目的基于术前血清IL-6、前列腺素E2(PGE2)、TNF-α构建预测膀胱癌术后复发的列线图模型。方法回顾性收集2018年6月至2023年2月临平区第一人民医院收治的348例膀胱癌患者的临床资料,经计算机产生随机数表并以2∶1比例将其分为训练集(232...目的基于术前血清IL-6、前列腺素E2(PGE2)、TNF-α构建预测膀胱癌术后复发的列线图模型。方法回顾性收集2018年6月至2023年2月临平区第一人民医院收治的348例膀胱癌患者的临床资料,经计算机产生随机数表并以2∶1比例将其分为训练集(232例)和验证集(116例)。所有患者均接受随访,将发生复发的患者纳入复发组,未发生复发的患者纳入未复发组。比较训练集复发组、未复发组血清IL-6、PGE2、TNF-α水平及一般资料;用Logistic回归模型分析训练集膀胱癌术后复发的影响因素,并建立回归方程;用ROC曲线分析术前IL-6、PGE2、TNF-α单独及联合预测膀胱癌术后复发的效能;建立膀胱癌术后复发的风险预测列线图模型,并验证其效能。结果与未复发组比较,复发组血清IL-6、PGE2、TNF-α水平升高,肿瘤直径增大,多发性肿瘤、肿瘤分期T 2~T 4、肿瘤WHO病理学分级Ⅱ~Ⅲ级的构成比升高,术后规律膀胱灌注的构成比降低(P<0.05)。Logistic回归分析显示,术前血清IL-6、PGE2、TNF-α、肿瘤分期、肿瘤WHO病理学分级是膀胱癌术后复发的影响因素(P<0.05),并建立Logistic回归方程:Y=1.718 X 1+2.081 X 2+1.815 X 3+2.319 X 4+1.868 X 5。ROC曲线显示,术前IL-6、PGE2、TNF-α预测膀胱癌术后复发的最佳截断点分别为0.60 ng/L、57.13 pg/mL、2.10 ng/mL,三者单独及联合预测膀胱癌的ROC曲线下面积(AUC ROC)分别为0.729、0.743、0.733和0.825。基于训练集Logistic回归分析结构建立膀胱癌术后复发的风险预测列线图模型,该模型预测训练集、验证集的敏感性分别为94.12%、90.20%,特异性分别为90.06%、87.29%,AUC ROC分别为0.940、0.914;Bootstrap法内部验证结果显示,训练集、验证集的C-index分别为0.918(95%CI:0.824~0.987)、0.901(95%CI:0.835~0.957)。结论术前血清IL-6、PGE2、TNF-α水平是膀胱癌术后复发的影响因素,据此建立的风险预测列线图模型具有良好的预测效能。展开更多
OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neur...OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile,ketamine has been showed to modulate the levels of inflammatory cytokines.Therefore,we sought to investigate whether the effects of ketamine on the central nervous system is associated with the inflammatory cytokines. METHODS We established acute(single or multiple intraperitoneal injection) and chronic(six months daily intraperitoneal injection) ketamine administration models in C57BL/6 mice,evaluated the spatial recognition memory and emotional response by applying the Y maze test and open field test. We analyzed the changes of inflammatory cytokines interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) levels in mouse hippocampus,employing Western blot,quantitative reverse transcriptase-polymerase chain reaction(qR T-PCR) and immunohistochemistry. RESULTS Ketamine induced spatial recognition memory deficit,reduced anxiety-like behaviors in mice after chronic administration,and it was dose-dependent. Moreover,we found that ketamine could increase the levels of mouse hippocampal inflammatory cytokines IL-6 and IL-1β after single,multiple and long-term administration in a dose-dependent manner. However,the level of TNF-α expressed differently in mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α,whereas multiple and long-term administration decreased it significantly. We considered that TNF-α might exist bi-directional regulatory pathway,which was associated with the dose and duration of ketamine administration. CONCLUSION Our results suggest that the alterations of inflammatory cytokines IL-6,IL-1β and TNF-α levels may be involved in the neurotoxicity of ketamine.展开更多
