Population pharmacokinetics(PPK),which is based on the principle of statistics,can be used to estimate various inter- and intra-individual factors which affect pharmacokinetics.By using Bayesian estimator,PPK can predict individual pharmacokinetic parameters accurately.PPK is widely used in the immunosuppressive therapy with cyclosporine,tacrolimus,mycophenolic acid and sirolimus.

The incidence of cholangiocarcinoma is rising, poor prognosis due to lack of viable treatment.Recent investigations into the underlying molecular mechanisms of cholangiocarcinogenesis and tumor growth have contributed greatly to our understanding of this disease, which will lead to the identification of therapeutic targets for this devastating cancer. The purpose of the following review is to address what has been learned over the past decade concerning the molecular basis of cholangiocarcinogenesis and factors regulating cholangiocarcinoma growth. Through a better understanding of these mechanisms, more specific diagnostic, therapeutic, and preventative strategies may be developed and hopefully improve the outcome of this devastating disease.

Objective To research the reversal the effect on multidrug resistance (MDR) and the effect on Ca~(2+) concentration of HL60/HT cell by psoralen, and observe its possible mechanism. Methods The cytotoxic effect of chemotherapeutic agents was determined by MTT assay, intracellular harringtonine (HT) content was assayed by HPLC, and intracellular Ca 2+ concentration in different periods and at different time points was detected by laser confocal microscope. Results Psoralen could reduce IC_ 50 value of HT to HL60/HT cells and increase HT content in cells in different degrees at the doses of 1-20 ?mol/L. Psoralen could influence Ca 2+ concentration with negative correlation at different time points (24, 48, and 96 h) at the doses of 1-20 ?mol/L, and influence Ca 2+ concentration with negative correlation at different times (5, 10, 15, 20, and 25 min) in the doses of 10 and 20 ?mol/L. Conclusion Psoralen can reverse MDR of HL60/HT cells, its reversal mechanism is associated with influence of intracellular Ca~(2+) concentration and the increase of intracellular accumulation of HT.

OBJECTIVE: To prepare and verify honokiol-hydroxypropyl-β-cyclodextrin inclusion complex (HK-HPCD). METHODS: HK-HPCD was prepared by the stirring method. The main factors affecting the inclusion rate were studied by single factor analysis and the optimum procedure for preparation was selected by central composite design. The inclusion complex was verified by differential scanning calorimetry (DSC) and infrared spectra. RESULTS: The optimum preparation process parameters were as follows: the molar ratio of honokiol to HP-β-CD was 1:5, the reaction temperature was 50°C and the reaction time was 3 h. CONCLUSION: Stable complex can be formed between honokiol and HP-B-CD, and the solubility of honokiol is increased by HP-B-CD significantly.

Objective To summarize the experience of perioperatively nursing patients with Hirschsprung’s disease after laparoscopic-assisted improved Soave operation to improve nursing experience.Method Psychological nursing to both patients and their families,well-planned preoperative preparation,postoperative nutritional support and perineal nursing were done.Result Sixty-six patients got recovered and discharged except one who quitted treatment.Conclusion Careful nursing before and after operation is critical for the prevention of complications and successful manipulation of aparoscopic-assisted improved Soave operation.

Objective To investigate the effect of ulinastatin on postoperative cardiac troponin I ( cTnI) in patients underwent carotid endarterectomy ( CEA) under general anesthesia. Methods Forty patients with severe symptomatic carotid artery stenosis underwent unilateral CEA under general anesthesia from January 2011 to March 2012 were divided into either a ulinastatin group or a control group according to a random number table ( n=20 in each group) . Patients in the ulinastatin group received 500 000 U of ulinastatin via veins before induction of anesthesia. The patients in the control group were given the same amount of isotonic saline. The serum concentrations of cardiac troponin I ( cTnI ) were detected before surgery and at day 1,2,and 3 after procedure. Myocardial injury was defined as the cTnI peak concentration>0. 04μg/L . Results The levels of serum cTnI before procedure and at day 1,2,and 3 after procedure in the ulinastatin group were median (M) 0. 00 (0. 00-0. 03) μg/L,0. 07 (0. 00-1. 45) μg/L,0. 01 (0. 00-1. 21)μg/L,and 0. 05 (0. 00-0. 89)μg/L,respectively;those in the control group were 0. 00 (0. 00-0. 01)μg/L,0. 00 (0. 00-1. 42)μg/L,0. 00 (0. 00-1. 39)μg/L,and 0. 00 (0. 00-1. 24)μg/L, respectively. At day 1 after procedure,6 patients ( 30%) in the control group and 11 ( 55%) in the ulinastatin group occurred myocardial injury. There was no significant difference between the two groups (P<0. 05). In all the patients with the increased cTnI levels,the peak cTnI occurred at the first day after procedure,however,they did not reach the level ( >1. 5μg/L) of indicating patients occurring myocardial infarction. Conclusion Ulinastatin may not decrease the postoperative serum cTnI levels in CEA patients under general anesthesia. For whether to the CEA patients have myocardial protective effect,more samples are needed to be confirmed.

