Comparative study of nasal cavity drug delivery efficiency with different nozzles in a 3D printed model.

Background: Nasal sprays are widely used in treating nasal and sinus diseases; however, there are very few studies on the drug delivery efficiency of nasal sprays. In this study, the drug delivery efficiency of three different nasal spray devices was evaluated in vitro using a 3D printed cast model of nasal cavity. Methods: Three nasal spray devices with different nozzles and angles of administration were used in the 3D model of the nasal cavity and paranasal sinuses. The spraying area (SA), maximal spraying distance (MSD), and spraying distribution scores on the nasal septum and lateral nasal wall were recorded. Results: Different nasal spray devices have their own characteristics, including volume of each spray, SA, and plume angle. The SA of the three nozzles on the nasal septum increased with an increasing angle of administration. When the angle of administration was 50°, each nozzle reached the maximal SA. There was no statistically significant difference in MSD among the three nozzles at the three angles. The total scores for each nozzle using the three different spraying angles were as follows: nozzle A, 40° > 30° > 50°; nozzle B, 30° > 40° > 50°; and nozzle C, 30° > 40° > 50°. The total scores for different nozzles using the same angle were statistically significantly different and the scores for nozzle C were the highest. Nozzle C had the minimum plume angle. None of the three nozzles could effectively delivered drugs into the middle meatus at any angle in this model. Conclusions: The design of the nozzle affects drug delivery efficiency of nasal spray devices. The ideal angle of administration is 50°. The nozzle with smaller plume angle has higher drug delivery efficiency. Current nasal spray devices can easily deliver drugs to most areas of the nasal cavity, such as the turbinate, nasal septum, olfactory fissure, and nasopharynx, but not the middle meatus. These findings are meaningful for nozzle selection and device improvements.

Development and Validation of a Pathomics Model Using Machine Learning to Predict CXCL8 Expression and Prognosis in Head and Neck Cancer.

OBJECTIVES: The necessity to develop a method for prognostication and to identify novel biomarkers for personalized medicine in patients with head and neck squamous cell carcinoma (HNSCC) cannot be overstated. Recently, pathomics, which relies on quantitative analysis of medical imaging, has come to the forefront. CXCL8, an essential inflammatory cytokine, has been shown to correlate with overall survival (OS). This study examined the relationship between CXCL8 mRNA expression and pathomics features and aimed to explore the biological underpinnings of CXCL8. METHODS: Clinical information and transcripts per million mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA)-HNSCC dataset. We identified correlations between CXCL8 mRNA expression and patient survival rates using a Kaplan-Meier survival curve. A retrospective analysis of 313 samples diagnosed with HNSCC in the TCGA database was conducted. Pathomics features were extracted from hematoxylin and eosin-stained images, and then the minimum redundancy maximum relevance, with recursive feature elimination (mRMR-RFE) method was applied, followed by screening with the logistic regression algorithm. RESULTS: Kaplan-Meier curves indicated that high expression of CXCL8 was significantly associated with decreased OS. The logistic regression pathomics model incorporated 16 radiomics features identified by the mRMR-RFE method in the training set and demonstrated strong performance in the testing set. Calibration plots showed that the probability of high gene expression predicted by the pathomics model was in good agreement with actual observations, suggesting the model's high clinical applicability. CONCLUSION: The pathomics model of CXCL8 mRNA expression serves as an effective tool for predicting prognosis in patients with HNSCC and can aid in clinical decision-making. Elevated levels of CXCL8 expression may lead to reduced DNA damage and are associated with a pro-inflammatory tumor microenvironment, offering a potential therapeutic target.

Effect of recombinant human acidic fibroblast growth factor on nasal mucosal healing after endoscopic sinus surgery.

