Cefalea rinogénica causada por mucopiocele en concha bullosa, un origen infrecuente. Reporte de caso / Rhinogenic headache caused by concha bullosa mucopyocele, an unusual origin. Case Report

Introducción: la cefalea rinogénica es secundaria al contacto permanente de la mucosa nasal y puede ser secundario a concha bullosa, si se infecta puede ser mucocele o mucopiocele. Caso clínico: paciente de 34 años con cefalea hemicraneal izquierda, dolor periocular ipsilateral, congestión y rinorrea hialina con cambios en consistencia y coloración del moco. En la tomografía computarizada (TAC) de senos paranasales (SPN) desviación septal derecha por concha bullosa izquierda, ocupación de líquido. Se sospecho mucocele y cefalea rinogénica secundaria, prueba de lidocaína positiva. Se detecto por cultivo, Eikenella corrodens. Manejo con antibiótico y posterior resolución de patología. Conclusiones: debe incluirse en el diagnóstico diferencial de cefalea y concha bullosa, realizarse endoscopia nasal y TAC de SPN. El manejo quirúrgico ha demostrado reducir la intensidad y la frecuencia de la cefalea a corto y largo plazo, y es exitoso si hay test de lidocaína positivo.

Introduction: rhinogenic headache is secondary to permanent contact with the nasal mucosa and may be secondary to concha bullosa, if infected it may be mucocele or mucopiocele. Clinical case: 34-year-old patient with left hemicranial headache, ipsilateral periocular pain, congestion, and hyaline rhinorrhea with changes in consistency and coloration of the mucus. In the computed tomography (CT) of the paranasal sinuses (SPN) right septal deviation due to left concha bullosa, fluid occupation. Mucocele and secondary rhinogenic headache were suspected, lidocaine test positive. Eikenella corrodens was detected by culture. Management with antibiotics and subsequent resolution of pathology. Conclusions: nasal endoscopy and SPN CT should be included in the differential diagnosis of headache and concha bullosa. Surgical management has been shown to reduce headache intensity and frequency in the short and long term, and is successful if there is a positive lidocaine test.

Research progress and clinical application of allergen nasal provocation test / 临床耳鼻咽喉头颈外科杂志

The allergen nasal provocation testing（NPT）, in which allergens are applied directly to the nasal mucosa under standard and controlled conditions to provoke the main symptoms of allergic rhinitis（AR）, reproduces the response of the upper respiratory tract to natural exposure to allergens under controlled conditions and is the only test currently available to confirm nasal reactivity to allergens. It is invaluable in studying the mechanisms of AR and in assessing the response to novel anti-allergic treatments. The test may play an increasingly important role in clinical practice, especially in the identification of local AR, the diagnosis of occupational AR, the clarification of the composition of allergens, the assessment of the efficacy of AR treatment and the selection of candidates undergoing allergen immunotherapy. This article reviewed the application of NPT in the diagnosis of allergic and non-allergic rhinitis, and also introduces the indications, contraindications, advantages and limitations of NPT in evaluating nasal response.

Factors affecting nasal drug delivery and design strategies for intranasal drug delivery / 浙江大学学报·医学版

Intranasal drug delivery system is a non-invasive drug delivery route with the advantages of no first-pass effect, rapid effect and brain targeting. It is a feasible alternative to drug delivery via injection, and a potential drug delivery route for the central nervous system. However, the nasal physiological environment is complex, and the nasal delivery system requires "integration of medicine and device". Its delivery efficiency is affected by many factors such as the features and formulations of drug, delivery devices and nasal cavity physiology. Some strategies have been designed to improve the solubility, stability, membrane permeability and nasal retention time of drugs. These include the use of prodrugs, adding enzyme inhibitors and absorption enhancers to preparations, and new drug carriers, which can eventually improve the efficiency of intranasal drug delivery. This article reviews recent publications and describes the above mentioned aspects and design strategies for nasal intranasal drug delivery systems to provide insights for the development of intranasal drug delivery systems.

Changes in percentage of GATA3+ regulatory T cells and their pathogenic roles in allergic rhinitis / 南方医科大学学报

OBJECTIVE@#To investigate the changes in percentage of GATA3+ regulatory T (Treg) cells in patients with allergic rhinitis (AR) and mouse models.@*METHODS@#The nasal mucosa specimens were obtained from 6 AR patients and 6 control patients for detection of nasal mucosal inflammation. Peripheral blood mononuclear cells (PBMC) were collected from 12 AP patients and 12 control patients to determine the percentages of Treg cells and GATA3+ Treg cells. In a C57BL/6 mouse model of AR, the AR symptom score, peripheral blood OVA-sIgE level, and nasal mucosal inflammation were assessed, and the spleen of mice was collected for detecting the percentages of Treg cells and GATA3+ Treg cells and the expressions of Th2 cytokines.@*RESULTS@#Compared with the control patients, AR patients showed significantly increased eosinophil infiltration and goblet cell proliferation in the nasal mucosa (P < 0.01) and decreased percentages of Treg cells and GATA3+ Treg cells (P < 0.05). The mouse models of AR also had more obvious allergic symptoms, significantly increased OVA-sIgE level in peripheral blood, eosinophil infiltration and goblet cell hyperplasia (P < 0.01), markedly lowered percentages of Treg cells and GATA3+ Treg cells in the spleen (P < 0.01), and increased expressions of IL-4, IL-6 and IL-10 (P < 0.05).@*CONCLUSION@#The percentage of GATA3+ Treg cells is decreased in AR patients and mouse models. GATA3+ Treg cells possibly participate in Th2 cell immune response, both of which are involved in the occurrence and progression of AR, suggesting the potential of GATA3+ Treg cells as a new therapeutic target for AR.

