目的 探讨TRIB2在结肠癌中的表达水平及与预后及免疫浸润之间的关系。方法 TIMER数据库分析TRIB2在泛癌种中的表达;TCGA、GSE17538下载结肠癌患者RNA-seq数据和临床信息,评估其与临床病理特征的相关性;生存曲线、单因素和多因素Cox分析探讨TRIB2与预后的相关性,并构建列线图;对TRIB2进行差异基因的富集分析;分析TRIB2表达水平与免疫细胞浸润、免疫检查点、肿瘤突变负荷（TMB）以及免疫治疗敏感性之间的相关性。结果 TRIB2在结肠癌组织中高表达（P<0.05）;CMS1结肠癌患者TRIB2 mRNA表达水平最高;TRIB2是结肠癌患者的独立预后因素（单因素Cox回归分析：HR=1.397,95%CI：1.100~1.774,P=0.006;多因素Cox回归分析：HR=1.502,95%CI：1.158~1.947,P=0.002）;TRIB2与免疫细胞的浸润密切相关,并且与免疫检查点分子表达水平以及TMB正相关（r=0.39,P<0.001）;TRIB2的表达水平与免疫检查点抑制剂的疗效相关。结论 TRIB2在结肠癌中高表达且与结肠癌患者预后差和免疫微环境密切相关。

Objective To explore the expression of TRIB2 in colon cancer and its relationship with prognosis and immune cell infiltration. Methods TIMER database was used to analyse the expression of TRIB2 in pan-cancer．RNA-seq data and clinical information of colon cancer patients were downloaded from TCGA and GSE17538 to assess the correlation between TRIB2 with clinicopathological features．Survival curves,univariate and multivariate COX regression analysis were performed to explore the correlation between TRIB2 and prognosis,and a nomogram was constructed．Gene enrichment analyses were performed for TRIB2．Correlations between TRIB2 expression and immune cell infiltration,immune checkpoints,tumor mutation burden（TMB）,and immunotherapy sensitivity were analyzed．Results TRIB2 was highly expressed in colon cancer tissues（P<0.05）．The highest level of TRIB2 mRNA expression was found in CMS1．TRIB2 was an independent prognostic factor for colon cancer patients（univariate Cox regression analysis：HR=1.397,95%CI：1.100-1.774,P=0.006;multivariate Cox regression analysis：HR=1.502,95%CI：1.158-1.947,P=0.002）．TRIB2 was closely associated with immune cell infiltration and positively correlated with the expression level of immune checkpoint molecules as well as TMB（r=0.39,P<0.001）．The expression of TRIB2 was correlated with the efficacy of immune checkpoint inhibitors．Conclusions TRIB2 is highly expressed in colon cancer and is closely associated with poor prognosis and the immune microenvironment of colon cancer patients．

目的 探讨子宫内膜异位症（EMT）患者卵泡液来源的外泌体差异微小RNA（miRNA）对卵母细胞质量的影响。方法 收集2021年12月—2022年3月在广州市第一人民医院生殖医学中心进行体外受精-胚胎移植/卵细胞浆内单精子注射助孕的20例不孕症患者的卵泡液,分为EMT组（EMT不孕症患者10例）和对照组（单纯男性因素不孕症患者10例）。采用高通量测序对卵泡液外泌体微小RNA（miRNA）谱进行分析,选出具有组间差异的miRNAs。结果 与单纯男性因素不孕患者相比,EMT组有18个外泌体miRNAs差异有统计学意义,其中上调9个、下调9个。靶基因预测并采用GO和KEGG富集分析发现,这些靶基因主要参与磷脂酰肌醇-3-激酶/蛋白激酶B（ PI3K-Akt）、核苷酸结合寡聚结构域NOD样受体、Ras等信号通路。结论 EMT患者卵泡液来源的外泌体miRNA存在差异,差异的外泌体miRNAs可能通过多个信号通路影响EMT患者卵母细胞质量。

