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 explore the relationship of delivery of parenteral fat emulsion and lipid peroxidation,and to observe the safety and effectiveness of parenteral nutrition(PN)in infants with very low birth weight(VLBWI).Methods Thirty infants with VLBWI were randomly divided into 3 groups:the preterm infants received pareneral nutrition containing amino acids and dextrose and soluvit,while intralipid provided separately,intralipid were light exposed(group A,n=10)or light protected(group B,n=10).In group C(n=10),soluvit and vitlipid were co-administered with intralipid and light protected.All the prematures received PN for 7 days and 10 cases of VLBWI not recei-ving PN were collected as control group.Anti-oxidation level,ascorbate,blood glucose,oxygen saturation,serum biochemistry index and body weight were determined before and after experiment.Results Seven days after PN,the MDA concentrations in the test groups all increased(⊿dA was the most,⊿dB was the next,⊿dC was the least).For superoxidedimutuse(SOD)reduction concentrations,⊿dA decreased sharply,then was ⊿dB,⊿dc decreased little,The blood Vit C increase in group B and C were more than group A.Significant changes of MDA,SOD and Vit C existed among the group B,C and A.In the 3 test groups,bilirubin,albumin,prealbumin concentrations were higher after the experiment,but there were no significant changes compared with control group.No significant changes in blood biochemistry,oxygen saturations were found before and after the observation in every group.Conclusions Multivitamin preparations protect fat emulsion against light-induced formation of lipid hydroperoxides,and administering multivitamins with fat emulsion via dark delivery tubing provide a practical way of preventing peroxidation of the lipid while limiting vitamin loss.Furthermore,it is relatively safe to apply fat emulsion intravenously with suitable dose and infusion rate for a few days to VLBWI from the second day of birth who require partial parenteral nutrition.

Objective To evaluate the outcomes of the payment reform at public hospitals in Sanming city.Methods Interrupted time series analysis was used to compare changes of the average days of stay,per capita hospitalization expense,outpatient expense per visit,proportion of medical expense and that of drugs during hospitalization at 21 public hospitals at or above county level before and after the DRGs reform.Results Comparisons before and after the reform found the average days of stay at the original momentum,poor control in curbing the proportion of medical expense and that of drugs during hospitalization,adropping followed by rising trend in the outpatient expense per visit,and minimal drop of the abovementioned proportions.Conclusions The rapid growth of outpatient and hospitalization costs at tertiary hospitals may be incurred by unreasonable cost transfer,structural trend of hospitalization expense makeup,and rationality pending scrutiny.

Tripartite-sector reform (a synergistic reform in public health services,medical insurance and medicine production-circulation) in Sanming city was described in the paper which centers on medical insurance.Tapping full potentials of the medical insurance,the city achieved efficient synergy among healthcare,medical insurance and medication systems.This reform has trimmed out inflated drug pricing to some extent for rooms of maneuver of medical service pricing changes,thus curbing excessive growth of medical costs successfully.The authors proposed areas of further improvements including the relationship between achieving such objective as curbing medical expenditure,and advancement of technical/medical service capacity;that between integrative control of medical insurance expenditure and protection of people's health;the equilibrium of interests between medical insurance,healthcare and medication.All these will contribute to the goal of healthy patients flow and a hierarchical medical system.

Objective To design a new vacant drowning rescuer in self-help can be effective and free when swimming.Meth-ods Vacant drowning rescuer includes the vacant,life-saving device,the waist straps and the ropes.Results Vacant drowning res-cuer has light weight,high strength,and small size.It is secured to the swimmer′s waist through waist strap and easy to operate. Conclusion Vacant drowning rescuer provides the security for the water activity,which can realize self-help or save others.It can be universally applied for the majority of swimming enthusiasts.

Objective To observe adhesion and growth of Sehwann cells(SCs) on small intestinal submueosa(SIS) and study the bioeompatibility of SIS with SCs.Methods The SCs of SD neonate rat were isolated and cultured in vitro,then were seeded on prepared SIS.At different times,the adhesion,growth and proliferation of SCs on SIS were observed by phase contrast microscope,histological examination,scanning e- lectron microscope and transmission electron microscope.Results By phase contrast microscope,SCs grew well on the edge of SIS after 3 and 5 days.SCs adhered tightly on the surface of SIS after 5 days through histo- logical examination.By scanning electron microscope,on the surface of SIS,SCs grew and adhered actively, prominence of cells body were obvious.They connected end-to-end with each other or arranged in clusters. Protein granules were secreted on cells surface.By transmission electron microscope,SCs grew in good condi- tion and adhered tightly on the surface of SIS.At the interface of SCs and SIS,prominence was seen to contact with SIS in the bottom of cell body.Conclusion SCs are able to adhere and grow well on the surface of SIS.As a scaffold,SIS has good biocompatibility with SCs.

