The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss through the Nrf2 Pathway.

Aims: Cisplatin (CDDP) is a commonly used chemotherapeutic agent for treating head and neck tumors. However, there is high incidence of ototoxicity in patients treated with CDDP, which may be caused by the excessive reactive oxygen species (ROS) generation in the inner ear. Many studies have demonstrated the strong antioxidant effects of ergothioneine (EGT). Therefore, we assumed that EGT could also attenuate cisplatin-induced hearing loss (CIHL) as well. However, the protective effect and mechanism of EGT on CIHL have not been elucidated as so far. In this study, we investigated whether EGT could treat CIHL and the mechanism. Results: In our study, we confirmed the protective effect of EGT on preventing CDDP-induced toxicity both in vitro and in vivo. The auditory brainstem response threshold shift in the EGT + CDDP treatment mice was 30 dB less than that in the CDDP treatment mice. EGT suppressed production of ROS and proapoptotic proteins both in tissue and cells. By silencing nuclear factor erythroid 2-related factor 2 (Nrf2), we confirmed that EGT protected against CIHL via the Nrf2 pathway. We also found that SLC22A4 (OCTN1), an important molecule involved in transporting EGT, was expressed in the cochlea. Innovation: Our results revealed the role of EGT in the prevention of CIHL by activating Nrf2/HO-1/NQO-1 pathway, and broadened a new perspective therapeutic target of EGT. Conclusion: EGT decreased ROS production and promoted the expression of antioxidative enzymes to maintain redox homeostasis in sensory hair cells. Overall, our results indicated that EGT may serve as a novel treatment drug to attenuate CIHL.

A deep learning approach to the diagnosis of atelectasis and attic retraction pocket in otitis media with effusion using otoscopic images.

BACKGROUND: This study aimed to develop and validate a deep learning (DL) model to identify atelectasis and attic retraction pocket in cases of otitis media with effusion (OME) using multi-center otoscopic images. METHOD: A total of 6393 OME otoscopic images from three centers were used to develop and validate a DL model for detecting atelectasis and attic retraction pocket. A threefold random cross-validation procedure was adopted to divide the dataset into training validation sets on a patient level. A team of otologists was assigned to diagnose and characterize atelectasis and attic retraction pocket in otoscopic images. Receiver operating characteristic (ROC) curves, including area under the ROC curve (AUC), accuracy, sensitivity, and specificity were used to assess the performance of the DL model. Class Activation Mapping (CAM) illustrated the discriminative regions in the otoscopic images. RESULTS: Among all OME otoscopic images, 3564 (55.74%) were identified with attic retraction pocket, and 2460 (38.48%) with atelectasis. The diagnostic DL model of attic retraction pocket and atelectasis achieved a threefold cross-validation accuracy of 89% and 79%, AUC of 0.89 and 0.87, a sensitivity of 0.93 and 0.71, and a specificity of 0.62 and 0.84, respectively. Larger and deeper cases of atelectasis and attic retraction pocket showed greater weight, based on the red color depicted in the heat map of CAM. CONCLUSION: The DL algorithm could be employed to identify atelectasis and attic retraction pocket in otoscopic images of OME, and as a tool to assist in the accurate diagnosis of OME.

A Deep Learning Approach to Predict Conductive Hearing Loss in Patients With Otitis Media With Effusion Using Otoscopic Images.

