Xia Gao

Supraglottic adenoid cystic carcinoma mimicking laryngeal amyloidosis: A case report.

Supraglottic adenoid cystic carcinoma (ACC) is extremely rare and may be misdiagnosed as laryngeal amyloidosis. The present report describes a case of supraglottic ACC, which went unrecognized until histopathological examination of the neoplasm 18 months after the first presentation. The present patient presented with progressive hoarseness for half a year and initially required partial resection. Following quick regional recurrence, the patient received a total laryngectomy while refusing radiotherapy. Adjuvant post-operational traditional Chinese medicine was accepted. Over 3 years’ follow-up, there was no evidence of regional relapse or distant metastases. The present case is compared with a second case of supraglottic submucosal mass in which the signs, symptoms and examinations were similar to the first case, but that was diagnosed as laryngeal amyloidosis. Attention should be paid to submucosal masses in the larynx to prevent underlying malignancy and subsequent disease progression. Immunocytochemistry, such as p63 staining, is mandatory for making an early differential diagnosis of supraglottic ACC. Traditional Chinese medicine may be a useful adjuvant therapy for this rare disease.

Characterization of Lgr5+ Progenitor Cell Transcriptomes after Neomycin Injury in the Neonatal Mouse Cochlea.

Lgr5+ supporting cells (SCs) are enriched hair cell (HC) progenitors in the cochlea. Both in vitro and in vivo studies have shown that HC injury can spontaneously activate Lgr5+ progenitors to regenerate HCs in the neonatal mouse cochlea. Promoting HC regeneration requires the understanding of the mechanism of HC regeneration, and this requires knowledge of the key genes involved in HC injury-induced self-repair responses that promote the proliferation and differentiation of Lgr5+ progenitors. Here, as expected, we found that neomycin-treated Lgr5+ progenitors (NLPs) had significantly greater HC regeneration ability, and greater but not significant proliferation ability compared to untreated Lgr5+ progenitors (ULPs) in response to neomycin exposure. Next, we used RNA-seq analysis to determine the differences in the gene-expression profiles between the transcriptomes of NLPs and ULPs from the neonatal mouse cochlea. We first analyzed the genes that were enriched and differentially expressed in NLPs and ULPs and then analyzed the cell cycle genes, the transcription factors, and the signaling pathway genes that might regulate the proliferation and differentiation of Lgr5+ progenitors. We found 9 cell cycle genes, 88 transcription factors, 8 microRNAs, and 16 cell-signaling pathway genes that were significantly upregulated or downregulated after neomycin injury in NLPs. Lastly, we constructed a protein-protein interaction network to show the interaction and connections of genes that are differentially expressed in NLPs and ULPs. This study has identified the genes that might regulate the proliferation and HC regeneration of Lgr5+ progenitors after neomycin injury, and investigations into the roles and mechanisms of these genes in the cochlea should be performed in the future to identify potential therapeutic targets for HC regeneration.

Role of epithelial-mesenchymal transition markers E-cadherin, N-cadherin, β-catenin and ZEB2 in laryngeal squamous cell carcinoma

Epithelial-mesenchymal transition (EMT) allows neoplastic cells to gain the invasive phenotype and become migratory, which is required for cancer progression and metastasis. In the present study, the expression of EMT-associated biomarkers and their association with clinicopathological parameters in laryngeal squamous cell carcinoma (LSCC) was investigated. E-cadherin, N-cadherin, β-catenin and zinc finger E-box binding homeobox 2 (ZEB2) protein expression was evaluated with immunohistochemistry in a cohort of 76 patients with operable LSCC. The association between these transition markers, clinicopathological parameters and their prognostic impact in LSCC was analyzed. Immunohistochemical analysis revealed that EMT-associated proteins were differentially expressed between LSCC and adjacent non-neoplastic laryngeal tissue. Negative E-cadherin expression and positive N-cadherin, β-catenin and ZEB2 expression were associated with a later tumor (T) stage, decreasing tumor differentiation and a reduced overall survival (OS) time (OS: E-cadherin, P=0.016; N-cadherin, P=0.003; β-catenin, P=0.002; ZEB2, P=0.0003). E-cadherin/β-catenin co-expression was significantly associated with the majority of clinicopathological parameters assessed, including lymph node metastases, T stage and tumor cell differentiation (P=0.004, P=0.005, and P<0.001, respectively). Multivariate analysis indicated that T stage and the positive expression of β-catenin and ZEB2 were independent risk factors for OS in LSCC (P=0.014, P=0.025 and P=0.003, respectively). It was concluded that EMT mediates tumor progression, and reduces OS time in patients with LSCC. E-cadherin/β-catenin co-expression may be associated with clinicopathological parameters. T stage, and the positive co-expression of β-catenin and ZEB2 may be independent predictors of prognosis in LSCC.

