ObjectiveTo investigate the potential mechanism of Danggui Shaoyaosan （DSS） in ameliorating renal injury in db/db mice. MethodsThirty 8-week-old specific pathogen-free （SPF）-grade male db/db mice and six db/m mice were acclimated for one week. Urinary microalbumin and blood glucose levels were measured weekly in both db/db and db/m mice. Successful modeling was determined by significantly higher microalbuminuria in db/db mice compared to db/m mice and a fasting blood glucose ≥16.7 mmol·L^-1. The 30 db/db mice were randomly divided into five groups： the model group， the irbesartan （IBN） group， and three DSS dose groups （low-， medium-， and high-dose DSS groups， administered at 16.77， 33.54， 67.08 g·kg^-1·d^-1， respectively）. Additionally， the six db/m mice served as the normal control group. The IBN group received irbesartan at 0.025 g·kg^-1·d^-1 by gavage， while the three DSS groups received DSS at 16.77， 33.54， and 67.08 g·kg^-1·d^-1 by gavage， respectively. The normal and model groups were administered with an equivalent volume of normal saline by gavage. All interventions lasted for 8 consecutive weeks. After intervention， serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary total protein （UTP）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured to evaluate the therapeutic efficacy of the treatments. Renal histopathological changes were observed with hematoxylin-eosin （HE） staining. Western blot was used to detect the protein expression of silencing information regulator 1 （SIRT1）， hypoxia-inducible factor-1α （HIF-1α）， very low-density lipoprotein receptor （VLDLr）， and cluster of differentiation 31 （CD31）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA levels of HIF-1α and VLDLr. Immunohistochemistry was used to observe the expression and distribution of HIF-1α and Caspase-3. ResultsCompared to the normal group， the model group showed significantly increased SCr， BUN， UTP， TG， and LDL-C. HE staining revealed glomerulosclerosis， mesangial matrix hyperplasia， capillary loop distortion and thickening， with extensive inflammatory cell infiltration. Protein expression of SIRT1 and CD31 significantly decreased （P<0.05）， while HIF-1α and VLDLr protein and mRNA levels increased （P<0.05）. Immunohistochemistry showed increased expression of HIF-1α and Caspase-3 （P<0.05）， indicating hypoxia and apoptosis in renal cells. In all treatment groups， SCr， BUN， TG， and LDL-C were significantly reduced compared to the model group （P<0.05）， and UTP was significantly improved in the medium-dose DSS group （P<0.05）. Renal tissue structure and morphology were improved， inflammatory cells were reduced， and no vascular hyaline degeneration was observed. SIRT1 and CD31 protein expression was elevated to varying degrees compared to the model group （P<0.05）， while HIF-1α and VLDLr protein and mRNA levels decreased （P<0.05）. Immunohistochemistry showed reduced expression of HIF-1α and Caspase-3 in all treatment groups （P<0.05）， with the most significant improvement observed in the IBN group and medium-dose DSS group （P<0.05）. ConclusionDSS can effectively ameliorate glomerulosclerosis and lipid deposition in db/db mice， and its mechanism may involve the SIRT1/HIF-1α/VLDLr signaling pathway.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 （TLR4/NF-κB p65/NLRP3） signaling pathway in the renal tissues of db/db mice with spontaneous diabetes， and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease （DKD）. MethodsThirty db/db mice were divided into five groups： A model group， Danggui Shaoyaosan low- （16.77 g·kg^-1·d^-1）， medium- （33.54 g·kg^-1·d^-1）， and high-dose （67.08 g·kg^-1·d^-1） intervention groups， as well as an irbesartan group （0.025 g·kg^-1·d^-1） by the random number table method， with 6 mice in each group. Additionally， 6 db/m mice were assigned to the normal group. After 8 weeks of intervention， the following parameters were determined by corresponding methods： body weight， fasting blood glucose （FBG）， 24-hour urinary protein （24 h-UTP）， and serum creatinine （SCr） levels， renal histopathological analysis by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-Schiff （PAS） staining， the protein and mRNA expression levels of TLR4， NF-κB p65， NLRP3， tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and interleukin-18 （IL-18） by Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR）， as well as TLR4， NF-κB p65， and NLRP3 protein expression in renal tissues by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group exhibited increased body weight， FBG， 24 h-UTP， and SCr levels （P<0.05）； disordered renal structure， thickened basement membrane， and interstitial inflammatory cell infiltration， elevated TLR4， NF-κB p65， NLRP3， TNF-α， IL-1β， IL-6， and IL-18 expression； as well as decreased IL-10 expression （P<0.05）. Compared with the model group， these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees （P<0.05）. ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.

