Objective:To optimize the formula and preparation process of prepare sorafenib dry suspension and detect the content by HPLC. Methods:The influence of single factor including different fillers, suspending agents, adhesives and disintegrants on the sedimentation rate, redispersibility and drying shrinkage of sorafenib dry suspension was observed. Orthogonal design was used to opti-mize the formula and preparation process of the suspension, and HPLC was used to determine the content of sorafenib. The chromato-graphic column was Inertsil ODS-3 (250 mm × 4. 6 mm, 5μm), the mobile phase was 20 mmol·L-1 ammonium acetate buffer-aceto-nitrile(28 ∶72), the detection wavelength was 266 nm, the flow rate was 1. 0 ml·min-1, the column temperature was 40℃, and the sample size was 20 μl. Results:The optimal formula and preparation process were as follows:sucrose (48%) was used as the filler, xanthan gum (28%) and CMC-Na (12%) were the suspending agents, MCC (10%) was used as the disintegrant, and 6% PVP (in 50% ethanol) was the adhesive. The linear range of sorafenib was 1-100 μg·ml-1(r=0.999 8), and the recovery was 98.96%(RSD=0. 75%, n=9). Conclusion:The optimal formula and preparation process are repeatable. The HPLC method is simple and specific, which can be used to determine sorafenib.

OBJECTIVE:To provide reference data for well understanding of high cost to access medical service for diabetic patients and controlling increase of medical costs.METHODS:Average daily cost of diabetic drugs in 1998 was compared with in 2008.At the same time it was compared with GDP and per-captia disposable income(PCDI).RESULTS:GDP,PCDI,consumption sum of total drugs and consumption sum of diabetic drugs in 2008 respectively were 3.78 times,3.11 times,3.87 times,2.73 times compared with in 1998.Amount of and daily average expenses of insulin respectively were 3.46 times,1.23 times;DDDs and daily average expense of oral hypoglycemics respectively were 1.69 times,1.41 times,compared with in 1998.Incremental rate of daily average expense of insulin injection and oral hypoglycemics were lower than that of PCDI.The daily average expense was increased as a result of the use of joint venture import drugs and new drugs and increase of diabetic patients.CONCLUSION:Incremental rate of daily average expense of diabetic drugs is lower than that of PCDI.High cost to access medical service for diabetic patients isn't equal to high cost of drugs.Many factors related should be considered from the point of view of society.

OBJECTIVE: To probe into the status quo and the tendency of the application of intravenous infusions. METHODS: Data on the application of intravenous infusions in one of the tertiary Grade A comprehensive hospital in 1996, 1999, 2002 and 2004 were analyzed statistically. RESULTS: The variety of infusion, the total quantity and the total amount of money of infusions increased year by year,the total consumption sum of infusions accounted for 10% of that of the whole year drugs; the majority of which were the consumption of nutritional and dielectric medicines, of which, glucose and sodium chloride injections accounted for 74% of the total; the infusion of treatment type increased fast, much as in cases of anti - infec-tives; the drug expense for each bottle of infusion increased year by year, the amount of money involved in infusion drugs accounted for 60% of the total year round drug consumption sum. CONCLUSION: There is an upward trend in both the quantity and consumption sum of infusions.

OBJECTIVE: To analyze the effect of bidding of antimicrobial drugs on hospital drugs consumption.METHODS: Based on the classification on drug bidding in 2007,the consumption data of antimicrobial drugs in 2006 in a 3-A grade hospital was analyzed,meanwhile,the price reduction rate,the consumption,the average daily cost and the impact factor of the antimicrobial drugs on the drug bidding list of 2007 were analyzed according to different specification or variety.RESULTS: The varieties winning the bid in 2007 which falls into the varieties winning the bid in 2006 represented 56.48% of all the varieties used in 2006,11 of the top 30 kinds of drugs in terms of consumption in 2006 also won the bid in 2007;accounting for 37.73% in consumption sum.In 2007 compared with 2006,cefamandole,cefodizime,pazufloxacin showed a biggest impact factor,whereas cefodizime and pazufloxacin ranked at the first 2 places in terms of weight impact factor.The proportion of the top 10 drugs in the total on the list of consumption sum remained steady from 2006 to 2007.CONCLUSIONS: The continuous drug bidding has positive meaning for patients,yet the benefit brought about by the drug price reduction is inconspicuous on account of the reduced consumption of the varieties which experienced drug reduction.Drug bidding remains to be improved because the average drug costs for patients haven't been brought down by the drug price reduction.

