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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Henan Key Laboratory of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British research Centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

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Clinical value of needleless sling in treatment of female stress urinary incontinence

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World Journal of Clinical Cases 2020年第18期8卷 4043-4050页

作者： Yu-Guo Chen Yao-Guang Zhang Wei Zhang Xin Li Xia Wang Dressing Room of Surgical Outpatient Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Department of Urology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Nursing Department Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China

BACKGROUND Stress urinary incontinence(SUI)is a common disease in *** emergence of the needle-free sling has led to a new clinical treatment for SUI in *** To explore the clinical value of the needleless sling without acupuncture in the treatment of SUI in *** From February 2017 to November 2018,according to the order of admission,44 patients(mid-suspension group)were treated by tension-free transobturator urethral suspension,and 44 patients(non-acupuncture group)were treated with a needleless non-acupuncture *** clinical effects of the two treatments were *** There was no significant difference between the two groups in the total clinical effectiveness rate(P=0.374),but intraoperative blood loss and visual analogue scale score at postoperative day 1 were significantly lower in the non-acupuncture suspension group than in the middle urethral suspension group(P=0.396).The incidence of complications in the needle-free sling group was significantly lower than that in the middle urethral suspension group(P=0.025).CONCLUSION The clinical effectiveness of acupuncture-free suspension in treating SUI in female patients is better than that of traditional tension-free transobturator mid-urethral suspension.

关键词： No needle sling Female stress urinary incontinence Mid-urethral suspension Controlled study Complications Application value

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Phosphorylation of Cofilin-1 Enhances Paclitaxel Resistance of Epithelial Ovarian Cancer Cells by Inhibiting Apoptosis

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Biomedical and Environmental Sciences 2021年第6期34卷 465-477页

作者： LI Min DONG Xu Dong LYU Qiu Bo ZHANG Wei HUANG Shuai YANG Chun Xue CUI Di LAI Hui Ying Department of Obstetrics and Gynecology Beijing Hospital National Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Department of Obstetrics the First People's Hospital of Yunnan ProvinceKunming 650032YunnanChina Department of Pathology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Peking University Health Science Center Beijing 100069China Clinical Laboratory Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China

Objective To investigate the molecular mechanism of high phosphorylation levels of cofilin-1(p-CFL-1)associated with paclitaxel resistance in epithelial ovarian cancer(EOC)*** Cells displaying varying levels of p-CFL-1 and CFL-1 were created by plasmid transfection and shRNA *** inhibition rate indicating paclitaxel efficacy was assessed by Cell Counting Kit-8(CCK-8)*** was assessed by flow cytometry and protein levels were detected by western *** real-time polymerase chain reaction(qRT-PCR)was used to measure the expression levels of phosphokinases and phosphatases of *** analysis evaluated the correlation between the prognosis of EOC patients and the levels of p-CFL-1 and slingshot-1(SSH-1).Results High levels of p-CFL-1 were observed in EOC cells that survived treatment with high doses of ***3 cell mutants with upregulated p-CFL-1 showed impaired paclitaxel efficacy,as well as decreased apoptosis rates and pro-survival patterns of apoptosis-specific protein *** accumulation of p-CFL-1 inhibited paclitaxel-induced mitochondrial ***-1 silencing mediated CFL-1 phosphorylation in paclitaxel-resistant SKOV3 ***,the high level of p-CFL-1 and the low level of SSH-1 in EOC tissues were closely related to chemotherapy resistance and poor prognosis in EOC *** The SSH-1/p-CFL-1 signaling pathway mediates paclitaxel resistance by apoptosis inhibition in EOC and is expected to be a potential prognostic predictor.

