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Hypothyroidism alone can lead to myocardial fibrosis and result in heart failure, but traditional hormone replacement therapy does not improve the fibrotic situation. Hydrogen sulfide (H 2 S), a new gas signaling molecule, possesses antiinflammatory, antioxidant, and anti-fibrotic capabilities. Whether H 2 S could improve hypothyroidism-induced myocardial fibrosis are not yet studied. In our study, H 2 S could decrease collagen deposition in the myocardial tissue of rats caused by hypothyroidism. Furthermore, in hypothyroidism-induced rats, we found that H 2 S could enhance cystathionine-gamma-lyase (CSE), not cystathionine β-synthase (CBS), protein expressions. Finally, we noticed that H 2 S could elevate autophagy levels and inhibit the transforming growth factor-β1 (TGF-β1) signal transduction pathway. In conclusion, our experiments not only suggest that H 2 S could alleviate hypothyroidism-induced myocardial fibrosis by activating autophagy and suppressing TGF-β1/ SMAD family member 2 (Smad 2) signal transduction pathway, but also show that it can be used as a complementary treatment to conventional hormone therapy.
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Objective:To explore the effects of BCR-ABL downstream pathway inhibitors, such as RAF inhibitor SB590885, JAK inhibitor AZD1480, PI3K-mTOR double target inhibitor BEZ235 on chronic myelogenous leukemia (CML) cells, and the effect of BEZ235 on the proliferation, apoptosis of CML cells and the sensitivity of imatinib in vitro.Methods:K562 cells were treated with different concentrations of the drugs. MTS method was applied to detect the proliferation inhibition rate of K562 cells, and 50% inhibitory concentration (IC 50) of all drugs for 48 h was calculated. The cell apoptosis rate was tested by using flow cytometry with Annexin V-FITC/PI double staining. The cell cycle was tested by using flow cytometry with PI staining. K562 cells, imatinib-resistant and T315I-mutant human CML KBM7R cells and imatinib-resistant CML primary cells of patients were treated with different concentrations of the drugs. MTS method was used to test the proliferation inhibition of cells, and IC 50 of all drugs for 48 h was evaluated. KBM7R cells or primary cells of CML patients were treated with 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib or the combination of both, respectively. Flow cytometry with PI staining was used to detect the cell cycle of KBM7R cells. Flow cytometry with Annexin V-FITC/PI double staining was used to detect the cell apoptosis rate in CML primary cells. The expressions of p-AKT, cleaved Caspase-3 and Cyclin D1 proteins were detected by using Western blot. Results:SB590885, AZD1480 and BEZ235 could inhibit the proliferation of K562 cells, and the IC 50 after the treatment of K562 cells for 48 h was (11.49±3.14), (4.83±1.26) and (0.37±0.21) μmol/L, respectively. SB590885, AZD1480 and BEZ235 could promote the apoptosis of K562 cells. The cell apoptosis rates were increased compared with the control group without drug treatment (all P < 0.01). SB590885 and BEZ235 induced G 0/G 1 block (both P < 0.05). AZD1480 induced G 2/M block ( P < 0.05). BEZ235 could inhibit the proliferation of K562 cells, KBM7R cells and CML primary cells, and their IC 50 for 48 h was (0.37±0.21), (0.43±0.27) and (0.49±0.24) μmol/L, respectively. Compared with imatinib alone, the different concentrations of imatinib combined with 0.2 μmol/L BEZ235 could increase the proliferation inhibition of K562 cells, KBM7R cells and CML primary cells, and could reduce the IC 50 of imatinib. After the treatment of imatinib alone and combination with BEZ235 for 48 h, the imatinib IC 50 of K562 cells was (0.14±0.05) and (0.09± 0.04) μmol/L ( t = 1.531, P = 0.249), the imatinib IC 50 of KBM7R cells was (3.93±2.29) and (0.44±0.22) μmol/L ( t = 2.837, P = 0.047), the imatinib IC 50 of the primary cells was (3.12±1.53) and (0.39±0.23) μmol/L ( t = 3.925, P = 0.042). The cell apoptotic rate of the primary cells was (4.9±1.4)%, (13.1±3.2)%, (8.8±2.0)% and (40.6±6.0)%, respectively in the control group without drug treatment, 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib and the combination of 1.0 μmol/L BEZ235 and 1.0 μmol/L imatinib after the treatment of 24 h ( F = 71.031, P < 0.01). Compared with imatinib alone, the expressions of p-AKT and Cyclin D1 proteins were decreased, and the expression of cleaved Caspase-3 protein was increased after the treatment of KBM7R cells for 12 h in the combination group of both BEZ235 and imatinib. Conclusions:BCR-ABL downstream pathway inhibitors can effectively inhibit the proliferation and promote the apoptosis of K562 cells. BEZ235 can inhibit the proliferation and promote the apoptosis of K562 cells, imatinib-resistant and T315I-mutant human KBM7R cells and imatinib-resistant CML primary cells of patients, which has a synergistic effect to imatinib.
