Noncoding telomeric repeat‐containing RNA inhibits the progression of hepatocellular carcinoma by regulating telomerase‐mediated telomere length

Telomeric repeat‐containing RNA (TERRA) is closely involved in the regulation of telomere length, which plays critical roles in tumorigenesis. However, the biological significance of TERRA in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we found that HCC cells show a frequent downregulation of TERRA and its positive regulator TTAGGG repeat binding factor‐1 (TRF1), whereas the negative regulator TTAGGG repeat binding factor‐1 (TRF2) was upregulated. We found that TERRA, TRF1, and TRF2 contributed to poor prognosis of HCC patients. Importantly, we found that the downregulation of TERRA significantly promoted HCC cell growth and metastasis in vitro and in vivo, whereas the upregulation of TERRA showed an opposite effect. Mechanistically, downregulation of TERRA significantly increased telomerase activity and promoted telomere elongation. Moreover, the inhibitory effects of TERRA overexpression on the growth and metastasis of HCC cells were reversed by treatment with TA‐65 that activates telomerase activity. In contrast, the protumor effect of TERRA downregulation was reversed by treatment with TMPyP4 that inhibits telomerase activity. Our findings reveal that TERRA plays a critical role in HCC cell growth and metastasis, indicating that TERRA is a potential therapeutic target for HCC.     

多学科会诊模式在结肠癌手术患者中的应用效果

目的分析多学科会诊(MDT)模式对结肠癌患者术后胃肠功能恢复及并发症的效果评价。方法将2017年1月至12月收治的50例结肠癌患者作为对照组,给予常规干预措施;将2018年1月至12月收治的50例结肠癌患者为观察组,采取MDT模式干预。比较两组患者的胃肠功能恢复情况及一般围手术期指标;干预前和干预后2周,采用世界卫生组织生存质量评估量表(WHOQOL-BREF)评估两组患者的生活质量;术后3天,采用视觉模拟评分法(VAS)评估两组患者腹胀发生情况;比较两组患者术后并发症发生情况。结果观察组患者肛门排气时间、首次排便时间、肠鸣音恢复时间、禁食时间、伤口愈合时间、住院时间、术后下床时间均短于对照组患者,差异均有统计学意义(P﹤0.05)。干预后2周,两组患者环境领域、社会领域、心理领域、生理领域及总体健康评分均高于本组干预前,且观察组患者环境领域、社会领域、心理领域、生理领域及总体健康评分均明显高于对照组患者,差异均有统计学意义(P﹤0.05)。术后3天,观察组患者的腹胀程度低于对照组患者,差异有统计学意义(P﹤0.05)。观察组患者术后并发症总发生率为6.0%,低于对照组患者的20.0%,差异有统计学意义(P﹤0.05)。结论MDT模式干预可促进患者术后胃肠功能恢复情况,缩短伤口愈合时间及住院时间,降低术后并发症发生率,并改善了患者的生活质量。     

计划镇静在高龄低肺功能肺癌术后机械通气患者程序化脱机中的应用

目的 研究计划镇静应用于高龄低肺功能肺癌术后机械通气患者程序化脱机的临床效果。方法 将60例高龄低肺功能肺癌术后机械通气患者分为对照组和计划镇静组，对照组患者按需镇静，计划镇静组患者实施计划镇静方案。两组患者在镇静过程中Richmond躁动-镇静量表评分的目标分值为-3～-1分,最终均行程序化脱机。结果 两组患者首次计划性气管插管拔除成功率分别为43%和80%，谵妄发生率分别为20%和7%，差异有统计学意义（P＜0.05），而已拔管患者48h内再插率分别为7%和3%，差异无统计学意义（P＞0.05），两组患者首次计划性气管插管拔除后2h血气分析比较，计划镇静组明显优于对照组（P＜0.05）。结论 高龄低肺功能肺癌术后机械通气患者给予计划镇静，可以改善患者的临床转归，提高患者对治疗的依从性，减少气管插管的非计划性拔除率。     

Prognostic and immunological roles of Fc fragment of IgG binding protein in colorectal cancer

Valuable diagnostic and prognostic biomarkers are urgently needed for colorectal cancer (CRC), which is one of the leading causes of mortality worldwide. Previous studies have reported altered expression of a mucin-like protein Fc fragment of IgG binding protein (FCGBP) in various types of cancer, but its potential diagnostic, prognostic and immunological roles in CRC remain to be determined. Therefore, the aim of current study was to investigate the potential roles of FCGBP in CRC. The present study investigated FCGBP mutations and changes in its expression levels using a combination of microarray and public dataset analyses, as well as immunohistochemistry. The results demonstrated a 10.5% mutation frequency in the FCGBP coding sequence in CRC tissues, and identified decreased FCGBP mRNA or protein expression levels in colorectal adenoma and CRC (compared with those in normal colorectal tissues from healthy control subjects), including pathologically advanced CRC (stage III+IV vs. I+II). Survival analysis using the GEPIA and Kaplan-Meier Plotter databases revealed that low FCGBP expression levels were associated with short overall, disease-free, relapse-free and event-free survival times in patients with CRC. Notably, analysis using the online Tumor IMmune Estimation Resource database revealed a positive correlation between FCGBP expression levels and the extent of infiltrating immune cells, such as B cells and dendritic cells. Consistently, the expression levels of most markers (51/57) for various types of immune cells were significantly correlated with FCGBP expression levels in CRC tissues. These findings suggested that FCGBP may serve as a diagnostic and prognostic biomarker, and that FCGBP may be associated with immune infiltration in CRC.     

