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Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia

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World Journal of Psychiatry 2024年第5期14卷 695-703页

作者： Wen-Peng Hou Xiang-Qin Qin Wei-Wei Hou Yun-Yi Han Qi-Jing Bo Fang Dong Fu-Chun Zhou Xian-Bin Li Chuan-Yue Wang Beijing Key Laboratory of Mental disorders National Clinical Research Center for Mental Disorders&National Center for Mental DisordersBeijing Anding HospitalCapital Medical UniversityBeijing 100088China Advanced Innovation center for Human Brain Protection Capital Medical UniversityBeijing 100069China

BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in ***,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still *** To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met *** In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative *** was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence *** COMT Met-carriers exhibited fewer negative symptoms than Val *** the total sample,significant negative correlations were found between negative symptoms and information,*** between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.

关键词： Catechol-O-methyltransferase Val/Met polymorphism Cognitive reserve Crystallized intelligence Negative symptoms Schizophrenia

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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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Timing of biomarker changes preceding Alzheimer's disease:for diagnosis, treatment or prevention?

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Science China Life Sciences 2024年

作者： Meina Quan Innovation center for Neurological disorders and Department of Neurology Xuanwu Hospital Capital Medical University National Medical center for Neurological Diseases and National Clinical Research center for Geriatric Diseases center of Alzheimer's Disease Beijing Institute of Brain Disorders Collaborative Innovation Center for Brain Disorders

The pathophysiological and behavioural features of Alzheimer’s disease (AD) have been extensively investigated in transgenic mouse models, including the temporal sequence of each pathophysiological change and behavioural abnormality, a summary of which was recently presented by our team in this Journal (Li et al.,2023). Nevertheless, studying such features and timings directly in human patients before symptoms occur is challenging. Starting from familial AD, then gradually shifting to sporadic AD, growing evidence from longitudinal studies indicates that biomarkers change at least10 to 20 years before the onset of symptoms in AD (Bateman et al., 2012;Villemagne et al., 2013; Gordon et al.,2018; Vermunt et al., 2019).

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Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration Research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of Pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric Medical Research center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular *** r,the causal relationship between hypertension and cerebral small vessel disease remains *** has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular *** hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and *** is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of *** review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive *** also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

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The roles of RACK1 in the pathogenesis of Alzheimer's disease

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Journal of Biomedical Research 2024年第2期38卷 137-148页

作者： Wenting He Xiuyu Shi Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Child Neurodevelopment and Cognitive DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China

The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative ***1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of ***,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C ***,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal ***1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 *** potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential *** this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.

关键词： RACK1 Alzheimer's disease PKC amyloid-β synaptic plasticity neuroinflammation

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Postoperativeinte rictalepil eptiform discharges predict seizure recurrence after antiepileptic drug withdrawal regardless of concordance with surgical site

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World Journal of Pediatric Surgery 2024年第1期7卷 33-41页

作者： Yuxin Wu ZaiYu Zhang Ping Liang Lusheng Li Bin Zou Difei Wang Xinyu Dong Haotian Tang Hanli Qiu Xuan Zhai Department of Neurosurgery Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqingChina

Objective The study aimed to explore the association between the site of interictal epileptic discharges(IEDs)on postoperative electroencephalogram(EEG)and seizure recurrence after antiepileptic drug(AED)*** study hypothesizes that the concordance of IED sites with surgical sites indicates incomplete resection of epileptic focus,while non-concordance of IED sites with surgical sites indicates postoperative changes or cortical *** former has a higher risk of seizure *** We retrospectively analyzed the postoperative EEG pattern of 182 consecutive children who underwent resection *** identify the risk factors for seizure recurrence,we compared the attributes of seizure recurred and seizure-free groups by univariate and multivariate *** tapering was standardized,involving a 25% reduction in the dose of a single type of AED every 2 weeks,independent of the presurgical AED *** We attempted AED withdrawal in 116(63.7%)***-eight(24.1%)children experienced seizure recurrence during or after AED withdrawal.A greater number of AEDs used at the time of surgery(p=0.005),incomplete resection(p=0.001),and presence of IED on postoperative EEG(p=0.011)are predictors of *** resectionand seizure recurrence after AED withdrawal were related to the presence of IED on the EEG,but not to the concordance of IED with surgical *** For children with abnormal EEG,the decision to discontinue AED should be made more cautiously,regardless of the relative location of the discharge site and the surgical site.

关键词： surgical seizure epileptic

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Network analysis of suicide ideation and depression-anxiety symptoms among Chinese adolescents

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General Psychiatry 2024年第2期37卷 216-223页

作者： Shuyin Xu Yumeng Ju Xiyu Wei Wenwen Ou Mohan Ma Guanyi Lv Xiaotian Zhao Yaqi Qin Yunjing Li Liang Li Mei Huang Siqi Yang Yimei Lu Yafei Chen Junwu Liu Jin Liu Bangshan Liu Yan Zhang Department of Psychiatry National Clinical Research Center for Mental Disordersand National Center for Mental DisordersThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina Mental Health Institute of Central South University China National Technology Institute on Mental DisordersHunan Technology Institute of PsychiatryHunan Key Laboratory of Psychiatry and Mental HealthHunan Medical Center for Mental HealthChangshaHunanChina