Nasosinusal Endoscopic Anatomy and Physiology

The present article focuses on the analysis of the nasal cavity's anatomy succinctly and descriptively. This essay was carried out through a bibliographic review, directed to the detailed anatomy of the nasal cavity, and the structures that form its sinuses. We have identified the need formore studies directed to the related anatomical area so that the improved knowledge of this region ensures a nasoendoscopic treatment with better effectiveness and no complications.

Studies of Mucosal Irritation and Cellular Uptake Mechanisms of Xingnaojing Nanoemulsion

Abstract Xingnaojing (XNJ) injection was used to treat pneumonia and stroke in clinic in China, but with poor patient compliance. Xingnaojing nanoemulsion for intranasal delivery was developed to improve it. This article tried to evaluate the mucosal irritation of Xingnaojing nanoemulsion and investigate cellular uptake mechanism of its encapsulated lipophilic drugs. The toad palate model and rat nasal mucosa model were used to study the nasal ciliotoxicity and nasal mucosal irritation of nanoemulsion to evaluate its safety intranasally. The cellular uptake mechanism was studied by Calu-3 cell model. Coumarin 6 was encapsulated in nanoemulsion and the endocytic pathways were studied by cellular uptake experiments after being treated with different inhibitors. In toad palate model, the cilia movement of Xingnaojing nanoemulsion group last for 467.40 ± 39.02 min, which was obviously longer than deoxycholate group (90.60 ± 15.40 min). Studies on rats showed that the damage caused by nanemulsion is capable of being recovered. Nanoemulsion uptake was reduced obviously when cells were treated with wortmannin, and it also decreased about 13% when the temperature reduced from 37ºC to 4ºC. Mucosal irritation caused by nanoemulsion is low and the damage is recoverable. The cellular uptake of Xingnaojing nanoemulsion is energy-dependent, and macropinocytosis was the most important pathway for cellular uptake.

Establishment of a culture system for human nasal mucosa organoids with controllable differentiation / 南方医科大学学报

OBJECTIVE@#To establish a culture system for human nasal mucosal organoids with controllable differentiation to reproduce the structure and function of the source tissue through staged expansion-differentiation culture.@*METHODS@#Fresh samples of surgically resected middle turbinate and nasal polyp tissues were collected, from which the nasal mucosa epithelial cells were isolated by enzymatic digestion and filtration for continuous culture at the air-liquid interface for expansion (EO group) or staged culture for expansion and differentiation (DO group). Immunohistochemical staining was used to characterize the structure, cellular composition and ciliary function of nasal mucosal organoids in the two groups. The secretion function of the differentiated nasal mucosal organoids in DO group was evaluated using PAS staining.@*RESULTS@#Both of the two organoid culture systems yielded vacuolar or solid spherical 3D organoids, and their diameters increased progressively with time. On day 16 of culture, more vacuolar organoids occurred in DO group, while more solid spherical organoids were seen in EO group, and the proportion of vacuoles was significantly greater in DO group than in EO group [(54.67±13.26)% vs (21.67±8.57)%, P < 0.05]. Short tandem repeat (STR) test of the nasal mucosal organoids and the source tissue showed a 100% match between them. On day 21 of culture, scanning and transmission electron microscopy of the nasal mucosal organoids identified ultrastructure of cilia in DO group and short villi structure in most of the organoids in EO group. Immunohistochemical staining showed positivity for P63 (basal cells), β-tubulin (ciliated columnar cells), and MUC5AC (goblet cells) in the organoids. Compared with those in EO group, the organoids in DO group showed significantly greater percentages of ciliated cells [(7.95±1.81)% vs (27.04±5.91)%, P < 0.05] and goblet cells [(14.46±0.93)% vs (39.85±5.43)%, P < 0.05) with a similar percentage of basal cells [(56.91±14.12)% vs (53.42±15.77)%, P > 0.05]. The differentiated nasal mucosal organoids in DO group were positively stained for glycogen.@*CONCLUSION@#The staged expansion-differentiation culture method allows more stable and prolonged growth of the cultured cells in vitro to produce organoids with controllable differentiation closely resembling the morphological structure and functions (ciliary function and secretory function) of the source tissue.

Experimental study of dopamine ameliorating the inflammatory damage of olfactory bulb in mice with allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the effects of dopamine on olfactory function and inflammatory injury of olfactory bulb in mice with allergic rhinitis (AR). Methods: AR mouse model was established by using ovalbumin (OVA), and the mice were divided into two groups: olfactory dysfunction (OD) group and without OD group through buried food pellet test (BFPT). The OD mice were randomly divided into 2 groups, and OVA combined with dopamine (3, 6, 9 and 12 days, respectively) or OVA combined with an equal amount of PBS (the same treatment time) was administered nasally. The olfactory function of mice was evaluated by BFPT. The number of eosinophils and goblet cells in the nasal mucosa were detected by HE and PAS staining. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of olfactory marker protein (OMP) in olfactory epithelium, the important rate-limiting enzyme tyrosine hydroxylase (TH) of dopamine, and the marker proteins glial fibrillary acidic protein (GFAP) and CD11b of glial cell in the olfactory bulb. TUNEL staining was used to detect the damage of the olfactory bulb. SPSS 26.0 software was used for statistical analysis. Results: AR mice with OD had AR pathological characteristics. Compared with AR mice without OD, the expression of OMP in olfactory epithelium of AR mice with OD was reduced (F=26.09, P<0.05), the expression of GFAP and CD11b in the olfactory bulb was increased (F value was 38.95 and 71.71, respectively, both P<0.05), and the expression of TH in the olfactory bulb was decreased (F=77.00, P<0.05). Nasal administration of dopamine could shorten the time of food globule detection in mice to a certain extent, down-regulate the expression of GFAP and CD11b in the olfactory bulb (F value was 6.55 and 46.11, respectively, both P<0.05), and reduce the number of apoptotic cells in the olfactory bulb (F=25.64, P<0.05). But dopamine had no significant effect on the number of eosinophils and goblet cells in nasal mucosa (F value was 36.26 and 19.38, respectively, both P>0.05), and had no significant effect on the expression of OMP in the olfactory epithelium (F=55.27, P>0.05). Conclusion: Dopamine can improve olfactory function in mice with AR to a certain extent, possibly because of inhibiting the activation of glial cells in olfactory bulb and reducing the apoptotic injury of olfactory bulb cells.

