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Early-life famine exposure,adulthood obesity patterns,and risk of low-energy fracture

Frontiers of Medicine 2024年第1期18卷 192-203页

作者： Hongyan Qi Chunyan Hu Jie Zhang Lin Lin Shuangyuan Wang Hong Lin Xiaojing Jia Yuanyue Zhu Yi Zhang Xueyan Wu Mian Li Min Xu Yu Xu Tiange Wang Zhiyun Zhao Weiqing Wang Yufang Bi Meng Dai Yuhong Chen Jieli Lu Department of Endocrine and metabolic diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai National Clinical Research center for Endocrine and metabolic diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People’s Republic of ChinaShanghai National Center for Translational MedicineRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains *** study included 5323 community-dwelling subjects aged⩾40 years from ***-life famine exposure was identified based on the participants’birth *** obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of⩾40 typically caused by falls from standing height or *** to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95%confidence intervals(CIs)of 3.55(1.57–8.05),3.90(1.57–9.71),and 3.53(1.05–11.88),respectively,but not in *** interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95%CI:3.32,1.17–9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.

关键词： famine obesity body mass index waist-to-hip ratio low-energy fracture

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Multi-omics analyses of G6PD deficiency variants in Chinese population

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Journal of Genetics and Genomics 2024年第1期51卷 100-104页

作者： He Ji Jiahuan Chen Peide Huang Zhimin Feng Weining Hu Mengyao Dai Xiaohui Sun Xiao Jin Guangquan Chen Guang Ning Lin Li Weiqing Wang Yanan Cao Department of Endocrine and metabolic diseases Shanghai Institute of Endocrine and Metabolic DiseasesNational Clinical Research Centre for Metabolic DiseasesState Key Laboratory of Medical GenomicsResearch Unit of Clinical and Basic Research on Metabolic Diseases of Chinese Academy of Medical SciencesRuijin Yangtze River Delta Health InstituteWuxi Branch of Ruijin HospitalRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China National Research center for Translational Medicine National Key Scientific Infrastructure for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China SJTU-BGI Innovation Research center Shanghai 200240China BGI-ShenZhen ShenzhenGuangdong 518083China

Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most prevalent hereditary and X-linked enzyme disorders caused by the pathogenetic G6PD(NM_001042351.2)variants(Yang et al.,2016).The clinical manifestations of G6PD deficiency offer a wide spectrum of diverse disease phenotypes(Hecker et al.,2013).Investigations of prevalence and molecular epidemiology demonstrate that G6PD deficiency affects over 400 milion individuals worldwide and leads to thousands of deaths annually(Mortality and Causes of Death,2015).

关键词： al. G6PD epidemiology

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Notch signaling pathway in cancer:from mechanistic insights to targeted therapies

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2527-2563页

作者： Qingmiao Shi Chen Xue Yifan Zeng Xin Yuan Qingfei Chu Shuwen Jiang Jinzhi Wang Yaqi Zhang Danhua Zhu Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Notch signaling,renowned for its role in regulating cell fate,organ development,and tissue homeostasis across metazoans,is highly conserved throughout *** Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences,typically necessitating receptor-ligand interaction to initiate classical Notch signaling *** evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer *** of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies,closely linked to cancer proliferation,invasion,and ***,the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells,thereby enhancing cancer *** regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive ***,the Notch signaling pathway is implicated in conferring chemoresistance to tumor ***,a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch *** review focuses on the research progress of the Notch signaling pathway in cancers,providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of ***,the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy,aiming to offer new insights into therapeutic strategies for human malignancies.

关键词： Notch invasion involvement

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Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment

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World Journal of Diabetes 2024年第4期15卷 735-757页

作者： Jing Gao Ying Zou Xiao-Yu Lv Li Chen Xin-Guo Hou Department of Endocrinology Qilu Hospital of Shandong UniversityCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina Institute of Endocrine and metabolic diseases Shandong UniversityJinan 250012Shandong ProvinceChina Key Laboratory of Endocrine and metabolic diseases Shandong Province Medicine&HealthJinan 250012Shandong ProvinceChina Department of Endocrinology Jinan Clinical Research Center for Endocrine and Metabolic DiseaseJinan 250012Shandong ProvinceChina

BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully ***-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the *** To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive *** To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database *** identify T2DM module genes,we used Weighted Gene Co-Expression Network *** the genes were subject to Gene Set Enrichment ***-protein interaction network construction and machine learning were utilized to identify three hub *** cell infiltration analysis was *** three hub genes were validated in GSE152539 via receiver operating characteristic curve *** experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in *** identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using *** taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were ***,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune *** three hub genes were validated in *** experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics ***,11 potential drugs associated with RAC3 and TFRC were identified based on the *** Immune-related genes that differ in expression in the hippocampus are closely linked to microgli

