Identification of core gene in chronic rhinosinusitis with nasal polyps and correlations with inflammation-related genes.

OBJECTIVE: Our aim in this study is to identify the core genes of chronic rhinosinusitis with nasal polyps and analyze the correlations between it and inflammation-related genes. METHODS: GSE72713 dataset containing gene expression data of ECRSwNP, nonECRSwNP and healthy samples was obtained from Gene Expression Omnibus (GEO) and filtered by limma to identify DEGs among three groups, then the functions and correlated pathways of DEGs were analyzed using GO and KEGG. The core DEGs were selected by the intersection of DEGs and the PPI network was constructed via STRING. The correlations between the expression levels of CRSwNP core gene and inflammation-related genes were analyzed via the Mann-Whitney U test. RESULTS: The DEGs among ECRSwNP, nonECRSwNP, and CTRL were filtered respectively, and enrichment analysis showed they were associated with olfaction and/or immune responses. The PPI network was constructed by 7 core DEGs obtained via the intersection among three groups, and ALOX15 was confirmed as the core gene in the network. Subsequently, the correlations between the expression levels of ALOX15 and inflammation-related genes were illustrated. CONCLUSION: In this study, the core gene ALOX15 was selected from the DEGs among ECRSwNP, nonECRSwNP, and CTRL. IL5, IL1RL1, and IL1RAP were found to exhibit a significant positive correlation with ALOX15. LEVEL OF EVIDENCE: Level 3.

Epidermal growth factor activates a hypoxia-inducible factor 1α-microRNA-21 axis to inhibit aquaporin 4 in chronic rhinosinusitis.

The pathogenesis of chronic rhinosinusitis (CRS) is largely unknown, but accumulating evidence supports the role of the airway epithelium in its pathophysiology. In our study here, we evaluated whether epidermal growth factor (EGF) regulates a hypoxia-inducible factor 1α (HIF-1α)-microRNA-21 (miR-21)-aquaporin 4 (AQP4) axis in nasal epithelial cells from CRS patients. We found that, compared with normal sinus mucosa, EGF, HIF-1α, and miR-21 were upregulated and AQP4 was downregulated in sinus mucosa from patients with CRS and in a CRS mouse model. It was established that EGF upregulated HIF-1α and miR-21 expression, that HIF-1α regulated miR-21 transcription, and that the AQP4 gene was a target of miR-21. Knockdown of EGF and HIF-1α mRNAs and of miR-21, or overexpression of AQP4 mRNA, inhibited proliferation and promoted apoptosis of hypoxia-exposed human nasal epithelial cells, effects that were associated with reduced levels of α-SMA, fibronectin, and vimentin, as well as promoted caspase-3 activity and E-cadherin levels. In the mouse CRS model, EGF elevation increased in vivo production of inflammatory IL-4 and IFN-γ to promote CRS, which was reversed by AQP4 elevation. Collectively, EGF upregulates HIF-1α and miR-21 expression to inhibit AQP4 expression, thereby promoting the proliferation of nasal epithelial cells and the development of CRS.

Transnasal Endoscopy and Combined Approach to Infratemporal Fossa Abscess and Parapharyngeal Abscess.

The infratemporal fossa is a very important anatomical space that is relatively closed with an irregular shape and is adjacent to the parapharyngeal space. Infratemporal fossa abscess is rare clinically. It can occur as a complication of maxillary sinusitis, maxillary sinus fracture, or odontogenic infection. If not handled in time, it may endanger the lives of patients. This paper reports the diagnosis and treatment of infratemporal fossa abscess in 2 diabetic patients. Computed tomography and magnetic resonance imaging are the best methods to diagnose suspected cases of this disease. The key treatment is to combine sensitive antibiotic treatment with endoscopic abscess drainage. Different approaches can be selected according to the range of lesions. If necessary, a combined approach to drain the pus is needed. Early diagnosis, timely initiation of antibiotics, and surgical intervention are essential for curing this disease.