ObjectiveTo investigate the therapeutic efficacy of Danggui Shaoyaosan （DSS） on renal injury in db/db mice and its impact on endoplasmic reticulum stress （ERS） in renal tissues. MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week， after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease （DKD） model. The model mice were randomly divided into a model group， an irbesartan group， and three DSS treatment groups with different doses （16.77， 33.54， and 67.08 g·kg^-1·d^-1）. A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention， general conditions were observed. Serum cystatin C （Cys-C）， 24-hour urinary total protein （24 h-UTP）， 24-hour urinary microalbumin （24 h-UMA）， urinary creatinine （Ucr）， and urea nitrogen （UUN） were measured. Transmission electron microscopy （TEM） was used to observe glomerular basement membrane （GBM） and ultrastructural changes of the endoplasmic reticulum （ER） in glomerular endothelial cells. Western blot， real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78， CHOP， and related markers. ResultsCompared with the normal group， the mice in the model group showed curled posture， sluggish response， poor fur condition， increased levels of Cys-C， 24 h-UTP， 24 h-UMA， and UUN （P<0.05）， while Ucr decreased （P<0.05）. The GBM was significantly thickened， with podocyte and foot process fusion. The protein expressions of GRP78， CHOP， and ATF6 were significantly upregulated （P<0.05）， the mRNA levels of GRP78 and CHOP increased （P<0.05）， and immunohistochemistry showed an enhanced GRP78 signal （P<0.05）. After treatment， the mice exhibited improved behavior， normalized GBM and podocyte structure， improved ER morphology and markedly better biochemical indicators. Western blot， Real-time PCR， and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups （P<0.05）， suggesting alleviated ERS and improved renal function. ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice， possibly by regulating ERS in glomerular endothelial cells， although the underlying signaling mechanisms require further investigation.

Objective:To investigate the mediating effects of medical inquiry ability and attitudes toward aging on the relationship between socioeconomic status and mental health among the elderly.Methods:Utilizing data from the 2021 China General Social Survey(CGSS), a sample of 957 individuals aged 60 years and older was selected for analysis.The influence of each variable was assessed through regression analysis, and the mediating effects were evaluated using the Bootstrap method.Results:The study samples ranged in age from 60 to 95 years, including 479 females and 478 males.Socioeconomic status significantly positively influenced mental health( β=0.208, P<0.001).Additionally, socioeconomic status had a notable positive effect on medical inquiry ability( β=0.244, P<0.001)and attitudes toward aging( β=0.163, P<0.001)among the elderly population.Furthermore, medical inquiry ability positively affected both attitudes toward aging( β=0.158, P<0.001)and mental health( β=0.139, P<0.001).The attitude toward aging also had a significant positive impact on mental health( β=0.216, P<0.001).Notably, both medical inquiry ability and attitudes toward aging served as significant mediators between socioeconomic status and mental health in the elderly, with a total indirect effect value of 0.091(95% CI: 0.063-0.123).The chain mediating effect of medical inquiry ability and pension mentality was also significant, with an effect size of 0.010(95% CI: 0.005-0.017). Conclusions:Enhancing the socioeconomic status of older adults can foster their medical inquiry ability, positively influence their attitudes toward aging, and ultimately contribute to the promotion of their mental health.

