The paper reported an investigation of the pharmacokinetics of SN-38 (7-ethyl-10-hydroxy-camptothecin) in rats and the tissue distribution in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11) via tail veins. An LC-MS/MS method was established to determine the concentrations of SN-38 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of SN-38 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with irinotecan solution, the elimination half-life of SN-38 was prolonged from 2.17 h to 2.67 h after the intravenous injection of CPT-11 NPs, but its AUC had little change. After the injection of CPT-11 NPs in mice, over time, the concentrations of CPT-11-metabolized SN-38 in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, followed by in the spleen and liver, but those in the heart and brain had no change. However, the amount of SN-38 in the kidneys was reduced with time. CPT-11 NPs could prolong SN-38's (one of its metabolites) blood circulation time in rats and significantly increased the concentration of CPT-11-metabolized SN-38 in the whole blood, colon and lungs of mice. CPT-11 NPs made SN-38 efficiently target-bind to the colon and lungs of mice.

Objective To clone and express human autoantigen Sm B'in methylotrophie yeast Pichia Pagtoris.Methods The gene Sm B' was cloned bv PCR The PCR product wag inserted into the vector pPIC9k.The recombinant plasmid pPIC9k.Sm B' was transformed into yeast Sm D1168 by electroporation.The positive clones were screened in MD plates.The high copy number transformants were rapidly selected by using G418 and were induced by methan01.Supematants after induction were analyzed by SDS-PAGE and western blot.Sera collected from thirty patients with SLE.thirty patients with mixed connective tissue disease(MCTD)and thirty healthy volunteers were detected by immunodot and immunoblot.Results The PCR product wag about 700 bD in size which Wag in accordance with predicted 657 bp.The pPIC9k-Sm B'showed the same seqencing result with GenBank's report and restriction enzyme analysis confirmed our prediction.The pPIC9k-Sm B' positive clone produced a 32 000 protein which had natural immunogenicitv of human autoantigen Sm B'by SDS-PAGE and western blot.The positive rate of immunodot and IBT were 46.7%(42/90)and 51.1%(46/90),respectively.The agreement between immunodot and IBT was very close(Kappa value=0.911 2,P＜0.01).Conclusion Successfully cloning and expression of human autoantigen Sm B' in methylotmphic yeast Pichia Pagtoris hid a foundation for further research work.

Aim To study the inhibitory effect of ginkgolide B (BN52021) on the PAF induced changes of chemotaxis of murine peritoneal macrophages and the related polymerization of F-actin.Methods Chemotaxis assays were performed using a modified 48-well Boyden chamber. Actin polymerization of murine peritoneal macrophages was analyzed by flow cytometry using a specific fluorescent stain. Results Peritoneal macrophages significantly migrated toward platelet-activating factor(PAF) through a micropore filter; however, in the presence of PAF receptor antagonist BN52021 (0. 01the actin polymerization of murine peritoneal macrophages induced by PAF in the presence of Ca2+ , but not in Ca2+ -free medium. Conclusion The results suggested that preventing polymerization of F-actin may be a pathway by BN52021 to inhibit the chemotaxis of macrophages, and this effect seems to be Ca2+dependent. The data further indicated that inhibition of PAF induced macrophage chemotaxis is an important mechanism underlying the anti-inflammatory action of BN52021.

The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.

87%. CONCLUSIONS The surveillance of overexpressing AmpC ?-lactamases in cefoxitin-resistant Gram-negative bacillus must be enhanced.The therapy of infections caused by related bacillus should make imipenem and meropenem a chief choice.DHA-1,CMY-2 and CMY-22 AmpC enzymes are found in Fuzhou.

Objective To investigate the prevalence and resistance mechanisms of Proteus mirabilis in the ward of neurology de‐partment of our hospital .Methods For a total of 20 clinic isolates of Proteus mirabilis ,PCR were used for the detection of AmpC , ESBLs ,KPC and MBLs and then DNA sequencing was performed .The integrons were also detected by using PCR and then sequen‐cing was carried out .The genetic relationship between isolates were detected and analysed by pulsed‐field gel electrophoresis(PF‐GE) .The results of drug sensitivity tests were analysed .Results TEM‐1 and CTX‐M‐14 gene were found in all the 20 isolates ,the 10 isolates of Proteus mirabilis were also found carrying CMY‐2 gene .Class Ⅰ integrons were amplified from 19 strains carrying gene cassettes aacA4+cmlA1,dfrA12+orfF+aadA2and dfrA32+ereA+aadA2 respectively .PFGE analysis revealed that the 20 isolates were grouped into 11 PFGE types P1-P11 ,the 12 isolates of P1-P3 were same clones .The sensitive rates of the i‐solates to Meropenem ,Amikacin ,Aztreonam ,Ceftazidime and Tazocin were high .Conclusion Nosocomial transmission of the same clone of Proteus mirabilis was appeared in the ward of neurology department of our hospital .The predominance drug‐resistance genes were CTX‐M‐14 andCMY‐2 .The incidence of carrying class Ⅰ integrons was high ,and the major gene cassettes wereaacA4+cmlA1and dfrA12+orfF+aadA2.The 20 isolates were all sensitive to Meropenem ,Amikacin and Aztreonam .Other Clinical departments should also pay attention to the nosocomial infection caused by Proteus mirabilis and strengthen the infection control measures .

