Search

To investigate the correlation of the Netrin-1 expression level with the clinical characteristics in children with acute lymphoblastic leukemia (ALL) and to explore its possible regulatory mechanism.ELISA was used to detect the expression level of Netrin-1 in peripheral blood serum from 48 child ALL patients (newly diagnosed, recurrent), and its relevance with clinical indicators was statistically analyzed. The blood serum samples from 27 children with non malignant hematological diseases were choosen as controls. Leukemia cell lines of Jurkat,Molt-4,SUP-B15 and Raji were cultivated in vitro, after treated with different concentrations of recombinant human Netrin-1 protein， the invasive ability of the cells was detected by Transwell method； the effect of Netrin-1 to the proli feration of cells was detected by CCK-8 method； The expression and phosphorylation level of key molecules, such as FAK,Erk1/2,PI3K and Akt signaling pathway were detected by Western blot.The expression of Netrin-1 in child patients was significantly higher than that of the control group (P0.05). With the increasing of Netrin-1 level, the level of Plt (r=0.483, P0.05) increased, while the level of WBC (r=-0.290, P0.05) decreased, and there were no significant correlation with age, Hb level and the proportion of immature cells in bone marrow. When the concentration of Netrin-1 was 25-50 ng/ml, the level of Netrin-1 positively correlated with WBC (r=0.886, P0.05) ; the level of Netrin-1 significantly decreased when the patient's WBC was ＞50×10There is abnormal expression of Netrin-1 in serum of children with ALL. Netrin-1 may affect the occurrence and development of ALL by increasing the proliferation and invasiveness of leukemia cells, and may become a risk factor of ALL or a potential target in biotherapy.Netrin-1在急性淋巴细胞白血病患者中的表达及意义.研究Netrin-1蛋白在儿童急性淋巴细胞白血病（ALL）患者中的表达及其与临床指标的相关性，并探讨其可能的调控机制.采用ELISA法检测48例ALL患儿（初诊、复发）外周血血清中Netrin-1的表达水平，并分析其与27例非恶性血液病患儿对照样本表达水平的差异，进而分析ALL外周血Netrin-1水平与临床指标的相关性。体外培养ALL细胞Jurkat、Molt-4、SUP-B15和Raji，经不同浓度重组人Netrin-1蛋白处理后，用Transwell法检测细胞的侵袭能力；CCK-8法测定Netrin-1对细胞增殖的作用；采用Western blot 检测FAK、Erk1/2、PI3K、Akt等信号通路关键蛋白的表达及其磷酸化水平.ALL患儿外周血中Netrin-1的表达量显著高于对照组（P＜0.05）。随着Netrin-1表达水平的上调，WBC水平（r=-0.290，P＜0.05）呈下降趋势，Plt水平（r=0.483，P＜0.05）呈上升趋势，且与年龄、Hb水平、骨髓幼稚细胞比例无显著相关性；Netrin-1浓度在25-50 ng/ml水平时，Netrin-1水平与WBC（r=0.886，P＜0.05）呈正相关； WBC50×10ALL患儿血清中存在Netrin-1的异常表达，Netrin-1可能通过增加白血病细胞的增殖、侵袭能力来影响ALL的发生发展，可能成为ALL的危险因素或生物治疗中的潜在靶点.

