Objective To investigate the angiographic coronary atheroslerosis findings with the plasma levels of von Willebrand factor (vWF) and ?-granule membrane protein (GMP-140). Methods 74 patients undergone selectrive coronary angiography (CAG) were divided into 3 groups based on plaque morphology, Group S(n=15), concentric or eccentric stenosis with smooth borders; Group C(n=37), eccentric stenosis with complex borders; Group N (n=22), CAG without coronary atheroslerosis. 37 patients in group C were divided into group Ⅰ (n=10, one-vessel involved CAD), group Ⅱ (n=12, two-vessel involved CAD) and group Ⅲ (n=15, three-vessel involved CAD) based on major epicardial coronary branches lesion. These 37 patients were divided into group x(n=21, ≤3 segments) and group y(n=16,≥4 segments) based on coronry stenotic segments. The plasma levels of vWF and GMP-140 were assayed by ELISA before angiography. Results (1)The plasma levels of vWF and GMP-140 in group C were significantly higher than those in group S(P

Objective To investigate the relation between microembolic signals (MES) and vertebral basilar artery ste?nosis in patients with brainstem infarction. Methods A total of 156 patients with acute brainstem infarction, who were de?termined the cerebral infarction lesion and vertebral basilar artery stenosis by cranial magnetic resonance imaging and CT an?giography, and were monitored by transcranial Doppler via occipital window of basilar arterial MES monitoring in 7 days of the onset, were divided into microembolus signal negative group (n=136) and positive group (n=20). The clinical data were compared between two groups. The differences of different degrees of stenosis were analyzed in two groups. The differences of different locations of stenosis in patients with vertebral basilar artery stenosis were analyzed in two groups. Logistic regres?sion analysis was used to analyse the factors affecting MES. Results There were no significant differences in age, gender, history of hypertension and diabetes mellitus between the two groups (P<0.05). There were significant differences in the dif?ferent degrees of stenosis between two groups, no or mild stenosis was found in MES-negative group and severe stenosis in MES-positive group (P<0.05). There were 70 cases with no vertebral basilar artery stenosis, 86 cases with mild, moderate and severe stenosis, in which 14 cases were MES-positive and 72 cases were negative. There were significant differences in different locations of stenosis between the two groups. The proportion of multiple infarctions was significantly higher in MES-positive group than that of MES-negative group (P<0.05). The intracranial vertebral basilar artery stenosis and 75%of ver?tebral basilar artery stenosis were the independent risk factors of MES-positive. Conclusion Severe stenosis of the verte?bral basilar artery is more vulnerable to occur MES of posterior circulation, leading to cerebral infarction. Microemboli may be the cause of multiple infarctions in patients with vertebral basilar artery stenosis.

Poly(β-amino esters) (PBAE) are used for drug carrier and have many advantages, such as pH-sensitivity, low toxicity, structural diversity and the synthetic method of PBAE is easy. Therefore they are possessed broad application prospect in tumor-targeted drugs delivery systems. In this paper, the structural features and target drugs delivery property of PBAE are reviewed. The application forms of PBAE and different anti-cancer drugs loaded in the copolymer for tumor-targeted drugs delivery systems are introduced particularly.

Objective To measure the parameters of mitral valve leaflets and mitral annulus in patientswithmildmitralregurgitation( MR )byreal timethree-dimensionaltransesophagealechocardiography (RT-3D-TEE),and explored the mechanism of MR.MethodsFifty-seven MR subjects were selected and twenty-eight subjects without mitral regurgitation were served as control group,all subjects were examined by RT-3D-TEE and acquired image,mitral valve quantification (MVQ) software was used for post-processing.Mitral annulus parameters (H/DAIPm,E2D,θAv-Mv,mitral annulus θnpa) and mitral valve leaflets parameters(A3DE,L2DAIPm,VA1-3tentVp1-3tentVtentHtentθnpa ) at the end of systolic were measured.The results of two groups were compared,and the most affected parameters to mild mitralregurgitation were selected.Results Compared with control group,VA3tent was decreased,mitral annulus θnpa and L2DAIPm increased,and the mitral valve leaflets θnpa was independently correlation factor of mild mitral regurgitation.ConclusionsThe mitral annulus geometry to flat in subjects with mild MR,the mitral valve local area is increased in subjects with mild MR,the mitral valve leaflets θnpa is independently correlation factor of mild mitral regurgitation.

Objective To investigate the effects of MG132 on diabetic nephropathy (DN) rats induced with streptozocin. Methods Seventy-two male SD rats were randomly divided into three groups: normal control group (NC, n=24), DN group (n=24) and DN treated with MG132 group (DN+MG132, n=24). At the end of 4, 8 and 12 weeks, 24 hour urinary protein excretion rate (UPER) was detected. Morphology of kidney was examined by special staining of periodic acid-schiff (PAS). Renal 26S proteasome activity was determined by quantifying the hydrolysis of S-LLVY-AMC in a fluorescence reader. Urinary malondialdehyde (MDA) level and renal SOD and GSH-PX activity were detected by commercial kits. Renal SOD, GSH-PX and p47phox mRNA expressions were determined by real-time fluorescence PCR. Renal p47phox protein expression wasdetermined by Western blotting. Results Compared with NC group, the DN group showed a significant increased of UPER at week 4, 8, 12 (all P<0.05), of mesangium proliferation and mesangial matrix expansion at week 12. In DN+MG132 group, UPER was significantly decreased compared with DN group at the end of 4, 8 and 12 weeks (P<0.05, respectively), and the glomeruler pathological alteration induced by diabetes was attenuated. Increased renal 26S proteasome activity in DN rats was significantly inhibited after MC132 administration (P<0.05). Moreover, renal p47phox mRNA expression in DN group was 155%, 149% and 120% more than those in NC group at 3 time points (all P<0.05), and so was the renal p47phox protein expression, 139%, 152% and 186% more (all P<0.05). Urinary MDA levels in DN group were 1.95-, 2.04-and 2.62-folds more than those in NC group (all P<0.05). In addition, compared with NC group at 3 time points, in DN group, renal SOD activity was decreased by 23.09%, 33.59% and 53.31% (all P<0.05); renal GSH-PX activity was decreased by 28.57%, 33.06% and 48.76% (all P< 0.05); renal SOD mRNA was decreased by 38.09%, 61.44% and 76.53% (all P<0.05); renal GSH-PX mRNA group was decreased by 29.16%, 37.26% and 62.40% (all P<0.05). Compared with DN group, renal p47phox mRNA and protein expression, and urinary MDA levels were significantly lower in DN+MG132 group (all P<0.05); renal SOD and GSH-PX activity as well as mRNA expression were significantly increased in DN+MG132 group (all P<0.05). Conclusions MG132 treatment can provide renoprotection for DN rats effectively maybe through enhancing renal anti-oxidative ability.

AIM: To study the cytoprotective role of NaNO_2 preconditioning against H_2O_2 induced damage in PC12 cells. METHODS: PC12 cells were treated with different concentrations of NaNO_2 for 6 h, 12 h, 24 h and 48 h, respectively. The viability of the cells was measured by MTT method and cell counting. The apoptotic rate of PC12 was determined by Hoechst 33258 staining to calculate the ratio of the cells between concentrated and broken nucleus in the total cell count. PC12 cells were pretreated with NaNO_2 at concentration of 3 mmol/L for 24 h. The cytoprotective role to the toxicity of H_2O_2 at concentration of 1.1 mmol/L for 6 h was observed by MTT. The cell apoptosis was measured by flow cytometry and staining with Hoechst 33258 and PI. The activities of catalase (CAT), superoxide dismutase (SOD), and the changes of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured by the method of colorimetry. RESULTS: The dose-response results showed that the effect of NaNO_2 on PC12 cell proliferation was a typical β-shape curve. The maximal stimulatory response was at 24 h, and the concentration of the maximum stimulatory response was 1.4 mmol/L. The maximal stimulation of the concentration-responses was 156% above the control. No observable adverse effect level (NOAEL) was 6 mmol/L. IC_(50) was 45 mmol/L. When the cells were pretreated by NaNO_2 at concentration of 3 mmol/L for 24 h, and then exposed to H_2O_2 at concentration of 1.1 mmol/L for 6 h, the proliferation rate was increased as compared to the cells treated with H_2O_2 alone. Under the conditions of treating the cells with NaNO_2 at concentration of 3 mmol/L to induce the adaptive response, then exposing the cells to H_2O_2 at concentration of 1.1 mmol/L, the apoptosis rate in non-preconditioning group was 44.9%, the apoptosis rate in preconditioning group was 19.1%, the difference was significant (P<0.05). The cytoprotective effect of NaNO_2 was inhibited by nitric oxide (NO) scavenger ferrohemoglobin. The activities of SOD, CAT and the level of GSH-Px were markedly increased, the content of MDA decreased in preconditioning group. CONCLUSION: Exposure of NaNO_2 at concentration of <6 mmol/L induces hormesis on PC12 cells. Low dose of nitrite plays an important role in cytoprotection by reducing nitrite to NO, indicating that decrease in lipid peroxidation and increase in endogenous antioxidants may play a key role in cytoprotection induced by preconditioning with low dose of NaNO_2 in PC12 cells.

