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.

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.

Purpose/Significance To analyze the technical situation of patent owners in the field of clinical decision support system(CDSS)in China as a whole,so as to provide references for CDSS related technical research.Method/Process Firstly,the CDSS patent data are analyzed from the aspects of application trend,patent disclosure,technology field distribution,etc.,then the patentees are di-vided into different categories,and their technical concerns are analyzed by word frequency and interword vector.Finally,the technology correlation and patent exclusives are analyzed based on the active patentees.Result/Conclusion The number of CDSS patent disclosure shows an overall increasing trend.This field has not formed a technological monopoly in China.Government departments and research in-stitutions should pay attention to the possible financial risks.

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.

Objective:To investigate the short-term and medium-term changes of the left ventricular ejection fraction (LVEF) and the predictive value of relevant electrocardiogram (ECG) indexes in children with dilated cardiomyopathy (DCM) complicated with complete left bundle branch block (CLBBB).Methods:Children clinically diagnosed with DCM in the Department of Heart Center, Women and Children′s Hospital, Qingdao University and Beijing Anzhen Hospital, Capital Medical University between November 2011 and August 2020 were retrospectively recruited.According to the combination of CLBBB, they were divided into CLBBB group and non-CLBBB group.Echocardiogram and ECG were regularly performed.Short-term and medium-term changes of LVEF based on the 1-5-year follow-up data were compared between groups.COX proportional hazards model and Kaplan-Meier multiplicative limit method were used to analyze the predictive value of ECG indexes of LVEF changes in children with DCM combined with CLBBB.Results:Ninety-four children with DCM were enrolled, including 35 cases in CLBBB group and 59 cases in non-CLBBB group.There was no difference in baseline LVEF between groups.However, significant differences were found in QRS duration, corre-cted QT interval(QTc), R peak time in lead V 5 (T V5R) and QRS notching or slurring between groups ( P<0.05). LVEF of all children showed an upward trend within one year after onset, while the Z value of eft ventricular end diastolic diameter(LVEDd) showed a downward trend, and the two indexes tended to be stable within 1 - 5 years.The Z value of LVEDd in CLBBB group was significantly higher than that of non-CLBBB group, while LVEF was significantly lower (all P<0.05). The mean LVEF of CLBBB group slightly fluctuated around 50%, that of LVEF in non-CLBBB group was 60%.The multivariate COX regression analysis showed that QRS duration ( HR=0.979; 95% CI: 0.960-0.999, P<0.05) and QTc ( HR=0.988; 95% CI: 0.979-0.998, P<0.05) were independent predictors of LVEF recovery in children with DCM.Kaplan-Meier method showed a significant difference of LVEF normalization between DCM children with different QRS durations ( P<0.05), which was also detected in those with QTc interval ( P<0.05). Conclusions:LVEF of children with DCM combined with CLBBB increases in the short term after standard treatment, and then being stable.CLBBB can affect the recovery of left ventricular systolic function in children with DCM.Moreover, QRS duration and QTc interval are independent predictors of LVEF recovery in DCM children.

A significant proportion of patients with chorea-acanthocytosis (ChAc) fail to respond to standard therapies. Recent evidence suggests that globus pallidus internus (GPi) deep brain stimulation (DBS) is a promising treatment option; however, reports are few and limited by sample sizes. We conducted a systematic literature review to evaluate the clinical outcome of GPi-DBS for ChAc. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published before August 2021. The improvement of multiple motor and nonmotor symptoms was qualitatively presented. Improvements in the Unified Huntington’s Disease Rating Scale motor score (UHDRS-MS) were also analyzed during different follow-up periods. A multivariate linear regression analysis was conducted to identify potential predictors of clinical outcomes. Twenty articles, including 27 patients, were eligible. Ninety-six percent of patients with oromandibular dystonia reported significant improvement. GPi-DBS significantly improved the UHDRS-motor score at < 6 months (p < 0.001) and ≥ 6 months (p < 0.001). The UHDRS-motor score improvement rate was over 25% in 75% (15/20 cases) of patients at long-term follow-up (≥ 6 months). The multiple linear regression analysis showed that sex, age at onset, course of disease, and preoperative movement score had no linear relationship with motor improvement at long-term follow-up (p > 0.05). GPi-DBS is an effective and safe treatment in most patients with ChAc, but no reliable predictor of efficacy has been found. Oromandibular dystonia-dominant patients might be the best candidates for GPi-DBS.

Objective:To analyze the feasibility and safety of microsurgical anastomosis for obstructive azoospermia (OA) patients with prior intracytoplasmic sperm injection (ICSI) failure.Methods:From September 2015 to May 2020, the data of 20 OA patients with previous ICSI-assisted pregnancy failure admitted to the Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The characteristics of seminal tract microsurgical reconstruction were summarized, and the postoperative recurrence rate and clinical pregnancy rate were calculated.Results:Vasal obstruction was found in 8 patients and epididymal obstruction in 12 patients during microscopically reconstructed seminal tract. Among the patients with vasal obstruction, 1 patient developed OA after trauma and underwent laparoscopic-assisted right vasovasostomy (VV). Totally 7 patients developed OA after juvenile bilateral hernia, among whom 6 patients underwent further laparoscopic-assisted VV and 1 patient underwent vasovasostomy and epididymal cross anastomosis. Of the 8 patients who underwent VV, 6 achieved postoperative patency, and 2 couples achieved natural pregnancy. Patients with epididymal obstruction underwent microscopic vasoepididymostomy (VE), and 6 out of 12 patients achieved postoperative pregnancy, while 3 couples achieved natural pregnancy. No significant complications occurred in all patients during and after operation.Conclusion:Microsurgical anastomosis is an effective remedy for patients with OA after ICSI pregnancy failure, which can help patients achieve natural pregnancy.

Objective:To analyze the feasibility and safety of microsurgical anastomosis for obstructive azoospermia (OA) patients with prior intracytoplasmic sperm injection (ICSI) failure.Methods:From September 2015 to May 2020, the data of 20 OA patients with previous ICSI-assisted pregnancy failure admitted to the Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The characteristics of seminal tract microsurgical reconstruction were summarized, and the postoperative recurrence rate and clinical pregnancy rate were calculated.Results:Vasal obstruction was found in 8 patients and epididymal obstruction in 12 patients during microscopically reconstructed seminal tract. Among the patients with vasal obstruction, 1 patient developed OA after trauma and underwent laparoscopic-assisted right vasovasostomy (VV). Totally 7 patients developed OA after juvenile bilateral hernia, among whom 6 patients underwent further laparoscopic-assisted VV and 1 patient underwent vasovasostomy and epididymal cross anastomosis. Of the 8 patients who underwent VV, 6 achieved postoperative patency, and 2 couples achieved natural pregnancy. Patients with epididymal obstruction underwent microscopic vasoepididymostomy (VE), and 6 out of 12 patients achieved postoperative pregnancy, while 3 couples achieved natural pregnancy. No significant complications occurred in all patients during and after operation.Conclusion:Microsurgical anastomosis is an effective remedy for patients with OA after ICSI pregnancy failure, which can help patients achieve natural pregnancy.