OBJECTIVETo observe the effect of ketoconazole on the activity of cytochrome P450 (CYP) 1A2 and 3A4 in hepatic microsomes of healthy adults.

METHODSHuman hepatic microsomes obtained from healthy adults were randomly divided into control group and ketoconazole-treatment groups at different concentrations. After 15 min of culture, the substrates (testosterone for CYP3A4 and phenacetin for CYP1A2) were added and incubated for another 20 min. The metabolites (6-testosterone and acetaminophen) were then measured with high-performance liquid chromatography (HPLC) to assess the activities of CYP3A4 and 1A2.

RESULTSSignificant difference was found between the groups in the quantity of 6-testosterone and the relative activity of CYP3A4 (P<0.05). The IC(50) of ketoconazole for CYP3A4 was 0. 16 mg/L. Both the quantity of 6-testosterone and the relative activity of CYP3A4 were reduced gradually with the increment of ketoconazole concentration. Significant differences were found between the ketoconazole groups and the control group in both the quantity of acetaminophen and the relative activity of CYP1A2 (P<0.05). Ketoconazole at low doses reduced CYP1A2 activity and but increased the activities at high doses (P<0.05).

CONCLUSIONIn the range of maximum clinical blood concentration, ketoconazole can inhibit the activity of CYP3A4, but not that of CYP1A2, in the hepatic microsomes in healthy adults.

Adult ; Antifungal Agents ; pharmacology ; Cytochrome P-450 CYP1A2 ; metabolism ; Cytochrome P-450 CYP3A ; metabolism ; Dose-Response Relationship, Drug ; Female ; Humans ; Ketoconazole ; pharmacology ; Male ; Microsomes, Liver ; drug effects ; enzymology

OBJECTIVETo present data from a baseline investigation on stroke-related cohort population in rural area of Shanghai.

METHODSA cross-sectional study was carried out in a cluster sampling population aged 40 years and over. General information and data on common risk factors in the population were gathered and cerebral vascular hemodynamic indexes were checked. Hemodynamic score was estimated according to single indexes by unified methods. 5335 persons who had met the inclusion criteria were enlisted in the study. Exposure level of risk factors, prevalence of stroke, and hemodynamic indexes were analyzed and distributional characteristics were described.

RESULTSExposure rate of hypertension, heart disease, diabetes, family history of hypertension, overweight or obesity in males were 31.74%, 6.09%, 1.16%, 3.22%, 17.64%, 29.68% and were 32.76%, 9.22%, 1.55%, 3.84%, 19.22%, 29.44% in female respectively. Standard prevalence of stroke was 1167.3/100000, which in male was significantly higher than that in female (P < 0.05). The change of cerebral vascular hemodynamic indexes was significantly associated with age. Hemodynamic score in 21.3% of the subjects was below 75 points.

CONCLUSIONSAmong population of 40 years old and over in rural areas, hypertension was the principal risk factor regarding the rate of stroke. Prevalence of stroke in males was significantly higher than that in females. Abnormal rate of hemodynamic score was about 20% in this population.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; Brain ; blood supply ; China ; epidemiology ; Cohort Studies ; Cross-Sectional Studies ; Female ; Hemodynamics ; Humans ; Hypertension ; complications ; epidemiology ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Rural Health ; Sampling Studies ; Sex Factors ; Stroke ; epidemiology ; physiopathology

OBJECTIVETo investigate the effect of small hairpin interfering RNA (shRNA) in suppressing cytochrome P450 3A4 (CYP3A4) gene expression in CHL-3A4 cells.

METHODSThree shRNA expression vectors targeting CYP3A4 gene (CYP3A4 I, C YP3A4 II, and CYP3A4 III, respectively) were designed, synthesized and transfected into CHL-3A4 cells via liposomes. The inhibitory effect of shRNA on CYP 3A4 gene expression was detected by Western blotting and RT-PCR, and the effect of shRNA transfection in suppressing cyclophosphamide-induced cytotoxicity was measured using MTT assay.

RESULTSThe vector carrying CYP3A4 III shRNA significantly reduced the expression of CYP3A4 gene at both the mRNA (75%) and protein levels (80%) in CHL3A4 cells. The cytotoxicity of cyclophosphamide was markedly inhibited by CYP3A4 III-mediated suppression of CYP3A4 gene expression by 75% in CHL-3A4 cells.

CONCLUSIONThe vector-mediated RNA interference can suppress CYP3A4 gene expression in CHL-3A4 cells, and RNA interference technique provides a new means for studying cytochrome P450 gene function in mammalian cells.

Animals ; Cells, Cultured ; Cricetinae ; Cytochrome P-450 CYP3A ; genetics ; Fibroblasts ; cytology ; metabolism ; Humans ; Lung ; cytology ; RNA Interference ; RNA, Small Interfering ; genetics

OBJECTIVETo explore the expression of MICA/B in human esophageal cancer, and to analyze its correlation with clinicopathological features.

METHODSThe expression of MICA/B in 40 cases of esophagus carcinoma and corresponding normal esophageal mucosa tissues were examined by immunohistochemistry.

