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MiR-214 Expression Is Elevated in Chronic Rhinosinusitis Mucosa and Regulates Lipopolysaccharide-Mediated Responses in Undifferentiated Human Nasal Epithelial Cell Culture. 在未分化的人鼻上皮细胞培养中,MiR-214在慢性鼻窦炎粘膜中的表达升高并调节脂多糖介导的反应
IF 2.6 3区 医学 Q1 Medicine Pub Date : 2023-07-01 DOI: 10.1177/19458924231152683
Zhou Wang, Dong Lin, Yuxiang Zhao, Hui Liu, Ting Yang, An Li
Background Chronic rhinosinusitis (CRS) is an inflammatory disorder of the upper airways. MicroRNAs (miRs) are reported to regulate several diverse physiological and pathological processes. Objective This study aimed to evaluate the impact of miR-214 on lipopolysaccharide (LPS)-mediated inflammation, and mucin 5AC (MUC5AC) expression in human nasal epithelial cells. Methods The expression of miR-214 was detected in CRS with polyps (CRSwNP) and CRS without polyps (CRSsNP) tissues. Cells were treated with LPS and a miR-214 inhibitor. The level of miR-214 was detected by quantitative real-time reverse transcriptase-PCR (qRT-PCR). The inflammatory cytokines (IL-6, IL-8, TNF, and IL-1β) and MUC5AC production were determined by qRT-PCR and ELISA. MUC5AC protein level was detected using western blot. Similarly, we determined the relationship between miR-214 and Sirtuin 1 (SIRT1) using the Dual luciferase activity assay. Results miR-214 was increased in CRSwNP and CRSsNP tissues. LPS triggered the expression of miR-214, while miR-214 inhibition diminished the level of miR-214. MiR-214 inhibition prevented LPS-mediated the production of inflammatory cytokines. LPS treatment augmented MUC5AC mRNA, protein levels, and secretion, whereas miR-214 loss inhibited MUC5AC production in the presence of LPS. SIRT1 is a direct target of miR-214. Impairing SIRT1 by siRNA (siSIRT1) or EX527 (a selective SIRT1 inhibitor) reversed the effects of miR-214 inhibitor on inflammation and MUC5AC expression. Furthermore, miR-214 depression inhibited the STAT3/GDF15 pathway via targeting SIRT1. Upregulation of STAT3 or GDF15 partly abolished the anti-inflammatory roles of miR-214 inhibitor. Conclusion Taken together, miR-214 regulates LPS-mediated inflammation and MUC5AC expression via targeting SIRT1, and STAT3/GDF15 may involve in the regulation of miR-214 inhibitor on inflammation and MUC5AC expression.
背景:慢性鼻窦炎(CRS)是一种上呼吸道炎症性疾病。据报道,MicroRNAs (miRs)调节多种不同的生理和病理过程。目的:本研究旨在评估miR-214对人鼻上皮细胞中脂多糖(LPS)介导的炎症和粘蛋白5AC (MUC5AC)表达的影响。方法:检测miR-214在有息肉的CRS (CRSwNP)和无息肉的CRS (CRSsNP)组织中的表达。细胞用LPS和miR-214抑制剂处理。采用实时定量逆转录pcr (qRT-PCR)检测miR-214水平。采用qRT-PCR和ELISA检测炎症因子(IL-6、IL-8、TNF和IL-1β)和MUC5AC的产生。western blot检测MUC5AC蛋白水平。同样,我们使用双荧光素酶活性测定法确定了miR-214和Sirtuin 1 (SIRT1)之间的关系。结果:miR-214在CRSwNP和CRSsNP组织中表达升高。LPS触发miR-214的表达,而miR-214的抑制降低了miR-214的水平。MiR-214抑制抑制lps介导的炎症细胞因子的产生。LPS处理增加了MUC5AC mRNA、蛋白水平和分泌,而miR-214缺失抑制了LPS存在下MUC5AC的产生。SIRT1是miR-214的直接靶点。通过siRNA (siSIRT1)或EX527(一种选择性SIRT1抑制剂)损伤SIRT1可以逆转miR-214抑制剂对炎症和MUC5AC表达的影响。此外,miR-214抑制通过靶向SIRT1抑制STAT3/GDF15通路。STAT3或GDF15的上调部分消除了miR-214抑制剂的抗炎作用。结论:综上所述,miR-214通过靶向SIRT1调控lps介导的炎症和MUC5AC表达,STAT3/GDF15可能参与了miR-214抑制剂对炎症和MUC5AC表达的调控。
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引用次数: 1
This Summer, Think Like a Vagabond. 这个夏天,像个流浪汉一样思考。
IF 2.6 3区 医学 Q1 Medicine Pub Date : 2023-07-01 DOI: 10.1177/19458924231180674
Sanjeet V Rangarajan
I am excited and honored to introduce the July 2023 issue of the American Journal of Rhinology and Allergy. As this issue finds its way to your desk, those of us in the northern hemisphere are enjoying the throes of summer. For many of us, summer brings warm temperatures, time off for longawaited vacations, and fuller homes as students take a break from school or college. Many of us in medicine more specifically recall July as a time of transition, when newly graduated residents take their first step into independent practice, fellows arrive in our institutions to hone their craft, and freshly minted interns take a stab (literally) at learning what it truly means to be a physician. For me, summer brings memories of growing up in Michigan, the birthplace of the American automotive industry, where I spent my summers playing, working, or taking the occasional road trip. When I was asked to introduce this summer edition of AJRA, an illustrative piece of Midwestern lore came to mind which, to me, mirrors the quest for innovation shared by our authors and readers alike. In the early 20th century, a few friends embarked on a series of legendary summer road trips across the United States. Between 1915 and 1924, their adventures took them from vast expanses of Great Lakes coastline to the Florida Everglades and many places in between. As they camped across the country, they found that they shared a penchant for innovation, and the trips became catalysts for remarkable conversations and fresh ideas which influenced their work upon returning home. One of these “fresh ideas” was to call themselves the Vagabonds. Today, the Vagabonds are better known to us as Thomas Edison, Harvey Firestone, and Henry Ford. The Vagabonds embodied the spirit of progress as they blended Edison’s inventive mind, Ford’s revolutionary approach to manufacturing, and Firestone’s tire expertise to leave an indelible mark on the automotive industry while road tripping down America’s first byways. The story of the Vagabonds serves as a reminder of the profound impact that friendship, enduring bonds, and collective ambition can have on inspiring progress. In the same way, the AJRA community’s pursuit of progress is driven by an inherent curiosity and a desire to improve patients’ lives. The impact of technology on our field cannot be overstated, and in this issue of AJRA we present several articles in which technological innovation is highlighted. Artificial intelligence (AI) represents one of the most highly publicized and discussed topics not just in rhinology, but across all fields. Since the introduction of natural language models such as ChatGPT at the end of 2022, AI has entered the public consciousness so rapidly and universally that it represents one of the most important themes of this year. In this issue, Osie et al examine AI in the field of rhinology in their timely scoping review. Their manuscript examines the current literature and highlights opportunities for future inves
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引用次数: 0
A Scoping Review of Artificial Intelligence Research in Rhinology. 鼻科学人工智能研究综述
IF 2.6 3区 医学 Q1 Medicine Pub Date : 2023-07-01 DOI: 10.1177/19458924231162437
Gabriel Osie, Rhea Darbari Kaul, Raquel Alvarado, Gregory Katsoulotos, Janet Rimmer, Larry Kalish, Raewyn G Campbell, Raymond Sacks, Richard J Harvey

