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 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.

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.

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.

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.

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

Angiotensins ; analysis ; Animals ; Animals, Newborn ; Biomarkers ; analysis ; Endothelin-1 ; analysis ; Hypertension, Pulmonary ; drug therapy ; metabolism ; physiopathology ; Lung ; chemistry ; pathology ; Magnesium Sulfate ; pharmacology ; Nitric Oxide Synthase ; analysis ; Nitric Oxide Synthase Type II ; Swine ; Vasomotor System ; chemistry

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.

Objective To evaluate the risk factors related to the failure of internal fixation for intertrochanteric fracture in Chinese patients.Methods A comprehensive Meta analysis of the clinical research from January 2005 to August 2016 on the failure of internal fixation for intertrochanteric fracture in Chinese patients was conducted after Pubmed,CNKI,Wanfang Data,et al.,had been searched.Revman5.0 was used to perform the heterogeneity test and calculate the OR value and 95％ CI after quality assessment and retrieval of the qualified data.Results Included for this analysis were 23 studies involving 4,031 patients of whom 588 failed.The factors related to the failure of internal fixation for intertrochanteric fracture included patient age [OR =0.51,95％ CI (0.30,0.90),P ＜ 0.05],osteoporosis [OR =1.91,95％ CI (1.05,3.47),P ＜0.05],fracture pattern[OR=0.23,95％ CI (0.18,0.30),P ＜0.05],quality of fracture reduction [OR =0.25,95％ CI (0.17,0.35),P ＜0.05],tip-apex distance (TAD) [OR =0.13,95％ CI (0.05,0.32),P ＜0.05],time for full weight bearing [OR=5.32,95％ CI (1.71,16.57),P ＜ 0.05],and associated internal diseases [OR =3.76,95％ CI (1.19,11.91),P ＜0.05].The relationship was not determined between the failure of internal fixation for intertrochanteric fracture and the following factors:gender [OR=0.78,95％ CI (0.54,1.11),P ＞ 0.05],injury cause [OR=1.68,95％ CI (0.66,4.25),P＞ 0.05] or type of internal fixation [OR=0.37,95％CI (0.06,2.14),P＞0.05].Conclusions High age,concomitant osteoporosis,complicated fracture pattern,unsatisfactory fracture reduction,TAD ≥ 25 mm,time for full weight bearing ＜ 6 weeks,and concomitant internal diseases may be the risk factors closely related to the failure of internal fixation for intertrochanteric fracture in Chinese patients.There has been no sufficient evidence to show that gender,injury cause or type of internal fixation may be associated with the failed internal fixation for intertrochanteric fracture.