Purpose:Granulomatous mastitis (GLM) is a rare and complex chronic inflammatory disease of the breast with an unknown cause and a tendency to recur. As medical science advances, the cause, treatment strategies, and comprehensive management of GLM have increasingly attracted widespread attention. The aim of this study is to assess the development trends and research focal points in the GLM field over the past 24 years using bibliometric analysis.Methods:Using GLM, Granulomatous mastitis (GM), Idiopathic granulomatous lobular mastitis (IGLM), and Idiopathic granulomatous mastitis (IGM) as keywords, we retrieved publications related to GLM from 2000 to 2023 from the Web of Science, excluding articles irrelevant to this study. Citespace and VOSviewer were employed for data analysis and visualization.Results:A total of 347 publications were included in this analysis. Over the past 24 years, the number of publications has steadily increased, with Turkey being the leading contributor in terms of publications and citations. The University of Health Sciences, Istanbul University, and Istanbul University Cerrahpasa were the most influential institutions. The Breast Journal, Breast Care, and Journal of Investigative Surgery were the journals that published the most on this topic. The research primarily focused on the cause, differential diagnosis, treatment, and comprehensive management of GLM. Issues related to recurrence, hyperprolactinemia, and Corynebacterium emerged as current research hotspots.Conclusion:Our bibliometric study outlines the historical development of the GLM field and identifies recent research focuses and trends, which may aid researchers in identifying research hotspots and directions, thereby advancing the study of GLM.

目的 探究桑黄素(Morin)在脂多糖(LPS)诱导的巨噬细胞RAW 264.7氧化应激过程中的作用及相关机制.方法 体外培养RAW 264.7细胞,分为二甲基亚砜(DMSO)组(DMSO)、LPS组(LPS 1 mg/L)、Morin组(Morin 25.0μmol/L)、LPS+Morin组(LPS 1 mg/L+Morin 25.0μmol/L).经不同浓度Morin预处理后,予LPS 1 mg/L刺激24 h,四唑盐(MTT)比色法检测不同处理对细胞活力的影响.蛋白免疫印迹法(western blot,WB)和实时荧光定量聚合酶链式反应(qRT-PCR)检测Morin(25.0μmol/L)对LPS诱导的RAW 264.7细胞中NADPH氧化酶1(NOX1)、NOX4、核因子2相关因子2(Nrf2)和血红素加氧酶1(HO-1)的表达.结果 MTT比色法结果显示,LPS(1 mg/L)和Morin(12.5、25.0μmol/L)对RAW 264.7细胞活力均未造成显著影响(P>0.05).WB和qRT-PCR结果显示,Morin预处理可显著抑制LPS诱导的RAW 264.7细胞中NOX1和NOX4的表达(P<0.05,P<0.01).此外,与DMSO组比较,LPS处理上调RAW 264.7细胞中Nrf2和HO-1的表达(P<0.01,P<0.001),Morin处理进一步上调Nrf2和HO-1的表达(P<0.01).结论 Morin通过激活Nrf2/HO-1信号通路,下调NOX1和NOX4表达,抑制LPS诱导的RAW 264.7巨噬细胞氧化应激反应.

目的:探究桑黄素在脂多糖(LPS)诱导的急性肺损伤(ALI)中的相关机制.方法:将32只雄性C57BL/6小鼠随机分为对照组(生理盐水)、ALI模型组(LPS处理)、LPS+桑黄素低浓度(25 mg/kg)处理组和LPS+桑黄素高浓度(50 mg/kg)处理组,共4组,每组8只.LPS(6 mg/kg)溶液经气管滴入小鼠气道刺激支气管及肺组织建立ALI模型.桑黄素溶液经腹腔注射给药3 d后,收取双肺,对一部分肺组织测定湿/干质量比,进行HE染色和组织病理学观察.采用实时荧光定量PCR(qPCR)和Western blot检测肺组织中氧化应激信号通路相关基因(NOX1、NOX4、Nrf2和HO-1)的表达情况.结果:HE染色和肺湿/干质量比测定结果显示气道滴入LPS成功构建了ALI小鼠模型,与对照组比较,桑黄素处理可有效缓解LPS诱导的急性肺损伤.qPCR和Western blot实验结果显示,与对照组比较,ALI模型组肺组织中,Nrf2和HO-1的表达上调(P<0.01);与ALI模型组比较,桑黄素处理可显著降低肺组织NOX1和NOX4的表达(P<0.05或P<0.01);且桑黄素处理可进一步上调Nrf2和HO-1的表达从而抑制氧化应激的发生(P<0.05或P<0.01).结论:氧化应激的发生参与ALI的发生发展,桑黄素可通过激活Nrf2-HO-1信号通路降低NOX1和NOX4表达抑制氧化应激,从而减缓LPS引起的肺损伤.

