Effects of six kinds of Chinese herb extracts, including Folium Crataegi extract, Herba Epimedii extract, Folium Acanthopanacis Senticosi extract, Trifolium pratense L. extract, Folium Ginkgo extract and Radix Puerariae extract, on the activities of CYP450 isozymes (CYP1A2, CYP2C, CYP2E1, CYP2D, CYP3A) in rat hepatic microsomals were studied by using a UPLC-MS/MS (MRM) and cocktail probe substrates method. The results showed that effects of six kinds of Chinese herb extracts on each CYP450 isozyme activity were inhibitory. The IC50 of Folium Crataegi extract for the inhibition of rat microsomal CYP2D activity was only for 4.04 microg x mL(-1), which showed the highest inhibition; Trifolium pratense L. extract had strong inhibitory action to CYP2D, the IC50 value was 5.73 microg x mL(-1); Folium Crataegi extract also had strong inhibitory action on CYP2E1, the IC50 value was 10.91 microg x mL(-1). Furthermore, the IC50 of Folium Ginkgo extract for the inhibition of rat microsomal CYP3A, 2D, 2E1 activities were 45.12, 35.45 and 22.41 microg x mL(-1), respectively, and the IC50 of Folium Acanthopanacis Senticosi extract on the inhibition of rat microsomal CYP2E1 activity was 32.89 microg x mL(-1). In addition, mechanism of inhibition experimental results showed that the inhibiting abilities of Folium Crataegi extract and Radix Puerariae extract on each CYP450 isozyme increased with the increasing of the preincubation time, therefore, the inhibitory effects were a mechanism-based inhibition.

Using a UPLC-MS/MS (MRM) and cocktail probe substrates method, the metabolic fingerprint of the compatibility of Radix Aconite (RA) and Radix Paeoniae Alba (RPA) and its effect on CYP450 enzymes were investigated. These main CYP isoforms include CYP 1A2, CYP 2C, CYP 2E1, CYP 2D and CYP 3A. Compared with the inhibition effect of RA decoctions on CYP450 isoforms, their co-decoctions of RA and RPA with different proportions can decrease RA' inhibition on CYP3A, CYP2D, CYP2C and CYP1A2, but can not reduce RA' effect on CYP2E1. The metabolic fingerprints of RA decoction and co-decoctions with different proportions of RPA in CYP450 of rat liver were analyzed by UPLC-MS. Compared with the metabolic fingerprints of RA decoction, the intensity of diester-diterpenoid aconitum alkaloids decreased significantly, while the intensity of monoester-diterpenoid alkaloids significantly increased in the metabolic fingerprints of co-decoctions of RA and RPA. The results suggest that RA coadministration with RPA increased the degradation of toxic alkaloid and show the effect of toxicity reducing and efficacy enhancing.

Mesaconitine was incubated with rat liver microsomes in vitro. The metabolites of mesaconitine in rat liver microsomes were identified by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method with high resolution power. A typical reaction mixture of 100 mol L-1 Tris-HCI buffer (pH 7.4) containing 0.5 gL-1 microsomal protein and 50 micro molL-1 mesaconitine was prepared. The above reaction mixture was divided into six groups, and the volume of each group was 200 micro L. The incubation mixture was pre-incubated at 37 degrees C for 2 min and the reactions were initiated by adding NADPH generating system. After 90 min incubation at 37 degrees C, 200 micro L of acetonitrile was added to each group to stop the reaction. The metabolites of mesaconitine were investigated by UPLC-MS/MS method. Mesaconitine and 6 metabolites M1-M6 were found in the incubation system. The structures were characterized according to the data from MS/MS spectra and literatures. The metabolic reactions of mesaconitine in rat liver microsomes included the demethylation, deacetylation, dehydrogenation and hydroxylation. The major metabolic pathways of mesaconitine in rat liver microsomes were determined by UPLC-MS/MS on multiple reaction monitoring (MRM) mode combined with specific inhibitors of cytochrome P450 (CYP) isoforms, including alpha-naphthoflavone (CYP1A2), quinine (CYP2D), diethyldithiocarbamate (CYP2E1), ketoconazole (CYP3A) and sulfaphenazole (CYP2C), separately. Mesaconitine was mainly metabolized by CYP3A. CYP2C and CYP2D were also more important CYP isoforms for the metabolism reactions of mesaconitine, but CYP1A2 and CYP2E1 haven't any contribution to MA metabolism in rat liver microsomes.

Objective Previous studies showed that hypoxia preconditioning could protect cardiac function against subsequent myo-cardial infarction injury. However, the effect of hypoxia on left ventricular after myocardial infarction is still unclear. This study therefore aims to investigate the effects of hypoxia training on left ventricular remodeling in rabbits post myocardial infarction. Methods Adult male rabbits were randomly divided into three groups: group SO (sham operated), group MI (myocardial infarc-tion only) and group MI-HT (myocardial infarction plus hypoxia training). Myocardial infarction was induced by left ventricular branch ligation. Hypoxia training was performed in a hypobaric chamber (having equivalent condition at an altitude of 4000 m, FiO214.9%) for 1 h/day, 5 days/week for four weeks. At the endpoints, vascular endothelial growth factor (VEGF) in the plasma was measured. Infarct size and capillary density were detected by histology. Left ventricular remodeling and function were as-sessed by echocardiography.Results After the 4-week experiment, compared with the group SO, plasma VEGF levels in groups MI (130.27 ± 18.58 pg/mL,P< 0.01) and MI-HT (181.93 ± 20.29 pg/mL,P< 0.01) were significantly increased. Infarct size in Group MI-HT (29.67% ± 7.73%) was deceased remarkably, while its capillary density (816.0 ± 122.2/mm2) was significantly increased. For both groups MI and MI-HT, left ventricular end-diastolic and end-systolic dimensions were increased whereas left ventricular ejection fraction was decreased. However, compared with group MI, group MI-HT diminished left ventricular end-diastolic (15.86 ± 1.09 mm,P< 0.05) and end-systolic dimensions (12.10 ± 1.20 mm,P< 0.01) significantly and im-proved left ventricular ejection fraction (54.39 ± 12.74 mm,P< 0.05).ConclusionHypoxia training may improve left ven-tricular function and reduce remodeling via angiogenesis in rabbits with MI.

