Protein synthesis modulation as a therapeutic approach for amyotrophic lateral sclerosis and frontotemporal dementia

Protein synthesis is essential for cells to perform life metabolic processes.Pathological alterations of protein content can lead to particular diseases.Cells have an intrinsic array of mechanisms and pathways that are activated when protein misfolding,accumulation,aggregation or mislocalization occur.Some of them(like the unfolded protein response)represent complex interactions between endoplasmic reticulum sensors and elongation factors that tend to increase expression of chaperone proteins and/or repress translation in order to restore protein homeostasis(also known as proteostasis).This is even more important in neurons,as they are very susceptible to harmful effects associated with protein overload and proteostatic mechanisms are less effective with age.Several neurodegenerative pathologies such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,amyotrophic lateral sclerosis and frontotemporal dementia exhibit a particular molecular signature of distinct,unbalanced protein overload.In amyotrophic lateral sclerosis and frontotemporal dementia,the majority of cases present intracellular inclusions of ubiquitinated transactive response DNA-binding protein of 43 kDa(TDP-43).TDP-43 is an RNA binding protein that participates in RNA metabolism,among other functions.Dysregulation of TDP-43(e.g.aggregation and mislocalization)can dramatically affect neurons,and this has been linked to disease development.Expression of amyotrophic lateral sclerosis/frontotemporal dementia TDP-43-related mutations in cellular and animal models has been shown to recapitulate key features of the amyotrophic lateral sclerosis/frontotemporal dementia disease spectrum.These variants can be causative of degeneration onset and progression.Most neurodegenerative diseases(including amyotrophic lateral sclerosis and frontotemporal dementia)have no cure at the moment;however,modulating translation has recently emerged as an attractive approach that can be performed at several steps(i.e.regulating activation of initiation and elongation factors,inhibiting unfolded protein response activation or inducing chaperone expression and activity).This review focuses on the features of protein imbalance in neurodegenerative disorders and the relevance of developing therapeutical compounds aiming at restoring proteostasis.We strive to highlight the importance of research on drugs that,not only restore protein imbalance without compromising translational activity of cells,but are also as safe as possible for the patients.     

Inflammation and apoptosis accelerate progression to irreversible atrophy in denervated intrinsic muscles of the hand compared with biceps: proteomic analysis of a rat model of obstetric brachial plexus palsy

In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial plexus palsy,denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps.In this study,isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins.Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis.At 3 weeks,119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation,while 67 dysregulated proteins were mapped to three such pathways at 5 weeks.At 3 weeks,27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis,while two upregulated proteins were mapped to one such pathway at 5 weeks.At 3 and 5 weeks,53 proteins from pathways involving regrowth and differentiation were downregulated.At 3 weeks,64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation,while,five dysregulated proteins were mapped to three such pathways at 5 weeks.One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks,while three proteins were downregulated from two other pathways at 5 weeks.Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks,while two proteins were downregulated in another pathway at 5 weeks.These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University,China(approval No.DF-325)in January 2015.     

Role of activin receptor-like kinase 1 in vascular development and cerebrovascular diseases

Activin receptor-like kinase 1(ALK1)is a transmembrane serine/threonine receptor kinase of the transforming growth factor beta(TGFβ)receptor superfamily.ALK1 is specifically expressed in vascular endothelial cells,and its dynamic changes are closely related to the proliferation of endothelial cells,the recruitment of pericytes to blood vessels,and functional differentiation during embryonic vascular development.The pathophysiology of many cerebrovascular diseases is today understood as a disorder of endothelial cell function and an imbalance in the proportion of vascular cells.Indeed,mutations in ALK1 and its co-receptor endoglin are major genetic risk factors for vascular arteriovenous malformation.Many studies have shown that ALK1 is closely related to the development of cerebral aneurysms,arteriovenous malformations,and cerebral atherosclerosis.In this review,we describe the various roles of ALK1 in the regulation of angiogenesis and in the maintenance of cerebral vascular homeostasis,and we discuss its relationship to functional dysregulation in cerebrovascular diseases.This review should provide new perspectives for basic research on cerebrovascular diseases and offer more effective targets and strategies for clinical diagnosis,treatment,and prevention.     

