ObjectiveThis study aims to investigate the dynamic changes in general body parameters, blood glucose, and blood lipid profiles in obese cynomolgus monkeys, exploring the correlations among these parameters and providing a reference for research on the obese cynomolgus monkey model. Methods30 normal male cynomolgus monkeys aged 5 - 17 years old (with body mass index < 35 kg/m² and glycated hemoglobin content < 4.50%) and 99 spontaneously obese male cynomolgus monkeys (with body mass index ≥35 kg/m² and glycated hemoglobin content < 4.50%) were selected. Over a period of three years, their abdominal circumference, skinfold thickness, body weight, body mass index, fasting blood glucose, glycated hemoglobin, and four blood lipid indicators were monitored. The correlations between each indicator were analyzed using repeated measurement ANOVA, simple linear regression, and multiple linear regression correlation analysis method. Results Compared to the control group, the obese group exhibited significantly higher levels of abdominal circumference, skinfold thickness, body weight, body mass index, and triglyceride (P＜0.05). In the control group, skinfold thickness increased annually, while other indicators remained stable. Compared with the first year, the obese group showed significantly increased abdominal circumference, skinfold thickness, body weight, body mass index, triglyceride, and fasting blood glucose in the second year(P＜0.05), with this increasing trend persisting in the third year (P＜0.05). In the control group, the obesity incidence rates in the second and third years were 16.67% and 23.33%, respectively, while the prevalence of diabetes remained at 16.67%. In the obese group, the diabetes incidence rates were 29.29% and 44.44% in years 2 and 3, respectively. Among the 11-13 year age group, the incidence rates were 36.36% and 44.68%, while for the group older than 13 years, the rates were 28.13% and 51.35%. Correlation analysis revealed significant associations (P＜0.05) between fasting blood glucose and age, abdominal circumference, skinfold thickness, body weight, and triglyceride in the diabetic monkeys. Conclusion Long-term obesity can lead to the increases in general physical indicators and fasting blood glucose levels in cynomolgus monkeys, and an increase in the incidence of diabetes. In diabetic cynomolgus monkeys caused by obesity, there is a high correlation between their fasting blood glucose and age, weight, abdominal circumference, skinfold thickness, and triglyceride levels, which is of some significance for predicting the occurrence of spontaneous diabetes.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective:To study the time evolution of financing burden and discuss the feasibility of provincial pooling by analyzing the panel data of"individual contribution burden ratio"and"government subsidy burden ratio"of residents'medical insurance in Shandong Province from 2015 to 2022.Methods:Spatial auto-correlation was used to analyze the spatial agglomeration and heterogeneity pattern;convergence analysis was used to analyze the inter-annual trends in the economic burden.Results:The"out-of-pocket ratio"increased year by year and the difference among cities was significant,the Moran's I value decreased year by year,and the geographical distribution pattern showed a random distribution pattern;the"government subsidy burden ratio"had little difference among cities,the global Moran's index value increased year by year,and the spatial agglomeration pattern was enhanced;both of them had σ convergence and absolute β convergence,showing a trend of balanced development.Conclusion:In order to promote provincial-level coordination,safeguard fund security and reduce the burden on residents,economic synergistic development strategies have been adopted to raise residents'incomes;emphasis has been placed on cutting back on income and expenditure,fine-tuning fund supervision;and reforming the financing mechanism,formulating fine-tuning financing standards and focusing on the increase in the cost of disease prevention and control have been adopted,so as to provide references for the improvement of the health insurance system and the promotion of the sustainable development of the health insurance cause.

The clinical practice guidelines of traditional Chinese medicine （TCM） have problems such as limited clinical application and unclear implementation effects， which may be related to the lack of clinical practice evidence. To provide reliable and precise evidence for clinical practice， this article proposes a model of combining TCM guidelines with real-world study， which includes 4 steps. Firstly， during the implementation process of the guidelines， a high-quality research database is established. Secondly， the recommendations in the guidelines are evaluated based on the established database in multiple dimensions， including applicability， effectiveness， safety， and cost-effectiveness， and thus their effectiveness in practical applications can be determined. Thirdly， based on the established database， core prescriptions are identified， and the targeted populations and medication plans are determined. That is， the best treatment regimen is established based on the analysis of abundant clinical data regarding the effects of different medication frequencies， dosages， and duration on efficacy. Fourthly， the guidelines are updated according to the real-world evidence. The research based on this model can provide real-world evidence for ancient and empirical prescriptions， improving their application in clinical practice. Moreover， this model can reduce research costs and improve research efficiency. When applying this model， researchers need to pay attention to the quality of real-world evidence， ensuring that it can truly reflect the situation in clinical practice. In addition， importance should be attached to the clinical application of guideline recommendations， ensuring that doctors can conduct standardized diagnosis and treatment according to the guidelines. Finally， full-process participation of multidisciplinary experts is encouraged to ensure the comprehensiveness and scientificity of the study. In conclusion， the application of this model will contribute to the development of TCM guidelines responsive to the needs of clinical practice and achieve the goal of promoting the homogenization of TCM clinical diagnosis and treatment.

