1.Pharmacogenetic research in the association between human leukocyte antigen and adverse drug reactions
Yan XIONG ; Wei ZHANG ; Xiaoping CHEN
Journal of Central South University(Medical Sciences) 2014;(7):749-757
With the rapid development of pharmacogenetics, more and more studies have shown evidence in the association between polymorphisms at the human leukocyte antigen (HLA) loci and severe adverse drug reactions (SADRs). Several HLA-B alleles proved to be associated with SADRs for drugs such as carbamazepine, allopurinol, lamotrigine, and lfucloxacillin. hTe USA Food and Drug Administration (FDA) has even recommended routine screening for HLA-B allele before the use of abacavir and carbamazepine. With the completion of human genome project and the Hapmapproject, several new pharmacogenetics approaches such as genome-wide association study (GWAS) have emerged. hTese newly developed methods will undoubtedly accelerate the identiifcation and clinical utilization of the pharmacogenetic biomakers. In addition, the immunogenetic mechanisms by which the HLA alleles cause SADRs are explored at the cellular and molecular level. hTis review focuses on the recent progresses in HLA alleles and ADRs regarding both the clinical translation and modern pharmacogenetic methods.
2.Vesicoureteral reflux caused by benign prostatic hyperplasia
Weimin CHEN ; Lishen XIONG ; Qing ZHANG
Chinese Journal of Urology 2001;0(06):-
Objective To study the correlation between benign prostatic hyperplasia (BPH) and vesicoureteral reflux (VUR). Methods Intravenous radionuclide cystography (IVRC) was performed on 88 BPH patients and micturition cystourethrography on 30 to find if there was any VUR and the degree of reflux. Results 31 patients had VUR of which there were 6 grade Ⅰ,7 grade Ⅱ,6 grade Ⅲ,6 grade Ⅳ and 6 grade Ⅴ.9 were on the right,6 on the left and 16 bilateral. Conclusions VUR do occur in some BPH patients and IVRC is the better method for its diagnosis and evaluation.
3.Soluble expression and characterization of mouse lactate dehydrogenase-C4 in Escherichia coli
Duo ZHANG ; Yongzhong XIONG ; Ping CHEN
Medical Journal of Chinese People's Liberation Army 1983;0(02):-
Objective A prokaryotic expression vector was constructed by inserting the coding sequence of mouse sperm specific lactate dehydrogenase C into pET-28a(+)and the recombinant mLDHC44 protein was purified by Ni+-NTA agrose.Methods The cDNA of mouse sperm specific lactate dehydrogenase C was obtained by RT-PCR,with total RNA of mouse testis tissues as templates.The coding sequence of mouse LDHC4 was amplified by PCR with specific primers.This recombinant vector was transformed into Escherichia coli BL21(DE3).The recombinant mLDHC4 protein was induced by isopropy-?-D-thiogalactoside(IPTG)and identified by sodium dodecyl sulfate polyacrylamide electrophoresis and LDH activity determination.After purified with Ni+-NTA agrose,the mLDHC4 protein was probed with antisera from the pVAX1-mLDHC4 vaccine(the eukaryotic expression vector of mouse sperm specific lactate dehydrogenase C)immunized BALB/c mice by Western blot analysis.Results After digested with BamH I-EcoR I,the recombinant plasmids produced right fragment which was about 1000bp.Sequencing showed that the sequence of the cloned fragment was in agreement with sequence in GenBank.This recombinant vector was named as pET-28a(+)-mLDHC4.With induction of IPTG,The recombinant protein with molecular weight of about 35 kD was expressed and the enzyme activity of this protein was high.After purified with Ni+-NTA agrose,this mLDHC4 protein formed a specific band by sodium dodecyl sulfate polyacrylamide electrophoresis and probed with antisera from immunized BALB/c mice and then formed a specific band in the nitrocellulose membrane.Conclusion The coding sequence of mouse lactate dehydrogenase subunit C had been cloned into the prokaryotic expression vector pET-28a(+)and the mLDHC4 protein could be expressed at a high level,the specificity of this protein was high and the activity was strong.
