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The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP-SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49-0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Radiomics can reflect the heterogeneity within the focus. We aim to explore whether radiomics can predict recurrent intracerebral hemorrhage (RICH) and develop an online dynamic nomogram to predict it., Methods: This retrospective study collected the clinical and radiomics features of patients with spontaneous intracerebral hemorrhage seen in our hospital from October 2013 to October 2016. We used the minimum redundancy maximum relevancy and the least absolute shrinkage and selection operator methods to screen radiomics features and calculate the Rad-score. We use the univariate and multivariate analyses to screen clinical predictors. Optimal clinical features and Rad-score were used to construct different logistics regression models called the clinical model, radiomics model, and combined-logistic regression model. DeLong testing was performed to compare performance among different models. The model with the best predictive performance was used to construct an online dynamic nomogram., Results: Overall, 304 patients with intracerebral hemorrhage were enrolled in this study. Fourteen radiomics features were selected to calculate the Rad-score. The patients with RICH had a significantly higher Rad-score than those without (0.5 vs. -0.8; P< 0.001). The predictive performance of the combined-logistic regression model with Rad-score was better than that of the clinical model for both the training (area under the receiver operating curve, 0.81 vs. 0.71; P = 0.02) and testing (area under the receiver operating curve, 0.65 vs. 0.58; P = 0.04) cohorts statistically., Conclusions: Radiomics features were determined related to RICH. Adding Rad-score into conventional clinical models significantly improves the prediction efficiency. We developed an online dynamic nomogram to accurately and conveniently evaluate RICH., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Post-stroke hyperglycemia as a common phenomenon is associated with unfavorable outcomes. Focusing on admission hyperglycemia, other markers of dysglycemia were overlooked. This study aimed to explore the contribution of acute phase blood glucose levels in combination with other radiological signs to the prognostication of functional outcomes in patients with spontaneous intracerebral hemorrhage (sICH)., Methods: Consecutive patients with sICH with at least five random plasma glucose measurements and complete radiological data during hospitalization were included. We calculated the average, maximum, minimum, standard deviation, and coefficient of variation of blood glucose levels for each patient. Radiological data, including island, black hole, blend, and satellite signs were collected. Functional outcomes were evaluated using the Barthel index. Unfavorable outcomes were defined as a Barthel index score ≤ 60. Univariate and multivariate analyses were performed to identify independent predictors of unfavorable outcomes., Results: Two hundred and thirty-eight patients (mean age 58.5, 163 men and 75 women) were included, and 71 had a history of diabetes. Unfavorable outcomes occurred in 107 patients (45.0%) at 3 months. Multivariate logistic regression analysis demonstrated that maximum blood glucose levels (odds ratio, 1.256; 95% confidence interval, 1.124‒1.404; p < 0.001) and island sign (odds ratio, 2.701; 95% confidence interval, 1.322‒5.521; p = 0.006) were independent predictors of unfavorable outcomes in the nondiabetic group. Meanwhile, patients without diabetes who experienced hematoma expansion had higher average (p = 0.036) and maximum blood glucose levels (p = 0.014)., Interpretation: Maximum blood glucose levels and island sign were independently associated with unfavorable outcomes in patients without diabetes, whereas no glycemic variability indices were associated with unfavorable outcomes. Glucose levels influenced hematoma expansion and functional outcomes, particularly in patients without diabetes with sICH. Thus, clinical management of blood glucose levels should be strengthened for patients with sICH with or without a history of diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhou et al.)

Background: The neutrophil-to-lymphocyte ratio (NLR) is a biomarker reflecting the balance between inflammation (as indicated by the neutrophil count) and adaptive immunity (as indicated by the lymphocyte count). We aimed to estimate ability of NLR at admission and at day 1 for predicting stroke outcome after two reperfusion therapies: intravenous thrombolysis (IVT) and mechanical thrombectomy (MT)., Methods: A retrospective analysis was performed on patients who received recombinant human tissue plasminogen activator (IVT) and/or underwent MT for acute ischemic stroke (AIS) at the First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China) from January 2018 to December 2020. Blood samples were taken on admission to hospital and on day 1 after stroke onset. Binary logistic regression models were applied to investigate potential associations between NLR at admission or day 1 and the following outcomes: symptomatic intracerebral hemorrhage (sICH), dependence, and mortality at 90 days. The ability of NLR to predict AIS outcome was analyzed using receiver operating characteristic (ROC) curves., Results: Data for 927 patients (576 IVT and 351 MT) were reviewed. High admission NLR was associated with dependence in IVT treatment [adjusted odds ratio (OR) 1.21, 95% confidence interval (CI) 1.14-1.23] and 90-day mortality in MT patients (OR 1.09, 95% CI 1.04-1.13). In IVT patients, high NLR at day 1 predicted dependence (OR 1.09, 95% CI 1.02-1.11), sICH (OR = 1.07, 95% CI 1.01-1.12), and 90-day mortality (OR 1.06, 95% CI 1.01-1.15). In MT patients, high NLR at day 1 also predicted dependence (OR 1.08, 95% CI 1.02-1.11) and sICH (OR 1.03, 95% CI 1.01-1.09). ROC analysis confirmed that NLR at day 1 could predict dependence (cut-off 4.2; sensitivity 68.7%; specificity 79.6%), sICH (cut-off 5.1; sensitivity 57.9%, specificity 73.5%), and death (cut-off 5.4; sensitivity 78.8%; specificity 76.4%) in IVT patients. Z values of area under the curves were compared between admissioin and day 1 NLR in IVT patients and showed day 1 NLR can better predict dependence ( Z = 2.8, p = 0.004) and 90-day death ( Z = 2.8, p = 0.005)., Conclusions: NLR is a readily available biomarker that can predict AIS outcome after reperfusion treatment and day 1 NLR is even better than admission NLR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Cheng, Ye, Ye, Zhang, Liu, Huang, Chen, Yang, Wang, Duan, Liu and Zhang.)

