This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.
Animals ; Chlorzoxazone ; metabolism ; Chromatography, Liquid ; Cytochrome P-450 Enzyme System ; metabolism ; Depression ; Dextromethorphan ; metabolism ; Liver ; enzymology ; Midazolam ; metabolism ; Omeprazole ; metabolism ; Rats ; Stress, Physiological ; Tandem Mass Spectrometry ; Theophylline ; metabolism ; Tolbutamide ; metabolism

AlM: To observe the effect of anterior chamber depth and angle change after pterygium excision.METHODS:Thirty cases (30 eyes) of primary pterygium were underwent pterygium excision. Central anterior chamber depth, four direction angle open distance ( AOD ) and open angle ( AA ) were measured preoperatively and postoperatively by ultrasound biomicroscopy ( UBM ) and the intraocular pressure was observed.RESULTS:Preoperative and Postoperative intraocular pressure were 15. 17±10. 6 and 16. 23±2. 61mmHg, and the central anterior chamber depth were 2. 28±0. 39 and 2. 33± 0. 24mm. The four directions of AOD and AA were no statistical difference.CONCLUSlON:The anterior chamber depth and the angle change is not obvious after pterygium excision.

Objective To evaluate the role of vascular endothelial growth factor-D(VEGF-D)in lymphangiogenesis of breast cancer,and investigate its relationship with some clinicopathological parameters and prognosis. Methods VEGF-D expression was detected in 85 cases with primary breast carcinoma by immunohistochemistry,and VEGF-D mRNA was detected by RT-PCR.Podoplanin monoclonal antibody was used to mark lymphatic endothelial cell and lymphatic vessel density(LVD) was counted.The relationship among the aboved parameters,clinicopathological parameters and prognosis was analysed. Results It was revealed by immunohistochemistry that VEGF-D expression was ranked by 5 levels: negative,n=5(5.88%);"+",n=17(20%);"++",n=34(40%);"+++",n=22(25.88%),and "++++",n=7(8.24%).VEGF-D expression was associated with tumor lymph node metastasis and TNM clinical stage(P

To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.
Animals ; Arthritis, Rheumatoid ; drug therapy ; immunology ; Biomarkers ; Female ; Interleukin-17 ; antagonists & inhibitors ; genetics ; Interleukin-6 ; genetics ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Tripterygium ; Triterpenes ; pharmacokinetics ; pharmacology

ObjectiveTo investigate the effect and significance of cyclooxygenase-2 (COX-2) inhibitors on the expression of the Acsl gene family in the ileum of rats with nonalcoholic fatty liver disease (NAFLD). MethodsA total of 45 Sprague-Dawley rats were randomly divided into normal control group (15 rats given normal diet), NAFLD model group (15 rats given high-fat diet), and nimesulide group (15 rats given high-fat diet and nimesulide). All rats were sacrificed after 12 weeks of feeding, and then blood samples were collected from the inferior vena cava to measure total cholesterol (TC) and triglyceride (TG). HE staining and oil red O staining were performed for the liver to evaluate the degree of hepatic steatosis in each group, and quantitative real-time PCR was used to measure the mRNA expression of the Acsl family genes in the ileum. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal control group, the NAFLD model group had significant increases in serum TC and TG and marked hepatic steatosis (all P＜0.05); compared with the NAFLD model group, the nimesulide group had significant reductions in serum TC and TG and degree of hepatic steatosis (all P＜0.05). Compared with the normal control group, the NAFLD model group had a significant increase in the expression of COX-2 in the ileum (P＜0.05), and compared with the NAFLD model group, the nimesulide group had a significant reduction in the expression of COX-2 in the ileum (P＜005). Compared with the normal control group, the NAFLD model group had significant increases in the mRNA expression of Acsl3 and Acsl5 in the ileum (both P＜0.05), and compared with the NAFLD model group, the nimesulide group had significant reductions in the mRNA expression of Acsl3 and Acsl5 (both P＜0.05). ConclusionThe COX-2 inhibitor nimesulide can regulate the expression of the Acsl gene family in the ileum of rats with NAFLD, suggesting that COX-2 inhibitors may inhibit the progression of NAFLD through the Acsl gene.

[Objective]To compare early serum beta-human chorionic gonadotropin (β-hCG) levels after cleavage or blastocyst embryo transfers (ET) in predicting pregnancy outcome.[Methods]A total of 2421 IVF-ET cycles in our center performed from June 2010 to May 2015 and resulted in clinical intrauterine pregnancies were analyzed retrospectively. The predictive value was compared betweenβ-hCG on day 14 after cleavage ET andβ-hCG on day 12 after blastocyst ET.[Results]Serumβ-hCG levels of patients re?sulted in clinical intrauterine pregnancies were significantly higher with blastocyst ET compared with cleavage ET. This significant dif?ference was also existed in patients resulted in miscarriage, ongoing pregnancy (OP) or live birth (LB). However, this significant differ?ence was only existed in frozen embryo transfers. For a frozen cleavage ET, the cut-off value was 475 U/L (sensitivity 79%, specificity 61.3%) in predicting LB. For a frozen blastocyst ET, the cut-off value was 575 U/L (sensitivity 74.9%, specificity 59.2%) in predicting LB.[Conclusion]In frozen embryo transfers, early serumβ-hCG level after blastocyst ET is higher than cleavage ET. The cut-off val?ue in predicting pregnancy outcome is different according to the stage embryo transferred. Early serum β-hCG can effectively predict live birth after blastocyst or cleavage ET.

