ADAMTS- 1 rs402007 Polymorphism Modulates Carotid Plaque Vulnerability and Atorvastatin Efficacy in Cerebral Infarction Patients

ADAMTS - 1 rs402007基因多态性调节脑梗死患者颈动脉斑块易损性及阿托伐他汀疗效

To investigate the association between rs402007 polymorphism in the ADAMTS-1 gene and carotid atherosclerotic plaque vulnerability, as well as the lipid-lowering efficacy of atorvastatin in cerebral infarction patients. Clinical data from 684 cerebral infarction patients admitted to The First Hospital of Hebei Medical University (2016-2019) were analyzed. Patients were stratified into stable plaque (n = 338) and vulnerable plaque (n = 346) groups based on carotid ultrasound. General information, biochemical markers, rs402007 (G/C) genotypes (dominant model), and allele frequencies were compared. Polymorphism genotyping was performed using TaqMan SNP assays (Applied Biosystems) on an ABI 7500 Fast Real-Time PCR system. Logistic regression evaluated plaque vulnerability risk factors and gene-risk factor interactions. Atorvastatin's lipid-lowering efficacy was compared across genotypes. Diabetes prevalence, LDL-C, TC, HCY, and FIB levels differed significantly between groups (P < 0.05). Genotypic distribution analysis revealed a higher frequency of the GG genotype in the stable plaque group (29.59% vs. 21.68%, χ2 = 5.618, P = 0.018). Diabetes, LDL-C, HCY, and FIB were independent risk factors for plaque vulnerability (P < 0.05). A significant interaction between rs402007 polymorphism and LDL-C was observed (P < 0.05). Atorvastatin efficacy rates were 82.29% (GG), 84.27% (GC), and 89.27% (CC), with significant post-treatment lipid improvements in all genotypes (P < 0.05). The CC genotype exhibited superior efficacy compared to GG (P < 0.05). The rs402007 polymorphism influences carotid plaque vulnerability and modulates atorvastatin efficacy, underscoring its potential role in genotype-guided therapeutic strategies.

探讨ADAMTS - 1基因rs402007多态性与脑梗死患者颈动脉粥样硬化斑块易损性的关系，以及阿托伐他汀的降脂疗效。分析河北医科大学第一医院2016 - 2019年收治的684例脑梗死患者的临床资料。根据颈动脉超声检查结果，将患者分为稳定斑块组（n = 338）和易损斑块组（n = 346）。比较两组患者的一般信息、生化指标、rs402007（G/C）基因型（显性模型）及等位基因频率。采用TaqMan SNP检测法（应用生物系统公司）在ABI 7500快速实时荧光定量PCR系统上进行多态性基因分型。运用Logistic回归分析评估斑块易损性的危险因素及基因与危险因素的相互作用。比较不同基因型患者阿托伐他汀的降脂疗效。两组患者的糖尿病患病率、低密度脂蛋白胆固醇（LDL - C）、总胆固醇（TC）、同型半胱氨酸（HCY）和纤维蛋白原（FIB）水平差异有统计学意义（P < 0.05）。基因型分布分析显示，稳定斑块组GG基因型频率较高（29.59% vs. 21.68%，χ² = 5.618，P = 0.018）。糖尿病、LDL - C、HCY和FIB是斑块易损性的独立危险因素（P < 0.05）。rs402007多态性与LDL - C之间存在显著的相互作用（P < 0.05）。阿托伐他汀治疗有效率分别为GG基因型82.29%、GC基因型84.27%、CC基因型89.27%，各基因型治疗后血脂均有显著改善（P < 0.05）。CC基因型的疗效优于GG基因型（P < 0.05）。rs402007多态性影响颈动脉斑块易损性并调节阿托伐他汀的疗效，凸显了其在基因型指导治疗策略中的潜在作用。

REF: Liu Y, Deng Y, Du Z, et al. ADAMTS- 1 rs402007 Polymorphism Modulates Carotid Plaque Vulnerability and Atorvastatin Efficacy in Cerebral Infarction Patients. Transl Stroke Res. Published online April 29, 2025. doi:10.1007/s12975-025-01350-4 PMID: 40299202

