This study is to compare the influence of CYP2D6 *3 and *4 genotypes and phenotypes on the metabolic activity of CYP2D6 in Chinese Han, Uygur and Kazakh ethnic groups. Allele specific amplification (ASA) was used to determine the CYP2D6*3 and CYP2D6*4 genotypes. Phenotypes of CYP2D6 in all subjects were determined using dextromethorphan as probe drug by HPLC methods. Among the 132 Han subjects, one subject (0.76%) exhibited the *1/*3 combination, and one (0.76%) exhibited the *1/*4. Among the 136 Uygur subjects, 4 subjects (2.94%) showed the *1/*3 combination, 12 (8.82%) showed *1/*4, 4 (2.94%) showed *4/*4, and one (0.74%) showed *3/*4. Among the 116 Kazakh subjects, 2 (1.72%) exhibited the *1/*3 combination, 7 (6.03%) exhibited *1/1*4, and one (0.86%) showed *4/*4. This research revealed significant differences in the occurrence frequencies of the CYP2D6 genotype between Han and Uygur ethnic groups, as well as between Uygur and Kazakh populations. However, no difference was found between Han and Kazakh populations. In addition, the prevalence of PMs of the Uygur is comparable to that of the Caucasians. However, the molecular mechanism underlying the poor metabolism is different in these two populations.

Objective To determine the efficacy and safety of the 308nm excimer laser in the treatment of vitiligo. Methods A Self-controlled study was conducted. The vitiligo lesions in stable stage of 75 patients were treated twice a week by the 308 nm excimer laser for 6 weeks. The efficacy and factors related to efficacy were evaluated 3 days later after the final treatment. Results No improvement was observed in any of the untreated vitiligo lesions. However, of the treated lesions, 6 completely disappeared, 33 obtained significant improvement, 30 moderate improvement, 6 no improvement. The effective rate was 92.0% and the markedly effective rate was 52.0%. The lesions on the face and neck had a better response to the treatment than those on the trunk or limbs, and the latter responded better than those on the joints of extremities. Conclusion The 308 nm excimer laser is safe and effective in treatment of vitiligo in stable stage and the efficacy is related to the anatomic sites.

Objective To study the effect of methylprednisolone on serum interleukin-1(IL-1),8,10 during immature myocardial ischemia reperfusion injury.Methods A total of 70 rats were randomly divided into 3 groups:control group(n=10),model group(n=30)and drug group(n=30).And the later 2 groups were observed at 0.5 h after ischemia and 2,4,8,12,24 h after reperfusion with 5 rats in each group and the control group were observed only at 12 h.The rat model of myocardial ischemia reperfusion injury(MIRI)was established.Morphology changes were observed and the levels of serum IL-1,8,10 were examined.Results Compared with model group,inflammatory response in drug group weaken clearly,IL-1,8 were lower(Pa

Recombinant Fl-V (rFl-V) fusion protein is the main ingredient of the current candidate vaccine against Yersinia pestis infection, which has been under investigation in clinical trial in USA. We investigated the soluble expression conditions of rF1-V in Escherichia coli BL21 (DE3) that we constructed before. After scale-up and optimization of fermentation processes, we got the optimized fermentation process parameters: the culture was induced at the middle exponential phase with 50 µmol/L of IPTG at 25 °C for 5 h. Soluble rFl-V protein was isolated to 99% purity by ammonium sulfate precipitation, ion exchange chromatography, hydrophobic chromatography and gel filter chromatography. The protein recovery was above 20%. Protein identity and primary structure were verified by mass spectrometry and Edman sequencing. Results of purity, quality and western blotting analysis indicated that the target protein is a consistent and properly folded product. Furthermore, the immunogenicity of various antigens formulated with aluminum hydroxide adjuvant was evaluated in mice. Serum antibody titers of 4 groups including 20 µg rFl, rV and rFl-V and 10 µg rFl+10 µg rV, were assayed by ELISA after 2 doses. The antibody titers of anti-Fl with 20 µg rFl-V were obviously higher than titers with other groups; meanwhile there were no significant difference of anti-V antibody titers among them. These findings confirm that rFl-V would be the active pharmaceutical ingredient of the plague subunit vaccine.
Adjuvants, Immunologic ; Animals ; Antibodies, Bacterial ; blood ; Antibody Formation ; Antigens, Bacterial ; immunology ; Blotting, Western ; Chromatography, Ion Exchange ; Enzyme-Linked Immunosorbent Assay ; Mice ; Plague ; prevention & control ; Plague Vaccine ; immunology ; Recombinant Fusion Proteins ; immunology ; Vaccines, Subunit ; immunology ; Yersinia pestis

