AIM To study the effects of strophanthidin (Str) on cardiac function and Na +,K +-ATPase activity in isolated guinea pig heart failure model. METHODS Langendorff isolated heart failure models made by perfusing heart with K-H solution containing sodium pentobarbital. Eight-channel physiological recording instrument was used to determine cardiac function. Colorimetry method was used to determine cardiac sarcolemmal Na +,K +-ATPase activity. RESULTS Str increased the heart rate, left ventricular systolic pressure and the maximum rise or decline rate of left ventricular pressure in a concentration-dependent manner at 1?10 -9～1?10 -7 mol?L -1. But Str caused first a rise, then a reduction of contractility and arrhythmia accompanied by inhibition of Na +,K +-ATPase when the concentration of Str was higher than 1?10 -6 mol?L -1. Str had no obvious effect on Na +,K +-ATPase activity at 1?10 -7 mol?L -1, but increased cardiac activity at 1?10 -10～1?10 -8 mol?L -1. CONCLUSION The inotropic effect and heart toxicity of Str at higher concentration is due to inhibition of Na +,K +-ATPase, but the inotropic effect of Str at lower concentration is not the result of inhibition of Na +,K +-ATPase activity.

Objective:To investigate the efficacy and safety of three-dimensional navigation template assisted osteotomy for fracture malunion of lateral condyle of humerus in children.Methods:Eighteen children with ma-lunion of fracture of lateral condyle of humerus were treated in Southern Medical University Third Affiliated Hospital from August 2012 to December 2019 and analyzed retrospectively.Among them, 12 cases were treated with routine ope-ration: according to CT reconstruction and empirical osteotomy during the operation, the location of deformity was analyzed.Six cases were treated with navigation template assisted osteotomy: according to the CT data of bilateral elbow joints, a three-dimensional bone model was established, and the coronal and sagittal deformities of the distal humerus were evaluated by comparing the images of the distal humerus of the affected side with the distal humerus of the healthy side, so as to determine the best plane of osteotomy and the target position of reduction.The preoperative simulation was carried out on the computer, and the osteotomy navigation template and reduction navigation template were designed.The navigation template was printed out with a 3D printer.During the operation, the osteotomy was corrected with the assistance of navigation template, and the broken end of osteotomy was fixed with hollow screw and fixed with 80 degree flexion plaster.The X-ray films of the two groups were reexamined regularly after operation.The amount of intraoperative blood loss, operation time, incidence of postoperative complications (necrosis of humeral head and trochlea, delayed ulnar nerve paralysis, and bone nonunion) and the recovery of flexion and the extension function of elbow joint were observed in the 2 groups.Results:The elbow joint activity of all children basically returned to normal, the orthopedic site of osteotomy achieved bony healing, and the orthopedic effects were satisfactory.All the 18 cases were followed up for 6-24 months (mean 15 months). According to the postoperative Dhillon score, the navigation template group was excellent in 1 case and better in 5 cases, while in the routine group, 11 cases were batter and 1 case was fair.There were no significant differences in Dhillon score between the 2 groups after operation ( P>0.05). There were no significant differences in the range of the motion of elbow joint between the 2 groups ( P>0.05). In the comparison of operation time and intraoperative blood loss, the navigation template group [(200.0±24.2) min, (85.0±10.9) mL]was better than the routine group[(232.0±20.1) min, (139.1±18.3) mL](all P<0.001). Conclusions:The application of three-dimensional humerus reconstruction and mirror image contrast to evaluate the distal humerus deformity of the affected side, and the design of osteotomy and reduction navigation template auxiliary operation can restore the normal anatomical structure of elbow joint to the greatest extent.Accurate correction, and the function of elbow joint recover well after operation, which optimizes the operation procedure, improves the safety and effectiveness of the operation.

AIM: To investigate the contribution of angiotensin-converting enzyme inhibitor (ACEI) to the regulation of calpain system in infarcted myocardium. METHODS: Rat myocardial infarction (MI) model was established by permanent ligation of the left coronary artery. The treatment with the ACEI inhibitor rampril (1 mg?kg~-1 ?d~-1 ) was started 7 days prior to surgery. On day 1, 3, 7 and 14 after MI, protein levels of calpainⅠ, Ⅱ and calpastatin were determined in left ventricular free wall (LVFW), interventricular septum (IS) and right ventricule. RESULTS: CalpainⅠprotein level was increased in IS 14 d post MI, whereas the protein level of calpainⅡ was maximally increased in LVFW 3 d post MI. Rampril decreased protein up-regulation of calpainⅠ and Ⅱ, and reduced infarct size and interstitial fibrosis. Calpastatin protein expression was not affected by ACEI. CONCLUSIONS: CalpainⅠ is involved in cardiac remodelling in the late and calpainⅡ contributes to cardiac tissue damage in the early phase of MI. The heart protective effect of ACEI may be related to the inhibition of calpain system in the pathogenesis of myocardial infarction.

