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.

Clinical Value of a Novel Magnetic Resonance Imaging Protocol and Prognostic Model Establishment for Sudden Sensorineural Hearing Loss: A Prospective Study.

INTRODUCTION: Sudden sensorineural hearing loss (SSNHL) is one of the most common acute symptoms in the otolaryngology department. Etiological diagnosis is the premise of effective treatment of SSNHL, and prognostic evaluation is the key. However, most of the patients are diagnosed as idiopathic due to a lack of overall assessment, while prognostic factors of SSNHL are numerous and controversial. Our purpose was to validate the potential value of a novel three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) MR protocol in SSNHL and to establish a clinical-image prognostic model for unilateral SSNHL. METHODS: This prospective study included consecutive patients from May 2019 to November 2021. Pathogenic diagnosis relied on expertise-based estimation and the associations of MR findings with clinical features of unilateral SSNHL were assessed. The prognostic evaluation of unilateral SSNHL was adopted for recovery and no recovery groups and complete and incomplete recovery groups. Significant clinical and MR features were compared and screened out by single-factor analyses. The primary clinical-image prognosis assessment model was built by multifactor logistic regression analyses. RESULTS: A total of 101 patients were enrolled in our study who acquired the correct etiological diagnosis based on the novel 3D-FLAIR MR combined with clinical examination. Among the 93 patients with unilateral SSNHL, 30.1% (28/93) showed labyrinthine abnormalities on 3D-FLAIR images. The severity of initial hearing loss in the MR+ group was worse than that in the MR- group (p < 0.05), and patients with positive MR findings tended to have poor recovery. An excellent prognostic model was built for hearing complete recovery and no recovery. The combination of three independent risk factors, including abnormal distortion products otoacoustic emission and transient evoked otoacoustic emission, the period from onset to treatment, and PTA at the onset, was adopted for hearing recovery/no recovery (accuracy = 90.2%, AUC = 0.820). Furthermore, adding the factor of positive MRI findings could improve the confidence for the judgment of hearing no recovery. The only independent risk factor, PTA at the onset, was adopted for complete/incomplete hearing recovery (accuracy = 86.1%, AUC = 0.874). CONCLUSION: The novel MR protocol had a good advantage in pathogenic diagnosis. Labyrinthine MR 3D-FLAIR signal abnormalities were related to the severity of an initial hearing loss and had a greater tendency to be found in patients with no recovery. A prognostic model with two main steps of unilateral SSNHL, mainly for SSNHL with no recovery and complete recovery, was built successfully and needed further verification by larger series of patients.

The Characteristic and Short-Term Prognosis of Tinnitus Associated with Sudden Sensorineural Hearing Loss.

Tinnitus is believed to result from the maladaptive plasticity of the auditory nervous system; reports regarding its severity and prognosis are conflicting. We evaluated the characteristic and short-term prognosis of tinnitus associated with sudden sensorineural hearing loss (SSNHL). A total of 230 cases were enrolled. The severity and 1-month prognosis of tinnitus (according to the Tinnitus Handicap Inventory (THI)) were assessed in terms of the patients' sex, age, level of hearing loss, type of audiogram results, and so on. According to our statistical analysis, the degree of handicap due to tinnitus was not related to sex, age, or level of hearing loss; the Tinnitus Handicap Inventory indicated that the low-frequency-audiogram group had a low tinnitus handicap (F = 7.516, P = 0.000). Furthermore, we found that the prognosis of tinnitus was not related to the type of audiogram or level of hearing loss. Recovery from a severe level of hearing loss was, however, found to be associated with a poor tinnitus prognosis (F = 5.203, P = 0.006). In summary, our study indicates that the association between tinnitus and SSNHL is extremely high. Tinnitus can be ameliorated by the successful treatment of hearing loss. The study was registered in the Chinese Clinical Trial Registry (ChiCTR1800014797).

The differentiation of Lgr5+ progenitor cells on nanostructures of self-assembled silica beads.

