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Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury

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Neural Regeneration Research 2024年第9期19卷 2010-2018页

作者： Yan Wang Dai Li Lan Zhang Zhenyu Yin Zhaoli Han Xintong Ge Meimei Li Jing Zhao Shishuang Zhang Yan Zuo Xiangyang Xiong Han Gao Qiang Liu Fanglian Chen Ping Lei Department of geriatrics Tianjin Medical University General HospitalTianjinChina Tianjin geriatrics institute Tianjin Medical University General HospitalTianjinChina Tianjin Neurological institute Tianjin Medical University General HospitalTianjinChina

We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain ***,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains *** this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of *** found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum ***,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured ***,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly *** findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum ***,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

关键词： apoptosis C/EBP homologous protein endoplasmic reticulum stress exosome inositol-requiring enzyme 1α microglia miR-124-3p neuron repetitive mild traumatic brain injury X-box binding protein 1

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PENG ZU Study on Healthy Aging in China(PENG ZU Cohort):Design and Goals

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China CDC weekly 2024年第34期6卷 876-882页

作者： Ju Cui Jing Pang Liqun Zhang Juan Li Xiaolan Wu Xinyi Zhu Wei Ma Senlin Luo Huafang Gao Zhao Wang Jianping Cai Tiemei Zhang The Key Laboratory of geriatrics Beijing Institute of GeriatricsInstitute of Geriatric MedicineChinese Academy of Medical ScienceBeijing Hospital/National Center of Gerontology of National Health CommissionBeijingChina Beijing institute of geriatrics Beijing HospitalBeijingChina institute of Geriatric Medicine Chinese Academy of Medical ScienceBeijing HospitalBeijingChina Center on Aging Psychology CAS Key Laboratory of Mental HealthInstitute of PsychologyChinese Academy of SciencesBeijingChina institute of Healthy Ageing China Research Center on AgeingBeijingChina institute of Statistics and Big Data Renmin University of ChinaBeijingChina Beijing institute of Technology BeijingChina National Human Genetic Resources Center National Research Institute for Family PlanningBeijingChina Department of Pharmacology School of Pharmaceutical SciencesTsinghua UniversityBeijingChina

Life expectancy is increasing,leading to the continuous aging of the population in *** the health status of the older population is crucial to achieving healthy *** primary objective of the PENG ZU Study on Healthy Aging in China(PENG ZU Cohort)is to understand the natural progression of health status among the aging Chinese ***,the PENG ZU cohort aims to identify and validate multidimensional aging markers,uncover the underlying mechanisms of systemic aging and functional decline,and develop novel strategies and measures to delay functional decline and adverse health outcomes,while maintaining overall good *** PENG ZU cohort consists of 26,000 individuals aged 25 to 89 years from seven major geographical regions in *** data and biospecimens are collected according to standardized procedures at baseline and follow-up *** recruitment for the PENG ZU cohort was completed in October *** extensive analysis of multidimensional health-related data and bioresources collected from the cohort is anticipated to develop methods for evaluating functional status and elucidating multilevel,cross-scale interactions and regulatory mechanisms of healthy *** findings from this study will enhance the understanding of health changes due to aging,facilitate efficient and effective interventions to maintain functional ability,and reduce the incidence and severity of age-related diseases,thereby further promoting healthy aging.

关键词： aging thereby maintain

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Cytogenetic Study on Couples with a History of Reproductive Failure in China

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Journal of Reproduction and Contraception 2009年第4期20卷 237-246页

作者： Ya-wen WANG Wei-tian HAN Chang-ji GUAN Ge WANG Xiao-quan ZHU Miao JIANG Chao-ying BIAN Jian-xin LI Ze YANG cytogenetics laboratry. geriatrics institute of ministo of Health. Beijing Hospital Beijing 100730 China The Key Laboratory of Reproductive Healthy of Liaoning Province Shenyang 110031 China

Objective To investigate the incidence of chromosome abnormalities in couples with reproductive failure in China and explore the relationship between chromosome abnormalities and reproductive failure.Methods A total of 2 158 couples with reproductive failure were enrolled. Lymphocyte culture and harvest were performed according to standard methods. Karyotypes were analyzed by G-banding in all cases and C-banding or R-banding in some cases if necessary.Results Altogether 137 abnormal karyotypes were found and the chromosomal abnormality rate was 3.17%. Among them 3 were numeral abnormalities, 134 were structural aberrations including 90 cases of reciprocal translocations, 34 cases of Roertsonian translocations, 9 cases of inversions, 1 case of deletion： and 43 kinds of which were identified as the first reported karyotypes in world by the National Teaching Center of Medical cytogenetics in Hunan, China. Totally 378 chromosome heteromorphisms were also detected and the rate was 8.76%.Conclusion Structural aberrations were the major abnormal karyotypes in couples with reproductive failure. Reciprocal and Robertsonian translocations occupied the largest proportions in structural aberrations, and a tendency that the rate of chromosome aberration increases with the times of miscarriages was presented. In addition, heteromorphism rate of chromosomes was high in such patients. Chromosome analysis is an important and necessary part of the etiological research in couples with reproductive failure.

