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Assessment of cheese sign and its association with vascular risk factors:Data from PUMCH dementia cohort

Chinese Medical Journal 2024年第7期137卷 830-836页

作者： Xinying Huang Bo Hou Jie Wang Jie Li Li Shang Chenhui Mao Liling Dong Caiyan Liu Feng Feng Jing Gao Bin Peng Department of neurology State Key Laboratory of Complex Severe and Rare DiseasePeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Department of Radiology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Background:In the clinic,practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging(MRI)signal in the basal ganglia,a phenomenon known as"cheese sign".This sign is reported as common in cerebrovascular diseases,dementia,and old ***,cheese sign has been speculated to consist of dense perivascular space(PVS).This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk ***:A total of 812 patients from Peking Union Medical College Hospital(PUMCH)dementia cohort were *** analyzed the relationship between cheese sign and vascular *** assessing cheese sign and defining its degree,the abnormal punctate signals were classified into basal ganglia hyperintensity(BGH),PVS,lacunae/infarctions and microbleeds,and counted *** type of lesion was rated on a four-level scale,and then the sum was calculated;this total was defined as the cheese sign *** and Age-Related White Matter Changes(ARWMC)scores were used to evaluate the paraventricular,deep,and subcortical gray/white matter ***:A total of 118 patients(14.5%)in this dementia cohort were found to have cheese ***(odds ratio[OR]:1.090,95%confidence interval[CI]:1.064-1.120,P<0.001),hypertension(OR:1.828,95%CI:1.123-2.983,P=0.014),and stroke(OR:1.901,95%CI:1.092-3.259,P=0.025)were risk factors for cheese *** was no significant relationship between diabetes,hyperlipidemia,and cheese *** main components of cheese sign were BGH,PVS,and lacunae/*** proportion of PVS increased with cheese sign ***:The risk factors for cheese sign were hypertension,age,and *** sign consists of BGH,PVS,and lacunae/infarction.

关键词： Dementia Cerebrovascular disease Cheese sign Dense punctate lesions Basal ganglia Risk factor White matter

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Neurocognitive Profile of People Living with Human Immunodeficiency Virus Initiating Treatment in Kinshasa in the Dolutegravir Era, Democratic Republic of Congo

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Neuroscience & Medicine 2024年第1期15卷 1-22页

作者： Candide About Kabamba Berry Ikolango Bongenya Jocelyn Ewuti Nonga Lambert Omombo Losenga Noëlla Maketi Dikati Thérèse Kasaka Ntumba Grace Ipaya Booto Rosalie Djamba Dembo Stéphanie Mauwa Selenge Benoit Obel Kabengele Guy Makila Mabe Bumoko Marie-Thérèse Ayane Safi Sombo Erick Ntambwe Kamangu Department of neurology Faculty of Medicine University of Kinshasa Kinshasa Democratic Republic of Congo Faculty of Medicine Bel Campus Technological University Kinshasa Democratic Republic of Congo “Focus HIV/AIDS” Research Group Kinshasa Democratic Republic of Congo Department of Internal Medicine University Clinic of Kinshasa Kinshasa Democratic Republic of Congo Molecular Biochemistry Department Department of Basic Sciences Faculty of Medicine University of Kinshasa Kinshasa Democratic Republic of Congo

