Objective To evaluate the effect of isoflurane or sevoflurane inhalation before and after gestation on the offspring brain development. Methods Thirty female adult Sprague Dawley rats were randomly assigned into 5 groups(n=6 each):control group(group C),group that ex?posed to isoflurane with the concentration of 1.6%for 6 hours before gestation(group BI),group that exposed to isoflurane with the concentration of 1.6%at the 6th,10th,14th and 18th day for 6 hours(group PI),group that exposed to sevoflurane with the concentration of 2.4%for 6 hours before gestation(group BS),and group exposed to sevoflurane with the concentration of 2.4%at the 6th,10th,14th and 18th day for 6 hours after gestation (group PS). Twelve offspring rats from pregnant rats in each group were chosen on the day of birth(T1),and 7th,14th and 28th days after birth(T2, T3 and T4)and sacrificed,and the hippocampi were then isolated. Hematoxylin and eosin stain were adopted to observe the tissue pathological change. Electron microscope was used to observe the neuron ultrastructure change of hippocampus. Immolunohistochemistry was used to detect cas?pase?3,the expression of growth associated protein?43(GAP?43)and neuronal nitric oxide synthase(nNOS). Results Compared with group C, no significant change was found in caspase?3,GAP?43 and nNOS expression in offspring rat hippocampus in groups BI and BS(P>0.05),and no damage change in hippocampal was seen by HE staining and electron microscopy. In group PI and PB,the expression of caspase?3 was significantly up?regulated,the expression of GAP?43 and nNOS was down?regulated at T1 to T3(P<0.01),and structural changes in cell were seen by electron microscopy. In group PI,significant pathological changes in hippocampal were seen by HE staining at T1 to T3. Compared with group PI,the expres?sion of GAP?43 and nNOS was significantly up?regulated(P<0.01),and the expression of caspase?3 was down?regulated at T1 to T3(P<0.01). Conclusion Isoflurane or sevoflurane inhalation before gestation does not affect the offspring brain development,while isoflurane or sevoflurane in?halation after gestation can induce transient abnormal change of offspring brain development,and isoflurane′s toxicity was greater than sevoflurane.

Objective To observe the effect of the advanced glycation end products(AGEs)on the iNOS expression in cultured cardiac microvascular endothelial cells.Methods Cultured the cardiac microvascular endothelial cells in vitro.After AGEs of the different dose(50～200 mg/L)and different times(0～24 h)played the role on the cells,we determined the NO generation and iNOS protein expression of all groups.Results NO generation and iNOS protein expression increased with the AGEs-dose increasing and treatment time.The results were significantly different.Conclusion These results demonstrate that AGEs may induce iNOS to produce toxic NO in cardiac microvascular endothelial cells,then the diabetic cardiomyopathy occures.

Objective To evaluate the effect of isoflurane or sevoflurane inhalation before and after gestation on the N-methyl-D-aspartate (NMDA) receptor expression in offspring rat hippocampus.Methods Thirty female adult Sprague-Dawley rats,aged 3 months,weighing 250-300 g,were randomly assigned into 5 groups (n =6 each):control group (group C),exposure to isoflurane before gestation group (group BI),exposure to isoflurane during gestation period group (group PI),exposure to sevoflurane before gestation group (group BS),exposure to sevoflurane during gestation period group (group PS).The rats inhaled 1.6％ isoflurane for 6 h at 1 day before gestation in group BI.The rats inhaled 1.6％ isoflurane for 6 h at 6,10,14 and 18 day gestation in group PI.The rats were exposed to 2.4％ sevoflurane for 6 h before gestation in group BS.The rats were exposed to 2.4％ sevoflurane for 6 h at 6,10,14 and 18 day gestation in group PS.Twelve offspring rats from pregnant rats in each group were chosen on the day of birth (T1),and 7th,14th and 28th days after birth (T2-4) and sacrificed,and the hippocampi were then isolated for determination of the expression NMDA receptor (NR1,NR2A and NR2B).Results Compared with group C,no significant change was found in NMDA receptor expression in off spring rat hippocampus in groups BI and BS (P ＞ 0.05),and the expression of NR1 and NR2A protein and mRNA was significantly up-regulated,and the expression of NR2B protein and mRNA was down-regulated at T1-3 (P ＜0.05),and no significant change was found in NMDA receptor expression at T4 in groups PI and PS (P ＞ 0.05).Compared with group PI,the expression of NRI and NR2A protein and mRNA was significantly up-regulated,and the expression of NR2B protein and mRNA was down-regulated at T1 3 (P ＜ 0.05 or 0.01),and no significant change was found in N MDA receptor expression at T4 in group PS (P ＞ 0.05).Conclusion Isoflurane or sevoflurane inhalation before gestation does not affect the NMDA receptor expression in offspring rat hippocampus,while isoflurane or sevoflurane inhalation after gestation can induce abnormal expression of the NMDA receptor in offspring rat hippocampus,which may result in apoptosis in hippocampal cells and abnormality in the development of nervous system and cognitive function.

Objective To investigate the active ingredients of Jingfang Baidu San for the prevention and treatment of COVID-19 by using network pharmacology and molecular docking, and to provide references for clinical applications. Methods The chemical constituents and action targets of all medicinal materials in Jingfang Baidu San were retrieved from TCMSP. Uniprot database was used to search the corresponding genes of targets. Cytoscape software was used to construct the network of medicinal materials-compounds-targets for visualization. The target proteins of COVID-19 were searched by disease databases. The intersection of both was considered to be analyzed to establish the protein-protein interaction (PPI) network by STRING database. GO function enrichment analysis and KEGG pathway enrichment analysis were performed through Metascape database to predict its mechanism. The effective strength of core constituents on preventing COVID-19 was calculated by molecular docking method. Results A total of 159 effective ingredients and 277 potential targets were obtained in Jingfang Baidu San within the given screening conditions [oral bioavailability (OB) ≥30%; drug-like (DL) ≥ 0.18], including 55 core targets with the intersection of 273 targets of COVID-19. According to the results of GO and KEGG enrichment analysis performed on the core targets, 1376 GO items and 136 KEGG pathways were obtained, involving infectious diseases, cancer, cell progress, immune system, signaling pathways etc. The results of molecular docking indicated strong binding capacity between the core ingredients and SARS-CoV-2 3CL hydrolase or angiotensin-converting enzyme II (ACE2). The hydrogen binding and hydrophobic effect were the main forms of the interaction. Conclusion The active ingredients in Jingfang Baidu San can inhibit the binding between SARS-CoV-2 protein and ACE2, thus regulating multiple targets and signal pathways, which plays a role in the prevention and the treatment of COVID-19.