OBJECTIVE:To investigate the function change of intestinal CYP3A4 and P-glycoprotein (P-gp) under diabetic conditions and its mechanism. METHODS:Caco-2 cells were respectively added with 25, 50 and 100 μmol/L midazolam (CYP3A4 probe substrate) for incubation for 15,30,60,120,180 min;with 0.1,0.2,0.4 μg/ml rhodamine 123 (P-gp sub-strate)for incubation for 15,30,60,90,120 min to determine the substrate concentrations and incubation time. Caco-2 cells were added with insulin,glucose and fatty acid (palmitic acid and oleic acid) at different concentrations,and then the production of 1′-OH-midazolam,the metabolite of midazolam,and the intake of rhodamine 123 were determined,in order to investigated the ef-fect on the function of CYP3A4 and P-gp. RESULTS:The optimal substrate concentrations and incubation time were as follows as 50 μmol/L midazolam,0.1 μg/ml rhodamine 123 and incubation for 2 h. With the increase in the concentration of insulin,glucose and palmitic acid,the production of 1′-OH-midazolam and the activity of CYP3A4 reduced;the intake of rhodamine 123 in-creased,and the efflux transport function of P-gp decreased. Oleic acid had no significant effect on the production of 1′-OH-mid-azolam or the intake of rhodamine 123. CONCLUSIONS:Under diabetes condition,the increase of insulin,glucose and palmitic acid may reduce the function of CYP3A4 and P-gp,while oleic acid has no effect on the function.

Aim To investigate the mechanism of dia-betes changing the hepatic CYP1 A2 through in vitro cell culture study.Methods The function of CYP1 A2 in HepG2 and Fa2N-4 cells were evaluated by determi-ning the level of phenacetin metabolism,and the mR-NA expression of CYP1 A2 in cells was detected by real time PCR.HepG2 cells were co-cultured with serum of diabetic rats(type 1 and type 2)and normal rats,then the CYP1 A2 function in cells were evaluated.Then, the HepG2 and Fa2N-4 cells were co-cultured with a series of concentrations of saturated (including palmitic acid and stearic acid)and unsaturated fatty acids(in-cluding oleic acid and linoleic acid)for 48 h,and the function and expression of CYP1 A2 in the cells were compared.Results It was found that the activities of CYP1 A2 were higher in cells incubated with diabetic serum of both type.All high concentration of fatty acids could increase the function and expression of CYP1 A2 in both HepG2 and Fa2N-4 cells.Conclusion It is speculated that the abnormal level of fatty acids under diabetic state might be part of the reasons why diabetes change the hepatic CYP1 A2,which provides the basis for future study.

Objective To investigate the clinical effect of gastric bypass operation on treating type 2diabetes,and analyze the management status.Methods Fifty-seven patients wiith type 2 diabetes treated by gastric bypass operation were divided by different body mass index(BMI) into 4 groups:group A( BMI ＜ 20kg/m2) with 8 cases,group B (20 kg/m2≤BMI ＜24 kg/m2) with 21 cases,group C (24 kg/m2≤BMI ＜27kg/m2) with 17 cases and group D (BMI ≥27 kg/m2) with 11 cases.The control of blood glucose and glycosylated hemoglobin,changes of diets and body weight,diabetes complications,adverse reactions after operation and postoperative management were followed up or reviewed.The clinical data were analyzed comprehensively.Results The cure rate of group C was the highest [ 70.6％( 12/17 ) ],while the cure rate of group A was the lowest (0).The overall cure rate was 43.9％(25/57) and the overall improvement rate was 28.1％(16/57).The overall efficient rate was 71.9％(41/57) and the overall inefficient rate was 28.1％(16/57).Apart from a few patients had malnutrition,amenorrhea,bad stomach,diarrhea and poor diet after leaving the hospital,other patients had no surgery complications and no patients died.There was no clinician to follow up and did education to these patients after operation.Conchusions Gastric bypass operation is safe and effective for obese and non-obese patients with type 2 diabetes.It is a new method to weat type 2diabetes at present,but the indications should be grasped and operation enlargement must he prevented.The management of teams of physicians,surgeons,dietitians,nurses should be established afler operation.

