Treatment of Meniere's disease with simultaneous triple semicircular canal occlusion and cochlear implantation.

OBJECTIVE: Report three cases of simultaneous triple semicircular canal occlusion (TSCO) and cochlear implantation (CI) as the treatment of intractable Meniere's disease (MD). CASE REPORTS: Patients with MD can present occasionally with intractable vertigo and profound sensorineural hearing loss (SNHL). TSCO and CI have been proposed to control vertigo and restore profound deafness in patients with MD separately. However, a few studies have reported simultaneous TSCO and CI in the same surgical procedure for the treatment of MD. In the present study, we described three patients with MD showing incapacitating vertigo and severe SNHL who underwent simultaneous TSCO and CI after examinations of auditory system, vestibular system, and imaging. Their symptoms were significantly alleviated during the follow-up period. CONCLUSION: The combined TSCO and CI remains a viable treatment option which is effective for the control of vertigo as well as the restoring of hearing in patients with MD.

Case Report: Suppurative Labyrinthitis Induced by Chronic Suppurative Otitis Media.

A discussion on suppurative labyrinthitis associated with chronic suppurative otitis media (CSOM) may seem to be an outdated issue due to the advent of antibiotics in the last century. In previous literature, limited cases of suppurative labyrinthitis have been reported. This case, therefore, is an excellent and rare opportunity to study its clinical symptoms, diagnoses, and treatments. This report described the case of a 39-year-old female with a history of CSOM for 20 years, and she often presented with otorrhea, vestibular disorder, and hearing impairment. CT of the temporal bone revealed fistulae in both the basal turn of the cochlea and the horizontal semicircular canal. Combined with the otolaryngology examination results, suppurative labyrinthitis was considered. During a three-month follow-up, her symptoms were improved significantly after surgery. In conclusion, suppurative labyrinthitis must not be overlooked and neglected; early diagnosis and treatments are of vital importance.

Effects of acoustic stimulation intensity on air-conducted vestibular evoked myogenic potential in children.

Objective: To investigate the effects of acoustic stimulation intensity on ocular and cervical vestibular evoked myogenic potential (oVEMP and cVEMP) responses elicited by air-conducted sound (ACS) in healthy children. Methods: Thirteen healthy children aged 4-10 years and 20 healthy adults aged 20-40 years with normal hearing and tympanometry were enrolled in this study. All subjects received oVEMP and cVEMP tests under different acoustic stimulation intensities (131, 126, 121, 116, 111 and 106 dB SPL). Mean n1 latency, p1 latency, interpeak latency, amplitude and response rate were investigated and analyzed. Results: As the acoustic stimulation intensity decreased, for oVEMP, the response rate of children decreased from 100% (131, 126 and 121 dB SPL) to 57.69% (116 dB SPL), 26.92% (111 dB SPL) and 11.54% (106 dB SPL). The response rate of adults decreased from 100% (131 and 126 dB SPL) to 95% (121 dB SPL), 55% (116 dB SPL), 12.5% (111 dB SPL) and 2.5% (106 dB SPL). There were lower n1 latency, p1 latency and higher amplitude in children when comparing by acoustic stimulation intensities (p < 0.05). Regarding cVEMP, the response rate of children decreased from 100% (131, 126 and 121 dB SPL) to 88.46% (116 dB SPL), 53.85% (111 dB SPL) and 26.92% (106 dB SPL). The response rate of adults decreased from 100% (131 and 126 dB SPL) to 95% (121 dB SPL), 85% (116 dB SPL), 37.5% (111 dB SPL) and 7.5% (106 dB SPL). A statistically significant difference was found in amplitude at different acoustic stimulation intensities in both children and adults (p < 0.05). When stimulated by 131 dB SPL acoustic stimulation, there were lower n1 latency, p1 latency and higher amplitude in children in oVEMP and cVEMP compared with adults (p < 0.05). Conclusion: The response rate and amplitude of oVEMP and cVEMP in children and adults presented significant differences with a decrease in acoustic stimulation intensity. In this study, using 121 dB SPL for children and 126 dB SPL for adults during VEMP test could be regarded as safer stimulation intensities and thus reduced sound exposure.

Vestibular dysfunction in pediatric patients with cochlear implantation: A systematic review and meta-analysis.