Immunoglobulin G4-related disease presenting with hypertrophy and sclerosis of the inferior turbinate.

Immunoglobulin G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4+ plasma cells.1 We report the case of a 56-year-old man who presented with nasal obstruction for 5 years. Rhinoscopy revealed hypertrophy and sclerosis of the inferior turbinate, whereas computed tomography revealed inflammation of the anterior ethmoid sinus and frontal sinuses. An endoscopic inferior turbinectomy was performed, and IgG4-RD was definitively diagnosed based on the histopathological features of the turbinate tissue. Prednisolone was administered postoperatively. IgG4-RD presenting with hypertrophy and sclerosis of the inferior turbinate is rare. Awareness of IgG4-RD originating in the sinonasal cavity is essential to avoid delayed diagnosis.

[Analysis of allergen distribution and clinical characteristics of autumn allergic rhinitis in Changchun and surrounding areas].

Objective:To investigate the allergen characteristics, allergen distribution and clinical symptoms of autumn allergic rhinitis in Changchun and surrounding areas. Methods:The allergen test results of 1080 allergic rhinitis（AR） suspected patients from Changchun and surrounding areas were collected, from August to October 2019 and August to October 2020 in the Department of Otorhinolaryngology Head and Neck Surgery, the Second Hospital of Jilin University. The positive rates of major allergens and their differences in gender, age, different years and clinical symptom were compared and analyzed. Results:①Among the 1080 suspected AR patients, 804 patients（74.44%） had positive allergens. ②The top 3 allergens of autumn AR in Changchun and surrounding areas were Artemisia（36.20%）, Dwarf ragweed（33.24%） and Candida/Penicillium notarum/Cladosporium/Alternaria/Aspergillus niger（19.81%）. The positive rates of Artemisia and Dwarf ragweed were higher in men than in women（P<0.05）. ③Artemisia was the major allergen of autumn AR in juvenile group, youth group and middle-aged group. ④The positive rate of two or more allergens was 2.39 times that of single allergen. ⑤Patients with positive autumn pollen allergens had more severe symptoms of nasal congestion, red eye/eye itching and epiphora than those in other groups. Conclusion:Seasonal AR had typical clinical symptom characteristics. Major allergens in autumn AR in Changchun and surrounding areas are autumn pollen allergens（Artemisia, Dwarf ragweed, Humulus）. The distribution of those allergens was different in gender, age, and different years.

Long Noncoding RNA TRPM2-AS Promotes the Growth, Migration, and Invasion of Retinoblastoma via miR-497/WEE1 Axis.

Long noncoding RNAs (lncRNAs) exhibit vital roles in many types of cancer, including retinoblastoma (RB), the most common primary intraocular malignancy tumor of infancy. A novel lncRNA TRPM2-AS has been demonstrated to be related to multiple cancers; however, its role in RB remains unclear. Here, we aimed to investigate the function of TRPM2-AS in RB. In this study, TRPM2-AS expression in 35 human RB tissues and RB cell lines was detected by real-time PCR. And, the relationship between its expression and clinicopathological characteristics of RB patients was analyzed. RB cells' proliferation, migration, invasion, apoptosis, and cell cycle were explored after silencing TRPM2-AS. The mechanism of TRPM2-AS in RB was focused on miR-497/WEE1 axis. Additionally, the role and mechanism of TRPM2-AS were confirmed in a xenograft mouse model. We found TRPM2-AS expression was enhanced in RB tissues and cells. And, higher TRPM2-AS expression was related to advanced clinical stage and optic nerve invasion in patients. Downregulation of TRPM2-AS significantly inhibited proliferation, migration, and invasion, elevated apoptosis, attenuated G2/M phase arrest in RB cells, and suppressed tumor growth in vivo. TRPM2-AS acted as a ceRNA for miR-497 to positively regulate WEE1 expression. miR-497 inhibitor or WEE1 overexpression dramatically reversed the effects of TRPM2-AS downregulating on the malignant phenotypes of RB cells. Therefore, TRPM2-AS is an oncogenic lncRNA in RB, and it functions largely through the miR-497/WEE1 pathway. Despite the limited sample size, this study indicates that TRPM2-AS may be a candidate target in RB therapies.

