Objective To study the ventricular-arterial coupling in the patients with type 2 diabetes mellitus (DM) by ultrasound.Methods Eighty patients with DM were divided into 2 groups:normal left ventricular ejection fraction (EF) group (DMN,EF≥50 ％,n =40) and abnormal EF group (DMA,EF＜50％,n =40).At the same time,42 healthy volunteers were selected as a control group.The left ventricular (LV) relative wall thickness (RWT),mass index (LVMI),stroke volume (SV),stroke works (SW),ratepressure product (RPP),systemic vascular resistance index (SVRI),LV end-systolic elastance (Ees),arterial elastance index (Ea) and ventricular vascular index (VVI) were measured and calculated.Longitudinal strain (LS) of myocardial segment including base(LSBA),papillary muscle (LSPM) and apex (LSAP) were analyzed by two-dimensional speckle tracking imaging.Results (1) Compared with the control,the RWT and LVMI were all increased (P ＜0.01),but the LSBA,LSPM and LSAP were decreased (P ＜ 0.01) in the DMN and DMA groups (P ＜0.01).In DMA group,the RWT,LSBA,LSPM and LSAP were decreased (P ＜0.01).Compared with the DMN group,the LSBA,LSPM and LSAP were decreased in DMN group (P ＜0.01).(2) Compared with the control,the Ea,VVI,RPP and SVRI were increased,but the Ees was decreased (P ＜0.05)in DMA group (P ＜0.01).In the DMN,RPP was increased compared with the control group (P ＜0.01).Compared with the DMN group,the Ea,VVI,RPP and SVRI were increased,but Ees was decreased in the DMA (P ＜0.05).(3)The LSBA,LSPM and LSAP were all positively correlated with VVI(P ＜0.01).Multiple regression analysis showed that the LSAP,RWT,LVMI and SW were independent predictor of VVI (b' =-0.613,-0.290,0.290 and-0.205,P ＜ 0.05).Conclusions The ventricular-arterial coupling is normal in the DMN group,but is abnormal in DNA group.LSAP is independent predictors for ventricular-arterial coupling.

The incidence rate of nonalcoholic fatty liver disease (NAFLD) is gradually increasing in recent years, and the treatment of NAFLD is unsatisfactory due to the failure in lifestyle adjustment and a lack of effective drugs. Farnesoid X receptor (FXR), as the main bile acid receptor, may affect NAFLD by participating in glucose and fat metabolism, and intestinal FXR (iFXR) acts on the intestinal tract alone and may thus avoid the side effects of systemic release. Therefore, it may have potential value in the treatment of NAFLD, but there are also certain controversies. This article reviews the research advances in the role of iFXR in NAFLD.

OBJECTIVETo study the reversal effect of nomegestrol acetate (NOM) on mutidrug resistance (MDR) in MCF7/ADR and its mechanism.

METHODSUsing tetrazolium dye assay, effects of various concentrations of NOM on sensitivity to ADR in MCF7/ADR was studied. Expression of MDR related genes MDR1, glutathoine S-transferase Pi (GSTpi), Topoisomerase II alpha (Topo II alpha) and MDR related protein (MRP) were assayed by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry assay. Using flow cytometry (FCM), intracellular ADR concentration effects on cell cycle were observed.

RESULTSNOM significantly reversed MDR in MCF7/ADR. After NOM 20, 10 and 5 micromol/L treatment, the chemosensitivity to ADR increased to 21, 12 and 8 times. The reversal activity of NOM was stronger than that of the precursor compound megestrol acetate, and was comparable to that of verapamail. After treatment with NOM 5 micromol/L both MDR1 and GSTpi mRNA genes expression began to decline on D2 (P < 0.05, & P < 0.01) and reached the lowest level on D3 (both P < 0.01), but the expression levels began to rise on D6 again (both P < 0.05). The expression of MRP and Topo II alpha gave no significant change. Changes of P-gp and GSTpi protein expressions were similar to those of their mRNA expressions, showing early decline and late rise. Two hours after NOM 20, 10, and 5 micromol/L treatment, intracellular ADR concentration increased 2.7, 2.3 and 1.5 times, respectively. FCM data showed that after forty-eight hours, combined administration of NOM (20 micromol/L) and ADR (from low concentration to high concentration), MCF7/ADR cells showed gradual arrest in the G(2)M phase with the increase of ADR dose.

