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Efficacy and safety of Tianqi Pingchan Granule,a compound Chinese herbal medicine,for levodopa-induced dyskinesia in Parkinson’s disease:A randomized double-blind placebo-controlled trial

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Journal of Integrative Medicine 2024年第5期22卷 545-551页

作者： Yu Zhang Xiao-bo Zhu Yang Zhao Gui-yun Cui Wen-tao Li Can-xing Yuan Jian-ping Huang Ying Wan Na Wu Lu Song Jia-hao Zhao Yan Liang Chuan-ying Xu Mei-juan Liu Chen Gao Xin-xin Chen Zhen-guo Liu Department of neurology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of neurology Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing 210022Jiangsu ProvinceChina Parkinson’s Disease Center the Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina Department of neurology Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200071China Department of neurology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Department of neurology Wenzhou Central HospitalWenzhou 325000Zhejiang ProvinceChina

Background Patients with Parkinson’s disease(PD)undergoing long-term levodopa therapy are prone to develop levodopa-induced dyskinesia(LID).Amantadine is the main drug recommended for the treatment of LID by current guidelines,but it is far from meeting clinical *** Pingchan Granule(TPG),a compound Chinese herbal medicine,has been developed to relieve symptom of *** This randomized controlled trial evaluated the efficacy and safety of the combination of TPG and amantadine for ***,setting,participants and interventions This is a randomized double-blind placebo-controlled trial,conducted from January 2020 to August 2021 at 6 sites in Jiangsu,Zhejiang and Shanghai,*** hundred PD patients with≥0.5 h of LID were randomly assigned to either the TPG plus amantadine group(TPG group)or the placebo plus amantadine group(placebo group),and treated for a period of 12 *** ensure unbiased results,all study participants,investigators and sponsors were unaware of group ***,the data analysts remained blinded until the analysis was *** outcome measures The primary outcome was assessed using the Unified Dyskinesia Rating Scale(UDysRS)(Range 0–104).The key secondary end point was improvement of motor and non-motor *** analyses included all enrolled *** One hundred patients were enrolled and randomized into the two treatment *** changes in UDysRS at week 12 were–11.02 for the TPG group and–4.19 for the placebo group(treatment difference–6.83[–10.53 to–3.12];P=0.0004).Adverse events were reported for 2 of 50 patients(4.0%)in each of the *** This study indicated that a 12-week treatment of amantadine plus TPG effectively reduced UDysRS scores and was well tolerated,demonstrating the efficacy and safety of TPG for the treatment of LID in PD.

关键词： Parkinson’s disease Tianqi Pingchan Granule Levodopa-induced dyskinesia

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GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease

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Neuroscience Bulletin 2024年第4期40卷 451-465页

作者： Huiqin Li Xiang Cao Xinya Gu Mengqi Dong Lili Huang Chenglu Mao Shengnan Xia Haiyan Yang Xinyu Bao Yongbo Yang Yun Xu Department of neurology and Neurosurgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of neurology and Neurosurgery Nanjing Drum Tower HospitalState Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical DiseasesNanjing UniversityNanjing210008China Department of neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical UniversityNanjing210008China Department of neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of neurology Nanjing210008China Nanjing neurology Medical Center Nanjing210008China

Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal *** inflammation is associated with the occurrence and development of ***,the mechanisms underlying the formation of the abnormal vascular network remain ***-eight patients with MMD,26 ischemic stroke patients,and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor(GM-CSF)were higher in MMD patients than in healthy controls(P<0.01),and GM-CSF was mainly from Th1 and Th17 cells in *** found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis,inflammation,and *** summary,our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

关键词： Moyamoya disease Vascular endothelial cells GM-CSF VEGF

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Mitochondrial recruitment in myelin:an anchor for myelin dynamics and plasticity?

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Neural Regeneration Research 2024年第7期19卷 1401-1402页

作者： Jean-David M.Gothié Timothy E.Kennedy Department of neurology and Neurosurgery Montreal Neurological InstituteMcGill UniversityMontrealQCCanada

Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by *** is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered *** is composed of a substantially higher proportion of lipids compared to other biological membranes and enriched in a small number of specialized proteins.

