Nasal Polyps

鼻息肉
  • 文章类型: Journal Article
    目的:对于正常检查或临床疾病,鼻内镜检查的关键组成部分尚未明确确定。这项研究旨在确定鼻学家之间关于检查结果对各种鼻部病变的重要性的一致性。
    方法:美国19位专家鼻学家组成的联盟被要求对5种不同的鼻窦症状表现的鼻内镜检查结果的重要性进行排名。
    方法:2023年7月发放了一份在线问卷。
    方法:问卷使用JotForm®软件,包含5个案例,每个案例有4个相同的问题,每个都涵盖了鼻内窥镜检查的常见适应症。排名被合成为归一化注意力得分(NASs)和加权归一化注意力得分(W-NASs),以代表每个特征的感知重要性。从0扩展到1。
    结果:每个病例的鼻内镜检查结果均具有总体一致性。根据临床表现,病例之间的重要性感知特征有所不同。例如,在评估鼻后滴漏时,中鼻道被选为最重要的检查结构(NAS,0.73),粘液被选为最重要的异常发现(W-NAS,0.66)。粘液的主要特征是它是否化脓(W-NAS,0.67)。在每种情况下对特征进行类似的分析。
    结论:鼻学家中存在的隐含框架可能有助于标准化检查并提高诊断准确性,加强学员的指导,并告知人工智能算法的发展,以提高鼻内窥镜检查期间的临床决策。
    OBJECTIVE: Critical components of the nasal endoscopic examination have not been definitively established for either the normal examination or for clinical disorders. This study aimed to identify concordance among rhinologists regarding the importance of examination findings for various nasal pathologies.
    METHODS: A consortium of 19 expert rhinologists across the United States was asked to rank the importance of findings on nasal endoscopy for 5 different sinonasal symptom presentations.
    METHODS: An online questionnaire was distributed in July 2023.
    METHODS: The questionnaire utilized JotForm® software and featured 5 cases with a set of 4 identical questions per case, each covering a common indication for nasal endoscopy. Rankings were synthesized into Normalized Attention Scores (NASs) and Weighted Normalized Attention Scores (W-NASs) to represent the perceived importance of each feature, scaled from 0 to 1.
    RESULTS: General concordance was found for examination findings on nasal endoscopy within each case. The perceived features of importance differed between cases based on clinical presentation. For instance, in evaluating postnasal drip, the middle meatus was selected as the most important structure to examine (NAS, 0.73), with mucus selected as the most important abnormal finding (W-NAS, 0.66). The primary feature of interest for mucus was whether it was purulent or not (W-NAS, 0.67). Similar analyses were performed for features in each case.
    CONCLUSIONS: The implicit framework existing among rhinologists may help standardize examinations and improve diagnostic accuracy, augment the instruction of trainees, and inform the development of artificially intelligent algorithms to enhance clinical decision-making during nasal endoscopy.
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  • 文章类型: English Abstract
    Objective: To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis. Methods: The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software. Results: Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP. Conclusion: The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.
