微小RNA-181b-5p对皮肤黑素瘤细胞株增殖和侵袭的作用及机制研究

【摘要】 目的 探讨微小RNA（miRNA）-181b-5p是否通过靶向普列克底物蛋白（PLEK）抑制皮肤黑素瘤（CM）细胞的增殖及侵袭能力。方法 生物信息学分析CM核心基因;双荧光素酶报告基因实验验证miRNA-181b-5p和PLEK的靶向结合。采用RNA oligo和siRNA分别调控A375细胞miRNA-181b-5p和PLEK的表达,具体分组为：模拟物阴性对照组、miRNA-181b-5p模拟物组、抑制剂阴性对照组、miRNA-181b-5p抑制剂组、PLEK siRNA组、siRNA阴性对照组、miRNA-181b-5p抑制剂和对照siRNA共转染组以及miRNA-181b-5p抑制剂和PLEK siRNA3共转染组。上述各组用相应试剂处理细胞48 h后,采用qPCR检测A375细胞中miRNA-181b-5p和PLEK mRNA的表达,Western印迹检测PLEK蛋白的表达,Transwell小室侵袭实验检测A375细胞的侵袭能力;继续培养24 ~ 96 h后,CCK8实验检测A375细胞增殖能力。结果 PLEK为CM的核心基因,CM原位癌组织较癌旁组织高表达PLEK（P = 0.031）,转移组织较原位癌组织高表达PLEK（P = 0.001）。与人表皮黑素细胞HEMa-LP相比,A375细胞高表达PLEK mRNA（3.884 ± 0.156比0.997 ± 0.010,t = 18.48,P < 0.001）及PLEK蛋白（2.840 ± 0.301比1.029 ± 0.094,t = 5.47,P = 0.005）,低表达miRNA-181b-5p（0.333 ± 0.042比0.967 ± 0.069,t = 7.83,P = 0.001）。双荧光素酶报告基因实验显示,miRNA-181b-5p和PLEK靶向结合。与模拟物阴性对照相比,miRNA-181b-5p模拟物转染后A375细胞的存活率显著降低（48 h,t = 7.96,P = 0.015;72 h,t = 7.50,P = 0.002;96 h,t = 7.96,P = 0.001）,侵袭能力也显著降低（t = 5.07,P = 0.007）;相反miRNA-181b-5p 抑制剂组A375细胞存活率高于抑制剂阴性对照组（24 h,t =5.38,P = 0.013;48 h,t = 5.36,P = 0.013;72 h,t =7.63,P = 0.005;96 h,t =5.99,P = 0.004）,侵袭能力也高于抑制剂阴性对照组（t = 7.24,P = 0.002）;与对照siRNA组相比,PLEK siRNA转染后A375细胞的增殖能力降低（48、72、96 h时,P值分别为0.015、0.011、0.001）,侵袭能力也降低（t = 4.93,P = 0.008）;与miRNA-181b-5p 抑制剂和对照 siRNA共转染组相比,miRNA-181b-5p 抑制剂和PLEK siRNA共转染组A375细胞的增殖率明显降低（24、48、72、96 h时,P值分别为0.042、0.042、0.037、0.017）,侵袭能力也明显降低（t = 8.52,P = 0.001）。结论 miRNA-181b-5p抑制A375细胞增殖和侵袭能力,其机制涉及靶向下调PLEK的表达。     

Skin occlusion and irritant and allergic contact dermatitis: an overview

Occlusion, widely used to enhance percutaneous absorption of drugs, also increases penetration of other chemicals and antigens, and hence may exacerbate irritant and allergic contact dermatitis. This overview summarizes the adverse effects of occlusion.     

对立违抗性障碍的研究现状

对立违抗性障碍是儿童常见的一种心理障碍。童年早期出现,青春期达到高峰。以不服 从、对抗、消极抵抗、易激惹或挑衅等行为特征为主要的临床表现。虽然对立违抗性障碍没有严重的违 法或冒犯他人的攻击行为,然而对于患儿的家庭、学校,以及社会生活仍会带来较大的麻烦。家长和学 校往往对于对立违抗性障碍缺乏认识,因而导致就诊率低,缺乏早期有效的干预。现就对立违抗性障 碍的发病机制、临床特征、诊断及治疗方面做全面综述。     

雷帕霉素对人宫颈癌HeLa细胞增殖和HIF-1α及VEGF表达的影响

目的 探讨不同浓度雷帕霉素对宫颈癌HeLa细胞生长的抑制作用及对HIF-1α、VEGF表达的影响.方法 采用四甲基偶氮唑盐(MTT)比色法检测分别以不同浓度雷帕霉素处理的体外培养人宫颈癌HeLa细胞的抑制率,采用反转录聚合酶链反应(RT-PCR)、Western blot法检测各组细胞HIF-1 α、VEGF mRNA和蛋白的表达.结果 不同浓度雷帕霉素对宫颈癌HeLa细胞的生长有明显的抑制作用,并呈剂量依赖性;随雷帕霉素浓度增加细胞内HIF-1α、VEGF mRNA和蛋白的表达均呈下调趋势.结论 雷帕霉素对宫颈癌HeLa细胞的生长有抑制作用并呈剂量依赖性,雷帕霉素具有明显下调HIF-1α、VEGF mRNA和蛋白表达的作用.     