Adult ; Bone Neoplasms ; diagnosis ; surgery ; Female ; Humans ; Osteoblastoma ; diagnosis ; surgery ; Patella

Objective To explore the reliability and validity of the Children' s Impact of Event Scale (Chinese version, CRIES-13) and to determine the value and the optimal cutoff point of the score of CRIES-13 in screening posttraumatic stress disorder(PTSD), so as to provide evidence for PTSD prevention and identify children at risk in Wenchuan earthquake areas. Methods A total of 253 children experienced the Wenchuan earthquake were tested through Stratified random cluster sampling. The authors examined CRIES-13's internal consistency, discriminative validity and predictive value of the cut-off. PTSD was assessed with the DSM-Ⅳ criteria. Area under the curve while sensitivity, specificity and Youden index were computed based on the receiver operating characteristic curve analysis. Optimal cutoff point was determined by the maximum of Youden index. Results 20.9% of the subjects were found to have met the DSM-Ⅳ criteria for PTSD 7 months after the Wenchuan earthquake accident. The Cronbach' s coefficient of CRIES-13 was 0.903 and the mean inter-item correlation coefficients ranged from 0.283 to 0.689, the correlation coefficient of the three factors with the total scale scores ranged from 0.836 to 0.868 while the correlation coefficient among the three factors ranged from 0.568 to 0.718, PTSD cases indicated much higher scores than non-PTSD cases, the Youden index reached maximum value when the total score approached 18 in CRIES-13 with sensitivity and specificity as 81.1% and 76.5% respectively. Consistency check showed that there were no significant differences between the results of CRIES-13 score ≥32 and clinical diagnosis (Kappa=0.529) from the screening program. Conclusion CRIES-13 appeared to be a reliable and valid measure for assessing the posttraumatic stress symptoms among children after the earthquake accident in the Wenchuan area. The CRIES-13 seemed to be a useful self-rating diagnostic instrument for survivors with PTSD symptoms as a clinical concern by using a 18 cut-off in total score. Consistency check showed that there was no significant difference between the screening result of CRIES- 13 score ≥ 32 and clinical diagnosis.

OBJECTIVETo investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA).

METHODSEquilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to reveal the target protein-compound interactions.

RESULTSThe binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA were (30.16∓2.82)%, (33.42∓4.21)%, and (34.61∓3.42)%, and those of and Rb1 were (50.13∓2.34)%, (51.23∓3.23)%, and (53.11∓3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13∓2.72)%, (21.42∓3.22)%, and (25.45∓3.52)%, and those of Rb1 to (40.13∓3.24)%, (41.25∓4.15)%, and (43.11∓3.31)%, receptively. The molecular docking suggested that these compounds competed to bind with RSA.

CONCLUSIONClopidogrel can competitively bind to RSA with ginsenosides to lower the plasma protein binding rates of ginsenosides.

OBJECTIVETo investigate the relationship between the pathologic responses and histologic type, grade, the expression of ER, PR and HER2 and their changes in breast carcinoma before and after neoadjuvant chemotherapy (NAC).

METHODSTwo-hundred and nine cases of breast cancer with NAC were analyzed and clinical, pathologic data were evaluated based on the Miller and Payne ( MP) grading system. The expression of ER, PR and HER2 in the cancers before and after NAC were detected by immunohistochemistry (MaxVision method). SPSS 15.0 software was used to conduct statistical analysis.

RESULTS(1) Pathologic responses to the NAC were graded as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases); (2) The expression of ER in core needle biopsy had related negatively to the pathologic response (chi2 = 33.083, P = 0.001). However, the histologic type, grade, ER and PR status, and HER2 expression in surgically-removed specimens had not related to the pathologic response (P>0.05); (3) After NAC, the pathologic type and grade changed in 6. 8% (9/132) and 34.9% (30/86) of the cases, and the rates of changes in the expression of ER, PR and HER2 were 42.4% (75/177), 55.4% (98/177) and 26.6% (46/173) , respectively. Only the expression of HER2 had significant difference between before and after neoadjuvant chemotherapy (P = 0.049). The changes in other data had no relationship with the pathologic response (P>0.05).

CONCLUSIONSAnalysis of core needle biopsy can provide important information to predict the pathologic responses to the NAC. The pathologic appearance, grade, ER, PR and HER2 in breast carcinoma may change after NAC. It is necessary to examine the histologic type, grade and the expression of ER, PR and HER2 after NAC once more.

Adenocarcinoma, Mucinous ; drug therapy ; metabolism ; pathology ; surgery ; Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Lobular ; drug therapy ; metabolism ; pathology ; surgery ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism