A prediction model based on random survival forest analysis of the overall survival of elderly female papillary thyroid carcinoma patients: a SEER-based study.

OBJECTIVE: Papillary thyroid carcinoma (PTC) is a common malignancy whose incidence is three times greater in females than in males. The prognosis of ageing patients is poor. This research was designed to construct models to predict the overall survival of elderly female patients with PTC. METHODS: We developed prediction models based on the random survival forest (RSF) algorithm and traditional Cox regression. The data of 4539 patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Twelve variables were analysed to establish the models. The C-index and the Brier score were selected to evaluate the discriminatory ability of the models. Time-dependent receiver operating characteristic (ROC) curves were also drawn to evaluate the accuracy of the models. The clinical benefits of the two models were compared on the basis of the DCA curve. In addition, the Shapley Additive Explanations (SHAP) plot was used to visualize the contribution of the variables in the RSF model. RESULTS: The C-index of the RSF model was 0.811, which was greater than that of the Cox model (0.781). According to the Brier score and the area under the ROC curve (AUC), the RSF model performed better than the Cox model. On the basis of the DCA curve, the RSF model demonstrated fair clinical benefit. The SHAP plot showed that age was the most important variable contributing to the outcome of PTC in elderly female patients. CONCLUSIONS: The RSF model we developed performed better than the Cox model and might be valuable for clinical practice.

Deferoxamine protects cochlear hair cells and hair cell-like HEI-OC1 cells against tert-butyl hydroperoxide-induced ototoxicity.

Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).

Functional to structural plasticity in unilateral sudden sensorineural hearing loss: neuroimaging evidence.

A cortical plasticity after long-duration single side deafness (SSD) is advocated with neuroimaging evidence while little is known about the short-duration SSDs. In this case-cohort study, we recruited unilateral sudden sensorineural hearing loss (SSNHL) patients and age-, gender-matched health controls (HC), followed by comprehensive neuroimaging analyses. The primary outcome measures were temporal alterations of varied dynamic functional network connectivity (dFNC) states, neurovascular coupling (NVC) and brain region volume at different stages of SSNHL. The secondary outcome measures were pure-tone audiograms of SSNHL patients before and after treatment. A total of 38 SSNHL patients (21 [55%] male; mean [standard deviation] age, 45.05 [15.83] years) and 44 HC (28 [64%] male; mean [standard deviation] age, 43.55 [12.80] years) were enrolled. SSNHL patients were categorized into subgroups based on the time from disease onset to the initial magnetic resonance imaging scan: early- (n = 16; 1-6 days), intermediate- (n = 9; 7-13 days), and late- stage (n = 13; 14-30 days) groups. We first identified slow state transitions between varied dFNC states at early-stage SSNHL, then revealed the decreased NVC restricted to the auditory cortex at the intermediate- and late-stage SSNHL. Finally, a significantly decreased volume of the left medial superior frontal gyrus (SFGmed) was observed only in the late-stage SSNHL cohort. Furthermore, the volume of the left SFGmed is robustly correlated with both disease duration and patient prognosis. Our study offered neuroimaging evidence for the evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month, which may explain, from a neuroimaging perspective, why early-stage SSNHL patients have better therapeutic responses and hearing recovery.

Comparative transcriptome profiling reveals RNA splicing alterations and biological function in patients exposed to occupational noise.

Genetic factors play an important role in susceptibility to noise-induced hearing loss (NIHL). Alternative splicing (AS) is an essential mechanism affecting gene expression associated with disease pathogenesis at the post-transcriptional level, but has rarely been studied in NIHL. To explore the role of AS in the development of NIHL, we performed a comprehensive analysis of RNA splicing alterations by comparing the RNA-seq data from blood samples from NIHL patients and subjects with normal hearing who were exposed to the same noise environment. A total of 356 differentially expressed genes, including 23 transcription factors, were identified between the two groups. Of particular note was the identification of 56 aberrant alternative splicing events generated by 41 differentially expressed genes between the two groups, with exon skipping events accounting for 54% of all the differentially alternative splicing (DAS) events. The results of functional enrichment analysis showed that these intersecting DAS genes and differentially expressed genes were significantly enriched in autophagy and mitochondria-related pathways. Together, our findings provide insights into the role of AS events in susceptibility and pathogenesis of NIHL.

Predictive value of serum proteomic biomarkers for noise-induced hearing loss.

Early detection of noise-induced hearing loss (NIHL) in patients with long-term noise exposure is vital for improving public health and reducing social burden. However, at present, the diagnosis of NIHL mainly depends on audiometric testing, and the primary test is pure-tone audiometry. Moreover, testing requires professional operators and complex equipment; thus, NIHL is often diagnosed at a later disease stage. Using a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic approach, we identified 9 differentially expressed proteins (DEPs), namely, 6 upregulated serum proteins and 3 downregulated serum proteins, in samples from 50 ground crew personnel working at an air force station. Then, according to the results, we predicted that caldesmon (CALD1), myocilin (MYOC), zyxin (ZYX), creatine kinase M-type (CKM), insulin-like growth factor-binding protein 2 (IGFBP2), complement factor H-related protein 4 (CFHR4), prenylcysteine oxidase 1 (PCYOX1), heat shock cognate 71 kDa protein (HSPA8), and immunoglobulin lambda variable 3-21 (IGLV3-21) were associated with NIHL. We selected these DEPs as variables to perform logistic regression. Finally, a logistic regression model was constructed based on IGFBP2, ZYX, CKM, and CFHR4. The area under the curve was 0.894 (95% CI = 0.812 to 0.977). These findings suggested that IGFBP2, ZYX, CKM, and CFHR4 in serum are differentially expressed in NIHL patients and have the potential to be biomarkers for predicting the risk for NIHL. Further experiments in mice showed that ZYX and IGFBP2 in the cochlear were increased after noise exposure. ZYX and IGFBP2 may be involved in the occurrence and development of NIHL.

Ablation of CD226 on CD4+ T cells modulates asthma progress associated with altered IL-10 response and gut microbiota.

To investigate the role of the costimulatory molecule CD226 in asthma pathogenesis, we produced a CD4+ T-cell-specific CD226 knockout mice model (Cd226ΔCD4) and induced airway allergic inflammation by administering ovalbumin (OVA). Our results revealed alleviated lung inflammation, decreased levels of OVA-specific IgE, and increased levels of IL-10 in the serum of Cd226ΔCD4 mice (P < 0.05). Moreover, IL-10 levels in CD4+ T cells were significantly elevated in the mediastinal lymph node, spleen, and Peyer's patches in the Cd226ΔCD4 mice compared with those in controls (P < 0.05 to P < 0.01). Notably, there was a significantly higher IL-10 mRNA levels in the large intestine of the mice (P < 0.05). The protective effect of CD226 deficiency is also associated with the accumulation of gut TCRγδ+ intraepithelial lymphocytes and reversion of the gut microbiome dysbiosis. The Bacteroidetes-to-Firmicutes ratio and the abundance of Akkermansia increased in the absence of CD226 after OVA treatment. Our data reveal the synchronous changes in the lung and intestine in OVA-treated CD226-knockout mice, supporting the gut-lung axis concept and providing evidence for novel therapeutic approaches for asthma.

Correlation between clinical characteristics and tinnitus severity in tinnitus patients of different sexes: an analytic retrospective study.

PURPOSE: This study aimed to explore whether sex is influences tinnitus severity and whether the risk factors for tinnitus severity are the same in tinnitus patients of different sexes. METHODS: This was a retrospective study of data from 1427 patients complaining of tinnitus in a local hospital otolaryngology clinic from November 2019 to January 2022. All patients were interviewed and assessed by otoscopy, pure-tone audiometry, tinnitus handicap inventory (THI), visual analogue scale (VAS), and tinnitus refinement test. RESULTS: THI values were higher in females than in males (P = 0.00). Types of tinnitus sounds (OR 0.667, P = 0.000) and degree of hearing loss (OR 1.318, P = 0.000) were risk factors for tinnitus severity in males. Types of tinnitus sounds (OR 0.789, P = 0.005), sensation level (OR 1.023, P = 0.037), tinnitus types (OR 1.163, P = 0.041), tinnitus location (OR 1.198, P = 0.026), and the degree of hearing loss (OR 1.303, P = 0.000) were risk factors for tinnitus severity in females. Sex was an influencing factor for tinnitus severity. There were different risk factors for the tinnitus severity in different sexes. CONCLUSION: The risk factors for tinnitus severity differed according to sex in tinnitus patients, and the risk factors for tinnitus severity were greater in women than in men. These findings add to the literature on sex differences in tinnitus and suggest that medical and psychological screening of affected individuals and customized tinnitus treatment for each individual with tinnitus are needed. TRIAL REGISTRATION NUMBER/DATE OF REGISTRATION: ChiCTR2200057958, 2022/3/24 (retrospectively registered trials).

