BACKGROUND: Several trials have shown the benefit and safety of endovascular therapy (EVT) compared with medical management (MM) of patients with a large ischemic core in the 90-day follow-up. However, the 1-year outcome comparison between EVT and MM in Asian patients with a large ischemic core has not been investigated. Our aim was to evaluate the 1-year outcomes of patients in the ANGEL-ASPECT trial (Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core). METHODS: In this phase 3, randomized, open-label, blinded end point assessment trial, patients with anterior circulation large vessel occlusion and an Alberta Stroke Program Early CT Score of 3 to 5 or an infarct core volume of 70 to 100 mL were enrolled across 46 hospitals in China. Patients were randomly assigned 1:1 to EVT or MM. The 90-day outcomes were previously reported. We report a prespecified analysis of the ANGEL-ASPECT trial, with 1-year functional outcome as the primary outcome in this study. The primary outcome was the shift of the modified Rankin Scale (mRS) score (range, 0–6, with a higher score reflecting greater disability) to better outcomes at 1-year. The secondary outcomes included functional independence (mRS score, 0–2), independent ambulation (mRS score, 0–3), and mortality. This trial is registered with https://www.clinicaltrials.gov (Unique identifier: NCT04551664). RESULTS: One-year data were available for 425 of 455 (93%) patients for the primary outcome, with 214 patients in the EVT group and 211 in the MM group in the complete case analysis. The mean age was 66 years, and 38.1% were female. There was a greater likelihood of shift toward improved 1-year mRS distribution in the EVT compared with the MM group (generalized odds ratio, 1.25 [95% CI, 1.01–1.56]; P =0.04). Functional independence and independent ambulation were higher in the EVT compared with MM groups (mRS score, 0–2: 30.4% [65/214] versus 17.1% [36/211]; relative risk, 1.87 [95% CI, 1.27–2.75]; mRS score, 0–3: 50.0% [107/214] versus 35.6% [75/211]; relative risk, 1.46 [95% CI, 1.15–1.85], respectively). The 1-year mortality rate was 31.3% (67/214) in the EVT group and 26.5% (56/211) in the MM group (relative risk, 1.12 [95% CI, 0.82–1.53]). In addition, no change was found in the rate of functional independence between 90 days and 1 year in the EVT group (29.4% [69/214] versus 30.4% [65/214], respectively); however, a gain in functional independence was observed in the MM group from 90 days to 1 year (10.9% [26/211] versus 17.1% [36/211]), narrowing the magnitude of EVT treatment effect from 18.5% at 90 days to 13.3% at 1 year. CONCLUSIONS: In patients with large ischemic stroke from a proximal arterial occlusion presenting within 24 hours of onset, EVT reduced disability with durable 1-year benefit compared with MM. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04551664.

Background: Intracranial atherosclerotic stenosis (ICAS) is a common cause of first and recurrent ischemic stroke worldwide. Circular RNAs (circRNA)s have been recently suggested as candidate biomarkers in diagnosing and prognosis of ischemic stroke. A few circRNAs even serve as therapeutic targets that improves neurological function after ischemic stroke. However, the roles of circRNAs in ICAS caused ischemic stroke (ICAS-stroke) have not been fully understood. Therefore, in this study, we attempted to find some clues by investigating the different expression profiles of circRNAs between patients diagnosed with ICAS-stroke and normal control (NC)s.Methods: The OE Biotech Human ceRNA Microarray 4 × 180 K (47, 899 probes) screened circRNAs differentially expressed in peripheral blood in a discovery cohort (5 NCs versus five patients with ICAS-stroke). Afterwards, a validation cohort (31 NCs versus 48 patients with ICAS-stroke) was performed by quantitative polymerase chain reaction (qPCR). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and CircRNA–microRNA-mRNA interaction network was performed to identify potential interactions with microRNAs and pathway-deregulated circRNAs.Results: There were 244 circRNAs differentially expressed in patients diagnosed with ICAS-stroke compared with NCs [fold change (FC) ≥ 2.0 and p-value<0.05]. Among the 244 circRNAs, 5 circRNAs (hsa_circ_0003574, hsa_circ_0010509, hsa_circ_0026628, hsa_circ_0074057, hsa_circ_0016993) were selected for following verification by qPCR. Only hsa_circRNA_0003574 was significantly upregulated in patients than in NCs. GO analysis indicated that predicted target genes involved various biological processes, cellular components, and molecular functions. KEGG analysis showed that many genes were enriched within the arginine and proline metabolism, pyrimidine metabolism, arginine and proline metabolism, lysosome, cytokine-cytokine receptor interaction, and RNA transport. The circRNA-miRNA-mRNA network analysis show the miRNAs that has_circ_0003574 likely interacts with.Conclusion: We observed that hsa_circRNA_0003574 is upregulated in patients with ICAS-stroke compared with NCs, indicating it may be a potential novel biomarker and therapeutic target for ICAS-stroke. In addition, we analyzed the laboratory results and found that homocysteine and glycosylated hemoglobin were elevated among ICAS-stroke patients. The relationship between hsa_circRNA_0003574 and these parameters requires further investigation.

Ischemic stroke (IS) remains a serious threat to human health. Neuroinflammatory response is an important pathophysiological process after IS. Circular RNAs (circRNAs), a member of the non-coding RNA family, are highly expressed in the central nervous system and widely involved in regulating physiological and pathophysiological processes. This study reviews the current evidence on neuroinflammatory responses, the role of circRNAs in IS and their potential mechanisms in regulating inflammatory cells, and inflammatory factors affecting IS damage. This review lays a foundation for future clinical application of circRNAs as novel biomarkers and therapeutic targets.

Circular RNAs (circRNAs) are novel noncoding RNAs that play regulatory roles in gene expression. Dysregulation of circRNAs is associated with the development and progression of several diseases, such as diabetes mellitus, nervous system diseases, cardiovascular diseases, and cancer. CircRNAs functionally participate in cell physiological activities through various molecular mechanisms. However, these molecular mechanisms are unclear. Oxidative stress is an essential factor in the pathogenesis of various diseases, including neurological diseases. Emerging roles of circRNAs have been identified in different systems in response to oxidative stress. In this review, we summarize the current understanding of circRNA biogenesis, properties, expression profiles, and the clues indicating the regulatory roles of circRNAs through oxidative stress in various systems, especially the nervous system.