OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

Objective:To investigate the impact of olanzapine and risperidone on the cognitive function, sensory gating function and clinical symptoms of patients with first-episode schizophrenia(FES).Additionally, to analyze the correlation between sensory gating inhibitory deficits and cognitive impairment in FES patients.Methods:A total of 71 FES patients were selected in the Third People's Hospital of Zhongshan City from March 2023 to March 2024, and 60 healthy controls were recruited during the same period.The FES patients were divided into olanzapine group and risperidone group by random number table.Olanzapine group was treated with variable doses of olanzapine(10-20 mg/d), and risperidone group was treated with variable doses of risperidone(3-6 mg/d).The MATRICS consensus cognitive battery(MCCB) was used to evaluate the cognitive function of the patients, P50 index was measured by auditory paired condition-stimulus paradigm, and the efficacy was evaluated by positive and negative syndrome scale(PANSS) score reduction rate before and after 6 weeks of treatment.Healthy controls were assessed cognitive function only once with P50.SPSS 25.0 software was used for data processing. Perform statistical analysis using paired sample t-test, Wilcoxon signed rank test, independent sample t-test, Mann Whitney U test, χ2 test and generalized linear model. Results:Before treatment, the S2 amplitude of FES (1.74 (0.91, 2.79) μV) was higher than that of healthy controls (1.70 (1.04, 2.71) μV) (Wald χ2=4.483, P=0.034), the S2/S1 ratio of FES (0.58 (0.43, 0.78)) was higher than that of healthy controls (0.41 (0.31, 0.57)) (Wald χ2=10.909, P=0.001), and the difference of FES amplitude of S1-S2 was (1.22 (0.43, 1.92) μV) was lower than that of healthy controls (2.23 (1.54, 3.07) μV) (Wald χ2=17.679, P<0.001). There was no significant difference in PANSS, MCCB and P50 between olanzapine group and risperidone group before treatment (all P>0.05). After treatment, there was no significant difference in response rate between the two groups ( χ2=0.059, P=0.808), the PANSS scores were lower than those before treatment, the MCCB test results were higher than those before treatment (both P<0.05), and the P50 results were not statistically significant different compared with those before treatment (both P>0.05). The generalized linear model showed that the S1, S2 amplitude of the P50 had positive impact on the connection test score in the MCCB test ( β=0.466, P=0.020; β=0.879, P=0.009), other indicators were not found to have an impact on the test scores of the MCCB test (all P>0.05). Conclusion:Olanzapine and risperidone can significantly improve the cognitive function of FES, but the improvement of sensory gating deficits is limited. The pathogenic mechanism of sensory gating inhibitory deficits in FES may be different from that of cognitive dysfunction.

Objective:To investigate the impact of olanzapine and risperidone on the cognitive function, sensory gating function and clinical symptoms of patients with first-episode schizophrenia(FES).Additionally, to analyze the correlation between sensory gating inhibitory deficits and cognitive impairment in FES patients.Methods:A total of 71 FES patients were selected in the Third People's Hospital of Zhongshan City from March 2023 to March 2024, and 60 healthy controls were recruited during the same period.The FES patients were divided into olanzapine group and risperidone group by random number table.Olanzapine group was treated with variable doses of olanzapine(10-20 mg/d), and risperidone group was treated with variable doses of risperidone(3-6 mg/d).The MATRICS consensus cognitive battery(MCCB) was used to evaluate the cognitive function of the patients, P50 index was measured by auditory paired condition-stimulus paradigm, and the efficacy was evaluated by positive and negative syndrome scale(PANSS) score reduction rate before and after 6 weeks of treatment.Healthy controls were assessed cognitive function only once with P50.SPSS 25.0 software was used for data processing. Perform statistical analysis using paired sample t-test, Wilcoxon signed rank test, independent sample t-test, Mann Whitney U test, χ2 test and generalized linear model. Results:Before treatment, the S2 amplitude of FES (1.74 (0.91, 2.79) μV) was higher than that of healthy controls (1.70 (1.04, 2.71) μV) (Wald χ2=4.483, P=0.034), the S2/S1 ratio of FES (0.58 (0.43, 0.78)) was higher than that of healthy controls (0.41 (0.31, 0.57)) (Wald χ2=10.909, P=0.001), and the difference of FES amplitude of S1-S2 was (1.22 (0.43, 1.92) μV) was lower than that of healthy controls (2.23 (1.54, 3.07) μV) (Wald χ2=17.679, P<0.001). There was no significant difference in PANSS, MCCB and P50 between olanzapine group and risperidone group before treatment (all P>0.05). After treatment, there was no significant difference in response rate between the two groups ( χ2=0.059, P=0.808), the PANSS scores were lower than those before treatment, the MCCB test results were higher than those before treatment (both P<0.05), and the P50 results were not statistically significant different compared with those before treatment (both P>0.05). The generalized linear model showed that the S1, S2 amplitude of the P50 had positive impact on the connection test score in the MCCB test ( β=0.466, P=0.020; β=0.879, P=0.009), other indicators were not found to have an impact on the test scores of the MCCB test (all P>0.05). Conclusion:Olanzapine and risperidone can significantly improve the cognitive function of FES, but the improvement of sensory gating deficits is limited. The pathogenic mechanism of sensory gating inhibitory deficits in FES may be different from that of cognitive dysfunction.

