Objective To prove the advantages of telemetry by comparing with the traditional methods in safety pharmacology.Methods To monitor continuously the heart rate, respiratory rate, blood pressure and ECG of Beagle dogs by traditional and telemetry methods respectively, analyze and compare the changes between anesthetized and conscious dogs before and after feeding.Results Maintenance of anesthesia changed significantly the heart rate, respiratory rate, blood pressure and QT interval in the ECG of animals.The changes of physiological indicators in 24 h is not obvious in conscious animals, and showed a certain biorhythm.Compared with the conscious animals, the anesthetized dogs’ heart rate was significantly higher, blood pressure increased significantly, QRS and QTcf interval prolonged significantly, respiratory frequency decreased, heart rate increased significantly after feeding, and QTcf interval extended very significantly.Conclusions Traditional methods in safety pharmacology affect animal physiological indicators such as heart rate, blood pressure, respiratory rate and QT interval, which affect the objectivity of drug evaluation.Using conscious animals by telemetry can reduce these errors, however, the interference from outside should be eliminated.

Objective To study the epidemiology and genotypes of extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli (EC) and Klebsiella pneumoniae (KP) that caused community-onset bloodstream infections (COBSI) in 9 county hospitals of Zhejiang Province.Methods This is a multi-center, prospective, observational study.The cases and isolates with COBSI caused by EC and KP were consecutively collected from 9 county hospitals in Zhejiang Province between 1st March 2014 and 30th April 2015.The double disk diffusion method was used to confirm the production of ESBL.The ESBL genotypes were determined by polymerase chain reaction(PCR) amplification and sequence analysis.Multi-locus Sequence Typing (MLST) was used to analyze the homology of ESBL-producing isolates.Minimal inhibitory concentration (MIC) of frequently used drugs for ESBL-producing isolates was determined by in-vitro antimicrobial susceptibility tests.Results During the study period, a total of 172 cases with COBSI were collected and 171 cases were eligible, among which 126 were caused by EC and 45 were caused by KP.The overall prevalence of ESBL was 34.5% (59/171),and the prevalence of ESBL-EC and-KP was 41.3% (52/126) and 15.6% (7/45), respectively.CTX-M-type ESBL accounted for 96.6% (57/59) of all the ESBLs-producing isolates, and the most common type was CTX-M-14 (27.1%, 16/59), followed by CTX-M-55 (22%, 13/59).MLST analyses revealed significant genetic diversity among ESBL-EC and-KP.The most prevalent ST of ESBL-EC was ST131 (23.1%).In addition to carbapenems, cefoperazone/sulbactam, piperacillin/tazobactam, moxalactam, amikacin and fosfomycin also showed good in-vitro activity against ESBL-EC and-KP.Conclusions The prevalence of ESBL in EC and KP is high in 9 county hospitals of Zhejiang Province, and the most common genotypes are CTX-M-14 and CTX-M-55.The detection rate of ESBL in EC is higher than in KP.It could be considered adequate empirical therapy according to the results of antimicrobial susceptibility tests.Carbapenems, cefoperazone/sulbactam, piperacillin/tazobactam, moxalactam, amikacin and fosfomycin have good in-vitro activity against ESBL-EC and-KP.