Context: Antiretroviral therapies improve the prognosis of NeuroAIDS contrasting with a high frequency of Minor Neurocognitive Disorders (MND) even in aviremic subjects. Objective: The objective of this study is to present the neurological and cognitive profile of People Living with HIV (PLHIV) initiating antiretroviral treatment in Kinshasa in the era of Dolutegravir (DTG). Methods: This is a multicenter, cross-sectional study with a descriptive aim carried out in 16 HIV Outpatient Treatment Centers (OTC) in Kinshasa from October 4, 2021 to February 15, 2022. The International HIV Dementia Scale (IHDS) correlated with the Activities of Daily Living (IADL) scale facilitated the categorization of NeuroCognitive Disorders (NCD) of PLHIV evaluated after carrying out a summary neurological examination. Results: Of the 96 patients recruited, 56.3% were women with a sex ratio of 0.68. The average age was 40.1 ± 12.1 years. The secondary education level was the majority at 64.6%. Malaria (44.8%) and tuberculosis (32.3%) were more common as opportunistic infections. They were alcoholics in (30.2%). Their history was heart disease (15.6%), high blood pressure (18.8%);drug abuse (10.4%). The IHDS score was light in 55.2% of cases. The correlation between IHDS/IADL watches asymptomatic neurocognitive impairments (ANI) in 77.1%, almost all of subjects are found with normal overall functioning (94.8%) and a disturbed neurological examination in 53.1% of cases with a predominance of motor impairments in 79.1%. Conclusion: In view of these results, early and systematic screening of NCD and associated factors remains necessary in our context. .

关键词： IHDS Dolutegravir Initiation Kinshasa Neurological Profile PLHIV

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Mitochondrial complex Ⅰ as a therapeutic target for Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2022年第2期12卷 483-495页

作者： Eugenia Trushina Sergey Trushin Md Fayad Hasan Department of neurology Mayo ClinicRochesterMN 55905USA Department of Molecular Pharmacology and Experimental Therapeutics Mayo ClinicRochesterMN 55905USA

Alzheimer’s disease(AD),the most prominent form of dementia in the elderly,has no *** focused on the reduction of amyloid beta or hyperphosphorylated Tau protein have largely failed in clinical *** therapeutic targets and strategies are urgently *** data suggest that in response to environmental stress,mitochondria initiate an integrated stress response(ISR)shown to be beneficial for healthy aging and ***,we review data that implicate mitochondrial electron transport complexes involved in oxidative phosphorylation as a hub for small molecule-targeted therapeutics that could induce beneficial mitochondrial ***,partial inhibition of mitochondrial complex I has been exploited as a novel strategy for multiple human conditions,including AD,with several small molecules being tested in clinical *** discuss current understanding of the molecular mechanisms involved in this counterintuitive *** this strategy has also been shown to enhance health and life span,the development of safe and efficacious complex Ⅰ inhibitors could promote healthy aging,delaying the onset of age-related neurodegenerative diseases.

关键词： Mitochondria Mitochondria signaling ComplexⅠinhibitors Alzheimer’s disease Integrated stress response Neuroprotection Mitochondria targeted therapeutics Healthy aging

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The proteome of distal nerves: implication in delayed repair and poor functional recovery

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Neural Regeneration Research 2022年第9期17卷 1998-2006页

作者： Song Guo Raymond M.Moore M.Cristine Charlesworth Kenneth L.Johnson Robert J.Spinner Anthony J.Windebank Huan Wang Department of Neurologic Surgery Mayo ClinicRochesterMNUSA Biomedical Statistics and Informatics Mayo ClinicRochesterMNUSA Proteomics Core Mayo ClinicRochesterMNUSA Department of neurology Mayo ClinicRochesterMNUSA

Chronic denervation is one of the key factors that affect nerve *** axotomy deteriorates the distal nerve stump,causes protein changes,and renders the microenvironment less permissive for *** of these factors/proteins have been individually *** better delineate the comprehensive protein expression profiles and identify proteins that contribute to or are associated with this detrimental effect,we carried out a proteomic analysis of the distal nerve using an established delayed rat sciatic nerve repair *** rats that received immediate repair after sciatic nerve transection served as control,whereas four rats in the experimental group(chronic denervation)had their sciatic nerve repaired after a 12-week *** the rats were sacrificed after 16 weeks to harvest the distal nerves for extracting ***-five micrograms of protein from each sample were fractionated in SDS-PAGE ***-MS/MS analysis was applied to the *** expression levels of nerves on the surgery side were compared to those on the contralateral *** protein with a P value of less than 0.05 and a fold change of 4 or higher was deemed differentially *** the differentially expressed proteins in both groups were further stratified according to the biological processes.A PubMed search was also conducted to identify the differentially expressed proteins that have been reported to be either beneficial or detrimental to nerve *** Pathway Analysis(IPA)software was used for pathway *** results showed that 709 differentially expressed proteins were identified in the delayed repair group,with a bigger proportion of immune and inflammatory process-related proteins and a smaller proportion of proteins related to axon regeneration and lipid metabolism in comparison to the control group where 478 differentially expressed proteins were *** experimental group also had more beneficial proteins that were d

