miR-124靶向STAT3改善脑恶性胶质瘤细胞辐射敏感性

目的 研究miR-124在放射敏感及耐受的脑恶性胶质瘤细胞LN229和LN229R中的表达以及miR-124对细胞放射敏感性的影响,并深入探讨miR-124调控LN229R细胞放射敏感性的作用机制。方法 将miR-124模拟物（miR-124）及阴性对照（miR-NC）,STAT3过表达质粒（STAT3）及pcDNA3.1质粒（pcDNA）单独或共转染到放射抵抗的胶质瘤细胞LN229R中。qRT-PCR检测LN229和LN229R细胞中miR-124的表达;克隆形成实验分析不同放射剂量下LN229R细胞的生存率以及敏感性相关参数值;流式细胞术分析LN229R细胞的凋亡情况;生物信息学预测miR-124和STAT3的靶向关系,并利用双荧光素酶报告分析加以验证;Western blot分析STAT3的蛋白表达水平。结果 与LN229组（1.02±0.09）相比,miR-124在LN229R细胞中的表达水平（0.32±0.03）显著降低,差异有统计学意义（t=12.780,P<0.05）;与miR-NC组（0.95±0.06）相比,转染miR-124模拟物可促进LN229R细胞中miR-124的表达（4.02±0.39）（t=13.476,P<0.05）;8 Gy照射条件下,miR-124过表达组癌细胞的生存率（0.003±0.000 4）显著低于miR-NC组（0.033±0.005 0）（t=5.655,P<0.05）,细胞凋亡率（22.34±2.42）%显著高于miR-NC组（4.69±0.51）%（t=12.361,P<0.05）;STAT3是miR-124的靶基因;外源回补STAT3可逆转miR-124对LN229R细胞生存的抑制作用。结论 miR-124通过靶向STAT3改善LN229R细胞的放射敏感性。     

匹伐他汀钙有关物质的合成

目的：为控制匹伐他汀钙的质量,合成原药中3种有关物质。方法：以（8）为原料经不对称羟醛缩合、反立体选择性还原得到了有关物质（3）和有关物质（4）。匹伐他汀钙经DDQ氧化得到了有关物质（7）。结果与结论：合成了匹伐他汀钙原药中3种有关物质,并经1H-NMR和MS等确证结构,纯度经HPLC 检测均在96%以上,可以作为匹伐他汀钙原药质量控制的对照品。     

Synthesis,molecular docking and biological evaluation of 1‐phenylsulphonyl‐2‐(1‐methylindol‐3‐yl)‐benzimidazole derivatives as novel potential tubulin assembling inhibitors

A series of new 1‐phenylsulphonyl‐2‐(1‐methylindol‐3‐yl)‐benzimidazole derivatives were designed, synthesized and evaluated as potential inhibitors of tubulin polymerization and anthropic cancer cell lines. Among them, compound 33 displayed the most potent tubulin polymerization inhibitory activity in vitro (IC₅₀ = 1.41 μM) and strong antiproliferative activities against A549, Hela, HepG2 and MCF‐7 cell lines in vitro with GI₅₀ value of 1.6, 2.7, 2.9 and 4.3 μM, respectively, comparable with the positive control colchicine (GI₅₀ value of 4.1, 7.2, 9.5 and 14.5 μM, respectively) and CA‐4 (GI₅₀ value of 2.2, 4.3, 6.4 and 11.4 μM, respectively). Simultaneously, we evaluated that compound 33 could effectively induce apoptosis of A549 associated with G2/M phase cell cycle arrest. Immunofluorescence microscopy also clearly indicated compound 33 a potent antimicrotubule agent. Docking simulation showed that compound 33 could bind tightly with the colchicine‐binding site and act as a tubulin inhibitor. Three‐dimensional‐QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent tubulin assembling inhibitory activity in the future.     

