p53基因突变与骨髓增殖性肿瘤临床特征及预后关系

探究p53 基因突变与骨髓增殖性肿瘤（MPN）临床特征及预后的关系。方法 选取2017年1月～2020年1月本院收治的MPN患者126例，二代测序法检测患者p53 基因突变情况。对患者进行随访，统计患者总生存（OS）时间和累计生存率；分析p53 基因突变对患者临床特征、预后的影响。结果 126例MPN患者中12例（9.52%）检出p53基因突变，突变主要位于4~8号外显子上，不同类型患者的p53 基因突变检出率比较差异无统计学意义（P＞0.05）。p53突变组患者年龄大于p53 非突变组，WBC水平低于p53 非突变组（P＜0.05），两组患者的染色体核型、IPSS预后分层比较差异无统计学意义（P＞0.05）；p53 非突变组患者的OS时间、累计生存率均明显高于p53突变组患者（P＜0.05）。结论 MPN患者p53 基因突变发生率较高，与患者年龄、WBC水平、异常核型及IPSS预后分层相关，p53 基因突变会影响患者的预后，可作为临床筛查预后不良高风险人群的客观指标。     

Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.     

miRNA-325-3p通过下调细胞角蛋白13 的表达降低鼻咽癌细胞CNE1 的放疗敏感性

目的：探究miRNA-325-3p 及其靶基因细胞角蛋白13（cytokeratin 13，CK13）对鼻咽癌细胞CNE1 的放疗敏感性的影响。方法：通过miRBase、Targetscan 及Microcosm 三大数据库预测miRNA-325-3p 的潜在靶基因，并通过双荧光素酶活性检测实验进行验证，qPCR检测不同放射剂量下鼻咽癌细胞CNE1 中miRNA-325-3p 及其靶基因的表达水平变化，通过克隆形成实验观察不同放射剂量下过表达miRNA-325-3p 及敲低靶基因后CNE1 细胞克隆形成率的变化，流式细胞术验证过表达miRNA-325-3p及敲低靶基因后CNE1 在不同放射剂量下凋亡水平的变化，MTT法检测miRNA-325-3p 过表达和CK13 敲低组鼻咽癌细胞CNE1在不同放射剂量下的细胞存活率以验证其放疗敏感性的变化。结果：CK13 确认为miRNA-325-3p 的潜在靶基因，鼻咽癌细胞CNE1 经放射处理后，miRNA-325-3p 的表达水平显著升高、CK13 的表达水平显著降低（均P<0.05）。miRNA-325-3p 表达量上调和CK13 基因沉默均显著提高CNE1 细胞的存活率[miRNA上调时：（60.14±3.55）% vs（19.23±3.42）%，t=14.37、P<0.01；CK13 沉默时：（76.15±5.13）% vs（28.53±3.68）%，t=13.06、P<0.01]和克隆形成率，降低了凋亡率[miRNA 上调时：（27.95±2.67）% vs（51.68±3.47）%，t=9.39、P<0.01；CK13 沉默时：（20.31±2.62）% vs（38.14±3.83）%，t=6.66、P<0.01]。结论：miRNA-325-3p 能够通过下调靶基因CK13的表达降低鼻咽癌细胞CNE1 对放疗的敏感性。     

miR-513a-5p慢病毒载体的构建及其对人骨肉瘤细胞放疗敏感性的影响

目的:构建miR-513a-5p慢病毒过表达载体，转染人骨肉瘤细胞株，观察miR-513a-5p对人骨肉瘤细胞放疗敏感性的影响。方法:PCR法扩增人miR-513a-5p基因，克隆入pLentis-CMV-GFP-MCS-PGK-PURO载体获得重组质粒pLentis-miR513a，双酶切鉴定并测序后将正确的重组质粒和对照质粒转染293FT细胞制备慢病毒，分别转染骨肉瘤HOS和U2OS细胞，qRT-PCR法及荧光显微镜鉴定转染结果。克隆形成实验、MTT法检测miR-513a-5p高表达HOS和U2OS细胞在X射线照射下细胞存活情况。结果:双酶切及测序结果确定成功构建miR-513a-5p慢病毒载体pLentis-miR513a。qRT-PCR结果提示，转染骨肉瘤细胞株后miR-513a-5p表达显著升高。克隆形成实验结果显示miR-513a-5p高表达后骨肉瘤细胞在X射线照射下细胞增殖减慢。MTT结果提示miR-513a-5p高表达骨肉瘤细胞经X射线照射后细胞存活减少。结论:成功构建了miR-513a-5p慢病毒载体，建立了高效稳定表达miR-513a-5p的骨肉瘤细胞株，高表达miR-513a-5p能显著增加X射线照射后骨肉瘤细胞的放疗敏感性。     

基于TGF-β1/p38MAPK/FN信号通路的放射性食管炎发病机制的研究

Objective To investigate the pathogenesis mechanism of radiation esophagitis from the perspective of mucosal regeneration and to determine whether it is associated with TGF-β1/p38MAPKs/FN signaling pathway. Methods The pathological analysis of esophageal specimens was performed by HE staining method. The expression of FN and TGF-β1 genes were observed by real time-PCR method, and the expression of tissue proteins TGF-β1, p38 and FN were detected by Western blot. Results The weights, food intakes and water intakes at the first week after the occurrence of radiation esophagitis were significantly decreased (P<0.05) and recovered at the fourth week. The esophageal mucosa was destructed at the first and second weeks, and the regeneration occurred in the fourth weeks; TGF-β1 and p38MAPK protein expression increased first and then decreased, while FN protein expression decreased first and then increased. Conclusion The TGF-β1/p38MAPK/FN signaling pathway may be involved in the process of mucosal repair. © 2020, CHINA RESEARCH ON PREVENTION AND TREATMENT. All rights reserved.     

LncRNA UCA1对肺癌细胞放射敏感性影响及机制研究

目的 研究长链非编码RNA (LncRNA) UCA1对肺癌细胞增殖、凋亡及放射敏感性影响及其机制。方法 运用qRT-PCR法检测肺癌细胞A549、H1299和人正常肺细胞HBE中UCA1、miR-513a-5p表达。将si-con组(转染si-con)、si-UCA1组(转染si-UCA1)、miR-513a-5p组(转染miR-513a-5p mimics)、miR-NC组(转染miR-NC)、IR+si-con组(转染si-con+照射)、IR+si-UCA1组(转染miR-NC+照射)、IR+miR-513a-5p组(转染miR-513a-5p mimics+照射)、IR+miR-NC组(转染miR-NC+照射)、IR+si-UCA1+anti-miR-513a-5p组(共转染si-UCA1和anti-miR-513a-5p+照射)均用脂质体法转染至A549、H1299细胞,然后部分组进行4Gy照射。MTT法检测各组细胞增殖,克隆形成实验检测细胞增敏比,流式细胞术检测各组细胞凋亡,双荧光素没报告基因检测实验检测各组细胞的荧光活性。结果 与HBE细胞相比,A549、H1299细胞中UCA1表达显著升高(P<0.05),miR-513a-5p表达显著降低(P<0.05)。抑制UCA1、过表达miR-513a-5p均可明显抑制A549、H1299细胞增殖、促进凋亡、提高放射敏感性(放射增敏比为1.897、2.146和1.615、1.872)。miR-513a-5p可抑制野生型UCA1细胞的荧光活性,且UCA1可负向调控miR-513a-5p的表达。抑制miR-513a-5p可逆转抑制UCA1对细胞的放射敏感性的增强作用。结论 抑制LncRNA UCA1可增强放射对肺癌细胞敏感性,其机制可能与靶向抑制miR-513a-5p有关。