[Clinical diagnosis and treatment analysis of spontaneous cerebrospinal fluid otorrhoea].

Objective:To investigate the clinical features, imaging findings, surgical methods， diagnostic and treatment experience of spontaneous cerebrospinal fluid otorrhoea. Methods:The clinical data of 11 patients with spontaneous cerebrospinal fluid otorrhoea treated surgically at our hospital from May 2018 to May 2023 were retrospectively analyzed. The medical data included medical history, imaging data, leak location, surgical repair method, treatment effect and postoperative follow-up. Results:Among the 11 surgical patients, 4 patients were initially diagnosed with secretory otitis media, 1 was initially diagnosed with purulent otitis media, and 5 patients had a history of meningitis or presented because meningitis as the initial diagnosis. There were 2 cases of cerebrospinal fluid leakage repaired through the ear canal pathway and 9 cases of cerebrospinal fluid leakage repaired through the mastoid pathway. During the operation, leaks were located in the stapes floor plate in 4 cases, sinus meningeal angle in 1 case, posterior cranial fossa combined with middle cranial fossa in 1 case, middle cranial fossa in 4 cases, and labyrinthine segment of the internal auditory canal and facial nerve canal in 1 case. Ten patient was successfully repaired, and another patient developed intracranial hypertension after surgery, with symptoms alleviated by a lateral ventriculoperitoneal shunt. Postoperative follow-up ranged from 6 months to 4 years, and there was no CSF otorrhoea and meningitis recurrence. Conclusion:The incidence of spontaneous cerebrospinal fluid otorrhea is low, the clinical symptoms are atypical, and the rate of delayed diagnosis or missed diagnosis and misdiagnosis is high. Surgery is currently the preferred treatment for spontaneous cerebrospinal fluid otorrhoea, and satisfactory results are usually achieved; During diagnosis and treatment, it is crucial to be vigilant for intracranial hypertension to prevent serious complications and irreversible damage.

[Application of intraoperative CT-assisted positioning in difficult cases of cochlear implantation].

Objective:To report the experience of using CT-guided cochlear implant surgery in difficult cases such as severe inner ear deformities and anatomical abnormalities, and to discuss the application value of intraoperative CT-assisted localization in difficult cases of cochlear implant surgery. Methods:Retrospectively analyzed the clinical data of 23 cases of difficult cochlear implant surgery cases completed by our team with the assistance of intraoperative CT, and collected their medical data, including preoperative imaging manifestations, surgical conditions, and intraoperative imaging images for evaluation. Results:During the study period, 23 difficult cases（27 ears） underwent cochlear implantation under the guidance of intraoperative CT, and 4 cases were bilaterally implanted. Including 6 cases of incomplete segmentation type Ⅰ（IP-Ⅰ）, 1 case of incomplete segmentation type Ⅱ（IP-Ⅱ）, 10 cases of incomplete segmentation type Ⅲ（IP-Ⅲ）, 3 cases of common cavity deformity（CC） and 3 cases of cochlear ossification after meningitis. Facial nerve anatomy was abnormal in 9 cases, cerebrospinal fluid "blowout" was serious in 14 cases, electrode position was abnormal in 3 cases requiring intraoperative adjustment of electrode position, anatomical difficulties required intraoperative CT to assist in finding anatomical landmarks in 2 cases, and electrodes were not fully implanted in 3 cases. Conclusion:When faced with difficult cases with challenging and complex temporal bone anatomy, intraoperative CT can accurately evaluate the electrode position and provide intraoperative anatomical details, allowing immediate adjustment of the electrode position if necessary, providing safety guarantee for difficult cases of cochlear implant surgery and ensure accurate implantation of electrodes.

N-6 methylation-related lncRNA is potential signature in lung adenocarcinoma and influences tumor microenvironment.

