Objective To investigate the association of AcrAB-tolC efflux pump and marA-soxS-rob regulon with ciprofloxacin-resistance in Shigella flexneri isolates.Methods Forty five strains of Shigella flexneri were isolated in stool samples collected from outpatient diarrhea clinics in Tianjin from 2009 to 2013.The antimicrobial susceptibility of bacteria was analyzed by Kirby-Bauer disk diffusion method.Ten ciprofloxacin-resistant Shigella flexneri isolates and 10 ciprofloxacin-sensitive isolates were randomly selected.The gyrA and parC genes,plasmid mediated quinolone resistant (PMQR) determinants,efflux pump genes (acrA,acrB) and regulation genes (marA,soxS,rob) were screened and sequenced.Minimum inhibition concentrations (MICs) of the strains were determined before and after efflux pump inhibitor carbonyl cyanide m-chlorophenylhydrazone (CCCP) was added.The expression of acrA,acrB,marA,soxS and rob genes in ciprofloxacin-resistant and ciprofloxacin-sensitive strains was detected by realtime fluorescence quantitative RCR (RT-PCR),and the differences of expression were evaluated using t test.Results Both gyrA and parC mutations were detected in all ciprofloxacin-resistant strains; qnrS1 was positive in ciprofloxacin-resistant strain CR2 and aac(6')-Ib-cr was positive in ciprofloxacin-resistant strain CR5.Efflux pump genes and regulation genes were not detected in ciprofloxacin-sensitive strains,while soxRS mutation was detected in all ciprofloxacin-resistant strains except CR10.MICs of quinolones in ciprofloxacin-resistant strains decreased to one-fourth or one-eighth when CCCP added,while not changed or only decreased to one-half in ciprofloxacin-sensitive strains.Expressions of acrA,acrB,marA and soxS were significantly higher in ciprofloxacin-resistant strains than those in ciprofloxacin-sensitive strains (P ＜ 0.05 or P ＜ 0.01).Conclusion Efflux pump may involve in the high-level ciprofloxacin resistance in Shigella flexneri through activating transcription of efflux pump genes by marA-soxS-rob regulon,in which soxRS mutation may play an important role.

Objective To study the distribution of CTX-M-ESBLs and class Ⅰ integron in enterobacter cloacae resistant to third generation cephalosporins,and discuss the relationship between CTX-M-ESBLs and class Ⅰ integron. Methods K-B test for resistance;DDST and PCR for CTX-M-(ESBLs);PCR,nested-PCR and sequence analysis for finding class Ⅰ integron carrying CTX-M-ESBLs gene cassette. Results Among 37 strains,there are 21 isolates producing CTX-M-ESBLs,20 isolates with class Ⅰ integron and 13 isolates carrying CTX-M-ESBLs as well as class Ⅰ integron.In 3 isolates: CH4,CH11 and Q1,each class Ⅰ integron haboured CTX-M-ESBLs gene cassette. Conclusions There is few report on class Ⅰ integron carrying CTX-M-ESBLs,which caused more dangers of horizontal transmission of ESBLs and was important factor to nosocomial outbreak of multiresistant clinical isolates.

Objective To establish the quality standard of Xiao'er resuqing gantules.Methods Rhei Radix et Rhizoma,Bupleuri Radix,Forsythiae Fructus,Puerariae Lobatae Radix in the granules were qualitatively identified by the method of thin layer chromatography (TLC).The content of baicalin was analyzed by the method of high performance liquid chromatography (HPLC).Results There were good specificities of the TLC method to identify Rhei Radix et Rhizoma,Bupleuri Radix,Forsythiae Fructus,Puerariae Lobatae Radix.The linear range of baicalin was 0.116 2-1.743 0 μg (r =1.000 0).The average of recovery and RSD were 100.61％,0.79％ (n =6),respectively.Conclusion The method established in this study is simple,accurate,reliable and suitable to be applied to quality control for the preparation of Xiao' er resuqing granules.

Objective To explore the relationships of post- traumatic growth with self- care efficacy and psychological resilience in patients with breast cancer. Methods Totally 303 patients with breast cancer were investigated with Post- traumatic Growth Inventory (PTGI), Chinese version of Strategies Used by People to Promote Health (C- SUPPH) and Connor- Davidson Resilience Scale (CD- RISC). Results The total score of PTGI was 63.74±13.00 and the status of post- traumatic growth in breast cancer patients was in middle level, with a highest interpersonal score of 24.49±5.05, a lowest mental change score of 3.84± 1.91. Correlation analysis showed that post- traumatic growth was positively correlated with the level of self- care efficacy and psychological resilience (P<0.01 or 0.05). Regression analysis showed that self- care efficacy and psychological resilience in breast cancer patients could effectively predict the post- traumatic growth with an explanation rate of 36.1%. Conclusions Self- care efficacy and psychological resilience in patients with breast cancer are closely correlated with post- traumatic growth. It is suggested to take appropriate measures to promote post-traumatic growth of the breast cancer patients.

