Objective To explore the curative effect of recombinant human erythropoietin(rHuEPO )on anaemia associated with regular chemotherapy in patients with blood cancer. Methods Eighty leuKemia patients who received regular chemotherapy were selected for the study. Patients in group A were also treated with erythropoietin therapy(47 cases),patients in group B received regular chemotherapy but without eryth-ropoietin therapy(33 cases). Blood hemoglobin level in the peripheral blood was detected in the second and fourth weeK after chemotherapy,and the third weeK after rHuEPO treatment. Hemoglobin level was compared between two groups. Results In group A,the mean hemoglobin level of 4 weeKs of chemotherapy was decreased obviously compared with 2 weeKs of chemotherapy( P < 0. 01)and it was significantly increased after 3 weeKs of rHuEPO treatment compared with that in the fourth weeK chemotherapy( P < 0. 01). In group B,the mean hemoglobin level of 4 weeKs of chemotherapy was obviously decreased compared with 2 weeKs of chemotherapy( P < 0. 01),and it was further decreased at the time corre-sponding to the third weeKs of rHuEPO treatment in group A in comparison with the value of 4 weeKs of chemotherapy( P < 0. 01). Conclusion Anemia caused by chemotherapy in patients with leuKemia can be improved by rHuEPO treatment.

Objective To investigate the function and mechanism of erythromycin in reversal of multidrug-resistance in human breast cancer cell line.Methods Rhodamine 123 excretion assay was used to measure the inhibition rate of P-glycoprotein (P-gp) activity in adriamycin (ADM) resistant breast cancer cell line MCF-7 (MCF-7/ADM) with different doses of erythromycin (1,5,10,20,50 and 100 μmol/L).Four methyl tetrazolium (MTT) method was used to measure the influence of erythromycin on the cytotoxic effect of different doses of ADM and fluorouracil on MCF-7/ADM.Results The erythromycin dose reduced the P-gp activity of MCF-7/ADM cells,with inhibitory rates of (5.1 ±1.2) ％,(4.7 ± 1.4) ％,(17.1 ± 1.4) ％,(18.4 ±3.1) ％,(41.0 ± 3.4) ％ and (48.8 ±4.5) ％ based on doses of 1,5,10,20,50 and 100 μmol/L.The erythromycin significantly enhanced the cytotoxic effect of 2.50,5.00,10.00 and 20.00 mg/L ADM,showing higher cell death rates in erythromycin ± ADM treated cells than those in ADM treated cells [(11.88 ± 0.80) ％,(24.36 ± 1.28) ％,(33.94 ±2.27)％,(57.19 ±2.00)％ vs (4.05 ±0.26)％,(5.56 ±0.27)％,(7.17 ±0.26)％,(16.76 ± 0.29)％] (P ＜ 0.05).The erythromycin significantly enhanced the cytotoxic effect of 5.00,10.00 and 20.00 mg/L fluorouracil,showing higher cell death rates in erythromycin ± fluorouracil treated cells than those in fluorouracil treated cells [(8.03 ±0.26)％,(10.93 ±0.57)％,(26.13 ±0.90)％ vs (4.97 ±0.55)％,(8.98 ± 0.52) ％,(23.93 ± 1.60) ％] (P ＜ 0.05).Conclusion Erythromycin can reverse the multidrug resistance of multidrug resistant human breast cancer cell line via inhibiting the P-gp activity.

This paper describes detections of gene-directed personalized medication based on pyrophosphoric acid sequencing typing of genes in the Department of Pharmacology,General Hospital of Beijing Military Command of PLA,including β1 adrenergic receptor(β1AR)and CYP2 D6 genes;CYP2C19 gene;vitamin K epoxide reductase complex subunit 1(VKORC1)and CYP2C9 genes;thiopurine methyltransferase(TPMT)gene;epidermal growth factor receptor(EGFR)gene;IL28B gene;O6-methylguanine-DNA methyltransferase(MGMT)gene;SLCO1B1 gene;HLA-B *1502and HLA-B *5801 alleles,etc.The implementation of these gene detection programs could provide sound evidence for the prediction of clinical efficacy and adverse effects of drugs possibly induced by genetic factors.

