急性缺血性卒中（acute ischemic stroke，AIS）具有高致残率和高死亡率，蛋白质糖基化作为翻译后修饰，在AIS病理进展中发挥着重要的调控作用。本文回顾近五年AIS相关研究，系统综述了蛋白质糖基化修饰（以O-糖基化、N-糖基化为主）在AIS中的核心作用机制，包括通过调控N-甲基-D-天冬氨酸受体等关键蛋白参与神经元兴奋性毒性调控，通过调节线粒体功能与内质网应激发挥神经保护作用，以及通过影响小胶质细胞极化和炎症因子分泌参与神经炎症调节。在临床意义方面，糖蛋白及其糖基化谱有望成为AIS早期诊断、风险分层和预后评估的潜在生物标志物，靶向糖基化调控酶的药物干预在动物模型中亦显示出良好的神经保护效果。蛋白质糖基化修饰作为AIS防治的新靶点具有重要前景，但相关机制仍需更多临床研究加以验证。 Acute ischemic stroke (AIS) is associated with high disability and mortality rates. Protein glycosylation, as a post-translational modification, plays an important regulatory role in the pathological progression of AIS. This article provides a comprehensive review of the research on AIS conducted over the past five years. It systematically summarizes the core mechanisms of protein glycosylation modification (mainly O-glycosylation and N-glycosylation) in AIS. These mechanisms include the regulation of neuronal excitotoxicity via modulation of key proteins such as N-methyl-D-aspartate receptors, the exertion of neuroprotective effects through regulation of mitochondrial function and endoplasmic reticulum stress, and the involvement in neuroinflammation by affecting microglial polarization and inflammatory factor secretion. In terms of clinical significance, glycoproteins and their glycosylation profiles hold promise as potential biomarkers for early diagnosis, risk stratification, and prognostic assessment of AIS. Drug interventions targeting glycosylation regulatory enzymes have also shown favorable neuroprotective effects in animal models. Protein glycosylation modification has important prospects as a new therapeutic target for AIS, although further clinical studies are still required to validate the underlying mechanisms.
目的 分析动脉瘤性蛛网膜下腔出血（aneurysmal subarachnoid hemorrhage，aSAH）患者院内消化道出血的影响因素，并构建列线图预测模型。 方法 回顾性连续纳入2021年1月—2023年1月收治于首都医科大学附属北京天坛医院重症监护室的aSAH患者。收集患者的人口学资料及既往病史、入重症监护室时评估资料、并发症及治疗相关资料。根据是否发生院内消化道出血，将患者分为消化道出血组和无消化道出血组，比较两组患者的基线资料差异。采用最小绝对收缩和选择算子回归进行变量筛选，采用二元logistic回归确定院内消化道出血的独立危险因素，并构建列线图预测模型。采用Bootstrap法（重复抽样1000次）对模型进行内部验证，采用ROC的AUC、Hosmer-Lemeshow拟合优度检验、校准曲线及决策曲线分析评估模型的预测效能。 结果 共纳入314例aSAH患者，男性123例，女性191例，中位年龄为57（47～65）岁。其中，消化道出血组62例（19.7%），无消化道出血组252例（80.3%）。消化道溃疡病史、Hunt-Hess分级为Ⅲ～Ⅴ级、迟发性脑缺血、肺部感染、低氯血症、腹泻是aSAH患者院内消化道出血的独立危险因素。构建的预测模型为logit（P）=-3.318+1.818×消化道溃疡病史+0.973×Hunt-Hess分级为Ⅲ～Ⅴ级+0.969×迟发性脑缺血+1.362×肺部感染+0.889×低氯血症+1.152×腹泻。该模型的AUC值为0.794（95%CI 0.736～0.853），Hosmer-Lemeshow拟合优度检验结果显示χ2为2.849（P=0.723），最大约登指数为0.481，最佳截断值为0.244，此时模型的敏感度为77.42%，特异度为70.63%。校准曲线显示，模型曲线与校准曲线基本吻合。决策曲线分析显示，当风险阈值在0.04～0.87时，模型的净获益较高。 结论 消化道溃疡病史、Hunt-Hess分级为Ⅲ～Ⅴ级、迟发性脑缺血、肺部感染、低氯血症及腹泻是aSAH患者发生院内消化道出血的独立危险因素。本研究构建的列线图预测模型具有良好的区分度、校准度及临床实用性，可为aSAH患者院内消化道出血的风险筛查及预防提供参考。 Objective To analyze the influencing factors for in-hospital gastrointestinal hemorrhage in patients with aneurysmal subarachnoid hemorrhage (aSAH) and to construct a nomogram prediction model. Methods Consecutive patients with aSAH admitted to the Department of Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, between January 2021 and January 2023 were retrospectively enrolled. Demographic data, previous medical history, assessment data at intensive care unit admission, complications, and treatment-related data were collected. Patients were divided into a gastrointestinal bleeding group and a non-gastrointestinal bleeding group according to the occurrence of in-hospital gastrointestinal bleeding. Baseline data were compared between the two groups. Least absolute shrinkage and selection operator regression was used for variable selection. Binary logistic regression was used to identify independent risk factors for in-hospital gastrointestinal bleeding, and a nomogram prediction model was constructed. The bootstrap method (1000 resamples) was used for internal validation. The predictive performance of the model was evaluated using the AUC of ROC, the Hosmer-Lemeshow goodness-of-fit test, calibration curve and decision curve analysis. Results A total of 314 patients with aSAH were enrolled, including 123 males and 191 females, with a median age of 57 (47-65) years. Among them, 62 patients (19.7%) were in the gastrointestinal bleeding group, and 252 patients (80.3%) were in the non-gastrointestinal bleeding group. History of peptic ulcer, Hunt-Hess grade Ⅲ-Ⅴ, delayed cerebral ischemia, pulmonary infection, hypochloremia, and diarrhea were identified as independent risk factors for in-hospital gastrointestinal bleeding in patients with aSAH. The prediction model was logit (P)=-3.318+1.818×history of peptic ulcer+0.973×Hunt-Hess grade Ⅲ-Ⅴ+0.969×delayed cerebral ischemia+1.362×pulmonary infection+ 0.889×hypochloremia+1.152×diarrhea. The AUC of the model was 0.794 (95%CI 0.736-0.853). The Hosmer-Lemeshow goodness-of-fit test yielded a χ2 of 2.849 (P=0.723). The maximum Youden index was 0.481, with an optimal cutoff value of 0.244, at which the sensitivity was 77.42% and the specificity was 70.63%. The calibration curve showed that the model curve was in good agreement with the ideal calibration curve. Decision curve analysis indicated that the model provided a high net benefit when the risk threshold ranged from 0.04 to 0.87. Conclusions History of peptic ulcer, Hunt-Hess grade Ⅲ-Ⅴ, delayed cerebral ischemia, pulmonary infection, hypochloremia, and diarrhea are independent risk factors for in-hospital gastrointestinal bleeding in patients with aSAH. The nomogram prediction model constructed in this study demonstrates good discrimination, calibration, and clinical utility, and may serve as a reference for risk screening and prevention of in-hospital gastrointestinal bleeding in patients with aSAH.
颈内动脉夹层（internal carotid artery dissection，ICAD）是中青年缺血性卒中的重要病因。本文报道1例ICAD致重度狭窄后早期快速自发完全再通的少见病例。患者男性，57岁，因“头痛2天”入院。长途驾驶后出现双侧太阳穴胀痛，无明显神经系统局灶体征，既往偏头痛史30年。头颅MRI示散在腔隙性脑梗死灶。颈动脉彩色多普勒超声联合经颅彩色多普勒超声示右侧颈内动脉低速单峰频谱、眼动脉血流反向，提示远段近全闭塞及侧支开放。CTA示右侧颈内动脉C1段重度狭窄。入院第14天DSA显示右侧颈内动脉C2、C3段双腔征，确诊为ICAD。予阿司匹林、氯吡格雷双联抗血小板及阿托伐他汀治疗。入院第15天复查，血流频谱完全恢复正常，头痛完全缓解。出院3个月后随访，患者已恢复正常工作，无不适。对于ICAD致重度狭窄但侧支循环良好的患者，在规范抗栓治疗下可采取保守策略。多模态影像的合理组合与阶梯式应用是避免过度介入、实现精准诊疗的关键。 Internal carotid artery dissection (ICAD) is an important cause of ischemic stroke in young and middle-aged adults. This article describes a rare case of early, rapid, and complete spontaneous recanalization following severe stenosis caused by ICAD. A 57-year-old male was admitted with a 2-day history of headache. He developed bilateral temple distension after prolonged driving, without focal neurological signs, and had a 30-year history of migraine. Brain MRI revealed scattered lacunar infarcts. Carotid color Doppler ultrasonography combined with transcranial color Doppler ultrasonography showed a low-velocity single-peak spectrum in the right internal carotid artery (ICA) and reversed ophthalmic artery flow, indicating distal near-occlusion with collateral opening. CTA demonstrated severe stenosis of the right ICA C1 segment. On day 14 of admission, DSA revealed a double-lumen sign in the right ICA C2-C3 segments, confirming the diagnosis of ICAD. He was treated with dual antiplatelet therapy (aspirin plus clopidogrel) and atorvastatin. On day 15 of admission, repeat carotid ultrasound showed complete normalization of flow spectra and complete resolution of headache. At 3-month follow-up, the patient had returned to work and remained asymptomatic. For patients with severe stenosis due to ICAD but with adequate collateral circulation, a conservative strategy under standard antithrombotic therapy is feasible. The judicious combination and stepwise application of multimodal imaging are key to avoiding over-intervention and achieving precision management.