BACKGROUND: Postoperative nasal treatment is an important factor affecting the outcomes of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). This study aimed to determine the effect of recombinant human acidic fibroblast growth factor (rh-aFGF) on nasal mucosal healing after ESS. METHODS: This study is a prospective, single-blind, and randomized controlled clinical study. Fifty-eight CRS patients with nasal polyps (CRSwNP) with bilateral ESS were enrolled and randomly given 1 mL of budesonide nasal spray and 2 mL of rh-aFGF solution (rh-aFGF group) or 1 mL of budesonide nasal spray and 2 mL of rh-aFGF solvent (budesonide group)-infiltrated Nasopore nasal packing after ESS. Preoperative and postoperative scores for Sino-Nasal Outcome Test (SNOT-22), Visual Analogue Scale (VAS), and Lund-Kennedy were collected and analyzed. RESULTS: Forty-two patients completed the 12-week follow-up. Postoperative SNOT-22 scores and VAS scores showed no significant differences between the two groups. In terms of the Lund-Kennedy scores, there was a statistically significant difference between the two groups at the 2-, 4-, 8-, and 12-week postoperative visits, but not at the 1-week visit. Twelve weeks after surgery, the nasal mucosa had completely epithelialized in 18 patients in the rh-aFGF group and in 12 patients in the budesonide group (χ2 = 4.200, P = 0.040). CONCLUSION: The combined application of rh-aFGF and budesonide significantly improved postoperative endoscopic appearance in the nasal mucosal healing process.

Genome-wide analysis of long noncoding RNA expression profile in nasal mucosa with allergic rhinitis.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in a variety of human immune diseases. However, the expression profile and precise function of lncRNAs in allergic rhinitis (AR) remain unknown. In the present study, genome-wide analysis of lncRNA expression was performed in the nasal mucosa tissue and mRNA regulatory relationship was examined among patients with or without AR. METHODS: Microarray assays were performed and the differential expressions of lncRNAs or mRNA were verified through RT-PCR. The lncRNA functions were annotated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The potential regulatory relationships between lncRNAs and the co-expressed mRNAs were analyzed using Cytoscape software. The expressions of specific lncRNAs and mRNAs were examined using an in vitro cell model. RESULTS: A total of 57 lncRNAs and 127 mRNAs were dysregulated in the nasal mucosa tissue of patients with AR, compared to those of patients without AR (fold change > 2.0 and P < 0.05). GO and pathway analysis indicated that the lncRNA-co-expressed mRNAs were enriched in several biological processes and cellular signaling pathways related to AR, such as positive regulation of the integrin biosynthetic process, cell adhesion, and leukocyte transendothelial migration. Some lncRNAs regulated the co-expressed genes in a cis- and/or trans-regulatory manner. Furthermore, allergen exposure significantly increased the expression of lnc-CXCL12-4, CXCL12, and CXCR4 in BEAS-2B cells compared to untreated cells (P < 0.01). CONCLUSION: The results of the present study suggest that lncRNAs participate in the biological pathways related to AR. Leukocyte transepithelial migration may be a potential target for lncRNAs to regulate allergic inflammation and CXCL12/CXCR4 axis plays an important role in the inflammatory process of AR.

Comparative study of nasal septal retainer and nasal packing in patients undergoing septoplasty.

PURPOSE: Nasal packing is frequently used after septoplasty and some complications caused by nasal packing are unavoidable. A nasal septal retainer has recently been developed. We evaluated the safety and clinical efficacy of the retainer in septoplasty, and the subjective symptoms of patients with the retainer were compared with Merocel nasal packing. METHODS: A prospective, randomized, controlled study was performed in patients who had undergone septoplasty. In total, 39 patients were randomized to receive Merocel (n = 17) or the retainer (n = 22) after septoplasty. The deviation of nasal septum and nasal mucosa was evaluated by endoscopy. The clinical efficacy and subjective symptoms were compared using the visual analog scale. RESULTS: During the packing/retaining period, the mean scores of headache, nasal obstruction, epiphora, and facial pressure in the retainer group were significantly lower than in the Merocel group (P < 0.05); the mean scores of nasal pain, nasal itching, rhinorrhea, dysphagia, and sleep disturbance in the retainer group were lower than in the Merocel group, but the difference did not reach statistical significance. On the removal of Merocel/retainer, nasal pain was significantly lower in patients with the retainer (P < 0.05). In the retainer group, the incidence of grade 1 bleeding was 45.5%, and grade 0 bleeding was 54.5%. In the Merocel group, the incidence of grade 2 bleeding was 23.5%, grade 1 was 47.1%, and grade 0 was 29.4%. CONCLUSIONS: The nasal septal retainer is suitable for use after septoplasty with more beneficial effects than nasal packing.

Beneficial effects of hydrogen gas inhalation on a murine model of allergic rhinitis.