Risk factors for corticosteroid insufficiency during the sub-acute phase of acute traumatic brain injury

Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency.Critical illness-related corticosteroid insufficiency can easily occur after traumatic brain injury,but few studies have examined this occurrence.A multicenter,prospective,cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.One hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China,and the critical illness-related corticosteroid insufficiency incidence,critical-illness-related corticosteroid insufficiency-related risk factors,complications,and 28-day mortality among these patients was recorded.Critical illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10μg/dL(275.9 nM)on post-injury day 4 or when serum cortisol was insufficiently suppressed(less than 50%)during a dexamethasone suppression test on post-injury day 5.The results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6%of patients with mild injury,22.5%of patients with moderate injury,and 52.2%of patients with severe injury.Traumatic brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain injury.Traumatic brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions,diffuse axonal injury,brain herniation,and hypotension.Differences in the incidence of hospital-acquired pneumonia,gastrointestinal bleeding,and 28-day mortality were observed between patients with and without critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.Hypotension,brain-injury severity,and the types of traumatic brain injury were independent risk factors for traumatic brain injury-induced critical illness-related corticosteroid insufficiency.These findings indicate that critical illness-related corticosteroid insufficiency is common during the sub-acute phase of traumatic brain injury and is strongly associated with poor prognosis.The dexamethasone suppression test is a practical assay for the evaluation of hypothalamic-pituitary-adrenal axis function and for the diagnosis of critical illness-related corticosteroid insufficiency in patients with traumatic brain injury,especially those with hypotension,hemorrhagic cerebral contusions,diffuse axonal injury,and brain herniation.Sub-acute infection of acute traumatic brain injury may be an important factor associated with the occurrence and development of critical illness-related corticosteroid insufficiency.This study protocol was approved by the Ethics Committee of General Hospital of Tianjin Medical University,China in December 2011(approval No.201189).     

Stroke gets in your eyes: stroke-induced retinal ischemia and the potential of stem cell therapy

Stroke persists as a global health and economic crisis,yet only two interventions to reduce stroke-induced brain injury exist.In the clinic,many patients who experience an ischemic stroke often further suffer from retinal ischemia,which can inhibit their ability to make a functional recovery and may diminish their overall quality of life.Despite this,no treatments for retinal ischemia have been developed.In both cases,ischemia-induced mitochondrial dysfunction initiates a cell loss cascade and inhibits endogenous brain repair.Stem cells have the ability to transfer healthy and functional mitochondria not only ischemic neurons,but also to similarly endangered retinal cells,replacing their defective mitochondria and thereby reducing cell death.In this review,we encapsulate and assess the relationship between cerebral and retinal ischemia,recent preclinical advancements made using in vitro and in vivo retinal ischemia models,the role of mitochondrial dysfunction in retinal ischemia pathology,and the therapeutic potential of stem cell-mediated mitochondrial transfer.Furthermore,we discuss the pitfalls in classic rodent functional assessments and the potential advantages of laser Doppler as a metric of stroke progression.The studies evaluated in this review highlight stem cell-derived mitochondrial transfer as a novel therapeutic approach to both retinal ischemia and stroke.Furthermore,we posit the immense correlation between cerebral and retinal ischemia as an underserved area of study,warranting exploration with the aim of these treating injuries together.     

