AIM:This study aims to investigate the changes in the lactylation levels of mitsugumin 53(MG53)protein during myocardial ischemia/reperfusion(I/R)and to further explore the potential molecular mechanisms by which MG53 lactylation impacts myocardial cell injury resulting from I/R.METHODS:A myocardial I/R model was established in mice through ligation of the left anterior descending coronary artery followed by reperfusion.Simultaneous-ly,a hypoxia/reoxygenation(H/R)model of rat myocardial H9C2 cells was created in vitro.In the mouse model,TTC and HE staining were employed to assess myocardial ischemia and injury.The levels of creatine kinase and cardiac troponin I were quantified using ELISA,while MG53 expression was evaluated through immunofluorescence.In the in vitro cell model,CCK-8 assay and flow cytometry were utilized to measure cell viability and apoptosis level,respectively.The levels of MG53 protein,its lactylation,and ferroptosis-related proteins in both mouse myocardial tissue and in vitro rat cardiomyo-cytes were analyzed using immunoprecipitation and Western blot.Additionally,the levels of reactive oxygen species,fer-rous ion,lactate dehydrogenase and malondialdehyde in tissues and cells were measured using appropriate assay kits.RE-SULTS:In the I/R group,mouse myocardial tissue exhibited significant injury following cardiac I/R.The expression of MG53 protein was reduced,while the lactylation level of MG53 protein and the ferroptosis of myocardial cells were in-creased.In the in vitro cardiomyocyte experiments,H/R exposure resulted in decreased cell viability,increased apoptosis and ferroptosis levels,reduced MG53 protein expression,and increased MG53 lactylation level.Treatment with 2-deoxy-D-glucose(2-DG)improved cardiomyocyte viability,decreased apoptosis and ferroptosis levels,increased MG53 expres-sion,and lowered MG53 lactylation level.Furthermore,the addition of exogenous lactate significantly countered the ef-fects of 2-DG on cell viability and MG53 expression,and increased the cell apoptosis,ferroptosis and MG53 lactylation levels.CONCLUSION:During myocardial I/R,there is a down-regulation of MG53 protein expression accompanied by an increase in the lactylation level of MG53 protein.The elevation of MG53 lactylation may exacerbate myocardial I/R inju-ry by facilitating the ferroptosis of cardiomyocytes.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

AIM:This study aims to investigate the changes in the lactylation levels of mitsugumin 53(MG53)protein during myocardial ischemia/reperfusion(I/R)and to further explore the potential molecular mechanisms by which MG53 lactylation impacts myocardial cell injury resulting from I/R.METHODS:A myocardial I/R model was established in mice through ligation of the left anterior descending coronary artery followed by reperfusion.Simultaneous-ly,a hypoxia/reoxygenation(H/R)model of rat myocardial H9C2 cells was created in vitro.In the mouse model,TTC and HE staining were employed to assess myocardial ischemia and injury.The levels of creatine kinase and cardiac troponin I were quantified using ELISA,while MG53 expression was evaluated through immunofluorescence.In the in vitro cell model,CCK-8 assay and flow cytometry were utilized to measure cell viability and apoptosis level,respectively.The levels of MG53 protein,its lactylation,and ferroptosis-related proteins in both mouse myocardial tissue and in vitro rat cardiomyo-cytes were analyzed using immunoprecipitation and Western blot.Additionally,the levels of reactive oxygen species,fer-rous ion,lactate dehydrogenase and malondialdehyde in tissues and cells were measured using appropriate assay kits.RE-SULTS:In the I/R group,mouse myocardial tissue exhibited significant injury following cardiac I/R.The expression of MG53 protein was reduced,while the lactylation level of MG53 protein and the ferroptosis of myocardial cells were in-creased.In the in vitro cardiomyocyte experiments,H/R exposure resulted in decreased cell viability,increased apoptosis and ferroptosis levels,reduced MG53 protein expression,and increased MG53 lactylation level.Treatment with 2-deoxy-D-glucose(2-DG)improved cardiomyocyte viability,decreased apoptosis and ferroptosis levels,increased MG53 expres-sion,and lowered MG53 lactylation level.Furthermore,the addition of exogenous lactate significantly countered the ef-fects of 2-DG on cell viability and MG53 expression,and increased the cell apoptosis,ferroptosis and MG53 lactylation levels.CONCLUSION:During myocardial I/R,there is a down-regulation of MG53 protein expression accompanied by an increase in the lactylation level of MG53 protein.The elevation of MG53 lactylation may exacerbate myocardial I/R inju-ry by facilitating the ferroptosis of cardiomyocytes.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective To explore the effect of the diagnosis and endoscopic minimally invasive surgical treatment of non-cystic congenital pyriform sinus fistula(CPSF)in children.Methods Clinical data of 76 children with non-cystic CPSF were retrospectively analyzed from October 2017 to May 2022.Larygoscope,neck color ultrasound,esophageal barium meal,neck CT,and magnetic resonance imaging(MRI)were performed,and temperature-controlled ablation radio-frequency was performed under general anesthesia supported by laryngoscope guidance.Results The internal fistula in the pyriform fossa was seen under laryngoscope.Imaging examination shows that the fistula was connected to the pharynx.Postoperative complications:hoarseness in 3 cases and deciduous tooth loss in 3 cases.After a follow-up period of 12～40 months,there was 1 recurrence in 46 newly treated patients and 1 recurrence in 30 non newly treated patients.No recurrence was observed during the follow-up period after re-endoscopic radiofrequency plasma surgical electrodes plasma cauterization.Conclusion The symptoms of CPSF are non-specific.The discovery of the internal fistula under endoscopy is the gold standard for diagnosis.Ultrasound can be used as the initial screening method for diagnosis.Esophageal barium meal combined with CT examination can improve the diagnostic rate,and MRI can assist in diagnosis.The temperature-controlled ablation radio-frequency technique under supportive laryngoscope has the advantages of safety,minimally invasive,aesthetic,convenient,and repeatable operation,and can be used as the preferred method for the treatment of non-cystic CPSF in children.