The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows: CL = θCL · (WT/60)θWT · θCYP · eηCL (if CYP2C9*1/*1, θCYP = 1; if *1/*3, θCYP = 0.708); EC50 = θEC50 · θVKOR · eηEC50 (if VKORC1- 1639AA, θVKOR = 1; if GA, θVKOR = 2.01; V = θV; K(E0) = θK(E0); Emax = θEmax; E0 = θE0 · eηE0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin.
Anticoagulants ; pharmacology ; Body Weight ; Cytochrome P-450 CYP2C9 ; genetics ; Genotype ; Humans ; International Normalized Ratio ; Nonlinear Dynamics ; Polymorphism, Genetic ; Vitamin K Epoxide Reductases ; genetics ; Warfarin ; pharmacokinetics

Objective To investigate the sexual problems during early postpartum period and the awareness of postpartum sexual health. Methods A questionnaire survey was carried out in 109 women who received routine postpartum check-up in our outpatient department between October and November 2010 to identify postpartum sexual problems and the awareness of postpartum sexual health. Results The first postpartum check-up was received 6 to 12 weeks after the delivery. Of 109 participants,6 (5.5%), 17(15.6%) and 46 (42.2%) resumed sexual activity within 6,6 to 8,and 12 weeks after the delivery,respectively. Postpartum sexual problems included dyspareunia (35/46,76. 09% ), vaginal dryness (29/46,63.04% ), hypoactive sexual desire (25/46,54. 35% ) and lack of orgasm ( 11/46,23.91% ). 10. 87% (5/46)took contraceptive measures,21.10% (23/109) understood the appropriate time to resume sexual activity, 12. 84% (14/109) was aware of the possible postpartum sexual problems, 13.76% (15/109) knew how to avoid pregnant,6.42% (7/109) would visit a doctor in case of the sexual disorders,and 9. 17%(10/109) hoped that their husband know about sexual health. Conclusion Postpartum sexual problems may be common and maternal awareness of postpartum sexual health could be low.

Objective To investigate the role of scavenger receptor class B type 1 (SR-B1) signaling pathway in serum amyloid A (SAA)-induced angiogenesis in rheumatoid arthritis (RA).Methods The expression and location of SR-B1 in RA and osteoarthritis (OA) synovial tissues were observed by immunohistochemistry.And SR-B1 expression in the resting human umbilical vein endothelial cells (HUVECs) was detected by immunoflourescence.Wound repair assessement and tube formation assessement were employed to evaluate the effect on cell migration and tube formation stimulated by SAA and/or anti-SR-B1 antibody.The t-test and one-way analysis of variance (ANOVA) were used for statistical analysis.Results ① SR-B1 was significantly highly expressed in RA tissue samples (A=6 788±819) when compared to the minimal expression in OA (A =31 849±6 977,t=3.567,P＜0.01).Positive staining of SR-B1 was observed in RA synovial vascular endothelial cells and perivascular areas.② Strong staining for SR-B1 was observed in all HUVECs tested.③ Significant wound healing induced by SAA (MI=2.50±0.17) was found compared with the untreated controls (MI=1.00±0.09,q=14.38,P＜0.01),and the effects were inhibited in the presence of anti-SR-B1 antibody (MI=1.16±0.14,q=13.02,P＜0.01).④ Compared to the untreated group (branch point number:6.6±0.8),there was an enhanced formation of branched and capillary-hke tube structure followed by SAA stimulation (branch point number:19.0±1.1,q=25.04,P＜0.01) after culturing for 72 h,whereas,tube formation decreased markedly upon pre-treated with anti-SR-B1 antibody (branch point number:7.6±1.3,vs SAA,q =23.32,P＜0.01).Conclusion Our present study suggests that serum amyloid A may induce angiogenesis via SR-B1 signaling pathway in RA.