Objective To investigate the effect of differential microRNA（miRNA）derived from follicular fluid exosomes on oocyte quality in patients with endometriosis（EMT）. Methods Follicular fluid was collected from 20 infertile patients undergoing IVF-ET / ICSI in the Reproductive Medicine Center of Guangzhou First People's Hospital from December 2021 to March 2022,including EMT group（10 patients with EMT infertility）and control group（10 patients with simple male factor infertility）．The miRNA spectrum in follicular fluid exosomes was analyzed by high-throughput sequencing and miRNAs with differences between groups were selected. Results Compared with patients with infertility due to simple male factors,there were significant differences in 18 exosomal miRNAs in the EMT group,of which 9 were up-regulated and 9 were down-regulated．GO and KEGG enrichment analysis showed that these target genes were mainly involved in phosphatidylinositol-3-kinase / protein kinase B,Nucleotide binding oligomerization domain-like receptor and other signaling pathways. Conclusions There are differences in follicular fluid-derived exosomal miRNAs in EMT patients．Differential exosomal miRNAs may affect oocyte quality in EMT patients through multiple signaling pathways．

目的 通过多种生物信息学方法分析MAML1在GC患者中的表达及与临床特征、预后和免疫治疗疗效的相关性。方法 利用TCGA数据库分析胃癌组织与正常胃黏膜组织中的MAML1表达水平;Kaplan-Meier在线工具对胃癌数据集GSE15459进行分析,阐明MAML1与患者临床特征及分期、治疗疗效的相关性;STRING软件预测与MAML1表达相关的基因,并用FUNRICH软件评估其富集的分子生物学功能和信号通路;TIMER和GEPIA数据库探索MAML1表达水平与肿瘤浸润免疫细胞及其相应基因标记集之间的关系。结果 MAML1在GC组织中的表达水平高于正常组织(P<0.001),且其表达水平与III期、有淋巴结转移、无远处转移的患者生存期相关(P<0.05),而与I、II和IV期、无淋巴结转移和有远处转移的患者生存期无相关性(P>0.05)。MAML1的相关作用基因主要分布在细胞核、参与转录调控,并且主要富集在雄激素受体、C-MYB转录因子和HIF-2α转录调控等相关的信号通路。MAML1表达水平与B细胞、CD4⁺ T细胞、巨噬细胞的表达水平存在正相关关系(P<0.05),但与肿瘤纯度、CD8⁺ T细胞、中性粒细胞、树突状细胞无相关性(P>0.05)。结论 MAML1有可能成为GC患者较差的临床预后标志物之一,其潜在分子机制可能与转录调控调节肿瘤微环境有关。

Objective To investigate the expression of MAML1 and its relationship with clinical characteristics, prognosis and the efficiency of immunotherapy in patients with GC. Methods MAML1 expression profile was observed by TCGA database. Kaplan-Meier survival analysis was applied to evaluate the correlation between the expression of MAML1 and clinical characteristics, prognosis and treatment efficiency of patients in GSE15459 dataset. MAML1-associated genes were predicted by STRING and were enriched in GO and KEGG by FUNRICH software. The relationship between MAML1 expression and markers of tumor infiltrated cells were explored by TIMER and GEPIA database. Results MAML1 was abnormally upregulated in GC tissues compared to normal gastric tissues (P<0.001). MAML1 expression was significantly associated with the overall survival of patients in stage III, with lymph node metastasis and without distant metastasis (P<0.001). There was no significant difference between MAML1 expression and the overall survival of patients in stage I, II, IV, without lymph node metastasis and with distant metastasis (P>0.05). MAML1-assoicated genes were mainly located at the nucleus, mediating transcriptional regulation and mainly enriching in androgen receptor, C-MYB transcription factor and HIF-2α transcription regulation and other related signaling pathways. MAML1 expression was positively related with the expression of B cell, CD4⁺ T cell and macrophages (P<0.05), but without significant difference with tumor purity, CD8⁺ T cell, neutrophils and dendritic cells (P>0.05). Conclusions MAML1 could be used as a marker of clinical prognosis of patients with GC. The potential molecular mechanism might be associated with its function in transcriptional regulation and changes in tumor microenvironment.

