卒中单元对急性缺血性卒中患者医疗质量和在院预后的影响

目的 调查中国卒中单元对缺血性卒中患者收治的现况，并探索卒中单元对改善卒中医疗质量绩效
指标及患者在院预后的影响。
方法 本研究数据来自中国多中心缺血性卒中住院患者登记研究。按照是否进入卒中单元，将
研究对象分为卒中单元组与非卒中单元组。比较两组间患者的卒中医疗质量关键绩效指标（key
performance index，KPI）和在院预后（卒中复发、联合血管事件、全因死亡）的差异，并采用多因素回归，
分析与卒中单元相关的KPI及卒中单元与缺血性卒中患者在院预后的相关性。
结果 本研究共纳入了全国1374家医院的269 428例急性缺血性卒中住院患者。其中，63 548例
（23.6%）患者纳入卒中单元组。卒中单元与较高比例的rt-PA静脉溶栓（OR 1.48，95%CI 1.43～1.53）、
早期抗栓治疗（OR 1.13，95%CI 1.10～1.17）、深静脉血栓预防（OR 1.19，95%CI 1.16～1.22）、吞
咽功能筛查（OR 1.36，95%CI 1.32～1.39）、康复评估（OR 1.31，95%CI 1.28～1.34）、出院抗栓治疗
（OR 1.12，95%CI 1.08～1.15）、合并心房颤动患者抗凝治疗（OR 1.13，95%CI 1.08～1.19）、戒烟宣教
（OR 1.22，95%CI 1.20～1.25）独立相关，与较低的在院卒中复发率（HR 0.79，95%CI 0.75～0.82）和
联合血管事件发生率（HR 0.80，95%CI 0.77～0.84）独立相关（均P <0.001）。
结论 进入卒中单元的缺血性卒中患者，卒中医疗质量KPI完成较好，在院卒中复发率及联合血管事
件率较低。     

急性缺血性卒中相关肺炎评分临床应用价值分析

目的 验证急性缺血性卒中相关肺炎评分（Acute Ischemic Stroke-Associated Pneumonia Score，AISAPS）
对缺血性卒中相关肺炎的预测效果，为临床早期发现卒中相关性肺炎提供适合的筛查工具。
方法 从任丘康济新图医院缺血性卒中急性期干预、二级预防相关登记研究数据库中选取2014年
1月20日-2016年8月31日住院治疗的急性缺血性卒中患者，采用AIS-APS评分量表进行评分，应用ROC
曲线下面积确定AIS-APS对缺血性卒中相关肺炎预测的灵敏度与特异度，验证该量表的有效性，同时
验证ISAN[prestroke Independence（mRS），sex，age，NIHSS]、A2DS2（age，atrial fibrillation，dysphagia，sex，
stroke severity）、Kwon等评分量表对缺血性卒中患者发生卒中相关性肺炎的预测作用。
结果 共纳入3104例急性缺血性卒中患者，其中有100例（3.2%）发生肺炎；AIS-APS的ROC曲线下面
积为0.737（95%CI 0.721～0.753），敏感度0.800，特异度0.611，Youden指数0.411，最佳界值为5分。与
其他评分量表相比，AI S-APS量表ROC曲线下面积、灵敏度最高，但ISAN量表特异度最高（0.759）。
结论 AIS-APS量表对于卒中相关性肺炎的预测有一定价值，可指导临床早期筛查卒中相关性肺炎。     

椎动脉发育不良与后循环缺血性卒中： 从假说到发病机制

椎动脉发育不良是临床常见的后循环血管变异。已有的研究结果显示,椎动脉发育不良是
后循环缺血性卒中的危险因素,并与之存在区域性关联。椎动脉发育不良在后循环缺血性卒中的发
生发展中起到重要作用。本文对椎动脉发育不良与后循环缺血性卒中之间的关系以及潜在的发病机
制进行综述,以期为后循环缺血性卒中的科学预防和临床治疗提供参考。     

