Initial steps on the analysis of the underlying pharmacological mechanisms of Wendan decoction on sudden deafness using network pharmacology and molecular docking

Background:Despite its widespread therapeutic use and effectiveness,the underlying pharmacologic mechanisms of Wendan decoction(WDD)and how it works to treat sudden deafness(SD)remain unclear.In this study,the pharmacological mechanisms of WDD underlying SD were analyzed using network pharmacology and molecular docking.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was employed to identify the active compounds and target genes of WDD,and genes associated with SD were screened on five databases.RGUI conducted Gene Ontology(GO)functional and the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.A compound-target network was established using Cytoscape,and the STRING database created a protein-protein interaction(PPI)network to identify the key compounds and targets.Subsequently,a network of crucial compound-target was generated for further molecular docking analysis.For molecular docking simulations of the macromolecular target proteins and their matching ligand molecules,AutoDock Vina and AutoDockTool were utilized.Results:TCMSP identified 162 active target genes and 36 active compounds for WDD.The active target genes were compared with the 2271 genes associated with SD to identify 70 intersecting active target genes linked to 34 active compounds.The GO functional enrichment and KEGG pathway enrichment analyses were undertaken,and compound–target,and PPI networks were built.The key compounds and protein targets were identified and integrated to form a key compound–target network.Eventually,molecular docking was performed to investigate the interactions of the protein targets with their respective compounds.Conclusion:This study highlights the mechanisms of multi-compounds,targets,and pathways of WDD acting on SD and provides further evidence of crucial compounds and their matching target proteins of WDD acting on SD.

Assessing Barriers to Mental Healthcare Interventions for Deaf People in Ghana

While mental health issues are increasingly gaining attention in Ghana, little is known about the situation among deaf people. This study assessed the mental health care needs of deaf people in Ghana. A descriptive design, consisting of interviews and focus group discussions, was used to collect data from 97 participants. Findings indicated that participants had limited knowledge on mental health issues. Mental health stigma, inaccessible mental health information and exclusion from mental health programmes were the major barriers hindering access to mental health care services. This study bridges the knowledge gap and provides evidence for the implementation of deaf-friendly services.

APPLICATION OF GENETIC DEAFNESS GENE CHIP FOR DETECTION OF GENE MUTATION OF DEAFNESS IN PREGNANT WOMEN

Objective The study is to identify the carrier rate of common deafness mutation in Chinese pregnant women via detecting deafness gene mutations with gene chip. Methods The pregnant women in obstetric clinic without hearing impairment and hearing disorders family history were selected. The informed consent was signed. Peripheral blood was taken to extract genom- ic DNA. Application of genetic deafness gene chip for detecting 9 mutational hot spot of the most common 4 Chinese deafness genes, namely GJB2 （35delG, 176del16bp, 235delC, 299delAT）, GJB3 （C538T） ,SLC26A4 （ IVS72A〉G, A2168G） and mito- chondrial DNA 12S rRNA （A1555G, C1494T） . Further genetic testing were provided to the spouses and newborns of the screened carriers. Results Peripheral blood of 430 pregnant women were detected, detection of deafness gene mutation carri- ers in 24 cases（4.2%）, including 13 cases of the GJB2 heterozygous mutation, 3 cases of SLC26A4 heterozygous mutation, 1 cases of GJB3 heterozygous mutation, and 1 case of mitochondrial 12S rRNA mutation. 18 spouses and 17 newborns took further genetic tests, and 6 newborns inherited the mutation from their mother. Conclusion The common deafness genes muta- tion has a high carrier rate in pregnant women group, 235delC and IVS7-2A〉G heterozygous mutations are common.

HUMAN MITOCHONDRIAL tRNA MUTATIONS IN MATERNALLY INHERITED DEAFNESS

Mutations in mitochondrial tRNA genes have been shown to be associated with maternally inherited syn-dromic and non-syndromic deafness. Among those, mutations such as tRNALeu(UUR) 3243A>G associated with syndromic deafness are often present in heteroplasmy, and the non-syndromic deafness-associated tRNA mu-tations including tRNASer(UCN) 7445A>G are often in homoplasmy or in high levels of heteroplasmy. These tRNA mutations are the primary factors underlying the development of hearing loss. However, other tRNA mutations such as tRNAThr 15927G>A and tRNASer(UCN) 7444G>A are insufficient to produce a deafness phe-notype, but always act in synergy with the primary mitochondrial DNA mutations, and can modulate their phenotypic manifestation. These tRNA mutations may alter the structure and function of the corresponding mitochondrial tRNAs and cause failures in tRNAs metabolism. Thereby, the impairment of mitochondrial protein synthesis and subsequent defects in respiration caused by these tRNA mutations, results in mitochon-drial dysfunctions and eventually leads to the development of hearing loss. Here, we summarized the deaf-ness-associated mitochondrial tRNA mutations and discussed the pathophysiology of these mitochondrial tRNA mutations, and we hope these data will provide a foundation for the early diagnosis, management, and treatment of maternally inherited deafness.

