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

OBJECTIVETo explore surgical management and the effects of surgical treatment of severely comminuted fractures of humeral intercondylar through approach of osteotomy olecranon with double-plate internal fixation.

METHODSThirty patients of severely comminuted fractures of humeral intercondylar were treated by double-plate internal fixation through osteotomy olecranon. There were 19 males and 11 females, with an average age of 42.3 years ranging from 21 to 62. According to AO/ASIF classification, there were 17 cases of type C2 and 13 of C3. Twenty-one cases were applied with reconstructive plate medially and laterally, 9 cases were applied with reconstructive plate laterally and 1/3 tubular plate medially.

RESULTSAll patients were followed-up for 6 months to 3 years (means 1.5 years). The complications such as bone defect, ossifying myositis, tardive ulnar nerve compression, internal fixation fail were no occurenced. According to Aitken-Rorabeck scale the function of the elbow showed excellent in 16 cases, good in 10, fair in 2 and poor in 2.

CONCLUSIONAnatomical reduction surgically reconstructed stabilization of the elbow and early active rehabilitation are crucial factors of functional rehabilitation of the elbow. The technique of osteotomy olecranon with double-plate internal fixation for treatment of severely comminuted fractures of humeral intercondylar is a good approach.

Adult ; Female ; Fracture Fixation, Internal ; methods ; Fractures, Comminuted ; therapy ; Humans ; Humerus ; surgery ; Male ; Middle Aged ; Osteotomy ; methods ; Rehabilitation ; Treatment Outcome ; Young Adult

The paper is to report the establishment of a population pharmacokinetic model for flurbiprofen (FP), an active metabolite of flurbiprofen axetil (FA). 246 FP serum concentration and clinical data were perspectively collected from 23 general anaesthesia patients receiving FA intravenously before operation in Dentofacial Surgery and Otorhinolaryngology Department of the First Affiliated Hospital of Fujian Medical University. Population pharmacokinetic data analysis was performed using NONMEM software. The measure of Bootstrap was applied for internal validation, while Visual Predictive check was adopted for external validation. The data of FP correspond with two-compartment model. The body weight (WT) had conspicuous effect on clearance and volume of central compartment, while sex, age and daily dose of administration had no marked effect on pharmacokinetic parameter of FP. The basic model was described as follows: CL (L x h(-1)) = 1.28x EXP(ETA(1)), V1 (L) = 5.03x EXP(ETA(2)), Q (L x h(-1)) = 8.5 x EXP(ETA(3)), V2 (L) = 4.39 x EXP(ETA(4)). The final model was described as follows: CL (L x h(-1)) = 1.32 x (WT/60) x EXP(ETA(1)), V1 (L) = 5.23 x (WT/60) x EXP(ETA(2)), Q (L x h(-1)) = 8.45 x EXP(ETA(3)), V2 (L) = 4.37 x EXP(ETA(4)). The population typical value of CL, V1, Q and V2 were: 1.32 L x h(-1), 5.23 L, 8.45 L x h(-1) and 4.37 L, respectively. Bootstrap and visual predictive check show that the final model of FP is stable, effective and predictable. A novel population pharmacokinetic model is developed to estimate the individual pharmacokinetic parameter for patients intravenous injecting FA in terms of patients' characteristics and dosing history, and to design a prior dosage regimen.
Adult ; Aged ; Analgesics ; blood ; pharmacokinetics ; Body Weight ; Female ; Flurbiprofen ; administration & dosage ; analogs & derivatives ; blood ; metabolism ; pharmacokinetics ; therapeutic use ; Head and Neck Neoplasms ; surgery ; Humans ; Injections, Intravenous ; Male ; Middle Aged ; Models, Biological ; Pain, Postoperative ; drug therapy ; prevention & control ; Prospective Studies ; Software ; Young Adult

Objective To investigate the anti-inflammatory effects on the vessel wall of rosuvastatin chow diet were treated with vehicle or various doses of rosuvagtatin(1,5,or 20 ms/kg)by subcutaneous injection for 2 or 6 weeks prior to sacrifice.Endothelial adhesiveness for monocytcs was determined by functional binding assay.The expressions of vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 in the vessel wall were detected by quantitative real-time polymerase chain reaction.Results Endothelial adhesiveness for monocytes was significantly attenuated after 2 or 6 weeks treatments with 5 or 20 mg/kg rosuvaatatin.Rosuvastatin also significantly reduced the expressions of vescular cell adhesion moIecule-1 and monocyte chemotactie protein-1 in the vessel wall Conclusion The anti-inflammatory effects of suvagtatin might be responsible for attenuating the pathogenesis of atherogenesis in apolipoprotein E-deficient mice.

OBJECTIVETo analyze the clinical and molecular characteristics of hemoglobin New York in populations from Guangxi and provide reference data for screening thalassemia.

