Objective: The efficacy of antidepressants is influenced by a combination of genetic, individual, and environmental factors. This study aimed to investigate the association between the miR-182 rs76481776 polymorphism and the response to antidepressant treatment in major depressive disorder (MDD) patients, and its underlying molecular mechanisms. Methods: This study enrolled 180 MDD patients and 180 healthy controls. The rs76481776 genotype was determined using TaqMan-based qPCR. The severity of depression and treatment response were assessed using the Hamilton Depression Rating Scale (HAMD). The expression of miR-182 and BDNF was measured using RT-qPCR. The regulatory relationship between miR-182 and BDNF was confirmed through a luciferase reporter gene assay. The correlation between miR-182 and BDNF expression was evaluated using the Pearson correlation coefficient. Results: The T allele of rs76481776 was a significant risk factor for MDD (OR = 2.182, 95% CI: 1.424−3.345, p ＜ 0.001) and was significantly associated with higher baseline scores on the HAMD. Moreover, individuals carrying the T allele (CT/TT genotype) exhibited a significantly poorer response to antidepressant treatment and a lower remission rate within 12 months compared to those with the CC genotype (p ＜ 0.05). Mechanistically, miR-182 was highly expressed in patients with MDD (p ＜ 0.05), and its expression was even higher in T allele carriers (p ＜ 0.05). miR-182 could directly target and suppress BDNF, leading to decreased BDNF expression in MDD patients, and its expression was significantly and inversely correlated with BDNF expression. Conclusion The T allele of rs76481776 diminished the therapeutic efficacy of antidepressants by up-regulating miR-182 expression and subsequently suppressing BDNF expression.

Objective To examine the prognostic value of flow diversion (FD) presented on transcranial Doppler ultrasound (TCD) in patients with large hemispheric infarction (LHI) caused by the unilateral middle cerebral artery (MAC) occlusion.Methods Seventy-three consecutive LHI patients who had occlusion in M1 segment of MAC and were admitted to neurological intensive care unit at Xijing Hospital from January 2012 to June 2016 were reviewed.All the participants had TCD examination after admission,and were grouped according to the presence or absence of FD into FD+ and FD-.Three-month,six-month,and twelve-month functional outcomes of all the participants were collected and analyzed.Long-term survival rates were compared using Kaplan-Meier survival analysis.Receiver operating characteristic curve (ROC) was used to examine the predictive power of FD in patients with LHI.Results Among 73 LHI patients,28 (38.36％) patients were presented with FD.The incidence rates of cerebral herniation,usage of mechanical ventilation,mortality during hospitalization and incidence rates of three-month,six-month and twelve-month poor outcomes were much higher in patients without FD than those with FD.Multivariate analyses demonstrated that FD was independently associated with cerebral herniation (OR=28.943,95％CI 1.922-435.918,P=0.015),usage of mechanical ventilation (OR=11.151,95％CI 1.614-77.018,P=0.014),three-month (OR=20.163,95％CI 3.048-133.362,P=0.002),six-month (OR=3.525,95％CI 1.153-10.773,P=0.027),and twelve-month (OR=4.400,95％CI 1.387-13.960,P=0.012) poor outcomes.FD yielded an area under the ROC of 0.756,allowing for prediction of three-month outcomes of LHI.Conclusion FD presented on TCD is an early predictor of outcomes in patients with LHI.