Gene ADAM10 (a disintegrin and metalloproteinase 10) is a member of ADAMs gene family. The corresponding membrane protein contains a disintegrin domain and a metalloproteinase domain. It is involved in various biological events such as cell adhesion, cell fusion, cell migration, and membrane protein shedding and proteolysis. ADAM10 protein is overexpressed in many tumors, which interacts with adhesion molecules and critical signaling molecules associated with cancer development and tumor progression, and promotes tumor invasion and metastasis. Regulating the expression of ADAM 10 can inhibit tumor invasion and metastasis , which may become a new strategy for anticancer therapy.

AIM　To prepare naftopidil bioadhesive sustained-release capsule and study their pharmacokinetics and relative bioavailability in the dog. METHODS　Bioadhesive polymers such as hydroxypropyl methylcellulse (HPMC) and Carbopol 934 (CP 934) were used in capsule prescriptions. Naftopidil capsule and two formulations of bioadhesive sustained-release capsules (I and II) were given to five healthy male dogs in a cross-over test. The naftopidil concentrations in plasma were determined by a newly developed HPLC method and the pharmacokinetic parameters as well as the relative bioavailability were measured. RESULTS　The C0→∞, Cmax and Tmax of naftopidil capsule was (3728±573) h*ng*mL-1, (697±94) ng*mL-1 and (1.2±0.5) h. These parameters of bioadhesive sustained-release capsule I and II, respectively, were (5518±391) h*ng*mL-1 and (5636±427) h*ng*mL-1; (468±61) ng*mL-1 and (512±72) ng*mL-1; both (4.0±0.7) h. Results from statistics showed that there were significant difference between bioadhesive formulations and the non-bioadhesive one in C0→∞, Cmax and Tmax. The bioadhesive formulations and the non-bioadhesive one were not bioequivalent, the relative bioavailability of the two bioadhesive sustained-release capsules were respectively 150%±14% and 154%±23% when compared with the non-bioadhesive capsule. CONCLUSION　It is much improving bioavailability of naftopidil by using bioadhesion.

Connexin43,the base of electrical and intercellular chemical signal communication in the myocardial cell,can promote the growth and development of the heart.The decreasing of the number of connexin 43 and its' distribution changes may lead to the changing of the conduction velocity and direction,meanwhile,increase the occurrence of ventricular arrhythmias.Mesenchymal stem cells transplantation and drug therapy can improve the levels and distribution of connexin43 in ill myocardium,and can reduce the occurrence of ventricular arrhythmias.

Objective To explore the value of time-invariant CTA in assessing collateral circulation of patients with acute ischemic stroke and assisting clinicians in predicting clinical outcomes.Methods The score of collateral circulation was compared between single-phase and time-invariant CTA.NIHSS score was calculated at admission and two weeks after admission.A 50% or greater decrease in NIHSS score over two weeks was considered as major neurologic improvement,which showed good clinical outcome;otherwise,it indicated bad outcome.The predictive ability of time-invariant CTA for clinical outcomes was assessed based on ROC curves.Results Compared with single-phase CTA,more collateral vessels could be viewed on time-invariant CTA.The average score of collateral circulation on time-invariant and single-phase CTA was 1.50±0.69 and 1.15±0.49 respectively (P=0.006<0.05 ).Time-invariant CTA had the moderate predictive ability for clinical outcomes in patients with acute ischemic stroke (AUC=0.810;P=0.032<0.05). Conclusion The time-invariant CTA showed potential value in assessing collateral circulation of patients with acute ischemic stroke and assisting clinicians in predicting clinical outcomes.

Objective To study the diagnosis value of serum retinol binding protein (RBP),cystatin C(Cys C) and β2 microglobulin (β2-M) in early renal injures of gcstational diabetes mellitus (GDM) patients.Methods 85 case of GDM pregnant women admitted to Shiyan Maternal and Child Health-Care Hospital from Jan.2009 to Jan 2015 were chosen as research objects,and were divided into simple diabetes group (35 cases),micro proteinuria group (30 cases) and massive proteinuria group (20 cases) according to the urinary albumin excretion rate (UAER),while 30 cases of healthy pregnant women were recruited randomly during the same period as control group.The 24h urine protein,serum RBP and renal function indicators [blood urea nitrogen (BUN),creatinine (Ser),Cys C and β2 M],the positive rates of RBP,Cys C,β2-M and combined detection of RBP,Cys C,β2-M of the four groups were compared.Results The 24h urine protein in simple diabetes group,micro proteinuria group and massive proteinuria group were significantly higher than that in the control group (t=3.91～ 16.33,all P＜0.01),the difference between the 3 groups were statistically significant (t=6.78～ 16.94,all P＜0.01).The levels of BUN,Scr,Cys C,β2-M and RBP in micro proteinuria group and massive proteinuria group were significantly higher than those in control group and simple diabetic group (t=3.68 ～ 18.54,all P＜0.01),there were significant difference in above indexes between micro proteinurine group and massive proteinuria group (t=4.70～ 10.87,all P＜0.01).The positive rates of RBP,Cys C,β2-M and combined detection of RBP,Cys C and β2-M in micro proteinuria group and massive proteinuria group were significantly higher than those in control group and simple diabetic group (x2 =20.27～38.57,all P＜0.01).There was no significant difference in the positive rates between micro proteinuria group and massive proteinuria group (x2 =0.62～0.93,all P＞0.05).The positive rate of combined detection of the three indicators was higher than that of the single detection in the same group (x2=3.97～6.65,P＜0.05 or P＜0.01).Conclusion The detection of serum Cys C,RBP and β2-M has a high clinical value in the diagnosis of early renal damage in patients with GDM.The positive rate of combined detection of 3 indexes was higher than that of single index.

Objective To observe the effect of Radix astragali (RA) on myocardial connexin-43 in rats with dilated cardiomyopathy (DCM). Methods The dilated cardiomyopathy model in rat was established through intraperitoneal injection with adriamycin. The rats in the model group were randomly divided into RA group and the model control group according to different methods of administration. Rats in RA group were gavaged with Astragalus particles and double-distilled water, and rats in model control group and normal control group were gavaged with an equal amount of double-distilled water daily for four weeks. At the end of 12 weeks, the left ventricular ejection fraction (LVEF) was measured with echocardiogram. The Cx43 mRNA level was tested by reverse transcriptase polymerase chain reaction (RT-PCR). Immunohistochemical method was used to observe myocardial Cx43 expression and distribution. Results Compared with the model control group, the Cx43 mRNA and protein expressions and LVEF were increased signiifcantly in RA group (P<0.05). The disorders in distribution of myocardial Cx43 improved in RA group in contrast to the model control group. Conclusions Radix astragali can improve myocardial Cx43 expression and distribution in DCM rats, and can further improve the cardiac function.

Objective To establish a sensitive HPLC method with UV detection for the determination of tanshinone Ⅱ_A(TSⅡ_A) and cryptotanshinone(CT) in rat plasma and to study pharmacokinetics of Radix Salviae Miltiorrhizae(RSM) liposoluble components in rat in vivo. Methods TS Ⅱ_A and CT in plasma of rat at different sampling time were determined by pretreatment with Gemifibrozil as internal standard,the protein was precipitated in methanol solution after iv administration of alcohol extract of RSM 5 mg/per animal.The mean plasma concentration-time curve was protracted and pharmacokinetic parameters were calculated by 3p87.Results The main pharmacokinetic parameters of TS Ⅱ_A were as follows: t_(1/2?) was(0.088?0.024) h;t_(1/2?) was(2.1?0.7) h;V_C was(0.8?0.6) L;CL was(2.0?1.1) L/h~(-1);AUC_(0-4) and AUC_(0-∞) were(2.2?0.9) mg?h/L and(3.4?1.7) mg?h/L,respectively.Conclusion The concentration-time curve of TS Ⅱ_A can be fitted to two-compartment model after ethanol extract of RSM iv administrated.Concentration of TS Ⅱ_A in rat plasma declines rapidly with large apparent volume of distribution.CT decreases also rapidly and it is difficult to acquire its pharmacokinetic parameters in rat.

