慢性鼻窦炎（CRS）的发病机制复杂，呈高度异质性。随着微生物组学与人体疾病研究的不断进展，微生物组参与CRS的发病受到越来越多的关注。现有研究认为，微生物组在CRS发病微环境中失平衡，进而影响鼻腔鼻窦免疫平衡、黏膜屏障及淋巴细胞分化，参与CRS的发生发展。进一步揭示微生物组与CRS发病机制的关系，将有利于为CRS的疾病预防、病情评估和临床治疗等提供新的视角。本文对近年来微生物组学与CRS发生和发展关系的相关研究进行综述。.

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。.

The nasal mucosa is often the initial site of respiratory viral infection, replication, and transmission. Understanding how infection shapes tissue-scale primary and memory responses is critical for designing mucosal therapeutics and vaccines. We generated a single-cell RNA-sequencing atlas of the murine nasal mucosa, sampling three regions during primary influenza infection and rechallenge. Compositional analysis revealed restricted infection to the respiratory mucosa with stepwise changes in immune and epithelial cell subsets and states. We identified and characterized a rare subset of Krt13+ nasal immune-interacting floor epithelial (KNIIFE) cells, which concurrently increased with tissue-resident memory T (TRM)-like cells. Proportionality analysis, cell-cell communication inference, and microscopy underscored the CXCL16-CXCR6 axis between KNIIFE and TRM cells. Secondary influenza challenge induced accelerated and coordinated myeloid and lymphoid responses without epithelial proliferation. Together, this atlas serves as a reference for viral infection in the upper respiratory tract and highlights the efficacy of local coordinated memory responses.

The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial blood flow, and circumvention of first-pass metabolism. In traditional medicinal practices, Bacopa monnieri, also known as Brahmi, is known for its benefits in enhancing cognitive functions and potential effects in epilepsy. This study aimed to develop and optimize a thermosensitive in-situ nasal gel for delivering Bacoside A, the principal active compound extracted from Bacopa monnieri. The formulation incorporated Poloxamer 407 as a thermogelling agent and HPMC K4M as the Mucoadhesive polymer. A 32-factorial design approach was employed for Optimization. Among the formulations. F7 exhibited the most efficient Ex-vivo permeation through the nasal mucosa, achieving 94.69 ± 2.54% permeation, and underwent a sol-gel transition at approximately 30.48 °C. The study\'s factorial design revealed that gelling temperature and mucoadhesive strength were critical factors influencing performance. The potential of in-situ nasal Gel (Optimized Batch-F7) for the treatment of epilepsy was demonstrated in an in-vivo investigation using a PTZ-induced convulsion model. This formulation decreased both the occurrence and intensity of seizures. The optimized formulation F7 showcases significant promise as an effective nasal delivery system for Bacoside A, offering enhanced bioavailability and potentially increased efficacy in epilepsy treatment.

Children resist COVID-19, and previous studies reported increased innate immunity in their upper airways. A new paper by Watkins et al. (https://doi.org/10.1084/jem.20230911) shows that the nasal mucosa of children is characterized by often asymptomatic viral and/or bacterial infections that dynamically regulate distinct innate immune programs.

Studies during the COVID-19 pandemic showed that children had heightened nasal innate immune responses compared with adults. To evaluate the role of nasal viruses and bacteria in driving these responses, we performed cytokine profiling and comprehensive, symptom-agnostic testing for respiratory viruses and bacterial pathobionts in nasopharyngeal samples from children tested for SARS-CoV-2 in 2021-22 (n = 467). Respiratory viruses and/or pathobionts were highly prevalent (82% of symptomatic and 30% asymptomatic children; 90 and 49% for children <5 years). Virus detection and load correlated with the nasal interferon response biomarker CXCL10, and the previously reported discrepancy between SARS-CoV-2 viral load and nasal interferon response was explained by viral coinfections. Bacterial pathobionts correlated with a distinct proinflammatory response with elevated IL-1β and TNF but not CXCL10. Furthermore, paired samples from healthy 1-year-olds collected 1-2 wk apart revealed frequent respiratory virus acquisition or clearance, with mucosal immunophenotype changing in parallel. These findings reveal that frequent, dynamic host-pathogen interactions drive nasal innate immune activation in children.

OBJECTIVE: To create a new mucoadhesive dosage form based on PluronicF127 followed by transformation into a gel form upon intranasal administration for targeted delivery to brain tissueMETHODS: Citicoline, cytidine diphosphocholine, designated as CDP-choline, was purchased as a white powder with the molecular weight of 510.31 g/mol. The triblock copolymers of polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol (PEG-PPG-PEG), branded as Pluronic F127, was used.
RESULTS: When instilled into the nasal cavity, Pluronic F127 for intranasal administration is transformed into a gel that remains retained for 45-55 minutes, which promotes better penetration of drugs into the brain tissue.
CONCLUSIONS: The polymer\'s gelling and adhesive properties performed well, which is crucial for further research at the preclinical stage (Tab. 1, Fig. 5, Ref. 28).