Acetone vapour-assisted growth of 2D single-crystalline organic lead halide perovskite microplates and their temperature-enhanced photoluminescence

We adopt an acetone vapour-assisted method to grow high quality single-crystalline microplates of two-dimensional (2D) perovskite, 2-phenylethylammonium lead bromide [(C₆H₅C₂H₄NH₃)₂PbBr₄]. The microplates, converted from the spin-coated films, are well-defined rectangles. Temperature dependent photoluminescence (PL) spectroscopy shows that the band gap PL is enhanced markedly with increasing temperature up to 218 K, accompanied by the quenching of the PL related to the trap states, which perhaps results from the exciton–phonon couplings. The optical phonon energy around 50 meV and the exciton binding energy around 120 meV are derived by fitting the band gap PL linewidths and intensities at different temperatures, respectively.

We report an acetone vapour-assisted method to grow single-crystalline 2D perovskite microplates and find their temperature-enhanced photoluminescence.     

Automated clinical trial eligibility prescreening: increasing the efficiency of patient identification for clinical trials in the emergency department

Objectives (1) To develop an automated eligibility screening (ES) approach for clinical trials in an urban tertiary care pediatric emergency department (ED); (2) to assess the effectiveness of natural language processing (NLP), information extraction (IE), and machine learning (ML) techniques on real-world clinical data and trials.Data and methods We collected eligibility criteria for 13 randomly selected, disease-specific clinical trials actively enrolling patients between January 1, 2010 and August 31, 2012. In parallel, we retrospectively selected data fields including demographics, laboratory data, and clinical notes from the electronic health record (EHR) to represent profiles of all 202795 patients visiting the ED during the same period. Leveraging NLP, IE, and ML technologies, the automated ES algorithms identified patients whose profiles matched the trial criteria to reduce the pool of candidates for staff screening. The performance was validated on both a physician-generated gold standard of trial–patient matches and a reference standard of historical trial–patient enrollment decisions, where workload, mean average precision (MAP), and recall were assessed.Results Compared with the case without automation, the workload with automated ES was reduced by 92% on the gold standard set, with a MAP of 62.9%. The automated ES achieved a 450% increase in trial screening efficiency. The findings on the gold standard set were confirmed by large-scale evaluation on the reference set of trial–patient matches.Discussion and conclusion By exploiting the text of trial criteria and the content of EHRs, we demonstrated that NLP-, IE-, and ML-based automated ES could successfully identify patients for clinical trials.     

A systematic review and meta‐analysis of randomized controlled trials: Skin‐patch of Chinese herbal medicine for patients with acute gouty arthritis

Aims

To evaluate the evidence of the effectiveness and safety of Chinese herbal medicine skin‐patches for patients with acute gouty arthritis.

Background

Acute gouty arthritis is a problem that can limit the level of activity and impair the quality of life. In China, many clinical studies have demonstrated that skin‐patches of Chinese herbal medicines benefit patients with acute gouty arthritis. However, the reported clinical effects vary.

Design

A systematic review and meta‐analysis of randomized controlled trials.

Data sources

Three English databases including CENTRAL (1993 to February 2017), PubMed (1966 to February 2017) and EMBASE (1974 to February 2017) and four Chinese databases including Chinese National Knowledge Infrastructure, Chinese VIP Information, SinoMed and Wanfang (all, 1949 ‐ February 2017) were searched. Randomized controlled trials that compared skin‐patches of Chinese herbal medicine with or without conventional treatments to conventional treatments, no treatment or a placebo treatment for patients with acute gouty arthritis were included.

Review methods

We conducted a systematic review and meta‐analysis following the Cochrane process. Two authors selected the studies, extracted the data and evaluated the risk of bias of the included trials.

Results

Nineteen studies met our inclusion criteria. After synthesizing the data, the results showed that skin‐patches of CHM combined with Western medicine seemed to be more effective than Western medicine alone for pain relief in patients with acute gouty arthritis and had fewer adverse events.

Conclusion

Due to the quality of the data, larger and more rigorously designed clinical trials with proper outcome measures are necessary.     

Superlattice-like structure and enhanced ferroelectric properties of intergrowth Aurivillius oxides

Aurivillius oxides with an intergrowth structures have been receiving increasing interest because of their special structures and potential outstanding ferroelectric properties. In this work, Bi₃LaTiNbFeO₁₂–Bi₅Ti₃FeO₁₅ and Bi₃TiNbO₉–Bi₃LaTiNbFeO₁₂ compounds were successfully synthetised using a simple solid-state reaction method. X-Ray diffraction patterns and scanning transmission electron microscopy high angle annular dark field (STEM-HAADF) images confirm the 2–3 and the 3–4 intergrowth structures in Bi₃TiNbO₉–Bi₃LaTiNbFeO₁₂ and Bi₃LaTiNbFeO₁₂–Bi₅Ti₃FeO₁₅ compounds, respectively. A superlattice-like distortion in these oxides was proposed resulting from the combination of sub-lattices with different a and b parameters, which was validated by XRD refinements and Raman spectra. Polarization-electric field tests and pulsed polarization positive-up negative-down measurements demonstrate that such superlattice-like structures can effectively enhance the intrinsic ferroelectric polarization and coercive field of these oxides, especially when compared with their component oxides Bi₃TiNbO₉, Bi₃LaTiNbFeO₁₂ and Bi₅Ti₃FeO₁₅. Simultaneously, ferroelectric Curie temperatures of Bi₃TiNbO₉–Bi₃LaTiNbFeO₁₂ and Bi₃LaTiNbFeO₁₂–Bi₅Ti₃FeO₁₅ oxides are lowered because of the internal stress in the superlattice-like structure. Nevertheless, the paramagnetism of the samples is hardly influenced by their structure, while mainly related to their iron content, in which iron has a similar effective magnetic moment around 3.4–3.9.

Aurivillius oxides with an intergrowth structures have been receiving increasing interest because of their special structures and potential outstanding ferroelectric properties.