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.
Animals ; Disease Models, Animal ; Dopamine ; Humans ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa/metabolism* ; Olfactory Bulb/pathology* ; Ovalbumin ; Rhinitis, Allergic/metabolism*

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.
Adult ; China ; Chronic Disease ; Epithelial Cells ; Female ; Humans ; Hypoxia/pathology* ; Male ; Middle Aged ; Nasal Mucosa/pathology* ; Nasal Polyps/pathology* ; Rhinitis/pathology*

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.
Chronic Disease ; Epithelial Cells ; Gene Expression Profiling ; Humans ; Nasal Mucosa/pathology* ; Nasal Polyps/pathology* ; Phosphatidylinositol 3-Kinases ; Rhinitis/pathology*

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.
Adolescent ; Adult ; Aged ; Chronic Disease ; Eosinophils ; Female ; Humans ; Male ; Middle Aged ; Nasal Mucosa/pathology* ; Nasal Polyps/pathology* ; Rhinitis/pathology* ; Sinusitis/pathology* ; Young Adult

Adaptation, Physiological ; Adenosine Monophosphate ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Administration, Intranasal ; Alanine ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Animals ; Betacoronavirus ; genetics ; physiology ; Chlorocebus aethiops ; Coronavirus Infections ; drug therapy ; virology ; Disease Models, Animal ; Female ; Host Specificity ; genetics ; Lung ; pathology ; virology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mutation, Missense ; Nasal Mucosa ; virology ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; RNA, Viral ; administration & dosage ; genetics ; Turbinates ; virology ; Vero Cells ; Viral Load ; Virus Replication

Maxillary implants are inserted in the upward direction, meaning that they oppose gravity, and achieving stable support is difficult if the alveolar bone facing the maxillary sinus is thin. Correspondingly, several sinus-lifting procedures conducted with or without bone graft materials have been used to place implants in the posterior area of the maxilla. Even with these procedures available, it has been reported that in about 5% of cases, complications occurred after implantation, including acute and chronic sinusitis, penetration of the sinus by the implant, implant dislocation, oroantral fistula formation, infection, bone graft dislocation, foreign-body reaction, Schneiderian membrane perforation, and ostium plugging by a dislodged bone graft. This review summarizes common maxillary sinus pathologies related to implants and suggests an appropriate management plan for patients requiring dental implantation.
Dental Implantation ; Dental Implants ; Dislocations ; Foreign-Body Reaction ; Gravitation ; Humans ; Maxilla ; Maxillary Sinus ; Maxillary Sinusitis ; Nasal Mucosa ; Oroantral Fistula ; Pathology ; Postoperative Complications ; Sinusitis ; Transplants

OBJECTIVES: Epistaxis is one of the most common otorhinolaryngologic emergencies representing more than 12% of conditions managed at the Ear, Nose and Throat (ENT) Emergency Consulting Room of our Otorhinolaryngologic Unit each year. The elevated frequency of this pathology makes it necessary to adopt the most effective and least expensive therapeutic strategy available. The aim of this study was to compare the efficacy, costs and morbidity of nasal packing (NP), which is the mainstay of treatment for anterior epistaxis in our ENT Emergency Consulting Room versus submucosal infiltrations of lauromacrogol (LA). METHODS: A retrospective study was designed from August 2012 to April 2013 involving 53 patients suffering from anterior epistaxis. Anterior NP was used in 27 patients versus 26 patients undergoing 27 procedures performed with submucosal infiltrations of LA (or polidocanol). Outcomes for each treatment were evaluated. Patients in group 1 were treated with LA 400 injection next to the bleeding point: 0.5- to 1-mL single or multiple infiltrations with a 27-gauge needle. The whitening of the nasal mucosa around the bleeding point during infiltration was considered a marker of correct procedure in order to achieve the best results. Bilateral treatment was also performed at the same time. Patients in group 2 were treated with standard NP. RESULTS: Bleeding recurrence was higher in the NP group even if it was not statistically significant (P=0.2935). However, the LA infiltrations were better tolerated with lower morbidity and costs as compared to NP. No complications were observed in either group. CONCLUSION: LA infiltrations were shown to be a viable alternative in anterior epistaxis treatment. They are safe, easy to use with good efficacy and have a low cost.
Ear ; Emergencies ; Epistaxis* ; Hemorrhage ; Humans ; Nasal Mucosa ; Needles ; Nose ; Pathology ; Pharynx ; Polyethylene Glycols ; Recurrence ; Retrospective Studies ; Sclerotherapy*

OBJECTIVETo study the clinicopathologic characteristics of IgG4-related sialodacryoadenitis and chronic rhinosinusitis (CRS).

METHODSA total of 13 patients (patient group) were evaluated clinically and biopsy specimens from the lacrimal/salivary glands (n=12) and nasal mucosa (n=8) were reviewed and immunohistochemistry was performed to assess IgG-and IgG4-positive cells. Similarly, nine patients with IgG4-related sialodacryoadenitis without CRS and 10 patients with common CRS were included as controls.

RESULTSThere were 8 male patients and 5 female patients. The age of patients ranged from 32 to 71 years (mean 50.2 years). The patient group had higher serum IgG4 concentration than that of the control group (P<0.05). Lymphoplasmacytic infiltration, lymphoid follicle formation and sclerosis were prominent in lacrimal/salivary glands in both groups; however the magnitude of IgG4-positive plasmacytic infiltration in the patient group was significantly higher than that of the control group (P<0.05). Similarly, evaluation of nasal mucosa revealed greater lymphocytic and plasmacytic infiltration, and lymphoid follicle formation, together with significantly higher amount of IgG4-positive plasma cell infiltration in the patient group compared to the common CRS group (P<0.05).

