High Apolipoprotein B Levels are Associated with an Increased Risk of Recurrent Acute Ischemic Stroke: A Nested Case–Control Study

载脂蛋白B水平升高与急性缺血性卒中复发风险增加相关：一项巢式病例对照研究

Mendelian randomization studies have identified that apolipoprotein B (ApoB) is the primary genetic determinant of ischemic stroke, rather than other lipid markers. However, its association with recurrent non-cardioembolic acute ischemic stroke (NCAIS) remains unclear. This study aimed to investigate this association. This study recruited 578 patients with acute ischemic stroke, excluding those with cardiogenic embolism. After a 3-year follow-up, a total of 428 patients completed the prospective cohort study. A Cox regression model was used to evaluate the association between ApoB levels at admission and the recurrence rate. Additionally, a nested case-control study was conducted by comparing blood samples collected at the time of recurrence from recurrent patients with those from non-recurrent patients. Binary logistic regression and ROC analysis were used to assess the association between serum ApoB, low-density lipoprotein cholesterol (LDL-C), and recurrent stroke at the time of recurrence. The Cox regression model demonstrated that ApoB levels at admission were independently associated with an increased risk of recurrent NCAIS (HR=6.697; 95%CI 2.581-17.374, P < 0.001). Recurrent stroke patients had significantly higher serum ApoB levels at admission than non-recurrent ones [0.85 g/L (IQR 0.21) vs. 0.63 g/L (IQR 0.15)]. In ROC analysis, ApoB (AUC = 0.732) showed a greater discriminatory ability for recurrent stroke than LDL-C (AUC = 0.685). Higher serum ApoB levels increased the risk of recurrence in patients with NCAIS, and ApoB demonstrated better discriminatory ability than LDL-C after therapy. These findings suggest that routine ApoB measurement may help improve secondary stroke risk assessment.

孟德尔随机化研究已确定，载脂蛋白B（ApoB）是缺血性卒中的主要遗传决定因素，而非其他血脂指标。然而，其与复发性非心源性急性缺血性卒中（NCAIS）的关联仍不清楚。本研究旨在探讨这种关联。本研究招募了578例急性缺血性卒中患者，排除心源性栓塞患者。经过3年的随访，共有428例患者完成了前瞻性队列研究。采用Cox回归模型评估入院时ApoB水平与复发率之间的关联。此外，通过比较复发患者复发时采集的血样与未复发患者的血样，进行了一项巢式病例对照研究。采用二元逻辑回归和受试者工作特征（ROC）分析评估复发时血清ApoB、低密度脂蛋白胆固醇（LDL - C）与复发性卒中的关联。Cox回归模型显示，入院时ApoB水平与复发性NCAIS风险增加独立相关（风险比=6.697；95%置信区间2.581 - 17.374，P < 0.001）。复发性卒中患者入院时的血清ApoB水平显著高于未复发患者[0.85 g/L（四分位距0.21） vs. 0.63 g/L（四分位距0.15）]。在ROC分析中，ApoB（曲线下面积=0.732）对复发性卒中的鉴别能力优于LDL - C（曲线下面积=0.685）。较高的血清ApoB水平会增加NCAIS患者的复发风险，且治疗后ApoB的鉴别能力优于LDL - C。这些发现表明，常规检测ApoB可能有助于改善卒中二级风险评估。

REF: Hu F, Wu R, Zhao X, et al. High Apolipoprotein B Levels are Associated with an Increased Risk of Recurrent Acute Ischemic Stroke: A Nested Case-Control Study. Transl Stroke Res. Published online October 28, 2025. doi:10.1007/s12975-025-01367-9 PMID: 41145743

Association of MR-proANP Circulating Levels with Ischemic Stroke of Cardioembolic Etiology: A Systematic Review and Meta-Analysis

