Aim To investigate the effects of CYP2C19 polymorphism on the pharmacokinetics and comparative bioavailability of omeprazole in Chinese population.Methods Eighteen healthy male volunteers were selected,of whom 6 were CYP2C19 wild type(w/w),6 were CYP2C19 heterozygous variant(w/m) and the rest were CYP2C19 homozygous variant(m/m).A randomized two-period crossover study was performed.Subjects were assigned to receive test or reference omeprazole as a single oral dose of 40 mg randomly.After a washout period of one week,subjects received the alternative omeprazole formulation.Multiple blood samples of 3 ml were obtained over 12 h after dosing and plasma concentrations of omeprazole were measured by LC/MS method.The modeling of individual pharmacokinetics and the pharmacokinetic parameters of omeprazole were estimated by 3P97.Results The AUC and Cmax of reference omeprazole formulation in w/w,w/m,m/m groups were 1178.44±340.24,2328.10±1011.83,5062.02±1097.29 μg·h·L~(-1) and 602.87±118.25,926.43±134.48,1406.29±233.58 μg·L~(-1),respectively,with significant differences among the three groups(P<0.05).Significant differences were also observed in other pharmacokinetic parameters such as k_e、CL/F、t_(1/2) and Vd/F among the three groups(P<0.05).With regard to test omeprazole formulation,the AUC and C_(max) in w/w,w/m,m/m groups were 1224.82±531.67,2723.34±519.29,5692.49±1575.35 μg·h·L~(-1) and 618.74±231.43,910.67±125.99,1303.31±152.01 μg·L~(-1),respectively,which,as well as k_e,CL/F,t_(1/2) and Vd/F were significant different among the three groups(P<0.05).No significant differences were observed in comparative bioavailability among groups with the values of 94.29%±14.06%,93.08%±11.22%,91.84%±13.03% in w/w,w/m,m/m groups respectively(P>0.05).Conclusions Different CYP2C19 genotypes,leading to functional heterogeneity of CYP2C19,may affect pharmacokinetic profile of omeprazole.Therefore,genotyping CYP2C19 gene before omeprazole therapy will be of great benefit for optimizing individual therapy regimen.There is no significant difference of omeprazole comparative bioavailability with regard to CYP2C19 genetic polymorphism.

Developmental changes in children can affect drug disposition and clinical effects. A physiologically-based pharmacokinetic (PBPK) model is a mathematical model that can be used to predict blood drug concentrations in children and gain insight into age-dependent physiological differences in drug disposition impact. Pediatric PBPK (P-PBPK) models have attracted attention over the past decade. With the concerted efforts of academia, pharmaceutical companies, and regulatory agencies, there are more and more examples of pediatric clinical studies using PBPK models. Nevertheless, the number of P-PBPK models and their predictive performance still lag behind adult models. By referring to the literature, we study the process of children adapting to adult absorption, distribution, metabolism, and excretion (ADME) parameters and analyze the general principles of P-PBPK model establishment. In addition, we summarize the functions and application examples of commonly used P-PBPK modeling software to provide a basis for the rational application of modeling software.

Objective To investigate the effects of acitretin on T helper cell (Th) 1/Th2 balance and Th17 cells in psoriasis vulgaris (PV) patients. Methods A total of 13 men and 17 women with PV were investigated. 10 mg of acitretin was administered twice a day for 8 weeks for intervention therapy. Serum levels of interferon-gamma (IFN-γ), interleukin (IL)-4 and IL-17 were measured by enzyme-linked immunosorbent assay. T, Th1, Th2 and Th17 cells in skin biopsies were counted with double-labeled immunofluorescence. Psoriasis Area and Severity Index (PASI) score was calculated before and 8 weeks after treatment. Results Before treatment PV patients had higher serum levels of IFN-γ and IL-17, and increased T, Th1 and Th17 cells in skin biopsies. After treatment, both serum levels of IFN-γ and IL-17, and T, Th1 and Th17 cells infiltrating in PV skin decreased significantly. Th1/Th2 balance was restored to normal. However, their IL-4 and Th2 cells showed no significant change throughout the therapy. Conclusion Acitretin exerts influence on dermal Th1/Th2 balance and Th17 cell infiltration, so does it on production of systematic inflammatory cytokines IFN-γ and IL-17 in PV patients. However, Th2 cells and its derivative cytokine-IL-4 are not affected.