Background: A considerable volume of possible applications of artificial intelligence (AI) in the field of rhinology exists, and research in the area is rapidly evolving.

Objective: This scoping review aims to provide a brief overview of all current literature on AI in the field of rhinology. Further, it aims to highlight gaps in the literature for future rhinology researchers.

Methods: OVID MEDLINE (1946-2022) and EMBASE (1974-2022) were searched from January 1, 2017 until May 14, 2022 to identify all relevant articles. The Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews checklist was used to guide the review.

Results: A total of 2420 results were identified of which 62 met the eligibility criteria. A further 17 articles were included through bibliography searching, for a total of 79 articles on AI in rhinology. Each year resulted in an increase in the number of publications, from 3 articles published in 2017 to 31 articles published in 2021. Articles were produced by authors from 22 countries with a relative majority coming from the USA (19%), China (19%), and South Korea (13%). Articles were placed into 1 of 5 categories: phenotyping/endotyping (n = 12), radiological diagnostics (n = 42), prognostication (n = 10), non-radiological diagnostics (n = 7), surgical assessment/planning (n = 8). Diagnostic or prognostic utility of the AI algorithms were rated as excellent (n = 29), very good (n = 25), good (n = 7), sufficient (n = 1), bad (n = 2), or was not reported/not applicable (n = 15).

Conclusions: AI is experiencing an increasingly significant role in rhinology research. Articles are showing high rates of diagnostic accuracy and are being published at an almost exponential rate around the world. Utilizing AI in radiological diagnosis was the most published topic of research, however, AI in rhinology is still in its infancy and there are several topics yet to be thoroughly explored.

背景:人工智能(AI)在鼻科学领域存在大量可能的应用,并且该领域的研究正在迅速发展。目的:本综述的目的是提供一个简短的概述所有当前文献的人工智能在鼻科学领域。此外,它旨在为未来的鼻科学研究人员强调文献中的空白。方法:检索2017年1月1日至2022年5月14日的OVID MEDLINE(1946-2022)和EMBASE(1974-2022),确定所有相关文章。系统评价和荟萃分析首选报告项目范围评价扩展清单用于指导评价。结果:共筛选到2420个结果,其中62个符合入选标准。通过文献检索,还收录了17篇文章,共计79篇关于人工智能在鼻科学中的应用。每年发表的文章数量都在增加,从2017年的3篇增加到2021年的31篇。文章的作者来自22个国家,其中相对多数来自美国(19%)、中国(19%)和韩国(13%)。文章被分为5类中的1类:表型/内源性分型(n = 12),放射诊断(n = 42),预后(n = 10),非放射诊断(n = 7),手术评估/计划(n = 8)。人工智能算法的诊断或预后效用被评为优秀(n = 29)、非常好(n = 25)、良好(n = 7)、足够(n = 1)、不好(n = 2)或未报告/不适用(n = 15)。结论:人工智能在鼻科学研究中的作用越来越重要。文章显示出很高的诊断准确率,并且在世界范围内以几乎指数级的速度发表。将人工智能应用于放射诊断是发表最多的研究课题,然而,人工智能在鼻科的应用仍处于起步阶段,还有几个课题有待深入探索。
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引用次数: 1
Allergic Rhinitis in Preschoolers: A Systematic Review of Diagnostics. 学龄前儿童变应性鼻炎:诊断的系统回顾。
IF 2.6 3区 医学 Q1 Medicine Pub Date : 2023-05-01 DOI: 10.1177/19458924221149267
Alana F Diniz, Juliana Ap Ribeiro, Georgia Vag Lira, Emanuel Sc Sarinho

Background: Most studies that seek to analyze the prevalence of allergic rhinitis do not include preschool children and the diagnosis in this age group is difficult.

Objective: Identify complementary tests to the diagnosis of allergic rhinitis in preschool children and verify if there is scientific robustness to propose a diagnostic algorithm for this condition in this age group.

Methods: Systematic review of the literature in four databases: SCIELO, PubMed/MEDLINE, LILACS and SCOPUS. Each article was initially chosen by title, abstract and by the keywords "allergic rhinitis," "diagnosis" and "preschool." Those articles selected entered the complete reading and data extraction phase. The study was registered in the International Prospective Register of Systematic Reviews under number CRD42020207053.

Results: Fourteen articles were suitable for analysis. In the assessment using Quality Assessment of Diagnostic Accuracy Studies - 2, all studies had at least one domain considered "high risk" or "undetermined risk." Seven reports of nasal cytology, seven of specific IgE, four of immediate hypersensitivity skin test, one of nasal nitric oxide, three of total IgE and one of urinary leukotriene E4 were found. Eight articles evaluated more than one diagnostic test.

Conclusion: There are no defined criteria for the diagnosis of allergic rhinitis in preschool children. Nasal cytology, serum specific IgE and immediate hypersensitivity skin test were the most used tests. A reliable diagnostic criterion in this age group is necessary so that in the future it is possible to propose a diagnostic algorithm for allergic rhinitis in preschool children.

背景:大多数试图分析过敏性鼻炎患病率的研究没有包括学龄前儿童,并且在这个年龄组的诊断是困难的。目的:确定学龄前儿童变应性鼻炎诊断的补充试验,验证提出该年龄段变应性鼻炎诊断算法是否具有科学稳健性。方法:系统检索SCIELO、PubMed/MEDLINE、LILACS和SCOPUS四个数据库的文献。每篇文章最初是通过标题、摘要和关键词“过敏性鼻炎”、“诊断”和“学龄前”来选择的。入选的文章进入完整的阅读和数据提取阶段。该研究已在国际前瞻性系统评论注册中注册,编号为CRD42020207053。结果:14篇文章适合分析。在使用诊断准确性研究质量评估- 2的评估中,所有研究至少有一个领域被认为是“高风险”或“不确定风险”。鼻细胞学检查报告7例,特异性IgE 7例,即刻过敏皮肤试验4例,鼻一氧化氮1例,总IgE 3例,尿白三烯E4 1例。8篇文章评估了一项以上的诊断测试。结论:学龄前儿童变应性鼻炎的诊断尚无明确的标准。鼻细胞学检查、血清特异性IgE检查和立即超敏皮肤试验是最常用的检查。有必要在这个年龄段制定一个可靠的诊断标准,以便将来有可能提出学龄前儿童变应性鼻炎的诊断算法。
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引用次数: 1
In-Hospital Cost Comparison for Open Versus Endoscopic Endonasal Approach for Meningioma Resection. 开放入路与内镜下鼻内入路脑膜瘤切除术的住院费用比较。
IF 2.6 3区 医学 Q1 Medicine Pub Date : 2023-05-01 DOI: 10.1177/19458924221145893
Arjun K Parasher, David K Lerner, Stephen P Miranda, Jennifer E Douglas, Jordan T Glicksman, Tyler Alexander, Theodore Lin, Darren Ebesutani, Michael Kohanski, John Y K Lee, Phillip B Storm, Bert W O'Malley, Daniel Yoshor, James N Palmer, M Sean Grady, Nithin D Adappa

Objective: To determine the in-hospital cost implications of an endoscopic expanded endonasal approach (EEEA) for meningioma resection relative to the open transcranial approach.

Methods: All anterior skull base meningioma surgeries performed over a period from January 1st, 2015 to October 31th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using R software. All cost data were converted into August 2021-equivalent dollar amounts using the United States Bureau of Labor Statistics consumer price index.

Results: Thirty-five patients met study criteria, including 27 patients undergoing an open transcranial approach and 8 undergoing an EEEA. Average length of stay for patients undergoing an open approach was 9.3 days compared to 5.6 within the EEEA group (P = .126). The average total in-hospital cost of patient undergoing an EEEA was $35417.1 compared to $46406.9 among patients undergoing an open transcranial approach (P = .168). On univariate analysis, the cost of an open transcranial approach relative to the EEEA was $10989.8 (P = .411).

Conclusions: The open transcranial approach remained the dominant surgical approach to anterior skull base meningiomas over our study time period. However, despite limited patient numbers the EEEA was associated with decreased total in-hospital costs.

目的:比较经颅开放入路与经鼻内镜扩大入路对脑膜瘤切除术的院内成本影响。方法:对2015年1月1日至2017年10月31日所有颅底前脑膜瘤手术进行回顾性分析。电子病历回顾了患者因素、肿瘤特征和与每次住院相关的成本变量,并使用R软件进行了单变量分析。所有成本数据都使用美国劳工统计局的消费者价格指数转换为相当于2021年8月的美元金额。结果:35例患者符合研究标准,其中27例接受经颅开放入路,8例接受EEEA。开放入路患者的平均住院时间为9.3天,而EEEA组为5.6天(P = .126)。接受EEEA的患者平均住院总费用为35417.1美元,而接受开放经颅入路的患者平均住院总费用为46406.9美元(P = 0.168)。在单变量分析中,相对于EEEA,经颅开放入路的成本为10989.8美元(P = 0.411)。结论:在我们的研究期间,开放经颅入路仍然是治疗前颅底脑膜瘤的主要手术入路。然而,尽管病人数量有限,EEEA与降低住院总费用有关。
{"title":"In-Hospital Cost Comparison for Open Versus Endoscopic Endonasal Approach for Meningioma Resection.","authors":"Arjun K Parasher,&nbsp;David K Lerner,&nbsp;Stephen P Miranda,&nbsp;Jennifer E Douglas,&nbsp;Jordan T Glicksman,&nbsp;Tyler Alexander,&nbsp;Theodore Lin,&nbsp;Darren Ebesutani,&nbsp;Michael Kohanski,&nbsp;John Y K Lee,&nbsp;Phillip B Storm,&nbsp;Bert W O'Malley,&nbsp;Daniel Yoshor,&nbsp;James N Palmer,&nbsp;M Sean Grady,&nbsp;Nithin D Adappa","doi":"10.1177/19458924221145893","DOIUrl":"https://doi.org/10.1177/19458924221145893","url":null,"abstract":"<p><strong>Objective: </strong>To determine the in-hospital cost implications of an endoscopic expanded endonasal approach (EEEA) for meningioma resection relative to the open transcranial approach.</p><p><strong>Methods: </strong>All anterior skull base meningioma surgeries performed over a period from January 1<sup>st</sup>, 2015 to October 31th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using R software. All cost data were converted into August 2021-equivalent dollar amounts using the United States Bureau of Labor Statistics consumer price index.</p><p><strong>Results: </strong>Thirty-five patients met study criteria, including 27 patients undergoing an open transcranial approach and 8 undergoing an EEEA. Average length of stay for patients undergoing an open approach was 9.3 days compared to 5.6 within the EEEA group (<i>P</i> = .126). The average total in-hospital cost of patient undergoing an EEEA was $35417.1 compared to $46406.9 among patients undergoing an open transcranial approach (<i>P</i> = .168). On univariate analysis, the cost of an open transcranial approach relative to the EEEA was $10989.8 (<i>P</i> = .411).</p><p><strong>Conclusions: </strong>The open transcranial approach remained the dominant surgical approach to anterior skull base meningiomas over our study time period. However, despite limited patient numbers the EEEA was associated with decreased total in-hospital costs.</p>","PeriodicalId":7650,"journal":{"name":"American Journal of Rhinology & Allergy","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9262011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Analysis of CRSsNP Proteome Using a Highly Multiplexed Approach in Nasal Mucus. 鼻腔黏液中CRSsNP蛋白组的高复用分析。
IF 2.6 3区 医学 Q1 Medicine Pub Date : 2023-05-01 DOI: 10.1177/19458924221136651
Vanessa-Vivien Pesold, Olaf Wendler, Lisa Morgenthaler, Franziska Gröhn, Sarina K Mueller

Background: Chronic rhinosinusitis without nasal polyps (CRSsNP) represents a phenotype of CRS, whose immunological mechanisms are still unclear. So far there are neither suitable biomarkers to determine the course of the disease nor an individual therapy.

Objective: The purpose of this study was to characterize the CRSsNP endotype by identifying and validating non-invasive proteomic biomarkers.

Methods: A highly-multiplexed proteomic array consisting of antibodies against 2000 proteins was used to identify proteins that are differentially expressed in the nasal mucus of the CRSsNP and control groups (n = 7 per group). The proteins identified to be most differentially expressed were validated in matched nasal mucus samples using western blots and enzyme-linked immunosorbent assay (ELISA). Validation was also done in a second cohort using western blots (CRSsNP n = 25, control n = 23) and ELISA (n = 30 per group). Additionally, immunohistochemistry in CRSsNP and control tissue samples was performed to characterize the selected proteins further.

Results: Out of the 2000 proteins examined, 7 from the most differentially expressed proteins were chosen to be validated. The validation results showed that 4 proteins were significantly upregulated in CRSsNP mucus, including macrophage inflammatory protein-1beta (MIP-1β), resistin, high mobility group box 1 (HMGB1), and forkhead box protein 3 (FOXP3). Cartilage acidic protein 1 (CRTAC1) was not significantly upregulated. Two proteins were significantly downregulated including scavenger receptor class F member 2 (SCARF2) and P-selectin. All proteins selected are mainly associated with inflammation, cell proliferation/differentiation, apoptosis and cell-cell or cell-matrix interaction.

Conclusion: Proteomic analysis of CRSsNP and control mucus has confirmed known and revealed novel disease-associated proteins that could potentially serve as a new biosignature for CRSsNP. Analysis of the associated pathways will specify endotypes of CRSsNP and will lead to an improved understanding of the pathophysiology of CRSsNP. Furthermore, our data contribute to the development of a reproducible, non-invasive, and quantitative "liquid biopsy" for rhinosinusitis.

