OBJECTIVE:To establish a method for the concentration determination of indigo in rats'plasma,and study the pharmacokinetic characteristics in rats in vivo. METHODS:18 rats were randomly divided into low-dose,medium-dose,high-dose groups,6 in each group,which were intragastrically administrated 10,20,40 mg/kg of indigo solution. The sample blood 0.3 mL was taken from eye socket before administration and 0.083,0.25,0.5,0.75,1,2,4,6,8,10,12,16,24,48,72 h after ad-ministration,separating the plasma,then LC-MS/MS was used to determine the plasma concentration of indigo after methanol pre-cipitation. The column was Agilent Poroshell EC-C18 with mobile phase consisting of methanol-5 mmol/L ammonium acetate solu-tion(95:5,V/V)at a flow rate of 0.4 mL/min;multiple reaction monitoring was conducted for the quantitative analysis,with ion pair of 263.1-218.8 (indigo) and 237.2-194.1 (carbamazepine,internal standard). Pharmacokinetic parameters were calculated by DAS 3.0 software. RESULTS:The linear range of indigo was 0.5-100 ng/mL(r=0.9999),intra-day and inter-day RSDs were low-er than 9%(n=5);matrix effects of low,medium and high does quality control samples were (98.25 ± 3.71)%,(102.23 ± 2.64)%,(102.29±3.79)%(n=5). The pharmacokinetic parameters of indigo in low-dose,medium-dose,high-dose groups were tmax of(8.6±1.1),(9.2±0.8)and(9.5±0.8)h;cmax of(30.9±8.6),(44.9±10.1),(96.1±17.4)ng/mL;t1/2 of(14.9±2.1), (16.3±2.9),(15.3±3.7)h;AUC0-72 h of(366.6±83.4),(694.9±105.8),(1223.42±108.7)ng·h/mL,respectively. CONCLU-SIONS:The method shows high sensitivity,good specificity,and can be used for the content determination of indigo in plasma samples of rats. The pharmacokinetics of indigo in rats in vivo fits non-compartment model.

Aim: To observe the influence of high fat-high sucrose diet and chronic stress on insulin resistance. Methods: Male rats were divided into four groups: control, high fat-high sucrose diet( HFSD), chronic stress( CS), high fat-high sucrose diet plus chronic stress( HFSD + CS). After feeding the animals for 10 weeks, fat, glucose and insulin concentrations in blood and PPAR-α mRNA expression in liver were examined, and glu-cose infusion rate was detected by a hyperinsulinemic euglycemic clamp experiment. Results: Insulin resistance was observed in all three treated groups, showing the highest in the HFSD + CS group. Dyslipidemia, hypergly-cosemia, hyperinsulinism and the decrease of PPAR-α mRNA expression in liver were also shown in all treated groups. There was an obvious interaction of insulin resistance, hyperglycosemia and high FFA between high fat-high sucrose diet and chronic stress. Conclusion: Combination of high fat-high sucrose diet and chronic stress could promote the development of insulin resistance, which is likely due to the high level of serum FFA.

OBJECTIVE To evaluate the cost-effectiveness of adebrelimab combined with chemotherapy versus chemotherapy alone in the first-line treatment of extensive stage small cell lung cancer from Chinese healthcare system perspective. METHODS Using the data obtained from the CAPSTONE-1 trial(230 cases for adebrelimab group, and 232 cases for chemotherapy group), Markov model was created for simulation of the disease development process of the extensive stage small cell lung cancer. The total costs, quality-adjusted life-years(QALYs) and incremental cost-effectiveness ratio(ICER) in each group were calculated. The sensitivity of key parameters was analyzed. RESULTS Compared with pure chemotherapy(etoposide plus carboplatin chemotherapy), the ICER of adebrelimab combined with chemotherapy was 157128.79 yuan·QALY−1 under the situation of charity assistance, and 351367.27 yuan·QALY −1 in the environment of no charity assistance. Sensitivity analysis showed that the utility and the cost of adebrelimab were the main influence parameter. CONCLUSION Adebrelimab combined with chemotherapy regimen has no cost-effective advantage versus chemotherapy alone in the treatment of extensive stage small cell lung cancer under the current economic level of China; the probability of adebrelimab combined with chemotherapy being cost- effectiveness was 44.5% under the situation of charity assistan.