关键词： chromosome abnormalities reproductive failure

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Microdeletion on Xq27.1 in a Chinese VACTERL-Like Family with Kidney and Anal Anomalies

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Biomedical and Environmental Sciences 2024年第5期37卷 503-510页

作者： LI Min ZHANG Yu Lan ZHANG Kai Li LI Ping Ping LYU Yu Han LIANG Ya Xin YU Yue Department of Gynecology and Obstetrics Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Chinese Academy of Medical Sciences and Peking Union Medical College Beijing HospitalBeijing 100730China The Key Laboratory of geriatrics Beijing Institute of GeriatricsBeijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China

Objective VATER/VACTERL-like association is associated with adverse pregnancy *** evidence of this disorder is *** this study,we aimed to provide genetic insights to improve the diagnosis of *** We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like *** and genetic analyses were conducted using genome and exome *** Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196–380 kb microdeletion on Xq27.1,which was identified by familial exome *** sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 *** family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in *** These results suggest that the 196–380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like ***,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.

关键词： Prenatal diagnosis VACTERL whole-genome sequencing whole-exome sequencing X-linked

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CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells,pulmonary microvascular endothelial cells,and pericytes under hypoxia

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Animal Models and Experimental Medicine 2024年第3期7卷 310-323页

作者： Xiaoyi Hu Shang Wang Hui Zhao Yaqin Wei Ruowang Duan Rong Jiang Wenhui Wu Qinhua Zhao Sugang Gong Lan Wang Jinming Liu Ping Yuan Department of Cardio-Pulmonary Circulation Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina institute of Bismuth Science University of Shanghai for Science and TechnologyShanghaiChina Department of geriatrics Shanghai Institute of GeriatricsHuadong HospitalFudan UniversityShanghaiChina Department of Anesthesiology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain ***,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under ***:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell *** analysis was used to predict their putative biological *** real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and ***:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,***1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular ***1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in ***:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.

关键词： circular postmeiotic segregation 1 circular RNAs hypoxia pulmonary hypertension vascular cells

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Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

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World Journal of Gastroenterology 2024年第8期30卷 855-862页

作者： Li-Hui Wang Bin-Bin Su Sheng-Shu Wang Guan-Chao Sun Kun-Ming Lv Yi Li Hui Shi Qian-Qian Chen College Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology Second Medical Center of Chinese PLA General HospitalBeijing 100853China institute of geriatrics The 2nd Medical CenterBeijing Key Laboratory of Aging and GeriatricsNational Clinical Research Center for Geriatrics DiseasesSecond Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse *** its risk factors is crucial to understanding the etiology,prevention,and management of the *** occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(***)infection,and metabolic *** To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,*** infection,and metabolic syndrome on reflux *** Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively *** patients’basic information,test results,gastroscopy results,*** test results,and IgG-mediated food intolerance results were *** logistic regression analysis was used to analyze risk factors for reflux *** mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on *** infection affecting reflux *** A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,*** infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,*** analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was *** infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on *** infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on *** infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intol

关键词： Gastroesophageal reflux Esophagitis Food intolerance Metabolic syndrome Helicobacter pylori Chemokines

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Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

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Neural Regeneration Research 2024年第2期19卷 440-446页

作者： Sumei Liu Baoguo Liu Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen Cell Therapy Center Beijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric Diseasesand Key Laboratory of Neurodegenerative DiseasesMinistry of EducationBeijingChina Center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina Center of Parkinson’s Disease Beijing Institute for Brain DisordersBeijingChina

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate *** a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury ***,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord *** neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury ***,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion *** of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the ***,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion ***-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

关键词： biomaterial fibrinogen functional recovery induced neural stem cell transplantation microenvironment microglia spinal cord injury thrombin

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Malnutrition Assessed Using the Geriatric Nutritional Risk Index Is Associated with Preoperative Incidence of Deep Vein Thrombosis in Japanese Patients Undergoing Total Knee Arthroplasty

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Open Journal of Orthopedics 2024年第8期14卷 355-365页

作者： Taizo Kaneko Kentaro Hayakawa Tsuyoshi Miyazaki Department of Orthopaedic Surgery Tokyo Metropolitan Institute for Geriatrics and Gerontology Tokyo Japan

