Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

The introduction of Integrated Care Systems in July 2022 is a significant reform of health services in UK.It introduces the audit of the Integrated Care Systems by the UK's National Audit Office,including risk assessment,conclusions and recommendations in order to provide reference for public policy prospective audit and medical system reform and development in China.

The introduction of Integrated Care Systems in July 2022 is a significant reform of health services in UK.It introduces the audit of the Integrated Care Systems by the UK's National Audit Office,including risk assessment,conclusions and recommendations in order to provide reference for public policy prospective audit and medical system reform and development in China.

The introduction of Integrated Care Systems in July 2022 is a significant reform of health services in UK.It introduces the audit of the Integrated Care Systems by the UK's National Audit Office,including risk assessment,conclusions and recommendations in order to provide reference for public policy prospective audit and medical system reform and development in China.

The introduction of Integrated Care Systems in July 2022 is a significant reform of health services in UK.It introduces the audit of the Integrated Care Systems by the UK's National Audit Office,including risk assessment,conclusions and recommendations in order to provide reference for public policy prospective audit and medical system reform and development in China.

The introduction of Integrated Care Systems in July 2022 is a significant reform of health services in UK.It introduces the audit of the Integrated Care Systems by the UK's National Audit Office,including risk assessment,conclusions and recommendations in order to provide reference for public policy prospective audit and medical system reform and development in China.

The introduction of Integrated Care Systems in July 2022 is a significant reform of health services in UK.It introduces the audit of the Integrated Care Systems by the UK's National Audit Office,including risk assessment,conclusions and recommendations in order to provide reference for public policy prospective audit and medical system reform and development in China.

The introduction of Integrated Care Systems in July 2022 is a significant reform of health services in UK.It introduces the audit of the Integrated Care Systems by the UK's National Audit Office,including risk assessment,conclusions and recommendations in order to provide reference for public policy prospective audit and medical system reform and development in China.

The introduction of Integrated Care Systems in July 2022 is a significant reform of health services in UK.It introduces the audit of the Integrated Care Systems by the UK's National Audit Office,including risk assessment,conclusions and recommendations in order to provide reference for public policy prospective audit and medical system reform and development in China.