A screening analysis of the GJB2 c.176 del 16 mutation responsible for hereditary deafness in a Chinese family

Objective:To determine whether a new-born child from a family carrying a deafness gene needs cochlear implantation to avoid dysphonia by screening and sequencing a deafness-related gene.Results:Both screening and sequencing results confirmed that the new born child had a normal GJB2 gene despite the fact that she has a brother suffering from hearing loss triggered by an allelic GJB2 c.176 del 16 mutation.We cloned the GJB2 genes derived from their respective blood genomic DNA into GFP fused plasmids and transfected those plasmids into the 293 T cell line to test for gene function.While the mutated GJB2gene(GJB2 c.176 del 16) of her deaf brother was found to be unable to form the gap junction structure between two adjacent cells,the baby girl’s GJB2 gene ran into no such problems.Conclusion:The screening and sequencing as well as the GJB2 gene function tests invariably showed results consistent with the ABR tested hearing phenotype,which means that the child,with a normal wild type GJB2 gene,does not need early intervention to prevent her from developing hearing loss and dysphonia at a later stage in life.

Outcomes of treatment of sudden deafness using different Protocols:a retrospective analysis of 104 cases

Objective To compare different treatment protocols for sudden deafness(SD), for the purpose of identifying an appropriate approach to SD. Methods A total of 104 patients with diagnosis of sudden hearing loss treated from Jan 2006 to December 2008 were included in this study, of which 31 received the typical pharmaceutical treatment (groupⅠ), 40 received the typical pharmaceutical treatment plus polarized liquid (GroupⅡ) and 33 received the hyperbaric oxygen in addition to the treatment included in Group Ⅱ(Group Ⅲ). Results The total improvement rate (67.74%, 62.50% and 75.76% for Groups Ⅰ, Ⅱ and Ⅲ respectively) was not statistically different between the three groups (P > 0.05). Conclusion The three treatment protocols are similar when judged by the treatment outcomes in SD, neither being superior to the others. The two important factors that appear to influence treatment outcomes are the audiogram pattern and duration of hearing loss before seeking treatment. Patients with upsloping or peak-type audiograms and treated within 7 days from the onset have better prognosis than others.

Concurrent symptoms and disease conditions in sudden deafness

Objective To study concomitant symptoms and disease conditions in sudden deafness. Methods Clinical data of 418 cases of sudden deafness treated in this department from 2000 to 2007 were reviewed. Results Of the 418 cases, 201 were males and 217 were females. Right ear was involved in 184 cases and left ear in 191 cases. Bilateral involvement was seen in 43 cases. The average age was 44.1 years. Tinnitus was reported in 369 cases (88.3%) either before or after hearing loss, of which 64.5% was of low pitch, 27.1% of high pitch and 8.4% of mixed tones. Constant tinnitus was reported in 83% of the cases, and muffled feelings in 33.3% of the cases. Hearing loss was the only complaint in 221 cases (52.9%). Dizziness was reported in 77 cases (18.4%) and vertigo attacks in 120 cases (28%). Hypertension, coronary artery disease and diabetes were found in 19.6% of 418 cases and hyperlipidemia in 54.5% of 211 cases. CT and / or MRI data were available in 147 cases, with positive findings in 18 cases (12.3%): 2 with acoustic neuroma (1.36%); 4 with emphraxis in the basal ganglia, cerebellum, temporal lobe or parietal lobe, and 12 with poor pneumatization of ipsior contralateral mastoid cells. Conclusion In this case series of sudden deafness, low-pitch constant tinnitus was a common complaint. Most of the studied cases presented with simple hearing loss. Vertigo attacks were more common than dizziness in this group of patients. The most common concomitant disorder was hyperlipidemia, especially high triglycerides. Imaging studies are important in managing sudden deafness in ruling out acoustic neuroma and other intracranial diseases.

Traditional Chinese Medicine Nursing Protocols for Sudden Deafness( Sudden Sensorineural Hearing Loss)

Sudden deafness is one of the commonest acute symptoms in otolaryngology.In recent years,the incidence of sudden deafness is on the rise all over the world,but its etiology is still unclear,and the prognosis is greatly different.Traditional Chinese medicine(TCM)believes that the onset of sudden deafness is related to the liver,gallbladder,heart and triple energizer meridians.This article mainly explored the key points of common syndromes,TCM nursing methods and health guidance of sudden deafness.