Development of an audiological assessment and diagnostic model for high occupational noise exposure.

PURPOSE: To explore the diagnostic auditory indicators of high noise exposure and combine them into a diagnostic model of high noise exposure and possible development of hidden hearing loss (HHL). METHODS: We recruited 101 young adult subjects and divided them according to noise exposure history into high-risk and low-risk groups. All subjects completed demographic characteristic collection (including age, noise exposure, self-reported hearing status, and headset use) and related hearing examination. RESULTS: The 8 kHz (P = 0.039) and 10 kHz (P = 0.005) distortion product otoacoustic emission amplitudes (DPOAE) (DPs) in the high-risk group were lower than those in the low-risk group. The amplitudes of the summating potential (SP) (P = 0.017) and action potential (AP) (P = 0.012) of the electrocochleography (ECochG) in the high-risk group were smaller than those in the low-risk group. The auditory brainstem response (ABR) wave III amplitude in the high-risk group was higher than that in the low-risk group. When SNR = - 7.5 dB (P = 0.030) and - 5 dB (P = 0.000), the high-risk group had a lower speech discrimination score than that of the low-risk group. The 10 kHz DPOAE DP, ABR wave III amplitude and speech discrimination score under noise with SNR = - 5 dB were combined to construct a combination diagnostic indicator. The area under the ROC curve was 0.804 (95% CI 0.713-0.876), the sensitivity was 80.39%, and the specificity was 68.00%. CONCLUSIONS: We expect that high noise exposure can be detected early with this combined diagnostic indicator to prevent HHL or sensorineural hearing loss (SNHL). TRIAL REGISTRATION NUMBER/DATE OF REGISTRATION: ChiCTR2200057989, 2022/3/25.

Treatment with the Ferroptosis Inhibitor Ferrostatin-1 Attenuates Noise-Induced Hearing Loss by Suppressing Ferroptosis and Apoptosis.

Hair cell death induced by excessive reactive oxygen species (ROS) has been identified as the major pathogenesis of noise-induced hearing loss (NIHL). Recent studies have demonstrated that cisplatin- and neomycin-induced ototoxicity can be alleviated by ferroptosis inhibitors. However, whether ferroptosis inhibitors have a protective effect against NIHL remains unknown. We investigated the protective effect of the ferroptosis inhibitor ferrostatin-1 (Fer-1) on NIHL in vivo in CBA/J mice and investigated the protective effect of Fer-1 on tert-butyl hydroperoxide (TBHP)-induced hair cell damage in vitro in cochlear explants and HEI-OC1 cells. We observed ROS overload and lipid peroxidation, which led to outer hair cell (OHC) apoptosis and ferroptosis, in the mouse cochlea after noise exposure. The expression level of apoptosis-inducing factor mitochondria-associated 2 (AIFM2) was substantially increased following elevation of the expression of its upstream protein P53 after noise exposure. The ferroptosis inhibitor Fer-1was demonstrated to enter the inner ear after the systemic administration. Administration of Fer-1 significantly alleviated noise-induced auditory threshold elevation and reduced the loss of OHCs, inner hair cell (IHC) ribbon synapses, and auditory nerve fibers (ANFs) caused by noise. Mechanistically, Fer-1 significantly reduced noise- and TBHP-induced lipid peroxidation and iron accumulation in hair cells, alleviating ferroptosis in cochlear cells consequently. Furthermore, Fer-1 treatment decreased the levels of TfR1, P53, and AIFM2. These results suggest that Fer-1 exerted its protective effects by scavenging of ROS and inhibition of TfR1-mediated ferroptosis and P53-AIFM2 signaling pathway-mediated apoptosis. Our findings suggest that Fer-1 is a promising drug for treating NIHL because of its ability to inhibit noise-induced hair cell apoptosis and ferroptosis, opening new avenues for the treatment of NIHL.

