Higher baseline serum bilirubin levels are associated with increased risk of early neurological deterioration in women with acute ischemic stroke.

Background and objectives: Early neurological deterioration (END) occurs in up to one-third of patients with acute ischemic stroke (AIS) and associated with poor outcome. The role of serum bilirubin in END remains controversial. This study aims to investigate the association of total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) with END. Methods: This study was a cross-sectional retrospective study with 344 AIS patients enrolled. We retrospectively reviewed consecutive AIS patients with END through a medical record retrieval system and enrolled patients as control randomly from the AIS patients without END at the same period. The bilirubin levels were compared between the END group and No END group. The correlations of bilirubin with END were assessed according to the bilirubin tertiles on the cohort of different genders. Results: In women, as the bilirubin level increased, the occurrence of END showed an increasing trend. The linear association was significant based on the tertiles of all bilirubin types (TBIL p = 0.003; DBIL p = 0.025; IBIL p = 0.025), while in men no similar trend was observed. After adjustment for confounders, higher TBIL (p for trend 0.009) and DBIL (p for trend 0.033) levels were associated with increased risk of END in women. The adjusted OR for T3 relative to T1 was 5.240 (95% CI 1.496-18.347) in TBIL and 3.549 (95% CI 1.089-11.566) in DBIL. Multivariate logistic regression showed that DBIL was independently associated with END in women (OR 1.717, 95% CI 1.106-2.666). The study also found that DBIL was superior to TBIL and IBIL in prediction of END occurrence in women, with greater predictive value. Discussion: There were gender differences in the relationship between bilirubin and END, and DBIL level was positively associated with END occurrence in women, not in men. DBIL had greater incremental predictive value for END than TBIL and IBIL.

Correlation between risk factors of cognitive dysfunction and blood pressure variability after acute ischemic stroke in northwest Shanghai.

Abstract：Objective: To explore the relationship between risk factors of cognitive dysfunction and blood pressure variability after acute ischemic stroke in northwest Shanghai to establish a model for early identification of high-risk groups of cognitive dysfunction and formulation of more targeted prevention and treatment measures. Methods: Spearman test was used to evaluate the correlation between blood pressure variability and Montreal Cognitive Assessment (MoCA) score in patients with acute ischemic stroke and the partial regression coefficient model was constructed based on the above independent risk factors, and the receiver operating characteristic (ROC) curve was described to analyze the relevant independent risk factors. Results: ROC curve analysis results showed that the clinical prediction model was significantly more effective than a single factor in predicting the risk of cognitive impairment after acute ischemic stroke in northwest Shanghai（P < 0.05）. Conclusion: Cognitive dysfunction after acute ischemic stroke was closely related to high Homocysteine (Hcy) levels, high standard deviation of systolic blood pressure, previous infarction history and infarction of cognitive function area in northwest Shanghai. The prediction model based on the above factors showed satisfactory value in predicting of cognitive dysfunction risk after acute ischemic stroke and there was also the correlation between cognitive function and blood pressure variability.

Preliminary findings on diagnostic performance of computed tomography perfusion images for intracranial arterial stenosis: a retrospective study.

OBJECTIVES: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images. METHODS: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed. RESULTS: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001). CONCLUSIONS: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis.

White Matter High Signals Interfere with Noncontrast Computed Tomography in the Early Identification of Cerebral Infarction.

BACKGROUND: We developed an image patch classification-based method to detect early ischemic stroke. The accuracy of this method was >75%. We aimed to analyze patients' image data to identify interference factors that would affect its accuracy. METHODS: We conducted a retrospective analysis of 162 patients who were hospitalized with acute ischemic stroke. Factors related to the noncontrast computed tomography (ncCT) determination results were analyzed according to the patient's sex, age, clinical symptoms, cerebral infarction volume, cerebral infarction location, and whether or not the white matter high (WMH) signal was combined. RESULTS: The volume of cerebral infarction was positively correlated with the predicted results. The correct percentages of patients with volumes >1 and <1 mL were 59.18 and 83.19%, respectively, and the difference was statistically significant (p = 0.001). The correct percentage of the internal capsule region (47.1%) was significantly lower than that of the other groups (p = 0.011). The correct percentage of lateral ventricular paraventricular infarction was significantly lower than that of non-lateral ventricle patients (70.8 vs. 85.7%). In patients with lateral ventricular paraventricular infarction, if the WMH was combined, the correct percentage will decreased further as the Fazekas level increased. The correct percentage of lateral ventricle infarction combined with Fazekas 3 was 40.0%, which was statistically significant compared with the patient having Fazekas 0 with lateral ventricular infarction (p = 0.01). CONCLUSIONS: WMH had a similar computed tomography appearance to cerebral infarction and could interfere with the prediction of the cerebral infarction region by ncCT. This result provides a reference for clinicians to choose imaging methods for identifying acute cerebral infarction areas.

Significant Stroke Knowledge Deficiencies in Community Physician Improved with Stroke 120.