An efficient strategy for establishing a model of sensorineural deafness in rats

Ototoxic drugs can be used to produce a loss of cochlear hair cells to create animal models of deafness. However, to the best of our knowledge, there is no report on the establishment of a rat deafness model through the combined application of aminoglycosides and loop diuretics. The aim of this study was to use single or combined administration of furosemide and kanamycin sulfate to establish rat models of deafness. The rats received intravenous injections of different doses of furosemide and/or intramuscular injections of kanamycin sulfate. The auditory brainstem response was measured to determine the hearing threshold after drug application. Immunocytochemistry and confocal microscopy were performed to evaluate inner ear morphology. In the group receiving combined administration of furosemide and kanamycin, the auditory brainstem response threshold showed significant elevation 3 days after administration, higher than that produced by furosemide or kanamycin alone. The hair cells showed varying degrees of injury, from the apical turn to the basal turn of the cochlea and from the outer hair cells to the inner hair cells. The spiral ganglion cells maintained a normal morphology during the first week after the hair cells completely disappeared, and then gradually degenerated. After 2 months, the majority of spiral ganglion cells disappeared, but a few remained. These findings demonstrate that the combined administration of furosemide and kanamycin has a synergistic ototoxic effect, and that these drugs can produce hair cell loss and hearing loss in rats. These findings suggest that even in patients with severe deafness, electronic cochlear implants may partially restore hearing.

Profound deafness and the acquisition of spoken language in children

Profound congenital sensorineural hearing loss(SNHL) is not so infrequent,affecting 1 to 2 of every 1000 newborns in western countries.Nevertheless,universal hearing screening programs have not been widely applied,although such programs are already established for metabolic diseases.The acquisition of spoken language is a time-dependent process,and some form linguistic input should be present before the first 6 mo of life for a child to become linguistically competent.Therefore,profoundly deaf children should be detected early,and referred timely for the process of auditory rehabilitation to be initiated.Hearing assessment methods should reflect the behavioural audiogram in an accurate manner.Additional disabilities also need to be taken into account.Profound congenital SNHL is managed by a multidisciplinary team.Affected infants should be bilaterally fitted with hearing aids,no later than 3 mo after birth.They should be monitored until the first year of age.If they are not progressing linguistically,cochlear implantation can be considered after thorough preoperative assessment.Prelingually deaf children develop significant speech perception and production abilities,and speech intelligibility over time,following cochlear implantation.Age at intervention and oral communication,are the most important determi-nants of outcomes.Realistic parental expectations are also essential.Cochlear implant programs deserve the strong support of community members,professional bodies,and political authorities in order to be successful,and maximize the future earnings of pediatric cochlear implantation for human societies.

The Effect of a High-Frequency-Hearing-Threshold Weighted Value on the Diagnosis of Occupational-Noise-Induced Deafness

Objective: In order to provide a theoretical basis for the revision of the current diagnostic criteria for occupational noise-induced deafness (ONID), we evaluated the degree of ONID by analyzing different high-frequency-hearing- threshold-weighted values (HFTWVs). Methods: A retrospective study was conducted to evaluate the diagnosis of patients with ONID from January 2016 to January 2017 in Guangdong province, China. Based on 3 hearing tests (each interval between the tests was greater than 3 days), the minimum threshold value of each frequency was obtained using the 2007 edition’s diagnostic criteria for ONID. The speech frequency and the HFTWVs were analyzed based on age, noise exposure, and diagnostic classi-fication using SPSS21.0. Results: 168 patients in total were involved in this study, 154 males and 14 females, and the average age was 41.18 ± 6.07. The diagnosis rate was increased by the weighted value of the high frequencies and was more than the mean value of the pure speech frequency (MVPSF). The diagnosis rate for the weighted 4 kHz frequency level increased by 13.69% (χ2 = 9.880, P = 0.002), the weighted 6 kHz level increased by 15.47% (χ2 = 9.985, P = 0.002), and the weighted 4 kHz + 6 kHz level increased by 15.47% (χ2 = 9.985, P = 0.002). The differences were all statistically significant. The diagnostic rate of the different thresholds showed no obvious difference between the genders. The age groups were divided into less than or equal to 40 years old (group A) and 40 - 50 years old (group B). There were several groups with a high frequency: high frequency weighted 4 kHz ( group A χ2 = 3.380, P = 0.050;group B χ2 = 4.054, P = 0.032), high frequency weighted 6 kHz (group A χ2 = 6.362, P = 0.012;group B χ2 = 4.054, P = 0.032), weighted 4 kHz + 6 kHz (group A χ2 = 6.362 P = 0.012;B χ2 = 4.054, P = 0.032) than those of MVPSF in the same group on ONID diagnosis rate. The differences between the groups were statistically significant. There was no significant difference between the age groups (χ2 = 2.265, P = 0.944). The better ear’s (the smaller hearing threshold weighted value) MVPSF and the weighted values for the different high frequencies were examined in light of the number of working years;the group that was exposed to noise for more than 10 years had significantly higher values than those of the average thresholds of each frequency band in the groups with 3 - 5 years of exposure (F = 2.271, P = 0.001) and 6 - 10 years of exposure (F = 1.563, P = 0.046). The differences were statistically significant. The different HFTWVs were higher than those of the MVPSF values, and the high frequency weighted 4 kHz + 6 kHz level showed the greatest difference, with an average increase of 2.83 dB. The diagnostic rate that included the weighted high frequency values was higher for the mild, moderate, and severe cases than those patients who were only screened with the pure frequency tests. The results of the comparisons of the diagnosis rates for mild ONID were as follows: the weighted 3 kHz high frequency level (χ2 = 3.117, P = 0.077) had no significant difference, but the weighted 4 kHz level (χ2 = 10.835, P = 0.001), 6 kHz level (χ2 = 9.985, P = 0.002), 3 kHz + 4 kHz level (χ2 = 6.315, P = 0.012), 3 kHz + 6 kHz level (χ2 = 6.315, P = 0.012), 4 kHz + 6 kHz level (χ2 = 9.985, P = 0.002), and 3 kHz + 4 kHz + 6 kHz level (χ2 = 7.667, P = 0.002) were significantly higher than the diagnosis rate of the mean value of the PSF. There was no significant difference between the 2 groups for the moderate and severe grades (P > 0.05). Conclusion: Different HFTWVs increase the diagnostic rate of ONID. The weighted 4 kHz, 6 kHz, and 4 kHz + 6 kHz high frequency values greatly affected the diagnostic results, and the weighted 4 kHz + 6 kHz high frequency hearing threshold value has the maximum the effect on the ONID diagnosis results.