Systemic steroid administration combined with intratympanic steroid injection in the treatment of a unilateral sudden hearing loss prognosis prediction model: A retrospective observational study.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is an emergency ear disease that is referred to as a sensorineural hearing loss of at least 30 dB in three sequential frequencies and occurs over a period of < 72 h. Because of its etiology, pathogenesis, and prognostic factors, the current treatment methods are not ideal. Previous studies have developed prognostic models to predict hearing recovery from ISSNHL, but few studies have incorporated serum biochemical indicators into previous models. The aim of this study was to explore the factors influencing the ISSNHL prognosis of combination therapy (combined intratympanic and systemic use of steroids, CT), among the patient population data, the serum biochemical indicators before the treatment, and the clinical features of ISSNHL. The new prediction model was developed through these factors. From November 2015 to April 2022, 430 patients who underwent CT at the Department of Otorhinolaryngology Head and Neck Surgery, Tangdu Hospital, Air Force Medical University for ISSNHL, were reviewed retrospectively. We found significant differences in age (P = 0.018), glucose (P = 0.035), white blood cell (WBC) (P = 0.021), vertigo (P = 0.000) and type (P = 0.000) with different therapeutic efficacies. Multivariate logistic regression analysis showed that age (OR = 0.715, P = 0.023), WBC (OR = 0.527, P = 0.01), platelet to lymphocyte ratio (PLR) (OR = 0.995, P = 0.038), vertigo (OR = 0.48, P = 0.004), course (time from onset to treatment) (OR = 0.681, P = 0.016) and type (OR = 0.409, P = 0.000) were independent risk factors for ISSNHL prognosis. Based on independent risk factors, a predictive model and nomogram were developed to predict hearing outcomes in ISSNHL patients. The area under the curve (AUC) value of the model developed in this study was 0.773 (95% CI = 0.730-0.812), which has a certain predictive ability. The calibration curve indicated good consistency between the actual diagnosed therapeutic effectiveness and the predicted probability. The model and nomogram can predict the hearing prognosis of ISSNHL patients treated with CT and can provide help for medical staff to make the best clinical decision. This study has been registered with the registration number ChiCTR2200061379.

CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell Responses.

Allergic rhinitis (AR) is an immunoglobulin E-mediated type 2 inflammation of the nasal mucosa that is mainly driven by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s). CD226 is a costimulatory molecule associated with inflammatory response and is mainly expressed on T cells, natural killer cells, and monocytes. This study is aimed at elucidating the role of CD226 in allergic inflammatory responses in murine AR using global and CD4+ T cell-specific Cd226 knockout (KO) mice. AR nasal symptoms were assessed based on the frequency of nose rubbing and sneezing. Hematoxylin and eosin and periodic acid-Schiff staining and quantitative real-time PCR methods were used to determine eosinophils, goblet cells, and ILC2-associated mRNA levels in the nasal tissues of mice. CD226 levels on ILC2s were detected using flow cytometry, and an immunofluorescence double staining assay was employed to determine the number of ILC2s in the nasal mucosa. The results showed that global Cd226 KO mice, but not CD4+ T cell-specific Cd226 KO mice, exhibited attenuated AR nasal symptoms. Eosinophil recruitment, goblet cell proliferation, and Th2-inflammatory cytokines were significantly reduced, which resulted in the alleviation of allergic and inflammatory responses. ILC2s in the murine nasal mucosa expressed higher levels of CD226 after ovalbumin stimulation, and CD226 deficiency led to a reduction in the proportion of nasal ILC2s and ILC2-related inflammatory gene expression. Hence, the effect of CD226 on the AR mouse model may involve the regulation of ILC2 function rather than CD4+ T cells.

Nrf2 Knockout Affected the Ferroptosis Signaling Pathway against Cisplatin-Induced Hair Cell-Like HEI-OC1 Cell Death.