急性缺血性卒中预后评分的研究进展

急性缺血性卒中对人类生命和健康的危害极大,其发病率和死亡率在我国疾病谱中一直
处于前三位,给患者及其家庭带来沉重的生活障碍和经济负担。若能够早期判断急性缺血性卒中患
者的预后,积极干预,可有效降低不良预后的风险。最近国内外学者一直致力于急性缺血性卒中预
后评分的研发及应用。本文就急性缺血性卒中预后评分研究现状做一综述,期待帮助临床神经科
医师在接诊急性缺血性卒中患者时,对患者预后进行快速评判并指导决策。     

急性缺血性卒中患者的早期诊疗指南 ——美国心脏协会/美国卒中协会为医疗 保健专业人员制定的指南（第八部分）

背景与目的 本文作者全面回顾了成人急性缺血性卒中的现有证据及各类评估和诊疗建议。本文
的目标读者为院前急救人员、内科医师、专职医疗人员和医院内参与卒中发病后最初48 h诊疗的有关
人员。这一指南将取代此前的2007版和更新后的2009版指南。
方法 编写委员会成员由美国心脏协会卒中委员会的科学声明监督委员会指定，各成员来自不同专业
领域。共识编写的整个过程严格遵守美国心脏协会的利益冲突政策。小组成员被分配了与自己专业
领域相关的主题，重点回顾了前版指南发表之后的卒中文献，并按照美国心脏协会/美国卒中协会的
证据分级方案起草建议。
结果 指南的目的是降低卒中发病率和卒中相关死亡率。本指南既提倡卒中医疗系统的整体概念，
又体现卒中医疗的各个细节，从患者的识别到急救医疗服务启动、转运、分诊，包括了整个在急诊室
和卒中单元的最初几个小时内的救治过程。本指南讨论了卒中的早期评估和一般性治疗，以及缺
血性卒中特殊的干预措施，如再灌注策略以及脑复苏的最优化措施。
结论 由于很多建议基于有限的资料，急性缺血性卒中的治疗仍亟需进一步研究     

Essen评分在TIA、缺血性小卒中与大卒中 患者中预测效度的比较

目的 比较Essen卒中风险分层量表（Essen Stroke Risk Score,ESRS）预测短暂性脑缺血发作（transient
ischemic attack,TIA）、缺血性小卒中和缺血性大卒中患者的卒中复发和联合血管事件发生的效度。
方法 以前瞻性、多中心中国国家卒中登记研究（China National Stroke Registry,CNSR）中连续录入
的11 384例完成1年随访的TIA、非心房颤动性缺血性卒中的住院患者为研究人群,小卒中定义为入院
时缺血性卒中患者的美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale,NIHSS）
评分≤3分,大卒中定义为NIHSS评分＞3分。采用曲线下面积（area under the curve,AUC）评价ESRS对
TIA、缺血性小卒中和大卒中患者进行卒中复发和联合血管事件复发风险的分层能力,预测卒中复发
和联合血管事件发生的效度。
结果 本研究有1061例TIA,3254例小卒中,7069例大卒中患者。在TIA患者中,ESRS预测卒中复发
AUC=0.57,预测联合血管事件AUC=0.56;小卒中患者中,ESRS预测卒中复发的AUC=0.58,预测联合
血管事件AUC=0.59;大卒中患者中,ESRS预测卒中复发的AUC=0.60,预测联合血管事件AUC=0.60。
结论 ESRS评分对大卒中的卒中复发/联合血管事件发生的预测效度最高,其次是对小卒中,在TIA
中预测效度最低,但是三组人群中差异无显著性。     