METHODSA total of 30 691 samples were screened by capillary electrophoresis, and then suspicious samples of Hb New York were identified by DNA sequencing and analysis of blood cell count. Gap-PCR and reverse dot blot hybridization method were used for the detection of common mutations of α and β thalassemia in Chinese.

RESULTSThe incidence of Hb New York was 0.12% in Guangxi. The hematological phenotype index (MCV, MCH, Hb New York, Hb A2) of 32 Hb New York heterozygous cases were (91.00±5.19)fl, (29.42±2.04)pg, (44.10±3.12)% and (2.80±0.29)% , respectively. The hematological phenotype index of 4 Hb New York composited SEA heterozygous patients were (68.20±5.26) fl, (21.78±2.15) pg, (36.60±2.00)% and (2.90±0.14)% , of 2 Hb New York composited WS heterozygous patients were (83.90±2.69) fl, (27.70±1.70) pg, (39.70±1.70)% and (3.50±0.21)%. There were statistical differences between three groups (P<0.05). HGB, MCV and MCH of Hb New York heterozygous and Hb New York composited WS heterozygous were normal, and patients with Hb New York composited SEA heterozygous showed mild anemia, decreased MCV and MCH.

CONCLUSIONMost of Hb New York were heterozygous and no homozygotes in Guangxi. There were different hematological characteristics in different Hb New York heterozygous patients. Hb New York heterozygous had normal hematological phenotype, ant combined with other types of thalassemia could exhibit symptoms such as anemia.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Hemoglobins, Abnormal ; genetics ; Heterozygote ; Humans ; Infant ; Male ; Middle Aged ; Phenotype ; Sequence Analysis, DNA ; Thalassemia ; blood ; epidemiology ; genetics ; Young Adult

OBJECTIVETo investigate the effect of COX1 and COX2 on angiogenesis and endothelial progenitor cell mobilization in rats with experimental myocardial infarction (MI).

METHODSThe rats were randomly divided into 3 groups: MI group, MI plus rofecoxib group and MI plus valeryl salicylate group. At the 7th day after operation, circulating EPCs, plasma VEGF and HIF-1alpha mRNA of ischemic myocardium were measured. At the 28th day post operation, capillary densities were also measured in ischemic myocardium.

RESULTCompared with the MI group and the MI plus valeryl salicylate group, circulating EPCs, plasma VEGF, HIF-1alpha mRNA and capillary densities of ischemic myocardium were all decreased in MI plus rofecoxib group.

CONCLUSIONThe present study revealed that COX2 play an important role with angiogenesis and endothelial progenitor cell mobilization in rat with experimental MI by modulating expression of VEGF and HIF-1alpha.

Animals ; Cyclooxygenase 2 ; biosynthesis ; Cyclooxygenase Inhibitors ; pharmacology ; Endothelial Cells ; cytology ; Female ; Hypoxia-Inducible Factor 1, alpha Subunit ; biosynthesis ; Myocardial Infarction ; drug therapy ; pathology ; Neovascularization, Physiologic ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stem Cells ; metabolism ; Vascular Endothelial Growth Factor A ; blood

AIMTo explore the relationship between evoked potentials (EPs) and chronic anoxic brain damage by chronic intermittent hypoxia (CIH), and provide theory evidence for diagnosis and treatment of anoxic encephalopathy.

METHODSBAEP and SLSEP were recorded in rat model with CIH (hypoxia group) and rat with normoxia (normal group). Morris water maze was used to observe learning and memory ability. Immunohistochemical method was used to investigate the expression levels of caspase-3 in brain tissue.

RESULTSThe peak latency (PL) of wave I, III, V and the interpeak latency (IPL) of wave III - V, I - V in BAEP in hypoxia group were much longer than that of in normal group (P < 0.05). The PL of wave N1, P1 of SEP in hypoxia group were much longer than that of in normal group (P < 0.05). In the water mase test, the escape latency (EL) of hypoxia group was much longer than normal group (P < 0.01). The number of caspase-3 positive cells in hypoxia group was much larger than that of in normal group (P < 0.05). There was a positive correlation among BAEP, SLSEP, the number of caspase-3 positive neuron and EL of water mase.

CONCLUSIONThe alteration of BAEP and SLSEP has an apparent correlation with chronic anoxic brain damage. This provides theory evidence for diagnosis and treatment of anoxic encephalopathy.