Author Correction: CCT α is a novel biomarker for diagnosis of laryngeal squamous cell cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Long non-coding RNA CASC9 promotes the progression of retinoblastoma via interacting with miR-145-5p.

Abnormal expression of long non-coding RNA cancer susceptibility candidate 9 (CASC9) has been found to play vital roles in many human tumors. However, the role and the regulatory mechanism of CASC9 have not yet been demonstrated in retinoblastoma (RB). Hence, we performed this study to explore the function and mechanism of CASC9 in RB. CASC9 expression was firstly detected in human RB tissues and cells. The influence of CASC9 on the malignant phenotypes of RB cells, including cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and apoptosis, was analyzed by overexpressing or silencing CASC9. The association between CASC9, miR-145-5p and E2F transcription factor 3 (E2F3) was determined by dual-luciferase reporter assay and RNA immunoprecipitation. We found that CASC9 expression was elevated in RB tissues and cells. Overexpression of CASC9 significantly facilitated the proliferation, invasion and EMT of RB cells. On the contrary, knockdown of CASC9 inhibited the proliferation, invasion and EMT, while enhanced the apoptosis of RB cells. CASC9 acted as a competing endogenous RNA (ceRNA) for miR-145-5p to regulate E2F3. Additionally, miR-145-5p inhibitor and E2F3 overexpression both partly reversed the malignant phenotypes of RB cells affected by CASC9 knockdown. However, miR-145-5p overexpression further strengthened these features induced by CASC9 downregulation. These findings suggested that CASC9 contributed to RB development by regulating E2F3 via sponging miR-145-5p. CASC9 might be a possible therapeutic target for RB.

MicroRNA-761 suppresses remodeling of nasal mucosa and epithelial-mesenchymal transition in mice with chronic rhinosinusitis through LCN2.

BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by persistent symptomatic inflammation of the nasal passage and sinus mucosa. Various microRNAs (miRs) have been implicated in CRS. Hence, the current study was conducted to explore the effect of microRNA-761 (miR-761) on remodeling of nasal mucosa and epithelial-mesenchymal transition (EMT). METHODS: Bioinformatics analysis was initially performed to predict the differentially expressed genes (DEGs) associated with CRS. Gene targeting relationship between miR-761 and lipocalin 2 (LCN2) was analyzed by bioinformatics analysis and verified using dual-luciferase reporter gene assay. Histopathological analyses of the nasal mucosa tissues were conducted via hematoxylin-eosin (HE) and alcian blue (AB)-periodic acid Schiff (PAS) staining. ELISA was employed to determine the IL-8 and MMP-9 levels. To define downstream pathway of miR-761, levels of proteins related to LCN2/Twist1 signaling pathway were assessed. Additionally, the effects of miR-761 on EMT, proliferation, and apoptosis were determined. RESULTS: LCN2 was highly expressed in CRS. LCN2 was a target of miR-761. miR-761 overexpression or LCN2 silencing decreased IL-8 and MMP-9 levels and morphological changes in nasal epithelial tissue from CRS mice. Overexpressed miR-761 or silenced LCN2 decreased the expression of LCN2 and Twist1, indicating LCN2/Twist1 signaling pathway was inactivated. Moreover, miR-761 overexpression or LCN2 silencing reduced the expression of N-cadherin and vimentin, while increased that of E-cadherin, suggesting inhibition of EMT. Furthermore, miR-761 overexpression or LCN2 silencing promoted cell proliferation and inhibited cell apoptosis in CRS. CONCLUSION: Taken together, miR-761 suppressed the remodeling of nasal mucosa through inhibition of LCN2 and the LCN2/Twist1 signaling pathway.

