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Role of tissue microenvironment resident adipocytes in colon cancer

World Journal of Gastroenterology 2017年第32期23卷 5829-5835页

作者： Maria Tabuso Shervanthi Homer-Vanniasinkam Raghu Adya Ramesh P Arasaradnam Department of Gastro-enterology University Hospitals Coventry and Warwickshire Warwick Medical School University of Warwick leeds institute of car-diovascular and metabolic medicine Faulty of Medicine and HealthUniversity of Leeds Division of Surgical and Interventional Sciences UCL Medical School Building Applied Biological and Experimental Sciences University of Coventry

Colorectal cancer(CRC) is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells. It is increasingly recognized that tumour progression is also regulated by tumour microenvironment(TME). The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis. Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors(angiogenic/inflammatory/immune) which contribute to cancer cell proliferation, invasion, neoangiogenesis, evasion of immune surveillance and therapy resistance. Furthermore, adipocytes represent a fuel rich source for increasing energy demand of rapidly proliferating tumour cells. Interestingly, a relationship between obesity and molecular variants in CRC has recently been identified. Whether adipose tissue promotes cancer progression in subsets of molecular phenotypes or whether local tissue adipocytes are involved in inactivation of tumour suppressor genes and/or activation of oncogenes still needs to be explored. This editorial highlights the major findings related to crosstalk between adipocytes and colon cancer cells and how local paracrine interactions may promote cancer progression. Furthermore, we provide future strategies in studying colonic TME which could provide insights in bidirectional cross-talk mechanisms between adipocytes and colonic epithelial cells. This could enable to decipher critical signalling pathways of both early colonic carcinogenesis and cancer progression.

关键词： Tumour resident adipocytes Dysfunctional adipocytes Adipose tissue Cancer cell-tumour resident adipocyte cross-talk Colon cancer microenvironment

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Combining GLP-1 receptor agonists and SGLT-2 inhibitors for cardiovascular disease prevention in type 2 diabetes:A systematic review with multiple network meta-regressions

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World Journal of Diabetes 2024年第10期15卷 2135-2146页

作者： Jing-Jing Zhu John P H Wilding Xiao-Song Gu Department of Endocrinology and metabolic medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215004Jiangsu ProvinceChina Department of cardiovascular and metabolic medicine University of LiverpoolLiverpool L697ZXUnited Kingdom Clinical Sciences Centre Liverpool University Hospitals NHS Foundation TrustLiverpool L97ALUnited Kingdom Department of cardiovascular medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215004Jiangsu ProvinceChina

BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are associated with significant cardiovascular benefit in type 2 diabetes(T2D).However,GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular *** To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in *** The systematic review was conducted according to PRISMA *** protocol was registered on PROSPERO(ID:42022385007).A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination *** modification of prior myocardial infarction(MI)and heart failure(HF)was also explored to provide clinical insight as to when the INTRODUCTION The macro-and micro-vascular benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are independent of their glucose-lowering effects[1].In patients with type 2 diabetes(T2D),the major cardiovascular outcome trials(CVOT)showed that dipeptidyl peptidase-4 inhibitors(DPP-4I)did not improve cardiovascular outcomes[2],whereas cardiovascular benefit of GLP-1RA or SGLT-2I was significant[3,4].Further subgroup analyses indicated that the background cardiovascular risk should be considered when examining the cardiovascular outcomes of these newer glucose-lowering *** instance,prevention of major adverse cardiovascular events(MACE)was only seen in those patients with baseline atherosclerotic cardiovascular disease[3,4].Moreover,a series of CVOT conducted in patients with heart failure(HF)have demonstrated that(compared with placebo)SGLT-2I significantly reduced risk of hospitalization for HF or cardiovascular death,irrespective of their history of T2D[5-8].However,similar car

关键词： Type 2 diabetes Glucagon-like peptide-1 receptor agonist Sodium-glucose co-transporter-2 inhibitor Combination treatment cardiovascular outcome Systematic review Network meta-regression

