1.The association between resistance phenotypes and expression levels of efflux pumps of Pseudomonas aeruginosa
Yongfang LIU ; Xiaoju Lü ; Zhiyong ZONG ; Rujia YU ; Yanyu GAO ; Huili CHEN ; Xiaofang LI ; Sheng JIANG ; Qiangua HAN
Chinese Journal of Laboratory Medicine 2008;31(9):979-983
Objective To study the effects of efflux pump inhibitors(CCCP and PAβN)on carbapenems in Pseudomonas aernginosa(P.aeruginosa)clinical isolates and investigate the association between the resistance to imipenem or meropenem and expression levels of efflux pumps of P.aeruginosa.Methods MICs of imipenem or meropenem combined with efflux pump inhibitors including carbonyl cyanide m-chlorophenylhydrazone(CCCP,107 strains)and Phe-Arg-β-naphthylamide(PAβN,71 strains)against imipenem-resistant strains were determined by agar dilution method,and changes of MICs were observed.For 32 strains with different resistant phenotypes to imipenem and meropenem,the mRNA expression levels of three efflux pump genes(mexA,mexD and mexF)were quantified by real time fluorescent quantitative PCR.Results The resistance rate of imipenem and meropenem didn't prove any significant difference in the presence of efflux pump inhibitors.The X2 value of imipenem combined with CCCP and PAβN were 0.338 and 0.086,respectively(P>0.05),while that of meropenem combined with CCCP and PAβN were 1.065 and 1.458(P>0.05).No significant in MICs of carbapenems were seen in over half of P. aeruginesa isolates. MICs of carbapenems was significantly downregulated for 4-fold or above in eight isolates. Overexpression of efflux pumps genes were present in 24 of 27 carbapenem-resistant isolates(88. 9% ). Efflux pumps genes including MexAB-OprM, MexCD-OprJ and MexEF-OprN were all overexpressed in 13 isolates,constituting 54. 2% of all carbapenem-resistant isolates. There were 3 isolates in which beth MexAB-OprM and MexCD-OprJ showed overexpression,constituting 12. 5%. Also,MexAB-OprM and MexEF-OprN overexpressed in 3 isolates. There were 2 isolates (8.3%) showing MexEF-OprN overexpression and MexAB-OprM alone. MexCD-OprJ didn't showed overexpression alone. Furthermore,the expression levels of efflux pumps genes mexA,mexD and mexF in isolates susceptible to both in imipenem and meropenem were 0. 48±0. 48,0. 48±0. 53 and 0. 30±0. 41,respectively,which were much lower than that in carbapenem-resistant ones (P<0. 05 ). MexA gene was expressed at a higher level in meropenemresistant isolates than meropenem-susceptible ones (P<0. 05 ). Conclusions When the concentration of CCCP and PAβN were 5 μg/ml and 20 μg/ml respectively,the efforts on the carhapenems resistance of P.aeruginosa were small Overexpression of MexAB-OprM might play an important role in meropenemresistance in P. aerugines. Overexpression of MexCD-OprJ and MexEF-OprN was associated with imipenemresistance. However,the relationship between them and meropenem-resistance need to be explored in the future.
2.Genotoxicity evaluation of triptolide
Yijun TIAN ; Yiwen ZHENG ; Yuping ZHU ; Xiaofang ZHANG ; Ying ZONG ; Guocai LU
Journal of Pharmaceutical Practice 2016;34(3):215-218
Objective To study the genotoxicity of triptolide ,an important active component of Tripterygium wilfordii Hook f .Methods Ames test ,in vitro chromosomal aberration test of CHO cell and in vivo micronucleus assay were per-formed to investigate the genotoxicity of triptolide .Results The Ames test showed that triptolide did not increase mutagenicity for TA97 ,TA98 ,TA100 ,TA102 and TA1535 strains at the dosage of 1 .6~1000 μg per plate with and without metabolic ac-tivation system S9 .Results of in vitro CHO cell chromosomal aberration test indicated that there was no statistical difference between the triptolide groups (doses of 0 .01 ,0 .02 and 0 .04 μg/ml) and the solvent control group with and without metabolic activation system S9 .However ,triptolide significantly increased polychromatophilic erythrocyte micronucleus formation at the dosage of 720 μg/kg in ICR mice .Conclusion Triptolide did not induce genetic toxicity based on the Ames test and chromo-somal aberration test ,but could increase micronucleus formation at the dosage of 720 μg/kg .These results indicated that trip-tolide may have potential genotoxicity on human health .
