BACKGROUND: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window. METHODS: Patients with ischemic stroke presenting 4.5 to 24 hours from the last known well, with a favorable penumbral profile and an associated large/medium vessel occlusion, were randomized 1:1 to either 0.25 mg/kg tenecteplase or the best medical treatment. A favorable penumbral profile was defined as a hypoperfusion lesion volume to infarct core volume ratio >1.2, with an absolute volume difference >10 mL, and an ischemic core volume 50% of the involved ischemic territory. Secondary outcomes included recanalization, infarct growth, major neurological improvements, change in the National Institutes of Health Stroke Scale score, hemorrhagic transformation within 24 to 48 hours, systemic bleeding at discharge, and modified Rankin Scale (score 0–1, score 0–2, score 5–6, and modified Rankin Scale distribution) at 90 days. The comparison of the primary outcome between groups was conducted using modified Poisson regression with a log-link function and robust error variance, adjusted for time from the last known well to randomization, the site of vessel occlusion, and planned endovascular treatment. RESULTS: Among 224 enrolled patients, 111 were assigned to receive tenecteplase and 113 to receive the best medical treatment (including 23% [n=26] of participants who received intravenous tissue-type plasminogen activator). The mean (SD) age of the tenecteplase group and the best medical treatment group was 64.2 (10.4) and 63.6 (11.0) years old, with 72.1% (n=80) and 70.8% (n=80) male enrolled, respectively. A proportion of 54.9% (n=123) of patients were transferred to the catheter room for preplanned endovascular treatment. The primary outcome occurred in 33.3% (n=37) of the tenecteplase group versus 10.8% (n=12) in the best medical treatment group (adjusted relative risk, 3.0 [95% CI, 1.6–5.7]; P =0.001). Tenecteplase significantly increased the recanalization rate compared with the best medical treatment (35.8% [n=39] versus 14.3% [n=16], adjusted relative risk, 2.5 [95% CI, 1.4–4.4]; P =0.002). There were no significant differences in clinical efficacy outcomes or rates of hemorrhagic transformation between the groups. CONCLUSIONS: Administered at a dose of 0.25 mg/kg intravenously, tenecteplase increased reperfusion without symptomatic intracranial hemorrhage in patients with ischemic stroke selected by imaging in late-time window treatment but did not change clinical outcomes at 90 days. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04516993.

Objective. To observe and compare the efficacy and safety of electroacupuncture and antidepressants in the treatment of poststroke depression (PSD) using a meta‐analysis method. Methods. The VIP, CNKI, Wanfang, CMB, Embase, PubMed, and Cochrane databases were searched. All randomized controlled trials (RCT) on electroacupuncture treatment of PSD were searched and further screened. Meta‐analysis was performed on electroacupuncture and western medicine for PSD to explore the difference in efficacy between electroacupuncture and western medicine for PSD. Results. Nineteen RCTs were included in the meta‐analysis. Compared with the Western medicine group, the meta‐analysis showed no significant changes in Hamilton Depression Scale (HAMD) scores between the electroacupuncture group and the antidepressant group (P > 0.05). The number of adverse events in the electroacupuncture group was less than that in the antidepressant group. Conclusion. Compared with antidepressants, electroacupuncture is not less effective in improving depression symptoms in PSD patients with greater safety.

MicroRNAs, small non-encoding RNAs that post-transcriptionally modulate expression of their target genes, have been implicated as critical regulatory molecules in endothelial cells. In the present study, we found that overexpression of miR-19a protects endothelial cells from lipopolysaccharide (LPS)-induced apoptosis through the apoptosis signal-regulating kinase 1 (ASK1)/p38 pathway. Quantitative real-time PCR demonstrated that the expression of miR-19a in endothelial cell was markedly down-regulated by LPS stimulation. Furthermore, LPS-induced apoptosis was significantly inhibited by over-expression of miR-19a. Finally, both a luciferase reporter assay and western blot analysis showed that ASK1 is a direct target of miR-19a. MiR-19a regulates ASK1 expression by targeting specific binding sites in the 3’ untranslated region of ASK1 mRNA. Overexpression of miR-19a is an effective method to protect against LPS-induced apoptosis of endothelial cells.

Vascular remodelling is an adaptive response to physiological and pathological stimuli that leads to structural and functional changes in the vascular intima, media, and adventitia. Pathological vascular remodelling is a hallmark feature of numerous vascular diseases, including atherosclerosis, hypertension, abdominal aortic aneurysm, pulmonary hypertension and preeclampsia. Autophagy is critical in maintaining cellular homeostasis, and its dysregulation has been implicated in the pathogenesis of various diseases, including vascular diseases. However, despite emerging evidence, the role of autophagy and its dual effects on vascular remodelling has garnered limited attention. Autophagy can exert protective and detrimental effects on the vascular intima, media and adventitia, thereby substantially influencing the course of vascular remodelling and its related vascular diseases. Currently, there has not been a review that thoroughly describes the regulation of autophagy in vascular remodelling and its impact on related diseases. Therefore, this review aimed to bridge this gap by focusing on the regulatory roles of autophagy in diseases related to vascular remodelling. This review also summarizes recent advancements in therapeutic agents targeting autophagy to regulate vascular remodelling. Additionally, this review offers an overview of recent breakthroughs in therapeutic agents targeting autophagy to regulate vascular remodelling. A deeper understanding of how autophagy orchestrates vascular remodelling can drive the development of targeted therapies for vascular diseases.

The hallmark features of the development of pulmonary arterial hypertension (PAH) include the proliferation of pulmonary vascular smooth muscle cells, oxidative stress, inflammation, and pulmonary artery remodeling. Arctigenin is a bioactive component of Arctium lappa that exerts anti-inflammatory and antiproliferative effects in several diseases; however, its effects on pulmonary arteries are still unclear. This study aimed to investigate the efficacy of arctigenin to prevent PAH. Rats injected with monocrotaline (MCT) progressively developed PAH. Arctigenin treatment (50 mg per kg per day, intra-peritoneally) ameliorated right ventricular systolic pressure and pulmonary arterial remodeling, decreased the expression of inflammatory cytokines, and limited the proliferation of pulmonary vascular smooth muscle cells in lungs. Mechanistically, arctigenin effectively inhibited the MCT-induced elevation of NLRP3, caspase-1, and interleukin 1-beta expression in the lungs. These results indicate that arctigenin ameliorates MCT-induced PAH, at least in part, through exerting its anti-inflammatory, antioxidant, and antiproliferative effects, which inhibit the NLRP3 inflammasome signal pathway in rats.