Neuroimaging Marker-CT Perfusion of Early Neurological Deterioration in Patients with Minor Stroke and Large Vessel Occlusion after Intravenous Thrombolysis.

OBJECTIVE: Early Neurological Deterioration (END) is one of the complications in Acute ischemic stroke (AIS) and relates to prognosis. However, the reason why it occurs is still unclear. Our study is to investigate if CT perfusion (CTP) can predict END in patients with Minor Stroke and Large Vessel Occlusion after Intravenous Thrombolysis (IVT). METHODS: Patients who underwent IVT with Large Vessel Occlusion were enrolled continuously from January 2021 to August 2023. After evaluating the National Institutes of Health Stroke Scale (NIHSS) score, they were divided into the END group (n=21) and the Non-END group (n=20). Multivariate logistic regression analysis was performed to explore the factors of END. Receiver-operating characteristic (ROC) curve analysis was also used to assess the discriminative ability of CTP in predicting END. RESULTS: A total of 41 patients (mean age, 62.34 ± 10.82 years, 27 male) were finally included in the analysis; 21 patients had END, and 9 patients underwent Endovascular thrombectomy (EVT). Multivariate logistic regression analysis indicated that rCBV (OR=0.081, 95%CI=0.009- 0.721, p = 0.024) and admission-NIHSS (OR=1.990, 95%CI=1.049-3.772, p = 0.035) were significantly associated with END. The area under the curve (AUC) of rCBV and NIHSS to discriminate END were 0.708 and 0.758. We found patients with END had a higher modified Rankin Scale (mRS) in 3 months. CONCLUSIONS: The rCBV and NIHSS were associated with post-thrombolysis END and may become reliable markers to predicate END. END might predict a poor 3-month functional outcome.

Serum vaspin as a predictor of severity and prognosis in acute ischemic stroke patients.

Objective: The influence of vaspin on vascular health had been investigated, yielding conflicting results. This study is intended to investigate the relation between vaspin and stroke severity and stroke outcome in a cohort Chinese patient with acute ischemic stroke (AIS).Methods: This was a prospective single-center observational study in Xinxiang, China. From 1 July 2017 to 30 November 2019, all patients with first-ever AIS were consecutively included. Serum levels of vaspin, stroke severity at (assessed by NIHSS score) admission and functional outcome (assessed by modified Rankin Scale (mRS)) at discharge were recorded. Multivariate analyses were assessed using logistic regression models.Results: Finally, 340 patients with AIS were included. The median age of those patients was 65 (interquartile range [IQR], 56-74) years and 61.8% were men. At admission, 88 patients (25.9%) experienced severe stroke (NIHSS>10) and serum levels of vaspin (median [IQR]: 0.72[0.48-0.90]ng/ml) in those patients were significantly lower than in those mild(0.92[0.70-1.19]ng/ml) and moderate stroke (0.93[0.63-1.21]ng/ml). At discharge, 113 patients (33.2%) experienced poor functional outcome (mRS >2) and vaspin serum levels in those patients were lower as compared with patients who experienced good outcome (0.71[0.45-0.98] vs. 0.91[0.71-1.19]ng/ml). In multivariate analyses, lower level of vaspin (< median) was associated with a 2.5-fold (odds ratio [OR] 2.46; 95% confidence interval [CI]: 1.75-4.45) increased risk for severe stroke and a 2.1-fold (2.03; 1.42-3.58) increased risk for poor outcome.Conclusion: In conclusion, reduced serum levels of vaspin at admission are significantly related to stroke severity and prognosis, which illustrates a predictive role of reduced vaspin in ischemic stroke.

Clinical Features of Trousseau Syndrome With Cerebral Infarction as the Initial Manifestation.

