Background Maternal exposure to bisphenol A (BPA) during pregnancy is closely related to adverse growth and development conditions such as preterm birth and low birth weight, but the relevant mechanisms are still unclear. UDP-glucuronosyltransferases (UGTs) can regulate the excretion of BPA conjugating with glucuronic acid through urine, which is one of the important pathways for BPA elimination. Objective To explore the changes in the expression of UGTs in placenta and fetal liver of rats before birth induced by maternal exposure to BPA during pregnancy. Methods Thirty SPF-grade healthy SD pregnant rats were randomly divided into five groups: control group, 0.05, 0.5, 5, and 50 mg·kg⁻¹ BPA groups. The pregnant rats were exposed to BPA dissolved in corn oil via oral gavage daily from gestational day (GD) 5 to GD 19. After anesthesia, the pregnant rats were sacrificed on GD 20 and the placentas were collected. Body length, tail length, and weight of the fetal rats were measured. Fetal liver tissues were then separated, and organ weights were measured. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to determine the mRNA and protein levels of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in the placenta and fetal liver tissues in each group. Results There were no differences in body length and tail length of the pups after maternal exposure to BPA during pregnancy. The fetal body weight and placenta weight in the 5 and 50 mg·kg⁻¹ BPA groups and the liver weight in the 5 mg·kg⁻¹ BPA group reduced compared with the control group (P<0.05). The results of UGTs expressions in placenta showed that compared with the control group, the UGT1A1 mRNA levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) and the UGT1A1 protein level in placenta of the 50 mg·kg⁻¹ BPA group increased (P<0.05); the UGT1A6 mRNA and protein levels in placenta of each BPA group did not change (P>0.05); the UGT1A9 mRNA level in placenta of the 50 mg·kg⁻¹ BPA group and the UGT1A9 protein levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05); while the levels of UGT2B1 mRNA in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). The results of UGTs expressions in fetal liver showed that compared with the control group, the UGT1A1, UGT1A6, UGT1A9, and UGT2B1 mRNA levels of each BPA group increased (P<0.05); no obvious alternation was observed in UGT1A6 protein levels in each BPA group (P>0.05); the relative protein levels of UGT1A9 in fetal liver in the 50 mg·kg⁻¹ BPA group increased (P<0.05); conversely, the relative protein levels of UGT2B1 in fetal liver in the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). Conclusion Maternal exposure to BPA during pregnancy can elevate the UGT1A1 gene and protein expressions, inhibit the UGT1A9 gene and protein expressions and UGT2B1 gene expressions in placenta. Besides, maternal exposure to BPA during pregnancy can raise the gene expressions of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in fetal liver, as well as the protein expression of UGT1A9, but inhibit the protein expression of UGT2B1. These changes may contribute to fetal developmental abnormalities after maternal exposure to BPA during pregnancy.

Food additives are a kind of chemical substances added to food to enhance the taste,color and shelf life of food,and have become an indispensable part of the modern food industry.However,growing researches showed that synthetic chemicals used as food additives can be potentially harmful to health.Some food additives may be closely related to asthma,attention deficit hyperactivity disorder,heart disease,cancer,obesity and other health problems.In addition,some food additives may also interfere with hormone secretion,affect growth and development,and affect the healthy growth of children.This study reviews the damage effects of various food additives,such as preservatives,antioxidants,and colorants on body,and proposes the need to improve the safety evaluation of food additives from the perspective of the combined action of chemicals,in order to provide a scientific basis for food safety supervision and consumer health protection.

Objective:To understand the learning interest of college students majoring in Bioinformatics in Shenyang Medical College and its influencing factors,so as to provide a strong basis for future teaching reform and curriculum setting.Method:After the actual teaching,a self-made questionnaire was used to conduct a quantitative survey on the first-year students majoring in Bioinformatics of Shenyang Medical College to understand their learning interest and analyze its influencing factors.Results:The questionnaire survey found that students majoring in Bioinformatics had different interest points for all 9 courses,different teaching links and different teaching methods in the second semester of freshman.Students had a general high interest in Introduction to Bioinformatics and Introduction to Biometrics.In the Introduction to Bioinformatics course,students were more interested in the history of bioinformatics,but less interested in algorithm-related knowledge points.In the Introduction to Biometrics course,students were more interested in the application cases of biometric recognition,but less interested in laws and regulations of biometrics.The interest of students in learning mainly lied in whether it is conducive to the postgraduate entrance examination.Conclusion:Through strengthen the education of bioinformatics related courses,enhance students'understanding of bioinformatics knowledge and improve their interest in Bioinformatics by analyzing the results of students'questionnaire.