Importance: Otitis media with effusion (OME) is one of the most common causes of acquired conductive hearing loss (CHL). Persistent hearing loss is associated with poor childhood speech and language development and other adverse consequence. However, to obtain accurate and reliable hearing thresholds largely requires a high degree of cooperation from the patients. Objective: To predict CHL from otoscopic images using deep learning (DL) techniques and a logistic regression model based on tympanic membrane features. Design, Setting, and Participants: A retrospective diagnostic/prognostic study was conducted using 2790 otoscopic images obtained from multiple centers between January 2015 and November 2020. Participants were aged between 4 and 89 years. Of 1239 participants, there were 209 ears from children and adolescents (aged 4-18 years [16.87%]), 804 ears from adults (aged 18-60 years [64.89%]), and 226 ears from older people (aged >60 years, [18.24%]). Overall, 679 ears (54.8%) were from men. The 2790 otoscopic images were randomly assigned into a training set (2232 [80%]), and validation set (558 [20%]). The DL model was developed to predict an average air-bone gap greater than 10 dB. A logistic regression model was also developed based on otoscopic features. Main Outcomes and Measures: The performance of the DL model in predicting CHL was measured using the area under the receiver operating curve (AUC), accuracy, and F1 score (a measure of the quality of a classifier, which is the harmonic mean of precision and recall; a higher F1 score means better performance). In addition, these evaluation parameters were compared to results obtained from the logistic regression model and predictions made by three otologists. Results: The performance of the DL model in predicting CHL showed the AUC of 0.74, accuracy of 81%, and F1 score of 0.89. This was better than the results from the logistic regression model (ie, AUC of 0.60, accuracy of 76%, and F1 score of 0.82), and much improved on the performance of the 3 otologists; accuracy of 16%, 30%, 39%, and F1 scores of 0.09, 0.18, and 0.25, respectively. Furthermore, the DL model took 2.5 seconds to predict from 205 otoscopic images, whereas the 3 otologists spent 633 seconds, 645 seconds, and 692 seconds, respectively. Conclusions and Relevance: The model in this diagnostic/prognostic study provided greater accuracy in prediction of CHL in ears with OME than those obtained from the logistic regression model and otologists. This indicates great potential for the use of artificial intelligence tools to facilitate CHL evaluation when CHL is unable to be measured.

[Application of combined ossicular replacement prosthesis and total ossicular replacement prosthesis of type â ¢ tympanoplasty].

Objective:This study investigated the application of combined ossicular replacement prosthesis（The Kurz Omega Connector+TORP） in type Ⅲ tympanoplasty, and compared the surgical effect with traditional TORP. Methods:Twenty patients with unilateral chronic suppurative otitis media diagnosed in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2019 to June 2020 were included in this study.All the patients were treated with intra-auricular incision with a microscopic approach（tympanic exploration, lesion clearance+type Ⅲ tympanoplasty）. According to the placement of different types of ossicular replacement prosthesis in the ossicular chain reconstruction of type Ⅲ tympanoplasty, the patients were divided into two groups: the traditional TORP group（n=10） and the combined ossicular replacement prosthesis（The Kurz Omega Connector+TORP） group（n=10）. All patients underwent pure tone audiometry before and 1 year after the operation, and the average hearing threshold and air-bone conduction difference（ABG） were compared between the two groups before and after the operation. Results:The reconstruction of the ossicular chain was completed successfully in all patients. Endoscopic examination showed that the epithelialization of the operative cavity was good and the repair of the tympanic membrane recovered well one month after the operation. There was no significant difference in preoperative mean airway threshold between the combined ossicular replacement prosthesis and the traditional TORP group （74.13[41.50，80.50] dB vs 74.25[44.81，82.50] dB, P>0.05）, there was no significant difference in preoperative ABG （55.63[21.50，61.25] dB vs 54.13[23.63，60.38] dB, P>0.05）. After the operation, the ABG of the combined auriculus group was significantly lower than that of the traditional operation group （12.00[5.75，24.56] dB vs 34.88[14.19，46.44] dB, P<0.05）. Conclusion: The combined ossicular replacement prosthesis（The Kurz Omega Connector+TORP） can increase the stability of hearing reconstruction and improve hearing in type Ⅲ tympanoplasty.

[Clinical analysis of 32 cases of facial nerve schwannomas].

