Uptake of gadolinium and dexamethasone in rat inner ear and facial nerve using different administrations.

BACKGROUND: The pathway by which drugs are injected subcutaneously behind the ear to act on the inner ear has not been fully elucidated. OBJECTIVES: To compare the uptake of gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (Dex) in the cochlea and facial nerve of rats following different administrations. MATERIALS AND METHODS: Magnetic resonance imaging was applied to observe the distribution of Gd-DTPA in the facial nerve and inner ear. We observed the uptake of Dex after it was injected with different methods. RESULTS: Images of the intravenous (IV) and intramuscular (IM) groups showed that the bilateral cochlea of the rat was visualized almost simultaneously. While in the left post-auricular (PA) injection group, it was asynchronous. The maximum accumulation (Cmax) of the Gd in the left facial nerve of the PA group (35.406 ± 5.32) was substantially higher than that of the IV group (16.765 ± 3.7542) (p < .01). CONCLUSIONS: Compared with systemic administration, PA has the advantages of long Gd and Dex action time and high accumulation concentration to treat facial nerve diseases. SIGNIFICANCE: The distribution of Gd and Dex in the inner ear and facial nerve of rats following PA injection might be unique.

Compensation in neuro-system related to age-related hearing loss.

BACKGROUND: Age-related hearing loss (ARHL) is a major cause of chronic disability among the elderly. Individuals with ARHL not only have trouble hearing sounds, but also with speech perception. As the perception of auditory information is reliant on integration between widespread brain networks to interpret auditory stimuli, both auditory and extra-auditory systems which mainly include visual, motor and attention systems, play an important role in compensating for ARHL. OBJECTIVES: To better understand the compensatory mechanism of ARHL and inspire better interventions that may alleviate ARHL. METHODS: We mainly focus on the existing information on ARHL-related central compensation. The compensatory effects of hearing aids (HAs) and cochlear implants (CIs) on ARHL were also discussed. RESULTS: Studies have shown that ARHL can induce cochlear hair cell damage or loss and cochlear synaptopathy, which could induce central compensation including compensation of auditory and extra-auditory neural networks. The use of HAs and CIs can improve bottom-up processing by enabling 'better' input to the auditory pathways and then to the cortex by enhancing the diminished auditory signal. CONCLUSIONS: The central compensation of ARHL and its possible correlation with HAs and CIs are current hotspots in the field and should be given focus in future research.

The Breakdown of Blood-Labyrinth Barrier Makes it Easier for Drugs to Enter the Inner Ear.

PURPOSE: This study aimed to investigate dynamic change of permeability of blood-labyrinth barrier (BLB) after noise exposure and its effect on the drug delivery efficiency of systemic administration. METHODS: Gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (DEX) were used as tracers, and magnetic resonance imaging (MRI) and immunofluorescence were used to observe the change of the BLB after strong noise exposure in guinea pigs. High-performance liquid chromatography-mass spectrometry (LC-MS) was used to observe the effect of the breakdown of BLB after noise exposure on the drug delivery efficiency of intravenous DEX. The guinea pigs were divided into 6 groups: normal group (N), 1, 3, 5, 8, and 12 days after noise exposure groups (P1, P3, P5, P8, P12), with 5 animals in each group. RESULTS: The BLB changes dynamically after noise exposure. Increased permeability of the blood-endolymph barrier, the endolymph-perilymph barrier, and the blood-nerve barrier was observed at days 1-3, 1-5, and 1-8, respectively, after noise exposure in guinea pigs. Higher drug concentration in the cochlear tissue was obtained by intravenous administration of DEX in guinea pigs during the time window of increased permeability of the BLB. CONCLUSION: After noise exposure, the increased BLB permeability makes it easier for drugs to enter the inner ear from blood. In guinea pigs, 1-8 days after strong noise exposure, the drug delivery efficiency of systemic administration increased. After 8 days, the efficiency gradually returned to normal level. 1-8 days after noise exposure may be the best intervention time for systemic administration. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2377-2386, 2024.