关键词： plasticity insulation dynamics

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MFG-E8 Alleviates Cognitive Impairments Induced by Chronic Cerebral Hypoperfusion by Phagocytosing Myelin Debris and Promoting Remyelination

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Neuroscience Bulletin 2024年第4期40卷 483-499页

作者： Xiaohong Dong Zhi Zhang Xin Shu Zi Zhuang Pinyi Liu Renyuan Liu Shengnan Xia Xinyu Bao Yun Xu Yan Chen Department of neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of neurology Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing210008China Department of neurology Drum Tower Hospital of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of neurology Nanjing210008China

Chronic cerebral hypoperfusion is one of the pathophysiological mechanisms contributing to cognitive decline by causing white matter *** phagocytosing myelin debris in a timely manner can promote remyelination and contribute to the repair of white ***,milk fat globule-epidermal growth factor-factor 8(MFG-E8),a microglial phagocytosis-related protein,has not been well studied in hypoperfusion-related cognitive *** found that the expression of MFG-E8 was significantly decreased in the brain of mice after bilateral carotid artery stenosis(BCAS).MFG-E8 knockout mice demonstrated more severe BCAS-induced cognitive impairments in the behavioral *** addition,we discovered that the deletion of MFG-E8 aggravated white matter damage and the destruction of myelin microstructure through fluorescent staining and electron ***,MFG-E8 overexpression by AAV improved white matter injury and increased the number of mature oligodendrocytes after ***,in vitro and in vivo experiments showed that MFG-E8 could enhance the phagocytic function of microglia via theαVβ3/αVβ5/Rac1 pathway and IGF-1 production to promote the differentiation of oligodendrocyte progenitor cells into mature ***,we found that MFG-E8 was mainly derived from astrocytes,not *** findings suggest that MFG-E8 is a potential therapeutic target for cognitive impairments following cerebral hypoperfusion.

关键词： White matter injury Cognitive dysfunction MFG-E8 Remyelination Microglial phagocytosis

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Cerebral furin deficiency causes hydrocephalus in mice

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Genes & Diseases 2024年第3期11卷 438-451页

作者： Shiqi Xie Xiaoyong Xie Jing Tang Biao Luo Jian Chen Qixin Wen Jianrong Zhou Guojun Chen Nursing College Chongqing Medical UniversityChongqing 400016China Department of neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of Major Neurological and Mental DisordersChongqing Key Laboratory of NeurologyChongqing 400016China

Furin is a pro-protein convertase that moves between the trans-Golgi network and cell surface in the secretory *** have previously reported that cerebral overexpres-sion of furin promotes cognitive functions in ***,by generating the brain-specific furin conditional knockout(ckO)mice,we investigated the role of furin in brain *** found that furin deficiency caused early death and growth *** resonance im-aging showed severe *** the brain of furin cko mice,impaired ciliogenesis and the derangement of microtubule structures appeared along with the down-regulated expres-sion of RAB28,a ciliary vesicle *** line with the widespread neuronal loss,ependymal cell layers were *** proteomics analysis revealed that cell adhesion molecules including astrocyte-enriched ITGB8 and BCAR1 were altered in furin cKO mice;and astrocyte overgrowth was accompanied by the reduced expression of sox9,indicating a disrupted differ-entiation into ependymal ***,whereas alteration of RAB28 expression correlated with the role of vesicle trafficking in ciliogenesis,dysfunctional astrocytes might be involved in ependymal damage contributing to hydrocephalus in furin ckO *** structural and mo-lecular alterations provided a clue for further studying the potential mechanisms of furin.