Objective To investigate the clinical application of anti-β2 glyeoprotein Ⅰ antibodies (IgG, IgM, IgA)in systemic lupus erythematosus(SLE). Methods The anti-β2-GP Ⅰ antibodies and anti-cardiolipin antibodies(ACL) level were measured by ELISA in 100 SLE patients, 39 other rheumatoid arthri-tis patients and 30 healthy control people. Their clinical application was analyzed in SLE diagnose and thera-py. Results The level of anti-β2-GP Ⅰ (IgG, IgM, IgA)were significantly higher in SLE than that in healthy (P < 0. 01 ). Sensitivity, specificity, positive predictive value and negative predictive value were 17.2%, 95.7%, 85.0% and 44. 6%, respectively. There was a significant and positive correlation be-tween anti-β2-GP Ⅰ antibodies and ACL antibodies ( IgG, IgM, IgA) (r = 0.418, 0. 624, 0.518, 0. 583, P <0.01). In multivariate analysis the factors(anti-β2-GP Ⅰ antibodies, ACL antibodies, dsDAN, u1-RNP, Sm, SSA, SSB, Jo-1, Scl-70, P-protein, PT, APTT) associated with SLE disease activity index(SLEDAI) were anti-β2-GP Ⅰ (IgG) and dsDNA. Conclusion anti-β2-GP Ⅰ antibody has high specificity and positive predict value, also is associated with SLE's thrombosis. It has some values in the clinical application.

Aim To investigate the contribution of cardiac L-and L/T-type Ca~2+ channels in the calpain mediated myocardial damage following myocardial infarction(MI).Methods Rat MI model was established by permanent ligation of the left coronary artery, infarcted rats were orally treated with placebo, amlodipine(L-channel blockade, 4 mg?kg~-1 ?d~-1 ) or mibefradil(L/T-Channel blockade, 10 mg?kg~-1 ?d~-1 ) beginning 7 d before induction of myocardial infarction. Protein levels of u-calpain and m-calpain were measured 1,3,7 and 14 d post coronary occlusion in the noninfarcted and infarcted myocardium.Infarcted size,left ventricular dilation were determined in picrosirius red stained hearts.Results Myocardial infarction induced an up regulation of u-calpain protein and activity in the noninfarcted myocardium(maximum day 14 days post infarction), whereas protein and activity of m-calpain were increased in the infarcted myocardium 3 d post infarction. Amlodipine inhibited protein up-regulation of u-calpain and decreased left ventricular dilation and interventricular septal thickness. Mibefradil attenuated protein up regulation of m-calpain 14 days post infarction, reduced infarct size more obviously.Conclusions Infarction-induced cardiac hypertrophy was accompanied by an up-regulation of u-calpain, whereas m-calpain was up-regulated in the infarcted myocardium in the processing of cardiac infarcted pathogensisi. Cardiac L and L/T-type Ca~2+ channel blockade differentially reduced post infarction remodeling associated with selective inhibition of cardiac u-calpain and m-calpain, respectively.

Aim To investigate the effects of dipfluzine(Dip) on proliferation and collagen synthesis in cultured neonatal rat cardiac fibroblasts(CFB)stimulated by angiotensin Ⅱ(AngⅡ),and to explore the action mechanisms of dipfluzine.Methods CFB were treated with AngⅡ to induce fibrosis model.The effect of Dip on proliferation of CFB was observed by MTT coloricmetric assay;synthesis of collagen was observed by the hydroxyproline concentration detemined;cell cycle distribution and PCNA proein were determined with flow cytometer(FCM);The expression of collagenⅠmRNA,collagen Ⅲ mRNA and TGF-?_1 mRNA was examined using semi-quantitative RT-PCR analysis;The protein expression of cPKC? and ERK_1 in CFB was observed by immunohistochemical staining.Results ① Within a concentration coverage,Dip inhibited CFB proliferation and collagen synthesis(P

This paper is to report the exploration of the activation of Rho/ROCK signal pathway in 5-HT-induced proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and the inhibitory effect of m-Nis on this pathway. PASMCs were cultured with the explant technique. MTT assay was used to explore the proliferation of PASMCs after 5-HT treated for different time and the intervening effect of m-Nis. RT-PCR and Western blot were used respectively to explore the mRNA expression of RhoA, ROCK1 and the protein expression of p-MYPT1 in 5-HT-treated PASMCs and intervening effect of m-Nis. The results of MTT assay suggested that 5-HT (1 µmol · L(-1)) treatment for 12-72 h significantly induced the proliferation of rat PASMCs (P<0.05 or P < 0.01), which were inhibited by m-Nis (1 x 10(-5), 1 x 10(-6), l x 10(-7), 1 x10(-8) mol · L(-1)) in dose-dependent manners (P < 0.05 or P < 0.01). Similarly, the mRNA expression of RhoA, ROCK1 and the protein expression of p-MYPT1 were also inhibited by m-Nis in different degrees (P < 0.05 or P < 0.01). Thus, the results of this study suggested that Rho/ROCK pathway played an important role in 5-HT-induced proliferation of rat PASMCs, m-Nis inhibited 5-HT-induced proliferation obviously, which may be related to the blockage of Rho/ROCK signal pathway.