调强放射治疗在不可切除老年胃癌患者姑息治疗中的临床价值

目的:探讨调强放射治疗（intensity-modulated radiotherapy，IMRT）在老年不可切除胃癌患者中姑息减症治疗的临床价值。方法:回顾性分析23例老年病理确诊胃癌患者，手术无法切除，伴有出血(78.3%)、梗阻(52.2%)及疼痛(69.6%)症状；采用调强放射治疗为主的姑息治疗。观察治疗后症状缓解率、症状缓解时间以及中位生存时间（median overall survival，mOS）。结果: 全组患者男性16例，女性7例，年龄60~89岁(平均74岁)；Ⅲ期9例，Ⅳ期14例。全部采用6MV X线IMRT，常规分割，1.8~2.2 Gy/次，5次/周，总剂量35~50 Gy；同步放化5例，序贯化疗9例。出血、梗阻及疼痛症状缓解率分别为77.8%(14例)、58.3%(7例)和56.2%(9例)；中位症状缓解时间分别为101天、87天和99天。全组中位生存时间114天，症状缓解者中位生存时间较症状未缓解者明显延长(129天 vs 73天，P=0.01)。治疗期间出现Ⅲ级毒副反应者2例。结论:IMRT是一个有效的、可耐受的并能够缓解老年不可切除胃癌患者临床症状的治疗手段，可以改善患者生活质量，延长生存期。     

Protective role of histone deacetylase 4 from ultraviolet radiation-induced DNA lesions

Ultraviolet B (UVB) exposure is a core factor that leads to skin disease or carcinogenesis through the insufficient repair of DNA lesions. UVB-induced DNA lesions are mainly removed by the nucleotide excision repair (NER) mechanism. The expression of histone deacetylase 4 (HDAC4) is altered in the skin upon UVB exposure, indicating its possible implication in UVB-induced DNA lesions repair. Here, we investigated the role of HDAC4 in the NER removal of the main classes of UVB-induced DNA lesions consisting of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). We found that UVB irradiation increased HDAC4 expression at both the mRNA and protein levels. HDAC4 interacted with NER factor XPC, which played an important role in effectively removing the UVB-induced DNA lesions. This study provides an understanding of the HDAC4 function in DNA repair, which will allow the development of efficient strategies to protect the skin from UVR-induced diseases.     

同期多原发肺癌诊断标准更新与分子遗传学特征研究进展

由于高分辨率胸部CT和肺癌早期筛查的普及,同期多原发肺癌(或称同时性多原发肺癌,synchronous multiple primary lung cancer,sMPLC)的检出率逐步提高。sMPLC与肺癌肺内转移的鉴别诊断成为尤其重要的临床问题。借助高通量测序技术刻画sMPLC的分子遗传学特征是目前研究的热点,既能阐释sMPLC的发生发展规律,也可作为临床病理诊断标准的补充和完善。本文对sMPLC诊断标准的更新进行总结,并以克隆性分析领域为例,综述sMPLC分子遗传学特征的研究进展。     

NRAGE影响人食管癌细胞放射抗性的作用及其机制研究

背景与目的：食管癌是全球威胁人类生命和健康的常见恶性肿瘤之一，中国每年食管癌发病人数占全球发病总人数的一半以上，以食管鳞癌最为常见。放疗是食管癌三大治疗手段之一，而放射抗性是导致其治疗失败的主要原因。神经营养因子受体相互作用MAGE类药物（neurotrophin receptor-interacting MAGE homolog，NRAGE）在放射抗性细胞株TE13R120中表达量明显高于亲本TE13细胞，且NRAGE亚细胞定位变化可能参与食管癌细胞放射抗性的形成。通过基因转染构建NRAGE稳定表达的食管癌细胞系，以进一步明确NRAGE基因与食管鳞癌细胞放射抗性的关系，分析该基因影响放射抗性的具体机制。方法：通过基因转染构建NRAGE稳定表达的食管癌细胞系。采用细胞克隆形成实验检测细胞放射敏感性，采用流式细胞术检测细胞周期及凋亡；细胞划痕、Transwell侵袭实验检测细胞迁移、侵袭能力，采用实时荧光定量聚合酶链反应（real-time fluorescence quantitive polymerase chain reaction，RTFQ-PCR）和蛋白质印迹法（Western blot）检测细胞中β-catenin表达情况。组间差异采用t检验或方差分析。结果：实验分为转染过表达组（Eca109/NRAGE组）和空白对照组（Eca109组）。Eca109/NRAGE细胞中NRAGE的表达量明显高于Eca109（t=29.65，P<0.05）。照射后Eca109/NRAGE细胞的放射抗性显著高于Eca109。流式细胞术检测结果显示，Eca109/NRAGE细胞中对射线抵抗性最强的S期细胞比例增加，对射线最敏感的G ₂ /M期减少。Eca109/NRAGE细胞凋亡率较Eca109细胞降低（t=3.268，P<0.05）。Eca109/NRAGE细胞迁移和侵袭能力均高于Eca109。RTFQ-PCR和Western blot检测结果显示，β-catenin的mRNA表达及蛋白水平在Eca109/NRAGE细胞中明显高于Eca109（t=15.87，P<0.05）。结论：NRAGE参与Eca109细胞放射抗性的形成，改变细胞的细胞周期分布和凋亡情况，影响细胞迁移及侵袭能力并可能影响食管癌细胞的放射敏感性，该作用可能与激活Wnt/β-catenin信号转导通路有关。