The auditory function in migraine model rats induced by postauricular nitroglycerin injection.

Objective: The mechanism by which migraines produce inner ear-related symptoms is not well understood. Previous studies have found that the latency of auditory brainstem response (ABR) in animal models of migraine has changed, but the threshold has not changed significantly. Therefore, it is necessary to establish a better animal model with both migraine and hearing loss to explore the relationship between migraine and auditory function deeply. Methods: In this study, the rat model of migraine was induced by postauricular injection of nitroglycerin (NTG), and the effect on the auditory function of the inner ear was explored by comparing with intraperitoneal injection of nitroglycerin. The rats were given the drug repeatedly on alternate days, a total of 5 dosing, with the body weight monitored during the drug administration. The tactile threshold of the rats' forepaw was measured using von-Frey filaments and auditory function was assessed by ABR. Results: The results showed that the baseline tactile threshold of rats gradually decreased during the modeling process, and hyperalgesia appeared. Postauricular injection of NTG did not affect the weight gain of rats, while intraperitoneal injection of NTG showed slow or even negative weight gain. The ABR threshold of Click, 4 and 8 kHz of postauricular NTG injection rats increased, the latency was prolonged, and the ABR threshold in the right ear was higher than that in the left ear. Conclusions: We demonstrated that postauricular injection of nitroglycerin may be safer and more effective than intraperitoneal injection of nitroglycerin in the process of creating rat migraine model without affecting the weight gain. Postauricular injection of nitroglycerin has more damage to the auditory function of rats. Therefore, the migraine model rat induced by postauricular injection of nitroglycerin may be a new model of cochlear migraine.

A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss

Abstract Objectives: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. Methods: The basic clinical data of Ol proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. Results: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the Ol progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. Conclusion: The clinical symptoms of the Ol proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for Ol patients with hearing loss. Level of evidence: Level 4.

Case report: MRI changes of the inner ear in an MD patient with suspected immune dysfunction.

Objectives: The primary objective of this study was to present the progressive changes from labyrinthitis to endolymphatic hydrops (EH) demonstrated in the inner ear MRI of a patient with MD and suspected immune dysfunction. Patient: This 31-year-old male was diagnosed with MD and suspected autoimmune diseases. Interventions: Immunosuppressants and biological agents. Main outcomes measures: Inner ear MRI images. Results: Changes in the patient's progress revealed that inner ear immune and inflammatory changes might induce EH, which may eventually turn into MD. Conclusion: This case is the first documented case of MRI revealing progressive changes from inflammatory response to endolymphatic hydrops in the inner ear. It shows the correlation between MD and inflammation visually. It is of great significance to reveal the pathogenesis of MD to further assist in the guidance of treatment decision making.

A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss.

OBJECTIVES: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. METHODS: The basic clinical data of OI proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. RESULTS: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the OI progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. CONCLUSION: The clinical symptoms of the OI proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for OI patients with hearing loss. LEVEL OF EVIDENCE: Level 4.

Gene expression profiles of mRNA, lncRNA, miRNA, and circRNA and their clinical implications in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with complex pathophysiology and therapeutic strategies. Moreover, the molecular mechanisms underlying the pathogenesis of CRSwNP are incompletely understood. OBJECTIVE: This study aimed to investigate the transcriptomic characteristics, ceRNA networks, and whether these molecular markers play a role in the occurrence and development of CRSwNP. METHODS: Following RNA sequencing, a ceRNA network was predicted and constructed based on the sequencing results and multiple databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and disease ontology (DO) were applied to analyze the potential mechanisms in relation to the pathogenesis of CRSwNP. CIBERSORT was used to evaluate the immune cell infiltration levels in CRSwNP. The candidate genes of differentially expressed (DE) mRNA, DE-lncRNA, DE-miRNA, and DE-circRNA were verified by RT-qPCR, and the back-splice junction of circRNA was verified using Sanger sequencing. The clinical significance of differentially expressed genes was analyzed with correlation test and receiver operating characteristic curve. RESULTS: We identified 716 DE-mRNA, 230 DE-lncRNA, 42 DE-miRNA, and 46 DE-circRNA, and GO and KEGG enrichment analyses indicated that they were involved in multiple biological pathways, predominantly those associated with immunity and inflammation. DO analysis revealed CRSwNP is associated with diseases such as gastroesophageal reflux and allergic reactions. High expression of circ_0021727 was significantly and positively correlated with several important clinical indicators, and the area under the curve was 0.741. CONCLUSIONS: This study provides transcriptomic characteristics, which are potential biomarkers or therapeutic targets for the diagnosis and treatment of CRSwNP.