Background: Gliomas are primary malignant brain tumors. Despite recent advances in surgery and clinical neuro-oncology, the prognosis of patients with glioma is still poor. Therefore, there is an urgent need to find new therapeutic drugs., Methods: Here, we have studied the anticancer effect of maslinic acid in glioma and explored its potential molecular mechanism. CCK-8, Ki67 immunofluorescence, and colony formation tests are used to detect the proliferation of glioma cells. Transwell and migration experiments are used to detect the function of cell invasion and migration, and RNA-seq was performed to identify differentially expressed genes. Western blot analysis helps us identify important signaling pathways. Finally, the anticancer effect of maslinic acid was confirmed in vivo through tumor xenografting experiments., Results: Our experiments obtained high-throughput data on the treatment of maslinic acid in glioma. We found that maslinic acid significantly inhibits the proliferation, invasion, and migration of glioma cells and promotes the apoptosis of glioma cells via suppressing MAPK signaling., Conclusions: This is the first time to analyze the mechanism of maslinic acid against glioma based on transcription. Our experiments show that maslinic acid may be a useful natural product for the treatment of glioma., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yongqiang Wang et al.)

A genome-wide association study (GWAS) reported PLCL2 on chromosome 3p24. 3 (rs4618210:A>G) as a novel susceptibility locus for myocardial infarction in the Japanese population. As the most common pathological process, atherosclerosis leads to metabolic syndrome (MetS)-related ischaemic stroke (IS) and myocardial infarction. Hypothesizing that polymorphisms of the PLCL2 gene might be associated with the onset and prognosis of IS in MetS patients, we performed the following study in a Chinese Han population. A total of 709 cases (patients with MetS plus IS) and 711 controls (patients with MetS) were enrolled. A fine-mapping strategy was adopted to identify tagged single nucleotide polymorphisms (SNPs) of the PLCL2 gene, and improved multiplex ligation detection reaction (iMLDR) technology was used to genotype the selected SNPs. Logistic regression was used to analyse the values of the selected SNPs for the risk of IS between the cases and controls, adjusting for sex, age, hypertension, dyslipidaemia, hyperglycaemia, smoking and drinking. To compare the mean age of IS onset among different risk score groups, a genetic risk score was constructed for each case. The cumulative risk of IS events in the case group was presented using a cumulative incidence curve. All cases were followed up for 3 months, and functional outcomes were recorded prospectively. Two SNPs (rs4685423 and rs4618210) were significantly related to the risk of IS in MetS patients. For rs4685423, patients who were AA homozygotes were less likely to suffer from IS than C-allele carriers (OR 0.718; 95% CI 0.567-0.909; multivariate-adjusted, P = 0.006). For rs4618210, A-allele carriers were less likely to develop IS than patients who were GG homozygotes (OR 0.679; 95% CI 0.548-0.841; multivariate-adjusted, P < 0.001). As the genetic risk score increased, the mean age at IS onset decreased (log-rank P = 0.010). There was no statistically significant difference in the distribution of the 90-day modified Rankin Scale (mRS) outcomes across the rs4685423 ( P = 0.319) or rs4618210 polymorphisms ( P = 0.148). Our findings suggested that genetic polymorphisms of PLCL2 might be associated with the onset of MetS-related IS. Further studies are warranted to validate our findings in other ethnic populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Ye, Zhang, Chen, Li, Sun and Ye.)

