Background: Although several studies have compared conscious sedation (CS) with general anesthesia (GA) in patients undergoing mechanical thrombectomy (MT), there has been no affirmative conclusion. We conducted this trial to assess whether CS is superior to GA for patients undergoing MT for acute ischemic stroke (AIS).Methods: Acute ischemic stroke patients with anterior circulation large vascular occlusion were randomized into two groups. The primary outcome was modified Rankin scale score (0-2) at 90 days after stroke. Secondary outcomes included intraprocedural hemodynamics, time metrics, successful recanalization, neurointerventionalist satisfaction score, National Institutes of Health Stroke Scale (NIHSS) score, and Alberta Stroke Program Early CT Score (ASPECTS) at 48 h post-intervention, mortality at discharge and 3 months after stroke, and complications.Results: Compared with the CS group, heart rate was significantly lower at T1-T8 in the GA group except at T4 (P < 0.05). Mean arterial pressure (MAP) and systolic blood pressure were significantly lower in the GA group at T4-T6 and T9 (P < 0.05). Pulse oxygen saturation was significantly higher at T2-T9 in the GA group (P < 0.05). There were no significant differences in time metrics, vasoactive drug use, occurrence of >20% fall in MAP, pre-recanalization time spent with >20% fall in MAP, neurointerventionalist satisfaction, successful recanalization rate, NIHSS, and ASPECTS scores at 48 h post-intervention, and mortality rate at discharge and 3 months after stroke (P > 0.05). The cerebral infarction rate at 30 days was greater in the CS group, but not significantly (P > 0.05). There were no differences in complication rates except for pneumonia (P > 0.05). Conversion rate from CS to GA was 9.52%. Conclusion:Anesthetic management with GA or CS during MT had no differential impact on the functional outcomes and mortality at discharge or 3 months after stroke in AIS patients, but CS led to more stable hemodynamics and lower incidence of pneumonia.

F-box and WD repeat domain-containing 7 (FBW7), the substrate-binding subunit of E3 ubiquitin ligase SCF FBW7 (a complex of SKP1, cullin-1 and FBW7), plays important roles in various physiological and pathological processes. Although FBW7 is required for vascular development, its function in the endothelium remains to be investigated. In this study, we show that FBW7 is an important regulator of endothelial functions, including angiogenesis, leukocyte adhesion and the endothelial barrier integrity. Using RNA interference, we found that the depletion of FBW7 markedly impairs angiogenesis in vitro and in vivo. We identified the zinc finger transcription factor Krüppel-like factor 2 (KLF2) as a physiological target of FBW7 in endothelial cells. Knockdown of FBW7 expression resulted in the accumulation of endogenous KLF2 protein in endothelial cells. FBW7-mediated KLF2 destruction was shown to depend on the phosphorylation of KLF2 via glycogen synthase kinase-3 (GSK3) at two conserved phosphodegrons. Mutating these phosphodegron motifs abolished the FBW7-mediated degradation and ubiquitination of KLF2. The siRNAmediated knockdown of FBW7 showed that KLF2 is an essential target of FBW7 in the regulation of endothelial functions. Moreover, FBW7-mediated KLF2 degradation was shown to be critical for angiogenesis in teratomas and in zebrafish development. Taken together, our study suggests a role for FBW7 in the processes of endothelial cell migration, angiogenesis, inflammation and barrier integrity, and provides novel insights into the regulation of KLF2 stability in vivo.

Background:The role of cannabinoid receptor type 2 (Cnr2) in regulating immune function had been widely investigated, but the mechanism is not fully understood. Results: Cnr2 activation down-regulates 5-lipoxygenase (Alox5) expression by suppressing the JNK/c-Jun activation. Conclusion: The Cnr2-JNK-Alox5 axis modulates leukocyte inflammatory migration. Significance: Linking two important regulators in leukocyte inflammatory migration and providing a potential therapeutic strategy for treating human inflammation-associated diseases.