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Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

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Neural Regeneration Research 2024年第12期19卷 2773-2784页

作者： Hui Zhu James D.Guest Sarah Dunlop Jia-Xin Xie Sujuan Gao Zhuojing Luo Joe E.Springer Wutian Wu Wise Young Wai Sang Poon Song Liu Hongkun Gao Tao Yu Dianchun Wang Libing Zhou Shengping Wu Lei Zhong Fang Niu Xiaomei Wang Yansheng Liu Kwok-Fai So Xiao-Ming Xu Kunming Tongren Hospital KunmingYunnan ProvinceChina neurological Surgery and the Miami Project to Cure ParalysisMiller School of MedicineUniversity of MiamiMiamiFLUSA School of Biological sciences The University of Western AustraliaPerthWAAustralia Minderoo Foundation PerthWAAustralia Clinical Center for Spinal Cord Injury Kunming General Hospital of Chengdu Military CommandKunmingYunnan ProvinceChina department of Biostatistics and Health Data Science Indiana University School of MedicineIndianapolisINUSA department of Orthopedic Spinal Surgery Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Spinal Cord and Brain Injury Research Center Department of Physical Medicine and RehabilitationUniversity of Kentucky College of MedicineLexingtonKYUSA Guangdong-HongKong-Macao Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina W.M.Keck Center for Collaborative Neuroscience Rutgers UniversityPiscatawayNJUSA Neurosurgery department Chinese University of Hong KongPrince of Wales HospitalHong Kong Special Administration RegionChina Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA

For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein *** is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury *** of effective therapies fo r chronic spinal co rd injury patients is *** conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive *** clinical trial was registered at ***(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord *** found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training ***,the surgical procedures and intensive rehabilitation were *** Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 *** combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

关键词： chronic spinal cord injury intensive rehabilitation locomotor training neurological recovery surgical intervention weightbearing walking training

Neglected Mendelian causes of stroke in adult Chinese patients who had an ischaemic stroke or transient ischaemic attack

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Stroke & Vascular Neurology 2024年第3期9卷 194-201,I0001-I0103页

作者： Wei Li Hao Li Chaoxia Lu Jialu Zhao Huichun Xu Zhe Xu Braxton Mitchell Yong Jiang Hong-Qiu Gu Qin Xu Anxin Wang Xia Meng Jinxi Lin Jing Jing Zixiao Li Wanlin Zhu Zhigang Liang Mengxing Wang Yongjun Wang China National Clinical Research Center for neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Division of Endocrinology Diabetes and NutritionDepartment of MedicineUniversity of Maryland School of MedicineBaltimoreMarylandUSA department of Neurology Qindao University Medical College Affiliated Yantai Yuhuangding HospitalYantaiShandongChina Clinical Center for Precision Medicine in Stroke Capital Medical UniversityBeijingChina

Background and purpose Multiple factors play important roles in the occurrence and prognosis of ***,the roles of monogenic variants in all-cause ischaemic stroke have not been systematically *** aim to identify underdiagnosed monogenic stroke in an adult ischaemic stroke/transient ischaemic attack(TIA)cohort(the Third China National Stroke Registry,CNSR-III).Methods Targeted next-generation sequencing for 181 genes associated with stroke was conducted on DNA samples from 10428 patients recruited through *** genetic and clinical data from electronic health records(EHRs)were reviewed for completion of the diagnostic *** assessed the percentages of individuals with pathogenic or likely pathogenic(P/LP)variants,and the diagnostic yield of pathogenic variants in known monogenic disease genes with associated *** In total,1953 individuals harboured at least one P/LP variant out of 10428 ***,792(7.6%)individuals(comprising 759 individuals harbouring one P/LP variant in one gene,29 individuals harbouring two or more P/LP variants in different genes and 4 individuals with two P/LP variants in ABCC6)were predicted to be at risk for one or more monogenic diseases based on the inheritance ***,230 of 792 individuals manifested a clinical phenotype in the EHR data to support the diagnosis of stroke with a monogenic *** most diagnosed Mendelian cause of stroke in the cohort was cerebral autosomal dominant arteriopathy with subcortical infarcts and *** were no relationships between age or family history and the incidence of first symptomatic monogenic stroke in *** The rate of monogenic cause of stroke was 2.2%after reviewing the clinical *** reasons that Mendelian causes of stroke may be missed in adult patients who had an ischaemic stroke/TIA include a late onset of stroke symptoms,combination with common vascular risks and the absence of a promine