To investigate the correlation of E-cadherin expression level with the clinical characterastics in children with acute leukemia (AL), and to explore the possible regulatory mechanism.Real-time quantitative RT-PCR was applied to detect the expression level of E-cadherin in bone marrow samples from 135 child patients diagnosed as AL, and its relevance with clinical indicators was statistically analyzed. The expression levels of E-cadherin, β-catenin, and Akt/p-Akt were detected by using Western blot. The bone marrow samples from 22 children with non-malignant hematological diseases were used as controls.The expression level of E-cadherin significantly decreased in newly diagnosed patients with all 3 types of AL as compared with bone marrow samples from control group (P0.01). In B-ALL group, compared with standard risk group, E-cadherin expression level significantly decreased in intermediate risk group (P0.05). Moreover,the expression level of E-cadherin mRNA was also reduced in splenomegaly group (P0.01). However, the correlation of E-cadherin level with clinical characteristics was not found in T-ALL and AML (P0.05). The expression level of E-cadherin in the patients from Common-B-ALL group was higher than B-ALL patients with other immunophenotypes (P0.01), while no significant difference was found among patients grouped by FAB classification. By the correlation analysis of measured data, lower E-cadherin expression level was found to be related with high WBC count and serum lactic dehydrogenase level (LDH) (r=-0.419, r=-0.269), but with low blood platelet count in B-ALL (r=0.335). In T-ALL, expression of E-cadherin was found to be negatively correlated with LDH and percentage of immature cells in the bone marrow (r=-0.567, r=-0.557). In addition, the lower expression of E-cadherin was also found to be related with WBC count and percentage of immature cells in the bone marrow in newly diagnosed AML patients (r=-0.368, r=-0.391). Compared with control group, the expression of E-cadherin was down-regulated significantly (P0.01), while β-catenin, Akt significantly was up-regulated in 3 types of AL patients (P0.01). The expression of p-Akt and p-Akt/Akt was up-regulated significantly in T-ALL (P0.01).Lower expression of E-cadherin is related factor of unfavourable prognosis in children with acute leukemia. The expression deficiency or down-regulation of E-cadherin may activate Wnt/β-catenin and PI3K/ Akt signaling pathways to promote the genesis and progress of haematological malignancies, thus resulting in a series of malignant biological behaviors in cells. E-cadherin may be a new prognostic indicator for pediatric acute leukemia, thus to guide individualized hemotherapy.E-cadherin基因在儿童急性白血病中的表达及其临床意义.研究E-cadherin基因在儿童急性白血病（AL）中的表达及其与临床指标的相关性，并探讨其可能的调控机制。.采用实时荧光定量PCR检测135例初诊AL患儿骨髓单个核细胞中E-cadherin mRNA的表达水平，并分析其表达水平与临床指标的相关性；应用Western blot法检测E-cadherin、β-catenin、Akt、p-Akt信号通路相关蛋白的表达；同时收集22例非恶性血液病患儿的骨髓作为对照。.B-ALL、T-ALL、AML组中E-cadherin mRNA的表达均低于对照组（P＜0.01）。在B-ALL中，中危组患儿E-cadherin基因表达水平较标危组显著下降（P＜0.05）；伴有脾脏浸润的患儿E-cadherin基因表达水平亦显著降低（P＜0.01）；而在T-ALL、AML患儿各临床指标分组中，E-cadherin基因表达水平均无显著差异。在B-ALL患儿中，免疫分型为Common-B-ALL的患儿E-cadherin基因表达水平较其他B-ALL患儿显著升高（P＜0.01）。而在3种AL的FAB分组间均未见E-cadherin表达差异。基于计量资料的相关性分析表明，B-ALL患儿中，随着E-cadherin表达水平的下调，初诊外周血白细胞（WBC）计数、乳酸脱氢酶（LDH）水平有升高趋势（r=-0.419，r=-0.269），而初诊外周血血小板水平呈下降趋势（r=0.335）；在T-ALL患儿中，E-cadherin表达水平与LDH、初诊骨髓幼稚细胞比例呈显著负相关（r=-0.567，r=-0.557）；而在AML患儿中，随着E-cadherin表达水平下调，初诊WBC计数水平和初诊骨髓幼稚细胞比例呈上升趋势（r=-0.368，r=-0.391）。与对照组比较，3种AL患儿中E-cadherin表达水平下调（P＜0.001），而β-catenin、Akt则上调（P＜0.01），p-Akt、p-Akt/Akt表达量在T-ALL中上调（P＜ 0.01）。.E-cadherin基因表达降低或缺失是儿童急性白血病的预后不良相关因素，可能通过激活Wnt/β-catenin和PI3K/Akt信号通路，促进肿瘤的发生，并引起细胞的一系列恶性生物学行为，E-cadherin有望成为判断预后和指导个性化治疗的指标。.