背景:慢性鼻窦炎无鼻息肉(CRSsNP)是CRS的一种表型,其免疫学机制尚不清楚。到目前为止,既没有合适的生物标志物来确定疾病的进程,也没有单独的治疗方法。目的:本研究的目的是通过鉴定和验证非侵入性蛋白质组学生物标志物来表征CRSsNP的内型。方法:采用由抗2000种蛋白抗体组成的高复用蛋白质组学阵列,鉴定CRSsNP组和对照组鼻黏液中差异表达的蛋白(每组n = 7)。用western blots和酶联免疫吸附试验(ELISA)在匹配的鼻粘液样本中验证了鉴定出的差异表达最多的蛋白。在第二个队列中也进行了验证,使用western blots (CRSsNP n = 25,对照组n = 23)和ELISA(每组n = 30)。此外,对CRSsNP和对照组织样本进行免疫组化,进一步表征所选蛋白。结果:从2000个蛋白中筛选出7个差异表达最多的蛋白进行验证。验证结果显示,在CRSsNP黏液中,巨噬细胞炎症蛋白-1β (MIP-1β)、抵抗素、高迁移率组盒1 (HMGB1)、叉头盒蛋白3 (FOXP3)等4个蛋白显著上调。软骨酸性蛋白1 (CRTAC1)无显著上调。清道夫受体类成员2 (SCARF2)和p -选择素两种蛋白显著下调。所有选择的蛋白质主要与炎症、细胞增殖/分化、细胞凋亡和细胞-细胞或细胞-基质相互作用有关。结论:CRSsNP和对照粘液的蛋白质组学分析已经证实并揭示了新的疾病相关蛋白,这些蛋白可能作为CRSsNP的新的生物标记。对相关通路的分析将明确CRSsNP的内源性类型,并将提高对CRSsNP病理生理学的理解。此外,我们的数据有助于鼻窦炎的可重复性、非侵入性和定量“液体活检”的发展。
{"title":"Analysis of CRSsNP Proteome Using a Highly Multiplexed Approach in Nasal Mucus.","authors":"Vanessa-Vivien Pesold,&nbsp;Olaf Wendler,&nbsp;Lisa Morgenthaler,&nbsp;Franziska Gröhn,&nbsp;Sarina K Mueller","doi":"10.1177/19458924221136651","DOIUrl":"https://doi.org/10.1177/19458924221136651","url":null,"abstract":"<p><strong>Background: </strong>Chronic rhinosinusitis without nasal polyps (CRSsNP) represents a phenotype of CRS, whose immunological mechanisms are still unclear. So far there are neither suitable biomarkers to determine the course of the disease nor an individual therapy.</p><p><strong>Objective: </strong>The purpose of this study was to characterize the CRSsNP endotype by identifying and validating non-invasive proteomic biomarkers.</p><p><strong>Methods: </strong>A highly-multiplexed proteomic array consisting of antibodies against 2000 proteins was used to identify proteins that are differentially expressed in the nasal mucus of the CRSsNP and control groups (n = 7 per group). The proteins identified to be most differentially expressed were validated in matched nasal mucus samples using western blots and enzyme-linked immunosorbent assay (ELISA). Validation was also done in a second cohort using western blots (CRSsNP n = 25, control n = 23) and ELISA (n = 30 per group). Additionally, immunohistochemistry in CRSsNP and control tissue samples was performed to characterize the selected proteins further.</p><p><strong>Results: </strong>Out of the 2000 proteins examined, 7 from the most differentially expressed proteins were chosen to be validated. The validation results showed that 4 proteins were significantly upregulated in CRSsNP mucus, including macrophage inflammatory protein-1beta (MIP-1β), resistin, high mobility group box 1 (HMGB1), and forkhead box protein 3 (FOXP3). Cartilage acidic protein 1 (CRTAC1) was not significantly upregulated. Two proteins were significantly downregulated including scavenger receptor class F member 2 (SCARF2) and P-selectin. All proteins selected are mainly associated with inflammation, cell proliferation/differentiation, apoptosis and cell-cell or cell-matrix interaction.</p><p><strong>Conclusion: </strong>Proteomic analysis of CRSsNP and control mucus has confirmed known and revealed novel disease-associated proteins that could potentially serve as a new biosignature for CRSsNP. Analysis of the associated pathways will specify endotypes of CRSsNP and will lead to an improved understanding of the pathophysiology of CRSsNP. Furthermore, our data contribute to the development of a reproducible, non-invasive, and quantitative \"liquid biopsy\" for rhinosinusitis.</p>","PeriodicalId":7650,"journal":{"name":"American Journal of Rhinology & Allergy","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9616820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Topical Intranasal Insulin Enhances Healing of Nasal Mucosa: An Experimental Animal Study. 局部鼻内胰岛素促进鼻粘膜愈合的实验动物研究。
IF 2.6 3区 医学 Q1 Medicine Pub Date : 2023-05-01 Epub Date: 2022-11-16 DOI: 10.1177/19458924221139018
Çağrı Külekci, Serdar Özer, Selin Önen, Petek Korkusuz, Taner Yılmaz

Objective: Aim of this study was to evaluate the effect of topical intranasal insulin on healing of nasal mucosa in a rat model.

Methods: Forty-eight Wistar rats, weighing between 250 and 300 g and aged 10-12 weeks were used and randomized into two equal groups. 1.9 mm curette was introduced through the left nostril and 1.9 mm mucosa from the left nasal septum was curetted. Postoperatively, animals in the control group received 1 mL of physiologic saline, 3 times a day in a nasal irrigation fashion. Animals in the experimental group received 1 mL of 5 IU/mL regular insulin in saline solution. Subjects were sacrificed after 5, 10, and 15 days and macroscopic and histomorphometric evaluations were performed.