Background: Cardiac myxoma is the most common primary cardiac tumor. Even though it rarely causes a stroke, it is an important risk factor. Here, we compared our clinical experience in managing myxoma patients who developed stroke complications with those who did not present with this condition at the First Affiliated Hospital of Wenzhou Medical University., Patients and Methods: The medical records were reviewed of 160 cardiac myxoma patients who were treated in our facility from January 2006 to December 2019. They were separated into either a stroke group or non-stroke group., Results: Cardiac obstructive symptoms, embolic events and constitutional symptoms were observed in 92 (57.7%), 25 (15.6%) and 18 (11.2%) patients, respectively. Among 23 cardiac myxoma ischemic stroke patients, hypoesthesia (60.9%), hemiparesis (56.5%) and facial paresis (47.8%) were the three most common neurological symptoms. The middle cerebral artery (82.6%) was the most commonly affected vessel, whereas 73.9% of the ischemic patients had multiple stroke lesions. Binary logistic regression analysis showed that coronary heart disease and tumor sizes were independently associated in the stroke group (p <0.05). The 10 years cumulative survival rate was 87.9% for all patients after surgical intervention. There was no significant difference in the 10 years cumulative survival rate between the two groups (80.0% vs 88.9%, p =0.274 > 0.05)., Conclusion: The three most common neurological symptoms (hypoesthesia, hemiparesis and facial paresis), the middle cerebral artery and multiple lesions involvements were the definitive markers of patients afflicted with cardiac myxoma stroke. Small tumor sizes were independently associated with these patients. Surgical resection is a relatively safe procedure for treating both the stroke and non-stroke patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Zhang et al.)

Our group previously showed that 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) is a potent neuroprotective agent in the treatment of ischemic stroke in rats. As its mode of action was not well defined, we determined if its therapeutic effect includes altering an immune response to experimental ischemic stroke in rats. In the current study, 2-BFI significantly reduced stroke-induced brain infarct volume and it also decreased neurological deficits. Its anti-immune effects were determined based on flow cytometry measurements of both the 2-BFI-induced changes in the Th17/ Treg cell balance ratio and ELISA measurements of proinflammatory IL-17A and anti-inflammatory IL-10 cytokine expression levels in the brain and peripheral blood following ischemic strokes. 2-BFI blunted the stroke-induced increases in this ratio, which resulted from suppression of the rises in the Th17 cell number whereas the proportion of Treg cells increased. Stroke also induced increases in IL-17A expression levels whereas the IL-10 expression levels declined. 2-BFI treatment inhibited the rises in IL-17A expression levels whereas the corresponding declines in IL-10 were suppressed by this agent. Therefore, one of the neuroprotective effects of 2-BFI in the treatment of cerebral strokes stems from its suppression of rises in the Th17/Treg balance along with corresponding changes in related cytokines modulating development of this condition.

Aim: Intracerebral hemorrhage (ICH) is one of the most severe complications of thrombolysis. Symptomatic ICHs are associated with adverse outcomes. It has been reported that symptomatic ICHs most commonly occur within the first few hours after the initiation of intravenous thrombolysis. Our aim here was to determine the risk factors for early ICH (within 12 h) after thrombolysis., Methods: We analyzed patients with acute ischemic stroke who received intravenous alteplase at two hospitals affiliated to Wenzhou Medical University between March 2008 and November 2017. The ICH diagnosis time was defined as the time from the intravenous administration of alteplase to the first detection of hemorrhage on computed tomography. Demographic data, medical history, clinical features, and laboratory examination results were collected. Univariate analysis followed by multivariable logistic regression analysis was performed to determine the predictors of early ICH (within 12 h) after thrombolysis., Results: Among 197 patients, early ICH (within 12 h) after thrombolysis occurred in 13 patients (6.6%). In the univariate analysis, patients with early ICHs were significantly correlated with prior stroke (P=0.04). After adjusting for potential confounders in the multivariate analysis, prior stroke (odds ratio [OR]: 5.752, 95% confidence interval [CI]: 1.487-22.248; P=0.011) and atrial fibrillation (OR: 5.428, 95% CI: 1.427-20.640; P=0.013) were associated with early ICH., Conclusions: Prior stroke and atrial fibrillation are independent risk factors for early ICHs (within 12 h) after intravenous thrombolysis with alteplase.

Purpose: To investigate whether the Asp358Ala of interleukin 6 receptor related to the risk and outcome of large artery atherosclerotic (LAA) stroke in Han Chinese. Materials and methods: A prospective cohort study was conducted on 768 patients with LAA stroke and 686 non-stroke controls. The genotypes of Asp358Ala polymorphism were determined using SNPscan technology. Associations between genotypes and the risk of LAA stroke were analyzed with logistic regression model. Results: CC genotype ( P  < 0.001) and AC genotype ( P  = 0.023) decreased the risk of LAA stroke compared with AA genotype. Multivariate logistic regression analysis revealed that CC genotype was significantly associated with the risk of LAA stroke ( P  = 0.002). In the subgroup analyses, polymorphisms of Asp358Ala were significantly associated with the risk of LAA stroke in additive model, dominant model and recessive model ( P  = 0.009, P  = 0.017, P  = 0.012, respectively) for male, but not for female. Further regression analysis showed that compared with participants with AA genotype and obesity, participants with CC genotype and non-obesity were less likely to suffer LAA stroke ( P  = 0.003). For male participants, these associations were still existed (additive model, P  = 0.022). After 3-month follow-up, patients with C allele had good functional prognosis compared with patients with A allele ( P  = 0.009). Conclusion: The study demonstrated that the Asp358Ala polymorphism might be associated with susceptibility to the development and outcome of LAA stroke in Han Chines.