Proteomic and Demographic Comparisons of Recurrent Ischemic Stroke Patients

复发性缺血性脑卒中患者的蛋白质组学和人口统计学特征比较

Rates of recurrent strokes have remained relatively unchanged over the past couple decades, highlighting a need for advancements in secondary prevention of stroke recurrence. This study utilizes the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) tissue bank to identify proteomic and demographic differences in recurrent ischemic stroke patients. Blood samples were collected during mechanical thrombectomy of large-vessel occlusion ischemic strokes. Plasma levels for 184 inflammatory and cardiometabolic proteins were measured in systemic blood and intracranial blood from the infarction area. Differences between recurrent and first-stroke patients were analyzed using Fisher's Exact Test for categorical variables and Student's independent samples t tests or Welch's t tests for continuous variables. Proteins were divided into systemic and intracranial proteins, and independent samples t tests were performed with a False Discovery Rate of 5.0%. Significant variables were used in multiple logistic regression. There were 20 patients in the prior stroke group and 121 in the first stroke group. The prior stroke group had a significantly higher percentage of females (80.0% vs 50.4%, p = 0.016) and lower rate of hyperlipidemia comorbidity (10.5% vs 35.5%, p = 0.034). Two systemic proteins were significantly higher in those with a prior stroke: CCL14 and FGF-19. Multiple logistic regression found higher levels of CCL14 and FGF-19 to be predictive of a stroke being recurrent. Along with other demographics, these proteins could provide a predictive model to identify patients with risk of recurrent ischemic strokes. Serum CCL14 and FGF-19 levels are easily accessible biomarkers, making them possible therapeutic targets for recurrent stroke prevention.

在过去几十年里，复发性中风的发生率相对保持不变，这凸显了在中风复发二级预防方面取得进展的必要性。本研究利用血液与血栓取栓登记与协作（BACTRAC）组织库，来确定复发性缺血性中风患者在蛋白质组和人口统计学方面的差异。在大血管闭塞性缺血性中风的机械取栓过程中采集血液样本。测量梗死区域的全身血液和颅内血液中184种炎症和心脏代谢蛋白的血浆水平。使用Fisher精确检验分析分类变量，使用学生独立样本t检验或Welch t检验分析连续变量，以分析复发性中风患者和首次中风患者之间的差异。将蛋白质分为全身蛋白和颅内蛋白，并以5.0%的错误发现率进行独立样本t检验。使用显著变量进行多元逻辑回归分析。有中风病史组有20名患者，首次中风组有121名患者。有中风病史组女性比例显著更高（80.0%对50.4%，p = 0.016），高脂血症合并症发生率更低（10.5%对35.5%，p = 0.034）。有中风病史的患者有两种全身蛋白水平显著更高：CCL14和FGF - 19。多元逻辑回归分析发现，CCL14和FGF - 19水平较高可预测中风复发。结合其他人口统计学因素，这些蛋白质可为识别有复发性缺血性中风风险的患者提供预测模型。血清CCL14和FGF - 19水平是易于检测的生物标志物，使其有可能成为预防复发性中风的治疗靶点。

REF: Meredith N, Harp J, McLouth CJ, et al. Proteomic and Demographic Comparisons of Recurrent Ischemic Stroke Patients. Transl Stroke Res. Published online April 23, 2025. doi:10.1007/s12975-025-01353-1 PMID: 40268817

Activation of ATF6 Signaling Confers Long-Term Beneficial Effects in Young and Aged Mice After Permanent Stroke

