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.

Objectives:To investigate the imaging characteristics and incidence rate of nuchal ligament calci-fication in asymptomatic population.Methods:The clinical and imaging data of 318 asymptomatic volunteers were analyzed retrospectively,including the incidence,morphological classification,and segmental distribution of nuchal ligament calcification.The volunteers were divided into two groups based on the presence of nuchal ligament calcification,and differences in gender,age,body mass index(BMD,and lower cervical intervertebral parameters between the two groups were analyzed.Based on the Roussouly classification,differences in cervi-cothoracic parameters between the groups were analyzed.Finally,the correlation between the degree of nuchal ligament calcification and the aforementioned factors was studied to identify the risk factors for nuchal liga-ment calcification.Results:Among the 318 asymptomatic subjects,the incidence of nuchal ligament calcifica-tion was 23.27％.There were statistically significant differences in gender ratio,age,and BMI between the calcification of nuchal ligament group(ONL+)and non-calcification of nuchal ligament group(ONL-)(P＜0.001).The calcification of nuchal ligament was classified morphologically as follows:Local calcification 50.0％,con-tinuous calcification 27.0％,segmental calcification 7.0％,mixed calcification 9.0％and unclassified calcifica-tion 7.0％.The incidence of nuchal ligament calcification in each segment was as follows:C2/3 1.4％,C3/49.5％,C4/5 55.4％,C5/6 63.5％,and C6/7 18.9％.Compared with the ONL-group,the angular displacement(AD)and horizontal displacement(HD)of the ONL+group were significantly increased(P＜0.001).Based on the Roussouly classification,significant statistical differences in cervicothoracic parameters such as O-C2,C2-C7 SVA,and T1 slope(TS)were found between the ONL+group and the ONL-group(P＜0.05).Pearson correlation analysis showed that the degree of nuchal ligament calcification had a moderate correlation with AD,O-C2,and C2-C7 SVA,and a strong correlation with HD and TS.Multivariate logistic analysis revealed that HD was the most significant risk factor for nuchal ligament calcification,followed by O-C2,age,and AD.Conclusions:The incidence of nuchal ligament calcification was higher in asymptomatic men who were older and had a high body mass index.Cervicothoracic parameters(O-C2,C2-C7 SVA and TS)and segmental parameters(AD,HD)were significantly increased in the group of nuchal ligament calcification,and were correlated with the degree of nuchal ligament calcification.

Objectives:To introduce the definition of the spinal cord(SC)line,and its clinical classification and application strategies in posterior cervical open-door laminoplasty,and to examine and analyze the credibility and repeatability of this classification.Methods:The clinical data of a total of 86 patients who underwent cervical open-door laminoplasty via posterior approach in The Second Affiliated Hospital of Wen-zhou Medical University from January 2018 to December 2020 were analyzed retrospectively.There were 51 males and 35 females,aged 34-77 years old,with postoperative follow-up period ranging from 12 to 36 months.The patients were classified into three types based on the location relationships between the SC line and compressor in the preoperative MRI:Type Ⅰ,the compressor at compression level did not exceed the SC line;Type Ⅱ,the compressor contacted the SC line;Type Ⅲ,the compressor exceeded the SC line.Five spinal surgeons independently evaluated and classified the MRI images of the patients,and Kappa consistency tests were performed to analyze the credibility and repeatability.50 patients with multilevelcervical spinal cord compression diseases(cervical spondylotic myelopathy,ossification of the posterior longitudinal ligament,and developmental cervical spinal canal stenosis)were recruited and treated for a prospective study from January 2021 to December 2022,and the range of open-door segments was determined under the principle of improv-ing the SC line classification as much as possible.The patients were followed up for 12 to 34 months.The modified anterior spinal cord compression score,neck pain visual analogue scale(VAS),Japanese Orthopaedic Association(JOA)score and recovery rates of the patients were recorded pre-operatively and at final follow-up in both retrospective and prospective studies.Paired samples t test was used to compare the scores before and after surgery in each type of patients,and one-way ANOVA was used to compare the scores between the three groups,to assess the postoperative spinal cord decompression and clinical outcomes of the different SC line types.Results:Among the 86 patients analyzed retrospectively,38 were Type Ⅰ,31 were Type Ⅱand 17 were Type Ⅲ.The Kappa coefficient was 0.817-0.945 for inter-observer consistency,which was 0.891-0.963 for intra-observer consistency,indicating satisfactory credibility and repeatability.There was no significant difference in modified anterior spinal cord compression score and VAS score between the three types of patients before surgery(P＞0.05),and all of them were statistically different at the final follow-up compared with the preoperative period(P＜0.05).The modified anterior spinal cord compression score and VAS score were the lowest at the final follow-up in Type Ⅰ,which were the highest in Type Ⅲ(P＜0.05).The JOA recovery rate was(73.49±11.26)％in Type Ⅰ,(67.08±9.01)％in Type Ⅱ,and(53.74±7.93)％in TypeⅢ,with statistically significant differences between the three types(P＜0.05).Among the 50 patients analyzed prospectively,27 were Type Ⅰ,15 were Type Ⅱ and 8 were Type Ⅲ.The preoperative spinal cord com-pression score was 3.67±0.47 in Type Ⅰ,3.84±0.37 in Type Ⅱ,and 4.00±0.00 in Type Ⅲ,which was 1.24±0.62 in Type Ⅰ,2.60±0.58 in Type Ⅱ,and 3.40±0.52 in Type Ⅲ at the final follow-up,respectively.The VAS score decreased from 6.48±0.85 preoperatively to 1.11±0.51 at final follow-up in Type Ⅰ.Type Ⅱcases exhibited a decrease in VAS score from 6.67±0.90 preoperatively to 1.73±0.59 at final follow-up.And the VAS score decreased from a preoperative value of 7.13±0.64 to 2.38±0.52 at final follow-up in Type Ⅲ(P＜0.05).The modified anterior spinal cord compression score and VAS score were the lowest in Type Ⅰand the highest in Type Ⅲ at final follow-up(P＜0.05).The JOA score improved from 12.07±1.17 preopera-tively to 15.59±0.69 at final follow-up in Type Ⅰ.Type Ⅱ cases exhibited an improvement in JOA score from 10.93±0.80 preoperatively to 14.67±0.72 at final follow-up.And the JOA score improved from a preop-erative value of 10.13±1.13 to 13.63±0.74 at final follow-up in Type Ⅲ(P＜0.05).The JOA recovery rate was(72.50±12.38)％in Type Ⅰ,(61.99±9.78)％in Type Ⅱ,and(51.25±5.19)％in Type Ⅲ,which was statisti-cally different between the three groups(P＜0.05).Conclusions:The SC line and its classification are practical and reliable,demonstrating good credibility and repeatability.Suitable open-door segment in posterior open-door laminoplasty in patients of Type Ⅰ SC line can make anterior spinal cord compression relieved;And anterior surgery needs to be considered when anterior compression remained after posterior surgery in patients of Type Ⅲ SC line.