缺血性卒中患者静脉溶栓后不良预后危险因素的研究现状

急性缺血性卒中静脉溶栓的患者临床预后可受疾病严重程度、发病到溶栓的时间、脑小
血管病、血糖水平、中性粒细胞计数、血小板计数、溶栓后再灌注损伤及出血转化等多种因素的影响。
本文从流行病学、溶栓前后影响缺血性卒中静脉溶栓预后的危险因素及相关预测模型进行文献复习,
旨在加强对缺血性卒中患者静脉溶栓后不良预后危险因素及相关预测模型的认识,为其防治提供理
论依据和临床指导。     

急性缺血性卒中1年血管源性死亡危险因素分析

目的 分析急性缺血性卒中患者随访1年血管源性死亡的相关影响因素，为早期评估高危急性缺血
性卒中患者、积极控制危险因素、降低死亡率提供临床依据。
方法 回顾性纳入2014年1月-2018年9月于河北省任丘康济新图医院神经内科住院的急性缺血性
卒中患者，收集患者临床基线资料及实验室检查结果。采用多因素Cox回归分析方法分析急性缺血性
卒中患者1年内血管源性死亡的危险因素。
结果 研究共纳入符合入排标准的急性缺血性卒中患者3 6 61例，随访1年内死亡患者16 0
例（4.4%），其中血管源性死亡136例（3.7%），其中包括缺血性血管性死亡3.1%（114例），出血
性血管性死亡0.1%（4例），心源性血管性死亡0.2%（8例），其他血管性死亡0.3%（10例），非血
管源性死亡0.7%（24例）。非血管源性死亡患者作为删失数据，最终共纳入急性缺血性卒中患者
3637例。多因素Cox回归分析显示年龄＞60岁（OR 1.084，95%CI 1.062～1.105，P＜0.001）、颈动脉
狭窄（OR 1.835，95%CI 1.288～2.614，P =0.001）、入院时NIHSS评分（OR 1.200，95%CI 1.164～1.237，
P ＜0.001）、脂蛋白a（OR 1.001，95%C I 1.000～1.001，P ＜0.001）、白细胞计数（OR 1.093，
95%CI 1.031～1.159，P =0.003）、纤维蛋白原水平（OR 1.092，95%CI 1.025～1.164，P =0.006）、血肌
酐（OR 1.004，95%CI 1.001～1.007，P =0.009）是血管源性死亡的独立危险因素。HDL-C（OR 0.378，
95%CI 0.208～0.686，P =0.001）是血管源性死亡的保护因素。
结论 急性缺血性卒中1年内血管源性死亡的危险因素为高龄、颈动脉狭窄、入院时NIHSS评分、脂
蛋白a水平、白细胞计数、纤维蛋白原及血肌酐水平。高密度脂蛋白为其保护因素。     

缺血性卒中急性期血浆神经递质水平的 病例对照研究

目的 通过病例对照的方式研究缺血性卒中急性期血浆神经递质水平与正常人群之间的差异,同
时研究不同严重程度卒中患者的血浆递质水平的差异。
方法 选取连续入组、发病在14 d内的急性缺血性卒中患者,采集急性期的血样标本,通过液相色
谱-高分辨质谱外标法测量比较卒中组以及正常对照组血浆内的5-羟色胺、去甲肾上腺素、谷氨酸
和γ-氨基丁酸4种神经递质的浓度。同时比较不同卒中严重程度患者的4种神经递质浓度。
结果 共268例缺血性卒中患者入组,其急性期血浆神经递质与正常对照组相比,血浆5-羟色
胺（t =2.289,P =0.023）、去甲肾上腺素（t =0.0903,P =0.367）和谷氨酸有上升趋势（t =0.277,
P =0.782）,γ-氨基丁酸有下降趋势（t =－4.4145,P =0.000）,其中5-羟色胺和γ-氨基丁酸在
两组之间的差异有显著性。中重度卒中患者血浆5-羟色胺水平显著高于轻度卒中患者（t =2.197,
P =0.029）。
结论 缺血性卒中急性期血浆神经递质水平与正常对照相比有差异,中重度卒中患者的血浆5-羟
色胺水平升高较轻度卒中患者显著。     

