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[Opportunities and challenges in the research of chronic rhinosinusitis driven by multi-omics and big data]. [多组学和大数据驱动下的慢性鼻炎研究机遇与挑战]。
Q4 Medicine Pub Date : 2024-06-07 DOI: 10.3760/cma.j.cn115330-20240131-00072
H Wang, Z Liu
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引用次数: 0
[Unsupervised clustering analysis based on multidimensional features reveals distinct clinical characteristics and associated factors of different phenotypes in patients with chronic rhinosinusitis with nasal polyp]. [基于多维特征的无监督聚类分析揭示了慢性鼻窦炎伴鼻息肉患者不同表型的临床特征和相关因素】。]
Q4 Medicine Pub Date : 2024-06-07 DOI: 10.3760/cma.j.cn115330-20240131-00069
J Y Huang, Y G Luo, H Lyu, D Liu, Y F Wang, P Q Liu, L Tan, R Xiang, W Zhang, Y Xu

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.

目的利用常规临床参数,通过无监督聚类分析,发现慢性鼻炎伴鼻息肉(CRSwNP)患者不同聚类的临床特征。研究方法前瞻性地收集了2021年至2023年在武汉大学人民医院接受鼻内镜手术的155例CRSwNP患者的临床资料,其中男性112例,女性43例,年龄7至87岁。利用各种临床参数进行无监督聚类分析,包括年龄、性别、吸烟和饮酒史、局部嗜酸性粒细胞(EOS)和中性粒细胞(NEU)计数、合并过敏性鼻炎(AR)、合并哮喘、复发状况、血清特异性 IgE、总 IgE、细胞因子水平、通过外周血 EOS 计数和百分比、Lund-Mackay CT 评分、上颌窦和筛窦 CT 评分比值(E/M 比值)、视觉模拟量表(VAS)评分、Lund-Kennedy 内窥镜评分以及其他常见临床指标来阐明各组群的临床特征。统计分析使用 GraphPad Prism 9.5 软件进行。结果层次聚类分析确定了四个主要聚类(聚类 A1-A4),显示出不同的特征,如轻度鼻息肉伴有较高的外周血细胞因子水平、鼻息肉伴有过敏和哮喘、鼻息肉亚型以中性粒细胞为主且复发率高、鼻息肉伴有高嗜酸性粒细胞水平。进一步的子集聚类发现,两个轻度息肉群(群 B1-B2)具有细胞因子高表达和合并 AR 的特点;两个重度息肉群(群 B3-B4)症状严重,Lund-Mackay CT 评分高,Lund-Kennedy 内镜评分高。B3组和B4组之间的差异包括症状复杂程度、嗜酸性粒细胞浸润程度以及合并哮喘的可能性。对嗜酸性粒细胞鼻息肉的进一步聚类分析显示,该聚类的特点是高度嗜中性粒细胞浸润和鼻息肉反复发作。多指标相关性的综合分析表明了鼻息肉常见临床参数之间的关系,为深入了解 CRSwNP 的发病机制提供了宝贵的信息。结论本研究的聚类分析根据临床特征和疾病结局将 CRSwNP 患者分为不同的群组,为更精确的临床治疗策略提供了新的视角。
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引用次数: 0
[Application and prospect of artificial intelligence in the precision diagnosis and treatment of chronic rhinosinusitis]. [人工智能在慢性鼻炎精准诊疗中的应用及前景]。
Q4 Medicine Pub Date : 2024-06-07 DOI: 10.3760/cma.j.cn115330-20240130-00061
J J Li, W Q Wang, D S R D Aodeng, Z Z Zhu, W Lyu
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引用次数: 0
[Research progress of nonsyndromic familial non-medullary thyroid carcinoma]. [非综合征家族性非髓性甲状腺癌的研究进展]。
Q4 Medicine Pub Date : 2024-06-07 DOI: 10.3760/cma.j.cn115330-20240102-00006
Q Y Ma, Z J Ma, S Y Jiang, L Mao, Maimaiti Yusufu, Y F Wang, X W Wang
{"title":"[Research progress of nonsyndromic familial non-medullary thyroid carcinoma].","authors":"Q Y Ma, Z J Ma, S Y Jiang, L Mao, Maimaiti Yusufu, Y F Wang, X W Wang","doi":"10.3760/cma.j.cn115330-20240102-00006","DOIUrl":"10.3760/cma.j.cn115330-20240102-00006","url":null,"abstract":"","PeriodicalId":23987,"journal":{"name":"Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery","volume":"59 6","pages":"658-662"},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Characterizing immune microenvironment cell composition of chronic rhinosinusitis with nasal polyps based on mass cytometry technology]. [基于质谱技术表征慢性鼻炎伴鼻息肉的免疫微环境细胞组成]。
Q4 Medicine Pub Date : 2024-06-07 DOI: 10.3760/cma.j.cn115330-20240210-00085
L Wang, W Q Wang, D S R D Aodeng, Y Z Liu, Z Z Zhu, J J Li, W Lyu