Purpose: Few studies have evaluated the association between malnutrition and the risk of preoperative deep vein thrombosis (DVT) in patients undergoing primary total joint arthroplasty. This study aimed to investigate the prevalence of preoperative DVT in Japanese patients undergoing total knee arthroplasty (TKA) and the importance of malnutrition in the risk of preoperative DVT. Methods: We retrospectively analyzed 394 patients admitted for primary TKA at our institution between January 2019 and December 2023. All patients scheduled for TKA at our institution had serum D-dimer levels measured preoperatively. Lower-limb ultrasonography was examined to confirm the presence of DVT in patients with D-dimer levels ≥ 1.0 µg/mL or who were considered to be at high risk of DVT by the treating physician. Based on the results of lower-limb ultrasonography, all patients were divided into the non-DVT and DVT groups. The incidence of and risk factors for preoperative DVT were investigated, as well as the correlation of DVT with the patient’s nutritional parameters. We used two representative tools for nutritional assessment: the Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status Score. Results: The mean age was 77.8 ± 6.9 years. Preoperative DVT was diagnosed in 57 of the 394 (14.5%) patients. Multivariate logistic regression analysis showed that advanced age and malnutrition status, assessed using the GNRI, were independent risk factors for preoperative DVT. Conclusion: A high incidence of preoperative DVT was observed in patients who underwent TKA. Malnutrition status, as assessed using the GNRI, increased the risk of preoperative DVT. Our findings suggest that clinicians should consider these factors when tailoring preventive strategies to mitigate DVT risk in patients undergoing TKA.

关键词： Malnutrition Geriatric Nutritional Risk Index Controlling Nutritional Status Score Preoperative Deep Vein Thrombosis Total Knee Arthroplasty

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Malnutrition and Its Association with the Mortality of Patients with Femoral Intertrochanteric Fractures: A Retrospective Analysis of Japanese Patients

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Open Journal of Orthopedics 2024年第1期14卷 22-31页

作者： Taizo Kaneko Kyoko Matsudaira Kentaro Hayakawa Fumiaki Tokimura Tsuyoshi Miyazaki Department of Orthopaedic Surgery Tokyo Metropolitan Institute for Geriatrics and Gerontology Tokyo Japan

Background: The incidence of femoral intertrochanteric fractures in older adults is higher than that of femoral neck fractures;however, both conditions are often analyzed together as proximal femoral fractures. Considering the difference in treatment, postoperative complication, and mortality risk, these two fractures should be analyzed separately. This study aimed to analyze 1-year mortality and its risk factors in patients with surgically treated femoral intertrochanteric fractures. Methods: Consecutive patients with intertrochanteric fractures who underwent surgical interventions at our institution between January 2017 and December 2021 were retrospectively reviewed. A total of 238 patients were eligible for inclusion in this study. Patients’ demographic and clinical information were retrospectively collected. Patients were divided into the 1-year mortality (n = 16) and survival (n = 222) groups. The incidence of 1-year mortality and its independent risk factors were investigated using univariate and multivariate logistic regression analyses. Results: The mean age of patients was 85.6 ± 8.5 years. The 1-year mortality rate was 6.7% (16/238). Preoperative albumin level, the Geriatric Nutritional Risk Index (GNRI), and malnutrition status (GNRI p = 0.02, p = 0.02, and p = 0.0011, respectively). Multivariate analysis showed that malnutrition status (GNRI p = 0.035) was an independent risk factor for 1-year mortality. Conclusion: Malnutrition status assessed using GNRI (GNRI < 92) was an independent risk factor for 1-year mortality. Our findings suggest that GNRI may be an effective screening tool for predicting postoperative 1-year mortality of patients with surgically treated femoral intertrochanteric fractures.

关键词： Intertrochanteric Fracture Mortality Geriatric Nutritional Risk Index Malnutrition Risk Factor

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Decoding aging:examining the non-evolutionary event from an evolutionary perspective

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Science China(Life Sciences) 2024年第9期67卷 2026-2029页

作者： Yannan Guo Kang Xu Jianping Cai Zhao Wang Protein Science Key Laboratory of the Ministry of Education School of Pharmaceutical SciencesTsinghua UniversityBeijing 100084China Beijing institute of geriatrics Beijing HospitalNational Center of GerontologyNational Health CommissionBeijing 100730China

In an era marked by increased longevity,a deeper understanding of the older population is *** introducing an overlooked evolutionary perspective on aging,this article challenges traditional biogerontology,which primarily focuses on biological and clinical *** articulately differentiates between chronological and physiological aging,suggesting that aging is an evolutionary byproduct rather than a direct evolutionary event.

关键词： aging primarily evolutionary

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