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.

Cerebral small vessel disease （CSVD） has a high incidence rate， an insidious onset， a heterogeneous etiology， and serious damage. At present， there are still various critical issues in the clinical diagnosis and treatment of CSVD， including the difficulty in early warning， difficult etiological typing， and limited treatment methods. This article summarizes the clinical studies on the diagnosis and treatment of CSVD in recent years， in order to provide a reference for solving problems in diagnosis and treatment.
Biomarkers

Objective:To analyze the causal relationship between intestinal flora and vitiligo by two-sample Mendelian randomization (MR) analysis based on "co-diseases of skin and gut" in TCM.Methods:Genome-wide association study (GWAS) data of intestinal flora samples and vitiligo samples were obtained from the databases of MiBioGen and IEU OpenGWAS Project, respectively. Intestinal flora was used as exposure factor, vitiligo as outcome, and single nucleotide polymorphism (SNP) associated with various intestinal floras was used as instrumental variable. After screening qualified instrumental variable in this study, inverse variance weighting (IVW) was used for MR analysis to investigate the potential causal relationship between intestinal flora and vitiligo, MR-Egger regression, weighted median estimator (WME), weighted mode (WM), and simple mode (SM) were used as supplementary methods for IVW. The Cochran's Q test, MR-Egger intercept test, MR-PRESSO and leave one-out analysis were used for sensitivity analysis.Results:Euryarchaeota (IVW method: OR<1, P<0.05) were the protective factors for the occurrence of vitiligo, and Clostridialesvadin-BB60group (IVW method: OR>1, P<0.05) and Subdoligranulum (IVW method: OR>1, P<0.05) were the risk factors for the occurrence of vitiligo. No heterogeneity effect was found by the Cochran's Q test ( P>0.05), no horizontal pleiotropy was found by the MR-Egger intercept test ( P>0.05), no outliers were found in the MR-PRESSO analysis ( P>0.05), and the results of leave-one-out analysis indicated that the causal effects of the 3 identified intestinal floras on vitiligo were not driven by any single SNP. Conclusions:There are causal effects between some intestinal floras and vitiligo, but the specific mechanisms still need to be further studied. The gut microbiota affects the onset and treatment of vitiligo. Using TCM to regulate the gut microbiota may have a good therapeutic effect on treating vitiligo, providing a direction for clinical diagnosis and treatment of vitiligo.

This study explored the pathogenesis and treatment of postoperative pulmonary nodules from the perspective of deficient qi resulting into retention of pathogens,thus to expand the approach to its diagnosis and treatment.It is believed that deficient qi resulting into retention of pathogens contributes to the key pathogenesis of pulmonary nodules.As the root cause of the disease,deficient qi usually involves the deficiency of the lung and spleen.And as the incidental manifestations,retention of pathogens refers to the accumulation of pathological products such as stagnated qi,phlegm-stasis,and turbid toxins in the lung collaterals.The pathogenesis of postoperative pulmonary nodules is characterized by the collapse of pectoral qi,aggravated deficient qi,and the lingering presence of the relieved qi stagnation,phlegm-stasis,and turbid toxins.Based on the pathogenesis of deficient qi resulting into retention of pathogens,the treatment principles for postoperative pulmonary nodules should focus on tonifying deficiency and lifting collapse,and relieving qi stagnation and unblocking obstruction.Tonifying deficiency needs to prioritize strengthening the spleen and nourishing the lung to go first,lifting collapse aims at elevating the pectoral qi,relieving qi stagnation focuses on regulating qi and harmonizing the liver,and unblocking obstruction mainly involves resolving phlegm-stasis and eliminating turbid toxins.The pathogenesis of deficient qi resulting into retention of pathogens aligns with the pathological features and syndrome evolution of postoperative pulmonary nodules,and will provide dynamic and systematic guidance for its clinical diagnosis and treatment.