关键词： patients transient likely

Emergence of taurine as a therapeutic agent for neurological disorders

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Neural Regeneration Research 2024年第1期19卷 62-68页

作者： Ashok Jangra Priyanka Gola Jiten Singh Pooja Gond Swarnabha Ghosh Mahesh Rachamalla Abhijit Dey Danish Iqbal Mehnaz Kamal Punya Sachdeva Saurabh Kumar Jha Shreesh Ojha Dinesh Kumar Niraj Kumar Jha Hitesh Chopra Shing Cheng Tan department of Pharmaceutical sciences Central University of HaryanaMahendergarhHaryanaIndia department of Biology University of SaskatchewanSaskatoonSKCanada department of Life sciences Presidency UniversityKolkataWest BengalIndia department of Health Information Management College of Applied Medical SciencesBuraydah Private CollegesBuraydahSaudi Arabia department of Pharmaceutical Chemistry College of PharmacyPrince Sattam Bin Abdulaziz UniversityAl-KharjSaudi Arabia GloNeuro Vishwakarma RoadNoidaIndia department of Biotechnology School of Engineering&Technology(SET)Sharda UniversityGreater NoidaUttar PradeshIndia department of Pharmacology and Therapeutics College of Medicine and Health SciencesUnited Arab Emirates UniversityAl AinUnited Arab Emirates School of Bioengineering&Biosciences Lovely Professional UniversityPhagwaraIndia department of Biotechnology School of Applied&Life Sciences(SALS)Uttaranchal UniversityDehradunIndia Chitkara College of Pharmacy Chitkara UniversityPunjabIndia UKM Medical Molecular Biology Institute Universiti Kebangsaan MalaysiaKuala LumpurMalaysia

Taurine is a sulfur-containing,semi-essential amino acid that occurs naturally in the *** alternates between inflammation and oxidative stress-mediated injury in various disease *** part of its limiting functions,taurine also modulates endoplasmic reticulum stress,Ca^(2+)homeostasis,and neuronal activity at the molecular *** effectively protects against a number of neurological disorders,including stro ke,epilepsy,cerebral ischemia,memory dysfunction,and spinal cord *** various therapies are available,effective management of these disorders remains a global *** 30 million people are affected *** design of taurine fo rmation co uld lead to potential drugs/supplements for the health maintenance and treatment of central nervous system *** general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this *** article is a good resource for understanding the general effects of taurine on various *** the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms,it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics,with emphasis on mechanism and clinical studies to determine efficacy.

关键词： antioxidant epilepsy γ-amino butyric acid neurodegenerative disorders neuroprotection oxidative stress spinal cord injury taurine

Evaluation of the Neurodevelopmental Outcome of Toddlers with Spinal Dysraphism after Surgical Repair Using ASQ-3^™ Scores

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Open Journal of Modern Neurosurgery 2024年第1期14卷 14-29页

作者： Mujahid Imam Fawaz Eljili Marhoom Sawsan Aldeaf Ali Awad Ahmed Zidan Mohamed Mustafa Ahmed Sanna Taha Neurosurgery department National Center for Neurological Sciences (NCNS) Khartoum Sudan Neurosurgery department Royal Care International Hospital Khartoum Sudan Al Ribat Neurospine Center Khartoum Sudan Neurosurgery department Haj Almardi (Al Tamyouz) Hospital Khartoum Sudan Neurosurgery department Al Jazeera Trauma Center Khartoum Sudan