Objective:To investigate the effect and mechanism of vitamin K2 on vascular calcification in a type 2 diabetes rat model.Methods:Thirty male Wistar rats,6 weeks old,were acclimatized for 7 days.Ten rats were randomly selected as the negative control group,fed a normal diet,and injected with an equal amount of citrate buffer.The remaining rats were fed a high-fat and high-sugar diet for 4 weeks,and then type 2 diabetes was induced by intraperitoneal injection of streptozotocin.After successful induction of the diabetes model,the diabetic rats were numbered by body weight and divided into the diabetes group and the diabetes+vitamin K2 group according to the principle of stratified random grouping.These two groups were fed a high-fat diet and a high-fat diet containing vitamin K2,respectively,while the control group continued to be fed a normal diet.After 13 weeks of feeding,the rats were sacrificed for sample collection,and blood glucose and vascular calcium concentration were measured.Von Kossa staining was used for histopathological detection.The relative expression levels of hypoxia-inducible factor-1α(HIF-1α),pyruvate dehydrogenase kinase 4(PDK4),matrix Gla protein(MGP),and bone morphogenetic protein-2(BMP-2)mRNA and proteins were measured by qRT-PCR and Western blot,respectively.Results:Compared with the control group,blood glucose levels in the diabetes group and diabetes+vitamin K2 group were significantly elevated(P＜0.01),but there was no significant difference between the two groups.There was no significant difference in vascular calcium concentration among the three groups(P＞0.05).Von Kossa staining showed that the control group exhibited normal vascular structures,while the diabetes group showed a large number of brown-black calcification plaques between elastic fibers in the vascular media.The diabetes+vitamin K2 group had either no calcification plaques or only a few brown-black calcification plaques.Compared with the control group,the expression levels of PDK4,MGP,and BMP-2 mRNA and proteins were higher in the diabetes group(P＜0.05),but there was no significant difference in the expression level of HIF-1α.Only the expression level of PKD4 protein had significance between the control group and diabetes+vitamin K2 group(P＜0.05).There was no significant difference in the above indexes between the diabetic group and diabetic+vitamin K2 group(P＞0.05).Conclusions:Type 2 diabetes mellitus may cause vascular calcification by increasing the expression of PDK4,which in turn leads to increased expression of BMP-2 and MGP.Vitamin K2 can inhibit vascular calcification in diabetes.

Objective:To gain insights into the cognitive processes and utilization patterns of medical students regarding teaching information platforms and resources,and aims to provide valuable references for the implementation of modern medical information technology in educational reforms.Methods:A survey was conducted among all voluntary medical students of grade 2019 to grade 2022.Questionnaire surveys and semi-open interviews were used to investigate.Results:The findings indicated that medical students possess a comprehensive understanding of various teaching platforms,with a high frequency of accessing course materials through these platforms.However,the browsing rate for case analyses recommended by teachers on these platforms remains relatively low.Students demonstrated awareness and utilization of quality courses,particularly MOOCs and micro-courses,which were more frequently utilized compared to other courses.Conclusion:Medical students have a strong awareness of information technology and the ability to solve academic problems through multiple platforms and channels.The construction of teaching platform resources needs to further optimize and improve its simplicity and affinity,and teachers should selectively push high-quality teaching resources to realize the rational application of medical information technology in teaching.

