Objective:To investigate the effective ingredients and molecular mechanisms of Qizao oral liquid in the treatment of lead poisoning through network pharmacology and molecular docking technology.Methods:December 2023, the effective ingredients and their corresponding targets of Qizao oral liquid were searched from the TCM Systems Pharmacology database. Swiss Target Prediction was used to predict corresponding potential target genes of compounds. Targets associated with lead poisoning were obtained from GeneCards and OMIM databases. Cytoscape 3.10.1 software was employed to construct a components and corresponding target network as well as a components and corresponding target network, followed by visualization and cluster analysis. GO and KEGG enrichment analyses were conducted using the Metascape database, resulting in the generation of a signaling pathway-target network diagram. Molecular docking analysis between the principal compounds and target proteins was performed using Autodock 4.2.6 and Pymol 2.2.0 software to validate their underlying molecular mechanisms.Results:A total of 114 active chemical components, 361 potential targets, 2501 lead poisoning targets, and 191 intersection targets of "Qizao oral liquid and lead poisoning" were screened. Further analysis revealed that there were 2091 entries for GO biological processes and 202 KEGG signaling pathways. Enrichment analysis showed that the key targets were mainly enriched in cancer, lipid and atherosclerosis, PI3K-Akt signaling pathways. Molecular docking showed that there were 14 combinations with binding energy<-5 kcal/mol, among which PIK3R1-β-sitosterol binding energy was -9.71 kcal/mol.Conclusion:The primary active components found in Qizao oral liquid, such as β-sitosterol, nuciferine, stephanine, and stigmasterol, have the potential to modulate key targets including PIK3R1, AKT1, TP53, and NFKB1. These components are capable of influencing the PI3K-Akt signaling pathway as well as lipid and atherosclerosis pathways in order to mitigate the adverse effects of lead exposure.

Objective:To investigate the effective ingredients and molecular mechanisms of Qizao oral liquid in the treatment of lead poisoning through network pharmacology and molecular docking technology.Methods:December 2023, the effective ingredients and their corresponding targets of Qizao oral liquid were searched from the TCM Systems Pharmacology database. Swiss Target Prediction was used to predict corresponding potential target genes of compounds. Targets associated with lead poisoning were obtained from GeneCards and OMIM databases. Cytoscape 3.10.1 software was employed to construct a components and corresponding target network as well as a components and corresponding target network, followed by visualization and cluster analysis. GO and KEGG enrichment analyses were conducted using the Metascape database, resulting in the generation of a signaling pathway-target network diagram. Molecular docking analysis between the principal compounds and target proteins was performed using Autodock 4.2.6 and Pymol 2.2.0 software to validate their underlying molecular mechanisms.Results:A total of 114 active chemical components, 361 potential targets, 2501 lead poisoning targets, and 191 intersection targets of "Qizao oral liquid and lead poisoning" were screened. Further analysis revealed that there were 2091 entries for GO biological processes and 202 KEGG signaling pathways. Enrichment analysis showed that the key targets were mainly enriched in cancer, lipid and atherosclerosis, PI3K-Akt signaling pathways. Molecular docking showed that there were 14 combinations with binding energy<-5 kcal/mol, among which PIK3R1-β-sitosterol binding energy was -9.71 kcal/mol.Conclusion:The primary active components found in Qizao oral liquid, such as β-sitosterol, nuciferine, stephanine, and stigmasterol, have the potential to modulate key targets including PIK3R1, AKT1, TP53, and NFKB1. These components are capable of influencing the PI3K-Akt signaling pathway as well as lipid and atherosclerosis pathways in order to mitigate the adverse effects of lead exposure.

To effectively introduce and utilize global advanced educational resources, the implementation of Chinese-foreign joint education program in medical universities and the establishment of an internal quality assurance system with Chinese characteristics and substantially equivalent to international standards of medical education is crucial for improving the quality of Chinese medical talent cultivation and achieving high-quality development of education opening up to the outside world in the new era. Using the Chinese-Foreign Joint Education Program jointly run by Chongqing Medical University and University of Leicester as an example, this paper proposes a plan for the development of an internal quality assurance system with three core indicators of management mechanism, team building, and student services. This plan provides experience and a reference for domestic universities to carry out cross-border medical education and improve the quality and efficiency of Chinese-foreign joint education programs.