Results: There were no mucosal synechiae and septal perforation macroscopically. Histological examination revealed that the defect size reduction was 21% in the saline group versus 56% in the insulin group on the fifth day (p = 0.006). There was 62% defect reduction in the saline group versus 79% in the insulin group on the 10th day (p = 0.034). On the 15th day, only 67% of saline group animals had complete defect closure, whereas 100% of animals treated with insulin had complete closure (92% vs 100% mucosal defect reduction, p = 0.036). Both edema and inflammation were less in the insulin group on 15th day (p = 0.006; p = 0.023, respectively).

Conclusion: The results from this study support the safety and efficacy of topical insulin on wound healing in the literature. This study could guide further experimental studies that examine human sinonasal wound healing.

目的:本研究旨在评价局部鼻内胰岛素对大鼠鼻黏膜愈合的影响。方法:48只Wistar大鼠,体重250至300g,年龄10-12周,随机分为两组。1.9 mm刮匙通过左鼻孔引入,1.9 刮除左侧鼻中隔的mm粘膜。术后,对照组动物接受1 mL生理盐水,以鼻腔冲洗的方式每天3次。实验组动物接受1 mL生理盐水溶液中的5IU/mL常规胰岛素。在5、10和15天后处死受试者,并进行宏观和组织形态测量评估。结果:肉眼未见黏膜粘连和间隔穿孔。组织学检查显示,第5天,生理盐水组的缺损尺寸缩小了21%,而胰岛素组的缺损面积缩小了56%(p = 0.006)。在第10天,生理盐水组的缺损减少了62%,而胰岛素组的缺损降低了79%(p = 0.034)。在第15天,只有67%的生理盐水组动物完全闭合了缺损,而用胰岛素治疗的动物100%完全闭合(92%对100%粘膜缺损减少,p = 0.036)。胰岛素组在第15天水肿和炎症均减少(p = 0.006;p = 结论:本研究结果支持文献中外用胰岛素对伤口愈合的安全性和有效性。这项研究可以指导进一步的实验研究,以检查人类鼻腔伤口愈合。
{"title":"Topical Intranasal Insulin Enhances Healing of Nasal Mucosa: An Experimental Animal Study.","authors":"Çağrı Külekci,&nbsp;Serdar Özer,&nbsp;Selin Önen,&nbsp;Petek Korkusuz,&nbsp;Taner Yılmaz","doi":"10.1177/19458924221139018","DOIUrl":"10.1177/19458924221139018","url":null,"abstract":"<p><strong>Objective: </strong>Aim of this study was to evaluate the effect of topical intranasal insulin on healing of nasal mucosa in a rat model.</p><p><strong>Methods: </strong>Forty-eight Wistar rats, weighing between 250 and 300 g and aged 10-12 weeks were used and randomized into two equal groups. 1.9 mm curette was introduced through the left nostril and 1.9 mm mucosa from the left nasal septum was curetted. Postoperatively, animals in the control group received 1 mL of physiologic saline, 3 times a day in a nasal irrigation fashion. Animals in the experimental group received 1 mL of 5 IU/mL regular insulin in saline solution. Subjects were sacrificed after 5, 10, and 15 days and macroscopic and histomorphometric evaluations were performed.</p><p><strong>Results: </strong>There were no mucosal synechiae and septal perforation macroscopically. Histological examination revealed that the defect size reduction was 21% in the saline group versus 56% in the insulin group on the fifth day (<i>p</i> = 0.006). There was 62% defect reduction in the saline group versus 79% in the insulin group on the 10th day (<i>p</i> = 0.034). On the 15th day, only 67% of saline group animals had complete defect closure, whereas 100% of animals treated with insulin had complete closure (92% vs 100% mucosal defect reduction, <i>p</i> = 0.036). Both edema and inflammation were less in the insulin group on 15th day (<i>p</i> = 0.006; <i>p</i> = 0.023, respectively).</p><p><strong>Conclusion: </strong>The results from this study support the safety and efficacy of topical insulin on wound healing in the literature. This study could guide further experimental studies that examine human sinonasal wound healing.</p>","PeriodicalId":7650,"journal":{"name":"American Journal of Rhinology & Allergy","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9621370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Diagnostic Value and Clinical Application of Nasal Fractional Exhaled Nitric Oxide in Subjects with Allergic Rhinitis. 鼻腔呼出一氧化氮分数对变应性鼻炎的诊断价值及临床应用。
IF 2.6 3区 医学 Q1 Medicine Pub Date : 2023-05-01 DOI: 10.1177/19458924221145084
Aishah Harizah Abdullah Alwi, Farah Dayana Zahedi, Salina Husain, Aneeza Khairiyah Wan Hamizan, Baharudin Abdullah

Purpose: Nitric oxide (NO) is a potential marker in the diagnosis and monitoring of treatment for the management of patients with allergic rhinitis (AR). The study aimed to determine the value of nasal fractional exhaled nitric oxide (FeNO) in the diagnosis and treatment response of AR patients.

Methods: The participants were divided into control and allergic rhinitis groups based on the clinical symptoms and skin prick tests. The AR group was treated with intranasal corticosteroid after the diagnosis. The nasal fractional exhaled nitric oxide (FENO) levels were compared between control and AR groups. In the AR group, the visual analogue scale (VAS), Nasal Obstruction Symptoms Evaluation (NOSE) questionnaire, and nasal fractional exhaled nitric oxide (FeNO) were assessed pre- and post-treatment.