Objective To study the allelic frequency of UGT1A1 and UGT2B7 genes,and the relationship be-tween the mutations of UGT1A1 and UGT2B7 genes and colorectal cancer. Methods The DNA of blood sampls from 335 healthy subjects and 348 cases of colorectal cancer was extracted to determine the allelic frequency of the UGT1A1 and UGT2B7 mutant. Results The mutative frequency of UGT1A1*6 was 8. 07% in healthy subjects and 16. 52% in patients with colorectal cancer respectively,being significantly different( P ﹤0. 001,OR= 3. 34,95%CI:2. 12-6. 72). The muta-tive frequency of UGT1A1*28 was 7. 32% in healthy subjects and 11. 50% in patients with colorectal cancer respective-ly,also with significant difference( P =0. 011,OR=1. 73,95%CI:1. 21-1. 84). The mutative frequency of UGT2B7-1 and UGT2B7-2 was not significanthy different between healthy subjects and patients with colorectal cancer. Conclusion The gene mutation of UGT1A1*6 and UGT1A1*28 was related to colorectal cancer. The gene mutation of the UGT1A1*6may increase the risk of colorectal cancer,and UGT1A1*6 gene might be the high-risk predisposing gene of colorectal cancer.

Objective To study the allelic frequency of UGT1A7 and UGT1A8 genes, and relationship between the mutations of UGT1A7 and UGT1A8 genes with colorectal cancer. Methods To determine the allelic frequency of the UGT1A7 and UGT1A8 mutant in a group of 297 healthy subjects and 301 colorectal cancer. To study the relationship of UGT1A7 and UGT1A8 gene polymorphism with colorectal cancer. Results The allelic frequency of the UGT1A7*2*2 and UGT1A7*3*3 were 14.29%and 15.28%in colorectal cancer respectively, obviously super 3.70%and 3.37%in healthy subjects, to compare the allelic frequency of two groups, P=0.013, OR=4.31(95%CI:1.12-6.33) and P=0.002, OR=6.32 (95%CI:2.10-9.61) respectively. they were significant difference. The allelic frequency of the UGT1A8*1*3 were 16.94%and 3.03%in colorectal cancer and healthy subjects respectively, and had also significant difference, P<0.000, OR=8.46(95%CI:2.18-11.54). Conclusions The gene mutation of the UGT1A7*2*2, UGT1A7*3*3, UGT1A8*1*3 and UGT1A8*2*3 were correlation with colorectal cancer. The gene mutation of the UGT1A7*2*2, UGT1A7*3*3, UGT1A8*1*3 and UGT1A8*2*3 may increase risk of the colorectal cancer, and UGT1A7*3*3, UGT1A8*2*3 gene mutation were high risk predisposing gene of the colorectal cancer.

Objective To explore the correlation between polymorphism of UDP-glucuronosyltransferase 1A ( UGT1A1) and UGT1A3 genes with hyperbilirubinemia in neonates. Methods The DNA of blood samples were extrac-ted from 347 healthy neonates in three hospitals in Beijing ( healthy neonatal group) and 97 neonates with severe neonatal hyperbilirubinemia ( severe hyperbilirubinemia group ) and 139 neonates with hyperbilirubinemia ( hyperbilirubinemia group) to determine the UGT1A1 and UGT1A3 genotypes, and the correlation between the polymorphism of UGT1A1 and UGT1A3 genes and hyperbilirubinemia was also researched. Results The frequency of UGT1A1 gene mutations was compared between healthy neonatal group and severe hyperbilirubinemia and hyperbilirubinemia groups respectively, and the differences in frequencies (M%) of UGT1A1*6, UGT1A1*28 and UGT1A3*2 genes were statistically signif-icant (P<0. 01, P<0. 05);while the differences in the above frequencies between the severe hyperbilirubinemia group and hyperbilirubinemia group were not statistically significant ( P >0. 05 ) . The differences in frequencies of other UGT1A3 genes among the three groups were not statistically significant (P >0. 05). Conclusion Gene mutation of UGT1A1 *6, UGT1A1*28 and UGT1A3*2 is associated with neonatal hyperbilirubinemia, and it is a predisposing gene of hyperbilirubinemia disease, but it is not associated with the severity degree of hyperbilirubinemia.