BACKGROUND: N-6 methylation (m6A) pushes forward an immense influence on the occurrence and development of lung adenocarcinoma (LUAD). However, the methylation on non-coding RNA in LUAD, especially long non-coding RNA (lncRNA), has not been received sufficient attention. METHODS: Spearman correlation analysis was used to screen lncRNA correlated with m6A regulators expression from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories, respectively. Then, the least absolute shrinkage and selection operator (LASSO) was applied to build a risk signature consisting m6A-related lncRNA. Univariate and multivariate independent prognostic analysis were applied to evaluate the performance of signature in predicting patients' survival. Next, we applied Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) to conduct pathway enrichment analysis of 3344 different expression genes (DEGs). Finally, we set up a competing endogenous RNAs (ceRNA) network to this lncRNA. RESULTS: A total of 85 common lncRNAs were selected to acquire the components related to prognosis. The final risk signature established by LASSO regression contained 11 lncRNAs: ARHGEF26-AS1, COLCA1, CRNDE, DLGAP1-AS2, FENDRR, LINC00968, TMPO-AS1, TRG-AS1, MGC32805, RPARP-AS1, and TBX5-AS1. M6A-related lncRNA risk score could predict the prognostic of LUAD and was significantly associated with clinical pathological. And in the evaluation of lung adenocarcinoma tumor microenvironment (TME) by using ESTIMATE algorithm, we found a statistically significant correlation between risk score and stromal/immune cells. CONCLUSION: M6A-related lncRNA was a potential prognostic and therapy target for lung adenocarcinoma.

LncRNA PVT1 promotes malignant progression in squamous cell carcinoma of the head and neck.

Long non-coding RNAs (lncRNAs) are potentially critical regulators of cancer malignant behaviours. Aberrant expression and dysfunction of lncRNA PVT1 have been reported in multiple human cancers. However, its role in squamous cell carcinoma of the head and neck (SCCHN) remains largely unknown. Our current study demonstrated that PVT1 expression was increased in SCCHN. High PVT1 expression was positively correlated with SCCHN clinical parameters including T classification, clinical stages and cervical lymph node metastasis. More importantly, high PVT1 expression predicted a poor prognosis in SCCHN patients. Gain-of function and loss-of function studies further indicated that PVT1 promoted the proliferation and invasion of SCCHN both in vitro and in vivo, which was accompanied by epithelial-mesenchymal transition and enhanced cancer stem cell-like properties. Further mechanistic investigation revealed that PVT1 activated Wnt/ß-catenin signalling pathway, and inhibition of Wnt/ß-catenin signalling reversed the malignant progression caused by PVT1 overexpression. Together, our study reveals that PVT1 accelerates the malignant progression of SCCHN and represents a potential biomarker and therapeutic target in SCCHN.

Auditory and language development in Mandarin-speaking children after cochlear implantation.

OBJECTIVE: To evaluate early auditory performance, speech perception and language skills in Mandarin-speaking prelingual deaf children in the first two years after they received a cochlear implant (CI) and analyse the effects of possible associated factors. METHODS: The Infant-Toddler Meaningful Auditory Integration Scale (ITMAIS)/Meaningful Auditory Integration Scale (MAIS), Mandarin Early Speech Perception (MESP) test and Putonghua Communicative Development Inventory (PCDI) were used to assess auditory and language outcomes in 132 Mandarin-speaking children pre- and post-implantation. RESULTS: Children with CIs exhibited an ITMAIS/MAIS and PCDI developmental trajectory similar to that of children with normal hearing. The increased number of participants who achieved MESP categories 1-6 at each test interval showed a significant improvement in speech perception by paediatric CI recipients. Age at implantation and socioeconomic status were consistently associated with both auditory and language outcomes in the first two years post-implantation. CONCLUSION: Mandarin-speaking children with CIs exhibit significant improvements in early auditory and language development. Though these improvements followed the normative developmental trajectories, they still exhibited a gap compared with normative values. Earlier implantation and higher socioeconomic status are consistent predictors of greater auditory and language skills in the early stage.

Metadherin contributes to epithelial-mesenchymal transition and paclitaxel resistance induced by acidic extracellular pH in nasopharyngeal carcinoma.

