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Comparison of carotid endarterectomy and repeated carotid angioplasty and stenting for in-stent restenosis(CERCAS trial):a randomised study

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Stroke & Vascular Neurology 2023年第5期8卷 399-404页

作者： Tomáš Hrbáč Jiří Fiedler Václav Procházka Tomáš Jonszta Martin Roubec David Pakizer Daniel Václavík David Netuka Tomáš Heryán David Školoudík department of neuroscience Faculty of MedicineUniverzity of OstravaOstravaCzech Republic department of neurosurgery University Hospital OstravaOstravaCzech Republic department of neurosurgery ČeskéBudějovice HospitalČeskéBudějoviceCzech Republic department of Radiology University Hospital OstravaOstravaCzech Republic department of Neurology University Hospital OstravaOstravaCzech Republic center for Health Research Faculty of MedicineUniversity of OstravaOstravaCzech Republic department of Neurology Vítkovice HospitalOstravaCzech Republic department of neurosurgery Military University Hospital PraguePrahaCzech Republic

Background and aim In-stent restenosis(ISR)belongs to an infrequent but potentially serious complication after carotid angioplasty and stenting in patients with severe carotid stenosis.Some of these patients might be contraindicated to repeat percutaneous transluminal angioplasty with or without stenting(rePTA/S).The purpose of the study is to compare the safety and effectiveness of carotid endarterectomy with stent removal(CEASR)and rePTA/S in patients with carotid ISR.Methods Consecutive patients with carotid ISR(≥80%)were randomly allocated to the CEASR or rePTA/S group.The incidence of restenosis after intervention,stroke,transient ischaemic attack myocardial infarction and death 30 days and 1 year after intervention and restenosis 1 year after intervention between patients in CEASR and rePTA/S groups were statistically evaluated.Results A total of 31 patients were included in the study;14 patients(9 males;mean age 66.3±6.6 years)were allocated to CEASR and 17 patients(10 males;mean age 68.8±5.6 years)to the rePTA/S group.The implanted stent in carotid restenosis was successfully removed in all patients in the CEASR group.No clinical vascular event was recorded periproceduraly,30 days and 1 year after intervention in both groups.Only one patient in the CEASR group had asymptomatic occlusion of the intervened carotid artery within 30 days and one patient died in the rePTA/S group within 1 year after intervention.Restenosis after intervention was significantly greater in the rePTA/S group(mean 20.9%)than in the CEASR group(mean 0%,p=0.04),but all stenoses were<50%.Incidence of 1-year restenosis that was≥70%did not differ between the rePTA/S and CEASR groups(4 vs 1 patient;p=0.233).Conclusion CEASR seems to be effective and save procedures for patients with carotid ISR and might be considered as a treatment option.

关键词： carotid restenosis angioplasty

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Development of localized interictal epileptiform discharges following vagus nerve stimulation for lennox-gastaut syndrome: a case report

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Acta Epileptologica 2022年第4期5卷 286-291页

作者： Renli Qi Wei Wang Yaoduan Xu Zongling Shen Xin Geng Na Li Jinghui Li Hualin Yu second department of neurosurgery First Affiliated Hospital of Kunming Medical UniversityKunming650032China department of neurosurgery The Third People’s Hospital of Honghe PrefectureGejiu661000China department of Psychiatry First Affiliated Hospital of Kunming Medical UniversityKunming650032China Yunnan Provincial Clinical Research center for Neurological Disease Kunming650032China

Background Lennox-gastaut syndrome(LGS)is an epileptic encephalopathy often associated with behavioral and psychiatric disorders.Vagus nerve stimulation(VNS)has been approved effective for LGS treatment.Surgical resection is also an option for LGS patients with focal pathology,offering a high probability of seizure control.However,it is challenging to accurately localize the seizure focus.Case presentation The case presented here is a 19-year-old male with a 16-year history of epilepsy with comorbid severe cognitive and psychiatric disorders.He was diagnosed with LGS due to generalized slow spike-wave discharges and multiple seizure types.He was treated with VNS in 2017 at the age of 15.After that,the frequency of the short tonic seizures decreased from 4–5 times per day to 2–5 times per year,and the generalized tonic–clonic seizure pattern did not recur,which had a frequency of 2–4 times per month before the surgery.In 2019,the generalized abnormal interictal epileptiform discharges changed to be localized in the right frontal–temporal lobe at the age of 17 years(2019).Conclusions This case report suggested that the generalized epileptiform discharges evolve into localized discharges after VNS treatment,which may help reveal the primary seizure focus for resection surgery in patients with LGS.

