三联预康复策略在肝癌腹腔镜肝切除术中的应用价值

目的:探讨三联预康复策略在肝癌腹腔镜肝切除术中的应用价值。方法:选取2015年1月至2018年1月四川大学华西医院胆道外科收治的120例行腹腔镜肝切除术的肝癌患者，按随机数字表法分为观察组及对照组各60例。观察组在门诊收治当日开始三联预康复策略干预，干预时间约2～4周；对照组予以常规肝癌腹腔镜肝切除术术前准备。于干预前、术前1天及术后4周分别记录六分钟步行距离(6MWT)、医院焦虑抑郁量表(HADS)评分、健康调查简表(SF-36)评分及检测血清白蛋白(ALB)、前白蛋白(PA)、转铁蛋白(TRF)水平。结果:术前1天，观察组6MWT、血清ALB、PA、TRF水平高于干预前(P＜0.05)；对照组6MWT、血清ALB、PA、TRF水平与干预前差异无统计学意义(P＞0.05)；术后4周，观察组6MWT、血清ALB、PA、TRF水平与干预前差异无统计学意义(P＞0.05)；对照组6MWT、血清ALB、PA、TRF水平低于干预前(P＜0.05)；术前1天、术后4周观察组HADS评分低于干预前，SF-36评分高于干预前(P＜0.05)；对照组HADS、SF-36评分与干预前差异无统计学意义(P＞0.05)；术前1天、术后4周，观察组6MWT、SF-36评分、血清ALB、PA、TRF水平高于对照组，HADS评分低于对照组(P＜0.05)。结论:三联预康复策略应用于肝癌腹腔镜肝切除术可明显改善患者围术期活动能力、心理状态及营养状况，加速患者术后恢复。     

姑息性胃切除联合术后化疗评分在腹膜转移的胃癌患者预后评估中的临床意义

目的:探讨姑息性胃切除联合术后化疗评分在腹膜转移的胃癌患者预后评估中的临床意义。方法:回顾性分析2010年1月至2016年12月7年间收治的287例发生腹膜转移的胃癌患者的临床病理资料。通过χ2检验分析评分与患者临床病理因素间的关系。通过Kaplan-Meier法绘制生存曲线，Log-rank检验比较患者生存率的差异；采用Cox比例风险回归模型对患者进行预后分析。结果:与评分中得分为2分和1分的患者相比，得分为0分的患者肿瘤侵润至T4b 期的患者较少［31%(18/58)比50.8%(63/124)、56.2%(59/105)，P=0.039］。全组患者的中位生存时间仅为8.7月。对患者进行单因素预后分析结果显示，血清白蛋白浓度（≤40 g/L），腹水，腹膜转移范围较大，肿瘤T分期较晚，评分得分较高的患者预后较差（均P＜0.05）。将上述因素纳入Cox多因素分析结果显示:评分［HR（95%CI）:1.384（1.165~1.644），P=0.000］，血清白蛋白浓度［HR（95%CI）:0.759（0.593~0.971），P=0.028］，肿瘤T分期［HR（95%CI）:1.493（1.216~1.832），P=0.000］是患者预后的独立危险因素。结论:评分对于胃癌伴腹膜转移患者的预后生存评估具有重要的临床意义。     

甲状腺乳头状癌伴发桥本甲状腺炎的临床研究

背景与目的：甲状腺乳头状癌（papillary thyroid carcinoma，PTC）和桥本甲状腺炎（Hashimoto’s thyroiditis，HT）的发病率均呈上升趋势，两者之间的关系已成为目前研究的热点。探讨PTC和HT之间的关系。方法：回顾性分析2014—2015年期间在中国科学院大学附属肿瘤医院头颈肿瘤外科行甲状腺癌手术治疗的首诊患者306例，术后病理学检查均明确诊断为PTC，其中术后病理学确诊伴发HT者42例，比较伴发HT与未伴发HT患者的临床病理学特征。结果：PTC患者女性发病年龄高于男性（46.2岁 vs 41.9岁）。相较于与未伴发HT的PTC患者，伴发HT的患者中女性比例更高（93% vs77%），中央区淋巴结数目较多［（5.0±3.4）枚 vs （2.5±2.7）枚］，术前促甲状腺激素（thyroid-stimulating hormone，TSH）水平较高［（3.28±1.91）μU/mL vs （2.12±1.29）μU/mL］，术前抗甲状腺过氧化物酶抗体（thyroid peroxidaseantibody，TPOAb）阳性率较高（55% vs 14%），术前甲状腺球蛋白抗体（thyroglobulin antibodies，TgAb）阳性率较高（69% vs 13%）。发生中央区淋巴结转移的患者中，中央区淋巴结转移数目与中央区淋巴结总数显著相关（Pearson相关系数=0.582）。多因素logistic回归分析发现，男性、低龄、被膜侵犯是PTC患者中央区淋巴结转移的独立危险因素。结论：伴发HT对PTC患者的预后无显著影响。伴发HT的PTC患者TSH水平显著偏高，提示HT可能是PTC发病风险因素之一。中央区淋巴结转移数目与中央区淋巴结总数相关，推测PTC淋巴结转移可能与淋巴结炎症反应相关。     