Objective:To elucidate the clinical characteristics, surgical strategy, facial nerve repair methods and outcomes of facial nerve schwannomas（FNS）. Methods:The clinical data of patients with FNS treated between January 2010 and December 2018 at Sun Yat-sen Memorial Hospital of Sun Yat-sen University were retrospectively collected, including the sidedness of FNS, clinical manifestations, imaging data, the extent of tumor, clinical management, preoperative and postoperative facial nerve function. Results:The major clinical manifestations of the 32 patients with FNS were facial palsy（27, 84.4%）, hearing loss（27, 84.4%）, tinnitus（22, 68.8%）, ear mass（15, 46.9%）, and stuffy feeling in the ear（13, 40.6%） respectively. Thirty patients were preoperatively diagnosed with FNS and 2 patients were misdiagnosed. 31 patients underwent resection of FNS, except one patient who was selected for long-term follow-up observation. The choice of surgical approach was based on the location, extent and auditory function of the FNS involved as well as the patient's wishes. The surgical approach was decided based on the location and extent of the tumor: 9 patients were operated via the inferior temporal fossa type A（Fisch A） approach; 8 patients were operated via the mastoid approach; 7 patients were operated via the enlarged mastoid approach; 3 patients were operated via the combined mastoid-cranial middle fossa approach; 1 patient was operated via the cranial middle fossa approach; 3 patients were operated via the combined Fisch A-cranial middle fossa approach. 28 patients（87.5%） had FNS with multiple segments of facial nerve involved. The most involved segment was the vertical segment of the facial nerve（26, 81.3%）. 15 patients underwent facial nerve repair simultaneously, including 7 cases of auricular nerve-facial nerve graft and 8 cases of facial nerve-sublingual nerve anastomosis. 4 cases had improved facial nerve function after auricular nerve-facial nerve graft and 2 cases had improved function after facial nerve-sublingual nerve anastomosis. Among patients who underwent facial nerve repair,the best outcome was H-B Ⅲ. Conclusion:The patients with FNS mainly presented with facial palsy and hearing loss. Temporal bone CT and cranial MR plain & enhanced scan served well to confirm the diagnosis. The improvement rate of postoperative facial nerve function was significantly higher in patients who underwent nerve repair than in those who did not. Hence, facial nerve repair should be considered. Compared with facial nerve-sublingual nerve anastomosis, auricular major nerve-facial nerve graft might be a better choice for improving postoperative facial nerve function.

Mitochondrial dysfunction resulting from the down-regulation of bone morphogenetic protein 5 may cause microtia.

BACKGROUND: Bone morphogenetic protein 5 (BMP5) has been identified as one of the important risk factors for microtia; however, the link between them has yet to be clarified. In this study, we aimed to demonstrate the relationship of BMP5 with mitochondrial function and investigate the specific role of mitochondria in regulating microtia development. METHODS: BMP5 expression was measured in auricular cartilage tissues from patients with and without microtia. The effects of BMP5 knockdown on cellular function and mitochondrial function were also analyzed in vitro. Changes in genome-wide expression profiles were measured in BMP5-knockdown cells. Finally, the specific impact of BMP5 down-regulation on mitochondrial fat oxidation was analyzed in vitro. RESULTS: BMP5 expression was down-regulated in the auricular cartilage tissues of microtia patients. BMP5 down-regulation inhibited various cellular functions in vitro, including cell proliferation, mobility, and cytoactivity. The functional integrity of mitochondria was also damaged, accompanied by a decrease in mitochondrial membrane potential, reactive oxygen species (ROS) neutralization, and reduced adenosine triphosphate (ATP) production. Carnitine O-palmitoyltransferase 2 and diacylglycerol acyltransferase 2, two of the key regulators of mitochondrial lipid oxidation, were also found to be decreased by BMP5 down-regulation. CONCLUSIONS: Down-regulation of BMP5 affects glycerolipid metabolism and fatty acid degradation, leading to mitochondrial dysfunction, reduced ATP production, and changes in cell function, and ultimately resulting in microtia. This research provides supporting evidence for an important role of BMP5 down-regulation in affecting mitochondrial metabolism in cells, and sheds new light on the mechanisms underlying the pathogenesis of microtia.

Logistic regression analysis of factors influencing the effectiveness of intensive sound masking therapy in patients with tinnitus.

OBJECTIVES: To investigate factors influencing the effectiveness of intensive sound masking therapy on tinnitus using logistic regression analysis. DESIGN: The study used a retrospective cross-section analysis. PARTICIPANTS: 102 patients with tinnitus were recruited at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, China. INTERVENTION: Intensive sound masking therapy was used as an intervention approach for patients with tinnitus. PRIMARY AND SECONDARY OUTCOME MEASURES: Participants underwent audiological investigations and tinnitus pitch and loudness matching measurements, followed by intensive sound masking therapy. The Tinnitus Handicap Inventory (THI) was used as the outcome measure pre and post treatment. Multivariate logistic regression was performed to investigate the association of demographic and audiological factors with effective therapy. RESULTS: According to the THI score changes pre and post sound masking intervention, 51 participants were categorised into an effective group, the remaining 51 participants were placed in a non-effective group. Those in the effective group were significantly younger than those in the non-effective group (P=0.012). Significantly more participants had flat audiogram configurations in the effective group (P=0.04). Multivariable logistic regression analysis showed that age (OR=0.96, 95% CI 0.93 to 0.99, P=0.007), audiometric configuration (P=0.027) and THI score pre treatment (OR=1.04, 95% CI 1.02 to 1.07, P<0.001) were significantly associated with therapeutic effectiveness. Further analysis showed that patients with flat audiometric configurations were 5.45 times more likely to respond to intervention than those with high-frequency steeply sloping audiograms (OR=5.45, 95% CI 1.67 to 17.86, P=0.005). CONCLUSION: Audiometric configuration, age and THI scores appear to be predictive of the effectiveness of sound masking treatment. Gender, tinnitus characteristics and hearing threshold measures do not seem to be related to treatment effectiveness. A further randomised control study is needed to provide evidence of the effectiveness of prognostic factors in tinnitus interventions.