Individual treatment strategy of thyroglossal duct cyst carcinoma: a case report.

Background: Neoplasia of ectopic thyroid components is relatively rare in thyroglossal duct cysts. We report a case of histopathologically confirmed papillary thyroid carcinoma in a thyroglossal duct cyst, discuss its clinical characteristics of, and provide reference for diagnosis and treatment. Case Description: We presented a 25-year-old female went to hospital because of "a tumor in her neck". She was preoperatively diagnosed with thyroglossal duct cyst by cervical ultrasound, and enhanced computed tomography (CT). However, the solid component of the mass suggested intracystic neoplasia. She underwent Sistrunk surgical resection, and postoperative histopathology showed thyroglossal duct cyst, and papillary thyroid carcinoma in the cyst wall. The patient had no high-risk factors and had a low risk of recurrence. After full disclosure, the patient chose close follow-up, and to date there has been no recurrence. Conclusions: There are controversies regarding the origin of thyroglossal duct cyst carcinoma and the extent of surgery required, and a lack of unified treatment guidelines. We recommend tailoring individualized treatment based on individual risk stratification. By reporting this case, we hope to inform surgeons of the various abnormalities that may occur in ectopic thyroid tissue.

The plasma fibrinogen levels in the nitroglycerin-induced chronic migraine rat model and its association between migraine-associated vestibular dysfunction.

The purpose of this study was to measure the vestibular function and plasma fibrinogen level in the nitroglycerin (NTG)-induced chronic migraine rats, and explore the effect of defibrinogenation on migraine and associated vestibular dysfunction. The chronic migraine rat model was built by recurrent NTG injection. Batroxobin was administrated as a defibrinogenating drug. We measured the mechanical withdrawal threshold, vestibular function, and fibrinogen level of the rats 30 min before and 2 h following the model establishment, as well as 1 h after batroxobin administration. The results showed that vestibular function was impaired in NTG-induced chronic migraine rats. The fibrinogen levels were increased following repeated NTG injections. However, defibrinogenation did not affect either aggravating or alleviating mechanical hyperalgesia or vestibular dysfunction in the migraine model rats. These findings suggest that the NTG-induced chronic migraine rat model can be used for research on migraine-associated vestibular symptoms. Albeit the association between elevated fibrinogen levels and migraine attacks can be observed, the role of excessive fibrinogen in the pathogenesis of chronic migraine is yet to be determined.

Diagnosis, differential diagnosis, and treatment for sudden sensorineural hearing loss: Current otolaryngology practices in China.

Introduction: Although sudden sensorineural hearing loss (SSNHL) has been attempted to be understood for 70 years, diagnosis and treatment strategies still have strong heterogeneity worldwide, which are reflected in the guidelines issued by countries and the clinical practice of otolaryngologists. Methods: Questionnaires were sent to registered otolaryngologists nationwide via an online questionnaire system. We investigated the current views and clinical practices of otolaryngologists in mainland China about the diagnosis, examination, and treatment strategies of SSNHL. Results: Most otolaryngologists supported diagnostic classification via audiograms. Regional economic situation and hospital grade affected application strategies for differential diagnosis. Regarding corticosteroid therapy, 54.9% of respondents opted to discontinue the drug 5 days after systemic administration. Both intratympanic therapy and post-auricular injections were selected by more than half of the respondents as initial and salvage treatments. Discussion: Chinese otolaryngologists exhibit heterogeneity in clinical practices for SSNHL, including distinct approaches to combination therapy and local application of steroids. This study pointed out Chinese doctors' similarities, differences, and unique strategies in diagnosing and treating SSNHL and analyzed the possible reasons to help the world understand the current otolaryngology practices in China.