磁共振斑块成像与缺血性卒中的相关性研究进展

动脉粥样硬化易损斑块破裂是导致缺血性卒中的主要原因。与组织病理学对照研究证实,
高分辨率磁共振成像可以无创性评价动脉粥样硬化斑块的负荷、成分及其易损性。大量研究显示,
脑血管粥样硬化斑块的磁共振表现特征与缺血性卒中具有明显的相关性。本文将从磁共振斑块成
分特征与缺血性脑血管事件的相关性方面进行综述,为缺血性卒中的病因学诊断和疾病的预防提供
重要依据。     

Autophagy and inflammation in ischemic stroke

Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of neural tissue after ischemia.Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke.This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows.(1)Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR,the AMPK pathway,and inhibition of inflammasome activation.(2)Activation of inflammation triggers the formation of autophagosomes,and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1.Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK,reducing the flux and autophagy level,thereby inducing inflammatory activity.(3)By blocking the activation of autophagy,the activation of inflammasomes can alleviate cerebral ischemic injury.Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway,which is beneficial to the recovery of neural tissue after ischemia.Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway.These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.     

Neuronal autophagy in cerebral ischemia

Autophagy has evolved as a conserved process for the bulk degradation and recycling of cytosolic components, such as long-lived proteins and organelles. In neurons, autophagy is important for homeostasis and protein quality control and is maintained at relatively low levels under normal conditions, while it is upregulated in response to pathophysiological conditions, such as cerebral ischemic injury. However, the role of autophagy is more complex. It depends on age or brain maturity, region, severity of insult, and the stage of ischemia. Whether autophagy plays a beneficial or a detrimental role in cerebral ischemia depends on various pathological conditions. In this review, we elucidate the role of neuronal autophagy in cerebral ischemia.     

The role of autophagic and lysosomal pathways in ischemic brain injury******

Autophagy is involved in neural cell death after cerebral ischemia. Our previous studies showed that rapamycin-induced autophagy decreased the rate of apoptosis, but the rate of apoptosis was in-creased after the autophagy inhibitor, 3-methyladenine, was used. In this study, a suture-occluded method was performed to generate a rat model of brain ischemia. Under a transmission electron microscope, autophagic bodies and autophagy lysosomes were markedly accumulated in neurons at 4 hours post brain ischemic injury, with their numbers gradually reducing over time. Western blotting demonstrated that protein levels of light chain 3-II and cathepsin B were significantly in-creased within 4 hours of ischemic injury, but these levels were not persistently upregulated over time. Confocal microscopy showed that autophagy was mainly found in neurons with positive light chain 3 signal. Injection of rapamycin via tail vein promoted the occurrence of autophagy in rat brain tissue after cerebral ischemia and elevated light chain 3 and cathepsin B expression. However, in-jection of 3-methyladenine significantly diminished light chain 3-II and cathepsin B expression. Results verified that autophagic and lysosomal activity is increased in ischemic neurons. Abnormal components in cells can be eliminated through upregulating cell autophagy or inhibiting autophagy after ischemic brain injury, resulting in a dynamic balance of substances in cells. Moreover, drugs that interfere with autophagy may be potential therapies for the treatment of brain injury.     

Autophagy after experimental intracerebral hemorrhage.

