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

0.05).Conclusion Long-term inhaled glucocorticosteroids has no obvious effect on GH and height growth of asthmatic children.

ObjectiveTo investigate the relationship between platelet-derived growth factor (PDGF)-B and pre-eclampsia or eclampsia by comparing the expression of PDGF-B mRNA and PDGF-BB protein in the placentas from pregnant women with normal pregnancy,pre-eclampsia or eclampsia.Methods The expression of PDGF-B mRNA and PDGF-BB protein were respectively determined with RT-PCR and immunohistochemistry combined with the analysis of computer microphotography in the placentas from 20 mild pre-eclampsia (mild pre-eclampsia group),20 severe pre-eclampsia (severe pre-eclampsia group),3 eclampsia (eclampsia group) and 20 normal pregnancy (control group).ResultsThe expression of PDGF-B mRNA and PDGF-BB protein in the placentas of mild pre-eclampsia group,severe pre-eclampsia group and eclampsia group ( 1.56 ± 0.30 and 1.32 ± 0.34,1.91 ± 0.28 and 2.00 ± 0.41,2.57 ± 0.06 and 2.73 ± 0.15)were higher than those of control group ( 1.38 ± 0.25 and 1.01 ± 0.26) with significant differences (P＜ 0.01 ).The expression of PDGF-B mRNA and PDGF-BB protein in the placentas of severe pre-eclampsia group and eclampsia group were higher than those of mild pre-eclampsia group (P ＜ 0.01 ).The expression of PDGF-B mRNA and PDGF-BB protein were positively correlated with the degree of the disease (r =0.691,0.797,P ＜0.01 ).ConclusionsPregnant women with pre-eclampsia and eclampsia have higher expression of pDGF-B in the placentas.PDGF-B may play an important role in the development and progression of pre-eclampsia and eclampsia by promoting atherogenesis in the placental vessels.

Objective To investigate Iomoxicam,paracetamol,trarnadol in post-operative analgesia of surgical abortion.Methods 200 patients undergoing surgical abortion were randomly allocated into four groups:lornoxicam,paracetamol,tramadol and the control group.Intravenous anesthesia was conducted.Lomoxicam 16 mg,paracetamol 1000mg,tramadol 100 mg were administered before patients awaking.VAS scores and complications were observed post-operation.Pre-operative and post-operative salivary cortisol was detected.Results VAS scores were less in the 3 analgesic groups than in control group at 15,30 minutes post-operation(P＜0.05).VAS scores had no difference in all groups at 60,120 minutes.Cortisol was higher in the control on the next day(P＜0.05).Conclusion Post-operative analgesia was effective for surgical abortion.

Objective To compare the effect and compliance of Rifampicin by vein and oral in treating pulmonary tuberculosis in elderly patients who were primary treated and had positive sputum. Methods A total of 100 first-time smear-positive pulmonary tuberculosis patients were randomly divided into two groups, the treatment group and the control group,with 50 cases in each group. During the observation enhancement period,patients of the treatment group were given HZE added rifampin inoculation fluid and HEZ plus rifampin capsules for the control group.The indicators were recorded, such as:the rate of digestive discomfort, liver digfunction ,symptom improvement, sputum smear negative conversion at the end of the second month and chest X-ray improvement. Results In therapy group and control group,the rate of digestive discomfort was 14% and 82% respectively,P ＜0. 05 ;the rate of liver disfunction at the first weekend was 16% and 12% respectively(P ＞ 0. 05 ) ;The rate of liver disfunction at the second weekend was 36% and 30% respectively(P ＞0. 05) ;The rate of the symptom improvement was 96% and 70% respectively ( P ＜ 0. 05 ) ;The rate of improvement remarkably in chest film was 80% and 32% respectively( P ＜ 0. 05 ) ;The rate of sputum smear negative conversion at the end of the second month was 52% and 34% ,P ＞0. 05 ;the rate of.sputum smear negative conversion at the end of the sixth month was 96% and 82% (P ＜ 0. 05 ) ;The rate of chemotherapy formula changed during the therapy was 14% and 82% ( P ＜ 0. 05). Conclusion The Rifampicin was used by vein in elderly PTB that primary treated and got positive sputum could get better effect indexes,less side effect in digestive tract,similar liver disfunction and fine compliance to the standardized chemotherapy formula.

OBJECTIVE: To investigate imaging and audiology features of temporal bone and analyze the classification and prevalence of inner ear abnormalities in children with sensorineural hearing loss. METHOD: Children who were diagnosed with sensorineural hearing loss were examined by high resolution CT and the inner ear fluid of MRI. And each chart was retrospectively reviewed to determine the imaging and audiology features. RESULT: There were 125 patients(232 ears) found with inner ear malformation in 590 children with SNHL. About 21.71% of the inner ear malformation occurred in severe and profound hearing loss ears, and 12.85% occurred in r moderate hearing loss ears. The inner ear malformation rate in normal hearing ears were 13.59%. CONCLUSION CT and MRI examinations of temporal bone are important diagnostic tools to indentify inner ear malformations. Inner ear malformations are almost bilateral and hearing loss are profoud. Cochleo-vestibular malformations and large vestibular aqueduct are the 2 most frequent deformities. Among the children with SNHL, deformity rate in the severe and profound hearing loss ears is higher than that in moderate hearing loss ear. Inner ear malformations can exist in people with normal hearing.
Audiology ; Child ; Ear, Inner ; abnormalities ; Hearing Loss, Sensorineural ; congenital ; pathology ; Humans ; Magnetic Resonance Imaging ; Prevalence ; Retrospective Studies ; Temporal Bone ; Tomography, X-Ray Computed ; Vestibular Aqueduct ; abnormalities

OBJECTIVETo study the effect of Bushen Tongdu Capsule (BTC) on RANK/RANKL/ OPG pathway of collagen induced arthritis (CIA) rats, thereby laying theoretic evidence for treating rheumatic arthritis (RA) by Chinese medicine.

