Extensive hearing loss induced by low-frequency noise exposure.

Background: With little attention given to low-frequency traffic noise and our understanding that cochlear function may be highly susceptible to low-frequency noise, there is an urgent need to determine traffic noise-induced hearing loss (NIHL), not only the hearing loss at low frequency but also the possible high-frequency hearing loss. Methods: The current study aims to investigate the potential for extensive hearing loss induced by exposure to 0.063 kHz octave band noise (OBN), which is an important component of low-frequency traffic noise. The threshold of auditory brainstem response (ABR) was used to evaluate hearing function before and after noise exposure. Chinchillas were randomly assigned into seven different groups. Group 63-3 h/6 h, Group 2 k-3 h/6 h, and group 4 k-3 h/6 h were exposed for either 3 or 6 h to 0.063, 2, and 4 kHz OBN at 90 dB SPL, respectively. The control group was not exposed to noise. Results: Significant ABR threshold-shifts (TS) were observed at 0.88, 2, 4, and 5.7 kHz in Group 63-6 h, and at 2.8 and 4 kHz in Group 2 k-6 h, and at 5.7 kHz in Group 4 k-6 h. ABR-TS were consistent with outer hair cell (OHC) losses, exposure to 0.063 kHz OBN at 90 dB SPL for 6 h induced large-scale losses of OHC both in low- and high-frequency region. Conclusions: Exposure to 0.063 kHz low-frequency OBN at 90 dB SPL for 6 h leads to significant hearing loss over an extensive range from low to high frequencies.

Optimizing the Measurement of 0.5-kHz Cubic Distortion Product Otoacoustic Emission.

BACKGROUND: The measurement of low-frequency cubic distortion product otoacoustic emission, for example, 0.5-kHz cubic distortion product otoacoustic emission, is often severely affected by background noise, and currently 0.5-kHz cubic distortion product otoacoustic emission is not commonly applicable in clinical setting. METHODS: The fundamental part of current study was the optimization of recording technology to reduce noise interference with the measurement of 0.5-kHz cubic distortion product otoacoustic emission and to establish the response patterns of cubic distortion product otoacoustic emission across speech frequencies from 0.5 to 8kHz in the presence of normal hearing and noise-induced hearing loss. RESULTS: After a series of optimization, a clinically applicable technology of measuring 0.5-kHz cubic distortion product otoacoustic emission was successfully completed via animal model. Cubic distortion product otoacoustic emission was recorded in 6 guinea pigs across speech frequencies from 0.5 to 8kHz before and after exposure to white bandnoise between 0.5 and 2 kHz. After noise exposure, significant reduction in the signal-to-noise ratio of cubic distortion product otoacoustic emission was found at 0.5 and 2 kHz, indicating our recording technology was sensitive and accurate. Other interesting finding was the reduction in cubic distortion product otoacoustic emiss ion-s ignal -to-n oise ratio at 4 and 6 kHz although the reduction was not statistically significant probably because of short exposure time. The result implied that the damaging effect induced by low-frequency noise exposure might spread upward to high-frequency region. CONCLUSIONS: Our recording technology was stable and reliable and had the great potentiality to be used in clinical setting.

miR-574-5p Targets FOXN3 to Regulate the Invasion of Nasopharyngeal Carcinoma Cells via Wnt/ß-Catenin Pathway.

MicroRNAs (miR) are a class of non-coding endogenous RNA molecules that suppress the translation of protein-coding genes by destabilizing target mRNAs. The MiR-574-5p has been reported to be involved in the several types of cancer. However, the expression of miR-574-5p and its mechanism in nasopharyngeal carcinoma (NPC) remain unclear. We found that the expression level of miR-574-5p was significantly increased in the NPC cell lines. We further demonstrated that Forkhead box N3 (FOXN3) was a target gene of miR-574-5p. FOXN3 overexpression and inhibition reversed the promoting or suppressing effect, respectively, of NPC cell proliferation, migration and invasion caused by miR-574-5p. Furthermore, miR-574-5p enhanced the ß-catenin and TCF4 protein expression by repressing FOXN3 expression, resulting in the activation of the Wnt/ß-catenin signaling pathway, but the activity of the Wnt/ß-catenin signaling pathway was inhibited by a miR-574-5p inhibitor or FOXN3 overexpression, which reversed the effect of miR-574-5p. Wound-healing and Transwell assays also showed that miR-574-5p promotes the cell migration and invasion of NPC cells, whereas the promoting effect of miR-574-5p was also reversed by a miR-574-5p inhibitor or FOXN3 overexpression. Collectively, these data suggested that miR-574-5p promotes NPC cell proliferation, migration, and invasion at least partly by targeting the FOXN3/Wnt/ß-Catenin signaling pathway.

MMP14 regulates cell migration and invasion through epithelial-mesenchymal transition in nasopharyngeal carcinoma.