CONCLUSIONSIgG4-related disease (IgG4-RD) simultaneously involving lacrimal/salivary glands and nasal cavity/paranasal sinuses is rare and characterized by a combination of IgG4-positive plasma cell infiltration involving lacrimal/salivary glands and nasal mucosa along with an increased serum level of IgG4. As a systemic disease, early and accurate diagnosis is therefore of great importance, and unnecessary surgery should be avoided.

Adult ; Aged ; Chronic Disease ; Female ; Humans ; Immunoglobulin G ; blood ; Immunohistochemistry ; Lacrimal Apparatus ; pathology ; Male ; Middle Aged ; Nasal Mucosa ; pathology ; Paranasal Sinuses ; pathology ; Rhinitis ; diagnosis ; immunology ; Salivary Glands ; pathology ; Sialadenitis ; diagnosis ; immunology ; Sinusitis ; diagnosis ; immunology

OBJECTIVE: To study the role of JNK (c-Jun N-terminal kinase) signal transduction pathway on the nasal mucosa remodeling in allergic rhinitis rats, to explore whether IL-1β participates the nasal mucosa remodeling in allergic rhinitis by JNK signal transduction pathway. METHOD: Totally 60 male Wistar rats (weighing about 200-250 g)were randomly divided into A (AR group) and B group (control group). The rats in A group were sensitized for inducing AR by intraperitoneal injection ovalbumin and Al(OH)₃. Ovalbumin was respectively dropped in each nasal cavity of every rat for 4,8,12 weeks(A4,A8,or A12 group) each had 10 rats. The rats in B group were sensitized by intraperitoneal injection saline. Saline was respectively dropped in each nasal cavity of every rat for 4,8, 12 weeks(B4, B8, or B12 group), and each had 10 rats. The concentration of IL-1β in serum and nasal lavage fluid were tested by ELASA. The protein expressions of P-JNK and P-c-Jun were detected by immunohistochemical technique. Linear correlation analysis showed the correlation between levels of IL-1β in serum and P-JNK protein, levels of IL-1β in nasal lavage fluid and P-JNK protein. RESULT: The concentrations of IL-1β in serum and nasal lavage fluid of A group were all significantly higher than those of the corresponding B group (all P < 0.01). Compared with A4 group and A8 group, concentrations of IL-1β in nasal lavage fluid of A12 group were significantly increased (all P < 0.01). However the levels of IL-1β in serum were not significantly different among them (all P > 0.05). Mean absorbance values of P-JNK and P-c-Jun in A group were significantly higher than those in corresponding B group (all P < 0.01) and compared with A4 group and A8 group, those of A12 group were significantly increased (all P < 0.01). Strong positive correlation were found between P-JNK and concentration of IL-1β in serum or nasal lavage fluid (r = 0.835 and r = 0.902, all P < 0.01). CONCLUSION JNK signal transduction pathway plays important role in the nasal mucosa remodeling in allergic rhinitis rats. IL-1β participates in AR nasal mucosa remodeling possibly partly through activating JNK signal transduction pathway.
Animals ; Disease Models, Animal ; Interleukin-1beta ; metabolism ; JNK Mitogen-Activated Protein Kinases ; metabolism ; MAP Kinase Signaling System ; Male ; Nasal Mucosa ; pathology ; Ovalbumin ; Paranasal Sinuses ; Rats ; Rats, Wistar ; Rhinitis, Allergic ; metabolism ; pathology ; Signal Transduction

PURPOSE: The nasal mucosa is the first site to encounter pathogens, and it forms continuous barriers to various stimuli. This barrier function is very important in the innate defense mechanism. Additionally, inflammation of the nasal sinus is known to be a hypoxic condition. Here, we studied the effect of hypoxia on barrier function in normal human nasal epithelial (NHNE) cells. MATERIALS AND METHODS: The expression levels of various junction complex proteins were assessed in hypoxia-stimulated NHNE cells and human nasal mucosal tissues. We performed real-time polymerase chain reaction analysis, western blotting, and immunofluorescence assays to examine differences in the mRNA and protein expression of ZO-1, a tight junction protein, and E-cadherin in NHNE cells. Moreover, we evaluated the trans-epithelial resistance (TER) of NHNE cells under hypoxic conditions to check for changes in permeability. The expression of ZO-1 and E-cadherin was measured in human nasal mucosa samples by western blotting. RESULTS: Hypoxia time-dependently decreased the expression of ZO-1 and E-cadherin at the gene and protein levels. In addition, hypoxia decreased the TER of NHNE cells, which indicates increased permeability. Human nasal mucosa samples, which are supposed to be hypoxic, showed significantly decreased levels of ZO-1 and E-cadherin expression compared with control. CONCLUSION: Our results demonstrate that hypoxia altered the expression of junction complex molecules and increased epithelial permeability in human nasal epithelia. This suggests that hypoxia causes barrier dysfunction. Furthermore, it may be associated with innate immune dysfunction after encountering pathogens.
Anoxia/etiology/*metabolism ; Blotting, Western ; Cadherins/*analysis/genetics ; Epithelium/chemistry/pathology ; Humans ; Membrane Proteins/*analysis ; Nasal Mucosa/*chemistry/pathology/*secretion ; Permeability/*radiation effects ; RNA, Messenger/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Tight Junctions/*metabolism ; Zonula Occludens-1 Protein