Differences in clinical and genetic characteristics between early-and late-onset narcolepsy in a Han Chinese cohort

Early-and late-onset narcolepsy constitutes two distinct diagnostic subgroups.However,it is not clear whether symptomology and genetic risk factors differ between early-and late-onset narcoleptics.This study compared clinical data and single-nucleotide polymorphisms(SNPs)between early-and late-onset patients in a large cohort of 899 Han Chinese narcolepsy patients.Blood,cerebrospinal fluid,and clinical data were prospectively collected from patients,and patients were genotyped for 40 previously reported narcolepsy risk-conferring SNPs.Genetic risk scores(GRSs),associations of five different sets of SNPs(GRS1–GRS5)with early-and late-onset narcolepsy,were evaluated using logistic regression and receiver operating characteristic curves.Mean sleep latency was significantly shorter in early-onset cases than in late-onset cases.Symptom severity was greater among late-onset patients,with higher rates of sleep paralysis,hypnagogic hallucinations,health-related quality of life impairment,and concurrent presentation with four or more symptoms.Hypocretin levels did not differ significantly between early-and late-onset cases.Only rs3181077(CCR1/CCR3)and rs9274477(HLA-DQB1)were more prevalent among early-onset cases.Only GRS1(26 SNPs;OR=1.513,95%CI:0.893–2.585;P<0.05)and GRS5(6 SNPs;OR=1.893,95%CI:1.204–2.993;P<0.05)were associated with early-onset narcolepsy,with areas under the receiver operating characteristic curves of 0.731 and 0.732,respectively.Neither GRS1 nor GRS5 included SNPs in HLA regions.Our results indicate that symptomology and genetic risk factors differ between early-and late-onset narcolepsy.This protocol was approved by the Institutional Review Board(IRB)Panels on Medical Human Subjects at Peking University People’s Hospital,China(approval No.Yuanlunshenlinyi 86)in October 2011.     

Adipose-derived stem cells modified by BDNF gene rescue erectile dysfunction after cavernous nerve injury

Cavernous nerve injury is the main cause of erectile dysfunction following radical prostatectomy.The recovery of erectile function following radical prostatectomy remains challenging.Our previous studies found that injecting adipose-derived stem cells(ADSCs)into the cavernosa could repair the damaged cavernous nerves,but the erectile function of the treated rats could not be restored to a normal level.We evaluated the efficacy of ADSCs infected with a lentiviral vector encoding rat brain-derived neurotrophic factor(lenti-rBDNF)in a rat model of cavernous nerve injury.The rats were equally and randomly divided into four groups.In the control group,bilateral cavernous nerves were isolated but not injured.In the bilateral cavernous nerve injury group,bilateral cavernous nerves were isolated and injured with a hemostat clamp for 2 minutes.In the ADSCGFP and ADSCrBDNF groups,after injury with a hemostat clamp for 2 minutes,rats were injected with ADSCs infected with lenti-GFP(1×106 in 20μL)and lenti-rBDNF(1×106 in 20μL),respectively.Erectile function was assessed 4 weeks after injury by measuring intracavernosal pressures.Then,penile tissues were collected for histological detection and western blot assay.Results demonstrated that compared with the bilateral cavernous nerve injury group,erectile function was significantly recovered in the ADSCGFP and ADSCrBDNF groups,and to a greater degree in the ADSCrBDNF group.Neuronal nitric oxide synthase content in the dorsal nerves and the ratio of smooth muscle/collagen were significantly higher in the ADSCrBDNF and ADSCGFP groups than in the bilateral cavernous nerve injury group.Neuronal nitric oxide synthase expression was obviously higher in the ADSCrBDNF group than in the ADSCGFP group.These findings confirm that intracavernous injection with ADSCs infected with lenti-rBDNF can effectively improve erectile dysfunction caused by cavernous nerve injury.This study was approved by the Medical Animal Care and Welfare Committee of Wuhan University,China(approval No.2017-1638)on June 20,2017.     