[Discussion on diagnosis and treatment of dizziness from cases].

Dizziness or vertigo is a common clinical symptom, and its underlying etiology is complex. Many clinicians are confused about its diagnosis and treatment. This article presents a case about chronic vestibular syndrome. And case appreciation and academic discussion are conducted by well-known domestic neurologists and otologists, so as to provide a good thinking model and basic ideas for the diagnosis and treatment of dizziness or vertigo, hoping to further improve the diagnosis and treatment level among clinicians.

The circadian timing of noise exposure influences noise-induced inflammatory responses in the mouse cochlea

Abstract Introduction: Noise-induced hearing loss is one of the most common forms of sensorineural hearing loss. Nevertheless, the mechanisms of noise-induced hearing loss are still not fully understood. Objective: To investigate the dynamics of inflammatory responses in the mammalian cochlea following noise trauma at two different times, once during the light cycle and once during the dark. Methods: We challenged C57BL/6J mice with moderate, continuous noise trauma at either 9 a.m. or 9 p.m. Auditory function, histological changes in hair cells, and modifications in gene expression levels of inflammatory mediators were assessed at specific time points. Shifts in auditory brainstem response thresholds were measured at 1, 3, 7 and 14 days after noise exposure to measure potential noise-induced hearing loss. Cochlear basilar-membrane immunofluorescent staining was performed at 3 and 14 days after noise exposure. The mRNA levels of several inflammatory mediators were measured via quantitative real-time polymerase chain reaction before (pre) and after (0, 3, 12, 24 and 72 h) noise exposure. Results: We found that all noise-exposed mice developed a temporary threshold shift and that there were no significant differences between daytime and nighttime noise exposures in terms of inducing hearing-threshold shifts. Similarly, we did not detect significant histological changes in hair cells between these two groups. However, we discovered an interesting phenomenon in that the peak mRNA levels of IL-1β, IL-6, CCL2 and TNF-α were higher in day noise-exposed mice compared to those in night noise-exposed mice, and these mRNA levels subsided more slowly in day noise-exposed mice. Conclusion: Overall, these observations suggest that the circadian timing of noise exposure has a significant effect on noise-induced inflammatory responses in the mouse cochlea and that a greater inflammatory response might occur after daytime exposure.

[Summary of experience in cochlear implantation surgery in Tibet and analysis of postoperative rehabilitation effect].

Cochlear implant surgery is now recognized as the most effective intervention for patients with severe and profound sensorineural hearing loss. Due to various factors such as high altitude, low oxygen content, and ethnic differences in Tibet, the early hearing screening found that the incidence of neonatal hearing loss was significantly higher than in the mainland. With the great assistance of the China Disabled Persons' Federation, the first cochlear implant surgery was carried out in Tibet in 2011, and a total of 116 cases have been completed. This article aims to summarize the clinical experience of cochlear implant surgery in Tibet for ten years and retrospectively analyze the postoperative rehabilitation effect, so as to improve the understanding of cochlear implant surgery in plateau areas.

Effects of metformin on Sonic hedgehog subgroup medulloblastoma progression: In vitro and in vivo studies.