Results: One hundred ten adults were enrolled. The nasal FeNO level was significantly higher in AR compared to control (p < 0.001). Both the subjective (VAS and NOSE), both (p< 0.01) and objective (nasal FeNO, p < 0.001) assessments showed significant different pre- and post-treatment. The threshold level of nasal FeNO in the diagnosis of AR was 390.0 ppb (sensitivity of 73% and specificity of 80%) based on the receiver operator characteristic curve.

Conclusion: Nasal FeNO level is significantly higher in AR compared to control group with significant difference pre- and post-treatment. The findings suggest nasal FeNO can serve as an adjunct diagnostic tool together with the monitoring of treatment response in AR.

目的:一氧化氮(NO)是变应性鼻炎(AR)患者诊断和治疗监测的潜在标志物。本研究旨在确定鼻腔呼出一氧化氮分数(FeNO)在AR患者诊断和治疗反应中的价值。方法:根据临床症状和皮肤点刺试验分为对照组和变应性鼻炎组。AR组在诊断后给予鼻内皮质类固醇治疗。比较对照组和AR组鼻呼出一氧化氮分数(FENO)水平。AR组在治疗前后分别评估视觉模拟量表(VAS)、鼻塞症状评估问卷(NOSE)和鼻腔呼出一氧化氮分数(FeNO)。结果:纳入了110名成人。AR组鼻部FeNO水平显著高于对照组(p < 0.01)和客观组(p < 0.01)。结论:AR组鼻部FeNO水平显著高于对照组,治疗前后差异有统计学意义。研究结果表明,鼻腔FeNO可以作为辅助诊断工具,同时监测AR的治疗反应。
{"title":"Diagnostic Value and Clinical Application of Nasal Fractional Exhaled Nitric Oxide in Subjects with Allergic Rhinitis.","authors":"Aishah Harizah Abdullah Alwi,&nbsp;Farah Dayana Zahedi,&nbsp;Salina Husain,&nbsp;Aneeza Khairiyah Wan Hamizan,&nbsp;Baharudin Abdullah","doi":"10.1177/19458924221145084","DOIUrl":"https://doi.org/10.1177/19458924221145084","url":null,"abstract":"<p><strong>Purpose: </strong>Nitric oxide (NO) is a potential marker in the diagnosis and monitoring of treatment for the management of patients with allergic rhinitis (AR). The study aimed to determine the value of nasal fractional exhaled nitric oxide (FeNO) in the diagnosis and treatment response of AR patients.</p><p><strong>Methods: </strong>The participants were divided into control and allergic rhinitis groups based on the clinical symptoms and skin prick tests. The AR group was treated with intranasal corticosteroid after the diagnosis. The nasal fractional exhaled nitric oxide (FENO) levels were compared between control and AR groups. In the AR group, the visual analogue scale (VAS), Nasal Obstruction Symptoms Evaluation (NOSE) questionnaire, and nasal fractional exhaled nitric oxide (FeNO) were assessed pre- and post-treatment.</p><p><strong>Results: </strong>One hundred ten adults were enrolled. The nasal FeNO level was significantly higher in AR compared to control (<i>p</i> < 0.001). Both the subjective (VAS and NOSE), both (<i>p</i> <i><</i> 0.01) and objective (nasal FeNO, <i>p</i> < 0.001) assessments showed significant different pre- and post-treatment. The threshold level of nasal FeNO in the diagnosis of AR was 390.0 ppb (sensitivity of 73% and specificity of 80%) based on the receiver operator characteristic curve.</p><p><strong>Conclusion: </strong>Nasal FeNO level is significantly higher in AR compared to control group with significant difference pre- and post-treatment. The findings suggest nasal FeNO can serve as an adjunct diagnostic tool together with the monitoring of treatment response in AR.</p>","PeriodicalId":7650,"journal":{"name":"American Journal of Rhinology & Allergy","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9631206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Allegations of Failure to Obtain Informed Consent in Otolaryngology: Evidenced-Based Recommendations for Sinus Surgeons. 耳鼻喉科未获得知情同意的指控:对鼻窦外科医生的循证建议。
IF 2.6 3区 医学 Q1 Medicine Pub Date : 2023-05-01 DOI: 10.1177/19458924221148566
Christian G Fritz, Dominic J Romeo, Anne S Lowery, Karthik Rajasekaran

Background: Informed consent requires preoperative discussion of surgical risks, complications, and alternative treatment options. Allegations of incomplete informed consent are common in the field of otolaryngology.

Objectives: Analyze outcomes and case variables in cases of alleged informed consent failure involving otolaryngologists.

Methods: A legal research database containing state and federal case records from across the United States was retrospectively reviewed for malpractice claims involving informed consent and otolaryngology.

Results: Among the 128 informed consent cases identified, 72.6% resulted in favorable verdicts for otolaryngologists. Functional endoscopic sinus surgery (FESS) was the most common source of informed consent litigation in the field of otolaryngology, with an incidence four-fold higher than the next most litigated procedure of uvulopalatopharyngoplasty (21.9% vs 5.4%). The top four factors cited in FESS-related cases were CSF leak (10), inadequate discussion of alternative therapies (4), diplopia (3), and meningitis (3). Cases resulting in a transient injury were significantly less likely to result in a payment from a plaintiff verdict or settlement (9.1%) as compared to payment-rates among cases involving permanent complications (34.6%) (p = 0.005).