激活ATF6信号通路对永久性脑卒中小鼠（包括年轻和老年小鼠）具有长期有益作用

Ischemic stroke disrupts protein homeostasis in brain cells, causes endoplasmic reticulum (ER) stress, and consequently activates the unfolded protein response (UPR). The primary function of UPR activation is to help cells restore ER function, thereby promoting cell survival. A major adaptive UPR branch is mediated by activating transcription factor 6 (ATF6). We previously provided experimental evidence that activation of ATF6 signaling in neurons improves short-term outcome after both transient and permanent stroke. However, the effect of ATF6 activation in astrocytes on stroke outcome remains undetermined, and critically, the long-term therapeutic potential of targeting this UPR branch in permanent stroke has not been evaluated. The current study aimed to address these two critical unknowns. First, using conditional knock-in mice in which functional short-form ATF6 (sATF6) is specifically expressed in astrocytes, we demonstrated that astrocytic ATF6 activation modestly improved outcome after permanent stroke. Then, our pharmacokinetic analysis indicated that compound AA147, an ATF6-specific activator, can cross the blood-brain barrier. Lastly, we found that post-stroke treatment with AA147 had no significant beneficial effect on short-term outcome, but improved long-term functional recovery in both young and aged mice after permanent stroke. Together with previous findings, our data support the notion that the ATF6 pathway is a promising target for stroke therapy.

缺血性中风会破坏脑细胞中的蛋白质稳态，引发内质网（ER）应激，进而激活未折叠蛋白反应（UPR）。UPR激活的主要功能是帮助细胞恢复内质网功能，从而促进细胞存活。激活转录因子6（ATF6）介导了一条主要的适应性UPR分支。我们此前提供的实验证据表明，神经元中ATF6信号通路的激活可改善短暂性和永久性中风后的短期预后。然而，星形胶质细胞中ATF6激活对中风预后的影响仍未明确，而且至关重要的是，针对永久性中风中这一UPR分支的长期治疗潜力尚未得到评估。本研究旨在解决这两个关键的未知问题。首先，利用条件性敲入小鼠（功能性短形式ATF6 [sATF6]在星形胶质细胞中特异性表达），我们证实星形胶质细胞中ATF6的激活可适度改善永久性中风后的预后。随后，我们的药代动力学分析表明，ATF6特异性激活剂化合物AA147能够穿过血脑屏障。最后，我们发现中风后使用AA147治疗对短期预后无显著有益影响，但能改善永久性中风后年轻和老年小鼠的长期功能恢复。结合此前的研究结果，我们的数据支持ATF6通路是中风治疗的一个有前景的靶点这一观点。

REF: Yu X, Dang L, Dhar A, et al. Activation of ATF6 Signaling Confers Long-Term Beneficial Effects in Young and Aged Mice After Permanent Stroke. Transl Stroke Res. Published online April 21, 2025. doi:10.1007/s12975-025-01351-3 PMID: 40259100

Cost-Effectiveness of Carotid Endarterectomy vs. Carotid Stenting: a Systematic Review and Meta-Analysis

颈动脉内膜切除术与颈动脉支架置入术的成本效益：系统评价与荟萃分析

Carotid artery stenting (CAS) and carotid endarterectomy (CEA) are gold-standard treatments of carotid artery stenosis. This study aims to identify the cost-effectiveness of CEA vs CAS. CEA provides marginally improved cost-effectiveness over CAS, providing long-term cost benefits to centers with large surgical volumes. However, shorter procedural times and inpatient stays with CAS may improve overall productivity. Cost should hence not be a deciding factor when choosing between CEA and CAS.

颈动脉支架置入术（CAS）和颈动脉内膜切除术（CEA）是颈动脉狭窄的金标准治疗方法。本研究旨在确定CEA与CAS相比的成本效益。与CAS相比，CEA的成本效益略有提高，能为手术量大的中心带来长期成本效益。然而，CAS手术时间和住院时间较短可能会提高整体效率。因此，在CEA和CAS之间进行选择时，成本不应成为决定性因素。

REF: Akkara Y, Hon JJ, Ahmed M, et al. Cost-Effectiveness of Carotid Endarterectomy vs. Carotid Stenting: a Systematic Review and Meta-Analysis. Transl Stroke Res. Published online April 11, 2025. doi:10.1007/s12975-025-01347-z PMID: 40214933