The classification of traditional Chinese medicine （TCM） syndromes is one of the core technical elements in the industry standard of Specification of Diagnosis and Therapeutic Effect Evaluation of Diseases and Syndromes in TCM. In the past，when clinical standards for TCM were formulated，the determination of TCM syndrome classification relied heavily on textbooks and expert experience，lacking systematic research. This approach thus failed to reflect the advancement and scientificity of the standards，thereby affecting their implementation and application. This article reviewed the presentation forms and technical methods of TCM syndrome classification，including the two-tier syndrome classification model with primary and secondary symptoms，as well as the application of modern literature research，ancient literature research，Delphi method，in-depth expert interviews，consensus conferences，and real-world research. When syndrome classification standards are developed，it is necessary to build upon modern literature research，adopt a mixed approach combining qualitative research and quantitative analysis results，and reach expert consensus through consensus conferences. Through systematic research，the scientificity，applicability，and coordination of TCM syndrome classification standards can be enhanced，providing guidance for the standardization of TCM.

Objective:To study the time evolution of financing burden and discuss the feasibility of provincial pooling by analyzing the panel data of"individual contribution burden ratio"and"government subsidy burden ratio"of residents'medical insurance in Shandong Province from 2015 to 2022.Methods:Spatial auto-correlation was used to analyze the spatial agglomeration and heterogeneity pattern;convergence analysis was used to analyze the inter-annual trends in the economic burden.Results:The"out-of-pocket ratio"increased year by year and the difference among cities was significant,the Moran's I value decreased year by year,and the geographical distribution pattern showed a random distribution pattern;the"government subsidy burden ratio"had little difference among cities,the global Moran's index value increased year by year,and the spatial agglomeration pattern was enhanced;both of them had σ convergence and absolute β convergence,showing a trend of balanced development.Conclusion:In order to promote provincial-level coordination,safeguard fund security and reduce the burden on residents,economic synergistic development strategies have been adopted to raise residents'incomes;emphasis has been placed on cutting back on income and expenditure,fine-tuning fund supervision;and reforming the financing mechanism,formulating fine-tuning financing standards and focusing on the increase in the cost of disease prevention and control have been adopted,so as to provide references for the improvement of the health insurance system and the promotion of the sustainable development of the health insurance cause.

Objective:To analyze the status quo and influencing factors of the equity,accessibility and sustainability of the development of medical insurance for urban and rural residents in 2021,and provide a reference for improving the management and service level of medical insurance.Methods:Firstly,the"evaluation index system of medical insurance for urban and rural residents"was constructed,and the total index of the development level of medical insurance and its three subsystem indexes of equity,accessibility and sustainability were calculated.Secondly,the Theil index was used to measure the level differences of the three major regions in the east,central and west,and the spatial auto-correlation was used to analyze the spatial agglomeration and heterogeneity distribution pattern of the total index.Finally,a geographic weighted regression model was constructed to analyze the main influencing factors.Results:There were provincial differences in the development level of medical insurance,which showed a decreasing trend from east to west in geography and a random distribution pattern in space.Policy factors,economic factors,population structure,medical resource allocation and education level had a significant impact on the development level of medical insurance.Conclusions:It is proposed to promote the fairness at multiple levels,enhance the accessibility in all directions and dynamically improve the sustainability,and further explore the policy suggestions to improve the management and service level and enhance the residents'sense of experience,sense of gain and sense of happiness.

Objective:To study the time evolution of financing burden and discuss the feasibility of provincial pooling by analyzing the panel data of"individual contribution burden ratio"and"government subsidy burden ratio"of residents'medical insurance in Shandong Province from 2015 to 2022.Methods:Spatial auto-correlation was used to analyze the spatial agglomeration and heterogeneity pattern;convergence analysis was used to analyze the inter-annual trends in the economic burden.Results:The"out-of-pocket ratio"increased year by year and the difference among cities was significant,the Moran's I value decreased year by year,and the geographical distribution pattern showed a random distribution pattern;the"government subsidy burden ratio"had little difference among cities,the global Moran's index value increased year by year,and the spatial agglomeration pattern was enhanced;both of them had σ convergence and absolute β convergence,showing a trend of balanced development.Conclusion:In order to promote provincial-level coordination,safeguard fund security and reduce the burden on residents,economic synergistic development strategies have been adopted to raise residents'incomes;emphasis has been placed on cutting back on income and expenditure,fine-tuning fund supervision;and reforming the financing mechanism,formulating fine-tuning financing standards and focusing on the increase in the cost of disease prevention and control have been adopted,so as to provide references for the improvement of the health insurance system and the promotion of the sustainable development of the health insurance cause.

Objective:To analyze the status quo and influencing factors of the equity,accessibility and sustainability of the development of medical insurance for urban and rural residents in 2021,and provide a reference for improving the management and service level of medical insurance.Methods:Firstly,the"evaluation index system of medical insurance for urban and rural residents"was constructed,and the total index of the development level of medical insurance and its three subsystem indexes of equity,accessibility and sustainability were calculated.Secondly,the Theil index was used to measure the level differences of the three major regions in the east,central and west,and the spatial auto-correlation was used to analyze the spatial agglomeration and heterogeneity distribution pattern of the total index.Finally,a geographic weighted regression model was constructed to analyze the main influencing factors.Results:There were provincial differences in the development level of medical insurance,which showed a decreasing trend from east to west in geography and a random distribution pattern in space.Policy factors,economic factors,population structure,medical resource allocation and education level had a significant impact on the development level of medical insurance.Conclusions:It is proposed to promote the fairness at multiple levels,enhance the accessibility in all directions and dynamically improve the sustainability,and further explore the policy suggestions to improve the management and service level and enhance the residents'sense of experience,sense of gain and sense of happiness.