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基于大语言模型的糖尿病管理:潜力与展望

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Science Bulletin 2024年第5期69卷 583-588页

作者：盛斌管洲榆 Lee-Ling Lim 江泽铧 Nestoras Mathioudakis 李佳佳刘茹涵包玉倩 Yong Mong Bee 王亚星郑颖丰 Gavin Siew Wei Tan 纪宏伟 Josip car 王海波 David C.Klonoff 李华婷覃宇宗黄天荫贾伟平 Shanghai International Joint Laboratory of Intelligent Prevention and Treatment for metabolic Diseases Department of Computer Science and EngineeringSchool of ElectronicInformationand Electrical EngineeringShanghai Jiao Tong UniversityDepartment of Endocrinology and MetabolismShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Diabetes InstituteShanghai Clinical Center for DiabetesShanghai 200240China MOE Key Laboratory of Artificial Intelligence Artificial Intelligence InstituteShanghai Jiao Tong UniversityShanghai 200240China Department of medicine Faculty of MedicineUniversity of MalayaKuala Lumpur 50603Malaysia Department of medicine and Therapeutics The Chinese University of Hong KongHong KongChina Asia Diabetes Foundation Hong KongChina Tsinghua medicine of Tsinghua University Beijing 100084China School of Clinical medicine Beijing Tsinghua Changgung HospitalBeijing 102218China Division of Endocrinology Diabetes&MetabolismJohns Hopkins University School of MedicineBaltimoreMD 21211USA Department of Endocrinology Singapore General HospitalSingapore 169608Singapore Beijing institute of Ophthalmology Beijing Tongren HospitalCapital University of Medical ScienceBeijing Ophthalmology and Visual Sciences Key LaboratoryBeijing 100730China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060China Singapore Eye Research institute Singapore National Eye CentreSingapore 168751Singapore Department of cardiology the Affiliated Hospital of Qingdao UniversityQingdao 266011China Centre for Population Health Sciences Lee Kong Chian School of MedicineNanyang Technological University SingaporeSingapore 639798Singapore Department of Primary care and Public Health School of Public HealthImperial College LondonLondon SW72BUUK Clinical Trial Unit Research Centre of Big Data and Artificial Intelligence in Medicine

The increasing prevalence of diabetes has become a global public health concern in the 21st *** 2021,it was estimated that 537 million people had diabetes,and this number is projected to reach 643 million by 2030,and 783 million by 2045[1].Such a huge burden of diabetes brings great challenges in its prevention and management,including early diagnosis,timely interventions,and regular monitoring of risk factor control and complications *** self-care support and patient empowerment can enhance clinical and psychobehavioural outcomes[2],although these require additional resources including manpower,infrastructure(hard and technology),and *** emergence of digital health technologies(DHTs),especially artificial intelligence(AI),may help address these obstacles and alleviate the burden of diabetes[3].Large language models(LLMs),a generative AI that can accept image and text inputs and produce text outputs,have shown promise in various aspects of medical care.

关键词： prevention diagnosis finance

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Clinical characteristics of patients readmitted for stroke with double anti-platelet therapy after percutaneous coronary intervention

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South China Journal of cardiology 2014年第4期15卷 227-230,237页

作者： WANG Ling RAN Peng CAI An-ping CHEN Ji-yan Department of cardiology Guangdong Provincial Car-diovascular Institute Guangdong General Hospital/Guangdong Academy of Medical Sciences

Background The clinical characteristics of stroke patients treated with double anti-platelet therapy （DAPT） after percutaneous coronary intervention （PCI） is not clear. Methods In total, 2675 patients under- went PCI and DAPT in Guangdong General Hospital, and 68 out of them were hospitalized due to suspected stroke, of whom 23 were diagnosed as having stroke. Data of the 23 stroke patients were collected and tradi- tional risk factors associated with stroke were analyzed retrospectively. Results The mean age of these pa- tients was 75.6± 8.7 years, and 20 （87.0%） were males. Notably, 19 patients were complicated with hyper- tension, 7 with diabetes mellitus, 7 with previous history of stroke, none with atrial fibrillation （AF） or patent foramen ovale （PFO）. Specifically, 22 patients were diagnosed with ischemic stroke, and 1 patient with hemorrhagic stroke. Conclusion Stroke in patients treated with DAPT after PCI was correlated with ad- vanced age, gender, hypertension, diabetes mellitus, stroke history. Long term electrocardiography （ECG） may be needed for the diagnosis of AF, while trans-esophageal echocardiography （TEE） may be needed for PFO.