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. <

研究目的利用质谱流式细胞仪技术分析对照组、无鼻息肉慢性鼻炎(CRSsNP)、伴有鼻息肉的非嗜酸性慢性鼻炎(neCRSwNP)和伴有鼻息肉的嗜酸性慢性鼻炎(eCRSwNP)患者鼻腔组织免疫微环境的细胞组成特征。研究方法招募2022年3月至12月期间在北京协和医院耳鼻咽喉头颈外科接受鼻内镜手术的13例CRS患者,其中男8例,女5例,年龄在22.3岁至58.3岁之间。3份对照黏膜取自接受内窥镜手术的颞窝良性肿瘤或无功能垂体腺瘤患者的正常乙状窦或蝶窦,不包括过敏性鼻炎和鼻窦炎。16 份临床组织样本(3 份对照组、3 份 CRSsNP、4 份 neCRSwNP 和 6 份 eCRSwNP)被制备成单细胞悬浮液。使用 42 种分子标记物进行质谱流式检测,分析各组细胞亚群的差异。数据使用 GraphPad Prism 9 进行分析。结果根据质谱流式检测结果,对照组、CRSsNP 组、neCRSwNP 组和 eCRSwNP 组的细胞被分为七个主要细胞亚群,并对 T/NK 细胞和髓系细胞进行了详细分组。在 T/NK 细胞方面,与对照组相比,CRSsNP 组 NK CD56bright 细胞数量增加,而 NK CD56dim 细胞数量减少;与 CRSsNP 组相比,eCRSwNP 组 NKT 细胞和 CD4+Tem 细胞数量减少;与 CRSsNP 组相比,eCRSwNP 组 Treg 细胞中 CD25 的表达显著增加;与 CRSsNP 组相比,eCRSwNP 组 CD8+Teff 细胞和 CD8+TRM 细胞中 Tbet 的表达显著减少;eCRSwNP 组 CD8+TRM 细胞中 CD103 的表达显著低于 CRSsNP 组。在骨髓细胞中,与其他三组相比,eCRSwNP 组的巨噬细胞明显增加,而 cDC1 和单核细胞明显减少;与对照组和 CRSsNP 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 cDC2 和单核细胞中的 CX3CR1 水平明显降低;eCRSwNP 组 cDC2 和巨噬细胞中 NLRP3 的表达水平显著高于其他三组;与对照组相比,eCRSwNP 组 cDC2 和巨噬细胞中 Gata3 的表达水平也显著升高;此外,eCRSwNP 组单核细胞中 CCR2 的表达水平低于 CRSsNP 组。在 ILC 中,与对照组相比,eCRSwNP 组中 CCR6 的表达量减少。结论与对照组、CRSsNP 和 neCRSwNP 相比,eCRSwNP 显示巨噬细胞数量增加,cDC1 和静息状态巨噬细胞减少,保护性细胞 CD103+CD8+TRM 减少。此外,eCRSwNP 的单核细胞中 CCR2 和 CX3CR1 的表达水平也有所下降。
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引用次数: 0
[Progress and research on animal models of tinnitus]. [耳鸣动物模型的研究进展]。
Q4 Medicine Pub Date : 2024-06-07 DOI: 10.3760/cma.j.cn115330-20231031-00180
H W Zhou, C Zhang, P Liu, X M Xue, W D Shen, S M Yang, F Y Wang
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引用次数: 0
[Analysis of one-year outcomes after cochlear implantation in adults with single-sided deafness]. [单侧耳聋成人人工耳蜗植入术后一年效果分析]。
Q4 Medicine Pub Date : 2024-06-07 DOI: 10.3760/cma.j.cn115330-20231113-00202
J Y Chen, B Chen, Y Shi, L F Zhang, Z C Gao, Y Kong, Y X Li