Objective: To explore the effect of different concentrations of relaxin-2(RLN-2) on the proliferation and migration abilities of human immortalized keratinocytes(HaCaT cells). Methods: Methods HaCaT cells were cultured in media with different concentrations of RLN-2, and the cells were cultured in media without RLN-2 as the control group.The effect on cell proliferation was assessed by using the CCK-8 reagent, the cell migration ability was evaluated throughin vitrocell scratch assay, the cell cycle was examined by flow cytometry, and the expression levels of cell cycle proteins Cyclin B1 and Cyclin A2 were detected by Western blot. Results: After being cultured for 24 hours under RLN-2 concentration ranging from 10～100 ng/ml, HaCaT cells showed progressively increased proliferation and migration capabilities compared to the control group, with elevated expression levels of cell cycle proteins Cyclin B1 and Cyclin A2 and an increased proportion of cells in S and G2/M phases, peaking at 100 ng/ml. However, HaCaT cells cultured with 200 ng/ml of RLN-2 exhibited reduced proliferation and migration capabilities, decreased expression levels of Cyclin B1 and Cyclin A2, and a lower proportion of cells in S and G2/M phases compared to the 100 ng/ml group. Conclusion RLN-2 can enhance the migration ability of HaCaT cells within an appropriate concentration range and may also promote cell proliferation by increasing the expression of related cell cycle proteins and the proportion of cells in S and G2/M phases.

Objective:To investigate the effects of botulinum toxin type A (BTX-A) and magnesium sulfate on the survival rate of random-pattern skin flaps (RSF) with different length-to-width ratios.Methods:Using a random number table method, 45 SD rats were divided into three groups: the saline group (Group A), the BTX-A group (Group B), and the magnesium sulfate group (Group C), with 15 rats in each group. Each group was further subdivided into three subgroups based on different length-to-width ratios of RSF (1∶1, 2∶1, 3∶1), with 5 rats in each subgroup. The preparation of the RSF involved using the midline of the rat’s back as the axis and the level 1 cm below the iliac crest line as the base, extending towards the head. The skin tissue was incised to the dorsal fascia layer, separating the subcutaneous tissue at the superficial layer of the deep fascia, while severing the blood vessels and their branches on both sides and at the base. After hemostasis, the flap was sutured in place. Immediately after surgery, 0.2 ml of saline, BTX-A (25 U/ml), or magnesium sulfate solution (50 mg/ml) was injected into the proximal, middle, and distal ends of the flap. On the seventh day post-surgery, the gross appearance of the flap was assessed, and the survival rate was calculated. The surviving flap tissue underwent hematoxylin and eosin (HE) staining to evaluate microvascular density (MVD) and the degree of vasodilation (including vessel outer diameter, inner diameter, and wall thickness). Immunohistochemistry was used to detect the expression level of vascular endothelial growth factor (VEGF). Statistical analysis was performed using GraphPad Prism 9.0.1 software, with data expressed as Mean ± SD. One-way ANOVA was used for multiple group comparisons, and Tukey’s test was used for pairwise comparisons.Results:On the seventh day post-surgery, flaps with a length-to-width ratio of 1∶1 healed well in all subgroups. In the case of flaps with a 2∶1 ratio, Group A exhibited partial necrosis at the distal end, characterized by blackened, non-elastic scabs and exudate. Groups B and C generally healed well. For flaps with a 3∶1 ratio, Group A exhibited extensive necrosis at both the middle and distal ends, with similar blackened, non-elastic scabs, non-bleeding cut sections, and exudate. Groups B and C showed only partial blackening at the distal end, with most areas healing effectively. The survival rates of flaps with a 1∶1 ratio did not show significant differences among the three groups ( P>0.05). Compared to Group A, Groups B and C had significantly higher survival rates for flaps with 2∶1 and 3∶1 ratios ( P<0.01), with no significant difference between Groups B and C ( P>0.05). HE staining indicated that as the length-to-width ratios increased, tissue edema and inflammatory cell infiltration also increased in all groups. Groups B and C had significantly reduced inflammatory changes compared to Group A, with a greater number of newly formed microvessels observed. Quantitative analysis revealed that MVD in Groups B and C was significantly higher than in Group A, regardless of the flap ratio ( P<0.05), with no significant difference between Groups B and C ( P>0.05). Vasodilation analysis showed that the outer diameter and wall thickness of vessels in Groups B and C were significantly greater than those in Group A ( P<0.05), with no significant difference between Groups B and C ( P>0.05). Immunohistochemical staining revealed that VEGF expression levels in Groups B and C were higher than in Group A, regardless of the flap ratio ( P<0.01). In flaps with a 1∶1 ratio, VEGF expression was higher in Group C than in Group B ( P<0.05), with no significant difference between the two groups for other flap ratios ( P>0.05). Conclusion:In RSF with length-to-width ratios of 2∶1 and 3∶1, subcutaneous injections of BTX-A or magnesium sulfate after replantation can promote the expansion and formation of blood vessels in the flap, increase the expression of VEGF, and improve the survival rate of the RSF.