Acupuncture promotes functional recovery after cerebral hemorrhage by upregulating neurotrophic factor expression

Acupuncture is widely used in the treatment of cerebral hemorrhage,and it improves outcomes in experimental animal models and patients.However,the mechanisms underlying the effectiveness of acupuncture treatment for cerebral hemorrhage are still unclear.In this study,a model of intracerebral hemorrhage was produced by injecting 50μL autologous blood into the caudate nucleus in Wistar rats.Acupuncture at Baihui(DU20)and Qubin(GB7)acupoints was performed at a depth of 1.0 inch,12 hours after blood injection,once every 24 hours.The needle was rotated at 200 r/min for 5 minutes,For each 30-minute session,needling at 200 r/min was performed for three sessions,each lasting 5 minutes.For the positive control group,at 6 hours,and 1,2,3 and 7 days after induction of hemorrhage,the rats were intraperitoneally injected with 1 mL aniracetam(0.75 mg/mL),three times a day.The Bederson behavioral test was used to assess palsy in the contralateral limbs.Western blot assay was used to examine the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia.Immunohistochemistry was performed to count the number of Nestin-and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia.Acupuncture effectively reduced hemorrhage and brain edema,elevated the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia,and increased the number of Nestin-and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia.Together,these findings suggest that acupuncture promotes functional recovery after cerebral hemorrhage by increasing the expression of neurotrophic factors.The study was approved by the Committee for Experimental Animals of Heilongjiang Medical Laboratory Animal Center(approval No.2017061001)on June 10,2017.     

Urolithin A alleviates blood-brain barrier disruption and attenuates neuronal apoptosis following traumatic brain injury in mice

Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However,its effect against traumatic brain injury remains unknown.In this study,we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA.We found that UA greatly reduced brain edema;increased the expression of tight junction proteins in injured cortex;increased the immunopositivity of two neuronal autophagy markers,microtubule-associated protein 1A/B light chain 3A/B(LC3)and p62;downregulated protein kinase B(Akt)and mammalian target of rapamycin(mTOR),two regulators of the phosphatidylinositol 3-kinase(PI3K)/Akt/mTOR signaling pathway;decreased the phosphorylation levels of inhibitor of NFκB(IκB)kinase alpha(IKKα)and nuclear factor kappa B(NFκB),two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway;reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex;and improved mouse neurological function.These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury,and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways,thus reducing neuroinflammation and enhancing autophagy.     

颈动脉支架术后血流动力学相关因素分析

目的探讨颈内动脉狭窄支架置入术后影响血流动力学的相关因素。方法颈内动脉狭窄经过颈动脉支架成形术治疗的患者中术后出现血流动力学改变32例和35例未出现血流动力学改变的患者的临床资料进行分析:血流动力学改变与患者年龄、高血压、糖尿病、狭窄程度、球囊型号、支架的型号、病变靠近颈动脉球部及球囊扩张次数相关性。结果结果提示狭窄程度(B=0.536;P=0.024;OR=2.591)、高血压(B=-1.654;P=0.006;OR=0.131)、球囊型号(B=1.818;P=0.012:OR=0.133)和支架的型号(B=1.328;P=0.021;OR=2.29)、病变位于球部(B=1.613;P=0.014:OR=0.133)和球囊扩张的次数(B=1.328;P=0.022;OR=2.39)与血流动力学改变密切相关。结论颈动脉支架置入术后继发的颈动脉窦反射引起血流动力学损害是常见的并发症,其血压、狭窄的程度、病变位于球部、球囊的型号、支架的型号及球囊扩张次数这些因素将会直接影响术后患者血流动力学的变化。     

Predictors of hemodynamic instability during and persistent after carotid artery stenting