Objectives: To investigate the outcomes of cochlear implantation in Mandarin-speaking cochlear implant (CI) users with single-sided deafness (SSD). Methods: This study was a single-center prospective cohort study. Eleven Mandarin-speaking adult SSD patients who underwent CI implantation at Capital Medical University Beijing Tongren Hospital from August 2020 to October 2021 were recruited, including 6 males and 5 females, with the age ranging from 24 to 50 years old. In a sound field with 7 loudspeakers distributed at 180°, we measured root-mean-square error(RMSE)in SSD patients at the preoperative, 1-month, 3-month, 6-month, and 12-month after switch-on to assess the improvement of sound source localization. The Mandarin Speech Perception (MSP) was used in the sound field to test the speech reception threshold (SRT) of SSD patients under different signal-to-noise locations in a steady-state noise under conditions of CI off and CI on, to reflect the head shadow effect(SSSDNNH), binaural summation effect(S0N0) and squelch effect(S0NSSD). The Tinnitus Handicap Inventory (THI) and the Visual Analogue Scale (VAS) were used to assess changes in tinnitus severity and tinnitus loudness in SSD patients at each time point. The Speech, Spatial and Qualities of Hearing Scale(SSQ) and the Nijmegen Cochlear Implantation Scale (NCIQ) were used to assess the subjective benefits of spatial speech perception and quality of life in SSD patients after cochlear implantation. SPSS 19.0 software was used for statistical analysis. Results: SSD patients showed a significant improvement in the poorer ear in hearing thresholds with CI-on compared with CI-off; The ability to localize the sound source was significantly improved, with statistically significant differences in RMSE at each follow-up time compared with the preoperative period (P<0.05). In the SSSDNNH condition, which reflects the head shadow effect, the SRT in binaural hearing was significantly improved by 6.5 dB compared with unaided condition, and the difference was statistically significant (t=6.25, P=0.001). However, there was no significant improvement in SRT between the binaural hearing condition and unaided conditions in the S0N0 and S0NSSD conditions (P>0.05). The total score of THI and three dimensions were significant decreased (P<0.05). Tinnitus VAS scores were significantly lower in binaural hearing compared to the unaided condition (P<0.001). The total score of SSQ, and the scores of speech and spatial dimensions were significant improved in binaural hearing compared to the unaided condition (P<0.001). There was no statistical difference in NCIQ questionnaire scores between preoperative and postoperative (P>0.05), and only the self-efficacy subscore showed a significant increase(Z=

目的调查讲普通话的单侧耳聋(SSD)人工耳蜗(CI)使用者的人工耳蜗植入效果。研究方法本研究是一项单中心前瞻性队列研究。招募了 11 名讲普通话的成年单侧耳聋患者,他们于 2020 年 8 月至 2021 年 10 月在首都医科大学附属北京同仁医院接受了人工耳蜗植入手术,其中男性 6 人,女性 5 人,年龄在 24 岁至 50 岁之间。在7个扬声器呈180°分布的声场中,我们测量了SSD患者术前、术后1个月、3个月、6个月和12个月的均方根误差(RMSE),以评估声源定位的改善情况。在声场中使用普通话语音感知(MSP)测试 SSD 患者在稳态噪声中不同信噪比位置下的语音接收阈值(SRT),分别为 CI 关闭和 CI 开启条件下的语音接收阈值,以反映头影效应(SSSDNNH)、双耳求和效应(S0N0)和静噪效应(S0NSSD)。耳鸣障碍量表(THI)和视觉模拟量表(VAS)用于评估 SSD 患者在每个时间点的耳鸣严重程度和耳鸣响度的变化。言语、空间和听力质量量表(SSQ)和奈梅亨人工耳蜗植入量表(NCIQ)用于评估人工耳蜗植入后 SSD 患者在空间言语感知和生活质量方面的主观获益。统计分析采用 SPSS 19.0 软件。结果与CI-off相比,SSD患者较差耳的听阈在CI-on时有明显改善;声源定位能力明显提高,各随访时间的RMSE与术前相比差异有统计学意义(PSSDNNH状态,反映了头影效应,双耳听力SRT与无助状态相比明显提高了6.5 dB,差异有统计学意义(t=6.25,P=0.001)。然而,在 S0N0 和 S0NSSD 条件下,双耳听力与无助听条件下的 SRT 没有明显改善(P>0.05)。THI总分和三个维度的得分均有显著下降(PPPP>0.05),只有自我效能子得分有显著上升(Z=-2.497,P=0.013)。结论CI 可以帮助讲普通话的 SSD 患者在一定程度上恢复双耳听力,改善声音定位和噪声中的语音识别能力。此外,CI 还能抑制 SSD 患者的耳鸣,降低耳鸣的响度,改善空间听觉的主观感受和生活质量。
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引用次数: 0
[Analysis of risk factors and construction of nomogram model for local lymph node metastasis in salivary gland mucoepidermoid carcinoma]. [涎腺黏液表皮样癌局部淋巴结转移的危险因素分析及提名图模型构建]。
Q4 Medicine Pub Date : 2024-06-07 DOI: 10.3760/cma.j.cn115330-20231106-00187
M J Zhang, Y S Yao, X Chen, Y K Mou, Y M Li, X C Song

