OBJECTIVE：To explo re the potential molecular mechanism of ursolic acid in the treatment of osteoporosis （OP）. METHODS：TCMSP，PubMed database and UniProt database were used to screen potential targets of monomer compound ursolic acid. OP related target genes were searched with GeneCards database. The common target genes of component-disease were obtained by Venny 2.1 online mapping tool. The protein-protein interaction （PPI）network of component-disease common target genes was constructed by using STRING database ，and topological analysis was carried out ；the core target genes ，whose degree value was greater than the average degree value ，were screened. GO functional annotation and KEGG pathway enrichment analysis of component-disease common target genes were carried out by DAVID database. AutoDock Vina 1.1.2 software was used for molecular docking ，using protein encoded by the core target gene as receptor and ursolic acid as ligand. RESULTS ：A total of 55 ursolic acid related target genes and 4 273 OP related target genes were excavated ，with a total of 44 common target genes. PPI network with above common target genes included 44 nodes and 513 edges，with an average node degree of 23.3. There were 24 core target genes ，including VEGFA，TP53，IL6，CASP3. There were 340 GO functional items were enriched （corrected P＜ 0.05），including 263 biological processes （negative regulation of apoptosis ，etc.），25 molecular functions （protein binding ，etc.） and 52 cell components （cytosol，etc.）. There were 90 KEGG signaling pathways （corrected P＜0.05），such as tumor pathway ， hepatitis B pathway ，TNF signaling pathway ，viral carcinogenesis and phosphatidylinositol 3 kinase/protein kinase B （PI3K-Akt） signaling pathway. The binding energy between ursolic acid and 6 proteins encoded by core target genes such as TP53 was lower than －5 kcal/mol，which had strong binding activity. CONCLUSIONS ：The therapeutic effect of ursolic acid on OP may be achieved by regulating VEGFA，TP53，IL6，CASP3，JUN and other core target genes and acting on multiple key pathways such as cancer pathway ， hepatitis B and TNF signaling

OBJECTIVE: To investigate the relationship of the function and gene polymorphism of insulin receptor substrate (IRS) with type 2 diabetes mellitus (T2DM), and to provide a new perspective for T2DM drug development. METHODS: Relevant literatures included in CNKI, Wanfang, VIP, PubMed, SpringerLink and other databases from Jan. 1991 to Nov. 2017 were retrieved by using "Insulin receptor substrate" "Type 2 diabetes" "Insulin resistance" "Polymorphism" as Chinese keywords, and "Insulin receptor substrate" "IRS" "Type 2 diabetes" "Insulin resistance" "Polymorphism" as English keywords. The relationship of the function and gene polymorphism of IRS family with T2DM was reviewed. RESULTS & CONCLUSIONS: A total of 328 literatures were retrieved, of which there were 38 valid literatures. At present, IRS family has six members (IRS-1 to IRS-6). The dysfunction of IRS-1 and IRS-2 will lead to insulin resistance and induce T2DM. The relationship of IRS-3 and IRS-4 with T2DM remains controversial. IRS-5 and IRS-6 were newly found and their functions are not clear. The Gly972Arg mutation of IRS-1 is positively correlated with the pathogenesis of T2DM. Gly1057Asp mutation of IRS-2 combined with obesity can induce insulin resistance, but there is controversy. The mutation types of IRS family other members include Ala94Thr, Ala512Pro and Ser892Gly mutation of IRS-1, ACC, Ala157Thr and Leu647Val mutation of IRS-2. The relationship between these types of mutation and T2DM has not yet been fully supported. Multiracial and large-scale studies are required. Some achievements have been made in the present study, but the study is not yet comprehensive. Relationship of IRS family members and their mutation sites with T2DM still needs to be further tested in the expanded population.

OBJECTIVE:To provide reference for rational selection of antibiotics against non-fermentative Gram-negative bacilli in clinic. METHODS:Etiological data of clinical isolated Pseudomonas aeruginosa(PA),Acinetobacter baumanii(AB) and Stenotrophomonas maltophilia(SM)were collected from the Affiliated Hospital of Qingdao University(called"our hospital"for short)during Jan. 2004-Dec. 2016. Drug resistance of them to commonly used antibiotics was analyzed retrospectively. RESULTS:Totally 15 587 strains of PA,7 446 strains of AB and 2 950 strains of SM were detected. Resistance rates of PA to commonly used antibiotics fluctuated but were in a decreasing tendency. Except for imipenem,resistance rates of PA to commonly used antibiotics decreased significantly,and resistance rates of PA to amikacin and gentamicin decreased to 4.60% and 7.48%, respectively. Resistance rates of AB to most commonly used antibiotics were more than 40%,but it was sensitive to tigecycline (drug resistance of 0-4.03%). Resistance rates of SM to cefoperazone sodium and sulbactam sodium increased from 3.03% in 2004 to 39.01% in 2016,but it was sensitive to sulfamethoxazole,minocycline and levofloxacin. CONCLUSIONS:Non-fermentative Gram- negative bacilli detected in our hospital are mainly PA. Resistance rate of PA to most of the antibiotics is declining;drug resistance of AB is severe;resistance rates of SM to cefoperazone sodium and sulbactam sodium show increasing tendency.Above 3 non-fermentative Gram-negative bacilli are sensitive to amikacin,tegocycline and minocycline. Clinical selection should be based on the results of drug sensitivity test.