Objective To investigate the effects of different combinations of vitamin (Vit) C, Vit E and GSH on the biochemical markers and bone mineral density (BMD) in ovariectomized rats. Methods Seventy female SD rats aged 4 months were divided into two groups, 20 rats with sham operation in control group and 50 rats with bilateral oophorectomy in model group. 3 months later, 10 rats in the model group and 10 rats in the control group were randomly selected and their body weight, uterus weight, BMD of the left femurs and lumbar spines,biomeehanical characteristics of the left femurs, serum levels of Ca2+ , creatinine (Cr), alkaline phosphatase (ALP),superoxide dismutase (SOD) , malondialdehyde (MDA) , GSH-peroxidase (GSH-Px) and serum resisting abilities to OH- were determined. Then the rest rats were divided into five groups: A (sham), B (OVX control), C (Vit C +Vit E), D (GSH) and E (Vit C +Vit E +GSH). Vit C, Vit E and GSH were given 750rng/kg, 250 mg/kg, and 125 mg/kg, respectively daily for 3 months. And then the biochemical markers and BMD were measured. Results 3 months after treatment with antioxidants, BMD of left femurs and lumbars spines was increased, while the level of serum ALP was decreased markedly in B, C and D group as compared with that in B group. The serum level of SOD, GSH-Px and serum resisting ability to OH- were increased in D and E groups and the level of MDA decreased in C and D groups as compared with that in B group. Conclusion Vit C, Vit E and GSH increased BMD, prevented the decrease of SOD and GSH-Px and elevated serum resisting ability to OH-in ovariectomized rats.

Objective To investigate the effects of different combinations of antioxidants VitC, VitE and GSH on the biomechanical and biochemical markers in ovariectomized rats, Methods Seventy female SD rats, aged 4 months, were divided into 2 groups (control and model) randomly. Fifty rats in the model group underwent ovariectomy, while the other 20 rats in the control group had sham operations. Three month slater, 10 rats in the model group and 10 rats in the control group were selected randomly to detect their body weight, uterus weight, BMD of the left femur and lumbar vertebra, biomechanical characteristics of the left femur, levels of serum Ca2 +, Cr, ALP, SOD, MDA and GSH-Px and serumal resistance to OH<'->. Then the rest were divided into 5 groups: A (sham), B (model), C (VitC + VitE), D (GSH), and E (VitC + VitE +GSH). VitC, VitE and GSH were given in 750 mg/kg, 250 mg/kg, and 125 mg/kg every day for 3 months,respectively. And then the biomechanical and biochemical markers were measured. Results Three months after ovariectomy, the body weight of the rats in the model group increased markedly compared with the control group, while BMD of the left femur and lumbar vertebra, biomechanical maximal load and uterus weight decreased. The serum levels of Ca<'2+>, ALP and Cr increased. Three months after antioxidant treatment,the biomechanical maximal load and elastic load of the left femur and the maximal load of the 5th lumbar vertebra, the serum levels of SOD, GSH-Px and the serumal resistance to OH<'-> in groups D and E increased markedly, while the serum level of MDA decreased in groups C and D and the level of serum ALP decreased in all the treatment groups. Conclusion GSH and combination of VitC, VitE and GSH play a positive role in treatment of osteoperesis in ovariectomized rats.

Objective To investigate the clinical application of wave intensity (WI) technique in assessing the short-term effects of cardiac resynchronization therapy(CRT). Methods Sixteen patients with congestive heart failure treated with CRT were chosen. Before the implantation of CRT pacemaker and 1 week, 1 month,3 month after it,the diameters and volumes of left ventricle(LV) in the end-diastole and the end-systole were measured by echocardiography. LV ejection fractions(LVEF) were calculated by Simpson's way,and the variation ratio of left ventricular end-systolic volume(△ESV) was assessed each time after the CRT. The maximal rate of LV pressure rise (LVdP/dtmax) was assessed in the continuous-wave Doppler spectrum of mitral regurgitation. The magnitude of W1, and the length of R-W1 interval as well as W1-W2interval were recorded by WI technique applied on the left carotid artery of each patient. Results Compared to the data before CRT,W1 and W1-W2 interval were significantly higher in different period after CRT (P ＜0. 01). This result was conformed with echocardiographic remodeling data and LV systolic function.Conclusions WI provides a potential usage in conveniently and effectively assessing the CRT effects in short-term.