Paclitaxel resistance is a challenge to the treatment of nasopharyngeal carcinoma (NPC). An acidic extracellular pH (pHe), a hallmark of solid tumors, is demonstrated to decrease the efficacy of chemotherapy. However, the precise function of acidic pHe in mediating chemotherapy in NPC remains unknown. In the present study, acidic pHe significantly decreased the cytotoxicity of paclitaxel in NPC cells. In addition, epithelial-mesenchymal transition (EMT)-like changes were observed in NPC cells cultured at acidic pHe. Metadherin (MTDH), a novel oncogene, is expressed in multiple types of solid tumor, and is associated with several malignant cell characteristics, including malignant cell transformation, proliferation, angiogenesis, chemoresistance, invasion and metastasis. In the present study, MTDH expression was increased in NPC cells that had been cultured at an acidic pHe. Furthermore, the silencing of MTDH expression reversed EMT molecular marker expression and sensitized NPC cells to paclitaxel. Taken together, the results of the present study provide evidence to support an association between acidic pHe-induced paclitaxel resistance and MTDH-mediated EMT in NPC cells. Thus, targeting MTDH may provide a novel strategy for overcoming chemoresistance in NPC therapy.

Macrophage migration inhibitory factor knockdown inhibit viability and induce apoptosis of PVM/Ms.

Previous studies have suggested that macrophage migration inhibitory factor (MIF) serves an important role in hearing function; however, the underlying mechanism remains unclear. In the present study, perivascular­resident macrophage­like melanocytes (PVM/Ms) from the stria vascularis of the lateral cochlear wall in young and aged mice were isolated. The mRNA and protein expression levels of MIF were determined using reverse transcription­quantitative polymerase chain reaction analysis, and western blotting, respectively. MIF expression was knocked down in vitro and in vivo using small interfering RNA. Cell viability was determined using an MTT assay and cell apoptosis was determined using flow cytometry analysis. The hearing ability was assessed through the auditory brain stem response in vivo. The results of the current study demonstrated that the expression of MIF was significantly downregulated in aged mice compared with in young mice. Furthermore, the viability of PVM/Ms in aged mice was significantly decreased and the number of apoptotic PVM/Ms was significantly increased compared with that in young mice. Further studies demonstrated that the MIF knockdown accentuated hearing loss in young mice as compared with the scramble control group. In addition, the MIF knockdown in PVM/Ms significantly inhibited cell viability and lead to a significant increase in the apoptotic cell number as compared with the control group. In summary, these results revealed that the MIF knockdown significantly accentuates hearing loss in young mice in vivo, and significantly inhibits the viability and induces the apoptosis of PVM/Ms in vitro. Thus, the results of the present study may provide a novel potential therapeutic approach and prevention method for presbycusis.

Macrophage migration inhibitory factor mediates viability and apoptosis of PVM/Ms through PI3K/Akt pathway.

Macrophage migration inhibitory factor (MIF) plays an important role in hearing function; however, the underlying mechanism remains indistinct. PVM/Ms from the stria vascularis of lateral wall of cochlea in young and aged mice were isolated, and the mRNA and protein expression levels were detected. MIF was knocked down or overexpresssed in vitro, and transfection was performed in vivo. Cell viability and apoptosis were determined by MTT assay and flow cytometry analysis, respectively. The hearing ability was tested by the auditory brain stem response. The results showed that MIF expression was significantly downregulated in aged mice. In aged mice, the viability of PVM/Ms significantly decreased, but the apoptotic number markedly increased. MIF knockdown in PVM/Ms in vitro significantly inhibited cell viability and induced cell apoptosis, but MIF overexpression showed contrasting results. Further studies showed that MIF knockdown in young mice resulted in serious hearing loss, but MIF overexpression in aged mice restored the hearing. Si-MIF inhibited the viability and induced apoptosis of PVM/Ms from young mice, whereas Ad-MIF induced the viability and inhibited apoptosis of PVM/Ms from aged mice. Moreover, MIF effectively altered the expression levels of CDK1, BRAF, p-ERK1/2, p-PI3K, and p-Akt. Furthermore, ERK inhibitor PD98059 or PI3K inhibitor LY294002 significantly reversed the effects of Si-MIF on PVM/Ms from young mice, whereas ERK activator EGF or PI3K activator IGF significantly reversed the effects of Ad-MIF on PVM/Ms from aged mice. Taken together, MIF mediates the viability and apoptosis of PVM/Ms, at least partially, through MAPK and/or PI3K/Akt pathway.