OBJECTIVE:To study the metabolite and excretion of polydatin (Trans-resveratrol-3-O-glucoside,TRG) and its metabolites in Beagle dog feces,and provide experimental basis for the new drug development of TRG. METHODS:4 Beagle dogs were intragastrically administrated TRG 20％ polyethylene glycol 400 solution 50 mg/kg. LC/MS was used to identify the me-tabolites of TRG in dog feces after 12-24 h of administration,and HPLC was adopted to determine the cumulative excretion rate and excretion speed rate of the major metabolite resveratrol(TR)in feces samples after 0-12,12-24,24-36,36-48,48-72,72-96 h of administration. RESULTS:TR and two sulfate conjugates of TR were found in dog feces,and TR was a major metabolite, while TRG was undetermined. The excretion speed rate of TR in dog feces was the rapidest after 12-24 h of administration,reach-ing 9.65 mg/h. Its cumulative excretion rate was 39.3％,equivalent to 67.2％ of TRG. CONCLUSIONS:After TRG is intragastri-cally administrated to dogs,TRG was mainly excreted in the form of TR via dog feces.

Objective Meta-analysis the efficacy and safety of Exenatide and insulin therapy oral hypoglycemic drugs effect of obesity with type 2 diabetes .Methods According to the research purpose to set up the screening of related literature and exclusion criteria; formulatethe searching strategy, through PubMed、the Chinese Biological Medicine Datebase(CBM)、 CNKI、Wanfang Data Knowledge Service Platform, VIP to retrieve all theliterature selection of efficacy and safety by Exenatide oral hypoglycemic drugs and insulin therapy of obese type 2 diabetes mellitus.Choose met inclusion exclusion criteria, the complete data information randomized controlled trial (RCT) as the research object; Apply to the international commonly used Jadad score method to evaluate quality included in the test; To process the relevant data in the test ; Apply the ReviewManager 5.1 software to analysis the extracted research data.Analysis the results and put forward conclusions.Results Participants included 11 RCT , meta analysis results showed that compared with the Exenatide, in terms of reducing fasting glucose ,insulin effect more apparent [MD = 0.35, 95％CI: (0.11, 0.59), P = 0.004)]. In control effect of glycosylated hemoglobin, there was no statistically significant difference[MD=-0.04 ,95％CI:(-0.20,0.11), P=0.58],between Exenatide and insulin. Compared with the insulin, Exenatide reduce BMI more apparent[MD=-2.77,(95％CI: -3.34,-2.20),P<0.00001]; Compared with the insulin, Exenatide reduce insulin resistance index, the effect is more obvious[MD=-1.67,95％CI:(-1.93,-1.41), P<0.00001]; Adverse reaction in the process of treatment, the insulin is more likely to lead to hypoglycemia, [OR = 0.32, 95％ CI: 0.19, 0.54), P<0.0001]; While Exenatide are more likely to lead to gastrointestinal adverse reaction [OR = 4.04, 95％ CI: 2.35, 6.93), P<0.00001).Conclusion According to the Meta-analysis: Exenatide can be used in the treatment of oral hypoglycemic drugs of adult obesity with type 2 diabetes, and obvious effects of treatment of insulin resistance, long-term results still needs a large number of samples of high quality RCT to verify.

OBJECTIVE:To investigate the effect of Wuzhi soft capsule on the pharmacokinetics of sirolimus in rats. METH-ODS:Wistar rats were randomly divided into 5 groups,with 6 rats in each group. They were given very low-dose,low-dose,me-dium-dose and high-dose of Wuzhi soft capsule(67,134,268 and 536 mg/kg)ig or blank solvent,respectively;and then given si-rolimus 0.4 mg/kg. The blood 100 μl was sampled by capillary eyes before giving sirolimus(0 h)and 0.5,0.75,1,1.5,2,2.5, 3,4,6,8,12,24 and 36 h after giving sirolimus and put into edetic acid anticoagulation tube. Blood concentration of sirolimus was assayed by LC-MS/MS. The pharmacokinetic parameter was calculated by DAS 2.0 software using non-compartment model. RESULTS:The pharmacokinetic parameters of sirolimus in very low-dose,low-dose,medium-dose and high-dose groups and blank solvent group were cmax of(6.79±1.15),(17.40±3.13),(21.24±3.14),(22.06±4.82),(2.80±0.72)ng/ml;t1/2 of(11.01± 0.82),(12.20±2.02),(12.28±2.38),(12.36±0.73),(10.59±0.69)h;AUC0-∞ of(85.79±15.26),(162.18±41.75),(273.12± 73.69),(268.79±28.46),(36.72±3.01)ng·h/ml,respectively. Compared with blank solvent group,cmax and AUC0-∞ of sirolimus were all increased in very low-dose,low-dose,medium-dose and high-dose groups,but t1/2 changed slightly. CONCLUSIONS:Wu-zhi soft capsule can substantially enhance the absorption of sirolimus in rats.