目的 体外实验探究黄芪补肾活血汤通过HIF1α-Smad/Runx2/Osterix信号轴治疗乳腺癌骨转移的作用机制.方法 采用细胞增殖与毒性检测(CCK-8)法检测细胞活力,观察黄芪补肾活血汤(0、20、40 mg·mL-1)对乳腺癌细胞MCF-7的增殖和活力的影响;迁移实验检测黄芪补肾活血汤对乳腺癌细胞MCF-7迁移水平的影响;Transwell实验检测黄芪补肾活血汤对乳腺癌细胞MCF-7侵袭水平的影响;流式细胞术检测黄芪补肾活血汤对乳腺癌细胞MCF-7凋亡作用的影响;共培养乳腺癌细胞MCF-7、成骨细胞MC3T3-E1后蛋白免疫印迹法(Western blot,WB)检测黄芪补肾活血汤对共培养后的成骨细胞MC3T3-E1中缺氧诱导因子-1α(HIF1α)、Smad家族成员1(Smad1)、Smad家族成员5(Smad5)、Runt相关转录因子2(Runx2)以及锌指转录因子(Osterix)的蛋白表达情况的影响.结果 体外实验中,CCK-8法显示,与control组相比,20、40 mg·mL-1质量浓度的黄芪补肾活血汤干预MCF-7细胞48 h后能不同程度的降低MCF-7细胞的增殖和细胞活力,呈剂量依赖性.划痕实验表明,与control组相比,黄芪补肾活血汤(20 mg·mL-1、40 mg·mL-1)组细胞迁移率明显降低(P<0.01),呈剂量依赖性.Transwell检测结果显示,与control组相比,黄芪补肾活血汤(20 mg·mL-1、40 mg·mL-1)组穿膜细胞数明显减少(P<0.001),呈剂量依赖性.流式细胞术检测结果显示,与control组相比,黄芪补肾活血汤(20 mg·mL-1、40 mg·mL-1)组凋亡率明显升高(P<0.001),呈剂量依赖性.平板克隆实验结果显示,黄芪补肾活血汤(20 mg·mL-1、40 mg·mL-1)组的细胞克隆个数明显少于control组(P<0.05),呈剂量依赖性.EDU增殖实验显示,与control组相比,黄芪补肾活血汤(20 mg·mL-1、40 mg·mL-1)组细胞阳性率明显降低(P<0.05),呈剂量依赖性.Western blot实验表明,与control组比较,不同质量浓度的黄芪补肾活血汤作用于成骨细胞MC3T3-E1后,HIF1α、Osterix蛋白相对表达水平降低(P<0.01),Smad1、Smad5、Runx2蛋白表达升高(P<0.01),呈剂量依赖性.结论 黄芪补肾活血汤通过HIF1α-Smad/Runx2/Osterix信号轴剂量依赖性抑制乳腺癌细胞MCF-7活力,通过HIF1α靶点改善肿瘤缺氧微环境,通过Osterix靶点抑制肿瘤血管生成和癌细胞迁移;并通过Smad1、Smad5、Runx2等靶点等促进骨髓间充质细胞成骨分化、成熟,保护骨质,促进新骨形成,抑制并缓解骨转移.

