BACKGROUND:Total flavonoids from Sophora flavescens have a variety of pharmacological effects,including anti-inflammatory,immunomodulatory,antioxidant,and anti-hepatic injury,but the therapeutic effects and mechanisms in non-alcoholic fatty liver disease are not clear.OBJECTIVE:To reveal the mechanism of total flavonoids from Sophora flavescens in the treatment of non-alcoholic fatty liver disease using bioinformatics,network pharmacology and zebrafish experimental validation.METHODS:A zebrafish model of non-alcoholic fatty liver disease was constructed to observe lipid accumulation,pathomorphologic changes,and expression of inflammatory genes in the liver of zebrafish after treatment with total flavonoids from Sophora flavescens.The active ingredients of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease-related targets were obtained from TCMSP,Swiss Target Prediction,and Bat-man databases.STRING was used to perform protein-protein interaction network analysis,GO functional enrichment and KEGG pathway enrichment analysis.Based on the GSE33814 dataset,the differentially expressed genes of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease intersection targets were screened out.Correlation analysis and receiver operating characteristic curve were performed using R4.3.2 software.Core genes were verified by the validation set GSE89632.RT-qPCR and western blot assays were performed to verify the expression of core pathway-related genes and proteins.RESULTS AND CONCLUSION:(1)Total flavonoids from Sophora flavescens could improve lipid accumulation in the liver of zebrafish with non-alcoholic fatty liver disease,significantly inhibited the elevation of lipid and aminotransferase levels in zebrafish(P<0.05),and regulated the expression of genes related to inflammation and lipid metabolism.(2)A total of 168 common targets were obtained using the network pharmacology,and top 10 core genes,identified by Cytoscape topology analysis,were HSP90AA1,STAT3,PIK3R1,MAPK1,AKT1,RXRA,PIK3CA,EGFR,JAK2,and ESR1.GO and KEGG analysis pathways mainly included insulin resistance,lipids,and atherosclerosis.There were a total of 59 differentially expressed genes after intersection of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease targets.The receiver operating characteristic curve and validation set analyses yielded six core targets that were significantly different between healthy individuals and patients with non-alcoholic fatty liver disease(P<0.01).(3)RT-PCR and western blot results verified that total flavonoids from Sophora flavescens inhibited the activation of the JAK2/STAT3 signaling pathway in zebrafish.To conclude,total flavonoids from Sophora flavescens may alleviate the inflammatory response through the JAK2/STAT3 signaling pathway,thus inhibiting lipid accumulation and improving non-alcoholic fatty liver disease.

BACKGROUND:Total flavonoids from Sophora flavescens have a variety of pharmacological effects,including anti-inflammatory,immunomodulatory,antioxidant,and anti-hepatic injury,but the therapeutic effects and mechanisms in non-alcoholic fatty liver disease are not clear.OBJECTIVE:To reveal the mechanism of total flavonoids from Sophora flavescens in the treatment of non-alcoholic fatty liver disease using bioinformatics,network pharmacology and zebrafish experimental validation.METHODS:A zebrafish model of non-alcoholic fatty liver disease was constructed to observe lipid accumulation,pathomorphologic changes,and expression of inflammatory genes in the liver of zebrafish after treatment with total flavonoids from Sophora flavescens.The active ingredients of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease-related targets were obtained from TCMSP,Swiss Target Prediction,and Bat-man databases.STRING was used to perform protein-protein interaction network analysis,GO functional enrichment and KEGG pathway enrichment analysis.Based on the GSE33814 dataset,the differentially expressed genes of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease intersection targets were screened out.Correlation analysis and receiver operating characteristic curve were performed using R4.3.2 software.Core genes were verified by the validation set GSE89632.RT-qPCR and western blot assays were performed to verify the expression of core pathway-related genes and proteins.RESULTS AND CONCLUSION:(1)Total flavonoids from Sophora flavescens could improve lipid accumulation in the liver of zebrafish with non-alcoholic fatty liver disease,significantly inhibited the elevation of lipid and aminotransferase levels in zebrafish(P<0.05),and regulated the expression of genes related to inflammation and lipid metabolism.(2)A total of 168 common targets were obtained using the network pharmacology,and top 10 core genes,identified by Cytoscape topology analysis,were HSP90AA1,STAT3,PIK3R1,MAPK1,AKT1,RXRA,PIK3CA,EGFR,JAK2,and ESR1.GO and KEGG analysis pathways mainly included insulin resistance,lipids,and atherosclerosis.There were a total of 59 differentially expressed genes after intersection of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease targets.The receiver operating characteristic curve and validation set analyses yielded six core targets that were significantly different between healthy individuals and patients with non-alcoholic fatty liver disease(P<0.01).(3)RT-PCR and western blot results verified that total flavonoids from Sophora flavescens inhibited the activation of the JAK2/STAT3 signaling pathway in zebrafish.To conclude,total flavonoids from Sophora flavescens may alleviate the inflammatory response through the JAK2/STAT3 signaling pathway,thus inhibiting lipid accumulation and improving non-alcoholic fatty liver disease.