目的 探讨脑血流自动调节（cerebral autoregulation，CA）功能与不同亚型的急性缺血性卒中静脉溶栓患者90 d预后的关系。 方法 本研究为前瞻性队列研究，纳入2016年9月—2022年3月于吉林大学第一医院神经内科卒中中心接受静脉溶栓治疗的急性缺血性卒中患者，并依据TOAST分型标准分为大动脉粥样硬化型、小动脉闭塞型和不明原因型。分别于发病3 d内及发病后7～10 d评估CA功能，通过传递函数分析计算相位差、增益、相干函数等CA参数。发病后（90±7）d采用mRS评估功能预后，mRS评分0～2分定义为良好预后，评分3～6分定义为不良预后。通过多因素logistic回归分析CA功能与患者90 d预后的相关性。 结果 本研究最终共纳入202例患者，其中大动脉粥样硬化型66例（32.7%），小动脉闭塞型114例（56.4%），不明原因型22例（10.9%）。大动脉粥样硬化型患者中，良好预后组发病3 d内患侧（P=0.004）及健侧相位差（P<0.001）均高于不良预后组；多因素logistic回归分析显示，发病3 d内患侧相位差与90 d不良预后独立相关（校正OR 0.918，95%CI 0.844～0.999，校正P=0.046）。小动脉闭塞型患者中，良好预后组发病3 d内及发病后7～10 d双侧相位差均高于不良预后组（均P<0.05）；校正相关混杂因素后，发病3 d内患侧相位差（校正OR 0.967，95%CI 0.941～0.993，校正P=0.015）和健侧相位差（校正OR 0.966，95%CI 0.940～0.992，校正P=0.011）均与90 d不良预后独立相关。不明原因型患者中，CA参数与90 d预后未见显著相关性。 结论 发病3 d内相位差与大动脉粥样硬化型及小动脉闭塞型急性缺血性卒中静脉溶栓患者90 d功能预后显著相关。 Objective To investigate the association between cerebral autoregulation (CA) function and 90-day outcomes in patients with different subtypes of acute ischemic stroke (AIS) receiving intravenous thrombolysis. Methods This prospective cohort study included patients with AIS who received intravenous thrombolysis at the Stroke Center, Department of Neurology, the First Hospital of Jilin University between September 2016 and March 2022. Patients were classified according to TOAST criteria into large-artery atherosclerosis, small-artery occlusion, and undetermined etiology subtypes. CA function was assessed within 3 days and at 7-10 days after onset. CA parameters, including phase difference, gain, and coherence function, were calculated using transfer function analysis. Functional outcome was assessed using the mRS at (90±7) days after onset, with an mRS score of 0-2 defined as a favorable outcome, and a score of 3-6 defined as an unfavorable outcome. Multivariable logistic regression analysis was used to evaluate the association between CA function and 90-day outcomes. Results A total of 202 patients were included, of whom 66 had large-artery atherosclerosis (32.7%), 114 had small-artery occlusion (56.4%), and 22 had undetermined etiology (10.9%). Among patients with large-artery atherosclerosis, phase differences on both the affected (P=0.004) and unaffected sides (P<0.001) within 3 days after onset were higher in the favorable outcome group than in the unfavorable outcome group. Multivariable logistic regression analysis showed that phase difference on the affected side within 3 days was independently associated with a 90-day unfavorable outcome (adjusted OR 0.918, 95%CI 0.844-0.999, adjusted P=0.046). Among patients with small-artery occlusion, bilateral phase differences within 3 days and at 7-10 days after onset were higher in the favorable outcome group than in the unfavorable outcome group (all P<0.05). After adjusting for relevant confounders, phase differences on the affected side (adjusted OR 0.967, 95%CI 0.941-0.993, adjusted P=0.015) and unaffected side (adjusted OR 0.966, 95%CI 0.940-0.992, adjusted P=0.011) within 3 days remained independently associated with a 90-day unfavorable outcome. In patients with undetermined etiology, no significant association was observed between CA parameters and a 90-day outcome. Conclusions Phase difference within 3 days after stroke onset was significantly associated with a 90-day functional outcome in AIS patients with large-artery atherosclerosis and small-artery occlusion receiving intravenous thrombolysis.
目的 探讨对比增强经食管超声心动图（contrast-enhanced transesophageal echocardiography，cTEE）中发现的不同来源的右向左分流对缺血性卒中的影响。 方法 回顾性纳入2021年12月—2025年6月于深圳市第二人民医院神经内科及心血管内科住院，且经cTEE证实存在右向左分流的患者。根据右向左分流来源将患者分为单纯心内分流组、混合分流组（心内合并肺内分流）和单纯肺内分流组。依据cTEE单帧图像左心房最大微泡计数进行半定量分级：少量（Ⅰ级）、中量（Ⅱ级）及大量（Ⅲ级）。比较三组患者的人口学特征、分流严重程度及缺血性卒中发生情况。以是否发生缺血性卒中为因变量，构建多因素logistic回归模型探讨不同因素与卒中发生的关联。 结果 本研究共纳入286例患者，其中单纯心内分流组40例，混合分流组127例，单纯肺内分流组119例。单纯肺内分流组以少量分流为主（71.4%），其比例显著高于单纯心内分流组（22.5%，P校正＜0.001）和混合分流组（13.4%，P校正＜0.001）；而混合分流组的大量分流占比达51.2%。多因素logistic回归分析显示，以单纯肺内分流为参照，混合分流（OR 2.515，95%CI 1.217～5.197）与单纯心内分流（OR 2.727，95%CI 1.107～6.716）均与较高的卒中发生风险独立正相关；年龄增加（OR 1.037，95%CI 1.013～1.062）及合并糖尿病（OR 2.350，95%CI 1.138～4.854）与缺血性卒中独立正相关；而女性（OR 0.481，95%CI 0.257～0.901）与较低的卒中发生风险相关。 结论 单纯肺内分流人群的缺血性卒中发生风险较低，临床对于此类分流勿过度检查与干预。防治重心应回归至对高龄、性别、糖尿病及心内分流等传统脑血管危险因素的管控。 Objective To investigate the effects of shunts with different origins detected by contrast-enhanced transesophageal echocardiography (cTEE) on ischemic stroke. Methods This study retrospectively enrolled patients hospitalized in the Department of Neurology and the Department of Cardiovascular Medicine at Shenzhen Second People’s Hospital from December 2021 to June 2025, who were confirmed to have a right to left shunt by cTEE. Based on the origin of right to left shunt, patients were divided into three groups: isolated intracardiac shunt group, mixed shunt group (combined intracardiac and intrapulmonary shunt), and isolated intrapulmonary shunt group. The severity of RLS was semi‑quantitatively graded according to the maximum microbubble count in the left atrium on a single cTEE frame, as follows: mild (grade Ⅰ), moderate (grade Ⅱ), and severe (grade Ⅲ). Demographic characteristics, shunt severity, and the incidence of ischemic stroke were compared among the three groups. Furthermore, a multivariate logistic regression model was constructed to explore the association of various factors with the occurrence of ischemic stroke, with its occurrence as the dependent variable. Results A total of 286 patients were enrolled in this study, including 40 in the isolated intracardiac shunt group, 127 in the mixed shunt group, and 119 in the isolated intrapulmonary shunt group. The isolated intrapulmonary shunt group was predominantly characterized by mild shunting (71.4%), with a significantly higher proportion than that in the isolated intracardiac shunt group (22.5%, adjusted P＜0.001) and the mixed shunt group (13.4%, adjusted P＜0.001). In contrast, the mixed shunt group had a high proportion of severe shunting, accounting for 51.2%. Multivariate logistic regression analysis revealed that, using the isolated intrapulmonary shunt as the reference, mixed shunt (OR 2.515, 95%CI 1.217-5.197) and isolated intracardiac shunt (OR 2.727, 95%CI 1.107-6.716) were independently and positively associated with the occurrence of stroke. Increased age (OR 1.037, 95%CI 1.013-1.062) and comorbid diabetes mellitus (OR 2.350, 95%CI 1.138-4.854) were also independently associated with a higher risk of ischemic stroke, whereas female sex (OR 0.481, 95%CI 0.257-0.901) was associated with a lower risk of stroke. Conclusions The risk of ischemic stroke in patients with isolated intrapulmonary shunt is relatively low; therefore, excessive examination and intervention for this type of shunt should be avoided in clinical practice. The focus of prevention and treatment should revert to the management of conventional cerebrovascular risk factors, including advanced age, sex, diabetes mellitus, and intracardiac shunt.
