PURPOSE. To explore the causal links between antihypertension drugs usage and age-related macular degeneration (AMD). METHODS. Multiple genetic analyses, including summary data-based Mendelian randomization (SMR), traditional MR, and colocalization analysis, were used to explore the causal associations between antihypertension drugs and AMD. Clinical data from the UK Biobank and the National Health and Nutrition Examination Survey (NHANES) was applied to refined risk assessment of specific antihypertensive medications in the context of AMD development. In vitro and in vivo oxidative stress models, mediated by NaIO3, were utilized to study the impact of specific antihypertensive drugs and target genes on AMD pathogenesis. RESULTS. Genetic analyses substantiated the causal relationship between increased SLC12A3 expression and a lowered AMD risk. Colocalization analysis supported the shared causal attributes between SLC12A3 expression and AMD. Cross-sectional analysis results based on UK Biobank indicated that AMD risk was significantly lower in participants taking thiazide diuretics with other antihypertensives or not on antihypertensives compared to those on thiazides alone. The results based on NHANES support the above results. In vivo and in vitro experiments showed that thiazide diuretics worsened retinal damage in AMD mouse models, and SLC12A3 knockdown disrupted the balance of oxidative stress in retinal pigment epithelium (RPE) cells. Further molecular mechanism experiments showed that SLC12A3 knockdown promoted retinal degeneration by regulating RPE ferroptosis through activation of the Nrf2/HO-1 pathway. CONCLUSIONS. Our study underscores a notable causal association between thiazide diuretic use and AMD risk and reveals a potential mechanism by which inhibition or downregulation of SLC12A3 (sodium-chloride cotranspor ter [NCC]) contributes to AMD progression. However, deeper exploration is needed to enhance the accuracy and validity of our findings.

Background: Taking thrombosis and bleeding risks into consideration, little real world study data is available to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in elderly Chinese chronic total occlusion (CTO) patients. Objective: This study was designed to investigate the effectiveness and safety of Ticagrelor in comparison with Clopidogrel as an add-on therapy to Aspirin for elderly Chinese CTO patients who underwent elective PCI. Materials and Methods: We retrospectively enrolled 504 CTO patients (aged ≥75 years) who received PCI from December 2009 to May 2020 and DAPT for up to 12 months. The effectiveness endpoints were evaluated by major adverse cardiac events (MACE) including all-cause death, nonfatal myocardial infarction (MI) and clinically driven revascularization. The safety endpoints were recorded as the incidence of Bleeding Academic Research Consortium (BARC) bleeding. Results: Patients in Clopidogrel group, as was evidenced in our study, were older, and had a higher percentage of BMI, diastolic blood pressure and HDL-C than those in Ticagrelor group. Clopidogrel group had a lower percentage of hyperlipidemia, prior PCI, glucose, TG and LDL-C. No significant difference was found as to the Angiographic and procedural characteristics (P＞0.05 for all). After 12 months' follow-up, the incidence of MACE (12.19% vs. 11.04%, P=0.763) and bleeding (9.38% vs. 13.64%, P=0.205) showed no significant difference. After clinical characteristics balanced matching by inverse probability of treatment weighting (IPTW) model, we found that Ticagrelor had an unfavorable effect on reducing the incidence of bleeding with the IPTW model (IPTW-OR, 1.81, 95% CI: 1.18-2.76, P=0.006). Conclusions: Clopidogrel and Ticagrelor present similar effectiveness and safety to elderly Chinese CTO-PCI patients, yet Ticagrelor should be prescribed with caution to patients with a high bleeding risk.

巨噬细胞是机体内主要的炎症效应细胞,一般可分化为促炎(M1)型和抗炎(M2)型两大类,针对巨噬细胞极化调控成为炎症相关疾病治疗的新靶点.研究表明,过氧化物酶体增殖物激活受体-γ(PPAR-γ)作为一个配体激活的核转录因子,可抑制M1型巨噬细胞促炎信号通路的启动,并促进M2型巨噬细胞抗炎信号的表达.本文主要综述了PPAR-γ在巨噬细胞抗炎症反应中的关键作用,以及PPAR-γ激动剂在脓毒症、肠道炎症、代谢性炎症和自身免疫性炎症疾病治疗中的应用,以期为相关基础研究和临床用药提供指导.

Taking ischemic and bleeding risks into consideration, insufficient data exist on dual antiplatelet therapy after percutaneous coronary intervention in elderly Chinese patients with coronary artery disease. We aimed to investigate the effectiveness and safety of ticagrelor in comparison with clopidogrel on a background of aspirin for elderly Chinese patients with coronary artery disease 12 months after percutaneous coronary intervention. A single-center retrospective cohort study was conducted. Selected from patients with coronary artery disease aged ≥ 75 years from January 2010 to July 2019, 908 eligible subjects receiving dual antiplatelet therapy after percutaneous coronary intervention for up to 12 months were consecutively enrolled in the study. The included patients received ticagrelor in combination with aspirin (n = 264) or clopidogrel in combination with aspirin (n = 644). Effectiveness endpoints were evaluated by the major adverse cardiovascular events, encompassing all-cause death, non-fatal myocardial infarction, and clinically driven revascularization. The safety endpoints were recorded as the incidence of Bleeding Academic Research Consortium bleeding. The patients who were treated with ticagrelor were slightly younger than those who were treated with clopidogrel (79.1 ± 3.7 vs 80.7 ± 4.5 years, p < 0.01). The ticagrelor cohort contained a higher percentage of patients undergoing a prior percutaneous coronary intervention (37.9% vs 24.5%, p < 0.01), and a lower percentage of smokers (19.3% vs 27.2%, p < 0.05), compared with the clopidogrel cohort. The levels of glucose, total cholesterol, and low-density lipoprotein-cholesterol in the ticagrelor group were higher while the level of triglycerides and high-density lipoprotein-cholesterol were lower (p < 0.05) than those in the clopidogrel group. Left main percutaneous coronary intervention was performed more frequently among the ticagrelor-treated patients (23.5% vs 9.3%, p < 0.01), while patients in the clopidogrel group underwent more left circumflex percutaneous coronary intervention (34.3% vs 23.1%, p < 0.01). We found that ticagrelor was associated with a lower incidence of major adverse cardiovascular events than clopidogrel using the inverse probability of treatment weighting model (odds ratio, 0.493; 95% confidence interval 0.356–0.684). There was no difference in terms of the risk of Bleeding Academic Research Consortium bleeding between the two groups (p > 0.05). Ticagrelor was associated with a lower incidence of major adverse cardiovascular events than clopidogrel at 12 months in elderly Chinese patients with coronary artery disease, without a significant increase of Bleeding Academic Research Consortium bleeding events.