Hyperthermia and Early Growth of Cerebral Infarct: The Potential Role of Blood–Brain Barrier Permeability

高热与脑梗死早期进展：血脑屏障通透性的潜在作用

Hyperthermia within the first 24 h following ischemic stroke (IS) has been associated with poor outcomes. We sought to determine whether blood-brain barrier (BBB) permeability contributes to the relationship between hyperthermia and early infarct growth (EIG). A retrospective analysis was conducted on a prospective stroke biobank. EIG was defined as the percentage difference between the initial volume (mL) determined by the diffusion-weighted imaging at admission and the volume (mL) from the control CT image on the 4 th-7 th day. Hyperthermia was defined as an axillary body temperature ≥ 37.5 °C within the first 24 h. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) serum levels were measured by ELISA. One-hundred and two (19.7%) patients showed EIG from a cohort of 519 patients (45.6% females). Linear correlation was observed for axillar body temperature and EIG (Pearson's r = 0.46; p < 0.001). sTWEAK serum levels showed a c-statistic of 0.74 (95% CI: 0.69-0.79), with an optimal cut-off point > 3000 pg/mL for EIG prediction. Moreover, microalbuminuria levels strongly correlated with sTWEAK levels (Pearson's r = 0.75; p < 0.001). In the multivariate analysis for EIG was observed an independent association with hyperthermia (adjusted OR 24.21; 95% CI: 12.03-39.12), sTWEAK levels > 3000 pg/mL (adjusted OR 16.43; 95% CI: 3.71-72.70), leukoaraiosis (adjusted OR 10.42; 95% CI: 2.68-39.08), and microalbuminuria (adjusted OR 1.02; 95% CI: 1.00-1.12). In our cohort, hyperthermia was independently associated with EIG after IS. The fact that microalbuminuria, leukoaraiosis, and sTWEAK were also associated with EIG suggests a relationship with increased BBB permeability.

缺血性卒中（IS）后24小时内出现高热与不良预后相关。我们旨在确定血脑屏障（BBB）通透性是否与高热和早期梗死灶扩大（EIG）之间的关系有关。对一个前瞻性卒中生物样本库进行了回顾性分析。EIG定义为入院时弥散加权成像测定的初始体积（mL）与第4 - 7天对照CT图像显示的体积（mL）之间的百分比差异。高热定义为最初24小时内腋温≥37.5°C。采用酶联免疫吸附测定法（ELISA）检测血清可溶性肿瘤坏死因子样弱凋亡诱导因子（sTWEAK）水平。在519例患者（女性占45.6%）的队列中，有102例（19.7%）患者出现EIG。腋温与EIG呈线性相关（皮尔逊相关系数r = 0.46；p < 0.001）。sTWEAK血清水平的受试者工作特征曲线下面积（c统计值）为0.74（95%置信区间：0.69 - 0.79），预测EIG的最佳截断值为>3000 pg/mL。此外，微量白蛋白尿水平与sTWEAK水平密切相关（皮尔逊相关系数r = 0.75；p < 0.001）。在EIG的多因素分析中，发现高热（调整后比值比24.21；95%置信区间：12.03 - 39.12）、sTWEAK水平>3000 pg/mL（调整后比值比16.43；95%置信区间：3.71 - 72.70）、脑白质疏松（调整后比值比10.42；95%置信区间：2.68 - 39.08）和微量白蛋白尿（调整后比值比1.02；95%置信区间：1.00 - 1.12）与EIG独立相关。在我们的队列中，IS后高热与EIG独立相关。微量白蛋白尿、脑白质疏松和sTWEAK也与EIG相关这一事实表明其与BBB通透性增加有关。

REF: Oblitas CM, Sampedro-Viana A, Fernández-Rodicio S, et al. Hyperthermia and Early Growth of Cerebral Infarct: The Potential Role of Blood-Brain Barrier Permeability. Transl Stroke Res. Published online April 7, 2025. doi:10.1007/s12975-025-01349-x PMID: 40195239