Objective To study the genotype of UGT1A1 and ERCC1, and their relationship with the efficacy and toxicity of Irinotecan combined with Cisplatin for patients with advanced ovary cancer. Methods The allelic frequency of the UGT1A1 and ERCC1 mutant in a group of 89 advanced ovary cancer patients were determined. The relationship be-tween the adverse events of irinotecan-based chemotherapy and the efficacy of Cisplatin in patients with advanced ovary cancer were analyzed. Results For patients who carried the UGT1A1*28WW and UGT1A1*28WM+MM, the incidence of grade 2 or 3 tardiive diarrhea was 54.7%and 72.7%respectively, and the difference was statistically significant(P=0.031, OR=2.1, 95%CI:1.6~9.2). For grade 3 or4 tardive diarrhea, the incidence rate was 7.8%and 36.4%respectively in patients who carried UGT1A1*28WW and UGT1A1*28WM +MM,the difference was statistically significant (P= 0.000, OR=4.9, 95%CI:3.3~15.8). The response rate of ERCC1WW and ERCC1 WM+MM carriers was 30.3%and 20.2% respectively,the difference was significant (P=0.032, OR=3.2(95%CI):(1.4~9.1). Conclusion UGT1A1*28 is the target gene for tardive diarrhea, and UGT1A1*28 gene mutation increases the risk of diarrhea with irinotecan-based chemotherapy. ERCC1WW carriers can obtain better rate of clinical response than ERCC1 WM+MM carriers with Combined Irinotecan and Cisplatin Regimen.

Objective To study the association between UGT1A3 gene polymorphism and hypertensive disease or tumor disease.Methods The allelic frequency of the UGT1A3 mutant was determined using pyrosequencing apparatus.The relationship of UGT1A3 gene polymorphism to hypertensive disease,tumor disease and diabetic disease was studied.Results There was no significant difference in the allelic frequency of the UGT1A3 mutant between hypertensive disease volunteers,diabetic disease volunteers and healthy volunteers.But there was significant difference between tumor disease volunteers and healthy volunteers.The UGT1A3-1,UGT1A3-2,UGT1A3-3 and UGT1A3-4 gene mutation were predisposing gene of tumor disease.Conclusion The gene mutation of UGT1A3-1,UGT1A3-2,UGT1A3-3 and UGT1A3-4 can increase the chance of tumor disease.

Objective To observe the relationship between inducible nitric oxide synthase (iNOS) gene Ser608Leu allele polymorphism and chronic periodontitis.Methods A total of 116 chronic periodontitis patients were enrolled,and 80 healthy people from examination subjects were as a control group. To evaluate correlation between polymorphism of iNOS gene Ser608Leu and chronic severe periodontitis, DNA sequencing method was used to detect G to A mutation of gene and ELASA method was used to detect the active of iNOS in serum. iNOS gene Ser608Leu polymorphisms of the two groups were compared.Results The distribution of AA genotype between periodontitis and the control group has significant difference (P<0.05). A and G allele distribution between chronic severe periodontitis and the control group has significant difference (P<0.05), The risk of AA genotype with periodontitis was 1.45 times than that of other genotypes (P<0.05). There were statistical differences in the level of serum iNOS between AA genotype and AG or GG genotype in chronic severe periodontitis group(P<0.05). Conclusion Our study reveals some possible influence of single-nucleotide polymorphisms for iNOS Ser608Leu in chronic severe periodontitis.

Objective To investigate the effect of CYP2C9 polymorphism on the pharmacokinetics of meloxicam in Chinese healthy subjects.Methods The CYP2C9 genotypes of twenty-four Chinese healthy male subjects were selected by the pyrosequencing method.The subjects were genotyped with CYP2C9*3 wild-type and mutation.HPLC-MS-MS method was used for the determination of meloxicam in plasma.The important pharmacokinetic parameters were caculated by DAS 2.0 software.The pharmacokinetics of meloxicam based on identification of genotypes(CYP2C9*3 wild-type and mutation) was compared.Results Two kinds of CYP2C9*3 phenotype existed in the subjects.CYP2C9* 3(A/A) was found in twenty-two subjects while CYP2C9*3(A/C) in two subjects.For meloxicam,the A/A of CYP2C9*3 alleles was more active than the A/C.Conclusion CYP2C9 genetic polymorphism has significant influence on the pharmacokinetics of meloxicam.A/A is more active than A/C.Pharmacogenomic studies will help rational and individualized medication.