目的 探讨以小脑为靶点的重复经颅磁刺激（repetitive transcranial magnetic stimulation，rTMS）技术在卒中后失语（post-stroke aphasia，PSA）患者语言功能、非语言认知功能及日常生活能力康复中的作用，并与Broca区在右侧大脑半球的镜像区靶点进行对比，为临床优化PSA的康复治疗方案提供理论依据。 方法 本研究为随机对照临床试验，连续纳入2023年10月—2024年12月在首都医科大学附属北京天坛医院康复医学科住院治疗的左侧大脑半球（优势半球）PSA患者。将其按照统计学软件产生的随机序列分为3组：以Broca区在右侧大脑半球的镜像区为靶点组（即大脑靶点组）、以病灶对侧小脑为靶点组（即小脑靶点组）和对照组。大脑靶点组和小脑靶点组均接受语言康复训练［给予相应部位的rTMS治疗（频率为1 Hz，强度为健侧大脑半球静息运动阈值的110%，持续时间为18 s，脉冲数为18个，每18个脉冲为1串，串间隔为2 s，重复次数为60次，脉冲总数为1080个）后再进行言语-语言治疗（speech-language therapy，SLT）］，每日上午、下午各进行1次，其中rTMS治疗20 min，SLT 30 min，总计50 min，每周治疗5 d，为期2周。对照组仅每日上午、下午各进行1次SLT，每次30 min，每周进行5 d，为期2周。采用西部失语症成套测验（western aphasia battery，WAB）比较组内及组间治疗前后语言功能的差异，采用洛文斯顿作业疗法认知评定成套测验（Loewenstein occupational therapy cognitive assessment，LOTCA）比较非语言认知功能的差异，采用日常生活能力量表（activity of daily living scale，ADL）比较日常生活能力的差异。 结果 本研究最终纳入77例PSA患者，男性55例，其中大脑靶点组25例，小脑靶点组26例，对照组26例。治疗后，小脑靶点组的语言功能较治疗前有所改善（P＜0.05）；与对照组相比，小脑靶点组的改善更明显（P＜0.05）；与大脑靶点组相比，小脑靶点组各项得分改善均无统计学意义（P＞0.05）。治疗后，小脑靶点组的非语言认知功能较治疗前有所改善（P＜0.05）；与对照组相比，小脑靶点组的改善更明显（P＜0.05）；与大脑靶点组相比，小脑靶点组的改善更明显（P＜0.05）。治疗后，小脑靶点组的日常生活能力较治疗前有所改善（P＜0.05）；与对照组相比，小脑靶点组的改善更明显（P＜0.05）；与大脑靶点组相比，小脑靶点组的改善更明显（P＜0.05）。 结论 Broca区在右侧大脑半球的镜像区与病灶对侧小脑均为短期低频rTMS改善PSA患者语言功能的有效刺激靶点，二者疗效相近，均可用于PSA的语言康复治疗，联合SLT的疗效均优于单纯SLT。同样地，病灶对侧小脑也是短期低频rTMS改善PSA患者非语言认知功能和日常生活能力的有效刺激靶点，且疗效优于Broca区在右侧大脑半球的镜像区。 Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) targeting the cerebellum on the rehabilitation of language function, non-verbal cognitive function, and activities of daily living in patients with post-stroke aphasia (PSA), and compare its efficacy with rTMS targeting Broca’s mirror area in the right cerebral hemisphere, so as to provide a theoretical basis for optimizing clinical rehabilitation regimens for patients with PSA. Methods This study adopted a randomized controlled clinical trial design. Patients with PSA caused by lesions in the left cerebral hemisphere (dominant hemisphere) who received inpatient rehabilitation at the Department of Rehabilitation Medicine, Beijing Tiantan Hospital, Capital Medical University between October 2023 and December 2024 were consecutively enrolled. They were randomly divided into three groups according to the random sequence generated by statistical software: the group receiving rTMS targeting the right‑hemispheric homologue of Broca’s area (referred to as the cerebral target group), the group receiving rTMS targeting the contralesional cerebellum (referred to as the cerebellar target group), and the control group. Both the cerebral target group and the cerebellar target group received speech and language rehabilitation training: rTMS was delivered to the corresponding target sites first, followed by speech-language therapy (SLT). The rTMS parameters were set as follows: frequency 1 Hz, intensity 110% of the resting motor threshold of the unaffected cerebral hemisphere, duration 18 s, 18 pulses per train, inter-train interval 2 s, 60 repetitions, with a total of 1080 pulses. Treatments were conducted twice daily (morning and afternoon); each session included a 20-minute rTMS intervention followed by 30-minute SLT, totaling 50 min per training session, 5 days per week for a 2-week treatment course. The control group only received SLT twice daily (30 min each session), 5 days per week over 2 weeks. The differences in language function within and between groups before and after treatment were assessed using the western aphasia battery (WAB); the differences in non-verbal cognitive function were assessed using the Loewenstein occupational therapy cognitive assessment (LOTCA); and the differences in activities of daily living were assessed using the activity of daily living scale (ADL). Results A total of 77 patients with PSA were finally enrolled in this study, including 55 males: 25 patients in the cerebral target group, 26 patients in the cerebellar target group, and 26 patients in the control group. After treatment, the language function in the cerebellar target group was significantly improved relative to baseline (P<0.05). Improvements were significantly greater in the cerebellar target group than in the control group (P<0.05), while no inter-group difference in language function improvement was detected between the cerebellar target group and the cerebral target group (P>0.05). After treatment, non-verbal cognitive function in the cerebellar target group was significantly improved from baseline (P<0.05). Compared with the control group and the cerebral target group, the cerebellar target group showed significantly better improvements (P<0.05). After treatment, the activities of daily living in the cerebellar target group were significantly improved compared with those at baseline (P<0.05). Compared with both the control group and the cerebral target group, the cerebellar target group demonstrated significantly better improvements (P<0.05). Conclusions Both the right‑hemispheric homologue of Broca’s area and the contralesional cerebellum are effective targets of short‑term low‑frequency rTMS for improving language function in patients with PSA. They exert equivalent therapeutic effects for improving language function and can both be used for language rehabilitation in patients with PSA; when combined with SLT, both targets produce superior efficacy compared with SLT alone. Similarly, the contralesional cerebellum is also an effective target of short‑term low‑frequency rTMS for improving non‑linguistic cognitive functions and activities of daily living in PSA patients, with effects superior to those of the right‑hemispheric homologue of Broca’s area.