Objective To investigate the correlation between drug-resistant genes and mobile genetic elements in multi-drug resistant Escherichia coli,and to explore phylogeny among the strains.MethodsTotally 20 strains of multi-drug resistant Escherichia coli were collected from Pan' an Hospital,Zhejiang Province during June 2009 and June 2010.Beta-lactam-resistance genes,aminoglycoside-resistance genes,genetic markers of mobile genetic elements were analyzed by PCR.Index and sample cluster analysis were performed on above results. Results In 20 strains of Escherichia coli,4 kinds of beta-lactamresistance genes,4 kinds of aminoglycoside-resistance genes,and 5 kinds of genetic markers of mobile genetic elements were detected.Index cluster analysis showed that correlation existed between resistance genes TEM,CTX-M-1,aadA5 and mobile genetic elements traA,IS26,ISEcpl; and correlation also existed between resistance genes OXA-1,aac(6′)-Ⅰ b,ant(3)-Ⅰ,rmtB and mobile genetic elements trbC,IS903.Sample cluster analysis showed that this group of Escherichia coli could be divided into 2 groups which were genetically different.ConclusionsDrug-resistant genes in multi-drug resistant Escherichia coli are correlated with mobile genetic elements.Sample cluster analysis can reveal phylogeny among the strains,which is important for hospital infection control.

Objective: To understand the status quo and influencing factors of overweight and obesity in preschool children, and to provide scientific theoretical reference for the prevention and control of overweight and obesity in preschool children in Urumqi. Methods: Stratified cluster sampling method was adopted to select 1 897 preschool children from 10 kindergartens in Urumqi from October to December in 2021 to understand the status quo of overweight and obesity of preschool children by measuring their height and weight. The influencing factors were collected by questionnaire survey, including Chinese preschoolers eating behavior questionnaire, Chinese preschooler s caregivers feeding behavior scale, 3-6 year old children s home nurture environment scale, and characteristics and influencing factors of physical activity among preschool children. Results: The prevalence of overweight and obesity in preschool children was 31.21% (592), including 19.50% (370) overweight and 11.70% (222) obesity.Childhood overweight and obesity detection rates varied significantly by age, sex, child dietary habits, father BMI, maternal BMI, and maternal pre pregnancy BMI ( χ 2=19.63,28.75,9.45,18.21,18.45,19.36, P <0.05). Multivariate Logistic regression analysis showed that gender, children s eating habits, paternal BMI, pregnancy BMI, satiety responsiveness, external eating, initiative eating, weight concerns, behavior restricted feeding, physical activity and family physical activity environment were the influencing factors of overweight and obesity in preschool children( OR =0.52,1.43,1.51,1.44,0.69,0.74,1.35,1.71,0.81,0.96,1.10, P < 0.05 ). Conclusion Overweight and obesity in preschool children are popular in Urumqi. Education, diet control and scientific exercise should be strengthened to prevent childhood overweight and obesity.

In order to understand the knowledge, attitude and practice (KAP) of vaccination against influenza, pneumonia, human papillomavirus (HPV), herpes zoster (HZ), COVID-19, and hepatitis B among staff of vaccination units in Shandong Province, a sample survey was conducted among 797 staffs of adult vaccination units in 12 counties (cities and districts) of Shandong Province from August to September 2022. The results showed that the respondents had the highest total score of knowledge and attitude for the COVID-19 vaccine, with the M ( Q1, Q3) of 23 (20, 25) and 10 (10, 10), respectively, and had the lowest score of knowledge and attitude for the herpes zoster vaccine, with the M ( Q1, Q3) of 19 (15, 22) and 8 (8, 10), respectively. The vaccine-related knowledge point"vaccine applicable population"had the highest score, with the M (Q1, Q3) of 26 (23, 30). The "contraindications/adverse reactions" and "adverse reaction management" had the lowest score, with the M (Q1, Q3) of 24 (20, 29) and 24 (20, 28), respectively. About 89.71% of respondents received one adult vaccine within two years at least. The principal driver for vaccination of 53.58% of recipients was their understanding of vaccines, which was"it was necessary to receive the vaccine". About 66.00% of respondents who had not received any adult vaccine in the past two years had insufficient awareness of the necessity of vaccination and believed that they were in good health and did not need to receive it. In summary, the staff of adult vaccination units in Shandong Province have a poor understanding of the herpes zoster vaccine in terms of vaccines and a relatively poor understanding of"contraindications/adverse reaction and management"in adult vaccination knowledge points.

