Objective To investigate the inhibitory effect and associated mechanism of rapamycin on proliferation and extracellular matrix (ECM) secretion in myofibroblasts stimulated by connective tissue growth factor (CTGF). Methods Primary cultivated myofibroblasts were divided into 6 groups: control, CTGF (100 μg/L), rapamycin 20 μg/L+CTGF 100 μg/L, rapamycin 40 μg/L +CTGF 100 μg/L, rapamycin 20 μg/L, and rapamycin 40 μg/L alone. 5'-bromodeoxyuridine (BrdU) incorporation assay was used to detect the myofibroblast proliferation.Western blot was used to analysis the secretory FN protein in the supernatant medium of cultured myofibroblasts and the ERK1/2 phosphorylation in myofibroblasts. Results CTGF (100 μg/L)incubation significantly increased the number of Brdu positive myofibroblasts(P<0.01) and the level of FN protein secretory (P<0.05) in cell supernatant medium compared with control group,respectively. The number of Brdu positive myofibroblasts markedly decreased by 62% and 70% (P <0.05) in rapamycin 20 μg/L+CTGF 100 μg/L and rapamycin 40 μg/L+CTGF 100 μg/L groups, respectively. The FN protein levels in supernatant were decreased by 15% and 44% compared with CTGF 100 μg/L group, respectively; but the difference of FN protein levels was significant only in rapamycin 40 μg/L group (P<0.05). CTGF could activate ERK1/2 at 10 minutes; but as myofibroblasts were pretreated with rapamycin 40 μg/L for 30 min, it abolished CTGF-induced ERK1/2 phosphoralation. PD98059, the specific inhibitor of ERK1/2, could block the effect of CTGF-induced proliferation (7%±5% vs 85%±7%, P<0.01) and FN secretion (1.0±0.1 vs 1.6±0.3, P<0.05). Conclusions Rapamycin partially suppresses the proliferation and ECM secretion of myofibroblasts induced by CTGF. Its effect may be through inhibiting CTGF-induced activation of ERKI/2 signaling pathway.

Objective To analyze and discuss the expression of serum polymyositis‐scleroderma(PM‐Scl) antibody and its clinical significance in patients with systemic scleroderma(SSc) .Methods 315 hospitalized patients diagnosed with scleroderma by typical clinical manifestations or skin pathology from 2009 to 2012 were enrolled in the study .All patients were grouped into PM‐Scl antibody positive(PM‐Scl + ) group(90 cases) ,Scl‐70 antibody positive(Scl‐70+ ) group(70 cases) ,anti‐centromere antibody positive( ACA+ ) group(75 cases) and antibody negative group(80 cases) according to autoantibody spectrum .The severity of skin and visceral damage among all the groups were analyzed and compared .Results Patients in PM‐Scl+ group were characterized with different clinical manifestations .Compared with the other 3 groups ,the incidence of myositis in PM‐Scl+ group was significantly higher( all P< 0 .05) ;patients in Scl‐70+ group had higher incidence of visceral organ damage than PM‐Scl+ group(all P < 0 .05) .The incidence of skin lesions ,Raynaud′s phenomenon and capillary expansion in ACA+ group were higher than that of PM‐Scl+ ,while the incidence of interstitial lung disease ,heart disease and kidney disease were lower(all P< 0 .05) .Conclusion It is helpful for clinicists′ further understanding of common autoantibodies in Ssc patients and making correct assessment of the disease through analyzing the expression of PM‐Scl antibody .

Objective To explore the professional identity of medical students with long education periods and its influencing factors.Methods Survey on professional identity was conducted through self-designed questionnaire among 665 medical students with long education periods of every grade.Single factor analysis of variance and t test were applied to do statistical analysis.Results There were significantly statistical differences in influencing factors of professional identity among every grade of long periodical medical students (P ＜ 0.05).There were significant statistical differences among influencing factors of sex,educational background of parents and residing(P ＜ 0.05).Conclusions Because of characteristics of medical education and psychological changes of students,professional identity of students shows a first decline and then an increase.Personal and environmental factors exert influences on professional identity at varying degrees.

Objective: To develop a general module of self-administered quality of life instrument for Chinese patients with chronic disease. Methods: Using the structured group (nominal group and focus group) methods and the qualitative and quantitative theory and methodology in developing rating scales Items were preliminary screened, evaluated and modified, and the QoL data measuring from 201 cases of patients of 8 different chronic diseases were analyzed by the methods of coefficient of variation?factor analysis, clustering analysis and correlation analysis. Result: General module of quality of life instrument for patients with chronic disease (QLICD-GM) was developed and evaluated. It consists of three domains: physical function, psychological function and social function, 32 items. Conclusions: QLICD-GM possessed a reasonable good content validity for it reflect WHO 's definition and connotation of QoL, and also common issues of patients with chronic disease.