关键词： Bioinformatics analysis Type 2 diabetes mellitus Cognitive impairment Hippocampus Immune Microglia

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Clinical and molecular characterization of 10 Chinese children with congenital adrenal hyperplasia due to 11beta‑hydroxylase deficiency

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World Journal of Pediatrics 2024年第4期20卷 422-433页

作者： Wen‑Li Lu Xiao‑Yu Ma Jiao Zhang Jun‑Qi Wang Ting‑Ting Zhang Lei Ye Yuan Xiao Zhi‑Ya Dong Wei Wang Shou‑Yue Sun Chuan‑Yin Li Rong‑Gui Hu Guang Ning Li‑Dan Zhang Department of Pediatrics Ruijin HospitalShanghai Jiao Tong University School of MedicineNo.197Ruijin 2nd RdHuangpu DistrictShanghai 200025China Department of Pediatric Genetic and metabolic Endocrinology West China Second University HospitalSichuan UniversityNo.20Section 3Renmin South RoadSichuan 610041China Department of Endocrine and metabolic diseases Shanghai Clinical Center for Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Cancer center School of MedicineShanghai Tenth People’s HospitalTongji UniversityYanchang Zhong Lu 301St RdJing’an DistrictShanghai 200031China

Background The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of nonclassical 21-hydroxylase *** this study,we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature,which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal *** Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively *** examined the effects of gene mutations on protease activity and constructed threedimensional structure prediction models of *** We describe 10 patients with 11beta-hydroxylase gene mutations(n=5,46,XY;n=5,46,XX),with 10 novel mutations were *** patients received treatment at an early stage,with an average age of 2.08±1.66 years,whereas male patients received treatment significantly later,at an average age of 9.77±3.62 *** most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C>*** mutations lead to spatial conformational changes that affect protein *** Our study found that there was no significant correlation between each specific mutation and the severity of clinical *** patients with the same gene pathogenic variant may have mild or severe clinical *** correlation between genotype and phenotype needs further ***-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.

关键词： 11β-hydroxylase deficiency CYP11B1 Enzymatic activity Phenotype-genotype correlation Threedimensional protein simulations

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血糖控制良好患者发生糖尿病视网膜病变的生物标志物和治疗研究进展

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Science Bulletin 2024年第12期69卷 1799-1801页

作者： Yu A.An Department of Anesthesiology Critical Care and Pain MedicineMcGovern Medical SchoolHouston TX 77030USA Department of Biochemistry and Molecular Biology McGovern Medical SchoolHouston TX 77030USA center for metabolic and degenerative diseases The Brown Foundation Institute of Molecular MedicineThe University of Texas Health Science Center at HoustonHouston TX 77030USA

Diabetic retinopathy(DR)has exhibited a disconcerting surge over the past *** of 2021,global statistics indicate that over 537 million individuals were living with DR[1].With the diabetic population continually expanding,it is foreseen that the incidence of DR will soar to an estimated 800 million individuals worldwide by the year 2045[2].

关键词：糖尿病视网膜病变生物标志物 expanding

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Omics for deciphering oral microecology

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International Journal of Oral Science 2024年第2期16卷 197-207页

作者： Yongwang Lin Xiaoyue Liang Zhengyi Li Tao Gong Biao Ren Yuqing Li Xian Peng State Key Laboratory of Oral diseases&National center for Stomatology&National Clinical Research center for Oral diseases West China Hospital of StomatologySichuan UniversityChengduChina

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic *** technological innovations are propelling the characterization and manipulation of oral ***-throughput sequencing enables comprehensive taxonomic and functional profiling of oral *** long-read platforms improve genome assembly from complex ***-cell genomics provides insights into uncultured *** imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing *** techniques link phylogenetic identity with *** spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for *** facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput *** integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and ***,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic *** convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

关键词： insight holds oral

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Mitochondrial dysfunction: A promising therapeutic target for liver diseases

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Genes & diseases 2024年第3期11卷 324-337页

作者： Ping Chen Lichao Yao Mengqin Yuan Zheng Wang Qiuling Zhang Yingan Jiang Lanjuan Li Department of Infectious diseases Renmin Hospital of Wuhan UniversityWuhanHubei 430060China State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiang 310003China

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the *** tissues of pa-tients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mito-chondrial lesions,mitochondrial DNA damage,disturbed mitochondrial dynamics,and compromised ATP *** of mitochondrial reactive oxygen species in-duces oxidative damage to mitochondrial proteins and mitochondrial DNA,decreases mito-chondrial membrane potential,triggers hepatocyte inflammation,and promotes programmed cell death,all of which impair liver *** DNA may be a poten-tial novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B *** herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases,such as hepatocellular carcinoma,viral hepatitis,drug-induced liver injury,alcoholic liver disease,and non-alcoholic fatty liver *** review also discusses mito-chondrion-centric therapies for treating liver diseases.

