Pcolce2 overexpression promotes supporting cell reprogramming in the neonatal mouse cochlea.

Hair cell (HC) damage is a leading cause of sensorineural hearing loss, and in mammals supporting cells (SCs) are unable to divide and regenerate HCs after birth spontaneously. Procollagen C-endopeptidase enhancer 2 (Pcolce2), which encodes a glycoprotein that acts as a functional procollagen C protease enhancer, was screened as a candidate regulator of SC plasticity in our previous study. In the current study, we used adeno-associated virus (AAV)-ie (a newly developed adeno-associated virus that targets SCs) to overexpress Pcolce2 in SCs. AAV-Pcolce2 facilitated SC re-entry into the cell cycle both in cultured cochlear organoids and in the postnatal cochlea. In the neomycin-damaged model, regenerated HCs were detected after overexpression of Pcolce2, and these were derived from SCs that had re-entered the cell cycle. These findings reveal that Pcolce2 may serve as a therapeutic target for the regeneration of HCs to treat hearing loss.

Reduced Intra- and Inter-Network Functional Connectivity Identified in Patients with Tinnitus with and without Hearing Loss.

INTRODUCTION: The aim of the study was to investigate differences in the intra- and inter-network functional connectivity (FC) of the brain using resting-state functional magnetic resonance imaging (rs-fMRI) in patients with tinnitus, with (T + H) or without hearing loss (T). METHODS: We performed rs-fMRI on 82 participants (21 T, 32 T + H, and 29 healthy controls). An independent component analysis (ICA) was performed to obtain the resting-state networks (RSNs) and calculate the differences in FC. Moreover, we investigated the relationships between networks using functional network connectivity analysis. RESULTS: We identified nine major RSNs, including the auditory network; default mode network; executive control network (ECN), including the right frontoparietal network and left frontoparietal network (LFPN); somatomotor network (SMN); dorsal attention network; ventral attention network; salience network (SN); and visual network (VN). These RSNs were extracted in all groups using ICA. Compared with that in the control group, we observed reduced FC between the LFPN and VN in the T group and between the LFPN and SN in the T + H group. The inter-network connectivity analysis revealed decreased network interactions in the SMN (IC 22)-ECN (IC 2), SMN (IC 22)-VN (IC 8), and VN (IC 14)-SN (IC 3) connections in the T + H group, compared with the healthy control group. Furthermore, we observed significantly decreased network interactions in the SMN (IC 22)-VN (IC 8) in the T group. CONCLUSIONS: Our results indicated abnormalities within the brain networks of the T and T + H groups, including the SMN, ECN, and VN, compared with the control group. Furthermore, both T and T + H groups demonstrated reduced FC between the LFPN, VN, and SMN. There were no significant differences between the T and the T + H groups. Furthermore, we observed reduced FC between the right olfactory cortex and the orbital part of the right middle frontal gyrus, right precentral gyrus, left dorsolateral superior frontal gyrus, and right triangular part of the inferior frontal gyrus within the T and T + H groups. Thus, disruptions in brain regions responsible for attention, stimulus monitoring, and auditory orientation contribute to tinnitus generation.

Characteristics of large vestibular aqueduct syndrome in wideband acoustic immittance.