目的 探讨中青年脑出血（intracerebral hemorrhage，ICH）患者动态脑血流自动调节（cerebral autoregulation，CA）功能与预后的相关性。 方法 本研究采用前瞻性队列设计，纳入2024年11月—2025年10月于吉林大学第一医院卒中中心就诊的ICH患者，分别于发病3 d内与发病后7～10 d完成CA功能检测。应用传递函数分析计算CA参数：相位差、增益、相干函数。以发病90 d mRS评分作为预后评估标准，将患者分为良好预后（mRS评分0～1分）组与不良预后（mRS评分2～6分）组。采用多因素logistic回归模型分析CA与预后的相关性，并绘制ROC曲线评估CA参数对ICH患者良好预后的预测效能。 结果 本研究最终共纳入73例患者，年龄（49.8±7.2）岁，男性51例。其中，良好预后组33例，不良预后组40例。良好预后组发病3 d内患侧相位差高于不良预后组（P<0.001）。多因素logistic回归分析显示，发病3 d内患侧相位差与90 d良好预后独立相关（OR 0.947，95%CI 0.898～0.999，P=0.046）。ROC曲线分析显示，发病3 d内患侧相位差预测90 d良好预后的AUC为0.771，具有较好的区分能力。发病3 d内健侧相位差、双侧增益及发病后7～10 d的所有CA参数在两组间差异均无统计学意义。 结论 发病3 d内患侧相位差与中青年ICH患者90 d功能预后相关，且具有一定预测价值。 Objective To explore the association between dynamic cerebral autoregulation (CA) and outcomes in young and middle-aged patients with intracerebral hemorrhage (ICH). Methods This prospective study enrolled patients with ICH at the Stroke Center of the First Hospital of Jilin University from November 2024 to October 2025. CA function was tested within 3 days and at 7-10 days after ICH onset. Phase difference, gain, and coherence function were obtained through transfer function analysis. The mRS score at 90 days was used as the prognostic assessment criterion, and patients were divided into a favorable outcome (mRS score 0-1) group and an unfavorable outcome (mRS score 2-6) group. A multivariate logistic regression model was used to analyze the association between CA and clinical outcome, and the ROC curve was plotted to evaluate the predictive efficacy of CA parameters for favorable outcome. Results A total of 73 patients were included in this study, with a mean age of (49.8±7.2) years, 51 of whom were male. Of the 73 patients, 33 were in the favorable outcome group and 40 in the unfavorable outcome group. The phase difference on the affected side within 3 days after onset was higher in the favorable outcome group than in the unfavorable outcome group (P<0.001). Multivariate logistic regression analysis showed that the phase difference on the affected side within 3 days after onset was independently associated with a favorable outcome at 90 days (OR 0.947, 95%CI 0.898-0.999, P=0.046). ROC analysis showed that the phase difference on the affected side within 3 days after onset had an AUC of 0.771 for predicting a favorable outcome at 90 days, indicating good discriminatory ability. No statistically significant differences were found between the two groups in the phase difference on the contralateral side within 3 days, bilateral gain within 3 days, or any CA parameters at 7-10 days after onset. Conclusions The phase difference on the affected side within 3 days after onset is significantly associated with the 90-day functional outcomes of young and middle-aged ICH patients and may have predictive value.
作为脑出血的特殊亚型，脑叶出血复发率高，更容易出现局灶性神经功能障碍，制订个性化治疗方案对改善患者预后至关重要。在内科管理层面，脑叶出血应根据其特殊病因进行差异性治疗，如脑淀粉样血管病患者的血压控制应更严格，尽量避免长期抗凝，同时应开展持续神经功能监测和预防性抗癫痫治疗。在外科治疗层面，临床上虽多以血肿量＞30 mL作为脑叶出血的手术干预指征，但其手术时机及手术方式选择目前仍存在一定争议。本文系统梳理脑叶出血的病因分型、内外科分层治疗及预后影响因素的相关研究进展，以期为临床医师早期识别脑叶出血分型、制订精准治疗方案提供参考。 As a unique subtype of intracerebral hemorrhage, lobar intracerebral hemorrhage exhibits a high recurrence rate and a higher tendency to cause focal neurological deficits. Individualized treatment protocols are essential for improving patient prognosis. In terms of medical management, treatments for lobar intracerebral hemorrhage vary according to its distinct etiologies. For instance, stricter blood-pressure control is required in patients with cerebral amyloid angiopathy, and long-term anticoagulation ought to be avoided where possible. Continuous neurological monitoring and prophylactic antiepileptic therapy should also be administered. Regarding surgical intervention, a hematoma volume exceeding 30 mL is widely adopted as a surgical indication in clinical practice. Nevertheless, the optimal surgical timing and operative approaches remain controversial. This article systematically reviews research advances in etiological classification, stratified medical and surgical management and prognostic factors of lobar intracerebral hemorrhage. It aims to provide references for clinicians to accomplish early-stage classification and formulate precise therapeutic regimens.
头颈血管超声是卒中诊疗中应用广泛的无创影像工具。随着TCD、超声造影及脑血流自动调节检测等技术的发展，其角色已从单一的血管形态筛查扩展为覆盖病因分型、风险分层、治疗监测与预后评估的多维度诊疗体系。本文系统回顾了头颈血管超声的发展脉络，重点阐述了其在脑血流自动调节功能评估、隐源性卒中病因识别、颈动脉斑块易损性分层、再灌注治疗实时监测及蛛网膜下腔出血后血管痉挛动态管理中的应用进展。此外，本文还分析了颅骨声窗限制、操作者依赖性及功能学技术标准化不足等当前局限，并从多模态影像融合、人工智能辅助诊断及诊疗一体化等方向展望了头颈血管超声未来发展路径。 Cervicocephalic vascular ultrasound is a widely used non-invasive imaging modality in stroke care. With advances in TCD, contrast-enhanced ultrasound, and cerebral autoregulation assessment, its role has evolved from a single-purpose vessel morphology screening tool into a multidimensional diagnostic and therapeutic system encompassing etiological classification, risk stratification, real-time treatment monitoring, and prognostic evaluation. This review systematically summarizes the technical evolution of core cervicocephalic ultrasound modalities and highlights their clinical applications in cerebral autoregulation assessment, cryptogenic stroke workup, carotid plaque vulnerability stratification, real-time monitoring during reperfusion therapy, and dynamic management of vasospasm following subarachnoid hemorrhage. Current limitations—including inadequate temporal acoustic windows, operator dependency, and lack of standardization in functional techniques—are discussed, and future directions in multimodal image fusion, AI-assisted diagnosis, and integrated diagnosis-therapy platforms are outlined.
目的 分析2013—2021年山东省滕州市急性缺血性卒中（acute ischemic stroke，AIS）发病率的时间变化趋势和人群分布特征。 方法 本研究数据来源于山东省慢性病监测信息系统，提取2013—2021年AIS病例监测数据，同期户籍人口数据来源于滕州市公安局。基于2020年第7次全国人口普查数据计算AIS年龄和性别标化发病率，比较AIS粗发病率和标化发病率在不同特征人群中的分布差异，采用Cochran-Armitage趋势检验分析AIS总体，以及男性和女性、城区和农村居民粗发病率和标化发病率的时间变化趋势。 结果 2013—2021年，滕州市总体AIS粗发病率和标化发病率分别从170.94/10万和212.37/10万上升至379.21/10万和361.41/10万。总体AIS粗发病率和标化发病率分别在2015年及2018年形成两个高峰，粗发病率分别为314.99/10万和356.68/10万，标化发病率分别为365.12/10万和387.69/10万。2021年总体AIS粗发病率较2015年升高了20.39%，年均增长3.05%（P＜0.001）。除2017年粗发病率在性别间的差异无统计学意义外，其余各年份男性的AIS粗发病率和标化发病率均高于女性（均P＜0.001）。在AIS粗发病率方面，男性4个年龄段（＜35岁、45～54岁、55～64岁和≥65岁）和女性2个年龄段（55～64岁和≥65岁）于2015年形成第一峰，男性1个年龄段（35～44岁）和女性1个年龄段（45～54岁）于2016年形成第一峰；男性2个年龄段（55～64岁和≥65岁）和女性1个年龄段（≥65岁）于2018年形成第二峰，女性1个年龄段（55～64岁）于2017年形成第二峰。城区和农村AIS粗发病率分别在2015年及2018年形成两个高峰，2021年较2015年农村AIS粗发病率升高了24.95%（P＜0.001），城区的变化无统计学意义。 结论 2013—2021年滕州市AIS粗发病率在2015年后上升速度减缓。男性粗发病率高于女性且有年轻化趋势，农村粗发病率升幅高于城区。 Objective To analyze the temporal trends and population distribution characteristics of acute ischemic stroke (AIS) incidence in Tengzhou City, Shandong Province from 2013 to 2021. Methods Data for this study were obtained from the Shandong provincial chronic disease surveillance information system. AIS case records from 2013 to 2021 were extracted from this system, while the corresponding household registration population data for the same period were obtained from the Tengzhou Public Security Bureau. Age- and gender-standardized incidence rates of AIS were calculated based on the seventh national population census of 2020. The differences in the distribution of crude and standardized incidence rates of AIS among populations with different characteristics were compared. The Cochran-Armitage trend test was used to analyze the temporal trends in crude and standardized incidence rates of AIS for the overall population, as well as for males and females, and urban and rural residents separately. Results From 2013 to 2021, the overall crude and standardized incidence rates of AIS in Tengzhou City increased from 170.94/100 000 and 212.37/100 000 to 379.21/100 000 and 361.41/100 000, respectively. The overall crude and standardized incidence rates of AIS showed two peaks in 2015 and 2018, with the crude incidence rates of 314.99/100 000 and 356.68/100 000, and the standardized incidence rates of 365.12/100 000 and 387.69/100 000, respectively. Compared with the year 2015, the overall crude incidence rate of AIS in 2021 increased by 20.39%, with an average annual increase of 3.05% (P<0.001). Except for 2017, when the difference in crude incidence rate between genders was not statistically significant, the crude and standardized incidence rates in males were higher than those in females in all other years (all P<0.001). In terms of crude incidence rate of AIS, the first peak occurred in 2015 among males in four age groups (<35, 45-54, 55-64, and≥65 years) and among females in two age groups (55-64 and≥65 years); the first peak occurred in 2016 among males in one age group (35-44 years) and among females in one age group (45-54 years). The second peak appeared in 2018 among males in two age groups (55-64 and≥65 years) and among females in one age group (≥65 years), and in 2017 among females in one age group (55-64 years). Both urban and rural areas experienced two peaks in crude incidence rate of AIS in 2015 and 2018. From 2015 to 2021, the crude incidence rate of AIS in rural areas increased by 24.95% (P＜0.001), whereas the increasing trend in urban areas was not statistically significant. Conclusions From 2013 to 2021, the increase in crude incidence rate of AIS in Tengzhou City slowed after 2015. The crude incidence rate is higher in males than in females, accompanied by a trend of younger onset, and the increase in rural areas is greater than in urban areas.