Metformin is a first-line drug for type 2 diabetes, and its anticancer effects have also been widely studied in recent years. The Sonic hedgehog (Shh) signaling pathway is involved in the initiation and progression of medulloblastoma. In order to develop a new treatment strategy for medulloblastoma (MB), this study investigated the inhibitory effect of metformin on MB and the underlying mechanism of metformin on the Shh signaling pathway. The effect of metformin on proliferation was evaluated by the cell counting kit-8 (CCK-8) test and colony formation experiment. The effect of metformin on metastasis was assessed by the scratch-wound assay and transwell invasion assay. Cell cycle and apoptosis were evaluated by flow cytometry, and the associated proteins were examined by western blotting. The mRNA and protein expression levels related to the Shh pathway were measured by quantitative PCR, western blotting, and immunofluorescence staining. The xenograft murine model was carried out to evaluate the anticancer effect of metformin on medulloblastoma in vivo. Metformin inhibited proliferation and metastasis of the Shh subgroup MB cell line, and the inhibitory effect on proliferation was related to apoptosis and the block of the cell cycle at the G0/G1 phase. Animal experiments showed that metformin inhibits medulloblastoma growth in vivo. Moreover, metformin decreased mRNA and protein expression levels of the Shh pathway, and this effect was reversed by the AMP-activated protein kinase (AMPK) siRNA. Furthermore, the pro-apoptotic and cell cycle arrest effects of metformin on Daoy cells could be reversed by the Shh pathway activators. Our findings demonstrated that metformin could inhibit medulloblastoma progression in vitro and in vivo, and this effect was associated with AMPK-mediated inhibition of the Shh signaling pathway in vitro studies.

Correlation Analysis of Vestibular Symptoms and Migraine and Non-migraine Headaches: An Epidemiological Survey of 708 Female Nurses.

Objective: This study is oriented to study the correlation between different vestibular symptoms and migraine and non-migraine headaches. Materials and Methods: A questionnaire containing factors related to vestibular symptoms and migraine was designed to survey nurses in a tertiary hospital. Then, all study subjects were divided into three groups: no headache, migraine, and non-migraine headache, and the general physical condition and incidence of different vestibular symptoms were compared among the three groups. Results: Among all the 708 subjects, 233 had headaches. The incidence of migraine was 13.3%. There were 235 cases had vestibular symptoms. Dizziness and vertigo are independent factors related to headaches, especially migraine. The risk of migraine and other types of headaches in the vertigo group is 2.808 and 2.526 times of those without vertigo, while in the dizziness group, the risk is 8.248 and 5.732 times of those without dizziness. Conclusion: Different vestibular symptoms were all related to migraine. And different vestibular symptoms and non-migraine headaches also showed a clear correlation.

Effect of treatment modality on the long-term survival of patients with early glottic squamous cancer: a retrospective cohort study based on the SEER database.

Background: The optimal treatment strategy for patients with early glottic (T1-2N0M0) squamous cancer remains unclear. Methods: A retrospective population-based analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was used to balance treatment arms, and Cox regression analysis was used to determine prognostic factors for survival. Kaplan-Meier analysis, log-rank tests, and competing risk analysis were used to compare survival outcomes between treatment modalities (surgery vs. radiotherapy). Results: Among the 3,994 eligible patients in this study, surgery was associated with improved cancer-specific survival (CSS) and overall survival (OS) compared with radiotherapy (log-rank test, P<0.05). This survival trend favoring surgery was consistent in the T1a, well/moderately differentiated grade, male, and all age subgroups. However, after the baseline characteristics were balanced with PSM, the survival outcomes (CSS and OS) did not differ significantly between the surgery and radiotherapy groups. Interestingly, surgery was associated with a 39% reduced risk of cancer-related death compared with radiotherapy in patients aged ≥70 years (hazard ratio 0.61; 95% CI: 0.43-0.87; P=0.006). However, this survival trend favoring surgery was not observed in younger patients (age <70 years), T stage subgroups, male or female subgroups, or in any of the pathological grade subgroups. Conclusions: In patients with early glottic squamous cell carcinoma undergoing surgery or radiotherapy, there is no sufficient evidence favoring one method over another in terms of survival. However, surgery is recommended in patients aged ≥70 years because, in this group, it was associated with improved survival outcomes compared with radiotherapy.