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.

Objective:To investigate the safety and efficacy of posterior apical total intervertebral release (IVR) combined with posterior column osteotomy (PCO) in the treatment of rigid scoliosis.Methods:This study retrospectively analyzed the clinical and radiographic data of 27 patients with rigid scoliosis who underwent posterior total IVR combined with PCO in the apical region from July 2017 to September 2023. There were 10 males and 17 females with an age of 19.3±8.8 years (range 11-48 years). Among them, there were 16 cases of idiopathic scoliosis, 7 cases of neuromuscular scoliosis, 1 case of congenital scoliosis, 1 case of Marfan syndrome with scoliosis, 1 case of neurofibromatosis with scoliosis, and 1 case of osteogenesis imperfecta with scoliosis. The mean Cobb angle of the main curve was 75.4°±13.7° (range 58.7°-110.2°) preoperatively. The mean flexibility of the main curvature is 15.7%±4.7% (range 2.5%-24.3%). Preoperative computer tomography showed that the area of the IVR channel in the convex and concave side of the apical region was 128.1±23.3 mm 2 and 89.5±18.6 mm 2, respectively. The area of the convex IVR was significantly higher than that of the concave IVR. Results:All 27 patients underwent surgery successfully. Total IVR was performed at an average of 3.4±0.7 levels in the apical region. SPO and Ponte osteotomy were performed at 2.7±0.7 and 4.9±1.1 levels, respectively. The mean fusion segment is 11.2±2.0. The operation time, estimated blood loss, and follow-up time were 7.5±0.9 hours (range 6.0-9.8 hours), 1 103.7±845.1 ml (range 300-4 500 ml), and 20.0±14.2 months (range 5-56 months), respectively. The preoperative, postoperative, and final follow-up's mean coronal Cobb angles of the main curve were 75.4°±13.7°, 18.2°±6.5° and 18.6°±6.5°, respectively. The mean correction rate was 75.7%±5.3%. In cases of thoracolumbar kyphosis, the preoperative, postoperative, and final follow-up mean sagittal Cobb angles were 47.2°±4.7°, 22.8°±9.1° and 23.8°±8.9°, respectively. The mean correction rate was 49.5%±18.9%. The mean axial vertebral rotation (AVR) in the IVR region was 24.6°±7.6° preoperatively and was corrected to 11.6°±5.6° postoperatively. The mean correction rate for AVR was 54.0%±11.3%. The coronal, sagittal Cobb angles and AVR postoperatively were significantly lower than those preoperatively ( P<0.001). This case series reported 4 cases of postoperative pleural effusion and 1 case of pulmonary infection, and all of them were cured through conservative treatment. One patient developed incision infection 2 months postoperatively and recovered through debridement surgery. Two patients had proximal junctional kyphosis, one of them underwent revision surgery, and another case was treated with braces. Conclusion:Posterior multi-segment total IVR combined with PCO is a safe and effective surgical procedure for the treatment of rigid scoliosis. The procedure of total IVR was recommended as a supplement for better release of the rigid spine when traditional release methods are not effective.

Obsessive-compulsive disorder (OCD) is a chronic,disabling,mental disorder,which has been linked to significant abnormalities in certain brain areas,including the orbital frontal cortex and the anterior cingulate cortex.Neuroimaging studies have also shown that brain areas related to the decision-making function include the orbital frontal cortex and the dorsal prefrontal lobes.Furthermore,the association between OCD and decision-making function has been consistently demonstrated from a neurobiological perspective.Clinically,impaired decision-making ability is commonly observed in OCD patients,and there is a correlation between OCD and abnormal decision function.Decision-making tasks are typically divided into two types,decision-making under risk and decision-making under ambiguity,with the former commonly evaluated using the Iowa Gambling Task (IGT) and the latter using the Game of Dice Task (GDT).In this article the neural mechanism and evaluation methods of decision making in OCD were reviewed.