OBJECTIVE:To study the pharmacokinetics and the bioequivalence of mycophenolate mofetil(MMF)dry suspension versus its imported tablets counterpart in healthy volunteers.METHODS:In a randomized two period crossover study,each of the 20 healthy male volunteers received a single oral dose of 0.75 mg dry suspension or imported tablet of MMF.The plasma concentration of mycophenolic acid(MPA),which is the active metabolite of MMF,were determined by HPLC.The pharmacokinetics of MPA were estimated by the non-compartment model and the bioequivalence of the two formulations of MMF were evaluated by ANOVA and two one-sided-test.RESULTS:The main pharmacokinetic parameters of MMF dry suspension versus imported MMF tablet were as follows:t1/2? were(16.80?4.10)and(16.77?4.50)h;tmax were(0.4?0.1)and(0.7?0.4)h;Cmax were(19.29?6.78)and(18.22?7.19)?g?mL-1;AUC0～72 were(39.22?10.43)and(39.38?10.46)?g?h?mL-1,and AUC0～∞ were(40.58?10.49)and(41.00?10.88)?g?h ?mL-1 respectively.The relative bioavailability of the test preparation(dry suspension of MMF)was(100.9?10.6)%.CONCLUSION:The two formulations are bioequivalent in healthy volunteers.

Objective To evaluate the therapeutic effect of thymosin alpha -1 with glucocorticoid in treat-ment of HBV -related hepatic failure.Methods 130 cases were randomly divided into two groups,they were all giv-en antiviral therapy,protect liver,anti -inflammatory,yellow suit the back support,etc.comprehensive treatment;and patients in treatment group were given thymosin alpha -1 with methyl -prednisone intravenously at the early stage of treating process,and then observed the clinic situation and cure rate of those sufferers,The biochemiccal indicator, PTA and blood serum HBV DNA capacity ending with the period of 4 weeks were tested.Results In both groups,the TBil,TC in serum had apparently improved compared with the baseline after the medication,the difference was signifi-cant (t =3.12,P <0.05 and t =3.05,P <0.05).The time of gastrointestinal symptoms improvement and bilirubin subsided time in treatment group were significantly shorter than those of the control group(t =3.34,P <0.01 and t =4.52,P <0.01 ).During the treatment,there was no significant adverse reaction,and there were no differences between two groups in Alt,PTA,HBV DNA,infection,gastrointestinal bleeding,hepatic encephalopathy and hepatore-nal syndrome.The effective rate of treatment group was 75.2%,which was higher than 50.3% of the control group (χ2 =11.02,P <0.01).Conclusion Patients with HBV -related hepatic failure of short -term application of thy-mosin alpha -1 with glucocorticoid treatment,can quickly improve symptoms,greatly improve the efficiency of survival rate,shortem hospitalization period,reduce side effects and enhance security.

Objective The aim of this study is to understand the impairment and compensation mechanism of brain function in untreated primary insomnia (PI) patients.The approach of fractional amplitude of low frequency fluctuation (fALFF) is used to analyze raw data between the PI patients and the normal control group in resting state using functional magnetic resonance imaging (fMRI).Methods Fifty-nine PI patients,admitted to our hospital from November 2015 to November 2016,and 47 age-,education-,and gender-matched normal healthy subjects were chosen in our study.Pittsburg sleep quality index (PSQI),insomnia severity index (ISI) were employed to evaluate the sleep quality.Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were employed to evaluate the emotion.Resting state fMRI and fALFF analyses were used to compare the functional regional activities.The correlations of fALFF data with PSQI,SAS and SDS scores were analyzed.Results In PI patients,2 had mild to moderate insomnia,41 had moderate insomnia,and 16 had serious insomnia.ISI scores in the normal healthy subjects were less than 7.The PSQI,SAS,SDS and ISI scores in the PI patients were significantly higher than those in the normal healthy subjects (P＜0.05).As compared with the control group,the PI group had significantly increased fALFF value in the right hippocampus (HIP),right parahippocampa gyms,right amygdala,and bilateral thalamus.The fALFF value was positively correlated PSQI,SASandSDSscores (r=0.582,P=0.000;r=0.617,P=0.000;r=0.653,P=0.000).Conclusion Some brain regions in the PI patients are abnormal in the resting state,which can reflex functional regional activities of PI patients.

OBJECTIVE To evaluate the cost-effectiveness of apatinib combined with adriamycin in the second-line chemotherapy of platinum-resistant recurrent ovarian cancer （OC） from the perspective of the health system in China. METHODS A three-state partitioned survival model was constructed based on the APPROVE clinical trial and related literature data， with a model simulation time frame of 10 years and a 4-week cycle， and both cost and utility values were discounted using a 5% discount rate. Cost and quality-adjusted life years （QALYs） were used as a model output indicator and the incremental cost-effectiveness ratio （ICER） was calculated to evaluate the cost-effectiveness of apatinib combined with adriamycin versus adriamycin chemotherapy in the second-line treatment of platinum-resistant recurrent OC. One-way sensitivity analysis， probability sensitivity analysis and scenario analysis were used to verify the robustness of the base-case analysis results. RESULTS The results of base-case analysis indicated that compared with chemotherapy alone， ICER of patients receiving apatinib combined with adriamycin was 124 678.25 yuan/QALY， which was less than willingness-to-pay （WTP） threshold set in this study [3 times per capita gross domestic product （GDP） of China in 2022 （257 094 yuan）]. The results of scenario analysis showed that， with the extension of the simulation time limit， the ICER of apatinib combined with adriamycin was gradually reduced， and the decline was gradually reduced， but both were less than WTP threshold. The results of single factor sensitivity analysis showed that the factors that had the greatest impact on ICER were the utility value of progression， body surface area， discount rate，and the cost of best supportive treatment， etc. The results of probability sensitivity analysis showed that under WTP threshold set in this study， the economic probability of apatinib combined with adriamycin was about 99%. CONCLUSIONS From the perspective of China’s health system， using three times the per capita GDP in 2022 as the WTP threshold， the combination of apatinib and adriamycin is more cost-effective than adriamycin alone in second-line chemotherapy for platinum-resistant recurrent OC.