ObjectivesThe risk factors for post-carotid artery stenting severe hemodynamic instability remain elusive. This study aimed to identify the predictors of severe hemodynamic instability during and persisted after carotid artery stenting.Materials and methodsConsecutive patients who underwent carotid artery stenting for extracranial carotid artery stenosis at a single-center between September 2018 and July 2021 were retrospectively assessed. The predictive factors of severe hemodynamic instability intraoperation and post-operation were analyzed.ResultsAmong the 139 patients included, 63 experienced severe hemodynamic instability, with 45 and 18 cases occurring intra and postoperatively, respectively. Persistent was observed in 21 patients. Smoke exposure (odds ratio [OR], 2.38; p=0.039), carotid bifurcation stenosis (OR, 0.91; p=0.018), and large-diameter balloon (>4 mm) dilatation (OR, 11.95; p<0.001) were identified as independent risk factors for hemodynamic instability at any stage of carotid artery stenting. Intraoperatively, large-diameter balloon (>4 mm) dilatation was associated with an increased risk of hemodynamic instability occurrence (OR, 4.67; p=0.01), whereas general anesthesia (OR, 0.19; p=0.001) and a longer distance from the stenosis to the carotid bifurcation (OR, 0.89; p=0.01) were negatively associated with hemodynamic instability. Furthermore, smoking exposure (OR, 3.73; p=0.03), large diameter balloon dilatation (OR, 6.12; p=0.032), distance from stenosis to bifurcation (OR, 0.85; p=0.047) and long-stent (40 mm) implantation (OR, 0.84 [95% confidence interval, 0.74–0.95]; p=0.007) could independently predict persistent hemodynamic instability.ConclusionPatients with a smoking history, lesions near the carotid bulb, or dilatation using a large-diameter balloon were most likely to suffer severe hemodynamic instability. General anesthesia can protect against severe hemodynamic instability only intraoperatively. Long-term stent implantation may reduce persistent hemodynamic instability.     

正五聚蛋白3与缺血性卒中患者颈动脉狭窄的关系研究

目的 通过分析急性缺血性卒中患者血浆正五聚蛋白3（pentraxin 3,PTX3）和凝集素样氧化型低 密度脂蛋白受体-1（lectin-like oxidized low density lipoprotein receptor-1,LOX-1）与颈动脉狭窄的关系, 探索PTX3在颈动脉狭窄形成过程中的作用。 方法 前瞻性连续纳入2019年1-8月于首都医科大学附属北京友谊医院神经内科治疗的急性缺血 性卒中患者,收集患者的基线资料、头颅CTA、血脂、PTX3、LOX-1等检查结果。根据患者头颅CTA有无 颈动脉狭窄分为颈动脉狭窄组和无颈动脉狭窄组;以狭窄程度为标准,将颈动脉狭窄组患者分为严重 狭窄（≥50%）组和轻度狭窄（＜50%）组。采用单因素分析和多因素Logistic回归分析颈内动脉狭窄的 独立危险因素。 结果 共纳入102例患者,颈动脉狭窄组57例（55.9%）,无颈动脉狭窄组45例（44.1%）,颈动脉狭窄 组中轻度狭窄32例（56.1%）,严重狭窄25例（43.9%）;颈动脉狭窄组的缺血性脑血管病家族史比例、 LDL-C、PTX3及LOX-1水平均高于无颈动脉狭窄组（均P <0.05）;严重狭窄组的PTX3、LOX-1及LDL-C水 平均高于轻度狭窄组（均P <0.05）。多因素Logistic回归分析结果显示PTX3（OR 3.11,95%CI 2.11～4.58, P =0.007）、LOX-1（OR 5.47,95%CI 2.89～10.13,P =0.017）和LDL-C（OR 5.35,95%CI 2.45～10.65, P =0.021）水平升高是颈动脉狭窄发生的独立危险因素。 结论 血浆PTX3、LOX-1和LDL-C水平升高是颈动脉狭窄的独立危险因素。     

