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BackgroundData concerning sex differences in clinical characteristics and outcomes of young ischemic stroke (IS) patients in Eastern China are scarce. Understanding sex differences in clinical characteristics and long-term outcomes of young IS patients might provide valuable evidence for designing preventative measures and therapeutic interventions.MethodsThe study included 228 acute IS patients aged up to 50 years recruited in the prospective Nanjing First Hospital Stroke Registry over a 5-year period. Univariable and multivariable logistic regression analyses were performed to determine whether there were sex differences in clinical characteristics and outcomes of young IS patients.ResultsAdmission systolic blood pressure (130.12±24.3 vs 137.96±24.3 mmHg, P=0.005) of women was significantly lower than that of men. Logistic regression showed that young women had poorer outcomes defined as having modified Rankin Scale score of 3–6 at 12 months after the adjustment for history of prior stroke, NIHSS score, and complication of pneumonia (adjusted OR: 3.45; 95% CI: 1.43–8.32).ConclusionOur study indicates that there may be significant differences in clinical characteristics between young women and men with acute IS in East China. Young women were more likely to be dead or dependent at 12 months after stroke onset. More attention should be paid to young women’s IS prevention and management in East China.

Background Early pre-hospital initiation of blood pressure (BP) lowering could improve outcomes for patients with acute stroke, by reducing hematoma expansion in intracerebral hemorrhage (ICH), and time to reperfusion treatment and risk of intracranial hemorrhage in ischemic stroke (IS). We present the design of the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4). Methods A multi-center, ambulance-delivered, prospective, randomized, open-label, blinded endpoint (PROBE) assessed trial of pre-hospital BP lowering in 3116 hypertensive patients with suspected acute stroke at 50+ sites in China. Patients are randomized through a mobile phone digital system to intensive BP lowering to a target systolic BP of < 140 mmHg within 30 min, or guideline-recommended BP management according to local protocols. After the collection of in-hospital clinical and management data and 7-day outcomes, trained blinded assessors conduct telephone or face-to-face assessments of physical function and health-related quality of life in participants at 90 days. The primary outcome is the physical function on the modified Rankin scale at 90 days, analyzed as an ordinal outcome with 7 categories. The sample size was estimated to provide 90% power (α = 0.05) to detect a 22% reduction in the odds of a worse functional outcome using ordinal logistic regression. Discussion INTERACT4 is a pragmatic clinical trial to provide reliable evidence on the effectiveness and safety of ambulance-delivered hyperacute BP lowering in patients with suspected acute stroke. Trial registration ClinicalTrials.gov NCT03790800. Registered on 2 January 2019; Chinese Trial Registry ChiCTR1900020534. Registered on 7 January 2019. All items can be found in this protocol paper.

Stroke is one of the major causes of death and long-term disability, of which acute ischemic stroke (AIS) is the most common type. Although circular RNA (circRNA) expression profiles of AIS patients have been reported to be significantly altered in blood and peripheral blood mononuclear cells, the role of exosome-containing circRNAs after AIS is still unknown. Plasma exosomes from 10 AIS patients and 10 controls were isolated, and through microarray and bioinformatics analysis, the profile and putative function of circRNAs in the plasma exosomes were studied. A total of 198 circRNAs were differentially quantified (|log2 fold change| ≥ 1.00, p &lt; 0.05) between AIS patients and controls. The levels of 12 candidate circRNAs were verified by qRT-PCR, and the quantities of 10 of these circRNAs were consistent with the data of microarray. The functions of host genes of differentially quantified circRNAs, including RNA and protein process, focal adhesion, and leukocyte transendothelial migration, were associated with the development of AIS. As a miRNA sponge, differentially quantified circRNAs had the potential to regulate pathways related to AIS, like PI3K-Akt, AMPK, and chemokine pathways. Of 198 differentially quantified circRNAs, 96 circRNAs possessing a strong translational ability could affect cellular structure and activity, like focal adhesion, tight junction, and endocytosis. Most differentially quantified circRNAs were predicted to bind to EIF4A3 and AGO2—two RNA-binding proteins (RBPs)—and to play a role in AIS. Moreover, four of ten circRNAs with verified levels by qRT-PCR (hsa_circ_0112036, hsa_circ_0066867, hsa_circ_0093708, and hsa_circ_0041685) were predicted to participate in processes of AIS, including PI3K-Akt, AMPK, and chemokine pathways as well as endocytosis, and to be potentially useful as diagnostic biomarkers for AIS. In conclusion, plasma exosome-derived circRNAs were significantly differentially quantified between AIS patients and controls and participated in the occurrence and progression of AIS by sponging miRNA/RBPs or translating into proteins, indicating that circRNAs from plasma exosomes could be crucial molecules in the pathogenesis of AIS and promising candidates as diagnostic biomarkers and therapeutic targets for the condition.