急性缺血性卒中是全球人群致残和致死的主要原因之一。尽管血管再通治疗（静脉溶栓、机械取栓）可显著改善部分患者预后，但严格的时间窗限制和无效再通现象促使研究者探索血管再通治疗以外的辅助性脑细胞保护策略。过去数十年，逾千种脑细胞保护药物的临床试验接连呈现阴性结果，这促使研究焦点一定程度上转向了非药物治疗。本文系统梳理头低脚高位、远隔缺血适应、高压氧与常压高浓度氧、物理刺激疗法、针灸及低温治疗等非药物治疗在急性缺血性卒中脑细胞保护中的研究进展，重点阐述各疗法的分子生理机制、临床干预策略及现有证据强度，分析当前该领域面临的挑战并展望未来发展策略，以期为推动急性缺血性卒中非药物治疗的创新与临床转化提供参考。 Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide. Although vascular recanalization therapies, including intravenous thrombolysis and endovascular thrombectomy, can significantly improve the outcomes in eligible patients, the constraints of strict time windows and the phenomenon of futile recanalization have driven the search for adjunctive brain cytoprotection therapies independent of vascular recanalization therapies. Over the past decades, the consecutive negative results from clinical trials involving over a thousand brain cytoprotection drugs have partially shifted the research focus toward non-pharmacological treatments. This paper systematically summarizes the research progress of non-pharmacological treatments in brain cytoprotection for AIS, including Trendelenburg position, remote ischemic preconditioning, hyperbaric oxygen/normobaric hyperoxic oxygen, physical stimulation therapies, acupuncture, and hypothermia. It elaborates on the molecular physiological mechanisms, clinical intervention strategies, and the strength of existing evidence for each therapy, analyzes the current challenges in this field, and outlines future development strategies, with the aim of providing references for promoting the innovation and clinical translation of non-pharmacological treatments for AIS.
目的 探讨卒中严重程度对头低位治疗急性缺血性卒中疗效的影响。 方法 本研究为大动脉粥样硬化型急性缺血性卒中的头低位治疗（head-down position for acute ischemic stroke with large artery atherosclerosis，HOPES 2）试验的事后分析。根据入院NIHSS评分，将入组的急性缺血性卒中患者分为入院NIHSS评分6～10分（中度较轻）亚组和入院NIHSS评分11～16分（中度较重）亚组。各亚组内分别接受头低位治疗与常规体位治疗。采用线性回归分析评估两个亚组内不同治疗方法对患者7 d（ΔNIHSS7 d ）和12 d（ΔNIHSS12 d ）NIHSS评分变化值的影响；采用多因素logistic回归分析探讨两个亚组内不同治疗方法对患者90 d预后［良好预后（mRS评分0～2分）和极佳预后（mRS评分0～1分）］的影响。同时，在回归模型中纳入治疗与入院NIHSS评分分组的交互项，以判断是否存在交互作用。 结果 本研究最终纳入89例急性缺血性卒中患者，男性64例，平均年龄（62.6±11.5）岁。其中入院NIHSS评分6～10分亚组64例（头低位治疗31例、常规体位治疗33例），入院NIHSS评分11～16分亚组25例（头低位治疗11例、常规体位治疗14例）。主要结局方面，两个亚组内接受头低位治疗与常规体位治疗患者在90 d良好预后率方面的差异均无统计学意义。次要结局方面，在入院NIHSS评分6～10分亚组中，接受头低位治疗患者ΔNIHSS7 d （校正β=-2.23，95%CI -4.81～-0.35，P校正=0.004）和ΔNIHSS12 d （校正β=-2.67，95%CI -5.32～-0.02，P校正<0.001）的改善幅度均优于接受常规体位治疗的患者。在入院NIHSS评分11～16分亚组中，接受不同治疗患者在神经功能改善方面的差异均无统计学意义。48 h早期神经功能恶化仅在入院NIHSS评分6～10分亚组内接受常规体位治疗的患者中出现2例（6.1%）。在发病90 d全因死亡方面，入院NIHSS评分6～10分亚组中，接受头低位治疗患者死亡1例，常规体位治疗患者死亡3例；入院NIHSS评分11～16分亚组中，接受常规体位治疗患者死亡2例。交互作用分析显示，治疗方法与入院NIHSS评分的交互作用在主要及次要结局指标中均无统计学意义。 结论 头低位治疗可改善中度较轻急性缺血性卒中患者的早期神经功能缺损，但对90 d良好预后无显著影响。在中度较重急性缺血性卒中患者中未观察到头低位治疗的明确疗效。未来研究可进一步优化头低位治疗方案，并探索其在中度较轻急性缺血性卒中患者中的长期获益。 Objective To explore the effect of stroke severity on the efficacy of head-down position therapy in acute ischemic stroke. Methods This study was a post-hoc analysis of the head-down position for acute ischemic stroke with large artery atherosclerosis (HOPES 2) trial. Enrolled patients with acute ischemic stroke were stratified by admission NIHSS score into two subgroups: 6-10 points (moderately mild) and 11-16 points (moderately severe). Within each subgroup, patients received either head-down position therapy or routine position therapy. Linear regression analysis was performed to assess the effects of different treatments on the changes in NIHSS scores at 7 days (ΔNIHSS7 d) and 12 days (ΔNIHSS12 d) within each subgroup. Multivariable logistic regression analysis was used to investigate the effects of different treatments on the 90 d favorable (mRS score of 0-2) and excellent (mRS score of 0-1) outcomes outcome within each subgroup. Meanwhile, the interaction term between treatment and admission NIHSS score subgroup was included in the regression models to test for interaction. Results A total of 89 patients with acute ischemic stroke were enrolled, including 64 males, with a mean age of (62.6±11.5) years. Among them, 64 patients were in the admission NIHSS score 6-10 subgroup (31 received head-down position therapy, 33 received routine position therapy), and 25 patients were in the admission NIHSS score 11-16 subgroup (11 received head-down position therapy, 14 received routine position therapy). For the primary outcome, there was no significant difference in the proportion of patients with a 90-day favorable outcome between head-down position therapy and routine position therapy in either subgroup. For secondary outcomes, in the admission NIHSS score 6-10 subgroup, patients receiving head-down position therapy showed greater improvement in ΔNIHSS7 d (adjusted β=−2.23, 95%CI −4.81-−0.35, Padjusted=0.004) and ΔNIHSS12 d (adjusted β=−2.67, 95%CI −5.32-−0.02, Padjusted<0.001) than those receiving routine position therapy. In the admission NIHSS score 11-16 subgroup, there was no statistically significant difference in neurological improvement between patients receiving different treatments. Early neurological deterioration at 48 hours occurred in only 2 patients (6.1%) receiving routine position therapy within the admission NIHSS score 6-10 subgroup. For 90-day all-cause mortality, in the admission NIHSS score 6-10 subgroup, there was 1 death with head-down position therapy and 3 with routine position therapy, while in the 11-16 subgroup, there were 2 deaths with routine position therapy. Interaction analysis revealed that the interaction between treatment and admission NIHSS score was not statistically significant for either the primary or secondary outcomes. Conclusions Head-down position therapy can improve early neurological impairment in patients with moderately mild acute ischemic stroke, but has no significant effect on 90-day favorable outcome. No clear benefit of head-down position therapy was observed in patients with moderately severe acute ischemic stroke. Future studies may optimize the head-down position therapy protocol and further explore its long-term benefits in patients with moderately mild acute ischemic stroke.