关键词： Chronic diseases Liverdamage Mesenchymalstem cell Mitochondrial dysfunction Oxidativestress

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Mechanism of action of the bile acid receptor TGR5 in obesity

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Acta Pharmaceutica Sinica B 2024年第2期14卷 468-491页

作者： Weijun Lun Qihao Yan Xinghua Guo Minchuan Zhou Yan Bai Jincan He Hua Cao Qishi Che Jiao Guo Zhengquan Su Guangdong Engineering Research center of Natural Products and New Drugs Guangdong Provincial University Engineering Technology Research Center of Natural Products and DrugsGuangdong Pharmaceutical UniversityGuangzhou 510006China Guangdong metabolic Disease Research center of Integrated Chinese and Western Medicine Key Laboratory of Glucolipid Metabolic DisorderMinistry of Education of ChinaGuangdong TCM Key Laboratory for Metabolic DiseasesGuangdong Pharmaceutical UniversityGuangzhou 510006China School of Public Health Guangdong Pharmaceutical UniversityGuangzhou 510310China School of Chemistry and Chemical Engineering Guangdong Pharmaceutical UniversityZhongshan 528458China Guangzhou Rainhome Pharm&Tech Co. Ltd.Science CityGuangzhou 510663China

G protein-coupled receptors(GPCRs)are a large family of membrane protein receptors,and Takeda G protein-coupled receptor 5(TGR5)is a member of this *** a membrane receptor,TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism,including the processes of energy consumption,weight loss and blood glucose *** studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver,obesity and *** the global obesity situation becoming more and more serious,a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently *** this review,we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target,and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands,which can effectively provide new ideas for ligand research and promote drug research.

关键词： Obesity TGR5 Bile acids Ligand Appetite Metabolism GLP-1 Inflammation

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Enhanced wear resistance,antibacterial performance,and biocompatibility using nanotubes containing nano-Ag and bioceramics in vitro

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Bio-Design and Manufacturing 2024年第5期7卷 670-686页

作者： Qingge Wang Jia Liu Hong Wu Jingbo Liu Yaojia Ren Luxin Liang Xinxin Yan Ian Baker Shifeng Liu V.V.Uglov Chengliang Yang Liqiang Wang State Key Laboratory of Powder Metallurgy Central South UniversityChangsha 410083China Affiliated Hospital of Youjiang Medical University for Nationalities Guangxi Key Laboratory for Preclinical and Translational Research on Bone and Joint Degenerative DiseasesGuangxi Zhuang Autonomous Region Engineering Research Center for Biomaterials in Bone and Joint Degenerative DiseasesGuangxi Key Laboratory for Biomedical Material ResearchBaise 533000China Department of Orthopedics The Second Xiangya HospitalCentral South UniversityChangsha 410011China Department of Orthopedics Renmin HospitalWuhan UniversityWuhan 430060China Thayer School of Engineering Dartmouth CollegeHanoverNH 03755-8000USA School of Metallurgical Engineering Xi’an University of Architecture and TechnologyXi’an 710055China Belarusian State University 220030 MinskBelarus State Key Laboratory of Metal Matrix Composites School of Material Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240China

A good Ti-based joint implant should prevent stress shielding and achieve good bioactivity and anti-infection *** meet these requirements,the low-elastic-modulus alloy—Ti–35Nb–2Ta–3Zr—was used as the substrate,and functional coatings that contained bioceramics and Ag ions were prepared for coating on TiO_(2)nanotubes(diameter:(80±20)nm and(150±40)nm)using anodization,deposition,and spin-coating *** effects of the bioceramics(nano-β-tricalcium phosphate,microhydroxyapatite(micro-HA),and meso-CaSiO_(3))and Ag nanoparticles(size:(50±20)nm)on the antibacterial activity and the tribocorrosion,corrosion,and early in vitro osteogenic behaviors of the nanotubes were *** tribocorrosion and corrosion results showed that the wear rate and corrosive rate were highly dependent on the features of the nanotube ***-HA showed great wear resistance with a wear rate of(1.26±0.06)×10^(−3)mm^(3)/(N·m)due to adhesive and ***-CaSiO_(3)showed enhanced cell adhesion,proliferation,and alkaline phosphatase *** coatings that contained nano-Ag exhibited good antibacterial activity with an antibacterial rate of≥89.5%against Escherichia *** findings indicate that hybrid coatings may have the potential to accelerate osteogenesis.

关键词： βTi alloy Surface modification Wear resistance Corrosion resistance Osteogenic behavior Antibacterial activity

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