Objective: To analyze the risk factors affecting regional lymph node metastasis in salivary gland mucoepidermoid carcinoma (MEC) and to establish a nomogram model for individually predicting lymph node metastasis in salivary gland MEC. Methods: The clinical data of 2 152 patients with salivary gland MEC from 1975 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The collected data were divided into training cohort (1 506 cases) and validation cohort (646 cases) according to the ratio of 7∶3. Single-factor regression and multi-factor logistic regression were used to screen factors related to local lymph node metastasis in salivary gland MEC, with constructing of a nomogram. Calibration curve, receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and decision curve analysis were used to evaluate model performance in the validation cohort and the total cohort. Statistical tests were performed using SPSS (26.0) and R (4.3.0) software. Results: Multivariate logistic regression results showed that M stage [OR(95%CI):12.360(3.295-46.365), P=0.014], pathological grade Ⅱ、Ⅲ、Ⅳ[OR(95%CI): 1.956(1.329-2.879), 9.654(6.309-14.772), 9.298(6.072-14.238), P<0.001], T staging T2, T3, T4[OR(95%CI): 1.706(0.932-3.124), 3.021(1.790-5.096), 3.311(1.925-5.695), P<0.001], and gender [OR(95%CI):0.759(0.593-0.972), P=0.029] were independent factors affecting local lymph node metastasis in salivary gland MEC. Through verification in the validation cohort and the total cohort, the AUC values were greater than 0.8, and the calibration curve was close to the perfect reference line, proving that the constructed nomogram model had good specificity and sensitivity for predicting local lymph node metastasis in salivary gland MEC. Conclusion: M stage, pathological grade, T stage, and gender are risk factors for predicting regional lymph node metastasis and the established-nomogram has good predictive performance for local lymph node metastasis in salivary gland MEC.