OBJECTIVE: There are few reports of Trousseau syndrome with cerebral infarction as the initial manifestation before the discovery of the tumor, which is often missed and misdiagnosed, and there is no unified therapy. To explore the clinical features of the Trousseau syndrome and, among those features, the risk factors for cerebral infarction as the initial manifestation. METHODS: This was a retrospective study of 416 consecutive patients with cerebral infarction and malignant tumor admitted at The First Affiliated Hospital of Xinxiang Medical University between January 2015 and December 2017. The patients were grouped as: (1) cerebral infarction as the initial manifestation; and (2) tumor as the initial manifestation. A multivariable logistic regression analysis was used to analyze the relationship between the clinical features (age, sex, characteristics of the infarction, characteristics of the tumors, treatments, depression, coagulopathy, The National Institute of Health stroke scale score, platelet count, red cell count, hemoglobin, atherosclerosis, and coagulation parameters) and the hypercoagulable state. RESULTS: A total of 416 patients met the criteria were included: 212 (51.0%) in the group with cerebral infarction as the initial manifestation and 204 (49.0%) in the group with tumor as the initial manifestation. The multivariable analysis showed that metastatic cancer (odds ratio=2.517; 95% confidence interval, 1.193-5.311; P=0.015) and depressive state (odds ratio=3.158; 95% confidence interval, 1.522-6.551; P=0.002) were independently associated with the Trousseau syndrome with cerebral infarction as the main manifestation. CONCLUSIONS: Trousseau syndrome with cerebral infarction as the initial manifestation was associated with metastatic cancer and depressive state. There was no difference in coagulation status between the 2 groups.

Intracerebral Hemorrhage Induced Brain Injury Is Mediated by the Interleukin-12 Receptor in Rats.

BACKGROUND: IL-12 inhibition of the endothelial cell functions and angiogenesis is mediated by the cross-talk between the lymphocyte and the endothelial cells, which plays a key role in inhibiting the process of angiogenesis in the eyeballs and in malignant tumors. METHODS: We established the intracerebral hemorrhage (ICH) rat model, and IL-12 receptor beta monoclonal antibody was injected into the ICH rats. Western blot, immunofluorescence and RT-qPCR were used to detect the gene expression. Brain water content, EB staining, Garcia test, Beam walking test and wire hanging test were used to assess the injury of brain in ICH rats. RESULTS: IL-12 gene was significantly increase in hematoma border tissue of ICH rats, and IL-12 protein mainly localized in monocytes. Anti-IL-12 treatment with IL-12 monoclonal antibodies could not only significantly decrease the brain water content and EB content in brain tissues of ICH rats, but also significantly increase the score of the Garcia, Beam balance and the Wire hanging test in ICH rats. Moreover, anti-IL-12 treatment significantly decrease the expression of pro-inflammatory gene, inflammatory gene, p-JAK2/JAK2 and p-STAT4/STAT4 protein, but significantly increase the expression anti-inflammatory gene and CD31 protein, and M2 macrophage ratio in hematoma border tissues of ICH rats. In vitro, rmIL-12 inhibited the tube formation of brain microvascular endothelial cells (BMVES) in BMVES and bone marrow-derived monocytes (BMDM) co-culture systems, but not work in a separately cultured BMVES system. In addition, Fedratinib not only reduced p-JAK2/JAK2 and p-STAT4/STAT4 protein expression in BMDM after treating with b-FGF and rmIL-12, but also significantly increased the tube formation of BMVES in BMVES and BMDM co-culture systems after treating with b-FGF and rmIL-12. CONCLUSION: Blockade of IL-12 receptor attenuated brain injury after ICH in rat by promoting angiogenesis, and the mechanism might be related to blocking IL-12 could inhibit M2 cell activation via the JAK2/STAT4 pathway.

Plasma levels of ceramides relate to ischemic stroke risk and clinical severity.

Recent studies have suggested that specific plasma ceramides are independently associated with atherosclerosis and cardiovascular diseases, but it is currently unknown whether plasma ceramide levels are associated with ischemic stroke. Here, we examined whether ceramides were associated with both ischemic stroke risk and clinical severity at admission. We measured three previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/22:0), and Cer(d18:1/24:0)] in 202 patients with acute ischemic stroke and 202 age and sex matched control cases. Plasma ceramides levels were measured by a targeted liquid chromatography-tandem mass spectrometry assay at baseline. The median age of the 202 stroke patients was 66 (interquartile range [IQR], 58-75) years and 54.0 % were men. Plasma levels of C16:0, C22:0, and C24:0 ceramides in stroke patients were significantly higher than in those control cases (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of ischemic stroke (odd ratio [OR] for one IQR increase: 2.15[1.42-2.99]; 2.90[2.13-4.01] and 1.29[1.10-1.69]; respectively). At admission, 103 patients (51.0 %) had a minor stroke (NIHSS < 6). In these patients, plasma levels of C16:0, C22:0, and C24:0 ceramides were lower than that observed in patients with moderate-to-high clinical severity (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of moderate-to-high stroke (OR for one IQR increase: 2.96 [2.05-4.22], 3.03 [2.01-4.25] and 1.72 [1.25-3.31], respectively). An elevated plasma levels of ceramides were predictors of both risk and severity at admission in ischemic stroke patients. The underlying mechanisms of these associations remain to be investigated.

