ObjectiveTo investigate the association of physical activity and balance ability with disability, and to further examine the mediating role of balance ability in the relationship between physical activity and disability. MethodsBased on data from 2021 to 2023 National Health and Nutrition Examination Survey (NHANES) cycle, a multivariable Logistic regression model was constructed to evaluate the independent association of physical activity and balance ability with disability, with covariates adjusted in four steps. An interaction model was further developed to assess the multiplicative interaction between physical activity and balance ability. Mediation analysis was performed using the Baron and Kenny three-step approach to examine the mediating role of balance ability, and the proportion of the mediation effect was calculated. The significance of the mediation effect was assessed using the Delta method, and robustness was verified through the Bootstrap method with a fixed random seed. Multiple sensitivity analyses were conducted to ensure the stability of the results. ResultsA total of 3 902 participants were included, with a prevalence of disability of 17.7%. Multivariable regression analysis showed that, after adjusting for all covariates, both light-intensity physical activity (LIPA) (OR = 0.489, 95%CI 0.380 to 0.629, P < 0.001) and high-intensity physical activity (HIPA) (OR = 0.493, 95%CI 0.371 to 0.656, P < 0.001) were significantly associated with a reduced risk of disability, whereas impaired balance ability was significantly associated with an increased risk (OR = 1.579, 95%CI 1.266 to 1.970, P < 0.001). The interaction effect analysis showed that the interaction between physical activity and balance ability were not significant (P > 0.05), however, the main effect of LIPA remained robust (β = -0.597, SE = 0.221, OR = 0.550, P = 0.007), while impaired balance ability was significantly associated with an increased risk of disability (β = 0.577, SE = 0.231, OR = 1.780, P = 0.012). The mediation analysis further indicated that balance ability played a robust mediating role in the association between LIPA and disability, with a mediation proportion of 21.1%. The indirect effect (a × b) was statistically significant (P < 0.001), and the 95% confidence intervals derived from the bootstrap method did not include zero. ConclusionPhysical activity and balance ability are significantly associated with disability, and balance ability may mediate the relationship between physical activity and disability, highlighting its potential value in disability risk assessment and intervention strategies.

ObjectiveTo observe the clinical effectiveness and safety of Xiaozhong Zhitong Mixture （消肿止痛合剂） combined with antibiotic bone cement in the treatment of diabetic foot ulcer （DFU） with damp-heat obstructing syndrome. MethodsA total of 72 DFU patients with damp-heat obstructing syndrome were randomly assigned to treatment group （36 cases） and the control group （36 cases）. Both groups received standard treatment and topical antibiotic bone cement for ulcer wounds， while the treatment group received oral Xiaozhong Zhitong Mixture （50 ml per time， three times daily） in additionally. Both groups underwent daily wound dressing changes for 21 consecutive days. Ulcer healing rate， serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1 beta （IL-1β）， malondialdehyde （MDA）， superoxide dismutase （SOD）， C-reactive protein （CRP）， and white blood cell （WBC） count were observed before and after treatment， and visual analog scale （VAS） scores for wound pain， traditional Chinese medicine （TCM） syndrome scores， and the DFU Healing Scale （DMIST scale） were also compared. Liver and kidney function were evaluated before and after treatment， and adverse events such as allergic reactions， worsening ulcer pain were recorded. ResultsTotally 35 patients in the treatment group and 33 in the control group were included in the final analysis. The ulcer healing rate in the treatment group was （87.93±9.34）%， significantly higher than （81.82±12.02）% in the control group （P = 0.035）. Compared to pre-treatment levels， both groups showed significant reductions in serum CRP， WBC， MDA， IL-1β， and TNF-α levels， with an increase in SOD level （P＜0.05）. TCM syndrome scores， VAS， and DMIST scores also significantly decreased in both groups （P＜0.05）， with greater improvements in the treatment group （P＜0.05）. No significant adverse reactions were observed in either group during treatment. ConclusionXiaozhong Zhitong Mixture combined with antibiotic bone cement has significant advantages in promoting DFU healing， reducing inflammatory response， and alleviating oxidative stress in DFU patients with damp-heat obstructing syndrome， with good safety for DFU patients with damp-heat obstructing syndrome.

BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

Objective To investigate the effects of simulated-microgravity on the osteogenic differentiation,primary cilia status,cytoskeleton structure,and the YAP(Yes-associated protein)expression in primary osteoblasts.Methods Primary osteoblasts were isolated from the skull bones of neonatal Wistar rats and cultured in random positioning machine system to simulate the cellular effects of microgravity.The calcified nodules were stained with Arlizarin to assess the cellular mineralization ability,the primary cilia and cytoskeleton were detected by immunofluorescence staining of Arl13b/γ-Tubulin and α-Tubulin,respectively,and the expression of YAP was measured by western blot.Results The cellular osteogenic differentiation were markedly suppressed after treated with simulated microgravity for 24 h,and the ciliated cells decreased from(58.44±3.65)%to(15.76±1.84)%in parallel with a decline of average cilium length from(3.19±0.51)μm to(1.59±0.46)μm.In addition,simulated microgravity induced disassembly of microtubules.Notably,simulated microgravity interfered YAP expression and the inhibition of YAP into nucleus.Furthermore,knockdown of YAP expression in osteoblasts notably reduced primary cilia expression and inhibited osteogenic differentiation.Conclusion Primary cilia is a key organelle of osteoblasts in sensing microgravity and regulating osteogenic differentiation.Interference with YAP expression and inhibition of nuclear YAP entry may play an important role in the deaggregation of primary cilia induced by microgravity.

Flap surgery is a complex surgical procedure that has become an effective method for the treatment of many diseases and traumas.Flap survival is closely related to a variety of factors including cellular autophagy,oxidative stress,inflammatory response,mesenchymal stem cells(MSCs)function,and vascular regeneration.Cellular autophagy maintains intracellular homeostasis and plays a key role in reducing oxidative stress and inflammation and promoting injury repair.Excessive oxidative stress and inflammatory responses pose a threat to flaps,affecting their survival and successful transplantation.Endothelial cells are involved in vascu-lar regeneration through proliferation,migration,and production of angiogenic factors,and vascular endothelial growth factor directly promotes blood vessel formation and maintains endothelial cell function.MSCs play an important role in promoting flap survival and tissue repair due to their unique biological properties and multiple mechanisms of action.The multiple roles played by cellular autophagy,oxidative stress,inflammatory response,MSCs function,and vascular regeneration in influencing postoperative flap survival are hereby elaborated.The aim is to provide a basis for the clinical application of regulating the above factors to improve postoperative flap survival,improve the success rate of flap surgery,reduce complications,and bring more hope for the recovery and quality of life of patients.

Diabetic ulcer （DU） wound is one of the chronic and serious complications of diabetes characterized by prolonged wound healing， and it is more common in foot and lower extremity ulcers. DU has brought great economic and psychological pressure to patients and seriously affected the quality of life of patients because of its great difficulty in treatment， long treatment process， and high morbidity and mortality. Therefore， how to help the rapid healing of DU wounds， reduce the disability rate and mortality rate， protect limb function， and improve the quality of life is an important topic and hot spot in the field of medical research. The pathogenesis of DU is complex， mainly including microcirculation disorder， peripheral neuropathy， inflammation and infection， and excessive apoptosis of cells， involving physiological processes such as wound inflammation， granulation tissue hyperplasia and re-epithelialization. A large number of previous studies have found that Chinese medicine can regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Notch， nuclear factor E₂-related factor 2 （Nrf2）， transforming growth factor-β （TGF-β）/Smad， and other signaling pathways， regulate abnormal glucose metabolism， improve microcirculation， inhibit inflammation and oxidative stress， regulate cell proliferation and excessive apoptosis， and promote wound tissue growth to promote the rapid healing of DU wounds under the guidance of treatment based on traditional Chinese medicine （TCM） syndrome differentiation and internal and external treatment. Therefore， this paper reviewed Chinese medicinal monomers or Chinese medicinal compounds in recent years in regulating the above signaling pathways and the expression of key protein molecules and promoting the rapid healing of DU wounds， aiming to provide ideas and a theoretical basis for the in-depth study and clinical application of Chinese medicine in promoting the healing of DU wounds.

Flap surgery is a complex surgical procedure that has become an effective method for the treatment of many diseases and traumas. Flap survival is closely related to a variety of factors including cellular autophagy, oxidative stress, inflammatory response, mesenchymal stem cells (MSCs) function, and vascular regeneration. Cellular autophagy maintains intracellular homeostasis and plays a key role in reducing oxidative stress and inflammation and promoting injury repair. Excessive oxidative stress and inflammatory responses pose a threat to flaps, affecting their survival and successful transplantation. Endothelial cells are involved in vascular regeneration through proliferation, migration, and production of angiogenic factors, and vascular endothelial growth factor directly promotes blood vessel formation and maintains endothelial cell function.MSCs play an important role in promoting flap survival and tissue repair due to their unique biological properties and multiple mechanisms of action. The multiple roles played by cellular autophagy, oxidative stress, inflammatory response, MSCs function, and vascular regeneration in influencing postoperative flap survival are hereby elaborated. The aim is to provide a basis for the clinical application of regulating the above factors to improve postoperative flap survival, improve the success rate of flap surgery, reduce complications, and bring more hope for the recovery and quality of life of patients.