老年轻型急性缺血性卒中后认知障碍与血清β2微球蛋白的关系研究

目的 探讨血清β2微球蛋白水平与老年轻型急性缺血性卒中后认知障碍的关系,为预防老年轻型 卒中后认知障碍提供依据。 方法 回顾性分析2015年1月-2018年9月在北京中医药大学东方医院脑病科住院的老年轻型急性 缺血性卒中患者的临床资料,所有入组病例均在入院第2天采集空腹肘静脉血测定血清β2微球蛋白、 LDL-C、HDL-C等生化指标;发病第10～14天使用北京版MoCA量表进行评测,分为认知障碍组（MoCA评 分＜26分）和无认知障碍组（MoCA评分≥26分）,通过统计学分析,探讨老年轻型急性缺血性卒中后 认知障碍与血清β2微球蛋白之间的关系。 结果 研究共纳入106例老年轻型急性缺血性卒中患者,其中认知障碍组66例,无认知障碍 组40例。认知障碍组患者血清β2微球蛋白水平（P =0.040）、年龄（P =0.004）、高血压患者比例 （P =0.027）均高于无认知障碍组。多因素Logistic回归分析结果显示血清β2微球蛋白水平（OR 2.645, 95%CI 1.145～6.110,P =0.023）、年龄（OR 1.112,95%CI 1.041～1.188,P =0.002）、高血压（OR 2.806, 95%CI 1.057～7.452,P =0.038）是老年轻型急性缺血性卒中后认知障碍的危险因素。 结论 血清β2微球蛋白升高是老年轻型急性缺血性卒中后认知障碍的危险因素之一,血清β2微球 蛋白水平较高的老年轻型急性缺血性卒中患者应给予重视。     

脑小血管病步态障碍的影像特征与危险因素研究

目的 探讨与脑小血管病（cerebral small vessel disease,CSVD）步态障碍相关的影像特征。 方法 连续收集2018年7-9月在青岛西海岸新区人民医院神经内科住院的CSVD患者,记录入组 患者的性别、年龄、吸烟史、控制不良的高血压、高脂血症、HbA1c、无症状性梗死、室周白质高信 号（periventricular white matter hyperintensities,PWMHs）评分、深部白质高信号（deep white matter hyperintensities,DWMHs）评分、皮质萎缩（外侧裂比值）、皮质下萎缩（尾状核指数）及颞叶海马萎缩 （海马沟回比）等资料。按照Holden步行功能分级（functional ambulation classification,FAC）≤3,分为跌 倒低风险组（low risk of falling,LRF）和高风险组（high risk of falling,HRF）,采用多因素Logistic回 归分析CSVD患者步态障碍的独立危险因素。 结果 研究共纳入102例CSVD患者,其中HRF组59例（57.8%）。单因素分析提示HRF组与LRF组的年龄 （P＜0.001）、HbA1c（P =0.007）、PWMHs（P =0.002）、DWMHs（P＜0.001）、外侧裂比值（P＜0.001）、尾 状核指数（P =0.003）及海马沟回比（P＜0.001）差异有统计学意义,多因素Logistic回归分析显示年龄 （OR 1.173,95%CI 1.053～1.306,P =0.004）、DWMHs（OR 8.883,95%CI 2.674～29.512,P＜0.001）及外 侧裂比值（OR 1.433,95%CI 1.028～1.999,P =0.034）是CSVD步态障碍的独立危险因素。 结论 CSVD患者步态障碍的独立危险因素包括年龄、皮层萎缩及DWMHs评分。     

1729例卒中高危人群颈动脉超声筛查结果分析

目的 了解社区40岁以上卒中高危人群颈动脉粥样硬化情况,为卒中高危人群的干预措施提供依 据。 方法 研究方法为横断面研究,采用知情自愿的原则,从辖区内抽取40岁以上的常住人口,用问卷筛 选出1729例卒中高危人群,对所有高危人群进行体格检查、实验室检查及颈动脉超声检查(检测颈 动脉内膜中层及斑块形态)。 结果 问卷筛查出高危人群1729例,其中男性453例（26.2%）,女性1276例（73.8%）,平均年龄 为（58.8±9.6）岁。颈动脉超声显示异常的833例（48.2%）,其中颈动脉内膜中层单纯增厚、颈动脉粥 样硬化斑块分别为98例和735例,分别占总高危人群的5.7%和42.5%,分别占超声异常高危人群的 25.1%和88.2%。按照年龄分层,40～50岁、50～60岁、60～70岁和70岁及以上组左侧颈动脉内膜中层 增厚（χ2=15.5,P =0.001）和右侧颈动脉内膜中层增厚（χ2=26.7,P＜0.001）发生率差异具有显著性; 不同年龄组动脉粥样硬化斑块的比率差异也具有显著性（χ2=48.6,P＜0.001）。 结论 卒中高危人群中,颈动脉超声异常发生率较高,颈动脉内膜增厚和动脉粥样硬化斑块形成均 有随着年龄增加而增多的趋势。     