Cochlear Size and Shape Variability and Implications in Cochlear Implantation Surgery.

HYPOTHESIS: To study variations in cochlear size and shape with potential implications for cochlear implants. BACKGROUND: A comprehension of the cochlear morphology is essential for nontraumatic electrode insertion and hearing preservation in individual surgery. METHODS: A total of 310 normal developed cochleae with three-dimensional multiplanar reconstructed computed tomography images were studied. We measured the linear length of the half (1/2TL) and three quarters (3/4TL) of the basal turn, the first turn (1TL), the first two turns (2TL), and the cochlear length. The length and width of the cochlear base as well as the tilt angle within the first turn (α) and the angle between the first and second turns (γ) of the cochlea were also measured. RESULTS: The measurement results showed that cochlear size and shape vary greatly among individuals. The length and width of cochlear base had positive correlations with 1/2TL (r = 0.526 and r = 0.625), 3/4TL (r = 0.633 and r = 0.729), 1TL (r = 0.658 and r = 0.754), 2TL (r = 0.677 and r = 0.795) and cochlear length (r = 0.622 and r = 0.769) respectively. The mean tilt angle α was 9.72 ±â€Š1.85 degrees while the angle γ was 14.90 ±â€Š1.36 degrees, and both had significant positive correlations with the ratio of length to width of cochlear base (p = 0.040 and p = 0.013). CONCLUSION: The significant variations of the cochlear anatomy suggest that personalized cochlear implant is needed. The width of cochlear base has a stronger association with the linear length of cochlea. And the angle within the first turn and between the first and second turns can be predicted by the ratio of length to width of cochlear base.

MicroRNA-21 promotes the proliferation and invasion of cholesteatoma keratinocytes.

CONCLUSIONS: The present study revealed that miR-21 promotes the proliferation and invasion of cholesteatoma keratinocytes. These results provide a partial explanation for the more aggressive clinical behavior observed in cholesteatoma. OBJECTIVE: This study aims to investigate the post-transcriptional regulatory effects that control proliferation, apoptosis, and invasion in cholesteatoma keratinocytes. In particular, the potential role of miR-21 was focused on in this study. METHODS: Thirty cholesteatoma tissues were processed for RNA and cell culture. Cholesteatoma keratinocytes were transfected with miR-21 mimics, miR-21 inhibitors, or negative control miRNAs; and growth curves were drawn. RT-PCR was used to assess the expression levels of miR-21. EdU incorporation assay and TUNEL staining were used to assess the proliferation and apoptosis of cholesteatoma keratinocytes, respectively. The invasive abilities of cholesteatoma keratinocytes were examined using 6-well Transwell plates. RESULTS: MiRNA-21 was upregulated when cholesteatoma keratinocytes were transfected with miR-21 mimics. Furthermore, the number of proliferative EdU + cells increased in cholesteatoma keratinocytes transfected with miR-21 mimics; and the number of TUNEL-positive cells also increased in cells transfected with miR-21 mimics. In addition, the number of migrated cells transfected with miR-21 mimics was higher, compared with migrated cells transfected miR-21 inhibitors or control miRNA.

Influence of cochlear implantation on vestibular function.

