Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma

Hepatectomy is currently considered the most effective option for treating patients with early and intermediate hepatocellular carcinoma (HCC). Unfortunately, the postoperative prognosis of patients with HCC remains unsatisfactory, predominantly because of high postoperative metastasis and recurrence rates. Therefore, research on the molecular mechanisms of postoperative HCC metastasis and recurrence will help develop effective intervention measures to prevent or delay HCC metastasis and recurrence and to improve the long-term survival of HCC patients. Herein, we review the latest research progress on the molecular mechanisms underlying postoperative HCC metastasis and recurrence to lay a foundation for improving the understanding of HCC metastasis and recurrence and for developing more precise prevention and intervention strategies.     

呫吨酮并吡啶衍生物XP-15联合紫杉醇对耐药肝癌细胞QGY-7701 的体外抑制作用

目的:探索呫吨酮并吡啶衍生物XP-15联合紫杉醇对人肝癌QGY-7701耐药细胞株的体外抗肿瘤作用。方法:运用CCK8法、Transwell实验和流式细胞仪检测凋亡技术观察细胞功能学变化，运用Western Blot蛋白免疫印迹技术探索其可能的作用机制。结果:XP-15可明显增强紫杉醇对耐药QGY-7701细胞的抑制作用，XP-15联合紫杉醇作用于耐药QGY-7701细胞24 h后，QGY-7701细胞活力明显减弱，且其侵袭迁移能力明显降低，同时流式细胞仪凋亡检测提示细胞凋亡百分比明显增加。Western Blot蛋白免疫印迹亦证实细胞抗凋亡蛋白bcl-2表达明显降低，肝癌增殖分化相关PI3K及AKT蛋白分子表达减少。结论:XP-15具有增敏紫杉醇诱导耐药QGY-7701细胞凋亡同时抑制其增殖活力的作用，其作用机制可能与下调PI3K-AKT通路活性，同时减少bcl-2抑制凋亡蛋白表达相关。     

外周血单个核细胞内人类免疫缺陷病毒DNA和RNA定量对病毒转录活性的区分

目的基于人类免疫缺陷病毒Ⅰ型(HIV-1)感染者外周血单个核细胞(PBMCs)中HIV-1总DNA和RNA定量检测结果对感染细胞内病毒的转录活性进行区分。方法采集2017年10月至2018年12月于哈尔滨医科大学附属第四医院感染科就诊的HIV-1感染者血液样本,分离PBMCs细胞,采用PCR荧光探针法对PBMCs细胞内HIV-1总DNA和RNA进行定量检测,并计算两者比值(Ratio)。根据Ratio值筛选出HIV-1转录活跃组样本和相对非活跃组样本,另外选择健康人PBMCs样本作为对照组。对3组样本进行基因转录组表达谱检测以及人口特征差异性检验,并对基因表达谱检测结果进行主成分分析以验证对3组样本病毒转录活性区分的准确性。结果从60例感染HIV-1患者的PBMCs样本中筛选出HIV-1转录活跃组样本(10例)和相对非活跃组样本(11例),另外选择6例健康人PBMCs样本作为对照组。其中转录活跃组样本Ratio值为165.2~738.93,平均为(339.27±189.68);相对非活跃组Ratio值为4.67~42.39,平均为(17.65±11.78)。转录活跃组和相对非活跃组样本间的CD4+T细胞计数(P=0.049)和Ratio值(P<0.001)差异均具有统计学意义;3组样本年龄(P=0.989)和性别(P=0.650)分布差异无统计学意义。对3组样本的PBMCs基因表达谱主成分分析结果显示:对照组与HIV-1感染者(包括转录活跃组和相对非活跃组)间区分明显。转录活跃组和相对非活跃组间有部分样本重合,同时结果也显示当HIV-1感染者的CD4+T淋巴细胞计数与健康人无显著差异时,其细胞内的基因表达与健康人接近。结论基于HIV-1总DNA和RNA定量检测结果及两者间比值可以较好地区分PBMCs内病毒转录活性。HIV-1感染细胞内部病毒的不同转录激活状况可导致其基因表达谱的异质性。     

Spectrum-Toxicity Correlation Study Revealed the Influence of the Nine-Time Steaming and Sun Drying Method on Hepatotoxic Components of Polygoni Multiflori Radix

Objective: Polygoni Multiflori Radix (PM) is a traditional herbal medicine with repeated reports of liver injury events in recent years. We wondered whether the classical processing method, namely, nine-time steaming and sun drying (NSSD), had toxicity-attenuating effects on PM and the relationships between toxicity and times of processing, as well as with the alteration trends of its compounds. Materials and Methods: The chemical fingerprints of different PM extracts were developed using ultra-high-performance liquid chromatography. The spectrum-toxicity correlation between the chemical fingerprints and hepatocellular toxicity was analyzed with multiple correlation analysis. Results: The results suggested that the hepatotoxicity of NSSD processing products markedly decreased with the repeated steaming and sun drying, which was obviously superior to the product processed by the modern method. Comprehensive analysis revealed that the contents of cis-stilbene glycoside and emodin-8-O-β-D-glucoside related to liver injury susceptibility were reduced with the times of NSSD processing, which was consistent with the decreased trend of hepatocellular toxicity. After the five times of NSSD, the contents of them as well as the hepatotoxicity of PM were steady. Moreover, we found that the contents of catechin and physcion declined rapidly after the one time of NSSD and then remained stable until the nine times of NSSD. Based on the fact, they could be utilized to indicate whether PM products were processed by steaming and sun drying. Conclusions: This paper confirmed that the NSSD had a good influence on the toxicity attenuating to PM and found four compounds which could apply for the quality control of PM.     

肝内胆汁淤积对联合弹性成像评估肝纤维化的影响

目的评估肝内胆汁淤积对联合弹性成像诊断肝纤维化分期的影响。方法收集入组患者的弹性成像、生化学和组织学数据。比较不同总胆红素(TB)组的剪切波速度(Vs)及肝纤维化指数(LF index)。使用ROC曲线下面积计算联合成像的准确度。结果以肝活检为金标准,TB异常组的Vs高于正常组(P<0.001),LF index在TB正常组及异常组中无区别(P>0.05)。不同TB分组中联合成像的准确度并无明显差异。结论肝内胆汁淤积对LF index无任何影响,使Vs轻微升高,但不会降低联合弹性成像评估肝纤维化分期的整体诊断效能。