Bioinformatics analysis of nasal epithelial cell gene expression in seasonal and perennial allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

Objective: Transcriptome sequencing and bioinformatics analysis were performed on the gene expression of nasal epithelial cells in patients with seasonal allergic rhinitis (AR) and perennial AR, so as to obtain the differences in the gene expression of nasal epithelial cells between seasonal AR and perennial AR. Methods: The human nasal epithelial cell line(HNEpC) was cultured in vitro, treated with 100 μg/ml mugwort or house dust mite (HDM) extracts for 24 hours. Total cell RNA was extracted, and quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression of cytokines, including IL-6, IL-8, IL-33 and thymic stromal lymphopoietin (TSLP). From November 2019 to November 2020, 3 seasonal AR patients, 3 perennial AR patients, and 3 healthy controls who attended the Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University were analyzed. The patients' primary nasal epithelial cells were cultured in vitro, treated with corresponding allergens for 24 hours. Total RNA was extracted for transcriptome sequencing, and the sequencing results were analyzed by bioinformatics. Results: The qPCR results showed that the cytokines IL-6, IL-8, IL-33 and TSLP of HNEpC treated with mugworts extracts and HDM extracts had the same trend of change. After the nasal epithelial cells from patients with seasonal AR and perennial AR were treated with corresponding allergens, there were differences in biological processes and signal pathways between those and control. Gene ontology (GO) enrichment analysis showed that the differentially expressed genes (DEG) in AR patients allergic to mugwort were mainly enriched in the oxidation-reduction process, the negative regulation of apoptosis process, and the cell adhesion; the DEG in AR patients allergic to HDM were mainly enriched in cell adhesion, the negative regulation of cell proliferation and the response to drug. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway showed that the DEG of AR patients allergic to mugwort were significantly enriched in arachidonic acid metabolism, p53 signaling pathway and transforming growth factor β (TGF-β) signaling pathway, while the DEG of AR patients allergic to HDM were mainly enriched in cells cycle, Fanconi anemia pathway and DNA replication. Gene Set Enrichment Analysis (GSEA) showed that the inflammatory response, TNF-α/NF-κB signaling pathway and IL-2/STAT5 signaling pathway were significantly up-regulated in AR patients allergic to mugwort, indicating the promotion of inflammatory response; and AR patients allergic to HDM had significant down-regulation of G2M, E2F, and MYC, indicating the inhibition of cell proliferation. The protein-protein interaction network showed that TNF and CDK1 were the most interacting proteins in mugwort and HDM allergic AR patients, respectively. Conclusion: Seasonal AR and perennial AR may affect the different biological processes and signal pathways of nasal epithelial cells, leading to differences in the occurrence and development of AR.

Nuocytes from mesenteric lymph node promote allergic responses in a mouse model / Nuócitos de linfonodo mesentérico promovem respostas alérgicas em um modelo de camundongo

Abstract Introduction: Nuocytes play an important role in Type 2 immunity. However, the contribution of ILC2s to allergic rhinitis remains to be clearly elucidated. Objective: To evaluate the role of nuocytes from mesenteric lymph node on allergic responses in mice. Methods: After intraperitoneal administration of interleukin IL-25 and IL-33 to wild-type and Il17br-/-Il1rl1-/- double-deficient mice, nuocytes were purified from the the nasal-associated lymphoid tissue and mesenteric lymph nodes. Then, we assessed productions of IL-5 and IL-13 in nuocytes' cultures. Finally, we adoptively transferred the mesenteric lymph node-derived nuocytes from wild-type and Il17br-/-Il1rl1-/- mice to the murine model of allergic rhinitis to evaluate their roles in nasal allergic responses. Results: We showed that nuocytes in the mesenteric lymph nodes of wild-type mice were upregulated after application of IL-25 and IL-33, and were induced to produce IL-5 and IL-13. Numbers of sneezing and nasal rubbing as well as eosinophils were all enhanced after the adoptive transfer of wild-type nuocytes. Concentrations of IL-5, IL-13, IL-25 and IL-33 in nasal lavage fluid of allergic mice were also increased. However, nuocytes fromIl17br-/-Il1rl1-/- mice did not increase sneezing and nasal rubbing and eosinophilia, and upregulate the above cytokines in the nasal lavage fluid. Conclusion: The findings demonstrate that nuocytes from the mesenteric lymph nodes of wildtype mice promote allergic responses in a mouse model.

Resumo Introdução: Os nuócitos desempenham um papel importante na imunidade do tipo 2. No entanto, a contribuição das interleucinas ILC2s na rinite alérgica ainda precisa ser elucidada. Objetivo: Avaliar o papel dos nuócitos de linfonodos mesentéricos nas respostas alérgicas em camundongos. Método: Após a administração intraperitoneal de interleucina (IL)-25 e IL-33 em camundongos do tipo selvagem e camundongos Il17br-/-Il1rl1-/- com deficiência dupla, os nuócitos foram purificados do tecido linfoide associado a mucosa nasal e linfonodos mesentéricos. Em seguida, avaliamos as produções de IL-5 e IL-13 em culturas de nuócitos. Finalmente, transferimos adotivamente os nuócitos derivados de linfonodos mesentéricos de camundongos do tipo selvagem e camundongos Il17br-/-Il1rl1-/- para o modelo murino de rinite alérgica para avaliar seu papel nas respostas alérgicas nasais. Resultados: Mostramos que os nuócitos nos linfonodos mesentéricos de camundongos do tipo selvagem estavam up-regulados após a aplicação de IL-25 e IL-33 e foram induzidos a produzir IL-5 e IL-13. Os espirros e friçcão nasal, bem como os eosinófilos, aumentaram após a transferência adotiva de nuócitos do tipo selvagem. As concentrações de IL-5, IL-13, IL-25 e IL-33 no líquido da lavagem nasal de camundongos alérgicos também estavam aumentadas. Entretanto, os nuócitos de camundongos Il17br-/-Il1rl1-/- não aumentaram os espirros e a friçcão nasal ou eosinofilia e up-regularam as citocinas acima no líquido de lavagem nasal. Conclusão: Os achados demonstram que os nuócitos dos linfonodos mesentéricos de camundongos selvagens promovem respostas alérgicas em um modelo de camundongo.

