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.

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.

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 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.

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 Chlorination is often used to disinfect recreational water in large amusement parks;however,the health hazards of chlorination disinfection by-products(DBPs)to occupational populations are unknown.This study aimed to assess the exposure status of chlorinated DBPs in recreational water and the health risks to employees of large amusement parks. Methods Exposure parameters of employees of three large amusement parks in Shanghai were investigated using a questionnaire.Seven typical chlorinated DBPs in recreational water and spray samples were quantified by gas chromatography,and the health risks to amusement park employees exposed to chlorinated DBPs were evaluated according to the WHO's risk assessment framework. Results Trichloroacetic acid,dibromochloromethane,bromodichloromethane,and dichloroacetic acid were detected predominantly in recreational water.The carcinogenic and non-carcinogenic risks of the five DBPs did not exceed the risk thresholds.In addition,the carcinogenic and non-carcinogenic risks of mixed exposure to DBPs were within the acceptable risk limits. Conclusion Typical DBPs were widely detected in recreational water collected from three large amusement parks in Shanghai;however,the health risks of DBPs and their mixtures were within acceptable limits.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

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.