Objective: Vestibular dysfunction may delay the achievement of balance and perception milestones in pediatric patients after cochlear implantation (CIM). Methods: A strategic literature search was done following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Medline, Embase, Web of Science, and Cochrane Library databases from inception to July 2022. Studies were included on the otoliths, semicircular canals, and balance function changes in children after CIM. Two reviewers independently assessed the level of evidence, methodological limitations, risk of bias, and characteristics of the cases. Matched pre- and postoperative vestibular functional test data, including ocular and cervical vestibular-evoked myogenic potential (oVEMP and cVEMP), caloric test, video head impulse test (vHIT), and Bruininks-Oseretsky Test 2 (BOT-2), were used to calculate the relative risk of vestibular disorders. Subgroup analyses were performed according to surgical approach, CIM device status, and etiology. Results: Twenty studies that met the inclusion criteria were selected for the meta-analysis. We observed significant vestibular dysfunction in pediatric patients with CIM. The results showed a statistically significant increase in abnormal cVEMP response (RR = 2.20, 95% CI = 1.87, 2.58, P < 0.0001), abnormal oVEMP response (RR = 2.10, 95% CI = 1.50, 2.94, P < 0.0001), and abnormal caloric test results (RR = 1.62, 95% CI = 1.20, 2.19, P = 0.0018) after implantation. Statistically significant differences were not found in the vHIT test results of all three semicircular canals before and after the operation (P > 0.05). Regarding static and dynamic balance, we found significantly poorer BOT-2 scores in children with CIM than in the normal group (mean difference = -7.26, 95% CI = -10.82, -3.70, P < 0.0001). Conclusion: The results showed that vestibular dysfunction might occur after CIM in pediatric patients. Some children experience difficulties with postural control and balance. Our results suggest that a comprehensive evaluation of vestibular function should be performed before and after CIM.

[Progress of the diagnosis and treatment of congenital nasal dermoid sinus cysts].

Congenital midline nasal masses are rare. Nasal dermoid sinus cysts（NDSC） are the most common type of the congenital midline nasal masses in childhood. Clinical manifestations are midline nasal cysts, fistula and intracranial attachments. Nasal encephalocele and glioma should be included in the differential diagnosis. Radiologic images are instructive. NDSC are easily misdiagnosed, leading to recurrence and surgical trauma affecting the face. Early appropriate surgical excision is recommended. This article reviews the embryology pathogenesis, progress of diagnosis and treatment of congenital NDSC.

Connexin30-Deficiency Causes Mild Hearing Loss With the Reduction of Endocochlear Potential and ATP Release.

GJB2 and GJB6 are adjacent genes encoding connexin 26 (Cx26) and connexin 30 (Cx30), respectively, with overlapping expressions in the inner ear. Both genes are associated with the commonest monogenic hearing disorder, recessive isolated deafness DFNB1. Cx26 plays an important role in auditory development, while the role of Cx30 in hearing remains controversial. Previous studies found that Cx30 knockout mice had severe hearing loss along with a 90% reduction in Cx26, while another Cx30 knockout mouse model showed normal hearing with nearly half of Cx26 preserved. In this study, we used CRISPR/Cas9 technology to establish a new Cx30 knockout mouse model (Cx30-/-), which preserves approximately 70% of Cx26. We found that the 1, 3, and 6-month-old Cx30-/- mice showed mild hearing loss at full frequency. Immunofluorescence and HE staining suggested no significant differences in microstructure of the cochlea between Cx30-/- mice and wild-type mice. However, transmission electron microscopy showed slight cavity-like damage in the stria vascularis of Cx30-/- mice. And Cx30 deficiency reduced the production of endocochlear potential (EP) and the release of ATP, which may have induced hearing loss. Taken together, this study showed that lack of Cx30 can lead to hearing loss with an approximately 30% reduction of Cx26 in the present Cx30 knockout model. Hence, Cx30 may play an important rather than redundant role in hearing development.

Gene expression differences between thyroid carcinoma, thyroid adenoma and normal thyroid tissue.

To identify differences in gene expression profiles of infected cells between thyroid carcinoma (C), thyroid adenoma (A) and normal thyroid (N) epithelial cells, differentially expressed genes were identified using three pairwise comparisons with the GEO2R online tool. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to classify them at the functional level. The most significant cluster in the N vs. A pairwise comparison had four hub genes: Insulin-like growth factor 2, Von Willebrand factor (VWF), multimerin 1 (MMRN1) and complement factor D (CFD). In N vs. C, the most significant cluster had 19 genes: IGF2, early growth response 2, transcription factor 3, KIT proto­oncogene receptor tyrosine kinase, SMAD family member 9, MLLT3 super elongation complex subunit, runt related transcription factor 1, CFD, actinin α 1, SWI/SNF related matrix associated actin dependent regulator of chromatin subfamily a member 4, JunD proto­oncogene AP­1 transcription factor subunit, serum response factor (SRF), FosB proto­oncogene, AP­1 transcription factor subunit, connective tissue growth factor (CTGF), SRC proto­oncogene, non­receptor tyrosine kinase, MMRN1, SRY­box 9, early growth response 3 and ETS variant 4. In A vs. C, the most significant cluster had 14 genes: BCL2-like 1, galectin 3, MCL1 BCL2 family apoptosis regulator, DNA damage inducible transcript 3, BCL2 apoptosis regulator, CTGF, matrix metallopeptidase 7, early growth response 1, kinase insert domain receptor, TIMP metallopeptidase inhibitor 1, apolipoprotein E, VWF, cyclin D1 and placental growth factor. Histological evidence was presented to confirm the makeup of the hubs prior to logistic regression analysis to differentiate benign and malignant neoplasms. The results of the present study may aid in the search for novel potential biomarkers for the differential diagnosis, prognosis and development of drug targets of thyroid neoplasm.