Rhinophototherapy, an alternative treatment of allergic rhinitis: Systematic review and meta-analysis / Rinofototerapia, uma alternativa para o tratamento de rinite alérgica: revisão sistemática e metanálise

Abstract Introduction: Allergic rhinitis is a chronic inflammatory disease of the nasal mucosa, mediated by immunoglobulin E, affecting 1 in 6 individuals. The treatment aims at attaining symptomatic control with minimal side effects, a requirement for new alternative therapies, including phototherapy, as it has an immunosuppressive and immunomodulatory effect. Objective: To identify the effectiveness of phototherapy in the treatment of allergic rhinitis through a meta-analysis. Methods: We searched Web of Science, Scielo, PubMed, SCOPUS, PEDro, and LILACS databases, using the terms: ''intranasal irradiation'', ''phototherapy'' and ''allergic rhinitis''. The R software Metafor package was used for the meta-analysis and the effect size was calculated for each symptom individually. Results: All symptoms decreased considerably after phototherapy: rhinorrhea (ES• = -1.35; p < 0.0001; I2 = 91.84%), sneezing (ES• = -1.24; p < 0.0001; I2 = 91.43%), nasal pruritus (ES• = -1.10; p < 0.0001; I2 = 91.43%); nasal obstruction (ES• = -1.11; p < 0.0001; I2 = 91.88%). The effects were more significant in perennial allergic rhinitis than in the seasonal type. Conclusion: Considering the effect size and the statistical significance attained in our study, rhinophototherapy showed to be an effective treatment for reducing the nasal symptom scores triggered by AR.

Resumo Introdução: A rinite alérgica é uma doença inflamatória crônica da mucosa nasal, imunomediada por imunoglobulina E, que afeta 1/6 dos indivíduos. O tratamento visa o controle dos sintomas com efeitos colaterais mínimos, uma prerrogativa para novas terapias alternativas, como a fototerapia, por apresentar efeitos imunossupressor e imunomodulador. Objetivo: Identificar, mediante uma metanálise, a eficácia da fototerapia no tratamento da rinite alérgica. Método: Usamos as bases de dados: Web of Science, Scielo, PubMed, SCOPUS, PEDro e LILACS, com os termos de busca: intranasal irradiation, phototherapy, allergic rhinitis. Para a metanálise foi usado o pacote metafor do software R, o tamanho do efeito foi calculado para cada sintoma separadamente. Resultados: Todos os sintomas apresentaram diminuição significante após a fototerapia: coriza (ES =-1,35; p < 0,0001; I2 = 91,84%), espirros (ES =-1,24; p < 0,0001; I2 = 91,43%), prurido nasal (ES =-1,10; p < 0,0001; I2 = 91,43%); obstrução nasal (ES =-1,11; p < 0,0001; I2 = 91,88%), com efeitos mais expressivos na rinite alérgica perene do que na rinite alérgica sazonal. Conclusão: Considerando-se a magnitude do efeito e a significância estatística alcançadas em nosso estudo, a rinofototerapia demonstrou-se um tratamento eficaz para a redução dos escores dos sintomas nasais desencadeados pela rinite alérgica.

Eficácia e segurança do dupilumabe no tratamento da rinossinusite crônica com polipose nasal / Efficacy and safety of dupilumab in the treatment of chronic rhinosinusitis with nasal polyposis

A rinossinusite crônica (RSC) é uma síndrome caracterizada pela inflamação da mucosa nasal e dos seios paranasais por pelo menos 12 semanas, acometendo de 5% a 12% da população geral. A síndrome é associada a alta morbidade e considerada um grande problema de saúde pública devido a sua prevalência, seu custo para a sociedade e ao impacto que acarreta na qualidade de vida dos pacientes e em seu desempenho escolar ou profissional. Ademais, a RSC está associada a diversas comorbidades, como dermatite atópica, distúrbios respiratórios do sono, conjuntivite, otite média, asma e problemas emocionais. O dupilumabe é eficaz e seguro no tratamento da RSC com polipose nasal. A eficácia é progressiva no primeiro ano de tratamento, e a posologia de 300 mg a cada duas semanas é superior em relação à de cada quatro semanas. A interrupção do tratamento com 24 semanas acarreta a perda parcial de seus efeitos benéficos. O imunobiológico também é eficaz no controle da asma nos pacientes que apresentam essa doença como comorbidade. Alguns pacientes podem apesentar aumento transitório de eosinófilos sanguíneos, e 2,7% desenvolveram conjuntivite como reação adversa nos estudos SINUS-24 e SINUS-52. O dupilumabe é uma excelente opção terapêutica no tratamento concomitante de múltiplas doenças caracterizadas pela inflamação de tipo II.