Objective To explore whether serum amyloid A (SAA) can induce the formation of neutrophil extracellular traps(NETs)in neutrophils in vitro. Methods A stable method for inducing NETs formation in vitro was established, in-cluding isolation of peripheral blood neutrophils, cell culture, and NETs formation and observation. The neutrophils were iso-lated from peripheral blood of healthy volunteers. And cells were cultured in vitro and classified into three groups:negative control (NC) group, SAA group and lipopolysaccharide (LPS) group. Following the distinct stimulation in three groups, NETs formation was observed and its percentage was calculated. The concentration of hinstone (h) 3 in supernatant was detected by ELISA. Results The purification and vitality of isolated neutrophils were both more than 95%. The nuclei of neutrophils lost their shape and spread, NETs formation was found. More NETs formation was found in SAA group than that in NC group (P < 0.05). Moreover, the concentration of h3 in supernatant was significantly higher in SAA group than that in NC group (P<0.05). Conclusion SAA can induce the formation of NETs in vitro.

A total of 121 subjects comprising 40 normal subjects,58 patients with overweight or obesity and 23 patients with Cushing's syndrome were recruited in the study.The modified radioimmunoassay (RIA) for salivary cortisol test was established'and its normal range was determined.Then the diagnostic value of the salivary cortisol for the initial diagnosis of Cushing's syndrome was evaluated and single midnight salivary cortisol test demonstrated a sensitivity of 100.0% and specificity of 91.4 %.Salivary cortisol test can be recommended as a first-line diagnostic parameter for Cushing's syndrome.

Multi-component traditional Chinese medicines are an innovative research mode for traditional Chinese medicines. Currently, there are many design methods for developing multi-component traditional Chinese medicines, but their common feature is the lack of effective connection of the traditional Chinese medicine theory. In this paper, the authors discussed the multi-component traditional Chinese medicine design methods based on medicinal property combination modes, provided the combination methods with the characteristics of traditional Chinese medicine for the prescription combinations, and proved its feasibly with hypertension cases.
Animals ; Antihypertensive Agents ; administration & dosage ; chemistry ; Blood Pressure ; drug effects ; Drug Combinations ; Drug Therapy ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Humans ; Hypertension ; drug therapy ; physiopathology ; Medicine, Chinese Traditional ; Rats

Objective To compare the 7th edition of International Union Against Cancer ( UICC) staging system with the Chinese 2008 staging system for nasopharyngeal carcinoma ( NPC) , and to provide evidence for further updating of the staging system. Methods A retrospective analysis was performed among 767 patients who were pathologically and newly diagnosed with non?metastatic NPC and treated with intensity?modulated radiotherapy from 2006 to 2012. Based on the main prognostic indices, overall survival ( OS) , locoregional failure?free survival( LFFS) local relapse?free survival ( LRFS) , and distant metastasis?free survival ( DMFS) rates, the value of T stage, N stage, and clinical stage in prognostic prediction was compared between the two staging systems. The Kaplan?Meier method was used for calculating survival rates. The log?rank test was used for survival difference analysis. The Cox model was used for multivariate prognostic analysis. Results In terms of T stage, the Chinese 2008 staging system was a significantly better predictor of the OS and LRFS rates than the 7th edition of UICC staging system. In terms of N stage, they were comparable in the prediction of the OS and DMFS rates. In terms of clinical stage, the 7th edition of UICC staging system was a significantly better predictor of the OS rate than the Chinese 2008 staging system. For the new staging system proposed based on the statistical results, the T, N, and clinical staging gave significantly better prognostic prediction. Conclusions The 7th edition of UICC staging system and the Chinese 2008 staging system for NPC have their own advantages in prognostic prediction. The new staging system proposed in this study could contribute to the updating of the current staging system for NPC.