To investigate the pharmacokinetics of irinotecan hydrochloride (CPT-11) in rats and the tissue distribution of CPT-11 in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11 NPs) via tail veins, separately, a LC-MS/MS method was established to determine the concentration of CPT-11 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of CPT-11 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with CPT-11 solution, the elimination half-life of CPT-11 was prolonged from 2.28 h to 3.95 h after the intravenous injection of CPT-11 NPs, and its AUC was 1.47 times than that of CPT-11 solution. After the injection of CPT-11 NPs in mice, the concentrations of CPT-11 loaded in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, but lower in the spleen, liver, kidney and heart, but the least in brain. CPT-11 NPs could improve CPT-11 's AUC, and help CPT-11 to reach long circulation activity.

Objective: To investigate the clinical significance of the monocyte count/high-density lipoprotein cholesterol ratio(MHR)in evaluating imperfect ST-segment resolution in elderly patients with acute ST-elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI). Methods: This was a retrospective cohort study.A total of 274 elderly patients with STEMI underwent PCI in our hospital from December 2015 to December 2018 were enrolled.Based on the extent of the ST-segment resolution of the postoperative electrocardiogram, patients were divided into an imperfect ST-segment resolution group(observation group, n=79)and a favorable ST-segment resolution group(control group, n=195). General clinical data were compared between the two groups, and logistic regression equation was used to analyze the association of MHR with ST-segment resolution.Receiver operating characteristic(ROC)curve was performed to assess the predictive value of MHR for imperfect ST-segment resolution. Results: Compared with patients in the control group, patients in the observation group were associated with a significantly higher proportion of anterior wall myocardial infarction and heart failure(≥Killip 2), A longer duration of chest pain to balloon expansion, higher levels of creatine kinase isoenzyme, N-terminal pro-brain natriuretic peptide, hypersensitive C-reactive protein, blood sugar, blood uric acid, fibrinogen, triglyceride and mononuclear cell count, and lower levels of high density lipoprotein cholesterol and lymphocyte count(all P<0.05). Meanwhile, there was a significant difference in MHR between the observation group and the control group [(0.75±0.22)vs.(0.48±0.19), t=9.831, P=0.001]. Multivariate Logistic regression analysis showed that MHR was an independent risk factor for imperfect ST-segment resolution(OR=1.950, 95%CI: 1.646-5.430, P=0.003)and ROC curve showed the threshold value of MHR at 0.67, the area under the curve at 0.867, the sensitivity at 79.72%, and the specificity at 79.61%. Conclusions MHR may be an independent risk factor and a good predictive index for imperfect ST-segment resolution in elderly patients with STEMI after PCI.

Objective:To develop an inquiry learning community centered on learning experience in the course of Nursing Clinical Comprehensive Experiment to verify the influence of this teaching mode on the learning gains and practical ability of nursing students. Methods:A total of 132 undergraduate nursing students form grade 3 in Chongqing Medical University were enrolled. The participants were randomly assigned to a learning community group ( n = 69) and a control group ( n = 63) using Minitab 14.0 software. The students in the learning community group adopted the inquiry learning community mode in accordance with the curriculum map for online self-learning, group discussion and skills practice, while the control group received the teacher-led teaching mode for offline theory teaching, operation teaching and skills practice. After the teaching intervention, both groups of students received the assessment questionnaire of learning gains and the comprehensive experimental ability evaluation. Chi-square test or paired t-test was performed using SPSS 23.0. Results:Compared with the control group, students in the learning community group reported that their sense of learning gain was enhanced ( P<0.001, Cohen d=0.97); sub-items showed that the effect size for the understanding of learning content ( P<0.001, Cohen d=1.22), the overall course situation ( P<0.001, Cohen d=0.90), the course activities ( P=0.000, Cohen d=0.83), and the information obtained ( P<0.001, Cohen d=1.16) was significantly different. The total score of practical ability of comprehensive experiment was significantly improved ( P = 0.005, Cohen d=0.51), in which the experimental situation displays ( P=0.002, Cohen d=0.55) and experimental effect ( P=0.006, Cohen d=0.49) were better than the control group. There was no significant difference in the performance of experimental preparation and case analysis between the two groups. Conclusion:Developing an inquiry learning community in nursing clinical comprehensive experiment can effectively enhance student' sense of learning gains and promote the improvement of clinical practical ability.