The renin-angiotension system (RAS) plays an important role in cardiovascular and renal physiology and diseases. Recent discoveries of prorenin and prorenin receptor add new contents to RAS. Renin and prorenin binding to the prorenin receptor not only target and facilitate angiotensin generation but also lead to activation of prorenin receptor signal transduction pathways, which is distinct from classical RAS signaling. In this paper, the construction, function and signal trasduction of prorenin, prorenin receptor and handle region peptide are reviewed.

Objective To assess the effect of 5-azacytidine (5-AZ) on the expressions of atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC) genes in cultured rat bone marrow stromal cells (BMSCs). Methods Neonatal rat cardiomyocytes and adult rat BMSCs were isolated and cultured. BMSCs were incubated with 5-AZ and (or) myocardiocytes culture medium. RT-PCR was used to measure the expressions of cardiac ANP and β-MHC genes. Results Normally cultured rat BMSCs didn't express cardiac ANP or β-MHC. After inducing by 5-AZ, rat BMSCs expressed ANP or β-MHC. The myocardiocytes culture medium enhanced expression of β-MHC, but didn't affect the expression of ANP. Conclusions The 5-AZ induces the rat BMSCs to express either cardiac ANP or β-MHC, and the former could be enhanced by cardiomyocytes culture medium.

Objective To investigate the relationship of the beneficial effect of CsA on vascular reactivity to Rho-kinase,protein kinase C ( PKC) and mitochondrial permeability transition pore ( MPTP) in traumatic hemorrhagic shock rats. Methods With traumatic hemor-rhagic shock rats and hypoxia-treated vascular smooth muscle cells ( VSMCs) ,the role of Rho-kinase and PKC in CsA-regulating vascular re-activity following shock and their relationship to MPTP was observed. Meanwhile,the effects of CsA on inflammatory mediators including TNF-α, IL-1β and IL-6 were also studied. Results CsA significantly improved the vascular reactivity of superior mesenteric artery following hemor-rhagic shock. Rho-kinase inhibitor Y27632 significantly antagonized CsA-induced increase of vascular reactivity,while PKC inhibitor stauros-porine had no significant influences on the effects of CsA. Further studies showed that CsA and Rho-kinase agonist U46619 inhibited the o-pening of MPTP in hypoxia-treated VSMCs. In addition,shock induced a significant increase of TNF-αand IL-1β,but CsA did not show a sig-nificant inhibitory effect on their level. Conclusion CsA-induced restoration of vascular reactivity following traumatic hemorrhagic shock via inhibiting MPTP opening,and Rho-kinase participate in this process.

Objective To determine whether the supplementation of thyroid hormone(TH)improves β-adrenoceptors(β-AR)density and expression of peripheral blood lymphocyte in elderly patients with chronic heart failure(CHF). Methods A total of 42 elderly patients with advanced CHF(NYHA classⅢorⅣ)due to dilated cardiomyopathy(DCM)or ischemic cardiomyopathy (ICM)were randomly divided into a treatment group and a control group.Low-dose L-thyroxine(LT50)was added to the treatment group,both groups had routine anti-heart-failure treatment.Before and after 1 month of treatment,125I-Pindolol radioligand binding assay was used to measure β-AR in peripheral lymphocytes.Reverse-transcriptase polymerase chain reaction(RT-PCR)was used to measure β1-AR expression in peripheral lymphocytes. Results The density and expression of β-AR of lymphocytes in patients with CHF due to ICM or DCM were lower than those in normal health people.and the serum TH level in patients with CHF was lower than that in normal health people.The L-T4 administration induced an up-regulation of β-AR density and expression in peripheral lymphocytes. Conclusions Thyroxine administration induces an up-regulation of β-AR density and expression in peripharal lymphocytes.

Objective:To explore the clinical efficacy, especially the comprehensive improvement of blood glucose and lipid of probucol and metformin in the treatment of type 2 diabetes mellitus with hyperlipidemia. Methods:Totally 105 patients with type 2 di-abetes mellitus complicated with hyperlipidemia were randomly divided into the control group1 (35 cases), the control group 2 (34 ca-ses) and the observation group (36 cases). The control group 1 was treated with diet control, exercise and metformin, the control group 2 was treated with rosuvastatin calclum tablets based on the group 1, and the observation group was treated with probucol based on the group 1. The three groups were continuously treated for 12 weeks. The improvement of the fasting blood-glucose (FPG), 2h postprandial blood glucose (PBG), hemoglobin A1C (HbA1C), fasting insulin levels (Fins), insulin resistance indices (HOMA-IR) and TC, TG and HDL-C, and the adverse reactions among the three groups were compared. Results:The total effective rate in the ob-servation group was higher than that in the control group 1 and 2 (P<0. 05). After the treatment, all the indices of blood glucose and lipid in the three groups were significantly improved (P<0. 05), and those of blood glucose in the observation were better than those in the control group 1 and 2(P<0. 05), those of blood lipid in the observation group and the control group 2 were better than those in the control group 1 (P<0. 05), and the level of HDL-C in the observation group was much higher than that in the control group 2 (P<0. 05). The adverse drug reactions in the three groups were mild without statistical significance (P>0. 05). Conclusion:Probucol as one of lipid-lowing drugs with antioxidant action combined with metformin can improve blood lipid and lower blood glucose at the same time, which is worthy of promoted application in clinics.

Objective To study the changes of sodium currents(I_(Na))of ventricular cells in rats after acute pancreatitis.Methods Rats'models of acute panereatitis were produced by injecting sodium taurocholate into the pancreatic duet.After 24 hours,single ventrieular cells was isolated enzymatieally,and I_(Na),were recorded by using patch clamp techniques.Results I_(Na) peak from ventricular cells in the acute panereatitis group was significantly reduced(- 6.80?2.03)pA/pF compared with that in control group(-13.55?5.33)pA/pF,P＜0.001.The steady-state inactivation curve was shifted to upward direction,the half-maximal voltage dependence of inactivation(V_(0.5))was(-121?26)mV in ventrieular cells from panereatitis group and(-105?21)mV form the control group.I_(Na) returned to normal more slowly in ventrieular cells from panereatitis group than that from control group.Conclusion Inhibitation of I_(Na) was found in ventrieular cells,which might cause arrhythmias in rats with acute pancreatitis.

Aim To study the effects of telmisartan upon serum calcineurin.Methods 92 male SD rats with the same age were randomly divided into control group (N), sham operation group (S), 2K1C+distilled water group (K) and 2K1C+telmisartan group (T).S rats were performed the open-abdomen surgery without being restricted any renal artery, but the K and the T rats were restricted their left renal artery. Beginning from the third week after the surgery, the K rats started to be treated with the intragastric infusion of distilled water 10 ml·(kg·d)~(-1) , while the T rats with telmisartan 10 mg·(kg·d)~(-1) .And after being treated for 2, 4 and 8 weeks, rats were respectively measured the systolic blood pressure (SBP), the diastolic blood pressure (DBP) of the abdominal aorta. Before and after the operation, ultrasonography with probe of 7.5 MHz was used to obtain the structure and functional indexes, such as IVSd, IVSs, LVPWd, and serum calcineurin were evaluated by ELISA and colorimetric assay kit.Result Compared with the S group and the N group, ① the results of blood pressure (SBP, DBP) were significantly higher in K group (all P <0.01), after use of telmisartan, blood pressure was significantly reduced(P <0.01);② the thickness of interventricular septal and left ventricular posterior wall at the end of diastolic and systolic were significantly higher in K group (all P <0.01), after use of telmisartan, the thickness of those declined(all P <0.01);③ the level and activity of serum calcineurin were significantly higher in K group (all P <0.01), after use of telmisartan, the level and activity of calcineurin significantly fell(P <0.01).Conclusion The serum calcineurin of artery was also raised in the left ventricular remodeling. Telmisartan ameliorates ventricular remodeling effectively, which may be associated with decreasing the expression of artery serum calcineurin.

