To explore the in vitro and in vivo synergistic effect of paclitaxel in combination with co-listin against MDREscherichia coli(E.coli)and the corresponding mechanism of synergism,we measured the MICs of PTX alone and combination of PTX+antimicrobial drugs on E.coli and Staphylococcus aureus(S.aureus)by broth microdilution method.Then,checkerboard method was used to determine the FICI of PTX+COL combination,and the antibacterial synergies of PTX and COL was further explored through analyzing the membrane permeability and efflux pump ac-tivity.The MICs results showed that the MIC values of PTX alone against E.coli(G5,E25)and S.aureus S238 were＞1 024 mg/L and 512 mg/L,respectively.Meanwhile,we found that the anti-bacterial activity of COL against E.coli could be significantly enhanced(MIC decreased by 4 to 8 times)when used in combination with PTX.The checkerboard test showed that the FICI values of PTX combined with COL for E.coli(G5,E25)were 0.31 and 0.29,respectively,indicating a synergistic antibacterial effect on these strains.The FICI values of PTX combined with COL for E.coli G21,S.aureus(S237 and S238)were 0.51,0.75 and 0.53,respectively,indicating additive effects on these strains.In the mouse abdominal infection model,the combination group could ex-tremely significantly reduce the bacterial burden of E.coli in abdominal compared to the COL or PTX alone group(P＜0.001).The analysis of membrane permeability and efflux pump activity showed that PTX combined with COL significantly increased the inner and outer membrane per-meability of E.coli(G5 and E25),and markedly inhibited the efflux pumping activity of E.coli,when compared that of PTX and COL alone(P＜0.01).The above results indicated that the com-bination of PTX and COL could exert a synergistic in vivo and in vitro antibacterial effect on COL-resistant E.coli through increasing bacterial membrane permeability and inhibiting efflux pump activity.This study provides the theoretical foundation for the development of a novel combi-nation regimen for the treatment of MDR E.coli infection.

To explore the in vitro and in vivo synergistic effect of paclitaxel in combination with co-listin against MDREscherichia coli(E.coli)and the corresponding mechanism of synergism,we measured the MICs of PTX alone and combination of PTX+antimicrobial drugs on E.coli and Staphylococcus aureus(S.aureus)by broth microdilution method.Then,checkerboard method was used to determine the FICI of PTX+COL combination,and the antibacterial synergies of PTX and COL was further explored through analyzing the membrane permeability and efflux pump ac-tivity.The MICs results showed that the MIC values of PTX alone against E.coli(G5,E25)and S.aureus S238 were＞1 024 mg/L and 512 mg/L,respectively.Meanwhile,we found that the anti-bacterial activity of COL against E.coli could be significantly enhanced(MIC decreased by 4 to 8 times)when used in combination with PTX.The checkerboard test showed that the FICI values of PTX combined with COL for E.coli(G5,E25)were 0.31 and 0.29,respectively,indicating a synergistic antibacterial effect on these strains.The FICI values of PTX combined with COL for E.coli G21,S.aureus(S237 and S238)were 0.51,0.75 and 0.53,respectively,indicating additive effects on these strains.In the mouse abdominal infection model,the combination group could ex-tremely significantly reduce the bacterial burden of E.coli in abdominal compared to the COL or PTX alone group(P＜0.001).The analysis of membrane permeability and efflux pump activity showed that PTX combined with COL significantly increased the inner and outer membrane per-meability of E.coli(G5 and E25),and markedly inhibited the efflux pumping activity of E.coli,when compared that of PTX and COL alone(P＜0.01).The above results indicated that the com-bination of PTX and COL could exert a synergistic in vivo and in vitro antibacterial effect on COL-resistant E.coli through increasing bacterial membrane permeability and inhibiting efflux pump activity.This study provides the theoretical foundation for the development of a novel combi-nation regimen for the treatment of MDR E.coli infection.

