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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 *** 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 *** 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 *** aneuploidies,copy number variants(CNVs)and chromosomal structural rearrangements were also ***,candidate genes were used for pathway and gene ontology enrichment *** 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 ***-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 *** 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 *** 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 ***,candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic *** 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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深部脑刺激治疗帕金森病:下丘脑核团靶点定位的解剖与生理对比研究

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中华神经外科疾病研究杂志 2002年第2期1卷 107-110页

作者： Wai.S Poon Danny TM Chan XL Zhu vincent ct mok YL Chan 香港中文大学威尔士王子医院外科系香港中文大学威尔士王子医院药学及治疗学部香港中文大学威尔士王子医院放射及影像诊断学部

目的探讨脑深部STN刺激靶点时MRI直接定位法和MER术中导引定位法的解剖学偏差。方法本组5例帕金森病患者,分别表现为运动迟缓、步态不稳及躯干症状,共安放6例次微电极。结果采用MRI直接定位法和MER术中导引定位法,其定位靶点的平均... 详细信息

目的探讨脑深部STN刺激靶点时MRI直接定位法和MER术中导引定位法的解剖学偏差。方法本组5例帕金森病患者,分别表现为运动迟缓、步态不稳及躯干症状,共安放6例次微电极。结果采用MRI直接定位法和MER术中导引定位法,其定位靶点的平均偏差距离是1.25mm,尽管该偏差值较小,但是,基于影像学的立体定向法只能将刺激电极定位于距离靶点几毫米的范围内。结论电生理学方法（MER）对于调整和确定靶点位置至关重要。MER术中导引定位法有助于手术的完全成功。

关键词：帕金森病下丘脑核团解剖学生理学 MRI直接定位法 MER术中引导定位法深部脑刺激靶点定位

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Temperate Stutzerimonas Phage Encoding Toxin-Antitoxin System Genes Represents a Novel Genus

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JOURNAL OF OCEAN UNIVERSITY OF CHINA 2024年第4期23卷 1087-1101页

作者： Zhang, Hong Guo, Ruizhe Gao, Chen Zheng, Kaiyang Xiong, Yao Dong, Yue Liu, Yundan Wang, Ziyue Chen, Ying Wang, Hongmin Shao, Hongbing Sung, Yeong Yik mok, Wen Jye Wong, Li Lian Mcminn, Andrew Wang, Min Liang, Yantao Ocean Univ China Inst Evolut & Marine Biodivers Coll Marine Life Sci MOE Lab Evolut & Marine BiodiversFrontiers Sci Ct Qingdao 266003 Peoples R China UMT OUC Joint ctr Marine Studies Qingdao 266003 Peoples R China Univ Tasmania Inst Marine & Antarctic Studies Hobart Tas 7001 Australia Ocean Univ China Haide Coll Qingdao 266100 Peoples R China Qingdao Univ Affiliated Hosp Qingdao 266001 Peoples R China Univ Malaysia Terengganu Inst Marine Biotechnol Kuala Terengganu 21030 Malaysia

Stutzerimonas have been extensively studied due to their remarkable metabolic and physiological diversity. However, research on its phages is currently limited. In this study, we isolated a novel double-stranded DNA (dsDNA) phage, vB_SstM-PG1, from the marine environment that infects Stutzerimonas stutzeri G1. Its dsDNA genome is 37204 bp long with a G/C content of 64.14% and encodes 54 open reading frames. The phage possesses a tail packaging structure that is different from known Stutzerimonas stutzeri phages and exhibits structural protein characteristics similar to those of temperate phages. In addition, two genes of toxin-antitoxin system, including YdaS_antitoxin and HEPN_SAV_6107, were found in the vB_SstM-PG1 genome and play important roles in regulating host growth and metabolism. With phylogenetic tree and comparative genomic analysis, it has been determined that vB_ SstM-PG1 is not closely related to any phages previously identified in the GenBank database. Instead, it has a connection with enigmatic, uncultured viruses. Specifically, the vB_SstM-PG1 virus exhibits an average nucleotide identity of over 70% with six uncultivated viruses identified in the IMG/VR v4 database. This significant finding has resulted in the identification of a novel viral genus known as Metabovirus.

