Objective To investigate the influence of aspirin and/or clopidogrel treatment on platelet aggregation rate in coronary heart disease (CHD) patients,and discuss the factors related to anti-platelet drug resistance.Methods A total of 160 patients with CHD and received aspirin and/or clopidogrel treatment were enrolled in the Second Xiangya Hospital,Central South University,and were divided into stable coronary heart disease (SCHD) group (n =90) and acute coronary syndrome (ACS) group (n =70).Meanwhile,non-coronary heart disease (NCHD) patients who did not receive anti-platelet drug treatment were enrolled as controls (n =50).Clinical data of the subjects were recorded.The maximum platelet aggregation rate induced by arachidonic acid (MAR-AA) and adenosine diphosphate (MAR-ADP) were evaluated with sequential platelet counting method.The factors related to drug resistance were analyzed with Logistic regression analysis.Results Compared to NCHD group,there were lower MAR-AA and MAR-ADP in two groups of CHD (all P ＜ 0.05).In ACS patients,MAR-AA and MAR-ADP are significantly lower (P ＜0.05) in patients who receive the aspirin and clopidogrel.The rate of anti-platelet drug resistance in ACS group was significantly higher than that in SCHD group (20.0％ vs 10.0％,P ＜ 0.05).Multivariate logistic regression analysis showed that low HDL-C (＜ 1.0 mmol/L) was an independent risk factor related to the anti-platelet drug resistance (OR =4.36,95 ％ CI:1.36-14.02,P =0.025).Conclusions The antiplatelet treatment with aspirin and/or clopidogrel can significantly reduce the platelet reactivity in CHD patients,but some patients still present anti-platelet drug resistance.The combination of aspirin and clopidogrel is better.The rate of drug resistance in ACS patients is high.Low HDL-C might be associated with anti-platelet drug resistance.

BACKGROUND: Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust. METHODS: Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R₂₀₀ cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R₂₀₀ cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R₂₀₀ group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method. RESULTS: Both the cells in the R group and R₂₀₀ group express leptin receptor OB-R. Compared to the R₂₀₀ group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R₂₀₀ cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R₂₀₀ group (R₂₀₀L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R₂₀₀L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R₂₀₀L group exhibited faster cell aggregation compared to the U0126-induced R₂₀₀ (R₂₀₀LU) group. Additionally, the cells in the R₂₀₀L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R₂₀₀LU group and R₂₀₀ group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R₂₀₀L group. However, when the cells in the R₂₀₀L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased. CONCLUSIONS Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust.
Rats ; Animals ; Alveolar Epithelial Cells/pathology* ; Dust ; Tin/adverse effects* ; Lung Neoplasms/pathology* ; Leptin/adverse effects* ; Receptors, Leptin ; China ; Signal Transduction ; Epithelial Cells/pathology* ; Mitogen-Activated Protein Kinase Kinases/adverse effects*