Objective To evaluate the immunomodulatory effect of Haishen-Xiyangshen-Gouqizi Koufuye(HXGK),an oral liquid of healthy food product,on the immunocompromised mouse model. Methods The cytotoxicity was assayed by the MTT method using murine monocyte macrophagse Raw264.7 cells. The in vitro phagocytic activity of RAW264.7 cells was assayed by the colorimet-ric neutral red phagocytosis test. In the in vivo mouse test,animals were randomized into six groups,each with ten mice:the normal control,model control,positive control groups and three HXGK(5,10,and 20 ml/kg)test groups. The immunocompromised mouse model was created by the intraperitoneal injection of 40 mg/kg dexamethasone once every other day for a total of five times. After first time injection of dexamethasone,the normal control(without the dexamethasone injection)and model control groups were adminis-tered orally once a day with saline,the positive control group with 25 mg/kg levamisole,and the three test groups with 5,10 and 20 ml/kg HXGK,respectively,for a total of 21 days. Then the carbon particle clearance index,the spleen and thymus indices,and the leukocytes,lymphocytes,IgG and IgA in peripheral blood were measured respectively. Results Compared with the normal control, HXGK significantly enhanced the phagocytic index of RAW264.7 cells from 1.00 to 1.12(P<0.01)and 1.32(P<0.01)at the 100-and 20-fold diluted dosages,respectively,in the in vitro neutral red phagocytosis test. In the in vivo mouse test,compared with the model control group,HXGK at the doses of 5,10 and 20 ml/kg obviously increased the carbon particle clearance index about 1.8(P<0.01),1.5(P<0.05)and 1.7-fold(P<0.05)and improved the spleen index from 1.60 to 2.96(P<0.01),2.56(P<0.01)and 2.32(P<0.05),the thymus index from 1.31 to 1.46,1.59(P<0.05)and 1.71(P<0.05),respectively. Meanwhile,HXGH at the 5,10 and 20 ml/kg dosages also increased the leukocytes about 1.32,1.75(P<0.05)and 1.46 folds(P<0.05),the lymphocytes about 16 (P<0.01),20(P<0.01)and 19 folds(P<0.01),the IgG level about 19%,57%(P<0.01)and 64%(P<0.05),and the IgA lev-el about 65%(P<0.01),47%(P<0.05)and 44%(P<0.01),all in the peripheral blood respectively. Conclusion HXGH could significantly enhance the immune function of the immunocompromised mice.

Objective To investigate the relationship between hepatitis B virus (HBV) infection and hepatic metastasis from colorectal cancer.Methods Published literatures and unpublished conference papers from January 1990 to December 2011 were searched in PubMed,Cochrane library,Wanfang Database and CNKI.Data of the literatures were extracted by a table.All the patients with colorectal cancer were divided into the infected group and the control group according to the patients whether infected by HBV or not.The hepatic metastatic rate was analyzed.The Meta analysis was carried out by using the Review Manager 5.0 software,and the heterogeneity between studies was analyzed using the I2.Random effect regression model or fixed effects regression model was used according to the P value.The funnel plot was drawn to assess the potential for publication bias.The count data were presented by odds ratio (OR) and 95％ confidence intervals (95％ CI).Results Fifty-six articles were retrieved,and 11 of which met the criteria.The number of patients with colorectal cancer was 5622,and 924 were in the infected group,4698 in the control group.There was no statistical difference in the heterogeneity between all the articles (I2 =0,df=10,P ＞ 0.05).The hepatic metastatic rate was 10.61％ (98/924) in the infected group,which was significantly lower than 23.84％ (1120/4698) of the control group (OR =0.35,P ＜ 0.05).The funnel plot showed that there was no obvious publication bias in these studies.Conclusion Patients with colorectal cancer and infected by HBV have lower incidence of hepatic metastasis.

AIM　To establish an allele specific PCR amplification (ASA-PCR) for determination of the genotype of CYP2D6*10B polymorphism in Chinese subjects. METHODS　CYP2D6*10B alleles of 65 healthy Chinese subjects were analyzed by a two-step PCR assay and the correlation of genotype and phenotype was studied. RESULTS　There were 20 CYP2D6*10B heterozygous genotypes subjects (wt/m) in 35 very extensive metabolizers (VEMs), which consisted the major part of VEM subjects (57%). Meanwhile, 20 subjects consisting 69% of 29 intermediate metabolizers were CYP2D6*10B homozygous mutant genotypes (m/m). The poor metabolizer was also m/m. The metabolic ratio of CYP2D6*10B m/m subjects were larger than wt/m and wild type, the values were -1.49±0.54, -2.20±0.49 and -2.47±0.61 (P<0.01). CONCLUSION　PCR-ASA was shown to be a rapid and specific method. It can be used to study the genetic polymorphism, especially CYP2D6 intermediate metabolism.

Cancer of digestive system is one of the most common worldwidely cancers and seriously threats to human health. However its etiology and pathogenesis are still not clear. Toll-like receptor (TLR), a newly discovered transmembrane receptor, plays an important role in innate immunity. Recent researches suggested that TLRs had extensive relationship with inflammation, autoimmune diseases and cancer. A large number of researches indicated that TLRs not only participated in the occurrence, development and immune escape of cancer, but also acted in immunotherapy in digestive system. Further investigation of TLRs may re-veal the effects of TLRs in the development of malignant tumors of digestive system, moreover may find new therputic target for the treatment of cancers. We reviewed the relationship between TLRs and cancers of di-gestive system.