同源异型盒1 (sine oculis homeobox homolog 1,SIX1)基因参与多种肿瘤调控,在乳腺癌发生发展过程中发挥了重要作用,但具体机制仍有待探讨.本研究目的 在于分析SIX1基因在乳腺癌中的表达情况,研究其在乳腺癌细胞增殖与侵袭过程中所发挥的作用并探讨作用的机制.TCGA数据库和GEPIA2在线数据库分析发现,SIX1在乳腺癌中的表达高于正常组织,且在乳腺癌的不同分子亚型Basal-like、HER2、Luminal A、Luminal B中也证实了这一点(P＜0.05);HPA数据库分析发现,SIX1的免疫组化蛋白质表达水平高于正常乳腺组织,SIX1基因在乳腺癌中高表达,差异具有统计学意义(P＜0.001).在乳腺癌细胞株MDA-MB-231中,干扰SIX1的表达及在MCF-7中过表达SIX1后,生长曲线及EdU实验结果显示:敲低SIX1后乳腺癌细胞的生长增殖受到抑制,而过表达SIX1则会发挥促进作用(生长曲线实验:P＜0.05;EdU实验:P＜0.001);Transwell结果表明,SIX1能够增强乳腺癌细胞的侵袭能力(P＜0.001).利用TCGA数据库,根据SIX1基因表达值的上下四分位定义SIX1基因高表达及低表达人群,对两组队列进行差异基因分析,发现差异基因与代谢、干细胞调控等通路相关;对敲低SIX1的乳腺癌细胞系进行转录物组测序(RNA-sequencing,RNA-seq),并对测序结果进行一系列生物信息学分析发现,SIX1与代谢、干细胞调控以及EMT等通路密切相关.挑选代表性基因MYC、SNAI2、EGFR,通过已发表的GEO临床数据集以及KM-plot-ter验证靶基因与SIX1表达的相关性及与临床乳腺癌病人的预后关系,我们发现:SIX1与MYC、SNAI2、EGFR表达正相关.高表达的SIX1、MYC、SNAI2与EGFR不利于乳腺癌病人的生存.利用GCBI、GeneMANIA及String在线工具,我们发现了SIX1基因相互作用的蛋白质和相关的lncRNA及miRNA.综上,本研究中初步揭示了SIX1在乳腺癌中发挥的作用及其调控机制,为进一步深入研究该基因提供了线索.

Background : Triple-negative breast cancer (TNBC) progresses at a rapid pace. Chemotherapy is a major clinical application. However, resistance and metastases are key barriers to chemotherapy. Xiaojin pills (XJP) have been used clinically for treating TNBC for decades. However, the potential molecular mechanisms of the effect of XJP on breast cancer is still not understood. Methods: The cell viability was analyzed using Cell Counting Kit-8 (CCK-8). Flow cytometry was used to detect apoptosis, and the migration and invasion abilities of TNBC were assessed using Transwell assay. For molecular mechanisms, the protein expression levels were determined by Western blot analysis. The expression of β-catenin in the Wnt/β-serial protein (β-catenin) pathway was detected with immunofluorescence (IF). Results: XJP inhibited the viability and proliferation of the TNBC cell line in vitro . Flow cytometry analysis showed that apoptosis increased in both MDA-MB-231 and MDA-MB-468 cells induced by XJP. The expression of the proteins associated with invasion, for example, matrix metalloproteinase (MMP) and MMP9, was reduced. Among epithelial–mesenchymal transition markers, E-cadherin was upregulated and N-cadherin was downregulated. The apoptosis-related proteins caspase-8, caspase-3, caspase-9, and Parp were all upregulated. Additionally, XJP effectively suppressed the expression of β-catenin, which belonged to the Wnt/β-catenin pathway. Conclusions: These results suggested that XJP suppressed the progression of TNBC cells by suppressing apoptosis, invasion, EMT, and Wnt/β-catenin pathway.

目的:通过细胞实验及生信分析探究小金丸在乳腺癌骨转移中的作用机制.方法:采用细胞增殖与活性检测(CCK-8)法检测细胞活力,观察小金丸对MCF-7细胞活力的抑制作用.网络药理学及分子对接2种生信分析手段预测小金丸作用于乳腺癌骨转移的主要成分及靶点.小金丸的活性成分及靶点利用中药系统药理学数据库和分析平台(TCSMP)等传统草药数据库和SwissTargetPrediction数据库筛选,乳腺癌骨转移相关靶点通过GeneCards和DisGeNET数据库筛选,STRING平台构建蛋白质-蛋白质相互作用(PPI)网络,DAVID在线分析基因本体(GO)富集分析功能和京都基因和基因组百科全书(KEGG)富集分析.小金丸主要活性成分-乳腺癌骨转移疾病靶点-通路网络利用Cytoscape 3.7.2构建.利用AutoDock4软件对接验证分子.蛋白免疫印迹法(Westem blot)检测基质金属蛋白酶-9(MMP-9),缺氧诱导因子1α(HIF1A)和雄激素受体(AR)蛋白表达.结果:小金丸能抑制MCF-7细胞活力,通过氧化还原,蛋白质自磷酸化等过程作用于乳腺癌骨转移.KEGG富集分析得HIF-1,血管内皮生长因子(VEGF)和磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)等信号通路发挥作用.分子对接验证结果显示桉树素等有效成分能与AR,MMP-9等稳定结合.蛋白免疫印迹提示,小金丸剂量依赖性抑制MCF-7细胞中MMP-9和HIF1A蛋白的表达.结论:小金丸通过HIF,VEGF等相关信号通路作用于AR,MMP-9等主要靶点蛋白,从而改善肿瘤微环境缺氧,抑制血管生成,以及降低细胞侵袭性和细胞活力.