👤 Keqiang Linghu

Coronary artery disease (CAD) is showing a trend toward earlier onset. Premature CAD (PCAD) is clinically defined as CAD with onset before the age of 55 in males and 65 in females. Notably, many young patients subsequently hospitalized with acute cardiovascular events had undergone annual physical examinations before hospitalization, yet were not identified as high-risk by current risk stratification guidelines or traditional risk assessment tools. This study aims to investigate the diagnostic capacity of novel inflammatory biomarkers (including the monocyte-to-high-density lipoprotein cholesterol ratio (MHR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), apolipoprotein B to apolipoprotein A-1 ratio (apoB/apoA-1), and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LDL-c/HDL-c)) for PCAD, thereby providing the evidence-based foundation for PCAD screening. A total of 1,012 young subjects (male<55 years, female<65 years) undergoing diagnostic coronary angiography (CAG) at the Third Affiliated Hospital of Zunyi Medical University (from January 2022 to February 2023) were retrospectively analyzed. We stratified 1,012 eligible participants into two groups: 521 angiographically confirmed PCAD cases and 491 controls with normal coronary arteries. Comprehensive baseline characteristics, including cardiovascular risk profiles and core laboratory-measured inflammatory markers, were recorded. The Mann-Whitney U test and binary logistic regression analysis were employed to assess the associations between inflammatory biomarkers and PCAD. The areas under the receiver operating characteristic (ROC) curves (AUCs) were calculated to evaluate their diagnostic performance for PCAD. The odds ratio (OR) values for MHR, NLR, LDL-c/HDL-c, and apoB/apoA-1 were 5.592 (95% CI: 2.886-7.836), 1.671 (95% CI: 1.500-1.861), 1.663 (95% CI: 1.419-1.950), and 6.268 (95% CI: 2.765-8.213), respectively (all The apoB/apoA-1 outperformed MHR, NLR, and LDL-c/HDL-c as an inflammatory biomarker in PCAD. Its diagnostic capacity was notably enhanced in ACS subgroups. A comprehensive model combining apoB/apoA-1 with traditional risk factors demonstrated exceptional accuracy. Incorporating this biomarker into routine screening protocols could significantly strengthen preventive strategies. Show less

Widespread metastasis is the primary reason for the high mortality associated with ovarian cancer (OC), and effective targeted therapy for tumor aggressiveness is still insufficient in clinical practice. Therefore, it is urgent to find new targets to improve prognosis of patients. PDE4A is a cyclic nucleotide phosphodiesterase that plays a crucial role in the occurrence and development in various malignancies. Our study firstly reported the function of PDE4A in OC. Expression of PDE4A was validated through bioinformatics analysis, RT-qPCR, Western blot, and immunohistochemistry. Additionally, its impact on cell growth and motility was assessed via in vitro and in vivo experiments. PDE4A was downregulated in OC tissues compared with normal tissues and low PDE4A expression was correlated with poor clinical outcomes in OC patients. The knockdown of PDE4A significantly promoted the proliferation, migration and invasion of OC cells while overexpression of PDE4A resulted in the opposite effect. Furthermore, smaller and fewer tumor metastatic foci were observed in mice bearing PDE4A-overexpressing OVCAR3 cells. Mechanistically, downregulation of PDE4A expression can induce epithelial-mesenchymal transition (EMT) and nuclear translocation of Snail, which suggests that PDE4A plays a pivotal role in suppressing OC progression. Notably, Rolipram, the PDE4 inhibitor, mirrored the effects observed with PDE4A deletion. In summary, the downregulation of PDE4A appears to facilitate OC progression by modulating the Snail/EMT pathway, underscoring the potential of PDE4A as a therapeutic target against ovarian cancer metastasis. Show less

To investigate the effect of conbercept on macular microvascular system and retinal blood supply in the treatment of nonischemic branch retinal vein occlusion macular edema (BRVO-ME). Patients were divided into three groups: group A (containing 12 nonischemic BRVO-ME eyes), group B (containing contralateral 12 healthy eyes), and group C (containing 30 cataract eyes to obtain normal aqueous humor cytokine levels). Group A received monthly intravitreal injections of conbercept for 3 months. General data and best-corrected visual acuity (BCVA) were compared among the three groups. Optical coherence tomography angiography (OCTA) results (including central macular thickness [CMT], retinal vascular density and perfusion, and foveal avascular zone [FAZ]) at baseline were compared among groups A and B. Aqueous humor cytokine levels (including VEGF, IL-8, PDGF-AA, TNF-α, and ANGPTL-4) at baseline were compared between groups A and C. Moreover, BCVA, OCTA results, and aqueous humor cytokine levels of group A before and after conbercept treatment were compared. At baseline, group A had a significantly worse BCVA, lower retinal vascular density and perfusion, and numerically larger CMT and FAZ area comparing to the group B, and had a higher aqueous cytokine level (IL-8, VEGF, and ANGPTL-4) comparing to the group C (all ps < 0.05). After the injection of conbercept, group A presented a better BCVA (at initial diagnosis vs. after three conbercept injections: 1.16 ± 0.51 vs. 0.81 ± 0.30, logMAR, p < 0.05), higher retinal vascular density (11.56 ± 4.73 vs. 15.88 ± 2.31, mm This study demonstrated that intraocular injection of conbercept could effectively improve macular microcirculation and increase retinal blood supply in the treatment of nonischemic BRVO-ME based on the combination of visual acuity, OCTA parameters, and aqueous humor cytokine assay results. However, further study with a larger sample size and longer observation period is still needed in the future. Show less