Supporting cells(SCs) have been demonstrated to be a reliable source for regenerating hair cells(HCs). Previous research has reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo. However, there is limited knowledge about the impact of the material on Lgr5+ cells. In this study, Lgr5+ cells were isolated from neonatal Lgr5-EGFP-CreERT2 transgenic mice by flow cytometry and then plated on self-assembled silica beads (SB). Lgr5+ cell differentiation was observed by immunofluorescence. We found that in the direct differentiation assay, the SB group generated more hair cells than the control group(*p < 0.05). Especially in the SB group, Lgr5+ progenitors generated significantly more Myo7a+ HCs outside of the colony than in the control group(**p < 0.01). In the sphere differentiation assay, we found that the diameter of spheres in the SB group was significantly larger compared to those of the control group(**p < 0.01). However, the difference in the ratio of myo7a+ cell counts was not obvious(P>0.05). The experiment proved that the self-assembled silica beads could promote the differentiation of Lgr5+ progenitors in vitro. Our findings implicate that nanostructures of self-assembled silica beads can be used as vectors for stem cell research in the inner ear.

On the Intelligent Computing Model of Diagnosis Teaching in Preschool Education in Colleges and Universities under the Background of Big Data.

In order to infer the cognitive state of students and provide teachers with the potential learning state of students, a diagnostic teaching model for preschool education in colleges and universities under the background of big data is proposed. By increasing students' programming ability and modeling students' theoretical and practical abilities at the same time, the cognitive diagnosis is introduced into the field of computer teaching, so as to make it applicable to computer classrooms and provide students' cognitive information needed for teaching. The experimental results show that the advantages of the CDF-CSE approach gradually emerge as the training data become sparse (the proportion of training data decreases from 80% to 20%). In the combined questions of the three datasets, when the training set is 20% and MAE is used as the criterion, the CDF-CSE model improves by 47.8%, 65.8%, and 49.8%, respectively, compared with the other methods that perform best on the training set. When the number of questions is small, the CDF-CSE model improves by 37.8%, 42.5%, and 27.7% on RMSE on three datasets, respectively, compared with the best-performing other methods. When there are more questions, it has 32.3%, 36.5%, and 45.6% improvement, respectively. It is concluded that this model can accurately predict students' performance in computer courses and provide detailed and rich cognitive reports.

Graphene Substrates Promote the Differentiation of Inner Ear Lgr5+ Progenitor Cells Into Hair Cells.

The ideal treatment for sensory hearing loss is to regenerate inner ear hair cells (HCs) through stem cell therapy, thereby restoring the function and structure of the cochlea. Previous studies have found that Lgr5+ supporting cells (SCs) in the inner ear can regenerate HCs, thus being considered inner ear progenitor cells. In addition to traditional biochemical factors, physical factors such as electrical conductivity also play a crucial role in the regulation of stem cell proliferation and differentiation. In this study, the graphene substrates were used to culture Lgr5+ progenitor cells and investigated their regulatory effects on cells. It was demonstrated that the graphene substrates displayed great cytocompatibility for Lgr5+ progenitors and promoted their sphere-forming ability. Moreover, more Myosin7a+ cells were found on the graphene substrates compared with tissue culture polystyrene (TCPS). These results suggest that graphene is an efficient interface that can promote the differentiation of Lgr5+ progenitors into HCs, which is great significance for its future application in combination with Lgr5+ cells to regenerate HCs in the inner ear.

Treatment of subjective tinnitus: a comparative clinical study of intratympanic steroid injection vs. oral carbamazepine.

BACKGROUND: Over the last decade, more and more otologists have been using the intratympanic perfusion of steroids to treat SSHL, tinnitus, and vertigo. However, results of the treatment in the literature are controversial because most of the reports were retrospective and uncontrolled. Therefore a prospective random single-blind trial was conducted at the Affiliated Drum Tower Hospital of Nanjing University Medical School, P. R. China. The results were compared with oral carbamazepine treatment. Carbamazepine is a medication routinely used to treat tinnitus. MATERIAL/METHODS: Seventy-nine patients (84 ears) with subjective tinnitus which failed to respond to a minimum of four-week systemic medical therapy were assigned to a study group and a control group by a random, single-blind method. The study group was further randomly divided into two subgroups. The participants in the study group received either 0.5-ml intratympanic injections of prednisolone (study group 1) or dexamethasone (study group 2). The patients in the control group only took carbamazepine. The effective rates at the end of the therapy and the control rates at the end of a six-month follow-up were analyzed statistically. RESULTS: There were no statistical differences in the effective and control rates among the three groups. CONCLUSIONS: Intratympanic steroid injection has positive effects similar to those of oral carbamazepine in subjective tinnitus. Intratympanic steroid injection may be considered an alternative treatment for subjective tinnitus.

