The method of simultaneous administration of several probe substrates is called “Cocktail" approaches. The objective of the article is to review the application of this technique in characterizing the activity of multiple drug-metabolizing enzymes and in clinical researches. This paper also shows Five-drug and Six-drug Cocktail set for evaluating in vivo activity of drug-metabolizing enzymes.

Objective To compare the efficacy of laparoscopic or open surgery for gastrointestinal stromal tumors (GISTs) and investigate effects of different risk level on prognosis.Methods The retrospective cohort study was adopted.The clinical data of 192 patients with GISTs who were admitted to Zhongshan Hospital of Fudan University from January 2008 to December 2013 were collected.Among the 192 patients,88 undergoing laparoscopic surgeries were allocated into the laparoscopic surgery group,104 patients undergoing open surgeries were allocated into the open surgery group.The following indicators were observed:(1) operative status:surgical procedure,operation time,volume of intraoperative blood loss.(2) Status of postoperative recovery:time of gastrointestinal function recovery,time of drainage tube removal,complications and duration of hospital stay.(3) Follow-up status.(4) Prognosis of patients in different risk level.The follow-up using outpatient examination and telephone interview was performed to assess patients' survival,tumor recurrence and metastasis until June 2015.Measurement data with normal distribution were presented as (x) ± s and comparison between groups was evaluated by the t test.Comparison of count data was analyzed by the chi-square test.The Kaplan-Meier method was used to draw survival curve and calculate the overall survival rate and relapse-free survival rate.Results (1) Operative status:of the 88 patients in the laparoscopic surgery group,1 underwent laparoscopic wedge gastrectomy + cholecystectomy + appendectomy,6 underwent laparoscopic wedge gastrectomy + cholecystectomy,14 underwent laparoscopic assisted partial gastrectomy,67 underwent laparoscopic wedge gastrectomy.Of the 104 patients in the open surgery group,1 underwent partial gastrectomy + splenectomy,2 underwent partial gastrectomy combined with distal pancreatectomy + splenectomy,2 underwent total gastrectomy,7 underwent distal subtotal gastrectomy,7 underwent wedge gastrectomy + partial or total adjacent organ resection,8 underwent proximal subtotal gastrectomy,8 underwent wedge gastrectomy + cholecystectomy,69 underwent wedge gastrectomy.The operation time and volume of intraoperative blood loss were (105 ± 33)minutes and (43 ± 16)mL in the laparoscopic surgery group,(121 ± 52)minutes and (199 ± 81) mL in the open group,respectively,with statistically significant differences between the 2 groups (t =-2.104,2.632,P ＜ 0.05).(2) Status of postoperative recovery:the time of gastrointestinal function recovery,time of drainage tube removal and duration of hospital stay were (4.6 ± 1.8) days,(5.8 ± 2.2) days,(7.1 ± 2.9) days in the laparoscopic surgery group and (5.2 ± 1.6) days,(7.1 ± 2.8) days,(8.7 ± 4.3) days in the open surgery group,respectively,with statistically significant differences between the 2 groups (t =-2.783,-3.891,-3.078,P ＜ 0.05).Wound infection,gastric emptying delay,anastomotic leakage,lung infection and bleeding were detected in 1,3,0,0,0 patients in the laparoscopic surgery group and in 0,2,2,2,1 patients in the open surgery group,respectively,with no statistically significant difference between the 2 groups (x2=0.421,P ＞ 0.05).(3) Follow-up status:Of the 192 patients,149 received follow-ups.Of 88 patients in the laparoscopic surgery group,68 were followed up for an average time of 39 months.Of 104 patients in the open surgery group,81 were followed up for an average time of 51 months.During the follow-up,tumor recurrence rate in the laparoscopic surgery group and open surgery group was respectively 8.8％ (6/68) and 21.0％ (17/81),with no statistically significant difference between the 2 groups (x2=1.888,P ＞0.05).Postoperative 1-,3-,5 year survival rates were 98.5％,92.9％,87.4％ and 91.7％,85.2％,76.9％ in the laparoscopic surgery group and open surgery group,respectively,with no statistically significant difference between the 2 groups (x2 =1.967,P ＞ 0.05).(4) Prognosis of patients in different risk level:of the 149 who received the follow-up,the tumor recurrence rate of patients in low,intermediate and high recurrence risk was 7.0％ (5/71),13.6％ (6/44) and 35.3％ (12/34),respectively,with a statistically significant difference among the above indexes (x2 =14.637,P ＜ 0.05),showing statistically significant differences between low risk and high risk patients and between intermediate risk and high risk patients (x2=13.263,6.279,P ＜ 0.05),while no statistically significant difference between low risk and intermediate risk patients (x2 =0.894,P ＞ 0.05).Five-year relapse-free survival rate of low,intermediate and high risk patients was 94.2％,80.0％ and 61.8％ respectively,with a statistically significant difference (x2=13.547,P ＜ 0.05),showing statistically significant differences between low risk and high risk patients,intermediate risk and high risk patients (x2 =4.357,12.336,P ＜ 0.05),while no statistically significant difference between low risk and intermediate risk patients (x2 =0.696,P ＞ 0.05).Conclusions Compared to open resection,laparoscopic GISTs resection offers better short-term outcomes,however,the two surgical techniques offer equal long-term outcomes.Patients of high risk have poor prognosis.