    目的: 利用常规可用的临床标志物,通过对慢性鼻窦炎伴鼻息肉(CRSwNP)患者进行无监督聚类分析,揭示不同集群患者的临床特征。 方法: 收集2021—2023年于武汉大学人民医院接受鼻内镜手术治疗的155例CRSwNP患者(男112例,女43例,年龄7~87岁)的临床数据,包括年龄、性别、吸烟史、饮酒史、组织局部嗜酸粒细胞(EOS)计数及中性粒细胞(NEU)计数、共病变应性鼻炎(AR)、共病哮喘、是否复发、血清特异性免疫球蛋白E(IgE)、总IgE、细胞因子水平、外周血EOS计数及占比、Lund-Mackay CT评分、筛窦和上颌窦CT评分的比率(E/M比率)、视觉模拟量表(VAS)评分、Lund-Kennedy内镜评分等常见临床指标,进行无监督聚类分析,以明确每个群组对应的临床特征。采用GraphPad Prism 9.5软件对数据进行统计学分析。 结果: 通过临床核心指标的层次聚类分析,我们将患者分为4类(Cluster A1~A4),其主要特点是外周血细胞因子较高的轻症息肉、伴发过敏及哮喘的鼻息肉、高复发的NEU型鼻息肉亚组,以及高嗜酸性鼻息肉。核心指标及其子集的聚类结果展示了两类轻症息肉(Cluster B1~B2),其主要特点是细胞因子高表达、合并AR;以及两类重型息肉(Cluster B3~B4),临床表现为症状严重且Lund-Mackay CT评分、Lund-Kennedy内镜评分均高,其差异在于症状的复杂性、EOS浸润程度和伴发哮喘的概率。针对嗜酸性鼻息肉的进一步聚类分析,揭示了一类高度NEU浸润的复发性鼻息肉。多指标相关性分析的结果全面展示了鼻息肉常见临床参数之间的关联,为深入理解CRSwNP的临床表型提供了有价值的信息。 结论: 通过聚类分析,成功将CRSwNP患者分为不同亚型,深入探讨了它们在临床特征和疾病结果上的差异,为制定更精准的临床治疗方案提供了新的视角。.
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  • 文章类型: English Abstract
    Objective: To evaluate the predictive efficacy of sinus CT radiomics for treatment outcomes in nasal polyp patients undergoing endoscopic sinus surgery. Methods: A retrospective cohort study was conducted at the First Affiliated Hospital of Sun Yat-sen University, including 194 patients with nasal polyps treated between January 2015 and December 2019. The cohort comprised 132 males and 62 females, aged 16 to 75 years. Patients were divided into a training set (n=135) and an internal validation set (n=59). An external validation set (n=34), consisting of 22 males and 12 females aged 16 to 59 years, was included from January 2020 to December 2021. Disease control was evaluated using the criteria from the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS 2020). Radiomic features were extracted from sinus CT images and analyzed using the least absolute shrinkage and selection operator (LASSO) regression. Models combining radiomic and clinical features were developed to predict treatment efficacy. Results: The radiomics and combined models, based on four selected features, outperformed the clinical feature model in the training set, with AUC values of 0.901 and 0.915, versus 0.874, respectively. In the internal validation set, AUCs were 0.839, 0.832, and 0.716. Despite reduced AUCs in the external set, the radiomics model maintained good generalizability (0.748, 0.764, 0.620). Decision curve analysis showed significant clinical benefits in both radiomics and combined models. Conclusion: The CT-based radiomics model demonstrates significant predictive power in identifying refractory nasal polyps, suggesting its potential for clinical application in treatment outcome prediction.
    目的: 探讨鼻窦CT影像组学在预测鼻息肉术后疗效中的价值。 方法: 采用回顾性队列研究,分析2015年1月至2019年12月于中山大学附属第一医院接受内镜鼻窦手术的194例鼻息肉患者(男132例,女62例,年龄16~75岁),随机法以约7∶3的比例将病例分为训练集135例和内部验证集59例;同时,纳入2020年1月至2021年12月中山大学附第七医院的34例鼻息肉患者(男22例,女12例,年龄16~59岁)作为外部验证集。按照2020年欧洲鼻窦炎和鼻息肉意见书(EPOS 2020)对病例进行术后疾病控制状态评估,并将病情未控制的病例定义为难治性鼻息肉。提取影像组学特征后,利用套索算法(least absolute shrinkage and selection operator,LASSO)筛选特征,根据加权系数建立影像组学模型;并构建临床特征预测模型和影像组学-临床特征联合模型;评估3类模型在预测难治性鼻息肉中的诊断性能。采用R软件(版本4.3.1)进行统计学分析。 结果: 在训练集,基于4个特征的影像组学和联合模型预测难治性鼻息肉的曲线下面积(AUC)分别为0.901和0.915,均高于传统临床特征模型(AUC=0.874);在内部验证集,3种模型的AUC值分别为0.839、0.832和0.716;外部验证集的3种模型预测AUC值有所下降,分别为0.748、0.764和0.620。所有队列中,影像组模型和联合模型预测难治性鼻息肉在决策曲线分析(decision curve analysis,DCA)中均显示了临床效益。 结论: 基于鼻窦CT的影像组学模型对难治性鼻息肉具有良好的预测效能,展现了潜在的临床应用价值。.