ObjectiveTo investigate the effects of 1-3-n-Butylphthalide on the blood-brain barrier (BBB) following whole brain irradiation in rats.Methods144 male Sprague Dawley rats were randomly divided into sham-irradiation group,irradiation group,1-3-n-Butylphthalide group,and irradiation plus 1-3-n-Butylphthalide group.Whole-brain irradiation was given as a single-dose of 10 Gy using 4 MV X-ray.The rats were injected intraperitoneally with 1-3-n-Butylphthalide at 0.3 mg/kg,1.0 mg/kg,3.0 mg/kg once per day.The changes of the BBB were assessed by Evans blue (EB) assay.The expression of vascular endothelial growth factor (VEGF) in the brain tissue was determined by immunohistochemistry. The circulating endothelial cells (CECs) isolated from right ventricular blood were counted.MRI was evaluated with the T1-weighted images,T2-weighted images and MRI enhancement images induced by Gd-DTPA.The data were compared among the groups through Student-Newman-Keuls test.ResultsCompared with the sham-irradiation group,the EB content,the expression of VEGF in the brain tissue and the CECs were significantly increased in the irradiation group (2.81∶ 7.82,P =0.002;5.83∶ 10.26,P=0.003;3.16∶6.14,P =0.002).The signal intensity of T1-weighted images was significantly decreased while T2-weighted images and the enhancement rate significantly increased in the irradiation group (P =0.004 -0.018 ).Compared with irradiation group,the EB content,the expression of VEGF and the CECs were decreased significantly in the irradiation plus 1-3-n-Butylphthalide group ( 7.80∶ 3.86,P =0.007 ; 10.83 ∶ 5.26,P =0.008 ;6.36∶ 3.64,P =0.009 ).However,the changes in the MRI were significantly attenuated ( P =0.008-0.026,and 0.006 -0.038,respectively).Conclusions Following whole brain irradiation,1-3-n-Butylphthalide can decrease the permeability of the BBB in rats via decreasing VEGF expression and decreasing the CECs.

Objective To investigate the protective effect and its mechanism of DL-3-n-Butylphthalide on the brain damage in rats following whole brain irradiation.Methods A total of 120 male Sprague Dawley rats were randomly divided into sham-irradiation group,irradiatien group and DL-3-n-Butylphthalide group.The model of whole-brain irradiatien was established by exposuring rat brain to 4 MeV X-rays with a single-dose of 10 Gy.The rats were intraperitoneally injected with DL-3-n-Butylphthalide at the dosages of 0.3,1.0,and 3.0 mg/kg once a day.The contents of malondialdchyde and super oxide dismutase activity were measured,while the expressions of apoptosis-associated genes and the ultrastructural changes in hippocampus were examined by immunohistnchemisty staining and electron microscope,respectively.Results After irradiation,the content of malondialdehyde and the expression of apoptosis gene bax in rat brain tissue increased while the activity of super oxide dismutase(SOD) and the expression of anti-apoptosis gene bcl-2 decreased.Apoptosis was also observed in the neurons of hippocampus CA1.Compared with irradiation group,the content of malondialdehyde and the expression of bax gene in the DL-3-n-Butylphthalide group wen significantly reduced ( t =-3.89--1.96,2.72-3.48,P ＜ 0.05 ),while the activity of SOD and bcl-2 gene were significantly elevated ( t =2.94-3.76,-3.18--2.08,P ＜ 0.05),and the injury degree of neuron structure in the DL-3-n-Butylphthalide group was slighter than that in the irradiation group.Conclusions DL-3-n-Butylphthalide executes protective effects in a dose-dependent manner againest the radiation injury in rats brain by reducing the induction of malondialdehyde,raising the activity of SOD and inhibiting the generation of apoptosis.

