肝癌患者行肝动脉化疗栓塞术前营养风险筛查的应用研究

目的 探讨肝癌患者行肝动脉化疗栓塞术前营养风险筛查的应用及对手术疗效、生活质量和生存预后的影响。方法 选取2013年1月至2018年12月首都医科大学附属北京世纪坛医院介入治疗科收治的行肝动脉化疗栓塞术治疗的中晚期肝癌患者180例，根据营养风险筛查2002（NRS 2002）将研究人群分为有营养风险组（NRS 2002≥3分）和无营养风险组（NRS 2002<3分），比较两组患者的临床基线特征、反映营养状况的物理和生化指标以及行肝动脉化疗栓塞术（TACE）手术疗效及并发症和生活质量评分，采用Kaplan-Meier方法对两组患者进行生存分析，比较上消化道出血、肝性脑病等临床终点事件的发生率。结果 纳入标准的180例患者中，无营养风险患者有85例，有营养风险患者有95例，营养风险发生率52.8%。两组患者的肱三头肌皮褶厚度、上臂肌围、体质指数、白蛋白之间存在统计学差异（P<0.05）；两组患者的总蛋白和前蛋白之间没有显著的统计学差异（P>0.05）。两组患者的TACE治疗肿瘤的临床有效率和术后并发症没有显著的差异（P>0.05）。无营养风险患者生活质量评分比有营养风险患者评分高（P<0.05）。有营养风险患者3年生存率为54.74%；无营养风险患者3年生存率为68.24%，存在统计学意义（HR=0.61，P=0.05， 95%CI=0.38~0.98）。肝性脑病、低蛋白血症和贫血的发生率两组之间有统计学差异（P<0.05）。上消化道出血和门脉癌栓堵塞的发生率之间没有统计学差异（P>0.05）。结论 营养风险筛查对于行TACE手术患者具有重要意义，营养风险与临床结局密切相关。     

基因间长链非编码RNA152靶向微小RNA?103a?3p对非小细胞肺癌细胞增殖和侵袭迁移的影响

目的探讨基因间长链非编码RNA 152(LINC00152)靶向调控微小RNA-103a-3p(miR-103a-3p)表达及对非小细胞肺癌(NSCLC)细胞增殖和侵袭迁移的影响。方法采用实时定量PCR(QPCR)检测正常肺上皮细胞BEAS-2B及NSCLC细胞(ANIP-973、NCI-H157、A549和NCI-H1975)的LINC00152水平。选取LINC00152水平最高的细胞分别转染LINC00152特异性小干扰RNA(si-LINC00152组)或无关序列(si-NC组),另设未转染细胞为对照组。QPCR检测LINC00152水平,活细胞计数CCK-8法、Transwell小室和划痕实验测定细胞增殖、侵袭和迁移能力,Western blotting检测基质金属蛋白酶(MMP)-2、MMP-9和第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)的水平;荧光素酶报告实验验证LINC00152靶向结合miR-103a-3p的能力。结果NSCLC细胞的LINC00152水平均高于BEAS-2B细胞(P<0.05),尤其是NCI-H1975细胞的最高。si-LINC00152组的LINC00152水平为0.352±0.087,低于对照组的1.058±0.219和si-NC组的1.126±0.139(P<0.05)。与si-NC组和对照组相比,si-LINC00152组NCI-H1975细胞转染48、72 h的增殖活力下降(P<0.05);si-LINC00152组的划痕愈合率和穿膜细胞数分别为(27.386±2.428)%和(78.840±5.031)个,低于si-NC组的(77.675±4.803)%和(179.208±13.264)个及对照组的(76.371±5.385)%和(174.003±15.678)个(P<0.05);与si-NC组和对照组相比,si-LINC00152组的MMP-2和MMP-9水平均降低,而PTEN水平升高(P<0.05)。对照组和si-NC组上述指标的差异无统计学意义(P>0.05)。双荧光素酶报告分析证实,miR-103a-3p模拟物降低了野生型LINC00152的荧光素酶活性(P<0.05),但对突变型无影响(P>0.05)。结论LINC00152在NSCLC细胞中高表达并发挥促癌作用,与NSCLC的迁移侵袭密切相关,LINC00152与miR-103a-3p间的相互作用在NSCLC靶向治疗中有一定潜能。     

A Phase I Trial of Trametinib in Combination with Sorafenib in Patients with Advanced Hepatocellular Cancer

Lessons Learned

• The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy.
• Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily.
• The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.

BackgroundThe RAS/RAF/MEK/ERK signaling pathway is associated with proliferation and progression of hepatocellular carcinoma (HCC). Preclinical data suggest that paradoxical activation of the MAPK pathway may be one of the resistance mechanisms of sorafenib; therefore, we evaluated trametinib plus sorafenib in HCC.MethodsThis was a phase I study with a 3+3 design in patients with treatment‐naïve advanced HCC. The primary objective was safety and tolerability. The secondary objective was clinical efficacy.ResultsA total of 17 patients were treated with three different doses of trametinib and sorafenib. Two patients experienced dose‐limiting toxicity, including grade 4 hypertension and grade 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin over 7 days. Maximum tolerated dose was trametinib 1.5 mg daily and sorafenib 200 mg twice a day. The most common grade 3/4 treatment‐related adverse events were elevated AST (37%) and hypertension (24%). Among 11 evaluable patients, 7 (63.6%) had stable disease with no objective response. The median progression‐free survival (PFS) and overall survival (OS) were 3.7 and 7.8 months, respectively. Phosphorylated‐ERK was evaluated as a pharmacodynamic marker, and sorafenib plus trametinib inhibited phosphorylated‐ERK up to 98.1% (median: 81.2%) in peripheral blood mononuclear cells.ConclusionTrametinib and sorafenib can be safely administered up to trametinib 1.5 mg daily and sorafenib 200 mg twice a day with limited anticancer activity in advanced HCC.     

新型四腔水箱在腹外科腔镜电凝线清洗消毒中的应用研究

摘要〓目的〓研究四腔水箱在腹外科腔镜电凝线擦拭法清洗消毒中的应用效果。方法〓通过目测法和ATP生物荧光法,对本研究的四腔水箱用于腹外科腔镜电凝线的清洗效果进行评价。结果〓传统治疗碗清洗的206件腔镜电凝线清洗质量合格率为86.4%,四腔水箱清洗的206件腹腔镜电凝线清洗质量合格率为94.6%,差异有统计学意义（P＜0.01）。用四腔水箱清洗腔镜电凝线擦拭过程中的护理人员满意度较高。结论〓四腔水箱可提高腹外科腔镜电凝线清洗质量和护理人员满意度。