Objective To investigate the awareness and administration of antidiabetic drugs in patients with diabetes in Huairou district of Beijing.Methods A questionnaire survey on knowledge and administration of antidiabetic drugs were conducted in 900 diabetic patients from 16 communities in Huairou district of Beijing from November 2014 to February 2015.The related factors influencing antidiabetic drug use were analyzed with logistic regression method.Results A total of 899 questionnaires were recovered. Results showed that the rate of metformin single use was the highest (23.7%, 213/899), the rate of combination use of metformin and acarbose was 11.8%(106/899), and that of metformin and glipizide was 17.1% (154/899).Survey showed that 65.9% (592/899) patients were compliant immediately for antidiabetic agents, 32.2% (290/899) were not immediately compliant, 1.9% (17/899) did not use antidiabetic agents.Logistic regression analysis showed that the factors affecting the use of antidiabetic agents were the types of medication (t=-4.351, P=0.000) , adverse effects of drugs (t=6.999, P=0.000), awareness of diabetes to health hazard (t=-10.969, P=0.000) and the doctor′s recommendation (t=-3.352, P=0.001).Conclusion The results showed that the administration of antidiabetic drugs in diabetic patients from Huairou district is basically followed the recommendation by 2013 edition of type 2 diabetes guidelines and the compliance rate of medication need to be further raised.

Objective To observe the changes of tissue doppler Tei index (TDI-Tei index) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in children with atrial septal defect(ASD) before and after interventional therapy,in order to investigate the evaluation value of the two parameters on the improvements of right cardiac function.Methods Ninety children with ASD who were treated in the First Hospital of Hebei Medical University from June 2013 to June 2015 as the ASD group,including 48 male and 42 female at the age of (3.0-13.0) years old,and the average age was (5.4±2.7) years old.Fifty healthy children with matched age and gender as the control group.Concentrations of serum NT-proBNP were measured by using Bi-directional lateral flow immunoassay before and the 7th day and 6th month after cardiac catheterization,respectively.The right ventricular Tei index(RV-Tei index) was measured by tissue doppler Imaging.The changes and the correlations of parameters before and after interventional therapy were compared and analyzed respectively.Results (1) Before interventional therapy,the right ventricular TDI-Tei index in ASD group was higher than control group(0.56±0.09 vs 0.31 ±0.05,P＜0.01),and the TDI-Tei index was decreased gradually at different time points after interventional therapy in ASD group,especially at the 6th month was lowest(P＜0.01);TDI-Tei indexes at before and the 7th day and 6th month after the procedure were significantly different(0.56±0.09 vs 0.44±0.06,0.56±0.09 vs 0.33±0.04;t=22.56,23.27;P＜0.05).Compared with control group,there was significant difference about the TDI-Tei index in ASD group at the 7th day after transcatheter closure(P＜0.05),while there was no significant difference about TDI-Tei index at the 6th month (P＞0.05).(2) Before interventional therapy,the level of serum NT-proBNP in ASD group was higher than control group ((259.49± 43.99) ng/L vs (102.11 ± 34.53) ng/L,P＜0.01),and the levels of NT-proBNP were decreased gradually at different time points after interventional therapy in ASD group,especially at the 6th month was lowest(P＜0.01);the levels of NT-proBNP at before and the 7th day and 6th month after interventional therapy were significantly different ((259.49 ± 43.99) ng/L vs (192.93 ± 56.46) ng/L,(259.49±43.99) ng/L vs (108.46±36.88) ng/L;P＜0.05).Compared with control group,there was significant difference about the level of serum NT-proBNP in ASD group at the 7th day after transcatheter closure (P ＜0.05),while there was no significant difference about NT-proBNP at the 6th month(P＞0.05).(3) Before and the 7th day and 6th month after interventional therapy,NT-proBNP level and the right ventricular TDI-Tei index was significantly positive correlated in ASD group (r =0.719,0.753,0.732;P＜0.01).Conclusion The changes and correlations of the right ventricular TDI-Tei index and serum NT-proBNP in the children with ASD after intervention operation indicates that TDI-Tei index and serum NT-proBNP could evaluate the improvement of right cardiac function.

Purpose To investigate effect of valsartan on expression of Notch pathway and production of extracellular matrix. Methods Urine protein and production of extracellular matrix were measured after diabetic mice were treated with valsartan. The levels of Jag-ged1, Notch1, Notch intracellular domain 1 (NICD1), transforming growth factor-β1 (TGF-β1), TypeⅣcollagen and Laminin were determinated by immunohistochemistry, Western blot and real-time PCR. Results Valsartan suppressed urine protein and production of extracellular matrix in diabetic mice (P<0. 05). Valsartan also inhibits overexpression of Jagged1, Notch1, NICD1, TGF-β1, Type Ⅳ collagen and Laminin in glomerular tissues of diabetic mice (P<0. 05 or P<0. 01). Conclusion Valsartan inhibits activa-tion of Notch pathway in glomerular tissues of diabetic mice, inhibits production of extracellular matrix in glomerulus and delays glomer-ulosclerosis.