Cisplatin is a well-known and widely used anticancer drug with high therapeutic efficacy in solid tumors; however, side effects are common with its use. Because cisplatin can be retained in the cochlea, ototoxicity leading to hearing loss limits its clinical applications. Here, we report that Nrf2 knockout (KO) strongly increased cisplatin resistance in HEI-OC1 cells, which are immortalized cells from the murine organ of Corti. The underlying mechanism of this phenomenon was uncovered, and an important novel therapeutic target for combating cisplatin-induced hearing loss was identified. Preliminary investigations determined that Nrf2 KO markedly decreased TfR1 protein levels and increased GPX4 protein levels. Thus, ferroptosis may protect organisms from cisplatin-induced cell death. Furthermore, Nrf2 KO cells were resistant to the classical ferroptosis inducers RSL3 and erastin, providing solid evidence that Nrf2 KO inhibits ferroptosis and that knocking out Nrf2 may be a new clinical strategy to prevent cisplatin-induced hearing loss.

N-acetylcysteine protect inner hair cells from cisplatin by alleviated celluar oxidative stress and apoptosis.

Cisplatin is a well-known platinum-based chemotherapy drug widely used to treat a variety of malignant tumors. However, cisplatin has serious side-effects include nephrotoxicity and ototoxicity, Cisplatin chemotherapy causes permanent hearing loss at least 40% of treated patients. Our results showed that 20 mM N-acetylcysteine (NAC) can completely protect 50 µM cisplatin-induced hair cell loss in rat cochlear culture and protects against cisplatin-induced hair cell loss in zebrafish in vivo. The fluorescence intensity of mitochondrial ROS significantly increased after the cultures were treated with 15 µM cisplatin for 48 h and was decreased in the group treated with 15 µM cisplatin add 20 mM NAC. In addition, the number of TUNEL positive hair cells was increased after the cultures were treated with 15 µM cisplatin for 48 h and there are null in cisplatin and NAC co-treated group.

[A cross-sectional study and risk factors analysis of tinnitus in flight support personnel of PLA air force].

Objective:The aim of this study is to understand the epidemiological characteristics of tinnitus among flight support personnel and analyze its audiological characteristics and related risk factors. Methods:The information of tinnitus was collected by a method of cross-sectional investigation using questionnaire survey and audiology test among the flight support personnel of two stations of PLA air force. Results:The incidence of tinnitus among 666 subjects included was 24.2%, the THI grade was mainly grade 1 and grade 2. There were differences in THI scores among groups with different working years, but only differences in tinnitus incidence among groups with different frequency of hearing loss. Multivariate logistic regression analysis showed that grade of high frequency hearing loss（OR=1.39）, conscious hearing loss（OR=1.79） and frequency of asking others to repeat words（OR=1.64） were independent risk factors of tinnitus. The incidence of HF-HL and EHF-HL in ears with tinnitus among 0-5 working years was higher than that without tinnitus, while the incidence of EHF-HL in ears with tinnitus was not different from that without tinnitus among 6-10 and >10 working years. There was moderate correlation between THI scores and SAS standard scores（r=0.759）, and weak correlation between THI scores and PSQI scores（r=0.445）. Conclusion:The risk of tinnitus in high-frequency hearing loss and recessive hearing loss is increased; working years can affect the severity of tinnitus, while hearing conditions at different frequencies only affect the incidence of tinnitus; with increasing age, noise exposure plays a role in the occurrence of tinnitus decreasing gradually.

mito-TEMPO Attenuates Oxidative Stress and Mitochondrial Dysfunction in Noise-Induced Hearing Loss via Maintaining TFAM-mtDNA Interaction and Mitochondrial Biogenesis.