ObjectiveTo observe the effect of pulsed electromagnetic fields (PEMFs) on bone mineral density (BMD) of spinal cord injuried (SCI) patients. MethodsThe PEMFs group was composed of 12 SCI patients received regular PEMFs treatment as the treatment group, 12 SCI patients treated without PEMFs were as the control group.BMD of total proximal femur, Ward's trigonum and great trochanter of all patients were detected by dual-energy X-ray absorptiometry before and after treatment.ResultsBMDs of total proximal femur and great trochanter of patients of the treatment group were a little increased after PEMFs treatment, with no significant difference (P>0.05), but BMD change was significantly different compared with the control group (P<0.05～0.01).ConclusionPEMFs treatment along with routine exercise may help to reduce the loss of bone after SCI.

BackgroundSweep pattern visual evoked potential(SPVEP) acuity,as an objective detective technique of visual function,can be used to measure visual acuity in children and uncooperative adults.Recent studies have shown that the amplitude-logarithm of the visual angle (A-LogVA) function regression method was more accurate than the amplitude-spatial frequency (A-SP)function regression method in evaluating SPVEP acuity.Objective This study was to explore the clinical use of SPVEP acuity in visual developing children and compare the evaluating the SPVEP acuity of children between A-SP function regression method and A-LogVA function regression method.Methods Twenty-six eyes of 26 asthenopic children with age range of 3-12 years and 31 age-matched normal children were enrolled in this study.SPVEP acuity was recorded with GT-2000 NV ( GUOTE MEDICAL APPARATUS LTD,China) using sinusoidally modulated horizontal gratings of 10 different spatial frequencies from 0.99 to 12.89 cpd as stimulus.The responses were averaged and displayed through discrete Fourier transformations (DFT) on the monitor display.SPVEP acuity was estimated by using both the SPVEP A-SP function regression method and the SPVEP A-LogVA function regression method.The LogMAR chart was used to acquire LogMAR visual acuity.ResultsIn the normal group,the correlation coefficient between LogMAR visual acuity and acuity calculated by the A-SP function regression method was 0.600 (P＜0.01).The correlation coefficient between LogMAR visual acuity and acuity calculated by the A-LogVA function regression method was 0.733 ( P＜0.01 ).The ANOVA of the LogMAR acuity and the SPVEP acuity calculated from the A-SP function regression method and A-LogVA function regression method were 113.173 (P＜0.01 ),which indicated that there were significant difference among all of subjects.The differences of the mean values of LogMAR visual acuity and the SPVEP acuity calculated from the A-SP function regression method and A-LogVA function regression method were respectively 0.40±0.02,0.26 ±0.02 and 0.14 ± 0.02.In the amblyopia group,the correlation coefficient between LogMAR visual acuity and acuity calculated by the A-SP function regression method was 0.134 (P =0.515 ).The correlation coefficient between LogMAR visual acuity and acuity calculated by the A-LogVA function regression method was 0.456 ( P＜0.05 ).The ANOVA of the LogMAR acuity and the SPVEP acuity calculated from the A-SP function regression method and A-LogVA function regression method were 3.433 (P＜0.05),indicating that there were significant difference among all of subjects.The differences of the mean values of LogMAR visual acuity and the SPVEP acuity calculated from the A-SP function regression method and A-LogVA function regression method were 0.07±0.05,0.12±0.05 and 0.05 ±0.01 respectively.Conclusions SPVEP can evaluate the visual acuity in children,although SPVEP acuity may overestimate or underestimate acuity in comparison with different LogMAR visual acuities.The amplitude-LogVA function regression method is more accurate in extrapolating SPVEP acuity.

Objective To discuss a optimal culture method of primary hippocampal neurons and a more suitable method of mor-phological observation ,and provide basis to the study of synapse in Alzheimer′s Disease .Methods Postnatal 0 -1 days (P0 -1 ) C57BL/6J mice were decollated and bilateral hippocampus were separated .Low level concentration of trypsin and mechanical disso-ciation were adopted .And culture medium without serum was used to culture neurons .After 17 days culturing ,transfected neurons with Green Fluorescent Protein(GFP) by calcium phosphate precipitation ,and then observed neurons and spines by fluorescence mi-croscope .Results The neurons looked good and healthy by using this method .And the axons ,dendrites and spines which were typ-ical structure of neurons were observed clearly after transfected with GFP .Conclusion The cultured hippocampal neurons look good by this method .And the morphological characteristics of neurons and spines are observed much more clearly after transfected GFP by calcium phosphate precipitation .