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Objective To study the morphology and characteristics of the popliteal tibial nerve and measure relevant structural parameters of the peroneal nerve passing round the fibular head and neck by 3D(three-dimensional)MR advantage sequences,and provide valuable image information for basic research and clinical work.Methods Thirty-six left knee joints of healthy volunteers were scanned using 3D MR sequences,including 3D-FS-CUBE,3D-FS-SPGR.The anatomical features in MR imaging were observed by two doctors.The different level axis section areas of the popliteal tibial nerve were measured by reconstructed 3D MR advantage sequences.The coronal/sagittal diameters and the angle of the fibular head and neck(peroneal tunnel)were also measured and compared.SPSS 19.0 software was used for further statistical analysis.Results Optimum visual rates of the knee nerve of 3D-FS-CUBE,3D-FS-SPGR sequences were 25%,89%(P<0.01).Axial section of the tibial nerve of the popliteal space was as following:top level(Tn1,tibial nerve)(19.3 ± 1.02)mm2,midpoint level(Tn2)(23.6 ± 2.24)mm2,supracondylar level(Tn3)(29.1 ± 3.39)mm2.Coronal and sagittal diameters of the fibular head were(19.8 ± 2.95)mm,(19.7 ± 4.2)mm,and coronal and sagittal diameters of the fibular neck were(12.7 ± 3.1)mm, (13.6 ± 2.5)mm,respectively.The angle between the head and neck was 164°± 6.5°.Conclusion 3D-FS-SPGR sequence is the advantage sequence for displaying the knee nerves.The diameters of the popliteal tibial nerves gradually thicken from Tn 1 to Tn3.The structural measurements of the fibula head and neck have certain significance for fundamental research or prevention and treatment of common peroneal nerve entrapment.
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Objective To explore the application value of 3.0T MR diffusion tensor imaging (DTI)in 3D reconstruction of the knee peripheral nerve.Methods DTI with 25 motion probing gradients (MPGs)was performed on the left knee in 22 healthy young volunteers;By choosing the original images scaned in the vertical direction,three post-processing methods including maximum intensity proj ection (MIP),volume rendering (VR)and diffusion tensor tractography (DTT)were used.Two radiologists evaluated these images visually.For the same nerve,MIP,VR and DTT were compared using Friedman test.Intraclass correlation coefficient (ICC )analysis was used to compare the correlation among the three imaging methods.Score consistency between two observers was calculated by using the Kappa statistic.Results For the same nerve,there was no significant statistical difference for the MIP,VR and DTT imaging quality scores(P>0.05).The I CC value and the k value were 0.718-0.856,0.668-0.705,respectively.Conclusion Stereoscopic and clear displaying the tibial nerve/the common peroneal nerve in the knee can be achieved by using MIP,VR and DTT post-processing methods based on DTI original images.The reconstruction of MIP,VR is simple and efficient,in which the objectivity is better than DTT.The reconstruction of MIP,VR can be used as effective preview methods before the DTT reconstruction with complexity and strong subjective dependence.