Objective: To establish p53 trancated muteins group and analyse their expression and effects on p53 related downstream genes in HeLa cells. Methods: Using PCR-based site-directed mutagenesis technique, a group of P53 muteins with the N- and/or C-terminals differently trancated were set up. The plasmids with p53 mutein genes were used to transfect HeLa cells, the p53 muteins and some p53 related downstream genes' expression were analyzed by RT-PCR. Results: The p53 muteins were expressed in HeLa cells and they had effects on some of p53 related downstream genes. Conclusion: The P53 muteins may be a good tool to analyze P53 function and has effects on p53 related downstream genes' expression model.

AIM To compare the pharmacokinetics and bioequivalence of between capsule and solution of benzoylmetronidazole. METHODS Ten chinese healthy male volunteers in a randomized 2-way crossover study were given a single oral dose 960 mg capsule(test) and solution (control) respectively. The serum concentrations of metronidazole, one of the metabolites of benzoylmetronidazole, was measured by high performance liquid chromatography. RESULTS The serum concentration-time curves appeared one-compartment open model. The results of the capsule and the solution of benzoylmetronidazole showed that T max (5.10?1.60) h and (3.12?0.90) h; C max (5.32?0.87) mg?L -1 and (6.51?1.25) mg?L -1 ; T 12 (10.56?1.75) h and (10.16?1.65) h; AUC (106.96?19.62) mg?h -1 ?L -1 and (113.59?19.84) mg?h?L -1 . CONCLUTION No significant difference appears in the pharmacokinetic parameters between the two formulations except of T max and C max ( P

Aim To study effects of different dosage regimens of gentamicin(GTM) on impairment of renal functions, plasma concentrations and pharmacokinetics in rats. Method 108 rats were divided into 6 groups: control group; chronological once-daily dose groups (N100 and D100 group, in which 100 mg?kg -1 GTM were intramuscularly administrated at 01 ∶00 or 13 ∶[KG-*3]00 respectively), and chronological twice-daily different dose groups (N90+D10, N70+D30, N50+D50 group, in which 90 mg?kg -1+10 mg?kg -1, 70 mg?kg -1+30 mg?kg -1 and 50 mg?kg -1+50 mg?kg -1 GTM were given at 1:00 and 13:00 respectively). The blood urea nitrogen (BUN) and creatinine (Cr) levels were observed, the plasma concentrations of GTM at 0.25,0.5,1, 2, 5 and 8h were determined, the C-T curves were profiled and the pharmacokinetic parameters were calculated at the 1st, the 10th, and the 20th day of administrations. Results ① Impairment of renal function. At the 10th day of administration, the Cr and BUN levels of N50+D50 group were the highest. There was a significant difference when compared those of the 10th day of administration with those of the 1st day of administration and of control group at same time respectively (P

The concept of epigenetics was first proposed by Waddington in 1942,referring to phenotypic changes that are not related to the underlying DNA sequence,yet alterations in the level and function of gene expression can be heritable,such as DNA methylation,histone modifications,microRNA interference,etc.Phenotype changes while genotype remains unchanged,this controlled mechanism can be kept stable throughout cell division,proliferation,and subsequent process of development.This process thus may cause corresponding changes in the pathophysiology,which are correlated with the occurrence of cancer,immune disorder,cardiovascular disease,metabolic syndrome and so on.Diabetes mellitus is the third heaviest chronic diseases in the world,and does serious harm to human health,especially the diabetic vascular diseases.Even if the blood glucose level is controlled in an ideal state,vascular inflammation still persists,indicating the existence of metabolic memory.Studies have suggested that the pathogenesis can be elucidated at the level of epigenetics.This paper mainly focuses on DNA methylation,histone modifications,and is an overview of epigenetics research progress in diabetic vascular diseases.

