Background. To investigate the effect of hypoxia on pulmonary artery endothelial cells and the role of NOTCH3 in endothelial-mesenchymal transition (EnMT) and to provide a research model for pulmonary disease and explain the pathogenesis of the pulmonary disease. Methods. Pulmonary artery endothelial cells were divided into two groups and cultured in normoxic and hypoxic environments, respectively. QPCR, western blot, and immunofluorescence were used to detect endothelial cell-specific marker protein and mRNA expression in each group, and the ability of endothelial cells migration was evaluated by scratch and transwell experiment. Results. The pulmonary artery endothelial cells in the normoxic group presented a typical pebble-like arrangement, and the endothelial cells in hypoxic culture showed a long spindle appearance. Hypoxia induced high expression of NOTCH3, Jagged-1, Hes1, c-Src, and CSL. Immunofluorescence showed that endothelial cells in hypoxic culture began to express the α-SMA, and the expression of vWF increased with hypoxia. Cell viability, scratch, and transwell results showed that endothelial cells in the hypoxic group were more capable of viability and migration than those in the normoxic group. The induction of EnMT by hypoxia can be inhibited by using notch3-specific inhibitor DAPT and Jagged-1. This study also found that miR-7-5p can regulate endothelial NOTCH3, indicating that miRNA is also involved in the process of endothelial-mesenchymal transformation. Conclusion. Hypoxia promotes the transformation of endothelial cells into mesenchymal cells by opening the NOTCH3 pathway, which lays the foundation for disease progression or clinical prognosis, and is of great significance in the treatment of diseases.
Background: As the lesions in pulmonary nodules (PNs) are small and the clinical manifestations lack specificity, the etiology of PNs is complex, predisposing them to misdiagnoses missed diagnoses. Thus, the diagnosis and treatment of PNs remains challenging and an important clinical problem. Methods: This study prospectively enrolled 156 patients with computed tomography (CT)-diagnosed PNs who underwent circulating genetically abnormal cell (CAC) testing between January 2020 and December 2021. We collected data on clinical features closely related to the nature of PNs, such as age, smoking history, and type of nodule. All internal regions of interest (ROIs) of PNs in this study were segmented. Radiomic feature extraction was performed on the ROIs, and a radiomics model was constructed using least absolute shrinkage and selection operator (LASSO) regression to obtain a radiomics score (Rad-score). A comprehensive model combining clinical features, Rad-score, and liquid biopsy was constructed using logistic regression analysis. The diagnostic performance of the model was evaluated using receiver operating characteristic (ROC) curves. Results: In this study, 5 radiomics features were screened for model construction. The area under the ROC curve (AUC) of the radiomics model was 0.844 [95% confidence interval (CI): 0.766-0.915] in the training set. The Rad-score, clinical features, and CAC were further combined to construct a multidimensional analysis model. The AUC of the synthesized model was 0.943 (95% CI: 0.881-0.978) in the training set. Conclusions: A multidimensional model is an effective tool for the noninvasive diagnosis of malignant PNs. The validation and combination of multiple diagnostic methods is a productive avenue of research trend for the identification of malignant PNs.
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