BACKGROUND:Persistent hyperglycemia has been identified as promoting neurovascular dysfunction,leading to irreversible endothelial dysfunction,increased neuronal apoptosis,oxidative stress and inflammation.These changes in combination or alone lead to microvascular and macrovascular lesions as well as progressive neuropathy.Noncoding RNAs may provide a new strategy for understanding the etiology,pathogenesis and treatment of the disease. OBJECTIVE:To review the role and mechanism of noncoding RNAs in the occurrence and development of diabetic peripheral neuropathy by reviewing relevant literature at home and abroad,in order to provide new ideas and approaches for noncoding RNAs in the prevention,diagnosis and treatment of diabetes neuropathy. METHODS:CNKI and PubMed were retrieved for relevant literature published from database inception to 2022.The key words were"noncoding RNA;lncRNA;miRNA;diabetes peripheral neuropathy;expression profile"in Chinese and English,respectively.The retrieved documents were summarized and analyzed,and 61 articles were finally selected for further review. RESULTS AND CONCLUSION:(1)Noncoding RNA plays a key role in the pathophysiological process of diabetic peripheral neuropathy.Among the most widely studied regulatory noncoding RNA species,there are long noncoding RNAs,circular RNAs and microRNAs.(2)Through the regulation of noncoding RNAs,the activation or inhibition of related cell pathways,inflammatory genes and downstream-related cytokines will inhibit cell apoptosis,improve inflammation,and thus change the expression of target genes to participate in the process of diabetic neuralgia.(3)Although many microRNAs and long noncoding RNAs have been found to participate in diabetic peripheral neuropathy,the mechanisms of many noncoding RNAs are unclear,and the same noncoding RNAs may play different roles in different modes.Therefore,it is necessary to further study their action modes in disease etiology and pathology,thereby clarifying their role in the pathogenesis of diabetic peripheral neuropathy.However,the criteria for evaluating noncoding RNA activity have not yet been established,and further research is needed on which specific noncoding RNAs play a dominant regulatory role.(4)MicroRNAs,long noncoding RNAs and their target genes can regulate progressive neuropathy,which are expected to become new targets for the clinical prevention and treatment of diabetic peripheral neuropathy and new biomarkers for the development and prognosis of diabetic peripheral neuropathy.

BACKGROUND:Mesenchymal stem cells have great potential in the treatment of ischemia-reperfusion injury of skin flaps.However,their defects and the decline of their role in the treatment of ischemia-reperfusion injury of skin flaps restrict their wide application. OBJECTIVE:To review the strategies for improving the treatment of ischemia-reperfusion injury of skin flaps with mesenchymal stem cells,and provide a reference for its further theoretical research and clinical application. METHODS:Relevant documents included in CNKI,WanFang and PubMed were searched.The Chinese and English search terms were"mesenchymal stem cell,ischemia-reperfusion adjustment of skin flap,mesenchymal stem cells,stem cells,skin flap,ischemia-reperfusion injury,pretreatment,gene modification,biomaterial packaging,joint application".The relevant documents since 2007 were retrieved,and the documents with little relationship between the research content and the article theme,poor quality and outdated content were eliminated through reading the article,and finally 75 documents were included for summary. RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can inhibit inflammatory reactions,resist oxidative stress and induce angiogenesis,which has great potential in the treatment of skin flap ischemia-reperfusion injury.(2)Although mesenchymal stem cells have shown great potential in the treatment of skin flap ischemia-reperfusion injury,their shortcomings in treatment have limited their widespread clinical application.Through pre-treatment(cytokines,hypoxia,drugs,and other pre-treatment mesenchymal stem cells),gene-modified mesenchymal stem cells,biomaterial encapsulation of mesenchymal stem cells,as well as the combined use of mesenchymal stem cells and other drugs or therapeutic methods,can not only overcome the shortcomings of mesenchymal stem cells in treatment,but also improve their therapeutic effectiveness in skin flap ischemia-reperfusion injury.(3)Therefore,further improving the effectiveness of mesenchymal stem cells in treating skin flap ischemia-reperfusion injury and exploring its therapeutic potential are of great significance for the research of mesenchymal stem cells and the treatment of skin flap ischemia-reperfusion injury.