Allergic rhinitis (AR) is a common chronic inflammatory condition. It has been previously indicated that oxidative stress may contribute to allergic inflammation, including AR. Although molecular hydrogen (H2), an antioxidative agent, has been effective in treatment of numerous oxidative stress-associated diseases, the effect of inhalation of a high concentration of H2 on AR remains unknown. In the current study, female BALB/c mice were sensitized with ovalbumin (OVA) followed by intranasal OVA challenge to establish an animal model of AR. Mice were subjected to exposure to H2 and the inert gas helium at different frequencies and durations. The frequencies of sneezing/scratching and the body weights of mice were recorded. Histological analysis and multiplex cytokine assays were performed to evaluate the effects of H2 on AR. Challenge with OVA induced significant nasal mucosa inflammation. H2 inhalation reduced the infiltration of inflammatory cells into mucosa and lowered the levels of interleukin (IL)-5, IL-13 and monocyte chemoattractant protein-1 in serum. H2 inhalation slightly increased the level of interferon-γ, however the difference was not statistically significant. Treatment with H2 limited the weight increase in healthy mice and reversed the weight loss in mice with AR. Furthermore, H2 inhalation induced a therapeutic effect on AR in a dose-dependent manner. The current results demonstrate that H2 may demonstrate a therapeutic value for allergic diseases.

Super enhancer associated RAI14 is a new potential biomarker in lung adenocarcinoma.

PURPOSE: Tyrosine kinase inhibitors (TKIs) are widely used to treat lung adenocarcinoma patients with EGFR mutations or ALK-fusions. However, patients with wild-type genes or TKIs-resistant mutations lack effective therapeutic targets. Extensive studies reveal that super enhancer (SE), a large cis-regulatory element, is associated with key oncogenes in a variety of cancers. By comparing the effect of SE on lung adenocarcinoma cell lines with normal cell line, this work attempts to find new biomarkers and potential therapeutic targets for lung adenocarcinoma. EXPERIMENTAL DESIGN: Chromatin Immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) of H3K27ac (acetylation on lysine 27 of histone 3) was performed in lung adenocarcinoma cell lines SPC-A1 and SCH-1153. The differences in SE distribution were then analyzed among SPC-A1, SCH-1153, A549 and normal human lung fibroblasts (NHLF) to identify SE-associated oncogenes. The expression of SE-associated oncogenes was then detected by RNA-seq and further verified in 71 patients by real-time PCR. RESULTS: SE associated with many new oncogenes in lung adenocarcinoma, among which, RAI14 was up-regulated in A549 and 31 of 71 patients. High expression of RAI14 could inhibit cell proliferation, indicating its potential as a new biomarker for lung adenocarcinoma.

Peroxisome proliferator-activated receptor γ agonist suppresses mast cell maturation and induces apoptosis.

Peroxisome proliferator-activated receptor gamma (PPAR Î³), is important in the immunoregulation of the allergic response. Mast cells are the most important inflammatory cells in immediate hypersensitivity and allergic diseases. However, there is limited information regarding the effects of PPAR Î³ on mast cell maturation. In the present study, mouse bone marrow­derived mast cells (BMMCs) were cultured in interleukin (IL)­3 and stem cell factor (SCF), in the presence or absence of the PPAR Î³ agonist, pioglitazone (PIO). The expression levels of the tyrosine kinase receptor CD117 and the high affinity IgE receptor FcεRI α, were assessed by flow cytometry, cell viability was assessed by Alamar­Blue assay and histamine release was determined by measuring the activity of ß­hexosaminidase. IL­3 and SCF are required for the development of mast cells in vitro. PIO dose­dependently inhibited the expression of CD117 and FcεRI α, and the maturation of BMMCs. Treatment with PIO additionally inhibited the formation of granules and reduced the expression of ß­hexosaminidase. In addition, reverse transcription­polymerase chain reaction analysis revealed that BMMCs treated with PIO expressed a lower level of mast cell protease (MCP)­6 mRNA and PIO treatment enhanced the level of PPAR Î³ mRNA. Furthermore, PIO induced mast cell progenitor apoptosis. PPAR Î³ agonists may maintain mast cell homeostasis by inhibiting maturation of their precursors. The inhibitory effects of PPAR Î³ agonists include suppression of the activation of mast cells and a decrease in mast cell function in the inflammatory response. Therefore, PPAR Î³ agonists may serve as effective anti-inflammatory reagents in the treatment of allergic reactions.