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Ethical concerns in aging research:perspectives of global frontline researchers

Science China(Life Sciences) 2024年第10期67卷 2149-2156页

作者： Yaojin Peng Lulu Ding Zhenyu Xiao Moshi Song Jianwei Lv guang-hui liu Key Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive BiologyInstitute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Aging Biomarker Consortium(ABC) Beijing 100101China School of Life Science Beijing Institute of TechnologyBeijing 100081China School of Life Sciences Xiamen UniversityXiamen 361102China Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China

This study investigated the ethical landscape of aging research amid the increasing global focus on extending the human lifespan and health *** global survey of 180 researchers across 38 jurisdictions revealed divergent perceptions of aging,a consensus regarding the feasibility of delaying aging,and multiple perspectives regarding lifespan *** present findings underscore a paradigm shift toward inclusive and ethically sound research,emphasizing the need for an approach that strikes a balance between basic and clinical *** addition,this study highlighted key ethical concerns in aging research,including the effects of misleading advertising,potential inequality in access to aging interventions,and risks pertaining to the extrapolation of research findings from lower-model organisms to *** insights presented in this paper call for an integrated approach for overcoming the complex ethical and societal challenges in aging research to ensure responsible and equitable advancements in this burgeoning field.

关键词： aging ethical landscape ethics surveys and questionnaires

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Artificial intelligence for the detection of glaucoma with SD-OCT images:a systematic review and Meta-analysis

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 408-419页

作者： Nan-Nan Shi Jing Li guang-hui liu Ming-Fang Cao Department of Ophthalmology Affiliated People’s Hospital(Fujian Provincial People’s Hospital)Fujian University of Traditional Chinese MedicineFuzhou 350004Fujian ProvinceChina Eye Institute of Integrated Chinese and Western Medicine Fujian University of Traditional Chinese MedicineFuzhou 350004Fujian ProvinceChina

●AIM:To quantify the performance of artificial intelligence(AI)in detecting glaucoma with spectral-domain optical coherence tomography(SD-OCT)images.●METHODS:Electronic databases including PubMed,Embase,Scopus,ScienceDirect,ProQuest and Cochrane Library were searched before May 31,2023 which adopted AI for glaucoma detection with SD-OCT *** pieces of the literature were screened and extracted by two ***-analysis,Meta-regression,subgroup,and publication of bias were conducted by *** risk of bias assessment was performed in Revman5.4 using the QUADAS-2 tool.●RESULTS:Twenty studies and 51 models were selected for systematic review and *** pooled sensitivity and specificity were 0.91(95%CI:0.86–0.94,I2=94.67%),0.90(95%CI:0.87–0.92,I2=89.24%).The pooled positive likelihood ratio(PLR)and negative likelihood ratio(NLR)were 8.79(95%CI:6.93–11.15,I2=89.31%)and 0.11(95%CI:0.07–0.16,I2=95.25%).The pooled diagnostic odds ratio(DOR)and area under curve(AUC)were 83.58(95%CI:47.15–148.15,I2=100%)and 0.95(95%CI:0.93–0.97).There was no threshold effect(Spearman correlation coefficient=0.22,P>0.05).●CONCLUSION:There is a high accuracy for the detection of glaucoma with AI with SD-OCT *** application of AI-based algorithms allows together with“doctor+artificial intelligence”to improve the diagnosis of glaucoma.

关键词： artificial intelligence spectral-domain optical coherence tomography glaucoma Meta-analysis

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MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer

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Research 2024年第2期2023卷 239-257页

作者： Cui Wang Kuan Yang Xiaoqian liu Si Wang Moshi Song Juan Carlos Izpisua Belimonte Jing Qu guang-hui liu Weiqi Zhang CAS Key Laboratory of Genomic and Precision Medicine Beijng Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Bejing 100101China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ ***,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also regulates human stem cell *** answer this question,we used CRISPR/Cas9-mediated gene editing and directed differentiation techniques to generate various MAVS-knockout human stem cell *** found that human mesenchymal stem cells(hMSCs)were sensitive to MAVS deficiency,as manifested by accelerated senescence *** uncovered that the role of MAVS in maintaining mitochondrial structural integrity and functional homeostasis depends on its interaction with the guanosine triphosphatase optic atrophy type 1(OPA1).Depletion of MAVS or OPA1 led to the dysfunction of mitochondria and cellular senescence,whereas replenishment of MAVS or OPA1 in MAVS-knockout hMSCs alleviated mitochondrial defects and premature senescence *** together,our data underscore an uncanonical role of MAVS in safeguarding mitochondrial homeostasis and antagonizing human stem cell senescence.

