At present, no study has established a survival prediction model for non-metastatic primary malignant bone tumors of the spine (PMBS) patients. The clinical features and prognostic limitations of PMBS patients still require further exploration. Data on patients with non-metastatic PBMS from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate regression analysis using Cox, Best-subset and Lasso regression methods was performed to identify the best combination of independent predictors. Then two nomograms were structured based on these factors for overall survival (OS) and cancer-specific survival (CSS). The accuracy and applicability of the nomograms were assessed by area under the curve (AUC) values, calibration curves and decision curve analysis (DCA). Results: The C-index indicated that the nomograms of OS (C-index 0.753) and CSS (C-index 0.812) had good discriminative power. The calibration curve displays a great match between the model's predictions and actual observations. DCA curves show our models for OS (range: 0.09-0.741) and CSS (range: 0.075-0.580) have clinical value within a specific threshold probability range compared with the two extreme cases. Two nomograms and web-based survival calculators based on established clinical characteristics was developed for OS and CSS. These can provide a reference for clinicians to formulate treatment plans for patients.

As the most aggressive tumor, TNM staging does not accurately identify patients with pancreatic cancer who are sensitive to therapy. This study aimed to identify associated risk factors and develop a nomogram to predict survival in pancreatic cancer surgery patients and to select the most appropriate comprehensive treatment regimen. First, the survival difference between radiotherapy and no radiotherapy was calculated based on propensity score matching (PSM). Cox regression was conducted to select the predictors of overall survival (OS). The model was constructed using seven variables: histologic type, grade, T stage, N stage, stage, chemotherapy and radiotherapy. All patients were classified into high- or low-risk groups based on the nomogram. The nomogram model for OS was established and showed good calibration and acceptable discrimination (C-index 0.721). Receiver operating characteristic curve (ROC) and DCA curves showed that nomograms had better predictive performance than TNM stage. Patients were divided into low-risk and high-risk groups according to nomogram scores. Radiotherapy is recommended for high-risk patients but not for low-risk patients. We have established a well-performing nomogram to effectively predict the prognosis of pancreatic cancer patients underlying surgery. The web version of the nomogram https://rockeric.shinyapps.io/DynNomapp/ may contribute to treatment optimization in clinical practice.

目的 通过体外细胞实验,从分子水平探讨脑和肌肉芳香烃受体核转运样蛋白1(Bmal1)基因对结直肠癌细胞放疗敏感性的影响及其机制.方法 体外培养结直肠癌细胞,运用RNA干扰技术转染Bmal1 siRNA,构建Bmal1基因敲除的结直肠癌细胞株.将体外培养的细胞分为对照组、Bmal1基因敲除组(敲除组)、放疗组、Bmal1基因敲除联合放疗组(联合组).CCK-8检测各组结直肠癌细胞的增殖能力.RT-qPCR检测各组细胞Bmal1、缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)的mRNA表达水平.Western blot检测各组细胞Bmal1、HIF-1α和VEGF的表达水平.结果 CCK-8检测结果显示,细胞增殖能力由强到弱依次为:对照组、敲除组、放疗组、联合组,各组比较差异均有统计学意义(P<0.05).RT-qPCR检测结果显示,联合组细胞HIF-1α和VEGF mRNA的表达水平在4组细胞中均为最低,分别为对照组的0.40倍和0.38倍,其次为放疗组、敲除组,对照组HIF-1α和VEGF mRNA表达水平最高,各组比较差异均有统计学意义(P<0.05).Western blot检测结果显示,HIF-1α和VEGF在联合组细胞中表达水平最低,分别为对照组的0.45倍和0.35倍,其次为放疗组、敲除组,对照组HIF-1α和VEGF蛋白的表达水平最高,各组比较差异均有统计学意义(P<0.05).结论 敲除节律基因Bmal1可以增加结直肠癌细胞对放疗的敏感性,其机制可能与调节HIF-1α/VEGF信号通路有关.

目的 探讨生物钟基因Bmal1基于缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路对结肠癌细胞增殖的影响.方法 将对数生长期结肠癌MC38细胞随机分为对照组和Bmal1基因沉默组,2组细胞按照HiPerFect转染试剂说明书分别转染阴性对照干扰小RNA(siRNA)和Bmal1 siRNA.细胞转染后0、24、48 h,采用细胞计数试剂盒-8(cell counting kit-8,CCK-8)法检测2组细胞增殖能力;细胞转染后48 h,采用实时荧光定量聚合酶链式反应法检测2组细胞中Bmal1、HIF-1α、VEGF mRNA的相对表达量,Western blot法检测2组细胞Bmal1、HIF-1α、VEGF蛋白的相对表达量.结果 转染后0h,2组细胞增殖能力比较差异无统计学意义(P＞0.05);转染后24、48 h,Bmal1基因沉默组细胞增殖能力显著低于对照组(P＜0.05).细胞转染后48 h,Bmal1基因沉默组细胞中Bmal1 mRNA和蛋白相对表达量显著低于对照组(P＜0.05),Bmal1基因沉默组细胞中HIF-1α和VEGF的mRNA和蛋白相对表达量显著低于对照组(P＜0.05).结论 沉默Bmal1基因可抑制结肠癌细胞的增殖,其机制可能与抑制HIF-1α/VEGF信号通路有关.

ARNTL2（aryl hydrocarbon receptor nuclear translocator-like）基因属于bHLH-PAS（basic helix-loophelix-PER-ARNT-SIM）结构域转录因子家族，是控制昼夜节律的时钟基因之一。ARNTL2在多种肿瘤中高表达，并与肿瘤的进展、侵袭转移等恶性生物学行为密切相关。同时，ARNTL2的表达与肿瘤的发生和预后临床病理特征有关，有望成为肿瘤的预后指标和特异性肿瘤治疗标志物。本文分析了ARNTL2在不同肿瘤发生发展过程中的作用及潜在的机制，为临床早期发现、有效治疗肿瘤和改善病人预后提供新的理论依据。