关键词： Stutzerimonas vB_SstM-PG1 Metabovirus temperate phage genomic and phylogenetic analysis PSEUDOMONAS-AERUGINOSA CRYSTAL-STRUctURE GENOME SEQUENCE PROTEIN VIRUSES BActERIOPHAGES CLASSIFICATION CIRCULARIZES BIODIVERSITY NOMENCLATURE

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Demineralized Bone Matrix Fibers plus Allograft Bone for Multilevel Posterolateral Spine Fusion: A Game Changer?

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Open Journal of Orthopedics 2024年第2期14卷 105-113页

作者： Bodin Arnaud Barnouin Laurence Coulomb Remy Haignere vincent Kouyoumdjian Pascal Department of Orthopaedic and Traumatological Spine Surgery Groupe Hospitalier Mutualiste Grenoble France Tissue Bank of France Mions France Department of Orthopaedic and Traumatologic Surgery & Spinal Surgery Centre Hospitalier Universitaire N&icircmes France LMGC Université de Montpellier CNRS Montpellier France

Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been used to avoid the morbidity and insufficient quantity associated with harvesting autologous bone. The primary objective of this retrospective study was to determine whether, in patients with increased risk of operative nonunion related to multilevel fusion, adding DBM fibers to mineralized bone allograft resulted in better fusion than using allograft alone. The secondary objectives were to evaluate how adding DBM fibers affects functional disability, low back pain, intraoperative blood loss and the nonunion rate. Methods: This retrospective study involved a chart review of consecutive patients who underwent multilevel lumbar spinal fusion and were operated on by a single surgeon. The patients were divided into two groups: 14 patients received mineralized bone allograft (control group) and 14 patients received a combination of mineralized bone allograft and DBM (experimental group). Patients were reviewed at a mean of 16.4 ± 2.2 months after surgery at which point ct scans were analyzed to determine whether fusion had occurred;Oswestry disability index (ODI) and pain were also evaluated. Results: A mean of 5 levels [min 2, max 13] were fused in these patients. Posterolateral fusion as defined by the Lenke classification was not significantly different between groups. The experimental DBM group had a significantly better composite fusion score than the control group (P Discussion: Adding DBM fibers to allograft bone during multilevel posterolateral spinal fusion was safe and produced better composite fusion than using allograft only as an autograft extender.

关键词： Spine Surgery Demineralized Bone Fibers Bone Substitutes Retrospective Study

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Metastatic Spinal Tumors: Diagnostic Methods, Management and Prognosis at the Yaounde Central Hospital and Yaounde General Hospital

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Open Journal of Modern Neurosurgery 2024年第2期14卷 158-169页

作者： Nassourou Oumarou Haman Figuim Bello Orlane Ndome Toto Roland Ndouh Nchufor Nya Durand Bakop Ronaldo Foalou Anu vincent de Paul Djientcheu Faculty of Medicine and Biomedical Sciences University of Yaounde 1 Yaounde Cameroon Neurosurgery Department Yaounde General Hospital Yaounde Cameroon Cameroon Academy of Young Scientists Yaounde Cameroon Department of Neurosurgery Garoua General Hospital Garoua Cameroon Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon Department of Neurosurgery Douala General Hospital Douala Cameroon Facuty of Health Sciences University of Bamenda Bamenda Cameroon

Introduction: Metastatic spinal tumors (MST) refer to secondary involvement of the vertebral column by hematogenously-disseminated metastatic cells. They could affect either the bony structures or the spinal cords. Mechanical instability and neurologic deficits resulting from spinal cord compression are the most common manifestations. Surgical intervention remains the most effective treatment for about 20% of patients who present with spinal cord compression. The prognosis is relatively poor. This work has as objectives to describe: the diagnostic tools, the different modalities of management and the prognostic elements of spine metastasis. Methodology: We conducted an ambispective cross-sectional descriptive study;with retrospective data collection from January 2015 to December 2021 and prospective collection from January to April 2022 in the “Neurosurgery” unit of the Yaounde Central Hospital and the “Oncology and Neurosurgery” units of Yaounde General Hospital. Result: We included 101 patients. The M/F sex ratio was 1.66. The average age of the participants was 56.44 years (±14.19 SD) with a median of 58 years. Metastatic spinal tumors were discovered in 61.39% of patients with a previously known primary tumor and 21.78% of patients had newly discovered tumors. The neurologic examination revealed a vertebral syndrome in 79.21% of cases, radicular syndrome in 60.40% and sub-lesional syndrome in 59.89%. Sensory disorders accounted for 39.60% and sphincter disorders accounted for 34.65%. According to the degree of severity, the lesions were classified as Frankel E (37.62%) followed by Frankel D (21.78%). Metastatic lesions were mostly found at the thoracic vertebrae (68.25%) and lumbar vertebrae (22.22%). The most represented primary tumors were: prostate tumors (41.58%) and breast tumors (23.76%);followed by malignant hemopathies (15.84%). Computed-tomography scan (ct-scan) was the most frequent diagnostic imaging technique used (71.28%). Analgesic treatment mostly