关键词： Cofilin-1 Slingshot-1 Epithelial ovarian cancer Chemo-resistance Apoptosis

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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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Aging and aging-related diseases:from molecular mechanisms to interventions and treatments

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Signal Transduction and Targeted Therapy 2023年第1期8卷 77-116页

作者： Jun Guo Xiuqing Huang Lin Dou Mingjing Yan Tao Shen Weiqing Tang Jian Li The Key Laboratory of Geriatrics Beijing Institute of GeriatricsInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing Hospital/National Center of Gerontology of National Health CommissionBeijing 100730China

Aging is a gradual and irreversible pathophysiological *** presents with declines in tissue and cell functions and significant increases in the risks of various aging-related diseases,including neurodegenerative diseases,cardiovascular diseases,metabolic diseases,musculoskeletal diseases,and immune system *** the development of modern medicine has promoted human health and greatly extended life expectancy,with the aging of society,a variety of chronic diseases have gradually become the most important causes of disability and death in elderly *** research on aging focuses on elucidating how various endogenous and exogenous stresses(such as genomic instability,telomere dysfunction,epigenetic alterations,loss of proteostasis,compromise of autophagy,mitochondrial dysfunction,cellular senescence,stem cell exhaustion,altered intercellular communication,deregulated nutrient sensing)participate in the regulation of ***,thorough research on the pathogenesis of aging to identify interventions that promote health and longevity(such as caloric restriction,microbiota transplantation,and nutritional intervention)and clinical treatment methods for aging-related diseases(depletion of senescent cells,stem cell therapy,antioxidative and anti-inflammatory treatments,and hormone replacement therapy)could decrease the incidence and development of aging-related diseases and in turn promote healthy aging and longevity.

关键词： diseases alterations aging

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Cognitive magnetic resonance imaging-ultrasound fusion transperineal targeted biopsy combined with randomized biopsy in detection of prostate cancer

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World Journal of Clinical Cases 2021年第36期9卷 11183-11192页

作者： Cheng Pang Miao Wang Hui-Min Hou Jian-Yong Liu Zhi-Peng Zhang Xuan Wang Ya-Qun Zhang Chun-Mei Li Wei Zhang Jian-Ye Wang Ming Liu Department of Urology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Graduate School of Peking Union Medical College Chinese Academy of Medical SciencesBeijing 100730China Department of Radiology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730BeijingChina Department of Pathology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730BeijingChina

BACKGROUND Prostate cancer(PCa)is one of the most common cancers among *** strategies for targeted biopsy based on multiparametric magnetic resonance imaging(mp-MRI)have emerged,which may improve the accuracy of detecting clinically significant PCa in recent *** To investigate the diagnostic efficiency of a template for cognitive MRIultrasound fusion transperineal targeted plus randomized biopsy in detecting *** Data from patients with an increasing prostate-specific antigen(PSA)level but less than 20 ng/mL and at least one lesion suspicious for PCa on MRI from December 2015 to June 2018 were retrospectively *** patients underwent cognitive fusion transperineal template-guided targeted biopsy followed by randomized biopsy outside the targeted area.A total of 127 patients with complete data were included in the final analysis.A multivariable logistic regression analysis was conducted,and a two-sided P<0.05 was considered statistically *** PCa was detected in 66 of 127 patients,and 56 cases presented clinically significant *** fusion targeted biopsy alone detected 59/127 cases of PCa,specifically 52/59 cases with clinically significant PCa and 7/59 cases with clinically insignificant PCa.A randomized biopsy detected seven cases of PCa negative on targeted biopsy,and four cases had clinically significant *** density(OR:1.008,95%CI:1.003-1.012,P=0.001;OR:1.006,95%CI:1.002-1.010,P=0.004)and Prostate Imaging-Reporting and Data System(PI-RADS)scores(both P<0.001)were independently associated with the results of cognitive fusion targeted biopsy combined with randomized biopsy and targeted biopsy *** This single-centered study proposed a feasible template for cognitive MRIultrasound fusion transperineal targeted plus randomized *** with higher PSAD and PI-RADS scores were more likely to be diagnosed with PCa.