A genome-wide association study (GWAS) reported that the single nucleotide polymorphism (SNP) rs4618210 in the PLCL2 gene is related to myocardial infarction (MI) in the Japanese population, but no study has examined the correlation of PLCL2 with ischemic stroke (IS). The present study was designed to investigate whether the genetic variation in PLCL2 is associated with large artery atherosclerotic (LAA) stroke in a Han Chinese population. Tagging SNPs (tSNPs) of the PLCL2 gene were determined by a fine-mapping strategy and were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 669 LAA stroke patients and 668 healthy controls. A logistic regression model was used to analyze the associations between genetic variation at PLCL2 and the risk of LAA stroke. Two SNPs were significantly associated with the risk of LAA stroke after adjusting for potential confounders: for rs4685423, the AA genotype and CA genotype decreased the risk of LAA stroke compared with the CC genotype (multivariate-adjusted, P = 0.001); for rs4618210, the AA genotype and GA genotype decreased the risk of LAA stroke compared with the GG genotype (multivariate-adjusted, P = 0.007). In addition, haplotype analysis indicated that compared with haplotype TTT, haplotype TAT decreased the risk of LAA stroke in block 2 (adjusted OR, 0.706; 95% CI, 0.550-0.907; P = 0.006). The analysis of SNP-SNP interactions showed that rs4685423 was the most influential contributor to LAA stroke risk. SNPs rs4685423 and rs4618210 in the PLCL2 gene may be related to the risk of LAA stroke in Han Chinese.

The interleukin 6 receptor (IL6R) gene has been shown to locate in the chromosome 1q21 associated with metabolic syndrome (MetS), a condition related to the augmented risk of ischaemic stroke (IS), cardiovascular diseases and all-cause mortality. The aim of this study was to assess the relationship between IL6R gene polymorphisms and IS in patients with MetS in the Chinese Han population. We designed a case-control study enrolling 447 patients with MetS plus IS and 438 patients with MetS alone. Tag single nucleotide polymorphisms (SNPs) of the IL6R gene were determined by a fine-mapping strategy and genotyped using SNPscan technology. A logistic regression model was used to analzse the associations between the genetic variations in IL6R and the risk of IS in MetS patients. The linkage disequilibrium (LD) analysis was performed and four gamete rules were used to define the block. The haplotypes was reconstructed by the SNPstats software. Two SNPs were significantly related to the risk of IS in MetS patients after adjusting for potential confounders as follows: regarding rs12083537, the GG genotype and the GA genotype decreased the risk of IS in the MetS patients compared with the IS risk in the patients with the AA genotype (multivariate-adjusted, P = 0.005); and regarding rs8192284, the CC genotype and the AC genotype decreased the risk of IS compared with the IS risk in the patients with the AA genotype (multivariate-adjusted, P = 0.004). Strong LD was existed in block 2 and the haplotype analysis showed that compared with the ACCG haplotype, the ATCT haplotype (adjusted OR 1.700; 95% CI 1.246-2.319; P = 0.001) increased the risk of IS in the MetS patients. The analysis of the SNP-SNP interactions showed that rs8192284 was the most influential contributor to the risk of IS in the MetS patients. Our results indicate that rs12083537 and rs8192284 in the IL6R gene might be related to the risk of IS in MetS patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose: Although observational studies have reported a positive association between depression and ischemic stroke, causality remains inconclusive. We aimed to assess the causal relationship of major depressive disorder (MDD) with ischemic stroke, especially with the small vessel stroke (SVS) subtype., Methods: We used 72 independent single-nucleotide polymorphisms associated with MDD in a genome-wide association study (GWAS) from the Psychiatric Genetics Consortium as instrumental variables. The corresponding data for ischemic stroke and its subtypes of European ancestry were available from the MEGASTROKE consortium of 34,217 ischemic stroke cases and 406,111 controls. Primary Mendelian randomization estimates were calculated with inverse-variance weighted method, and several alternate methods and multiple sensitivity analyses were also performed., Results: We found that genetic predisposition to higher risk of MDD was associated with higher risk of SVS, with an odds ratio of 1.33 (95% confidence interval, 1.08-1.65; p = 0.009) per log-odds increment in MDD risk, but not with large artery stroke (OR, 1.08; 95% CI 0.83-1.41; p = 0.559), cardioembolic stroke (OR, 0.98; 95% CI 0.80-1.20; p = 0.833), or all ischemic stroke (OR, 1.03; 95% CI 0.92-1.15; p = 0.633). The association of MDD with SVS was overall robust to sensitivity analyses., Conclusions: We provided evidence for a possible causal effect of MDD on increased risk of SVS. Future researches are required to investigate whether rational intervention on depression may help to reduce societal burden of SVS.