OBJECTIVE: To observe the hepatic injury induced by combined exposure to diethylhexyl phthalate( DEHP) and bisphenol A( BPA) in rats and explore the mechanism of oxidative stress. METHODS: Thirty-two specific pathogen free healthy male SD rats were randomly divided into control group,DEHP(750 mg/kg body weight) group,BPA(100 mg/kg body weight) group and combined exposure group,with 8 rats in each group. The rats were gavaged once per day,7 days per week,for 6 weeks. The changes of liver organ coefficient and histopathology were observed. The activities of superoxide dismutase( SOD), glutathione peroxidase( GSH-Px) and the levels of hydrogen peroxide( H2 O2),malondialdehyde( MDA) were detected by spectrophotometry. The relative mRNA expression of antioxidant gene nuclear factor erythroid-2 related factor 2( Nrf2),heme oxygenase-1( HO-1),glutamate cysteine ligase catalytic subunit( Gclc),thioredoxin reductase( Txnrd),superoxide dismutase 3( Sod3) and glutathione peroxidase 1( Gpx1) in liver tissue were examined by real-time fluorescent quantitative polymerase chain reaction. RESULTS: The body weight of DEHP exposure group was lower than that of control group from the beginning of the 2 nd week( P < 0. 05),and the body weight of combined exposure group was lower than control group from the beginning of the 3 rd week( P < 0. 05). The liver mass and organ coefficients in DEHP group and combined exposure group were significantly higher than that of control group( P <0. 05). The results of pathology examination showed that there was necrosis of liver cells in DEHP group,vacuolar degeneration in cytoplasm of BPA group,and severe inflammatory cell infiltration in combined exposure group. The activity of SOD and GSH-Px of each exposure group was reduced( P < 0. 05),the H2 O2 level of each exposure group was increased(P < 0. 05),meanwhile the MDA level in the liver tissue of the BPA group and the combined exposure group increased compared with the control group( P < 0. 05). The relative mRNA expression of Nrf2,HO-1 and Gpx1 in each exposure group were decreased( P < 0. 05),the relative mRNA expression of Gclc,Txnrd and Sod3 in DEHP group and mixed exposure group were decreased compared with the control group( P < 0. 05). The relative mRNA expression of Nrf2,HO-1,Gclc,Txnrd and Sod3 in combined exposure group were decreased compared with the BPA group( P < 0. 05).CONCLUSION: Under the conditions of this study,DEHP and BPA alone or in combination could cause hepatic injury. The combined effect was greater than single effect. The effect of DEHP was greater than that of BPA. The liver injury induced by DEHP and BPA was related to Nrf2 signaling pathway.

OBJECTIVE: To investigate the mechanism of calcium ion(Ca~(2+))/calcineurin(CaN) signaling pathway in bisphenol A(BPA)-induced interleukin-6(IL-6) secretion in macrophages. METHODS: Raw 264.7 cells in logarithmic growth phase were divided into control group, activator group, BPA low-, medium-and high-dose groups and inhibitor group. The cells in control group were treated with 0.10% dimethyl sulfoxide. The activator group was treated with lipopolysaccharide at mass concentration of 2 mg/L. The 3 BPA groups were treated with BPA at final concentrations of 1, 10, or 100 μmol/L. Two sets of verapamil or tacrolimus(FK506) groups were given verapamil at the final concentration of 10 or 30 μmol/L; or final concentration of FK506 at 250 or 500 nmol/L. Then the cells were treated with final concentration of 100 μmol/L BPA. The cells were collected at 4, 12, and 24 hours. The mRNA expression of IL-6 and CaN at 4 and 12 hours were detected by real-time fluorescence quantitative polymerase chain reaction. The relative expression of IL-6 and CaN protein was detected at 24 hours by enzyme-linked immunosorbent assay, and the intracellular Ca~(2+) level was detected at 4 hours using a single-tube multi-function detector. RESULTS: At 12 hours, the mRNA expression of IL-6 in the 100 μmol/L BPA group was higher than that in control group, activator group and the 1 and 10 μmol/L BPA groups(P<0.05), and higher than that in the 10 and 30 μmol/L verapamil groups, and in the 250 and 500 nmol/L FK506 groups(P<0.05). The mRNA expression of CaN in the 100 μmol/L BPA group was higher than that in control group, activator group and 1 and 10 μmol/L BPA groups(P<0.05), and higher than in 10 and 30 μmol/L verapamil groups(P<0.05). The relative expression of IL-6 protein in the 100 μmol/L BPA group was higher than that in control group, activator group and 1 and 10 μmol/L BPA groups(P<0.05). The relative expression of CaN protein in 100 μmol/L BPA group and 10 and 30 μmol/L verapamil groups were higher than that in control group and activator group(P<0.05). The relative expression of CaN protein in the 10 and 30 μmol/L verapamil groups were lower than that in the 100 μmol/L BPA group(P<0.05). The intracellular Ca~(2+) level in the 100 μmol/L BPA group was higher than that in control group and activator group(P<0.05). The intracellular Ca~(2+) level in the 10 μmol/L verapamil group was lower than that in the 100 μmol/L BPA group(P<0.05). CONCLUSION: BPA might promote the secretion of IL-6 through Ca~(2+)/CaN signaling pathway in macrophages.

