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

No abstract available.
Breast Neoplasms* ; Breast* ; Phenobarbital*

Objective: To observe the inhibitory effects of biotic royal jelly on the ascitic hepatoma cell H22. Methods: Mice bearing H22 tumor were fed on different types of royal jelly: No.1, 2 and 3. Their anti-tumor effects were observed in vivo. The general royal jelly and normal saline were observed as control. Results: Among these biotic royal jelly, the biotic royal jelly No.1 showed obvious tumor-inhibiting and survival-prolonging effects. In addition, it increased the number of WBC and augmented the amount of IL-2 and IFN-γ; the pathological study also indicated the denaturing and necrosis of most tumor cells with nuclei constraining and cell membrane rupturing, and large amount of lymphocytes and plasmacytes infiltrating around the mass. Conclusion: The No.1 biotic royal jelly has obvious anti-tumor effect, and it may take effects by inhibiting or killing tumor cells and improving the immunity of the host.

Objective To explore the relationship between mental health status and intentional self harm and parenting style among adolescent students.Methods Using Parenting Style Questionnaire (PBI),Chinese middle school student mental health scale questionnaire and deliberate self harm questionnaire,6 middle schools in Quzhou City were randomly selected and a total of 876 students were investigated.Results A total of 869 questionnaires were recovered and the recovery rate was 99.20％.Totally 42.58％ of the adolescents had psychological problems,and 8.40％ and 7.36％ of the students feel bad themselves.Those who had thought or deliberately hurt themselves accounted for 15.54％ and 5.64％,respectively.The parenting style of father was mainly high care and low control(50.50％),while that of mother was mainly high control and low care(74.00％).Multivariate logistic regression analysis showed that the mental health status was self reported poor among those their father parenting style was high control and low care (OR =3.291,95％ CI:1.724-6.285) and the possibility of intentional self harm behaviors were higher (OR =2.278,95％ CI:1.042-4.983) when the confounding factors were controlled.Conclusion The proportion of middle school students who have psychological problems were high and high control and low care of father parenting style were the risk factors of psychological problems and intentional self harm behaviors among adolescents.

Objective To study the genotypes of 102 strains of methicillin-resistant Staphylococcus aureus(MRSA)collected consecutively in 2002 in our hospital Method Multiplex PCR was used to genotype Staphylococcal chromosomal cassette mec(SCCmec)element and its variants.Results Among 102 strains of MRSA,the genotypes were as follows:SCCmec-Ⅲ(94 strains),SCCmec-ⅢA(4 strains), SCCmec-Ⅳ(2 stains),SCCmec-Ⅰ(2 stains).Conclusion The predominant genotype of MRSA circulating in this hospital in 2002 was SCCmec-Ⅲ by multiplex PCR.

OBJECTIVETo study the relationship between CYP1A1 genetic polymorphism and intrahepatic cholestasis of pregnancy (ICP) in Chengdu of China.

METHODSMspI and Ile/Val genotypes of CYP1A1 gene were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific amplification-PCR (ASA-PCR) in a case-control study, including 100 cases of ICP and 100 controls.

RESULTSThere was no significant correlation between MspI polymorphism and ICP susceptibility (P>0.05). However, the Ile/Val+Val/Val genotypes of CYP1A1 significantly increased the risk of ICP (P=0.047, OR=1.768).

CONCLUSIONThe Ile/Val polymorphism in exon 7 of CYP1A1 may be associated with the susceptibility of ICP in Chengdu. The MspI polymorphism of CYP1A1 is not associated with the risk of ICP in Chengdu.

Case-Control Studies ; Cholestasis, Intrahepatic ; genetics ; Cytochrome P-450 CYP1A1 ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Genetic ; Pregnancy ; Pregnancy Complications ; genetics

OBJECTIVETo study and research the transcription pattern of UL131A-128 mRNA in human cytomegalovirus (HCMV) clinical low passage strains.

METHODSThe UL131A-128 mRNAs of from different clinical strains and kinetic periods were amplified using 3' RACE and analyzed by sequencing. Meanwhile, clones containing UL131A-128 transcripts in a HCMV cDNA library of clinical strain were selected and sequenced.

RESULTSIt is successful to obtain the transcription pattern of UL131A, UL130 and UL128 gene in HCMV clinical low passage strains, the UL131A gene consisted of two exons and the coding region of UL130 gene was not interrupted by any intron in the region as reported before. However, the transcript of UL128 gene showed two patterns, one pattern consisted of the three exons, the length is 519bp, and the other one contained the three exons and the sequence of the first intron further, the length is 642bp. The quantities of UL128 transcript containing the sequence of the first intron were higher than that of transcript only containing the three exons in the studied clinical strains at all kinetic classes. It was demonstrated that the UL131A-128 mRNA were expressed with immediately early, early and late kinetics. The result of 3'RACE and HCMV cDNA library of clinical strain is conformity.

CONCLUSIONSOur results demonstrated that the UL131A, UL130 and UL128 genes were transcribed with 3'-coterminal, although the initiation points of their mRNA may be different. The variation of the transcripts found in our study indicated complex nature of transcription of UL131A-128 genes in HCMV clinical strains.

Cytomegalovirus ; genetics ; Gene Library ; Humans ; Membrane Glycoproteins ; genetics ; RNA, Messenger ; analysis ; Transcription, Genetic ; Viral Envelope Proteins ; genetics

BACKGROUNDChronic obstructive pulmonary disease (COPD) is usually complicated with mucus overproduction in airway. Recently the increased expression of the human calcium-activated chloride channel 1 (CaCC(1)) was found to play an important role in mucus overproduction in the asthmatic airways. To investigate the relationship of CaCC(1) and mucus overproduction in the airway of Chinese patients with COPD, the expressions of CaCC(1), MUC5AC and mucus in bronchial tissues were examined.