BACKGROUND: Tri-ponderal mass index (TMI) has been reported to be a more accurate estimate of body fat than body mass index (BMI). This study aims to compare the effectiveness of TMI and BMI in identifying hypertension, dyslipidemia, impaired fasting glucose (IFG), abdominal obesity, and clustered cardio-metabolic risk factors (CMRFs) in 3- to 17-year-old children. METHODS: A total of 1587 children aged 3 to 17 years were included. Logistic regression was used to evaluate correlations between BMI and TMI. Area under the curves (AUCs) were used to compare discriminative capability among indicators. BMI was converted to BMI- z scores, and accuracy was compared by false-positive rate, false-negative rate, and total misclassification rate. RESULTS: Among children aged 3 to 17 years, the mean TMI was 13.57 ± 2.50 kg/m 3 for boys and 13.3 ± 2.33 kg/m 3 for girls. Odds ratios (ORs) of TMI for hypertension, dyslipidemia, abdominal obesity, and clustered CMRFs ranged from 1.13 to 3.15, higher than BMI, whose ORs ranged from 1.08 to 2.98. AUCs showed similar ability of TMI (AUC: 0.83) and BMI (AUC: 0.85) in identifying clustered CMRFs. For abdominal obesity and hypertension, the AUC of TMI was 0.92 and 0.64, respectively, which was significantly better than that of BMI, 0.85 and 0.61. AUCs of TMI for dyslipidemia and IFG were 0.58 and 0.49. When 85th and 95th of TMI were set as thresholds, total misclassification rates of TMI for clustered CMRFs ranged from 6.5% to 16.4%, which was not significantly different from that of BMI- z scores standardized according to World Health Organization criteria. CONCLUSIONS TMI was found to have equal or even better effectiveness in comparison with BMI in identifying hypertension, abdominal obesity, and clustered CMRFs TMI was more stable than BMI in 3- to 17-year-old children, while it failed to identify dyslipidemia and IFG. It is worth considering the use of TMI for screening CMRFs in children and adolescents.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Body Mass Index ; Dyslipidemias ; East Asian People ; Hypertension ; Obesity, Abdominal ; Pediatric Obesity/diagnosis* ; Cardiometabolic Risk Factors

Objective To investigate the cellular and molecular mechanisms of the anti-inflammatory effect of peroxisome proliferator-activated receptor α (PPARαt).Methods Firstly,bone marrow-derived macrophages (BMDMs) were randomly divided into control group,LPS group,WY14643 10 μmol/L group,WY14643 25 μmol/L group,and WY14643 50 μmol/L group using a random number table.Secondly,BMDMs were randomly dividcd into LPS group,WY14643+LPS group,and 3-MA+WY14643+LPS group.Primary BMDMs were stimulated by LPS (20 ng/ml) to establish the cellular model of inflammation.The selective agonist of PPARα WY14643 was administered at doses of 10,25,and 50 μmol/L (50 μmol/L for the second part of the experiment) at 2 hours before model establishment.The autophagy inhibitor 3-MA was administered at a dose of 10 mmol/L at 2 hours before model establishment.The cells in the control group were treated with dimethylsulfoxide (DMSO) at the same dose.The calls were transfected with GFP-LC3 plasmids at 24 hours before model establishment.The cells were harvested at 6 hours after LPS stimulation and related tests were performed.Green fluorescent protein was measured under a fluorescence microscope to evaluate autophagy activity.Quantitative real-time PCR was used to measure tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),interleukin-6 (IL-6),and mRNA expression of chemokine-1 (CXCL-1) and chemokine-10 (CXCL-10).Westem blot was used to measure PPARα and autophagy-related proteins LC3,ATG-5,ATG-7,and LAMP-1.A one-way analysis of variance was used for comparison between groups,and the LSD-t test was used for comparison between any two groups.Results In vitro,PPARα activation inhibited LPS-induced inflammatory response in primary macrophages in a dose-dependent manner.The results of gene expression showed that the relative expression of TNF-α,IL-1β,IL-6,CXCL-1,and CXCL-10 was as follows in the control group,LPS group,WY14643 10 μmol group,WY14643 25 μmol group,and WY14643 50 μmol group:TNF-α (0.085±0.009,4.065±0.544,3.281±0.368,1.780±±0.293,and 0.781±0.303,P ＜ 0.01),IL-1β (0.081±0.017,0.776±0.303,0.225±0.154,0.161±0.068,and 0.101±0.025,P ＜ 0.05),IL-6 (0.041±0.011,0.189±0.014,0.144±0.033,0.126±0.013,and 0.048±0.015,P ＜ 0.01),CXCL-1 (0.051±0.011,0.515±0.145,0.356±0.078,0.257±0.068,and 0.069±0.030,P ＜ 0.01),and CXCL-10 (0.126±0.068,0.831±0.093,0.508±0245,0.474±0.047,and 0.204±0.021,P ＜ 0.05).In vitro,PPARα activation promoted autophagy in vitro in a dose-dependent manner.The results of Westem blot and fluorescence microscopy in the control group,LPS group,WY14643 10 μmol group,WY14643 25 μmol group,and WY14643 50 μmol group showed that the expression of autophagy-related proteins and autophagosome formation gradually increased with the increasing concentration of WY14643.In vitro,WY 14643 inhibited autophagy,promoted inflammatory response in primary macrophages,and reversed the anti-inflammatory effect of PPARα.The results of gene expression showed that the relative expression of TNF-α,IL-1β,IL-6,CXCL-1,and CXCL-10 was as follows in the LPS group,WY14643+LPS group,and 3-MA+WY14643+LPS group:TNFα (4.327±.478,1.218±0.424,and 3.901±0.447,P ＜ 0.05),1L-1β (4.277±0.407,1.418±0.424,and 3.029±0.192,P ＜ 0.01),IL-6 (4.175±0.549,1.373±0.499,and 4.031±0.475,P ＜ 0.05),CXCL-1 (8.199±1.149,2.024±0.547,and 5.973±0.843,P ＜ 0.05),and CXCL-10 (1.208±0.148,0.206±0.069,and 0.798±0.170,P ＜ 0.05).Conclusion PPARα can promote cell autophagy and inhibit inflammatory response and may become a new therapeutic target for clinical prevention and treatment of inflammatory disease.