关键词： percutaneous coronary intervention double anti-platelet therapy stroke clinical characteris-tics

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Zinc lactate alleviates oxidative stress by modulating crosstalk between constitutive androstane receptor signaling pathway and gut microbiota profile in weaned piglets

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Animal Nutrition 2024年第1期16卷 23-33页

作者： Wenjie Tang Xuan Xiang Houfu Wang Wentao Zhou Liuqin He Yulong Yin Tiejun Li College of Animal Science and Technology Hunan Agricultural UniversityChangsha 410128China Hunan Provincial Key Laboratory of Animal Nutritional Physiology and metabolic Process CAS Key Laboratory of Agro-Ecological Processes in Subtropical RegionNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation Laboratory of Animal Nutrition and Human HealthCollege of Life SciencesHunan Normal UniversityChangsha 410081China College of Advanced Agricultural Science University of Chinese Academy of SciencesBeijing 100049China Sichuan Academy of Animal Sciences Animal Breeding and Genetics Key Laboratory of Sichuan ProvinceChengdu 610066China Livestock and Poultry Biological Products Key Laboratory of Sichuan Province Sichuan Animtech Feed Co.LtdChengdu 610000China

This study aimed to determine the regulatory mechanism of dietary zinc lactate(ZL)supplementation on intestinal oxidative stress damage in a paraquat(PQ)-induced piglet ***-eight piglets(mean body weight 9.51±0.23 kg)weaned at 28 d of age were randomly divided into control,ZL,PQ,and ZL+PQ groups(n=7 in each group).The ZL-supplemented diet had little effect on growth performance under normal physiological ***,under PQ challenge,ZL supplementation significantly improved average daily gain(Pcar)signaling(Pcar signaling and gut microbiota.

关键词： Zinc lactate Intestinal barrier Oxidative stress Inflammation Constitutive androstane receptor Gut microbiota

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car-T overdrive:harnessing inosine for metabolic rewiring and stemness induction

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2347-2348页

作者： MartíFarrera-Sal Michael Schmueck-Henneresse Berlin institute of Health(BIH)at Charité—Universitatsmedizin Berlin BIH Center for Regenerative Therapies(BCRT)Experimental ImmunotherapyAugustenburger Platz 1BerlinGermany

In a recent Cancer Cell publication,Klysz et *** the impact of inosine(INO),a catabolic product of adenosine(Ado),on Chimeric Antigen Receptor(car)T-cell function,stemness,and *** provided insights into T-cell exhaust... 详细信息

关键词： programming. car Ado

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Predictive value of neutrophil-to-lymphocyte ratio in coronary chronic total occlusion patients

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Journal of Geriatric cardiology 2024年第5期21卷 542-549页

作者： Qian LI Yue YU Ya-Qiong ZHOU Yi ZHAO Jin WU Yuan-Jing WU Bin DU Pei-Jian WANG Tao ZHENG Department of cardiovascular medicine the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina Department of cardiology First Affiliated Hospital of Chengdu Medical CollegeChengduChina Department of Neurology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina

BACKGROUND The neutrophil to lymphocyte ratio(NLR)has been reported as a novel predictor for atherosclerosis and car-diovascular *** study aimed to determine the effects of NLR on long-term clinical outcomes of chronic total occlusion(CTO)*** A total of 670 patients with CTO who met the inclusion criteria were included at the end of the follow-up *** were divided into tertiles according to their baseline NLR levels at admission:low(n=223),intermediate(n=223),and high(n=224).The incidence of major adverse cardiac events(MACEs)during the follow-up period,including all-cause death,nonfatal myocardial infarction(MI),or ischemia-driven revascularization,were compared among the three *** Major adverse cardiac events were observed in 27 patients(12.1%)in the low tertile,40(17.9%)in the intermediate tertile,and 61(27.2%)in the high NLR tertile(Pcardiovascular risk in patients with CTO.