文摘目的基于术前血清IL-6、前列腺素E2(PGE2)、TNF-α构建预测膀胱癌术后复发的列线图模型。方法回顾性收集2018年6月至2023年2月临平区第一人民医院收治的348例膀胱癌患者的临床资料,经计算机产生随机数表并以2∶1比例将其分为训练集(232例)和验证集(116例)。所有患者均接受随访,将发生复发的患者纳入复发组,未发生复发的患者纳入未复发组。比较训练集复发组、未复发组血清IL-6、PGE2、TNF-α水平及一般资料;用Logistic回归模型分析训练集膀胱癌术后复发的影响因素,并建立回归方程;用ROC曲线分析术前IL-6、PGE2、TNF-α单独及联合预测膀胱癌术后复发的效能;建立膀胱癌术后复发的风险预测列线图模型,并验证其效能。结果与未复发组比较,复发组血清IL-6、PGE2、TNF-α水平升高,肿瘤直径增大,多发性肿瘤、肿瘤分期T 2~T 4、肿瘤WHO病理学分级Ⅱ~Ⅲ级的构成比升高,术后规律膀胱灌注的构成比降低(P<0.05)。Logistic回归分析显示,术前血清IL-6、PGE2、TNF-α、肿瘤分期、肿瘤WHO病理学分级是膀胱癌术后复发的影响因素(P<0.05),并建立Logistic回归方程:Y=1.718 X 1+2.081 X 2+1.815 X 3+2.319 X 4+1.868 X 5。ROC曲线显示,术前IL-6、PGE2、TNF-α预测膀胱癌术后复发的最佳截断点分别为0.60 ng/L、57.13 pg/mL、2.10 ng/mL,三者单独及联合预测膀胱癌的ROC曲线下面积(AUC ROC)分别为0.729、0.743、0.733和0.825。基于训练集Logistic回归分析结构建立膀胱癌术后复发的风险预测列线图模型,该模型预测训练集、验证集的敏感性分别为94.12%、90.20%,特异性分别为90.06%、87.29%,AUC ROC分别为0.940、0.914;Bootstrap法内部验证结果显示,训练集、验证集的C-index分别为0.918(95%CI:0.824~0.987)、0.901(95%CI:0.835~0.957)。结论术前血清IL-6、PGE2、TNF-α水平是膀胱癌术后复发的影响因素,据此建立的风险预测列线图模型具有良好的预测效能。
文摘OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile,ketamine has been showed to modulate the levels of inflammatory cytokines.Therefore,we sought to investigate whether the effects of ketamine on the central nervous system is associated with the inflammatory cytokines. METHODS We established acute(single or multiple intraperitoneal injection) and chronic(six months daily intraperitoneal injection) ketamine administration models in C57BL/6 mice,evaluated the spatial recognition memory and emotional response by applying the Y maze test and open field test. We analyzed the changes of inflammatory cytokines interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) levels in mouse hippocampus,employing Western blot,quantitative reverse transcriptase-polymerase chain reaction(qR T-PCR) and immunohistochemistry. RESULTS Ketamine induced spatial recognition memory deficit,reduced anxiety-like behaviors in mice after chronic administration,and it was dose-dependent. Moreover,we found that ketamine could increase the levels of mouse hippocampal inflammatory cytokines IL-6 and IL-1β after single,multiple and long-term administration in a dose-dependent manner. However,the level of TNF-α expressed differently in mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α,whereas multiple and long-term administration decreased it significantly. We considered that TNF-α might exist bi-directional regulatory pathway,which was associated with the dose and duration of ketamine administration. CONCLUSION Our results suggest that the alterations of inflammatory cytokines IL-6,IL-1β and TNF-α levels may be involved in the neurotoxicity of ketamine.