Background and Purpose: Studies have shown that peptic ulcer increased the risk of ischemic stroke and stroke recurrence. This study aimed to evaluate the impacts of peptic ulcer on functional outcomes of ischemic stroke., Methods: Patients with first-ever ischemic stroke were grouped as with and without history of peptic ulcer. Functional outcomes were evaluated with modified Rankin scale at 90 days after the index stroke. Favorable functional outcomes were defined as with a modified Rankin scale score of 0-2. Logistic regression was used to identify predictors for favorable functional outcomes at 90 days., Results: Among the 2577 enrolled patients with ischemic stroke, 129 (5.0%) had a history of peptic ulcer. The proportion of favorable outcome was higher in patients without peptic ulcer than those with (59.3% versus 42.6%, P < .001). Multivariate logistic analysis detected that history of peptic ulcer (odds ratio [OR] = 2.89, 95% confidence interval [CI], 1.03-8.10, P = .043), National Institute of Health Stroke Scale score (OR = 2.11, 95% CI, 1.79-2.48, P < .001), and large-artery atherosclerosis stroke subtype (OR = 4.08, 95% CI, 1.11-15.03, P = .035) decreased the likelihood of favorable outcomes., Conclusions: Ischemic stroke patients with peptic ulcer may have an increased risk of less favorable neurological outcome at 90 days after the index stroke., (Copyright © 2018. Published by Elsevier Inc.)

Background: Peptic ulcer has been associated with an increased risk of stroke. This study aimed to evaluate the impacts of peptic ulcer on stroke recurrence and mortality., Subjects and Methods: Patients with first-ever ischemic stroke were retrospectively confirmed with or without a history of peptic ulcer. The primary end point was defined as fatal and nonfatal stroke recurrence. Risks of 1-year fatal and nonfatal stroke recurrence were analyzed with the Kaplan-Meier method. Predictors of fatal and nonfatal stroke recurrence were evaluated with the Cox proportional hazards model., Results: Among the 2577 enrolled patients with ischemic stroke, 129 (5.0%) had a history of peptic ulcer. The fatal and nonfatal stroke recurrence within 1 year of the index stroke was higher in patients with peptic ulcer than in patients without peptic ulcer (12.4% versus 7.2%, P = .030). Cox proportional hazards model detected that age (hazard ratio [HR] = 1.018, 95% confidence interval [CI] 1.005-1.031, P = .008), hypertension (HR = 1.397, 95% CI 1.017-1.918, P = .039), and history of peptic ulcer (HR = 1.853, 95% CI 1.111-3.091, P = .018) were associated with stroke recurrence., Conclusions: Ischemic stroke patients with peptic ulcer may have an increased risk of stroke recurrence. The results emphasize the importance of appropriate prevention and management of peptic ulcer for secondary stroke prevention., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Elevated C-reactive protein (CRP) levels increase the risk of poor functional disability in patients with ischemic stroke (IS). This study aimed to investigate the association between CRP gene polymorphisms and 3-month functional disability of large artery atherosclerotic (LAA) stroke in Han Chinese. Patients with first-ever LAA IS were prospectively enrolled in Nanjing Stroke Registry Program between August 2013 and October 2015. Five single-nucleotide polymorphisms (SNPs) (rs876537, rs2794520, rs3093059, rs7553007 and rs11265260) in CRP gene related to CRP levels in Asian by genome-wide association study were genotyped. The functional outcome at 3 months after the index stroke was assessed by the modified Rankin scale. Associations between genotypes and functional outcome of LAA IS were analyzed with logistic regression model. A total of 690 eligible patients (507 males) were evaluated. SNPs rs11265260 (multivariate-adjusted, p = 0.022), rs2794520 (multivariate-adjusted, p = 0.036) and rs3093059 (multivariate-adjusted, p = 0.027) were significantly associated with elevated CRP in acute IS. Two SNPs, rs3093059 (dominant model: adjusted OR 2.49; 95% CI 1.55-4.00; recessive model: adjusted OR 3.67; 95% CI 1.22-11.03) and rs11265260 (dominant model: adjusted OR 2.51; 95% CI 1.56-4.02; recessive model: adjusted OR 4.70; 95% CI 1.63-13.56) independently predicted 3-month poor outcome of first-ever LAA IS, after adjusting for covariates. In addition, haplotype analysis indicated that haplotype GCTGC (adjusted OR 1.76; 95% CI 1.05-2.95; p = 0.031) increased the poor outcome risk. SNPs rs3093059 and rs11265260 in CRP gene may influence the 3-month functional outcome of first-ever LAA IS in Han Chinese.