4.Comparison and analyse FAB classification of myelodysplastic syndrome with WHO classification of myelodysplastic syndrome
Jing ZHANG ; Shumin XIONG ; Bing CHEN
Chinese Journal of Postgraduates of Medicine 2006;0(03):-
Objective By compared FAB classification of myelodysplastic syndrome with WHO classification of myelodysplastic syndrome,understanded the proposed WHO new classification of myelodysplastic syndrome as soon as possible.Methods Retraced and analysed 78 cases of myelodysplastic syndrome based on examination of the bone marrow.Restults(1)According to the FAB classification,divided myelodysplastic syndrome into 5 kinds:RA,RARS,RAEB,CMML,RAEB-T.(2)According to the WHO classification,its subtypes were adjusted again,and its concluded:RA,RARS,RCMD,RAEB-Ⅰ,RAEB-Ⅱ,5q-del.(3)There were 9 cases possess chromosome to revise particularly in the chromosome check 28 cases myelodysplastic syndrome. Conclusion WHO classification has clinical guiding significance for early diagnosis,therapy observation and prognosis decision.
5.Color Doppler imaging feature of localized Castleman disease
Luzeng CHEN ; Liangliang ZHANG ; Bin WANG ; Hui ZHANG ; Yan XIONG
Chinese Journal of Ultrasonography 2012;21(8):701-703
Objective To summary the color Doppler imaging feature of localized Castleman disease.Methods From January 1997 to November 2011,32 localized Castleman diseases which were proved by pathology were analyzed.Results Round-like,hypoechoic,hypervascular lesions were showed in 23 hyalinevascular type lesions,2 of them with calcium,3 of them with structure liked lymph node hilum.Round-like,hypoechoic,hypervascular lesions or normal lymph node were showed in 5 plasma- type lesions and 4 mixed type lesions.Conclusions When round like,hypoechoic,hypervascular lesion is found by ultrasonography,Castleman should be considered.Calcium or lymph nod hilum-like structure is special finding in diagnosis of Castleman disease by ultrasonography.
6.Prostaglandin E_2 inhibits transforming growth factor-?_1 triggered lung fibroblast-myofibroblast transdifferentiation and collagen Ⅰ production in vitro
Xiang LONG ; Shengdao XIONG ; Weining XIONG ; Yongjian XU ; Zhenxiang ZHANG ; Yong CAO ; Jun CHEN ; Xiaohong XU
Chinese Journal of Pathophysiology 1989;0(05):-
AIM:To observe the effects of prostaglandin E2 on transforming growth factor-?1(TGF-?1)triggered human lung fetus fibroblast(HLF)transdifferentiation and connective tissue growth factor(CTGF),collagen type I(COLⅠ)expression.METHODS:HLFs were treated with TGF-?1,the cells underwent phenotypic change to myofibroblast.The marker of myofibroblast-?-smooth muscle actin(?-SMA)was detected by immunofluorescence.The ?-SMA content was measured by Western blotting.The changes in CTGF and COL Ⅰ at transcription levels were estimated by RT-PCR method.CTGF protein expression was evaluated by immunocytochemical.Cell culture medium hydroxyproline amount was measured by colormetric assay.RESULTS:PGE2 blocked TGF-?1 induced ?-SMA positive myofibroblast transformation(P
7.Clinical analysis of multiply antimicrobial-resistant bacteria and monitoring of antimicrobial resistance
Yan XIONG ; Hong ZHANG ; Yantian CHEN ; Yongzhang RONG
Chinese Journal of Primary Medicine and Pharmacy 2013;20(1):26-28
Objective To provide an effective basis for clinical control methods of multi-drug-resistant bacterial (MDRB) infections by analyzing the distribution and antimicrobial resistance of MDRB.Methods The French Merieux ATB Expression Automated Analysis System was used for bacterial identification,whereas a drug susceptibility testing was performed by K-B methods.Drug-resistance rate was calculated,and the predisposing factors were analyzed.Results Altogether 811(8.1%) strains were isolated from 9 954 specimens,and the majority of multiply antimircobial-resistant bacteria were Escherichia coli,Coagulase-negative staphylococci,Klebsiella Pneumoniae Staphylococcus aureus,Acinetobacter Baumannii,Pseudommonas aeruginosa,whereas the last two appeared pan resistant strains.Specimen source was mainly from respiratory specimens,accounted for 47.8%,and was mainly distributed in the ICU unit,atout41.8% ;MDRB enterobacter was highly sensitive to Carbapenems with resistance rates less than 1.5% and to Amikacin and other inhibitor drugs that rate was less than 30.0%.The resistance rates of MDRB nonfermentative bacteria was > 77.0% to Carbapenem antibacterial drugs whereas to non-resistance was found to polymyxin and only 20.0% resistance rate to Cefoperazone/sulbactam.MDRB staphylococcus was 100.0% sensitive to Vancomyci,Teicoplanin and Linezolid and less sensitive (< 30.0%) to chloramphenicol and rifampicin.MDRB showed high resistance rate to other antibacterial drugs.The predisposing factors included age,other disease,hospitalization over two weeks,the usage of multiply antimicrobial especially cephalosporins overtoppinh 7 days,and invasive operations.Conclusion The major MDRBs are resistant to common-used antimicrobial drugs.It is nesessary to pay attention to the differences.