Identification of Susceptibility Genes to Allergic Rhinitis by Gene Expression Data Sets.

As an extremely prevalent disease worldwide, allergic rhinitis (AR) is a condition characterized by chronic inflammation of the nasal mucosa. To identify the finer molecular mechanisms associated with the AR susceptibility genes, differentially expressed genes (DEGs) in AR were investigated. The DEG expression and clinical data of the GSE19187 data set were used for weighted gene co-expression network analysis (WGCNA). After the modules related to AR had been screened, the genes in the module were extracted for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, whereby the genes enriched in the KEGG pathway were regarded as the pathway-genes. The DEGs in patients with AR were subsequently screened out from GSE19187, and the sensitive genes were identified in GSE18574 in connection with the allergen challenge. Two kinds of genes were compared with the pathway-genes in order to screen the AR susceptibility genes. Receiver operating characteristic (ROC) curve was plotted to evaluate the capability of the susceptibility genes to distinguish the AR state. Based on the WGCNA in the GSE19187 data set, 10 co-expression network modules were identified. The correlation analyses revealed that the yellow module was positively correlated with the disease state of AR. A total of 89 genes were found to be involved in the enrichment of the yellow module pathway. Four genes (CST1, SH2D1B, DPP4, and SLC5A5) were upregulated in AR and sensitive to allergen challenge, whose potentials were further confirmed by ROC curve. Taken together, CST1, SH2D1B, DPP4, and SLC5A5 are susceptibility genes to AR.

CCT α is a novel biomarker for diagnosis of laryngeal squamous cell cancer.

Choline phosphate-based delivery systems can target the acidic tumor microenvironment. In this study, we set out to evaluate the diagnostic value of Choline phosphate cytidylyltransferase-α (CCTα) in laryngeal squamous cell cancer (LSCC). The expression of CCTα was detected using immunohistochemistry in 50 LSCC patients' tissues and 16 vocal polyps as control group. Then, clinical data was collected and we used receiver operating characteristic curve (ROC) to estimate the potential of CCTα as diagnostic biomarker. We found CCTα levels to be significantly high in the tissues derived from LSCC patients, (p < 0.001). Further, we observed a positive correlation of CCTα with tumor size (p < 0.001), TNM stage (p < 0.001), lymph node metastasis (p < 0.001) as well as the grade of LSCC malignancy (p < 0.001). Furthermore, AUC was determined to be 0.939 by ROC, and the optimal cutoff value 3.100, with 76.0% sensitivity and 100% specificity. We also found an epigenetic basis of CCTα over-expression in LSCC tissues with significantly reduced methylation of CCTα in LSCC tissues, compared to vocal polyps (p < 0.001). These results support epigenetically-induced over-expression of CCTα as a potential diagnostic marker for LSCC.

Efficacy of posterior nasal neurectomy for allergic rhinitis combined with chronic rhinosinusitis with nasal polyps.

Background: Allergic rhinitis combined with chronic rhinosinusitis with nasal polyps (ARwCRSwNP) is very common clinically. Conventionally, the treatment for these patients is surgical method for CRSwNP followed by treatment with a nasal steroid spray or other antiallergic drugs to control AR. In recent years, some rhinologists introduced vidian neurectomy (VN) or posterior nasal neurectomy (PNN) into endoscopy to treat refractory AR and reported an encouraging outcome. Furthermore, we explore the control of recurrence of nasal polyps and improvement in symptoms after endoscopic PNN for the treatment of ARwCRSwNP. Objective: To investigate the control of recurrence of nasal polyps and improvement in symptoms after endoscopic PNN for the treatment of ARwCRSwNP. Methods: Eighty-five patients with ARwCRSwNP who were admitted to our hospital from November 2016 to July 2018 were enrolled in two groups. Group A underwent conventional functional endoscopic sinusitis surgery (FESS) combined with PNN; group B underwent conventional FESS alone. VAS, RQLQ, SNOT-22 and postoperative nasal endoscopy were used to evaluate the improvement in symptoms and the recurrence of nasal polyps. Results: The experimental group had better control of sneezing (p < .05) and rhinorrhea (p < .01) than the control group. For those who underwent surgery more than 6 months prior in both groups, the recurrence rate was 29.6% (8/27) in the experimental group and 44.4% (8/18) in the control group, and there was no significant difference (χ2 = .483, p = .487). Conclusion: FESS combined with PNN can improve the symptoms of sneezing and rhinorrhea caused by ARwCRSwNP more obviously than FESS alone, but there is no clear statistical advantage of this procedure for improving the overall symptoms and controlling the recurrence of nasal polyps.