Animals ; Brain ; enzymology ; pathology ; physiopathology ; Caspase 3 ; genetics ; metabolism ; Chronic Disease ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Evoked Potentials, Somatosensory ; physiology ; Hypoxia, Brain ; physiopathology ; Male ; Maze Learning ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To explore the curative effect of progressively integrated sandplay therapy on core symptoms and sleep management in preschool children with mild-to-moderate autism spectrum disorder (ASD). METHODS: A total of 50 mild-to-moderate ASD preschool children were randomly divided into an experimental group (n=25) and a control group (n=25). The control group was treated with structured teaching and auditory integration training (AIT). Based on these, the experimental group was treated with progressively integrated sandplay therapy. The Autism Behavior Checklist (ABC), Children Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Children's Sleep Habit Questionnaire (CSHQ) and emotion recognition tools were used to evaluate the overall curative effect before treatment and 3 months after treatment. RESULTS: The experimental group had significantly lower scores of feeling, social interaction, somatic motor, language factor, total ABC and total CARS than the control group (P<0.05). The experimental group had also significantly lower scores of social cognition, social communication, social motivation, autistic behavior factor and total SRS than the control group (P<0.05). The experimental group had a significantly higher accurate rate of recognition of the upper facial expression and lower facial expression than the control group (P<0.05). The experimental group had significantly lower scores of bedtime resistance, sleep onset, sleep duration, night waking, daytime sleepiness, and total CSHQ than the control group (P<0.05). The experimental group had significantly reduced themes of wounding and significantly increased themes of healing after sandplay therapy (P<0.05). CONCLUSIONS Progressively integrated sandplay therapy can effectively improve the core symptoms and sleep quality of preschool children with mild-to-moderate ASD, which can be used as an early rehabilitation measure.
Autism Spectrum Disorder ; Child, Preschool ; Facial Expression ; Humans ; Play Therapy ; Social Behavior

OBJECTIVE: To study the clinical efficacy of interactive group sandplay versus individual sandplay in the treatment of preschool children with autism spectrum disorder (ASD). METHODS: A total of 80 ASD children, aged 4-6 years, were enrolled and randomly divided into experimental and control groups, with 40 children in each group. The children in the experimental group joined group sandplay with normal children at a ratio of 1: 3, and those in the control group were treated with individual sandplay. The Aberrant Behavior Checklist (ABC) and Autism Treatment Evaluation Checklist (ATEC) were used to evaluate the treatment outcome after three months of intervention. RESULTS: There were 33 children in the experimental group and 28 in the control group. After three months of intervention, the experimental group had significant reductions in the scores of irritability, social withdrawal, and stereotypic behavior and the total score of the ABC scale (P<0.05), and the control group had significant reductions in the scores of behavior and inappropriate speech and the total score of the ABC scale (P<0.05). Compared with the control group, the experimental group had significantly greater improvements in the score of social withdrawal and the total score of the ABC scale after three months of intervention (P<0.05). After three months of intervention, the experimental group had significant reductions in the scores of sociability, sensory and cognitive awareness, and physical/health behavior and the total score of the ATEC scale (P<0.05), and the control group had significant reductions in the scores of speech, sociability, and physical/health behavior and the total score of the ATEC scale (P<0.05). Compared with the control group, the experimental group had significantly greater improvements in the scores of speech, sociability, and sensory and cognitive awareness and the total score of the ATEC scale after intervention (P<0.01). Compared with the control group, the experimental group also had significantly greater improvements in eye contact and sand stereotyped arrangement (P<0.05). CONCLUSIONS Both interactive group sandplay and individual sandplay are effective in the treatment of ASD in preschool children. Interactive group sandplay is better than individual sandplay in the treatment of ASD, with significant improvements in sociability, emotion and stereotypic behavior.
Autism Spectrum Disorder ; therapy ; Child ; Child, Preschool ; Emotions ; Humans ; Play Therapy ; Treatment Outcome

OBJECTIVE: To study the clinical effect of integrated sandplay therapy in preschool children with Asperger syndrome (AS). METHODS: A total of 44 preschool children with AS were randomly divided into an experimental group and a control group, with 22 children in each group. The children in the control group were given routine training, and those in the experimental group were given integrated sandplay therapy in addition to the routine training. The treatment response was assess by the Social Responsiveness Scale (SRS), emotional recognition tools and changes in sandplay theme characteristics after 6 months of treatment. RESULTS: Before intervention, there were no significant differences between the two groups in the total score of SRS, the score of each factor of SRS, and correct rates of facial expression recognition of the upright position, inverted position, upper face and lower face (P>0.05). After 6 months of intervention, both groups had significant reductions in the total score of SRS and the score of each factor of SRS (P<0.01); the control group had significant increases in the correct rates of facial expression recognition of all positions except the upright position (P<0.05), while the experimental group had significant increases in the correct rates of facial expression recognition of all positions (P<0.05). Compared with the control group after intervention, the experimental group had significantly lower total score of SRS and scores of all factors of SRS except social perception (P<0.01) and significantly higher correct rates of facial expression recognition of all positions (P<0.01). The experimental group had a significant change in the number of sandplay theme characteristics after intervention (P<0.01). CONCLUSIONS Integrated sandplay therapy can improve social responsiveness and emotion recognition ability in preschool children with AS.
Asperger Syndrome ; Child, Preschool ; Emotions ; Facial Expression ; Humans ; Play Therapy