Objective To sort out the main subjects of China's medical insurance fund supervision and their change process in different periods,to provide a basis for deepening the reform of the medical insurance fund regulation sys-tem.Methods Social network analysis method is used to quantify the national-level policies and tap the core subjects of China's medical insurance fund supervision.Results A total of 63 policies were included,and 195 regulatory sub-ject codes were obtained.The main regulatory subjects during the embryonic period of medical insurance fund super-vision were mainly insurance operators and relied on medical insurance fund supervision organizations.The main regu-latory subjects during the exploration period were mainly the insurance administration and the insurance agency and began to pay attention to social participation.The main regulatory subjects in the development period were mainly the Healthcare Security Administration and its handling agencies,with the collaboration of relevant departments.The participation of social subjects is obvious,and third-party professional institutions become important subjects.Con-clusion The supervisory subjects of China's medical insurance fund have embodied the logic of change from decen-tralization of responsibilities to centralized and unified functions,from multi-regulation to integrated multi-sectoral linkage,and from government-led to the introduction of social and market forces.The participation of multiple sub-jects is the development trend of medical insurance fund supervision in the future,and the capacity of collaborative governance of medical insurance fund supervision should be continuously improved.

Digital supervision of the medical insurance fund is the process of using digital information technology to map real-world medical scenarios and activities into the digital world,in which the medical insurance fund is super-vised and managed.The objectives of digital supervision include not only ensuring the safe and rational use of the medical insurance fund,but also promoting the quality of medical services,safeguarding the public's rights and interests,ensuring the long-term sustainability of the medical insurance system,and promoting social equity and stability at multiple levels.Based on the theory of Public Value theory,it interprets and explores the model and critical path of digital supervision of China's medical insurance fund from the three dimensions of Public Value Proposition,Autho-rizing Environment,and Operational Capacity,which concludes that the key to digital supervision of medical insurance funds lies in the search for consistency and balance between the three of real-world value objectives.Digital regulation should be oriented towards public value creation and return to value rationality;strengthen institutional design and build a pluralistic governance pattern for digital regulation;and strengthen core capacity building to make up for the shortcomings of digital regulatory capacity.The public value of digital supervision should be created from three as-pects:concept optimization,support and guarantee,and capacity improvement.The public value of digital supervision should be created from three aspects:concept optimization,support and guarantee,and capacity improvement.