Studies have demonstrated that matrix metalloproteinase-3 (MMP-3) is involved in the development and progression of atherosclerosis. However, there is no information available on the association of MMP-3 5A/6A polymorphism with recurrent ischemic stroke (IS) in different IS subtypes. We investigated the potential associations between MMP-3 serum level and -1171 5A/6A polymorphism and the recurrence of IS in a Chinese population. Consecutive acute first-ever IS patients were enrolled between August 2008 and October 2013. The genotypes of MMP-3 5A/6A polymorphism were determined using polymerase chain reaction-restriction fragment length polymorphism. IS recurrence was monitored after the index event and multivariate Cox proportional hazards model was constructed to identify factors related to future IS recurrence. A total of 1282 eligible patients were enrolled. During a 2-year follow-up period, 157 (12.25%) patients had recurrent events. MMP-3 level was significantly higher in patients with 5A/6A or 5A/5A genotype (22.72±7.29ng/ul) than in patients with 6A/6A genotype (20.48±7.58ng/ul), P<0.001. No interaction between MMP-3 5A/6A polymorphism and the risk of recurrence in total IS patients was found. The variant 5A/6A+5A/5A genotype and the 5A allele were significantly associated with a high risk of recurrence for large-artery atherosclerosis (LAA) (multivariate-adjusted, P=0.002, 0.001, respectively), but not for small-artery occlusion and cardioembolism. Our finding showed that MMP-3 5A/6A may be a useful biomarker for predicting recurrence for LAA stroke patients and 5A allele carrier may bear a higher risk of recurrence among patients with the subtype of LAA., (Copyright © 2017. Published by Elsevier B.V.)

Recently, a single nucleotide polymorphism (SNP) rs505922 in ABO gene was related to large artery atherosclerotic (LAA) stroke in Caucasian populations by genome-wide association study (GWAS). This study aimed to determine whether ABO gene polymorphisms are associated with LAA stroke in Chinese Han population. A case-control study was designed, and 644 patients with LAA stroke and 642 healthy controls were enrolled. Ten tagging SNPs (tSNPs) located in ABO gene were genotyped. Associations between genotypes and LAA stroke were analyzed with logistic regression model after adjustment of potential confounders. Although rs505922 was not associated with LAA stroke (TT genotype, adjusted OR = 1.32; 95 % CI, 0.94 to 1.87), two novel SNPs, rs8176668 (AT genotype, adjusted OR = 0.71; 95 % CI, 0.55 to 0.92) and rs2073824 (AA genotype, adjusted OR = 0.72; 95 % CI, 0.57 to 0.92), were associated with LAA stroke. Haplotype analysis indicated that haplotype TC (adjusted OR = 0.72; 95 % CI, 0.54 to 0.95; P = 0.018) in block 1 and haplotype ACA in block 2 (OR = 0.73; 95 % CI, 0.58 to 0.91; P = 0.005) were associated with LAA stroke. Multifactor dimensionality reduction (MDR) analysis in the single-locus model indicated that rs2073824 was the most important attributor for predicting risk of LAA stroke. No significant SNP-SNP interactions among the tested SNPs were detected. The results indicated that the genetic variants in ABO gene may influence the risk of LAA stroke in Chinese Han population.