Objective:This study aims to investigate the impact of socioeconomic status on cognitive function in older adults, while analyzing the mediating role of health-related social determinants.The findings will provide a foundation for the implementation of an active aging strategy.Methods:Utilizing data from the China Health and Retirement Longitudinal Study(CHARLS)2020, this study employed multiple linear regression analysis to investigate the relationship between socioeconomic status and cognitive function among older adults.A multiple mediation model was applied to evaluate the mediating effects of health-related social determinants on the association between socioeconomic status and cognitive function, with these mediation effects assessed using the Bootstrap method.Results:The results of the multiple linear regression analysis indicated that socioeconomic status significantly positively influences cognitive function in older adults.Factors such as younger age, male gender, Han ethnicity, and urban residence were associated with higher cognitive scores.The mediation analysis demonstrated that, of the total effect of socioeconomic status on cognitive function, health status accounted for 1.564%, individual lifestyle for 14.820%, social support networks for 2.719%, living conditions for 1.632%, and other social structural factors for 1.496%.In the multiple mediation model, a total of 17.945% of the effect of socioeconomic status on cognitive function in older adults was jointly mediated by health-related social determinants.Conclusions:Socioeconomic status is a critical determinant of cognitive impairment among older adults in China.To address this issue, comprehensive interventions should be implemented to promote the equitable distribution of economic and social resources, reduce socioeconomic disparities, and mitigate health inequalities, thereby enhancing the overall cognitive function of disadvantaged groups.Preventive measures and strategies aimed at improving health status, encouraging healthy lifestyle choices, strengthening social support networks, enhancing living conditions, and optimizing social structural factors could serve as essential intervention points to improve the cognitive function of older adults with lower socioeconomic status.

Objective:To evaluate the topological alterations of resting-state brain networks in patients with idiopathic generalized epilepsy with generalized tonic-clonic seizure (IGE-GTCS) using minimum spanning tree (MST) based on graph theoretic analysis, and to further analyze the relationships between topological features, duration, and antiepileptic drug response.Methods:This study was a cross-sectional study. Retrospectively, 75 IGE-GTCS patients and 37 healthy controls (HC) who underwent brain MR imaging at the Affiliated of Nanjing University Medical School Drum Tower Hospital from January 2013 to December 2020 were enrolled. IGE-GTCS patients were grouped into well-controlled subgroup (WC; n=55) and drug-resistant subgroup (DR; n=20) according to their response to antiepileptic drugs. Firstly, the time series correlations between 116 regions of the whole brain of each subject were calculated to construct functional connectivity matrices. For each functional connectivity matrix, the Kruskal algorithm was used to MST, and the topological metrics of each MST were calculated, including leaf fraction, tree hierarchy, and diameter. The comparison of MST topological metrics between the two groups was performed using two-sample t-test. Pearson correlation analysis was used to calculate the correlation between disease duration and MST metrics in the WC subgroup and the DR subgroup. Results:Compared with the HC group, the MST leaf fraction ( t=2.27, P=0.025) increased in the IGE-GTCS patient group, and the diameter decreased ( t=-2.24, P=0.027), there was no statistically significant difference in tree hierarchy between IGE-GTCS patient group and HC group ( t=0.98, P=0.328). The MST leaf fraction ( t=-2.39, P=0.019) and tree hierarchy ( t=-2.24, P=0.027) in the WC subgroup was decreased compared with the DR subgroup, while there was no statistically significant difference in diameter between WC subgroup and DR subgroup ( P=0.093). The correlation analysis showed the MST diameter in WC subgroup was significantly correlated with disease duration ( r=0.452, P<0.001), while the MST diameter in DR subgroup was not significantly correlated with disease duration ( r=-0.062, P=0.847). Conclusions:Patients with IGE-GTCS exhibit specific alterations in the global topology of brain network, characterized by increased centralization and efficiency. The effective antiepileptic drug treatment is associated with a recovery of brain network abnormalities.

Objective:To investigate the mediating effects of medical inquiry ability and attitudes toward aging on the relationship between socioeconomic status and mental health among the elderly.Methods:Utilizing data from the 2021 China General Social Survey(CGSS), a sample of 957 individuals aged 60 years and older was selected for analysis.The influence of each variable was assessed through regression analysis, and the mediating effects were evaluated using the Bootstrap method.Results:The study samples ranged in age from 60 to 95 years, including 479 females and 478 males.Socioeconomic status significantly positively influenced mental health( β=0.208, P<0.001).Additionally, socioeconomic status had a notable positive effect on medical inquiry ability( β=0.244, P<0.001)and attitudes toward aging( β=0.163, P<0.001)among the elderly population.Furthermore, medical inquiry ability positively affected both attitudes toward aging( β=0.158, P<0.001)and mental health( β=0.139, P<0.001).The attitude toward aging also had a significant positive impact on mental health( β=0.216, P<0.001).Notably, both medical inquiry ability and attitudes toward aging served as significant mediators between socioeconomic status and mental health in the elderly, with a total indirect effect value of 0.091(95% CI: 0.063-0.123).The chain mediating effect of medical inquiry ability and pension mentality was also significant, with an effect size of 0.010(95% CI: 0.005-0.017). Conclusions:Enhancing the socioeconomic status of older adults can foster their medical inquiry ability, positively influence their attitudes toward aging, and ultimately contribute to the promotion of their mental health.