Desmoglein 3 Silencing Inhibits Inflammation and Goblet Cell Mucin Secretion in a Mouse Model of Chronic Rhinosinusitis via Disruption of the Wnt/ß-Catenin Signaling Pathway.

Chronic rhinosinusitis (CRS) is a common disease characterized by inflammation of the nose and paranasal sinuses lasting over 12 weeks. This study aims to evaluate the effect of desmoglein 3 (DSG3) on inflammatory response and goblet cell mucin secretion in a mouse model of CRS. The CRS-related differentially expressed genes and disease genes were screened using microarray-based gene expression analysis. Subsequently, CRS mouse models were established. The levels of pro-inflammatory factors TNF-α, IL-6, and IL-8 were measured by ELISA. In addition, loss-of-function experiment was conducted using siRNAs targeting DSG3 and ß-catenin. The secretion of mucins MUC5B and MUC5AC in goblet cells was detected, and the apoptosis of goblet cells was assessed. The regulatory effect of DSG3 on the Wnt/ß-catenin signaling pathway was analyzed by determining the mRNA and protein levels of DSG3, Wnt, ß-catenin, and GSK3ß. DSG3 was identified to be an upregulated gene in CRS, which was further documented in CRS mice models. Elevated inflammation and mucin production were noted in CRS mice models. Also, it was found that DSG3 or ß-catenin silencing could decrease the levels of TNF-α, IL-6, and IL-8, and the positive rates of MUC5B and MUC5AC while enhancing goblet cell apoptosis. The Wnt/ß-catenin signaling pathway was blocked by DSG3, evidenced by downregulated Wnt and ß-catenin as well as upregulated GSK3ß mRNA and protein levels. Overall, this study provides evidence that silencing DSG3 could inhibit the activation of the Wnt/ß-catenin signaling pathway, thus alleviating CRS.

Epigenetic changes: An emerging potential pharmacological target in allergic rhinitis.

The importance of epigenetics has increased due to identification of its role in the pathophysiology of a number of diseases including allergic rhinitis. Amongst the different epigenetic changes in allergic retinitis, deacetylation of histone proteins by histone deacetylase (HDACs), hypermethylation of DNA by DNA methyltransferases (DNMT) and alteration in post-transcriptional process by the changes in the levels of miRNA are widely studied. Studies conducted related to allergic rhinitis have shown the elevation in the levels of HDAC1, 3 and 11 in the nasal epithelia and HDAC inhibitors have shown effectiveness in decreasing the symptoms of rhinitis. Their beneficial effects are attributed to restoration of the expression of TWIK-related potassium channel-1, correction of cytokine profile along with normalization of Th1/Th2 imbalance. Another epigenetic change due to increase in DNMT activity may induce DNA hypermethylation in CpG sites in the airway epithelial cells and CD4+ T-cells. The reduction in DNA methylation decreases allergic symptoms and normalizes the over-reactive immune system. Mechanistically, allergens may promote the hypermethylation in the promoter region of IFN-γ gene in CD4+ T cells via activation of ERK pathway to decrease the expression of IFN-γ. In allergic rhinitis patients, there is also a downregulation of certain miRNAs including miR-135a, miR-146a, miR-181a, miR-155 and upregulation of miRNA19a. This review discusses the studies describing the epigenetic changes taking place in the host cells in response to allergen along with possible mechanisms.