Autophagy contributes to ischemic brain injury, but it is not clear if autophagy occurs after intracerebral hemorrhage (ICH). This study examined whether ICH-induced cell death is partly autophagic. It then examined the role of iron in inducing this form of cell death after ICH. Male, adult Sprague-Dawley rats received an infusion of autologous whole blood or ferrous iron into the right basal ganglia. Control rats (sham) had a needle insertion. The rats were killed at 1, 3, 7, or 28 days later. Some rats were treated with either deferoxamine or vehicle after ICH. Microtubule-associated protein light chain-3 (LC3), a biomarker of autophagosome, and cathepsin D, a lysosomal biomarker, were measured by Western blot analysis and immunohistochemistry. Immunofluorescent double-labeling was used to identify the cell types expressing cathepsin D. Electron microscopy was performed to examine the cellular ultrastructure changes after ICH. We found that conversion of LC3-I to LC3-II, cathepsin D expression, and vacuole formation are increased in the ipsilateral basal ganglia after ICH. Intracerebral infusion of iron also resulted in enhanced conversion of LC3-I to LC3-II and increased cathepsin D levels. Deferoxamine (an iron chelator) treatment significantly reduced the conversion of LC3-I to LC3-II and cathepsin D levels after ICH. Our results demonstrated that autophagy occurs after ICH, and iron has a key role in ICH-induced autophagy. This also suggests that iron-induced autophagy may play a role in brain injury in other diseases associated with iron overload.     

The role of autophagy in quality control inside neural cells]

Autophagy is an intracellular, bulk degradation process, through which a portion of cytoplasm is delivered to lysosomes to be degraded. In many organisms, the primary role of autophagy is adaptation to starvation. However, we have found that autophagy is also important for intracellular quality control, particularly in quiescent cells such as neurons. Atg5 -/- mice die shortly after birth due, at least in part, to nutrient deficiency. These mice also exhibit an intracellular accumulation of protein aggregates in neurons and hepatocytes. Neural cell-specific Atg5-deficient mice, Atg5(flox/flox); Nestin-Cre mice, show progressive deficits in motor function and degeneration of some neural cells. In autophagy-deficient cells, diffuse accumulation of abnormal proteins occurs, followed by generation of aggregates and inclusions. This study emphasizes that basal autophagy is important even in individuals who do not express neurodegenerative disease-associated mutant proteins. Further, the primary targets of autophagy are diffused cytosolic proteins, not protein aggregates themselves. These data suggest that basal autophagy has a critical role in intracellular protein quality control under normal conditions, which is independent of the role of induced autophagy as an adaptation to starvation.     

Exogenous Netrin-1 Inhibits Autophagy of Ischemic Brain Tissues and Hypoxic Neurons via PI3K/mTOR Pathway in Ischemic Stroke

Background and Objective: Ischemic stroke is a serious disease that endangers human health. How to reduce the damage of neurons in ischemic regions is an urgent problem to be explored. Autophagy is an important pathophysiological process in cerebral ischemia and Netrin-1 is an effective neuroprotective protein. This study aims to investigate the effect of Netrin-1 on autophagy of ischemic brain tissues and hypoxic neurons. Methods: We constructed rat persistent middle cerebral artery occlusion model in vivo and constructed the Oxygen Glucose-Deprivation model in vitro. Rats and cells were treated with or without Netrin-1. Western blot analysis was performed to detect autophagy related proteins LC3B, P62 and pathway related proteins PI3K, p-PI3K, mTOR, p-mTOR. CCK-8 assay was performed to detect the viability of hypoxic neurons. We also performed western-blot analysis and qRT-PCR test to detect levels of Netrin-1 protein and mRNA. Results: Autophagy enhanced both in ischemic brain tissues and hypoxic neurons. Netrin-1 inhibited autophagy through PI3K/mTOR pathway both in vivo and in vitro. At the same time, we found that exogenous Netrin-1 can promote the secretion of Netrin-1 protein by neurons themselves, which indicated that Netrin-1 can further amplify the neuroprotective effect through the positive feedback mechanism. Conclusions: Exogenous Netrin-1 alleviates damage of ischemic brain tissues and enhances viability of hypoxic neurons by inhibiting autophagy via PI3K/mTOR pathway. This effect can be amplified by positive feedback mechanism.     