ObjectiveTo describe the incidence and distribution characteristics of congenital heart disease in newborns， and to analyze the trend of the notification rate from 2009 to 2018 in Chongming District， Shanghai. MethodsBased on the shanghai birth defects surveillance system， newborns delivered in all medical institutions in Chongming District from 2009 to 2018 were examined for congenital heart disease at birth and followed up to 42 days. The notification rate and trends of various congenital heart diseases were described. ResultsThere were 548 cases of neonatal congenital heart disease in Chongming District from 2009 to 2018， and the notification rate was 20.11‰ （95%CI： 18.47‰-21.85‰）， with statistically significant differences between years during the study period （Z=10.616， P<0.001）. The four most common types of congenital heart disease were patent ductus arteriosus （313， 11.49%）， patent foramen ovale （312， 11.45%）， atrial septal defect （88， 3.64%） and ventricular septal defect （73， 2.68%）. Majority of the congenital heart disease cases were patent ductus arteriosus and patent foramen ovale that could be further closed during growth and development. Isolated patent ductus arteriosus and isolated patent foramen ovale accounted for 18.61% and 23.18% respectively of the total cases. ConclusionThe notification rate of congenital heart disease in Chongming District shows a trend of fluctuating decline followed by an increase. Community follow-up and outcome tracking should be strengthened for children with congenital heart disease， especially those with patent ductus arteriosus or patent foramen ovale.

Objective:To investigate the use of contraceptives among postpartum women in the urban areas of Shanghai and to understand women's demands and utilization of contraceptive service.Methods:A cross-sectional survey was conducted using questionnaires in postpartum women in the clinics for 42-day postpartum follow-up and child health care in 4 districts in Shanghai (including Changning District, Jingan District, Putuo District and Yangpu District) from August 2019 to December 2019. Data were analyzed using frequency description and logistic regression.Results:In total, 1170 postpartum women were enrolled. Among them, 420 women resumed sexual intercourse at an average length of (3.6±1.5) months postpartum and the proportions of consistent contraceptive use were 69.4%(43/62), 77.2% (186/241), 79.2% (57/72) and 71.1% (32/45), at periods of 1 to 3 months, 4 to 6 months, 7 to 9 months and 10 to 12 months after delivery respectively. Planned pregnancy, willingness to reproduce, and postpartum contraceptive guidance were associated with contraceptive behavior. Condom was the main approach used by postpartum women, while long-acting reversible contraceptive method was seldom used. The proportion of receiving guidance on contraception during postpartum home visits and 42-day postpartum follow-up were 43.3% (395/913) and 34.6% (369/1067) respectively. Totally, 37.6% (420/1117) of the total considered that the best time for contraceptive health education was at the 42-day postpartum follow-up, while 30.5% (341/1117) of them preferred health education during pregnancy.Conclusion:About one-quarter of postpartum women do not adhere to contraception in the urban areas of Shanghai. The proportion of using long-acting reversible contraceptive methods, such as intrauterine devices and subcutaneous, remains low. It is necessary to strengthen postpartum contraceptive services, to provide professional training, and strengthen guidance on the proper selection and use of contraceptive methods, especially for long-acting contraceptive methods. Meanwhile, the guidance for contraception should be advanced during pregnancy.