Long noncoding RNA NEAT1 promotes the growth of human retinoblastoma cells via regulation of miR-204/CXCR4 axis.

Retinoblastoma (RB) is an aggressive eye cancer of infancy and childhood with high mortality. Studies have shown that long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) is closely related to the progression of multiple cancers. However, its role in RB remains unknown. This study aimed to investigate the role and underlying mechanism of NEAT1 in RB. We first detected the expression of NEAT1 in human RB tissues and cell lines. The effects of NEAT1 on the proliferation, migration, and apoptosis of RB cells were analyzed by loss-of-function. The underlying mechanism of NEAT1 in RB was mainly focused on the microRNA 204/C-X-C chemokine receptor type 4 (miR-204/CXCR4) axis. In addition, the role and mechanism of NEAT1 in RB were further evaluated in a mouse xenograft tumor model. We found NEAT1 and CXCR4 expression levels were elevated, whereas miR-204 expression was decreased in RB tissues and cells. Downregulation of NEAT1 significantly decreased the proliferation and migration but promoted the apoptosis of RB cells. NEAT1 functioned as a competing endogenous RNA for miR-204 to regulate CXCR4 expression. Knockdown of NEAT1 suppressed the tumor volume, tumor weight, and CXCR4 expression, whereas increased miR-204 expression in mice. In conclusion, NEAT1 promotes the development of RB via miR-204/CXCR4 axis, which provides a new target for the treatment of RB disease.

Modified endoscopic inferior meatal fenestration with mucosal flap for maxillary sinus diseases.

INTRODUCTION: This is a novel minimally invasive surgical method for maxillary sinus mucoceles and antrochoanal polyps. AIM: To describe a modified technique of inferior meatal fenestration with a mucosal flap for maxillary sinus diseases and to present a case series of subjects who underwent this procedure. The novel surgical technique and indications for this approach are also discussed. MATERIAL AND METHODS: The authors analyzed data from 32 cases involving patients who underwent resection of maxillary sinus mucoceles and antrochoanal polyps via modified endoscopic inferior meatal fenestration with a mucosal flap in the period from January, 2011 to January, 2016. The group included 19 men and 13 women, and the patients' mean age was 36.2 years (range: 11-56 years). Preoperative and postoperative imaging studies were available in all cases and were reviewed. RESULTS: Thirty-two cases are included in this study. The appearance of nasal and (or) maxillary sinus mucosa was observed in the follow-up at 1 month, 3 months and 6 months using endoscopes. Postoperative computed tomography was performed for only 9 patients in this study. The mean follow-up period was 56 (range: 10-82) months in these cases. All patients had an uneventful post-operative period. Postoperative symptoms were relieved gradually for 1 to 2 weeks after the operation. No patients experienced recurrent symptoms related to the mucocele. Mucocele and polyps recurrence was not observed. No patient showed re-stenosis and obstruction of the nasal cavity, facial pain or numbness during follow-up. CONCLUSIONS: Maxillary sinus mucoceles and antrochoanal polyps are completely excised via modified endoscopic inferior meatal fenestration with a mucosal flap. It could keep the nasal lateral wall intact.

Knockdown of Snail inhibits epithelial-mesenchymal transition of human laryngeal squamous cell carcinoma Hep-2 cells through the vitamin D receptor signaling pathway.

