Association between high-resolution magnetic resonance vessel wall imaging characteristics and recurrent stroke in patients with intracranial atherosclerotic steno-occlusive disease: A prospective multicenter study.

BACKGROUND: High-resolution magnetic resonance vessel wall imaging (HRMR-VWI) is a promising technique for identifying intracranial vulnerable plaques beyond lumen narrowing. However, the association between HRMR-VWI characteristics and recurrent stroke remains uncertain. AIMS: This study aimed to investigate the association between HRMR-VWI characteristics and recurrent ipsilateral stroke in patients with symptomatic intracranial atherosclerotic steno-occlusive disease (ICAS). METHODS: This multicenter, observational study recruited first-ever acute ischemic stroke patients attributed to ICAS (>50% stenosis or occlusion) within 7 days after onset. Participants were assessed by multiparametric magnetic resonance imaging (MRI) including diffusion-weighted imaging, three-dimension time-of-flight magnetic resonance angiography, and three-dimensional T1-weighted HRMR-VWI. The patients were recommended to receive best medical therapy and were systematically followed up for 12 months. The association between HRMR-VWI characteristics and the time to recurrent ipsilateral stroke was investigated by univariable and multivariable analysis. RESULTS: Two hundred and fifty-five consecutive patients were enrolled from 15 centers. The cumulative 12 month ipsilateral recurrence incidence was 4.1% (95% confidence interval (CI): 1.6-6.6%). Patients with recurrent ipsilateral stroke exhibited higher rates of intraplaque hemorrhage (IPH) (30.0% vs 6.5%) and eccentric plaque (90.0% vs 48.2%), and lower occurrence of occlusive thrombus (10.0% vs 23.7%). Plaque length (5.69 ± 2.21 mm vs 6.67 ± 4.16 mm), plaque burden (78.40 ± 7.37% vs 78.22 ± 8.32%), degree of stenosis (60.25 ± 18.95% vs 67.50% ± 22.09%) and remodeling index (1.07 ± 0.27 vs 1.03 ± 0.35) on HRMR-VWI did not differ between patients with and without recurrent ipsilateral stroke. In the multivariable Cox regression analysis, IPH (hazard ratio: 6.64, 95% CI: 1.23-35.8, p = 0.028) was significantly associated with recurrent ipsilateral stroke after adjustment.Conclusions:Our results suggest intraplaque hemorrhage (IPH) is significantly associated with recurrent ipsilateral stroke and has potential value in the selection of patients for aggressive treatment strategies. DATA ACCESS STATEMENT: Data from this study are available and can be accessed upon request.

Chinese Stroke Association guidelines for clinical management of ischaemic cerebrovascular diseases: executive summary and 2023 update.

BACKGROUND: China is one of the countries with the highest burden of stroke. Implementing multidimensional management guidelines will help clinicians practise evidence-based care, improve patient outcomes and alleviate societal burdens. This update of the 2019 edition will provide the latest comprehensive recommendations for the diagnosis and treatment of ischaemic cerebrovascular diseases. METHODS: We conducted a comprehensive search on MEDLINE (via PubMed) up to 31 August 2023. The writing team established the recommendations through multiple rounds of online and offline discussions. Each recommendation was graded using the evidence grading algorithm developed by the Chinese Stroke Association (CSA). The draft was reviewed and finalised by the CSA Stroke Guidelines Writing Committee. RESULTS: This update included revisions of 15 existing recommendations and 136 new recommendations in the following areas of stroke care: emergency assessment and diagnosis of ischaemic cerebrovascular disease, acute-phase reperfusion therapy, evaluation of underlying mechanisms, antithrombotic therapy, prevention and treatment of complications, and risk factor management. CONCLUSIONS: This guideline updated the recommendations for the clinical management of ischaemic cerebrovascular disease from 2019.

Stroke incidence and cognitive outcomes of intracranial atherosclerotic stenosis: study protocol for a multicenter, prospective, observational cohort study.