北京市2019年腹泻病例中札如病毒基因特征分析

目的 了解北京市肠道门诊散发腹泻病例中札如病毒的基因型别及特征。方法 收集2019年北京市肠道门诊散发腹泻病例的粪便样本,应用实时荧光RT-PCR对样本进行札如病毒核酸检测,对阳性样本应用不同种RT-PCR方法进行札如病毒衣壳蛋白VP1区和聚合酶RdRp区部分基因片段扩增,对扩增阳性产物进行测序,应用BioEdit 7.0.9.0软件对序列进行比对,应用Mega 6.06软件构建进化树进行分析。结果 札如病毒总检出率为2.89%（44/1 522）,<5岁病例的检出率为3.34%（18/539）,≥5岁病例的检出率为2.64%（26/983）。衣壳蛋白VP1区基因测序成功23株,包括8个基因型（GⅠ.2型6株、GⅠ.1型和GⅡ.3型各5株,GⅠ.3型和GⅡ.5型各2株,GⅠ.5型、GⅡ.1型和GⅣ.1型各1株）;≥5岁病例占16株,GⅠ.2型构成比最高（37.50%,6/16）,<5岁病例占7株,GⅠ.1型和GⅡ.3型构成比最高（均为42.86%,3/7）;每个基因型内部相似性为95.5%~100.0%,与不同年份、不同国家的人源或污水源的51株参考株相似性为92.2%~100.0%。聚合酶RdRp区测序成功25株8个基因型（9株GⅡ.P3型,4株GⅠ.P3型,GⅠ.P1型、GⅠ.P2型和GⅡ.P1型各为3株,GⅠ.P5型、GⅡ.P5型和GⅣ.P1型各为1株）;≥5岁病例占15株,GⅡ.P3型构成比最高（40.00%,6/15）,<5岁病例占10株,GⅠ.P1型、GⅡ.P1型和GⅡ.P3型构成比最高（均为30.00%,3/10）;每个基因型内部相似性为94.0%~100.0%,与不同年份、不同国家的人源或污水源的39株参考株相似性为90.2%~99.1%。结论 札如病毒是北京市散发腹泻病例的病原之一,主要基因组为GⅠ和GⅡ,基因型多样且分散;≥5岁和<5岁人群腹泻病例主要基因型不同。     

Lung function impairment in relation to cognition and vascular brain lesions: the Rotterdam Study

Journal of Neurology - To investigate the association of chronic obstructive pulmonary disease (COPD) and Preserved Ratio Impaired Spirometry (PRISm) with cognitive performance and presence of...     

间充质干细胞外泌体对海马神经元氧化应激的调控作用

目的 探讨间充质干细胞外泌体(Mesenchymal stem cell derived-exosomes,MSC-Exo)对海马神经元氧化应激的作用。方法 首先体外培养原代小鼠海马神经元,用H₂O₂刺激建立氧化应激模型,细胞计数试剂盒(Cell counting kit-8,CCK8)筛选最佳H₂O₂水平并检测不同水平MSC-Exo对细胞活力的作用,试剂盒检测超氧化物歧化酶(Superoxide dismutase,SOD)的活性,酶联免疫吸附测定法(Enzyme linked immunosorbent assay,ELISA)检测DNA氧化损伤分子8-羟基脱氧鸟苷(8-hydroxy-2 deoxyguanosine,8-OHdG)的表达水平,然后免疫荧光和免疫印迹检测应激和损伤分子一氧化氮合成酶(Inducible nitric oxide synthase,iNOS)、高迁移率族蛋白B1(High mobility group box 1,HMGB1)的表达水平。结果 CCK8细胞活力实验显示,10 μg/mL及以上水平的MSC-Exo对海马神经元氧化损伤具有明显的保护作用; 与对照组比较,H₂O₂组SOD的活性显著下降,而在MSC-Exo+H₂O₂组有所提高,趋于正常; 与对照组比较,H₂O₂作用后iNOS,HMGB1,8-OHdG等分子的表达水平显著上调(P<0.01),MSC-Exo作用于模型后与H₂O₂组比较,这些分子的表达水平显著下调(P<0.01)。结论 MSC-Exo作用于H₂O₂诱导的海马神经元氧化应激模型后能够增加SOD的活性,抑制海马神经元iNOS,HMGB1,8-OHdG等分子的表达,表明MSC-Exo对海马神经元氧化应激有一定的调控作用。     

