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Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy. Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment (aspirin+clopidogrel). CYP2C19 genotype was detected by microarray hybridization during hospitalization, and CYP2C19 gene polymorphisms were classified into fast metabolism group, medium metabolism group and slow metabolism group according to the type of drug metabolism. Patients were tested for platelet inhibition induced by adenosine diphosphate (ADP) according to thromboelastographic (TEG) on 7~14 d of drug administration. ADP <30% was classified as clopidogrel drug resistance group and ADP ≥30% as non-resistance group. Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance. Results Among 202 patients with ischemic stroke, 87 were in the resistant group and 115 in the non-resistant group. The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group, and the differences were statistically significant (P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group, and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group, all with statistically significant differences (P<0.05). Conclusion Combined diabetes mellitus, high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.
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Objective: To investigate the regulation of CYP3A4 and P-gp by berberine hydrochloride ( BBR) via pregnane X re-ceptor (PXR) pathway. Methods: pLKO. 1-PXR vector, a lentivirus plasmid expressing PXR shRNA, was packaged into 293T cells. Human hepatoma (HepG2) cells were infected with the lentivirus and the cell clones stably expressing PXR shRNA were selected by puromycin according to pLKO. 1 vector characteristics. Real-time RT-PCR and Western blot were used to evaluate CYP3A4 and P-gp mRNA and protein in berberine treated HepG2 cells and PXR-silenced HepG2 cells. Results: The PXR expression in PXR silenced cells significantly decreased (P<0.01) when compared with that in HepG2 cells, while there was no significant difference (P >0. 05) in the expression of CYP3A4 and P-gp between the groups. Compared with that in HepG2 cells, the inhibition of berberine on the mRNA and protein expression of CYP3A4 and P-gp in PXR-silenced HepG2 cells was weakened (P<0. 05 or P<0. 01). Conclu-sion: Berberine can regulate the expression of CYP3A4 and P-gp via PXR signaling pathway, while it is not the only one.
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The main components of Schisandra chinensis are γ-schizandrin, schisandrin A,deoxyschizandrin,schisandra B, schisandrol B and so on. Schisandra contains a variety of bioactive ingredients mainly used in clinics and combined with other drugs. Many of the drugs currently used in clinical practice can cause drug-induced liver injury(DILI),which is one of the main adverse drug reactions,therefore,the clinical use of drugs for the prevention and treatment of liver damage is particularly important. In this paper, the effective components of Schisandra chinensis and their related therapeutic effects on DILI were reviewed.
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Objective To investigate the influence of deoxyschizandrin (Deo) on P-glycoprotein (P-gp).Methods The effect of P-gp on Deo (20,40,80 μg·mL-1) was studied in the Caco-2 cell model in vitro,and the apparent permeability coefficient (Papp) of Deo (20-160 μg·mL-1) on a P-gp substrate,rhodamine123 or cyclosporine A,was calculated.Healthy male Sprague-Dawley rats were randomly divided into five groups:blank control group,verapamil group,low-,medium-and high-dose Deo group (8 rats in each group).Rats in the low-,medium-and high-dose Deo group were intragastrically administered once daily with Deo at 8,16 and 32 mg·kg-1 for 3 consecutive days,while rats similarly received gavagewith verapamil (4 mg·kg-1) in the verapamil group and equal volume of purified water in the blank control group.Thirty minutes after the rats were treated with their respective drugs,rhodamine123 (5 mg· kg-1) was orally administrated.Then the pharmacokinetic profiles of rhodamine 123 were analyzed to evaluate the inhibitory ability of Deo on P-gp in vivo.Results The bidirectional transport rates of Deo (20,40,80 μg·mL-1) were similar,with non-selectivity.Deo (20-160 pg·mL-1)significantly inhibited the basolateral→apical(BL→AP) directional transports of rhodamine 123 and cyclosporine A in Caco-2 cell model (P ＜ 0.05) in a concentration-dependent manner.And Deo (8-32 mg· kg-1) also dose-dependently decreased the peak concentrations (Cm.) and the area under the plasma concentration-time curve (AUC0-t) of Rho123.Conclusion Deo can inhibit P-gp in vitro and in vivo,but it is not a P-gp substrate.