Conclusion Vestibular function in patients can be damaged following cochlear implantation. Therefore, assessing the pre-operative vestibular status, carefully choosing the side of implantation, and preserving function by using minimally invasive surgical techniques are important. Objectives The aim of this study was to assess the influence of cochlear implantation on vestibular function in patients with severe and profound sensorineural hearing loss, and to analyze a possible correlation between the changes in vestibular testing and post-operative vestibular symptoms. Methods Thirty-four patients were evaluated for vestibular function using the cervical and ocular vestibular-evoked myogenic potentials (cVEMP and oVEMP, respectively), and 29 patients underwent caloric tests pre-operatively and 4 weeks post-operatively. Results Before surgery, the cVEMPs were recorded bilaterally in 22 patients, unilaterally in eight patients, and absent bilaterally in four patients. The oVEMPs were recorded bilaterally in 19 patients, unilaterally in six patients, and absent bilaterally in nine patients. After implantation, the cVEMPs were absent in 10 patients and the oVEMPs were absent in seven patients on the implanted side. Caloric tests demonstrated canal paresis in 17 patients, and normal responses were recorded in 12 of the 29 patients pre-operatively. There was a significant decrease post-implantation in the ear implanted, with the exception of two patients. Two patients presented with vertigo and another two patients reported slight unsteadiness post-operatively, but all symptoms resolved within 7 days. The impaired vestibular function did not correlate with vestibular symptoms, age, or gender. Function on the contralateral side remained unaffected.

Revision surgery for canal wall down mastoidectomy: intra-operative findings and results.

CONCLUSION: Canal wall down mastoid surgery following multiple earlier surgical failures can be revised by a well-trained experienced surgeon. A dry and safe ear is obtainable in most patients, and hearing preservation is also possible. OBJECTIVES: To analyze the intra-operative findings in revision surgery for canal wall down (CWD) mastoidectomy and to ascertain the prognosis. METHODS: A total of 76 revision mastoidectomies with tympanoplasties performed from March 2008 to May 2014 at the First Affiliated Hospital of Zhengzhou University in China were reviewed. The pre-operative, intra-operative, and post-operative data was recorded and analyzed. RESULTS: The possible reason of previous surgical failures were confirmed by the operative findings, which included inadequate mastoidectomy or persistent air-cell disease (66/76 [86.8%]), recurrent or persistent cholesteatoma (44/76 [57.9%]), excessive opened cavity combined with complications (9/76 [11.8%]), and infected cavities (68/76 [89.5%]). In this study, disease control was achieved in 70 (92.1%) patients. Complications following previous surgery were modified by revision surgery. Hearing was significantly improved in the 54 cases with ossicular replacement prosthesis. After a mean follow-up of 22 months, the group of revision surgery with ossiculoplasty as a whole experienced a statistically significant hearing gain of 16.57 ± 11.96 dB (p < 0.05) at air conduction pure tone average (PTA).

[Analyses prognostic factors relevant to sudden sensorineural hearing loss].

OBJECTIVE: To investigate the prognostic factors relevant to sudden sensorineural hearing loss. METHODS: The internationally accepted standardized clinical research methods, unified design, and unified program were adopted to conduct the prospective clinical multi-center study. The sudden deafness patients between 18 to 65 years old, with the course of this disorder less than two weeks, and without any medical treatments were collected, and then, divided into four types according to the hearing curve: type A, acute sensorineural hearing loss in low tone frequencies; type B, acute sensorineural hearing loss in high tone frequencies; type C, acute sensorineural hearing loss in all frequencies; and type D, total deafness. The factors, in terms of age, gender, type of initial audiogram, time delay before the first visit, and severity of hearing loss, were included in the analyses. RESULTS: A total of 1 024 cases with single side sudden deafness were collected in the study from 33 hospitals in China from August 2007 to October 2011, inclusive of for 492 males (48.05%) and 532 females (51.95%). The average age was (41.2 ± 12.8) years old. There were 553 cases (54.00%) in left ear, and 471 cases (46.00%) in right ear. The curative effects of different types were shown as follows: the type in low tone frequencies had the highest rate of 90.73%, the type in all frequencies was 82.59%; the type of total deafness was 70.29%; and the type in high tone frequencies had the lowest rate of 65.96%. It had significant difference of the effective rate between different types (χ(2) = 231.58, P = 0.000). Age, time delay before first visit, and severity of initial hearing loss were significantly correlated with hearing improvement. CONCLUSIONS: Initial audiogram of SSNHL might predict hearing recovery. The young in age and a short time delay before starting treatment are positive prognostic factors for hearing recovery in SSNHL. The initial severity of hearing loss is negative prognostic factor of hearing recovery.