Background The co-occurrence of depression and anxiety among adolescents is typically associated with suicide *** The study aimed to investigate the symptom-level relationship between suicide ideation and the comorbidity of depression and *** 1501 adolescents aged 12-19 years were assessed using the Patient Health Questionnaire(PHQ-9)and the Generalized Anxiety Disorder Scale,and 716 adolescents who scored≥5 on both scales were selected as *** analysis was used to identify the network structure of depressive symptoms and anxiety *** were categorised into either the suicide ideation or non-suicide ideation groups based on their scoring on the suicide-related item in PHQ-9.A comparison was made between the depression-anxiety symptom networks of the two ***‘Restlessness’,‘sad mood’and‘trouble relaxing’were the most prominent central symptoms in the depression-anxiety symptom network,and‘restlessness’,‘nervousness’and‘reduced movement’were the bridge symptoms in this network.‘Sad mood’was found to be directly related to‘suicide ideation’with the highest *** network structure was significantly different in properties between the suicide ideation group and the non-suicide ideation group,with‘restlessness’and‘sad mood’exhibiting significantly higher influence in the network of the suicide ideation group than that in the non-suicide ideation *** Restlessness and sad mood could be targeted for the intervention of depression-anxiety symptoms among adolescents with suicide ideation.

关键词： symptoms adolescent assessed

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A systematic review of the role of TREM2 in Alzheimer’s disease

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中华医学杂志(英文版) 2024年第14期137卷 1684-1694页

作者： Yin Yunsi Yang Hanchen Li Ruiyang Wu Guangshan Qin Qi Tang Yi Department of Neurology & Innovation center for Neurological disorders Xuanwu Hospital Capital Medical University National Center for Neurological Disorders Beijing China

Background: Given the established genetic linkage between triggering receptors expressed on myeloid cells 2 (TREM2) and Alzheimer’s disease (AD), an expanding research body has delved into the intricate role of TREM2 within the AD context. However, a conflicting landscape of outcomes has emerged from bothin vivo andin vitro investigations. This study aimed to elucidate the multifaceted nuances and gain a clearer comprehension of the role of ***: PubMed database was searched spanning from its inception to January 2022. The search criteria took the form of ( "Alzheimer’s disease" OR "AD" ) AND ( "transgenic mice model" OR "transgenic mouse model" ) AND ( "Triggering receptor expressed on myeloid cells" OR "TREM2" ). Inclusion criteria consisted of the following: (1) publication of original studies in English; (2) utilization of transgenic mouse models for AD research; and (3) reports addressing the subject of ***: A total of 43 eligible articles were identified. Our analysis addresses four pivotal queries concerning the interrelation of TREM2 with microglial function, Aβ accumulation, tau pathology, and inflammatory processes. However, the diverse inquiries posed yielded inconsistent responses. Nevertheless, the inconsistent roles of TREM2 within these AD mouse models potentially hinge upon factors such as age, sex, brain region, model type, and detection ***: This review substantiates the evolving understanding of TREM2’s disease progression-dependent impacts. Furthermore, it reviews the interplay between TREM2 and its effects across diverse tissues and temporal stages.

关键词： TREM2 Alzheimer’s disease Mouse model Microglia Amyloid-β accumulation Tau pathology Inflammation

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Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids

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Genes & Diseases 2024年第2期11卷 1066-1081页

作者： Junyan Yan Lu Xiao Di Feng Baolin Chen Ting Yang Bei Tong Ruifang Luo Yuting Wang Jie Chen Children Nutrition Research center Children's Hospital of Chongqing Medical UniversityChongqing Key Laboratory of Child Nutrition and HealthMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing 401122China Department of Gastroenterology Children's Hospital of Chongqing Medical UniversityChongqing 401122China

Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier ***-chain fatty acids (SCFAs),as metabolites of the gut microbiota,protect the physiological intestinal barrier;however,they are compromised when VA is ***,there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD).Herein,compared with normal VA rats (VAN),at the beginning of pregnancy,we confirmed that the colonic desmosome junction was impaired in the VAD group,and the amounts of acetate,propionate,and butyrate declined because of the decreased abundance of SCFA-producing bacteria (Romboutsia ,Collinsella ,and Allobaculum ).The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA *** the VAD group,the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated,and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were ***,the above changes in the VAD groups were rescued by VA supplementation in the early postnatal *** study indicated that in Caco-2 cells,butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the CEACAM1 gene to induce its *** findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD,and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy.

关键词： CEACAM1 Colonic epithelial barrier HDAC3 Short-chain fatty acids Vitamin A deficiency

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Single-cell RNA sequencing in juvenile idiopathic arthritis

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Genes & Diseases 2024年第2期11卷 633-644页

作者： Xiwen Luo Xuemei Tang Department of Rheumatology and Immunology Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Key Laboratory of Child Infection and Immunity Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China

Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory rheumatic diseases in children,with onset before age 16 and lasting for more than 6 *** is a highly heterogeneous condition with various consequences for health and quality of *** some JIA patients,early detection and intervention remain *** a result,further investigation of the complex and unknown mechanisms underlying JIA is *** in technology now allow us to describe the biological heterogeneity and function of individual cell populations in *** this review,we hope to provide novel ideas and potential targets for the diagnosis and treatment of JIA by summarizing the current findings of single-cell RNA sequencing studies and understanding how the major cell subsets drive JIA pathogenesis.

关键词： Juvenile idiopathic arthritis Macrophage Macrophage activation syndrome Monocyte Single-cell RNA sequencing Synoviocyte T cell

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