BACKGROUND AND PURPOSE: In the existing model of community health service in China, community general practitioners play important roles in health promotion as well as prehospital stroke recognition and management. We recently engineered Stroke 120 based on FAST for China. This investigation aimed to investigate its acceptance in community physicians and promote their stroke related knowledge. METHODS: We conducted an stroke education session to community physicians or family doctors (total of 435 participants), teaching both FAST and Stroke 120. Online survey was distributed to the participants before and after the education session to evaluate the awareness of stroke and the acceptance of the stroke recognition tool. RESULTS: Significant stroke knowledge deficiencies were found in community physicians. After the education session, percent of the participants knew that the thrombolytic therapeutic window (<4.5 hours) was improved from 54.0% to 91.6% (P < .001). A total of 88.5% of them would send their patients who had stroke to the nearest hospital with stroke center by emergency medical service, compared to baseline (64.4%, P < .001). In total, 95.2% of them would recommend thrombolytic therapy in the treatment of acute ischemic stroke compared to 82.7% (baseline P < .001). Although majority mastered both FAST (95.5%) and Stroke 120 (98.0%) through our education session, 96.3% of them believe that Stroke 120 is the most suitable for Chinese in stroke education. CONCLUSIONS: Stroke 120 strategy was well accepted by the community physicians in China and in the meantime improved knowledge regarding stroke was observed.

AMPK activation by Tanshinone IIA protects neuronal cells from oxygen-glucose deprivation.

The current study tested the potential neuroprotective function of Tanshinone IIA (ThIIA) in neuronal cells with oxygen-glucose deprivation (ODG) and re-oxygenation (OGDR). In SH-SY5Y neuronal cells and primary murine cortical neurons, ThIIA pre-treatment attenuated OGDR-induced viability reduction and apoptosis. Further, OGDR-induced mitochondrial depolarization, reactive oxygen species production, lipid peroxidation and DNA damages in neuronal cells were significantly attenuated by ThIIA. ThIIA activated AMP-activated protein kinase (AMPK) signaling, which was essential for neuroprotection against OGDR. AMPKα1 knockdown or complete knockout in SH-SY5Y cells abolished ThIIA-induced AMPK activation and neuroprotection against OGDR. Further studies found that ThIIA up-regulated microRNA-135b to downregulate the AMPK phosphatase Ppm1e. Notably, knockdown of Ppm1e by targeted shRNA or forced microRNA-135b expression also activated AMPK and protected SH-SY5Y cells from OGDR. Together, AMPK activation by ThIIA protects neuronal cells from OGDR. microRNA-135b-mediated silence of Ppm1e could be the key mechanism of AMPK activation by ThIIA.

A functional variant in the 3'-UTR of VEGF predicts the 90-day outcome of ischemic stroke in Chinese patients.

Vascular endothelial growth factor (VEGF) plays critical roles in angiogenesis and vasculogenesis, which are associated with post-stroke functional recovery. However, the effects of the VEGFA polymorphisms on the outcome of ischemic stroke (IS) have been rarely reported. We therefore investigated the associations of +936C/T variant (rs3025039) with the susceptibilities and the 90-day outcomes from 494 IS patients and 337 healthy controls in Chinese population through the establishment of logistic multivariate regression model. Stroke severity at admission and outcome of 90 days were respectively assessed according to the National Institutes of Health Stroke Scale and the modified Rankin Scale. The analysis showed that there were no significant associations of the rs3025039 genotypes with the susceptibility (P = 0.229) and the severity (P = 0.734). However, when we divided the 308 IS patients into two groups according to the different outcomes, we found that the rs3025039 TC+TT genotype significantly increased the risk of poor recovery [adjusted odds ratio (OR), 1.99; 95% confidence interval (CI), 1.18-3.37]. Interestingly, we observed another 3'UTR variant, +1451C/T (rs3025040), exhibited strong linkage disequilibrium (r2 = 1.0) with +936C/T and was located in a predicted microRNA-binding site. The rs3025040 T allele significantly decreased the luciferase activities in four cell lines, which indicated a potential disruption of the miRNA-mRNA interaction that would result in lower VEGF expression levels. Our data suggested that the +936C/T variants significantly increased the risk of poorer stroke outcome by affecting the bindings of miR-199a and miR-199b to VEGF mRNA at the rs30250340 polymorphic site.

Polymorphism of the complement 5 gene is associated with large artery atherosclerosis stroke in Chinese patients.

METHODS: C5 rs17611 genetic variants were investigated in 494 IS patients and 330 control individuals .Ischemic stroke was classified into subtypes and patients were assessed 90 days post-stroke with the modified Rankin Scale to determine stroke outcome. RESULTS: The presence of C5 polymorphism was associated with the incidence of large artery atherosclerosis (LAA)-subtype IS (n =2 00; p = 0.031), which even persisted after adjustment for covariates (OR = 1.518; 95%CI = 1.093-2.018; p = 0.013). However, no association was found between genotypes and the severity and outcome of stroke (p = 0.978; p = 0.296). CONCLUSIONS: The C5 polymorphism might contribute to the risk of LAA-subtype IS independently of other known risk predictors.