关键词： chronic axotomy chronic denervation delayed repair distal nerve functional recovery nerve regeneration peripheral nerve prolonged denervation proteome sciatic nerve sciatic nerve transection

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Getting a Sense of ATP in Real Time

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Neuroscience Bulletin 2022年第7期38卷 834-836页

作者： Anthony D.Umpierre Koichiro Haruwaka Long-Jun Wu Department of neurology Mayo ClinicRochesterMN55905USA Department of Neuroscience Mayo ClinicJacksonvilFL32224USA Department of Immunology Mayo ClinicRochesterMN55905USA

Adenosine 5'-triphosphate(ATP)is a purinergic signal that can be sensed by all major cell classes in the *** is a key signal released during periods of physical damage/injury,inflammation,and neurological events,such as *** ATP signaling in the living brain is complicated by its fast enzymatic degradation,its action at multiple receptors,and its somewhat elusive.

关键词： signal damage somewhat

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Improving detection of cerebral small vessel disease aetiology in patients with isolated lobar intracerebral haemorrhage

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Stroke & Vascular neurology 2023年第1期8卷 26-33页

作者： Alvin S Das Elif Gokcal Robert W Regenhardt Mitchell J Horn Kristin Schwab Nader Daoud Anand Viswanathan W Taylor Kimberly Joshua N Goldstein Alessandro Biffi Natalia Rost Jonathan Rosand Lee H Schwamm Steven M Greenberg M Edip Gurol Department of neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMassachusettsUSA Department of neurology Massachusetts General HospitalHarvard Medical SchoolBostonMassachusettsUSA Department of Neurosurgery Massachusetts General HospitalHarvard Medical SchoolBostonMassachusettsUSA Department of Emergency Medicine Massachusetts General HospitalHarvard Medical SchoolBostonMassachusettsUSA

Background and purpose We evaluate whether non-haemorrhagic imaging markers(NHIM)(white matter hyperintensity patterns,lacunes and enlarged perivascular spaces(EPVS))can discriminate cerebral amyloid angiopathy(CAA)from hypertensive cerebral small vessel disease(HTN-cSVD)among patients with isolated lobar intracerebral haemorrhage(isolated-LICH).Methods In patients with isolated-LICH,four cSVD aetiologic groups were created by incorporating the presence/distribution of NHIM:HTN-cSVD pattern,CAA pattern,mixed NHIM and no *** pattern consisted of patients with any combination of severe centrum semiovale EPVS,lobar lacunes or multiple subcortical spots ***-cSVD pattern consisted of any HTN-cSVD markers:severe basal ganglia PVS,deep lacunes or peribasal ganglia white matter hyperintensity *** NHIM consisted of at least one imaging marker from either *** hypothesis was that patients with HTN-cSVD pattern/mixed NHIM would have a higher frequency of left ventricular hypertrophy(LVH),which is associated with *** In 261 patients with isolated-LICH,CAA pattern was diagnosed in 93 patients,HTN-cSVD pattern in 53 patients,mixed NHIM in 19 patients and no NHIM in 96 *** frequency of LVH was similar among those with HTN-cSVD pattern and mixed NHIM(50%vs 39%,p=0.418)but was more frequent in HTN-cSVD pattern compared with CAA pattern(50%vs 20%,p<0.001).In a regression model,HTN-cSVD pattern(OR:7.38;95%CI 2.84 to 19.20)and mixed NHIM(OR:4.45;95%CI 1.25 to 15.90)were found to be independently associated with *** Among patients with isolated-LICH,NHIM may help differentiate HTN-cSVD from CAA,using LVH as a marker for HTN-cSVD.

