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

Background: As a traditional Chinese medicine, Cordyceps sinensis (CS) possesses a variety of immunoregulatory properties. This study aimed to explore the therapeutic potential of CS in a mice model of multiple sclerosis (MS)?experimental autoimmune encephalomyelitis (EAE). Methods: Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein35–55 to induce EAE, followed by an instant intragastric feeding with a low dosage of CS (low?CS group, n = 5), high dosage of CS (high?CS group, n = 5), or the same volume of normal saline (control group, n = 5).All the mice were observed for clinical assessment. Over the 30 days of CS treatment, flow cytometry was used to detect the frequency of helper T?cell (Th) subsets, Th1 and Th17, and CD4+ CD25+ regulatory T cells in the spleen and lymph nodes. Meanwhile, pathological changes in brain were determined using both hematoxylin?eosin and luxol fast blue staining. Data were analyzed using the one?way analysis of variance (ANOVA). Results: Over the 15 and 30 days of CS treatment, the clinical assessment for EAE demonstrated that both high?CS group (2.51 ± 0.31 and 2.26 ± 0.39 scores, respectively) and low?CS group (2.99 ± 0.40 and 2.69 ± 0.46, respectively) had lower disease severity scores than those of control group (3.57 ± 0.53 and 3.29 ± 0.53, all P < 0.01, respectively). Meanwhile, after 15 and 30 days, the high?CS group (19.18 ± 1.34 g and 20.41 ± 1.56 g, respectively) and low?CS group (18.07 ± 1.18 g and 19.48 ± 1.69 g, respectively) had a lower body weight, as compared with control group (16.85 ± 1.15 g and 18.22 ± 1.63 g, all P < 0.01, respectively).At 30 days post?CS treatment, there was a lower Th1 frequency in the lymph nodes (2.85 ± 1.54% and 2.77 ± 1.07% vs. 5.35 ± 1.34%, respectively; P < 0.05) and spleens (3.96 ± 1.09% and 3.09 ± 0.84% vs. 5.07 ± 1.50%, respectively; P < 0.05) and less inflammatory infiltration and demyelination in the brain of CS?treated mice than that of control group. Conclusions: Our preliminary study demonstrated that CS efficiently alleviated EAE severity and EAE?related pathology damage and decreased the number of Th1s in the periphery, indicating its effectiveness in the treatment of murine EAE. Thus, our findings strongly support the therapeutic potential of this agent as a new traditional Chinese medicine approach in MS treatment.

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

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 set-up error of CR in total body irradiation localization and lung shielding.Methods TOR 18FG software was employed to measure the image quality of images at kV and MV levels.The clinical processes were established and the positioning error was analyzed.Results The low contrast resolution and spatial resolution of MV level images were much worse than those at kV level in the condition of total body irradiation,but the image at MV level could be used to identify the high contrast tissues and employed in total body irradiation.The longitudinal errors were (0.50 ± 1.65) cm for left lung and (1.16 ± 1.56)cm for right lung in A P direction,while (1.12 ± 2.22)cm and (0.41 ± 2.16)cm respectively in PA direction.The errors of lateral were (0.81 ± 1.19)cm for left lung and (0.43 ±1.20)cm for right lung in AP direction,while (0.31 ± 1.64)cm and (0.55 ± 1.49)cm respectively in PA direction.Conclusions Application of CR in total body irradiation could make positioning in treatment much easily and reduce the localization errors.

Immunohistocheraistry and RT-PCR were used to examine the expression of toll-like receptor 4 (TLR4) in the kidney of diabetic rats.Compared with normal control group,the expression of TLR4 in diabetes mellitus group was increased ( P ＜ 0.05 ).Compared with diabetes mellitus group,the expression of TLR4 in simvastatin treated group was decreased( P＜0.05 ).The results suggest that TLR4 may play a role in the pathogenesis of diabetic nephropathy.Simvastatin seems to delay the progress of diabetic nephropathy via reducing TLR4 expression.

Objective To explore the underlying relationship between hyperglycemic factors in type 2 diabe- tes.Methods Fifty seven type 2 diabetes with obesity (DM-OB)and 64 without obesity(DM-NOB)were recruited. Age,body mass index(BMI),hemoglobin A1c (HbA1c),homeostasis model assessment-2 insulin resistance (HO- MA-IR),high-sensitivity C-reactive protein (hsCRP),fasting plasma glucose,postprandial plasma glucose (PPG), postprandial glucose excursion(PPGE),lipid profile,blood pressure were determined.Results DM-OB subjects had significantly higher HOMA-IR,BMI,DBP,TC,hsCRP,HbAlc,LDL-C when compared with DM-NOB sub- jects.Pearson correlation analysis,in DM-OB subjects,BMI,FBG,FPG,HOMA-IR,hs-CRP were all the posi- tive relative factors(P all

[ 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.