Objective: To describe the characteristics of large vestibular aqueduct syndrome (LVAS) in wideband acoustic immittance (WAI) and to explore whether inner ear deformity has an impact on WAI results. Methods: Subjects with typical LVAS (LVAS group) and control subjects with a normal anatomical structure of the inner ear (control group) were screened from pediatric patients with cochlear implants using thin-slice computed tomography (CT) images of the temporal bone. With inflammation of the auditory canal and middle ear excluded by routine ear examination and 226 Hz acoustic immittance, WAI data were acquired. Then, the maximum absorbance as the major observation indicator on the mean tympanogram was compared between the LVAS group and control group, and a descriptive comparison of the mean tympanogram and frequency-absorbance curve at peak pressure was performed between the two groups. Results: The LVAS group included 21 cases (38 ears), and the control group included 27 cases (45 ears). All LVAS subjects met the Valvassori criteria, and the VA at the horizontal semicircular canal displayed flared expansion. On the mean tympanogram, the maximum absorbance in the LVAS group (0.542 ± 0.087) was significantly higher than that in the control group (0.455 ± 0.087) (p < 0.001). The tympanogram in the LVAS group showed an overall elevation, and the absorbance at all pressure sampling points was significantly higher than that in the control group (p < 0.001). The frequency-absorbance curve at peak pressure first increased and then decreased in both groups, and the LVAS group showed higher absorbance than the control group in the frequency range below 2,828 Hz. The absorbance at 343-1,124 Hz was significantly different between the two groups (p < 0.001), and 343-1,124 Hz was the major frequency range at which the maximum absorbance on the mean tympanogram increased in the LVAS group. Conclusion: Large vestibular aqueduct syndrome (LVAS) shows increased absorbance in low and medium frequency ranges in WAI. The maximum absorbance on the mean tympanogram can serve as a reliable evaluation indicator. Inner ear factors must be considered when middle ear lesions are analyzed by WAI.

[Long-term hearing outcomes of children with cochlear implant].

Objective:To investigate the long-term rehabilitation outcomes of children with cochlear implants（CI） and provide constructive guidance for clinical application. Methods:Fifteen children with unilateral CI over 5 years（CI group） were recruited. Ten children with normal hearing were recruited as the healthy control group. The project collected aided sound-field hearing thresholds and speech recognition scores using disyllabic words and C-HINT sentences with and without speech noise for 15 children with unilateral CI. In addition, children's guardians were requested to fill out the Mandarin Parental Perspectives questionnaire（MPP） in order to evaluate the hearing aspects of quality of life. MPP results from the 15 children were then compared with previous responses from 17 unilateral CI children whose overall CI wearing time was one year（CI control group）. Results:The aided pure-tone average（PTA） of the recruited children was below 35 dB HL, all children reached 80% for the speech recognition test in a quiet environment, yet their performance decreased in a noisy environment. Regarding the hearing aspects of the MPP questionnaire results, recruited children demonstrated better results than those from CI control group（P<0.05）. Speech noise had a significant impact on the recognition rate, and the CI group had higher recognition rate scores in the quiet environment than in the noise environment（two-syllable words t=18.81, P<0.001, short sentences t=16.48, P<0.001）. In the comparison of quality of life, in the dimension of "support for children", both the CI group and the CI control group can obtain better benefits, and there is no statistically significant difference between the groups（P>0.05）. The CI group benefited more significantly, and the scores were higher than those of the CI control group（P<0.05）. Conclusion:The long-term hearing outcome of children with CI is adequate for daily communication, but there is still a gap compared with hearing children of the same age, and they still need support from the entire society.

[Effect of cochlear implantation on speech recognition under different listening modes in children].

Objective:To investigate speech recognition among children with a unilateral cochlear implant（CI）, bilateral CI, and bimodal hearing and identify the benefits of binaural hearing. Methods:A total of 67 children with severe sensorineural hearing loss who received bilateral CI, bimodal hearing, and unilateral CI from 2012 to 2021 were recruited, including 23 cases with unilateral CI, 25 cases of bimodal hearing, and 19 cases of bilateral CI. The aided hearing threshold at 250-4000 Hz and speech recognition performance of two-syllable words and short sentences in quiet and noisy environments were tested, respectively. Results:There was no significant difference in the hearing threshold results of the bilateral CI group, the bimodal hearing group, and the unilateral CI group by ANOVA（P>0.05）. According to the paired t-test within the group, the speech recognition of disyllabic words and short sentences in quiet and noisy environments were significantly different among the three groups（P<0.05）. There was no significant difference in the speech recognition rates of disyllabic words and short sentences among the three groups in a quiet environment（P>0.05）, but there was a statistically significant difference in a noisy environment（P<0.05）. Additional multiple linear regression analysis showed no significant difference in the recognition rates of disyllabic words and short sentences between the bimodal group and the bilateral CI group in quiet and noisy environments（ß=-0.567, P>0.05; ß=-0.643, P>0.05）. There was a statistically significant difference in speech recognition of disyllabic words and short sentences between the bimodal group and the unilateral CI group in the noise environment（ß=-0.124, P<0.05）, but the difference was not statistically significant in a quiet environment（ß=-0.671, P>0.05）; there was a statistically significant difference in the recognition rate of disyllabic words and short sentences between the bilateral CI group and the unilateral CI group in the noise environment（ß=-0.226, P<0.05）, but the difference was not statistically significant in a quiet environment（ß=-0.341, P>0.05）. Conclusion:Clinicians and guardians are encouraged to provide the most comprehensive audiological evaluation for children with hearing loss. Bilateral CI and bimodal hearing have demonstrated enormous advantages over unilateral CI regarding speech recognition in noise. Bimodal hearing deems a strong recommendation if the contralateral ear has sufficient speech recognition capability. Bilateral CI should be warranted if hearing aids deemed to be ineffective.