Matrix metalloproteinase 14 (MMP14) has been shown to play a significant role in several types of cancers, but little is known about the function of MMP14 in nasopharyngeal carcinoma (NPC) carcinogenesis. The aim of this study was to investigate the role of MMP14 in NPC using NPC tumor samples or tissue microarray. We have shown that MMP14 was increased in NPC samples compared with normal nasopharynx (NP) tissues in microarray data (GSE13597). Both MMP14 mRNA and protein expression were markedly higher in NPC tissues than in NP tissues. High levels of MMP14 protein were found positively correlate with the status of late clinical stages of tumor and tumor with lymph node metastasis. Moreover, we have shown that MMP14 expression promoted the cell migration and invasion of NPC cells in vitro and regulated the expression of EMT-associated genes. Our data demonstrated that MMP14 plays an important role in regulation of migration and invasion of NPC cells, and constitutes a potential novel therapeutic target for NPC.

Matrix Metalloproteinase 14 Overexpression Is Correlated with the Progression and Poor Prognosis of Nasopharyngeal Carcinoma.

BACKGROUND AND AIMS: Matrix metalloproteinase 14 (MMP14) has been identified to play a significant role in several types of cancers, but little is known about the significance of MMP14 in nasopharyngeal carcinoma (NPC) patients. The aim of this study was to explore the association of MMP14 expression with clinicopathologic features and prognosis in NPC. METHODS: MMP14 mRNA and protein expressions were examined in NPC and nasopharyngeal tissues through real-time PCR and immunohistochemistry. Meanwhile, the relationship of MMP14 expression levels with clinical features and prognosis of NPC patients was analyzed. RESULTS: MMP14 mRNA expression was markedly higher in NPC tissues than in nasopharyngeal epithelium tissues (p = 0.002). Using immunohistochemistry, staining for MMP14 protein was found in the normal nasopharyngeal epithelial cells and malignant epithelial cells, but increased expression of MMP14 was observed in NPC samples compared with normal nasopharyngeal epithelium samples (p = 0.027). In addition, high levels of MMP14 protein were positively correlated with the status of clinical stage (p = 0.009), N classification (p = 0.006), and distant metastasis (p = 0.005) of NPC patients. Patients with higher MMP14 expression had a significantly shorter overall survival time than did patients with low MMP14 expression. Multivariate analysis indicated that the level of MMP14 expression was an independent prognostic indicator (p < 0.001) for the survival of patients with NPC. CONCLUSIONS: MMP14 overexpression is a potentially unfavorable prognostic factor for NPC patients.

[Significance of heparanase, bFGF and VEGF in angiogenesis for nasopharyngeal angiofibroma outspreading].

OBJECTIVE: To observe the expression of HPA, bFGF and VEGF in nasopharyngeal angiofibroma, and then explore its significance of inducing angiogenesis in the tumor's expansibility growth. METHOD: The expression of heparanase, bFGF, VEGF and CD105 were examined in 30 (I - II period 9 cases, III - IV period 21 cases) samples from nasopharyngeal angiofibroma and 20 inferior turbinate tissues by immunohistochemical staining technique. The microvascular density (MVD) were measured by the immunohistostaining of CD105. The MVD was analyzed with the clinical stage. RESULT: The positive rates of the HPA, bFGF and VEGF expression in JNA tissues were significantly higher than that in inferior turbinate group (P < 0.05). The positive rates of HPA, bFGF and VEGF expression in III - IV period were obviously higher than that in I - II period (P < 0.05). The expression of bFGF and VEGF in JNA tissues was respectively positive correlated with the HPA (r = by 0.499, 0.582, P < 0.05); In JNA tissues, the mean MVD in both HPA and bFGF positive group was higher than each one single positive group or both negative express group (P < 0.05). And the mean MVD in both HPA and VEGF positive group was higher than each one single positive group or both negative express group (P < 0.05). CONCLUSION: HPA can induce angiogenesis to promote tumor growth by releasing bFGF and VEGF. Targeting the HPA can be a new direction in JNA adjuvant treatment.

[Study and analysis on the hemorrhage of pterygoid venous plexus in large nasopharyngeal angiofibroma resection].

OBJECTIVE: To our knowledge, study of the intraoperative profuse bleeding of pterygoid venous plexus (PVP) in large nasopharyngeal angiofibroma resection has not yet been reported. Attention should be paid to this topic in clinical practice. METHOD: From 1981 to 2009, 44 cases of JNAs were treated in our hospital. Twenty-six of 44 cases were large nasopharyngeal angiofibromas according to the Fisch classification system(Fisch type III 16, type IV 10). The amount of intraoperative blood loss in these 26 cases varied from 200 ml to 5200 ml. Factors influencing intraoperative bleeding of 26 large nasopharyngeal angiofibroma resections were analyzed retrospectively. The intra-operative observations and imaging data of three typical cases were hereby studied. RESULT: After embolization of the tumor-supplying branches of the external carotid artery(ECA), both the intraoperative observations and imaging data demonstrated that the pterygoid venous plexus (PVP) played a crucial role in intraoperative hemorrhage. CONCLUSION: PVP in the infratemporal fossa communicates with craniofacial veins. There is no valve between these veins. Once PVP is seriously damaged, venous blood of all craniofacial veins will flow out profusely. In the first operation, the intact PVP in the fatty pad generally can be identified and separated from the tumor by delicate surgical managements. If an unsuccessful operation due to serious hemorrhage had been done previously, then scar tissue might tightly adhere with PVP, tumor and the pterygoid muscles, and separation of the tumor from PVP without bleeding is more difficult. Appropriate surgical approach and correct hemostatic procedure of every bleeding point should be done carefully under direct vision. Using finger or instrument for quick blind dissection should be prohibited.