Background: Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of stroke worldwide. Current diagnostic evaluations and treatments remain insufficient to assess the vulnerability of intracranial plaques and reduce the recurrence of stroke in symptomatic ICAS. On the other hand, asymptomatic ICAS is associated with an increased risk of cognitive impairment. The pathogenesis of ICAS related cognitive decline is largely unknown. The aim of SICO-ICAS study (stroke incidence and cognitive outcomes of ICAS) is to elucidate the pathophysiology of stroke and cognitive impairment in ICAS population, comprehensively evaluating the complex interactions among life-course exposure, genomic variation, vascular risk factors, cerebrovascular burden and coexisting neurodegeneration. Methods: SICO-ICAS is a multicenter, prospective, observational cohort study. We aim to recruit 3,000 patients with symptomatic or asymptomatic ICAS (>50% or occlusion) who will be followed up for ≥12 months. All participants will undergo pre-designed magnetic resonance imaging packages, blood biomarkers testing, as well as detailed cognitive domains assessment. All participants will undergo clinical visits every 6 months and telephone interviews every 3 months. The primary outcome measurement is ischemic stroke or cognitive impairment within 12 months after enrollment. Discussion: This study will establish a large prospective ICAS cohort, hopefully discover new biomarkers associated with vulnerable intracranial plaques, identify subjects at high risk for incident ischemic stroke or cognitive impairment, and eventually propose a precise diagnostic and treatment strategy for ICAS population. Trial Registration: Chinese Clinical Trials Register ChiCTR2200061938.

Monogenic basis of young-onset cryptogenic stroke: a multicenter study.

Background: The prevalence of stroke in young adults is increasing. We investigated the monogenic basis of young adult cryptogenic stroke patients. Methods: This multicenter study enrolled cryptogenic stroke patients under 55 years old, and individuals with nonstroke diseases were included as controls. Targeted next-generation sequencing (NGS) was applied with a custom-designed gene panel that included 551 genes. Rare variants were classified into 2 groups: pathogenic variants and variants of unknown significance. Results: A total of 153 individuals, including 30 (21 males, 70%; mean age 36.1±10.2 years) in the disease group and 123 (59 males, 48.0%; mean age 40.4±13.1 years) in the control group, were recruited. In the disease group, 32 rare variants were identified. Among these individuals, 18 pathogenic variants in 16 patients were detected, with a 53.3% (16/30) diagnostic yield of monogenic causes for cryptogenic stroke. None of these mutations were observed in the control group. Among the mutant genes, the most prevalent were Notch receptor 3 (NOTCH3), protein kinase AMP-activated noncatalytic subunit gamma 2 (PRKAG2), and ryanodine receptor 2 (RYR2). Genes associated with cardiogenic diseases showed the highest mutation frequency (10/18, 55.6%) followed by genes associated with small-vessel diseases (SVDs) and coagulation disorders. None of the patients with mutations had evident abnormalities in the heart or other systems checked by routine tests. For the imaging phenotype-genotype association analysis, infarctions in both the anterior and posterior cerebral circulation were only observed in patients with genes related to cardiogenic disease. Conclusions: In this study, pathogenic variants were identified in nearly half of the young-onset cryptogenic stroke patients, with genes related to cardiogenic diseases being the most frequently mutated. This may have implications for future clinical decision-making, including the development of finer and more sensitive examinations.

Identification of Risk Factors for Stroke in China: A Meta-Analysis of Prospective Cohort Studies.

This study aimed to identify independent risk factors for first occurrence of stroke in Chinese individuals based on prospective cohort studies. Forty prospective cohort studies assessing 1,984,552 individuals were selected for the final meta-analysis. The identified risk factors for stroke in the Chinese population included old age (RR = 1.86, 95%CI: 1.47-2.36), hypertension (RR = 2.76, 95%CI: 2.26-3.37), cardiovascular disease history (RR = 1.98, 95%CI: 1.06-3.69), chronic kidney disease (RR = 1.65, 95%CI: 1.36-2.01), diabetes mellitus (RR = 1.71, 95%CI: 1.34-2.18), metabolic syndrome (RR = 1.59, 95%CI: 1.33-1.90), hyperglycemia (RR = 1.49, 95% CI: 1.31-1.69), obesity (RR = 1.45, 95%CI: 1.29-1.63), smoking (RR = 1.42, 95% CI: 1.27-1.58), prolonged sleep time (> 7.5 h, RR = 1.44, 95%CI: 1.19-1.75), higher levels of triglyceride (RR = 1.19, 95%CI: 1.07-1.32), C-reactive protein (RR = 1.34, 95%CI: 1.07-1.69). High fruit-rich diet (RR = 0.68, 95%CI: 0.58-0.80) was associated with a lower risk of stroke. The spectrum and power of risk factors varied among different cohort inclusion years. These findings provide a comprehensive tool for the primary prevention of stroke in Chinese individuals.