8.Pre-administration of Ganoderma lucidum spore reduces incidence of neural tube defects induced by retinoic acid in pregnant mice
Wei ZHANG ; Yuanshan ZENG ; Yi XIONG ; Suijun CHEN ; Zhiqiang ZHONG
Journal of Integrative Medicine 2006;4(4):368-73
OBJECTIVE: To explore whether pre-administration of Ganoderma lucidum spore (GASP) can reduce incidence of neural tube defects (NTDs) induced by all-trans retinoic acid (ATRA) in pregnant mice. METHODS: Twenty pregnant mice were randomly divided into four groups: normal control group, solvent-treated group, ATRA-induced group, and GASP-treated plus ATRA-induced group. GASP solution, which was prepared with solvent (sodium carboxymethyl cellulose), was fed to the pregnant mice in the GASP-treated plus ATRA-induced group twice a day from embryo (E) 0 d to E10.5 d. The same dose of solvent was given to the pregnant mice in the solvent-treated group. At E7.75 d, ATRA (50 mg/kg) was given to the pregnant mice in both ATRA-induced group and GASP-treated plus ATRA-induced group for single time. Embryos were sampled from pregnant mice at E10.5 d. Then the incidence rate of NTDs in mouse embryo was calculated and the crown-rump length of mouse embryo was measured. The positive rate of nestin expression and the distribution of cell cycle of embryonic neural tube neuroepithelial cells were detected by histochemical staining technique and flow cytometry respectively. Reverse transcription-polymerase chain reaction method was used to detect the gene expressions of cyclin-dependent protein kinase 2 (Cdk2) and Cdk4 mRNAs. RESULTS: The incidence rates of NTDs in mouse embryos in the ATRA-induced group and the GASP-treated plus ATRA-induced group were 79.41% and 21.67% respectively, while the crown-rump length of mouse embryos in these two groups were (3.62+/-1.27) mm and (5.84+/-0.92) mm respectively. The positive rate of nestin expression in embryonic neural tube neuroepithelial cells of mouse embryo at E10.5 d in the ATRA-induced group was 32.44%, while that in the GASP-treated plus ATRA-induced group was 77.65%. The cell cycle of embryonic neural tube neuroepithelial cells was obviously arrested at G(0)/G(1) phase in the ATRA-induced group as compared with that in the GASP-treated plus ATRA-induced group. The Cdk4 mRNA was transcripted at a high level in embryonic neural tube in the GASP-treated plus ATRA-induced group, but the Cdk2 mRNA was not detected in this group. CONCLUSION: Pre-administration of GASP can reduce the incidence of NTDs induced by ATRA in pregnant mice.
9.Dynamic changes of platelets and white blood cells in patients with traumatic brain injury and its clinical sigulficance
Yehua JIA ; Xin CHEN ; Jianhua XIONG ; Jianning ZHANG
Chinese Journal of Trauma 2009;25(8):725-728
Objective To investigate the dynamic changes of platelets (PLT) and white blood cells (WBC) after traumatic brain injury (TBI) and discuss its clinical significance. Methods The number of PLT and WBC were examined in 63 patients with TBI by using cytoanalyze and also analyzed together with Glasgow Outcome Scale and concurrent infection, in the meantime, enzyme-linked immu-nosorbent was used to investigate concentration changes of C reactive protein (CRP) and thrombospondin 1 (TSPI) and analyze the correlation between CRP and TSP1. Results The number of WBC in all pa-tients, whether concurred with infection or not, was significantly increased within 24 hours after TBI (P < 0.01), with no statistical difference between patients without infection at day 4 and normal patients (P >0.05). However, the number of WBC was decreased to below 10 × 109/L in patients without infec-tion, which was significantly higher than that in normal patients (P < 0.05). In patients with infection and unfavorable prognosis, the number of WBC was increased again ay days 7-14, whereas that of PLT rose significantly at days 14-21 (P <0. 01). The concentration of TSPI was positively correlated with that of CRP (r = 0.720, P < 0.01). Conclusions Monitoring the dynamic changes of PLT and WBC is promising. The change of WBC at day 4 post injury is a key indicator to provide evidences of prophylactic antibiotic usage. Much attention should be paid to the dynamic change of PLT at days 14-21 post injury so as to evaluate the condition of hypercoagulability that can be potentially caused by inflammation response. Secondary increase of WBC and later increase, of PLT may affect prognosis of the patients. TSP1 and CRP may participate in thrombosis formation induced by inflammation.