Association between PDE4D polymorphism and ischemic stroke in young population.

OBJECTIVE: To explore the association between the polymorphisms of the phosphodiesterase (PDE) 4D gene (SNP83 and SNP87) and the risk of ischemic stroke (IS) in Chinese young population. METHODS: This study included 393 patients who were divided into IS group and non-IS group. Semiconductor high-throughput sequencing technology and multivariate logistic regression analysis were performed. RESULTS: In the case group, the frequency of CC genotype and C allele of the SNP83 gene was significantly higher than that in the control group. There was no significant difference in genotype frequency distribution of SNP87 between the two groups. CONCLUSION: We found an association between SNP83 and the risk of IS in Chinese young population from northern Henan province. There was not a significant association between SNP87 and IS in Chinese young population.

Elevated Lipoprotein (a) and Risk of Poor Functional Outcome in Chinese Patients with Ischemic Stroke and Type 2 Diabetes.

The aim of this study was to evaluate the short-term prognostic value of early measurement of serum lipoprotein (a) [Lp(a)] levels in Chinese patients with type 2 diabetes (T2D) and acute ischemic stroke (AIS). The study population comprised 232 consecutive patients with an AIS diagnosis complicated with T2D. Functional outcome was obtained on month 3 according to the modified Rankin Scale (mRS). Unfavorable functional outcome was defined as a mRS score of 3 to 6 points. The prognostic value of Lp(a) at admission to predict the unfavorable functional outcome 3 months after stroke onset was compared with the National Institutes of Health Stroke Scale score and other known outcome predictors. The Lp(a) levels in those patients were obtained with a median value of 16.8 mg/dl (IQR, 9.5-34.4 mg/dl). At 3-month follow-up, an unfavorable functional outcome was found in 86 patients (37.1%). In multivariate models comparing the second (Q2), third, and fourth quartiles against the first quartile of Lp(a), concentrations of Lp(a) in Q2, Q3, and Q4 were associated with unfavorable outcome, and increased risk of unfavorable outcome by 42, 131, and 211%. Interestingly, an elevated Lp(a, > 30 mg/dl) was also associated with unfavorable outcome, and with adjusted OR of 2.25 (95% CI 1.39-3.68). The AUC was significantly increased by adding Lp(a) to established risk factors (difference, 0.041 [95% CI, 0.034-0.053]; P = 0.02). The addition of Lp(a) to established risk factors significantly improved net reclassification improvement and integrated discrimination improvement. Higher Lp(a) levels at admission were associated with increased risk of unfavorable functional outcome and might be useful in identifying stroke patients with T2D at risk for unfavorable functional outcome for early prevention strategies.

Dl-3-n-butylphthalide can improve the cognitive function of patients with acute ischemic stroke: a prospective intervention study.

OBJECTIVES: The present study investigated the effects of dl-3-n-butylphthalide on cognitive function of patients with acute ischemic stroke (AIS). METHODS: A total of 104 patients with AIS admitted between October 2012 and June 2013 were assigned to either the Treatment (standardized treatment plus dl-3-n-butylphthalide) or Control (standardized treatment alone) groups. Cognitive function was assessed by the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) and Mini-Mental State Examination (MMSE) before and 1 month after treatment, when high-sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) were also detected. A multivariate logistic regression analysis was done for explore the independent risk factors for vascular dementia (VD). RESULTS: The proportion of cognitive impairment was significantly lower after treatment than before in both the Treatment (88% vs. 64%, P = 0.023) and Control (87% vs. 70%, P = 0.047) groups. Vascular dementia dropped from 30 to 10% in the Treatment (P = 0.035) and from 25.9 to 16.7% in the Control (P = 0.027) groups. Total cognitive improvement was more significant in the Treatment Group (P = 0.018); naming, memory, attention, and linguistic abilities were significantly improved (all P < 0.05). Serum Hcy and hs-CRP levels were significantly lower in the Treatment Group than in the Control Group 1 month after treatment (P < 0.05). DISCUSSION: Dl-3-n-butylphthalide could significantly improve the cognitive function of AIS patients 1 month after stroke. Hcy was involved in the incidence of VD 1 month after AIS. However, further studies are necessary because of differences between groups at baseline.