关键词： Vagus nerve stimulation Lennox-gastaut syndrome Epileptiform discharges

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Exploration and functionalization of M1-macrophage extracellular vesicles for effective accumulation in glioblastoma and strong synergistic therapeutic effects

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1271-1286页

作者： Xiaojun Wang Hui Ding Zongyang Li Yaonan Peng Hui Tan Changlong Wang Guodong Huang Weiping Li Guanghui Ma Wei Wei Shenzhen Key Laboratory of neurosurgery Department of NeurosurgeryShenzhen Second People’s HospitalShenzhen University 1st Affiliated HospitalGuangdong 518035P.R.China State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190P.R.China department of Ophthalmology Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020P.R.China department of Otolaryngology and Institute of Translational Medicine Shenzhen Second People’s Hospitalthe First Affiliated Hospital of Shenzhen University Health Science CenterShenzhenGuangdong 518110P.R.China department of neurosurgery Jinling HospitalJiangsuNanjing 210000P.R.China School of Chemical Engineering University of Chinese Academy of SciencesBeijing 100049P.R.China

Glioblastoma multiforme(GBM)is a highly aggressive brain tumor with an extremely low survival rate.New and effective approaches for treatment are therefore urgently needed.Here,we successfully developed M1-like macrophage-derived extracellular vesicles(M1EVs)that overcome multiple challenges via guidance from two macrophage-related observations in clinical specimens from GBM patients:enrichment of M2 macrophages in GBM;and origination of a majority of infiltrating macrophage from peripheral blood.To maximize the synergistic effect,we further functionalized the membranes of M1EVs with two hydrophobic agents(the chemical excitation source CPPO(C)and the photosensitizer Ce6(C))and loaded the hydrophilic hypoxiaactivated prodrug AQ4N(A)into the inner core of the M1EVs.After intravenous injection,the inherent nature of M1-derived extracellular vesicles CCA-M1EVs allowed for blood-brain barrier penetration,and modulated the immunosuppressive tumor microenvironment via M2-to-M1 polarization,which increased hydrogen peroxide(H_(2)O_(2))levels.Furthermore,the reaction between H_(2)O_(2) and CPPO produced chemical energy,which could be used for Ce6 activation to generate large amounts of reactive oxygen species to achieve chemiexcited photodynamic therapy(CDT).As this reaction consumed oxygen,the aggravation of tumor hypoxia also led to the conversion of non-toxic AQ4N into toxic AQ4 for chemotherapy.Therefore,CCA-M1EVs achieved synergistic immunomodulation,CDT,and hypoxia-activated chemotherapy in GBM to exert a potent therapeutic effect.Finally,we demonstrated the excellent effect of CCA-M1EVs against GBM in cell-derived xenograft and patient-derived xenograft models,underscoring the strong potential of our highly flexible M1EVs system to support multi-modal therapies for difficult-to-treat GBM.

关键词： therapeutic chemotherapy synergistic

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Abnormal characterization of dynamic functional connectivity in Alzheimer’s disease

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Neural Regeneration Research 2022年第9期17卷 2014-2021页

作者： Cui Zhao Wei-Jie Huang Feng Feng Bo Zhou Hong-Xiang Yao Yan-E Guo Pan Wang Lu-Ning Wang Ni Shu Xi Zhang department of Neurology Second Medical CenterNational Clinical Research Center for Geriatric DiseaseChinese PLA General HospitalBeijingChina department of Geriatrics Affiliated Hospital of Chengde Medical UniversityChengdeHebei ProvinceChina State Key Laboratory of Cognitive neuroscience and Learning Beijing Normal UniversityBeijingChina center for Collaboration and Innovation in Brain and Learning Sciences Beijing Normal UniversityBeijingChina Beijing Key Laboratory of Brain Imaging and Connectomics Beijing Normal UniversityBeijingChina department of Neurology First Medical CenterChinese PLA General HospitalBeijingChina department of Neurology PLA Rocket Force Characteristic Medical CenterBeijingChina department of Radiology Second Medical CenterChinese PLA General HospitalBeijingChina department of Neurology Tianjin Huanhu HospitalTianjinChina

Numerous studies have shown abnormal brain functional connectivity in individuals with Alzheimer’s disease(AD)or amnestic mild cognitive impairment(aMCI).However,most studies examined traditional resting state functional connections,ignoring the instantaneous connection mode of the whole brain.In this case-control study,we used a new method called dynamic functional connectivity(DFC)to look for abnormalities in patients with AD and aMCI.We calculated dynamic functional connectivity strength from functional magnetic resonance imaging data for each participant,and then used a support vector machine to classify AD patients and normal controls.Finally,we highlighted brain regions and brain networks that made the largest contributions to the classification.We found differences in dynamic function connectivity strength in the left precuneus,default mode network,and dorsal attention network among normal controls,aMCI patients,and AD patients.These abnormalities are potential imaging markers for the early diagnosis of AD.

关键词： Alzheimer’s disease amnestic mild cognitive impairment blood oxygen level-dependent default mode network dynamic functional connectivity frontoparietal network resting-state functional magnetic resonance imaging support vector machine

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Characteristics of diffusion-tensor imaging for healthy adult rhesus monkey brains

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Neural Regeneration Research 2013年第31期8卷 2951-2961页

作者： Xinxiang Zhao Jun Pu Yaodong Fan Xiaoqun Niu Danping Yu Yanglin Zhang department of Radiology Second Affiliated Hospital of Kunming Medical University department of neurosurgery Second Affiliated Hospital of Kunming Medical University department of neurosurgery Third Affiliated Hospital of Kunming Medical University department of Pneumology Second Affiliated Hospital of Kunming Medical University Yiwu hospital affiliated to Zhejiang University School of Medicine

Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional ani- sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus callosum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, semioval center, thalamus, and corpus callosum （splenium and genu） as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy rhesus monkeys aged 4-8 years. Results showed no laterality dif- ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of cau- date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the sple- nium of corpus callosum in the white matter, followed by genu of the corpus callosum and the pos- terior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4-8-year-old rhesus monkeys are similar to those of healthy young people.

关键词： neural regeneration neuroimaging rhesus monkey fractional anisotropy brain white matter graymatter MRI diffusion-tensor imaging grants-supported paper neuroregeneration

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DLG7/DLGAP5 as a potential therapeutic target in gastric cancer

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Chinese Medical Journal 2022年第13期135卷 1616-1618页

作者： Kang Li Xiangsheng Fu Ping Wu Bianba Zhaxi Hanhuan Luo Qijie Li department of Gastroenterology People’s Hospital of Tibet Autonomous RegionLhasaTibet 850000China department of Gastroenterology First Affiliated Hospital of Chengdu Medical CollegeChengduSichuan 610041China department of Occupational Diseases The Second Affiliated Hospital of Chengdu Medical College Nuclear Industry 416 HospitalChengduSichuan 610051China department of Anesthesiology Laboratory of Anesthesia and Critical Care MedicineTranslational Neuroscience CenterWest China HospitalSichuan UniversityChengduSichuan 610041China.

To the Editor:Gastric cancer is a highly invasive disease.An estimated 1.09 million cases were diagnosed and 770,000 gastric cancer-related deaths occurred only in 2020.[1]Advanced gastric cancer can no longer be subjected to surgery and can only be treated with sequential lines of chemotherapy.However,the survival period is usually short.[2]Therefore,it is of utmost importance to identify new and more effective treatments and therapeutic targets to combat gastric cancer.Disc large homolog 7(DLG7)is the microtubule-associated protein encoded by the DLG associated protein 5(DLGAP5)gene,which affects chromosome rearrangement and gene stability[3];thus,its overexpression may cause canceration.Some studies revealed that DLGAP5 is highly expressed in gastric cancer tissues,suggesting that it may also have a role in this disease.However,the role and mechanism of DLGAP5 in gastric cancer are still unclear.[4]Therefore,this study aimed at exploring the role of DLGAP5 in the growth and invasion of gastric cancer as well as the potential use as a therapeutic target to combat this disease.