The metabolic characteristics of ligustrazin (TMPz) in liver microsomes were investigated in the present study. The reaction phenotyping of TMPz metabolism was also identified by in vitro assessment using recombinant human cytochrome P450 enzymes (CYP) and UDP glucuronosyltransferases (UGT). TMPz was incubated at 37 degrees C with human (HLM) and rat liver microsomes (RLM) in the presence of different co-factors. The metabolic stability and enzyme kinetics of TMPz were studied by determining its remaining concentrations with a LC-MS/MS method. TMPz was only metabolically eliminated in the microsomes with NADPH or NADPH+UDPGA. In the HLM and RLM with NADPH+UDPGA, t1/2, K(m) and V(max) of TMPz were 94.24 +/- 4.53 and 105.07 +/- 9.44 min, 22.74 +/- 1.89 and 33.09 +/- 2.74 micromol x L(-1), 253.50 +/- 10.06 and 190.40 +/- 8.35 nmol x min(-1) x mg(-1) (protein), respectively. TMPz showed a slightly higher metabolic rate in HLM than that in RLM. Its primary oxidative metabolites, 2-hydroxymethyl-3, 5, 6-trimethylpyrazine (HTMP), could undergo glucuronide conjugation. The CYP reaction phenotyping of TMPz metabolism was identified using a panel of recombinant CYP isoforms (rCYP) and specific CYP inhibitors in HLM. CYP1A2, 2C9 and 3A4 were found to be the major CYP isoforms involved in TMPz metabolism. Their individual contributions were assessed b) using the method of the total normalized rate to be 19.32%, 27.79% and 52.90%, respectively. It was observed that these CYP isoforms mediated the formation of HTMP in rCYP incubation. The UGT reaction phenotyping of HTMP glucuronidation was also investigated preliminarily by using a panel of 6 UGT isoforms (rUGT). UGT1A1, 1A4 and 1A6 were the predominant isoforms mediated the HTMP glucuronidation. The results above indicate that the metabolism of TMPz involves multiple enzymes mediated phase I and phase II reactions.

Aim To investigate the inhibitory and in-duction effects of the active components of SIWU de-coction on cytochrome P450 enzymes ( CYP ) and as-sess the CYP based drug interaction. Methods Ac-tive components fructose, ferulic acid, paeoniflorin, li-gustrazine and their combinations were incubated sepa-rately with human liver microsomes ( HLM) and probe substrates. Metabolites of the CYP probe substrates were determined by LC-MS/MS to assess the inhibitory activities on human CYP1 A2 , 2 B6 , 2 C9 , 2 C19 , 2 D6 and 3 A4 . Sandwich-cultured rat hepatocytes model was used to evaluate the CYP1 A2 and CYP3 A1/2 induc-tion. Results The inhibitory rates on CYP1A2, 2B6, 2 C9 and 2 C9 by the test groups at 100 μmol · L-1 were all < 62%, while the activities of CYP3 A4 and 2D6 were not affected. The CYP1A2 activities in the test groups of peoniflorin and its combinations ( 50μmol·L-1 ) were significantly enhanced, with the in-creasing fold more than 40% of positive control group. No significant induction on rat CYP3 A1/2 was ob-served for four principles and their combinations. Con-clusions The active components of SIWU decoction do not show significant inhibitory effects on six CYP isoforms. Peoniflorin could induce the CYP1A2 activity in rat hepatocytes. The induction activity is enhanced by the concomitant use of peoniflorin with ferulic acid and/or ligustrazine.

Aim To investigate the expression of Notch pathway and Nephrin in angiotensin Ⅱ ( AngⅡ)-stimulated mice podocyte. Methods Mice podo-cyte was stimulated by AngⅡ, and then was treated with valsartan. The levels of Notch1, Notch intracellu-lar domain 1 ( NICD1 ) , Hes1 and Nephrin were deter-mined by immunofluorescence, Western blot and Real-time PCR. Results AngⅡincreased Notch1, NICD1 and Hes1 expression, and decreased Nephrin expres-sion in a time-dependent manner ( P<0. 01 ) . Valsar-tan inhibited AngⅡ-induced activation of Notch path-way and enhanced Nephrin level ( P <0. 01 ) . Con-clusion AngⅡdecreases Nephrin expression in podo-cyte by activating Notch pathway.