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  • 文章类型: English Abstract
    Objective: To identify diagnostic markers related to oxidative stress in chronic rhinosinusitis with nasal polyps (CRSwNP) by analyzing transcriptome sequencing data, and to investigate their roles in CRSwNP. Methods: Utilizing four CRSwNP sequencing datasets, differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning methods for Hub gene selection were performed in this study. Subsequent validation was carried out using external datasets, as well as real-time quantitative polymerase chain reaction (Real-time qPCR), and immunofluorescence staining of clinical samples. Moreover, the diagnostic efficacy of the genes was assessed by receiver operating characteristic (ROC) curve, followed by functional and pathway enrichment analysis, immune-related analysis, and cell population localization. Additionally, a competing endogenous RNA (CeRNA) network was constructed to predict potential drug targets. Statistical analysis and plotting were conducted using SPSS 26.0 and Graphpad Prism9 software. Results: Through data analysis and clinical validation, CP, SERPINF1 and GSTO2 were identified among 4 138 DEGs as oxidative stress markers related to CRSwNP. Specifically, the expression of CP and SERPINF1 increased in CRSwNP, whereas that of GSTO2 decreased, with statistically significant differences (P<0.05). Additionally, an area under the curve (AUC)>0.7 indicated their effectiveness as diagnostic indicators. Importantly, functional analysis indicated that these genes were mainly related to lipid metabolism, cell adhesion migration, and immunity. Single-cell data analysis revealed that SERPINF1 was mainly distributed in epithelial cells, stromal cells, and fibroblasts, while CP was primarily located in epithelial cells, and GSTO2 was minimally present in the epithelial cells and fibroblasts of nasal polyps. Consequently, a CeRNA regulatory network was constructed for the genes CP and GSTO2. This construction allowed for the prediction of potential drugs that could target CP. Conclusion: This study successfully identifies CP, SERPINF1 and GSTO2 as diagnostic and therapeutic markers related to oxidative stress in CRSwNP.
    目的: 通过分析慢性鼻窦炎伴鼻息肉(CRSwNP)的转录组测序数据,鉴定与氧化应激相关的诊断标志物,并初步探究其在CRSwNP中的作用。 方法: 使用4个CRSwNP测序数据集,运用差异表达基因(differentially expressed genes,DEGs)分析、加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)和3种机器学习方法筛选Hub基因,并通过外部数据集、临床样本实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,Real-time qPCR)及免疫荧光染色进行验证,通过受试者工作特征曲线(ROC)评估基因诊断效能,并对这些基因进行功能和通路富集分析、免疫相关性分析及细胞群定位,构建竞争性内源RNA(competing endogenous RNA,CeRNA)网络并预测潜在靶向药物。采用SPSS 26.0和Graphpad Prism9软件进行统计分析及作图。 结果: 通过数据分析和临床验证,我们在4 138个DEGs中发现CP、SERPINF1和GSTO2是与CRSwNP相关的氧化应激标志物。CRSwNP中CP和SERPINF1表达上升,GSTO2表达下降,差异具有统计学意义(P<0.05);曲线下面积(AUC)>0.7,显示其为有效诊断指标。功能分析表明,这些基因主要与脂质代谢、细胞黏附迁移、免疫等功能相关。单细胞数据分析及免疫荧光染色发现SERPINF1主要分布在上皮细胞、基质细胞和成纤维细胞,CP主要分布在上皮细胞,GSTO2在鼻息肉的上皮细胞及成纤维细胞中仅有少量分布。随后,我们构建了CP和GSTO2的CeRNA调控网络,并预测了靶向CP的潜在药物。 结论: 本研究鉴定并通过临床样本验证发现CP、SERPINF1和GSTO2可作为CRSwNP氧化应激相关的诊疗标志物。.
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  • 文章类型: English Abstract
    Objective: To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs. Methods: Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing. Results: An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the \"yellow module\" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes (CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC+cells in CRS. Conclusion: This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.
