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

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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The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 71-76页

作者： Alessandro Fugazza Matteo Colombo Michel Kahaleh V.Raman Muthusamy Bick Benjamin Wim Laleman Carmelo Barbera Carlo Fabbri Jose Nieto Abed Al-Lehibi Mohan Ramchandani Amy Tyberg Haroon Shahid Avik Sarkar Dean Ehrlich Stuart Shermand Cecilia Binda Marco Spadaccini Andrea Iannone Kareem Khalaf Nageshwar Reddy Andrea Anderloni Alessandro Repici Division of Gastroenterology and digestive Endoscopy Humanitas Research Hospital-IRCCSVia Manzoni 5620089RozzanoMilanoItaly Gastroenterology Rutgers Robert Wood JohnsonNew BrunswickNew JerseyUSA Vatche and Tamar Manoukian Division of digestive Diseases University of CaliforniaLos Angeles School of Medicine at UCLALos AngelesCaliforniaUSA Division of digestive and Liver disorders Indiana University School of MedicineIndianapolisINUSA Department of Gastroenterology and Hepatology University Hospitals LeuvenKU Leuven3000 LeuvenBelgium U.O.C.di Gastroenterologia ed Endoscopia Digestiva Ospedale Giuseppe MazziniASL TeramoItaly Gastroenterology and digestive Endoscopy unit Forlì-Cesena HospitalsAUSL RomagnaForlì-CesenaItaly Borland Groover Clinic JacksonvilleFloridaUSA Department of Gastroenterology and Hepatology King Fahad Medical CityRiyadhSaudi Arabia Asian Institute of Gastroenterology HyderabadIndia Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy Department of Biomedical Sciences Humanitas UniversityVia Rita Levi Montalcini 420090Pieve EmanueleMilanItaly

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 ***: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

关键词： Single-operator cholangioscopy Single-use duodenoscope Endoscopic retrograde cholangiopancreatography Indeterminate biliary stricture Difficult biliary stones

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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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Pro and anti-inflammatory diets as strong epigenetic factors in inflammatory bowel disease

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World Journal of Gastroenterology 2024年第27期30卷 3284-3289页

作者： Adele Rostami Kristen White Kamran Rostami digestive Health Clinic Palmerston North 4410New Zealand digestive Health Clinic&Kōtare Wellness Ltd Palmerston North 4410New Zealand Department of Gastroenterology Palmerston North HospitalPalmerston North 4442New Zealand

Inflammatory bowel disease(IBD)is the consequence of a complex interplay between environmental factors,like dietary habits,that alter intestinal microbiota in response to luminal antigens in genetically susceptible *** represents an auspicious area for the discovery of how environmental factors influence the pathogenesis of inflammation,prognosis,and response to ***,it relates to gene expression control in response to environmental *** increasing number of patients with IBD globally is indicative of the negative effects of a food supply rich in trans and saturated fats,refined su-gars,starches and additives,as well as other environmental factors like seden-tarism and excess bodyweight,influencing the promotion of gene expression and increasing DNA hypomethylation in *** many genetic variants are now associated with Crohn's disease(CD),new therapeutic strategies targeting modi-fiable environmental triggers,such as the implementation of an anti-inflammatory diet that involves the removal of potential food antigens,are of growing interest in the current ***,as a strong epigenetic factor in the pathogenesis of inflammatory disorders like IBD,provides novel insights into the pathophysio-logy of intestinal and extraintestinal inflammatory disorders.

关键词： Inflammatory bowel disease Epigenetic Anti-inflammatory diet Immunogenetics Microbiome Polymeric diet Elemental diet

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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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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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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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Dysfunction of synaptic endocytic trafficking in Parkinson's disease

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Neural Regeneration Research 2024年第12期19卷 2649-2660页

作者： Xin Yi Ng Mian Cao Programme in Neuroscience and Behavioural disorders Duke-NUS Medical SchoolSingaporeSingapore Department of Physiology National University of SingaporeSingaporeSingapore

Parkinson's disease is characterized by the selective degeneration of dopamine neurons in the nigrostriatal pathway and dopamine deficiency in the *** precise reasons behind the specific degeneration of these dopamine neurons remain largely *** investigations have identified over 20 causative PARK genes and 90 genomic risk loci associated with both familial and sporadic Parkinson's ***,several of these genes are linked to the synaptic vesicle recycling process,particularly the clathrinmediated endocytosis *** suggests that impaired synaptic vesicle recycling might represent an early feature of Parkinson's disease,followed by axonal degeneration and the eventual loss of dopamine cell bodies in the midbrain via a"dying back"***,several new animal and cellular models with Parkinson's disease-linked mutations affecting the endocytic pathway have been created and extensively *** models faithfully recapitulate certain Parkinson's disease-like features at the animal,circuit,and cellular levels,and exhibit defects in synaptic membrane trafficking,further supporting the findings from human genetics and clinical *** this review,we will first summarize the cellular and molecular findings from the models of two Parkinson's disease-linked clathrin uncoating proteins:auxilin(DNAJC6/PARK19)and synaptojanin 1(SYNJ1/PARK20).The mouse models carrying these two PARK gene mutations phenocopy each other with specific dopamine terminal pathology and display a potent synergistic ***,we will delve into the involvement of several clathrin-mediated endocytosis-related proteins(GAK,endophilin A1,SAC2/INPP5 F,synaptotagmin-11),identified as Parkinson's disease risk factors through genome-wide association studies,in Parkinson's disease *** will also explore the direct or indirect roles of some common Parkinson's disease-linked proteins(alpha-synuclein(PARK1/4),Parkin(PARK2),and LRRK2(PARK

关键词： autophagy auxilin/PARK19 clathrin-mediated endocytosis dopamine neurons neurodegeneration nigrostriatal pathway Parkinson's disease synaptic vesicle recycling synaptojanin1/PARK20

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Enhancing the understanding between exercise and brain health:A new tool of oxygen imaging

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Journal of Sport and Health Science 2024年第6期13卷 751-752页

作者： Zhibo Wang Jianping Jia Innovation Center for Neurological disorders and Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China

Oxygen is pivotal for brain metabolism,1 and understanding its dynamics within the cerebral cortex is essential for both fundamental neuroscience and clinical ***,Beinlich et al.2 introduced a novel tool,the Green enhanced Nano-lantern(GeNL),a bioluminescent oxygen sensor that allows for the real-time,high-resolution monitoring of oxygen distribution in the living mouse cerebral cortex.

关键词： metabolism cerebral

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Current understanding of ELF4 deficiency:a novel inborn error of immunity

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World Journal of Pediatrics 2024年第5期20卷 444-450页

作者： Hong-Qiang Du Xiao-Dong Zhao Department of Rheumatology&Immunology National Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Child Rare Diseases in Infection and ImmunityChildren’s Hospital of Chongqing Medical UniversityZhongshan Er Road 136Yuzhong DistrictChongqingChina

Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this condition,reported by our team and others,are very limited *** such,our current knowledge of this new disease remains *** review aims to provide a brief overview of the clinical manifestations,pathogenesis,and treatment strategies for this novel *** sources A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 *** search strategy was“ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor”as of the time of manuscript *** The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer,abdominal pain,and diarrhea in pediatric *** some cases,immunodeficiency and autoimmunity can also be *** Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 *** blotting for ELF4 expression of the patient’s cells can confirm the pathogenic effect of the *** fully confirm the pathogenicity of the variant,further functional test is strongly *** and biologics are the mainstream management of ELF4 deficiency *** Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of *** atypical presentations are prominent,variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 *** of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.

关键词： ELF4 transcription factor Immune dysregulation Inborn errors of immunity Mechanism Recurrent infections

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