Objective To investigate the effect and significance of regulating endoplasmic reticulum stress on the expression of histone methyltransferases SET7/9 in the kidneys of db/db mice.Methods Db/db mice were randomly divided into two groups according to random number table method:diabetic nephropathy model group (DN group,n=18) and betaine treatment group (DN+B group,n =18),db/m mice were defined as normal control group (NC group,n =18).At the end of 4,8 and 12 weeks,the expression of GRP78,SET7/9,H3K4me2,and monocyte chemoattractant protein 1 (MCP-1) was determined by real-time fluorescence PCR and Western blotting.24-hour urinary protein excretion rate (UPER) and urine MCP-1 were measured by enzyme linked immunosorbent assay (ELISA).The dynamic changes of blood glucose(BG),serum creatinine (Scr),blood urea nitrogen (BUN) were tested by completely automatic biochemistry analyzer.The morphology of kidney was estimated by special staining of periodic acid-schiff (PAS).Results The levels of BG,BUN,UAER and MCP-1 were significantly higher in DN group than those in NC group (P ＜ 0.05),and were in time-dependent manner.Glomerular basement membrane thickening and mesangial cells proliferation began to emerge in DN group at the end of week 4 and mesangial matrix expansion was more obvious at the end of week 12.The mRNA and protein expression of GRP78 and SET7/9 were elevated significantly in DN group as compared to NC group.The H3K4me2 protein expression level was also increased in time-dependent manner.Compared with the DN group,in DN+B group glomerular lesions attenuated and the GRP78 and SET7/9 expression levels obviously decreased (P ＜ 0.05).Furthermore,the levels of BG,BUN,UPER,MCP-1,H3K4me2 in DN+B group were also reduced (P ＜ 0.05).Conclusion Endoplasmic reticulum stress may be the upstream mechanism of mediating the expression of SET7/9 in the kidneys of DN mice.

Objective To suppress the proliferation of lens epithelial cells (LECs) is a primary goal in prevention of after cataract. Recent study demonstrated an effective inhibition of elemene(Ele) on tumor cells. Present study was to investigate the effects of Ele on proliferation and cell cycle of human LECs B3 (HLE-B3). Methods Recombinant human basic fibroblast growth factor(rhbFGF) was utilized to induce proliferation of HLE-B3. Proliferative HLE-B3 was incubated with 80 mg/L Ele in CO_2 incubator for 24 hours. Then the inhibitory effects of Ele on proliferation of HLE-B3 was evaluated by methyl thiazolyl tetrazolium(MTT). The effect of Ele on HLE-B3 morphology was observed under the optical microscope. The effect of Ele on HLE-B3 cell cycle was analyzed by flow cytometer(FCM). Results MTT test showed that the optical density (OD) value of rhbFGF group was remarkably higher than that of control group(0. 599 0 ± 0. 053 1 versus 0. 409 1 ± 0. 042 2) (P ＜ 0. 01), and that of Ele group(0. 450 0 ±0. 061 4) was obviously declined in comparison to rhbFGF group(P ＜0. 01) . The inhibitory rate of Ele was 24.90 %. In proliferation group, the number of HLE-B3 was increased with the normal cell structure and abundant cytoplasm under the optical microscope. However, in Ele group, the number of HLE-B3 was evidently decreased with less cytoplasm, undistinguished cell structure, condensed and aggregated nucleuses. The result of flow cytometer showed that the percentage of HLE-B3 in G_1 phase in rhbFGF group was 42. 062% ± 1. 270% and that in control group was 46. 422% ±3. 765% with a significant difference(P ＜ 0. 05). HLE-B3 in G_1 phase in Ele group (60. 665% ±2.069%) was evidently increased in comparison with rhbFGF group (P ＜ 0. 01). HLE-B3 in S phase in rhbFGF group compared with control group was increased (51.647% ±1.123% versus 31.842% ± 2. 798%) (P ＜ 0. 01), but that in S phase in Ele group(30. 222% ±3.429%) was lower than rhbFGF group (P ＜ 0. 01). HLE-B3 in G_2 phase in rhbFGF group was decreased in comparison with control group (6. 288% ± 0. 966% versus 21. 735% ± 3. 806%, P ＜ 0. 01), and that in G_2 phase in Ele group (9. 112% ± 1. 659%) compared with proliferation group was increased (P ＜ 0. 01). Conclusion Ele could alter the cell cycle of HLE-B3 and effectively inhibit the HLE-B3 proliferation induced by rhbFGF. Ele may be a reliable and effective drug for prevention and treatment of after cataract.