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 compare the midterm outcomes of the Bentall procedure versus isolated aortic valve replacement(AVR)in patients with bicuspid aortic valve(BAV)complicated with severe stenosis and ascending aortic dilation in order to assess the therapeutic value of these surgical approaches for this complex cardiac condition.Methods A retrospective cohort study was conducted on 96 eligible patients who underwent surgical treatment in our institute between January 2018 and December 2022.According to surgical approaches,they were divided into an AVR group(65 cases)and a Bentall group(31 cases).Demographic features,comorbidities,preoperative status,and echocardiographic parameters were collected in all patients.Propensity score matching(PSM)was applied in a 1:1 ratio to balance baseline characteristics.Perioperative indicators and follow-up data were compared and analyzed between matched cohorts after control of cofounding factors.Results After PSM,25 matched pairs were screened out and analyzed with comparable baseline data(all P>0.05).The Bentall group demonstrated significantly more superior intraoperative effective orifice area(EOA,2.69±0.47 vs 2.35±0.47 cm2,P=0.013)and EOA index(EOAI,1.69±0.30 vs 1.47±0.29 cm2/m2,P=0.010),and obviously longer cardiopulmonary bypass time[190.00(147.00,257.00)vs 101.00(88.50,124.50)min,P<0.01]and aortic cross-clamp time[141.00(120.00,166.00)vs 66.00(55.00,81.50)min,P<0.01]when compared with the AVR group.During a median follow-up of 28 months,the AVR group had notably larger aortic sinus diameter[32.00(30.00,34.00)vs 26.80(26.00,28.00)mm,P<0.01]and ascending aortic diameter[38.00(34.50,42.00)mm vs 26.00(26.00,28.00)mm,P<0.01],with ongoing dilation in the ascending aorta,while the Bentall group maintained stable dimensions.The Bentall group also showed statistically lower peak aortic valve pressure gradients[21.00(15.50,27.00)vs 25.00(19.50,31.00)mmHg,P=0.049].Conclusion Both Bentall procedure and AVR are effective in treatment of BAV complicated with severe stenosis and ascending aortic dilation.But,Bentall procedure offers advantages in hemodynamic optimization and aortic stability.

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.

Baricitinib is a new type and small molecule targeted disease-modifying antirheumatic drug.By targeting tyrosine protein kinase(JAK)1 and JAK2,it selectively inhibits the transcription,expression and response function of inflammatory cytokines,chemokines and cell growth factors that are involved in immune abnormalities regulated by the JAK-STAT pathway.A variety of pharmacological effects,such as anti-inflammatory,protecting musculoskeletal,reducing proteinuria and preventing inflammatory cytokine storm effects,and protecting skin and hair from immune damage,have shown good efficacy in a variety of rheumatic and autoimmune skin diseases.Based on the current basic and clinical research of baricitinib,this article gives an overview of the pharmacological effects and clinical application of baricitinib,and provides certain reference for the standardized and rational use of baricitinib in clinical practice.

Baricitinib is a new type and small molecule targeted disease-modifying antirheumatic drug.By targeting tyrosine protein kinase(JAK)1 and JAK2,it selectively inhibits the transcription,expression and response function of inflammatory cytokines,chemokines and cell growth factors that are involved in immune abnormalities regulated by the JAK-STAT pathway.A variety of pharmacological effects,such as anti-inflammatory,protecting musculoskeletal,reducing proteinuria and preventing inflammatory cytokine storm effects,and protecting skin and hair from immune damage,have shown good efficacy in a variety of rheumatic and autoimmune skin diseases.Based on the current basic and clinical research of baricitinib,this article gives an overview of the pharmacological effects and clinical application of baricitinib,and provides certain reference for the standardized and rational use of baricitinib in clinical practice.

Objective To understand the trends and characteristics of clinical trials on cancer pain medications in recent years,and to provide a reference basis for the development and clinical research of cancer pain medications.Methods Relevant information on clinical trials of cancer pain medications from 1987 to 2022 was retrieved from the ClinicalTrials.gov database,and a descriptive analysis was conducted from the perspectives of trial types,registration dates,reporting regions,cancer pain type,and cancer pain medications.Results A total of 376 clinical trials were selected,Among them,the number of investigator-initiated trials(IIT)was greater than that of industry-sponsored trials(IST).North America had the highest total number of projects,IIT and IST projects.The total number of trials and IST projects increased first and then decreased,while the number of IIT trials steadily increased.There was relatively higher amount nof research focused on chronic cancer pain,breakthrough cancer pain,and severe cancer pain.The highest proportion of subjects studied were opioids,with fentanyl being particularly prominent among them.Conclusion Clinical trials of cancer pain medications have played an important role in advancing cancer pain medication,but there is a need to further strengthen IST research on novel cancer pain medications and conduct more IIT studies to better optimize cancer pain treatment outcomes.

Objective To observe the clinical efficacy of Redo-Bentall surgery in the reoperation of aortic root lesions.Methods A retrospective analysis was performed on 46 patients who underwent Redo-Bentall surgery for aortic root lesions in our department from June 2010 to April 2022.They were 35 males and 11 females,at a mean age of 43.37±12.79 years,in 4.96±6.76 years since the last operation.General clinical data in perioperative period and during follow-up were collected and analyzed.Kaplan-Meier survival analysis was used to compare the survival rates of each etiological group.Results There were 9 cases of central end otitis,12 cases of Behset's disease,and 25 cases of other causes.After operation,4 cases(8.70％)experienced cardiac arrest,4 cases(8.70％)renal failure,2 cases(4.35％)gastrointestinal bleeding,2 cases(4.35％)new third-degree atrioventricular block and 2 cases(4.35％)permanent pacemaker placement.In perioperative period,3 cases(6.52％)died in hospital.During a mean follow-up of 5.03±3.27 years after discharge,5 cases(11.63％)were lost to follow-up,1 case died(2.33％),1 case had lacunar infarction(2.33％),and no severe bleeding or embolism complications was observed in the rest patients.The long-term survival rate was significantly lower in the endocarditis group(62.3％)and the Behcet's disease group(70％)than the other etiological groups(80％,P＜0.05).Conclusion The application of Redo-Bentall in the reoperation of aortic root lesions is safe and effective,but the survival rate is quite lower in the patients with infective endocarditis and Behcet's disease.

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.

Background: Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. Objectives: The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. Methods: 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. Results: Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. Conclusions Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.

Background: Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. Objectives: The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. Methods: 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. Results: Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. Conclusions Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.