Background: Our objective is to investigate whether C-reactive protein (CRP) and homocysteine (Hcy) levels in the acute phase of large-artery atherosclerotic stroke predict long-term functional disability and recurrent vascular events., Methods: Patients with first-ever large-artery atherosclerotic ischemic stroke were prospectively registered in the Nanjing Stroke Registry Program between January 2012 and June 2014. Venous blood samples were collected within 2 weeks after the index stroke. Patients were followed up for 1 year. The Kaplan-Meier method was performed in survival analysis. Multiple logistic regression analysis and Cox proportional hazard model were applied to identify predictors of functional disability and recurrent vascular events, respectively., Results: A total of 625 eligible patients (458 males) were evaluated. During the 1-year follow-up period, 63 patients suffered recurrent vascular events. An elevated CRP level is an independent predictor of poor functional disability at 1 year (P for trend = .002), in both males (P for trend = .017) and females (P for trend = .042). Hcy showed no relationship with functional disability. No significant relationship between CRP and Hcy levels and recurrent vascular events was found in total patients in multiple models. Stratified by sex, high Hcy levels were associated with recurrent vascular events in females (P for trend = .036) but not in males., Conclusions: Elevated CRP levels are associated with poor functional disability in patients with large-artery atherosclerotic stroke at 1 year, and Hcy is a relatively moderate predictor of recurrent vascular events in female patients with large-artery atherosclerotic stroke at 1 year., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Intracranial hemorrhage is a major complication of endovascular treatment in patients with acute ischemic stroke. Controlled clinical trials reported varied incidences of intracranial hemorrhage after endovascular treatment. This meta-analysis aimed to estimate whether endovascular treatment, compared with medical treatment, increases the risk of intracranial hemorrhage in patients with acute ischemic stroke., Methods: The current publications on endovascular treatment for acute ischemic stroke were systematically reviewed. Rates of intracranial hemorrhage after endovascular treatment for acute ischemic stroke reported in controlled clinical trials were pooled and analyzed. Random and fixed-effect models were used to pool the outcomes. For analyzing their individual risks, intracranial hemorrhages after endovascular treatment were classified as symptomatic and asymptomatic., Results: Eleven studies involving 1,499 patients with endovascular treatment and 1,320 patients with medical treatment were included. After pooling the data, the risk of any intracranial hemorrhage was significantly higher in patients with endovascular treatment than in patients with medical treatment (35.0 vs. 19.0%, OR = 2.55, 95% CI: 1.64-3.97, p < 0.00001). The risk of asymptomatic intracranial hemorrhage was also significantly higher in patients with endovascular treatment than in those with medical treatment (28 vs. 12%, OR = 3.16, 95% CI: 1.62-6.16, p < 0.001). However, the risks of symptomatic intracranial hemorrhage were similar in patients with endovascular treatment and in those with medical treatment (5.6 vs. 5.2%, OR = 1.09, 95% CI: 0.79-1.50, p = 0.61)., Conclusion: Although the risk of any intracranial hemorrhage may increase after endovascular treatment, the risk of symptomatic intracranial hemorrhage may remain similar as compared with medical treatment.

Objectives: To investigate whether curcumin regulates Notch signaling to cause neuroprotection and neurogenesis after focal ischemia reperfusion injury., Method: Focal ischemia reperfusion injury was modeled in rats by occluding the middle cerebral artery. These animals were given either curcumin (300 mg/kg) or corn oil (vehicle) by intraperitoneal injection starting 1 h after stroke and continuing for 7 d. In parallel, sham-operated control animals received vehicle. All animals were killed on day 12. The different treatment groups were compared in terms of neurobehavioral deficits, BrdU incorporation, and levels of doublecortin (DCX) and Notch intracellular domain (NICD) using immunohistochemistry, immunofluorescence and Western blotting., Results: Animals treated with curcumin showed significantly smaller neurobehavioral deficits than vehicle-treated animals after 3, 7, and 12 d of reperfusion (all p < 0.05). Tissue sections from curcumin-treated animals contained significantly greater numbers of BrdU-positive cells (p < 0.05) and BrdU/DCX-positive cells (p < 0.01), as well as significantly higher NICD levels (p < 0.01)., Conclusion: Curcumin may protect from focal cerebral ischemia reperfusion injury as well as stimulate neurogenesis by activating the Notch signaling pathway.

Caveolin-1 (Cav-1) plays pivotal roles in the endothelial damage following stroke. The present study aimed to investigate whether serum Cav-1 level is associated with the presence of cerebral small vessel disease (cSVD) in patients with acute ischemic stroke. To this end, 156 patients were consecutively enrolled. Cranial magnetic resonance imaging was analyzed to determine the surrogates of cSVD, including cerebral microbleeds (CMBs), silent lacunar infarcts (SLIs), and white matter hyperintensities (WMHs). After adjusting for potential confounders, patients with low Cav-1 level had a higher risk of CMBs than patients with high Cav-1 level (OR: 4.05, 95% CI: 1.77-9.30). However, there was no relationship between Cav-1 and the presence of SLIs or WMHs. When CMBs were stratified by location and number, a similar association was found in patients with deep or infratentorial CMBs (OR: 4.04, 95% CI: 1.59-10.25) and with multiple CMBs (OR: 3.18, 95% CI: 1.16-8.72). These results suggest lower serum Cav-1 levels may be associated with CMBs, especially those that are multiple and located in deep brain or infratentorial structures, in patients with acute ischemic stroke. Cav-1 may be involved in the pathophysiology of CMBs, and may act as a potential target for treating cSVD.

The present study is to use meta-analysis to explain the association between alpha-1 antichymotrypsin (ACT) gene A/T polymorphism and the risk of primary intracerebral hemorrhage (PICH). Relevant studies before 1 June 2015 were identified by searching PubMed, Cochrane database and Science Citation Index Expanded (SCIE), and the references of retrieved articles. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were used to assess the strength of the association. Five independent publications, with 774 PICH cases and 940 controls, were included. There was no statistical evidence of association between ACT polymorphism and PICH risk under all genetic models in overall estimates (allele model: OR = 1.01, 95% CI = 0.80-1.28; heterozygote model: OR = 0.93, 95% CI = 0.60-1.45; homozygote model: OR = 1.03, 95% CI = 0.59-1.80; dominant model: OR = 0.97, 95% CI = 0.65-1.46; recessive model: OR = 1.06, 95% CI = 0.72-1.57). No association was found in subgroup analysis based on ethnicity, Hardy-Weinberg equilibrium, location of hematoma and blood pressure. Sensitivity analysis suggested that the combined results were stable and reliable. No significant publication bias was found by Begg's test and Egger's regression test. The results of our meta-analysis indicate that ACT polymorphism is unlikely to contribute to PICH susceptibility.