Dihydromyricetin-mediated inhibition of the Notch1 pathway induces apoptosis in QGY7701 and HepG2 hepatoma cells.

AIM: To investigate whether Dihydromyricetin (DHM) inhibits cell proliferation and promotes apoptosis by downregulating Notch1 expression. METHODS: The correlation between Notch1 and Hes1 (a Notch1 target molecule) expression in hepatoma samples was confirmed by qRT-PCR. In addition, MTT assays, flow cytometry and TUNEL analysis showed that DHM possessed strong anti-tumor properties, evidenced not only by reduced cell proliferation but also by enhanced apoptosis in QGY7701 and HepG2 hepatocellular carcinoma (HCC) cells. The expressions of Notch1, Hes1, Bcl-2 and Bax were determined by Western blot. RESULTS: Among the tested samples (n = 64), the expression levels of Notch1 (75% of patients) and Hes1 (79.7% of patients) mRNA in tumor tissues were higher than in the normal liver tissues. There was a negative correlation between the expression of Notch1 and the degree of differentiation and positively correlated with the Alpha Fetal Protein concentration. The viability of HCC cells treated with DHM was significantly inhibited in a dose and time-dependent manner. Apoptosis was induced in HepG2 and QGY7701 cell lines following 24 h of DHM treatment. After treatment with DHM, the protein expression of Notch1 was downregulated, the apoptosis-related protein Bax was upregulated and Bcl2 was downregulated. Notch1 siRNA further enhanced the anti-tumor properties of DHM. CONCLUSION: Notch1 is involved in the development of HCC and DHM inhibits cell proliferation and promotes apoptosis by down-regulating the expression of Notch1.

F10, a novel hydatidiform mole-associated gene, inhibits the paclitaxel sensitivity of A549 lung cancer cells by downregulating BAX and caspase-3.

F10 is a novel hydatidiform mole (HM)-associated gene that was initially identified during a study into the pathogenesis of HMs. However, the role of the F10 gene requires further investigation. Our, previous studies have indicated that F10 may be involved in the malignant transformation of HMs and the development of certain types of adenocarcinoma, and that the overexpression of F10 may lead to excessive proliferation and decreased apoptosis of A549 cells. The present study aimed to investigate whether F10 may suppress the sensitivity of A549 lung cancer cells to paclitaxel therapy. A previously established F10-overexpressing A549 cell line (A549-F10) was treated with paclitaxel, using untransfected A549 cells and A549-mock cells (non-carrier A549) as the controls. These three groups of cells were subsequently examined by an MTT cell proliferation assay and a TUNEL-fluorescein isothiocyanate/Hoechst 33258 apoptosis assay. A western blot analysis was used to determine the expression levels of the pro-apoptotic genes B-cell lymphoma-2-associated X protein (BAX) and caspase-3. The effects of paclitaxel treatment on the proliferation and apoptosis of A549 cells were compared between the aforementioned cell lines. It was revealed that F10 inhibited the chemosensitivity of A549 cells to paclitaxel, as demonstrated by the decreased rates of growth inhibition and apoptosis in the A549-F10 group compared with the two control groups. Furthermore, the A549-F10 cells treated with paclitaxel exhibited significantly lower expression levels of the pro-apoptotic genes. The results of the current study demonstrate that F10 may inhibit the chemosensitivity of A549 cells to paclitaxel and that this inhibitory effect may be mediated by the downregulation of BAX and caspase-3 expression, which subsequently inhibits cell apoptosis.