Objective This study aimed to assess the effects of active and passive smoking on chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM).Methods Seven hundred and five patients with T2DM were recruited in the study and were divided into three groups based on smoking status as active smokers,passive smokers and non-smokers.Twenty-four hour urinary albumin excretion (24hUAE) was measured,and estimate glomerular filtration rate (eGFR) was calculated with age and blood creatinine levels.Results (1) The proportion of CKD in T2DM in the present study was 31.63％ (223/705) with 28.6％ (22/77),30.0％ (15/50) and 29.6％ (73/247) for non-smokers,passive smokers and active smokers in men,and 29.9％ (40/134),35.9％ (66/184) and 7/13 for non-smokers,passive smokers and active smokers in women,respectively.In comparison with non-smokers,a higher risk of CKD was found in both passive and active smokers (OR =1.07 and OR =1.05 in men ; OR =1.31 and OR =2.74 in women,respectively).(2) Compared with non-smokers,passive smokers had a significant higher risk for albuminuria in women (OR =2.02,P =0.016).(3) After adjusting for gender,age,duration of T2DM,BMI,systolic blood pressure,glycosylated hemoglobin A1C and lipids,there was a significant decrease in eGFR between active and never smokers (P =0.018)or passive smokers (P =0.000) in women.No differences could be found in eGFR between each smoking statues in men.Conclusions Smoking exposure alone confers a high risk for CKD in patients with T2DM.Our results highlight an importance in implementation of a smoke-free environment for patients with T2DM.

Objective To investigate the effect of solute cartier organic anion transporter family, member 1B1 (SLCOIBI) gene variants on the response to therapy with repaglinide in type 2 diabetes. Methods 100 newly-diagnosed type 2 diabetic patients were treated with repaglinide during a course of 48 weeks. Anthropometrie parameters and indices related to glucose metabolism were measured periodically. Genotypes of SLCO1B1 D130N and V174A were detected by PCR-restriction fragment length polymorphism (RFLP) and sequencing respectively. Results Eighty-nine patients accomplished the 48-week follow-up visits. D130N variant in SLCO1B1 gene was associated with repaglinide treatment, DD genotype had better HbA1C lowering effect than N allele carrier [△HbA1C: (-2.29±0.23) % vs (-1.49±0.21)%, P<0.05]. No association was detected between D130N and the other effects of repaglinide on glucose metabolism related phenotypes. Conclusion D130N variant in SLCO1B1 gene is associated with the response to repaglinide treatment in patients with type 2 diabetes. DD homozygotes had a better effect than N allele carriers.

ObjeclJve To definine the corresponding value to glycated albumin(GA)for a specific target of HbAlc,and to elvaluate the relationship between GA and HbA1c.Methods From Oct.2006 TO Apr.2009, 2 532 subjects were enrolled who accepted oral glucose tolerance test(OGtt)in out-patient department,including 898 with normal glucose regulation,695 with impaired glucose regulation,and 939 with newly-diagnosed diabetes.GA was measured with liquid enzymatic method.HbA1c was measured with high performance liquid chromatography method.The plasma glucose was measured at fasting,0.5 h,1 h,2 h,and 3h after glucose load.The correlation among GA,HbA1c and the other parameters monitored was analyzed.Results (1)The levels of HbA1c and GA in 2 532 subjects were(6.3±1.1)% and(17.9±4.5)%.The ratio of GA/HbA1c was 2.85±0.51.(2)HbAlc and GA were positively correlated with fasting,0.5 h,1 h,2 h and 3 h plasma glucose(r was in 0.567-0.776,atl P<0.01).(3)GA was significantly correlated with HbA1c(r=0.701,P<0.01).Linear regression analysis,using GA and HbA1c summarized by patient(n=2 532),produced a relationship of GA=2.871×HbA1c-0.112.The change in GA per increase of 1% HbA1c was 2.87%.When HbA1c level was 6.5%,the expected value of GA was 18.5%.The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy with GA≤18.5% to predict HbA1c≤6.5% were 82.32%,72.49%,86.48%.65.73%,and 79.19%,respectively.When HbA1c level was 7.0%,the expected value of GA was 20.O%.When HbA1c level was 7.5%.the expected value of GA was 21.4%.Conclusions We initially establish the corresponding value to GA for a specific target of HbA1c and provide the basis for clinical application.