CONCLUSIONNOM has strong reversal effects on MDR in MCF7/ADR. The reversal takes place via different routes, i.e. down regulating mRNA and protein expression levels of MDR1 and GSTpi, increasing intracellular drug concentration, and enhancing the arrest of ADR in cells at G(2)M phase.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Antigens, Neoplasm ; Breast Neoplasms ; genetics ; pathology ; Cell Survival ; drug effects ; DNA Topoisomerases, Type II ; genetics ; metabolism ; DNA-Binding Proteins ; Drug Resistance, Neoplasm ; genetics ; Gene Expression Regulation, Neoplastic ; drug effects ; Glutathione S-Transferase pi ; Glutathione Transferase ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Inhibitory Concentration 50 ; Isoenzymes ; genetics ; metabolism ; Megestrol ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Norpregnadienes ; pharmacology ; Progesterone Congeners ; pharmacology ; RNA, Messenger ; drug effects ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; Verapamil ; pharmacology

The stability and pharmacokinetic properties of hyaluronic acid-modified asparaginase (Asp) self-assembled bionic nanocapsules (ASNCs) were preliminarily investigated. ASNCs were prepared by molecular self-assembly method to investigate their morphology, particle size, zeta potential and antitrypsin stability. After intravenous injection of free Asp and ASNCs, rat plasma samples at different times were taken to determine Asp activity. Pharmacokinetic parameters were calculated by DAS pharmacokinetic software. The particle size of ASNCs was (99.17 ± 0.21) nm and the potential was -(13.13 ± 0.60) mV. In trypsin solution, ASNCs showed more excellent stability. The area under the activity-time curve (AUC0-48 h) of ASNCs was about 2 times higher than that of Asp; the mean residence time (MRT0-48 h) was about 1.7 times higher than that of Asp, and the bioavailability was 195% of Asp. The results showed that ASNCs could improve the stability and bioavailability of Asp against trypsin and prolong the circulation time of Asp in vivo.

Objective To investigate the role of combined analysis of E2F3a and CASP8AP2 expression in prognosis evaluation in pediatric acute lymphoblastic leukemia (ALL). Methods The study included 141 newly diag-nosed pediatric ALL patients enrolled at the Hematology Center,Beijing Children′s Hospital,Capital Medical Universi-ty between March 2008 and July 2010,including 97 boys and 44 girls(aged 1. 2 - 15. 5 years,median 5. 2 years). E2F3a and CASP8AP2 expressions were quantified in 141 children with ALL by adopting real - time quantitative poly-merase chain reaction (qPCR). Receiver operating characteristic (ROC)curve was used to find the best cut - off point to divide the patients into E2F3a or CASP8AP2 low - and high - expression groups,and the treatment outcome between the groups was compared. Cox regression was used to analyze the prognostic significance of the combined expression of E2F3a and CASP8AP2. Results The estimated 5 - year relapse free survival(RFS)rate,event free survival(EFS) rate and overall survival (OS)rate of patients with low - E2F3a and low - CASP8AP2 expression were (58. 9 ± 10. 0)％,(56. 0 ± 9. 9)％ and (72. 0 ± 9. 0)％,respectively. They were significantly lower than those of patients with high - E2F3a and high - CASP8AP2 expression,whose RFS,EFS and OS were (94. 9 ± 2. 5)％,(93. 7 ± 2. 7)％ and (96. 2 ± 2. 2)％,and the differences were all statistically significant(all P < 0. 05),respectively. Compared with other patients,the one with low expression of both E2F3a and CASP8AP2 had a poorer prognosis. In addition to MLL rear-rangements and minimal residual disease level at the end of remission induction,low expression of both E2F3a and CASP8AP2 remained as independent prognostic factors. Conclusion Low expressions of E2F3a and CASP8AP2 pre-dict poor prognosis in pediatric ALL. Combined assessment of E2F3a and CASP8AP2 expression could predict poor prognosis and relapse more accurately.