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.

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.

Inhibitory cells derived from bone marrow are a kind of inhibitory cells derived from bone marrow.These cells are not only related to tumor growth,but also participate in the inflammatory immune process.Therefore,we established a rat model of chronic osteomyelitis,and used gemcitabine to inhibit the cell growth ratio of MDSCs.We detected the ratio of MDSCs in bone marrow and spleen of rats by flow cytometry and immunofluorescence,detected the changes of inflammatory factors in peripheral blood by ELISA,and analyzed the inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-11)in peripheral blood of normal rats,osteomyelitis rats and rats after gemcitabine inhibition.The results showed that the proportion of MDSCs cells in bone marrow and spleen of osteomyelitis model rats was increased,but it was significantly decreased in gemcitabine group(P<0.05).Levels of inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-17,IFN-γ,TGF-β)were positively correlated with the change of MDSCs cell proportion(P<0.05).From the results,it can be inferred that the change of the proportion of MDSCs cells in rat osteomyelitis is positively related to the inflammatory factors,and gemcitabine can reduce inflammatory factors by inhibiting MDSCs.

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.

Azoospermia accounts for 10%-15% of male infertility, with the prevalence of 1% in male population. Obstructive azoospermia (OA) accounts for 40% of azoospermia and can be caused by a variety of factors, including male reproductive duct inflammation and genetic factors. Given the fact that the spermatogenesis is normal in the testis of OA patients, the OA patients can have their own offspring through testicular biopsy and sperm retrieval followed by assisted reproductive technology (ART). Therefore, the genetic etiology of OA is often overlooked. Subsequently, studies of the following ART strategies and offspring birth defects are also ignored. This article reviewed the genetic disorders of OA patients, and the animal model with OA, providing new ideas for management of OA patients, genetic counseling, and development of male contraceptives.

Azoospermia accounts for 10%-15% of male infertility, with the prevalence of 1% in male population. Obstructive azoospermia (OA) accounts for 40% of azoospermia and can be caused by a variety of factors, including male reproductive duct inflammation and genetic factors. Given the fact that the spermatogenesis is normal in the testis of OA patients, the OA patients can have their own offspring through testicular biopsy and sperm retrieval followed by assisted reproductive technology (ART). Therefore, the genetic etiology of OA is often overlooked. Subsequently, studies of the following ART strategies and offspring birth defects are also ignored. This article reviewed the genetic disorders of OA patients, and the animal model with OA, providing new ideas for management of OA patients, genetic counseling, and development of male contraceptives.

Objective To explore the lower limbs joints movement of patients with unilateral and primary artificial hip replacement in convalescence. Methods 100 cases of patients with unilateral and primary artificial hip replacement in convalescence were chosen as the ob-servation group,while 100 cases of matched healthy subjects were included as the control groups. The three-dimensional kinematics and mo-tion of lower extremities were monitored. Results The difference in operated knee flexion,operated ankle planter flexion and operated hip flexion of the observation group and the observation group were statistically significant(P<0. 05). The difference in the joint angle peak of hip backward extension of sagittal section,hip adduction of frontal plane,knee adduction of frontal plane,ankle adduction and outreach of frontal plane,hip internal rotation and extorsion of horizontal plane,ankle rotation and extorsion of horizontal plane in two groups were statisti-cally significant(P<0. 05). Conclusion There are abnormal prosthetic joint movement,limited range of operated movement in patients with unilateral and primary artificial hip replacement in convalescence,and coterminous kinematic chains appear compensatory changes,it should strengthen the muscle exercises of operated hip.