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Background: Breast cancer is a complex multifactorial disease and polymorphisms in nucleotide excision repair pathway are associated with the potential risk of breast cancer. Pathological processes linked to breast cancer are associated with oxidative stress. Catalase plays an essential role in cell defense against oxidative stress. Curcumin has antioxidant activity that can significantly reduce oxidative stress levels. The aims of this study were to determine ERCC5 rs751402 polymorphism was associated with oxidative stress in breast carcinogenesis. The impact of curcumin on catalase activity for inhibiting breast cancer progression was also studied. Methods: The effect of ERCC5 rs751402 polymorphism on oxidative stress was studied with different H2O2 concentrations in HCC 1937 cell line for 24 h and then analysed by MTT assay. The impact of curcumin on catalase activity was studied in MCF-7 cell line treated with different curcumin concentrations for 24 h and then analysed by trypan blue exclusion assay and catalase activity assay. Results: It showed that this polymorphism involved in oxidative stress (p < 0.05) and curcumin caused the antiproliferative effect by the catalase activity increase (p < 0.05). Conclusion: Our study indicated that ERCC5 rs751402 polymorphism may contribute to the etiology of breast carcinogenesis about the failure of oxidative stress protection and lead to breast carcinogenesis. The antiproliferative effect of curcumin may be associated with catalase activity and protect breast carcinogenesis.  相似文献   
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We propose a Deep learning-based weak label learning method for analyzing whole slide images (WSIs) of Hematoxylin and Eosin (H&E) stained tumor tissue not requiring pixel-level or tile-level annotations using Self-supervised pre-training and heterogeneity-aware deep Multiple Instance LEarning (DeepSMILE). We apply DeepSMILE to the task of Homologous recombination deficiency (HRD) and microsatellite instability (MSI) prediction. We utilize contrastive self-supervised learning to pre-train a feature extractor on histopathology tiles of cancer tissue. Additionally, we use variability-aware deep multiple instance learning to learn the tile feature aggregation function while modeling tumor heterogeneity. For MSI prediction in a tumor-annotated and color normalized subset of TCGA-CRC (n=360 patients), contrastive self-supervised learning improves the tile supervision baseline from 0.77 to 0.87 AUROC, on par with our proposed DeepSMILE method. On TCGA-BC (n=1041 patients) without any manual annotations, DeepSMILE improves HRD classification performance from 0.77 to 0.81 AUROC compared to tile supervision with either a self-supervised or ImageNet pre-trained feature extractor. Our proposed methods reach the baseline performance using only 40% of the labeled data on both datasets. These improvements suggest we can use standard self-supervised learning techniques combined with multiple instance learning in the histopathology domain to improve genomic label classification performance with fewer labeled data.  相似文献   
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目的 探究N6-甲基腺苷(m6A)去甲基化酶ALKBH5对紫外线诱导的晶状体上皮细胞(LEC)氧化损伤模型中DNA损伤修复的影响。方法 运用qRT-PCR和免疫印迹实验检测年龄相关性白内障(ARC)患者和对照组晶状体前囊膜上皮细胞中ALKBH5的mRNA和蛋白的表达。通过紫外线B(UVB)构建晶状体上皮细胞株SRA01/04细胞氧化损伤模型和靶向ALKBH5设计小干扰RNA(siRNA)转染构建敲降模型,运用qRT-PCR和免疫印迹实验检测氧化损伤模型和敲降模型中ALKBH5的mRNA和蛋白表达。运用CCK-8法检测Control组、UVB组、UVB+siNC组和UVB+siALKBH5#3组中SRA01/04细胞活力变化。免疫荧光染色检测UVB+siNC组和UVB+siALKBH5#3组中15A3的荧光强度变化。运用qRT-PCR检测转染对照siNC组和转染siALKBH5#3组中11个DNA氧化损伤修复基因(ODRGs)的mRNA表达变化。结果 在ARC患者的晶状体前囊膜上皮细胞中,ALKBH5的mRNA和蛋白表达水平均显著升高。在UVB以时间梯度诱导SRA01/04的细胞氧化损伤模型中,ALKBH5的mRNA和蛋白表达水平均呈上升后下降趋势,其中UVB照射10 min后ALKBH5 mRNA和蛋白表达升高最为显著。ALKBH5敲降效率结果显示,与转染对照siNC组相比,转染靶向ALKBH5的siRNA后,ALKBH5的mRNA和蛋白表达均显著下降。CCK-8法检测结果显示,与UVB+siNC组相比,UVB+siALKBH5#3组SRA01/04细胞活力明显降低。免疫荧光染色检测结果显示,与UVB+siNC组相比,UVB+siALKBH5#3组SRA01/04细胞内DNA氧化损伤指标15A3染色显著增加。同时,与转染对照siNC组相比,转染ALKBH5#3组SRA01/04细胞的ODRGs中,TREX1、FANCD2、LIG1、MSH2、MSH3、RPA2、SMUG1、XRCC6 mRNA的表达均显著上升,DCLRE1A mRNA的表达显著下降,MGMT和MRE11A mRNA的表达则未见明显差异。结论 m6A去甲基化酶ALKBH5在UVB诱导的LEC氧化损伤模型中诱导性表达上升,敲降ALKBH5可促进LEC内大部分ODRGs表达升高,参与调控LEC内损伤DNA的修复,阻止ARC的发生。  相似文献   
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目的 探讨18F-氟代脱氧葡萄糖(18F-FDG)PET/CT的代谢参数及临床指标在弥漫性大B细胞淋巴瘤(DLBCL)中期评估及预后预测中的意义。方法 收集194例DLBCL患者临床资料,记录患者的中期评估结果,比较不同临床指标[β2 -微球蛋白(β2-MG)、双表达、三表达、Ann Arbor分期、淋巴瘤国际预后评分 (IPI)、多维尔5分法(D5PS)评分]和18F-FDG PET/CT代谢参数[最大标准化摄取值(SUVmax)、病灶累及部位SUVmax的总和(SUVmaxsum)、平均标准化摄取值(SUVmean)和SUVmax下降幅度(△SUVmax)]中达完全缓解(CR)者所占比例的差异,应用Cox回归和Kaplan-Meier生存分析法分析18F-FDG PET/CT代谢参数及临床指标对DCBCL患者2年无进展生存期(PFS)的影响,并对SUVmax与β2-MG、Ann Arbor分期和IPI评分进行相关性分析。结果 β2-MG > 2.3 mg/L、Ann Arbor分期Ⅲ/Ⅳ期、IPI > 2分、SUVmax > 17.00和SUVmaxsum > 38.60者达CR的比例较低;疗效达CR者△SUVmax大于未达CR者(P均 < 0.05)。Cox单因素分析显示,β2-MG、Ann Arbor分期、IPI评分、双表达、三表达、SUVmaxsum及D5PS评分均与DLBCL患者2年PFS有关(P均 < 0.05);多因素分析显示,Ann Arbor分期Ⅲ/Ⅳ期(HR = 4.486,P = 0.001)为DLBCL患者2年PFS的独立危险因素,D5PS 评分1~3分(HR = 0.256,P < 0.001)为DLBCL患者2年PFS的独立保护因素。Spearman秩相关分析显示,SUVmax与β2-MG(rs = 0.348,P = 0.001)、Ann Arbor分期(rs = 0.236,P = 0.022)和IPI评分(rs = 0.305,P = 0.003)均有关。结论 18F-FDG PET/CT的代谢参数与临床指标相关,Ann Arbor分期和D5PS可作为DLBCL患者预后的参考指标。  相似文献   
6.
目的 探讨砭石疗法对中青年慢性失眠患者睡眠质量及伴随症状的辅助治疗作用,并分析相关机制。方法 将92例中青年慢性失眠患者随机分为砭石组与对照组各46例。对照组睡前口服佐匹克隆片7.5 mg;砭石组在对照组治疗基础上接受中医砭石疗法治疗,每周1次、每次40 min、30 d为1个疗程。采用匹兹堡睡眠质量指数(PSQI)评分减少率评估2组患者的失眠改善率,记录治疗前后2组的失眠严重程度指数(ISI)、焦虑自评量表(SAS)评分、抑郁自评量表(SDS)评分,检测治疗前后患者血清的5-羟色胺(5-HT)水平。比较上述各项2组间差异。结果 治疗开始前,砭石组与对照组的ISI、SAS及SDS评分比较差异均无统计学意义(P均> 0.05)。治疗1个疗程后,砭石组的失眠改善率为 93.5%,高于对照组的76.1%(P < 0.05)。治疗1个疗程后,2组患者的ISI、SAS及SDS评分均低于治疗前,血清5-HT水平高于治疗前(P均< 0.05);砭石组患者的ISI、SAS及SDS评分均低于对照组,血清5-HT水平高于对照组(P均< 0.05)。结论 砭石疗法安全、环保,有助于改善中青年慢性失眠患者的睡眠质量及伴随症状。砭石疗法辅助治疗慢性失眠及其伴随症状的机制可能涉及神经递质5-HT。  相似文献   
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BackgroundIdentifying the MIC wild-type distribution and its delineation of species targeted for receiving antimicrobial agent breakpoints is an important first step for determining clinical breakpoints. Having the main responsibility in the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for characterizing the wild-type distributions and setting epidemiological cut-off values (ECOFFs), we explain the why, the how, and frequent misconceptions of wild-type MIC distributions and ECOFFs.ObjectivesTo clarify how wild-type MIC distributions and ECOFFs for agents and important target organisms are defined and determined and why these are important tools in microbiology, as well as to point to common misunderstandings and inappropriate use.SourcesThe EUCAST database of >40 000 MIC distributions; publications addressing the definition of wild-type MIC distributions, and ECOFFs in bacteria and fungi; and the EUCAST Standard Operating Procedure 10 Documents published by the European Centre for Disease Control and the European Food Safety Agency.ContentThe rationale for defining wild-type distributions and ECOFFs is explained. Setting breakpoints that bisect wild-type MIC distributions leads to poor methodological reproducibility and poor correlation between clinical outcome and susceptibility testing results. The methods applied by EUCAST to select distributions for aggregation and website display are described, highlighting the importance of incorporating data from multiple sources and methods. The methods used by EUCAST to estimate ECOFFs are outlined. Finally, the common misunderstandings of these processes are addressed.ImplicationsThe international community needs to agree on the phenotypic definitions of wild-type distributions. Systematic methods for developing and applying ECOFFs are essential to the conduct of phenotypic antimicrobial susceptibility testing and interpretation, which will remain the dominant laboratory method for the foreseeable future.  相似文献   
9.
目的探讨关节镜下半月板成形术(AMP)对膝关节半月板损伤患者血清疼痛因子、一氧化氮(NO)、透明质酸(HA)及关节活动度的影响。方法选取2019年5月—2020年12月收治的90例膝关节半月板损伤为研究对象,根据治疗方法不同分为对照组和治疗组,每组45例。对照组接受保守治疗,治疗组行AMP治疗。比较两组的临床疗效,治疗前后的血清前列腺素E2(PGE2)、5-羟色胺(5-HT)、NO、HA、疼痛视觉模拟评分法(VAS)评分和膝关节活动度。记录两组治疗并发症发生情况。结果治疗组疗效优良率高于对照组(P<0.05)。治疗后,两组血清PGE2、5-HT、NO、HA水平均较治疗前下降,且治疗组低于对照组(P<0.05)。治疗后1、2、3、4周,两组VAS评分均较治疗前降低,且治疗组低于对照组(P<0.05)。治疗后,两组膝关节屈伸活动度均较治疗前升高,且治疗组高于对照组(P<0.05)。两组并发症发生率比较差异无统计学意义(P>0.05)。结论AMP对膝关节半月板损伤疗效良好,可减少疼痛因子生成,控制NO、HA水平,提高关节活动度。  相似文献   
10.
《Clinical breast cancer》2022,22(6):560-566
BackgroundIn the United States, Europe, and Asia, a consensus has been reached that there is a higher risk of breast cancer in high density breasts. However, there are some contrary reports that suggest the absence of an association between breast composition and breast cancer subtype; thus, there is conflicting evidence. The purpose of this study was to investigate trends in the incidence of breast cancer subtypes according to breast composition and analyze the survival rates in Japanese women.Patients and MethodsBetween 2007 and 2008, 1258 Japanese patients with invasive breast cancer who underwent mammography and obtained a pathological diagnosis in our institution were included in the study. We compared cancer subtypes with breast composition types (dense and non-dense breast), and classified them based on initial mammography findings. Information on 5- and 10-year survival rates was collected by chart review for patients with dense and nondense breasts. Statistical analysis was performed using the Pearson's chi-square test for breast composition and cancer subtype. The effect of breast composition on mortality was examined using a multivariate Cox proportional hazards model, and adjusted hazard ratios were calculated.ResultsNo significant difference was found between breast cancer subtype and breast composition (P = .08). Five-year (log-rank test, P = .09) and 10-year (log-rank test, P = .31) survival rates were not significantly different between breast composition types.ConclusionThere was no significant association between breast composition and cancer subtypes. There was also no significant difference in the prognosis between patients with and without dense breasts.  相似文献   
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