Recent-onset and persistent tinnitus: Uncovering the differences in brain activities using resting-state functional magnetic resonance imaging technologies.

Objective: This study aimed to investigate the differences in intra-regional brain activity and inter-regional functional connectivity between patients with recent-onset tinnitus (ROT) and persistent tinnitus (PT) using resting-state functional magnetic resonance imaging (rs-fMRI), including the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and voxel-wise functional connectivity (FC). Method: We acquired rs-fMRI scans from 82 patients (25 without recent-onset tinnitus, 28 with persistent tinnitus, and 29 healthy controls). Age, sex, and years of education were matched across the three groups. We performed ALFF, ReHo, and voxel-wise FC analyses for all patients. Results: Compared with the control group, participants with ROT and PT manifested significantly reduced ALFF and ReHo activity within the left and right dorsolateral superior frontal gyrus (SFG) and gyrus rectus (GR). Additional voxel-wise FC revealed decreased connectivity between the dorsolateral SFG (left and right) and the right superior parietal gyrus (SPG), right middle frontal gyrus (MFG), and left medial superior frontal gyrus (mSFG) within these two groups. Significant differences were observed between the ROT and PT groups, with the ROT group demonstrating reduced FC. Conclusion: Our data suggest that patients with PT have more difficulty monitoring external stimuli and reorienting attention than patients with ROT. In addition, patients who perceive higher levels of disruption from tinnitus are more likely to develop persistent and debilitating tinnitus once the tinnitus lasts longer than six months. Therefore, we strongly recommend that clinicians implement effective tinnitus management strategies in patients with ROT as soon as possible.

Influence of cochlear implants on hearing-related quality of life: results from Chinese children with cochlear implants entering mainstream education.

OBJECTIVES: This study aimed to 1) assess the hearing-related Quality of Life (QoL) of children with cochlear implants (CIs) in China and 2) investigate the impact of CI in children and of the socio-demographic backgrounds of their guardians on the hearing-related QoL of children with CIs in the Chinese mainstream education system. METHODS: This study used the Mandarin Children with Cochlear Implants: Parental Perspectives questionnaire (MPP), which assessed the communication capability, auditory perception, self-independence, level of happiness with family, social interaction, academic performance, outcome assessment for CI, and level of family support in children with CIs. Both univariate and multiple linear regression analyses were performed to identify the relationship of CI in children and the socio-demographic backgrounds of their guardians with hearing-related QoL in children with CI. RESULT: A total of 124 responses were collected, and they indicated satisfaction and improvement across all aspects of the MPP Questionnaire. Statistical analysis revealed that an earlier age of cochlear implantation (≤3 years old) could improve the communication capabilities, self-independence, social interaction performance, and academic performance of children with CIs. In addition, children with CI from the urban regions demonstrated better social interaction performance than that by those from the rural regions of China. CONCLUSION: CIs can improve hearing-related QoL in children with pre-lingual or congenital hearing loss entering the mainstream education system in China. This study showed that early age of cochlear implantation was critical for successful long-term auditory development and academic achievement in children with CIs in China. Therefore, healthcare professionals and educators in China should advocate for CI for children with severe congenital or pre-lingual hearing loss.