Resection of recurrent third branchial cleft fistulas assisted by flexible pharyngotomy.

BACKGROUND: Treatment of fistulas arising from the third branchial cleft includes endoscopic cauterization or open cervical fistulectomy. Both approaches are associated with recurrence rates of 14%-18%, and possibly greater rates when the fistula has been treated operatively beforehand. Treatment of fistulas arising from the third branchial cleft is associated with an inordinate recurrence rate. Recurrence may be multifactorial and related to incomplete resection of all of the anatomical elements of the fistula. AIM: To present a new approach that involves complete resection of the recurrent fistula by a combined therapeutic approach. METHODS: Here, 12 adult patients diagnosed with recurrent third branchial cleft fistulas underwent a combined therapy assisted by flexible fiber-optic pharyngoscopy to identify and resect the entry site of the fistula into the pyriform sinus. The fistulous opening into the pyriform sinus was identified by flexible fiber-optic pharyngoscopy. The application of intubation with a guidewire by pharyngoscopy, in addition to the removal of the partial excision of the thyroid cartilage, allowed complete resection of the opening and all parts of the fistula tract. RESULTS: All of the internal openings of the fistulas in the pharynx were found and easily identified by flexible fiber-optic pharyngoscopy. All of the 12 patients underwent complete resection of the recurrent fistula by the combined therapeutic approach. There were no postoperative complications such as parapharyngeal abscess or wound infection, injury or dysfunction of the recurrent laryngeal or superior laryngeal nerves. The pharyngeal edema had degraded, and the pharyngeal wound healed postoperatively within 1 wk. Laryngeal endoscopy and voice analysis were performed on the 14th d post-operatively. Vocal cord movements did not change. The characters of voice for jitter, shimmer, and normalized noise energy were all within normal limits. In addition, no recurrences were observed during the 13-60 mo follow-up period. CONCLUSION: It can be concluded that the proposed combined therapy is associated with excellent results, minimal morbidity, and no recurrence.

Autophagy protects auditory hair cells against neomycin-induced damage.

Aminoglycosides are toxic to sensory hair cells (HCs). Macroautophagy/autophagy is an essential and highly conserved self-digestion pathway that plays important roles in the maintenance of cellular function and viability under stress. However, the role of autophagy in aminoglycoside-induced HC injury is unknown. Here, we first found that autophagy activity was significantly increased, including enhanced autophagosome-lysosome fusion, in both cochlear HCs and HEI-OC-1 cells after neomycin or gentamicin injury, suggesting that autophagy might be correlated with aminoglycoside-induced cell death. We then used rapamycin, an autophagy activator, to increase the autophagy activity and found that the ROS levels, apoptosis, and cell death were significantly decreased after neomycin or gentamicin injury. In contrast, treatment with the autophagy inhibitor 3-methyladenine (3-MA) or knockdown of autophagy-related (ATG) proteins resulted in reduced autophagy activity and significantly increased ROS levels, apoptosis, and cell death after neomycin or gentamicin injury. Finally, after neomycin injury, the antioxidant N-acetylcysteine could successfully prevent the increased apoptosis and HC loss induced by 3-MA treatment or ATG knockdown, suggesting that autophagy protects against neomycin-induced HC damage by inhibiting oxidative stress. We also found that the dysfunctional mitochondria were not eliminated by selective autophagy (mitophagy) in HEI-OC-1 cells after neomycin treatment, suggesting that autophagy might not directly target the damaged mitochondria for degradation. This study demonstrates that moderate ROS levels can promote autophagy to recycle damaged cellular constituents and maintain cellular homeostasis, while the induction of autophagy can inhibit apoptosis and protect the HCs by suppressing ROS accumulation after aminoglycoside injury.

The assessment of hearing impairment among healthy children in rural and urban areas in China.