3.Practice on the construction of Introduction to Hearing and Speech Rehabilitation and the teaching model of bisection combined with flipped classroom
Xiaofang ZONG ; Houyong KANG ; Yan LEI ; Bing LI
Chinese Journal of Medical Education Research 2023;22(7):983-986
This study investigates the application effect of bisection combined with flipped classroom in the teaching of the course Introduction to Hearing and Speech Rehabilitation. A total of 74 students majoring in hearing and speech rehabilitation in the classes of 2019 and 2020 were selected as research subjects, and flipped classroom was applied in the teaching of the course Introduction to Hearing and Speech Rehabilitation. A questionnaire survey was conducted to compare the difference between traditional teaching model and flipped classroom in improving the comprehensive abilities of students. Research findings show that the teaching model of bisection combined with flipped classroom can significantly improve the abilities of self-expression, creative thinking, teamwork, and interpersonal communication among students, and there was no significant difference in improving learning enthusiasm between the two teaching models.
4.Progress in pathophysiology and related drug development of hypoxia-inducible factor-1
Shijie FENG ; Xiujuan MA ; Ying ZONG ; Yu MAO ; Xiaodong ZHANG ; Xuelian GONG ; Xiaofang ZHANG ; Guocai LU
Journal of Pharmaceutical Practice 2014;(3):161-166
Hypoxia-inducible factor-1 (HIF-1) is a critical nuclear transcriptional factor mediating cell adaptive response to hypoxia in mammalian and human .It is the key mediator which modulates oxygen homeostasis exclusively .In the one hand , HIF-1 can protect and promote kinds of physiological processes , such as embryo normal development , cartilage and bone formation .In the other hand, it is also involved in lots of human deceases which is caused by ischemia and hypoxia , such as tumor, diabetes and its complica-tions.The molecular mechanisms of HIF-1 involved in these diseases have become a research hotspot and such studies will provide the new therapeutic means for these diseases , recent new drug researches have been focused on HIF-1 related signal pathway inhibitors , HIF-1 activity inhibitors, HIF-1 targeted therapy, etc.
5.Repeat-dose toxicity study of fibrin sealant in SD rats
Xiaoyu DAI ; Hai ZHU ; Xiaodong ZHANG ; Xiaofang ZHANG ; Ying ZONG ; Yimin DAI ; Shuying ZHANG ; Bojun YUAN ; Guocai LU
Journal of Pharmaceutical Practice 2015;(3):231-234
Objective To evaluate the safety of fibrin sealant (FS) intraperitoneal injection in SD rats .Methods 80 male and female SD rats were randomly divided into four groups (0 ,85.5 ,171 .0 ,342 .0 mg/kg) by body weight .All rats were in-traperitoneally injected with vehicle or FS daily for 14 days followed by a 28-day recovery period .The clinical signs ,hematolog-ical and biochemical indices were measured .The pathology were observed .Results Increase of white blood cell count (WBC) and decrease of fibrinogen (FIB) in d 14 were found in 171 .0 mg/kg and 342 .0 mg/kg dosage groups .Furthermore ,the tend-ency of weight increase of spleen were found in 171 .0 mg/kg and 342 .0 mg/kg dosage groups .Pathological exams of peritoneal cavity found that there were granulation tissues containing FS in some of the rats in 342 .0 mg/kg group .All of these changes got reversed after the recovery period .Conclusion The safety dose in this study is considered to be 85.5 mg/kg ,and the toxic-ity dose is 171 .0 mg/kg .The target toxicity systems or site of FS in SD rats are hematological system ,immune system and in-jection site .The toxic effects of FS are reversible .