关键词： Prostate neoplasms Magnetic resonance imaging Cognitive fusion Prostate biopsy Prostate cancer

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Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the CRISPR/Cas9 system

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Journal of Genetics and Genomics 2021年第2期48卷 134-146页

作者： Lin Zhu Xiaoyan Yang Juyi Li Xiong Jia Xiangli Bai Ying Zhao Wenzhuo Cheng Meng Shu Yan Zhu Si Jin Department of Endocrinology Institute of Geriatric MedicineLiyuan HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pediatrics Tongji HospitalTongji Medicine CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pharmacology Hubei Key Laboratory of Drug Target Research and Pharmacodynamic EvaluationSchool of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pharmacy The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Laboratory medicine Liyuan HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Gene therapy has become the most effective treatment for monogenic *** LEPTIN deficiency is a rare autosomal recessive monogenic obesity syndrome caused by mutations in the Leptin ***/ob mouse is a monogenic obesity model,which carries a homozygous point mutation of C to T in Exon 2 of the Leptin ***,we attempted to edit the mutated Leptin gene in ob/ob mice preadipocytes and inguinal adipose tissues using CRISPR/Cas9 to correct the C to T mutation and restore the production of LEPTIN protein by *** edited preadipocytes exhibit a correction of 5.5%of Leptin alleles and produce normal LEPTIN protein when differentiated into mature *** ob/ob mice display correction of 1.67%of Leptin alleles,which is sufficient to restore the production and physiological functions of LEPTIN protein,such as suppressing appetite and alleviating insulin *** study suggests CRISPR/Cas9-mediated in situ genome editing as a feasible therapeutic strategy for human monogenic diseases,and paves the way for further research on efficient delivery system in potential future clinical application.

关键词： CRISPR/Cas9 Gene editing Leptin Monogenetic disease Obesity

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Presence of columnar-lined esophagus is negatively associated with the presence of esophageal varices in Japanese alcoholic men

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World Journal of Gastroenterology 2017年第39期23卷 7150-7159页

作者： Akira Yokoyama Kenro Hirata Rieko Nakamura Tai Omori Takeshi Mizukami Junko Aida Katsuya Maruyama Tetsuji Yokoyama National hospital Organization Kurihama Medical and Addiction Center Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Department of Health Promotion National Institute of Public HealthSaitama Endoscopy Center Kawasaki Municipal Ida Hospital research Team for Geriatric Pathology Tokyo Metropolitan Institute of Gerontology

AIM To determine whether the presence of columnar-lined esophagus(CLE) is associated with the presence of esophageal varices(EVs) in male Japanese alcoholics. METHODS The subjects were 1614 Japanese alcohol-dependent men(≥ 40 years of age) who had undergone upper gastrointestinal endoscopic screening. Digitalized records of high-quality endoscopic images that included the squamocolumnar junction and esophagogastric junction were retrospectively jointly reviewed by four expert endoscopists for the purpose of diagnosing CLE. The authors investigated whether and to what extent there were associations between the presence of CLE and the presence of EVs, especially in the group with liver cirrhosis(LC).RESULTS CLE ≥ 5 mm in length was found in 355 subjects(≥ 30 mm in 6 of them), LC without EVs in 152 subjects, LC with EVs in 174 subjects, and EVs without LC in 6 subjects. Advanced EVs, i.e., nodular, large or coiled forms, red color sign, or post-treatment, were found in 88 subjects. The incidence of CLE ≥ 5 mm decreased in the following order(P < 0.0001): 23.3% in the group without EVs, 17.4% in the group with small and straight EVs, and 5.7% in the group with advanced EVs. The multivariate ORs(95%CI) for EVs and advanced EVs in the group with LC were lower when CLE ≥ 5 mm was present [0.46(0.23-0.93) and 0.24(0.08-0.74), respectively, vs 0-4 mm CLE]. CONCLUSION The presence of CLE in male Japanese alcoholics was negatively associated with the presence of EVs.

关键词： Alcohol Columnar-lined esophagus Hiatal hernia Liver cirrhosis Portal hypertension Esophageal varices

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Hypertension Exacerbates Severity and Outcomes of COVID-19 in Elderly Patients:A Retrospective Observational Study

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Current Medical Science 2022年第3期42卷 561-568页