To study the effects of astragaloside Ⅳ, which was obtained from Astragalus membranaceus Bge., on myocardiac dynamics and cardiac function on normal and cardiac depressant rat. Methods　Left ventricular pressure (LVP) and differential value of dp/dt were recorded by left ventricular catherization to observe the effect of 1 mg/kg iv astragaloside Ⅳ on normal and cardiac depressant rat induced by iv 0.75 mg/kg of Propanolol. Results　Astragaloside Ⅳ decreased heart rate slightly, and showed inotropic activity by increasing dp/dtmax significantly, with improvement of cardiac diastolic function. It shortened the time constant (T) and caused no obvious change on the tension time index (TTI) in normal rat. These results suggested that astragaloside Ⅳ did not increase cardiac oxygen consumption while exerting its inotropic effect. Conclusion　Astragaloside Ⅳ can improve both cardiac systolic and diastolic functions, and may be used as a candidate for the treatment of cardiac disfunction.

The present study was to estimate pharmacokinetic parameters of metformin hydrochloride in 20 Chinese healthy volunteers with a limited sampling strategy (LSS), which will provide scientific data for bioequivalence and clinical application. A single dose of metformin was administrated to 20 healthy volunteers. The concentration of metformin in whole blood was determined by validated high performance liquid chromatography (HPLC) method. Multi-linear regression analysis was performed to establish a model to estimate AUC(0-24 h) and Cmax of metformin by LSS method. The LSS models were validated by the Jackknife method. The result indicated: the linearity relationship between AUC(0-24 h) or Cmax and single concentration point was poor. Several models for metformin AUC(0-24 h) or Cmax, estimation were better (r2 > 0.9, P < 0.05). Validation tests indicated that most informative sampling points (C2, C6 for AUC(0-24 h), C1.5, C2 for Cmax) provided accurate estimations of these parameters. So, a multi-linear regression model for estimation pharmacokinetic parameters of metformin by using LSS method is feasible.

Aim To analyze THANK gene expression in peripheral blood mononuclear cells(PBMC) stimulated with different stimulators and to clone whole length human THANK gene. Methods PBMC were conventionally isolated and cultured in RPMI1640 containing 10％ FCS. After stimulated with LPS,TNF α ,IL 2,IFN γ ,PHA or PMA,the THANK gene expression in PBMCs was analyzed by RT PCR and THANK cDNA was cloned. Result RT PCR detection showed that THNAK gene expressed in PBMCs after stimulated with interferon γ for 3 days, whereas THANK'expression could not be detected after stimulated with LPS,TNF α ,IL 2,IFN γ ,PHA or PMA respectively. Then THANK gene was cloned by cloning PCR product and sequenced. Conclusion Human THANK gene is cloned successfully, thus providing the possibility for further research of THANK'function.

Object To study the effects of astragaloside Ⅳ, which was obtained from Astragalus membranaceus Bge., on myocardiac dynamics and cardiac function on normal and cardiac depressant rat Methods Left ventricular pressure (LVP) and differential value of dp/dt were recorded by left ventricular catherization to observe the effect of 1 mg/kg iv astragaloside Ⅳ on normal and cardiac depressant rat induced by iv 0 75 mg/kg of Propanolol Results Astragaloside Ⅳ decreased heart rate slightly, and showed inotropic activity by increasing dp/dt max significantly, with improvement of cardiac diastolic function It shortened the time constant (T) and caused no obvious change on the tension time index (TTI) in normal rat These results suggested that astragaloside Ⅳ did not increase cardiac oxygen consumption while exerting its inotropic effect Conclusion Astragaloside Ⅳ can improve both cardiac systolic and diastolic functions, and may be used as a candidate for the treatment of cardiac disfunction