研究目的分析影响涎腺黏液表皮样癌(MEC)区域淋巴结转移的风险因素,并建立单独预测涎腺黏液表皮样癌淋巴结转移的提名图模型。方法:从美国国立癌症研究所的监测、流行病学和最终结果(SEER)数据库中收集1975年至2020年间2 152例唾液腺黏液瘤患者的临床数据。所收集的数据按照 7∶3 的比例分为训练队列(1 506 例)和验证队列(646 例)。采用单因素回归和多因素Logistic回归筛选涎腺MEC局部淋巴结转移的相关因素,并构建提名图。采用校准曲线、接收器操作特征曲线(ROC)、ROC 曲线下面积(AUC)和决策曲线分析来评估模型在验证队列和总队列中的表现。统计测试使用 SPSS (26.0) 和 R (4.3.0) 软件进行。结果多变量逻辑回归结果显示,M期[OR(95%CI):12.360(3.295-46.365), P=0.014]、病理分级Ⅱ、Ⅲ、Ⅳ[OR(95%CI): 1.956(1.329-2.879), 9.654(6.309-14.772), 9.298(6.072-14.238),POR(95%CI):1.706(0.932-3.124),3.021(1.790-5.096),3.311(1.925-5.695),POR(95%CI):0.759(0.593-0.972),P=0.029]是影响唾液腺 MEC 局部淋巴结转移的独立因素。通过在验证队列和总队列中的验证,AUC 值均大于 0.8,校正曲线接近完美参考线,证明所构建的提名图模型在预测涎腺 MEC 局部淋巴结转移方面具有良好的特异性和灵敏度。结论M分期、病理分级、T分期和性别是预测区域淋巴结转移的危险因素,所建立的提名图对涎腺癌局部淋巴结转移具有良好的预测效果。
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引用次数: 0
[Identification of oxidative stress-related biomarkers in chronic rhinosinusitis with nasal polyps using WGCNA combined with machine learning algorithms]. [利用 WGCNA 结合机器学习算法识别慢性鼻窦炎伴鼻息肉患者的氧化应激相关生物标记物]。
Q4 Medicine Pub Date : 2024-06-07 DOI: 10.3760/cma.j.cn115330-20240202-00076
Y Yuan, X Y Shi, X Y Ma, X Y Xie, C H Wu, L Q Zhang, X Z Li, P Wang, X Feng

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.

目的通过分析转录组测序数据,确定慢性鼻炎伴鼻息肉(CRSwNP)中与氧化应激相关的诊断标记物,并研究它们在 CRSwNP 中的作用。方法本研究利用四个 CRSwNP 测序数据集,进行了差异表达基因(DEGs)分析、加权基因共表达网络分析(WGCNA)和三种用于 Hub 基因选择的机器学习方法。随后,利用外部数据集、实时定量聚合酶链反应(Real-time qPCR)和临床样本的免疫荧光染色进行了验证。此外,还通过接收者操作特征曲线(ROC)评估了基因的诊断效果,随后进行了功能和通路富集分析、免疫相关分析和细胞群定位。此外,还构建了竞争性内源性 RNA(CeRNA)网络,以预测潜在的药物靶点。统计分析和绘图使用 SPSS 26.0 和 Graphpad Prism9 软件进行。结果通过数据分析和临床验证,在 4 138 个 DEGs 中,CP、SERPINF1 和 GSTO2 被确定为与 CRSwNP 相关的氧化应激标志物。具体而言,CP 和 SERPINF1 在 CRSwNP 中的表达量增加,而 GSTO2 的表达量减少,差异有统计学意义(P0.7),表明它们是有效的诊断指标。重要的是,功能分析表明这些基因主要与脂质代谢、细胞粘附迁移和免疫有关。单细胞数据分析显示,SERPINF1 主要分布在上皮细胞、基质细胞和成纤维细胞中,CP 主要分布在上皮细胞中,而 GSTO2 在鼻息肉的上皮细胞和成纤维细胞中含量极少。因此,为 CP 和 GSTO2 基因构建了 CeRNA 调控网络。该网络的构建有助于预测针对 CP 的潜在药物。结论本研究成功地将 CP、SERPINF1 和 GSTO2 鉴定为与 CRSwNP 氧化应激有关的诊断和治疗标志物。
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引用次数: 0
[Hinokiol regulates the cell cycle and apoptosis of nasopharyngeal carcinoma CNE1 cells via Hippo-YAP signaling pathway]. [桧醇通过Hippo-YAP信号通路调节鼻咽癌CNE1细胞的细胞周期和凋亡】。]
Q4 Medicine Pub Date : 2024-06-07 DOI: 10.3760/cma.j.cn115330-20231212-00287
K Y Wu, L Liu, Z H Wu, Q Huang, R J Xie, L Zhou, M Wang