Objective To investigate the lowest concentration of iodine contast medium which can ensure CT pulmonary angiography (CTPA) imaging quality at tube voltage of 80 kVp.Methods Ten New Zealand rabbits underwent CTPA four times every three days with the iodine concentrations of contrast medium at each time were 350,300,270 and 250 mg I/mL respectively.The attenuation values of trunk pulmonary artery and air around the body on the same level,as well as right and left pulmonary arteries,and the pulmonary artery branches were compared among different groups.Meanwhile,image noise (N),contrasvto-noise ratio (CNR) and signal-to-noise ratio (SNR) were calculated.All those data were analyzed with One way classification ANOVA test.When multiple samples compared,Dunnett-t test was employed.The pulmonary arteries were divided into large and small arteries and assessed by multiple sample Kruskal-Wallis H test and analyzed with LSD-t test when multiple samples compared.When the attenuation of trunk pulmonary artery of different viewers or the different times of the same viewer compared,paired t test was employed.Wilcoxon signed rank testing was employed for comparing the scores of pulmonary arteries among different groups.Results All the images of CTPA could demonstrate sixthorder branches of pulmonary artery.The attenuation of pulmonary arteries of the 300-group was the highest,however no statistical difference was found between 270 and 300-group [major pulmonary arteries:(687.17±167.83) HU,(848.68±185.03) HU,t=-161.52,P =0.097].The CNR (6.3±1.30) and SNR (10.9±2.01) of the 270-group were the highest (t=-45.99,P=0.008;t=3.73,P=0.088),and N (62.84±6.05) was the lowest (t=-11.09,P=0.016).No statistical difference was found between 270-group and other 3 groups.And for the subjective scores of large arteries,no statistical differences (from 350-group to 250 group,3.91±0.35,3.90±0.38,3.90±0.42 and 3.86±0.42,H=6.588,P=0.086) were found.The scores of small arteries of 270-group were lower than those of 350 and 300 group,but the image quality of 270-group (3.34±0.51) met the diagnostic requirements.Conclusion When the tube voltage being 80 kVp,the contrast medium of 270 mg I/mL is more suitable for rabbits' CTPA.Thus,the iodine dose per unit can decrease effectively.

Objective To investigate the effect of restraint stress on liver injury in mice induced by D-galactosamine and lipopolysaccharide (D+L).Methods Normal BALB/c (B/c) mice were randomly divided into normal control, stress control, D+L group, and D+L+stress group.The mice of normal control group were bred routinely.The stress group was giv-en stress regularly and quantitatively.Mice in the D+L group were injected intraperitoneally with mixed solution of D-galac-tosamine and lipopolysaccharide at final concentration of 30 mg/mL and 2μg/mL, respectively, once every two days.The D+L+stress group was given equal stress as stress group after injection of D-galactosamine and lipopolysaccharide mixed solution. Eight weeks later, blood samples were collected to test serum aminotransferase (ALT) and aspartate aminotransferase (AST), liver tissue samples from all animals were collected to evaluate the degree of liver fibrosis by HE and Masson staining.Results At the 8th week, the ALT and AST values in the D+L+stress group were significantly reduced( P＜0.01) and AST/ALT value was significantly increased(P＜0.01)compared with that in the D+L group.For HE and Masson staining, disordered structure of hepatic lobules, nodular hyperplasia, and necrosis of epithelial cells were present in animals of the D+L group.However, no obvious pathological changes were observewd in the D+L+stress group.For fibrosis scores, the fibrosis grade in the D+L+stress group was significantly decreased than that of the D+L group (P＜0.05).Conclusions Constraint stress presents pro-tective effect on D-galactosamine and lipopolysaccharide induced liver injury in mice.

Objective To investigate the changes of gene expression profile in Beagle dogs' peripheral blood lymphocytes after acute irradiation.Methods Totally 20 male adult Beagle dogs were randomly divided into four groups including non-treatment blank control group and three radiation groups exposed to 0.5,2.0,and 5.0 Gy of γ-rays,respectively.Six hours after radiation,the peripheral blood were collected for lymphocytes isolation.Total RNA was extracted from the lymphocytes and analyzed by microarray hybridization.The differential gene profiles of radiation groups were analyzed by gene ontology (GO) analysis and kyoto encyclopedia of genes and genomes (KEGG) pathways analysis,and the alerted genes were further confirmed by the real time quantitative PCR (qRT-PCR) assay.Results Compared to the blank control group,the expressions of 308 genes in the radiation groups were perturbed over 2-fold of control,including 61 genes up-regulated and 247 genes down-regulated,which were mainly associated with immune response and cancer occurrence.The GO analysis indicated that the differential expressed genes were associated with cell connection,signal transduction,oxidation-reduction reaction and metabolism.The KEGG pathway analysis showed that some physiological and biochemical processes were involved,such as phagocytosis,tumor pathway,p53 signaling pathway,JAK-STAT signal pathway,cell differentiation,and proliferation,oxidative phosphorylation,glycogen dysplasia and other pathways.The microarray data of the alterations of apoptosis enhancing nuclease (AEN) and mitogenactivated protein kinase 13 (MAP3K13) gene expressions were further confirmed by qRT-PCR.Conclusions Exposure to different doses of acute γ-ray irradiation had significant impact on the gene expressions in Beagle dogs' peripheral blood lymphocytes and those differential expressed genes were related to a series of biological processes and pathways including immune response,metabolism and carcinogenesis.