Adult ; Bone Diseases, Metabolic ; etiology ; Female ; Fractures, Spontaneous ; etiology ; Humans ; Liver Diseases, Alcoholic ; complications

ObjectiveTo observe the effect of Astragalus membranaous on angiotensinⅡ (AngⅡ)-induced transform-ing growth factor β1 (TGF-β1) production of cardiac ifbroblasts.Methods Cardiac ifbroblasts were culturedin vitro. Cells were allocated into 3 groups: control group, Astragalus membranaous groups (50, 100, 200 mg/ml), Ang II group (10-7 mol/L) and AngⅡ/Astragalus membranaous groups (50, 100, 200 mg/ml). The proliferation of each group was tested by methyl thiazolyl tetrazolium method. TGF-β1 was measured by ELISA.Results The proliferation of cardiac ifbroblasts had signiifcant difference between each groups (F=71.84,P=0.000). The proliferation of cardiac ifbroblasts with Ang II stimulation was higher than that of cells without Ang II stimulation (P<0.05). Astragalus membranaous inhibited Ang II-induced cardiac ifbroblasts proliferation dose dependently (P<0.05). The TGF-β1 production had signiifcant difference between each groups (F=786.81,P=0.000). The TGF-β1 production in AngII/astragalus membranaous groups was lower than that in Ang II group (P<0.05). The TGF-β1 production in Ang II group was the highest, and had signiifcant difference as compared to other groups (P<0.05). Astragalus membranaous inhibited Ang II-induced TGF-β1 production dose dependently (P<0.05).Conclusions Ang II can stimulate the proliferation of cardiac ifbroblasts, and promote the TGF-β1 production. Astragalus membranaous can inhibit the proliferation of Ang II-induced cardiac ifbroblasts, and reduce the TGF-β1 production of cardiac ifbroblasts.

Objective To investigate the expressions of Wnt2 and β-catenin in Doxorubicin (DOX)-induced myocardial injury and to explore their roles in myocardial cell apoptosis.Methods Cardiomyoblast cells were damaged by different concentrations of DOX(1 mg/L,2 mg/L,3 mg/L,4 mg/L) for 72 h.The effect of different concentrations of DOX on cardiomyocyte growth curve was detected according to the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-h-tetrazolium bromide(MTT) assay.DOX(1 mg/L) was used to induce the model of cardiomyoblast cell injury.Cardiomyocytes were divided into 4 groups:group A:DOX-injured cardiomyocytes for 12 h ;group B:DOX-injured cardiomyocytes for 24 h ; group C:DOX-injured cardiomyocytes for 48 h; group D:normal cardiomyocytes.The expressions of Wnt2,β-catenin and p53 were observed by Western blot and reverse transcription polymerase chain reaction(RT-PCR) at the time point of 12 h,24 h and 48 h.Results DOX significantly inhibited cardiomyocyte proliferation in a dose dependent fashion.The protein and mRNA expressions of Wnt2 increased in the DOX-induced myocardial injury group compared with the group D,with statistical significance (F =224.115,P ＜ 0.05) ;The expressions of β-catenin,p53 were significantly increased compared with the group D,and the higher expression appeared with the time extending(F =188.145,231.927,all P ＜ 0.05).Significantly positive correlation between Wnt2 and β-catenin expression was observed(r =0.940,P ＜ 0.05).Conclusions These findings suggest that Wnt2/β-catenin signaling pathway may play important roles in the cardiovascular disease and be useful for exploring the molecular mechanism of myocardial injury..