Association between a functional interleukin 6 receptor genetic variant and the risk and functional outcome of large artery atherosclerotic stroke.

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.

2-(-2-Benzofuranyl)-2-imidazoline reciprocally regulates Th17/Treg balance induced by ischemic stroke in rats.

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.

The Impacts of Peptic Ulcer on Functional Outcomes of Ischemic Stroke.

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.

Eight-and-a-half syndrome caused by a pontine haemorrhage: a case report and review of the literature.

BACKGROUND: Eight-and-a-half syndrome is caused by a lesion in the dorsal tegmentum of the caudal pons involving parapontine reticular formation and median longitudinal fasciculus, as well as the nucleus and/or the fasciculus of the facial nerve. It is characterized by one-and-a-half syndrome and an ipsilateral cranial nerve VII palsy. Also, many variants of eight-and-a-half syndrome have been described, including nine syndrome, thirteen-and-a-half syndrome and fifteen-and-a-half syndrome. METHODS: We describe a case of a 49-year-old man who presented with eight-and-a-half syndrome combined with contralateral hemiparesis. We reviewed the literature describing the related spectrum of eight-and-a-half syndrome associated with various etiologies. RESULTS: Brain computed tomography scan revealed a hyperdensity located in the left paramedian aspect of the dorsal pons. T2-weighted magnetic resonance imaging at the 11-month follow-up showed hyperintensity and enlargement of the inferior olivary nuclei, which were compatible with a diagnosis of hypertrophic olivary degeneration. In light of our observations and cases reported in the literature, we categorize the spectrum of eight-and-a-half syndrome into three types, namely classic eight-and-a-half syndrome, eight-and-a-half syndrome variants and eight-and-a-half plus syndrome. Besides, the clinical feature and outcome of the three types are discussed in this article. CONCLUSIONS: Recognition of the spectrum of eight-and-a-half syndrome allows precise anatomic localization of the lesion to pontine tegmentum region.

The Impacts of Peptic Ulcer on Stroke Recurrence.

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.

Association of Matrix Metalloproteinase-1 and Matrix Metalloproteinase-3 Gene Variants with Ischemic Stroke and Its Subtype.

BACKGROUND: Genetic variations in the genes of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of ischemic stroke (IS). Here we investigate the association between MMP-1 -1607 1G/2G and MMP-3 -1171 5A/6A genetic polymorphisms and etiological subtypes of IS in the Han Chinese population. METHODS: A total of 640 eligible patients with IS and 637 age- and gender-matched apparently healthy volunteers were enrolled. Subtypes of IS were classified by Trial of Org 10172 in Acute Stroke Treatment criteria. MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were evaluated using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequencies of the 5A/6A + 5A/5A genotypes and 5A allele were significantly higher in patients with IS than in controls (P <.001, P <.001, respectively). No association was found between MMP-1 1G/2G polymorphism and overall IS. In subgroup analyses, MMP-1 1G/2G and 2G/2G genotypes increased the risk of small-artery occlusion (SAO) subtype (multivariate-adjusted, P <.001, P = .002, respectively), and MMP-3 5A/6A + 5A/5A genotypes were related with large-artery atherosclerosis (LAA) subtype (multivariate-adjusted, P <.001). Haplotype analyses indicated that 2G-6A and 1G-5A increased the risk of SAO (multivariate-adjusted, P = .029) and LAA (multivariate-adjusted, P <.001), respectively. CONCLUSIONS: MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms may contribute to different subtypes of IS susceptibility.

Prognostic Value of C-Reactive Protein and Homocysteine in Large-Artery Atherosclerotic Stroke: a Prospective Observational Study.

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.

Impact of 5A/6A polymorphism of matrix metalloproteinase-3 on recurrent atherosclerotic ischemic stroke in Chinese.