    目的: 旨在深入探索慢性鼻窦炎(CRS)的分子机制,识别关键细胞亚群和基因,构建有效的诊断模型,并筛选潜在的治疗药物。 方法: 通过单细胞转录组测序数据鉴定CRS中的关键细胞亚群。通过高维加权基因共表达网络分析(high dimensional weighted gene co-expression network analysis,hdWGCNA)和多种机器学习算法的联合应用,筛选CRS的关键基因并构建CRS的诊断模型。通过孟德尔随机化和共定位分析进行因果推断分析。使用分子对接技术进行靶点药物的鉴定,并通过免疫荧光染色对生信分析的结果进行验证。采用Graphpad Prism、R、python和Adobe Illustrator软件进行数据及图像处理。 结果: CRS尤其是嗜酸性慢性鼻窦炎伴鼻息肉(ECRSwNP)中基底细胞和基上皮细胞占比增加(P=0.001)。hdWGCNA显示“黄色模块”与CRS中基底细胞和基上皮细胞密切相关。采用单因素逻辑回归和最小绝对值收敛和选择算法(least absolute shrinkage and selection operator,LASSO)筛选出13个关键基因(CTSC、LAMB3、CYP2S1、TRPV4、ARHGAP21、PTHLH、CDH26、MRPS6、TENM4、FAM110C、NCKAP5、SAMD3和PTCHD4)。基于这13个基因,使用多种机器学习算法构建出有效的CRS诊断模型(AUC=0.958)。孟德尔随机化分析显示组织蛋白酶C(cathepsin C,CTSC)与CRS具有因果关系(逆方差加权:OR=1.06,P=0.006),共定位分析证实CTSC与CRS具有共享的遗传变异(PPH4/PPH3>2)。分子对接结果显示,对乙酰氨基酚与CTSC具有较好的结合能力(结合能:-5.638 kcal/mol)。免疫荧光染色实验表明CRS中CTSC+细胞增多。 结论: 本研究综合运用多种生物信息学方法,识别了CRS中的关键细胞类型和基因,构建了有效的诊断模型,强调了CTSC在CRS中的关键作用,为CRS的治疗提供了新的靶点。.
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  • 文章类型: English Abstract
    Objective: To analysis the molecular characteristics of chronic rhinosinusitis with nasal polyps (CRSwNP), to unravel its pathophysiological mechanisms, and to develop a prognostic model capable of effectively predicting postoperative recurrence. Methods: The data from three datasets (GSE198950, GSE179265, and GSE136825) were integrated, comprising 39 control cases, 16 cases of chronic rhinosinusitis without nasal polyps, and 89 cases of CRSwNP. Differential expression genes (DEGs) were identified based on adjusted P<0.05 and Log2FC>1. KEGG and GO enrichment analyses, as well as STRING node scoring, were conducted. Variable selection was performed using random forest and least absolute shrinkage and selection operator regression (LASSO), with key nodes identified through intersection analysis. Mann-Whitney U test was applied, and variables with P<0.05 were included in the model. A prognostic model for CRSwNP was constructed using logistic regression, externally validated using RNA-seq data, and evaluated with receiver operating characteristic (ROC) curve analysis to calculate the area under the curve (AUC). Results: This research illustrated both upregulated and downregulated DEGs in CRSwNP, activating pathways like neuroactive ligand-receptor interaction and IL-17 signaling, while inhibiting calcium signaling and gap junctions. Key nodes identified through random forest and LASSO, including G protein subunit γ4 (U=3.00 P=0.028), Cholecystokinin (U=0.50, P=0.006), Epidermal growth factor (U=1.00 P=0.008), and Neurexin-1 (U=0.00, P=0.004), showing statistical significance in external validation. The prognostic model, visualized in a line graph, exhibited high reliability (C-index=0.875,AUC=0.866). The ROC curve in external validation indicated its effectiveness in predicting postoperative recurrence (AUC=0.859). Conclusions: This study integrates multiple datasets on CRSwNP to provide a comprehensive description of its molecular features. The prognostic model, built upon key nodes identified through random forest and LASSO analyses, demonstrates high accuracy in both internal and external validations, thus providing robust support for the development of personalized treatment strategies for CRSwNP.