In order to understand the knowledge, attitude and practice (KAP) of vaccination against influenza, pneumonia, human papillomavirus (HPV), herpes zoster (HZ), COVID-19, and hepatitis B among staff of vaccination units in Shandong Province, a sample survey was conducted among 797 staffs of adult vaccination units in 12 counties (cities and districts) of Shandong Province from August to September 2022. The results showed that the respondents had the highest total score of knowledge and attitude for the COVID-19 vaccine, with the M ( Q1, Q3) of 23 (20, 25) and 10 (10, 10), respectively, and had the lowest score of knowledge and attitude for the herpes zoster vaccine, with the M ( Q1, Q3) of 19 (15, 22) and 8 (8, 10), respectively. The vaccine-related knowledge point"vaccine applicable population"had the highest score, with the M (Q1, Q3) of 26 (23, 30). The "contraindications/adverse reactions" and "adverse reaction management" had the lowest score, with the M (Q1, Q3) of 24 (20, 29) and 24 (20, 28), respectively. About 89.71% of respondents received one adult vaccine within two years at least. The principal driver for vaccination of 53.58% of recipients was their understanding of vaccines, which was"it was necessary to receive the vaccine". About 66.00% of respondents who had not received any adult vaccine in the past two years had insufficient awareness of the necessity of vaccination and believed that they were in good health and did not need to receive it. In summary, the staff of adult vaccination units in Shandong Province have a poor understanding of the herpes zoster vaccine in terms of vaccines and a relatively poor understanding of"contraindications/adverse reaction and management"in adult vaccination knowledge points.

OBJECTIVE:To establish population pharmacokinetics(PPK)model of vancomycin so as to evaluate the effects of cystatin C(Cys C)on the pharmacokinetics parameters of vancomycin. METHODS:Totally 333 times therapeutic drug monitoring (TDM)were retrospectively collected from 225 patients who received vancomycin. Using sex,age,body weight(mT),Scr and Cys C as covariates,PPK model was established by using nonlinear mixed effect model method. Bootstrap method and normal prediction distribution error(NPDE)method were adopted for internal validation of model. Forty times of TDM data were collected from other 27 patients for external validation. Predicted accuracy and precision of model were investigated with mean prediction error (MPE) and root mean square error (RMSE). The effects of Cys C change on pharmacokinetic parameters of vancomycin were evaluated with steady state trough concentration and apparent clearance rate (CL/F) of vancomycin in typical patient (65 year-old,64 kg,Scr 66 μmol/L,1 000 mg,q12 h)forecasted with the final model at different levels of Cys C. RESULTS:CL/F of vancomycin was significantly influenced by age,body weight,the levels of Scr and Cys C. The final model was CL/F(L/h)＝3.68×(Scr/66)－0.431×(mT/64)1.1×(Age/65)－0.368×(Cys C/1.04)－0.693,V/F was equal to 82.5 L. The robust rate verified by Bootstrap method was 100%. Except for the interindividual variation of V/F,the relative bias of other pharmacokinetic parameters was less than 5%,and the estimated parameters of the final model were in the 95% confidence intervals of estimated values of Bootstrap. NPDE results showed that the homogeneity of variance was consistent with normal distribution (P＞0.05). In external validation,MPE and RMSE of the simplest model were －1.52 μg/mL and 6.87 μg/mL. MPE and RMSE of the final model were －0.32 μg/mL and 4.27 μg/mL,the accuracy and precision were improved significantly in the final model. When Cys C levle of typical patient was 0.3-4.0 mg/L,the steady state trough concentration predicted by final model were 5.25-29.97 μ g/mL and CL/F were 1.45-8.71 L/h. CONCLUSIONS:Age,body weight,the levels of Scr and Cys C significantly influence the pharmacokinetic parameters of vancomycin;moreover,the level of Cys C can change blood concentration of vancomycin. Established PPK model is of great predictive performance,which can be used to estimate the individual pharmacokinetics parameters of vancomycin.