ovel GCK-E339K mutation might be linked to this MODY2 pedigree.

Objective To explore the level of uric acid and lipid metabolism in 120 patients with psoriasis and their clinical diagnostic significance.Methods A total of 120 patients with psoriasis were selected.Uric acid and blood lipids were detected.Levels of TC,TG,HDL-C,LDL-C,ApoA1,ApoB,uric acid were compared between psoriasis group and control group.Lipid metabolism in patients with different types of psoriasis was compared.Results The levels of TC,HDL-C and ApoA1 in the psoriasis group were significantly lower than those in the control group (P ＜ 0.05),and the level of TG was significantly higher than that of the control group (P ＜ 0.05).Levels of TC,HDL-C,LDL-C,ApoA1 and ApoB in psoriasis pustulosa group were significantly lower than the other two groups (P ＜ 0.05).Serum uric acid values of male and female in psoriasis group were significantly higher than the control group (P ＜ 0.05).Conclusion Analysis of uric acid,lipid metabolism in psoriasis patients has very important diagnostic significance.

Objective To explore the level of uric acid and lipid metabolism in 120 patients with psoriasis and their clinical diagnostic significance.Methods A total of 120 patients with psoriasis were selected.Uric acid and blood lipids were detected.Levels of TC,TG,HDL-C,LDL-C,ApoA1,ApoB,uric acid were compared between psoriasis group and control group.Lipid metabolism in patients with different types of psoriasis was compared.Results The levels of TC,HDL-C and ApoA1 in the psoriasis group were significantly lower than those in the control group (P ＜ 0.05),and the level of TG was significantly higher than that of the control group (P ＜ 0.05).Levels of TC,HDL-C,LDL-C,ApoA1 and ApoB in psoriasis pustulosa group were significantly lower than the other two groups (P ＜ 0.05).Serum uric acid values of male and female in psoriasis group were significantly higher than the control group (P ＜ 0.05).Conclusion Analysis of uric acid,lipid metabolism in psoriasis patients has very important diagnostic significance.

BACKGROUND:Repetitive magnetic stimulation of either S3 nerve root or M1 area can improve the urination function of patients with urinary retention after spinal cord injury,but there are few reports on the repetitive magnetic stimulation of both sites in patients with urinary retention after spinal cord injury. OBJECTIVE:To observe the effect of repetitive magnetic stimulation of both S3 nerve root and M1 area on urinary retention after spinal cord injury. METHODS:Forty patients with urinary retention after spinal cord injury were enrolled and were randomly divided into two groups(n=20 per group):group A(repetitive magnetic stimulation in both S3 nerve root and M1 area)and group B(repetitive magnetic stimulation in the S3 nerve root and sham stimulation in the M1 area).Patients in both groups were given 4-week repetitive magnetic stimulation based on conventional bladder function intervention.The stimulation time and duration of treatment were same in both groups,with a treatment time of 21 minutes daily,5 days per week,for 4 weeks in total.The urination diary and urodynamics were compared between two groups. RESULTS AND CONCLUSION:Before treatment,there were no statistically significant differences in the average daily catheterization times,average daily catheterization volume,average single urinary volume,urinary storage period(maximum bladder volume,bladder pressure),and urinary voiding period(detrusor pressure,residual urine volume)between the two groups(P>0.05).After 4 weeks of treatment,the average daily catheterization times in group A were lower than before treatment(P<0.05),while the average single urination volume in group A was higher than that before treatment(P<0.05);and the average daily catheterization times in group B were lower than before treatment(P<0.05).After 4 weeks of treatment,the average daily catheterization times in group A were lower than those in group B,and the average single urination volume was higher than that in group B(P<0.05).After 4 weeks of treatment,the maximum bladder volume and detrusor pressure during urination were increased in both groups compared with before treatment(P<0.05),while the bladder pressure and residual urine volume at the maximum volume of the two groups were decreased compared with those before treatment(P<0.05).Compared with group B,the maximum bladder volume and detrusor pressure during urination were higher in group A,while the bladder pressure and residual urine volume at maximum volume were lower in group A(P<0.05).To conclude,two treatments can both improve the urination function of patients with urinary retention after spinal cord injury,and repetitive magnetic stimulation of both S3 nerve root and M1 area is superior to repetitive magnetic stimulation of S3 nerve root alone.Repetitive magnetic stimulation of both S3 nerve root and M1 area can effectively improve the urination function of patients with urinary retention after spinal cord injury.