中段心房利钠肽原循环水平与心源性栓塞性缺血性卒中的相关性：一项系统评价和荟萃分析

The accurate identification of acute ischemic stroke (AIS) etiology is fundamental for its management. Midregional pro-atrial natriuretic peptide (MR-proANP) shows potential as a biomarker of cardioembolic (CE) etiology. We aimed to review and synthesize all data on the association between MR-proANP and CE stroke. Articles were searched in Scopus, Web of Science, and Medline databases up to March 2025. Search terms included the free-text words to identify "stroke" and "MR-pro-ANP" and the Mesh term "Stroke." A meta-analysis was performed using the random-effects model. ROBINS-E Tool was used for quality assessment. Eight studies were included, from which six evaluated the association between MR-proANP and CE etiology in patients with AIS and two evaluated MR-proANP levels in the general population and their association with the risk of future CE stroke. All studies were consistent in describing significantly higher levels of MR-proANP in patients with CE stroke when compared to non-CE stroke. Four studies were included in the meta-analysis, confirming a significant association between MR-proANP and CE etiology (OR 6.04, 95% CI 2.79-13.07). Also, MR-proANP showed moderate to high discriminative ability in identifying CE strokes, significantly improving the discriminative capacity of clinical models, and a strong association with atrial fibrillation (AF). Finally, higher MR-proANP levels were associated with an increased risk of future CE stroke. MR-proANP circulating levels were consistently associated with CE etiology of ischemic stroke, improving the discriminative ability of clinical models, suggesting a role for this biomarker in the accurate classification of AIS etiology.

准确识别急性缺血性卒中（AIS）的病因是其治疗的基础。中段心房利钠肽前体（MR - proANP）有潜力作为心源性栓塞（CE）病因的生物标志物。我们旨在回顾并整合所有关于MR - proANP与CE性卒中之间关联的数据。截至2025年3月，我们在Scopus、Web of Science和Medline数据库中搜索相关文章。搜索词包括用于识别“卒中”和“MR - pro - ANP”的自由文本词以及医学主题词“卒中”。采用随机效应模型进行荟萃分析。使用ROBINS - E工具进行质量评估。共纳入八项研究，其中六项评估了AIS患者中MR - proANP与CE病因的关联，两项评估了普通人群中MR - proANP水平及其与未来发生CE性卒中风险的关联。所有研究在描述CE性卒中患者的MR - proANP水平显著高于非CE性卒中患者方面是一致的。四项研究被纳入荟萃分析，证实了MR - proANP与CE病因之间存在显著关联（优势比为6.04，95%置信区间为2.79 - 13.07）。此外，MR - proANP在识别CE性卒中方面表现出中到高的鉴别能力，显著提高了临床模型的鉴别能力，并且与心房颤动（AF）有很强的关联。最后，较高的MR - proANP水平与未来发生CE性卒中的风险增加相关。MR - proANP循环水平与缺血性卒中的CE病因始终相关，提高了临床模型的鉴别能力，表明该生物标志物在准确分类AIS病因方面具有一定作用。

REF: Sousa-Costa J, Moura H, Ponte J, et al. Association of MR-proANP Circulating Levels with Ischemic Stroke of Cardioembolic Etiology: A Systematic Review and Meta-Analysis. Transl Stroke Res. Published online October 14, 2025. doi:10.1007/s12975-025-01387-5 PMID: 41083810

Hematoma Resorption in Intracerebral Hemorrhage: A Translational Overview on Pathophysiology, Biomarkers, and Innovative Therapies

脑出血血肿吸收：关于病理生理学、生物标志物和创新疗法的转化性综述

Spontaneous intracerebral hemorrhage (ICH) is a severe cerebrovascular condition with limited therapeutic options. One of the major contributors to ICH pathophysiology and secondary brain injury is the toxicity of blood products. As a result, removing parenchymal blood has emerged as a potential strategy to reduce mortality and improve patient outcomes. While minimally invasive surgical techniques have shown promising results, their broader application is limited by stringent patient selection criteria and technical challenges. Consequently, a pharmacological approach aiming at modulating the endogenous clearance of blood is of particular interest. Recent advances, from experimental models to human studies, have enhanced our understanding of the mechanisms involved in spontaneous hematoma resorption, leading to the identification of several biomarkers and potential therapeutic targets. This narrative review takes a translational approach to provide an update on the current knowledge of hematoma resorption, including its natural history, underlying mechanisms, and associated imaging and biological biomarkers. Special focus will be given to the most promising pharmacomodulatory strategies.