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Background Even undergoing mechanical thrombectomy (MT), patients with acute vertebrobasilar artery occlusion (AVBAO) still have a high rate of mortality. Tirofiban is a novel antiplatelet agent which is now widely empirically used in acute ischemic stroke (AIS). In this study, we aimed to evaluate the safety and efficacy of tirofiban as adjunctive therapy for MT in AVBAO. Methods From October 2016 to July 2021, consecutive AVBAO patients receiving MT were included in the prospective stroke registry. The short-term outcomes were (1) symptomatic intracerebral hemorrhage (sICH); (2) in-hospital death; (3) National Institute of Health Stroke Scale (NIHSS) at discharge. The Long-term outcomes were: (1) modified Rankin Scale (mRS) at 3 months; (2) death at 3 months. Results A total of 130 eligible patients were included in the study, 64 (49.2%) patients received tirofiban. In multivariate regression analysis, no significant differences were observed in all outcomes between the tirofiban and non-tirofiban group [sICH (adjusted OR 0.96; 95% CI, 0.12–7.82, p = 0.97), in-hospital death (adjusted OR 0.57; 95% CI, 0.17–1.89, p = 0.36), NIHSS at discharge (95% CI, -2.14–8.63, p = 0.24), mRS (adjusted OR 1.20; 95% CI, 0.40–3.62, p = 0.75), and death at 3 months (adjusted OR 0.83; 95% CI, 0.24–2.90, p = 0.77)]. Conclusions In AVBAO, tirofiban adjunctive to MT was not associated with an increased risk of sICH. Short-term (in-hospital death, NIHSS at discharge) and long-term outcomes (mRS and death at 3 months) seem not to be influenced by tirofiban use.

The interaction between platelets and vascular endothelial cells plays a pivotal role in the pathophysiology of acute ischemic stroke (AIS), especially in atherosclerosis formation. However, the underlying mechanism is not entirely clear. The aim of this study was to elucidate the role of platelets-derived miRNA in the development of atherosclerosis and AIS. We evaluated the miRNA expression profiles of serum microvesicles (MV) in five AIS patients and five healthy controls using RNA-seq, and then measured the levels of selected platelets derived miRNAs by qRT-PCR. miR-200a-3p expression in the serum MV and platelets had increased to 1.41 (p &lt; 0.05) and 3.29 times (p &lt; 0.001), respectively, in AIS patients compared with healthy controls, and was modified by severity of AIS. We transferred Cy5-miR-200a-3p into platelets, collected and identified platelets-derived MV (PMVs). Then, the gene expression of p38 MAPK/c-Jun pathway was analyzed using both miR-200a-3p gain- and loss-of-function experiments and PMVs coincubation with HUVEC. The results showed that activated platelets remotely modulated endothelins 1 (ET-1) and vascular endothelial growth factor A (VEGFA) levels in HUVEC through the release of miR-200a-3p-containing PMVs via targeting MAPK14. The results of ROC analyses showed that combination of platelet miR-200a-3p, serum ET-1 and VEGFA levels had an AUC of 0.817, a sensitivity of 70%, and a specificity of 89%. Our results presented new evidence that activated platelets could remotely modulate ET-1 and VEGFA expression in HUVEC via releasing miR-200a-3p-enriched PMVs, which provides a potential miRNA-based predictive biomarker and therapeutic strategy for atherosclerosis and AIS.

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