关键词： CRISPR/Cas9 homeostasis Mitochondrial

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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu guang-hui liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling

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Protein & Cell 2024年第6期15卷 441-459页

作者： Feifei liu Yi Lu Xuebao Wang Shuhui Sun huize Pan Min Wang Zehua Wang Weiqi Zhang Shuai Ma Guoqiang Sun Qun Chu Si Wang Jing Qu guang-hui liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Sports Medicine Department Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Division of Life Sciences and Medicine School of Life SciencesUniversity of Science and Technology of ChinaHefei 230001China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China

The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint ***,the mechanism underlying human synovial aging remains poorly ***,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged *** delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged ***,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue *** particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged *** human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged *** data indicate an important role of FOXO1 in the regulation of human synovial ***,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.

关键词： FOXO1 degeneration inflammation

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A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

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Protein & Cell 2024年第2期15卷 98-120页

作者： Shanshan Yang Chengyu liu Mengmeng Jiang Xiaoqian liu Lingling Geng Yiyuan Zhang Shuhui Sun Kang Wang jian Yin Shuai Ma Si Wang Juan Carlos Izpisua Belmonte Weiqi Zhang Jing Qu guang-hui liu Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Xuanwu Hospital Capital Medical University Beijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Aging Biomarker Consortium Beijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Aging increases the risk ofliver diseases and systemic susceptibility to aging-related ***,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely ***,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche *** in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during *** particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular *** study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.

关键词： single-nucleus RNA sequencing liver hepatocytes aging senescence SREBP2

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Multimodal Omics Approaches to Aging and Age‑Related Diseases

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Phenomics 2024年第1期4卷 56-71页

作者： Qianzhao Ji Xiaoyu Jiang Minxian Wang Zijuan Xin Weiqi Zhang Jing Qu guang‑hui liu State Key Laboratory of Membrane Biology Instituteof ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and ReproductiveBiology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academyof Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academyof SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China School of Future Technology University of ChineseAcademy of SciencesBeijing 100190China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for GeriatricDisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Centerfor Aging and CancerXuanwu HospitalCapital MedicalUniversityBeijing 100053China

Aging is associated with a progressive decline in physiological capacities and an increased risk of aging-associated *** increasing body of experimental evidence shows that aging is a complex biological process coordinately regulated by multiple factors at diferent molecular ***,it is difcult to delineate the overall systematic aging changes based on single-layer ***,multimodal omics approaches,in which data are acquired and analyzed using complementary omics technologies,such as genomics,transcriptomics,and epigenomics,are needed for gaining insights into the precise molecular regulatory mechanisms that trigger *** recent years,multimodal omics sequencing technologies that can reveal complex regulatory networks and specifc phenotypic changes have been developed and widely applied to decode aging and age-related *** review summarizes the classifcation and progress of multimodal omics approaches,as well as the rapidly growing number of articles reporting on their application in the feld of aging research,and outlines new developments in the clinical treatment of age-related diseases based on omics technologies.