Our aim was to evaluate the mortality rate of primary pontine hemorrhage (PPH) and to determine the factors related to the prognosis. Limited data exist on the long-term prognosis and determinants of death in patients with PPH in China. Our study analyzed consecutive cases of first-ever PPH from April 2007 to March 2011 in a hospital-based stroke registry. Mortality rates during 30 day and 3 year follow-ups were analyzed. We used the Kaplan-Meier method to estimate the event rates and binary logistic regression analysis, and Cox proportional hazard regression analysis to identify predictors of short-term and long-term prognosis, respectively. A total of 76 patients were identified, 44 (57.89%) were men. Both 30 day and 3 year overall mortalities in men were higher than women but this different was not statistically significant. Coma on admission, hematoma ⩾ 4 mL and a massive hemorrhage were significantly related to 30 day mortality of PPH. Multivariate Cox proportional hazard regression revealed that coma on admission (hazard ratio [HR] 2.18; 95% confidence interval [CI] 1.16-4.13; p = 0.02) and hematoma ⩾ 4 mL (HR 2.23; 95% CI 1.25-3.96; p = 0.01) were independent predictors of 3 year mortality. In conclusion, the short-term mortality rate and factors related to the prognosis of Chinese patients with PPH are similar to those reported for other populations. A low Glasgow coma scale score on admission and a large hematoma volume may be related to poor 3 year prognosis after PPH., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Little is known about the clinical character of stroke patients with metabolic syndrome (MetS) in Chinese population. In this hospital-based cross-sectional study, we elucidated the prevalence of MetS among patients with acute noncardiogenic cerebral infarction from south China, the topographic infarction patterns in magnetic resonance imaging, and vascular angiography findings of stroke patients with MetS., Methods: The patients with acute noncardiogenic stroke were clinically evaluated including waistline circumference, blood pressure, glycemia, serum triglyceride, high-density lipoprotein cholesterol level, magnetic resonance imaging, and angiography evaluation, including magnetic resonance angiography, computed tomography angiography, or digital subtraction angiography for intracranial (IC) and extracranial arteries. According to the National Cholesterol Education Program Adult Treatment Panel III criterion, the patients were classified into the MetS and non-MetS groups., Results: Among 222 patients studied, the prevalence of MetS was 54.5%, and there were more women in the MetS group than in the non-MetS group (P < .05). Frequency of all the individual factors of MetS was higher in the MetS group than in the non-MetS group (P < .05). The lesion pattern of border-zone (BZ) infarction was more prevalent in MetS patients (P < .05). The frequency of IC artery stenosis was higher in the MetS group than in the non-MetS group (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0-3.0). After adjustment for age and gender, IC stenosis was significantly associated with large waistline circumference (OR, .95; 95% CI, .91-.99)., Conclusions: According to our findings, MetS was of high prevalence in noncardiogenic stroke patients in China, and female patients were more likely to have MetS. The MetS patients tended to have more BZ infarctions and more IC artery stenosis than the non-MetS stroke patients., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the association of matrix metalloproteinase-3 (MMP-3) serum level and the promoter 5A/6A polymorphism of the MMP-3 gene with atherosclerotic cerebral infarction (ACI) in a Chinese Han population., Methods: Two hundred and fifteen patients with acute ACI from the Department of Neurology of Taizhou Hospital and 226 healthy controls were included in the study. Serum MMP-3 level was measured by enzyme-linked immunosorbent assay (ELISA). Genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the common 5A/6A functional promoter polymorphism of the MMP-3 gene., Results: The genotype distribution of the MMP-3 promoter 5A/6A polymorphism between the ACI patients group and the control group was significantly different (chi (2)= 9.389, P= 0.002). The frequencies of the 5A allele were 14.2% and 7.7% in the ACI patients group and the control group respectively (chi (2)= 9.430, P= 0.002). Serum level of MMP-3 in the ACI patients group was significantly higher than that in the control group (t= 24.867, P= 0.000). Among the ACI patients group, serum MMP-3 levels also had significant difference between the 5A/6A+ 5A/5A and the 6A/6A genotype (t= 2.057, P= 0.041)., Conclusion: The present findings suggest that serum level of MMP-3 obviously increased within 48 hours of ischemic stroke and the genetic polymorphism of 5A/6A in the MMP-3 promoter is associated with ACI and MMP-3 expression in the Chinese Han population.