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Terahertz Irradiation Improves Cognitive Impairments and Attenuates Alzheimer’s Neuropathology in the APPSWE/PS1DE9 Mouse:A Novel Therapeutic Intervention for Alzheimer’s Disease

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Neuroscience Bulletin 2024年第7期40卷 857-871页

作者： Jun Zhang Yixin Chen Yarui Zhao Panpan Wang Hongbin Ding Cong Liu Junhong Lyu Weidong Le Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of neurological Diseases the First Affiliated HospitalDalian Medical UniversityDalian 116011China School of Physics Dalian University of TechnologyDalian 116024China Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China Advanced Research Institute Chinese Academy of SciencesShanghai 201203China Department of Neurology and Institute of Neurology Sichuan Academy of Medical Sciences‑Sichuan Provincial HospitalMedical SchoolUniversity of Electronic Science and Technology of ChinaChengdu 610072China

Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by the deposition of amyloid-β(Aβ),neurofibrillary tangles,neuroinflammation,and neurodegeneration in the *** recent years,considering the unsatisfied benefits of pharmacological therapies,non-pharmacological therapy has become a research hotspot for AD ***(THz)waves with a range between microwave and infrared regions in the electromagnetic spectrum and high permeability to a wide range of materials have great potential in the bioengineering ***,its biological impacts on the central nervous system,under either physiological or pathological conditions,are poorly *** this study,we first measured the 0.14 THz waves penetration across the skull of a C57BL/6 mouse and found the percentage of THz penetration to be~70%,guaranteeing that THz waves can reach the relevant brain *** then exposed the APPSWE/PS1DE9 mouse model of AD to repeated low-frequency THz waves on the *** demonstrated that THz waves treatment significantly improved the cognitive impairment and alleviated AD neuropathology including Aβdeposition and tau hyperphosphorylation in the AD ***,THz waves treatment effectively attenuated mitochondrial impairment,neuroinflammation,and neuronal loss in the AD mouse *** findings reveal previously unappreciated beneficial effects of THz waves treatment in AD and suggest that THz waves may have the potential to be used as a novel therapeutic intervention for this devastating disease.

关键词： Alzheimer's disease Cognitive impairment Senile plaque Tau protein Terahertz

Intra-arterial tenecteplase during thrombectomy for acute stroke(BRETIS-TNK II):rationale and design

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Stroke & Vascular Neurology 2024年第1期9卷 59-65页

作者： Zi-Ai Zhao Jing Qiu Wei Li Thanh Nguyen Shouchun Wang Huaizhang Shi Ming Wei Feng Wang Di Li Hui-Sheng Chen Department of Neurology General Hospital of Northern Theater CommandShenyangLiaoning ProvinceChina Neurology RadiologyBoston Medical CenterBostonMassachusettsUSA Department of Neurology First Affiliated Hospital of Jilin UniversityChangchunJilinChina Department of Neurosurgery First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina Department of Neurosurgery Tianjin Huanhu HospitalTianjinTianjinChina Department of Interventional Therapy First Affiliated Hospital of Dalian Medical UniversityDalianChina neurological Intervention Department Dalian Municipal Central HospitalDalianLiaoningChina

Background Our recent pilot study suggests intra-arterial tenecteplase(TNK)during the first pass of endovascular treatment(EVT)seems safe,may increase first-pass reperfusion and good outcome in acute ischaemic stroke(AIS)patients with large-vessel occlusion(LVO).Aims To determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients presenting up to 24 hours from symptom *** size estimates A maximum of 380 patients are required to test the superiority hypothesis with 80%power according to a two-side 0.05 level of significance,stratified by age,gender,baseline systolic blood pressure,prestroke modified Rankin Scale(mRS),baseline National Institute of Health stroke scale,baseline ASPECTS,time from onset to groin puncture,intravenous thrombolysis before EVT,stroke territory and stroke *** Intra-arterial TNK during thrombectomy for acute stroke(BRETIS-TNK II)study is a prospective,randomised,adaptive enrichment,open-label,blinded end point,multicentre *** AIS-LVO patients are randomly assigned into the experimental group and control group with a ratio of 1:*** experimental group will be treated with intra-arterial infusion of TNK during *** control group will be treated with standard *** The primary end point is a favourable outcome,defined as an mRS score of 0–2 at 90 *** primary safety end point is symptomatic intracranial haemorrhage within 48 hours,which is defined as an increase in the National Institutes of Health Stroke Scale score of≥4 points as a result of the intracranial *** The results of BRETIS-TNK II will provide evidence for the efficacy and safety of intra-arterial TNK administration during EVT in AIS patients with LVO.