关键词： Astrocyte Ciliogenesis Conditionalknockout Ependymal Furin Hydrocephalus Proteomics

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Early anticoagulation in patients with stroke and atrial fibrillation is associated with fewer ischaemic lesions at 1 month: the ATTUNE study

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Stroke & Vascular neurology 2024年第1期9卷 30-37,I0034页

作者： Angelos Sharobeam Longting Lin Christina Lam Carlos Garcia-Esperon Yash Gawarikar Ronak Patel Matthew Lee-Archer Andrew Wong Michael Roizman Amanda Gilligan Andrew Lee Kee Meng Tan Susan Day Christopher Levi Stephen M Davis Mark Parsons Bernard Yan Melbourne Brain Centre at Royal Melbourne Hospital ParkvilleVictoriaAustralia University of New South Wales South Western Sydney Clinical School LiverpoolNew South WalesAustralia Department of neurology John Hunter HospitalNewcastleNew South WalesAustralia Department of neurology Calvary Public HospitalCanberraAustralian Capital TerritoryAustralia Department of neurology Northern Hospital EppingEppingVictoriaAustralia Department of neurology Royal Brisbane and Women's HospitalHerstonQueenslandAustralia The University of Queensland School of Medicine HerstonQueenslandAustralia Neurosciences Clinical Institute Epworth HealthcareRichmondVirginiaAustralia Department of neurology Austin HealthUniversity of MelbourneHeidelbergVictoriaAustralia Flinders University College of Medicine and Public Health AdelaideSouth AustraliaAustralia Department of neurology Gold Coast University HospitalSouthportQueenslandAustralia The University of Sydney Northern Clinical School St LeonardsNew South WalesAustralia Department of neurology and Neurophysiology Liverpool HospitalLiverpoolNew South WalesAustralia

Background The optimal time to commence anticoagulation in patients with atrial fibrillation(AF)after ischaemic stroke or transient ischaemic attack(TIA)is unclear,with guidelines differing in recommendations.A limitation of previous studies is the focus on clinically overt stroke,rather than radiologically obvious diffusion-weighted imaging ischaemic *** aimed to quantify silent ischaemic lesions and haemorrhages on MRI at 1month in patients commenced on early(276 patients of whom 208 met the eligibility *** average age was 74.2 years(SD±10.63),and 79(38%)patients were *** National Institute of Health Stroke Scale score was 5(IQR 1–12).Median baseline ischaemic lesion volume was 5mL(IQR 2–17).There were a greater number of new ischaemic lesions on follow-up MRI in patients commenced on anticoagulation≥4days after index event(17%vs 8%,p=0.04),but no difference in haemorrhage rates(22%vs 32%,p=0.10).Baseline ischaemic lesion volume of≤5mL was less likely to have a new haemorrhage at 1month(p=0.02).There was no difference in haemorrhage rates in patients with an initial ischaemic lesion volume of>5mL,regardless of anticoagulation *** Commencing anticoagulation<4days after stroke or TIA is associated with fewer ischaemic lesions at 1month in AF *** is no increased rate of haemorrhage with early *** results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated w

关键词： patients lesions ischaemic

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Relationship among Parkinson’s disease, constipation, microbes, and microbiological therapy

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World Journal of Gastroenterology 2024年第3期30卷 225-237页

作者： Xin-Yang Yuan Yu-Sen Chen Zhou Liu Department of neurology Affiliated Hospital of Guangdong Medical UniversityZhanjiang 524000Guangdong ProvinceChina Institute of neurology Guangdong Key Laboratory of Age-Related Cardiac and Cerebral DiseasesZhanjiang 524000Guangdong ProvinceChina

This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson’s disease(PD),a prevalent non-motor symptom contributing significantly to patients’morbidity.A marked alteration in the gut microbiota,predominantly an increase in the abundance of Proteobacteria and Bacteroidetes,is observed in PD-related *** treatments,although safe,have failed to effectively alleviate symptoms,thereby necessitating the development of novel therapeutic *** interventions such as prebiotics,probiotics,and fecal microbiota transplantation(FMT)hold therapeutic *** prebiotics improve bowel movements,probiotics are effective in enhancing stool consistency and alleviating abdominal *** shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with *** promising developments,the causal relationship between changes in gut microbiota and PD-related constipation remains elusive,highlighting the need for further research in this expanding field.

关键词： Parkinson disease Constipation Gut microbiota Prebiotics Probiotics Fecal microbiota transplantation

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Type-B monoamine oxidase inhibitors in neurological diseases:clinical applications based on preclinical findings

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Neural Regeneration Research 2024年第1期19卷 16-21页

作者： Marika Alborghetti Edoardo Bianchini Lanfranco De Carolis Silvia Galli Francesco E.Pontieri Domiziana Rinaldi neurology Unit NESMOS DepartmentFaculty of Medicine&PsychologySapienza-University of RomeSant’Andrea University HospitalRomeItaly Department of Clinical and Behavioral neurology IRCCS-Fondazione Santa LuciaRomeItaly

Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's *** drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the *** is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and *** studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic ***,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from *** to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now *** potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain *** purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.