Objective: To explore the effects of hinokiol on the cell cyle and apoptosis of CNE1 nasopharyngeal carcinoma cells and the relevant molecular mechanism. Methods: The CNE1 cells were cultured in vitro and incubated with different concentrations of honokiol, and the cells were divided into blank control group, 10 μmol/L, 20 μmol/L and 40 μmol/L hinokiol treatment groups, and 10 μg/ml cisplatin group. Cell viability was determined by methylthiazolyldiphenyl- tetrazolium bromide (MTT) method, the cell cycle distribution was detected by flow cytometry, mitochondrial membrane potential was detected by mitochondrial membrane potential test kit, apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method, and the proteins expression of proliferating cell nuclear antigen (PCNA) and G1/S specific cyclin D1 (cyclin D1) were detected by immunoblotting. RNA-Seq was conducted in the hinokiol-treated cells. The mRNA expression of yes-associated protein delta (YAP) was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The proteins expression of phosphor-YAP (p-YAP) and nuclear YAP were detected by immunoblotting, the nuclear distribution of YAP protein was detected by immunofluorescence in the cells with or without treated with the mammalian STE20-like kinase 1/2 (MST1/2) inhibitor (XMU-MP-1), hinokiol, and XMU-MP-1+hinokiol. Statistical analysis of the data was conducted using GraphPad Prism 8.0 software. Resluts Compared with the control group, the cell viablity of CNE1 cells, the levels of mitochondrial membrane potential, the proteins expression of PCNA and cyclin D1 in hinokiol treatment groups were markedly decreased (all P values<0.05), while the proportion of G0/G1 phase cells and the ratio of TUNEL-positive cells were significantly increased (both P values<0.05). Transcriptome analysis showed that differential genes were mainly enriched in Wnt signaling pathway, tumor necrosis factor pathway, and Hippo signaling pathway. The mRNA level of YAP and the protein expression of YAP in the nucleus were decreased and the level of p-YAP protein was increased in cells treated with hinokiol, which were significantly different from control group (all P values<0.05). Compared with the hinokiol group, XMU-MP-1+hinokiol groups showed the decrease of p-YAP protein expression (1.157±0.076 vs 0.479±0.038, t=37.120, P<0.05), the increase of YAP protein expression in the nucleus (0.143±0.012 vs 0.425±0.031, t=29.181, P<0.05), the reduced proportion of cells in G0/G1 phase [(72.494±3.309)% vs (58.747±2.865)%, t=17.265, P<0.05], and the decrease of apoptosis ratio [(53.158±3.376)% vs (29.621±2.713)%, t=28.584, P<0.05]. Conclusion: Hinokiol can arrest the cell cycle and induce the cell apoptosis of CN

研究目的探讨桧醇对CNE1鼻咽癌细胞凋亡的影响及相关分子机制。方法:体外培养 CNE1 细胞:体外培养CNE1鼻咽癌细胞,用不同浓度的honokiol培养,将细胞分为空白对照组,10 μmol/L、20 μmol/L和40 μmol/L的hinokiol处理组,以及10 μg/ml顺铂组。细胞活力用甲基噻唑二苯基溴化四唑法(MTT)测定,细胞周期分布用流式细胞仪检测,线粒体膜电位用线粒体膜电位检测试剂盒检测、免疫印迹法检测增殖细胞核抗原(PCNA)和G1/S特异性细胞周期蛋白D1(cyclin D1)的蛋白表达。对 hinokiol 处理过的细胞进行了 RNA-Seq 扩增。通过定量反转录聚合酶链反应(RT-qPCR)检测了是相关蛋白δ(YAP)的 mRNA 表达。免疫印迹法检测磷酸-YAP(p-YAP)和核YAP蛋白的表达,免疫荧光法检测YAP蛋白在添加或未添加哺乳动物STE20样激酶1/2(MST1/2)抑制剂(XMU-MP-1)、桧醇和XMU-MP-1+桧醇的细胞中的核分布。使用 GraphPad Prism 8.0 软件对数据进行统计分析。结果 与对照组相比,hinokiol处理组CNE1细胞活力、线粒体膜电位水平、PCNA和细胞周期蛋白D1的蛋白表达均明显下降(P值均为0/G1期细胞),TUNEL阳性细胞比例明显升高(P值均为P值vs 0.479±0.038,t=37.120,Pvs 0.425±0.031,t=29.181,P0/G1期[(72.494±3.309)% vs (58.747±2.865)%,t=17.265,Pvs (29.621±2.713)%,t=28.584,PConclusion:Hinokiol可通过Hippo/YAP信号通路阻滞CNE1细胞的细胞周期并诱导细胞凋亡。
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引用次数: 0
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Chinese journal of otorhinolaryngology head and neck surgery
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