Nrf-2 as a novel target in radiation induced lung injury.

Radiation-induced lung injury (RILI) is a common and fatal complication of chest radiotherapy. The underlying mechanisms include radiation-induced oxidative stress caused by damage to the deoxyribonucleic acid (DNA) and production of reactive oxygen species (ROS), resulting in apoptosis of lung and endothelial cells and recruitment of inflammatory cells and myofibroblasts expressing NADPH oxidase to the site of injury, which in turn contribute to oxidative stress and cytokine production. Nuclear factor erythroid 2-related factor 2 (Nrf-2) is a vital transcription factor that regulates oxidative stress and inhibits inflammation. Studies have shown that Nrf-2 protects against radiation-induced lung inflammation and fibrosis. This review discusses the protective role of Nrf-2 in RILI and its possible mechanisms.

Association of inflammatory indicators with intensive care unit mortality in critically ill patients with coronary heart disease.

Objective: Coronary heart disease (CHD) is one of the major cardiovascular diseases, a common chronic disease in the elderly and a major cause of disability and death in the world. Currently, intensive care unit (ICU) patients have a high probability of concomitant coronary artery disease, and the mortality of this category of patients in the ICU is receiving increasing attention. Therefore, the aim of this study was to verify whether the composite inflammatory indicators are significantly associated with ICU mortality in ICU patients with CHD and to develop a simple personalized prediction model. Method: 7115 patients from the Multi-Parameter Intelligent Monitoring in Intensive Care Database IV were randomly assigned to the training cohort (n = 5692) and internal validation cohort (n = 1423), and 701 patients from the eICU Collaborative Research Database served as the external validation cohort. The association between various inflammatory indicators and ICU mortality was determined by multivariate Logistic regression analysis and Cox proportional hazards model. Subsequently, a novel predictive model for mortality in ICU patients with CHD was developed in the training cohort and performance was evaluated in the internal and external validation cohorts. Results: Various inflammatory indicators were demonstrated to be significantly associated with ICU mortality, 30-day ICU mortality, and 90-day ICU mortality in ICU patients with CHD by Logistic regression analysis and Cox proportional hazards model. The area under the curve of the novel predictive model for ICU mortality in ICU patients with CHD was 0.885 for the internal validation cohort and 0.726 for the external validation cohort. The calibration curve showed that the predicted probabilities of the model matched the actual observed probabilities. Furthermore, the decision curve analysis showed that the novel prediction model had a high net clinical benefit. Conclusion: In ICU patients with CHD, various inflammatory indicators were independent risk factors for ICU mortality. We constructed a novel predictive model of ICU mortality risk in ICU patients with CHD that had great potential to guide clinical decision-making.

Safety and efficacy of anlotinib hydrochloride capsules in advanced non-small-cell lung cancer: a multicenter, real-world study.

Objective: To investigate the safety and efficacy of anlotinib hydrochloride capsules in stage III-IV non-small-cell lung cancer (NSCLC). Methods: NSCLC patients received anlotinib monotherapy or combination therapy. The primary end point was adverse reactions during anlotinib treatment and the secondary end point was progression-free survival. Results: During anlotinib treatement, 41.85% (167/399) of patients experienced adverse reactions, and the monotherapy group had a lower incidence than the combination group (36.89 vs 49.68%; p = 0.012). The median progression-free survival of patients in the monotherapy group was significantly lower than that in the combination group (5 vs 6 months; p = 0.0119). Conclusion: Compared with anlotinib monotherapy, combination therapy resulted in longer PFS and a higher incidence of adverse reactions in patients with NSCLC.

ROS1-positive non-small cell lung cancer (NSCLC): biology, diagnostics, therapeutics and resistance.

ROS1 is a proto-oncogene encoding a receptor tyrosine protein kinase (RTK), homologous to the v - Ros sequence of University of Manchester tumours virus 2 (UR2) sarcoma virus, whose ligands are still being investigated. ROS1 fusion genes have been identified in various types of tumours. As an oncoprotein, it promotes cell proliferation, activation and cell cycle progression by activating downstream signalling pathways, accelerating the development and progression of non-small cell lung cancer (NSCLC). Studies have demonstrated that ROS1 inhibitors are effective in patients with ROS1-positive NSCLC and are used for first-line clinical treatment. These small molecule inhibitors provide a rational therapeutic option for the treatment of ROS1-positive patients. Inevitably, ROS1 inhibitor resistance mutations occur, leading to tumours recurrence or progression. Here, we comprehensively review the identified biological properties and Differential subcellular localisation of ROS1 fusion oncoprotein promotes tumours progression. We summarise recently completed and ongoing clinical trials of the classic and new ROS1 inhibitors. More importantly, we classify the complex evolving tumours cell resistance mechanisms. This review contributes to our understanding of the biological properties of ROS1 and current therapeutic advances and resistant tumours cells, and the future directions to develop ROS1 inhibitors with durable effects.

Role of STK11 in ALK-positive non-small cell lung cancer.

Anaplastic lymphoma kinase (ALK) inhibitors have been shown to be effective in treating patients with ALK-positive non-small cell lung cancer (NSCLC), and crizotinib, ceritinib and alectinib have been approved as clinical first-line therapeutic agents. The availability of these inhibitors has also largely changed the treatment strategy for advanced ALK-positive NSCLC. However, patients still inevitably develop resistance to ALK inhibitors, leading to tumor recurrence or metastasis. The most critical issues that need to be addressed in the current treatment of ALK-positive NSCLC include the high cost of targeted inhibitors and the potential for increased toxicity and resistance to combination therapy. Recently, it has been suggested that the serine/threonine kinase 11 (STK11) mutation may serve as one of the biomarkers for immunotherapy in NSCLC. Therefore, the main purpose of this review was to summarize the role of STK11 in ALK-positive NSCLC. The present review also summarizes the treatment and drug resistance studies in ALK-positive NSCLC and the current status of STK11 research in NSCLC.