    目的: 分析慢性鼻窦炎伴鼻息肉(CRSwNP)的分子特征,揭示其病理生理机制,并构建能有效预测术后复发的预后模型。 方法: 整合3个数据集GSE198950、GSE179265及GSE136825,其中对照组39例,慢性鼻窦炎不伴鼻息肉组16例,CRSwNP组89例,提取校正P值<0.05且Log2FC>1的差异基因,随后进行KEGG和GO富集分析及蛋白互作评分。采用随机森林和最小绝对值收敛和选择算法(least absolute shrinkage and selection operator,LASSO)进行变量筛选,交集分析后得到关键节点。回顾性分析二代RNA测序数据(对照4例,CRSwNP 8例),利用Mann-Whitney U检验对前述关键节点进行比较,将P<0.05的变量纳入模型。利用既往测序数据(原发CRSwNP 16例,复发CRSwNP 15例)通过Logistic回归构建CRSwNP的预后模型,绘制列线图,利用校准曲线和受试者工作特征曲线(ROC),并计算曲线下面积(AUC)以验证模型可信性。 结果: 对CRSwNP组中上调和下调的差异基因进行分析,其中神经活性配体-受体相互作用、白细胞介素17信号通路被激活,而钙信号通路及间隙连接被抑制。利用随机森林和LASSO鉴定出关键节点,其中G蛋白γ亚基4(U=3.00,P=0.028)、胆囊收缩素(U=0.50,P=0.006)、表皮生长因子(U=1.00,P=0.008)和神经突触细胞黏附分子1(U=0.00,P=0.004)在Whitney U检验中具有统计学意义,将其纳入回归模型。将预后模型制成列线图,验证模型校准曲线和ROC表明其高度可信(C-index=0.875,AUC=0.866),而测试集中的ROC曲线显示其可有效预测CRSwNP的术后复发(AUC=0.859)。 结论: 本研究利用CRSwNP相关数据集,全面描述了该疾病的分子特征。通过随机森林和LASSO回归筛选出的关键节点构建的预后模型在验证中表现出高准确性,为推进CRSwNP的个体化诊疗提供了有力支持。.
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  • 文章类型: English Abstract
    Objective: To analyze the cellular composition characteristics of the nasal tissue immune microenvironment in patients with control, chronic rhinosinusitis without nasal polyps (CRSsNP), non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP), and eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) using mass cytometry flow technology. Methods: Thirteen CRS patients who underwent endoscopic nasal surgery at the Department of Otorhinolaryngology Head and Neck Surgery of Peking Union Medical College Hospital from March to December 2022 were recruited, including 8 males and 5 females, aged 22.3 to 58.3 years. Three control mucosae were obtained from normal ethmoid or sphenoid sinuses of patients with benign tumors of the temporal fossa or non-functional pituitary adenomas who underwent endoscopic surgery, excluding allergic rhinitis and sinusitis. Sixteen clinical tissue samples (3 of control, 3 of CRSsNP, 4 of neCRSwNP, and 6 of eCRSwNP) were prepared into single-cell suspensions. Mass cytometry flow detection was performed using a combination of 42 molecular markers to analyze the differences in cell subpopulations among the groups. Data were analyzed using GraphPad Prism 9. Results: Based on the mass cytometry flow results, cells from control, CRSsNP, neCRSwNP, and eCRSwNP were divided into seven main cell subgroups, with detailed subgrouping of T/NK cells and myeloid cells. In T/NK cells, compared with the control group, the number of NK CD56bright cells increased in the CRSsNP group, while NK CD56dim cells decreased; compared with the CRSsNP group, the eCRSwNP group showed a decrease in NKT cells and CD4+Tem cells; compared with the CRSsNP group, the eCRSwNP group showed a significant increase in CD25 expression within Treg cells; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in Tbet expression in CD8+Teff cells and CD8+TRM cells; in eCRSwNP, the expression of CD103 in CD8+TRM cells was significantly lower than in CRSsNP. In myeloid cells, compared with the other three groups, the eCRSwNP group showed a significant increase in macrophages and a significant decrease in cDC1 and monocytes; compared with the control group and CRSsNP, the eCRSwNP group also showed a significant decrease in resting state macrophages; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in the level of CX3CR1 within cDC2 and monocytes; the expression levels of NLRP3 in cDC2 and macrophages in the eCRSwNP group were significantly higher than in the other three groups; compared with the control group, the expression levels of Gata3 in cDC2 and macrophages in the eCRSwNP group were also significantly increased; additionally, the expression of CCR2 within monocytes in the eCRSwNP group was lower than in the CRSsNP group. In ILC, compared with the control group, the expression of CCR6 decreased in the eCRSwNP group. Conclusions: Compared with the control group, CRSsNP, and neCRSwNP, eCRSwNP shows an increase in macrophage number, a decrease in cDC1 and resting state macrophages, and depletion of protective cells CD103+CD8+TRM. Additionally, the expression levels of CCR2 and CX3CR1 in monocytes of eCRSwNP are decreased.
