血清25-羟基维生素D3浓度水平与成人支气管哮喘及COPD的相互关系

目的通过检测支气管哮喘、COPD患者血清25（OH）D3水平,分析其与两种疾病的关系。方法随机选择哮喘患者59例、COPD患者35例,与之年龄、性别等相仿的健康对照组49例。通过电化学发光法检测25（OH）D3水平,并分析成人哮喘及COPD患者与对照组血清25（OH）D3水平的差异性。检测哮喘患者肺功能指标,分析与25（OH）D3水平相关性,以P〈0．05为有统计学意义。结果病例组血清25（OH）D3水平低于对照组,差异有统计学意义（P〈0．05）,哮喘患者血清25（OH）D,水平与FEV1、FEV1／FVC、FVC实测值之间无相关性（P〉0．05）。结论支气管哮喘及COPD患者均普遍存在维生素D缺乏现象。在成人支气管哮喘患者低的25（OH）D3水平与其肺功能之间无相关性。     

Research,Modelling and Prediction of the Influence of Technological Parameters on the Selected 3D Roughness Parameters,as Well as Temperature,Shape and Geometry of Chips in Milling AZ91D Alloy

The main purpose of the study was to define the machining conditions that ensure the best quality of the machined surface, low chip temperature in the cutting zone and favourable geometric features of chips when using monolithic two-teeth cutters made of HSS Co steel by PRECITOOL. As the subject of the research, samples with a predetermined geometry, made of AZ91D alloy, were selected. The rough milling process was performed on a DMU 65 MonoBlock vertical milling centre. The machinability of AZ91D magnesium alloy was analysed by determining machinability indices such as: 3D roughness parameters, chip temperature, chip shape and geometry. An increase in the feed per tooth f_z and depth of cut a_p parameters in most cases resulted in an increase in the values of the 3D surface roughness parameters. Increasing the analysed machining parameters did not significantly increase the instantaneous chip temperature. Chip ignition was not observed for the current cutting conditions. The conducted research proved that for the adopted conditions of machining, the chip temperature did not exceed the auto-ignition temperature. Modelling of cause-and-effect relationships between the variable technological parameters of machining f_z and a_p and the temperature in the cutting zone T, the spatial geometric structure of the 3D surface “Sa” and kurtosis “Sku” was performed with the use of artificial neural network modelling. During the simulation, MLP and RBF networks, various functions of neuron activation and various learning algorithms were used. The analysis of the obtained modelling results and the selection of the most appropriate network were performed on the basis of the quality of the learning and validation, as well as learning and validation error indices. It was shown that in the case of the analysed 3D roughness parameters (Sa and Sku), a better result was obtained for the MLP network, and in the case of maximum temperature, for the RBF network.     

The Effect of Heavy Fe-Doping on 3D Growth Mode and Fe Diffusion in GaN for High Power HEMT Application

The high electron mobility transistor (HEMT) structures on Si (111) substrates were fabricated with heavily Fe-doped GaN buffer layers by metalorganic chemical vapor deposition (MOCVD). The heavy Fe concentrations employed for the purpose of highly insulating buffer resulted in Fe segregation and 3D island growth, which played the role of a nano-mask. The in situ reflectance measurements revealed a transition from 2D to 3D growth mode during the growth of a heavily Fe-doped GaN:Fe layer. The 3D growth mode of Fe nano-mask can effectively annihilate edge-type threading dislocations and improve transfer properties in the channel layer, and consequently decrease the vertical leakage current by one order of magnitude for the applied voltage of 1000 V. Moreover, the employment of GaN:C film on GaN:Fe buffer can further reduce the buffer leakage-current and effectively suppress Fe diffusion.     

