OBJECTIVE:To prepare redox-responsive pluronic F127 micelles with high drug-loading efficiency. METHODS:The thiol derivative F127-SH with strong hydrophobicity was synthesized by introducing tert-butyl methacrylate and cysteamine to the hydrophobic segments of F127. Paclitaxel (PTX)-loaded redox-responsive pluronic F127 micelles with high drug-loading effi-ciency(F127-SS/PTX)were prepared by film-hydration method as well as oxidation reaction of thiol groups. The diameter,encap-sulation efficiency and drug-loading amount were detected,and the change of diameter and drug release behavior of micelles were investaged under reducing environment or non-reducing environment. RESULTS:Mean diameter of F127-SS/PTX micelles was about(77.87±1.79)nm,and encapsulation efficiency and drug-loading amount were(92.73±2.35)% and(16.25±0.99)%,re-spectively. The diameter of the micelles increased rapidly and drug release rate of PTX increased significantly in the presence of 10 mmol/L dithiothreitol. CONCLUSIONS:The redox-responsive pluronic F127 micelles with high drug-loading efficiency are pre-pared successfully.

OBJECTIVE:To evaluate the association between UGT1A1 gene polymorphism and irinotecan-induced 3-4 degree neutropenia,and to provide evidenced-based reference for clinical treatment. METHODS:Retrieved from CJFD,Wanfang data-base,VIP,PubMed,EMBase,Science direct and Cochrane library,related studies about UGT1A1*28 and UGT1A1*6 gene polymorphism and irinotecan-induced 3-4 degree neutropenia were collected. After data extraction and quality evaluation of included studies,Meta-analysis was conducted by using Review Man 5.3 software. RESULTS:A total of 29 studies were included,involv-ing 2408 patients. UGT1A1*28 includ wild genotype TA 6/6(UGT1A1*1/*1)and mutations genotype TA 6/7(UGT1A1*1/*28)、TA 7/7(UGT1A1*28/*28),UGT1A1*6 includ wild genotype GG and mutations genotype GA、AA. Results of Meta-analysis showed:the incidence of 3-4 degree neutropenia in UGT1A1*28 and UGT1A1*6 mutations genotype were significantly higher than wild genotype,with statistical significance [UGT1A1*28:OR=1.92,95%CI(1.52,2.44),P<0.001;UGT1A1*6:OR=2.49, 95%CI(1.46,4.26),P<0.001]. Using medium-dose and high-dose of irinotecan,the incidence of 3-4 degree neutropenia in UGT1A1*28 and UGT1A1*6 mutations genotype were significantly higher than wild genotype,with statistical significance [UGT1A1*28:OR=2.06,95%CI(1.57,2.70),P<0.001);UGT1A1*6:OR=1.92,95%CI(1.35,2.74),P<0.001]. Using low-dose of irinotecan,there was no statistical significance in the incidence of 3-4 degree neutropenia between UGT1A1*28,UGT1A1*6 mutations genotype and wild genotype [UGT1A1*28:OR=1.20,95%CI(0.70,2.08),P=0.51;UGT1A1*6:OR=3.19,95%CI (0.85,11.89),P=0.08]. CONCLUSIONS:Using medium-dose and high-dose of irinotecan,UGT1A1*28 and UGT1A1*6 muta-tions will increase the risk of severe neutropenia in cancer patients. Using low-dose of irinotecan,there is no clear correlation be-tween gene polymorphism and the neutropenia.

Objective The objective of this study was to investigate the relationship between the methylation of phosphodies-terase 4C(PDE4C)gene in peripheral blood leukocytes,and its interaction with environmental factors and the pathogenesis of breast cancer. Methods A case-control study was conducted to select 402 cases of breast cancer and 470 cancer-free controls from Octo-ber 2010 to December 2014. The specific DNA methylation-modified quantitative PCR method was used to detect the methylation of PDE4C gene. The use of crossover analysis and multivariate logistic regression was used to analyze the relationship between the level of gene methylation and its interaction with environmental factors and the pathogenesis of breast cancer. Results PDE4C methylation was not found to be significantly associated with the onset of breast cancer. High-frequency/high-intake of whole grains,vegetables, onion-based plants,poultry,milk,and regular exercise could reduce the risk of breast cancer;high-frequency/high-intake of pork, irregular menstrual cycle,and a high psychological stress index could increase the risk of breast cancer. PDE4C hypermethylation had a significant combining effect with edible onion-producing plants greater than 3 times/week,with an OR of 0. 373(95% CI:0. 208~0. 668,P=0. 001). Conclusion Hypermethylation of PDE4C is not an independent risk factor for breast cancer,and its combination with environmental factors affects the risk of breast cancer.