Background: Spinal dysraphism represents a wide spectrum of congenital abnormalities of the spine. Myelomeningocele is considered the most common malformation and the most common we saw in our community, with its morbidity problems seen commonly in the postoperative period. ASQ-3TM Scores are the ages and stages questionnaire, third edition, and represent a tool to assess the development progress, especially in toddlers. Objectives: Evaluation of neurodevelopmental outcome among Sudanese toddlers with spinal dysraphism after surgical closure with or without a VP shunt using ASQ-3TM Scores. Methodology: This is a retrospective hospital-based study of 84 patients who underwent myelomeningocele repair at the National Center for neurological sciences (NCNS) during the period from 2017 up to 2019. Data were collected through a constructed questionnaire, including ASQ-3TM Scores. Data were processed and analyzed using the Statistical Package for Social Science (SPSS) computer program. Version 25. Results: 84 patients were included in this study;all patients were diagnosed with spinal dysraphism. Out of them, 51 (60.7%) were 2 years old, 33 (39.3%) were 3 years old, 45 (53.6%) were male, 45 (53.6%) of patients mothers attended ANC irregularly, and 54 (64.3%) their mothers didn’t receive folate supplements. 44 (52.3%) of patients underwent MMC repair only, while 40 (47.7%) underwent MMC repair and VP shunt. The commonest postoperative complication was infection, reported in 12 (14.3%) of patients, followed by VP shunt revision in 9 (10.7%) of patients. neurological assessment showed that the majority of patients need further assessment with a professional, 57 (67.9%) of children don’t walk, run, or climb like other toddlers as their parent’s state;also, half of patients (42, 50%) had medical problems, and 27 (32.1%) of their parent’s state that they do not talk like other toddlers their age. There was a statistically significant association

关键词： Toddlers’ Neurodevelopmental Outcome Myelomeningocele Evaluation ASQ-3™ Scores Spinal Dysraphasim Neurodevelopmental Outcome

The Multiple Roles of Autophagy in Neural Function and Diseases

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Neuroscience Bulletin 2024年第3期40卷 363-382页

作者： Yan-Yan Li Zheng-Hong Qin Rui Sheng department of Pharmacology and Laboratory of Aging and Nervous Diseases Jiangsu Key laboratory of Neuropsychiatric DiseasesCollege of Pharmaceutical Sciences of Soochow UniversitySuzhou 215123China

Autophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes,where proteins,lipids,and organelles are degraded and *** to the way the cytoplasmic components are engulfed,autophagy can be divided into macroautophagy,microautophagy,and chaperone-mediated ***,many studies have found that autophagy plays an important role in neurological diseases,including Alzheimer's disease,Parkinson's disease,Huntington's disease,neuronal excitotoxicity,and cerebral *** maintains cell homeostasis in the nervous system via degradation of misfolded proteins,elimination of damaged organelles,and regulation of apoptosis and ***-mTOR,Beclin 1,TP53,endoplasmic reticulum stress,and other signal pathways are involved in the regulation of autophagy and can be used as potential therapeutic targets for neurological ***,we discuss the role,functions,and signal pathways of autophagy in neurological diseases,which will shed light on the pathogenic mechanisms of neurological diseases and suggest novel targets for therapies.

关键词： Autophagy Neurodegenerative diseases Cerebral ischemia AMPK mTOR Beclin 1 TP53 Endoplasmic reticulum stress

Harnessing innate immune pathways for therapeutic advancement in cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1506-1564页

作者： Ankang Hu Li Sun Hao Lin Yuheng Liao Hui Yang Ying Mao department of Neurosurgery Huashan HospitalFudan UniversityShanghaiP.R.China Institute for Translational Brain Research Shanghai Medical CollegeFudan University ShanghaiPR.China National Center for neurological Disorders Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration Shanghai Clinical Medical Center of NeurosurgeryNeurosurgical Institute of Fudan UniversityHuashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science and MOE Frontiers Center for Brain Science Institutes of Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)and Key Laboratory of Metabolism and Molecular Medicine(Ministry of Education)and Molecular and Cell Biology LabInstitutes of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghaiP.R.China

The innate immune pathway is receiving increasing attention in cancer *** pathway is ubiquitous across various cell types,not only in innate immune cells but also in adaptive immune cells,tumor cells,and stromal *** targeting the innate immune pathway have shown profound changes in the tumor microenvironment(TME)and improved tumor prognosis in preclinical ***,to date,the clinical success of drugs targeting the innate immune pathway remains ***,recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor *** uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate *** this review,we observe that the role of the innate immune pathway demonstrates heterogeneity,linked to the tumor development stage,pathway status,and specific cell *** propose that within the TME,the innate immune pathway exhibits multidimensional *** diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling *** pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative *** our understanding of the tumor's innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinicalapplication.