目的 利用GEPIA数据库,包括TCGA数据库和GTEX数据库,探讨二氢丹参酮I通过氧化应激治疗胃癌的潜在靶点。方法 在数据库中检索二氢丹参酮I在胃癌中潜在靶点的文献,利用GEPIA数据库工具分析二氢丹参酮I在胃癌中的潜在作用机制,分析潜在靶基因与表达关键抗氧化应激蛋白基因的相关性;二氢丹参酮I对胃癌潜在靶基因表达水平的分析;二氢丹参酮I对胃癌潜在靶基因的预后分析。结果 二氢丹参酮I对潜在靶基因的主要靶向基因(蛋白)为缺氧诱导因子-1(hif-1)和瓜氨酸组蛋白h3(cith3),其基因分别为HIF1 A和NOS2;GEPIA数据库显示HIF1 A与CAT(P=e-04,r=0.18)、GPX1(P=0.033,r=0.11)或NFE2L2呈正相关。(P=0,r=0.41),而NOS2与SOD1仅呈正相关(P=0.21,r=0.18),与其它三个基因均无相关性;HIF1 A和NOS2在胃癌组织中的表达水平高于正常胃旁组织;HIF1 A的高表达降低了胃癌患者的总生存率。结论 二氢丹参酮I可通过活性氧介导的氧化应激诱导AGS细胞凋亡,抑制HIF1 A和NOS2的表达,从而抑制AGS细胞的抗氧化应激,提高胃癌患者的总生存率。

Objective In this study, GEPIA database, including TCGA database and GTEx database, were used to explore the potential targets of dihydrotanshinone I on gastric cancer through oxidative stress. Methods Literatures on potential targets of dihydrotanshinone I in gastric cancer were searched in the database;GEPIA database tool was used to analyze the potential mechanism of dihydrotanshinone I on gastric cancer;taking analysis of the correlation between potential target genes and genes expressing key antioxidant stress proteins;We had analysis of expression level of dihydrotanshinone I on potential target genes in gastric cancer patients;and prognostic analysis of dihydrotanshinone I on potential target genes in gastric cancer patients. Results The main targeting genes(proteins) of dihydrotanshinone I on potential target genes were hypoxia inducible factor-1(hif-1) and citrulline histone H3(CITH3), whose genes were HIF1 A and NOS2, respectively;GEPIA database showed that there was a positive correlation between HIF1 A and CAT(P=2e-04, R=0.18), GPX1(P=0.033, R=0.11), or NFE2L2(P=0, R=0.41), while NOS2 only had a positive correlation with SOD1(P=0.21, R=0.18), and no correlation with other three genes. The expression levels of HIF1 A and NOS2 in gastric cancer tissues were higher than those in normal adjacent gastric tissues. The overall survival rate of patients with gastric cancer decreased with the high expression of HIF1 A. Conclusion Dihydrotanshinone I may induce apoptosis of AGS cells through reactive oxygen species mediated oxidative stress, and inhibit the expression of HIF1 A and NOS2, thus inhibit their antioxidative stress, which may improve the overall survival rate of gastric cancer patients.

目的 通过生物信息分析途径,从分子水平揭示非酒精性脂肪性肝病（NAFLD）的发病发展机制,为NAFLD研究提供新的思路。方法 从公共数据库GEO中下载NAFLD相关的基因芯片数据GSE48452,利用Transcriptome Analysis Console软件筛选差异表达基因,FunRich软件和STRING在线分析工具对差异基因进行下一步的生物信息学分析。结果 正常组与NAFLD组差异基因52个,正常组与非酒精性脂肪性肝炎（NASH）基因64个,共同差异基因15个。这些差异表达基因参与脂质转运、胆汁酸合成、脂质和脂蛋白代谢、生物氧化等过程。通过通路分析及蛋白质相互作用分析进一步筛选出与NAFLD发病发展密切相关的18个差异表达基因。结论 通过生物信息学分析筛选出MSN、CDC45、ANXA5、PIK3CG和DTL基因可能为研究乃至阻断NAFLD发展进程的重要靶点,需进一步验证。

