The study suggested for the first time that nongenomic pathway was involved in GCs' rapid inhibition on allergic asthma, and raised the possibility of new therapeutic strategies for allergic diseases including asthma.

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Glucocorticoids (GCs) are routinely believed to work solely through genomic mechanisms. Recent evidence indicates that GCs can act at the membrane to exert rapid nongenomic effects on various tissues and cells. To ascertain whether nongenomic effects of GCs exist on the allergic asthma reaction, Hartley guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received inhaled budesonide (3 mg/ml suspended in Hydroxypropyl methylcellulose vehicle) for 5 minutes before ovalbumin challenge; Other animals received saline or blank vehicle as control. We measured the changes of lung resistance and dynamic lung compliance, the pulmonary function used to evaluate allergic asthma severity. Inhaled budesonide inhibited allergic reaction within 10 minutes, which would preclude genomic-mediated responses that normally takes several hours to occur. This study infers for the first time that rapid nongenomic effect of GCs exists on allergic asthma reaction, and provides a new way to investigate nongenomic mechanism of GCs. Further study would raise the possibility of new therapeutic strategies for allergic disease including asthma.

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Background and Objective: Branch atheromatous disease (BAD) is distinctive from large-artery atherosclerosis and small-vessel disease, which is single subcortical infarction caused by the occlusion of perforator's orifice. This study aimed to indicate whether intravenous thrombolysis (IVT) with alteplase could prevent early neurological deterioration (END) and improve functional outcome for patients with BAD within 4.5 h after symptom onset. Methods: We retrospectively analyzed data collected from patients with BAD who were admitted to our hospital from January 2015 to August 2019. To investigate the efficacy and safety of IVT, subjects were classified into alteplase and control groups. A propensity score matching analysis was performed to control substantial heterogeneity of subgroup. The coprimary outcomes were END that is defined as an increase of ≥2 points in the National Institutes of Health Stroke Scale (NIHSS) score within 7 days after stroke, and favorable outcome at 3 months after stroke that defined by a score of 0–1 point on the modified Rankin scale (mRS). Results: A total of 135 patients were eventually enrolled in this study ( n = 51 for the alteplase group and n = 84 for the control group). Additionally, 42 pairs of subjects were successfully matched by propensity score matching. Intravenous alteplase within 4.5 h after stroke onset reduced the incidence of END [unadjusted odds ratio (OR), 3.32; 95% confidence interval (CI), 1.06–10.37] and improved the clinical outcome at 3 months after stroke, with more patients achieving favorable functional prognosis (mRS, 0–1 point; unadjusted OR, 0.25; 95% CI, 0.10–0.62). Patients in the alteplase group were more likely to be independent (mRS, 0–2 points) at 3 months after stroke (unadjusted OR, 0.33; 95% CI, 0.12–0.90). The rate of death or dependence (mRS, ≥4 points) in the alteplase group was also markedly lower than that in the control group (unadjusted OR, 4.06; 95% CI, 1.03–16.02). Conclusion: Our findings indicated that intravenous thrombolysis may be a safe and effective therapy for patients with BAD.

Glucocorticoids are steroids endowed with powerful anti-inflammatory properties, which are routinely believed to require several hours to take effect through modulation of gene expression. Our recent report has shown that glucocorticoids could inhibit allergic reaction within 10 minutes, which the classical genomic mechanism could not explain. Histamine is thought to be one of major mediators in the allergic reaction, and IgE-mediated histamine release from mast cells plays a pivotal role in allergic diseases. Here, we have determined a rapid effect of corticosterone on histamine release from rat peritoneal mast cells, using fluorometric assay. The results showed that corticosterone could inhibit antigen-induced histamine release from rat peritoneal cells within 15 minutes (p<0.05), which could be mimicked by membrane-impermeable BSA conjugated corticosterone (p<0.05). Neither glucocorticoid nuclear receptor antagonist nor protein synthesis inhibitor could block the rapid action (p<0.05). The study provided evidence that nongenomic mechanism might be involved in rapid effect of glucocorticoids on mast cells in allergic disease.

BackgroundAcute basilar artery occlusion (BAO) is the most potentially disastrous outcome and has a high risk of recurrence stroke in posterior circulation infarction (PCI). However, the rate of futile recanalization remains high despite successful recanalization. The objective of this study was to investigate 90 days functional outcomes among patients with BAO who underwent endovascular thrombectomy (EVT) and to identify the risk factors associated with futile recanalization.MethodsWe retrospectively analyzed 72 patients with acute BAO who received EVT from January 2018 to June 2021. CT angiography source images posterior circulation Acute Stroke Prognosis Early CT Score (CTA-SI pc-ASPECTS) evaluated the extensive hypoattenuation in patients with BAO. Futile recanalization defined an modified Rankin Scale (mRS) of 3-6 at 90 days despite a successful recanalization. Logistic regression analysis was performed to investigate the predictors of futile recanalization.ResultsOur sample included a total of 55 eligible patients. Patients with poor outcomes showed that the pc-ASPECTS score was lower in patients with poor outcomes than that in patients with good outcomes (P = 0.017). Longer time from symptoms onset-to-the puncture (P = 0.014) and elevation of leucocytes (P = 0.012) were associated with poor outcomes. The multivariable logistic analysis showed that pc-ASPECTS and onset-to-puncture time (OPT) were independent predictors of futile recanalization.ConclusionsThis study suggested that pc-ASPECTS and OPT are independent predictors of futile recanalization after EVT in patients with BAO. The lower pc-ASPECTS score and longer puncture time will have a poor clinical outcome.

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