关键词： patients cerebral hypertensive

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FSAP aggravated endothelial dysfunction and neurological deficits in acute ischemic stroke due to large vessel occlusion

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Signal Transduction and Targeted Therapy 2022年第2期7卷 466-478页

作者： Dai-Shi Tian Chuan Qin Luo-Qi Zhou Sheng Yang Man Chen Jun Xiao Ke Shang Dale BBosco Long-Jun Wu Wei Wang Department of neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030 WuhanChina'2Department of NeurologyMayo ClinicRochesterMN 55905USA

Revascularization and angiogenesis,as substrates of sustained collateral circulation,play a crucial role in determining the severity and clinical outcome of acute ischemic stroke(AIS)due to large vessel occlusion(LVO).Developing an adjunct biomarker to help identify and monitor collateral status would aid stroke diagnosis and *** screen the potential biomarkers,proteomic analysis was performed in this study to identify those distinct plasma protein profiles in AIS due to LVO with different collateral ***,we found that levels of Plasma Factor VII Activating Protease(FSAP)significantly increased in those AIS patients with poor collaterals,and were correlated with worse neurological ***,both in vitro and in vivo models of ischemic stroke were used to explore pathological mechanisms of FSAP in endothelial *** demonstrated that the FSAP inhibitor,high-molecular-weight hyaluronan(HMW-HA),enhanced the pro-angiogenic vascular factors,improved the integrity of brain blood barrier,and promoted newly formed cerebral microvessels in the ischemic penumbra,consequently improving neurological *** elucidate the pathways that might contribute to revascularization during LVO,we applied transcriptomic analysis via unbiased RNA sequencing and showed that Wnt signaling was highly involved in FSAP mediated endothelial ***,inhibition of Wnt5a largely reversed the protective effects from HMW-HA treatment,implying that FSAP might aggravate endothelial dysfunction and neurological deficits by regulating Wnt5a ***,FSAP may represent a potential biomarker for collateral status after LVO and a promising therapeutic target to be explored in the treatment of stroke.

关键词： Wnt5a neurological protective

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Microglial voltage-gated proton channel Hv1 in spinal cord injury

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Neural Regeneration Research 2022年第6期17卷 1183-1189页

作者： Jiaying Zheng Madhuvika Murugan Lingxiao Wang Long-Jun Wu Department of neurology Mayo ClinicRochesterMNUSA Department of Neurosurgery Rutgers Robert Wood Johnson Medical SchoolPiscatawayNJUSA Department of Neuroscience Mayo ClinicJacksonvilleFLUSA Department of Immunology Mayo ClinicRochesterMNUSA

After spinal cord injury,microglia as the first responders to the lesion display both beneficial and detrimental *** microglia phagocyte and eliminate cell debris,release cytokines to recruit peripheral immune cells to the injury *** activated microglia can aggravate the secondary damage by producing extravagant reactive oxygen species and pro-inflammatory *** studies demonstrated that the voltage-gated proton channel Hv1 is selectively expressed in microglia and regulates microglial activation upon *** mouse models of spinal cord injury,Hv1 deficiency ameliorates microglia activation,resulting in alleviated production of reactive oxygen species and pro-inflammatory *** reduced secondary damage subsequently decreases neuronal loss and correlates with improved locomotor *** review provides a brief historical perspective of advances in investigating voltage-gated proton channel Hv1 and home in on microglial *** discuss recent studies on the roles of Hv1 activation in pathophysiological activities of microglia,such as production of NOX-dependent reactive oxygen species,microglia polarization,and tissue acidosis,particularly in the context of spinal cord ***,we highlight the rationale for targeting Hv1 for the treatment of spinal cord injury and related disorders.