关键词： glial cell line-derived neurotrophic factor(GDNF) glutamate neurological disorders neuroprotection Parkinson's disease preclinical studies rasagiline safinamide selegiline type-B monoamine oxidase(MAO_(B))inhibitors

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Pathological and Physiological High-frequency Oscillations on Electroencephalography in Patients with Epilepsy

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Neuroscience Bulletin 2024年第5期40卷 609-620页

作者： Hongyi Ye Cong Chen Shennan A.Weiss Shuang Wang Department of neurology Epilepsy CenterSecond Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009China Department of neurology State University of New York DownstateBrooklynNY11203USA Department of Physiology and Pharmacology State University of New York DownstateBrooklynNY11203USA Department of neurology New York City Health+Hospitals/Kings CountyBrooklynNY11203USA

High-frequency oscillations(HFOs)encompass ripples(80 Hz–200 Hz)and fast ripples(200 Hz–600 Hz),serving as a promising biomarker for localizing the epileptogenic zone in *** fast ripples are always pathological,while ripples may be physiological or *** physiological from pathological ripples is important not only for designating epileptogenic brain regions,but also for investigations that study ripples in the context of memory encoding,consolidation,and recall in patients with *** studies have sought to identify distinguishing features between pathological and physiological ripples over the past two *** and pathological ripples differ with respect to their spatial location,cellular mechanisms,morphology,and coupling with background electroencephalographic *** studies have demonstrated that differentiating between pathological and physiological ripples can improve surgical outcome *** this review,we summarize the characteristics,differences,and applications of pathological and physiological HFOs and discuss strategies for their clinical translation.

关键词： Ripples Epilepsy Memory Sleep Surgical outcome

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Dural sinus septum:an underlying cause of cerebral venous sinus stenting failure and complications

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Stroke & Vascular neurology 2024年第2期9卷 174-180页

作者： Yangang Zhao Xiaolan Zhang Bin Lv Jun Wang Xinfeng Liu Zhihua Du Fang Cui Baoming Li Xing Chen Xiangyu Cao Beijing Advanced Innovation Center for Biomedical Engineering School of Engineering MedicineBeihang UniversityBeijingChina Department of neurology Hainan Hospital of Chinese PLA General HospitalSanyaHainanChina Department of neurology Chinese PLA General HospitalBeijingChina

Objectives The presence of dural sinus septum has long been identified anatomically but is often neglected for its clinical *** findings revealed the association of dural sinus septum with venous sinus stenting failure and complications supported by clinical *** This retrospective study included 185 consecutive patients treated with cerebral venous sinus stenting from January 2009 to May *** identified the dural sinus septa using digital subtraction angiography(DSA)and classified them into three types based on their *** septa at the transverse sinus were defined as typeⅠ,those at the junction between the transverse sinus and sigmoid sinus were defined as typeⅡand those at the sigmoid sinus were defined as typeⅢ.Based on the anatomic features and neuroimaging clues,we investigated the correlation of dural sinus septa with stenting failure and *** 32(17.1%)out of 185 patients(121 with idiopathic intracranial hypertension and 64 with venous pulsatile tinnitus)were identified with dural sinus septa by *** than half of the septa were typeⅠ(18/32,56.2%),followed by typeⅡ(11/32,34.4%)and typeⅢ(3/32,9.4%).The dural sinus septa caused three stenting failures and complications,including one case of venous sinus injury with subdural haemorrhage and two cases of incomplete stent *** analysis revealed that the presence of dural sinus septum(p<0.01)was associated with complications of cerebral venous sinus *** The dural sinus septum is a common structure in the cerebral venous *** found that the presence of dural sinus septa introduces uncertainties to cerebral venous sinus stenting and suggested precautions and ingenious skills in imaging and treatment.

关键词： septum cerebral venous

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