Chronic rhinosinusitis (CRS) is a syndrome characterized by inflammation of the nasal mucosa and paranasal sinuses for at least 12 weeks, affecting 5% to 12% of the general population. The syndrome is associated with high morbidity and is considered a major public health problem because of its prevalence, its cost to society, and the impact it has on patients' quality of life and on their school or professional performance. Furthermore, CRS is associated with several comorbidities, such as atopic dermatitis, sleep-disordered breathing, conjunctivitis, otitis media, asthma, and emotional problems. Dupilumab is effective and safe in the treatment of CRS with nasal polyposis. Effectiveness is progressive in the first year of treatment, and a dosage of 300 mg every two weeks is more effective than that of every four weeks. Discontinuing treatment at 24 weeks results in partial loss of its beneficial effects. The biological drug is also effective in controlling asthma in patients who have this disease as a comorbidity. Some patients may experience a transient increase in blood eosinophils, and 2.7% developed conjunctivitis as an adverse reaction in the SINUS-24 and SINUS-52 studies. Dupilumab is an excellent therapeutic option in the concomitant treatment of multiple diseases characterized by type II inflammation.

Estrogen receptor mRNA determined by Quantitative Real-Time PCR in the nasal mucosa of women taking oral contraceptives / Receptor ARNm de estrógeno determinado por PCR Cuantitativa en Tiempo Real en la mucosa nasal de mujeres tratadas con anticonceptivos orales

SUMMARY: Estrogen receptors (ER) have been identified in human nasal mucosa, but its physiologic and pathologic impacts are not totally established. ER have been demonstrated in nasal mucosa by several authors, mainly by immunohistochemical method in nasal mucosa samples surgically removed. The present study aimed to quantify ERα and ERβ mRNA concentration by using an absolute quantitative real-time PCR in cells from nasal mucosa smear of women under oral contraceptive therapy. Nasal epithelium smear samples were collected from 110 patients divided in two groups: 55 women who present regular menstrual cycle without using contraceptives and 55 women who present regular menstrual cycle and have been using oral contraceptives for more than 3 months. All the patients answered a rhinitis symptoms questionnaire. The current study showed the potential usefulness of nasal turbinate mucosa cell sourcing, collected through swab, for extracting useful RNA for gene expression. We have identified the predominant expression of ERα isoform in a ratio 10-15 times higher compared to ERβ isoform. There is a tendency for positive correlation between the ERb isoform and the rhinitis severity score.

RESUMEN: Se han identificado receptores de estrógeno (RE) en la mucosa nasal humana, sin embargo sus impactos fisiológicos y patológicos aún no están totalmente establecidos. Varios autores han demostrado RE en la mucosa nasal, principalmente por método inmunohistoquímico en muestras obtenidas quirúrgicamente. El presente estudio tuvo como objetivo cuantificar la concentración de ARNm de REa y REb mediante el uso de una PCR cuantitativa absoluta en tiempo real en células de frotis de mucosa nasal de mujeres bajo terapia anticonceptiva oral. Se recolectaron muestras de frotis de epitelio nasal de 110 pacientes divididas en dos grupos: 55 mujeres que presentan ciclo menstrual regular sin uso de anticonceptivos y 55 mujeres que presentan ciclo menstrual regular con uso de anticonceptivos orales durante más de 3 meses. Todas las pacientes respondieron un cuestionario de síntomas de rinitis. El estudio actual mostró la utilidad de la obtención de células de la mucosa de la concha nasal, recolectadas a través de un hisopo, para extraer ARN para la expresión génica. Hemos identificado la expresión predominante de la isoforma REμ en una proporción de 10 a 15 veces mayor en comparación con la isoforma REß. Hemos identificado la expresión predominante de la isoforma REα en una proporción de 10 a 15 veces mayor en comparación con la isoforma REß. Existe una tendencia a una correlación positiva entre la isoforma REß y la puntuación de gravedad de la rinitis.

Different concentrations of specialized pro-resolving mediators in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the difference of concentrations of specialized pro-resolving mediators (SPMs) derived from fatty acids in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP). Methods: A total of 36 patients with bilateral chronic rhinosinusitis with nasal polyps (CRSwNP) who underwent endoscopic nasal surgeries in Peking Union Medical College Hospital from May 2019 to September 2020 were enrolled, including 27 males and 9 females, with the age from 13 to 67 years. There were 23 cases of ECRSwNP and 13 cases of nECRSwNP. At the same time, 12 control subjects were enrolled. The concentrations of multiple SPMs, including lipoxins (LXA4 and LXB4), resolvins (RvD1, RvD2, RvD3, RvD5 and RvE1), protectins (PDX) and maresins (Mar-1) in nasal polyps with different histological subtypes and normal nasal mucosa were analyzed using liquid chromatography-tandem mass spectrometry. The concentrations of SPMs between groups were compared using Mann-Whitney U test. Spearman's rank correlation coefficient was used to measure the correlation between the concentrations of SPMs in nasal polyps and tissue eosinophil counts. Results: The concentrations of RvD2, RvD3, RvD5, LXA4, LXB4, Mar-1 and PDX in ECRSwNP group were significantly higher than that in controls (Z value was -2.276, -2.313, -3.371, -2.094, -2.051, -3.104 and -2.294, respectively, all P<0.05). The concentrations of RvD2, RvD5, Mar-1 and PDX in ECRSwNP group were significantly higher than those in nECRSwNP group (Z value was -2.175, -2.289, -2.243 and -2.124, respectively, all P<0.05). There was no significant difference in all these SPMs between nECRSwNP and controls (all P>0.05). The concentrations of RvD2, RvD3, RvD5, LXB4, Mar-1 and PDX in nasal polyps correlated positively with tissue eosinophil counts (r value was 0.443, 0.436, 0.371, 0.502, 0.340 and 0.386, respectively, all P<0.05). Conclusions: A varienty of SPMs are elevated in ECRSwNP. Dysregulation of fatty acid metabolism might play an important role in the chronic inflammation of ECRSwNP.

