1.Preparation and evaluation of doxorubicin hydrochloride liposomes modified by poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate.
Di ZHANG ; Jianying LI ; Xiaochan WANG ; Hongxin YUE ; Meina HU ; Xiu YU ; Huan XU
Acta Pharmaceutica Sinica 2015;50(9):1174-9
In this study, the buffering capacity of amphiphilic pH-sensitivity copolymer poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (PEOZ-CHMC) was evaluated. The ammonium sulfate gradient method was used to prepare doxorubicin hydrochloride (DOX x HCl)-loaded liposomes (DOX-L), and then the post-insertion method was used to prepare PEOZ-CHMC and polyethylene glycol-distearoyl phosphatidyl ethanolamine (PEG-DSPE) modified DOX x HCl-loaded liposomes (PEOZ-DOX-L and PEG-DOX-L). The physico-chemical properties, in vitro drugs release behavior, cellular toxicity and intracellular delivery of liposomes were evaluated, separately. The results showed that PEOZ-CHMC has a satisfactory buffering capacity. The sephadex G-50 column centrifugation method and dynamic light scattering were used to determine the encapsulation efficiency (EE) and particle size of liposomes. The EE and particle size of DOX-L were (97.3 ± 1.4) % and 120 nm, respectively, and the addition of PEOZ-CHMC or PEG-DSPE had no influence on EE and particle size. The zeta potentials of three kinds of liposomes were negative. The release behavior of various DOX liposomes in vitro was investigated by dialysis method. In phosphate buffer solution (PBS) at pH 7.4, DOX x HCl was released from PEOZ-DOX-L in a sustained manner. While in PBS at pH 5.0, the release rate of DOX x HCl from PEOZ-DOX-L increased significantly, which suggested DOX x HCl was released from PEOZ-DOX-L in a pH-dependent manner. The intracellular delivery of liposomes was investigated by confocal laser scanning microscopy (CLSM). The CLSM images indicated that PEOZ-DOX-L showed efficient intracellular trafficking including endosomal escape and release DOX x HCl into nucleus, as well as the DOX-L and PEG-DOX-L had no this effect. The cytotoxicity of liposomes against MCF-7 cells was detected by using MTT assay. The results showed that antiproliferative effects of PEOZ-DOX-L enhanced with pH value decreased, whereas DOX-L and PEG-DOX-L did not have any significant difference in inhibitions at different pH conditions. Therefore, the problems of the inhibition of cellular uptake of liposomes and the failed endosomal escape of pH-sensitive liposomes by PEG chain can be overcome by the pH-sensitive liposomes constructed by PEOZ-CHMC.
2.Epidemiological survey of common enterovirus infections among children in Hangzhou ,2016
Jun ZHOU ; Yidong WU ; Meina YUE ; Di LIU ; Xiaoyu LI ; Xinfeng ZHAO
Chinese Journal of Infectious Diseases 2018;36(3):160-163
Objective To investigate the prevalence of common enterovirus infections among children in Hangzhou ,2016 .Methods A total of 2977 of throat swabs samples or stool samples from suspected children with enterovirus infection at Hangzhou Children′s Hospital in 2016 were collected . Enterovirus universal nucleic acid ,enterovirus type 71 (EV71) ,Coxsackievirus A (CoxA)16 ,CoxA6 , CoxA4 and CoxA10 were detected by real-time fluorescent quantitative polyoneras chain reaction .The detection positive rates among children with different genders and ages were compared by χ2 test .Results The total enterovirus positive rate of 2977 specimens was 49 .7% (1480/2977) .Among them ,CoxA6 , EV71 ,CoxA16 ,CoxA4 ,CoxA10 and other enteroviruses accounted for 30 .2% (447) ,19% (281) , 10 .2% (151) ,6 .8% (101) ,3 .4% (51) and 30 .3% (449) ,respectively .Among 1480 enterovirus positive children ,882 cases were male and 598 were female ,with no statistical significance (χ2 = 4 .564 , P=0 .471) .The detection rates of enterovirus in children with hand ,foot and mouth disease (HFMD ) , herpangina and other diseases were 64 .4% (1051/1632) ,52 .4% (323/616) and 14 .5% (106/729) , respectively .The difference among groups was significant (χ2 =503 .387 , P<0 .01) .The prevalences of CoxA6 ,EV71 and CoxA16 in enterovirus-positive HFMD children were 36 .7% (386) ,25 .3% (266) and 12 .4% (130 ) , respectively . The prevalences of CoxA4 , CoxA6 and CoxA10 in enterovirus-positive herpangina children were 20 .1% (65 ) , 14 .9% (48 ) and 8 .7% (28) , respectively , and those of entrovirus ,CoxA4 and CoxA6 in other enterovirus-positive specimens were 59 .4% (63) ,14 .2% (15) and 12 .3% (13 ) , respectively . The enterovirus constituent ratios among children with HFMD , herpangina and other diseases was statistically different (χ2 =399 .758 ,P<0 .01) .The positive rates of enterovirus among different age groups were statistically different (χ2 = 142 .899 , P< 0 .01 );the constituent ratios of enterovirus among different age groups were also statistically different (χ2=106 .160 , P<0 .01) .Conclusion The enterovirus detection rate of CoxA6 is highest ,followed by EV71 and CoxA16 among children in Hangzhou ,2016 .
3.Correlation between single nucleotide polymorphisms of ERα gene and bone loss associated with aromatase inhibitors in postmenopausal women with breast cancer
Yulian YIN ; Weihong ZHANG ; Yue ZHOU ; Meina YE ; Hongfeng CHEN
Practical Oncology Journal 2018;32(1):14-18
Objective The aim of this study was to explore the correlation between postoperative aromatase inhibitor(AIs) -based bone metabolism and ERα gene rs9340799,rs2234693 single nucleotide polymorphisms(SNPs)in breast cancer.Methods One hundred and sixty-six breast cancer patients who underwent AIs treatment(≤2 years)were enrolled and hospitalized in our hospital from October 2015 to April 2017.The ERα gene rs9340799 and rs2234693 sites were sequenced and compared subtype of lumbar spine and femur,bone mineral density BMD value and the relationship between BMD value and T value.Results The BMD of lumbar spine in patients with ERα gene rs9340799 was significantly different when compared to those of A/A,A/G and G/G(P<0.01).The BMD of lumbar spine in patients with A/A and A/G genotypes were significantly higher than those in G/G genotypes(P<0.05).The BMD of lumbar spine in patients with ERα gene rs2234693 was significantly different when compared to those of T/T,T/C and C/C(P<0.01). The BMD of lumbar spine in patients with T/T and C/T genotypes were significantly higher than those in C/C genotypes(P<0.05). However,there was no difference in femoral BMD,lumbar spine,and femur T between the 2 subtypes of patients with genotypes(P>0.05).Conclusion Aromatase inhibitor-related bone loss(AIBL)may be related to ERα gene phenotype.In ERα gene rs9340799 and rs2234693 loci,C and G alleles may be susceptible genes for aromatase inhibitor-related bone loss(AIBL).