OBJECTIVE: To investigate the effect of bisphenol A exposure on the expression of DNA methyltransferase(Dnmt) gene in mouse Leydig cell line TM3 cells. METHODS: TM3 cells were randomly divided into 0, 20, 50, 125 and 300 μmol/L dose group(0 μmol/L dose group was the control group). Cells were treated with various concentration of bisphenol A solution for 24 hours.The viability of TM3 cells was determined by CCK-8 method, and the mRNA expression of Dnmt1, Dnmt3 a and Dnmt3 b was detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS:The viability of TM3 cells decreased with the increasing doses of bisphenol A(P<0.01). The relative mRNA expression of Dnmt1 in TM3 cells decreased with the increase of doses of bisphenol A(P<0.01).The relative mRNA expression of Dnmt3 b in TM3 cells in the 20, 50, 125, 300 μmol/L dose group was lower than that in the control group(P<0.05).There was no statistical significant difference in the relative mRNA expression of Dnmt3 a in TM3 cells in these 5 groups(P>0.05). CONCLUSION: Bisphenol exposure is cytotoxic to TM3 cells. This toxic effect may be related to changes in Dnmt mRNA expression.

OBJECTIVE: To investigate the effects of combined exposure to di(2-ethylhexyl) phthalate(DEHP) and bisphenol A(BPA) on glucose metabolism in female rats during gestational and lactation periods, and its possible mechanism. METHODS: Twenty-four specific pathogen free pregnant SD rats were randomly divided into control group, DEHP group, BPA group, and combined exposure group, with 6 rats in each group. From the 5 th day of gestation to the 21 st day after birth of the offspring, the rats in the DEHP group were treated with DEHP 600 mg/kg body weight(bw); rats in BPA group were treated with 80 mg/kg bw BPA, and rats in combined exposure group were treated with 600 mg/kg bw DEHP and 80 mg/kg bw BPA by intragastric perfusion, while the rats in the control group were given the same amount of corn oil, once per day. After exposure, maternal rats were sacrificed immediately. The levels of glucose metabolism related indicators in liver tissues and serum were examined, and the mRNA and protein expression of phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(AKT) signaling pathway related factors in liver tissues were detected by real-time fluorescence quantitative polymerase chain reaction and Western blot. RESULTS: Except for the activity of phosphoenolpyruvate carboxykinase(PEPCK) in BPA group, the levels of liver glycogen and serum high density lipoprotein cholesterol(HDL-C) in rats of the 3 exposure groups decreased(P<0.05), while the activity of serum PEPCK and the level of low density lipoprotein cholesterol(LDL-C) increased(P<0.05) compared with rats in the control group. The levels of liver glycogen and serum HDL-C in the combined exposure group were lower than that in the BPA group(P<0.05), while the level of serum LDL-C were lower than that in DEHP group and BPA group(P<0.05). The levels of serum glycosylated serum protein, total cholesterol and triglyceride in the 4 groups were not statistically different when compared with each other(P>0.05). Except for the PI3 K protein in DEHP group, the mRNA and protein expression of PI3 K, AKT, and glucose transporter 4 in liver tissues of rats in the 3 exposure groups decreased(P<0.05), and the mRNA expression of forkhead box protein 1(Foxo1) decreased(P<0.05), but the protein expression of FOXO1 increased(P<0.05) compared with the control group. CONCLUSION: Exposure to DEHP or BPA during pregnancy and lactation can cause glucose metabolism disorders in rats. The combined exposure of DEHP and BPA has certain synergistic effect. This process may be achieved through the PI3 K/AKT signaling pathway.