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Risk stratification in symptomatic intracranial atherosclerotic disease with conventional vascular risk factors and cerebral haemodynamics

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Stroke & Vascular Neurology 2023年第1期8卷 77-85页

作者： Xuan Tian Hui Fang Linfang Lan Hing Lung Ip Jill Abrigo Haipeng Liu Lina Zheng Florence S Y Fan Sze Ho Ma Bonaventure Ip Bo Song Yuming Xu Jingwei Li Bing Zhang Yun Xu Yannie O Y Soo vincent mok Ka Sing Wong Thomas W Leung Xinyi Leng Department of Medicine and Therapeutics The Chinese UniversityHong KongChina Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina Department of Neurology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Imaging and Interventional The Chinese UniversityHong KongChina Research Centre of Intelligent Healthcare Faculty of Health and Life ScienceCoventry UniversityCoventryUK Department of Neurology Nanjing University Medical School Affiliated Nanjing Drum Tower HospitalNanjingJiangsuChina Department of Radiology Nanjing University Medical School Affiliated Nanjing Drum Tower HospitalNanjingJiangsuChina

Background and purpose Symptomatic intracranial atherosclerotic stenosis(sICAS)is associated with a considerable risk of recurrent stroke despite contemporarily optimal medical treatment.Severity of luminal stenosis in sICAS and its haemodynamic significance quantified with computational fluid dynamics(CFD)models were associated with the risk of stroke recurrence.We aimed to develop and compare stroke risk prediction nomograms in sICAS,based on vascular risk factors and these metrics.Methods Patients with 50%-99%sICAS confirmed in CT angiography(CTA)were enrolled.Conventional vascular risk factors were collected.Severity of luminal stenosis in sICAS was dichotomised as moderate(50%-69%)and severe(70%-99%).Translesional pressure ratio(PR)and wall shear stress ratio(WSSR)were quantified via CTA-based CFD modelling;the haemodynamic status of sICAS was classified as normal(normal PR&WSSR),intermediate(otherwise)and abnormal(abnormal PR&WSSR).All patients received guideline-recommended medical treatment.We developed and compared performance of nomograms composed of these variables and independent predictors identified in multivariate logistic regression,in predicting the primary outcome,recurrent ischaemic stroke in the same territory(SIT)within 1 year.Results Among 245 sICAS patients,20(8.2%)had SIT.The D2H2A nomogram,incorporating diabetes,dyslipidaemia,haemodynamic status of sICAS,hypertension and age≥50 years,showed good calibration(P for Hosmer-Lemeshow test=0.560)and discrimination(C-statistic 0.73,95%CI 0.60 to 0.85).It also had better performance in risk reclassification and provided larger net benefits in decision curve analysis,compared with nomograms composed of conventional vascular risk factors only,and plus the severity of luminal stenosis in sICAS.Sensitivity analysis in patients with anterior-circulation sICAS showed similar results.Conclusions The D2H2A nomogram,incorporating conventional vascular risk factors and the haemodynamic significance of sICAS as assessed in CFD models,could be a useful tool

关键词： intracranial otherwise stratification

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Neurovascular ageing:transcriptomic readout and implications on therapeutic targeting in Alzheimer’s disease

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Neural Regeneration Research 2021年第12期16卷 2411-2412页

作者： Zhongqi Li Bonaventure Ip vincent C.T.mok Ho Ko Division of Neurology Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong Kong Special Administrative RegionChina Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongHong Kong Special Administrative RegionChina(Li ZKo H)Margaret K.L.Cheung Research Centre for Management of ParkinsonismThe Chinese University of Hong KongHong Kong Special Administrative RegionChina Chow Yuk Ho Technology Centre for Innovative Medicine The Chinese University of Hong KongHong Kong Special Administrative RegionChina Gerald Choa Neuroscience Centre School of Biomedical SciencesDepartment of PsychiatryPeter Hung Pain Research InstituteFaculty of MedicineThe Chinese University of Hong KongHong Kong Special Administrative RegionChina

Ageing is one of the greatest risk factors for neurodegenerative diseases.How the complex biological changes in ageing increase the brain’s susceptibility to neurodegeneration remains incompletely understood.Research into neurodegenerative disorders has shifted from a neuron-centric approach,to the contributing roles of age-related neurovascular and glial cell dysfunction.