Objective To observe the protective effects of different doses of hydrogen-rich water on radiation injury in mice,so as to provide scientific basis for the application of hydrogen-rich water.Methods The ICR mice were randomly divided into control group,irradiation group,amifostine group and hydrogen-rich water of low,medium and high dose groups.The 30 days survival rate,body weight,hematology parameters,serum biochemical parameters,organ weight and coefficient,bone marrow micronucleus rate,bone marrow nucleated cell count were observed after total body irradiation with 9.0 Gy gamma rays.Results After 30 d of irradiation,the hydrogen-rich water showed obvious protective effect on the survival rate and body weight in a dose dependent manner so that the survival was significantly higher than that of irradiation group (t =-2.67,P ＜ 0.05).The biochemical index,such as TP,ALB and CRE in the low dose group,TP,ALB,TBIL and CRE in the medium dose group,and TP,ALB,GLU,TBIL,BUN,GRE and UA in the high dose group also indicated the protective effects of hydrogen-rich water (t =-2.04--4.11,P ＜ 0.05).But the protective effect of hydrogen-rich water was not observed in hematology,organ weight and coefficient,and bone marrow micronucleus induction.Conclusions The hydrogen-rich water has anti-radiation effect,which may depend on the dose of hydrogen.

Objective The aim of this study was to establish a mouse model of chronic hepatic injury induced by low dose carbon tetrachloride ( CCl4 ) .Methods Twenty SPF male B/C mice ( body weight 18-20 g) were randomly di-vided into three groups including the CCl 4-treated group , oil-treated group and non-treated control group ( n=5/group ) . Mice in the CCl4-treated group were intraperitoneally injected with 0.5% CCl4 prepared in oil.Mice in the oil group re-ceived intraperitoneal injection of oil .Mice in the non-treated control group were left untreated .After 6 weeks, the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, as well structure, cellular morphology and degree of fibrosis of the hepatic tissues were examined by histology with HE and Masson staining .Results After low dose CCL4 treatment, the serum ALT and AST were significantly increased (P =0.00).Histology with HE stai-ning showed extensive vacuolar degeneration of hepatic epithelial cells and large number of necrotic foci .Histology with Masson staining revealed fibrous hyperplasia mainly located around hepatic lobules .Quantitative analysis of the fibrosis showed that the degree of fibrosis and the integrated optical density of fibrosis were significantly increased after CCl 4 induc-tion( P=0.00) .Conclusion Low dose carbon tetrachloride can induce hepatic injury in B /C mouse models presenting pathological changes of hepatic injury and fibrosis .