卒中后疲劳危险因素的系统评价

目的 系统评价卒中后疲劳危险因素,为卒中后疲劳的防治及健康教育提供参考依据。 方法 计算机检索The Cochrane Library、PubMed、Web of SCIence、EMbase、CNKI、WanFang Data和VIP 数据库,搜集有关卒中后疲劳相关危险因素的病例-对照研究、队列研究、横断面研究,检索时限均 为建库至2019年10月30日。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采 用RevMan5.3进行Meta分析。 结果 共纳入14 项研究,包括3 2 01例患者。M e t a分析结果显示：卒中前疲劳（O R 5.9 3, 95%CI 3.41～10.32,P＜0.001）、抑郁症（OR 2.48,95%CI 1.83～3.36,P＜0.001）、女性（OR 1.67, 95%CI 1.24～2.26,P＜0.001）、家庭功能障碍（OR 2.57,95%CI 1.86～3.57,P＜0.001）、mRS评分 （OR 2.65,95%CI 2.04～3.45,P＜0.001）、冠心病（OR 3.41,95%CI 1.97～5.90,P＜0.001）、不能自 理（OR 4.32,95%CI 2.47～7.54,P＜0.001）、高脂血症（OR 2.27,95%CI 1.20,4.27,P =0.01）、镇静药 物使用（OR 4.10,95%CI 2.14～7.87,P＜0.001）是卒中后疲劳的危险因素;卒中前规律运动（OR 0.50, 95%CI 0.36～0.70,P＜0.001）是卒中后疲劳的保护因素。 结论 本研究结果显示,性别（女性）、卒中前疲劳、抑郁、家庭功能障碍、mRS评分、冠心病、自理 能力差、高脂血症、镇静药物使用可能是卒中后疲劳的危险因素,其余风险因素相关性有待进一步研 究。受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证。     

症状性大脑中动脉粥样硬化性狭窄的血流动力学数值模拟研究

目的 探讨血流动力学因素在大脑中动脉粥样硬化性狭窄患者急性脑缺血事件中的作用。 方法 收集10例第二军医大学附属长海医院脑血管病中心收治的症状性单侧大脑中动脉（middle cerebral artery,MCA）M1段局限狭窄的患者,依据脑血管造影建立病例特异三维数值模型,测量M1段 狭窄程度,并应用计算机流体力学方法测算血流动力学参数,分析动脉不同部位及不同狭窄程度血 流动力学参数的变化。狭窄段至远端正常血管段壁面剪切力（wall shear stress,WSS）变化用标准化 WSS表示,为狭窄段WSS（WSSS）与远端正常血管段WSS（WSSP）的比值,记为WSSS/P;血流速度（velocity） 及震荡剪切指数（oscillatory shear index,OSI）的变化用标准化的velocityS/P、OSI S/P表示。 结果 MCA狭窄段WSS明显高于远端正常段（中位数81.85 vs 18.81,P =0.000）;狭窄段流速快于远 端正常段（中位数2.26 vs 0.33,P =0.000）;而MCA最狭窄处OSI低于远端正常血管段（中位数0.000 39 vs 0.015 70,P =0.000）;不同狭窄程度间,标准化血流动力学参数不同;狭窄程度增大,WSSS/P、 velocityS/P增加（r S=0.828,P =0.003;r S=0.79,P =0.007）,OSI S/P逐渐下降（r S=-0.822,P =0.004）。 结论 大脑中动脉狭窄病变伴有血流动力学改变,血流动力学因素可能参与了颅内动脉粥样硬化形 成和发展。     