关键词： incomplete susceptibility ageing

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Magnetic resonance imaging manifestations of cerebral small vessel disease:automated quantification and clinical application

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Chinese Medical Journal 2021年第2期134卷 151-160页

作者： Lei Zhao Allan Lee Yu-Hua Fan vincent C.T.mok Lin Shi BrainNow Research Institute ShenzhenGuangdong 518000China Department of Neurology The First Affiliated HospitalSun Yat-sen UniversityGuangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological DiseasesNational Key Clinical Department and Key Discipline of NeurologyGuangzhouGuangdong 510080China Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong 999077China Gerald Choa Neuroscience Centre Margaret KL Cheung Research Centre for Management of ParkinsonismTherese Pei Fong Chow Research Centre for Prevention of DementiaLui Che Woo Institute of Innovative MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Imaging and Interventional Radiology The Chinese University of Hong KongHong Kong 999077China

The common cerebral small vessel disease(CSVD)neuroimaging features visible on conventional structural magnetic resonance imaging include recent small subcortical infarcts,lacunes,white matter hyperintensities,perivascular spaces,microbleeds,and brain atrophy.The CSVD neuroimaging features have shared and distinct clinical consequences,and the automatic quantification methods for these features are increasingly used in research and clinical settings.This review article explores the recent progress in CSVD neuroimaging feature quantification and provides an overview of the clinical consequences of these CSVD features as well as the possibilities of using these features as endpoints in clinical trials.The added value of CSVD neuroimaging quantification is also discussed for researches focused on the mechanism of CSVD and the prognosis in subjects with CSVD.

关键词： Cerebral small vessel disease Neuroimaging manifestations Automated quantification Clinical relevance

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The potential development of drug resistance in rheumatoid arthritis patients identified with p53 mutations

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Genes & Diseases 2023年第6期10卷 2252-2255页

作者： Congling Qiu Joyce Tsz Wai Chan David Wei Zhang Io Nam Wong Yaling Zeng Betty Yuen Kwan Law Simon Wing Fai mok Ivo Ricardo De Seabra Rodrigues Dias Wenfeng Liu Liang Liu vincent Kam Wai Wong Dr.Neher's Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao SAR 999078China Department of Public Health and Preventive Medicine School of MedicineJinan UniversityGuangzhouGuangdong 510000China Faculty of Medicine Macao University of Science and TechnologyMacao SAR 999078China School of Biotechnology and Health Sciences Wuyi UniversityJiangmenGuangdong 529000China

Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by cartilage and bone damage with the presence of pannus formation which causes uncontrollable proliferation and invasion of fibroblast-like synoviocytes(FLS).Since rheumatoid arthritis is a chronic disorder,the patients normally need to undergo prolonged antirheumatic treatment with the use of disease-modifying antirheumatic drugs(DMARDs),steroids,and nonsteroidal anti-inflammatory drugs(NSAIDs).The efficacy of such long-term pharmaceutical intervention can be significantly affected by the development of drug resistance.The pathological relationship between rheumatoid arthritis and cancer hinted that some chemotherapeutic drugs,such as methotrexate(MTX),could be used for RA treatment.This idea was reinforced by the analysis of mutations in p53 tumor suppressor gene.Around 50%of p53 somatic mutations observed from various cancers are also identified in the synovium of RA patients1(Fig.1A).Of note,the hyperplastic synovium in RA with overexpressed p53 mutants contributed to the destruction of joints in patients with erosive RA.

关键词： patients drugs rheumatoid

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The host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2039-2055页

作者： Kan Xing Wu Thinesshwary Yogarajah Marcus Wing Choy Loe Parveen Kaur Regina Ching Hua Lee Chee Keng mok Yi Hao Wong Patchara Phuektes Li Sze Yeo vincent T.K.Chow Yong Wah Tan Justin Jang Hann Chu Department of Microbiology and Immunology Yong Loo Lin School of MedicineNational University Health SystemNational University of SingaporeSingapore 117597Singapore Department of Pathobiology Faculty of Veterinary MedicineKhonkaen UniversityKhonkaen 40002Thailand Infectious Disease Programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A∗STAR)Singapore 138648Singapore Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore 308232Singapore NUSMed Biosafety Level 3 Core Facility Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore

Positive-sense RNA viruses modify intracellular calcium stores,endoplasmic reticulum and Golgi apparatus(Golgi)to generate membranous replication organelles known as viral factories.Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity.Here,we identified the vital role of a broadspectrum antiviral,peruvoside in limiting the formation of viral factories.Mechanistically,we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1(GBF1)phosphorylation and Golgi vesiculation by peruvoside treatment.The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation.Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337(T1337).We also showed 100%of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum.These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside,host-directed antivirals for positive-sense RNA virus-mediated disease,in the interim where no vaccine is available.