Objective: To detect the mutation of epidermal growth factor receptor (EGFR) gene in peripheral blood of non-small cell lung cancer (NSCLC) patients in Yunnan area with Super-ARMS, and to explore its correlation with clinicopathological characteristics. Methods: A total of 222 blood samples from patients with NSCLC were collected between January 2017 to December 2018 in the Molecular Diagnostic Center of Yunnan Cancer Hospital. The EGFR gene mutation in peripheral blood samples was detected by SuperARMS, and the relationship between EGFR gene mutation and clinicopathological features was analyzed. Meanwhile, the independent risk factors influencing EFGR mutation were also analyzed. Results: In the peripheral blood of 222 NSCLC patients, there were 81 cases (36.5%) with EGFR gene mutation. Among them, exon 19 deletion and L858R gene point mutation were the most common (75.3% of total mutation); female patients had a higher mutation rate than male patients (45.9% vs 27.0%); patients <60 years old had a higher incidence of mutation than patients≥60 years old (43.2% vs 28.8%) (P<0.05 or P<0.01); moreover, patients with no history of smoking, no history of radical surgery, adenocarcinoma, advanced stage and no history of chemotherapy had higher incidence of EGFR mutation (43.9% vs 21.6%, 39.2% vs 21.2%, 43.9% vs 4.8%, 39.7% vs 23.3% and 44.0% vs 23.5%) (P<0.05 or P<0.01). Multivariate logistic analysis showed that young, no smoking history, adenocarcinoma and no surgical history were independent risk factors for EGFR gene mutation (all P<0.01). Conclusion: In the peripheral blood of patients with NSCLC in Yunnan, the mutation rate of EGFR gene is higher in patients with age<60 years old, adenocarcinoma and non-smoking. Super-ARMS method is more sensitive in the detection of EGFR mutation in peripheral blood of lung cancer patients.

Objective To systematically review the nursing preventive interventions and their effects on venous thromboembolism (VTE) in ICU patients. Methods We searched PubMed, Cochrane Library, EMBASE, SCI, CINAHL, Science Direct, BM, CNKI, WanFang and VIP, to collect the randomized controlled trials of nursing prophylaxis on VTE in ICU patients. Results 57 studies were included, meta-analysis provided that: the incidence rates of VTE and bleeding between Intermittent Pneumatic Compression Devices(IPC) group and low molecular weightheparin group in severe trauma patients had no statistical significance (P=0.14); comparing with graduated compression stockings (GCS) only group, the incidence rates of deep vein thrombosis(DVT) were lower in combination with IPC and GCS group (P=0.003);comparing with routine nursing group, the incidence rates of VTE were lower in IPC group and GCS group (P<0.01), the blood flow velocity and the average velocity of venous flow in lower limbs were increased in IPC group (P<0.01). The results of descriptive analysis show that early comprehensive nursing interventions and corresponding nursing interventions after risk assessment can reduce the incidence of VTE in ICU. Conclusion According to the present projects, using IPC, GCS, adopting early comprehensive nursing interventions and giving corresponding nursing interventions after DVT risk assessment are the effective interventions on ICU VTE.

Objective To investigate the impact of spatial distribution of emphysema on pulmonary function and clinical severity in patients with chronic obstructive pulmonary disease (COPD).Methods Chest MSCT was performed in 84 patients with COPD.The percentage of low attenuation areas were automatically calculated for each lobe with the COPD analysis software.The correlations between low-attenuation area percent(LAA％) of each lobe and the parameters of pulmonary function were analyzed.According to the pulmonary emphysema heterogeneity index,the patients were divided into non-emphysema group and emphysema group,and the latter were divided into the predominantly upper lobe subgroup and the predominantly lower-lobe subgroup.The differences of pulmonary function parameters between the 2 groups and clinical severity between the 2 subgroups in emphysema group were compared.Results LAA％ of each lobe was negatively correlated with single breath carbon monoxide diffusing capacity to predicted value ratio (DLcoSB％pred).Except for the right middle lobe,LAA％ of the remaining lobes were negatively correlated with forced expiratory volume in one second/forced vital capacity (FEV1/FVC) and FEV1％pred,while positively correlated with resonance frequency (Fres).The differences of pulmonary function parameters between the 2 groups were statistically significant (all P ＜ 0.05).The differences of FEV1％pred and FEV1/FVC between the 2 subgroups in emphysema group were statistically significant (all P ＜0.05),and the differences of Fres and DLcoSB％pred between the 2 subgroups were not statistically significant (all P＞0.05).The difference of clinical severity between the 2 subgroups was statistically significant (x2 =4.17,P=0.041).Conclusion The spatial distribution of pulmonary emphysema affects pulmonary function and clinical severity in COPD patients.The patients with the predominantly lower-lobe emphysema are relatively worse in lung function,and more serious in the clinical severity.