铁死亡是一种以铁依赖性脂质过氧化为特征的程序性细胞死亡形式。近年来研究表明，铁死亡与缺氧应答的关键调控因子——缺氧诱导因子（HIF）存在密切关联。HIF（包括HIF-1α、HIF-2α、HIF-3α三种亚型）调控的铁死亡在结直肠癌、胃癌、溃疡性结肠炎及其他胃肠黏膜损伤性疾病中发挥作用，影响疾病的发生发展。但目前关于HIF-铁死亡通路在不同胃肠道疾病中的差异化作用及调控机制尚未完全阐明。因此，本文对HIF各亚型调控铁死亡的分子机制及其在胃肠道疾病中的作用进行综述，以期为靶向HIF-铁死亡通路治疗相关疾病提供新的思路。

       Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation．Recent 

studies have demonstrated a close association between ferroptosis and hypoxia-inducible factor（HIF），the key  regulator of the hypoxic response．Ferroptosis regulated by HIF（comprising three isoforms：HIF-1α，HIF-2α，and HIF-3α）plays a  role in colorectal cancer，gastric cancer，ulcerative colitis，and other gastrointestinal mucosal injury diseases，impacting their initiation and progression．However，the differential roles and regulatory mechanisms of the HIF-ferroptosis pathway in various gastrointestinal diseases remain incompletely elucidated．Therefore，this  review  summarizes the molecular mechanism networks through which individual HIF isoforms regulate ferroptosis and their roles in gastrointestinal diseases，with the aim of providing new perspectives for targeting the HIF-ferroptosis pathway to treat relevant diseases．

目的 探究铁死亡相关的lncRNA在肺鳞状上皮细胞癌(简称肺鳞癌)患者中的预后意义。方法 从美国癌症和肿瘤基因图谱数据库(the Cancer Genome Atlas,TCGA)中下载肺鳞癌数据551例,包括49例正常对照样本和502例肺鳞癌患者样本。筛选出与铁死亡相关基因的共表达的lncRNA,使用单变量Cox回归进一步筛选lncRNA,然后,使用Lasso回归和多元Cox回归分构建铁死亡相关的lncRNA模型。建立基于模型的风险评分,并使用Cox回归测试其是否为独立的预后因素。铁死亡相关lncRNAs的功能富集使用基因本体(Gene Ontology)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes)可视化。结果 4个预后铁死亡相关的lncRNA(AC253536.6,FLJ46906LUCAT,AC022150.2)显著不同,这构建了铁死亡相关的lncRNA模型。此模型将肺鳞癌患者分为低风险组和高风险组。基于模型的风险评分是肺鳞癌患者的显著独立因素(HR =2.116,95％CI=1.513~2.961;P<0.001)。此外,4个lncRNA在铁死亡过程,代谢和肿瘤经典途径中均显著富集。结论 4个铁死亡相关的lncRNAs可能是肺鳞癌患者的分子生物标志物和治疗靶标。

Objective To explore the prognostic significance of ferroptosis related lncRNAs in patients with lung squamous cell carcinoma. Methods Data of 551 lung squamous cell carcinoma cases was downloaded from the Cancer Genome Atlas (TCGA) of the United States, including 49 normal control samples and 502 lung squamous cell carcinoma samples. The lncRNAs co-expressed with genes related to ferroptosis was screened out. Univariate Cox regression was used to further screen out the lncRNAs. Then, Lasso regression and multiple Cox regression were used to construct lncRNA models related to ferroptosis. A model-based risk score system was established and Cox regression was used to test whether it was an independent prognostic factor. The functional enrichment of ferroptosis related lncRNAs were visualized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Results The four prognostic ferroptosis related lncRNAs (AC253536.6, FLJ46906 LUCAT, AC022150.2) were significantly different, and the ferroptosis lncRNAs model was constrncted with them. This model divided lung squamous cell carcinoma patients into low-risk group and high-risk group. The model-based risk score was a significant independent factor for patients with lung squamous cell carcinoma (HR=2.116, 95% CI=1.513-2.961; P<0.001). In addition, the four lncRNAs were significantly enriched in metabolism and tumor classical pathways during the ferroptosis process. Conclusions The four ferroptosis lncRNAs could be molecular biomarkers and therapeutic targets for patients with lung squamous cell carcinoma.

