Objective To studyexplore the reversal effect of S-adenosylmethionine(SAM)on chemotherapy resistancechemoresis-tance of pancreatic cancer and explore its related mechanisms.Methods After treatment of human pancreatic cancer resistant cell lines PANC-1/GEM with SAM,the cell proliferation activity of PANC-1/GEM cells and their resistance to gemcitabine(GEM)were ana-lyzed by MTT assay;The the effect of SAM on apoptosis rate of PANC-1/GEM cells was detected by flow cytometry;the change of SAM on the migration activity of drug-resistant cell lines was detected by cell scratch assay;the expression of NEDD4-1 protein in drug-re-sistant cell lines and the changes of NEDD4-1,p-JAK2,p-STAT3 and P-gp protein levels after SAM treatment were detected by Western blot.Results SAM could inhibit the activity of pancreatic cancer PANC-1/GEM resistant cell lines and significantly decreased its resistance to GEM chemotherapy.The IC50 value decreased from 1557.50±201.10nmol/L to 218.39±20.61 nmol/L(P＜0.01);SAM can obviously induced the apoptosis of drug-resistant cell lines and inhibited their migration activity;the expression of NEDD4-1 protein was up-regulated in drug-resistant cell lines,and SAM could inhibit the activation levels of NEDD4-1,p-JAK2,p-STAT3 and P-gp proteins.Conclusion SAM can reduce the chemotherapy resistance of PANC-1/GEM cells to GEM by regulating NEDD4-1 to inhibit the activity of JAK2/STAT3 pathway and regulate the activity of P-gp protein,which provides some experimental evidence for the clinical application of SAM in the treatment of chemotherapy resistance in tumor patients.

Objective: To establish comprehensive laboratory reference intervals for Chinese children. Methods: This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex. Results: In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old. Conclusion This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.