关键词： patients coronary occlusion

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Current status and perspectives of regulatory T cell-based therapy

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Journal of Genetics and Genomics 2022年第7期49卷 599-611页

作者： Guojun Qu Jieqiong Chen Yangyang Li Yaqin Yuan Rui Liang Bin Li Shanghai institute of Immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200025China Shanghai Affinity Biopharmaceutical Co. Ltd.781 Cailun RoadShanghai 201203China Unit of Immune and metabolic Regulation School of Life Science and TechnologyShanghaiTech UniversityShanghai 201210China

The CD4FOXP3regulatory T(Treg)cells are essential for maintaining immune homeostasis in healthy *** from clinical trials of Treg cell-based therapies in patients with graft versus host disease(GVHD),type 1 diabetes(T1D),liver transplantation,and kidney transplantation have demonstrated that adoptive transfer of Treg cells is emerging as a promising strategy to promote immune *** we provide an overview of recent progresses and current challenges of Treg cell-based *** summarize the completed and ongoing clinical trials with human Treg ***,a few of the chimeric antigen receptor(car)-Treg cell therapies are currently undergoing clinical ***,we describe the new strategies for engineering Treg cells used in preclinical ***,we envision that the use of novel synthetic receptors,metabolic regulators,combined therapies,and in vivo generated antigen-specific or engineered Treg cells through the delivery of modified mRNA and CRISPR-based gene editing will further promote the advances of next-generation Treg cell therapies.

关键词： Regulatory T cell FOXP3 Chimeric antigen receptor Cell therapy CRISPR-Based gene editing mRNA-based therapy

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Gadd45b is required in part for the anti-obesity effect of constitutive androstane receptor(car)

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Acta Pharmaceutica Sinica B 2021年第2期11卷 434-441页

作者： Xinran Cai Ye Feng Meishu Xu Chaohui Yu Wen Xie Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Department of Endocrinology and metabolic Disease the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Gastroenterology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Pharmacology and Chemical Biology University of PittsburghPittsburghPA 15261USA

Crosstalk between xenobiotic metabolism and energy metabolism in the liver has provided a potential opportunity to target xenobiotic receptors to treat metabolic *** of constitutive andro stane receptor(car),a xenobiotic-sensing nuclear receptor,has been shown to inhibit obesity,suppress hepatic gluconeogenesis,and ameliorate hyperglycemia in rodent models of obesity and type 2 ***,the underlying molecular mechanism remains to be *** growth arrest and DNA damage-inducible gene 45 b(Gadd45 b),a well-known anti-apoptotic factor,has been shown to be an inducible coactivator of car in promoting rapid liver *** is unknown whether the effect of car on energy metabolism depends on GADD45 *** the present study and by using a high fat diet(HFD)-induced obesity model,we show that reduced body weight gain and improved insulin sensitivity by the car agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene(TCPOBOP)were markedly blunted in Gadd45 b knockout ***,the TCPOBOP-responsive inhibition of hepatic lipogenesis,gluconeogenesis,and adipose inflammation observed in wild type mice were largely abolished in Gadd45 b knockout *** conclude that Gadd45 b is required in part for the metabolic benefits of car activation.