OBJECTIVE:To evaluate the clinical efficacy of Shuanghuanglian injection in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD),and to observe its effects on the plasma levels of C-reactive protein (CRP),procalcitonin(PCT)and interleukin-6(IL-6). METHODS:A total of 100 AECOPD patients were randomly divided into observation group and control group,with 50 cases in each group. Control group received routine treatment,such as controlled oxygen therapy,intravenous dripping of moxifloxacin,bronchodilator for relieving asthma,mucolytic for eliminating phlegm,nu-tritional support. Observation group was additionally given Shuanghuanglian injection 1 ml/(kg·d)added into 5% Glucose injec-tion 250 ml intravenously,qd,on the basis of control group. Treatment course of 2 groups lasted for 10 d. Clinical efficacies of 2 groups were compared as well as the changes of serum levels of CRP,PCT and IL-6 before and after treatment and the occur-rence of ADR. RESULTS:After treatment,total effective rate of observation group was 96.0%,which was significantly higher than 82.0% of control group,with statistical significance(P<0.05). Before treatment,there was no statistical significance in se-rum levels of CRP,PCT and IL-6 between 2 groups (P>0.05). After treatment,serum levels of CRP,PCT and IL-6 were de-creased significantly in 2 groups,and those of observation group were significantly lower than those of control group,with statis-tical significance (P<0.05). There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CON-CLUSIONS:Shuanghuanglian injection can effectively improve serum inflammatory factors of AECOPD patients,and shows good clinical efficacy and safety.

OBJECTIVE:To establish the quality standard for Solanum tuberdsm. METHODS:The microscopic characteristics were detected;TLC was used for qualitative identification;moisture,ash,heavy metals and the amount of extract were deter-mined;HPLC was conducted for content determination of oxidized cyanidin:the column was Alltima C18 with mobile phase of ace-tonitrile-0.1% trifluoroacetic acid(80∶20,V/V)at a flow rate of 1.0 ml/min,detection wavelength was 538 nm,column tempera-ture was 30℃. RESULTS:It showed clear microscopic identification map. S. tuberdsm TLC had clear spots and well separated. The water content was 8.5%-11.0%;total ash was 2.0%-2.9%;Pb was lower than 5 ppm and alcohol-soluble extracts was 15.6%-22.3%. The linear range of oxidized cyanidin was 0.043-0.215 μg(r=0.999 8);RSDs of precision,stability and reproduc-ibility tests were lower than 2.0%;recovery was 95.50%-99.65%(RSD=1.35%,n=9). CONCLUSIONS:The established method can be used for the quality control of S. tuberdsm.

OBJECTIVE:To investigate the dosage and consumption sum of opioid analgesic drug in Qingdao district. METH-ODS:The consumption data of drugs in 29 public hospitals at secondary or above level in Qingdao district were analyzed statistical-ly by ABC analytic methods and defined daily dose methods. RESULTS:In ABC analysis,5 kinds of class A drugs accounted for 20% of the total number of species,and the percentage of consumption sum was 77.38%;4 kinds of class B drugs accounted for 16.00% of all species numbers,and the percentage of consumption sum was 11.98%;other 16 kinds of drugs accounted for 64.00% of the total number of species,and the percentage of consumption sum was 10.64%. Oxycodone sustained-release tablets and Morphine sustained-release tablets with the highest DDDs consumed more health care costs,serial number ratio was 1.00,syn-chronization was good and conform to the actual needs of clinical work. CONCLUSIONS:The composition ratio of opioid analge-sic drug costs is consistent with the theoretical value,significant discrepancy between cost and DDDs does not appear.

OBJECTIVE:To observe the correlation of vitamin D with the incidence of cardiovascular disease and risk factors in elderly patients with type 2 diabetes mellitus. METHODS:94 patients,aged 60 years old above,with type 2 diabetes mellitus were collected retrospectively. Those patients were divided into diabetes group(41 cases)and diabetes complicated with cardiovas-cular disease group(53 cases)according to the condition of disease. 25(OH)D levels and lab indicators of 2 groups were detect-ed. The relationship of cardiovascular lesion with risk factor was analyzed by Multivariate Logistic regression;the correlation be-tween 25(OH)D and risk factors was analyzed by pearson analysis. RESULTS:There was statistical significance in the levels of 25 (OH)D,TC,TG,UA and Ca between diabetes group and diabetes complicated with cardiovascular disease group,with statistical significance(P<0.05). pearson analysis showed that the level of 25(OH)D was negatively related to age,FIB,TC and UA,and positively related to D-dimer and HDL-C,especially correlated with FIB and TC significantly,with statistical significance (P<0.01). Multivariate Logistic regression analysis showed that the deficiency of 25(OH)D was pathogenic factors of type 2 diabetes mellitus. CONCLUSIONS:There is a correlation between the level of 25(OH)D and cardiovascular risk factors as age,FIB,TC, UA,D-dimer,HDL-C. Vitamin D deficiency is the independent risk factors for cardiovascular disease in elderly patients with type 2 diabetes mellitus.