The excessive generation of reactive oxygen species (ROS) and mitochondrial damage have been widely reported in noise-induced hearing loss (NIHL). However, the specific mechanism of noise-induced mitochondrial damage remains largely unclear. In this study, we showed that acoustic trauma caused oxidative damage to mitochondrial DNA (mtDNA), leading to the reduction of mtDNA content, mitochondrial gene expression and ATP level in rat cochleae. The expression level and mtDNA-binding function of mitochondrial transcription factor A (TFAM) were impaired following acoustic trauma without affecting the upstream PGC-1α and NRF-1. The mitochondria-target antioxidant mito-TEMPO (MT) was demonstrated to enter the inner ear after the systemic administration. MT treatment significantly alleviated noise-induced auditory threshold shifts 3d and 14d after noise exposure. Furthermore, MT significantly reduced outer hair cell (OHC) loss, cochlear ribbon synapse loss, and auditory nerve fiber (ANF) degeneration after the noise exposure. In addition, we found that MT treatment effectively attenuated noise-induced cochlear oxidative stress and mtDNA damage, as indicated by DHE, 4-HNE, and 8-OHdG. MT treatment also improved mitochondrial biogenesis, ATP generation, and TFAM-mtDNA interaction in the cochlea. These findings suggest that MT has protective effects against NIHL via maintaining TFAM-mtDNA interaction and mitochondrial biogenesis based on its ROS scavenging capacity.

Dynamic alterations of functional connectivity and amplitude of low-frequency fluctuations in patients with unilateral sudden sensorineural hearing loss.

Unilateral sudden sensorineural hearing loss (SSNHL) adversely affects the quality of life, leading to increased risk of depression and cognitive decline. Our previous studies have mainly focused on the static brain function abnormalities in SSNHL patients. However, the dynamic features of brain activity in SSNHL patients are not elucidated. To explore the dynamic brain functional alterations in SSNHL patients, age- and sex- matched SSNHL patients (n = 38) and healthy controls (HC, n = 44) were enrolled. The dynamic functional connectivity (dFC) and dynamic amplitude of low-frequency fluctuation (dALFF) methods were used to compare the temporal features and dynamic neural activity between the two groups. In dFC analyses, the multiple functional connectivities (FCs) were clustered into 2 different states; a greater proportion of FCs in SSNHL patients showed sparse state compared with HC. In dALFF analyses, SSNHL individuals exhibited decreased dALFF variability in bilateral inferior occipital gyrus, middle occipital gyrus, calcarine, right lingual gyrus, and right fusiform gyrus. dALFF variability showed a negative correlation with activated partial thromboplatin time. The dynamic characteristics of SSNHL patients were different from static functional connectivity and static amplitude of low-frequency fluctuation, especially within the visual cortices. These findings suggest that SSNHL patients experience cross-modal plasticity and visual compensation, which may be closely related to the pathophysiology of SSNHL.

Facial Nerve Meningioma: A Case Mimicking Facial Nerve Schwannoma.

Facial nerve meningioma is exceedingly rare and tends to affect the geniculate ganglion. We present a case of facial nerve meningioma located in the internal auditory canal with a "labyrinthine tail," mimicking facial nerve schwannoma. The clinical and radiological features, growth patterns, and surgical management were reviewed. Progressive facial paralysis was the main syndrome, similar to other facial nerve tumors. When facial nerve function is worse than House-Brackmann grade III, surgical resection should be performed with facial nerve reconstruction.

Hsp70/Bmi1-FoxO1-SOD Signaling Pathway Contributes to the Protective Effect of Sound Conditioning against Acute Acoustic Trauma in a Rat Model.

Sound conditioning (SC) is defined as "toughening" to lower levels of sound over time, which reduces a subsequent noise-induced threshold shift. Although the protective effect of SC in mammals is generally understood, the exact mechanisms involved have not yet been elucidated. To confirm the protective effect of SC against noise exposure (NE) and the stress-related signaling pathway of its rescue, we observed target molecule changes caused by SC of low frequency prior to NE as well as histology analysis in vivo and verified the suggested mechanisms in SGNs in vitro. Further, we investigated the potential role of Hsp70 and Bmi1 in SC by targeting SOD1 and SOD2 which are regulated by the FoxO1 signaling pathway based on mitochondrial function and reactive oxygen species (ROS) levels. Finally, we sought to identify the possible molecular mechanisms associated with the beneficial effects of SC against noise-induced trauma. Data from the rat model were evaluated by western blot, immunofluorescence, and RT-PCR. The results revealed that SC upregulated Hsp70, Bmi1, FoxO1, SOD1, and SOD2 expression in spiral ganglion neurons (SGNs). Moreover, the auditory brainstem responses (ABRs) and electron microscopy revealed that SC could protect against acute acoustic trauma (AAT) based on a significant reduction of hearing impairment and visible reduction in outer hair cell loss as well as ultrastructural changes in OHCs and SGNs. Collectively, these results suggested that the contribution of Bmi1 toward decreased sensitivity to noise-induced trauma following SC was triggered by Hsp70 induction and associated with enhancement of the antioxidant system and decreased mitochondrial superoxide accumulation. This contribution of Bmi1 was achieved by direct targeting of SOD1 and SOD2, which was regulated by FoxO1. Therefore, the Hsp70/Bmi1-FoxO1-SOD signaling pathway might contribute to the protective effect of SC against AAT in a rat model.