Background Exosomes are small vesicles containing a wide range of functional proteins, mRNA and miRNA. Exosomal miRNAs from cancer cells play crucial roles in mediating cell-cell communication and tumor-microenvironment cross talk, specifically in enabling metastasis and promoting angiogenesis. We focused on miR-9 that was identified as a tumor suppressor previously in nasopharyngeal carcinoma (NPC) tumorigenesis. Methods Differential centrifugation, transmission electron microscopy and nanoparticle tracking analysis were used to isolate and identify exosomes. Quantitative PCR and western blotting analysis were used to detect miR-9, pri-miR-9, CD63, TSG101, MDK, P70S6K P-Ser424 and PDK1 P-Ser241 expression. Laser confocal microscopy was used to trace exosomal miR-9 secreted by NPC cells into HUVECs. The effect of exosomal miR-9 on cell migration and tube formation of HUVECs in vivo and vitro was assessed by using migration assay, tube formation assay and matrigel plug assay, respectively. Bioinformatics analysis and luciferase reporter assay were utilized to confirm the binding of exosomal miR-9 to the 3′untranslated region (3′-UTR) of MDK, while Phosphorylation Array was performed to identify AKT Pathway in HUVECs treated with exosomal miR-9. Furthermore, Immunohistochemistry (IHC) and in situ hybridization (ISH) was used to detected miR-9, CD31 and MDK expression in human NPC tumor samples. Results NPC cells transfected with miR-9-overexpressing lentivirus, released miR-9 in exosomes. Exosomal miR-9 directly suppressed its target gene - MDK in endothelial cells. Mechanistic analyses revealed that exosomal miR-9 from NPC cells inhibited endothelial tube formation and migration by targeting MDK and regulating PDK/AKT signaling pathway. Additionally, the level of MDK was upregulated in NPC tumor samples and was positively correlated with microvessel density. Notably, the level of exosomal miR-9 was positively correlated with overall survival, and MDK overexpression was positively associated with poor prognosis in NPC patients, suggesting the clinical relevance and prognostic value of exosomal miR-9 and MDK. Conclusions Taken together, our data identify an extracellular anti-angiogenic role for tumor-derived, exosome-associated miR-9 in NPC tumorigenesis and prompt further investigation into exosome-based therapies for cancer treatment. Electronic supplementary material The online version of this article (10.1186/s13046-018-0814-3) contains supplementary material, which is available to authorized users.

In order to investigate the impacts of large scale PV power plants on the stability of power system, dynamic PV models are of particular interest to the industry for simulating large-scale power systems. The transient model of large scale grid-connected PV generation system was given based on the model of each component of PV generation system. Response of the model was simulated respectively when the illumination changes. The methods proposed could be applied to the power grid with photovoltaic generation integration.

The dynamic model of DFIG for power flow calculation and transient simulation is proposed and becoming a hot spot of research. Based on the principle of DFIG model which is newly released by the International Electrotechnical Commission (IEC), analyzes model structure and the control block. The type 3 wind turbine generator (WTG) is implemented in PSCAD environment, Case studies under both normal and grid fault conditions are done with the implemented IEC generic models of type3 WTG, simulation results of IEC type3 WTG are compared with the full order model .The case study results show that the IEC generic models of Type3 WTG can correctly represent the performances of Type3 WTG under both normal and fault conditions, the validation of the model are verified, the model will promote the standardization of domestic wind turbine model, and provide correct and effective dynamic model of wind turbine for study of the wind power integration into grid.

This article puts forward a simplified method of the doubly-fed induction generator (DFIG for short) model innovatively based on the DFIG control principle. This paper establishes two different degrees of simplification models with equivalence of the converter model and the generator model respectively, and compares the operating performance of each model under the same operating condition. The simulation results show that, the two simplified models have high accuracy, and speed up the simulation efficiency effectively, which is suitable for the study of large-scale wind power generation in power system.

As the increasing of the wind power capability， in order to ensure the stability of the grid while the voltage dips， the LVRT ability of the wind power turbine has become necessary. Realizing LVRT， is not only the question the built and will build wind power system are facing, but also the challenge of the will build and operating ones. Actually, many connected operating wind power system can’t meet the LVRT, this is why the large scale wind power off-grid events happened frequently, so the reformation of the wind power system LVRT is an emergency question to be solved. This paper introduced the main methods for LVRT reformation, based on this, some LVRT reform equipment was summarized for the wind turbine; and further, some reform methods were introduced for wind farm.

The output of photovoltaic generation system is influenced by the factors such as solar radiation, temperature and so on. So the change of photovoltaic generation power is a non-stationary random process that will impact on the grid. In order to promote large-scale photovoltaic generation connected to the grid, we need to configure energy storage devices for photovoltaic power station and in order to coordinate the allocation of photovoltaic system with energy storage system, we requires a thorough understanding of output characteristics of the photovoltaic system. This paper firstly analyzes the influence brought by the large-scale photovoltaic generation system connected to the grid and then introduces the effect factors of photovoltaic output. Based on the history data of the 100 kWp photovoltaic power station and the statistical method, the paper qualitatively and quantitatively analyzes the photovoltaic output performance; finally puts forward the PV output power evaluation index. The conclusions of this study will provide powerful data references for follow-up studies and have practical value.

The current management situation of the diet low-cost materials inventory in the university is analyzed in this paper and two solutions are given: ABC inventory analysis method and inventory control strategies. The calculation method of the ABC inventory analysis method is introduced through the management data of the low-cost materials inventory in some university, and the different control strategies are also explained according to different raw materials in the inventory control strategies. The order place and the calculation method of order quantity are given under the condition of determining the demand and lead time, and under the condition of uncertain of the demand and lead time, that provide a theoretical basis for the inventory control management.