Gene transcriptome analysis of nasal epithelial cells in chronic rhinosinusitis with nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To identify the differentially expressed genes in nasal epithelial cells from chronic rhinosinusitis with nasal polyps (CRSwNP), and to analyze related genes which are involved in deficiency of nasal epithelial barrier in CRSwNP patients by analyzing the datasets download from the gene expression omnibus(GEO) database. Methods: The mRNA expression microarray data numbered GSE107624 (7 CRSwNP and 7 controls) and GSE69093 (13 CRSwNP and 11 controls) were downloaded from the publicly available GEO database. These two datasets were jointly analyzed to screen the differentially expressed genes in nasal epithelial cells of controls and CRSwNP patients. In the meanwhile, we further evaluated the function annotation and regulatory pathways of the differentially expressed genes. To further confirmed what we have observed, sinus tissues were collected from patients with CRSwNP (14 cases, 46.8±17.9 years) and uncinate process tissues were collected from patients with nasal septum deviation (7 cases, 23.4±2.3 years) as control group. The primary epithelial cells of nasal mucosa were cultured and the mRNA level of screened genes were measured by Q-PCR. SPSS 22.0 software was used to for statistical analysis. Results: GSE107624 dataset showed that there were 3 856 differentially genes in nasal epithelial cells between CRSwNP and control group, while there were 771 differentially expressed genes in GSE69093 dataset. Finally, 55 up-regulated genes and 3 down-regulated genes were noticed in nasal epithelial cells of CRSwNP patients in the two datasets. GO gene functional annotation analysis showed that SPTBN1, FNBP1L, VAPB and SNX1 were involved in cell adhesion function, MAP1B was participated in the formation of microtubule related complex. KEGG pathway enrichment analysis indicated that BAMBI and SIAH1 were involved in regulation of Wnt pathway, COL6A1 and EIF4E were involved in the regulation of PI3K-AKT pathway. String protein interaction network analysis assumed that MAP1B and VAPB were the core functional proteins. Among top 3 differentially expressed genes COL6A1, MAP1B and BAMBI, only MAP1B gene was increased in nasal epithelial cells of CRSwNP patients in comparison to controls. Conclusion: The increased MAP1B gene in epithelial cells of CRSwNP, as well as abnormal regulation of Wnt and PI3K-AKT signal pathways may mediate the barrier dysfunction in CRSwNP.

Hypoxic stimulation leads to the changes of inflammatory factors in mucosal epithelial cells of nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the roles of hypoxic stimulation in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) by comparing the variation and differences of inflammatory factors secreted from epithelial cells of nasal polyps and normal nasal mucosa under hypoxic stimulation. Methods: Sixty-eight patients who were diagnosed with CRSwNP from June 2015 to January 2018 at China-Japan Union Hospital of Jilin University were analyzed, including 36 males and 32 females, aged (45.2±12.5) years. Nasal polyps mucosa was included in CRS-NP group and inferior turbinate mucosa was included in CRS-IT group. According to the degree of eosinophil infiltration in histopathologic results, each of these two groups was further divided into eosinophil infiltration and non-eosinophil infiltration as Eos-NP group (n=34), Non-Eos-NP group (n=34), Eos-IT group (n=20) and Non-Eos-IT group (n=20). The inferior turbinate mucosa of twenty-five patients who were diagnosed with cyst of paranasal sinus or deviation of nasal septum was classified as control group (n=25), including 14 males and 11 females, aged (42.8±10.2) years. The expression of interleukin 17A (IL-17A), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1α (HIF-1α) in each group was analyzed by immunohistochemical staining. After 0, 24 and 48 h hypoxic stimulation, the secretion of IL-17A, IFN-γ, TNF-α in primary nasal mucosa epithelial cells of each group was tested by enzyme-linked immune sorbent assay (ELISA) experiment; the expression of HIF-1α was tested by immunofluorescent staining and imaging and Western blot. SPSS 17.0 software and two-way ANOVA were used for statistical analysis. Results: Immunohistochemical staining showed that the expression of IL-17A and TNF-α was much higher in control group (optical density (OD) value was 0.37±0.03, 0.53±0.02, respectively) and the expression of IFN-γ and HIF-1α was much higher in Eos-IT group (OD value was 0.47±0.03, 0.39±0.02, respectively). The secretion of IL-17A and TNF-α was much lower in control group than that in other groups under normal condition. After 48 h hypoxic stimulation, the secretion of IL-17A and TNF-α was much higher in control group compared with other groups. The secretion of IFN-γ in Eos-NP group was much higher than that in control group under normal condition ((13.7±1.3) pg/ml vs (11.1±1.6) pg/ml, P<0.05). After 48 h hypoxic stimulation, there was no difference of IFN-γ between control group and Eos-NP group. The expression of HIF-1α decreased in Eos-NP group and Non-Eos-NP group while increased in CRS-IT group and control group upon prolonged exposure to hypoxia. HIF-1α was mostly located at cytoplasm of epithelial cells in control and CRS-IT group while mainly located at nucleus of epithelial cells in CRS-NP group. Conclusions: The secretion of IL-17A, TNF-α, IFN-γ and the expression of HIF-1α show significant difference between normal nasal mucosa, polyps and inferior turbinate of CRSwNP under hypoxic stimulation, presenting different subcellular localization. This illustrates the proteins above are involved in transcription and regulation of the gene responsible for the pathogenesis of CRSwNP.

Self-applied sphenopalatine ganglion block for postdural puncture headache: four case reports / Bloqueio do gânglio esfenopalatino autoaplicado para cefaleia pós-punção dural: relato de quatro casos

Abstract Background and objectives The Sphenopalatine Ganglion Block (SGB) is an effective, low-risk treatment option for Postdural Puncture Headache (PDPH) refractory to conservative management. Case report This report presents four complex cases of patients with headache related to low cerebrospinal fluid pressure. Three of them were successfully treated with the application of local anesthetic topical drops through the nasal cavity. Conclusion The novel approach described in this report has minimal risks of discomfort or injury to the nasal mucosa. It is quick to apply and can be administered by the patient himself.