关键词： Obesity Diabetes car Gadd45b Glucogenogenesis Lipogenesis Xenobiotics Nuclear receptor

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Physical Activity,Sedentary Behavior,and the Risk of cardiovascular Disease in Type 2 Diabetes Mellitus Patients:The MIDiab Study

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Engineering 2023年第1期20卷 26-35页

作者： Yafei Wu Guijun Qin Guixia Wang Libin Liu Bing Chen Qingbo Guan Zhongshang Yuan Xu Hou Ling Gao Chao Xu Haiqing Zhang Xu Zhang Qiu Li Yongfeng Song Fei Jing Shizhan Ma Shanshan Shao Meng Zhao Qingling Guo Nanwei Tong Hongyan Zhao Xiaomin Xie Chao Liu Zhongyan Shan Zhifeng Cheng Xuefeng Yu Shulin Chen Tao Yang Yangang Wang Dongmei Li Zhaoli Yan Lixin Guo Qiuhe Ji Wenjuan Wang Jiajun Zhao Department of Endocrinology&Shandong Clinical Research Center of Diabetes and metabolic Diseases Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China Shandong Key Laboratory of Endocrinology and Lipid Metabolism&Shandong Prevention and Control Engineering Laboratory of Endocrine and metabolic Diseases Shandong First Medical UniversityJinan 250021China Department of Endocrine and metabolic Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Endocrinology and Metabolism First Hospital of Jilin UniversityChangchun 130021China Department of Endocrinology and Metabolism Fujian Medical University Union HospitalFuzhou 350001China Endocrinology Department The Southwest Hospital of AMUChongqing 400038China Department of Biostatistics School of Public HealthShandong UniversityJinan 250012China Department of Endocrinology and Metabolism West China Hospital of Sichuan UniversityChengdu 610041China Department of Endocrine and metabolic Diseases Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200020China Department of Endocrinology The First People’s Hospital of YinchuanYinchuan 750001China Department of Endocrinology Nanjing Integrated Traditional Chinese and Western Medicine Hospital(the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine)Nanjing 210046China Department of Endocrinology and Metabolism&institute of Endocrinology the First Hospital of China Medical UniversityShenyang 110000China Department of Endocrinology the Fourth Affiliated Hospital of Harbin Medical UniversityHarbin 150001China Division of Endocrinology Department of Internal MedicineTongji HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhan 430030China Department of Endocrinology Yantai Yuhuangding Hospital Affiliated to Qingdao University Medical CollegeYantai 264000China Department of Endocrinology the First Affiliated Hospital of Nanjing Medical University

The aim of this study was to explore the associations of moderate-to-vigorous-intensity physical activity(MVPA)time and sedentary(SED)time with a history of cardiovascular disease(CVD)and multifactorial(i.e.,blood pressure(BP),body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),and glycated hemoglobin A1c(HbA1c))control status among type 2 diabetes mellitus(T2DM)patients in China.A cross-sectional analysis of 9152 people with type 2 diabetes from the Multifactorial Intervention on Type 2 Diabetes(MIDiab)study was *** were grouped according to their self-reported MVPA time(low,<150 min·week−1;moderate,150 to<450 min·week−1;high,≥450 min·week−1)and SED time(low,<4 h·d–1;moderate,4 to<8 h·d–1;high,≥8 h·d–1).Participants who self-reported a history of CVD were identified as having a CVD *** ratios(ORs)and 95%confidence intervals(CIs)of CVD risk and multifactorial control status associated with MVPA time and SED time were estimated using mixed-effect logistic regression models,adjusting for China’s geographical region *** participants had a mean±standard deviation(SD)age of(60.87±8.44)years,44.5%were women,and 25.1%had *** adjustment for potential confounding factors,an inverse association between high MVPA time and CVD risk that was independent of SED time was found,whereas this association was not observed in the moderate-MVPA group.A higher MVPA time was more likely to have a positive effect on the control of *** with the reference group(i.e.,those with MVPA time≥450 min·week−1 and SED time<4 h·d–1),CVD risk was higher in the low-MVPA group:The OR associated with an SED time<4 h·d–1 was 1.270(95%CI,1.040–1.553)and that associated with an SED time≥8 h·d–1 was 1.499(95%CI,1.149–1.955).We found that a high MVPA time(i.e.,≥450 min·week−1)was associated with lower odds of CVD risk regardless of SED time among patients with T2DM.

关键词： Type 2 diabetes Physical activity Sedentary time car diovascular disease

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