Objective:This study aims to investigate the impact of socioeconomic status on cognitive function in older adults, while analyzing the mediating role of health-related social determinants.The findings will provide a foundation for the implementation of an active aging strategy.Methods:Utilizing data from the China Health and Retirement Longitudinal Study(CHARLS)2020, this study employed multiple linear regression analysis to investigate the relationship between socioeconomic status and cognitive function among older adults.A multiple mediation model was applied to evaluate the mediating effects of health-related social determinants on the association between socioeconomic status and cognitive function, with these mediation effects assessed using the Bootstrap method.Results:The results of the multiple linear regression analysis indicated that socioeconomic status significantly positively influences cognitive function in older adults.Factors such as younger age, male gender, Han ethnicity, and urban residence were associated with higher cognitive scores.The mediation analysis demonstrated that, of the total effect of socioeconomic status on cognitive function, health status accounted for 1.564%, individual lifestyle for 14.820%, social support networks for 2.719%, living conditions for 1.632%, and other social structural factors for 1.496%.In the multiple mediation model, a total of 17.945% of the effect of socioeconomic status on cognitive function in older adults was jointly mediated by health-related social determinants.Conclusions:Socioeconomic status is a critical determinant of cognitive impairment among older adults in China.To address this issue, comprehensive interventions should be implemented to promote the equitable distribution of economic and social resources, reduce socioeconomic disparities, and mitigate health inequalities, thereby enhancing the overall cognitive function of disadvantaged groups.Preventive measures and strategies aimed at improving health status, encouraging healthy lifestyle choices, strengthening social support networks, enhancing living conditions, and optimizing social structural factors could serve as essential intervention points to improve the cognitive function of older adults with lower socioeconomic status.

Objective:To evaluate the topological alterations of resting-state brain networks in patients with idiopathic generalized epilepsy with generalized tonic-clonic seizure (IGE-GTCS) using minimum spanning tree (MST) based on graph theoretic analysis, and to further analyze the relationships between topological features, duration, and antiepileptic drug response.Methods:This study was a cross-sectional study. Retrospectively, 75 IGE-GTCS patients and 37 healthy controls (HC) who underwent brain MR imaging at the Affiliated of Nanjing University Medical School Drum Tower Hospital from January 2013 to December 2020 were enrolled. IGE-GTCS patients were grouped into well-controlled subgroup (WC; n=55) and drug-resistant subgroup (DR; n=20) according to their response to antiepileptic drugs. Firstly, the time series correlations between 116 regions of the whole brain of each subject were calculated to construct functional connectivity matrices. For each functional connectivity matrix, the Kruskal algorithm was used to MST, and the topological metrics of each MST were calculated, including leaf fraction, tree hierarchy, and diameter. The comparison of MST topological metrics between the two groups was performed using two-sample t-test. Pearson correlation analysis was used to calculate the correlation between disease duration and MST metrics in the WC subgroup and the DR subgroup. Results:Compared with the HC group, the MST leaf fraction ( t=2.27, P=0.025) increased in the IGE-GTCS patient group, and the diameter decreased ( t=-2.24, P=0.027), there was no statistically significant difference in tree hierarchy between IGE-GTCS patient group and HC group ( t=0.98, P=0.328). The MST leaf fraction ( t=-2.39, P=0.019) and tree hierarchy ( t=-2.24, P=0.027) in the WC subgroup was decreased compared with the DR subgroup, while there was no statistically significant difference in diameter between WC subgroup and DR subgroup ( P=0.093). The correlation analysis showed the MST diameter in WC subgroup was significantly correlated with disease duration ( r=0.452, P<0.001), while the MST diameter in DR subgroup was not significantly correlated with disease duration ( r=-0.062, P=0.847). Conclusions:Patients with IGE-GTCS exhibit specific alterations in the global topology of brain network, characterized by increased centralization and efficiency. The effective antiepileptic drug treatment is associated with a recovery of brain network abnormalities.

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg^-1） groups， and a trimetazidine group （0.002 g·kg^-1）. By intragastric administration of vitamin D₃ and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.