目的 调查卒中患者对智慧化二级预防管理工具的需求特征、使用障碍原因，并分析支付意愿的影响因素。 方法 连续纳入2025年4—5月于首都医科大学附属北京天坛医院脑血管病门诊就诊的卒中患者。基于技术接受与使用统一理论（unified theory of acceptance and use of technology，UTAUT）模型，设计卒中患者数字素养及其对智慧化二级预防管理工具需求的调查问卷。其中数字素养采用电子健康素养简化量表（short-form ehealth literacy scale，eHEALS-3）评估，分为低（≤6分）、中（7～10分）和高（11～15分）3级。分析患者对智慧化二级预防管理工具不同项目的需求和支付意愿，以及使用障碍等情况，并采用多因素logistic回归分析支付意愿的影响因素。 结果 共纳入256例患者，其中低数字素养者有211例（82.4%）。患者对智慧化二级预防管理工具需求程度最高的前3项为定期监测记录（96.9%）、个性化健康报告（96.9%）及智能血压计（96.5%）。多因素logistic回归分析显示，教育支持需求（OR 2.324，95%CI 1.212～4.457，P=0.011），中/高级智能手机使用熟练程度（OR 2.583，95%CI 1.153～5.784，P=0.021）及中等水平数字素养（OR 2.568，95%CI 1.233～5.350，P=0.012）是支付意愿的独立影响因素。智慧化二级预防管理工具的主要使用障碍为操作复杂（77.3%）和数据安全顾虑（11.3%）。 结论 卒中患者对智慧化二级预防管理工具呈现“高需求强度、低数字素养”特征，教育支持需求、智能手机使用熟练程度和数字素养水平是其支付意愿的独立影响因素。 Objective To characterize the needs for intelligent secondary prevention management tools, usage barriers, and factors associated with willingness to pay among patients with stroke. Methods This cross-sectional study consecutively enrolled patients with stroke who attended the cerebrovascular disease outpatient clinic of Beijing Tiantan Hospital, Capital Medical University, between April and May 2025. A questionnaire was designed based on the unified theory of acceptance and use of technology (UTAUT) model to assess stroke patients’ digital literacy and their needs for intelligent secondary prevention management tools. Digital literacy was assessed using the short-form ehealth literacy scale (eHEALS-3) and categorized as low (≤6 points), moderate (7-10 points), or high (11-15 points). Patients’ needs and willingness to pay for intelligent secondary prevention management tools, and usage barriers were assessed. Multivariable logistic regression was performed to identify factors independently associated with willingness to pay. Results A total of 256 patients were included, 211 (82.4%) and low digital literacy. The top three most highly demanded functions were regular monitoring and recording (96.9%), personalized health reports (96.9%), and smart blood pressure monitors (96.5%). Multivariable logistic regression analysis revealed that a high demand for educational support (OR 2.324, 95%CI 1.212-4.457, P=0.011), moderate-to-high smartphone proficiency (OR 2.583, 95% CI 1.153-5.784, P=0.021), and moderate digital literacy (OR 2.568, 95%CI 1.233-5.350, P=0.012) were independent influencing factors for willingness to pay. The most commonly reported usage barriers were operational complexity (77.3%) and data security concerns (11.3%). Conclusions Patients with stroke demonstrated a pattern of high demand intensity and low digital literacy for intelligent secondary prevention management tools. Educational support needs, smartphone proficiency, and digital literacy level were independent factors associated with willingness to pay.
迷走神经刺激（vagus nerve stimulation，VNS）作为非药物神经调控策略，近年来在卒中治疗领域受到广泛关注。VNS可通过增强神经可塑性、调节炎症反应、促进血管修复、改善脑血流与代谢稳态，以及影响兴奋性毒性、氧化应激、细胞凋亡与自噬等过程，改善卒中后神经功能。临床前研究显示，侵入性VNS和非侵入性VNS均能减轻卒中相关脑损伤并促进运动功能恢复。临床研究进一步表明，VNS在卒中急性期与慢性期均与运动、认知与感觉功能改善相关，其对卒中后吞咽功能障碍、卒中后抑郁等并发症具有潜在获益，且安全性与耐受性良好。未来需围绕刺激参数优化、个体化策略与多模式联合等开展深入研究，以提高VNS疗效的可预测性并拓展其临床应用。 As a non-pharmacological neuromodulation strategy, vagus nerve stimulation (VNS) has attracted extensive attention in the field of stroke therapy in recent years. VNS can ameliorate neurological dysfunction after stroke by enhancing neuroplasticity, regulating inflammatory responses, promoting vascular repair, improving cerebral blood flow and metabolic homeostasis, as well as modulating excitotoxicity, oxidative stress, apoptosis, autophagy, and other biological processes. Preclinical studies have demonstrated that both invasive and non-invasive VNS can alleviate stroke-related brain injury and promote the recovery of motor function. Clinical trials have further indicated that VNS is associated with the improvement of motor, cognitive and sensory functions in both acute and chronic stages of stroke, and has potential benefits for complications such as post-stroke dysphagia and post-stroke depression, with favorable safety and tolerabilityprofiles. Future research should focus on the optimization of stimulation parameters, individualized strategies and multimodal combination to improve the predictability of VNS efficacy and expand its clinical applications.
目的 系统评价电针治疗发病7 d内急性缺血性卒中（acute ischemic stroke，AIS)的疗效及安全性。 方法 检索中国知网、维普网、万方数据、Cochrane Library、PubMed、Embase和Web of Science数据库，检索时间范围为建库至2026年3月，收集电针治疗发病7 d内AIS的随机对照试验（randomized controlled trials，RCT）。由2名研究者独立筛选文献、提取资料，并采用Cochrane偏倚风险评估工具评价纳入文献的方法学质量。采用RevMan 5.3软件进行荟萃分析，评估对照组（常规治疗）与电针组（在对照组治疗基础上进行电针治疗）的疗效及安全性差异。 结果 共纳入23项RCT，总样本量2243例，其中对照组1113例，电针组1130例。荟萃分析结果显示，与对照组相比，电针可显著提高总有效率和Fugl-Meyer运动功能评定量表评分，并有效降低NIHSS评分及血清肿瘤坏死因子-α水平（均P＜0.05）。 结论 本研究结果表明，电针治疗可改善AIS患者的神经功能缺损和运动功能，降低炎症因子水平，且安全性良好。受纳入研究数量和质量限制，上述结论仍需更多高质量、大样本RCT验证。 Objective To systematically evaluate the efficacy and safety of electroacupuncture in the treatment of acute ischemic stroke (AIS) within 7 days of onset. Methods Randomized controlled trials (RCT) on electroacupuncture therapy for AIS within 7 days of onset were retrieved from CNKI, VIP, Wanfang, Cochrane Library, PubMed, Embase, and Web of Science databases from inception to March 2026. Two researchers independently screened the literature, extracted data, and assessed methodological quality using the Cochrane risk of bias tool. Meta-analysis was performed using RevMan 5.3 software to evaluate the efficacy and safety between the control group (conventional treatment) and the electroacupuncture group (electroacupuncture combined with conventional treatment). Results A total of 23 RCTs involving 2243 patients were included, with 1113 patients in the control group (conventional treatment) and 1130 patients in the electroacupuncture group (electroacupuncture combined with conventional treatment). Meta-analysis results showed that the electroacupuncture group showed significantly higher total effective rate and Fugl-Meyer assessment scores, as well as significantly lower NIHSS scores and serum tumor necrosis factor-α levels compared with the control group (all P<0.05). Adverse events were reported in three studies, and no serious adverse events occurred. Conclusions The results of this study indicate that electroacupuncture can improve neurological deficits and motor function, reduce inflammatory factor levels, and has a favorable safety profile in AIS patients. Due to the limitations in the number and quality of included studies, the above conclusions still need to be validated by more high-quality, large-scale RCTs.