Effects of Semont maneuver on benign paroxysmal positional vertigo: a meta-analysis

Abstract Background: Benign paroxysmal positional vertigo (BPPV) is the most common type of peripheral vertigo. This study aimed to evaluate the effects of the Semont maneuver (SM) for BPPV treatment, compared with other methods. Methods: Studies were selected in relevant databases under pre-defined criteria up to June 2015. The Cochrane evaluation system was used to assess the quality of the studies. Effect size was indicated as a risk-ratio (RR) with corresponding 95% confidential interval (CI). Statistical analysis was conducted under a randomized- or fixed-effects model. Sub-group analysis was performed. Results: Ten studies were included in the meta-analysis. All of the studies presented a low attrition bias, but a high selection and reporting bias. SM had a much higher recovery rate (SM vs no treatment: RR = 2.60, 95% CI = 1.97–3.44, p < 0.01; SM vs sham: RR = 4.89, 95% CI = 3.01–7.94, p < 0.01), and lower recurrence rate than those from controls (SM vs no treatment: RR = 0.11, 95% CI = 0.04–0.31, p < 0.01). Overall, SM had similar outcomes with Epley maneuver (EM) and Brandt-Daroff exercise (BDE) in terms of recovery rate, recurrence rate, and side-effects. Conclusion: SM is as effective as EM and BDE for BPPV treatment.

Schwannoma of the Sinonasal Tract and the Pterygopalatine Fossa with or without Intracranial Extension.

Aims: Compared with those in other head and neck regions, schwannomas in the nasal cavity or paranasal sinuses are rare. The aim of this study was to present the experience of the authors in 11 schwannoma cases of the sinonasal tract and pterygopalatine fossa over a decade. Methods: A retrospective study from 2003 to 2014. Results: Three female and 8 male patients from 22 to 61 years of age (mean age 42 years) were admitted. The most common complaints were unilateral nasal congestion. A total of 10 of the patients received surgery, including 6 functional endoscopic sinus surgeries (FESS). The postoperative course was generally uneventful. Among the patients, 10 remained regionally asymptomatic, and there has been no clinical or radiological evidence of recurrence or residual tumor. Conclusion: Surgical treatment is effective for schwannomas of the sinonasal tract and the pterygopalatine fossa with a low recurrence rate. Conducting CT and MRI (particularly fluid-attenuated inversion recovery) before surgery is mandatory. FESS could become the primary treatment of choice.

Myosin light-chain kinase is necessary for membrane homeostasis in cochlear inner hair cells.

The structural homeostasis of the cochlear hair cell membrane is critical for all aspects of sensory transduction, but the regulation of its maintenance is not well understood. In this report, we analyzed the cochlear hair cells of mice with specific deletion of myosin light chain kinase (MLCK) in inner hair cells. MLCK-deficient mice showed impaired hearing, with a 5- to 14-dB rise in the auditory brainstem response (ABR) thresholds to clicks and tones of different frequencies and a significant decrease in the amplitude of the ABR waves. The mutant inner hair cells produced several ball-like structures around the hair bundles in vivo, indicating impaired membrane stability. Inner hair cells isolated from the knockout mice consistently displayed less resistance to hypoosmotic solution and less membrane F-actin. Myosin light-chain phosphorylation was also reduced in the mutated inner hair cells. Our results suggest that MLCK is necessary for maintaining the membrane stability of inner hair cells.

The role of FOXG1 in the postnatal development and survival of mouse cochlear hair cells

&NA; The development of therapeutic interventions for hearing loss requires a detailed understanding of the genes and proteins involved in hearing. The FOXG1 protein plays an important role in early neural development and in a variety of neurodevelopmental disorders. Previous studies have shown that there are severe deformities in the inner ear in Foxg1 knockout mice, but due to the postnatal lethality of Foxg1 knockout mice, the role of FOXG1 in hair cell (HC) development and survival during the postnatal period has not been investigated. In this study, we took advantage of transgenic mice that have a specific knockout of Foxg1 in HCs, thus allowing us to explore the role of FOXG1 in postnatal HC development and survival. In the Foxg1 conditional knockout (CKO) HCs, an extra row of HCs appeared in the apical turn of the cochlea and some parts of the middle turn at postnatal day (P)1 and P7; however, these HCs gradually underwent apoptosis, and the HC number was significantly decreased by P21. Auditory brainstem response tests showed that the Foxg1 CKO mice had lost their hearing by P30. The RNA‐Seq results and the qPCR verification both showed that the Wnt, Notch, IGF, EGF, and Hippo signaling pathways were down‐regulated in the HCs of Foxg1 CKO mice. The significant down‐regulation of the Notch signaling pathway might be the reason for the increased numbers of HCs in the cochleae of Foxg1 CKO mice at P1 and P7, while the down‐regulation of the Wnt, IGF, and EGF signaling pathways might lead to subsequent HC apoptosis. Together, these results indicate that knockout of Foxg1 induces an extra row of HCs via Notch signaling inhibition and induces subsequent apoptosis of these HCs by inhibiting the Wnt, IGF, and EGF signaling pathways. This study thus provides new evidence for the function and mechanism of FOXG1 in HC development and survival in mice. HIGHLIGHTSThe first study to conditionally knockout FoxG1 in hair cells that avoid the embryonic lethality of FoxG1 systemic knockout mice.The first study to assess the influence of FoxG1 knockout on hair cells survival in adult mice.The first study to analyse the molecular mechanism of FoxG1 regulation network in hair cells development and survival.