Objective:To propose a monosegment thoracic and lumbar fracture dislocation (mTLFD) classification, and to evaluate its reliability and clinical application.Methods:All of 298 cases of thoracic and lumbar fracture dislocation who received surgical management in our hospital from January 2014 to December 2019 were retrospectively analyzed. 123 cases were included in the study according to inclusion and exclusion criteria. mTLFD classification was proposed based on the imaging characteristics: type I (intervertebral disc injury mainly) and type II (vertebral burst fracture mainly). The type II was classified based on distribution of injury segment: type IIa (T 11 and above) and Ttype IIb (below T 11). Six spinal surgeons (3 residents, 3 associate chief physicians) were selected to classify the 123 cases according to preoperative imaging data, and to perform reliability test of each type. The repeatability and reliability of the classification were evaluated by ICC index. Different management strategies were performedf or each type: type I was managed with posterior decompression interbody fusion and internal fixation; type IIa underwent posterior decompression and fixation, subtotal vertebral resection and fusion was performed if bony compromise was still present through intra-operative exploration. Type IIb underwent posterior decompression, posterolateral fusion and internal fixation on the first stage, while anterior subtotal vertebral resection and reconstruction was performed on the second stage if the bony compromise was still present based on post-operative CT examination. The American Spinal Injury Association (ASIA) grading of all patients was recorded, and the visual analogue scale (VAS), Oswetry disability Iindex (ODI) and local Cobb angle of each type was compared between pre-operation and final follow-up. Results:The average follow-up time of all patients was 10.4±1.8 months. The average repeatability and reliability ICC index of mTLFD of 3 residents and 3 deputy chief physicians were 0.926 and 0.964, respectively, and 0.746 and 0.907, respectively. The reliability ICC index of type I, type IIa and type IIb was 0.918, 0.947 and 0.962, respectively, and the repeatability ICC index was 0.930, 0.940 and 0.966, respectively. The neurological function recovery was obtained in 56 patients. The preoperative VAS of type I, type IIa and type IIb were 8.5±1.0, 8.4±1.0 and 8.3±0.9, and 2.0±1.1, 1.8±1.0 and 1.8±0.9 at the final follow-up (all P<0.001). The ODI of type I, type IIa and type IIb were 97.0%±2.1%, 97.1%±1.9% and 97.3%±2.1% before surgery, and 29.5%±6.8%, 27.0%±6.0% and 29.0%±6.7% at the final follow-up (all P<0.001). The local Cobb angles of type I, type IIa and type IIb were 20.9°±7.1°, 29.0°±9.1° and 26.4°±6.9° before surgery, and 12.5°±5.4°, 18.0°±9.1° and 13.1°±5.1° at the final follow-up (all P<0.001). Conclusion:The mTLFD classification proposed in this study has strong repeatability and reliability, and management strategy of each type have achieved satisfactory clinical efficacy, indicating that the classification has certain significance for management of thoracic and lumbar spine fracture dislocation.