RESULTSThe positive rate of expression of MICA/B protein in the esophageal carcinoma was 75.0% (30/40), and that in the corresponding normal esophageal mucosa was 0 (0/40). Up-regulation of MICA/B expression was found in the esophageal carcinomas. The expression of MICA/B was related with histological grade of the esophageal carcinoma (P = 0.012).

CONCLUSIONMICA/B protein plays an important role in the esophageal carcinogenesis, and my become a useful molecular marker for the diagnosis of esophageal carcinoma.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; metabolism ; Esophageal Neoplasms ; diagnosis ; metabolism ; pathology ; Female ; Histocompatibility Antigens Class I ; metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Up-Regulation

OBJECTIVETo probe into the relationship between hypertension and hemodynamic score of cerebral vascular accumulative function by though studying the history of hypertension and level of blood pressure.

METHODSThe database of blood pressure and cerebral vascular hemodynamic indexes (CVHI) were from baseline data and measurement in a cohort. 18,512 participants who met the included criteria were enlisted in the study. The function scores were estimated using uniform methods according to CVHI. Participants were grouped by age, years of having hypertension and level of blood pressure. Differences of the function score between different groups were compared.

RESULTSThe function score in hypertension group was significantly lower than that of normal tension group, which decreased by 13.3 points. Within 5 years of hypertension history, the function score decreased as course of hypertension prolonged. The same trend was found between the score and level of both systolic and diastolic blood pressure. When systolic blood pressure elevated to 140 mmHg or diastolic blood pressure elevated to 95 mmHg, the function score was below 75 points.

CONCLUSIONThere were significant relationship between decrease of the function scores and medical history, course of hypertension as well as level of blood pressure.

Adult ; Age of Onset ; Aged ; Blood Pressure ; physiology ; Cerebrovascular Circulation ; physiology ; China ; epidemiology ; Cohort Studies ; Female ; Hemodynamics ; physiology ; Humans ; Hypertension ; epidemiology ; physiopathology ; Male ; Middle Aged

OBJECTIVETo explore the indications of arthroscope for the treatment of knee osteoarthritis and investigate the correlation between knee osteoarthritis imaging and effects of arthroscope.

METHODSFrom 2005.8 to 2008.4, 86 patients with knee osteoarthritis underwent arthroscope examination and treatment. Among the patients, 44 patients were male, and 42 patients were female, ranging in age from 46 to 67 years, averaged 56.3 years. Arthrodial cartilage of knee was graded by ICRS MR, and by Kellgern Laqrence X-ray. All the patients were followed up, and the duration ranged from 12 to 30 months. The Lysholm score was evaluated at the follow-up time.

RESULTSAmong 86 knees in 86 cases, cartilage injury degree of knees was graded as follows: grade 4 in 30 cases, grade 3 in 22 cases, grade 2 in 20 cases, grade 1 in 12 cases, grade 0 in 2 cases, mean grade (2.77 +/- 1.138). Postoperative Lysholm score ranged from 59 to 100, averaged (95.17 +/- 7.556), Kendall's correlation coefficient was -0.089, P = 0.317. There was no correlations between cartilage injury degree and Lysholm score. X-ray of knees was graded as follows: grade 4 in 0 cases, grade 3 in 24 cases, grade 2 in 38 cases, grade 1 in 17 cases, grade 0 in 7 cases, mean grade was (2.13 +/- 0.67), the Kendall's correlation coefficient was -0.851 with negative correlations (P = 0.036) between postoperative Lysholm score and K/L grade.

CONCLUSIONThere is no correlation between the grade of knee cartilage injury confirmed by MRI (1.5T) and effects of arthroscopy, and the grade is not a gold standard as an operation indication in arthroscope procedure. The K/L grade in X-ray had important effects.

Aged ; Arthroscopes ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Osteoarthritis, Knee ; diagnostic imaging ; pathology ; Radiography

OBJECTIVETo probe into changes of cerebral vascular hemodynamics indexes (CVHI) from normal population to different clinical stage before and after occurring of stroke.

METHODSParticipants were selected from 25,355 stroke cohort study population aged 35 years and over in Northeast of China and 55 acute stroke patients were selected from Fuzhou PLA General Hospital. CVHI indexes were checked during baseline investigation or within one week after acute stroke. Participant enlisted in the study were divided into following 5 groups, normal population, high risk population, individuals before stroke, acute stroke patients and convalescence stroke patients. Characteristics of CVHI indexes in different population were analyzed and compared.

RESULTSV(min) of cerebral vascular in previous defined 5 group participants were 11.39 +/- 3.27, 9.66 +/- 3.18, 6.71 +/- 3.30, 4.13 +/- 1.27, 6.78 +/- 3.09, respectively. V(mean) and V(max) were with the same decreasing trends as V(min). However, RV in 5 group participants were 62.35 +/- 21.11, 82.32 +/- 31.16, 122.72 +/- 52.73, 137.46 +/- 49.56 and 115.89 +/- 55.51, respectively. Zcv, WV, DR and CP were also with the same increasing trends as RV. Abnormal rate of CVHI score (< 75 points) from normal population to convalescence stroke patients were 13.3%, 34.7%, 74.1%, 100% and 66.7%, respectively.