Loss of ARHGEF6 Causes Hair Cell Stereocilia Deficits and Hearing Loss in Mice

ARHGEF6 belongs to the family of guanine nucleotide exchange factors (GEFs) for Rho GTPases, and it specifically activates Rho GTPases CDC42 and RAC1. Arhgef6 is the X-linked intellectual disability gene also known as XLID46, and clinical features of patients carrying Arhgef6 mutations include intellectual disability and, in some cases, sensorineural hearing loss. Rho GTPases act as molecular switches in many cellular processes. Their activities are regulated by binding or hydrolysis of GTP, which is facilitated by GEFs and GTPase-activating proteins, respectively. RAC1 and CDC42 have been shown to play important roles in hair cell (HC) stereocilia development. However, the role of ARHGEF6 in inner ear development and hearing function has not yet been investigated. Here, we found that ARHGEF6 is expressed in mouse cochlear HCs, including the HC stereocilia. We established Arhgef6 knockdown mice using the clustered regularly interspaced short palindromic repeat-associated Cas9 nuclease (CRISPR-Cas9) genome editing technique. We showed that ARHGEF6 was indispensable for the maintenance of outer hair cell (OHC) stereocilia, and loss of ARHGEF6 in mice caused HC stereocilia deficits that eventually led to progressive HC loss and hearing loss. However, the loss of ARHGEF6 did not affect the synapse density and did not affect the mechanoelectrical transduction currents in OHCs at postnatal day 3. At the molecular level, the levels of active CDC42 and RAC1 were dramatically decreased in the Arhgef6 knockdown mice, suggesting that ARHGEF6 regulates stereocilia maintenance through RAC1/CDC42.

Prodigiosin Inhibits Proliferation, Migration, and Invasion of Nasopharyngeal Cancer Cells

Background/Aims: Nasopharyngeal carcinoma remains a devastating and difficult disease to treat. This study explores the antineoplastic effect of prodigiosin on nasopharyngeal cancer cells. Methods: Human nasopharyngeal carcinoma CNE2 cells and human normal nasopharyngeal epithelial NP69 cells were obtained and treated with prodigiosin or fluorouracil (5-FU). Colony formation assay was performed to screen for the optimal experimental concentrations of prodigiosin and 5-FU, and MTT assay was used to examine cell proliferative ability. Flow cytometry was used to examine cell cycle distribution, the scratch test was employed to examine cell migration, and Transwell migration assay (Boyden chamber) was used to study cell invasion. Results: The optimal concentrations of prodigiosin and 5-FU for treatment were 4 mg/L and 0.35 mg/L, respectively. Both prodigiosin and 5-FU inhibited tumor cell proliferation. The percentage of cells in G0/G1 phase was higher and the percentage of cells in S phase was lower in the prodigiosin and 5-FU groups than in the untreated groups. Both prodigiosin and 5-FU inhibited tumor cell migration and tumor cell invasion. Conclusions: Our results suggest that prodigiosin can inhibit proliferation, migration, and invasion of nasopharyngeal carcinoma cells.

A Cross-Sectional Study on the Hearing Threshold Levels Among People in Qinling, Qinghai, and Nanjing, China

Purpose This study aimed to investigate the hearing threshold among different age groups, genders, and geographic areas in China to provide some insight into the appropriate clinical interventions for hearing loss. Method Using a systematic random sampling technique, 562 participants from Qinling, Qinghai, and Nanjing were included. Participants in the same area were divided into 3 groups according to their age. Pure-tone audiometric thresholds were measured at octave and interoctave frequencies of 0.125-16 kHz for each subject. Results There were significant differences in auditory thresholds at nearly all frequencies among young, middle-aged, and elderly people, and hearing thresholds increased with increasing age. People generally had the best hearing ability in Nanjing, better hearing ability in Qinghai, and the worst hearing ability in Qinling. Significant differences in hearing thresholds were found between males and females at several frequencies in Qinling. Conclusion People living in the rural area of Qinling in China had higher hearing threshold levels, particularly males, and hearing thresholds increased with age.