关键词： rational stratified TNK

Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome

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Neuroscience Bulletin 2024年第4期40卷 439-450页

作者： Xiaotong Wu Yali Liu Xiaomeng Wang Lu Zheng Libiao Pan Hao Wang Department of Neurosurgery of Second Affiliated Hospital and School of Brain Science and Brain Medicine Key Laboratory for Biomedical Engineering of Education MinistryZhejiang University School of MedicineHangzhou310058China Nanhu Brain-computer Interface Institute Hangzhou311100China NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Research and Brain Machine IntegrationKey Laboratory of Precise Treatment and Clinical Translational Research of Neurological DiseasesSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou310058China Lingang Laboratory Shanghai200031China

While somatosensory over-reactivity is a common feature of autism spectrum disorders such as fragile X syndrome(FXS),the thalamic mechanisms underlying this remain ***,we found that the developmental elimination of synapses formed between the principal nucleus of V(PrV)and the ventral posterior medial nucleus(VPm)of the somatosensory system was delayed in fragile X mental retardation 1 gene knockout(Fmr1 KO)mice,while the developmental strengthening of these synapses was *** showed excessive VGluT2 puncta in mutants at P12–13,but not at P7–8 or P15–16,confirming a delay in somatic pruning of PrV-VPm *** synaptic function was associated with a reduction in the frequency of quantal AMPA events,as well as developmental deficits in presynaptic vesicle size and *** results uncovered the developmental impairment of thalamic relay synapses in Fmr1 KO mice and suggest that a thalamic contribution to the somatosensory over-reactivity in FXS should be considered.

关键词： Fragile X syndrome Synaptic refinement VPm Sensory over-reactivity

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi James D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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

Targeting tau in Alzheimer's disease:from mechanisms to clinical therapy

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Neural Regeneration Research 2024年第7期19卷 1489-1498页

作者： Jinwang Ye Huali Wan Sihua Chen Gong-Ping Liu Shenzhen Key Laboratory of Marine Biotechnology and Ecology College of Life Sciences and OceanographyShenzhen UniversityShenzhenGuangdong ProvinceChina Department of Laboratory Medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Co-innovation Center of Neurodegeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Pathophysiology School of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China and Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older *** features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the *** there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side *** evidence suggests significant involvement of tau protein in Alzheimer’s disease-related *** an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal *** fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the *** therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s ***,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular *** causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive *** review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.

关键词： acetylation Alzheimer’s disease cognitive deficits gliosis mitochondria damage neuroinflammation phosphorylation synaptic impairments tau tau immunotherapy

Circulating proteomic biomarkers for diagnosing sporadic amyotrophic lateral sclerosis:a cross-sectional study

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Neural Regeneration Research 2024年第8期19卷 1842-1848页

作者： Lu He Qinming Zhou Chaoyang Xiu Yaping Shao Dingding Shen Huanyu Meng Weidong Le Sheng Chen Department of Neurology and Institute of Neurology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Hospital of Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina Center for Translational Research on neurological Diseases the First Affiliated HospitalDalian Medical UniversityDalianLiaoning ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Institute of Neurology Sichuan Academy of Medical Sciences-Sichuan Provincial HospitalChengduSichuan ProvinceChina Department of Neurology Xinrui HospitalWuxiJiangsu ProvinceChina

Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive *** is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke *** this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy *** bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral *** biomarke rs were selected based on functionality and expression *** validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent *** substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle ***,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and transl

关键词： amyotrophic lateral sclerosis cathelicidin-related antimicrobial peptide hemoglobin label-free quantitative proteomics multi-protein combined diagnostic panel serum biomarkers talin-1 translationally-controlled tumor protein zyxin

Making the case for the evolving role of social media in health professions education and a literature review on the application of some in ophthalmology

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Annals of Eye Science 2024年第2期9卷 1-11页

作者： Helena Prior Filipe Mila Kostic Mildred Lopez Karl Golnik West Lisbon Hospitals Center Hospital Egas MonizLisbonPortugal Egas Moniz Center for Interdisciplinary Research LisbonPortugal Continuing Education and Development in Health Professions RichboroPAUSA Coordinación de Educación en Salud Instituto Mexicano del Seguro Social(IMSS)Mexico CityMexico Department of Neurology Barrow Neurological InstitutePhoenixAZUSA Department of Ophthalmology University of CincinnatiCincinnatiOHUSA

Background and Objective:Social media(SoMe)has emerged as a tool in health professions education(HPE),particularly amidst the challenges posed by the coronavirus disease 2019(COVID-19)*** the academia’s initial skepticism SoMe has been gaining traction in supporting learning communities,and offering opportunities for innovation in *** study aims to explore the integration of SoMe in *** key components were outlined as necessary for a successful integration,and include designing learning experiences,defining educator roles,selecting appropriate platforms,and establishing educational ***:This article stemmed from the online Teaching Skills Series module on SoMe in education from the Ophthalmology Foundation,and drew upon evidence supporting learning theories relevant to SoMe integration and models of ***,we conducted a literature review considering Englishlanguage articles on the application of SoMe in ophthalmology from PubMed over the past *** Content and Findings:Early adopters of SoMe platforms in HPE have leveraged these tools to enhance learning experiences through interaction,dialogue,content sharing,and active learning *** integrating SoMe into educational programs,both online and in-person,educators can overcome time and geographical constraints,fostering more diverse and inclusive learning *** consideration is,however,necessary to address potential limitations within ***:This article lays groundwork for expanding SoMe integration in HPE design,emphasizing the supportive scaffold of various learning theories,and the need of furthering robust research on examining its advantages over traditional educational *** literature review underscores an ongoing multifaceted,random application of SoMe platforms in ophthalmology *** advocate for an effective incorporation of SoMe in HPE education,with the need to comply with good educational practice.

关键词： Social media(SoMe) health professions education(HPE) active learning social learning technology enhanced learning

High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong Bin Zhang Baiyun Liu Beijing Tiantan Hospital Capital Medical UniversityBeijingChina Department of Neurology The First Hospital of Tsinghua UniversityBeijingChina Department of Neurotrauma and Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Critical Care Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury