Beyond superquenching: hyper-efficient energy transfer from conjugated polymers to gold nanoparticles

Gold nanoparticles quench the fluorescence of cationic polyfluorene with Stern-Volmer constants (KSV) approaching 1011 M-1, several orders of magnitude larger than any previously reported conjugated polymer-quencher pair and 9-10 orders of magnitude larger than small molecule dye-quencher pairs. The dependence of KSV on ionic strength, charge and conjugation length of the polymer, and the dimensions (and thus optical properties) of the nanoparticles suggests that three factors account for this extraordinary efficiency: (i) amplification of the quenching via rapid internal energy or electron transfer, (ii) electrostatic interactions between the cationic polymer and anionic nanoparticles, and (iii) the ability of gold nanoparticles to quench via efficient energy transfer. As a result of this extraordinarily high KSV, quenching can be observed even at subpicomolar concentrations of nanoparticles, suggesting that the combination of conjugated polymers with these nanomaterials can potentially lead to improved sensitivity in optical biosensors.     

Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferation and deformability

We demonstrated recently that chronic administration of aldosterone to rats induces glomerular mesangial injury and activates mitogen-activated protein kinases including extracellular signal-regulated kinases 1/2 (ERK1/2). We also observed that the aldosterone-induced mesangial injury and ERK1/2 activation were prevented by treatment with a selective mineralocorticoid receptor (MR) antagonist, eplerenone, suggesting that the glomerular mesangium is a potential target for injuries induced by aldosterone via activation of MR. In the present study, we investigated whether MR is expressed in cultured rat mesangial cells (RMCs) and involved in aldosterone-induced RMC injury. MR expression and localization were evaluated by Western blotting analysis and fluorolabeling methods. Cell proliferation and micromechanical properties were determined by [3H]-thymidine uptake measurements and a nanoindentation technique using an atomic force microscope cantilever, respectively. ERK1/2 activity was measured by Western blotting analysis with an anti-phospho-ERK1/2 antibody. Protein expression and immunostaining revealed that MR was abundant in the cytoplasm of RMCs. Aldosterone (1 to 100 nmol/L) dose-dependently activated ERK1/2 in RMCs with a peak at 10 minutes. Pretreatment with eplerenone (10 micromol/L) significantly attenuated aldosterone-induced ERK1/2 phosphorylation. Aldosterone (100 nmol/L) treatment for 30 hours increased [3H]-thymidine incorporation and decreased the elastic modulus, indicating cellular proliferative and deforming effects of aldosterone, respectively. These aldosterone-induced changes in cellular characteristics were prevented by pretreatment with eplerenone or an ERK (MEK) inhibitor, PD988059 (100 micromol/L). The results indicate that aldosterone directly induces RMC proliferation and deformability through MR and ERK1/2 activation, which may contribute to the pathogenesis of glomerular mesangial injury.     

复方血栓通胶囊改善肾功能机制研究

[目的] 研究复方血栓通胶囊对糖尿病肾病(DN)大鼠24 h尿白蛋白、尿肌酐、血肌酐和血尿素氮等相关代谢指标的影响,及应用基因芯片探讨复方血栓通胶囊改善DN 大鼠肾功能的机制。[方法] 选用SD 大鼠45 只,高脂喂养/ 链尿佐菌素(STZ)注射法制备DN 模型,将DN 成模大鼠40 只随机分为小剂量、中剂量、大剂量血栓通组[ 分别给予0.3、0.6、1.2 g/(kg·d)的血栓通粉末悬浊液]、DN 模型组(给予生理盐水)。另外选用SD 大鼠10 只为正常对照组(给予生理盐水),均连续灌胃12 周。每月末测定大鼠空腹血糖(FBG)和体质量。3 个月末测定大鼠24 h尿白蛋白、尿肌酐、血肌酐和血清尿素氮水平。取大鼠肾脏组织进行Illumina基因芯片实验以期从整体基因角度揭示复方血栓通胶囊改善肾功能的机制。实时定量PCR 实验验证基因芯片的结果。[结果] 复方血栓通胶囊能以剂量依赖的方式降低24 h尿白蛋白、血肌酐和血清尿素氮,升高尿肌酐(P<0.05或P<0.01)。基因芯片显示大剂量血栓通组较模型组有67 个基因显著改变,其中34 个上调,33 个下调。实时定量PCR 实验发现大剂量血栓通组胶原蛋白1 型1(Col1a1)、结缔组织生长因子(Ctgf)和转化生长因子1(Tgfb1)基因较模型组显著下调,细胞色素P450 家族2 亚族C 肽23(Cyp2c23)和Nephrin-1(Nphs1)显著上调。[结论] 复方血栓通胶囊能有效改善DN 大鼠肾脏功能,其机制可能涉及Bmp2-Tgfβ-Ctgf通路,Cyp2c23 和足细胞损伤修复。     

PF4通过NF-κB上调巨噬细胞MMP-9表达

目的观察血小板因子4(PF4)是否通过核因子κB(NF-κB)上调THP-1单核源性巨噬细胞基质金属蛋白酶9(MMP-9)表达。方法佛玻酯诱导THP-1细胞分化成巨噬细胞。巨噬细胞分别在NF-κB抑制剂(PDTC)缺乏或存在情况下与溶媒或PF4(100μg/L)孵育一定时间,RT-PCR检测MMP-9 mRNA水平;同时,巨噬细胞与PF4(25~200μg/L)单独或结合Toll样受体4(TLR4)阻断剂(抗体HTA125,anti-TLR4)孵育,ELISA法检测NF-κB含量。结果 PF4较对照组上调巨噬细胞MMP-9 mRNA水平。而NF-κB抑制剂抑制PF4诱导的巨噬细胞MMP-9表达上调。PF4呈浓度依赖性增加巨噬细胞的NF-κB含量,最大效应浓度为100μg/L。TLR4阻断剂逆转PF4诱导的巨噬细胞NF-κB含量增加。结论 PF4可能通过NF-κB上调巨噬细胞MMP-9的表达。TLR4可能是PF4-NF-κB通路中NF-κB的上游信号分子。     

缺氧诱导因子-1α在胆囊癌侵袭转移中的作用研究

目的 :研究缺氧诱导因子-1α在胆囊癌侵袭转移中的作用,并探讨HIF-1α在判断胆囊癌治疗效果及预测胆囊癌复发转移方面的价值。方法 :采用慢病毒对胆囊癌细胞系(GBC-SD)进行转染,干扰该细胞系中HIF-1α的表达,得到HIF-1α表达不受干扰的胆囊癌细胞系(GBC-SD-NC)和HIF-1α表达受干扰的胆囊癌细胞系GBC-SD-HIF。通过将两组细胞系裸鼠鼠尾静脉注射建立胆囊癌血行转移模型,检测两组细胞在小鼠肺部形成转移瘤的能力。结果 :GBC-SD-NC组裸鼠肺部转移瘤数量、大小都比GBC-SD-HIF组高,GBC-SD-NC组转移瘤的平均数量显著多于GBC-SD-HIF组。结论 :干扰胆囊癌细胞中HIF-1α的表达,可以显著减低胆囊癌细胞系GBC-SD的血行肺转移能力。说明缺氧诱导因子-1α在胆囊癌侵袭转移中存在独立影响。     

GPS导航超声系统引导下超细经皮肾镜取石术治疗无积水肾下盏结石的临床应用

目的探讨GPS导航超声系统引导超细经皮肾镜取石术(UMP)治疗无积水肾下盏结石的临床疗效及安全性。方法回顾性分析2017年1月-2017年9月该院23例采用GPS引导UMP治疗无积水肾下盏患者的临床资料。其中,单发结石17例,多发结石6例。结石大小14.0~25.0 mm,平均(18.3±3.6)mm,结石CT值880~1 610 Hu,平均(1 253.6±182.8)Hu。俯卧位建立"人工肾积水"后在GPS导航引导下16G穿刺针穿刺入目标肾盏,退出针芯见灌注液流出后,将F3超细肾镜直接沿穿刺针鞘进入肾集合系统,进一步确认穿刺针鞘头端在目标肾盏位置,并找到肾盏颈口,调整穿刺针鞘方向及深度使其头端靠近盏颈口或进入肾盂内。退出超细肾镜,置入斑马导丝,扩张通道至F14后置入F13外鞘,使用超细经皮肾镜进行碎石取石。结果 23例均单通道经下盏穿刺行UMP。定位穿刺时间2~8 min,平均(4.2±1.6)min,一次穿刺成功率为100.00%。手术时间30~65 min,平均(42.3±7.6)min;术后住院天数2~5 d,平均(2.6±0.5)d;血红蛋白下降0~27 g/L,平均(11.2±5.1)g/L。术后止痛药的使用率为0。术后第1或2天复查腹平片(KUB)评估结石清除率为95.65%(22/23)。所有患者围手术期未出现发热、严重出血、集合系统穿孔、通道丢失和胸膜损伤等并发症。结论 GPS导航超声系统结合UMP治疗无积水肾下盏结石安全、有效,结石清除率高,术后恢复快,值得临床推广应用。     

牙线牵引辅助在内镜黏膜下剥离术治疗食管早癌及癌前病变中的应用

目的初步探讨牙线在内镜黏膜下剥离术(ESD)治疗食管早癌及癌前病变中的应用价值。方法回顾性分析2015年7月-2016年7月由同一操作者熟练应用ESD方法治疗食管早癌及癌前病变40例,观察组为采用牙线牵引辅助ESD 20例、对照组为传统ESD方法治疗20例,比较手术时间、一次性病变完整切除率、住院时间及术后并发症发生率等方面的差异。结果观察组牙线辅助ESD法平均手术时间、住院时间少于对照组传统ESD术,差异有统计学意义(P0.05);观察组牙线辅助一次性病变完整切除率高于对照组,差异有统计学意义(P0.05);两组均无出现术后大出血和穿孔等并发症,差异无统计学意义(P0.05)。结论牙线牵引辅助应用于ESD术安全、方便、有效,能够缩短手术操作时间,提高一次性完整切除率,缩短住院时间,降低并发症发生率。     

208例药品不良反应报告分析

摘 要 目的:分析药品不良反应（ADR）的发生情况、发生特点及相关因素,为临床合理用药提供参考。方法：对2013年收集并上报的208例ADR,分别从性别与年龄、给药途径、因果关系评价、报告人职业分布、涉及的药品种类、累及的器官或系统及临床表现等方面进行统计、分析。结果：208例ADR报告中,40岁以上的中老年患者所占比例最大,占76.92%;女患者构成比略高,占51.44%;静脉滴注引起ADR为144例（69.23％）;涉及的药品中,抗肿瘤药物、抗感染药物、心血管系统用药致ADR构成比高;ADR临床主要表现为皮肤及其附件损害（55例）、全身性损害（50例）、血小板和出血凝血障碍（46例）。结论：抗肿瘤药物、抗感染药物、心血管系统用药是ADR监测的重点药物,医药护要共同努力,加强特殊人群和重点药物的ADR监测,提高合理用药水平,减少药源性疾病的发生。     

护士在临床合理用药中的关注点

目的:探讨护士如何在临床合理用药中发挥作用。方法:结合临床实践和对医护人员的合理用药培训经验,根据护士工作特点,归纳总结护士在临床合理用药中的关注点。结果:护士在临床实践中应使用正确的药物、避免无适应证用药、关注注射用药的合理使用(包括过敏试验、配伍禁忌、溶媒的选择、输液配制、输液速度、给药间隔)、合理保存药品、重视患者用药教育、加强药品不良反应的监测。结论:护士加强对合理用药的关注,可保证患者用药安全、有效。     

Synthesis of DNA-guided silver nanoparticles on a graphene oxide surface: enhancing the antibacterial effect and the wound healing activity

The occurrence of antibiotic resistance against pathogens is rapidly increasing and endangering the efficacy of antibiotics. Thus, finding a way to address this problem has become a major challenge due to the inability of conventional antibiotics to kill these multidrug-resistant bacteria. In order to further enhance the antibacterial ability and reduce the possibility of antibiotic resistance, we developed a simple two-step approach and synthesized a new nanocomposite by directly loading single-stranded DNA (ssDNA)-guided silver nanoparticles (AgNPs) on graphene oxide (ssDNA-AgNPs@GO). Through systematically evaluating the bactericidal activity and wound healing capability, we found that ssDNA-AgNPs@GO exhibited synergistic antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis with low minimum inhibitory concentrations (6.8 μg mL⁻¹, 6.8 μg mL⁻¹, 11.9 μg mL⁻¹ and 10.2 μg mL⁻¹, respectively) and large-diameter inhibition zones (12.83 ± 0.63 mm, 13.14 ± 0.37 mm, 8.6 ± 0.9 mm and 8.93 ± 0.47 mm, respectively). Furthermore, the wound healing experiment indicated that it has a striking ability to remedy wound infection caused by Staphylococcus aureus bacteria. In conclusion, the properties of ssDNA-AgNPs@GO with enhanced antibacterial and wound healing capability will give it broad applications in the future.

A simple two-step approach to synthesize a new nanocomposite by directly loading single-stranded DNA (ssDNA)-guided silver nanoparticles (AgNPs) on graphene oxide (ssDNA-AgNPs@GO) is developed.