Activation of G protein-coupled receptor 30 protects neurons by regulating autophagy in astrocytes

Ischemic stroke leads to neuronal damage induced by excitotoxicity, inflammation, and oxidative stress. Astrocytes play diverse roles in stroke and ischemia-induced inflammation, and autophagy is critical for maintaining astrocytic functions. Our previous studies showed that the activation of G protein-coupled receptor 30 (GPR30), an estrogen membrane receptor, protected neurons from excitotoxicity. However, the role of astrocytic GPR30 in maintaining autophagy and neuroprotection remained unclear. In this study, we found that the neuroprotection induced by G1 (GPR30 agonist) in wild-type mice after a middle cerebral artery occlusion was completely blocked in GPR30 conventional knockout (KO) mice but partially attenuated in astrocytic or neuronal GPR30 KO mice. In cultured primary astrocytes, glutamate exposure induced astrocyte proliferation and decreased astrocyte autophagy by activating mammalian target of rapamycin (mTOR) and c-Jun N-terminal kinase (JNK) and inhibiting p38 mitogen-activated protein kinase (MAPK) pathway. G1 treatment restored autophagy to its basal level by regulating the p38 pathway but not the mTOR and JNK signaling pathways. Our findings revealed a key role of GPR30 in neuroprotection via the regulation of astrocyte autophagy and support astrocytic GPR30 as a potential drug target against ischemic brain damage.     

铁死亡在神经系统肿瘤中的作用及其机制研究进展

铁死亡(ferroptosis)是近年来新提出的细胞死亡方式,其不同于传统的细胞死亡方式,区别于细胞凋亡、细胞坏死及自噬[1].其分子层面的特性有脂质活性氧(ROS)的铁依赖性积累、线粒体形态改变和膜通透性损伤[2I.在神经系统方面,研究发现其在帕金森病(PD)、阿尔兹海默病(AD)等神经变性疾病中起到了重要作用[3]...     

Endoplasmic reticulum stress in brain ischemia

Endoplasmic reticulum (ER) stress is an intricate mechanism that mediates numerous responses during brain ischemia, thus being essential to determine the fate of neurons. In recent years, studies of the mechanisms of brain ischemic injury have centered on ER stress, glutamate excitotoxicity, dysfunction of mitochondria, inflammatory reactions, calcium overload and death receptor pathways. The role of ER stress is highly important. In addition to resulting in neuronal cell death through calcium toxicity and apoptotic pathways, ER stress also triggers a series of adaptive responses including unfolded protein response (UPR), autophagy, the expression of pro-survival proteins and the enhancement of ER self-repair ability, leading to less ischemic brain damage. This paper provides an overview of recent advances in understanding of the relations between ER stress and brain ischemia.     

A Double‐Edged Sword with Therapeutic Potential: An Updated Role of Autophagy in Ischemic Cerebral Injury

Cerebral ischemia is a severe outcome that could cause cognitive and motor dysfunction, neurodegenerative diseases and even acute death. Although the existence of autophagy in cerebral ischemia is undisputable, the consensus has not yet been reached regarding the exact functions and influence of autophagy in cerebral ischemia. Whether the activation of autophagy is beneficial or harmful in cerebral ischemia injury largely depends on the balance between the burden of intracellular substrate targeted for autophagy and the capacity of the cellular autophagic machinery. Furthermore, the mechanisms underlying the autophagy in cerebral ischemia are far from clear yet. This brief review focuses on not only the current understanding of biological effects of autophagy, but also the therapeutic potentials of autophagy in ischemic stroke. There are disputes over the exact role of autophagy in cerebral ischemia. Application of chemical autophagy inhibitor (e.g., 3‐methyladenine) or inducer (e.g., rapamycin) in vitro and in vivo was reported to protect or harm neuronal cell. Knockdown of autophagic protein, such as Beclin 1, was also reported to modulate the cerebral ischemia‐induced injury. Moreover, autophagy inhibitor abolished the neuroprotection of ischemic preconditioning, implying a neuroprotective effect of autophagy. To clarify these issues on autophagy in cerebral ischemia, future investigations are warranted.