The protective effect of autophagy on ischemia/reperfusion-induced hearing loss: implications for sudden hearing loss.

The present study aimed to determine the effects of ischemia/reperfusion (IR) injury for the carotid system on hearing, particularly, the role of autophagy in this process. Sixty-three Sprague-Dawley rats were divided randomly into three groups: sham surgery animals (S), temporary carotid artery occlusion (ischemia) for 30 min (I30), and temporary carotid artery occlusion for 60 min (I60). Auditory brainstem response measurements were performed on mice. After 72 h of reperfusion, the microcirculation was measured in mice after ischemia injury. Immunofluorescence was used to examine the expression of caspase-3 and light chain 3B in the cochlear sections. Temporary carotid artery occlusion lasting for 30 (I30) or 60 min (I60) caused significant hearing loss in the ischemia phase. Following a recovery during the postreperfusion phase, the temporal threshold shift occurred in the I30 group, whereas a permanent threshold shift occurred in the I60 group. Moreover, both microcirculation and autophagy affected hearing 24 h after reperfusion, whereas at 72 h, autophagy works as an intrinsic cellular process that protects against death from the IR effect. These results suggest that the sooner the reperfusion, the better the hearing recovery. In conclusion, autophagy promotes cell survival in the cochlea; however, excessive IR damage counteracts the beneficial potential of autophagy protection and leads to a permanent threshold shift.

The miR-34a/Bcl-2 Pathway Contributes to Auditory Cortex Neuron Apoptosis in Age-Related Hearing Loss.

HYPOTHESIS: The miR-34a/Bcl-2 signaling pathway may play a role in the mechanisms related to age-related hearing loss (AHL) in the auditory cortex. BACKGROUND: The auditory cortex plays a key role in the recognition and processing of complex sound. It is difficult to explain why patients with AHL have poor speech recognition, so increasing numbers of studies have focused on its central change. Although micro (mi)RNAs in the central nervous system have recently been increasingly reported to be associated with age-related diseases, the molecular mechanisms of AHL in the auditory cortex are not fully understood. METHODS: The auditory brainstem response was used to assess the hearing ability of C57BL/6 mice, and q-PCR, immunohistochemistry, and Western blotting were used to detect the expression levels of miR-34a and Bcl-2 in the mouse auditory cortex. TUNEL and DNA fragmentation were adopted to detect the apoptosis of neurons in the auditory cortex. To verify the relationship of miR-34a and Bcl-2, we transfected an miR-34a mimic or miR-34a inhibitor into primary auditory cortex neurons. RESULTS: In this study, miR-34a/Bcl-2 signaling was examined in auditory cortex neurons during aging. miR-34a and apoptosis increased in the auditory cortex neurons of C57BL/6 mice with aging, whereas an age-related decrease in Bcl-2 was determined. In the primary neurons of the auditory cortex, miR-34a overexpression inhibited Bcl-2, leading to an increase in apoptosis. Moreover, miR-34a knockdown increased Bcl-2 expression and diminished apoptosis. CONCLUSION: Our results support a link between age-related apoptosis in auditory cortex neurons and miR-34a/Bcl-2 signaling, which may serve as a potential mechanism of the expression of AHL in the auditory cortex.

miR-34a/Bcl-2 signaling pathway contributes to age-related hearing loss by modulating hair cell apoptosis.

