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Association of atherosclerotic plaque features with collateral circulation status in elderly patients with chronic carotid stenosis

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Journal of Geriatric Cardiology 2020年第4期17卷 202-209页

作者： Hui-Min XU Ran HUO Rui-Jing XIN Dan-Dan YANG Ying LIU Ning LANG Xi-Hai ZHAO Tao WANG Hui-Shu YUAN Department of Radiology Peking University Third HospitalBeijingChina Department of Radiology Zhongda HospitalMedical School of Southeast UniversityNanjingChina Beijing Institute of brain Disorders Laboratory of Brain DisordersMinistry of Science and TechnologyCollaborative Innovation Center for Brain DisordersCapital Medical UniversityBeijingChina Center for Biomedical Imaging Research Department of Biomedical EngineeringTsinghua University School of MedicineBeijingChina Department of Neurosurgery Peking University Third HospitalBeijingChina

Objective To determine the association of carotid plaque features with collateral circulation status in elderly patients with moderate to severe carotid *** Elderly patients(>60 years)with moderate to severe carotid stenosis were recruited and categorized into good and poor collateral circulation groups,and underwent magnetic resonance imaging and computed tomography *** carotid plaque features including lipid-rich necrotic core,intraplaque hemorrhage,calcification,and fibrous cap rupture(FCR)were evaluated,and maximum wall thickness,normalized wall index(NWI),and luminal stenosis were *** association between these variables and collateral circulation status was *** Of the 97 patients(78 males,mean age:69.0±6.1 years),19(19.6%)had poor *** poor collateral group had a significantly higher NWI(93.7%±5.0%vs.89.0%±7.9%,P=0.011),a greater extent of stenosis(80.0%±11.4%vs.75.3%±9.4%,P=0.036)and FCR(84.2%vs.55.1%,P=0.020)compared with good collateral *** NWI(OR=3.83,95%CI:1.36–10.82,P=0.011)and more FCR(OR=6.77,95%CI:1.35–33.85,P=0.020)were associated with poor collateral circulation after adjustment for the confounding *** combination of NWI,FCR,systolic blood pressure,and triglycerides had the highest area-under-the-curve(AUC=0.85)for detection of poor *** Carotid plaque features,specifically NWI and FCR,are independently associated with poor collateral circulation,and the combination of carotid plaque features and traditional risk factors has a stronger predictive value for poor collateral circulation than plaque features alone.

关键词： Atherosclerosis Carotid stenosis Collateral circulation Computed tomography angiography Magnetic resonance imaging

Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases

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Neural Regeneration Research 2022年第12期17卷 2623-2631页

作者： Qing Wang Li-Juan Song Zhi-Bin Ding Zhi Chai Jie-Zhong Yu Bao-Guo Xiao Cun-Gen Ma Research Center of Neurobiology The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese MedicineShanxi University of Chinese MedicineJinzhongShanxi ProvinceChina Department of Physiology Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Institute of brain Science Shanxi Key Laboratory of Inflammatory Neurodegenerative DiseasesShanxi Datong UniversityDatongShanxi ProvinceChina Department of Neurology Datong Fifth People’s HospitalDatongShanxi ProvinceChina Institute of Neurology Huashan HospitalInstitutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan UniversityShanghaiChina

Ras homolog(Rho)-associated kinases(ROCKs)belong to the serine-threonine kinase family,which plays a pivotal role in regulating the damage,survival,axon guidance,and regeneration of *** are also involved in the biological effects of immune cells and glial cells,as well as the development of neurodegenerative disorders such as Alzheimer’s disease,Parkinson’s disease,and multiple *** studies by us and others confirmed that ROCKs inhibitors attenuated the symptoms and progression of experimental models of the abovementioned neurodegenerative diseases by inhibiting neuroinflammation,regulating immune imbalance,repairing the blood-brain barrier,and promoting nerve repair and myelin ***,the first ROCKs inhibitor to be used clinically,has a good therapeutic effect on neurodegenerative *** increases the activity of neural stem cells and mesenchymal stem cells,thus optimizing cell *** review will systematically describe,for the first time,the effects of abnormal activation of ROCKs on T cells,B cells,microglia,astrocytes,oligodendrocytes,and pericytes in neurodegenerative diseases of the central nervous system,summarize the therapeutic potential of fasudil in several experimental models of neurodegenerative diseases,and clarify the possible cellular and molecular mechanisms of ROCKs *** review also proposes that fasudil is a novel potential treatment,especially in combination with cell-based *** from this review add support for further investigation of ROCKs and its inhibitor fasudil for the treatment of neurodegenerative diseases.

