RESUMO
Background: Bone is one of the most common metastatic sites of advanced lung cancer, and the median survival time is significantly shorter than that of patients without metastasis. This study aimed to identify prognostic factors associated with survival and construct a practical nomogram to predict overall survival (OS) in lung cancer patients with bone metastasis (BM). Methods: We extracted the patients with BM from lung cancer between 2011 and 2015 from the Surveillance, Epidemiology, and End Result (SEER) database. Univariate and multivariate Cox regressions were performed to identify independent prognostic factors for OS. The variables screened by multivariate Cox regression analysis were used to construct the prognostic nomogram. The performance of the nomogram was assessed by receiver operating characteristic (ROC) curve, concordance index (C-index), and calibration curves, and decision curve analysis (DCA) was used to assess its clinical applicability. Results: A total of 7861 patients were included in this study and were randomly divided into training (n=5505) and validation (n=2356) cohorts using R software in a ratio of 7:3. Cox regression analysis showed that age, sex, race, grade, tumor size, histological type, T stage, N stage, surgery, brain metastasis, liver metastasis, chemotherapy and radiotherapy were independent prognostic factors for OS. The C-index was 0.723 (95% CI: 0.697-0.749) in the training cohorts and 0.738 (95% CI: 0.698-0.778) in the validation cohorts. The AUC of both the training cohorts and the validation cohorts at 3-month (0.842 vs 0.859), 6-month (0.793 vs 0.814), and 1-year (0.776 vs 0.788) showed good predictive performance, and the calibration curves also demonstrated the reliability and stability of the model. Conclusions: The nomogram associated with the prognosis of BM from lung cancer was a reliable and practical tool, which could provide risk assessment and clinical decision-making for individualized treatment of patients.
RESUMO
Osteoarthritis, a prevalent orthopedic disease, can affect the elderly and causes impairment. The degradation and aberrant homeostasis of cartilage extracellular matrix figure pivotally in the progression of osteoarthritis. Thioredoxin systems plays a role in a wide range of biological processes, including cell proliferation, apoptosis, and oxidative stress. The present study aimed to investigate the unique function and underlying pathophysiological mechanism of TXNRD1 in chondrocytes. An upregulated expression of TXNRD1 was observed in the articular cartilage of osteoarthritis patients compared with normal articular cartilage. Furthermore, in vitro experiments showed that the expression of TXNRD1 was also abnormally increased in IL-1ß-induced primary mouse chondrocytes. Silencing TXNRD1 using siRNA in chondrocytes could effectively inhibit the expression of ADAMTS5 and MMP13, and enhance the expression of COL2A1 and SOX9. The same was true for auranofin, an inhibitor of TXNRD1. This phenomenon indicated that inhibition of TXNRD1 attenuated il-1ß-induced metabolic imbalance of extracellular matrix (ECM) and the progression of chondrocyte osteoarthritis. Further mechanism analysis revealed that the activation of Nrf2 signaling pathway and the expression of heme oxygenase-1 (HO-1) were increased upon TXNRD1 inhibition. Furthermore, auranofin was found to attenuate DMM-induced osteoarthritis progression in vivo. Therefore, the pharmacological downregulation of TXNRD1 may provide an effective novel therapy for OA.