    目的: 利用质谱流式技术分析对照、慢性鼻窦炎不伴鼻息肉(CRSsNP)、非嗜酸粒细胞型慢性鼻窦炎伴鼻息肉(neCRSwNP)和嗜酸粒细胞型慢性鼻窦炎伴鼻息肉(eCRSwNP)患者的鼻腔组织免疫微环境细胞构成特征。 方法: 招募2022年3—12月就诊于北京协和医院耳鼻咽喉头颈外科行鼻内镜手术的CRS患者13例,其中男8例,女5例,年龄22.3~58.3岁。3例对照黏膜来自经鼻内镜手术的颞下窝良性肿瘤或无功能垂体腺瘤患者的正常筛窦或蝶窦,并排除了变应性鼻炎和鼻窦炎。将16例临床组织样本(对照组3例、CRSsNP 3例、neCRSwNP 4例、eCRSwNP 6例)制备成单细胞悬液。用42种分子标志物构成的组合进行质谱流式检测,分析细胞亚群在各组间的差异。采用GraphPad Prism 9对数据进行分析。 结果: 根据质谱流式结果将对照、CRSsNP、neCRSwNP和eCRSwNP的细胞划分为7个主要的细胞亚群,并对T/NK细胞和髓样细胞进行详细的分群。在T/NK细胞中,与对照组相比,CRSsNP组的NK CD56bright细胞数量增加,NK CD56dim细胞数量减少;与CRSsNP组相比,eCRSwNP组的NKT细胞和CD4+Tem细胞数量减少;与CRSsNP组相比,eCRSwNP组中CD25在Treg细胞内的表达水平显著增加;与CRSsNP组相比,eCRSwNP组的CD8+Teff细胞和CD8+TRM细胞中Tbet表达显著减少;eCRSwNP组中,CD103在CD8+TRM细胞中的表达明显少于CRSsNP组。在髓样细胞中,与其他3组相比,eCRSwNP组中巨噬细胞明显增多、cDC1和单核细胞显著减少;与对照组和CRSsNP组相比,eCRSwNP组的静息状态巨噬细胞也明显减少;与CRSsNP组相比,eCRSwNP组的cDC2和单核细胞内CX3CR1的水平显著降低;eCRSwNP组的cDC2和巨噬细胞中NLRP3的表达水平显著高于其他3组;与对照组相比,eCRSwNP组中cDC2和巨噬细胞中Gata3的表达水平也显著升高;此外,eCRSwNP组中单核细胞内CCR2的表达低于CRSsNP组。在ILC中,与对照组相比,eCRSwNP组中CCR6的表达减少。 结论: 与对照、CRSsNP、neCRSwNP相比,eCRSwNP中巨噬细胞数量增多,cDC1、静息状态巨噬细胞等减少,保护性细胞CD103+CD8+TRM耗竭;此外,eCRSwNP的单核细胞中CCR2和CX3CR1表达水平降低。.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:慢性鼻-鼻窦炎(CRS)是一种炎症性疾病,分为伴鼻息肉的慢性鼻-鼻窦炎(CRSwNP)和不伴鼻息肉的慢性鼻-鼻窦炎(CRSsNP)。Th细胞管理CRS中的炎性细胞。细胞因子信号抑制蛋白(SOCS)通过向Th1,Th2和Th17细胞极化来调节Th细胞中的Janus激酶(JAK)-信号转导子和转录激活因子(STAT)途径。这项研究评估了CRS患者中SOCS1,3,5的水平,以发现与Th细胞的关联。方法:在这项横断面研究中,20名CRSwNP患者,12名CRSsNP患者,和12个控制参与。使用免疫组织化学确定CD4+T细胞的浸润。使用实时PCR评估特定转录因子和SOCS蛋白的表达。使用ELISA评估细胞因子水平。使用蛋白质印迹分析研究SOCS蛋白水平。结果:与CRSsNP组和对照组相比,CRSwNP组中SOCS3的表达增加(p<0.001)。与CRSsNP组(p<0.05)和对照组(p<0.001)相比,CRSwNP组的SOCS3蛋白水平增加。尽管CRSsNP组和对照组之间的SOCS5表达存在显着差异,SOCS5蛋白水平在CRSsNP与对照组(p<0.001)和CRSwNP(p<0.05)组之间显著不同。结论:可以通过调节SOCS3和SOCS5蛋白来建议CRS的靶向治疗,这些蛋白负责Th细胞向Th2或Th1细胞的极化。分别。JAK-STAT通路靶向,包括许多细胞,可以限于SOCS蛋白以更有效地协调Th细胞分化。
    Background: Chronic rhinosinusitis (CRS) is an inflammatory condition classified into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). Th cells manage inflammatory cells in CRS. Suppressor of Cytokine Signaling (SOCS) proteins regulate Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in Th cells by polarizing toward Th1, Th2, and