关键词： Metastases Spinal Tumors Diagnosis Prognosis Spinal Cord Compression

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Current Epidemiology of Intracranial Metastases in Two University Teaching Reference Hospitals of the Town of Yaounde, Cameroon: Analysis of 35 Cases Recorded in the Neurosurgery Departments

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Open Journal of Modern Neurosurgery 2024年第2期14卷 124-136页

作者： Nassourou Oumarou Haman Ronaldo Fonju Anu Orlane Ndome Toto Bello Figuim Indira Baboke Marguerite Gwladys Nzedzou vincent de Paul Djientcheu Department of Surgery and Specialties Faculty of Medicine and Biomedical Sciences University of Yaounde 1 Yaounde Cameroon Department of Neurosurgery Yaounde General Hospital Yaounde Cameroon Department of Surgery and Specialties Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon Department of Neurosurgery Douala General Hospital Douala Cameroon Department of Neurosurgery Garoua General Hospital Garoua Cameroon

Background: The incidence of intracranial metastases (ICMET) has been steadily rising, and its frequency with respect to primary brain tumours is relatively high. Objective: The objectives of this study were to elucidate the current epidemiology and describe the clinical, diagnostic and therapeutic features of ICMET in Yaounde. Method and findings: A descriptive cross-sectional study was done in the neurosurgery departments of the General and Central Hospitals of Yaounde during the period from January 2016 to December 2022. We included all medical booklets of patients admitted for a tumoral intracranial expansive process with our target population being patients with histological evidence of ICMET, and did a retrospective inclusion of data using a pre-established technical form aimed at collecting sociodemographic data, clinical data, paraclinical data, and the treatment procedures. Analysis was done using the SPSS statistical software. A total of 614 cases of intracranial tumors were included among whom 35 presented histological evidence of ICMET. This gives a frequency of 5.7%. The sex ratio was 0.94, the mean age was 55.68 +/- 14.4 years, extremes 28 and 86 years and the age range 50 - 59 was affected in 28.57% of cases. The clinical presentation included signs of raised intracranial pressure (headache, blurred vision, vomiting) in 26 cases (74.3%), motor deficit 48.6%, seizures 17.1%. The mode of onset was metachronous in 71.4% and synchronous in 28.6%. The imaging techniques were cerebral ct scan in 82.9%, cerebral MRI in 40%, TAP scan in 22.9%. The metastatic lesions were supratentorial in 94.3% and single in 62.9%. The primary cancers found were breast cancer (31.4%), lung cancer (25.7%), prostate cancer (17.1%), thyroid cancer (5.7%), colon cancer (2.9%), and melanoma (2.9%). The therapeutic modalities were total resection (68.6%), radiotherapy (37.1%). Conclusion: Intracranial metastases are relatively frequent. There is a female sex predominance and the ag

关键词： Intracranial Metastases Epidemiology Yaounde

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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 *** the complex biological changes in ageing increase the brain’s susceptibility to neurodegeneration remains incompletely *** 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 *** CSVD neuroimaging features have shared and distinct clinical consequences,and the automatic quantification methods for these features are increasingly used in research and clinical *** 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 *** 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 *** pathological relationship between rheumatoid arthritis and cancer hinted that some chemotherapeutic drugs,such as methotrexate(MTX),could be used for RA *** idea was reinforced by the analysis of mutations in p53 tumor suppressor *** 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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