Simultaneous inhibition of mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways augment the sensitivity to actinomycin D in Ewing sarcoma

Purpose  Ewing sarcoma cells, of which over 85% retain chimeric fusion gene EWS/Fli-1, are by and large more resistant to chemotherapeutics compared to nonneoplastic cells. The purpose of this study is to determine the role of EWS/Fli-1 fusion and its downstream targets regarding the cells’ resistance against actinomycin D (ActD), which is one of the most commonly used antitumor agents in combination chemotherapy of Ewing sarcomas. Methods  Cytotoxicity was measured by WST-8 assay. Caspase-dependent and -independent cell death was examined by fluorescence microscope. Protein expression was analyzed by western blotting. Caspase activity was determined by Caspase-Glo assay. Results  ActD-induced caspase-dependent apoptotic cell death to Ewing sarcoma TC-135 cells in a dose- and time- dependent manner. Knockdown of EWS/Fli-1 fusion by siRNA resulted in enhancement of ActD-induced apoptosis. ActD treatment activated both mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways although in a distinctive manner. Combined administration of U0126 (MEK inhibitor) and LY294002 (PI3K inhibitor) significantly enhanced ActD-induced apoptosis in vitro and suppressed xenograft tumor growth in vivo. Conclusions  The present study demonstrated for the first time that combination of U0126 and LY294002 can augment the cytotoxicity of ActD against Ewing sarcoma cells in vitro and in vivo. Our results indicate that further study on combination of conventional chemotherapies with MEK and PI3K inhibitors may be considered for innovative treatments of Ewing sarcoma patients.     

Concordant Atrioventricular Connection to L-Looped Ventricles with the Left Ventricle on Top of the Right Ventricle in Situs Solitus: A Case Report with 3D Modelling and Printing

We report the case of a rare complex cardiac anomaly involving situs solitus, concordant atrioventricular connection with left-hand ventricular topology, and L-looped ventricles. The ventricles had a superior-inferior relationship with an inferiorly located right ventricle, which had a double outlet with far posteriorly located great arteries. The left atrium was elongated, with juxta-positioned atrial appendages on the right side. The 3D-printed model using a computed tomography scan taken on the fourth day of birth demonstrated the anatomy clearly and helped us decide on the surgical management.     

1,25(OH)_2D_3对去卵巢大鼠骨组织成骨细胞、骨细胞凋亡的影响

目的观察1,25(OH)_2D_3对去卵巢大鼠骨组织中成骨细胞、骨细胞凋亡的影响。方法 36只雌性SD大鼠随机分成四组,对尼尔雌醇组和1,25(OH)_2D_3组分别给予尼尔雌醇(0.1mg/kg)和1,25(OH)_2D_3(0.05μg/kg)治疗12周。12周后,以DXA法测定大鼠全身的骨密度;放射免疫法测定各组大鼠血清中骨钙素及雌二醇的水平;处死各组大鼠,采用3′-OH末端DNA原位标记技术和透射电镜检测骨细胞、成骨细胞凋亡。结果 12周后,去卵巢组大鼠的骨密度和血清雌二醇水平明显降低,骨钙素含量升高,与假手术组相比,差异有显著性(P0.05)。1,25(OH)_2D_3可以增加去卵巢大鼠的全身骨密度和血清骨钙素含量(P0.05),但是不增加血清雌二醇的水平(P0.05)。1,25(OH)_2D_3可以抑制骨细胞、成骨细胞凋亡,与去卵巢组相比差异有显著性(P0.05)。结论 1,25(OH)_2D_3对去卵巢大鼠骨质疏松症具有防治作用,其部分机制可能为1,25(0H)_2D_3抑制了骨细胞、成骨细胞凋亡,从而调节骨重建。     

O-去甲基文拉法辛对大鼠肝微粒体细胞色素P450酶含量及CYP2D6、CYP3A4活性的影响

目的研究O-去甲基文拉法辛对大鼠肝微粒体内细胞色素P450(CYP450)含量及CYP2D6、CYP3A4活性的影响。方法生理盐水为对照,大鼠灌胃22.90mg.kg-1.d-1的O-去甲基文拉法辛琥珀酸盐一水合物,连续7d,然后测定其肝微体中CYP450含量及CYP2D6、CYP3A4活性。结果与生理盐水组比较,ODV组CYP450含量和CYP3A4活性无变化(P>0.05),CYP2D6活性明显被抑制(P<0.01)。结论ODV对CYP450含量和CYP3A4活性无影响,但对CYP2D6活性有抑制作用。     