According to numerous animal studies, adverse environmental stimuli, including physical, chemical, and biological factors, can cause low-grade chronic inflammation and subsequent tumor development. Human epidemiological evidence has confirmed the close relationship between chronic inflammation and tumorigenesis. However, the mechanisms driving the development of persistent inflammation toward tumorigenesis remain unclear. In this study, we assess the potential role of reactive oxygen species (ROS) and associated mechanisms in modulating inflammation-induced tumorigenesis. Recent reports have emphasized the cross-talk between oxidative stress and inflammation in many pathological processes. Exposure to carcinogenic environmental hazards may lead to oxidative damage, which further stimulates the infiltration of various types of inflammatory cells. In turn, increased cytokine and chemokine release from inflammatory cells promotes ROS production in chronic lesions, even in the absence of hazardous stimuli. Moreover, ROS not only cause DNA damage but also participate in cell proliferation, differentiation, and apoptosis by modulating several transcription factors and signaling pathways. We summarize how changes in the redox state can trigger the development of chronic inflammatory lesions into tumors. Generally, cancer cells require an appropriate inflammatory microenvironment to support their growth, spread, and metastasis, and ROS may provide the necessary catalyst for inflammation-driven cancer. In conclusion, ROS bridge the gap between chronic inflammation and tumor development; therefore, targeting ROS and inflammation represents a new avenue for the prevention and treatment of cancer.

目的 观察PCSK9抑制剂对超高危动脉粥样硬化性心血管疾病(atherosclerotic cardiovascular disease,ASCVD)患者的降脂治疗有效性与安全性.方法 收集2017年9月～2020年3月于空军军医大学第一附属医院接受PCI治疗的超高危ASCVD患者138例,划分为术后单纯他汀类药物降脂治疗的他汀对照组(n=100)和他汀联合PCSK9降脂治疗的PCSK9抑制剂组(n=38).用药3月后复查血脂水平,观察血脂降幅及药物不良反应发生情况.结果 两组患者年龄、BMI、收缩压、舒张压等多项指标差异无统计学意义.与他汀对照组比较,PCSK9抑制剂组的男性比例低,既往心肌梗死病史率低,多次PCI史率低(P＜ 0.01),多血管床病变率低,术后应用β-受体阻滞剂率低(P＜0.05).接受降脂治疗后与他汀对照组比较,PCSK9抑制剂组LDL-C明显降低,其中低密度脂蛋白胆固醇(LDL-C)(＜1.4 mmol/L)组和LDL-C平均降幅降低程度的统计学差异为(P＜0.01),LDL-C(＜ 1.8 mmol/L)组降低的统计学差异为(P＜0.05).所有患者均未观察到肝肾功损害及血糖升高,PCSK9抑制剂组患者未观察到药物不良反应的发生.结论 PCSK9抑制剂能够有效降低超高危ASCVD患者的LDL-C水平,显著提高其LDL-C达标率,具有良好的有效性和安全性.

视频剪辑作为《大学计算机基础》课程的重要组成部分,旨在使学生熟悉常用的视频剪辑软件,掌握非线性编辑、素材管理、转场添加及字幕制作等视频剪辑技巧,并应用所学技术制作视频作品.其中,素材搜集是进行视频剪辑的重要基础,但许多来源于网络的视频素材存在水印和字幕,严重影响视频剪辑作品的质量和效果.对此,介绍利用Vegas 16.0软件去除水印和字幕的几种方法和技巧,以期加深读者对Vegas 16.0软件功能与应用的理解,并为后续课程教学及教研保障活动提供经验和思路.

JAK-STAT信号通路是近年来备受关注的一条细胞因子信号转导通路,在细胞的增殖、凋亡、分化和免疫应答中发挥重要调控作用.巨噬细胞是机体内最主要的炎症效应细胞,在不同的环境和因素刺激下,可分化为促炎和抗炎两种类型,并参与多种疾病的发生发展过程.然而,在炎症因子刺激下JAK-STAT信号是如何激活的,JAK-STAT又是如何调控巨噬细胞极化分型和炎症走向,其机制并不明确.本文综述了JAK-STAT与巨噬细胞炎症反应调控的最新进展,旨在阐明JAK-STAT在巨噬细胞炎症调控中的关键作用,以期为机体炎症疾病的防治提供新的依据和策略.