机器人手术系统在结直肠手术的应用

腹腔镜手术改善了结直肠手术患者的短期预后且有着不劣于开腹手术的长期预后,但对骨盆狭窄的低位直肠癌男性患者或肥胖的右半结肠癌患者,因其空间窄、暴露困难及腔镜器械灵活不足,腹腔镜手术的开展存在一定难度。机器人手术系统有视野更清晰、操作更灵活等优点而逐渐在结直肠手术中得到推广,但目前对于机器人手术系统在结直肠领域的应用现状和效果并不明确。本文将从手术机器人在传统结直肠手术中应用、机器人结直肠手术新进展、机器人手术不足三方面进行综述。     

钩钢板治疗Neer II型锁骨骨折术后锁骨中段骨折的危险因素分析

目的分析钩钢板治疗Neer II型锁骨骨折术后锁骨中段骨折的潜在危险因素。 方法在2009年3月至2019年7月期间,有294例患者使用了钩钢板治疗锁骨远端骨折并符合入选标准,其中279例术后未发生锁骨中段骨折的患者（对照组）、15例发生了术后锁骨中段骨折的患者（并发症组）。本研究收集了患者的数据,包括性别、年龄、骨折患侧、体重指数、吸烟情况、最内侧螺钉的种类、是否由住院医师作为术者进行手术、术中钩钢板是否进行了塑型、钢板的孔数、钩的深度、并发症的发生时间和发生时有无第二次创伤。本研究采用卡方检验对所有潜在的危险因素在对照组和并发症组间进行了比较。最后对具有统计学差异的变量进行了Logistic回归分析。 结果高龄患者在使用钩钢板治疗锁骨远端骨折后,更容易出现锁骨中段骨折（OR= 3.478; 95% CI : 1.719~15.407; P= 0.003）。 结论患者高龄可以显著增加钩钢板固定后锁骨中段骨折的发生率。     

Pyridoxamine ameliorates methylglyoxal-induced macrophage dysfunction to facilitate tissue repair in diabetic wounds

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during hyperglycaemia. MGO combines with proteins to form advanced glycation end products (AGEs), leading to cellular dysfunction and organ damage. In type 2 diabetes mellitus (T2DM), the higher the plasma MGO concentration, the higher the lower extremity amputation rate. Here, we aimed to identify the mechanisms of MGO-induced dysfunction. We observed that the accumulation of MGO-derived AGEs in human diabetic wounds increased, whereas the expression of glyoxalase 1 (GLO1), a key metabolic enzyme of MGO, decreased. We show for the first time that topical application of pyridoxamine (PM), a natural vitamin B6 analogue, reduced the accumulation of MGO-derived AGEs in the wound tissue of type-2 diabetic mice, promoted the influx of macrophages in the early stage of tissue repair, improved the dysfunctional inflammatory response, and accelerated wound healing. In vitro, MGO damaged the phagocytic functions of M1-like macrophages induced by lipopolysaccharide (LPS), but not those of M0-like macrophages induced by PMA or of M2-like macrophages induced by interleukins 4 (IL-4) and 13 (IL-13); the impaired phagocytosis of M1-like macrophages was rescued by PM administration. These findings suggest that the increase in MGO metabolism in vivo might contribute to macrophage dysfunction, thereby affecting wound healing. Our results indicate that PM may be a novel therapeutic approach for treating diabetic wounds. MGO forms protein adducts that cause macrophage dysfunction. These adducts cause cell and organ dysfunction that is common in diabetes. Pyridoxamine scavenges MGO to ameliorate this dysfunction, promoting wound healing. Pyridoxamine could be used therapeutically to treat non-healing diabetic wounds.