Objective To evaluate the effects of metabolic factors on the quality of 18F-fluorode oxyglucose (18F-FDG) myocardial metabolic imaging in coronary artery disease (CAD) patients with type 2 diabetes mellitus (T2DM). Methods Seventy CAD patients aged 60 years or over with T2DM were studied with myocardial 18 F-FDG dual isotope simultaneous acquisition (DISA) single photon emission computed tomography (SPECT). Fasting plasma glucose, total triglyceride (TG),total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-eholesterol(LDL-C), insulin, C peptide and glyeosylated hemoglobia (HbAlc) were detected. Insulin resistance and islet β cell function were calculated by using the Homeostasis Model Assessment (HOMA) equation. Results Compared with the bad image quality group (36 cases), patients in the excellent image quality group (34 cases) were younger [with average age of (62.2±8.5) years vs. (67.6±8.3) years, P<0.01] and slimmer [with BMI of (24.7±2.6)kg/m2 vs. (26.1±2.5)kg/m2, P<0.05]. The levels of fasting insulin and C peptide were lower in the excellent image quality group than those in the bad image quality group [with fasting insulin level of 8.3 (5.1～12.4) mIu/L vs. 12.7,(6.1～17.9)mIu/L and C-peptide level of 0.6(0.5～0.9)nmol/L vs. 0.9(0.6～1.2)nmol/L, respectively,both P<0.05]. The HOMA insulin resistant index was reduced in the excellent image group [2.7(1.6～4.0) vs. 4.1(1.7～6.5), P<0.05]. Logistic regression analysis showed that obesity and age≥65 years were independent risk factors for image quality, with OR value of 3.73 (95% CI: 1.12～12.45,P=0.022)and 3.75 (95%CI:0.96～14.6,P=0.058)after adjustment of other metabolic factors. Conclusions Insulin resistance is the main factor that influences the quality of 18F-FDG myocardial metabolic imaging in patients with T2DM. In addition, age≥65 years and obesity are also risk factors for image quality.

AIM:To investigate the production and activation of caspase-3 in primary rat renal proximal tubule cells in response to tumor necrosis factor-α(TNF-α) and the implication of nuclear factor-κB (NF-κB) in the process. METHODS:Isolated rat renal proximal tubule cells (PTCs) from male adult Sprague Dawley rats were treated with TNF-α according to the indicated time courses. A specific NF-κB inhibitor,Bay11-7082,was used alone or as a pretreatment for 1 h followed by exposure to TNF-α for 24 h.The protein levels of cleaved caspase-3,caspase-3,I-κBα,phosphorylated I-κBα,and GAPDH were detected by Western blotting using specific antibodies. RESULTS:The protein level of cleaved caspase-3 relative to caspase-3 was significantly increased in the presence of TNF-α for 6 h,12 h,and 24 h. Protein levels of caspase-3 were significantly decreased by 12 h and returned to baseline by 24 h in the presence of TNF-α. Treatment with Bay11-7082 for 25 h alone or pretreatment with Bay11-7082 for 1 h followed by addition of TNF-α for 24 h caused a remarkable reduction in both cleaved caspase-3 and caspase-3 as compared to control and TNF-α treated groups. An increase in phosphorylated I-κBα was observed from 15 min to 60 min after treatment with TNF-α at a dose of 10 μg/L in PTCs. CONCLUSION:NF-κB is not only associated with the activation of caspase-3 but also the production of caspase-3 in primary rat renal proximal tubule cells in response to TNF-α.

Objective To study the difference of gene expression profile between the radioresistant human nasopharyngeal carcinoma cell line CNE-2R and CNE-2,and to screen the signaling pathway associated with radioresistance of nasopharyngeal carcinoma.Methods The radioresistant nasopharyngeal carcinoma cell line CNE-2R was constructed from the original cell line CNE-2.CNE-2R and CNE-2 cells were cultured and administered with 60Co γ-ray irradiation at the dose of 400 cGy for 15 times.Human-6v 3.0 whole genome expression profile was used to screen the differentially expressed genes.Bioinformatic analysis was used to identify the pathways related to radioresistance.Results The number of the differentially expressed genes that were found in these 2 experiments was 374.The Kegg pathway and Biocarta pathway analysis of the differentially expressed genes showed the biological importance of Toll-like receptor signaling pathway and IL-1 R-mediated signal transduction pathway to the radioresistance of the CNE-2R cells and the significant differences of 13 genes in these 2 pathways,including JUN,MYD88,CCL5,CXCL10,STAT1,LY96,FOS,CCL3,IL-6,IL-8,IL-1α,IL-1B,and IRAK2(t=13.47-66.57,P<0.05).Conclusions Toll-like receptor signaling pathway and IL-1R-mediated signal transduction pathway might be related to the occurrence of radioresistance.