To investigate the relationship between serum glutamic acid decarboxylase antibody (GAD-Ab)titer and the first-phase insulin release (1PH)in newly-diagnosed type 2 diabetic patients. 1053 newly-diagnosed type 2 diabetic patients were divided into 3 groups, including 71 individuals with GAD-Ab≥1 U/ml (positive group), 171 individuals with GAD-Ab ranging from 0 to 1 U/ml (negative-1 group), and 811 individuals with GAD-Ab=0 (negative-2 group). IPH was evaluated by arginine stimulation test. In the patients of negative-2, negative-1, and positive groups, the respective values of 1 PH were subsequently decreased significantly (P< 0. 01) , and the detection rates of the decreased insulin secretion were 74. 85%, 87. 13%, and 100%, respectively. Stepwise regression analysis indicated that disease duration, GAD-Ab titer, HbA_1C, and body mass index were the major independent contributing factors. The titer of GAD-Ab has an important impact on 1PH defect in type 2 diabetic patient. Detection of GAD-Ab not only provides an evidence for clinical type, but would also be helpful in determining the islet β-cell function.

Objective To investigate the role of AcrAB-TolC efflux pump in fluoroquinolones resistance by Shigella. spp and to explore the significance of AcrAB-TolC efflux pump on mutation of acrR, soxS and marOR as well as on drug re?sistence. Methods Drug resistant bacteria were selected by Kirby-Bauer disk diffusion test. After addition of efflux pump inhibitor carbonylcyanide-m-chlorophenylhydrazone (CCCP), change of minimal inhibitory concentration (MIC)s of nilidixic acid, Levofloxacin, ofloxacin, ciprofloxacin and Norfloxacin were examined. The DNA binding region of acrA, acrB, soxS, acrR and marOR gene in these mutants were amplified by PCR and sequenced. Results Among the 159 clinical isolates of Shigella,11 strains are resistant to fluoroquinolone. After the addition of CCCP, MICs of 2 fluoroquinolone resistant strains decreased; the MICs of 7 fluoroquinolone resistant strains did not change; MICs of 2 fluoroquinolone resistant strains in?creased. The corresponding nucleotides C, A, T, T on the 36th to 39th of marOR gene were missing, showing by sequencing, in fluoroquinolone resistent strains which might be regulated by the efflux pump gene AcrAB-TolC. Conclusion Efflux pump inhibitor could restrain the activity of efflux partially. The mutations of marOR might play an important role in fluoroquino?lone resistent by shigella.

Background Heavy metals may play an important role in environmental risk factors associated disorders of activities of daily living (ADL) in older adults. Objective To investigate the associations between plasma levels of six heavy metals (zinc, arsenic, cadmium, lead, manganese, and copper) and ADL disorders in older adults. Methods A cross-sectional survey was conducted from 2018 to 2019 among 1412 rural elderly people in Gongcheng Yao Autonomous County, Guangxi Zhuang Autonomous Region. The plasma metal concentrations were detected by inductively coupled plasma mass spectrometry (ICP-MS), and subsequently classified into three groups (T1-T3) based on tertiles, with the T1 group as the reference. The samples were assessed for ADL disorders using the ADL scale. Logistic regression and restricted cubic spline model (RCS) were used to estimate the odds ratio (OR) and 95% confidence interval (CI) to assess the associations between heavy metals and the prevalence of reporting ADL disorders. Results The mean age of the study population was (68.52 ± 5.92) years, 825 (58.4%) female and 587 (41.6%) male. Of these, 372 (26.34%) subjects reported ADL disorders, and most of them were female (74.30%). The results of logistic regression showed that the participants in the cadmium T2 group (0.15-0.25 µg·L⁻¹) had a higher risk of ADL disorders compared to the T1 group (≤0.15 μg·L⁻¹) (OR=1.552, 95%CI: 1.086, 2.134). After stratification by sex, the relative risk of ADL disorders was lower in the plasma copper T3 group (>1019.58 µg·L⁻¹) compared to the T1 group (≤868.12 μg·L⁻¹) in men (OR=0.481, 95%CI: 0.232, 0.998). The relative risk of ADL disorders was higher in the plasma cadmium T2 group (0.15-0.25 µg·L⁻¹) compared to the T1 group (≤0.15 μg·L⁻¹) in women (OR=1.758, 95%CI: 1.182, 2.616). The RCS results showed that the risk of ADL disorders in men was nonlinearly associated with copper (P_nonlinear=0.011, P_overall<0.05). Conclusion High levels of cadmium are positively associated with the risk of reporting ADL disorders, while high levels of copper are negatively associated with the risk of reporting ADL disorders in men.