关键词： Positive-sense RNA viruses Peruvoside Antiviral CDKI signaling Viral factories Calcium efflux Broad-spectrum Golgi apparatus

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Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease

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Stroke & Vascular Neurology 2022年第3期7卷 182-189页

作者： Mengmeng Shi Xinyi Leng Ying Li Zihan Chen Ye Cao Tiffany Chung Bonaventure YM Ip vincent HL Ip Yannie OY Soo Florence SY Fan Sze Ho Ma Karen Ma Anne Y Y Chan Lisa WC Au Howan Leung Alexander Y Lau vincent CT mok Kwong Wai Choy Zirui Dong Thomas W Leung Department of Obstetrics and Gynaecology The Chinese University of Hong KongHong KongChina Key Laboratory for Regenerative Medicine Ministry of Education(Shenzhen Base)Shenzhen Research InstituteThe Chinese University of Hong KongShenzhenChina Hong Kong Hub of Paediatric Excellence The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongPrince of Wales HospitalHong KongChina Department of Paediatrics The Chinese University of Hong KongHong KongChina The Chinese University of Hong Kong-Baylor College of Medicine Joint Center For Medical Genetics The Chinese University of Hong KongHong KongChina

Objectives The predisposition of intracranial atherosclerotic disease(ICAD)to East Asians over Caucasians infers a genetic basis which,however,remains largely unknown.Higher prevalence of vascular risk factors(VRFs)in Chinese over Caucasian patients who had a stroke,and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD.Methods Unrelated symptomatic patients with ICAD were recruited for genome sequencing(GS,60-fold).Rare and potentially deleterious single-nucleotide variants(SNVs)and small insertions/deletions(InDels)were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes.Rare aneuploidies,copy number variants(CNVs)and chromosomal structural rearrangements were also investigated.Lastly,candidate genes were used for pathway and gene ontology enrichment analysis.Results Among 92 patients(mean age at stroke onset 61.0±9.3 years),GS identified likely ICAD-associated rare genomic variants in 54.3%(50/92)of patients.Forty-eight patients(52.2%,48/92)had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes.None of the 59 rare variants were identified in local subjects without ICAD(n=126).31 SNVs/InDels were related to conventional VRFs,and 28 were discovered in genes related to other stroke subtypes.Our study also showed that rare CNVs(n=7)and structural rearrangement(a balanced translocation)were potentially related to ICAD in 8.7%(8/92)of patients.Lastly,candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process.Conclusions Our GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.

关键词： patients metabolism intracranial

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Atrophy of the left dorsolateral prefrontal cortex is associated with poor performance in verbal fluency in elderly poststroke women

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Neural Regeneration Research 2013年第4期8卷 346-356页

作者： Yang-Kun Chen Wei-Min Xiao Defeng Wang Lin Shi Winnie CW Chu vincent CT mok Ka Sing Wong Gabor S Ungvari Wai Kwong Tang Department of Neurology Dongguan People's Hospital Department of Diagnostic Radiology and Organ Imaging the Chinese University of Hong Kong Department of Medicine and Therapeutics the Chinese University of Hong Kong Graylands Hospital School of Psychiatry & Clinical NeurosciencesUniversity of Western AustraliaPerth 6005Australia Department of Psychiatry the Chinese University of Hong Kong

This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged -〉 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions： anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only （partial coefficient = 0.453, P = 0.045）, after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test （partial coefficient = 0.661, P = 0.001） and between the left prefrontal cortex volume and Verbal Fluency Test （partial coefficient = 0.573, P = 0.004） in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.

关键词： neural regeneration neuroimaging brain atrophy verbal fluency executive function stroke sex differences prefrontal cortex dorsolateral prefrontal cortex magnetic resonance imaging grants-supported paper photographs-containing paper neuroregeneration

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低分子肝素与阿司匹林治疗颅内大血管狭窄所致急性缺血性脑卒中的比较研究:FISS-tris试验的亚组分析

低分子肝素与阿司匹林治疗颅内大血管狭窄所致急性缺血性脑卒中的...