关键词： Alzheimer’s disease cell-based therapy central nervous system cells fasudil immunocytes multiple sclerosis Parkinson’s disease pericytes Rho kinase inhibitor Rho-associated kinases

Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment

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Cellular & Molecular Immunology 2024年第1期21卷 47-59页

作者： Yu Zheng Haihui Jiang Naixue Yang Shaoping Shen Daosheng Huang Lemei Jia Jing Ling Longchen Xu Mingxiao Li Kefu Yu Xiaohui Ren Yong Cui Xun Lan Song Lin Xin Lin Institute for Immunology and School of Medicine Tsinghua UniversityBeijing100084China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityChina.National Clinical Research Center for Neurological DiseasesCenter of Brain TumorBeijing Institute for Brain Disorders and Beijing Key Laboratory of Brain TumorBeijing100070China Department of Neurosurgery Peking University Third HospitalPeking UniversityBeijing100191China Tsinghua-Peking Center for Life Sciences Beijing100084China

A highly immunosuppressive tumor microenvironment(TME)and the presence of the blood‒brain barrier are the two major obstacles to eliciting an effective immune response in patients with high-grade glioma(HGG).Here,we tried to enhance the local innate immune response in relapsed HGG by intracranially injecting poly(I:C)to establish a robust antitumor immune response in this registered clinical trial(NCT03392545).During the follow-up,12/27(44.4%)patients who achieved tumor control concomitant with survival benefit were regarded as responders in our *** found that the T-cell receptor(TCR)repertoire in the TME was reshaped after poly(I:C)*** on the RNA-seq analysis of tumor samples,the expression of annexin A1(ANXA1)was significantly upregulated in the tumor cells of nonresponders,which was further validated at the protein *** vitro and in vivo experiments showed that ANXA1 could induce the production of M2-like macrophages and microglia via its surface receptor formyl peptide receptor 1(FPR1)to establish a Treg cell-driven immunosuppressive TME and suppress the antitumor immune response facilitated by poly(I:C).The ANXA1/FPR1 signaling axis can inhibit the innate immune response of glioma patients by promoting an anti-inflammatory and Treg-driven ***,ANXA1 could serve as a reliable predictor of response to poly(I:C),with a notable predictive accuracy rate of 92.3%.In light of these notable findings,this study unveils a new perspective of immunotherapy for gliomas.

关键词： glioma ANXA1 TLR3 poly(I:C) immunotherapy

Development of machine learning-based models to predict 10-year risk of cardiovascular disease:a prospective cohort study

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Stroke & Vascular Neurology 2023年第6期8卷 475-485页

作者： Jia You Yu Guo Ju-Jiao Kang Hui-Fu Wang Ming Yang Jian-Feng Feng Jin-Tai Yu Wei Cheng Institute of Science and Technology for brain-Inspired Intelligence Department of NeurologyHuashan HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghaiChina Key Laboratory of Computational Neuroscience and brain-Inspired Intelligence Fudan UniversityMinistry of EducationShanghaiChina Zhangjiang Fudan International Innovation Center Fudan UniversityShanghaiChina School of Data Science Fudan UniversityShanghaiChina Fudan ISTBI-ZJNU Algorithm Centre for brain-inspired Intelligence Zhejiang Normal UniversityZhejiangChina Shanghai Medical College and Zhongshan Hospital Immunotherapy Technology Transfer Center Fudan UniversityShanghaiChina