Resumo Justificativa e objetivos: O Bloqueio do Gânglio Esfenopalatino (BGEP) é opção de tratamento efetivo associado a baixo risco para Cefaleia Pós-Punção Dural (CPPD) refratária às medidas conservadoras. Relato de caso: Este relato apresenta quatro pacientes com alta complexidade que apresentaram cefaleia relacionada à baixa pressão do líquido cefaloraquidiano. Três pacientes foram tratados com sucesso pela instilação de gotas de anestésico local tópico na cavidade nasal. Conclusões: A nova abordagem descrita neste relato apresenta riscos mínimos de desconforto ou lesão à mucosa nasal. A aplicação é rápida e pode ser administrada pelo próprio paciente.

Nasal lavage cytology and mucosal histopathological alterations in patients with rhinitis / Citologia do lavado nasal e alterações histopatológicas na mucosa nasal de pacientescom rinite

Abstract Introduction The extent of epithelial lesion in allergic and non-allergic rhinitis and its association with inflammatory changes in nasal lavage has not been clarified. Objective To verify the association between the inflammatory cells in the nasal lavage, epithelial lesion extent and basement membrane thickness, in the nasal mucosa of patients with rhinitis; to determine the cutoff point of the percentage of eosinophils in the nasal lavage associated with the atopic patients. Methods Patients with rhinitis and indication for septoplasty and (or) turbinectomy for turbinate hypertrophy were selected, and were submitted to allergy skin tests, nasal lavage with measurement of albumin and interleukin-8 levels, total and differential counting of cells, and mucosal histopathological analysis to determine the extent of epithelial lesion, and degree of basement membrane thickening. Results Fifty-six patients with a median age of 24.5 years and a diagnosis of allergic rhinitis (n = 36) and non-allergic rhinitis (n = 20) were studied. In atopic subjects, allergy skin tests were positive for Dermatophagoides pteronyssinus in 35 (97.0%) and Lolium perenne in 18 (50.0%). Atopic subjects showed a higher clinical score index of rhinitis compared to non-atopic ones. The total count of cells, neutrophils, and levels of albumin and IL-8 were not different in the nasal lavage of atopic and non-atopic subjects. The cutoff point for eosinophil count in nasal fluid for the distinction between allergic rhinitis and non-allergic rhinitis was 4%. Some degree of epithelial lesion was more frequent in allergic rhinitis (94%) than in non-allergic rhinitis (65%) patients. In the presence of basement membrane thickness, as a marker of remodeling, there was no difference in the nasal lavage of patients with allergic rhinitis and non-allergic rhinitis. Conclusion In this series, 4% was the cutoff point for the number of eosinophils in the nasal lavage, for atopy differentiation. Upper airway remodeling accessed by basement membrane thickness showed similar inflammatory cell infiltrate in the nasal lavage, regardless of the presence of atopy.

Resumo Introdução A extensão da lesão epitelial na rinite alérgica e não alérgica e sua associação com alterações inflamatórias no lavado nasal ainda não estão esclarecidas. Objetivo Verificar a relação entre o processo inflamatório no lavado nasal, extensão da lesão epitelial e espessamento da membrana basal na mucosa nasal de pacientes com rinite; determinar o ponto de corte do percentual de eosinófilos no lavado nasal associado à presença de atopia. Método Foram selecionados pacientes com rinite e indicação de septoplastia e (ou) turbinectomia por hipertrofia de conchas nasais, os quais foram submetidos aos testes cutâneos alérgicos, lavado nasal com determinação das concentrações de albumina, interleucina-8 (IL-8), contagem total e diferencial de células, análise da extensão da lesão epitelial, e grau de espessamento da membrana basal por meio de histopatologia da mucosa. Resultado Foram estudados 56 pacientes, mediana de 24,5 anos com diagnóstico de rinite alérgica (n = 36) e rinite não alérgica (n = 20). Nos atópicos os testes cutâneos alérgicos foram positivos para D. pteronyssinus em 35 (97,0%) e L. perenne em 18 (50,0%). Atópicos apresentaram maior índice de escore clínico para rinite em comparação a não atópicos. A contagem total de células, neutrófilos e níveis de albumina e IL-8 não foi diferente entre o lavado nasal de atópicos e não atópicos. O ponto de corte da contagem de eosinófilos no fluido nasal para a distinção de rinite alérgica e rinite não alérgica foi de 4%. Algum grau de lesão epitelial foi mais frequente em pacientes com rinite alérgica (94%) do que em pacientes com rinite não alérgica (65%). Na presença de espessamento da membrana basal, como marcador de remodelamento, não houve diferença no lavado nasal entre pacientes com rinite alérgica e não alérgica. Conclusão Nesta casuística, 4% foi o ponto de corte do número de eosinófilos no lavado nasal, para diferenciação de atopia. Remodelamento da via aérea superior pelo espessamento da membrana basal revelou infiltrado semelhante de células inflamatórias no lavado nasal, independentemente da presença de atopia.