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Objective:To observe the effects of Shexiang Baoxin Pill (SBP) on isoprenaline (Iso)-induced changes in myocardial cell volume,shape,and connexin 43 (Cx43) expression.Methods:HgC2 myocardial cells were randomly divided into a control group,a Iso group and a Iso+SBP group.After 72 h of culture,the average surface area of HgC2 cells was measured under phase contrast microscope.Bicinchoninic acid (BCA) protein assay was carried out to determine the concentration of proteins.The survival rate of myocardial cells was measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay,and the Cx43 expression was detected by Western blot.Results:The mean surface area and Cx43 concentration in Iso-treated myocardial cells were increased under the phase contrast microscope (P<0.05).Compared with the Iso group,the mean surface area was decreased,and the Cx43 concentration was reduced in the Iso+SBP group (both P<0.05).Compared with the control group,the Cx43 expression was obviously down-regulated in the H9C2 cells of the Iso group (P<0.05);while compared with the Iso group,the Cx43 expression was obviously up-regulated in the Iso+SBP group (P<0.05).Conclusion:Shexiang Baoxin Pills can prevent Iso-induced myocardial hypertrophy and down-regulate Cx43 expression.
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Objective To explore the influnce and related factors analysis postpartum community visit for 6 months old infants exclusive breastfeeding (EBF).Methods 800 women in Daqing city communities delivered in January,2009 to December,2010 were selected into study based on simple random sampling.Using the questionnaire surveyed the influence of the postpartum community visit for 6 months old infants EBF.Results Reclaimed effective questionnaires were 790 ;6 months old infants EBF rate was 65.06％ ;the receiving postpartum community visit group's 6 months of EBF rate 7 4.8 7 ％) was significantly higher than the not receiving postpartum community visit group (38.50％),difference was statistically significant(x2 =90.54,P ＜ 0.01).Logistic regression analysis showed that main related factors of 6 months old infants EBF were the first breast feeding time,whether or not to accept the postpartum visit,mode of delivery and mother's education degree,respectively.Conclusion Postpartum community visit can promote 6 months old infants for EBF,but still need to pay more attention to coordination and improvement.
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Objective To explore the diagnostic value of tibial nerve short-latency somatosensory evoked potential( SLSEP)and F wave in proximal diabetic neuropathy.Methods Excluding stroke,waist cervical vertebra sickness and nerve-muscle diseases caused by other diseases,there were clinical signs of neuropathy but normal nerve conduction EMG(Ⅰ group)32 cases,there weren't clinical signs of neuropathy normal nerve conduction EMG(Ⅱ group)30 cases and abnormal nerve conduction EMG(Ⅲgroup)30 cases.Tibial nerve SLSEP and F wave were measured in 92 patients and 30 normal persons.Results The highest whole abnormality rate of tibial nerve SLSEP's and F wave's all parameters was the sub-group (there were neuropathy symptom lower limbs n=43)of Ⅰ group(97.7% (42/43)).In Ⅰ group Fdur,NI3CV,N24CV, N13-N24CV,N9-N24CV were significantly different from the control group (q value:5.887 and 6.780,-4.568 and-5.062,-6.799 and -6.905,-5.978 and -5.609,-5.433 and -5.190, P＜0.01);The abnormality rate of Fdur and N13-N24CV (25.0%(15/60),23.3% (14/60))in Ⅱgroup were significantly different from the control group (0,1.7%(1/60))also (x2=17.143,12.876, both P=0.0050).In Ⅲ group,except for N9-N24CV,N13 and N24 wave amplitude other parameters'abnormality rates were significantly different from the control group,and the abnormality rate of N9CV was the highest (76.7%(46/60)).Conclusion(1)SLSEP can provide information of proximal sensory nerve segment.(2)SLSEP and F wave can improve the diagnosis rate of proximal diabetic neuropathy,and the diagnostic value is particularly significant to the diabetes patients who have clinical signs of neuropathy but normal nerve conduction EMG.