Background Previous prediction algorithms for cardiovascular diseases(CVD)were established using risk factors retrieved largely based on empirical clinical *** study sought to identify predictors among a comprehensive variable space,and then employ machine learning(ML)algorithms to develop a novel CVD risk prediction *** From a longitudinal population-based cohort of UK Biobank,this study included 473611 CVD-free participants aged between 37 and 73 years *** implemented an ML-based data-driven pipeline to identify predictors from 645 candidate variables covering a comprehensive range of health-related factors and assessed multiple ML classifiers to establish a risk prediction model on 10-year incident *** model was validated through a leave-one center-out *** During a median follow-up of 12.2 years,31466 participants developed CVD within 10 years after baseline visits.A novel UK Biobank CVD risk prediction(UKCRP)model was established that comprised 10 predictors including age,sex,medication of cholesterol and blood pressure,cholesterol ratio(total/high-density lipoprotein),systolic blood pressure,previous angina or heart disease,number of medications taken,cystatin C,chest pain and pack-years of *** model obtained satisfied discriminative performance with an area under the receiver operating characteristic curve(AUC)of 0.762±0.010 that outperformed multiple existing clinical models,and it was well-calibrated with a Brier Score of 0.057±***,the UKCRP can obtain comparable performance for myocardial infarction(AUC 0.774±0.011)and ischaemic stroke(AUC 0.730±0.020),but inferior performance for haemorrhagic stroke(AUC 0.644±0.026).Conclusion ML-based classification models can learn expressive representations from potential high-risked CVD participants who may benefit from earlier clinical decisions.

关键词： cardiovascular prediction learning

β-Arrestin-2 inhibits preference for alcohol in mice and suppresses Akt signaling in the dorsal striatum

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Neuroscience Bulletin 2013年第5期29卷 531-540页

作者： Haohong Li Yezheng Tao Li Ma Xing Liu Lan Ma The State Key Laboratory of Medical Neurobiology and the Pharmacology Research Center Shanghai Medical Collegeand the Institute of Brain Science Fudan University

In this study,we investigated the role ofβ-arrestin-2in alcohol preference using the two-bottle choice and conditioned place preference procedures in wild-type（WT）andβ-arrestin-2 knockout（KO）*** and righting reflex tests were performed to test alcohol *** possible molecular signals regulated byβ-arrestin-2 were analyzed by Western *** found thatβ-arrestin-2 KO mice showed a marked increase in voluntary alcohol consumption without significant differences in preference for saccharin or aversion to *** animals also exhibited higher conditioned place preference scores for alcohol than WT ***,KO mice showed reduced sensitivity to alcohol and increased blood alcohol ***,after the free consumption of alcohol,the activities of protein kinase B and glycogen synthase kinase 3β（GSK3β）increased in the dorsal striatum of WT mice,but not in KO mice,which showed high basal activity of Akt in the dorsal *** results suggest thatβ-arrestin-2 negatively regulates alcohol preference and reward,likely through regulating the activation of signaling pathways including Akt/GSK3βin the dorsal striatum.

关键词： β-arrestin alcohol preference Akt

Meningeal Lymphatic vessels:A Drain of the brain Involved in Neurodegeneration?

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Neuroscience Bulletin 2020年第5期36卷 557-560页

作者： Yuan Cheng Yan-Jiang Wang Department of Neurology and Center for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing 400042China Chongqing Key Laboratory of Aging and brain Diseases Chongqing 400042.China The Institute of brain and Intelligence Third Military Medical UniversityChongqing 400042China

Neurodegenerative diseases include several kinds of neurological disorder that are caused by the progressive death of neurons in different regions of the *** diseases affect millions of people worldwide and impose a heavy health burden on modern ***,their pathogenesis remains elusive,and disease-modifying methods are not currently available to prevent,halt,or reverse them[1].