The role of Efr3a in age-related hearing loss.

Efr3a has been found to be involved in the functional maintenance and structural degeneration of sensory and motor nervous tissues. Our previous data have suggested that Efr3a may be associated with the initiation of the degeneration of spiral ganglion neurons (SGNs). In this study, we used Efr3a knockdown (Efr3a KD) and Efr3a overexpression (Efr3a OE) mice to determine the role of Efr3a in age-related hearing loss. Measurements of hearing thresholds showed that Efr3a had little or no influence on the hearing threshold at all frequencies in adult mice, whereas in an early stage of senescence, Efr3a reduction resulted in better hearing function, especially at 10 and 12months of age. No significant differences were observed in hair cell loss among the three groups until 14months. The number of surviving hair cells in the OE mice was lower than that in the KD mice. As indicated by the density of SGNs in the upper basal turn, the Efr3a OE mice displayed earlier and more severe degeneration than the KD mice. In addition, the p-Akt levels in the cochlear spiral ganglions were higher in adult Efr3a KD mice than in WT and OE mice, although there was no difference in Akt expression among the three groups. Our study suggests that down-regulation of Efr3a might improve hearing function and alleviate the degeneration of SGNs in an early stage of senescence, probably via enhancing the basal expression of activated Akt.

Lentivirus-mediated RNA interference inhibits the tumorigenicity of cluster of differentiation 44+ tumor cells in hypopharyngeal cancer.

The present study aimed to investigate whether the inhibition of cluster of differentiation (CD)44 expression reduces the tumorigenicity of CD44+ cancer stem cells in hypopharyngeal cancer. To assess this, effective recombinant CD44 short hairpin RNA-expressing lentiviruses were produced. Lentivirus-mediated RNA interference (RNAi) was then used to knockdown CD44 gene expression in the hypopharyngeal cancer FaDu cell line. The viability of FaDu cells in the two control groups and the RNAi group (RNAi-CD44 lentiviral vector) was detected using an MTT assay in vitro. Cells from each group were injected into non-obese diabetic/severe combined immunodeficiency mice and their tumorigenicity determined in vivo. Following lentivirus-mediated RNAi, an MTT assay indicated that cells from the RNAi group exhibited lower viability than the control group. The in vivo tumorigenicity study further revealed a significant difference in tumorigenic rates between the RNAi group and the control group (Fisher's exact test, P<0.05). In addition, tumors in the RNAi group of animals had a longer incubation period than those in the control groups, and the mean tumor volume was also significantly smaller (t=3.47, P<0.05). Pathological study confirmed that all tumors were poorly differentiated squamous cell carcinomas with cellular heterogeneity. The viability of the hypopharyngeal cancer FaDu cells in vitro and their tumorigenicity in vivo were markedly inhibited once CD44 was knocked down. The results of the present study therefore suggest that CD44 may confer tumorigenic characteristics upon CD44+ cancer stem cells in hypopharyngeal cancer.

Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after Hair Cell Loss.

Sensorineural hearing loss (SNHL) is caused by an irreversible impairment of cochlear hair cells and subsequent progressive degeneration of spiral ganglion neurons (SGNs). Eighty-five requiring 3 (Efr3) is a plasma membrane protein conserved from yeast to human, and knockout of Efr3a was reported to facilitate the survival of hippocampal newborn neurons in adult mice. Previously, we found Efr3a expression in the auditory neural pathway is upregulated soon after the destruction of hair cells. Here we conducted a time-course analysis of drug-caused damage to hearing ability, hair cells and SGNs in Efr3a knocking down mice (Efr3a-/+, Efr3a KD) and their wild type littermates. Functional examination showed that both groups of mice suffered from serious hearing loss with a higher level of severity in wild type (WT) mice. Morphologic observation following drugs administration showed that both WT and Efr3a KD mice went through progressive loss of hair cells and SGNs, in association with degenerative changes in the perikarya, intracellular organelles, cell body conformation in SGNs, and the changes of SGNs in WT mice were more severe than in Efr3a KD mice. These beneficial effects of Efr3a KD could be ascribed to an increase in the expression of some neurotrophic factors and their receptors in Efr3a KD mice. Our results indicate that Efr3a insufficiency suppresses drug-caused SNHL neurodegeneration in association with an increase in the expression of some neurotrophic factors and their receptors, which may be targeted in the treatment of neurodegeneration.