MicroRNA let-7a suppresses the growth and invasion of cholesteatoma keratinocytes.

Cholesteatomas are benign epidermally­derived lesions of the temporal bone that are caused by migration of hyperproliferative keratinocytes into the middle ear and mastoid cavity. The molecular mechanisms that regulate the pathogenesis of cholesteatomas are currently not fully understood. The present study demonstrated the antigrowth and anti­invasive effects of let­7a microRNA (miRNA) on cholesteatoma keratinocytes. Let­7a inhibited the growth of cholesteatoma keratinocytes through two different mechanisms: Restriction of the proliferation of keratinocytes by promoting cell cycle arrest in the G0/G1 phase, and the induction of apoptosis of the cells. In addition to its role in the inhibition of cell growth, let­7a suppressed the migration and invasion of cholesteatoma keratinocytes. A mechanistic study showed that let­7a downregulated the expression of miR­21. Considering the function of miR­21 in the regulation of proliferation and apoptosis, let­7a may control cell proliferation and apoptosis by regulating miR­21, and its targets, in cholesteatoma keratinocytes. In conclusion, the present study showed that let­7a downregulates the expression of miR­21, resulting in the suppression of proliferation and induction of apoptosis. The results of the present study reveal the crucial role of let­7a miRNA in the inhibition of growth and invasion of cholesteatoma keratinocytes.

Molecular analysis of hair cells in sensorineural hearing loss.

PURPOSE: Since the completion of the human genome project, the exploration of the molecular basis of sensorineural hearing loss has been an area of intensive research. In this review, we attempt to summarize the knowledge on genes or proteins in hair cells related to sensorineural hearing loss. Investigating expression and function of these genes will help us to understand the molecular mechanisms of deafness. FINDINGS: There are about 70-100 genetic loci which are related to deafness. Some of them are signal proteins while others are membrane proteins. Some of them can deter hair cell development or accelerate aging. CONCLUSION: Most of these genes and proteins are related to signal transduction pathways. These gens are located in the outer hair cells, which is the site for receiving sound.

Early complications following cochlear implantation in children and their management.

OBJECTIVES: To report the early postoperative complications of cochlear implantation (CI) in the pediatric population and discuss the intervention measures. METHODS: We retrospectively analyzed 260 consecutive pediatric cochlear implantations performed at the First Affiliated Hospital of Zhengzhou University between March 2010 and July 2013. All patients were younger than 12 years old at the time of implantation, with a mean age of 4.3 years, and 47 cases had inner ear malformations. Complications correlated to age at CI and inner ear malformations were analyzed using the χ(2) test. RESULTS: Of the 260 patients, early postoperative complications were observed in 17 (6.54%) cases, of which 16 (6.15%) were minor and one (0.38%) was major, none required surgical device removal or reimplantation. Among the 16 minor complications, transient vertigo was the most common (nine cases, 3.46%), three (1.15%) of them with severe CSF gusher during the surgery; followed by transient facial nerve palsy (two cases, 0.77%, both were reversible); external auditory canal injury, subcutaneous hematoma each in two cases (0.77%), and minor dural injury in one case (0.38%). One major complication included an epidural hematoma in a 7-year-old boy who recovered completely without any neurologic deficits following immediate evacuation. Inner ear malformations were significantly associated with the surgical complications, especially vertigo and gusher (P<0.05). CONCLUSIONS: Cochlear implantation in children is fairly a safe procedure with a relatively low complication rate. The most common early postoperative complications are minor, but serious and life threatening complications rarely may occur. Awareness of complications helps clinicians to adopt the specific preventive measures and immediate interventions so that the outcome will be successful.