MicroRNAs, such as miR-34, have been reported to influence age-related diseases. In this study, we explored the role of the miR-34a/Bcl-2 signaling pathway in age-related hearing loss (AHL). Using an AHL mouse model (C57BL/6), we found that the expression of miR-34a in the cochlea increased with age, whereas expression of Bcl-2 decreased. Increasing the amount of a miR-34a mimetic in a mouse auditory cell line (HEI-OC1) inhibited Bcl-2, leading to enhanced apoptosis; in contrast, miR-34a inhibition produced the opposite effect. Our results support a link between age-related cochlear hair cell apoptosis and miR-34a/Bcl-2 signaling. The latter may thus serve as a potential target for AHL therapy.

Differential Expression of Bcl-2 in the Cochlea and Auditory Cortex of a Mouse Model of Age-Related Hearing Loss.

Bcl-2, the first gene shown to be involved in apoptosis, is a potent regulator of cell survival and known to have protective effects against a variety of age-related diseases. However, the possible relationship between hearing and Bcl-2 expression in the cochlea or auditory cortex of C57BL/6 mice, a mouse model of age-related hearing loss, is still unknown. Using RT-PCR, immunohistochemistry, and Western blot analysis, our results show that Bcl-2 is strongly expressed in the inner hair cells and spiral ganglion neurons of young mice. In addition, moderate Bcl-2 expression is also detected in the outer hair cells and in the neurons of the auditory cortex. A significant reduction of Bcl-2 expression in the cochlea or auditory cortex is also associated with elevated hearing thresholds and hair cell loss during aging. The expression pattern of Bcl-2 in the peripheral and central auditory systems suggests that Bcl-2 may play an important role in auditory function serving as a protective molecule against age-related hearing loss.

TREM-2 promotes acquired cholesteatoma-induced bone destruction by modulating TLR4 signaling pathway and osteoclasts activation.

Triggering receptor expressed on myeloid cells (TREM) has been broadly studied in inflammatory disease. However, the expression and function of TREM-2 remain undiscovered in acquired cholesteatoma. The expression of TREM-2 was significantly higher in human acquired cholesteatoma than in normal skin from the external auditory canal, and its expression level was positively correlated with the severity of bone destruction. Furthermore, TREM-2 was mainly expressed on dendritic cells (DCs). In human acquired cholesteatoma, the expression of proinflammatory cytokines (IL-1ß, TNF-α and IL-6) and matrix metalloproteinases (MMP-2, MMP-8 and MMP-9) were up-regulated, and their expression levels were positively correlated with TREM-2 expression. Osteoclasts were activated in human acquired cholesteatoma. In an animal model, TREM-2 was up-regulated in mice with experimentally acquired cholesteatoma. TREM-2 deficiency impaired the maturation of experimentally acquired cholesteatoma and protected against bone destruction induced by experimentally acquired cholesteatoma. Additional data showed that TREM-2 up-regulated IL-1ß and IL-6 expression via TLR4 instead of the TLR2 signaling pathway and promoted MMP-2 and MMP-8 secretion and osteoclast activation in experimentally acquired cholesteatoma. Therefore, TREM-2 might enhance acquired cholesteatoma-induced bone destruction by amplifying the inflammatory response via TLR4 signaling pathways and promoting MMP secretion and osteoclast activation.

Clinical outcomes following ear reconstruction with adjuvant 3D template model.

CONCLUSIONS: The use of the 3D template model in microtia surgery leads to satisfactory results, for its contribution to the engraving and localization of the microtia auricle in auricle reconstruction. OBJECTIVES: The aim of the study was to create an anatomical correct 3D rapid prototyping model for patients with microtia, to assist with the accurate fabrication and localization of a coastal cartilage framework for auricular reconstruction, and patients, who had undergone rib-cartilage reconstruction to treat a congenital auricular defect, were evaluated for aesthetic outcomes following ear reconstruction with a different template model. METHODS: Forty patients with unilateral congenital microtia were enrolled in this study during the last 2 years, they were divided into two groups randomly before surgery; 20 patients who had a 3D digital template made for clinical application and the other 20 who underwent ear reconstruction with a 2D template. RESULTS: The patients who had undergone ear reconstruction with the 3D template model had a better result of the appearance and location of the constructed auricle, and a higher level of satisfaction with their clinical outcomes (p < .05).

Effect of the combination of balloon Eustachian tuboplasty and tympanic paracentesis on intractable chronic otitis media with effusion.

