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关键词： Cardiovascular disease   Carotid intima-media thickness   Carotid plaque   Metabolic syndrome  

摘要： Objective To investigate the effect of changes in metabolic syndrome status and persistence on carotid plaque risk. Methods This retrospective cohort study analyzed individuals who underwent routine health check-ups at the health management center of the Second Affiliated Hospital of Dalian Medical University from 2014 to 2023. Participants with at least three carotid ultrasound records meeting the inclusion criteria were classified into 4 groups based on changes in metabolic status: persistently metabolic health, transitioning from metabolic health to unhealth, transitioning from metabolic unhealth to health, and persistently metabolic unhealth. The cumulative incidence of carotid plaque in these groups was compared. A Cox proportional risk model was used to evaluate the relationship between changes in metabolic syndrome status, the number of metabolic syndrome components, and the risk of carotid plaque development. Restricted cubic spline analysis was applied to explore the association between changes in individual metabolic syndrome components and carotid plaque risk. Results Compared to the persistently metabolic health group, the persistent unhealth group had the highest risk of developing carotid plaque(HR=1.35, 95%CI 1.05-1.74, P=0.021), followed by those who transitioned from metabolic health to unhealth and those who improved from metabolic unhealth to health. Furthermore, the risk of carotid plaque increased progressively with the number of metabolic syndrome components. Restricted cubic spline analysis revealed a nonlinear relationship between fasting blood glucose change and carotid plaque risk, while systolic blood pressure, diastolic blood pressure, waist circumference, triglycerides, and high-density lipoprotein-cholesterol showed a linear dose-response relationship with carotid plaque. Conclusions The change of metabolic syndrome is associated with the risk of developing carotid plaque, and maintaining metabolic health, recovering from metabolic synd

关键词： 改良型新药   505(b)(2)途径   高端制剂   临床优势   临床需求  

摘要： 化药注册分类2.2类新药是一大类介于创新药和仿制药之间的改良型新药的统称,其部分有效性和安全性证据可借鉴已上市药物信息,其中的高端制剂因技术壁垒高、市场潜力大,已成为药企研发重点.该类药物需基于临床需求,通过构建高端制剂平台、筛选适宜活性分子及优化开发路径,实现临床优势的高效验证.然而,如何将临床需求、技术平台与分子特性这三者进行精准匹配,仍是行业的痛点和难点.对高端制剂进行定义,剖析临床优势内涵,创新性提出"五段论"临床开发辅助工具,从临床价值定位、分子选择、制剂平台优化到临床开发路径设计,全面阐述高端制剂的开发策略,旨在为国内药企突破制剂技术瓶颈、实现产业升级提供思路与参考.

摘要： "主体行为原因类"思想政治主观题让考生探究某个主体行使某种行为的原因,即某主体为什么做某件事.此类试题是高考的常考题型,考查考生的信息获取与加工能力和逻辑思维能力,对考生要求较高.行为主体可以是个人(如法律关系当事人等),可以是党政机关、社会团体、企业,也可以是国家、国际组织等.主体的行为可以是具体行动(如脱贫攻坚、科技创新、企业发展、法治建设、文化传承、国际交往等),也可以是抽象行动(如制定政策、作出决定、提出主张等).主体的行为有时候是单一的,即行使了一个行为;有时候是复杂的,即行使了多个行为.