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中华医学会第十八次全国神经病学学术会议

作者：宋明睿王乔树 Christopher Chen Xiangyan Chen Jinghao Han YannieSoo Thomas W Leung vincent mok Ka Sing Lawrence Wong 上海市第一人民医院神经内科香港中文大学威尔斯亲王医院内科及药物治疗学系神经科

背景和目的对于颅内大动脉狭窄导致的缺血性脑卒中尚缺乏有效的急性期治疗手段,除静脉溶栓和药物治疗外,动脉取栓治疗主要适用于发病后最初几小时。FISS-tris试验(Fraxparin in Stroke Study for the Treatment of Ischemic Stroke Stu...

背景和目的对于颅内大动脉狭窄导致的缺血性脑卒中尚缺乏有效的急性期治疗手段,除静脉溶栓和药物治疗外,动脉取栓治疗主要适用于发病后最初几小时。FISS-tris试验(Fraxparin in Stroke Study for the Treatment of Ischemic Stroke Study)的主要研究对象

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脑卒中伴融合型脑白质病变患者的他汀类药物治疗

脑卒中伴融合型脑白质病变患者的他汀类药物治疗

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2013年全国老年性痴呆与相关疾病学术会议

作者：熊云云 Adrian Wong Margherita Cavalieri Reinhold Schmidt Winnie W.C.Chu Ka Sing Wong 刘新峰 vincent mok 南京军区南京总医院神经内科香港中文大学药物与治疗学系香港教育学院心理学研究部心理健康和老龄化中心

目的:脑白质病变(white matter hyperintensity,WMH)和腔隙性脑梗死是两种脑小血管病。他汀类药物可降低各类脑卒中的复发率,其中包括腔隙性脑梗死。本文旨在研究他汀类药物对脑卒中伴融合型WMH的患者是否存在延缓WMH进展和/或认知功能...

目的:脑白质病变(white matter hyperintensity,WMH)和腔隙性脑梗死是两种脑小血管病。他汀类药物可降低各类脑卒中的复发率,其中包括腔隙性脑梗死。本文旨在研究他汀类药物对脑卒中伴融合型WMH的患者是否存在延缓WMH进展和/或认知功能障碍的作用。方法:研究入组了100例基线MRI上存在融合型WMH的患者,其中81例完成了2年随访。使用MMSE和MDRS I/P量表分别评估总体认知功能和执行功能。比较他汀治疗组和非他汀治疗组WMH体积和认知的变化,同时评估他汀类药物对新发脑梗死灶和新发微出血发生率的影响。结果:他汀治疗组(50例)较非他汀治疗组(31例)的WMH体积进展慢(1.54±4.52cm VS 5.01±6.00 cm,P=0.01)。他汀类药物的使用是WMH体积进展的独立预测因子(β=-0.322,P=-0.010),并与MDRS I/P评分呈正相关(β=0.474,P=0.001),而与MMSE变化无相关性,与新发脑梗死灶和新发微出血无相关性。结论:对于脑卒中伴融合型白质病变的患者,他汀类药物可减缓WMH的进展以及执行功能的下降。

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Vascular contribution to cognition in stroke and Alzheimer's disease

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Translational Neuroscience and Clinics 2018年第1期4卷 39-48页

作者： Yuanhan Yang Jongling Fuh vincent C.T.mok Department of Neurology Kaohsiung Municipal Ta-Tung Hospital Department of Neurology Kaohsiung Medical University Hospital Department of and Master's Program in Neurology Faculty of Medicine Kaohsiung Medical University Faculty of Medicine National Yang-Ming University School of Medicine Department of Neurology Neurological Institute Taipei Veterans General Hospital Department of Medicine and Therapeutics The Chinese University of Hong Kong

Vascular factors to cognitive impairment in degenerative on nondegenerative diseases have been reported, examined, and debated for several decades. The various definitions of cognitive impairment due to vascular origins will make these results diverse. During this review, we are going to report currently update information of vascular contributions to cognitive function, in clinical or neuroimaging findings. Risks factors and their managements also will be discussed and reported to have a comprehensive review.

关键词： Alzheimer’s disease vascular cognitive impairment post stroke dementia white matter hyperintensity diabetic mellitus hypertension

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