CONCLUSIONFrom normal population to clinical stage of stroke, cerebral vascular velocity showed decreasing trends while other indexes, such as RV, Zcv, WV, DR and CP were increasing.

Brain ; blood supply ; Female ; Hemodynamics ; physiology ; Humans ; Male ; Stroke ; etiology ; physiopathology

OBJECTIVETo establish a predicting model for stroke according to cerebral vascular hemodynamic indexes and major risk factors of stroke.

METHODSParticipants selected from a stroke cohort with 25,355 population in China. The first step was to carry out principal component analysis using CVHI. Logistic regression with principal component and main risk factors of stroke were then served as independent variables and stroke come on as dependent variables. The predictive model was established according to coefficient of regression and probability of each participant was also estimated. Finally, ROC curve was protracted and predictive efficacy was measured.

RESULTSThe accumulative contribution rates of four principal components were 58.1%, 79.4%, 88.4% and 94.6% respectively. Seven variables were being selected into the equation with the first to fourth principal component as history of hypertension, age and sex. Area under ROC curve was 0.855 and optimal cut-off point was probability over 0.05. Sensitivity, specificity and accuracy of stroke prediction were 80.7%, 78.5% and 78.5% respectively.

CONCLUSIONThe model established by principal component and regression could effectively predict the incidence of stroke coming on.

Brain ; blood supply ; Hemodynamics ; physiology ; Humans ; Logistic Models ; Models, Biological ; Principal Component Analysis ; Risk Factors ; Stroke ; etiology

BACKGROUNDSterol regulatory element binding protein (SREBP)-2 plays a key role in lipid homeostasis by stimulating gene expression of cholesterol biosynthetic pathways. The insulin-like growth factor binding protein (IGFBP) family regulates growth and metabolism, especially bone cell metabolism, and correlates with osteonecrosis. However, association of their gene polymorphisms with risk of avascular necrosis of the femoral head (ANFH) has rarely been reported. We determined whether SREBP-2 and IGFBP-3 gene polymorphisms were associated with increased ANFH risk in the Chinese population.

METHODSTwo single nucleotide polymorphisms of SREBP2 gene, rs2267439 and rs2267443, and one of IGFBP-3 gene, rs2453839, were selected and genotyped in 49 ANFH patients and 42 control individuals by direct sequencing assay.

RESULTSThe frequencies of rs2267439 TT and rs2267443 GA of SREBP2 and rs2453839 TT and CT of IGFBP-3 in the ANFH group showed increased and decreased tendencies (against normal control group), respectively. Interaction analysis of genes revealed that the frequency of carrying rs2267439 TT and rs2267443 GA genotypes of SREBF-2 in ANFH patients was significantly higher than in the control group (P < 0.05). Association analysis between polymorphisms and clinical phenotype demonstrated that the disease course in ANFH patients with the rs2453839 TT genotype of IGFBP-3 was significantly shorter than that of CT + CC carriers (P < 0.01). CT + CC genotype frequency in patients with stage III/IV bilateral hip lesions was significantly higher than in those with stage III/IV unilateral lesions and stage II/III bilateral lesions (P < 0.05 - 0.02).

CONCLUSIONSOur results suggested that interaction of SREBP-2 gene polymorphisms and the relationship between the polymorphisms and clinical phenotype of IGFBP-3 were closely related to increased ANFH risk in the Chinese population. The most significant finding was that the CT + CC genotype carriers of IGFBP-3 rs2453839 were highly associated with the development of ANFH.

Adult ; Asian Continental Ancestry Group ; genetics ; Female ; Femur Head Necrosis ; genetics ; Genetic Predisposition to Disease ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Sterol Regulatory Element Binding Protein 2 ; genetics

OBJECTIVETo study the effects of expansion fashion and expansion quantity on retention of cement-expanded composition screw post (CECSP).

METHODSNinety simulated tooth roots made of polymethylmethacrylate were divided into ten groups, each fashion induded five groups. The expanded plastic sheath of tricuspid valve was made with the special separated valve device and cemented and tightened up into root with the screw post at the same time by ZPC. Then the root and screw post-core system was tested by the speed of 10 mm/min on the INSTRON 4302 and the retention force was recorded.

RESULTSIt appeared that the difference between different expansion fashion and different expansion quantity were significantly (P < 0.05). The retention of expansion fashion one was significantly greater than those of fashion two. The retention was best when expansion quantity was within 10%.

CONCLUSIONDuring clinic operation, we should apply definite fashion and control the expansion quantity within 10%, and the screw post should tighten up to the bottom of prepared root.

Bone Screws ; Cementation ; Composite Resins ; Dental Cements ; Dental Cementum ; Dental Prosthesis Retention ; Glass Ionomer Cements ; Humans ; Post and Core Technique ; Tooth Root