METHODSRA model was induced by CIA. Totally 42 rats were randomly divided into six groups, i.e., the normal control group, the model group, the low dose BTC (BSL) group, the medium dose BTC (BSM) group, the high dose BTC (BSH) group, and the Tripterygium Glycosides (TG) group, 7 in each group. BTC at the daily dose of 120, 240, and 480 mg/kg was given by gastrogavage to rats in the BSL, BSM, and BSH group respectively from the 13th day of modeling. TG at the daily dose of 24 mg/kg was given by gastrogavage to rats in the TG group. All medication was given once daily, 2 mL each time. Two mL normal saline was administered to rats in the normal control group and the model group. All medication lasted for 18 days. Samples were taken at day 31. The TRAP section of the ankle joint was fixed in 10% formalin for TRAP stain. Serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), and macrophage colony-stimulating factor (M-CSF) were detected using ELISA.

RESULTSCompared with the normal control group, positive reactions of pathological ankle joint section, inflammation, and osteoclasia degree were significantly improved in the model group, serum levels of RANKL and M-CSF were up-regulated, levels of OPG and OPG/RANKL were significantly lowered (all P < 0.01). Compared with the model group, positive reactions of pathological ankle joint section, inflammation, and osteoclasia degree also significantly decreased in the BSH group and the TG group (all P < 0.01). RANKL and M-CSF were significantly down-regulated in each medicated group, while levels of OPG and OPG/RANKL were significantly up-regulated (all P < 0.01). Compared with the TG group, M-CSF was lower, but levels of OPG and OPG/RANKL were significantly up-regulated in the normal control group (all P < 0.01). RANKL and M-CSF were significantly up-regulated, while levels of OPG and OPG/RANKL were significantly down-regulated in the model group and each BS group (all P < 0.01).

CONCLUSIONBTC could relieve bone damage of CIA rats possibly through regulating and controlling osteoclasts.

Animals ; Arthritis, Experimental ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Inflammation ; Macrophage Colony-Stimulating Factor ; metabolism ; Osteoclasts ; Osteoprotegerin ; metabolism ; RANK Ligand ; metabolism ; Rats ; Receptor Activator of Nuclear Factor-kappa B ; metabolism ; Tripterygium

Objective To explore the relationship between blood lipids level with creatinine clearance rate(Ccr)in patients with heart failure(HF). Methods A total of 955 patients who were diagnosed with heart failure(cardiac function NYHAⅡ~Ⅳclassification)upon discharge from the Department of Cardiology of the Second Hospital of Tianjin Medical University, between January 2010 to June 2013 were enrolled as HF group. Healthy adults (n=200) with normal cardiac function which approximately matched basic condition with HF group were selected as control group. The HF group was fur?ther divided intoⅡ,Ⅲ,Ⅳclassification according to their cardiac function(NYHA classification). HF group was also divid?ed into normal renal function group, mild renal injury group and moderate-severe renal injury group based on their Ccr. Ef?fect of gender and lipid parameters were also compared. Binary logistic regression was used to analyze factors influencing renal function in patients with HF. Results Compared with people in the control group, the levels of triacylglycerol(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDL-c)and non high density lipoprotein cholesterol(non-HDL-c)in patients of HF group were increased while Ccr and high density lipoprotein cholesterol(HDL-c)were decreased. Ccr and lipids were obviously decreased in patients with HF of Ⅳclassification. TG and HDL-c were decreased in moderate-severe renal injury group. Females had a higher lipid levels than males in HF group(P<0.05 or P<0.01). Advanced age, coronary heart disease and hypertension were all risk factors for renal impairment in patients with HF by binary logistic re?gression. On the other hand, weight gain and HDL-c were the protection factors for renal function in HF patients. Conclu?sion Dyslipidemias may lead to renal insufficiency in patients with HF. It was important to control lipids and improve re?nal function in patients with HF.

Objective To study the correlation between pulse pressure(PP) and cardiovascular structure and function in aged patients with essential hypertension. Methods Forty-eight aged patients with essential hypertension were enrolled into the study and divided into the following two groups by the mean value of PP: PP

Objective To analyze the clinical infection distribution and drug resistance status of 442 strains of Escherichia coli to provide the basise for the treatment of Escherichia coli infection and the control of nosocomial infection.Methods The clinically submitted various kinds of specimens during 2013 were performed the bacterial culture and identification.The susceptibility of Escherichia coli to commonly used bacterial drugs were detected by adopting the MIC method.The data were analyzed by WHO-NET V5.5 and SPSS V13.0 softwares.Results 442 strains of Escherichia coli were isolated from the middle urine and secretion. The detection rate of ESBLs-producing Escherichia coli was 61.3%.442 strains of Escherichia coli had the high resistance to peni-cillins,cephalosporins and fluoroquinolones,better sensitivity toβ-lactam/β-lactamase inhibitor compounds and highest sensitivity to carbapenems.ESBLs-producing Escherichia coli had the higher resistance to commonly used antibacterial drugs than non-ESBLs-producing Escherichia coli .Conclusion The drug resistance of Escherichia coli is severe.ESBLs-producing Escherichia coli are u-sually resistant to many different types of antimicrobial drugs.Carbapenems are the first choice to treatment of severe infections of Escherichia coli .