甲状腺未分化癌发生肺转移的危险因素分析

目的:探讨甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)发生肺转移的危险因素。方法:回顾性分析2010年至2015年SEER数据库中被确诊为ATC的405例患者临床病理资料。通过对年龄、种族、性别、原发灶最大径、原发灶数量、甲状腺外组织侵犯、食管侵犯、气管侵犯、中央区淋巴结转移、颈侧区淋巴结转移10个因素进行单因素分析,进而对单因素分析中有统计学差异的指标行多因素Logistic回归分析,寻找ATC患者发生肺转移的危险因素。结果:405例ATC患者中,发生肺转移107例,未发生肺转移298例。单因素分析显示:原发灶最大径>4 cm、甲状腺外组织侵犯、颈侧区淋巴结转移是预测发生肺转移的显著性因素(均P<0.05)。多因素Logistic回归分析显示:原发灶最大径>4 cm及颈侧区淋巴结转移是ATC患者发生肺转移的独立危险因素(均P<0.05)。结论:原发灶最大径>4 cm、颈侧区淋巴结转移的ATC患者极易发生肺转移,因此,一定要认真参考病理结果,若发现存在以上肺转移危险因素,则积极采取多模式治疗方案,并缩短随访时间,行相关检查(如胸部CT扫描、PET-CT等)。     

Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

BACKGROUNDDue to the special clinical features and biologic characteristics of adolescent and young adult (AYA) cancers, AYA cancers are different from cancers in children and elderly individuals. However, there are few reports on AYA hepatocellular carcinoma (HCC).AIMTo investigate the overall survival (OS) of AYA (15-39 years) and elderly (40-74 years) patients with HCC.METHODSThe data of all the HCC cases were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2015 and were then divided into two groups based on age: AYA group (15-39 years) and older group (40-74 years). Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups. Propensity score matching (PSM) was employed to analyze the OS difference between the two groups. The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTSCompared to elderly cancer patients, AYA patients with HCC had a worse Surveillance, Epidemiology, and End Results stage, including the distant stage (22.1% vs 15.4%, P < 0.001), and a more advanced American Joint Committee on Cancer (AJCC) stage, including AJCC III and IV (49.2% vs 38.3%, P < 0.001), and were more likely to receive surgery (64.5% vs 47.5%, P < 0.001). Before PSM, the AYA group had a longer survival in months (median: 20.00, interquartile range [IQR]: 5.00-62.50) than the older group (median: 15.00, IQR: 4.00-40.00) (P < 0.001). After PSM, the AYA group still had a longer survival in months (median: 21.00, IQR: 5.00-64.50) than the older group (median: 18.00, IQR: 6.00-53.00) (P < 0.001). The Cox proportional hazards regression model showed that advanced age (hazard ratio [HR] = 1.405, 95%CI: 1.218-1.621, P < 0.001) was a risk factor for OS of HCC patients. In the subgroup analysis, the Cox proportional hazards regression model showed that in AJCC I/II HCC patients, advanced age (HR = 1.749, 95%CI: 1.352-2.263, P < 0.001) was a risk factor for OS, while it was not a risk factor in AJCC III/IV HCC patients (HR = 1.186, 95%CI: 0.997-1.410, P = 0.054) before PSM. After PSM, advanced age (HR = 1.891, 95%CI: 1.356-2.637, P < 0.001) was still a risk factor for OS in AJCC I/II HCC patients, but was not a risk factor for OS in AJCC III/IV HCC patients (HR = 1.192, 95%CI: 0.934-1.521, P = 0.157) after PSM.CONCLUSIONAYA patients with HCC have different clinical characteristics from older adults. In different AJCC stages, the two groups of patients have different OS: In AJCC I/II HCC patients, advanced age is a risk factor for OS, but it is not a risk factor for OS in the AJCC III/IV HCC patient group.     

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.     

洛克米兰醇对肝癌HepG2细胞的抗增殖作用及其机制研究

目的研究传统中药米仔兰Aglaiaodorata中洛克米兰醇对肝癌细胞HepG2增殖的影响及抗肿瘤作用机制。方法 MTT、细胞克隆形成、EdU染色和CFDA染色方法考察洛克米兰醇对HepG2细胞的抗增殖效果;流式细胞仪检测洛克米兰醇对HepG2细胞细胞周期和细胞凋亡的变化;Western blotting检测洛克米兰醇对细胞周期调控蛋白和丝裂原活化蛋白激酶(MAPK)信号通路相关蛋白表达的影响。结果洛克米兰醇可以时间和浓度依赖性抑制HepG2细胞增殖。同等浓度下洛克米兰醇抗HepG2细胞增殖的效果好于阿霉素,而对正常肝细胞(L02)的毒性弱于阿霉素。流式细胞技术检测发现洛克米兰醇给药48 h能够诱导HepG2细胞G_2/M期细胞周期阻滞,但不诱导细胞凋亡。Western blotting研究发现该化合物抑制调控G_2/M周期相关蛋白cdc25C、cdc2和cyclin B1的表达并且激活细胞外调节蛋白激酶(ERK)和c-Jun氨基末端激酶(JNK)。对其机制深入研究发现,ERK抑制剂(U0126)可以部分逆转洛克米兰醇对HepG2的抗增殖和G_2/M周期阻滞及其抑制蛋白cdc25C和cdc2表达的效果。结论洛克米兰醇在抑制肝癌细胞增殖的效果和对正常肝细胞的选择性方面优于阿霉素。洛克米兰醇能够通过过度活化ERK,从而引起HepG2细胞G_2/M周期阻滞而达到抗增殖效果。     

动态增强MRI成像在鼻咽癌诊疗中的应用价值

动态增强磁共振成像(Dynamic contrast enhanced MRI,DCE-MRI)是一种非常有价值的定量MRI技术,在提高肿瘤诊断的敏感度、良恶性肿瘤的鉴别、肿瘤分级等方面有良好的应用价值。本文就鼻咽癌分期、疗效评价、鉴别鼻咽癌放疗后瘢痕纤维化与肿瘤复发的DCE-MRI研究现状进行综述,供同道们在工作中参考。     

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。