Objective To solve the problem that the rat retina paraffin sections are easily exfoliated from the slides and each layer are easily separation and fracture,we need to find a way to improve the retina paraffin section method and evaluate the tissue fixation. Methods We used 4 fixation liquids including 10%paraformaldehyde,4%paraformaldehyde, 4% paraformaldehyde and 95% alcohol and glacial acetic acid mixed liquid (FAA fixatiue solution ) combined with paraformaldehyde to fix the retinal tissue, and observed the fixation efficacy under microscope after HE staining. Results The effects of 10%paraformaldehyde and 4%paraformaldehyde fixed samples showed moderate separation and fracture of retina,but the HE staining retinal slices pre-treated by the FAA fixafive solution had bright and uniform color,although occasionally some parts of the retina were exfoliated from the slide, but it was not easy to take off,and had complete structure without separation and rupture. Conclusion The retina paraffin section fixed by FAA ixafive solution with 4% paraformaldehyde is superior to pure paraformaldehyde, and the paraformaldehyde concentration has no obviously influence on HE staining results.

Objective To explore the cancer incidence in registration areas in Shanxi Province. Methods Data of 8 cancer registration areas in 2011 were taken into account and cancer incidence in different areas with different ages was compared with that in other domestic areas. Results 8 395 new cases in Shanxi all cancer sites were reported in 2011, including 4 810 male and 3 585 female. The incidence of malignant cancer of Shanxi was 207.53/100 000, and the standardized incidence of Chinese population and world population were 125.20/100 000 and 165.72/100 000, respectively. In urban areas, the incidence of Shanxi and the standardized incidence of Chinese population were 202.49/100 000 and 112.81/100 000, respectively. In rural areas, incidence rate of Shanxi was 211.96/100 000 and the standardized incidence of Chinese population was 138.43/100 000. In Shanxi Province, the major malignant cancer sites for males involved stomach, lung, esophagus, liver and colorectum, and cancer sites for females were more on cervix, lung, breast, stomach and esophagus. Conclusions Upper gastrointestinal cancer and uterine cervix cancer are the major cancers in Shanxi registration areas. The incidence of stomach cancer and uterine cervix cancer in Shanxi Province are much higher than national average.

Objective To investigate clinical curative effect of partial foraminotomy after C4.5 ossification of posterior longitudinal ligament (OPLL) on preventing C5 nerve root palsy.Methods A total of 155 patients with OPLL were treated with expansion open-door laminoplasty (EOLP) between January 2008 and October 2012,including 75 male patients and 80 female patients,with average age of 54.5 (ranging from 38 to 75).Among them,90 cases took EOLP (open team),and 65 cases took EOLP and C4.5 partial foraminotomy (incision team).Clinical curative effect and imaging evaluation were used in 8 weeks and 12 months after operation.JOA scores,JOA scores improvement rate,C5 nerve root palsy occurrence rate,neurological function of patients with C5 nerve root palsy and the prognosis,cervical curvature index,opening angular variation,backward drift distance of anterior margin and posterior margin of the spinal cord were evaluated after 8 weeks and 1 year after the surgery.Results The operation time was 90-140 min,with the average time of 110±14 min;mean bleeding volume was 160±45 ml (ranging from 100 to 250 ml);follow-up visit time was 15.4 months on average (ranging from 12 to 18 months).JOA score and improvement rate after 8 weeks and 1 year of the operation have no statistical significance.The C5 nerve root palsy occurrence rate in open team was 8.89％ (8/90),while that in incision team was 4.62％ (3/65).The difference of two groups has statistical significance.C5 nerve root palsy all happened in laminar opening side.Comparison of cervical curvature index of two groups before the operation and after 8 weeks of the operation and inter-group comparison have no statistical significance.The difference between laminar opening angle after 1 year of the operation and laminar opening angle after 8 weeks has no statistical significance.The difference of backward drift distance of anterior margin of the spinal cord at different time after the operation and inter-group difference have no statistical significance.The difference in backward drift distance of posterior margin of the spinal cord between 1 year after the operation and 8 weeks after the operation has no statistical significance.Conclusion Treating OPLL with EOLP and C4.5 partial foraminotomy can reduce occurrence rate of C5 nerve root palsy,but has no significant influence on JOA score improvement rate.