It has been well documented that Snail plays a decisive role in various tumors. However, the direct effect of Snail on laryngeal squamous cell carcinoma (LSCC) has not been elaborated. In this study, we firstly detected the expression of Snail in 14 samples of patients with LSCC and found that its content was high in cancer tissues compared with adjacent tissues. Then we established LSCC Hep-2 cells with Snail silencing and validated the knockdown efficiency by Western blotting and real-time PCR. Results showed that silencing of Snail significantly inhibited the ability of adhesion, migration, and invasion of Hep-2 cells. Further study revealed that knockdown of Snail suppressed the epithelial-mesenchymal transition (EMT) process of Hep-2 cells, as evidenced by downregulation of matrix metallopeptidase (MMP)-2, MMP-9, integrin subunit beta 1 (ITGß1), ß-catenin, vimentin, N-cadherin, and fibronectin and upregulation of vitamin D receptor (VDR) and E-cadherin. Additionally, transfection with the small interfering RNA of VDR reversed the effect induced by Snail silencing in Hep-2 cells. Taken together, these results demonstrate that knockdown of Snail can inhibit the EMT process of LSCC cells through the VDR signaling pathway in vitro.

Resection of Adenoid Cystic Carcinoma Originating From the Cavernous Sinus Via Endoscopic Endonasal Approach.

A 50-year-old woman presented with gradually increasing right-sided facial numbness. Neuroimaging revealed a lesion in the right cavernous sinus mimicking meningioma. The resection of the right cavernous sinus neoplasm was implemented via endoscopic endonasal approach under general anesthesia. Histological examination of the surgical specimen revealed adenoid cystic carcinoma. Adenoid cystic carcinoma in the cavernous sinus is extremely rare as a primary lesion and challenging to manage. Little data exist to guide treatment when this tumor extends to involve the structure of cavernous sinus. Our study illustrates that endoscopic endonasal approach is a good choice for resection of the tumor in the cavernous sinus.

Identification of genes associated with tongue cancer in patients with a history of tobacco and/or alcohol use.

The present study aimed to identify genes associated with tongue cancer in patients with a history of tobacco and/or alcohol use. Microarray dataset GSE42023, including 10 tissue samples of tongue cancer from patients with a history of tobacco and/or alcohol use (habit group) and 11 tissue samples of non-habit-associated tongue cancer (non-habit group), were downloaded from the Gene Expression Omnibus database. Differentially-expressed genes (DEGs) between the habit and non-habit groups were identified using the Linear Models for Microarray Data software package. The enrichment functions and pathways of these genes were subsequently predicted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Transcription factors (TFs) and tumor-associated genes (TAGs) were selected from the DEGs using the Encyclopedia of DNA Elements database and the TAG database, respectively. Protein-protein interaction (PPI) networks for DEGs were constructed using Cytoscape. In addition, functional module analysis was performed using BioNet. This analysis identified 642 DEGs between the habit and non-habit groups, including 200 upregulated and 442 downregulated genes. The majority of upregulated DEGs were functionally enriched in the regulation of apoptosis and the calcium signaling pathway. The majority of downregulated DEGs were functionally enriched in fat cell differentiation and the adipocytokine signaling pathway. In addition, 31 TFs and 42 TAGs were identified from the DEGs. Furthermore, this analysis demonstrated that certain DEGs, including AKT serine/threonine kinase 1 (AKT1), E1A binding protein p300 (EP300), erb-b2 receptor tyrosine kinase 2 (ERBB2) and epiregulin (EREG), had high connectivity degrees in the PPI networks and/or functional modules. Overall, DEGs in a functional module, such as AKT1, EP300, ERBB2 and EREG, may serve important roles in the development of tongue cancer in patients with a history of tobacco and/or alcohol use. These DEGs are potential therapeutic targets for the treatment of tongue cancer in these groups.

The Epidemiology of Olfactory Disorders.

Insights into risk factors for olfactory decline are needed, because knowledge about its origin is limited. This impairment has important implications for human health. Several epidemiologic studies of olfaction provide insight into the prevalence of olfactory disorders. Here, we review the major population studies carried out on this topic to date. Our purpose is to characterize knowledge about olfactory disorders from human studies. We also describe the existing methods for measuring the sense of smell in population studies, present recent insights into the epidemiology of smell disorders, and discuss the risk factors identified to date. Synthesis of these data shows that olfactory dysfunction increases as people age and is worse in men. Further study of olfaction is warranted for gaining better information on the etiologies affecting its impairment, research that will have a large public health impact.