Inflammation-induced miR-802 promotes cell proliferation in cholesteatoma.

Cholesteatoma is a destructive and abnormal skin growth consisting of keratinizing squamous epithelium in the middle ear. Its molecular mechanisms remain poorly understood. Here, we found that the NF-κB inflammatory signaling pathway was highly activated in cholesteatoma. NF-κB activation increased the expression of microRNA-802 (miR-802) and chromatin immunoprecipitation assays showed that P65 could uniquely bind to miR-802 promoter. miR-802 overexpression promoted keratinocyte cell proliferation and cell cycle progression, while inhibition of miR-802 decreased these effects. From computational analysis and luciferase report assays, miR-802 directly repressed PTEN expression by targeting its 3'-UTR. Our results demonstrate that the NF-κb/miR-802/PTEN signaling pathway plays an important role in the development of cholesteatoma.

Measurement of conductive hearing loss in mice.

In order to discriminate conductive hearing loss from sensorineural impairment, quantitative measurements were used to evaluate the effect of artificial conductive pathology on distortion-product otoacoustic emissions (DPOAEs), auditory brainstem responses (ABRs) and laser-Doppler vibrometry (LDV) in mice. The conductive manipulations were created by perforating the pars flaccida of the tympanic membrane, filling or partially filling the middle-ear cavity with saline, fixing the ossicular chain, and interrupting the incudo-stapedial joint. In the saline-filled and ossicular-fixation groups, averaged DPOAE thresholds increased relative to the control state by 20-36 and 25-39 dB, respectively with the largest threshold shifts occurring at frequencies less than 20kHz, while averaged ABR thresholds increased 12-19 and 12-25 dB, respectively without the predominant low-frequency effect. Both DPOAE and ABR thresholds were elevated by less than 10 dB in the half-filled saline condition; no significant change was observed after pars flaccida perforation. Conductive pathology generally produced a change in DPOAE threshold in dB that was 1.5-2.5 times larger than the ABR threshold change at frequencies less than 30 kHz; the changes in the two thresholds were nearly equal at the highest frequencies. While mild conductive pathology (ABR threshold shifts of <10 dB) produced parallel shifts in DPOAE growth with level functions, manipulations that produced larger conductive hearing losses (ABR threshold shifts >10 dB) were associated with significant deceases in DPOAE growth rate. Our LDV measurements are consistent with others and suggest that measurements of umbo velocity are not an accurate indicator of conductive hearing loss produced by ossicular lesions in mice.

Potential role of Notch1 signaling pathway in laryngeal squamous cell carcinoma cell line Hep-2 involving proliferation inhibition, cell cycle arrest, cell apoptosis, and cell migration.

Head and neck cancer is the sixth most common cancer worldwide and laryngeal cancer represents the largest subgroup. However, the molecular mechanism underlying its malignant behavior and progression is not clarified. Accumulating evidence has shown that Notch1 signaling pathway plays a central role in carcinogenesis, but its potential role in regulating the development of laryngeal carcinoma, has not been characterized. Here, we identified that Notch1 signaling pathway was activated in laryngeal carcinoma accompanied with up-regulation of Notch1 and Hes1 expression. Overexpression of Notch1 in laryngeal carcinoma cell line Hep-2 led to suppression of tumor cellular proliferation and arrested cell cycle in the G0/G1 phase and induced cell apoptosis, which were coupled with the down-regulation of cyclin D1, cyclin E, cdk2 and bcl-2 and up-regulation of caspase-3, caspase-9 and p53. Most importantly, up-regulation of Notch1 expression also reduced the migration of Hep-2 cells, which was closely associated with down-regulation of MMP-2 and MMP-9. The finding may lay a foundation for further investigations into the Notch1 signaling pathway as a potential target for laryngeal carcinoma.