目的 探讨远隔缺血适应训练对老年轻型缺血性卒中患者衰弱及焦虑、抑郁的影响。 方法 本研究前瞻性纳入2024年3月—2025年2月在华北理工大学附属医院神经内科治疗的老年轻型缺血性卒中患者。对照组接受常规护理与康复治疗，试验组在常规诊疗基础上进行远隔缺血适应训练。干预后第14天和第90天分别比较两组衰弱筛查量表（the frail scale，FRAIL）评分、肌力、焦虑自评量表（self-rating anxiety scale，SAS）评分、抑郁自评量表（self-rating depression scale，SDS）评分及卒中生活质量量表（stroke-specific quality of life scale，SS-QOL）评分。 结果 共纳入99例老年轻型缺血性卒中患者，对照组50例，试验组49例。干预后第14天和第90天，试验组FRAIL评分均低于对照组（|Z|≥3.174，均P<0.01），肌力均高于对照组（|Z|≥2.733，均P<0.01）；干预后第90天，试验组SAS评分（t=4.147，P<0.001）和SDS评分（t=3.327，P=0.001）均低于对照组，SS-QOL评分高于对照组（|Z|=3.721，P<0.001）。 结论 远隔缺血适应训练有利于改善老年轻型缺血性卒中患者衰弱状况，增强肌力，缓解焦虑及抑郁情绪并提高生活质量。 Objective To investigate the effect of remote ischemic conditioning training on frailty, anxiety and depression in elderly patients with mild ischemic stroke. Methods This prospective study consecutively enrolled elderly patients with mild ischemic stroke who were treated in the Department of Neurology, North China University of Science and Technology Affiliated Hospital from March 2024 to February 2025. The control group received routine nursing care and rehabilitation therapy, while the experimental group received remote ischemic conditioning training in addition to routine treatment. The frail scale (FRAIL) score, muscle strength, self-rating anxiety scale (SAS) score, self-rating depression scale (SDS) score, stroke-specific quality of life scale (SS-QOL) score were compared between the two groups on day 14 and 90 after intervention. Results A total of 99 elderly patients with mild ischemic stroke were included, with 50 in the control group and 49 in the experimental group. On day 14 and 90 after intervention, the FRAIL scale scores in the experimental group were significantly lower than those in the control group (|Z|≥3.174, all P<0.01), and muscle strength was significantly higher (|Z|≥2.733, all P<0.01). On day 90 after intervention, the SAS score (t=4.147, P<0.001) and SDS score (t=3.327, P=0.001) in the experimental group were significantly lower than those in the control group, and the SS-QOL score in the experimental group was significantly higher than that in the control group (|Z|=3.721, P<0.001). Conclusions Remote ischemic conditioning training is beneficial for improving frailty, enhancing muscle strength, alleviating anxiety and depression, and improving quality of life in elderly patients with mild ischemic stroke.
目的 本研究旨在鉴定颅内动脉瘤中差异表达的泛凋亡相关基因，挖掘其参与颅内动脉瘤形成和破裂的相关机制，并构建诊断模型。 方法 从基因表达综合数据库（gene expression omn ibu s，GEO）和GeneCards数据库分别获取了GSE54083、GSE122897、GSE36791、GSE75436、GSE6551、GSE13353共6个数据集及泛凋亡相关基因。使用R 4.3.1对GSE54083数据集进行分析，识别颅内动脉瘤差异表达基因与泛凋亡相关基因的交集，接着在GSE54083、GSE75436中对差异表达的泛凋亡相关基因进一步筛选；利用基因本体与京都基因和基因组数据库富集分析方法，对差异表达基因进行功能富集分析；使用多个基因集多次筛选并通过最小绝对收缩和选择算子（least absolute shrinkage and selection operator，LASSO）回归识别关键基因；通过CIBERSORT算法评估GSE54083中每个样本的免疫浸润情况；使用基因/蛋白质相互作用检索工具（STRING）数据库检索toll样受体4（toll like receptor 4，TLR4）、ATP结合盒转运蛋白B1（ATP-binding cassette transporter B1，ABCB1）和胱天蛋白酶激活募集结构域16（caspase activation and recruitment domain 16，CARD16）3个关键基因以构建蛋白质-蛋白质相互作用网络，探索关键基因间的相互作用。接着使用LASSO回归构建诊断模型，并分别在数据集GSE54083、GSE75436、GSE122897、GSE6551和GSE13353中对诊断模型效能进行内部及外部验证。 结果 本研究共鉴定出119个差异表达的泛凋亡相关基因（上调71个、下调48个），这些基因富集于MAPK、ERK1/ERK2、PKB及I-κB激酶/NF-κB等信号通路，并与黏着斑、细胞骨架及核膜相关。通过2个独立数据集筛选及LASSO回归，获得3个关键基因（TLR4、ABCB1、CARD16）。免疫浸润分析显示颅内动脉瘤患者记忆B细胞、CD8+ T细胞、活化记忆CD4+ T细胞、调节性T细胞及嗜酸性粒细胞的比例升高，而浆细胞、初始CD4+ T细胞、滤泡辅助T细胞、活化自然杀伤细胞、M0/M2巨噬细胞、活化树突状细胞、静息肥大细胞及中性粒细胞的比例降低。蛋白质-蛋白质相互作用网络分析表明，3个关键基因共同参与了包含53个节点和196条边的互作网络，提示其间存在紧密的生物学关联。基于上述3个关键基因构建的LASSO诊断模型在内部验证集（AUC分别为0.949、0.920）及外部验证集中（AUC分别为0.731、0.837）均表现出良好的预测效能。 结论 本研究系统揭示了泛凋亡相关基因在颅内动脉瘤中的关键作用，确立了TLR4、CARD16和ABCB1作为潜在生物标志物的价值。这些发现不仅深化了对颅内动脉瘤病理机制的理解，也为开发基于泛凋亡的颅内动脉瘤精准诊疗策略提供了新的理论依据。未来研究可进一步探索这些基因在颅内动脉瘤发生发展中的具体调控机制及其临床转化潜力。 Objective This study aimed to identify differentially expressed PANoptosis-related genes involved in intracranial aneurysm, explore their mechanisms related to aneurysm formation and rupture, and construct a diagnostic model. Methods Six data sets of GSE54083, GSE122897, GSE36791, GSE75436, GSE6551, GSE13353 and PANoptosis-related genes were obtained from the gene expression omnibus (GEO) and GeneCards databases, respectively. R 4.3.1 was used to analyze the GSE54083 data set to identify the intersection of differentially expressed genes and PANoptosis-related genes in intracranial aneurysms, and then the differentially expressed PANoptosis-related genes were further screened in GSE54083 and GSE75436. Functional enrichment analysis of differentially expressed genes was performed using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis methods. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a diagnostic model and identify key genes, and the diagnostic model performance was verified internally and externally in the data sets GSE54083, GSE75436, GSE122897, GSE6551 and GSE13353, respectively. The immune infiltration of each sample in GSE54083 was evaluated by CIBERSORT algorithm. The search tool for the retrieval of interacting genes/proteins (STRING) database was used to search for three key genes of toll like receptor 4 (TLR4), ATP-binding cassette transporter B1 (ABCB1) and caspase activation and recruitment domain 16 (CARD16) to construct a protein protein interaction network and explore the interaction among key genes. Results A total of 119 differentially expressed PANoptosis related genes (71 up-regulated and 48 down-regulated ) were identified in this study, which were enriched in MAPK, ERK1/ERK2, PKB and I-κB kinase/NF-κB signaling pathways, and were associated with focal adhesion, cytoskeleton and nuclear membrane. Through two independent data sets screening and LASSO regression, three key genes (TLR4, ABCB1, CARD16) were obtained. Immune infiltration analysis showed that the proportion of memory B cells, CD8+ T cells, memory activated CD4+ memory activated T cells, regulatory T cell and eosinophils increased in patients with intracranial aneurysms, while the proportion of plasma cells, naive CD4+ T cells, follicular helper T cell, activated natural killer cells, M0/M2 macrophages, activated dendritic cells, mast cells and neutrophils decreased. Protein-protein interaction network analysis showed that the three key genes were involved in an interaction network containing 53 nodes and 196 edges. The LASSO diagnostic model based on the above three key genes showed good predictive performance in both the internal validation set (AUC 0.949, 0.920 respectively) and the external validation set (AUC 0.713, 0.837 respectively). Conclusions This study systematically revealed the key role of PANoptosis-related genes in intracranial aneurysms, and established the value of TLR4, CARD16 and ABCB1 as potential biomarkers. These findings not only deepen the understanding of the pathological mechanism of intracranial aneurysms, but also provide a new theoretical basis for the development of accurate diagnosis and treatment strategies for intracranial aneurysms based on PANoptosis. Future studies can further explore the specific regulatory mechanisms and clinical transformation potential of these genes in the development of intracranial aneurysms.