OBJECTIVE: To evaluate the effect of the combination of balloon Eustachian tuboplasty (BET) and tympanic paracentesis (TP) on intractable chronic otitis media with effusion (COME). METHODS: Ninety patients with intractable COME were included and randomly assigned to three groups: BET only (30 patients), BET+paracentesis (30 patients), and paracentesis only (30 patients). Otic endoscopic findings and tympanograms were recorded before the surgery and at the month 1, month 3, and month 6 follow-up evaluations. RESULTS: Both the BET only and BET+paracentesis groups achieved better outcomes than the paracentesis group. The BET+paracentesis group exhibited better otic endoscopic scores than the BET only group (p<0.05) at 1month post-operation. However, no significant difference was found at month 3 or month 6 post-operation. No significant difference in the tympanograms was observed between these two groups at month 1, month 3, or month 6 post-operation. The otic endoscopic sign scores improved from month 1 to month 6 in the BET only group and from month 1 to month 3 in the BET+paracentesis group. The conversion of type B tympanograms improved from month 1 to month 6 in the BET and BET+paracentesis groups but not in the paracentesis only group. CONCLUSIONS: Our results suggested that the combination of BET and TP was effective for intractable COME and can help shorten the recovery period for middle ear effusion.

Circulating miR-34a levels correlate with age-related hearing loss in mice and humans.

Age-related hearing loss (AHL) is a progressive neurodegenerative disease that is largely silent in its initial stages. There is no sensitive blood biomarker for diagnosis or early detection of AHL. MicroRNAs (miRNAs or miRs) are abundant and highly stable in blood, and have been recently described as powerful circulating biomarkers in a wide range of diseases. In the present study, we identified concordant increases in miR-34a levels in the cochlea, auditory cortex, and plasma of C57BL/6 mice during aging. These increases were accompanied by elevated hearing thresholds and greater loss of hair cells. Levels of miR-34a targets, silent information regulator 1 (SIRT1), B-cell lymphoma-2 (Bcl-2), and E2F transcription factor 3 (E2F3), in the cochlea, auditory cortex, and plasma decreased with aging inversely to miR-34a. Moreover, plasma miR-34a levels were significantly higher in patients with AHL compared with controls who had normal hearing and had a receiver-operating characteristic curve that distinguished AHL patients from controls. However, SIRT1, Bcl-2, and E2F3 showed no correlation with AHL in humans. In summary, circulating miR-34a level may potentially serve as a useful biomarker for early detection of AHL.

Activation of miR-34a/SIRT1/p53 signaling contributes to cochlear hair cell apoptosis: implications for age-related hearing loss.

The molecular mechanisms underlying age-related hearing loss are not fully understood, and currently, there is no treatment for this disorder. MicroRNAs have recently been reported to be increasingly associated with age-related diseases and are emerging as promising therapeutic targets. In this study, miR-34a/Sirtuin 1 (SIRT1)/p53 signaling was examined in cochlear hair cells during aging. MiR-34a, p53 acetylation, and apoptosis increased in the cochlea of C57BL/6 mice with aging, whereas an age-related decrease in SIRT1 was observed. In the inner ear HEI-OC1 cell line, miR-34a overexpression inhibited SIRT1, leading to an increase in p53 acetylation and apoptosis. Moreover, miR-34a knockdown increased SIRT1 expression and diminished p53 acetylation, and apoptosis. Additionally, resveratrol, an activator of SIRT1, significantly rescued miR-34a overexpression-induced HEI-OC1 cell death and significantly reduced hearing threshold shifts and hair cell loss in C57BL/6 mice after a 2-month administration. Our results support a link between age-related cochlear hair cell apoptosis and miR-34a/SIRT1/p53 signaling, which may serve as a potential target for age-related hearing loss treatment.

[Eustachian tube balloon dilation in eustachian tube dysfunction related diseases].