Objective:To investigate the effects of botulinum toxin type A (BTX-A) and magnesium sulfate on the survival rate of random-pattern skin flaps (RSF) with different length-to-width ratios.Methods:Using a random number table method, 45 SD rats were divided into three groups: the saline group (Group A), the BTX-A group (Group B), and the magnesium sulfate group (Group C), with 15 rats in each group. Each group was further subdivided into three subgroups based on different length-to-width ratios of RSF (1∶1, 2∶1, 3∶1), with 5 rats in each subgroup. The preparation of the RSF involved using the midline of the rat’s back as the axis and the level 1 cm below the iliac crest line as the base, extending towards the head. The skin tissue was incised to the dorsal fascia layer, separating the subcutaneous tissue at the superficial layer of the deep fascia, while severing the blood vessels and their branches on both sides and at the base. After hemostasis, the flap was sutured in place. Immediately after surgery, 0.2 ml of saline, BTX-A (25 U/ml), or magnesium sulfate solution (50 mg/ml) was injected into the proximal, middle, and distal ends of the flap. On the seventh day post-surgery, the gross appearance of the flap was assessed, and the survival rate was calculated. The surviving flap tissue underwent hematoxylin and eosin (HE) staining to evaluate microvascular density (MVD) and the degree of vasodilation (including vessel outer diameter, inner diameter, and wall thickness). Immunohistochemistry was used to detect the expression level of vascular endothelial growth factor (VEGF). Statistical analysis was performed using GraphPad Prism 9.0.1 software, with data expressed as Mean ± SD. One-way ANOVA was used for multiple group comparisons, and Tukey’s test was used for pairwise comparisons.Results:On the seventh day post-surgery, flaps with a length-to-width ratio of 1∶1 healed well in all subgroups. In the case of flaps with a 2∶1 ratio, Group A exhibited partial necrosis at the distal end, characterized by blackened, non-elastic scabs and exudate. Groups B and C generally healed well. For flaps with a 3∶1 ratio, Group A exhibited extensive necrosis at both the middle and distal ends, with similar blackened, non-elastic scabs, non-bleeding cut sections, and exudate. Groups B and C showed only partial blackening at the distal end, with most areas healing effectively. The survival rates of flaps with a 1∶1 ratio did not show significant differences among the three groups ( P>0.05). Compared to Group A, Groups B and C had significantly higher survival rates for flaps with 2∶1 and 3∶1 ratios ( P<0.01), with no significant difference between Groups B and C ( P>0.05). HE staining indicated that as the length-to-width ratios increased, tissue edema and inflammatory cell infiltration also increased in all groups. Groups B and C had significantly reduced inflammatory changes compared to Group A, with a greater number of newly formed microvessels observed. Quantitative analysis revealed that MVD in Groups B and C was significantly higher than in Group A, regardless of the flap ratio ( P<0.05), with no significant difference between Groups B and C ( P>0.05). Vasodilation analysis showed that the outer diameter and wall thickness of vessels in Groups B and C were significantly greater than those in Group A ( P<0.05), with no significant difference between Groups B and C ( P>0.05). Immunohistochemical staining revealed that VEGF expression levels in Groups B and C were higher than in Group A, regardless of the flap ratio ( P<0.01). In flaps with a 1∶1 ratio, VEGF expression was higher in Group C than in Group B ( P<0.05), with no significant difference between the two groups for other flap ratios ( P>0.05). Conclusion:In RSF with length-to-width ratios of 2∶1 and 3∶1, subcutaneous injections of BTX-A or magnesium sulfate after replantation can promote the expansion and formation of blood vessels in the flap, increase the expression of VEGF, and improve the survival rate of the RSF.

AIM:To investigate the effect of vaccarin(VAC)on endothelial dysfunction in type 2 diabetes mellitus(T2DM),and to uncover the underlying mechanisms.METHODS:(1)C57BL/6 mice received intraperitoneal injection of streptozotocin and were fed with a high-fat diet(21.8 kJ/kg,60%of the energy source was fat)to construct a T2DM mouse model.Thirty mice were randomly divided into control,T2DM and T2DM+VAC groups,with 10 mice in each group.The mice in T2DM+VAC group were given 1 mg/kg VAC via oral gavage for 6 weeks,while those in control and T2DM groups were given the same volume of PBS.The mRNA and protein expression levels of BCL2-interacting pro-tein 3(BNIP3),PTEN-induced kinase 1(PINK1)and parkin in the thoracic aorta were detected by RT-qPCR and West-ern blot.(2)Human umbilical vein endothelial cells(HUVECs)were stimulated by high glucose(HG;35 mmol/L glu-cose).Mitochondrial membrane potential,autophagy and mitochondrial superoxide levels were detected using JC-1,acri-dine orange(AO)and MitoSOX staining,respectively.RESULTS:Compared with control group,the mRNA and protein levels of BNIP3,PINK1 and parkin were significantly increased in the thoracic aorta of T2DM mice(P<0.05).Compared with T2DM group,the mRNA and protein levels of BNIP3,PINK1 and parkin in the thoracic aorta were significantly re-duced in T2DM+VAC group(P<0.05).The results of JC-1,AO and MitoSOX staining showed that VAC attenuated the decrease in mitochondrial membrane potential and the increase in autophagy and mitochondrial superoxide levels in HG-in-duced HUVECs.Treatment with VAC also inhibited HG-mediated mitochondrial damage in HUVECs after BNIP3 overex-pression.The effect of miR-570-3p mimic on mitochondrial damage was similar to VAC.RT-qPCR and Western blot showed that both miR-570-3p mimic and VAC significantly reduced the mRNA and protein levels of BNIP3,PINK1 and parkin.In contrast,inhibition of miR-570-3p exhibited the opposite effects.CONCLUSION:Treatment with VAC alle-viated endothelial dysfunction in T2DM by inhibiting HG-induced mitochondrial dysfunction through miR-570-3p/BNIP3.