布地奈德联合特异性免疫治疗对支气管哮喘患儿1，25-二羟维生素D3及IL-6、IL-10水平的影响

目的探究布地奈德联合特异性免疫治疗对支气管哮喘患儿1,25-二羟维生素D3及白介素6(interleukin-6, IL-6)、白介素10(interleukin-10, IL-10)水平的影响。 方法选取我院2017年6月至2019年6月73例支气管哮喘患儿作为研究对象,分为观察组38例和对照组35例。对照组给予布地奈德治疗,观察组则再联合舌下含服粉尘螨滴剂行特异性免疫治疗。比较治疗前后两组患儿哮喘症状评分、肺功能和血清1,25-二羟维生素D3及IL-6、IL-10水平。 结果治疗1年、2年后,两组患者哮喘症状及ACT评分均有下降,且观察组患者哮喘症状及ACT评分分别为(0.95±0.46、0.46±0.38)分和(1.14±0.51、0.74±0.42)分,差异均有统计学意义(P<0.05)。观察组患者肺功能观察组患者第1 s用力呼气量(forced expiratory volume in 1 s, FEV₁)、用力肺活量(forced vital capacity, FVC)、FEV₁%预计值、FVC%预计值及FEV₁/FVC和对照组比较均明显上升(P<0.05)。治疗后,两组患儿血清IgE、IL-6水平下降,1,25-二羟维生素D3和IL-10水平明显升高,且观察组上述指标均明显优于对照组(P<0.05)。 结论特异性免疫疗法联合布地奈德治疗儿童支气管哮喘可有效增加患儿血清1,25-二羟维生素D3和IL-10水平,减少IgE及IL-6,改善机体组织过敏原的免疫耐受能力,同时还能显著改善哮喘症状及肺功能,具有良好的临床疗效。     

Bradykinin limits infarction when administered as an adjunct to reperfusion in mouse heart: the role of PI3K,Akt and eNOS

Attenuation of reperfusion injury by growth factors has recently been linked to recruitment of phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt), a pathway also linked to the phosphorylation of eNOS by bradykinin. We, therefore, hypothesised that bradykinin would limit infarct size when given as an adjunct to reperfusion. Using an isolated perfused mouse heart model of ischaemia/reperfusion injury, we show that 100 nmol/l bradykinin, administered upon reperfusion, attenuates infarct size (32 +/- 2% to 22 +/- 2%, P < 0.01). This protection was abrogated by concomitant administration of the PI3K inhibitor, wortmannin (100 nmol/l), whereas wortmannin alone had no impact upon infarct size (31 +/- 3% and 30 +/- 1%, respectively). In eNOS knockout hearts, bradykinin was not seen to be protective (31 +/- 2% versus 32 +/- 2%), yet knockout hearts could be rescued with the nitric oxide donor, S-nitroso-N-acetyl penicillamine (SNAP) (1 micromol/l) (17 +/- 4%, P < 0.01). Using western blot analysis, we show that bradykinin administration results in rapid, robust phosphorylation of both Akt and eNOS, greater than that seen in control hearts upon reperfusion (Akt/eNOS phosphorylation: 68 +/- 7/122 +/- 29 AU versus 32 +/- 5/47 +/- 10 AU respectively, P < 0.01). This pattern of Akt phosphorylation was mimicked in the absence of eNOS, whereas Akt phosphorylation was inhibited by wortmannin. Exogenous nitric oxide administration had no impact upon Akt phosphorylation. Therefore, we demonstrate that exogenous bradykinin, administered at reperfusion, limits infarct size with concomitant rapid phosphorylation of Akt and eNOS, and that this protection is dependent upon the presence of eNOS. These results may open new avenues for research into clinical limitation of reperfusion injury following acute myocardial infarction.     

Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads: an in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis

Granulocyte and monocyte adsorptive apheresis (GMA) using a column filled with cellulose acetate (CA) beads (carriers) has been associated with a significant clinical efficacy in patients with rheumatoid arthritis and ulcerative colitis. To obtain further understanding on the mechanisms of disease modification by cellulose acetate-carrier-based GMA, in the present study, we investigated the mechanisms of granulocyte and monocyte adhesion to CA beads following exposure of human peripheral blood to the carriers at 37 degrees C for up to 60 min under controlled conditions. Cellulose acetate beads selectively adsorbed granulocytes, monocytes. CD19+ (B cells) and CD56+ (NK cells) lymphocyte subpopulations. The granulocyte and monocyte adsorption was inhibited by heat-inactivated plasma and EDTA, indicating that the adsorption was plasma protein (immunoglobulin, complement) and calcium dependent. Accordingly, granulocyte and monocyte adsorption was markedly enhanced by coating the carriers with IgG. Similarly, C3b was adsorbed onto the CA beads as a marker of complement activation. The results indicated that IgG and active complement fragments mediated leukocyte adhesion to CA beads via the FcgammaR and/or leukocyte complement receptor like CR3. Additionally, CA beads induced loss of expression of TNF receptors on CD16- granulocytes and CD14+ monocytes, but not on CD3+ lymphocytes In conclusion, CA beads might be an appropriate biomaterial for inducing extracorporeal immunomodulation as a treatment for auto-immune diseases which are associated with pathological leukocyte activity.     

Inhibitory effects of the D(-)isomer of 3-hydroxybutyrate on cardiac non-esterified fatty acid uptake and oxygen demand induced by norepinephrine in the intact dog

The effects of ketosis on the norepinephrine-induced high rates of cardiac uptake of non-esterified fatty acids (NEFA = free fatty acids = FFA) and oxygen consumption were studied in anesthetized intact dogs. After a control infusion of norepinephrine (500 ng/kg.min into the left ventricle), the D(-) isomer or natural form of 3-hydroxybutyrate was infused intravenously as the arginine salt at rates of 20 mumol/kg.min in group A (10 dogs) and 80 mumol/kg.min in group B (10 dogs) and a second norepinephrine infusion was superimposed on the ketone treatment. At the time the effects of the second catecholamine infusion were measured, the arterial 3-hydroxybutyrate concentration averaged 1.2 +/- 0.1 mM in group A and 8.3 +/- 0.4 mM in group B, and the cardiac uptake of the ketone amounted to 17.4 +/- 0.6 and 35.8 +/- 5.3 mumol/min.100 g, respectively. Relative to the control norepinephrine infusion, the arterial NEFA concentration was reduced to 88 +/- 4% in group A and to 62 +/- 8% in group B, but the cardiac uptake of NEFA was significantly more depressed, to 65 +/- 7% in group A and to 35 +/- 8% in group B. These changes were not observed in ten non-ketotic animals under repeated norepinephrine infusion. Thus, ketosis inhibited the norepinephrine-stimulated uptake of NEFA, presumably through (1) a lowered availability of NEFA from arterial blood, attributable to a reduction of extracardiac lipolysis, and (2) competition of 3-hydroxybutyrate with NEFA for metabolism by the myocardium in the face of still high arterial NEFA concentrations, 1.7 +/- 0.1 mM in group A and 1.1 +/- 0.2 mM in group B. In both groups, the lowering of the contribution of NEFA to cardiac metabolism was associated with a reduction of the estimated oxygen demand per beat (ratio of cardiac oxygen consumption/min to the pressure-rate product), while the pressure response to norepinephrine was not modified. There was no evidence for abnormal cardiac function.