OBJECTIVE: To investigate the auditory function of healthy children and provide experimental data to protect children's hearing in China. METHODS: Total of 191 normally growing children (6-12 years old) in Qinling mountain area, the pasturing area around Qinghai Lake and Nanjing city were randomly included in this study. The whole-frequency auditory thresholds of these children were examined. RESULTS: There was significant difference between the boys' and girls' auditory thresholds at nearly the whole frequencies in the Qinling area. Significant difference was also found between the boys' and girls' auditory thresholds at high frequencies and super high frequencies in the pasturing area around Qinghai Lake. Overall, the girls' auditory function was much better than the boys'. In contrast, there was no significant difference between the boys' and girls' auditory thresholds in Nanjing city. The auditory thresholds in high frequencies and super high frequencies of the boys in Nanjing city were lower than those of the boys in mountain and plateau pasturing areas, while there was no significant difference of the girls' auditory thresholds between city and rural areas except for a few low frequencies. CONCLUSIONS: Hearing impairment was found in Chinese children of rural areas, especially among the boys. Since the children in rural areas should have no chance to be exposed to the modern industrial noises, it is most likely that the impulse noises from firecrackers caused the partial loss of hearings.

[Comparative evaluation of over-under myringoplasty and underlay myringoplasty for repairing tympanic membrane perforation].

OBJECTIVE: To evaluate the effect of over-under myringoplasty technique on repairing tympanic membrane perforation regarding with the rate of perforation closure, the frequency of postoperative complications occurrence and the level of hearing improvement. METHOD: In this retrospective study, a total of 74 patients (77 ears) underwent myringoplasty and had been followed up for over 6 months, which was performed by means of the underlay technique in 44 patients (45 ears) and over-under technique in 30 patients (32 ears) from Jan 2002 to Jan 2007. In the underlay group, the grafted membrane was placed medial to the remaining drum and the manubrium of the malleus. In the over-under group, the grafted membrane was placed under the remaining drum and over the malleus. Comparatively evaluate the effect of the underlay technique and that of the over-underlay technique on repairing tympanic membrane perforation. RESULT: The rate of perforation closure and hearing improvement in the underlay group of 45 ears was 89.0% and 57.5% respectively, while that in the over-under group of 32 ears were 87.5% and 71.9% respectively. The air-bone gap decreased by 4.9 dB in the underlay group, while it decreased by 9.7 dB in over-under group. After more than 6 months of following-up, the frequency of postoperative atelectasis of the underlay group and the over-under group was 17.8% and 6.25% respectively. Meanwhile, the frequency of postoperative reperforation of these two groups was 5.9% and 6.25% respectively. Blunting of the anterior angle of the tympanic membrane occurred in 3 ears in the over-under group. Lateralization of the graft was not observed in either group. CONCLUSION: Over-under technique could reduce the occurrence of the adhesions between the grafted membrane and promontorium tympani by placing the grafted membrane between the remaining drum and the malleus. Furthermore, the level of hearing improvement in over-under group was higher than that in underlay group. Over-under myringoplasty is a more effective technique as comparison to underlay myringoplasty for repairing middle to large tympanic membrane perforations.

[Analysis of auditory function on normal growth children in city and rural areas].

OBJECTIVE: To study the auditory function of Chinese normal growth children, and to get a first hand data for protecting children's hearing. METHOD: The normal growth children (6 to 12 years old) in Qinling mountain area, pasturing area around Qinghai Lake and Nanjing city were included in the study, and their whole frequency auditory thresholds were examined on the spot. The auditory thresholds were analyzed. RESULT: There was significant difference between the boys' and girls' auditory thresholds among nearly the whole frequency in Qinling mountain. And there was significant difference between the boys' and girls' auditory thresholds among high frequency and super high frequency in pasturing area around Qinghai Lake, while the girls' auditory function was better than the boys'. In contrast, in Nanjing city no difference was found between the boys' and girls' auditory thresholds. The auditory thresholds in high frequency and super high frequency of the boys in Nanjing city were lower than those of the boys in mountain area and plateau pasturing area, while there was no difference between the girls except for low frequency. CONCLUSION: Worse auditory function was found in Chinese rural areas, especially among the boys. According to the local residents' living condition, the children in remote area nearly had no chance to receive the modern industrial noise and other strong noise. So the firecrackers' noise perhaps made this situation. And the education to avoid the firecrackers' noise must be put into practice in Chinese rural area since childhood.