Aumento da projeção da ponta nasal com "pseudoretalhos" obtidos dos excessos cefálicos laterais das cartilagens alares / Increased projection of the nasal tip with "pseudo-flaps" obtained from lateral cephalic excesses of the alar cartilages

Introdução: O aumento da projeção da ponta nasal às vezes se torna necessário para a obtenção de uma boa proporção entre ela e o dorso. Inúmeras técnicas e táticas são descritas com essa finalidade utilizando enxertos cartilaginosos obtidos do septo nasal, concha auricular e cartilagem costal. Quando esse aumento deve ser discreto é proposto o uso dos excedentes de cartilagens alares laterais em forma de "pseudo-retalhos". Métodos: Em rinoplastias abertas primárias os excedentes das cartilagens alares, geralmente removidas, são utilizados como "pseudo-retalhos", dobrados sobre si mesmos, em forma de "suspensório de soldado francês", sobre o domus das cartilagens alares, tendo como acolchoamento de apoio os tecidos moles delas próprias, e o tecido mole interdomal, geralmente desprezado, que é liberado, e elevado para sobre os domus. Ele é mantido, descolado e deslocado para a ponta nasal, e fica contido pelos "pseudo-retalhos" das cartilagens alares ali suturados ou cobrindo o extremo do enxerto estrutural da columela. Foram operados com essa tática 36 pacientes. Resultados: 35 com bons resultados e um apresentou um abcesso de ponta nasal, provocado pela exposição endonasal de um fio de sutura não absorvível, que foi removido. Houve necessidade de uma segunda intervenção, utilizando novo enxerto auricular, ainda com resultado insatisfatório. O método é relativamente simples para quem opera narizes. Conclusão: A ponta nasal pode ser discretamente mais projetada utilizando os excessos de cartilagens alares, "pediculadas" no domus.

Introduction: An increased nasal tip projection is sometimes necessary to achieve an appropriate proportion between nasal tip and dorsum. Numerous techniques and tactics have been described for this purpose using cartilaginous grafts obtained from the nasal septum, auricular concha, and costal cartilage. When this increased projection must be discrete, the use of excess lateral alar cartilage in the form of "pseudo-flaps" is proposed. Methods: In primary open rhinoplasty, excess alar cartilage, which is generally removed, was used to produce "pseudo-flaps". The cartilages were folded over themselves in the form of a "French soldier's suspender" over the domes of the alar cartilage and supported by interdomal soft tissue padding raised over the domus. It was kept detached, and relocated to the nasal tip and was contained by "pseudoflaps" of the alar cartilages sutured there or covering the columella's structural graft. Thirty-six patients underwent surgery using this technique. Results: Thirty-five had good results and one had a nasal tip abscess, caused by endonasal exposure to a non-absorbable suture, which was removed. A second intervention was then performed using a new auricular graft, but the result was still unsatisfactory. The "pseudoflaps" method is relatively simple for those performing nasal surgery. Conclusion: The nasal tip can be projected discretely using the excess of alar cartilage "pedicled" in the domus.

Colonización nasal por Staphylococcus aureus resistente a la meticilina en pacientes sometidos a cirugía cardiovascular en un hospital universitario de Bogotá, Colombia / Methicillin-resistant Staphylococcus aureus nasal colonization in cardiovascular surgery patients at a university hospital in Bogotá, Colombia

Introducción. Staphylococcus aureus resistente a la meticilina (SARM) es un microorganismo que coloniza las fosas nasales y diferentes partes del cuerpo, lo cual se considera un factor de riesgo para adquirir infecciones invasivas, especialmente en pacientes sometidos a cirugía cardiovascular. Objetivo. Determinar la colonización nasal por SARM y establecer las características clínicas en pacientes programados para cirugía cardiovascular. Materiales y métodos. Se hizo un estudio descriptivo entre febrero y diciembre de 2015. Se incluyeron pacientes adultos programados para cirugía cardiovascular en el Hospital Universitario San Ignacio de Bogotá. La colonización se identificó mediante reacción en cadena de la polimerasa (Polymerase Chain Reaction, PCR) en tiempo real en muestras obtenidas mediante hisopados nasales. Los pacientes fueron descolonizados con mupirocina al 2,0 % intranasal dos veces al día y baños con gluconato de clorhexidina al 4 % del cuello hacía abajo durante cinco días, al cabo de lo cual se hizo una PCR de control. Resultados.Se incluyeron 141 pacientes, 52 hospitalizados y 89 ambulatorios. Del total, 19 (13,4 %) tenían colonización nasal por SARM, correspondientes a 9 (17,3 %) de los 52 hospitalizados y 10 (11,2 %) de los 89 ambulatorios. Todos los pacientes sometidos a descolonización tuvieron resultado negativo en la PCR al final del proceso y ninguno presentó infección del sitio operatorio por S. aureus. Conclusiones.Se demostró colonización nasal por SARM tanto en los pacientes hospitalizados como en los ambulatorios. La descolonización con mupirocina fue efectiva para erradicar el estado de portador a corto plazo, lo que podría tener efecto en las tasas de infección del sitio operatorio en las cirugías cardiovasculares.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is a microorganism that colonizes nostrils and different parts of the body, which is considered a risk factor to acquire invasive infections, especially in cardiovascular surgery patients. Objective: To determine the frequency of nasal colonization by MRSA and to establish the clinical characteristics in patients scheduled for cardiovascular surgery. Materials and methods: This was a descriptive study conducted between February and December, 2015. We included adult patients scheduled for cardiovascular surgery at the Hospital Universitario San Ignacio in Bogotá, Colombia. Colonization was identified by real-time PCR from nasal swabs. Colonized patients were treated with mupirocin 2.0% intranasally twice a day and bathed with chlorhexidine 4% from the neck downwards for five days. At the end of this treatment, PCR control was carried out. Results: We included 141 patients with a percentage of nasal colonization of 13.4% (19/141). There were 52 hospitalized patients and 89 outpatients with a percentage of nasal colonization of 17.3% (9/52), and 11.2% (10/89), respectively. All colonized patients who received treatment had a negative PCR at the end of the regime and none of the participating patients had a surgical site infection by S. aureus at the end of the study. Conclusions: Nasal colonization was observed both in hospitalized patients and outpatients. Decolonization treatment with mupirocin was effective to eradicate the carrier state in the short term, which could impact the rates of surgical wound infection associated with cardiovascular surgery.