Herpesviruses is one of the most common human infectious diseases, which can be divided into different types based on clinical infection degree.Herpes simplex virus usually results in buccal and genital mucocutaneous infections, while cytomegalovirus is the most common opportunistic pathogen associated with significant morbidity and mortality in immunocompromised hosts, especially in transplant and cancer patients.Although nucleoside analogues are effective antiviral drugs, the emergence of drug-resistant viruses has created a barrier for the treatment of herpesviruses infections, especially in immunocompromised patients.Therefore, novel therapeutic agents are needed to avoid the limitations of drug resistance.In this article, research progress in the therapeutic agents for drug-resistant herpesviruses was reviewed from the aspects of non-nucleoside analogues, novel antiviral targets and newly antiviral mechanisms.

Objective:To study influence of renal sympathetic denervation (RDN)on cardiac function of dogs with heart failure (HF).Methods:A total of 40 dogs were randomly and equally divided into RDN group [received bilat- eral renal artery radiofrequency ablation (RFA)]and model group (only received femoral puncture).Pacemaker was implanted in every dog,and dog HF model was established using rapid right ventricular pacing.Cardiac and re-nal function indexes,BNP and sympathetic activity index levels were observed and compared between two groups be- fore RFA/sham operation,instant and four weeks after model establishment.Results:After operation four weeks, compared with model group,there were significant reductions in levels of epinephrine (E)[(362.69±42.54)ng/ml vs.(290.36±42.32)ng/ml],renin (R)[(305.46± 39.68)ng/ml vs.(230.04±32.80)ng/ml],aldosterone (AD)[(408.00±38.56)ng/ml vs.(246.00± 48.37)ng/ml],angiotensin Ⅱ (ATⅡ)[(280.00±48.08)pg/ml vs.(172.00±25.04)pg/ml]and norepinephrine (NE)[(425.65±50.54)ng/ml vs.(316.76±46.29)ng/ml]in RDN group (P<0.05 all);there were significant reductions in HR,respiratory rate (RR)and BNP level in RDN group,P<0.05 all;there were significant rise in SBP,LVEF,CO,CI,left ventricular pressure maximal rising rate (+dp/dtmax),left ventricular pressure maximal dropping rate (-dp/dtmax)and left ventricular end-systolic pressure (LVESP),and significant reductions in left ventricular end-systolic dimension (LVESd),left ventricular end-diastolic dimension (LVEDd)and left ventricular end-diastolic pressure (LVEDP)in RDN group,P<0.05 all.Conclusion:RDN can decrease renal sympathetic activity,improve heart function,inhibit myocardial remode- ling,its therapeutic effect is significant

Objective To explore the effect and molecular mechanism of CC chemokine ligand 2 (CCL2) on epithelial-mesenchymal transition in human breast cancer cells.Methods Breast cancer Michigan cancer foundation-7 (MCF-7) cells were treated with 50 ng/ml CCL2.The abilities of invasion were detected by Transwell assay.The expression of epithelial-mesenchymal transition (EMT)-associated markers,E-cadherin and vimentin were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR).The expressions of Snail,protein kinase B (AKT),phosphorylated protein kinase B (p-AKT),phosphorylated glycogen synthase kinase 3β (p-GSK3β3) and GSK3β were detected by Western blot.Snail nuclear localization was detected by immunoflurescence staining.Results We found that CCL2 treatment could induce morphological alteration of MCF-7 cells from epithelial morphology to mesenchymal morphology.CCL2 significantly increased the migration of MCF-7 cells,and increased the expression of mesenchymal maker vimentin and decreased epithelial marker E-cadherin.More important,treatment of CCL2 significantly increased the expression of Snail,and promoted the nuclear localization of Snail.Knockdown of Snail significantly reverse the effects of CCL2 on the EMT in MCF-7 cells.Moreover,treatment of CCL2 significantly increased the phosphorylation levels of p-AKT and p-GSK3β,and AKT inhibitor LY294002 significantly inhibited CCL2-induced Snail and p-GSK3β expression.Conclusion CCL2 might induce EMT in MCF-7 cells,by which mechanism is related to activate AKT/GSK3β Snail pathway.