Polymorphism of the complement 5 gene is associated with large artery atherosclerosis stroke in Chinese patients / O polimorfismo do gene C5 do complemento está associado a acidentes vasculares cerebrais de grandes artérias com aterosclerose em pacientes chineses

ABSTRACT The complement system has been confirmed to play an increasingly important role in ischemic stroke (IS). This study aimed to determine whether the single-nucleotide polymorphism of the complement 5 (C5) gene independently influences the occurrence, severity, and long-term outcome of IS in Chinese patients. Methods C5 rs17611 genetic variants were investigated in 494 IS patients and 330 control individuals .Ischemic stroke was classified into subtypes and patients were assessed 90 days post-stroke with the modified Rankin Scale to determine stroke outcome. Results The presence of C5 polymorphism was associated with the incidence of large artery atherosclerosis (LAA)-subtype IS (n =2 00; p = 0.031), which even persisted after adjustment for covariates (OR = 1.518; 95%CI = 1.093–2.018; p = 0.013). However, no association was found between genotypes and the severity and outcome of stroke (p = 0.978; p = 0.296). Conclusions The C5 polymorphism might contribute to the risk of LAA-subtype IS independently of other known risk predictors.

RESUMO Já se confirmou que o sistema do complemento exerce um papel cada vez mais importante nos acidentes vasculares cerebrais isquêmicos. Este estudo teve o objetivo de determinar se o polimorfismo de nucleotídeo único (SNP) do gene codificador do componente 5 (C5) influencia de forma independente a ocorrência, a severidade e o desfecho em longo prazo do acidente vascular cerebral isquêmico (AVCI) em pacientes chineses. Métodos Variantes genéticas rs17611 do C5 foram investigadas em 494 pacientes com AVCI e em 330 indivíduos controles. O AVCI foi classificado em subtipos e os pacientes foram avaliados 90 dias após o acidente vascular, através da Escala Modificada de Rankin (mRS), para determinação do desfecho do acidente. Resultados A presença de polimorfismo do C5 foi associada à incidência de AVCI do subtipo com aterosclerose de grandes artérias (AGA) (n = 200; p = 0,031), que persistiu mesmo após os ajustes de covariáveis (RP = 1,518; 95% IC = 1,093–2,018; p = 0,013). Entretanto, nenhuma associação foi observada entre os genótipos e a severidade ou o desfecho do acidente vascular (p = 0,978; p = 0,296). Conclusões O polimorfismo do C5 pode contribuir para o risco de AVCI do tipo com AGA, independentemente de outros riscos preditores conhecidos.

Brain-derived neurotrophic factor G196A polymorphism predicts 90-day outcome of ischemic stroke in Chinese: a novel finding.

BACKGROUND AND PURPOSE: Recovery after stroke varies considerably between individuals. An abundance of evidence suggests that genetic factors contribute to stroke recovery. The aim of this study was to determine whether or not the BDNF G196A polymorphism independently influences the occurrence, severity, and 90-day functional outcome in Chinese patients with ischemic stroke (IS). METHODS: BDNF G196A genetic variants were investigated in 494 IS and 346 controls. Severity was assessed by the National Institutes of Health Stroke Scale at the time of admission. Three hundred and eight patients were assessed 90 days post-stroke using the Modified Rankin Scale to determine stroke outcome. RESULTS: We showed that a significant association existed between the BDNF G196A AA genotype and the occurrence of IS (P=0.021), even after adjustment for covariates (P=0.028). The AA genotype of the BDNF G196A was associated with a poor outcome of recovery 3 months after stroke onset (P=0.008) was a novel finding, independent of other known predictors of poor outcome (P=0.012). CONCLUSIONS: The BDNF G196A polymorphism was significantly associated with the occurrence and long-term outcomes of IS, thus BDNF G196A may be used as a prognostic biomarker and therapeutic target in IS.

Association of thromboxane A2 receptor gene polymorphisms with cerebral infarction in a Chinese population.

Platelet aggregation is crucial for the development of cerebral infarction (CI) and it is markedly increased due to the binding of thromboxane A2 (TXA2) to its receptor (TXA2R). Therefore, TXA2R plays a central role in the pathogenesis of atherosclerosis and thrombosis. This study aimed to investigate the relationship between human TXA2R gene single nucleotide polymorphisms (SNPs) and non-cardiogenic CI in a Chinese cohort. Two SNPs, rs768963 and rs4523, located in the regulatory and coding regions of TXA2R gene, respectively, were examined in DNA samples from 407 Chinese patients with CI and 270 controls. 407 CI was categorized into subtypes using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. There was no significant association between rs4523 variants and CI. However, there was a significant difference in the overall distribution of genotypes and dominant/recessive models of rs768963 between CI and control groups. In addition, multiple logistic regression analysis revealed that the C allele of rs768963 was significantly associated with total CI (P = 0.023), large artery atherosclerosis subtype (P = 0.009), small artery occlusion subtype (P = 0.044) after adjusting for confounding factors (odds ratio = 1.533, 1.918 and 1.573, respectively). We conclude that TXA2R rs768963 polymorphism is associated with CI in a Chinese population.