroenterology 2024年第7期30卷 636-643页

作者： Xuan-Yu Hao Kai Zhang Xing-Yong Huang Fei Yang Si-Yu Sun Department of Gastroenterology Endoscopic CenterShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina Department of Gastroenterology Endoscopic CenterEngineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic TechniquesShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical ***,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle *** of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin *** studies have focused on the relationship between sarcopenia or muscle strength and ***,studies investigating the relationship between muscle strength and MAFLD are *** to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is ***,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.

关键词： Muscle strength Non-alcoholic fatty liver disease Metabolic-associated fatty liver disease Sarcopenia Insulin resistance Inflammation