Altered Brain Activity and Functional Connectivity in Unilateral Sudden Sensorineural Hearing Loss.

Background: Sudden sensorineural hearing loss (SSNHL) is an otologic emergency and could lead to social difficulties and mental disorders in some patients. Although many studies have analyzed altered brain function in populations with hearing loss, little information is available about patients with idiopathic SSNHL. This study is aimed at investigating brain functional changes in SSNHL via functional magnetic resonance imaging (fMRI). Methods: Thirty-six patients with SSNHL and thirty well-matched normal hearing individuals underwent resting-state fMRI. Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and functional connectivity (FC) values were calculated. Results: In the SSNHL patients, ALFF and fALFF were significantly increased in the bilateral putamen but decreased in the right calcarine cortex, right middle temporal gyrus (MTG), and right precentral gyrus. Widespread increases in FC were observed between brain regions, mainly including the bilateral auditory cortex, bilateral visual cortex, left striatum, left angular gyrus (AG), bilateral precuneus, and bilateral limbic lobes in patients with SSNHL. No decreased FC was observed. Conclusion: SSNHL causes functional alterations in brain regions, mainly in the striatum, auditory cortex, visual cortex, MTG, AG, precuneus, and limbic lobes within the acute period of hearing loss.

Treating ischaemic stroke with intravenous tPA beyond 4.5 hours under the guidance of a MRI DWI/T2WI mismatch was safe and effective.

Purpose: Clinical trials have provided evidence that treating patients with acute ischaemic stroke (AIS) beyond 4.5 hours was feasible. Among them using MRI diffusion-weighted imaging/fluid attenuation inversion response (DWI/FLAIR) mismatch to guide intravenous tissue plasminogen activator (tPA) was successful. Our study explored the outcome and safety of using DWI/T2-weighted imaging (T2WI) mismatch to guide intravenous tPA therapy for patients with AIS between 4.5 hours and 12 hours of onset. Method: This was a retrospective study. Records of 1462 AIS patients with the time of onset of <12 hours were reviewed. Those had MRI rapid sequence study and had hyperintense signal on DWI but normal T2WI and received intravenous tPA up to 12 hours of onset were included in the analysis. Their demographics, risk factors, post-tPA complications, National Institutes of Health Stroke Scale (NIHSS) scores and outcome were recorded and analyse. χ2 was used to compare the intergroup variables. SAS was used to perform statistical calculation. A p<0.05 was considered statistically significant. Results: Of 1462 identified, 601 (41%) patients were entered into the final analysis. Among them, 327 (54%) had intravenous tPA within 4.5 hours of onset and 274 (46%) were treated between 4.5-12 hours. After intravenous tPA, 426 cases (71%) had >4 pints of improvement on NIHSS score within 24 hours. Postintravenous tPA, 32 (5.32%) cases had haemorrhagic transformation. 26 (4.33%) were asymptomatic ICH and 4 (0.67%) died. At 90 days, 523 (87%) achieved a modified Rankin scale of 0-2. Conclusion: Using MRI DWI/T2WI mismatch to identify patients with AIS for intravenous tPA between 4.5 hours and 12 hours was safe and effective. The outcome was similar to those used DWI/PWI or DWI/FLAIR mismatch as the screening tool. However, obtaining DWI/T2WI was faster and avoided the need of contrast material.