Objective To study the effect of SYUIQ-5,a novel antitumor agent,on gene expression of hepatic cytochrome P450 in rats.Methods Male Sprague-Dawley rats were administered daily intraperitoneal dose of SYUIQ-5(0.1mg/kg,5mg/kg and 10mg/kg body weight) for 5 consecutive days.The levels of CYP 3A1,2B1/2,1A1,1A2 and 2E1 mRNA in rat liver were analyzed by reverse transcription-polymerase chain reaction(RT-PCR).Results The level of gene expression of CYP 1A1 was increased significantly compared with the control.The levels of CYP 3A1,2B1/2,1A2 and 2E1 mRNA were not changed by SYUIQ-5 treatment compared with the control.Conclusion A significant increase in the CYP 1A1 rather than CYP3A1,2B1/2,1A2 and 2E1 gene expression by SYUIQ-5 treatment is observed.

Aim To investigate the antidepressive-like effect of ethyl alcohol extract of Polyrhachis vicina Rog-er(EAPR),and its mechanism.Methods EAPR was prepared by ethanol extraction.Its anti-depressive effect was investigated by tail suspension test (TST) and forced swimming test (FST).Furthermore,repeated doses of reserpine was used for preparing the depres-sive rats.Results EAPR has definitely anti-depres-sive effect,as evidenced by the decreased immobility time in FST and TST at the doses of 8 and 4 g·kg -1 (P <0.05).In the repeated reserpine evoked depres-sive rats,EAPR antagonized the symptoms induced by monoamines depletion and attenuated the anhedonia, as manifested by reversed hypothermia,akinesia and sucrose consumption at the doses of 8 and 2 g·kg -1 (P <0.05,P <0.01).Neuro-chemical studies showed that AFPR significantly increased the concentration of monoamines,including 5-hydroxytryptamine (5-HT) and noradrenaline(NA)at the dose of 8 g·kg -1 (P <0.05),and had no effect on normal rats .Furthermore, EAPR increased the activity of superoxide dismutase (SOD)in serum,hippocampus and cerebral cortex at the dose of 8 g·kg -1 (P <0.05).Conclusion EA-PR possesses the definite antidep ressive properties, connected with the regulation of neurotransmitter me-tabolism and the nerve cells antioxidant effect.

Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang(SC)root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments.Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database,the protein-protein interaction network was constructed,and pathways,functional enrichment and molecular docking analyses were performed.CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines,and its effects on invasion,migration,proliferation,and apoptosis of pancreatic cancer cells were evaluated.Western blotting was performed to verify the results of network pharmacology analysis.Results We identified a total of 18 active components in SC,which regulated 21 potential key targets in pancreatic cancer.GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation,signal transduction,and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways.Among the 8 cancer cell lines,The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells,and significantly inhibited the invasion,migration,and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells(P<0.05).Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells(P<0.001).Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Objective:To explore whether NSBB is suitable for the primary prevention of liver cirrhosis accompanied by CSPH with no or small esophageal varices.Methods:Relevant literatures were retrieved from Cochrane library, PubMed, EMBASE, SinoMed, CNKI and Wanfang databases until December 12, 2020. All randomized controlled trials (RCTs) on NSBB use for primary prevention of cirrhosis accompanied by CSPH with no or small esophageal varices were collected. The literature was strictly screened according to the established inclusion and exclusion criteria, odds ratio (OR), and 95% confidence interval (CI) combined effect size. The development of esophageal varices and the initial upper gastrointestinal bleeding were the primary outcome measures. Death (with a maximum average follow-up of about five years) and adverse events (adverse drug reactions, etc.) were the secondary outcome measures.Results:A total of 9 RCTs with 1396 cases were included. Meta-analysis results showed that, compared with placebo, NSBB significantly reduced the incidence of liver cirrhosis accompanied by CSPH with no or small esophageal varices to large esophageal varices progression ( OR=0.51, 95% CI: 0.29-0.89, P=0.02), and mortality (with maximum average follow-up of about five years) ( OR=0.64, 95% CI: 0.44-0.92, P=0.02); however, there was no statistically significant difference in the initial upper gastrointestinal bleeding rate between the two groups ( OR=0.82, 95% CI: 0.44-1.52, P=0.53). Adverse event incidence was greater in the NSBB than the placebo group ( OR=1.74, 95% CI: 1.27-2.37, P=0.0005). Conclusions:NSBB use cannot reduce the initial upper gastrointestinal bleeding rate or adverse event incidence in patients with liver cirrhosis accompanied by CSPH with no or small esophageal varices, but it can delay the progression of gastroesophageal varices and reduce patient mortality.

Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang(SC)root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments.Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database,the protein-protein interaction network was constructed,and pathways,functional enrichment and molecular docking analyses were performed.CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines,and its effects on invasion,migration,proliferation,and apoptosis of pancreatic cancer cells were evaluated.Western blotting was performed to verify the results of network pharmacology analysis.Results We identified a total of 18 active components in SC,which regulated 21 potential key targets in pancreatic cancer.GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation,signal transduction,and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways.Among the 8 cancer cell lines,The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells,and significantly inhibited the invasion,migration,and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells(P<0.05).Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells(P<0.001).Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Hepatotoxicity is a common side effect for patients treated with gefitinib, but the related pathogenesis is unclear and lacks effective predictor and management strategies. A multi-omics approach integrating pharmacometabolomics, pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution. Here, we found that patients with rs4946935 AA, located in Forkhead Box O3 (FOXO3) which is a well-known autophagic regulator, had a higher risk of hepatotoxicity than those with the GA or GG variant (OR = 18.020, 95%CI = 2.473 to 459.1784, P = 0.018) in a gefitinib-concentration dependent pattern. Furthermore, functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity, increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury. In contrast, erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3. This study reveals that FOXO3 mutation, leading to autophagic imbalance, plays important role in gefitinib-induced hepatotoxicity, especially for patients with high concentration of gefitinib. In conclusion, FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.