RESCUE BT Trial Investigators E ndovascular treatment has been shown to significantly increase the reperfusion rate and improve the functional outcomes of patients with acute ischemic stroke due to large vessel occlusion. [1][2][3][4] However, endovascular thrombectomy has historically failed to yield successful reperfusion in approximately 30% of patients. 5 Unsuccessful reperfusion likely arises in part from mechanical thrombectomy devices causing traumatic damage to the vascular endothelium with subendothelial matrix exposure, leading to platelet activation, adhesion, and aggregation and potentially resulting in reocclusion and thromboembolic complications. 6,7 Tirofiban, a highly selective nonpeptide platelet glycoprotein IIb/IIIa inhibitor with a relatively short half-life that can reversibly prevent platelet aggregation, has been proven to reduce the risk of thrombotic complications during percutaneous coronary intervention. [8][9][10] Given the benefit of treatment of acute coronary syndromes, a growing number of studies have evaluated tirofiban as an adjunctive treatment in patients with large vessel occlusion ischemic stroke IMPORTANCE Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy.OBJECTIVE To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion.DESIGN, SETTING, AND PARTICIPANTS This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well.

Intracerebral haemorrhage (ICH) is a devastating subtype of stroke with high morbidity and mortality. It has been reported that paeonol (PAN) inhibits the progression of ICH. However, the mechanism by which paeonol mediates the progression of ICH remains unclear. To mimic ICH in vitro, neuronal cells were treated with hemin. An in vivo model of ICH was established to detect the effect of paeonol on ferroptosis in neurons during ICH. Cell viability was tested by MTT assay. Furthermore, cell injury was detected by GSH, MDA and ROS assays. Ferroptosis was examined by iron assay. RT-qPCR and western blotting were used to detect gene and protein expression, respectively. The correlation among HOTAIR, UPF1 and ACSL4 was explored by FISH, RNA pull-down and RIP assays. Paeonol significantly inhibited the ferroptosis of neurons in ICH mice. In addition, paeonol significantly reversed hemin-induced injury and ferroptosis in neurons, while this phenomenon was notably reversed by HOTAIR overexpression. Moreover, paeonol notably inhibited ferroptosis in hemin-treated neuronal cells via inhibition of ACSL4. Additionally, HOTAIR bound to UPF1, and UPF1 promoted the degradation of ACSL4 by binding to ACSL4. Furthermore, HOTAIR overexpression reversed paeonol-induced inhibition of ferroptosis by mediating the UPF1/ACSL4 axis. Paeonol inhibits the progression of ICH by mediating the HOTAIR/UPF1/ACSL4 axis. Therefore, paeonol might serve as a new agent for the treatment of ICH.

Psoralen (PSO) exerts anti-inf lammatory pharmacological effects and plays an important role in a variety of inflammatory diseases. However, the effects of PSO with allergic rhinitis (AR) are yet to be reported. In the present study, an in vitro AR model was generated by inducing JME/CF15 human nasal epithelial cells with IL-13, after which MTT was used to assess the cytotoxicity of PSO. The expression levels of inflammatory cytokines (granulocyte-macrophage colony-stimulating factor and Eotaxin) were determined by ELISA. Furthermore, the expression of inflammatory IL-6 and -8, as well as mucin 5AC, was assessed by reverse transcription-quantitative PCR and western blotting, and cellular reactive oxygen species were detected using a 2',7'-dichlorodihydrofluorescein diacetate fluorescent probe. Western blotting was also used to detect the expression and phosphorylation of c-Fos and c-Jun in the activator protein 1 (AP-1) pathway, as well as the expression of cystatin-SN (CST1). PSO inhibited the inflammatory response and mucus production in IL-13-induced JME/CF15 cells. Furthermore, the levels of c-Fos and c-Jun phosphorylation in the AP-1 pathway were decreased in IL-13-induced JME/CF15 cells following PSO treatment. The expression of pathway proteins was activated by the addition of PMA, an AP-1 pathway activator, which concurrently reversed the inhibitory effects of PSO on the inflammatory response and mucus formation. The addition of an AP-1 inhibitor (SP600125) further inhibited pathway activity, and IL-13-induced inflammation and mucus formation was restored. In conclusion, PSO regulates the expression of CST1 by inhibiting the AP-1 pathway, thus suppressing the IL-13-induced inflammatory response and mucus production in nasal mucosal epithelial cells.

BACKGROUND:It is estimated that >50% of acute basilar artery occlusion (ABAO) patients with successful reperfusion after endovascular treatment (EVT) have futile recanalization. However, few studies investigated the reasons behind this.OBJECTIVE:To identify the factors associated with futile recanalization in ABAO after successful reperfusion.METHODS:We recruited patients with successful reperfusion (expanded Thrombolysis In Cerebral Infarction score of ≥2b) after EVT from the Basilar Artery Occlusion Study registry. Patients were divided into meaningful recanalization (90-day modified Rankin Scale 0-3) and futile recanalization (90-day modified Rankin Scale 4-6) groups. Multivariable logistic regression analyses were used to identify the predictors of futile recanalization.RESULTS:A total of 522 patients with successful reperfusion were selected. Of these, 328 patients had futile recanalization and 194 had meaningful recanalization. Multivariable logistic regression shows that higher neutrophil-to-lymphocyte ratio (P = .01), higher baseline National Institutes of Health Stroke Scale score (P < .001), longer puncture to recanalization time (P = .02), lower baseline posterior circulation Alberta Stroke Program Early CT score (P < .001), lower posterior circulation collateral score (P = .02), incomplete reperfusion (P < .001), and diabetes mellitus (P < .001) were predictors of futile recanalization.CONCLUSION:Higher neutrophil-to-lymphocyte ratio, longer puncture to recanalization time, incomplete reperfusion, stroke severity, lower baseline posterior circulation Alberta Stroke Program Early CT score, poor collaterals, and diabetes mellitus were independent predictors of futile recanalization in patients with ABAO with successful reperfusion after EVT. Moreover, multiple stent retriever passes were associated with a high proportion of futile recanalization in patients with late time windows.