Objective To explore the effects and mechanism of Dahuang Tangluo Pills on intestinal inflammatory injury in type 2 diabetes mellitus(T2DM)rats based on TLR4/NF-κB signaling pathway.Methods Eight ZDF(fa/+)rats were used as the blank group,and 40 ZDF(fa/fa)rats were fed with high-fat diet and then randomly divided into model group,metformin group(0.18 g/kg metformin)and TCM high-,medium-and low-dosage groups(2.16,1.08,0.54 g/kg Dahuang Tangluo Pills),respectively.The medication groups were gavaged with corresponding dosages for 12 consecutive weeks.The body mass and fasting blood glucose(FBG)of rats before and after intervention were detected.After the intervention,an oral glucose tolerance test(OGTT)was performed,the serum glucose(GLU),glycosylated serum protein(GSP),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)contents were detected.ELISA was used to detect serum fasting insulin(FINS),free fatty acids(FFA)and tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-22,lipopolysaccharide(LPS),secreted immunoglobulin A(SIgA)contents in colonic tissue.HE staining was used to observe the morphology of colonic tissue,and Western blot was used to detect the expressions of Toll like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,NF-κB inhibitor α(IκBα),p-IκBα,myeloid differentiation factor 88(MyD88)and zona pellucida protein-1(ZO-1)in colonic tissue.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.01),blood glucose significantly increased at all time points of OGTT(P<0.01),serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly increased,serum HDL-C and colonic tissue SIgA contents significantly decreased(P<0.01),with colonic tissue nuclear condensation,cytoplasmic dissolution,inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly increased,while the protein expressions of IκBα and ZO-1 significantly decreased(P<0.01).Compared with the model group,the body mass and FBG significantly decreased in metformin group,TCM high-and medium-dosage groups(P<0.01),blood glucose decreased at different time points of OGTT,and serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly decreased,serum HDL-C and colonic tissue SIgA contents significantly increased(P<0.05,P<0.01),with significant improvement in colonic tissue structure and reduction in inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly decreased,while the proteins expression of IκBα and ZO-1 significantly increased(P<0.05,P<0.01).Conclusion Dahuang Tangluo Pills may inhibit the activation of the TLR4/NF-κB signaling pathway,reduce the release of inflammatory factors,improve intestinal inflammatory injury,restore intestinal homeostasis,thereby improving glucose and lipid metabolism and exerting therapeutic effects on T2DM.

Background Prenatal exposure to chlorinated polyfluorinated ether sulfonic acid (Cl-PFESA, commercially known as F-53B) during pregnancy has been associated with fetal growth restriction and adverse birth outcomes. These effects may be mediated by structural and functional impairments of the placenta, potentially resulting from disrupted placental angiogenesis. However, the underlying mechanisms remain unclear. Objective To explore the impact of prenatal F-53B exposure on fetal development, placental pathology, and the expression of genes involved in angiogenesis by establishing an F-53B exposure animal model. Methods A total of 48 sexually mature female SD rats aged 8 weeks were selected, along with 24 proven male breeders. The rats were acclimatized for one week before mating. Pregnant rats were assigned to four groups: control (0 mg·kg⁻¹), low-dose (0.1 mg·kg⁻¹), medium-dose (1 mg·kg⁻¹), and high-dose (5 mg·kg⁻¹). Half of the pregnant rats in each group were administered the test substance by oral gavage once daily from gestational day (GD) 5.5 to GD17.5. The fetuses and placentas were dissected and weighed, and placental efficiency was calculated as the ratio of fetal weight to placental weight, reflecting the placenta’s capacity to supply nutrients to the fetus. Placental histopathological alterations were assessed after hematoxylin and eosin (HE) staining. Quantitative real-time polymerase chain reaction (qPCR) was conducted to assess the mRNA expression levels of angiogenesis-related genes, including hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA) and its receptor (VEGFR2), as well as downstream genes in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. To evaluate the potential impact of prenatal F-53B exposure on birth outcomes, including birth weight and gestational age, the remaining half of the pregnant rats in each group were continuously exposed to the test substance until delivery. Results F-53B exposure significantly reduced fetal weight across all exposure groups (P<0.05) and markedly increased the incidence of intrauterine growth restriction (P<0.01). Although placental weights did not differ significantly among groups, placental efficiency was significantly decreased in the high-dose group (P<0.05). The histological analysis after HE staining revealed disorganized trophoblast cell structure and a significant reduction in labyrinthine blood sinus area in the medium- and high-dose groups. The qPCR analysis showed that HIF-1α expression was significantly upregulated in the low-dose group (P<0.001), while VEGFA (P<0.01), PI3K (P<0.001), and AKT (P<0.05) expression levels were significantly downregulated in the medium- and high-dose groups. Conclusion Maternal exposure to F-53B during pregnancy may impair placental angiogenesis via VEGFA and its downstream PI3K/AKT signaling pathway, leading to placental pathological damage and increasing the risk of intrauterine growth restriction and reduced birth weight in fetuses.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry（UPLC-Orbitrap Fusion Lumos Tribrid-MS）， the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration， and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group， the model group received intraperitoneal cisplatin（10 mg·kg^-1） to establish the acute kidney injury model， the normal group was given the same volume of saline. After successful modeling， rats in the normal and model groups were randomly divided into the normal low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1） and the model low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1）， 6 rats in each group， and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then， the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS， and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software， and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ， its concentration increased first and then decreased， and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve（AUC_0-t） and mean retention time（MRT_0-t） of normal and model rats increased with the increased dose， and the clearance（CL） decreased with the increasing dose. Compared with the normal group， the AUC_0-t was significantly increased（P<0.01）， peak concentration（C_max） and CL decreased in model rats at different doses， indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats， which may be due to the change of the body environment in the pathological state， then lead to changes in absorption and metabolic processes.