Objective The purpose of the present study was to investigate the effect of peroxisome proliferator-activated receptors δ（PPAR δ）activation with dietary GW610742X on the expression of tenascin-C in the infarcted and remodeling myocardium.Methods Sixty male Wistar rats were divided into four groups,including control group,sham group,myocardial infarction（MI） group,and MI＋GW610742X（GW）group.The left coronary artery was ligated to establish the MI model.PPAR δ activator GW610742X（100mg/kg/d）was administrated into the rats of GW group.At 3 months after procedure,the expression and distribution of tenascin-C in left ventricular free wall from each group were examined by Western blotting and immunofluorescence,respectively.Results After 3 months following procedure,there were obvious necrosis and fibrosis in left ventricular free wall from MI group.The expression of tenascin-C in MI and GW group was significantly higher than those in control and sham group（P 〈 0.01）.Moreover,tenascin-C expression in GW group was remarkably decreased compared to MI group（P 〈 0.05）.Additionally,tenascin-C expression in sham group was similar to that in control group（P 〉 0.05）.Conclusion The tenascin-C is upregulated in infarcted myocardium during the remodeling process,which can be significantly attenuated by PPAR δ activation.

Effect of strophanthidin (Str) on intracellular calcium concentration ([Ca2+]i) was investigated on isolated ventricular myocytes of guinea pig. Single ventricular myocytes were obtained by enzymatic dissociation technique. Fluorescent signal of [Ca2+]i was detected with confocal microscopy after incubation of cardiomycytes in Tyrode's solution with Fluo3-AM. The result showed that Str increased [Ca2+]i in a concentration-dependent manner. The ventricular myocytes began to round-up into a contracture state once the peak level of [Ca2+]i was achieved in the presence of Str (10 μmol·L-1), but remained no change in the presence of Str (1 and 100 nmol·L-1). Tetrodotoxin (TTX), nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str (1 and 100 nmol·L-1), but had no obvious effects on the action of Str (10 μmol·L-1). The elevation of [Ca2+]i caused by Str at all of the detected concentrations was partially antagonized by rynodine (10 μmol·L-1) or the removal of Ca2+ from Tyrode's solution. In Na+, K+-free Tyrode's solution, the response of cardiomycytes in [Ca2+]i elevation to Str (10 μmol·L-1) was attenuated, while remained no change to Str (1 and 100 nmol·L-1). TTX, nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str at all of the detected concentrations in Na+, K+-free Tyrode's solution. The study suggests that the elevation of [Ca2+]i by Str at the low (nomomolar) concentrations is partially mediated by the extracellular calcium influx through Ca2+ channel or a "slip mode conductance" of TTX sensitive Na+ channel. While the effect of Str at high (micromolar) concentrations was mainly due to the inhibition of Na+, K+-ATPase. Directly triggering the release of intracellular Ca2+ from sarcoplasmic reticulum (SR) by Str may be also involved in the mechanism of [Ca2+]i elevation.

AIM To investigate whether dipfluzine (Dip) possesses antiarrhythmic effect on experimental arrhythmias and effect on cytosolic calcium in ventricular myocytes of guinea-pig. METHODS Experimental arrhythmias were induced by strophanthin G infusion through jugular vein in guinea-pigs and by myocardial ischemia-reperfusion (I-R) in rats respectively. Cytosolic calcium concentration ([Ca2+]i) of isolated guinea-pig ventricular myocytes was examined with laser confocal scanning microscope. RESULTSIn guinea-pigs pretreatment with Dip 20 mg·kg-1 increased the dosages of strophanthin G required to induce ventricular premature contraction (VP), ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrest (CA), pretreatment with Dip 10 mg·kg-1 increased the dosages of strophanthin G required to induce VP. In the I-R-induced arrhythmic model of rats, Dip 20 mg·kg-1 decreased the number of rats exhibiting VT, VF and CA, and the number of rats exhibiting VF and CA was decreased by Dip 10 mg·kg-1. Both Dip and verapamil (Ver) decreased [Ca2+]i of the ventricular myocytes in normal Tyrode′s solution. The Ca2+ overload evoked by high extracellular Ca2+ levels was inhibited by Dip and Ver, and the prophylactic effect of Dip was less than that of Ver, while the curative effect of Dip was more obvious than that of Ver. CONCLUSION Dip has antiarrhythmic effect, which is likely related to the modulation on the intracellular calcium homeostasis.