关键词： therapeutic gastric cancer

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Towards a comprehensive understanding of p75 neurotrophin receptor functions and interactions in the brain

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Neural Regeneration Research 2022年第4期17卷 701-704页

作者： Joel F.Ritala Seán BLyne Antti Sajanti Romuald Girard Janne Koskimäki Division of Clinical neurosciences Department of NeurosurgeryTurku University Hospital and University of TurkuTurkuFinland Neurovascular Surgery Program Section of NeurosurgeryThe University of Chicago Medicine and Biological SciencesChicagoILUSA department of Psychiatry Central Hospital of Southern OstrobothniaSeinäjokiFinland neuroscience center HiLIFEUniversity of HelsinkiHelsinkiFinland

The role of neurotrophins in neuronal plasticity has recently become a strong focus in neuroregeneration research field to elucidate the biological mechanisms by which these molecules modulate synapses,modify the response to injury,and alter the adaptation response.Intriguingly,the prior studies highlight the role of p75 neurotrophin receptor(p75^(NTR))in various injuries and diseases such as central nervous system injuries,Alzheimer's disease and amyotrophic lateral sclerosis.More comprehensive elucidation of the mechanisms,and therapies targeting these molecular signaling networks may allow for neuronal tissue regeneration following an injury.Due to a diverse role of the p75^(NTR)in biology,the body of evidence comprising its biological role is diffusely spread out over numerous fields.This review condenses the main evidence of p75^(NTR)for clinical applications and presents new findings from published literature how data mining approach combined with bioinformatic analyses can be utilized to gain new hypotheses in a molecular and network level.

关键词： bioinformatics brain injury data mining neuron neurotrophins p75^(NTR) plasticity regeneration

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A novel phenotype of B cells associated with enhanced phagocytic capability and chemotactic function after ischemic stroke

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Neural Regeneration Research 2023年第11期18卷 2413-2423页

作者： Rui Wang Huaming Li Chenhan Ling Xiaotao Zhang Jianan Lu Weimin Luan Jianmin Zhang Ligen Shi department of neurosurgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Brain Research Institute Zhejiang UniversityHangzhouZhejiang ProvinceChina Stroke Research center for Diagnostic and Therapeutic Technologies of Zhejiang Province HangzhouZhejiang ProvinceChina Clinical Research center for Neurological Diseases of Zhejiang Province HangzhouZhejiang ProvinceChina

Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration.However,the role of B cells in ischemic stroke remains unclear.In this study,we identified a novel phenotype of macrophage-like B cells in brain-infiltrating immune cells expressing a high level of CD45.Macrophage-like B cells chara cterized by co-expression of B-cell and macrophage markers,showed stronger phagocytic and chemotactic functions compared with other B cells and showed upregulated expression of phagocytosis-related genes.Gene Ontology analysis found that the expression of genes associated with phagocytosis,including phagosome-and lysosome-related genes,was upregulated in macrophage-like B cells.The phagocytic activity of macrophage-like B cells was ve rified by immunostaining and three-dimensional reconstruction,in which TREM2-labeled macrophage-like B cells enwrapped and internalized myelin debris after cerebral ischemia.Cell-cell interaction analysis revealed that macrophage-like B cells released multiple chemokines to recruit peripheral immune cells mainly via CCL pathways.Single-cell RNA sequencing showed that the transdiffe rentiation to macrophage-like B cells may be induced by specific upregulation of the transcription factor CEBP fa mily to the myeloid lineage and/or by downregulation of the transcription factor Pax5 to the lymphoid lineage.Furthermore,this distinct B cell phenotype was detected in brain tissues from mice or patients with traumatic brain injury,Alzheimer’s disease,and glioblastoma.Overall,these results provide a new perspective on the phagocytic capability and chemotactic function of B cells in the ischemic brain.These cells may serve as an immunotherapeutic target for regulating the immune response of ischemic stroke.