Objective To explore the molecular mechanism of nonalcoholic fatty liver disease （NAFLD） with bioinformatics analysis. Methods The microarray data of NAFLD were downloaded from the Gene Expression Omnibus （GEO） database and analyzed using Transcriptome Analysis Console （TAC） for screening differentially expressed genes. The further analysis of differentially expressed genes was conducted by FunRich software and the online tool STRING. Results For the comparison of control group vs. NAFLD group,52 genes have differentially expressed,while control groups vs. nonalcoholic steatohepatitis （NASH） group,64 genes have differentially expressed. 15 differentially expressed genes were found in both comparisons. These genes were involved in the biological pathway of lipid transport,bile acid biosynthesis,metabolism of lipids and lipoproteins and biological oxidations. With biological pathway analysis and protein-protein interaction analysis,18 differentially expressed genes were found closely associated with the progression of NAFLD. Conclusion MSN、CDC45、ANXA5、PIK3CG and DTL may be the important target for study the progression of NAFLD,which needs a further study to confirm.

       目的  探讨TRIB2在结肠癌中的表达水平及与预后及免疫浸润之间的关系。方法  TIMER数据库分析TRIB2在泛癌种中的表达；TCGA、GSE17538下载结肠癌患者RNA-seq数据和临床信息，评估其与临床病理特征的相关性；生存曲线、单因素和多因素Cox分析探讨TRIB2与预后的相关性，并构建列线图；对TRIB2进行差异基因的富集分析；分析TRIB2表达水平与免疫细胞浸润、免疫检查点、肿瘤突变负荷（TMB）以及免疫治疗敏感性之间的相关性。结果  TRIB2在结肠癌组织中高表达（P＜0.05）；CMS1结肠癌患者TRIB2 mRNA表达水平最高；TRIB2是结肠癌患者的独立预后因素（单因素Cox回归分析：HR=1.397，95%CI：1.100~1.774，P=0.006；多因素Cox回归分析：HR=1.502，95%CI：1.158~1.947，P=0.002）；TRIB2与免疫细胞的浸润密切相关，并且与免疫检查点分子表达水平以及TMB正相关（r=0.39，P＜0.001）；TRIB2的表达水平与免疫检查点抑制剂的疗效相关。结论  TRIB2在结肠癌中高表达且与结肠癌患者预后差和免疫微环境密切相关。

       Objective  To explore the expression of TRIB2 in colon cancer and its relationship with prognosis and immune cell infiltration．Methods  TIMER database was used to analyse the expression of TRIB2 in pan-cancer．RNA-seq  data and clinical information of colon cancer patients were downloaded from TCGA and GSE17538 to assess the correlation between TRIB2 with clinicopathological features．Survival curves，univariate and multivariate COX regression analysis were performed to explore the correlation between TRIB2 and prognosis，and a nomogram was constructed．Gene enrichment analyses were performed for TRIB2．Correlations between TRIB2 expression and immune cell infiltration，immune checkpoints，tumor mutation burden（TMB），and immunotherapy sensitivity were analyzed．Results  TRIB2 was highly expressed in colon cancer tissues（P＜0.05）．The highest level of TRIB2 mRNA expression was found in CMS1．TRIB2 was an independent prognostic factor for colon cancer patients（univariate Cox regression analysis：HR=1.397，95%CI：1.100-1.774，P=0.006；multivariate Cox regression analysis：HR=1.502，95%CI：1.158-1.947，P=0.002）．TRIB2 was closely associated with immune cell infiltration and positively correlated with the expression level of immune checkpoint molecules as well as TMB（r=0.39，P＜0.001）．The expression of TRIB2 was correlated with the efficacy of immune checkpoint inhibitors．Conclusions  TRIB2 is highly expressed in colon cancer and is closely associated with poor prognosis and the immune microenvironment of colon cancer patients．