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OBJECTIVE:To investigate the association of synergistic effects of Wuzhi capsules on tacrolimus with CYP3A5*3 (6986A>G,rs776746) gene polymorphisms. METHODS:One hundred and severty patients underwent renal transplantation receiving tacrolimus maintenance therapy after surgery were selected from our hospital during Jan. 1997-Dec. 2015,and then divided into Wuzhi capsules(+)group(74 cases)and Wuzhi capsules(-)group(96 cases)according to the use of Wuzhi capsules. Both groups received tacrolimus+mycophenolate mofetil+prednisone;Wuzhi capsules (+)group was additionally given Wuzhi capsules,one capsule each time,bid,for more than 12 months. Trough concentration of tacrolimus was detected by CMIA 0,1,3,6,12 months after medica-tion,and the blood concentrations(C0/D)were calculated at different time points after correcting daily dose. CYP3A5*3 gene polymor-phisms was detected by PCR-RFLP. The association of C0/D value with gene polymorphism was investigated by analysis of covariance. RESULTS:Among 170 patients,there were 65 cases of CYP3A5 GG genotype,83 cases of AG genotype and 22 cases of AA geno-type;genotype frequencies were 38.2%,48.8% and 12.9%,which was in line with Hardy-Weinberg balance (P>0.05). There was statistical significance in the distribution frequencies of GG,AG+AA genotype between Wuzhi capsules(+)group and Wuzhi capsules (-)group (P0.05). CON-CLUSIONS:Wuzhi capsules can increase C0/D of tacrolimus in CYP3A5*3 AG+AA genotype,but have no significant effect on C0/D of tacrolimus in GG genotype;CYP3A5*3 genotype should be considered when using Wuzhi capsules as synergist of tacrolimus.
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This article analyzed the difference between Chinese and Russian traditional medical treatments from the part of herbs,acupuncture/acupressure therapy,manual therapy,psychotherapy,and sports.TCM had a separate comprehensive diagnosis and treatment system,Russia traditional medicine,attached to Western medicine,had not formed the independent diagnostic and treatment system.
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The strategy of One Belt and One Road established new era for China to open-door to the world. It is an important way to establish and strengthen the relationship among countries along the belt and the road. This paper has analyzed and shown the history, prespects and development of Chinese medicine trade between China and Russia in context of “One Belt and One Road”. And then counter measures were proposed, such as promoting diversification of Chinese medicine service, developing international standard in Chinese medicine, strengthening cultural exchanges of Chinese medicine, advertising Chinese medicine in Russia, and so on.
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Objective:To investigate the effects of schizandrin B on P- glycoprotein by a classical in vitro cell model. Methods:Caco-2 cell model was used as the carrier,and rhodamine 123 and cyclosporin A were employed as the P-gp substrates, the transmembrane transportation of schizandrin B,rodamine 123 and cyclosporin A were detected by HPLC and a liquid scintillation counting assay,and the apparent permeability coefficient and permeability directional ratio were calculated. Results:The bidirectional transportation rates of schizandrin B(20 μg·ml -1 ,40 μg·ml -1 and 80μg·ml-1 )were similar,and showed non-selective difference. Schizandrin B(20-160 μg ·ml -1 )significantly inhibited the BL → AP directional transportation of rhodamine 123 and cyclosporine A in Caco-2 cell model(P < 0. 05) in a concentration-dependent manner. Conclusion:Schizandrin B is a P-gp inhibitor,while it isn’t a P-gp substrate.
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Objective:To investigate the effects of HLA-B?1502 genetic polymorphism on cyclosporine( CsA)-induced liver injury in Chinese renal transplant recipients. Methods:HLA-B?1502 genotypes were determined by polymerase amplification chaln reaction of sequence-specific primers( PCR-SSP) in a total of 339 renal transplant recipients receiving CsA. All the subjects were divided into the CsA-induced liver injury group, non-CsA-induced liver injury group and the control group according to the liver injury occurrence. Results:In the 339 renal transplant recipients, the frequency of HLA-B?1502 mutation allele was 22. 64%. The distribution frequen-cy of HLA-B?1502 mutation allele had no significant difference among the three groups. There were no significant differences in the clinical characteristics of HLA-B?1502 genotypes among three groups(P>0. 05). Conclusion: No association is observed between HLA-B?1502 genetic polymorphism and cyclosporine-induced liver injury in Chinese renal transplant recipients.
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Objective: To establish an HPLC-fluoremetry method for determination of the plasma concentration of mycophenolic acid ( MPA) in renal transplantation patients. Methods:The sample was subjected to precipitate proteins using acetonitrile, and the supernatant (20 μl) was used for the sample injection and determination on a Hypersil BDS C18 (250 mm × 4. 6 mm, 5 μm) column with temperature at 25℃. The mobile phase consisted of acetonitrile-methanol-0. 2 mol·L-1 dipotassium hydrogen phosphate buffer (pH=9. 0)( 18∶2∶80)with the flow rate of 1. 0 ml·min-1. The excitation wavelength (Ex) was 342 nm and the emission wave-length ( Em) was 425 nm. Results:The endogenous plasma impurities and drug combinations had no interference with the determina-tion. The calibration curve was linear over the range of 0. 25-50. 00 mg·L-1(r=0. 999 7), and the lower limit of quantification was 0. 25 mg·L-1 . The mean methodological recovery was 99. 12% and the mean extraction recovery was 93. 27%, the intra-day RSD was less than 2% and the inter-day RSD was less than 6%. Totally 10 cases of renal transplantation patients were with mycophenolate mofetil at the dose of 0. 5-1. 75 g·d-1 , and MPA in plasma was within the range of 0. 43-21. 58 mg·L-1 . Conclusion:The method is rapid, sensitive, accurate and convenient, which can be used in the quantitative determination of plasma concentration of MPA in re-nal transplantation patients.