嗜肺军团菌致病性与效应蛋白的研究进展

嗜肺军团菌是一种可以引起军团菌肺炎和庞蒂亚克热的兼性胞内病原菌，主要侵染阿米巴原虫和人类巨噬细胞。该菌在宿主胞内能依靠Dot/Icm IVB型分泌系统产生的效应蛋白成功逃避溶酶体的降解。本文主要对嗜肺军团菌的致病物质、胞内存活与增殖机制及其效应蛋白的生物学功能进行综述，详细介绍嗜肺军团菌的毒力因子与致病机制，为军团病防治的研究提供新思路，也为其他胞内病原菌所致感染性疾病的研究提供重要的借鉴意义。     

中西医结合护理对剖宫产术后乳汁分泌的影响

目的探析对剖宫产产妇采取中西医结合护理的效果。方法本次研究72例剖宫产产妇均为本院2018年3月-2018年11月接收,随机分为2组,对照组(n=36)行常规护理,研究组(n=36)开展中西医结合护理,统计各组护理效果。结果在初乳泌乳始动优良率、母乳喂养、乳汁分泌充足及乳房胀痛发生率方面,研究组均优于对照组,差异有统计学意义(P<0.05)。结论中西医结合护理在剖宫产产妇护理中效果突出,有助于改善产妇术后的乳汁分泌情况,值得推广。     

miR-802靶向Hnf1B抑制胰岛素分泌的作用研究

探究miR-802对于胰岛β细胞分泌胰岛素的影响及其作用机制。利用miR-802类似物及miR-802抑制剂分别在胰岛原代细胞及Min6细胞过表达或敲降miR-802；采用ELISA法检测miR-802对胰岛素分泌的影响；通过miRNA靶基因数据库预测、荧光素酶报告法和Western blot法确证miR-802的靶基因；最后开展功能回复实验阐明miR-802调控胰岛β细胞分泌胰岛素的作用机制。结果表明:在胰岛原代细胞和Min6细胞中过表达miR-802能抑制胰岛β细胞分泌胰岛素；qPCR和Western blot实验证明miR-802通过抑制靶基因肝细胞核因子1B(hepatocyte nuclear factor 1β，Hnf1B)的转录和翻译，从而抑制胰岛素的分泌。     

肺癌患者血浆肿瘤异常糖链蛋白（TAP）的表达及其临床分析

目的 探讨肺癌患者血浆肿瘤异常糖链蛋白(TAP)的表达及其临床分析。方法 回顾性分析2018年1月～2019年1月在我院呼吸内科治疗的100例肺癌患者的临床资料,将其作为观察组,选取同期100例健康体检者作为对照组,比较两组血标本中TAP浓度,分析TAP表达的差异性及临床资料。结果 观察组血TAP凝聚物面积为(187.92±52.28)μm~2,对照组为(67.38±21.62)μm~2,观察组显著高于对照组(P0.05);观察组化疗后TAP凝聚物面积为(136.84±36.59)μm~2,明显低于化疗前(P0.05);观察组TAP阳性率为84.00%,对照组为3.00%,差异有统计学意义(P0.05);TAP检测的敏感度为84%(84/100),特异度为97%(97/100),约登指数为84%+97%-1≈0.81;TAP阳性与胸水、远处转移有明显关联(P0.05),与性别、年龄、临床分期等无明显关联(P0.05)。结论 肺癌患者血浆TAP表达明显升高,对肺癌的早发现、早诊断有重要意义,并可用于疗效监测,评估治疗效果及预后。     

P2Y13 and P2X7 receptors modulate mechanically induced adenosine triphosphate release from mast cells

Subcutaneous mast cells (MCs) are vulnerable to mechanical stimulation from external environment. Thus, MCs immune function could be modulated by their mechanosensitivity. This property has been identified as the trigger mechanism of needling acupuncture, a traditional oriental therapy. Previously we have demonstrated the release of adenosine triphosphate (ATP), a stress-responsive signalling molecule, from mechanical-perturbed MCs. The current work explores its underlying mechanisms. We noticed that propagation of intracellular free Ca²⁺ occurred among HMC-1 cells in response to 50% hypotonic shock. Additionally, amplifying cascade of ATP-induced ATP release was observed in RBL-2H3 cells stimulated by medium displacement, which could be mimicked by exogenous ATP (exoATP). Secondary ATP liberation induced by low level (50 nmol/L) of exoATP was reduced by inhibiting ecto-ATPase-dependent ADP production with ARL67156, or blocking P2 receptors with suramin or PPADS, or with specific P2Y₁₃ receptor antagonist MRS2211, or siRNA. Secondary ATP release induced by higher dose (200 μmol/L) of exoATP, sufficient to stimulate P2X₇ receptor, was attenuated by suramin, PPADS or specific P2X₇ receptor antagonist BBG, or siRNA. Finally, RT-PCR confirmed mRNA expression of P2Y₁₃ and P2X₇ in RBL-2H3 cells. Additionally, such secondary ATP release was attenuated by DPCPX, specific antagonist of adenosine A1 receptor, but not by MRS2179, specific inhibitor of P2Y₁ receptor. In summary, mechanosensitive ATP release from MCs is facilitated by paracrine/autocrine stimulation of P2Y₁₃ and P2X₇ receptors. This multi-receptor combination could mediate transmission of information from a local site to distal areas, enabling communication with multiple surrounding cells to coordinate and synchronize their function.     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.