Objective To explore the prognostic value and immune infiltration landscape of anoikis-related long noncoding RNAs (arlncRNAs) in lung adenocarcinoma. Methods RNA-seq and clinical data of lung adenocarcinoma were downloaded from the TCGA database, and anoikis-related genes were obtained from the GeneCards and Harmonizome databases. Coexpression, differential, and WGCNA analyses were performed to screen differentially expressed arlncRNAs closely related to the occurrence of lung adenocarcinoma. A prognostic risk model was then constructed based on the arlncRNAs, and its predictive efficacy was further validated. Finally, consensus clustering was used to identify the molecular subtypes associated with anoikis in lung adenocarcinoma. Results Seven prognostic arlncRNAs were identified, and the prognostic risk models established based on them had AUC values of ROC curves greater than 0.7. Survival and immune infiltration analyses revealed that low-risk patients had high overall survival and immune infiltration, implying that they experienced good immune treatment effects. Drug sensitivity analysis showed that the high-risk patients were more sensitive to commonly used chemotherapeutic agents than the low-risk patients. According to the expression of model genes, subtypes C1 and C2 were identified through consensus clustering, and C1 showed a good prognosis. Conclusion The prognostic risk model based on the seven arlncRNAs can effectively predict the prognosis of lung adenocarcinoma patients. The results of immune-related and drug sensitivity analyses provide a reference for the precise individualized treatment of patients with lung adenocarcinoma.

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.

ObjectiveTo investigate the changes of serum creatine kinase isoenzyme (CK-MB) and creatine kinase (CK) ratio(CK-MB/CK) and cardiac troponin I(cTnI) simultaneously in patients with acute organophosphorus pesticide poisoning (AOPP) and the clinical value in disease condition judgment.Methods Eight hundred and sixty-eight AOPP patients without disease history of heart,lung,brain,kidney,muscle and other connective tissue were extracted 4 ml of fasting venous blood to determine CK,CK-MB and cTnI simultaneously at 2,12,24,48,96 and 120 hours after poisoning,and the CK-MB/CK was calculated.There were 279 mild poisoning cases (mild poisoning group),289 moderate poisoning cases (moderate poisoning group) and 300 severe poisoning group (severe poisoning group) ; and 208 cases with intermediate myasthenia syndrome (IMS)(IMS group) and 660 cases without IMS (non-IMS group).The result was compared with 288 healthy people (control group) in the same period.Results ( 1 ) The CK,CK-MB and cTnI of mild,moderate and severe poisoning groups between 2 to 12 h,13 to 24 h,25 to 120 h after poisoning were significandy higher than those in control group,CK-MB/CK was obviously lower (P ＜ 0.01 ).The CK,CK-MB,cTnI and CK-MB/CK had significant differences between each two of mild,moderate and severe poisoning groups (P＜ 0.01 or ＜ 0.05).The CK,CK-MB and cTnI of IMS group in 2 to120 h after poisoning were significantly higher than those in non-IMS group,and CK-MB/CK was lower (P ＜ 0.05 or ＜ 0.01 ).In IMS group,the rates of sudden cardiac death (SCD) and multiple organ dysfunction syndrome (MODS) were 23.08％(48/208),37.50％(78/208) respectively,while 4.24％(28/660),9.85％(65/660) in non-IMS group.The incidence of SCD and MODS of two groups had statistical significance (P ＜ 0.01 ).(2) According to IMS and non-IMS group,discriminant equation with independent variables of cTnI (X1), CK (X2) and CK-MB/CK (X3) was established:Y =-0.0014X1 + 0.0225X2 + 65.2376X3,F=21.4911,P ＜ 0.01.The discriminant critical value(Y0) was 2.8124.If Y ＜ 2.8124 belonged to IMS group and Y ≥2.8124 was in non-IMS group,the contribution rates of X1,X2 and X3 were 34.5％,25.4％ and 40.1％ respectively.The coincident rate of return was 91.26％.ConclusionsCK-MB/CK change has negative correlation with poisoning degree of AOPP;cTnI level is positively correlated with AOPP poisoning degree.they may be used to assist the clinical classification,disease judgement and to guide the emergency,treatment and prognosis assessment of AOPP.The function equation with cTnI,CK and CK-MB/CK can be used as effective prediction indexes of IMS,MODS and SCD in early period.

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.