关键词： Multimodal omics approaches Aging Genome Epigenome

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Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

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Protein & Cell 2024年第5期15卷 364-384页

作者： huifen Lu Ying Jing Chen Zhang Shuai Ma Weiqi Zhang Daoyuan Huang Bin Zhang Yuesheng Zuo Yingying Qin guang-hui liu Yang Yu Jing Qu Si Wang Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem cell and Regeneration CASBeijing 100101China China National Center for Bioinformation Beijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking UniversityThird HospitalBeijing 100191China Clinical Stem Cell Research Center Peking UniversityThird HospitalBeijing 100191China Center for Reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250012China Key Laboratory of Reproductive Endocrinology of Ministry of Education National Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthJinan 250012China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Biomarker Consortium Beijing 100101China

The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of ***,the molecular basis of ovarian aging in higher vertebrates remains poorly ***,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate *** a global view,somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region,likely constituting a hostile microenvironment that facilitates ovarian ***,we uncovered that inflammation,the senescent-associated secretory phenotype,senescence,and fibrosis are the likely primary contributors to ovarian aging(PCOA).Of note,we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2(Metallothionein 2)highly expressing spot(MT2^(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ***,with advanced age,a subpopulation of MT2^(high)accumulates,likely disseminating and amplifying the senescent signal *** study establishes the first primate spatiotemporal transcriptomic atlas,advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.

关键词： spatial transcriptome primate ovary aging senescence inflammation

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Degeneration Directory:a multi-omics web resource for degenerative diseases

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Protein & Cell 2024年第5期15卷 385-392页

作者： Haoteng Yan Changfa Lu Chenyang Lan Si Wang Weiqi Zhang Zan He Jinghao Hu Jiaqi Ai guang-hui liu Shuai Ma Yuanchun Zhou Jing Qu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China Computer Network Information Center Chinese Academy of SciencesBeijing 100190China The Fifth People’s Hospital of Chongqing Chongqing 400062China Aging Biomarker Consortium Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Background of *** degeneration refers to the gradual decline in organ function and structure deterioration that occurs during aging,which represents the greatest risk factor for various degenerative diseases,including cardiovascular diseases,neurodegenerative diseases,and osteoarthritis,etc.(Aging Biomarker et al.,2023;Becker et al.,2018;Cai et al.,2022).

关键词： Directory web Becker

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Neurosyphilis complicated by anti-γ-aminobutyric acid-B receptor encephalitis: A case report

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World Journal of Clinical Cases 2024年第11期12卷 1960-1966页

作者： Ya-Xiu Fang Xiao-Ming Zhou Dong Zheng guang-hui liu Peng-Bo Gao Xiao-Zhen Huang Zhi-Cheng Chen hui Zhang Lin Chen Ya-Fang Hu Department of Neurology The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhou 510000Guangdong ProvinceChina Department of Neurology Nanfang HospitalSouthern Medical UniversityGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Syphilis is an infectious disease caused by Treponema pallidum that can invade the central nervous system,causing *** cases of anti-N-methyl-Daspartate receptor autoimmune encephalitis(AE)secondary to neurosyphilis have been *** report a neurosyphilis patient with anti-γ-aminobutyric acid-B receptor(GABABR)*** SUMMARY A young man in his 30s who presented with acute epileptic status was admitted to a local *** was diagnosed with neurosyphilis,according to serum and cerebrospinal fluid(CSF)tests for *** 14 d of antiepileptic treatment and anti-Treponema pallidum therapy with penicillin,epilepsy was controlled but serious cognitive impairment,behavioral,and serious psychiatric symptoms were *** was then transferred to our *** Mini-Mental State Examination(MMSE)crude test results showed only 2 *** magnetic resonance imaging revealed significant cerebral atrophy and multiple fluidattenuated inversion recovery high signals in the white matter surrounding both lateral ventricles,left amygdala and bilateral ***-GABABR antibodies were discovered in CSF(1:3.2)and serum(1:100).The patient was diagnosed with neurosyphilis complicated by anti-GABABR AE,and received methylprednisolone and *** treatment,his mental symptoms were *** impairment was significantly improved,with a MMSE of 8 *** anti-GABABR antibody titer decreased to 1:*** patient received methylprednisolone and penicillin after *** months later,the patient’s condition was stable,but the serum anti-GABABR antibody titer was 1:*** This patient with neurosyphilis combined with anti-GABABR encephalitis benefited from immunotherapy.

关键词： Anti-γ-aminobutyric acid-B receptor GABABR Neurosyphilis Tissue-based assay Magnetic resonance imaging Mini-mental state examination Case report

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