BACKGROUND: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose Colchicine 2) studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques. METHODS: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up. RESULTS: Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] μm versus 87.2 [95% CI, 69.9 to 104.5] μm; difference, 34.2 [95% CI, 9.7 to 58.6] μm; P =0.006), and reduced average lipid arc (–25.2° [95% CI, –30.6° to –19.9°] versus –35.7° [95% CI, –40.5° to –30.8°]; difference, –10.5° [95% CI, –17.7° to –3.4°]; P =0.004), mean angular extension of macrophages (–8.9° [95% CI, –13.3° to –4.6°] versus –14.0° [95% CI, –18.0° to –10.0°]; difference, –6.0° [95% CI, –11.8° to –0.2°]; P =0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P =0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P =0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P =0.047). CONCLUSIONS: Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04848857.

Growth differentiation factor-15 (GDF-15) is proposed to be strongly associated with several cardiovascular diseases, such as heart failure and atherosclerosis. Moreover, some recent studies have reported an association between GDF-15 and platelet activation. In this study, we isolated peripheral blood platelets from healthy volunteers and evaluated the effect of GDF-15 on adenosine diphosphate (ADP)-induced platelet activation using the platelet aggregation assay. Subsequently, we detected the expression of GDF-15-related receptors on platelets, including the epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 3 (HER3), transforming growth factor-beta receptor I (TGF-βRI), transforming growth factor-beta receptor II (TGF-βRII), glial-cell-line-derived neurotrophic factor family receptor α-like (GFRAL), and those rearranged during transfection (RET). Then, we screened for GDF-15 receptors using the GDF-15-related receptor microarray comprising these recombinant proteins. We also performed the immunoprecipitation assay to investigate the interaction between GDF-15 and the receptors on platelets. For the further exploration of signaling pathways, we investigated the effects of GDF-15 on the extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and Janus kinase 2 (JAK2) pathways. We also investigated the effects of GDF-15 on the ERK and AKT pathways and platelet aggregation in the presence or absence of RET agonists or inhibition. Our study revealed that GDF-15 can dose-independently inhibit ADP-induced human platelet aggregation and that the binding partner of GDF-15 on platelets is GFRAL. We also found that GDF-15 inhibits ADP-induced AKT and ERK activation in platelets. Meanwhile, our results revealed that the inhibitory effects of GDF-15 can be mediated by the GFRAL/RET complex. These findings reveal the novel inhibitory mechanism of ADP-induced platelet activation by GDF-15.

Background: Integrated care for patients living with HIV in rural and economically disadvantaged regions remains a critical challenge. This study aims to develop a 3D evaluation index system to assess the effectiveness of integrated medical care and prevention for patients living with HIV in county-level regions of China. The framework encompasses disease prevention, clinical treatment, and the integration of medical services with public health interventions. Objective: This study aims to develop a scientifically validated, 3D evaluation index system for assessing the effectiveness of integrated medical care and prevention for patients living with HIV in county-level regions of China. Methods: A structured Delphi method will be used to establish consensus among experts on key evaluation indicators. The study will begin with focus group discussions guided by the Valentijn Rainbow Model, followed by multiple rounds of Delphi surveys to refine the indicator system. A total of 75 experts will include clinical professionals, public health specialists, health policy researchers, and representatives from nongovernmental organizations. Experts will participate in iterative rounds, ranking and validating indicators using statistical methods such as the analytic hierarchy process and Kendall W coefficient to assess consensus. Results: The Delphi study was initiated in April 2025, with 3 rounds of questionnaires distributed between May and September 2025. Data analysis is ongoing, and the finalized county-level HIV integration index system is expected to be published by spring 2026. The study is projected to be completed by January 2026. Conclusions: The developed evaluation system will offer a comprehensive and scientifically validated tool for assessing health care outcomes in resource-constrained settings, contributing to policy improvements for HIV service integration in China and other low-resource settings globally.