Objective To investigate independent prognostic factors influencing the prognosis of connective tissue disease-associated interstitial lung disease with pulmonary hypertension (CTD-ILD-PH), and construct a nomogram model using machine learning to predict 1-, 3- and 5-year mortality risks, providing evidence for clinical diagnosis and treatment. Methods Patients diagnosed with CTD-ILD-PH and treated at the First Affiliated Hospital of Zhengzhou University from February 2011 to June 2021 were screened. The least absolute shrinkage and selection operator (Lasso), univariate Cox regression, and multivariate Cox regression analyses were combined to identify independent prognostic factors for CTD-ILD-PH patients. A novel nomogram prognostic model was constructed and internally validated using 1000 bootstrap resamples. The receiver operating characteristic (ROC) curve and Harrell's C-index assessed the predictive performance of the model. Calibration curves evaluated the model fit. Decision curve analysis (DCA) assessed the clinical utility of the model, and external validation was conducted using a separate test set. Results The study included 313 patients, with 108 deaths observed during the follow-up. Using the Lasso-Cox method, albumin, alanine aminotransferase (ALT), red cell volume distribution width (RDW), age, smoking history, rural residence, and pulmonary artery systolic pressure were identified as independent prognostic factors. The Harrell's C-index in the training set was 0.802, and the area under ROC curve was 0.880 (95%CI 0.833 - 0.928). Internal validation showed an average Harrell's C-index of 0.791. Calibration curves indicated high consistency between predicted and observed results. DCA confirmed the model's good clinical utility. External validation results demonstrated the model's favorable predictive performance and clinical utility. Conclusions Our research suggest that lower albumin, elevated ALT, elevated RDW, advanced age, smoking history, rural areas and higher pulmonary artery systolic blood pressure are independent prognostic risk factors for patients with CTD-ILD-PH. In this study, a prognostic model was developed for the first time to predict 1-, 3- and 5-year mortality in CTD-ILD-PH patients, which provides some reference value for future mortality risk assessment in CTD-ILD-PH.
Objective To evaluate the effectiveness of biodegradable magnesium alloy materials in promoting tendon-bone healing during rotator cuff tear repair and to investigate their potential underlying biological mechanisms. Methods Forty-eight 8-week-old Sprague Dawley rats were taken and randomly divided into groups A, B, and C. Rotator cuff tear models were created and repaired using magnesium alloy sutures in group A and Vicryl Plus 4-0 absorbable sutures in group B, while only subcutaneous incisions and sutures were performed in group C. Organ samples of groups A and B were taken for HE staining at 1 and 2 weeks after operation to evaluate the safety of magnesium alloy, and specimens from the supraspinatus tendon and proximal humerus were harvested at 2, 4, 8, and 12 weeks after operation. The specimens were observed macroscopically at 4 and 12 weeks after operation. Biomechanical tests were performed at 4, 8, and 12 weeks to test the ultimate load and stiffness of the healing sites in groups A and B. At 2, 4, and 12 weeks, the specimens were subjected to the following tests: Micro-CT to evaluate the formation of bone tunnels in groups A and B, HE staining and Masson staining to observe the regeneration of fibrocartilage at the tendon-bone interface after decalcification and sectioning, and Goldner trichrome staining to evaluate the calcification. Immunohistochemical staining was performed to detect the expression of angiogenic factors, including vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2), as well as osteogenic factors at the tendon-bone interface. Additionally, immunofluorescence staining was used to examine the expression of arginase 1 and Integrin beta-2 to assess M1 and M2 macrophage polarization at the tendon-bone interface. The role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in tendon-bone healing was further analyzed using real-time fluorescence quantitative PCR. Results Analysis of visceral sections revealed that magnesium ions released during the degradation of magnesium alloys did not cause significant toxic effects on internal organs such as the heart, liver, spleen, lungs, and kidneys, indicating good biosafety. Histological analysis further demonstrated that fibrocartilage regeneration at the tendon-bone interface in group A occurred earlier, and the amount of fibrocartilage was significantly greater compared to group B, suggesting a positive effect of magnesium alloy material on tendon-bone interface repair. Additionally, Micro-CT analysis revealed that bone tunnel formation occurred more rapidly in group A compared to group B, further supporting the beneficial effect of magnesium alloy on bone healing. Biomechanical testing showed that the ultimate loads in group A were consistently higher than in group B, at 4 weeks, the stiffness of group A was also greater than that of group B, indicating stronger tissue-carrying capacity following tendon-bone interface repair and highlighting the potential of magnesium alloy in enhancing tendon-bone healing. Immunohistochemical staining results indicated that the expression of VEGF and BMP-2 was significantly upregulated during the early stages of healing, suggesting that magnesium alloy effectively promoted angiogenesis and bone formation, thereby accelerating the tendon-bone healing process. Immunofluorescence staining further revealed that magnesium ions exerted significant anti-inflammatory effects by regulating macrophage polarization, promoting their shift toward the M2 phenotype. Real-time fluorescence quantitative PCR results demonstrated that magnesium ions could facilitate tendon-bone healing by modulating the PI3K/AKT signaling pathway, which represented one of the molecular mechanisms driving this healing process. ConclusionBiodegradable magnesium alloy material accelerated fibrocartilage regeneration and calcification at the tendon-bone interface in rat rotator cuff tear repair by regulating the PI3K/AKT signaling pathway, thereby significantly enhancing tendon-bone healing.