目的 探讨衰老是否通过调控小胶质细胞反应加重缺血性卒中，并挖掘其潜在机制与治疗靶点。 方法 基于缺血性卒中模型公共数据集，采用DESeq2筛选与衰老-卒中交互作用相关的差异表达基因；运用加权基因共表达网络分析（weighted gene co-expression network analysis，WGCNA）识别关键共表达模块并进行基因本体论（gene ontology，GO）富集分析；利用单细胞转录组数据解析模块基因的细胞表达特征；通过模体活性响应分析集成系统（integrated system for motif activity response analysis，ISMARA）预测调控关键模块的转录因子活性。 结果 共鉴定出711个与衰老-卒中交互作用相关的差异表达基因。WGCNA识别出3个核心模块：maroon模块（正相关）富集于细胞形态重塑与代谢通路调控；blue3模块（负相关）富集于蛋白质稳态维持与基因表达调控；red模块（负相关）富集于异常化合物分解代谢过程。单细胞分析显示，maroon与blue3模块基因在活化小胶质细胞中高表达，red模块基因则表达水平较低。ISMARA分析发现Mecp2的活性及表达与blue3模块的模块特异性基因值高度相关。 结论 衰老可能通过损害活化小胶质细胞的蛋白质稳态维持与基因表达调控能力，削弱其卒中后的适应性反应，从而加剧脑损伤，Mecp2可能是潜在的关键调控因子。 Objective To investigate whether aging exacerbates ischemic stroke by regulating microglial responses, and to explore its underlying mechanisms and therapeutic targets. Methods Based on public datasets of ischemic stroke models, DESeq2 was used to screen differentially expressed genes associated with the interaction between aging and stroke. Weighted gene co-expression network analysis (WGCNA) was performed to identify key co-expression modules, followed by gene ontology (GO) enrichment analysis. Single-cell transcriptomic data were utilized to dissect the cellular expression profiles of module genes. The integrated system for motif activity response analysis (ISMARA) was applied to predict the activity of transcription factors governing the key modules. Results A total of 711 genes associated with the interaction between aging and stroke were identified. WGCNA uncovered three core modules: the maroon module (positively correlated), enriched in cellular morphological remodeling and regulation of metabolic pathway; the blue3module (negatively correlated), enriched in protein homeostasis and regulation of gene expression; and the red module (negatively correlated), enriched in catabolism of abnormal compounds. Single-cell analysis revealed that genes from the maroon and blue3 modules were highly expressed in activated microglia, whereas genes of the red module exhibited low expression. ISMARA analysis indicated that the activity and expression of Mecp2 were strongly correlated with eigengene value of the blue3 module. Conclusions Aging may impair the protein homeostasis and gene regulatory capacity of activated microglia, blunting their adaptive responses post-stroke and thereby aggravating brain injury. Mecp2 may serve as a potential master regulatory factor.
老年患者缺血性卒中后存在认知功能下降和生活空间受限的问题，二者的关联性也引起关注。本研究拟从认知功能下降和生活空间受限的定义、评估测量、纵向变化特点及关联性等方面进行综述，以期通过长期追踪阐明二者关联，探索其神经机制，并为开发综合干预措施以延缓认知功能衰退和提高生活质量提供参考。 Elderly patients experience cognitive decline and limited living space after ischemic stroke, and the association between the two has also attracted attention. This review summarizes the definitions, assessments, longitudinal trends, and associations of cognitive decline and limited living space in elderly patients after ischemic stroke. It aims to provide a reference for clarifying their relationship in future long-term follow-up studies, exploring their neural mechanisms, and developing comprehensive intervention measures to delay cognitive decline and improve quality of life.
目的 分析自动化技术对临床研究生物样本质量控制的影响。 方法 依托北京天坛医院生物样本库平台，对比自动化法与手工法在血液样本处理中的效率与质量。分别采用自动化法和手工法对不同通量（8、24、48和96例）血清样本进行移液分装，比较两种方法的平均耗时；采用自动化法和手工法将超纯水按1.000 g的目标质量分装至冻存管，通过称量法评估两种方法的分装准确度（误差）与精密度（变异系数）。对比自动化法（磁珠法）和手工法（离心柱法）在24例和48例通量下提取白细胞悬液脱氧核糖核酸（deoxyribonucleic acid，DNA）的平均耗时；另选取3例全血样本，分别采用手工法（洗脱体积50 μL）与自动化法（洗脱体积100 μL）提取DNA，各重 复6次，比较两种方法提取DNA的浓度和纯度（A260/A280、A260/A230）。此外，对国内主流自动化生物样本存储设备的性能进行现状调研。 结果 血清分装实验中，自动化法在8例（P<0.001）、24例（P<0.001）和48例（P=0.009）通量下的平均耗时长于手工法；在96例高通量下的平均耗时低于手工法［（44.64±0.08）min vs.（56.35±3.55）m in，P=0.002］。超纯水分装结果显示，自动化法的平均分装误差较手工法更接近目标值［（-0.0008±0.0021）g vs.（0.0041±0.0020）g，P<0.001］。在白细胞悬液DNA提取方面，自动化法在24例和48例通量下的平均耗时均低于手工法（均P<0.001）。在全血样本DNA提取方面，自动化法对3例样本提取的DNA浓度均高于手工法（均P<0.001）；3例全血样本中有2例采用自动化法提取的A260/A280比值高于手工法（P=0.026，P<0.001），1例两种方法提取的A260/A280比值差异无统计学意义（P=0.235）。3例全血样本采用自动化法提取的A260/A230比值均高于手工法（P值分别为0.001、<0.001和<0.001）。现状调研显示，自动化生物样本存储技术有利于提高空间利用率、改善生物样本的存储质量并利于数据溯源。 结论 自动化法移液分装生物样本的准确度与精密度均高于手工法，且高通量场景下的移液分装效率高于手工法。自动化法提取的DNA浓度与纯度均优于手工法。科研机构应结合研究对生物样本通量、存储温区、质量控制的需求和建设成本，选择适宜的自动化处理与存储方案。 Objective To analyze the impact of automation technology on the quality control of biological samples in clinical research. Methods The study leverages the Beijing Tiantan Hospital Biobank to compare the efficiency and quality of automated versus manual methods in blood sample processing. Serum samples were aliquoted using both automated and manual methods (n=8, 24, 48, 96), and the average time required for each method was compared. Additionally, ultrapure water was aliquoted into cryovials using both automated and manual methods to achieve a target mass of 1.000 g; the accuracy (error) and precision (coefficient of variation) of the two methods were evaluated by weighing. The average time required for deoxyribonucleic acid (DNA) extraction from leukocyte suspensions (n=24, 48) was compared between the automated method (magnetic bead method) and the manual method (spin-column method). Furthermore, DNA was extracted from three whole blood samples, using both the manual method (elution volume: 50 μL) and the automated method (elution volume: 100 μL), with each method repeated six times. The concentrations and purities of the extracted DNA (A260/A280 and A260/A230 ratios) were compared between the two methods. In addition, a survey was conducted on the current status of mainstream automated biosample storage devices available in China. Results In serum aliquoting, the automated method was slower than that of the manual method at 8 (P<0.001), 24 (P<0.001), and 48 (P=0.009) samples, but faster at 96 samples [(44.64±0.08) min vs. (56.35±3.55) min, P=0.002]. For ultrapure water, the automated method showed significantly lower error than that of the manual method [(-0.0008±0.0021) g vs. (0.0041±0.0020) g, P<0.001]. For DNA extraction from leukocyte suspensions, the automated method was significantly faster than that of the manual method at both 24 and 48 samples (both P<0.001). For DNA extraction from whole blood samples, the automated method yielded higher DNA concentrations across all three samples (all P<0.001). Among the three whole blood samples, two showed higher A260/A280 ratios with the automated method than with the manual method (P=0.026; P<0.001), with no significant difference in the third (P=0.235). A260/A230 ratios obtained by the automated method for all three samples were higher than those obtained by the manual method (P=0.001; P<0.001; P<0.001). The survey indicated that automated storage improves space utilization, sample quality, and data traceability. Conclusions Automated liquid aliquoting demonstrates superior accuracy, precision, and high-throughput efficiency compared to manual methods. Similarly, the automated method yields DNA with higher concentration and purity than the manual method. Institutions should select automation solutions based on sample throughput, storage requirements, quality control standards, and cost-effectiveness.