METHODSBronchial tissues were obtained from fiberoptic bronchoscopy and bronchial biopsy in West China Hospital from April to July in 2004. Twenty-five patients were diagnosed as the patients with COPD overproduction, and other 20 were the control subjects. The expressions of CaCC(1), MUC5AC and mucin in bronchial tissues were detected by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization with digoxigenin (DIG)-labeled RNA probe, immunohistochemical and alcian blue-periodic acid Schiff (AB-PAS) staining, respectively.

RESULTSCompared with the control group, the stronger expressions of CaCC(1) were further detected throughout the bronchial tissues from patients with COPD (P < 0.01). Furthermore, the stronger expressions of the CaCC(1) mRNA were related to the severity of airflow obstruction. Samples from COPD showed a stronger staining for MUC5AC than those in control subjects (P < 0.01) and AB-PAS staining revealed more mucins in COPD patients' submucosal gland comparing with that in control subjects (P < 0.01). Expression levels of the CaCC(1) mRNA were respectively negatively correlated with the patients' forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) data, FEV(1)% predicted data, V(50)% predicted data, V(25)% predicted data (r = -0.43, r = -0.43, r = -0.35, r = -0.36, P < 0.01, P < 0.01, P < 0.05, P < 0.05). While the expression levels of the CaCC(1) mRNA were well correlated with the expression levels of the MUC5AC mRNA of airway epithelium and the PAS-AB stained area of submucosal glands (r = 0.39, r = 0.46, P < 0.05, P < 0.01). Expression levels of the MUC5AC mRNA were negatively correlated with the patients' FEV(1)/FVC data (P = 0.01), FEV(1)% pred data (P = 0.01), V(50)% predicted data, V(25)% predicted data (r = -0.53, r = -0.53, r = -0.48, r = -0.43, P < 0.01, P < 0.01, P < 0.01, P < 0.01). While the expression levels of the MUC5AC mRNA were well correlated with the positively PAS-AB stained area of submucosal gland (P < 0.05), and the correlation coefficients were 0.43.

CONCLUSIONThese results suggest that the stronger gene expression of CaCC(1) exists, complicated with mucus overproduction in the airway of Chinese patients with COPD.

Adult ; Aged ; Bronchi ; metabolism ; Chloride Channels ; genetics ; Female ; Forced Expiratory Volume ; Gene Expression Regulation ; Humans ; Male ; Middle Aged ; Mucin 5AC ; Mucins ; genetics ; Mucus ; physiology ; Pulmonary Disease, Chronic Obstructive ; metabolism ; physiopathology ; RNA, Messenger ; analysis ; Vital Capacity

OBJECTIVEThe epidemiological characteristics of congenital heart disease (CHD) in children aged from 4 to 18 years were investigated in Qinghai province.

METHODSAltogether 288 066 children inhabiting at 6 prefectures and 3 counties were examined by the following three steps: pre-screening, re-examination and diagnosis with color Doppler. And the entity distribution was analyzed while the differences were compared by age, gender, altitudes and nationalities respectively.

RESULTSAltogether 1633 cases of CHD were discovered. The total prevalence of CHD was 5.71 per thousand. The prevalence of CHD was found to increase with the increase of altitude by 4.89 per thousand at the altitude of 2535 m, 5.71 per thousand at 3600 m, and 8.74 per thousand at 4200 m respectively. There were significant differences among different altitude (chi(2) = 54.696, P < 0.001). chi(2) trend analysis showed the increase with chi(2) = 41.826(P < 0.001). The total incidence of CHD in females was 6.95 per thousand, which was significantly higher than that in males with 4.54 per thousand (chi(2) = 73.79, P < 0.001). There were significant differences between males and females at the altitude of 3000 m (chi(2) = 84.733, P < 0.001) and 4000 m (chi(2) = 16.313, P < 0.001) except at the altitude of 2000 m (chi(2) = 0.807, P > 0.05). The prevalence of CHD in different age groups was statistically significant at the every altitude of 2000 m (chi(2) = 18.138, P < 0.001), 3000 m (chi(2) = 18.544, P < 0.001) and 4000 m (chi(2) = 27.535 P < 0.001). The prevalence of CHD was increasing with the increase of age groups at the altitude of 3000 m (chi(2) = 19.230, P < 0.001) and 4000 m (chi(2) = 26.894, P < 0.001) except at the altitude of 2000 m. Within the prevalence of CHD of different nationalities, there was a significant difference with chi(2) = 24.456 (P < 0.001). Within the constituent rate of CHD, the prevalence of atrial septal defect (ASD) was as high as 37.42%, followed by the prevalence of patent ductus arteriosus (PDA) as 28.47% and ventricular septal defect (VSD) as 26.01%. Regarding the four categories of CHD, the constituent rate varied at different altitudes. For example, the prevalence rate of ASD constituted 37% at the altitude of 2000 m and 3000 m, and that of PDA accounted for 46.36% at the altitude of 4200 m.

CONCLUSIONThe epidemiological characteristics of CHD in Qinghai children were possibly associated with altitude levels.

Adolescent ; Altitude ; Child ; Child, Preschool ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Heart Defects, Congenital ; epidemiology ; Humans ; Male ; Prevalence