华法林是抗凝首选药物。由于个体差异大,有效治疗范围窄,影响了药物的使用。该文针对目前研究较为深入的、影响华法林代谢及作用机制的相关基因多态性进行了综述。

Objective To investigate the effects and mechanism of oleum cinnamomi(OC) on primary rat myocardial cells infected with Coxsackie virus B3(CVB3) by the serum pharmacological method.Methods The primary rat myocardial cells from the ventricle muscle of new born Sprague-Dawley rats were prepared.After 72 hours,different doses of OC contained sera obtained via i.v.injection with OC in rats were added in myocardial cells infected with CVB3,to establish the model and control groups at the same time.The cinnamaldehyde and cinnamic acid in sera were detected at different time points.And the relative content of CVB3mRNA was assayed by Real-time PCR.The survival rate of myocardial cells was determined through a metabolic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide(MTT) assay.A simple correlation test was implemented to analyze the relationship by using the SPSS software.Results The results showed that the effect of OC contained serum on the myocardial cell survival rate and relative amount of CVB3 mRNA was contributed to cinnamic acid P0.05 or P0.01) rather than cinnamaldehyde.Conclusion Oleum cinnamon is an effective antiviral agent against viral myocarditis,the cinnamic acid is the main effective component for which.

Objective To study the quality control of Lianqiaopikang Ointment.Methods TLC was used to identify Rheum officinale Baill,Radix et rhizome Clematidis and dexamethasone.HPLC system was used to determine the content of emodin,chrysophanol and dexamethasone in Lianqiaopikang Ointment.Results The spots of emodin,chrysophanol and dexamethasone of the test sample were consistent with the control.The linear range of emodin and chrysophanol was both 1-80 μg/ml,r=0.9999.The average recovery was 100.83% and 101.70%,respectively,and the relative deviation(RSD) was 3.03% and 3.51%,respectively.The linear range of dexamethasone was 5-80 μg/ml,and the average recovery rate was 100.36%,RSD was 1.54%.Conclusion The methods of TLC and HPLC used in this study are simple and accurate for quality control of Lianqiaopikang Ointment.

尿甘二磷酸葡醛酸转移酶是重要的Ⅱ相代谢酶,尿甘二磷酸葡醛酸转移酶的活性对药物代谢和药物疗效具有重要影响.本文就影响尿甘二磷酸葡醛酸转移酶活性的主要因素年龄、激素水平、底物、疾病状态、遗传多态性以及基因表达调控作一综述.

The aim of the study is to identify the effect of UDP-glucuronosyltransferase (UGT) genetic polymorphism on the interindividual variability in mitiglinide pharmacokinetics (PK) in Chinese. PK and genetic data were obtained from 42 healthy Chinese volunteers (Han ethnic group) treated with single-dose and multiple-dose oral mitiglinide using liquid chromatography/mass spectrometry and DNA sequencing technologies. And the result showed there were great interindividual variabilities in main PK parameters (AUC, Cmax and CL/F) for multiple oral mitiglinide. The enzyme activity of the carriers of UGT1A3 *2/*4 or UGT2B7-1 T/T was stronger than that of the carriers of other genotypes. These results demonstrate that UGT1A3 and UGT2B7-1 genetic polymorphism may have a significant impact on interindividual variability in the PK of mitiglinide in Chinese.

目的 比较拭样增菌或不增菌对实时荧光PCR法检测孕妇产道B族链球菌感染率的影响.方法收集临床孕35～37周妇女阴道直肠拭子1 000例,平均分为增菌检测组和未增菌检测组.增菌组拭子置于增菌液室温过夜增菌后4℃保存待检,未增菌组拭子直接4℃保存待检,所有PCR检测在临床采样后48h内完成,检验指标为B族链球菌的阳性检出率.结果 χ2检验结果显示,拭样增菌显著影响实时荧光PCR法对B族链球菌的阳性检出率,增菌后B族链球菌阳性检出率提高了1.7倍(P=0.006).结论 提取前对临床标本适当增菌在临床PCR检验实验室具有可操作性,更好地避免了假阴性的出现,提升了B族链球菌产前筛查的意义.