Objective To explore the expressions and clinical significance of epidermal growth factor receptor (EGFR),COOH-terminus tensin-like molecule (CTEN)and epithelial cadherin (E-cad)in non-small cell lung cancer (NSCLC).Methods The expressions of EGFR,CTEN and E-cad in 36 cases of normal lung tissue and 82 cases of NSCLC tissues were observed with immunohistochemical SP method and their correlation with NSCLC invasion,metastasis and prognosis was analyzed.Results The positive rate of EGFR,CTEN and E-cad was 58.5% (48/82),69.5% (57/82)and 28.1% (23/82)in 82 cases of lung cancer,while 13.9% (5/36),0.0% (0/36)and 100% (36/36)in normal tissues;the differences were all significant (P<0.05).EGFR,CTEN and E-cad expressions in NSCLC tissues were significantly correlated with tumor differentiation,TNM stage and lymph node metastasis (P<0 .0 5 ).The expressions of EGFR and CTEN were correlated with each other in NSCLC (r=0 .5 3 0 , P<0.001),while the expressions of EGFR and CTEN were correlated with that of E-cad (r=0.499,P<0.001;r=0.333,P=0.001 ).Multivariate Cox regression analysis showed that CTEN expression in NSCLC was an independent prognostic factor (P<0.05 ).Conclusion EGFR,CTEN and E-cad may play a role in the development,invasion and metastasis of NSCLC and have some significance in predicting the prognosis of NSCLC.

BACKGROUND:The measure and prediction of the shape of optic nerve head are the key issues for early diagnosis and duration prediction of glaucoma. Therefore, it is significant to research the shape variation of optic nerve head under high intraocular pressure.
OBJECTIVE:To establish three-dimensional finite element model of optic nerve head and to analyze the deformation of optic nerve head and the change in retina thickness after acute high intraocular pressure.
METHODS:Animal model of acute ocular hypertension was established by methods of anterior chamber perfusion. The tomographic images of the optic nerve head of a cat were obtained at the normal intraocular pressure and 5 320 Pa, 7 980 Pa, 10 640 Pa, 13 300 Pa, 15 960 Pa intraocular pressures using optical coherence tomography. Then, we measured the variation of retinal thickness at typical location. Basing on the tomographic images of optic nerve head of a cat at normal intraocular pressure, we obtained three-dimensional structure of retina and choroid using software MIMICS. Then three-dimensional model of optic nerve head was established by assembling the retina and choroid. The deformation of optic nerve head and the change in retinal thickness under high intraocular pressure were observed using software ABAQUS. The effectiveness of the model was verified by the experimental result.
RESULTS AND CONCLUSION:With the increase of intraocular pressure, the retinal thickness is thinner, the optic nerve head depth, width and the ratio of the depth to width are gradual y increased. It suggests that the acute high intraocular pressure causes retinal thinning, optic nerve head widening and deepening. It is feasible to establish optic nerve head modeling in vivo by using optical coherence tomography, mechanical analysis can be applied to predict the shape variation of optic nerve head, which is significant to further deduce the pathological process of glaucoma.

Objective To explore the application of serum SELDI proteomic patterns to screen breast cancer biomarkers.Methods Serum protein profiles of 110 breast cancer patients and 100 healthy controls were analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOFMS).The spectra were generated on weak cation exchange (WCX2) chips and protein peaks clustering and classification analyses were made using Biomaker Wizard software.Differences in protein intensity between breast cancer cases and controls were measured with the Mann-Whitney U test and adjusted for confounding in a multivariate logistic regression model.Results Forty-nine of these proteins were found to have statistically differential expression levels between breast cancer and normal control sera (P ＜ 0.05).Based on literatures reported,six protein biomarkers,with mass-to-charge ratio (M/Z) (4376,8126,8924,3264,3968,and 9180) were selected.Proteins with M/Z 4376,4126,and 8924 were statistically significantly decreased in breast cancer cases compared to those in healthy controls (P ＜ 0.05).Proteins with M/Z 3264,3968,and 9180 were significantly increased in breast cancer cases compared to those in healthy controls,Protein with M/Z 9180 was associated with TNM stage and Her-2 expression in breast cancer (P ＜ 0.05).Protein with M/Z 8926 was related with lymph node metastasis (P ＜0.05).Conclusion These results suggest that serum SELDI protein profiling can distinguish breast cancer patients from normal subjects with relatively high sensitivity and specificity.SELDI-TOF-MS plays a valuable role in the diagnosis of breast cancer and the discovery of new tumor-specific protein biomarkers.