Objective:To investigate the predictive value of different body obesity measures for non-alcoholic fatty liver disease (NAFLD).Methods:It was a cross-sectional study. The present study was a case-control study involving 553 subjects who underwent physical examination from January to April 2022. The subjects were divided into NAFLD group ( n=321 cases) and control group ( n=232 cases) according to abdominal ultrasound imaging parameters. All subjects completed a general information questionnaire, liver ultrasound examination, serum biochemical indices and physical measurements. Logistic regression model was used to analyze the correlation between human obesity measures (neck circumference, triceps skinfold thickness (TSF),body mass index (BMI), waist-to-hip ratio, lipid accumulation index (LAP), visceral fat index (VAI), body roundness index (BRI) and a body shape index (ABSI)) and NAFLD. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the predictive value of single and combined measures of obesity for NAFLD. Results:The subjects were stratified by gender, and the quartile levels of BMI, neck circumference, TSF, waist-to-hip ratio, LAP, VAI and BRI were all correlated with NAFLD in both male and female (all P<0.05). After further adjustment for confounding factors, compared with those in group Q 1, group Q 4 of the above-mentioned indexes still had higher odds ratios ( P<0.05). The AUC value of LAP in predicting NAFLD was the largest in both men and women, which was 0.836(0.788-0.876) and 0.885(0.839-0.921), and the cut-off value was 41.93 and 33.27, respectively. There was no significant difference in AUC of ROC predicting NAFLD among LAP, BRI and BMI ( P>0.05). The AUC of ABSI in predicting NAFLD was less than 0.7(namely 0.584(0.525-0.641) and 0.679(0.618-0.735) in men and women, respectively), which indicated poor predictive performance for NAFLD. In the pairwise combination index, the AUC of ROC predicting NAFLD with TSF+LAP in male was the largest, which was 0.864(0.819-0.901), and there was statistical significance when compared with BRI (AUC=0.818(0.769-0.860)) and BMI (AUC=0.816(0.767-0.858)) ( P<0.05), but there was no statistical significance when compared with LAP (AUC=0.836(0.788-0.876)) ( P>0.05). The AUC of ROC predicting NAFLD with VAI+LAP in women was the largest, it was 0.894(0.849-0.928), there was statistical significance when compared with BMI (AUC=0.849(0.799-0.890)) ( P<0.05), but there was no statistical significance when compared with LAP (AUC=0.885(0.839-0.921)) and BRI (AUC=0.870(0.822-0.908)) ( P>0.05). Conclusion:BMI, neck circumference, TSF, waist-to-hip ratio, LAP, VAI and BRI all have good predictive value for NAFLD.

To investigate activities of three isomers of α-conotoxin TxID on human α3β4 and α6/α3β4 nicotinic acetylcholine receptors(nAChRs). The three isomers of α-conotoxin TxID were synthesized using solid phase Fmoc chemistry and fully folded by two-step oxidations. Human α3β4 and α6/α3β4 nAChRs were expressed in oocytes of Xenopus laevis, which were used for bioassay of the three isomers, including inhibition and washout reversibility. There were obvious differences between the inhibition potency of each isomers at human α3β4 and α6/α3β4 nAChRs. The blocking was reversible and washout rapidly. The most potent isomer is the globular form with an IC50 of 9. 3 nmol/L on human α3β4 and α6/α3β4 nAChRs respectively. The 2nd potent isomer was the ribbon form with much less potency, which had an IC50 of > 5 μmol/L. The bead isomer had little or no block on human α3β4 and α6/α3β4 nAChRs with an IC50 of > 10 μmol/L. The three isomers of α-conotoxin TxID were synthesized successfully with two pairs of desired disulfide bond. Inhibition activities of the 3 isomers on human α3β4 and α6/α3β4 nAChRs were obtained respectively, which would be basis for new marine drug development of α-conotoxin TxID.