吸烟对脑梗死患者脑血管反应性的影响

目的探讨吸烟对脑梗死患者脑血管反应性的影响。方法前瞻性连续纳入2018年1月-2019年1月于深圳市人民医院神经内科住院治疗的发病1周内的急性脑梗死患者,应用经颅多普勒超声以屏气指数(breath-holding index,BHI)评价脑血管对高碳酸血症的反应性。根据脑血管反应性(cerebrovascular reactivity,CVR)是否正常,分为BHI正常组与BHI受损组。将两组临床资料进行单因素分析,将有统计学意义的变量(P<0.05)进行多因素Logistic回归分析。计算ROC曲线下面积,从而判断吸烟对脑梗死患者CVR结局的早期预测价值。结果共纳入112例患者,BHI受损组(76例)的吸烟、高血压病、颅内动脉狭窄的比例明显高于BHI正常组(36例)(56.6%vs 30.6%,P=0.01;85.5%vs 66.7%,P=0.021;47.4%vs 25%,P=0.024)。高尿酸血症的患病率低于BHI正常组(10.5%vs 25%,P=0.046)。多因素Logistic回归分析结果显示吸烟(OR 3.438,95%CI 1.397~8.463,P=0.007)、高血压病(OR 3.075,95%CI 1.110~8.518,P=0.031)、颅内动脉狭窄(OR 2.571,95%CI 1.016~6.506,P=0.046)是脑梗死患者CVR受损的独立危险因素。绘制吸烟的ROC曲线下面积为0.630(95%CI 0.521~0.740,P=0.027),吸烟预测脑梗死患者CVR受损的敏感度为56.6%,特异度为69.4%。结论吸烟、高血压病、颅内动脉狭窄是脑梗死患者CVR受损的独立危险因素,吸烟对脑梗死患者CVR受损具有一定的预测价值。     

缺血性卒中患者左心室质量指数与颅内、外动脉狭窄的相关性

目的 探讨左心室质量指数（left ventricular mass index,LVMI）与颅内外动脉粥样硬化狭窄程度的 关系。 方法 从东部战区总医院南京卒中登记系统纳入2017年1-10月间进行超声心动图和DSA检查的缺血 性卒中患者。对颅外和颅内动脉粥样硬化性狭窄程度进行评估,分为动脉轻度狭窄组和动脉中重度 狭窄组。LVMI根据美国超声心动图协会标准计算。在颅外和颅内动脉粥样狭窄患者中分别比较动脉 轻度狭窄和中重度狭窄组传统脑动脉粥样硬化的危险因素,如年龄、性别、高血压、糖尿病、冠状动 脉硬化心脏病、血脂及左心室质量（left ventricular mass,LVM）和LVMI。单因素分析及二元回归分析 影响颅内外动脉粥样硬化狭窄程度的独立危险因素并对LVMI与颅内外动脉狭窄率进行相关性分析。 结果 169例登记患者中,85例（50.3%）为颅外动脉粥样硬化性狭窄,84例（49.7%）为颅内动 脉粥样硬化狭窄。在颅外动脉粥样硬化性狭窄患者中,中重度狭窄患者年龄比轻度狭窄患者大 [（64.3±12.4）岁 vs（56.0±13.2）岁,P =0.001],LVMI较轻度狭窄患者高[（43.6±10.3）g/m2.7 vs （36.6±7.2）g/m2.7,P <0.001]。在颅内动脉粥样硬化性狭窄患者中,轻度狭窄患者LVMI低于中重度狭 窄患者（[ 36.5±7.2）g/m2.7 vs（46.1±13.6）g/m2.7,P <0.001]。Spearman相关分析结果表明LVMI与颅内 外动脉狭窄率呈正相关（r=0.553,P<0.001）。二元回归分析发现LVM（I OR 1.13,95%CI 1.05～1.21）、 年龄（OR 1.06,95%CI 1.01～1.11）是颅外动脉粥样硬化性重度狭窄的独立危险因素。 结论 缺血性卒中患者LVMI与颅内外动脉粥样硬化性狭窄率正相关,LVMI是颅外动脉粥样硬化性重 度狭窄的独立危险因素。