ObjectiveTo investigate the recurrence of ischemic stroke (IS) and to analyze the association between four indices of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and the risk of IS recurrence by analyzing the follow-up data related to IS in the community-based natural population of Songjiang District, Shanghai, so as to provide a scientific basis for improving the prognosis of stroke patients in the community and controlling IS recurrence. MethodsA prospective follow-up study was conducted among the IS patients in the community-based cohort population, collecting data about patient’s age, gender, disease history, biochemical indicators, and etc. Cox regression model and restricted cubic spline model were used to analyze the relationship between different levels of plasma lipids and the recurrence of IS in these patients. ResultsA total of 1 368 patients with IS were included. The total follow-up duration was 7 171.46 person-years, with a median follow-up time of 6.24 years. There were 420 cases of IS recurrence, resulting in a cumulative recurrence rate of 30.70%. The results of multivariate Cox regression analysis showed that the recurrence risk of IS was reduced when the baseline TC and LDL-C levels of IS patients were in the ranges of 4.65‒5.67 mmol·L^-1 and 2.52‒3.46 mmol·L^-1, respectively. The results of restricted cubic spline analysis showed a U-shaped relationship between baseline TC and LDL-C levels and the recurrence risk in IS patients. ConclusionThe cumulative recurrence rate of patients with IS in the community of Songjiang District in Shanghai is high, and the levels of TC and LDL-C at baseline survey are correlated with the recurrence of IS in these patients. It is suggested to pay more attention to the levels of LDL-C and TC in patients with IS, so as to improve the prognosis.

Objective To explore the effects and mechanism of Dahuang Tangluo Pills on intestinal inflammatory injury in type 2 diabetes mellitus(T2DM)rats based on TLR4/NF-κB signaling pathway.Methods Eight ZDF(fa/+)rats were used as the blank group,and 40 ZDF(fa/fa)rats were fed with high-fat diet and then randomly divided into model group,metformin group(0.18 g/kg metformin)and TCM high-,medium-and low-dosage groups(2.16,1.08,0.54 g/kg Dahuang Tangluo Pills),respectively.The medication groups were gavaged with corresponding dosages for 12 consecutive weeks.The body mass and fasting blood glucose(FBG)of rats before and after intervention were detected.After the intervention,an oral glucose tolerance test(OGTT)was performed,the serum glucose(GLU),glycosylated serum protein(GSP),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)contents were detected.ELISA was used to detect serum fasting insulin(FINS),free fatty acids(FFA)and tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-22,lipopolysaccharide(LPS),secreted immunoglobulin A(SIgA)contents in colonic tissue.HE staining was used to observe the morphology of colonic tissue,and Western blot was used to detect the expressions of Toll like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,NF-κB inhibitor α(IκBα),p-IκBα,myeloid differentiation factor 88(MyD88)and zona pellucida protein-1(ZO-1)in colonic tissue.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.01),blood glucose significantly increased at all time points of OGTT(P<0.01),serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly increased,serum HDL-C and colonic tissue SIgA contents significantly decreased(P<0.01),with colonic tissue nuclear condensation,cytoplasmic dissolution,inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly increased,while the protein expressions of IκBα and ZO-1 significantly decreased(P<0.01).Compared with the model group,the body mass and FBG significantly decreased in metformin group,TCM high-and medium-dosage groups(P<0.01),blood glucose decreased at different time points of OGTT,and serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly decreased,serum HDL-C and colonic tissue SIgA contents significantly increased(P<0.05,P<0.01),with significant improvement in colonic tissue structure and reduction in inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly decreased,while the proteins expression of IκBα and ZO-1 significantly increased(P<0.05,P<0.01).Conclusion Dahuang Tangluo Pills may inhibit the activation of the TLR4/NF-κB signaling pathway,reduce the release of inflammatory factors,improve intestinal inflammatory injury,restore intestinal homeostasis,thereby improving glucose and lipid metabolism and exerting therapeutic effects on T2DM.