关键词： degeneration diseases death

Assessment of platelet function: Laboratory and point-of-care methods

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World Journal of Translational Medicine 2014年第2期3卷 69-83页

作者： Rita Paniccia Raffaella Priora Agatina Alessandrello Liotta Niccolò Maggini Rosanna Abbate Department of Experimental and Clinical Medicine Thrombosis Center University of Florence Department of Heart and vessels Azienda Ospedaliero-Universitaria Careggi

In the event of blood vessel damage, human platelets are promptly recruited on the site of injury and, after their adhesion, activation and aggregation, prevent blood loss with the formation of a clot. The consequence of abnormal regulation can be either hemorrhage or the development of thrombosis. Qualitative and/or quantitative defects in platelets promote bleeding, whereas the residual reactivity of platelets, despite antiplatelet therapies, play an important role in promoting arterial thrombotic complications. Platelet function is traditionally assessed to investigate the origin of a bleeding syndrome, to predict the risk of bleeding prior surgery or during pregnancy or to monitor the efficacy of antiplatelet therapy in thrombotic syndromes that, now, can be considered a new discipline. "Old" platelet function laboratory tests such as the evaluation of bleeding time and the platelet aggregation analysis inplatelet-rich plasma are traditionally utilized to aid in the diagnosis and management of patients with platelet and hemostatic disorders and used as diagnostic tools both in bleeding and thrombotic diathesis in specialized laboratories. Now, new and renewed automated systems have been introduced to provide a simple, rapid assessment of platelet function including point of care methods. These new methodologies are also suitable for being used in non-specialized laboratories and in critical area for assessing platelet function in whole blood without the requirement of sample processing. Some of these methods are also beginning to be incorporated into routine clinical use and can be utilized as not only as first panel for the diagnosis of platelet dysfunction, but also for monitoring anti-platelet therapy and to potentially assess risk of both bleeding and/or thrombosis.

关键词： Platelets Method Test Point of care testing Laboratory assessment Bleeding Thrombosis Platelet function

The pleiotropic vasoprotective functions of high density lipoproteins(HDL)

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The Journal of Biomedical Research 2018年第3期32卷 164-182页

作者： Guilaine Boyce Emily Button Sonja Soo Cheryl Wellington Department of Pathology and Laboratory Medicine Djavad Mowafaghian Centre for Brain Health University of British Columbia

The pleiotropic functions of circulating high density lipoprotein（HDL） on peripheral vascular health are well established. HDL plays a pivotal role in reverse cholesterol transport and is also known to suppress inflammation,endothelial activation and apoptosis in peripheral vessels. Although not expressed in the central nervous system, HDL has nevertheless emerged as a potential resilience factor for dementia in multiple epidemiological studies. Animal model data specifically support a role for HDL in attenuating the accumulation of P-amyloid within cerebral vessels concomitant with reduced neuroinflammation and improved cognitive performance. As the vascular contributions to dementia are increasingly appreciated, this review seeks to summarize recent literature focused on the vasoprotective properties of HDL that may extend to cerebral vessels, discuss potential roles of HDL in dementia relative to brainderived lipoproteins, identify gaps in current knowledge, and highlight new opportunities for research and discovery.

关键词： high density lipoprotein vascular function vascular disease alzheimer disease HDL-proteome HDL-lipidome

Roles of NG2 Glia in Cerebral Small Vessel Disease

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Neuroscience Bulletin 2023年第3期39卷 519-530页

作者： Yixi He Zhenghao Li Xiaoyu Shi Jing Ding Xin Wang Department of Neurology Zhongshan HospitalFudan UniversityShanghai 200032China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for brain Science Institutes of Brain ScienceFudan UniversityShanghai 200032China Institute of Neuroscience MOE Key Laboratory of Molecular NeurobiologyNMUShanghai 200433China

Cerebral small vessel disease(CSVD)is one of the most prevalent pathologic processes affecting 5%of people over 50 years of age and contributing to 45%of dementia *** evidence has demonstrated the pathological roles of chronic hypoperfusion,impaired cerebral vascular reactivity,and leakage of the blood–brain barrier in ***,the pathogenesis of CSVD remains elusive thus far,and no radical treatment has been ***2 glia,also known as oligodendrocyte precursor cells,are the fourth type of glial cell in addition to astrocytes,microglia,and oligodendrocytes in the mammalian central nervous *** novel functions for NG2 glia in physiological and pathological states have recently been *** this review,we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

关键词： NG2 glia Oligodendrocyte precursor cell Cerebral small vessel disease White matter injury