关键词： drugs therapeutic innate

One-year direct and indirect costs of ischaemic stroke in China

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Stroke & Vascular Neurology 2024年第4期9卷 380-389,I0032-I0043页

作者： Wei Lv Anxin Wang Qianyi Wang Ruimin Wang Qin Xu Shuqing Wu Yi Han Yong Jiang Jinxi Lin Jing Jing Hao Li Yongjun Wang Xia Meng department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina School of Basic Medical Science Capital Medical UniversityBeijingChina department of Cardiology Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityGuangzhouChina Health Economic Research Institute Sun Yat-Sen UniversityGuangzhouChina

Background This is the first real-world study to estimate the direct costs and indirect costs of first-ever ischaemic stroke with 1-year follow-up in China,based on a nationally representative *** Patients were chosen from 20 geographically diverse sites from the nationally representative database China National Stroke Registry-III(CNSR-III).The inclusion criteria were surviving patients who were hospitalised with first-ever ischaemic stroke from February 2017 to February 2018(the index event);aged 18–80 during the index event;no history of other stroke *** primary endpoints were direct medical costs,direct non-medical costs,indirect costs and total cost(ie,the sum of all cost components).Patient characteristics and clinical data were extracted from ***-related in-hospital direct medical costs were collected from hospital electronic medical *** patient survey collected data related to out-of-hospital direct medical costs,direct non-medical costs and indirect *** secondary objective was to explore clinical factors associated with cost outcomes through univariate analysis and multiple *** The study enrolled 520 *** total cost was 57567.48 CNY,with 26612.67 CNY direct medical costs,2787.56 CNY direct non-medical costs and 28167.25 CNY indirect *** analysis showed that longer lengths of stay during the index event,higher National Institutes of Health Stroke Scale(NIHSS)and modified Rankin Scale scores were associated with higher costs in all ***,EuroQol 5 Dimension utility scores were associated with decreased costs except direct non-medical *** regressions showed that higher admission NIHSS scores were independently associated with higher direct medical costs,indirect costs and total *** 3-month utilities were associated with lower total *** This real-world study showed substantial 1-year economic burden following first-ever ischaemic stroke

关键词： indirect costs Dimension

The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

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Neural Regeneration Research 2024年第9期19卷 1998-2003页

作者： Yiqing Wang Chuheng Chang Renzhi Wang Xiaoguang Li Xinjie Bao 4+4 Doctor Medical Program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina department of Neurosurgery Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

关键词： ischemic stroke mesenchymal stem cells metabolomics multilevel omics neural stem/progenitor cells neuroinflammation pathophysiology proteomics stem cell therapy transcriptomes

Alzheimer’s disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling

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The Innovation 2024年第1期5卷 118-126页

作者： Qing-Qing Tao Xue Cai Yan-Yan Xue Weigang Ge Liang Yue Xiao-Yan Li Rong-Rong Lin Guo-Ping Peng Wenhao Jiang Sainan Li Kun-Mu Zheng Bin Jiang Jian-Ping Jia Tiannan Guo Zhi-Ying Wu department of Neurology and Research Center of Neurology in the Second Affiliated Hospital and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of MedicineHangzhou 310009China Liangzhu Laboratory Zhejiang UniversityHangzhou 311100China Westlake Laboratory of Life sciences and Biomedicine Key Laboratory of Structural Biology of Zhejiang ProvinceSchool of Life SciencesWestlake UniversityHangzhou 310024China Institute of Basic Medical sciences Westlake Institute for Advanced StudyHangzho 310024China department of Neurology First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China department of Neurology First Affiliated HospitalSchool of MedicineXiamen UniversityXiamen 361009China Innovation Center for neurological Disorders and department of Neurology Xuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric DiseasesBeijing 100053China MOE Frontier Science Center for Brain Science and Brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai 200031China

Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlying AD,and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic *** ADspecific early diagnostic and disease staging biomarkers are *** this study,we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid(CSF)and serum samples in a discovery cohort comprising 98 *** biomarkers were validated by parallel reaction monitoring–based targeted proteomic assays in an independent multicenter cohort comprising 288 *** quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort,identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers,*** the validation cohort,58 and 21 CSF proteins,as well as 12 and 18 serum proteins,were verified as early diagnostic and staging biomarkers,*** 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment(MCI)due to AD from normal cognition with areas under the curve of 0.984 and 0.881,*** 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative ***,we identified 21 CSF and 18 serum stage-associated proteins re-flecting AD *** findings provide a foundation for developing bloodbased tests for AD screening and staging in clinical practice.

关键词： cerebrospinal Alzheimer fluid