自发性脑出血（ICH）是一种严重的脑血管疾病，治疗选择有限。血液成分的毒性是脑出血病理生理过程和继发性脑损伤的主要原因之一。因此，清除脑实质内的血液已成为降低死亡率和改善患者预后的一种潜在策略。尽管微创外科技术已显示出良好的效果，但其广泛应用受到严格的患者选择标准和技术挑战的限制。因此，旨在调节血液内源性清除的药物治疗方法尤为引人关注。从实验模型到人体研究的最新进展，加深了我们对自发性血肿吸收机制的理解，从而确定了多个生物标志物和潜在的治疗靶点。本篇综述采用转化医学的方法，对目前血肿吸收的相关知识进行更新，包括其自然病程、潜在机制以及相关的影像学和生物学标志物。将特别关注最有前景的药物调节策略。

REF: Puy L, Mazzoleni V, Samarasekera N, et al. Hematoma Resorption in Intracerebral Hemorrhage: A Translational Overview on Pathophysiology, Biomarkers, and Innovative Therapies. Transl Stroke Res. Published online October 11, 2025. doi:10.1007/s12975-025-01389-3 PMID: 41075069

Associations of Soluble Inflammatory and Endothelial Activation Biomarkers with Cognitive Function Over Three Years After Ischemic Stroke—PROSCIS-B

缺血性卒中后三年期间可溶性炎症和内皮激活生物标志物与认知功能的关联——PROSCIS - B研究

Vascular inflammation is involved in the pathophysiology of post-stroke cognitive impairment. We aimed to assess whether blood-based biomarkers of inflammation and endothelial dysfunction, such as interleukin 6 (IL-6), vascular cell adhesion molecule (VCAM-1), and tumor necrosis factor-alpha (TNF-α), are associated with cognitive function over time in a prospective cohort of first-ever ischemic stroke patients. Data were obtained from the Prospective Cohort with Incident Stroke Berlin (NCT01363856). Cognitive function was assessed with the Telephone Interview for Cognitive Status-modified (TICS-m) at 1 to 3 years of follow-up. Associations of baseline levels of IL-6, VCAM-1, and TNF-α with cognitive function over time were estimated using a linear mixed model adjusted for demographics, education, vascular risk factors, stroke severity, ischemic stroke subtype, and severity of white matter hyperintensity. We included 570 patients with mild-to-moderate ischemic stroke and baseline data on biomarker levels. The mean age was 67 (± 12 SD), 38.6% were female, and the median National Institutes of Health Stroke Scale (NIHSS) was 2 (IQR 1-4). Frequency of cognitive impairment defined as TICS-m score ≤ 31 was 21.9% at year one, 15.4% at year two, and 11.6% at year three. Higher log-transformed levels of IL-6 and VCAM-1 were associated with lower TICS-m scores over time in the adjusted linear mixed model including white matter hyperintensity burden (IL-6: β = -2.0, 95% CI -3.3 to -0.7, p = 0.003; VCAM-1: β = -4.1, 95% CI -7.3 to -1.0, p = 0.01). In patients with mild-to-moderate first-ever ischemic stroke, higher baseline levels of IL-6 and VCAM-1 were associated with lower Telephone Interview for Cognitive Status-modified during 3 years of follow-up.ClinicalTrials.

血管炎症参与了卒中后认知障碍的病理生理过程。我们旨在评估基于血液的炎症和内皮功能障碍生物标志物，如白细胞介素6（IL - 6）、血管细胞黏附分子（VCAM - 1）和肿瘤坏死因子 - α（TNF - α），是否与首次缺血性卒中患者前瞻性队列的认知功能随时间的变化相关。数据来自柏林首次卒中前瞻性队列研究（NCT01363856）。在随访1至3年时，采用改良的电话认知状态访谈（TICS - m）评估认知功能。使用线性混合模型评估IL - 6、VCAM - 1和TNF - α的基线水平与认知功能随时间的关联，并对人口统计学特征、教育程度、血管危险因素、卒中严重程度、缺血性卒中亚型和脑白质高信号严重程度进行校正。我们纳入了570例轻至中度缺血性卒中患者，并获取了其生物标志物水平的基线数据。患者平均年龄为67岁（标准差±12），女性占38.6%，美国国立卫生研究院卒中量表（NIHSS）中位数为2（四分位距1 - 4）。以TICS - m评分≤31定义的认知障碍发生率在第1年为21.9%，第2年为15.4%，第3年为11.6%。在校正了脑白质高信号负荷的线性混合模型中，经对数转换后的IL - 6和VCAM - 1水平越高，随时间推移TICS - m评分越低（IL - 6：β = - 2.0，95%置信区间 - 3.3至 - 0.7，p = 0.003；VCAM - 1：β = - 4.1，95%置信区间 - 7.3至 - 1.0，p = 0.01）。在首次发生轻至中度缺血性卒中的患者中，IL - 6和VCAM - 1的基线水平越高，在3年随访期间改良的电话认知状态访谈评分越低。临床试验。