Effects of long-term salicylate administration on synaptic ultrastructure and metabolic activity in the rat CNS.

Tinnitus is associated with neural hyperactivity in the central nervous system (CNS). Salicylate is a well-known ototoxic drug, and we induced tinnitus in rats using a model of long-term salicylate administration. The gap pre-pulse inhibition of acoustic startle test was used to infer tinnitus perception, and only rats in the chronic salicylate-treatment (14 days) group showed evidence of experiencing tinnitus. After small animal positron emission tomography scans were performed, we found that the metabolic activity of the inferior colliculus (IC), the auditory cortex (AC), and the hippocampus (HP) were significantly higher in the chronic treatment group compared with saline group (treated for 14 days), which was further supported by ultrastructural changes at the synapses. The alterations all returned to baseline 14 days after the cessation of salicylate-treatment (wash-out group), indicating that these changes were reversible. These findings indicate that long-term salicylate administration induces tinnitus, enhanced neural activity and synaptic ultrastructural changes in the IC, AC, and HP of rats due to neuroplasticity. Thus, an increased metabolic rate and synaptic transmission in specific areas of the CNS may contribute to the development of tinnitus.

[Surgical management for severe congenital laryngomalacia: 16 consecutive cases].

OBJECTIVE: Laryngomalacia is the most common cause for stridor in neonate and infant. Our study aims at assessing the outcome of surgical management in patients diagnosed by fibrolaryngoscope as congenital Laryngomalacia. METHOD: Retrospective study of 16 patients undergoing surgery for severe laryngomalacia. The patients' symptoms, associated medical conditions and surgical management were recorded. RESULT: Stridor and feeding difficulty were observed in 16 patients on admission, while dyspnea was found in 11 patients. Medical co-morbidities exist in 14 cases. The mean age of surgery was 23 weeks, 15 patients had follow-up records for 24 months. Fourteen cases underwent supraglortoplasty. Tracheotomy was performed on the other 2 cases complicated with tracheomalacia. Nine cases showed full recovery of stridor 48 hours post-supraglottoplasty, and 7 were free of feeding difficulties. In the 6 months follow-up, complete or partial relief was achieved in all main symptoms and signs. CONCLUSION: Supraglottoplasty is effective in relieving stridor and feeding difficulty as well as respiratory insufficiency, which makes it a first line option for managing severe laryngomalacia.

[Cochlear implants for the patients with cochlear nerve defects].

OBJECTIVE: By watching the effects of cochlear implants in the children with cochlear nerve defects, to evaluate the relationship and efficiency of HRCT AND MRI in diagnostic for cochlear nerve defects. METHOD: The imaging dates and the post-operative effects of the 10 cochlear nerve defect patients were retrospectively analyzed. RESULT: Three patients with bilateral IAC stenosis by HRCT and cochlear nerve defects by MRI but no other abnormal. Seven other patients showed normal IAC by HRCT including 1 showed type IP- I plus vestibular semi circular canal dysplasia. These 7 patients MRI showed 3 bilateral cochlear nerve absent and 4 bilateral cochlear nerve dysplasia. Ten cases of children after 12-32 month follow-up, 3 patients began speaking simple language, whose MAIS scale, CAP and SIR scores improved. One case just began speaking but pronunciation vague. Four cases had reactions to sounds, and can say monosyllabic words. Two cases without effects (1 CI abolished). Compared with other patients with normal cochlear nerve, the effects of the 10 cases were disappointed. CONCLUSION: The effects of cochlear implant for the patients with cochlear nerve defects were poor. The preoperative MRI as sessment including oblique sagittal view for cochlear nerve is necessary. The preoperative communication with the parents telling ineffective result possibility is important.

[Th1/Th2 cytokines and its clinical significance in obstructive sleep apnea hypopnea syndrome children without allergic rhinitis and asthma].

OBJECTIVE: To analyze Th1 and Th2 immune balance related cytokines and clinical significance in obstructive sleep apnea hypopnea syndrome children without allergic rhinitis and asthma. METHOD: Collected 91 cases of obstructive sleep apnea hypopnea syndrome children with obstructive level data, and measured the serum Th1 cytokine TNF-beta and IFN-gamma, Th2 cytokines IL-4 and IL-5 levels. One hundred and five normal children were enrolled for the same detection of serum cytokines. RESULT: Non-allergic rhinitis and asthma children serum levels of IFN-gamma was lower than control group children, the difference was statistically significant (P < 0. 01). Other cytokines (TNF-beta, IL-4 and IL-5) were no significant difference with the control group. CONCLUSION: Th1 and Th2 immune response was imbalance in non-allergic rhinitis and asthma obstructive sleep apnea hypopnea syndrome children. The decline in Th1 cell-mediated protective immune response cells may cause disease.