关键词： Hv1 proton channel ion channels microglia NADPH oxidase pH regulation reactive oxygen species spinal cord injury

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Ventriculo-atrial shunt with occlusion of the internal jugular vein: operative experience and surgical technique

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中华神经外科杂志(英文) 2024年第2期10卷 1-8页

作者： Quintero Silvia Tatiana Ramirez-Velandia Felipe Moreno Andres Felipe Hortua Vera Lina Rugeles Paula Gonzalez Rafael Augusto Azuero Pontificia Universidad Javeriana Clinica Medilaser S.A.S. Clinica Chicamocha Bucaramanga Santander Colombia neurology and Neurosurgery Research Group Pontificia Universidad Javeriana Bogotá D.C. Colombia Universidad Industrial de Santander Clinica Chicamocha Bucaramanga Colombia Universidad Autónoma de Bucaramanga Clinica Chicamocha Bucaramanga Colombia clinica Chicamocha Bucaramanga Santander Colombia

Background Ventricular shunts are one of the most frequent techniques used for the management of hydrocephalus. The ventriculoperitoneal shunt (VPS) is the most commonly performed procedure, and the ventriculoatrial shunt (VAS) is the second option in most medical centers. The main objective of this study is to introduce and describe a surgical approach for VAS outlining our experience and comparing it with traditional shunting *** In this retrospective cohort comparison study, we included patients with hydrocephalus treated with a surgical procedure between January 2010 and February 2021 at a single academic institution. We categorized the procedures into two groups: patients with VPS and conventional VAS grouped together into the conventional technique (CT) group, and the second group was patients with whom we performed VAS with complete internal jugular vein occlusion (IJVOT). We compared the surgical time, postoperative complications, and occurrence of shunt failure among the groups by performing univariate analysis using the Fisher exact *** Out of the 106 patients included in the analysis, IJVOT was performed in 66 patients, and CT in 40 patients. The median surgical time was 60 min (IQR 60-90) for IJVOT versus 100 min (IQR 60-120) for CT (p clinical trials, to fully explore and establish efficacy, long-term outcomes, and an in-depth comparison among shunting techniques

关键词： Hydrocephalus Ventriculoatrial shunting Internal jugular vein Operative time Complications Shunt removal

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Chemogenetic and Optogenetic Manipulations of Microglia in Chronic Pain

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Neuroscience Bulletin 2023年第3期39卷 368-378页

作者： Sebastian Parusel Min-Hee Yi Christine L.Hunt Long-Jun Wu Department of neurology Mayo ClinicRochesterMN 55905USA Faculty of Psychology and Neuroscience Maastricht UniversityMaastricht MD6200The Netherlands Department of Pain Medicine Mayo ClinicJacksonvilleFL 32224USA Department of Neuroscience Mayo ClinicJacksonvilleFL 32224USA Department of Immunology Mayo ClinicRochesterMN 55905USA

Chronic pain relief remains an unmet medical *** research points to a substantial contribution of glia-neuron interaction in its ***,microglia play a crucial role in the development of chronic *** better understand the microglial contribution to chronic pain,specific regional and temporal manipulations of microglia are ***,two new approaches have emerged that meet these *** tools allow the expression of designer receptors exclusively activated by designer drugs(DREADDs)specifically in ***,optogenetic tools allow for microglial manipulation via the activation of artificially expressed,light-sensitive ***-and optogenetic manipulations of microglia in vivo are powerful in interrogating microglial function in chronic *** review summarizes these emerging tools in studying the role of microglia in chronic pain and highlights their potential applications in microglia-related neurological disorders.

关键词： Chronic pain Microglia Optogenetics Chemogenetics DREADDs ReaChR

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