High fat diet is one of the important factors leading to type 2 diabetes mellitus and insulin resistant symptom.Developing a steady and applied model using high-fat diet-fed animals becomes an important part of type 2 diabetes mellitus and insulin resistant symptom researches.Whether high fat diet leads to insulin resistant symptom in experimental animals depends on the following factors: the artifactitious pattern and the fat proportion of the feed,the total amount of calories absorbed by the experimental animal,the duration of the animal model development,the breed and gender of experimental animals and the assistant medicament etc.

Objective To investigate the influence of different diluents(physiologic saline, dis-tilled water and human inactivated serum) on measurement of 15 items of biochemical parameters.Methods Fifteen items of biochemical parameters [alanine transaminase(ALT), aspartic transaminase (AST), alkaline phosphatase( ALP), gamma glutamyl transpeptidase ( GGT), creatine kinase ( CK),lactate dehydrogenase(LD), hydroxybutyrate dehydrogenase(HBDH), total bilirubin(TBIL), direct bilirubin(DBIL), total bile acid(TBA), ereatinine(Cr), uric acid(UA), eholesterol(CHO), glucose (GLU), and blood urea nitrogen(BUN)] were chosen. For each parameter, 45 serum samples with different eoncentrations of the parameter were collected. After diluted with different diluents(physio-logic saline, distilled water or human inactivated serum), the serum samples were detected by applying the fully automated biochemical analyzer. The mean value was calculated and statistical analysis was performed. Results There were some differences of detection results when the specimens were diluted with different diluents. ALT, AST, GGT, DBIL, and HBDH serum samples could be diluted by 10 times with physiologic saline, distilled water or human inactivated serums ALP and TBA serum sam-ples could only be diluted with inactivated serum, otherwise its result would be lower; GLU, TBIL samples could be diluted with distilled water and inactivated serums for BUN, CR, UA, CK, LDH,and CHO samples, physiologic saline or human inactivated serum might be optimal; if distilled water was chosen, the results of other parameters tented to decline except UA. It was BUN was improper to dilute the BUN samples with distilled water. In addition, there was no significant difference between the items diluted by 5 times and 10 times with physiologic saline. All the 15 items could be diluted with inactivated serum. Conclusion The inactivated serum should be the first choice of diluents to e-nure the accurate results of biochemical parameters. If the prepared inactivated serum is absent, we may choose other diluents according to the above-mentioned results.

AIM　To quatitatively disclose the relationship between activity and structure of a new class of COX-II inhibitors containing dialkylphenyl-linked heterocyclic moieties. METHODS AND RESULTS Seventeen COX-II inhibitors from literature as a training set were investigated with the aim of developing a 3D-QSAR model using comparative molecular field analysis (CoMFA). To reveal the pharmacophoric pattern, several modes of superimposition were explored. The significant model shows a higher ability to explain and predict the activity of COX-II inhibitors, with the cross-validation RCV2=0.718, non cross-validation R2=0.992, F=260.624, and SEE (standard error of estimate)=0.072. Three compounds were selected as a predicting set, the low deviations of calculated values from the measured ones suggesting a powerful predictive ability of the model. CONCLUSION　The 3D-QSAR explains the dependence of COX-2 inhibition upon the structures of the compounds. Some structure information for design of new COX-II inhibitors with higher activity has been given.

OBJECTIVE:To establish a method for the content determination of total flavonoids in onion extracts.METH_ ODS:UV spectrophotometry was adopted in the determination with the detection wavelength set at270nm.RESULTS:Good linear relationship with the absorbability was achieved when the detection concentration of eldrin was within a range of0.002～0.01mg/ml(r=0.9978),the average recovery was99.15%(RSD=1.52%).CONCLUSION:This method was simple,rapid and accurate.

Liuwei-Dihuang Pill is a famous medicine in the clinical practice of traditional Chinese medicine (TCM), and it is important and interesting to explore its new clinical indications. This study is based on the data downloaded from the SinoMed by querying on term of Liuwei-Dihuang Pill. By applying the data slicing algo-rithm, we achieved outstanding symptoms associated with Liuwei-Dihuang Pill. Examining these symptoms, besides those which are widely known as common knowledge, some other potential symptoms are found. These potential symptoms are aphtha, (sexual) dysfunction, constipation, and heel pain which might be taken as new clinical indi-cations of Liuwei-Dihuang Pill.

ObjectiveTo evaluate the effects of ventilator circuit change frequency on ventilatorassociated pneumonia (VAP).MethodsMeta-analysis of effects of ventilator circuit change frequency on VAP was conducted with study-level data from 1995 to 2010 in Pubmed,Embase,Web of Science databases.ResultsNine articles were included (sample size:20 326 mechanically ventilated patients).Analysis of six articles showed that the incidence of VAP in ventilator circuit change every 2 or 3 days was 4.05％,while 3.65％ in ventilator circuit change every 7 days.Compared with change ventilator circuit every 2 or 3 days,the risk ratio (RR) of VAP in weekly changes was 0.77 [0.54,1.09] ( P =0.14 ).Analysis three articles showed that compared to ventilator circuit change every 7 days with 15.89％ incidence of VAP,the incidence of VAP in circuit change more than 14 days was 14.9％,and RR was 0.98 [0.69,1.39](P =0.91 ).ConclusionsRegular ventilator circuit change frequency in various intervals can't difference in the incidence of VAP in mechanical ventilation patients.