10.Effects of sodium arsenite on the expression of microRNA-191 and tissue inhibitor of metalloproteinase 3 in L-02 cells
Qingling WANG ; Aihua ZHANG ; Lu MA ; Xiong CHEN ; Dapeng WANG
Chinese Journal of Endemiology 2016;35(5):338-343
Objectives To investigate the effects of sodium arsenite (NaAsO2) on the expression ot microRNA-191 (miR-191) and tissue inhibitor of metalloproteinase 3 (TIMP-3) in human normal hepatic cells (L-02 cells).Methods L-02 cells were exposed to different doses of NaAsO2 [0 (control group),5,25,50 and 75 μmol/L]for 24 h,or treated with 5 and 25 μmol/L NaAs02 for 0 (control group),12,24 and 48 h.The miR-191 inhibitor was used to suppress the expression of miR-191.qRT-PCR was performed to detect the expression level of miR-191 and TIMP-3 mRNA,and the protein level of TIMP-3 was analyzed by Western blotting.Results Dose-effect study:There were significant differences in the expressions of miR-191,TIMP-3 mRNA and protein between the 5 groups (F =85.674,20.952,123.393,all P < 0.05).The expressions of miR-191 in all groups (1.702 ± 0.124,2.077 ±0.234,2.145 ± 0.105,2.003 ± 0.077) were higher than that of control group (0.990 ± 0.035,all P < 0.05);the mRNA expressions of TIMP-3 in 25,50,75 μmol/L groups (0.848 ± 0.067,0.804 ± 0.081,0.813 ± 0.076) were all lower than that of control group (0.996 ± 0.007,all P < 0.05),but there was no significant difference in the mRNA expression of TIMP-3 between the 5 μmol/L group and control group (0.939 ± 0.133 vs 0.996 ± 0.007,P> 0.05),and the protein expressions of TIMP-3 in all groups (0.846 ± 0.093,0.611 ± 0.123,0.554 ± 0.098,0.529 ± 0.067) were lower than that of control group (1.006 ± 0.003,all P < 0.05).Time-effect study:there were significant differences in the expressions of miR-191,TIMP-3 mRNA and protein between the exposure groups of 5 and 25 μmol/L (For 5 μmol/L:F =86.355,16.404,22.898,all P < 0.05;For 25 μmol/L:F =104.321,20.123,52.321,all P < 0.05).The expressions of miR-191 in all exposure groups of 5 and 25 μmol/L (1.392 ± 0.152,1.691 ± 0.167,2.018 ± 0.130 and 1.456 ± 0.167,1.946 ± 0.178,2.259 ± 0.256) were higher than those of control groups (1.001 ± 0.014,1.008 ±0.027,all P < 0.05);the mRNA expressions of TIMP-3 in 48 h exposure group of 5 μmol/L and all exposure groups of 25 μmol/L (0.824 ± 0.093 and 0.897 ± 0.033,0.815 ± 0.089,0.709 ± 0.103) were lower than those of control groups (1.004 ± 0.018,0.997 ± 0.057,all P < 0.05),but there were no significant differences in the mRNA expressions of TIMP-3 between the 12,24 h exposure groups of 5 μmol/L and control group (0.952 ± 0.072,0.929 ± 0.121 vs1.004 ± 0.018,all P > 0.05);the protein expressions of TIMP-3 in all exposure groups of 5 and 25 μmol/L (0.857 ±0.068,0.832 ± 0.106,0.691 ± 0.112 and 0.785 ± 0.097,0.620 ± 0.066,0.453 ± 0.075) were lower than those of control groups (1.006 ± 0.045,1.004 ± 0.078,all P < 0.05).The treatment of miR-191 inhibitor:there were significant differences in the expressions of miR-191 and TIMP-3 protein between different groups (F =104.306,67.015,all P < 0.05).The elevated expression level of miR-191 induced by NaAsO2 was significantly suppressed after transfected with miR-191 inhibitor (0.314 ± 0.094 vs 2.051 ± 0.371,P < 0.05),which in turn up-regulated the protein expression of TIMP-3 (1.965 ± 0.277 vs 0.541 ± 0.183,P < 0.05).Conclusion The expression level of miR-191 is elevated in response to NaAsO2 exposure,and miR-191 has subsequently suppressed the expression of TIMP-3,a potential target of miR-191.