目的基于网络毒理学和分子对接技术探究补骨脂酚致肝毒性的潜在机制。方法通过TCM-BATMAN挖掘补骨脂酚靶点,DisGeNET挖掘肝毒性基因;Cytoscape 3.7.0分别构建补骨脂酚靶点和肝毒性基因蛋白互作关系(PPI)网络,并Merge取交集,运用软件中...目的基于网络毒理学和分子对接技术探究补骨脂酚致肝毒性的潜在机制。方法通过TCM-BATMAN挖掘补骨脂酚靶点,DisGeNET挖掘肝毒性基因;Cytoscape 3.7.0分别构建补骨脂酚靶点和肝毒性基因蛋白互作关系(PPI)网络,并Merge取交集,运用软件中插件分析获得关键靶点,构建生物学总调控网络,并对其进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析;分子对接评价补骨脂酚与潜在关键靶点结合的亲和力。结果共获得补骨脂酚靶点3952个,肝毒性基因6025个和交集基因2221个。经分析,补骨脂酚主要作用于TP53、HSP90AA1、EP300等关键靶点,参与氧化应激反应与细胞增殖、分化、凋亡过程的调控,涉及多种酶调控等生物过程,主要通过PI3K-Akt、MAPK、细胞周期等信号通路引起肝毒性。补骨脂酚与EP300、HSP90AA1靶点的亲和力最强,能够与二者的结合口袋形成较强的疏水作用,total score值为8.8582、7.2178。结论补骨脂酚致肝毒性具有多靶点、多途径的作用规律,主要通过PI3K-Akt、MAPK、细胞周期等信号通路引起肝毒性。展开更多
Background The use of post-enucleation adjuvant therapy to decrease the extraocular relapse rate is frequently considered, but there is much controversy about the indications for adjuvant therapy. The aim of this retr...Background The use of post-enucleation adjuvant therapy to decrease the extraocular relapse rate is frequently considered, but there is much controversy about the indications for adjuvant therapy. The aim of this retrospective study was to observe the treatment and prognosis for different degrees of invasion of eye tissue in retinoblastoma （RB） and identify the indications for post-enucleation adjuvant therapy. Methods We recruited 537 children who had been diagnosed with unilateral RB and had received enucleation from January 2006 to December 2012 in our hospital, and divided them into three groups according to their number of histopathologic risk factors： 0 factor, 1 factor, or 〉2 factors. Histopathologic high-risk factors included invasion of the optic nerve posterior to the ethmoid plate （including optic nerve stumps） and extensive invasions of the choroid, sclera, anterior chamber, iris, and ciliary body. Treatment was delivered accordingly, and the prognosis of different degrees of histopathologic invasion was observed. The subjects were followed up for 6 months to 7 years （average follow-up time： 35 months）. Statistical analysis was analyzed using X2 test. P 〈0.05 was considered significant. Results Of the 537 RB patients who received enucleation, 25 died （overall survival： 95.3%）. Of the 369 （68.7%） with no histopathologic risk factors, 1 died of recurrence, with a mortality rate of 0.3%, whereas of the 168 （31.3%） with histopathologic risk factors, 26 had recurrences and 24 died （mortality rate： 14.3%; P=0.000）. Of the 93 patients （17.3%）, each of whom had a single risk factor, nine had recurrences, 16 died （8.6%）. Of the 75 patients （14%） with two or more high-risk factors, 16 died （21.3%）. These differences were statistically significant between the three （P=0.000）. Conclusion Chemotherapy is recommended for patients with histopathologic risk factors, especially those with two or more histopathologic risk factors.展开更多
文摘目的基于网络毒理学和分子对接技术探究补骨脂酚致肝毒性的潜在机制。方法通过TCM-BATMAN挖掘补骨脂酚靶点,DisGeNET挖掘肝毒性基因;Cytoscape 3.7.0分别构建补骨脂酚靶点和肝毒性基因蛋白互作关系(PPI)网络,并Merge取交集,运用软件中插件分析获得关键靶点,构建生物学总调控网络,并对其进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析;分子对接评价补骨脂酚与潜在关键靶点结合的亲和力。结果共获得补骨脂酚靶点3952个,肝毒性基因6025个和交集基因2221个。经分析,补骨脂酚主要作用于TP53、HSP90AA1、EP300等关键靶点,参与氧化应激反应与细胞增殖、分化、凋亡过程的调控,涉及多种酶调控等生物过程,主要通过PI3K-Akt、MAPK、细胞周期等信号通路引起肝毒性。补骨脂酚与EP300、HSP90AA1靶点的亲和力最强,能够与二者的结合口袋形成较强的疏水作用,total score值为8.8582、7.2178。结论补骨脂酚致肝毒性具有多靶点、多途径的作用规律,主要通过PI3K-Akt、MAPK、细胞周期等信号通路引起肝毒性。
文摘Background The use of post-enucleation adjuvant therapy to decrease the extraocular relapse rate is frequently considered, but there is much controversy about the indications for adjuvant therapy. The aim of this retrospective study was to observe the treatment and prognosis for different degrees of invasion of eye tissue in retinoblastoma （RB） and identify the indications for post-enucleation adjuvant therapy. Methods We recruited 537 children who had been diagnosed with unilateral RB and had received enucleation from January 2006 to December 2012 in our hospital, and divided them into three groups according to their number of histopathologic risk factors： 0 factor, 1 factor, or 〉2 factors. Histopathologic high-risk factors included invasion of the optic nerve posterior to the ethmoid plate （including optic nerve stumps） and extensive invasions of the choroid, sclera, anterior chamber, iris, and ciliary body. Treatment was delivered accordingly, and the prognosis of different degrees of histopathologic invasion was observed. The subjects were followed up for 6 months to 7 years （average follow-up time： 35 months）. Statistical analysis was analyzed using X2 test. P 〈0.05 was considered significant. Results Of the 537 RB patients who received enucleation, 25 died （overall survival： 95.3%）. Of the 369 （68.7%） with no histopathologic risk factors, 1 died of recurrence, with a mortality rate of 0.3%, whereas of the 168 （31.3%） with histopathologic risk factors, 26 had recurrences and 24 died （mortality rate： 14.3%; P=0.000）. Of the 93 patients （17.3%）, each of whom had a single risk factor, nine had recurrences, 16 died （8.6%）. Of the 75 patients （14%） with two or more high-risk factors, 16 died （21.3%）. These differences were statistically significant between the three （P=0.000）. Conclusion Chemotherapy is recommended for patients with histopathologic risk factors, especially those with two or more histopathologic risk factors.