Objective:To investigate the response of mandibular condylar chondroprogenitors to flow fluid shear stress(FFSS).Methods:Chondroprogenitors were in vitro cultured and stimulated with FFSS that can cause cell degeneration,and treated with sec-ond-generation high-throughput RNA sequencing.Differential gene expression was screened using DESeq2 software for gene ontology(GO)functional enrichment analysis,kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis and protein-protein interaction(PPI)network analysis.qRT-PCR was performed to validate the core genes screened by PPI.Results:A total of 1996 differentially expressed genes were obtained,mainly including inflammatory response and cell cycle related molecules.Among them,Actal,Atf3,Ccl2,116,Nfkbia,Ret and Vcaml were identified as the core genes.Conclusion:FFSS stimulation affects chondroprogenitor function by acting on inflammatory responses and cell cycle-related signaling pathways in chondroprogenitors.

"Toxicity Testing in the 21st Century—A Vision and Strategy"proposed by the National Research Council of US has brought innovative directives and objectives for toxicity evaluation and risk assessment,pushing forward the next generation of toxicity testing and risk assessment.In this initiative,the concept of adverse outcome pathways(AOPs)has emerged as a prominent methodology,capturing the attention of toxicologists and researchers due to its promising applications in recent years.The quantitative AOP(qAOP)is an extension of the adverse outcome pathway,which is built upon the foundational qualitative adverse outcome pathway model and leverages mathematical frame-works to depict dose-response and/or response-response relationships.This article reviews the princi-ples and advancement surrounding qAOP,introduceds two prevalent methodologies for constructing qAOP,Bayesian network models and regression models,and demonstrates diverse applications of qAOP.Actual cases are used to underscore the transformative role of qAOP in contemporary toxicology and risk assessment practices.

Objective To investigate the relationship between serum uric acid level and renal function decline by retrospective cohort study.Methods Through the physical examination system of the First People's Hospital of Foshan,the physical examination data from 2015 to 2018 of a public institution in Foshan city were obtained.The gender,age,blood cell analysis,liver function,serum creatinine,uric acid,fasting blood glucose were obtained.The change of eGFR (△eGFR=eGFR2018-eGFR2015) was analyzed.Results A total of 2505 subjects were followed up for four years.The subjects were divided into △eGFR ≥0 group and △eGFR ＜ 0 group.There were 845 subjects in △eGFR ≥0 group,and 1660 subjects in △eGFR ＜ 0 group.Compared with that in △eGFR ＜ 0 group,the base-level of uric acid in △eGFR ≥ 0 group was higher [(349.48±87.62) μmol/L vs (325.72±82.58) μmol/L,t=6.669,P ＜ 0.001],but the rate of uric acid decline was greater [-15.00(-53.50,17.00) μmol/L vs 15.50(-18.00,49.00) μmol/L,Z=-13.470,P ＜ 0.001].According to the levels of uric acid in 2015 and 2018,then the subjects were divided into four groups,normal to normal group (N-N,1551 cases),normal change into high uric acid group (N-H,299 cases),high uric acid drop to normal group (H-N,238 cases),and high to high uric acid group (H-H,417 cases).The △eGFR was-1.58(-4.17,1.01) ml · min-1 · (1.73 m2) 1 in N-N group,and-3.60(-7.24,-0.98) ml · min-1 · (1.73 m2)-1 in N-H group,-0.20(-3.14,3.27) ml· min-1· (1.73 m2)-1 in H-N group,-0.96(-4.07,1.93) ml· min-1· (1.73 m2)-1 in H-H group,respectively.The △eGFR decreased most significantly in N-H group than the other three groups (x2=103.130,P ＜ 0.001).Multivariate logistic regression analysis showed that elevated uric acid was an independent risk factor for eGFR decline (OR=1.739,95％CI 1.587-1.906,P ＜ 0.001),while elevated indirect bilirubin (OR=0.968,95％CI 0.943-0.993,P=0.013),elevated red blood cells (OR=0.815,95％ CI 0.680-0.976,P=0.026) were independent protective factors for eGFR decline.Conclusion Elevated uric acid is an independent risk factor for the decline of renal function.Good control of hyperuricemia is beneficial to the protection of renal function.