OBJECTIVE: To investigate the effect of Eustachian tube balloon dilation (ETBD) in treatment of eustachian tube related diseases. METHOD: Fifteen cases (20 ears) of otitis media with effusion and 22 cases (30 ears) of symptomatic Eustachian tube dysfunction were recruited. Technique of tubomanometry (TMM) showed obstructive Eustachian tube dysfunction in all patients. All the patients were received ETBD and followed up with VAS evaluation of ear fullness, muffled hearing, poping sound in the ear and tinnitus. And also the TMM change and middle ear effusion. RESULT: Ear fullness, muffled hearing released with 1 week (ear fullness: 8.2 ± 1.4 vs. 2.0 ± 1.2, P < 0.05, muffled hearing: 6.2 ± 1.2 vs. 3.1 ± 0.8, P < 0.05). No recurrence was seemed within 6 months. The eustachian function test turned better. Symptomatic Eustachian tube dysfunction had an effective rate of 96.6% while otitis media with effusion was 95.0%. CONCLUSION: ETBD have good short-term effect in obstructive eustachian tube dysfunction related middle ear dysfunction, which might provide a good way to solve the eustachian tube related diseases.

[Effect of nasal cavity expansion surgery on chronic nasal obstructive diseases on the blood supply of the cerebral arterial system].

OBJECTIVE: To investigate the effect of nasal cavity expansion surgery on the abnormal blood supply of the cerebral arterial system. METHODS: Fifty-nine inpatients with abnormal blood supply of cerebral arterial system confirmed by transcranial doppler (TCD) and chronic nasal obstructive diseases were included in this study. All patients accepted nasal cavity expansion surgery and were followed-up with TCD every month after operation until TCD became normal, or up to seven months even if the TCD was still abnormal. SPSS 17.0 software was used to analyze the data. RESULTS: In all 59 patients, there were 164 TCD-abnormal cerebral arteries. Among them, 37 patients(62.71%) with abnormal TCD arteries became normal within 1 to 7 months after operation, 8 patients (13.56 %) got better, but 14 patients (23.73 %) did not improve. CONCLUSIONS: Abnormal blood flow of some cerebral arteries was possibly induced by increasing the activation of sympathetic nervous system around the vertebral arterial system, caused by chronic nasal obstruction. Nasal dilatancy surgery can improve the blood supplement of the cerebral arterial system.

Measurements of the position relationship between the inferior margin of the oval window and the endosteum of basal cochlear turn in histologic and HRCT study.

HYPOTHESIS: To identify the optimum and safe location histologically for drilling and fenestration on promontory inferior to the oval window in stapedectomy. The value of application of high-resolution computed tomography (HRCT) scanning and multiple-planar reconstruction (MPR) for this purpose is also assessed. METHODS: By means of histologic sections and HRCT scanning and MPR for coronal image, measurements were conducted on 3 perpendicular planes in temporal bone sections through the anterior, posterior, and midpoint of the inferior margin of the oval window, respectively. RESULTS: The promontory bone inferior to the posterior portion of the oval window is thickest, which has an average thickness of about 1.1 mm. The endosteum of the basal turn here is deepest under the promontory, which has an average height of about 0.2 mm above the plane of footplate, whereas the distance between the inferior margin of the oval window and the endosteum here is no more than 0.3 mm. The coincidence rate of the measurements by HRCT and histology is up to 90.5%. CONCLUSION: Relatively safe location for bone of the promontory removal should be restricted in the posterior portion inferior to the oval window, and the burr should be lifted laterally while drilling. Preoperative HRCT scanning and MPR for coronal image would offer a valuable reference to estimate the safe area for bone of the promontory removal in stapedectomy.

Hypoxia-inducible factor and vascular endothelial growth factor pathway for the study of hypoxia in a new model of otitis media with effusion.

The hypoxia-inducible factor and vascular endothelial growth factor (HIF-VEGF) pathway in hypoxic conditions of the middle ear due to dysfunction of the eustachian tube is still unknown, but it is considered as one pathogenetic mechanism in otitis media. This study was designed to investigate the possible involvement of the HIF-VEFG pathway in otitis media with effusion induced by dysfunction of the eustachian tube. We adopted a soft palate approach to obstruct the orifice of the eustachian tube to establish otitis media in a rat model. Auditory evoked brainstem response and tympanometry were used as hearing function tests, hypoxia-related factors were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of hypoxia-related proteins was detected by Western blot and immunostaining. The model of otitis media with effusion was successfully induced by cauterizing the orifice of the eustachian tube. RT-PCR showed up-regulation of hypoxia-related factors in cauterized ears. Western blot and immunostaining showed that the expression of hypoxia-related proteins in cauterized ears was increased. Hypoxia-induced vascular proliferation and an increase in permeability may be one pathogenetic mechanism of otitis media due to dysfunction of the eustachian tube.