Little is known about the impact of the 5A/6A polymorphism of matrix metalloproteinase-3 (MMP-3) on recurrence of atherosclerotic ischemic stroke in Chinese. The aim of this study was to investigate the association of MMP-3 serum level and 5A/6A genetic polymorphism with the recurrence of atherosclerotic ischemic stroke in the Chinese Han population. We analyzed 106 large artery atherosclerosis (LAA) recurrent ischemic stroke patients and 545 LAA first onset ischemic stroke patients from January 2009 to June 2014. Serum MMP-3 concentrations were measured with an enzyme-linked immunosorbent assay. The genotypes of MMP-3 promoter polymorphism (-1171 5A/6A) were determined using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of MMP-3 5A/6A+5A/5A (32.08% vs. 21.47%, p = 0.02) genotype and 5A (16.98% vs. 11.01%, p = 0.01) allele in the recurrent group was significantly higher than those in the first onset group. After adjustment for vascular risk factors, multivariate logistic regression analysis suggested that the MMP-3 5A/6A+5A/5A genotype was an independent risk factor for LAA recurrent ischemic stroke (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.09-2.79, p = 0.021). No significant difference was observed for the MMP-3 serum concentrations between the recurrent group and the first onset group (22.23 ± 8.31 vs. 21.49 ± 7.89 ng/ul, t = 0.88, p = 0.38). The MMP-3 (-1171 5A/6A) polymorphism may contribute to LAA recurrent ischemic stroke susceptibility. Analysis of 5A/6A polymorphism in MMP-3 may identify patients at higher risk for LAA ischemic stroke recurrence, who may be selected for intensive preventive therapy.

Noncardiogenic stroke patients with metabolic syndrome have more border-zone infarction and intracranial artery stenosis.

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.

Variants in 3p24.3 predicts the risk of early neurological deterioration in large artery atherosclerotic stroke.

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.

An Online Dynamic Radiomics-Clinical Nomogram to Predict Recurrence in Patients with Spontaneous Intracerebral Hemorrhage.

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.

Acute Phase Blood Glucose Levels and Functional Outcomes in Patients with Spontaneous Intracerebral Hemorrhage.

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.

TMAO as a Novel Predictor of Major Adverse Vascular Events and Recurrence in Patients with Large Artery Atherosclerotic Ischemic Stroke.

OBJECTIVES: To explore the association of plasma trimethylamine N-oxide (TMAO) concentration with large artery atherosclerotic (LAA) ischemic stroke and its role in predicting neurological outcome and major vascular event recurrence. MATERIALS AND METHODS: We performed a case-control study that included patients with first-ever LAA stroke as cases (n = 291) and asymptomatic patients as controls (n = 235). Clinical data and venous blood samples were collected within 72 hours after stroke. All subjects were followed for 3 months. TMAO level was detected by liquid chromatography mass spectrometry (LC-MS). Logistic and Cox proportional hazard regression were performed to evaluate plasma TMAO concentration as a predictor of LAA stroke and major vascular event recurrence, respectively. Kaplan-Meier survival analysis was performed to compare major vascular event recurrence between patients with high and low TMAO concentration. RESULTS: After adjusting for traditional stroke risk factors, the plasma TMAO level was significantly higher in the LAA stroke group than the control group (OR = 1.031, 95% CI 1.024-1.037, P < .001). At a cutoff level of 106.9 pg/ml, TMAO had a sensitivity of 63.23% and specificity of 80.00% in discriminating the LAA stroke subjects from the controls in Receiver operator characteristic (ROC) analysis. Kaplan-Meier survival analysis demonstrated TMAO plasma concentration was significantly relevant with recurrent vascular events (Log Rank, P = .006). Moreover, this association was still existed after adjusting for traditional risks (adjusted HR, 3.128; 95% CI, 1.018-9.610) in Cox regression model. But TMAO plasma levels were not relevant with functional disability after 3 months of the LAA stroke. CONCLUSION: Elevated plasma TMAO concentration was independently associated with LAA ischemic stroke. The risk of major vascular event recurrence increased by 2.128 times in the LAA stroke subjects with plasma TMAO level higher than 126.83 pg/mL. Plasma TMAO concentration might be a potential biomarker of major vascular event recurrence.

Maslinic Acid Inhibits the Growth of Malignant Gliomas by Inducing Apoptosis via MAPK Signaling.

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.

Day 1 neutrophil-to-lymphocyte ratio (NLR) predicts stroke outcome after intravenous thrombolysis and mechanical thrombectomy.

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.

Fine-Mapping of the PLCL2 Gene Identifies Candidate Variants Associated With Ischaemic Stroke Risk in Metabolic Syndrome Patients.

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.

Characterizations of Ischemic Stroke Complications in Cardiac Myxoma Patients at a Single Institution in Eastern China.

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.

Risk Factors for Early Intracerebral Hemorrhage after Intravenous Thrombolysis with Alteplase.

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.

Two Novel SNPs in the PLCL2 Gene Associated with Large Artery Atherosclerotic Stroke Identified by Fine-Mapping.

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.

Polymorphism of IL6 receptor gene is associated with ischaemic stroke in patients with metabolic syndrome.

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.