       目的  探讨重楼皂苷Ⅰ（PPI）对慢性髓系白血病细胞（K562）细胞的抑制作用及可能的作用机制。方法  采用CCK-8法筛选药物最适浓度，将培养时间为24 h的药物最适浓度作为后续实验的干预浓度。分组如下：（1）空白组；（2）PPI组；（3）抑制剂组；（4）PPI+抑制剂组。采用CCK-8法检测细胞增殖率；AO/EB染色观察细胞形态；流式细胞术检测凋亡率；ROS检测试剂盒检测活性氧（ROS）含量、还原型谷胱甘肽含量检测试剂盒检测谷胱甘肽（GSH）含量、细胞亚铁比色法测试盒检测细胞亚铁（Fe²⁺）含量；qRT-PCR法和蛋白免疫印迹法检测各组肿瘤蛋白53（p53）、钠氯离子依赖性氨基酸转运蛋白11（SLC7A11）、谷胱甘肽过氧化物酶4（GPX4）mRNA及蛋白表达量。结果  PPI抑制K562细胞的生长，且呈一定的剂量及时间依赖性（与同时间段的对照组0μmol/L比较，均P＜0.01）。与空白组相比，PPI抑制K562细胞的增殖，提高了凋亡率，而铁死亡抑制剂（Ferrostian-1）的使用逆转了PPI对K562凋亡的促进作用（P＜0.01）。与空白组相比，PPI组ROS、Fe²⁺含量升高，GSH含量下降，而铁死亡抑制剂的使用可下调ROS、Fe²⁺，上调GSH的含量（P＜0.01）。PPI组较空白组p53 mRNA和蛋白表达水平升高，而SLC7A11、GPX4 mRNA和蛋白表达水平下降（P＜0.05）；PPI+抑制剂组细胞较重楼皂苷组p53 mRNA和蛋白表达水平下降，而SLC7A11、GPX4 mRNA和蛋白表达水平升高（P＜0.05）。结论  PPI能够有效抑制K562细胞增殖，促进K562细胞铁死亡，其分子机制可能与p53信号通路的调控有关。

       Objective  To investigate the inhibitory effect of polyphyllin I（PPI）on chronic myeloid leukemia cells（K562）and its possible mechanism．Methods  K562 cell line was cultured in suitable environment，and the optimal concentration of the drug was screened by CCK-8 method．The optimal concentration of the drug cultured for 24 hours was used as the intervention concentration of the follow-up experiment．Cells were divided into the following groups：（1）blank group，（2）saponins group，（3）inhibitor group and（4）saponins + inhibitor group．The cell proliferation rate was detected by CCK-8 method．The cell morphology was observed by AO/EB staining．The apoptosis rate was detected by flow cytometry．The contents of  reactive oxygen species（ROS），glutathione（GSH）and ferrous（Fe²⁺）in different groups were detected，and the expression of mRNA and protein in different groups were detected by qRT- PCR and Western blot respectively．Results  PPI significantly inhibited the growth of K562 cells in a dose-and time-dependent manner．Compared with the blank group，PPI significantly inhibited the proliferation of K562 cells and increased the apoptosis rate of K562 cells，while the use of ferroptosis inhibitor（Ferrostian-1）reversed the promoting effect of PPI on apoptosis of K562 cells．Compared with the blank group，the contents of reactive oxygen species（ROS）and ferrous iron（Fe²⁺）increased and the content of glutathione（GSH）decreased in the saponins group．The use of Ferrostian-1 could down-regulate the contents of ROS and Fe²⁺ and increase the content of GSH in the cells treated with the drug．Compared with the blank group，the expression of p53 mRNA and protein in the saponins group increased，while the expression of SLC7A11，GPX4 mRNA and protein decreased．The expression of p53 mRNA and protein in the saponins + inhibitor group was lower than that in the saponins group，while the expression levels of SLC7A11，GPX4 mRNA and protein increased．Conclusions  PPI can effectively inhibit the proliferation of K562 cells and promote ferroptosis in K562 cells．The molecular mechanism can be related to the regulation of p53 signal pathway．