Objective:To investigate the use of contraceptives among postpartum women in the urban areas of Shanghai and to understand women's demands and utilization of contraceptive service.Methods:A cross-sectional survey was conducted using questionnaires in postpartum women in the clinics for 42-day postpartum follow-up and child health care in 4 districts in Shanghai (including Changning District, Jingan District, Putuo District and Yangpu District) from August 2019 to December 2019. Data were analyzed using frequency description and logistic regression.Results:In total, 1170 postpartum women were enrolled. Among them, 420 women resumed sexual intercourse at an average length of (3.6±1.5) months postpartum and the proportions of consistent contraceptive use were 69.4%(43/62), 77.2% (186/241), 79.2% (57/72) and 71.1% (32/45), at periods of 1 to 3 months, 4 to 6 months, 7 to 9 months and 10 to 12 months after delivery respectively. Planned pregnancy, willingness to reproduce, and postpartum contraceptive guidance were associated with contraceptive behavior. Condom was the main approach used by postpartum women, while long-acting reversible contraceptive method was seldom used. The proportion of receiving guidance on contraception during postpartum home visits and 42-day postpartum follow-up were 43.3% (395/913) and 34.6% (369/1067) respectively. Totally, 37.6% (420/1117) of the total considered that the best time for contraceptive health education was at the 42-day postpartum follow-up, while 30.5% (341/1117) of them preferred health education during pregnancy.Conclusion:About one-quarter of postpartum women do not adhere to contraception in the urban areas of Shanghai. The proportion of using long-acting reversible contraceptive methods, such as intrauterine devices and subcutaneous, remains low. It is necessary to strengthen postpartum contraceptive services, to provide professional training, and strengthen guidance on the proper selection and use of contraceptive methods, especially for long-acting contraceptive methods. Meanwhile, the guidance for contraception should be advanced during pregnancy.

Objective:To assess the health status and health service utilization of children born to syphilis infected mothers during pregnancy, in order to prevent mother-to-child transmission of syphilis to the newborns.Methods:Women with maternal syphilis were studied by trained researchers via phone calls, in Shanghai during 2014-2015. Data related to demographics, status of infection and health care, utilization by both mothers and their children were collected through specifically designed questionnaires. Non-parametric tests including chi-square were used to assess the health status and health service utilization of children born to mothers with different demographic and socioeconomic characteristics.Results:A total of 495 children born to mothers with maternal syphilis were recruited from 1 000 syphilis infected parturient women. A total of 61 out of the 495 children were diagnosed as having congenital syphilis (57 children were diagnosed at birth and another 4 were diagnosed during the follow-up period). Children born to women who received syphilis treatment during pregnancy were at lower risk on congenital syphilis ( χ2=7.214, P=0.027). 37.8 % of the children were reported to have had different illnesses in the past three months, mainly involving upper respiratory infections (32.3 %) or diarrhea (3.6 %). Children diagnosed with congenital syphilis showed a higher prevalence of different kinds of diseases, compared to those without congenital syphilis (47.5 % vs. 36.6 %). 81.6 % of the children had received regular child health care services. Subjects with the following factors as: being immigrant, with lower education, unemployed, unmarried and multipara, were related to the less use of regular child healthcare services. Only 39.7 % of the parents would inform the care-takers about the risk of congenital syphilis infection of their own children at the child health care centers. Mothers with residency of Shanghai, having higher education level and employed, were less willing to inform doctors about the risk of congenital syphilis infection of their children. Conclusions:Loss to follow-up among children born to syphilis infected pregnant women remained a serious problem. Few parents would be willing to inform the healthcare takers that their children are at risk of syphilis, when receiving child health care services at the centers. It was necessary to integrate the congenital syphilis follow-up programs into the routine child care services so as to timely diagnose and treat the patients with congenital syphilis.