BACKGROUND: Current studies on CD62P have focused mainly on cardiovascular diseases, while only few studies have evaluated the effects of CD62P on the development of sepsis and the association between endothelial cell injury with inflammation and coagulation. This study attended to explore the association between endothelial cell injury with inflammation and coagulation by evaluating the expression of soluble CD62P (s-CD62P) in plasma and its mechanism in patients with sepsis, thus to provide the evidence of effective treatment of sepsis with anti-adhesion therapy targeted CD62P. METHODS: A total of 70 critically ill patients with systemic inflammatory response syndrome (SIRS) admitted to intensive care unit (ICU) between September 2009 and February 2010 were enrol ed for a prospective and control study. According to the diagnostic criteria of sepsis/SIRS, the patients were divided into two groups: a sepsis group (n=38) and a SIRS group (n=32). Another 20 healthy volunteers served as a control group. Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure, diabetes and its complications. The demographics of the patients including age, sex, body mass index (BMI), smoking and alcohol addict were compared among the groups. Six mL peripheral blood samples were collected within 24-hour admission in ICU for enzyme-linked immunosorbent assay (ELISA) to detect the plasma levels of s-CD62P, TNF-α, and hs-CRP. And variables of coagulation function such as platelet (PLT), prothrombin (PT), activated partial thromboplastin time (APTT), D-dimer and antithrombin-III (AT-III) were analyzed during 24 hours after admission to ICU. Meanwhile sequential organ failure assessment (SOFA) score of critically ill patients was evaluated. Data were expressed as mean±standard deviation and were statistical y analyzed by using SPSS 17.0 statistical software. The differences in plasma levels of s-CD62P of patients in each group were analyzed by ANOVA and the Kruskal-Wallis test. The relations between s-CD62P and inflammatory cytokines as well as with coagulation were determined by Pearson's product moment correlation coefficient analysis. Changes were considered as statistically significant if P value was less than 0.05. RESULTS: Compared with the control group and SIRS group, the sepsis group demonstrated significantly higher levels of s-CD62P, TNF-α and highly sensitive C-reactive protein (hs-CRP) (P<0.05). The plasma levels of D-dimer, PT, and APTT in the sepsis and SIRS groups were significantly higher than those in the control group, while the platelet count and the activity of AT-III were obviously lower (P<0.05). In the sepsis group, the plasma levels of hs-CRP and TNF-α were positively correlated with PT, APTT, and D-dimer, and negatively correlated with AT-III and PLT (P<0.05). The plasma levels of s-CD62P were significantly correlated with the plasma levels of TNF-α, hs-CRP, D-dimer, PT, and APTT, whereas they were correlated negatively well with PLT and AT-III (P<0.05). CONCLUSIONS: The concentration of plasma s-CD62P is elevated as a early biomarker in patients with sepsis, and it serves as one of the pathogenic factors responsible for endothelial cell damage. Coagulation and mediators of inflammation promote each other, aggravating the severity of sepsis. Plasma s-CD62P may be an important factor for the development of coagulation and inflammatory reaction.

Electrolytes ; Therapeutic Irrigation ; methods

Objective To study the effect of sub-chronic exposure to dehamethrin(DM) on the behavior of mice in learning and memory.Methods 60 Female SPF Kunming mice were randomly divided into 4 groups and given DM by gavaging for 60 days.Morris water maze (MWM) was used to evaluate spatial memory in mice.Results After exposure to DM,the escape latency of the solvent control group and the treatment groups were (12.20±6.5)s,(14.99±5.4) s,(15.64±8.3)s,(22.71±6.2)s on the fifth day.The escape latency of the high-dose group was higher than those of the low-dose group (P=0.0041) and the solvent control group (P=0.019) in the navigation test.The number of crossing position of the platform in the high-dose group ((2.93± 1.53)times) and the middle-dose group ((3.40± 1.12) times) were lower than that in the solvent control group ((5.87 ± 1.55) times) and the low-dose group ((4.90± 1.41)times)(P＜0.05).Conclusion Sub-chronic exposure to DM can damage the spatial learning and memory of mice.