Objective Based on Network pharmacology to explore the mechanism of Compound Danshen Dripping Pills in treating Psycho-cardiological disease.Methods To obtain the validated targets of the complete formulation of Compound Danshen Dripping Pills,data were sourced from databases including China National Knowledge Infrastructure,Wanfang,VIP,and PubMed.Additionally,genes associated with Psycho-cardiological disease were retrieved from the Genecards database.Utilizing the Digital Intelligence Traditional Chinese Medicine Innovation Platform,network proximity was calculated for the obtained targets and genes.The potential targets of Compound Danshen Dripping Pills in the treatment of Psycho-cardiological disease conduct enrichment analysis,trace the source of medicinal materials and effective components absorbed into the blood.Results Obtained 192 targets for the Compound Danshen Dripping Pills,1137 genes for Psycho-cardiological disease,and the network proximity calculation showed a significant correlation between the two(Z-score=-6.5282).The enrichment analysis of the 95 potential targets predominantly reveals their association with several key pathways,including AGE-RAGE signaling in diabetic complications,Lipid and atherosclerosis,fluid shear stress and atherosclerosis,the HIF-1 signaling pathway,TNF signaling.The traceability analysis indicates that 80 targets are associated with three distinct medicinal materials,10 targets are linked to two medicinal materials,and 5 targets are connected to a single medicinal material.95 targets are mainly related to 17 effective blood components such as salvianolic acid B,tanshinone ⅡA,and salvianolic acid A.The top 16 key genes were obtained by sorting the targets based on the Betweenness values corresponding to the blood components.The enrichment analysis of the key gene indicated that the treatment of Psycho-cardiological disease with Compound Danshen Dripping Pills is associated with the positive regulation of smooth muscle cell proliferation and the hypoxia response.Additionally,it is linked to the AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,the relaxin signaling pathway,lipid and atherosclerosis,and the TNF signaling pathway,etc.Conclusion The Compound Danshen Dripping Pills may improve Psycho-cardiological disease by regulating inflammatory response,oxidative stress,myocardial ischemia,neuroprotection,and neurotoxicity inhibition through components such as salvianolic acid B,tanshinone ⅡA,tanshinone Ⅰ,salvianolic acid A,protocatechuic acid,etc.

Objective Based on Network pharmacology to explore the mechanism of Compound Danshen Dripping Pills in treating Psycho-cardiological disease.Methods To obtain the validated targets of the complete formulation of Compound Danshen Dripping Pills,data were sourced from databases including China National Knowledge Infrastructure,Wanfang,VIP,and PubMed.Additionally,genes associated with Psycho-cardiological disease were retrieved from the Genecards database.Utilizing the Digital Intelligence Traditional Chinese Medicine Innovation Platform,network proximity was calculated for the obtained targets and genes.The potential targets of Compound Danshen Dripping Pills in the treatment of Psycho-cardiological disease conduct enrichment analysis,trace the source of medicinal materials and effective components absorbed into the blood.Results Obtained 192 targets for the Compound Danshen Dripping Pills,1137 genes for Psycho-cardiological disease,and the network proximity calculation showed a significant correlation between the two(Z-score=-6.5282).The enrichment analysis of the 95 potential targets predominantly reveals their association with several key pathways,including AGE-RAGE signaling in diabetic complications,Lipid and atherosclerosis,fluid shear stress and atherosclerosis,the HIF-1 signaling pathway,TNF signaling.The traceability analysis indicates that 80 targets are associated with three distinct medicinal materials,10 targets are linked to two medicinal materials,and 5 targets are connected to a single medicinal material.95 targets are mainly related to 17 effective blood components such as salvianolic acid B,tanshinone ⅡA,and salvianolic acid A.The top 16 key genes were obtained by sorting the targets based on the Betweenness values corresponding to the blood components.The enrichment analysis of the key gene indicated that the treatment of Psycho-cardiological disease with Compound Danshen Dripping Pills is associated with the positive regulation of smooth muscle cell proliferation and the hypoxia response.Additionally,it is linked to the AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,the relaxin signaling pathway,lipid and atherosclerosis,and the TNF signaling pathway,etc.Conclusion The Compound Danshen Dripping Pills may improve Psycho-cardiological disease by regulating inflammatory response,oxidative stress,myocardial ischemia,neuroprotection,and neurotoxicity inhibition through components such as salvianolic acid B,tanshinone ⅡA,tanshinone Ⅰ,salvianolic acid A,protocatechuic acid,etc.