Objective: To investigate the role of gut microbiota in the amelioration of liver fibrosis induced by CCl4 in mice by 3-methyladenine (3-MA). Methods: Fifteen mice were randomly divided into normal control group, liver fibrosis group and 3-MA treatment group. The liver fibrosis model was established by injecting CCl4, and the mice in the 3-MA treatment group were injected 3-MA additionally from the third week onwards. After 8 weeks, all of the mice were sacrificed and their blood, liver tissue and fecal samples were collected to analyze serum ALT, AST, GGT levels, liver histopathology and gut microbiota. Results: Compared with the liver fibrosis group, serum ALT and AST levels in 3-MA treatment group decreased obviously ([68.6±4.2] U/L vs [111.0±7.8] U/L, [179.0±12.9] U/L vs [253.2±26.7] U/L, P＜0.01), and the degree of hepatic histopathological changes was reduced. The intestinal flora in three groups were distinguished by principal coordinate analysis (PCoA) and non-metric multi-dimensional scaling (NMDS) analysis. Compared with the normal control group, there were decreased Alpha diversity of intestinal community, reduced significantly abundance of Lachnospiraceae, and increased obviously abundance of Actinobacteria and Desulfovibrionacea in the liver fibrosis group (P＜0.05). Compared with the liver fibrosis group, there were increased Alpha diversity of intestinal community, increased significantly abundance of Lachnospiraceae and Blautia, and reduced abundance of Bifidobacteriaceae in the 3-MA treatment group (P＜0.05). In addition, the abundance of Lactobacillaceae in the 3-MA treatment group was significantly higher than that in the normal control group (P＜0.05). Conclusion 3-MA improves the liver fibrosis of mice induced by CCl4, and gut microbiota may play an active role in this process.

Objective To investigate the clinical value of circulating miR-125b-5p in coronary atherosclerotic heart disease.Methods With case-control study,80 cases of coronary atherosclerotic heart disease were recruited in Affiliated Hospital of Nantong University from February 2014 to august 2015.According to coronary angiography result they were divided into two groups: there are coronary artery stenosis group(n=49)and control group(n=31).All patients were also divided into non-ST-segment elevation myocardial infarction and ST-segment elevation myocardial infarction group(n=35),unstable angina group group(n=25),stable angina group(n=20).The level of miR-125b-5p before coronary angiograph was detected.By independent sample t test and variance analysis,the levels of miR-125b-5p were compared between the groups of coronary artery stenosis and the group with no stenosis of the coronary artery,the coronary artery lesions in each group,and between the various types of coronary atherosclerotic heart disease respectively.Results MiR-125b-5p expression level of Coronary artery stenosis group(0.35±0.10)was lower than that in group coronary artery with no stenosis(0.95±0.12),the difference was statistically significant(t=24.179,P<0.000 1).With the increase in the number of diseased coronary arteries,miR-125b-5p expression level decreased gradually.There is also statistical significance(t=8.399,P<0.000 1; t=13.067,P<0.000 1)in miR-125b-5p expression among NSTEMI+STEMI,UA and SAP groups.miR-125b-5p expression level was negatively correlated with Gensini score(R2=0.822,P<0.05).The area under the ROC curve(AUC)of miR-125b-5p was 0.86(95％CI 0.67-0.90),and 0.66 was the optimal cut-off value with sensitivity of 81.22％and specificity of 78.62％.Conclusions With the increase of the number of stenosis,plasma miR-125b-5p expression level decreased gradually.The expression level of miR-125b-5p was negatively correlated with the Gensini score of coronary artery,which indicated that the expression level of miR-125b-5p may be a potential biomarker that can reflect the lesion degree of coronary artery.

OBJECTIVE:To observe the effect of2%anisodamine plus1%lidocaine block therapy on injury caused by extravasation of vincrisine.METHODS:60animal models were established by injecting1%vincrisine5ml into ear vein with1ml purposely extravasating to subcutaneous tissue in rabbits.The rabbits were divided randomly into groupⅠ,groupⅡand control group.GroupⅠreceived2%anisodamine+1%lidocaine,groupⅡ2%anisodamine and control group normal saline.RESULTS:After2weeks treatment,the total effective and curative rate in three groups were90%and80%,63%and42%,15%and0%respectively.CONCLUSION:2%anisodamine plus1%lidocaine block therapy is superior to normal saline in treating extravasation injury of vincrisine.