构建circ_UBE3/miR-16-5p、let-7b-5p为核心的儿童哮喘加重危险度预测评估模型与实证研究

儿童期哮喘加重(CAE)严重危害儿童的身心健康，CAE防控是儿童哮喘治疗的首要目标，申请人发现颗粒物(PM)暴露与CAE显著相关，PM高暴露CAE的巨噬细胞外泌体(MEV)circ_UBE3高表达，MEV与气道上皮细胞(BEC)共培养，发现circ_UBE3结合的miR-16-5p、let-7b-5p低表达，BEC炎症反应和细胞增殖显著,可能诱发CAE。基于一系列生物信息学预测与前期验证，本研究拟：明确circ_UBE3、miR-16-5p、let-7b-5p是巨噬细胞与BEC在PM暴露致CAE中通信的关键因子，阐明circ_UBE3结合miR-16-5p/let-7b-5p靶向调控PGAP3在PM高暴露致CAE过程中的作用机制，利用队列人群构建基于circ_UBE3、miR-16-5p、let-7b-5p的CAE危险度评估模型，为CAE的早期预警和精准防控提供重要的理论和实验依据。

Childhood Asthma Exacerbation(CAE) seriously damage children's physical and mental health. CAE prevention is the primary goal of the childhood asthma treatment. Our study found particulate matter(PM) exposure was significantly associated with CAE occurrence in Northeast China. Preliminary experiments found high expression of circ_UBE3 in macrophage exosome vesicles(MEV) in CAE with high PM exposure. Co-culture of MEV with bronchial epithelial cell(BEC) after PM exposure found low expressions of miR-16-5p and let-7b-5p as well as increased inflammation and proliferation in BEC. We also found high expression of circ_UBE3 and low expressions of miR-16-5p and let-7b-5p in children of CAE with high PM exposure in our cohort. Based on a series bio-informatic prediction and preliminary verification, we aim to clarify the key factors of circ_UBE3, miR-16-5p and let-7b-5p between Alveolar Macrophage and Bronchial Epithelial Cell communication in CAE caused by PM exposure, and illuminate the molecular mechanism of circ_UBE3 binding miR-16-5p/let-7b-5p and regulating PGAP3 in CAE caused by PM exposure, finally we will construct CAE risk prediction model based on circ_UBE3, miR-16-5p and let-7b-5p, which might provide scientific evidence for early prediction and precise prevention for CAE.