作者： Li-song DAI Meng-pei ZHU Yu-min LI Hong-mei ZHOU Hong-li LIAO Pan-pan CHENG Xin-yue XIA Xue-yun YAO Hui-juan ZHANG Xiao-qi LIU Wei HUANG Lei WAN Xiang-yang XU Fu-rong WANG Cheng-qi XU Department of Radiology Liyuan HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430070China Department of Respiratory Liyuan HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430070China Department of Radiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430015China Department of Radiology Wuhan Eighth HospitalWuhan 430014China Department of Cardiology Liyuan HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430070China Department of Ultrasound Liyuan HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430070China Key Laboratory of Molecular Biophysics of the Ministry of Education Cardio-X InstituteCollege of Life Science and Technology and Center for Human Genome ResearchHuazhong University of Science and TechnologyWuhan 430070China

Objective To evaluate the impact of hypertension on the clinical outcome of COVID-19 patients aged 60 years old and *** This single-center retrospective cohort study enrolled consecutive COVID-19 patients aged 60 years old and older,who were admitted to liyuan hospital from January 1,2020 to April 25,*** included patients were divided into two groups:hypertension and nonhypertension *** baseline demographic characteristics,laboratory test results,chest computed tomography(CT)images and clinical outcomes were collected and *** prognostic value of hypertension was determined using binary logistic *** Among the 232 patients included in the analysis,105(45.3%)patients had comorbid *** to the nonhypertension group,patients in the hypertension group had higher neutrophil-to-lymphocyte ratios,red cell distribution widths,lactate dehydrogenase,high-sensitivity C-reactive protein,D-dimer and severity of lung lesion,and lower lymphocyte counts(all Phospital death in elderly patients with *** The elderly COVID-19 patients with hypertension tend to have worse conditions at baseline than those without *** may be an independent prognostic factor of poor clinical outcome in elderly COVID-19 patients.

关键词： COVID-19 SARS-CoV-2 hypertension prognosis mortality risk factor

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Bupi Hewei decoction ameliorates 5-fluorouracil-induced intestinal dysbiosis in rats through T helper 17/T regulatory cell signaling pathway

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Journal of Traditional Chinese medicine 2020年第1期40卷 38-48页

作者： Sun Zhigao Hu Yazhuo Wang Yuguo Feng Jian Dou Yongqi Department of Traditional Chinese medicine Chinese PLA General HospitalBeijing 100853China&Department of Traditional Chinese MedicineHainan Branch of Chinese PLA General HospitalSanya 572013China institute of gerontology Chinese PLA General HospitalBeijing 100853China Department of Traditional Chinese medicine Chinese PLA General HospitalBeijing 100853China

OBJECTIVE:To observe the effects of the Bupi Hewei(BPHW)decoction on diarrhea and intestinal flora disorder induced by 5-fluorouracil(5-FU)and investigate the possible mechanism underlying these ***:Thirty-five male Sprague-Dawley rats were randomly divided into four groups:normal control,5-FU,5-FU+BPHW decoction(10.5 g/kg for 5 consecutive days),and 5-FU+Bacillus licheni-formis capsule groups(0.2 g/kg for 5 consecutive days).Animal models were established via the intraperitoneal injection of 5-FU(30 mg/kg for 5 consecutive days).At the end of the treatment period,diarrhea was assessed,and the change of the intestinal flora was examined using 16 S r DNA highthroughput ***(IL)-17,IL-21,IL-6,IL-10,RAR-related orphan receptor gamma(RORγt),and forkhead box P3(Foxp3)expression in the jejunum was detected using immunohistochemistry,quantitative real-time polymerase chain reaction(PCR),Western blotting,and enzymelinked immuno sorbent ***:In this study,the BPHW decoction effectively lowered the diarrhea score,increased the proportions of Bacteroidetes and Prevotellaceae-Alloprevotella species,and reduced the proportions of Proteobacteria,Escherichia-Shigella,Ruminococcaceae NK4 A214,and Ruminococcaceae UCG-005 species in the rat intestine after 5-FU *** addition,the BPHW decoction significantly suppressed the expression of IL-17,IL-21,IL-6,IL-10,RORγt,and Foxp3 in the ***:Our findings suggest that the BPHW decoction can improve the intestinal immune balance and reduce intestinal inflammation by targeting T helper cell/T regulatory cell-associated factors.

关键词： Gastrointestinal microbiome Fluorouracil Drug therapy T-Lymphocytes,regulatory Th17 cells Bupi Hewei decoction

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