Th17 cells. This study evaluated the levels of SOCS1,3,5 in CRS patients to find associations with Th cells. Methods: In this cross-sectional study, 20 CRSwNP patients, 12 CRSsNP patients, and 12 controls participated. The infiltration of CD4+ T cells was determined using immunohistochemistry. The expression of specific transcription factors and SOCS proteins was assessed using real-time PCR. Cytokine levels were evaluated using ELISA. SOCS protein levels were investigated using western blot analysis. Results: The expression of SOCS3 increased in the CRSwNP group compared to CRSsNP and control groups (p <0.001). SOCS3 protein levels increased in the CRSwNP group compared to CRSsNP (p <0.05) and control (p <0.001) groups. Although there was a significant difference in SOCS5 expression between CRSsNP and control groups, SOCS5 protein levels were significantly different between CRSsNP and control (p <0.001) and CRSwNP (p <0.05) groups. Conclusions: Targeted therapies may be suggested for CRS by modulating SOCS3 and SOCS5 proteins that are responsible for polarization of Th cells toward Th2 or Th1 cells, respectively. JAK-STAT pathway targeting, which encompasses numerous cells, can be limited to SOCS proteins to more effectively orchestrate Th cell differentiation.
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  • 文章类型: Letter
    结论:关于治疗慢性鼻-鼻窦炎伴鼻息肉的当前实践模式的数据,包括耳鼻喉科医生认为哪些药物可以更好地管理患者的症状,是有限的。这项研究表明,当代实践模式与已发表的临床共识声明基本一致。非标签鼻类固醇冲洗和dupilumab是最常用的局部和全身治疗慢性鼻-鼻窦炎伴鼻息肉,分别。
    CONCLUSIONS: Data on current practice patterns for the management of chronic rhinosinusitis with nasal polyps, including which medications are deemed by otolaryngologists to better manage patient symptoms, are limited. This study demonstrated that contemporary practice patterns are largely consistent with published clinical consensus statements. Off-label nasal steroid irrigations and dupilumab are the most commonly used topical and systemic therapies for chronic rhinosinusitis with nasal polyps, respectively.
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