REF: Giesers NK, Schaeff V, Gertz K, Endres M, Liman TG. Associations of Soluble Inflammatory and Endothelial Activation Biomarkers with Cognitive Function Over Three Years After Ischemic Stroke-PROSCIS-B. Transl Stroke Res. Published online October 8, 2025. doi:10.1007/s12975-025-01388-4 PMID: 41057606

Identification of Biomarkers Related to the Pathogenesis and Prognosis of Pediatric Moyamoya Disease Via Cerebrospinal Fluid Proteomics

通过脑脊液蛋白质组学鉴定与儿童烟雾病发病机制和预后相关的生物标志物

Developing cost-effective, noninvasive biomarker-based tests could transform moyamoya disease (MMD) management. This study aimed to identify clinically relevant cerebrospinal fluid (CSF) biomarkers through comprehensive proteomic screening in a large MMD cohort. CSF protein profiles from 104 MMD patients and 14 non-tumorous hydrocephalus patients were analyzed via liquid chromatography-tandem mass spectrometry. Enrichment analysis was conducted on canonical pathways and differentially expressed proteins (DEPs). The protein-protein interaction network data included all proteins involved in canonical pathways. Potential markers were validated via ELISA. Weighted gene coexpression network analysis (WGCNA) revealed clinical factor-related modules. We identified 2463 proteins, and 2307 were quantified in at least one sample. A total of 321 significant DEPs were identified, with 8 proteins upregulated and 11 proteins downregulated in MMD samples. ELISA confirmed the increased expression of ALB and SLITRK1. WGCNA revealed seven modules correlated with clinical factors, linking preoperative cerebral infarction to the module eigengene (ME) red module and favorable modified Rankin scale scores to the MEblack module. BASP1 and LDHA were significantly upregulated in MEred, whereas CD9 and EMILIN1 were upregulated in MEblack. Our findings shed light on the proteomics of CSF from MMD patients, identifying potential novel biomarkers such as SLITRK1 and markers of preoperative cerebral infarction (BASP1, LDHA) and clinical outcome (CD9, EMILIN1). These markers have potential as new diagnostic and therapeutic targets for MMD.

开发具有成本效益、基于生物标志物的无创检测方法可能会改变烟雾病（MMD）的管理方式。本研究旨在通过对大型MMD队列进行全面的蛋白质组学筛查，确定具有临床相关性的脑脊液（CSF）生物标志物。通过液相色谱 - 串联质谱法分析了104例MMD患者和14例非肿瘤性脑积水患者的脑脊液蛋白质谱。对经典通路和差异表达蛋白（DEP）进行了富集分析。蛋白质 - 蛋白质相互作用网络数据包括参与经典通路的所有蛋白质。通过酶联免疫吸附测定（ELISA）验证了潜在标志物。加权基因共表达网络分析（WGCNA）揭示了与临床因素相关的模块。我们鉴定出2463种蛋白质，其中至少在一个样本中对2307种进行了定量。总共鉴定出321种显著的差异表达蛋白，在MMD样本中有8种蛋白上调，11种蛋白下调。ELISA证实了白蛋白（ALB）和SLITRK1的表达增加。WGCNA揭示了七个与临床因素相关的模块，将术前脑梗死与模块特征基因（ME）红色模块相关联，将良好的改良Rankin量表评分与ME黑色模块相关联。在ME红色模块中，脑酸性可溶性蛋白1（BASP1）和乳酸脱氢酶A（LDHA）显著上调，而在ME黑色模块中，分化簇9（CD9）和弹性蛋白微原纤维界面蛋白1（EMILIN1）上调。我们的研究结果揭示了MMD患者脑脊液的蛋白质组学特征，确定了潜在的新型生物标志物，如SLITRK1，以及术前脑梗死标志物（BASP1、LDHA）和临床结局标志物（CD9、EMILIN1）。这些标志物有潜力成为MMD新的诊断和治疗靶点。

REF: Shim Y, Choi SA, Dan K, et al. Identification of Biomarkers Related to the Pathogenesis and Prognosis of Pediatric Moyamoya Disease Via Cerebrospinal Fluid Proteomics. Transl Stroke Res. Published online October 1, 2025. doi:10.1007/s12975-025-01384-8 PMID: 41034428