Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

OBJECTIVES: To investigate the mechanism by which Guijianyu ameliorates podocyte injury in a mouse model of diabetic kidney disease (DKD) induced by advanced glycation endproducts (AGEs). METHODS: Sixty db/db mouse models of DKD were randomized equally into 5 groups for treatment with saline, Guijianyu extract at 3 doses or irbesartan for 12 weeks, and the changes in renal pathology and structure were observed using transmission electron microscopy, and the expressions of related genes and key proteins were detected using RT-qPCR and immunohistochemistry. In cultured MPC-5 cells incubated with 50 mg/L AGEs-BSA for 24 h, the effect of different concentrations of Guijianyu extract on cell viability was examined with CCK-8 assay; Western blotting was performed to detect the protein expressions of RAGE, VEGFA, TNF-α, NF-κB(p65), IL-6 and caspase-3, and the mRNA expressions of RAGE, NF-κB (p65), VEGFA and IL-6 were detected with RT-qPCR. RESULTS: In mouse models of DKD, treatment with high-dose Guijianyu extract significantly reduced renal expressions of RAGE, VEGFA, NF-κB(p65), and IL-6 proteins and the mRNA expressions of RAGE, NF-κB, and IL-6. In MPC-5 cells, exposure to AGEs significantly reduced cell viability and increased the protein expressions of RAGE, NF‑κB (p65), VEGFA, TNF-α, IL-6 and caspase-3 (P<0.05) and mRNA expressions of RAGE, NF-κB (p65), VEGFA, and IL-6. Treatment with Guijianyu extract obviously improved cell viability and reduced the expressions of RAGE, NF-κB(p65), VEGFA, TNF-α, IL-6, and caspase-3. Furthermore, Guijianyu extract effectively reversed RAGE agonist-induced elevation of protein expressions of RAGE, VEGFA, TNF-α, IL-6, and caspase-3 and mRNA expressions of RAGE, NF-κB (p65), IL-6, and VEGFA in MPC-5 cells. CONCLUSIONS Guijianyu extract ameliorates AGEs-induced mouse renal podocyte injury in DKD by inhibiting the activation of AGEs-RAGE signaling pathway and reducing the expressions of pro-inflammatory cytokines and vascular endothelial growth factors.
Animals ; Glycation End Products, Advanced ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Signal Transduction/drug effects* ; Podocytes/pathology* ; Diabetic Nephropathies/drug therapy* ; Receptor for Advanced Glycation End Products ; Vascular Endothelial Growth Factor A/metabolism* ; Interleukin-6/metabolism* ; Male

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

Objective To evaluate the clinical effect of Tension-free laparoscopic lateral suspension with mesh for pelvic organ prolapse.Methods A total of 85 patients who underwent pelvic organ prolapse were selected as the study group,and 40 patients underwent Laparoscopic sacral fixation surgery(LSC)as the control group in Henan Provincial People's Hospital from March 1,2021 to October 31,2023.The patients were divided into two subgroups:uterine preservation group and uterine resection group and followed up until April 30,2024.The intra-operative conditions and postoperative complications were recorded and analyzed.POP quantitative staging(POP-Q)scores were used for evaluation.Preoperative and postoperative quality of life and therapeutic effect were evaluated using the pelvic floor distress inventory short form-20(PFDI-20),urinary distress inventory-6(UDI-6),colorectal-anal distress inventory-8(CRADI-8),pelvic organ prolapse distress inventory-6(POPDI-6),pelvic floor impact questionnaire-7(PFIQ-7),prolapse and Incontinence sexual function questionnaire short form(PISQ-12).Results The median follow-up time for patients in the study group is 13.13 months,with an objective cure rate of 96.47%and a reoperation rate of 1.18%.The perioperative complication rates are 6.45%for uterine resection and 4.35%for uterine preservation,while the mesh exposure rate is 1.61%for uterine resection.In comparison,the median follow-up time for patients in the control group is slightly longer at 13.76 months,with an objective cure rate of 92.5%and a reoperation rate of 2.5%.The perioperative complication rates are higher at 14.71%for uterine resection and as high as 33.33%for uterine preservation,while the mesh exposure rate is also elevated at 8.82%for uterine resection.Despite these differences,there was no significant disparity in objective cure rates or reoperation rates between the study group and the control group.Furthermore,it was observed that the study group experienced shorter operation times,less bleeding,faster postoperative recovery,shorter hospitalization periods,lower perioperative complications,and reduced mesh exposure rates-especially among patients with uterine preservation.Additionally,intra-group comparisons revealed significant improvements in all POP-Q indicators one year after surgery(P<0.05),along with significantly lower scores on PFDI-20,UDI-6,CRADI-8,POPDI-6,PFIQ-7,and PISQ-12 scales com-pared to pre-surgery levels(P<0.05).However,no significant inter-group differences were noted.Conclusions Tension-free laparoscopic lateral suspension with mesh proves to be an effective surgical approach for treating ante-riorand middle pelvic organ prolapse.It demonstrates few perioperative complications while significantly improving prolapse symptoms and enhancing patient qualityof life.It stands as a viable alternative to sacrocolpopexy,particu-larly beneficial for patients with a preserved uterus.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Objective To empirically analyze the status quo of high-quality development of public hospitals in S Province,provides reference for promoting high-quality development of public hospitals.Methods SPSS 26.0 soft-ware and text analysis method were used to process the high-quality development monitoring data of tertiary public hospitals in S Province,and the qualitative interview results obtained by field investigation were comprehensively ana-lyzed.Results In terms of capacity improvement,public hospitals actively take measures such as the construction of medical union and the reform of payment methods to improve their capacity.Specialized hospitals and maternity and child care hospitals need to be improved in some indicators.In terms of structural optimization,the quality of medi-cal services is high in all regions.The proportion of medical service revenue and the proportion of high-grade surgery still need to be increased.In terms of innovation and efficiency improvement,the application level of electronic medi-cal records has made remarkable progress in various regions.There are differences in the funding of scientific re-search projects.In terms of cultural cohesion,patient satisfaction was higher.There is improvement room in the satisfaction of medical staff.Conclusion Third-level public hospitals in S province have achieved certain results in high-quality de-velopment,but there are still problems,such as the need to further integrate party building work with hospital busi-ness work,the lack of connection between performance incentive and performance evaluation index system,and the need to improve the satisfaction of medical staff.It is necessary to solve the problem and improve the quality and efficiency of medical service.

Objective To sort out and quantitatively evaluate the policies of"Internet+Nursing Service",and provide reference for the formulation and improvement of policies.Methods It uses ROST CM 6.0 software to mine the text data of 6"Internet+Nursing service"policies,constructs Policy Modeling Consistency(PMC)index model,and uses 9 first-class variables and 43 second-class variables to quantitatively evaluate the"Internet+Nursing service"policies.Results Among the 6 policies,1 policies were of good grade,5 policies were of acceptable grade,and the mean value of PMC index was 6.40,which was at the level of qualified or above,with higher scores on the primary variables X7 policy tools(0.95),X1 policy nature(0.92)and X9 policy evaluation(0.83),and lower scores on X8 incentive methods(0.63),X2 issuing organizations(0.58),and X5 policy timeliness(0.25).Conclusion The construction of the policy framework of"Internet+Nursing Service"in China is in the exploratory stage,and there is still room for improvement.It is recommended to improve the continuity and standardization of"Internet+Nursing Service"through rational planning of policy timing,comprehensive implementation of division of labour and coordination,and adoption of diversified incentives,etc.,so as to facilitate the high-quality development of public hospitals.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Objective To empirically analyze the status quo of high-quality development of public hospitals in S Province,provides reference for promoting high-quality development of public hospitals.Methods SPSS 26.0 soft-ware and text analysis method were used to process the high-quality development monitoring data of tertiary public hospitals in S Province,and the qualitative interview results obtained by field investigation were comprehensively ana-lyzed.Results In terms of capacity improvement,public hospitals actively take measures such as the construction of medical union and the reform of payment methods to improve their capacity.Specialized hospitals and maternity and child care hospitals need to be improved in some indicators.In terms of structural optimization,the quality of medi-cal services is high in all regions.The proportion of medical service revenue and the proportion of high-grade surgery still need to be increased.In terms of innovation and efficiency improvement,the application level of electronic medi-cal records has made remarkable progress in various regions.There are differences in the funding of scientific re-search projects.In terms of cultural cohesion,patient satisfaction was higher.There is improvement room in the satisfaction of medical staff.Conclusion Third-level public hospitals in S province have achieved certain results in high-quality de-velopment,but there are still problems,such as the need to further integrate party building work with hospital busi-ness work,the lack of connection between performance incentive and performance evaluation index system,and the need to improve the satisfaction of medical staff.It is necessary to solve the problem and improve the quality and efficiency of medical service.

Objective To sort out and quantitatively evaluate the policies of"Internet+Nursing Service",and provide reference for the formulation and improvement of policies.Methods It uses ROST CM 6.0 software to mine the text data of 6"Internet+Nursing service"policies,constructs Policy Modeling Consistency(PMC)index model,and uses 9 first-class variables and 43 second-class variables to quantitatively evaluate the"Internet+Nursing service"policies.Results Among the 6 policies,1 policies were of good grade,5 policies were of acceptable grade,and the mean value of PMC index was 6.40,which was at the level of qualified or above,with higher scores on the primary variables X7 policy tools(0.95),X1 policy nature(0.92)and X9 policy evaluation(0.83),and lower scores on X8 incentive methods(0.63),X2 issuing organizations(0.58),and X5 policy timeliness(0.25).Conclusion The construction of the policy framework of"Internet+Nursing Service"in China is in the exploratory stage,and there is still room for improvement.It is recommended to improve the continuity and standardization of"Internet+Nursing Service"through rational planning of policy timing,comprehensive implementation of division of labour and coordination,and adoption of diversified incentives,etc.,so as to facilitate the high-quality development of public hospitals.