Overweight and Obesity in Young Adulthood and the Risk of Stroke: a Meta-analysis.

BACKGROUND: A systematic review assessing the association between overweight and obesity in young adulthood and stroke risk is lacking. Therefore, we conducted a meta-analysis to evaluate the association between overweight and obesity in young adulthood and stroke risk. METHODS: We systematically searched PubMed and Embase databases for related studies of human subjects in the English language. Two investigators independently selected original studies in a 2-step process. Fixed- and random-effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Subgroup analyses were also performed. RESULTS: Eight studies met the inclusion criteria. The pooled adjusted RR of stroke was 1.36 (95% CI: 1.28-1.44) for overweight in young adulthood and 1.81 (95% CI: 1.45-2.25) for obesity in young adulthood. In subgroup analyses, overweight and obesity in young adulthood increased the risk of stroke in most groups, except for the group of stroke subtype. For ischemic stroke, the adjusted RR was 1.40 (95% CI: 1.24-1.58) for overweight in young adulthood and 1.78 (95% CI: 1.003-3.16) for obesity in young adulthood, whereas adjusted RR for hemorrhagic stroke was 1.25 (95% CI: .83-1.90) for overweight in young adulthood and 1.80 (95% CI: .97-3.35) for obesity in young adulthood. CONCLUSIONS: Overweight and obesity in young adulthood are associated with an increased risk of stroke, probably, independent of other cardiovascular risk factors. The risk effect gradually increases with increasing body weight.

Effect of Urinary Kallidinogenase on Transforming Growth Factor-ß1 and High-Sensitivity C-Reactive Protein Expression in Rat Focal Cerebral Ischemic Injury.

BACKGROUND In this study we investigated the effect of urinary kallidinogenase (UK) on transforming growth factor beta 1 (TGF-ß1) expression in brain tissue. We also explored the neuroprotective mechanism of UK against ischemic injury by measuring serum high-sensitivity C-reactive protein (hs-CRP) level changes after rat cerebral ischemic injury. MATERIAL AND METHODS The rat middle cerebral artery ischemia/reperfusion model was established using the suture method. Sprague-Dawley rats were randomly divided into 3 groups: treatment, Gegen control, and blank control. Each group was subsequently divided into 5 subgroups according to time (6, 12, 24, 48, and 72 h). Rats in the treatment group were administered UK as treatment. TGF-ß1 expression was observed at each time point using SABC and immunohistochemical staining methods to estimate cerebral infarct volume percentage. Serum hs-CRP levels were also measured. RESULTS TGF-ß1 protein expression in ischemic brain tissues of the treatment group significantly increased at each time point (P<0.01) compared with both control groups. Treatment group serum hs-CRP levels significantly decreased at each time point (P<0.05) compared with both control groups. CONCLUSIONS UK exerts a neuroprotective effect by upregulating TGF-ß1 expression and inhibiting excessive inflammatory responses.

MicroRNA-383 expression regulates proliferation, migration, invasion, and apoptosis in human glioma cells.

This study aims to evaluate microRNA-383 (miR-383) expression level in glioma cells and its influences on proliferation, migration, invasion, apoptosis, and cell cycle in glioma cells. miR-383 expression levels were determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Thirty BALB/c-nu mice were randomly assigned into three groups: U87-miR-383 group, vector-control group, and blank group. Tumorigenicity experiment was conducted to confirm the function of miR-383. U251 and U87 glioma cells were divided into three groups: non-transfected control cells (NT group), glioma cells transfected with miR-383 (miR-383 group), and glioma cells transfected with negative sequence (NC group). Transfection efficiency was measured by qRT-PCR. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. Cell migration and invasion were examined by utilizing a Transwell chamber. Cell cycle and apoptosis were analyzed by flow cytometry. The qRT-PCR results revealed that miR-383 expression was down-regulated in human glioma cells, and was negatively related to the pathological grading of glioma. The rates of tumor growth in vector-control group and blank group were significantly faster than that in U87-miR-383 group, and the average tumor volume and weight in vector-control group and blank group were increased as compared with U87-miR-383 group. Additionally, miR-383 levels in miR-383 group were higher than those in NT group and NC group. CCK-8 assay indicated lower cell viability in miR-383 group as compared with NT group and NC group. Flow cytometry implied that the percentages of cells in miR-383 group reduced, while the cell apoptosis rate enhanced compared with NT group and NC group. In conclusion, our findings suggest that miR-383 expression is down-regulated in glioma cells, inhibiting cell proliferation, migration, and invasion, affecting the cell cycle, and inducing cell apoptosis.