关键词： B cell chemotaxis immune infiltration immunity ischemic stroke phagocytosis single-cell RNA sequencing transcription factor transcriptome transient cerebral ischemia/reperfusion

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Glioma stem cells and neural stem cells respond differently to BMP4 signaling

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Cell Regeneration 2022年第1期11卷 374-388页

作者： Xin-Xin Han Chunhui Cai Li-Ming Yu Min Wang Wenhan Yang Dai-Yu Hu Jie Ren Lu-Ying Zhu Jia-Jia Deng Qing-Qing Chen Hua He Zhengliang Gao Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases Shanghai Stomatological Hospital&School of StomatologyFudan UniversityShanghai 200001China Yangzhi Rehabilitation hospital(Shanghai Sunshine Rehabilitation center) Tongji University School of MedicineShanghai 200072China Institute of Geriatrics(Shanghai University) Affiliated Nantong Hospital of Shanghai University(The Sixth People’s Hospital of Nantong)School of MedicineShanghai UniversityNantongChina School of Medicine Jiax-ing UniversityJiaxingChina department of neurosurgery Changzheng HospitalSecond Military Medical UniversityShanghaiChina department of neurosurgery Third Affiliated Hospital of Second Military Medical UniversityShanghaiChina

Malignant glioma is a highly heterogeneous and invasive primary brain tumor characterized by high recurrence rates,resistance to combined therapy,and dismal prognosis.Glioma stem cells(GSCs)are likely responsible for tumor progression,resistance to therapy,recurrence,and poor prognosis owing to their high self-renewal and tumorigenic potential.As a family member of BMP signaling,bone morphogenetic protein4(BMP4)has been reported to induce the differentiation of GSCs and neural stem cells(NSCs).However,the molecular mechanisms underlying the BMP4-mediated effects in these two cell types are unclear.In this study,we treated hGSCs and hNSCs with BMP4 and com-pared the phenotypic and transcriptional changes between these two cell types.Phenotypically,we found that the growth of hGSCs was greatly inhibited by BMP4,but the same treatment only increased the cell size of hNSCs.While the RNA sequencing results showed that BMP4 treatment evoked significantly transcriptional changes in both hGSCs and hNSCs,the profiles of differentially expressed genes were distinct between the two groups.A gene set that specifically targeted the proliferation and differentiation of hGSCs but not hNSCs was enriched and then validated in hGSC culture.Our results suggested that hGSCs and hNSCs responded differently to BMP4 stimulation.Understanding and investigating different responses between hGSCs and hNSCs will benefit finding partner factors working together with BMP4 to further suppress GSCs proliferation and stemness without disturbing NSCs.

关键词： Glioma stem cells BMP4 Neural stem cells Cell differentiation Cell proliferation

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Targeting glioma stem cells： enough to terminate gliomagenesis？

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Chinese Medical Journal 2011年第17期124卷 2756-2763页

作者： DONG Jun HUANG Qiang department of neurosurgery Second Affiliated Hospital of Suzhou University Suzhou Jiangsu 215004 China

Objective To review the leading roles of glioma stem cells （GSCs） and their sophisticated interactions with other cells in the tissue remodeling process of gliomagenesis. Data sources Published articles about assessing GSCs in tumor initiation, progression, and multiple interactions with other cells in the special microenvironment were selected using PubMed. The search terms were ＂glioma stem cells＂, ＂tumorigenesis＂, and ＂microenvironment＂. Study selection Articles regarding the tissue remodeling of GSCs in gliomagenesis were selected. Results GSCs exhibit enhanced tumor-initiating ability, could reestablish tumor, and were resistant to radiotherapy and chemotherapy. Studying the role of GSCs in gliomagenesis helps to develop targeting therapy against GSCs, which seems to be a cure for gliomas. However, sophisticated interactions between GSCs and their local microenvironment during tumor remodeling, including integrating with partially differentiated tumor cells, GSCs niche, neural stem cells （NSCs）, normal glia, tumor-infiltrating lymphocytes, may obscure the leading role of GSCs during gliomagenesis, and make single targeting therapy unsuccessful. Conclusions Understanding the biological behavious of GSCs and their regulatory mechanisms may directly impact current efforts for more directed therapeutics against the highly aggressive gliomas. For multiple possible sources to turning into GSCs, simply eradicating the existing GSCs is not enough to be a cure for gliomas, blocking the potential sources of GSCs and ameliorating the local tumor inducing/promoting microenvironment should be a reasonable strategy.

关键词： glioma stem cells tumorigenesis microenvironment

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