Objective To explore the role of Cyclin B1 and Cyclin D1 on Barrett esophagus,Barrett's esophagus mixed with atypical dysplasia and esophageal adenocarcinoma.Methods Cyclin B1 and Cyclin D1 were examined with immunohistochemistry.76 esophageal tissues of patients werB collected,including severe reflux esophagitis(RE,25 cases),Barrett esophagus(BE,35 cases),Barrett esophagus mixed with atypical dysplasia(DY,8 cases),esophageal carcinoma(CA,8 cases).Ten cases with normal esophageal mucosa were examined as the control. Results Cyclin B1 and Cyclin D1 were high expression in the specimens of the BE,DY and CA groups and very low expression in the control and RE group.Statistieal difference Was showed(P<0.01).Expression of Cyclin D1 was increasing gradually from the tissues of intestinal metaplasia,atypical dysplasia to adenocarcinoma(50.04 vs 67.94 vs 74.31).There Was significant difference among these three groups(P<0.01).Conclusion Cyclin B1 and Cyclin D1 as markers of tumour development could evaluate the risk from Barrett esophagus to adenocarcinoma.Perhaps it is the earlv event in the development of esophageal carcinoma.

Objective To explore the relationship between the expression levels of excision repair cross complementation group 1(ERCC1), breast cancer susceptibility gene 1(BRCA1), thymidylate synthase (TS) mRNA and clinicopathological features, prognosis in advanced colorectal cancer, and the correlation between the expression levels of ERCC1 and BRCA1. Methods The expression levels of ERCC1, BRCA1 and TS mRNA of postoperative paraffin embedded tissue were tested by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) in 49 advanced colorectal cancer cases. The results were analyzed by χ2 test of the correlation between the expression levels and clinicopathological characteristics. Patients were followed up by clinic or telephone. The prognosis was analyzed by small sample Kaplan-Meier survival analysis and Log-rank time series analysis, and P<0.05 was statistically significant. Results The expression level of ERCC1 mRNA in patients with colorectal carcinoma had no obvious correlation with the clinical and pathological characteristics such as gender, age, tumor location, lymph node metastasis, distant metastasis, CEA and differentiation degree (P>0.05). The expression level of BRCA1 mRNA had no significant correlation with the above clinical and pathological features (P>0.05) except distant metastasis (P=0.030) and differentiation degree (P=0.002). The expression level of TS mRNA had no significant correlation with the above clinical and pathological features (P>0.05) except distant metastasis (P=0.003). The expression level of ERCC1 and BRCA1 mRNA obviously correlated (P=0.002). The 1 year overall survival rate was 95.92%(47/49);the 2 year overall survival rate was 83.67%(41/49);and the 3 year overall survival rate was 73.47%(36/49). Overall survival and progression-free survival time in ERCC1 mRNA low expression group (47.8, 41.0 months) was higher than that in ERCC1 mRNA low expression group (27.3, 20.0 months) respectively (P=0.001, P=0.001). Overall survival and progression-free survival time in BRCA1 mRNA low expression group (43.7, 42.7 months) was higher than that in BRCA1 mRNA high expression group (29.3, 25.1 months) respectively (P=0.009, 0.006). Overall survival time in TS mRNA low expression group (39.8 months) was higher than that in BRCA1 mRNA high expression group (25.2 months). Conclusions The expression level of ERCC1 mRNA is not correlated with its clinical and pathological characteristics, but with its biological characteristics. BRCA1 and TS levels are correlated with invasion and metastasis. Low levels of ERCC1 and BRCA1 expression have a better prognostic effect on platinum based first-line chemotherapy for advanced colorectal cancer, and they are correlated. Low level of TS also has longer disease-free survival. Three joint detection could be used as a prognostic factor for colorectal cancer chemotherapy.

Objective To detect the correlation of serum p53 antibody and p53 protein expression of cancer tissue in patients with colorectal cancer (CRC), and to evaluate if the serum p53 antibody might reflect the mutation of p53 gene in CRC. Methods One hundred and thirty-two patients with CRC and 36 patients with non-tumor disease were included in this prospective study. The presence of serum p53 antibody was determined by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis of tumors was performed to detect the accumulation of p53 protein. Results The positive rate of p53 antibody was 40.2% in patients with colorectal cancer and 2.9% in non-tumor patients,( P