UNASSIGNED: Computed tomography (CT) is the gold standard for diagnosing canine nasal diseases. However, it cannot easily detect minor abnormalities in inflammatory diseases because they are not accompanied by obvious morphological changes.
UNASSIGNED: The present study aimed to compare the differences in normal CT findings of turbinate structure and mucosa between breeds to establish criteria for CT diagnosis of inflammatory diseases of the nasal cavity.
UNASSIGNED: CT data from 77 dogs of 5 breeds without nasal diseases were retrospectively studied. The nasal air percentage, which reflects the volume of the nasal turbinate structure and mucosa, was measured. The nasal turbinate mucosa was measured for contrast enhancement reflecting blood flow. Measurements were performed in the ventral and ethmoid turbinate (ET) regions. Comparisons were made between breeds and sections.
UNASSIGNED: The air percentage in the ventral and ET regions was significantly different between breeds. Contrast enhancement was significantly different between breeds only in the ET. Moreover, different breeds had different correlations between body weight, age, nose length, and air percentage.
UNASSIGNED: In this study, reference values for normal CT findings of the nasal structure and mucosa were obtained, taking into account the breed, measurement section, and patient factors. The results showed that the volume of the turbinate structure and contrast enhancement of nasal mucosa differed depending on the breed. The measured values also differed depending on the cross-sections and patient factors.

Mucosal immunity may contribute to clearing SARS-CoV-2 infection prior to systemic infection, thereby allowing hosts to remain seronegative. We describe the meaningful detection of SARS-CoV-2-specific nasal mucosal antibodies in a group of exposed-household individuals that evaded systemic infection. Between June 2020 and February 2023, nasopharyngeal swab (NPS) and acute and convalescent blood were collected from individuals exposed to a SARS-CoV-2-confirmed household member. Nasal secretory IgA (SIgA) antibodies targeting the SARS-CoV-2 spike protein were measured using a modified ELISA. Of the 36 exposed individuals without SARS-CoV-2 detected by the RT-PCR of NPS specimens and seronegative for SARS-CoV-2-specific IgG at enrollment and convalescence, 13 (36.1%) had positive SARS-CoV-2-specific SIgA levels detected in the nasal mucosa at enrollment. These individuals had significantly higher nasal SIgA (median 0.52 AU/mL) compared with never-exposed, never-infected controls (0.001 AU/mL) and infected-family participants (0.0002 AU/mL) during the acute visit, respectively (both p < 0.001). The nasal SARS-CoV-2-specific SIgA decreased rapidly over two weeks in the exposed seronegative individuals compared to a rise in SIgA in infected-family members. The nasal SARS-CoV-2-specific SIgA may have a protective role in preventing systemic infection.

BACKGROUND: The incidence rate of allergic rhinitis (AR) is on the rise, which seriously affects the quality of life, work efficiency, mental state of patients, and sleeping in AR sleep. This experiment aimed to investigate the changes in Treg/Th17 cells in the nasal mucosa of an AR mouse model and the intervention effect of an Anti-IL-17 antibody.
METHODS: A mouse model of AR was induced by intraperitoneal ovalbumin (OVA) injection for sensitization and stimulation with nasal drops. The times of rubbing, sneezing, and symptomatology scores were counted and analyzed. Pathological damage to the nasal mucosa was observed by Hematoxylin-Eosin (HE) staining. Peripheral blood CD4+CD25+CD127- Treg cell levels and the content of Th17 cells were measured by flow cytometry (FCM). ELISA kits were used to detect the levels of relevant cytokines (IL-10 and TGF-β1) secreted by Treg cells. The intervention effect of Anti-IL-17 antibody was observed by giving Anti-IL-17 antibody treatment.
RESULTS: The times of rubbing, sneezing, and symptomatology scores were significantly higher in mice in the OVA group than in the Control group (p < 0.001). The percentage of CD4+CD25+CD127- Treg cells in CD4+CD25+ T cells (p < 0.05) and the levels of IL-10 (p < 0.001) and TGF-β1 (p < 0.001) were significantly decreased. After OVA induction, the continuity of the nasal mucosa of mice was interrupted, the percentage of Th17 cells, IL-17, and IL-4 levels were increased, and IFN-γ levels were significantly reduced (p < 0.001). And protein expression of RORγt was significantly upregulated (p < 0.001). In addition, all of these results were reversed by Anti-IL-17 antibody treatment, significantly improving AR-related symptoms (p < 0.05).
CONCLUSIONS: Anti-IL-17 antibodies may regulate the body\'s immune response by promoting CD4+CD25+CD127- Treg cell differentiation, thereby ameliorating the symptoms associated with AR.