N-terminal probrain natriuretic peptide levels as a predictor of functional outcomes in patients with ischemic stroke.

The prognostic value of the N-amino terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) in acute ischemic stroke (AIS) is uncertain. We sought to determine whether NT-proBNP levels were associated with functional outcomes after AIS. From August 2012 to October 2013, consecutive first-ever AIS patients admitted to the Department of Emergency of the First Affiliated Hospital of Xinxiang Medical University, China, were included in this study. Plasma NT-proBNP levels were measured from admission. Outcomes were measured as 90-day modified Rankin Scale score ('good outcome'=0-2 vs. 'poor'). Multivariate logistic regression was used to assess associations between NT-proBNP levels and outcomes. Predictive performance of NT-proBNP as compared with the clinical model was assessed by comparing receiver-operating characteristic curves. During this study period, 217 consecutive patients with AIS were included and completed 90 days of follow-up. There was a strong positive correlation between the plasma level of NT-proBNP and the National Institutes of Health Stroke Scale score (r=0.415, P=0.000). Plasma levels of NT-proBNP in patients with an unfavorable outcome were significantly higher than those in patients with a favorable outcome [3432 (interquartile range, 1100-54991) vs. 978 (interquartile range, 123-1705) pg/ml; P=0.000]. In multivariate analyses, after adjusting for all other significant outcome predictors, the NT-proBNP level that remained can be seen as an independent unfavorable outcome predictor, with an adjusted odds ratios of 4.14 (95% confidence interval, 2.72-7.99; P=0.000). Our results show that plasma NT-proBNP levels were significantly elevated in patients with an unfavorable outcome and might be of clinical importance as a supplementary tool for the assessment of functional outcomes in patients with AIS.

Improvement of the suture-occluded method in rat models of focal cerebral ischemia-reperfusion.

The aim of the present study was to provide a simple method of establishing a rat model for focal cerebral ischemia-reperfusion (FCIR). The suture-occluded method was used to establish FCIR in male Sprague-Dawley rats. An incision was made over the bifurcation of the common carotid artery (CCA), through which a suture was inserted up to the internal carotid artery (ICA). The suture remained in the skin subsequent to model establishment and was withdrawn to the CCA to enable reperfusion. The reliability of the rat model was assessed via analysis of nerve function, tetrazolium (TTC) staining and pathological examination. Following FCIR in rats, the resulting neurological impairments were observed. TTC staining revealed infarcts and pathological examination revealed typical pathological changes. This modified method was simple, reliable and, therefore, may be used to investigate FCIR.

Tissue factor pathway inhibitor-2 silencing promotes hepatocellular carcinoma cell invasion in vitro.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the world and metastasis is an essential aspect of HCC progression. Tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a potential suppressor gene to regulate tumor invasion and metastasis. In this study, we silenced TFPI-2 in the HCC cell line MHCC97-L and evaluated the role of TFPI-2 in cell invasion and its impact on gene expression. We showed in this study that stable TFPI-2 downregulation in MHCC97-L cells resulted in increased cell adhesion and invasion. We also showed that mRNA and protein expression levels of MMP-1/3, CD44, and ICAM-1 were increased, while those of MMP-2/9 were not changed by TFPI-2 silencing. Furthermore, silencing of TFPI-2 caused increased Akt phosphorylation level and NF-κB transcription in MHCC97-L cells. In conclusion, this study confirms that TFPI-2 downregulation can contribute to tumor invasion of HCC cells through alteration in the expression of metastasis-related genes.