Conclusions: Failure to obtain informed consent is an important factor in medical malpractice litigation. This report identifies specific, actionable recommendations aimed at protecting sinus surgeons from liability and ensuring that patients are better informed.

背景:知情同意要求术前讨论手术风险、并发症和替代治疗方案。不完全知情同意的指控在耳鼻喉科领域很常见。目的:分析耳鼻喉科医生涉嫌知情同意失败的病例的结果和病例变量。方法:一个包含美国各州和联邦案件记录的法律研究数据库对涉及知情同意和耳鼻喉科的医疗事故索赔进行回顾性审查。结果:在确定的128例知情同意病例中,72.6%的患者对耳鼻喉科医生做出了有利的判决。功能性内窥镜鼻窦手术(FESS)是耳鼻喉科领域最常见的知情同意诉讼来源,其发生率比次之的舌腭咽成形术高4倍(21.9%比5.4%)。fess相关病例中最常见的四个因素是脑脊液泄漏(10)、替代疗法讨论不足(4)、复视(3)和脑膜炎(3)。与永久性并发症(34.6%)的支付率相比,导致短暂性损伤的病例(9.1%)获得原告判决或和解的可能性显著降低(p = 0.005)。结论:未取得知情同意是医疗事故诉讼中的重要因素。本报告确定了具体的、可操作的建议,旨在保护鼻窦外科医生免受责任,并确保患者更好地了解情况。
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引用次数: 2
Mechanism of Kruppel-Like Factor 4 in Pyroptosis of Nasal Mucosal Epithelial Cells in Mice With Allergic Rhinitis. 克虏伯样因子4在变应性鼻炎小鼠鼻黏膜上皮细胞焦亡中的作用机制。
IF 2.6 3区 医学 Q1 Medicine Pub Date : 2023-05-01 DOI: 10.1177/19458924221148568
Jiaoli Yao, Qingfeng Kong, Yin Wang, Yanting Zhang, Qinxue Wang

Background: Allergic rhinitis (AR) is a chronic nasal inflammation, characterized by nasal epithelial dysfunction. Gene therapy targeting transcription factors is a promising strategy for quenching allergic inflammation, including AR.

Objective: This study sought to probe the mechanism of Kruppel-like factor 4 (KLF4) in pyroptosis of nasal mucosal epithelial cells (NEpCs) in AR mice and provide targets for AR treatment.

Methods: AR mouse models were established using sensitization with ovalbumin, followed by injection with short hairpin RNA KLF4 (sh-KLF4). AR symptoms were assessed by the times of sneezing and nose rubbing, hematoxylin-eosin, and periodic acid-Schiff staining. Levels of KLF4, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, and N-terminal domain (GSDMD-N) in nasal mucosal tissues were determined by Western blot assay, and levels of interleukin (IL)-1β and IL-18 in nasal lavage fluid were determined by enzyme-linked immunosorbent assay. The binding of KLF4 to the NLRP3 promoter was verified using chromatin immunoprecipitation and dual-luciferase assays. The functional rescue experiment was performed with oe-NLRP3 and sh-KLF4 in AR mice.

Results: KLF4 was upregulated in nasal mucosal tissues of AR mice. KLF4 inhibition reduced the times of sneezing and nose rubbing, inflammatory cell infiltration, and goblet cell hyperplasia in nasal mucosal tissues, and levels of NLRP3, cleaved caspase-1, GSDMD-N, IL-1β, and IL-18. KLF4 was enriched on the NLRP3 promoter and improved NLRP3 expression. NLRP3 overexpression reversed the inhibition of sh-KLF4 on pyroptosis of NEpCs in AR mice.

Conclusion: KLF4 bound to the NLRP3 promoter and promoted pyroptosis of NEpCs in AR mice via activating NLRP3.

背景:变应性鼻炎(AR)是一种以鼻上皮功能障碍为特征的慢性鼻部炎症。目的:探讨Kruppel-like factor 4 (KLF4)在AR小鼠鼻黏膜上皮细胞(NEpCs)焦亡中的作用机制,为AR的治疗提供靶点。方法:采用卵清蛋白致敏法建立AR小鼠模型,然后注射短发夹RNA KLF4 (sh-KLF4)。通过打喷嚏和擦鼻次数、苏木精-伊红、周期性酸-希夫染色来评估AR症状。采用Western blot法检测鼻黏膜组织中KLF4、核苷酸结合寡聚化结构域样受体家族pyrin domain containing 3 (NLRP3)、cleaved caspase-1和n-末端结构域(GSDMD-N)的表达水平;采用酶联免疫吸附法检测鼻灌洗液中白细胞介素(IL)-1β和IL-18的表达水平。利用染色质免疫沉淀和双荧光素酶测定验证了KLF4与NLRP3启动子的结合。用e- nlrp3和sh-KLF4对AR小鼠进行功能挽救实验。结果:AR小鼠鼻黏膜组织中KLF4表达上调。KLF4抑制降低了打喷嚏和擦鼻次数,降低了鼻黏膜组织炎症细胞浸润和杯状细胞增生,降低了NLRP3、cleaved caspase-1、GSDMD-N、IL-1β和IL-18的水平。KLF4富集于NLRP3启动子上,提高了NLRP3的表达。NLRP3过表达逆转了sh-KLF4对AR小鼠NEpCs焦亡的抑制作用。结论:KLF4结合NLRP3启动子,通过激活NLRP3促进AR小鼠NEpCs的焦亡。
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引用次数: 1
期刊
American Journal of Rhinology & Allergy
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