Objective To study the therapeutic effect of cholinergie receptor,an nicotinic acetylcholine receptor(nAChR)α7 agonist,on trinitrobeazene sulfonic acid(TNBS)-induced colitis in mice.Methods BALB/C mice were randomly divided into control group,TNBS group,anabaseine(AN)as the agonist of nAChRα7(AN group),and chlorisondamine diiodide(CHD)as the antagonist of nAChRα7(CHD group).TNBS-induced colitis was produced at day 1,either 10 μg anabaseine or 1.5 μg chlorisondamine diiodide was administrated after the induction of colitis,and repeated on interval day till the mice were sacrificed at day 8.The myeloperoxidase(MPO)activity and level of tumor necrosis factors(TNF)-α in colonic tissue were examined by histological method and enzyme-linked immunosorbent assay (ELISA),respectively.Lamina propria mononuclear cells(LPMCs)were isolated,and NF-κB activation was further detected by Western blot.Results Compared with TNBS group,the tissue damage,MPO activity and concentration of TNF-α in mice treated with anabaseine were decreased[MPO activity:(7.6±2.1)U/mg vs(12.2±2.6)U/mg,TNF-α level:(396±98)pg/g vs(627±112)Pg/g],and NF-κB activation in LPMCs was inhibited.Whereas the MPO activity[(14.1±1.8) U/mg)]and concentration of TNF-α[(692±79)pg/g)]in mice treated with chlorisondamine diiodide were increased and NF-κB activation in LPMCs were amplified. Conclusion nAChRa7 agonist can inhibit colonic inflammatory response by down-regulating the consentration of TNF-α and inhibiting NF-κB activation.

Objective To investigate the role of genistein (Gen) in the expression of connective tissue growth factor (CTGF) induced by parathyroid hormone (PTH) in human renal tubular epithelia cells. Methods Real-time PCR, Western blotting and reporter gene assay were employed to detect the role of Gen in PTH-induced CTGF expression in HK-2 cells. The activity of NF-κB was measured by EMSA to investigate the mechanism by which PTH induced CTGF expression in HK-2 cells. Inhibitors of NF-κB signaling pathway were used to ascertain which signal pathway was involved. Results HK-2 cells had basic amount of CTGF mRNA and protein, which, however, increased significantly after treatment with PTH, and the luciferase activity increased to a higher level as compared with control group after treatment with 10-10 mol/L PTH for 12 h (1.89±0.08 vs 0.99±0.03, P＜0.01). Gen decreased the expressions of CTGF mRNA and protein induced by PTH in dose-dependent manner. The NF-κB of nucleus was inactivation without PTH, while the activity of NF-κB significantly increased after exposed to PTH, with the maximal response of PTH at a concentration of 10-10 mol/L and the best stimulating time at 30 minute. The NF-κB inhibitor PDTC reduced the increase of CTGF transcript levels in response to PTH stimulation. Gen blunted PTH-mediated NF-κB activation. Conclusion Gen inhibits CTGF expression induced by PTH through bloking NF-κB signaling pathway in human renal tubular epithelial cells.

Objective To evaluate the safety and efficacy of dosage-escalated sorafenib in pa-tients with metastatic renal cell carcinoma. Methods Twelve male patients and 4 female patients with median age of 53 (37-71 years) were included in this study. They were with refractory meta-static renal-clear-cell carcinoma and received sorafenib from 800 mg/d to 1200mg/d or 1800 mg/d gradually until intolerable or disease progression occurred. Overall response rate, toxicity and progres-sion free survival (PFS) were recorded and analyzed. Results The median follow-up was 11 months (9-16 months). The overall rate of objective response and disease control rate were 44%(7/16)and 81%(13/16), respectively. Serious adverse effects (≥Grade Ⅲ) included hand-foot skin reaction (25%, 4/16), mucositis (19%, 3/16), diarrhea (19%, 3/16), hypertension (12%, 2/16) and my-elosuppression (12%, 2/16). PFS for high risk patient was 9.2 months at the end of this study. Conclusions The dosage-escalated sorafenib could obtain a high response rate and prolong PFS of high-risk patients. The toxicities are tolerable for metastatic renal cell carcinoma patients treated with sorafenib.

Objective To evaluate the safety and efficacy of sorafenib as first line treatment in patients with metastatic renal cell carcinoma. Methods Eleven patients with metastatic renal cell carcinoma after radical nephrectomy and 1 patient with locally advanced renal cell carcinoma and unre-sectable primary renal tumor were eligible for this study. The regimen was oral intake of sorafenib (400 mg twice daily) until the disease progression or toxicity becoming intolerable. Results All pa-tients were evaluable for response and toxicity assessment. The overall objective response rate and dis-ease control rate were 25%(3/12) and 83%(10/12, 3 partial responses and 7 disease stabilizations). The actuarial 6-month progression-free survival was 83% (10/12), while the median survival time was 16 months. The most common adverse effects included hand-foot skin reaction, rash, alopecia and hy-pertension. Conclusion Sorafenib is effective and safe as first line treatment for patients with meta-static renal cell carcinoma.