Objective To determine the role and mechanism of peroxisome proliferator activated receptors (PPAR) α in a mouse model of D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced acute liver failure(ALF).Methods Firstly,C57BL/6 mice were randomly divided into control group(n =8),ALF 2h group(n =8),ALF 4h group (n =8),ALF 6h group (n =8).Secondly C57BL/6 mice were randomly divided into control group(n =8),ALF group(n =8),WY14643 group(n =8).To induce ALF,the mice were injected intraperitoneally with D-GalN (700 mg/kg) and LPS (10 μg/kg).WY14643 (6 mg/kg),the selective agonist of PPAR α,was administered via tail vein two hours prior to D-GalN/LPS exposure.Two,four,and six hours after D-GalN/LPS treatment in the first study,mice were anesthetized and blood was collected,6h after D-GalN/LPS treatment in the second study,blood was collected.The liver tissue was harvested for histology and mRNA extraction.Serum levels of ALT and AST were measured to evaluate the hepatic damage.Inflammatory cytokines (TNFα,IL-1β,IL-6) and chemokines (CXCL-1,CXCL-10) were detected by real-time quantitative PCR.Differential protein expression of p-NF-κBp65,p-JNK,p-ERK,p-p38 in inflammatory pathways was detected by Western blotting.Significance of inter-group differences was assessed by one-way ANOVA,and pairwise comparison was performed by the least significant difference test.Results The gene and protein expression of PPAR α were gradually reduced during the development of ALF.Compared with the model group,the liver architecture was better preserved almost with normal morphology in WY14643-treated mice.Serum ALT and AST levels in WY14643-treated group were significantly lower [ALT:(555 ±62)U/L vs (2 898 ±822) U/L,P ＜0.05; AST:(791 ±58) U/L vs (3 013 ±997)U/L,P ＜ 0.05].The expression of proinflammatory cytokines and chemokines was significantly suppressed during the activation of PPAR α.In the second study,the levels of gene expression of proinflammatory cytokines and chemokines were detected in control group,ALF group and WY14643 group respectively as followings:TNFα (0.161 ± 0.085,7.996 ± 1.068,3.346 ± 0.94,P ＜ 0.05),IL-1β(0.041 ±0.002,3.657 ±0.904,0.176±0.089,P＜0.01),IL-6 (0.018 ±0.008,1.762 ±0.589,0.163±0.0487,P ＜0.05),CXCL-1 (0.063 ±0.008,7.881 ±0.966,2.737 ±0.864,P ＜0.01),CXCL-10 (0.054 ±0.005,5.671 ±0.948,2.578 ±0.804,P ＜0.05).Conclusion Our findings first demonstrate that PPARα protects liver from injury in an ALF mouse model by suppressing inflammatory response,indicating PPARα as a potential new therapeutic target for ALF.