Vasorelaxant properties of N-2-(ferulamidoethyl)-nitrate (ferulate nitrate, FLNT), a newly synthesized nitrate, were compared with those of isosorbide dinitrate, nicorandil, nitroglycerin, and 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP) in rat aorta pre-contracted by phenylephrine. FLNT produced vasorelaxation in a concentration-dependent manner (0.1 - 100 µM). The degree of relaxation induced by FLNT was similar to that induced by isosorbide dinitrate. In addition, removal of endothelium did not affect the relaxant effect of FLNT. FLNT caused a rightward shift of the cumulative concentration-response curves of phenylephrine and reduced the maximal efficacy of contraction. 1H-[1,2,4]Oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 µM) and K(+)-channel blockers charybdotoxin (CHT, 0.1 µM) and BaCl(2) (1 µM) reduced the relaxant effect of FLNT in the endothelium-denuded arteries, whereas glibenclamide (1 µM) and 4-aminopyridine (1 mM) failed to influence FLNT-induced vasorelaxation. Furthermore, in the presence of ODQ, both CHT (0.1 µM) and BaCl(2) (1 µM) still significantly reduced the relaxation evoked by FLNT. Pretreatment of vessels with hydroxocobalamin, a nitric oxide scavenger, abolished the FLNT effect. These findings demonstrate that FLNT induces relaxation of the rat aorta rings endothelium-independently. Furthermore, we demonstrated that FLNT-induced vasorelaxation is related to its stimulation of soluble guanylate cyclase and activation of K(+) channels.

AIM: To investigate the effect of Modified Xiaoyao pill on CYP2C19,and provide foundation for clinical drug using. METHODS: Twenty volunteers were divided into two groups according to CYP2C19*2 gene type,ten for WW gene type and ten for MM gene type.Omeprazole used as probe drug of CYP2C19,the effect of Modified Xiaoyao pill on the activity of CYP2C19 were investigated.Genetic classification was fulfilled by pyrosequencing method,and the blood concentration of probe drug and its metabolic product were determined by HPLC-MS/MS.RESULTS:The volunteers took Modified Xiaoyao pill for two weeks,AUC0-12 was used as the standard of the activity of CYP2C19.The activity value was 5.7±1.6 before drug and 6.0±1.7 after drug using.So the activity of CYP2C19 was increased after drug using,t-test was used for comparison,there was no remarkable difference between the data.CONCLUSION: Modified Xiaoyao pill has no obvious affection on the activity of CYP2C19.

Objective To study the distribution of polymorphisms of antihypertensive drug related genes in Chinese Han population.Methods Genotype analysis was performed using gene microarray of antihypertensive drug related genes.The allelic frequency of the β-receptor block,AT1-receptor antagonism and ACE inhibitors was determined in a group of 220 healthy subjects and in a group of 334 hypertension patients.Results In the 554 Chinese Han subjects,the frequency of CYP2C9*3,AGTR1(1166A>C),ADRB1(1165G>C),ACE(I/D),and CYP2D6*10 mutant allele was 4.96%,5.87%,71.84%,33.22% and 56.41%,respectively.The allelic frequency of AGTR1(1166A>C) in the 334 hypertensive patients was statistically lower than in the 220 healthy subjects.Conclusion Among the 334 hypertensive patients,the allelic frequency of CYP2C9*3,AGTR1(1166A>C)and CYP2D6*10 in Chinese females was statistically higher than in Chinese males.

目的建立可舒胶囊中葛根素与橙皮苷2种有效成分的定量分析方法。方法采用反相高效液相色谱法,固定相:Zorbax SB-C18(4.6 mm×250 mm,5μm);流动相:甲醇-水(40∶60);DVD检测器:葛根素和橙皮苷分别在250和283 nm波长处同时测定。结果葛根素与橙皮苷含量测定在50～1 000 ng范围内线性关系良好,平均加样回收率为葛根素(250 nm)100.43%,RSD为1.73%;橙皮苷(283 nm)99.90%,RSD为1.61%。结论葛根素与橙皮苷的含量测定方法操作简便,结果准确,重复性好,适用于该制剂的质量控制。