To establish a LC-MS/MS method for quantification of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid in rats plasma and study its pharmacokinetics after administration of Mailuoning injection at a single dose to rats. Plasma samples were acidified with hydrochloric acid and extracted with ethyl acetate. The analytes were determined by LC-MS-MS using a ZOBAX SB C18 column with a mobile phase of methanol-water (containing 2 mmol x L(-1) ammonium acetic) (60:40)at a flow rate of 0.5 mL x min(-1) and detected using ESI with negative ionization mode. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 353.1/191.0 [M-H]- for chlorogenic acid, m/z 178.9/134.9 [M-H]- for caffeic acid, m/z 515.2/353.0 [M-H]-for 3,4-DCQA, m/z 193.0/133.9 [M-H]-for ferulic acid, m/z 146.9/102.9 [M-H]- for cinnamic acid and m/z 246.0/125.8 [M-H]- for tinidazole (IS). After administration of Mailuoning injection at a single dose to eight Sprague-Dawley rats, the concentrations of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid in plasma were determined by LC-MS/MS method. The main pharmacokinetics parameters of measured data were caluculated by using DASver 1.0 software. The linear concentration ranges of the calibration curves for chlorogenic acid, caffeic acid, 3,4-DCQA and cinnamic acid were 2.006-1,027 microg x L(-1) (r = 0.999 6), 1.953-1,000 microg x L(-1) (r = 0.999 7), 28.51-1.459 x 10(4) microg x L(-1) (r = 0.998 9), 1.836-940.0, g x L(-1) (r = 0.997 7) and 4.780-2,447 microg x L(-1) (r = 0.998 6) respectively. The inner and inter-days relative standard deviations were both less than 5.0%, indicating legitimate precise and accuracy to the requirement of biological sample analysis. For chlorogenic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (49.78 +/- 12.81) min, (123.55 +/- 14.82) mg x min x L(-1) and (0.004 3 +/- 0.000 5) L x min(-1), respectively. For caffeic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (36.65 +/- 10.59) min, (91.67 +/- 11.77) mg x min L(-1) and (0.005 7 +/- 0.000 7) L x min(-1), respectively. For 3,4-DCQA, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (50.08 +/- 13.78) min, (278.34 +/- 31.82) mg x min x L-1 and (0.001 6 +/- 0.000 2) L x min(-1), respectively. For ferulic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (51.39 +/- 15.52) min, (34.72 +/- 4.67) mg x min x L(-1) and (0.000 4 +/- 0.0001) L x min(-1), respectively. For cinnamic acid, the pharmacokinetic parameter t1/2, AUCo-t, and CL were (74.42 +/- 18.32) min, (34.63 +/- 4.82) mg x min x L(-1) and (0.007 7 +/- 0.001 1) L x min-', respectively. The assay method is proved to be sensitive, accurate and convenient. It can be applied to the pharmacokinetic study of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid.
Animals ; Chromatography, Liquid ; methods ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Female ; Hydroxybenzoates ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; methods

Objective: To investigate the impact and its possible mechanism of hydrogen sulfide (H2S) on myocardial collagen remodeling in experimental rats with diabetic mellitus (DM).
Methods: Rat’s DM model was established by intraperitoneal injection of STZ at 40 mg/kg. A total of 40 SD rats were randomly divided into 4 groups:Control group, DM group, DM+NaHS group, in which NaHS worked as exogenous donor of H2S and NaHS control group. n=10 in each group, all animals were treated for 8 weeks. The cardiac collagen deposition was observed by Masson staining, protein expressions of cardiac collagen types I, III, IV and transforming growth factorβ1 (TGF-β1), connective tissue growth factor (CTGF) were examined by Western blot analysis.
Results: Compared with Control group, DM group showed increased protein expressions of cardiac collagen types I and III, up-regulated expressions of TGF-β1 and CTGF, P<0.05;while the expressions of collagen type IV were similar between 2 groups. Compared with DM group, DM+NaHS group presented reduced cardiac collagen expression, decreased expression of collagen types I and III, down-regulated expressions of TGF-β1 and CTGF, P<0.05;while the expressions of collagen type IV were similar between 2 groups.
Conclusion: H2S may improve the myocardial collagen remodeling in experimental DM rats, the mechanism might be related to the down-regulation of TGF-β1 and CTGF expression.

[ ABSTRACT] AIM:To explore the effects of hydrogen sulfide ( H2 S) on the myocardial fibrosis in a rat model of diabetes and its mechanism.METHODS:Single intraperitoneal injection of streptozotocin ( STZ) was utilized to establish a rat model of diabetes.Sodium hydrosulfide was used as an exogenous donor of hydrogen sulfide.Male SD rats were ran-domly divided into control group, STZ group, STZ+H2 S group and H2 S group.Eight weeks later, HE and VG staining methods were used to observe the collagen distribution and collagen volume fraction was measured by image analysis.The expression levels of type I collagen, PPARγand NF-κB in the cardiac tissues were determined by Western blotting.RE-SULTS:Compared with control group, collagen distribution and the expression levels of type I collagen and NF-κB in the cardiac tissues were markedly increased (P<0.05), while PPARγwas significantly decreased in STZ group (P<0.05), but these indexes were reversed significantly in STZ+H2S group (P<0.05).The expression levels of type I collagen, PPARγand NF-κB had no significant difference between H2 S group and control group.CONCLUSION:Hydrogen sulfide attenuates cardiac fibrosis in diabetic rats, and its mechanism may be related to PPARγ-NF-κB signaling pathway.