ObjectiveTo analyze the incidence， recovery rate and associated factors of nonalcoholic fatty liver disease （NAFLD） among residents aged 65 years old and above in Xinqiao Community of Songjiang， Shanghai， and to provide basic data for further efficient community management. MethodsData of annual geriatric physical examination program for residents aged 65 and above were collected in Xinqiao Community， Songjiang from 2016 to 2022. Those residents who participated twice or more were included in this analysis. Data were collated into longitudinal form. For each participant， data of the first physical examination was used as baseline， and each subsequent examination was taken as follow-up. Incidence and recovery rate of NAFLD were calculated. Cox proportional hazard models were used to explore the associated factors and their changes with the onset and recovery of NAFLD. ResultsDuring the study period， a total of 11 983 residents participated in physical examinations， of which 8 644 participated twice or more， and 8 154 had no history of excessive alcohol consumption. B-ultrasound showed that there were 5 267 residents without NAFLD and 2 887 with NAFLD at baseline. After a median follow-up of 3.3 years， the incidence density of NAFLD in this population was estimated to be 11.5 per 100 person-years， and the recovery density was 23.4 per 100 person-years. The incidence density of NAFLD was negatively associated with age， and positively associated with baseline BMI， abdominal obesity， high fasting blood glucose， and high triglycerides. The recovery density was negatively associated with baseline BMI and abdominal obesity. Compared with those with normal BMI at both baseline and follow-up， those with persistent obesity showed the highest risk of NAFLD （males： HR： 3.19， 95%CI： 2.16-4.70； females： HR： 3.34， 95%CI： 2.46-4.54） and the lowest potential of recovery （males： HR： 0.58， 95%CI： 0.42-0.82； females： HR： 0.58， 95%CI： 0.44-0.77）. Persistently high triglycerides were also associated with a higher risk of developing the disease. ConclusionResidents aged 65 years old and above in Xinqiao， Shanghai had a higher incidence and recovery rate of NAFLD. Women， being obese and having hyperlipidemia are at a higher risk for the development and persistence of NAFLD.

Diabetic kidney disease(DKD)is one of the major complications of diabetes mellitus(DM),which significantly affects the survival and quality of life of DM patients.Currently,existing first-line treatment approaches for DKD are ineffective in effectively preventing the occurrence and progression of DKD.Traditional Chinese medicine(TCM)has the advantages of"ultiple pathways,multiple targets,and multiple mechanisms"in treating DKD,and has a broad prospect in the treatment of DKD.Aquaporin-2(AQP2)is a membrane channel protein widely expressed in the kidneys,and its physiological function is highly similar to the function of kidney filtration and reabsorption.Studies have found that various effective components and related formulae of Chinese medicine can improve symptoms in DKD patients by inhibiting the abnormal expression of AQP2.This article provides a review on the role of AQP2 in DKD and the research progress of TCM intervention,aiming to provide insights and references for the development of drugs related to the prevention and treatment of DKD.

OBJECTIVE To investigate the effects of renally inappropriate medication （RIM） on the frailty of elderly patients with diabetes. METHODS The data of elderly patients with diabetes mellitus admitted to a third-grade class A hospital in Yunnan province from January to December 2022 were collected， and Beers criteria （2019 edition） and Chinese version of FRAIL scale were used to evaluate RIM and the frailty of the patients； the patients were divided into the trial group （with RIM） and the control group （without RIM） according to whether there was RIM. The propensity score matching was used to balance confounding factors between two groups， and the influence of RIM on the frailty of elderly diabetic patients was analyzed by the Logistic regression model. RESULTS Among the 367 patients， 80 patients （21.80%） had RIM， the drugs involved RIM were spironolactone （82.56%）， rivaroxaban （13.95%） and gabapentin （3.49%）. After reaching the balance between groups using the propensity score matching method， the incidence of frailty was 77.94% in trial group and 27.94% in control group （P＜0.001）； the difference was not statistically significant in other confounding factors between the two groups （P＞0.05）. Results of Logistic regression analysis showed that the risk of frailty in the experimental group was 3.118 times that of the control group （odds ratio was 3.118，95% confidence interval was 1.758-5.530， P＜0.001）. CONCLUSIONS RIM is a risk factor for the frailty of elderly patients with diabetes， which can be considered as an indicator for early identification and screening of the frailty of elderly diabetes patients.