Sudden deafness as a prodrome of cerebellar artery infarction:Three case reports

BACKGROUND To summarize the clinical characteristics of acute cerebral infarction(ACI)in patients with sudden deafness(SD)as the first symptom,improve the awareness of the disease,and help diagnosis and treatment.CASE SUMMARY From 2019 to 2020,three patients with ACI with SD as the first symptom were admitted to our hospital.Pure tone audiometry,head magnetic resonance imaging(MRI),vertebral artery and carotid artery B-ultrasound,head and neck computed tomography angiography,and other examinations were performed.Following the treatment of SD,hearing and dizziness were not significantly improved.Then,the patients developed symptoms of related cranial nerve injury,and brain MRI showed cerebral infarction in the cerebellopontine angle area.All three cases were transferred to the neurology department for relevant conservative treatment.CONCLUSION Patients with ACI with SD as the first symptom usually attend the otolaryngology clinic.Here a diagnosis of SD,which is based on an audiological examination,is made and the corresponding treatment is administered.To reduce the misdiagnosis of this disease,close attention should be paid to the changes in the patient's clinical symptoms and related auxiliary examinations should be performed,such as brain MRI and cerebrovascular imaging.Otolaryngologists should pay attention to the type and severity of hearing loss,the accompanying symptoms,age,high-risk factors for cerebral infarction,and related cranial nerve symptoms in patients with SD.If the patient's early brain MRI does not show abnormalities,monitoring remains essential.The head MRI should be analyzed quickly based on the changes in the symptoms of the patient,to make an accurate diagnosis and provide the timely and correct treatment for the patients.

Child Deafness in Sub-Saharan Africa: Experience of Two ENT Services in Casamance, South of Senegal

Introduction: Hearing impairment is the most common sensory deficit at birth. It is a public health problem because of the repercussions on the communication development, on the education and subsequent social integration of the child. The objective of this study was to determine the epidemiological, clinical, audiometric and etiological profiles of child deafness in Casamance, South of Senegal. Materials and Methods: This was a retrospective multicenter study, which extended a period of 7 years from January 1st, 2012 to December 31st, 2019. All children aged between 1 to 18 years old and received during their first ENT consultations at the regional and PEACE hospital in Ziguinchor were included. Results: One hundred and seventy-eight records of children were collected during this period, that is a prevalence of 1.30%. The average age was 9 years old. Conductive hearing loss was found in 68% of patients, followed by reception hearing deafness in 24%. The deafness was acquired in the majority of cases (93%) and the predominant etiology was infectious. However, the cause was unknown in 7.51% of cases. Conclusion: Child deafness is common in Casamance and is most often underdiagnosed. The acquired forms are the most common, hence the importance of early detection after a rigorous family investigation.

Audiometric Profile of Deafness at the University Hospital Center Gabriel Toure of Bamako

Objective: To determine the audiometric profile of deafness in our practice. Materials and Methods: Longitudinal prospective study was conducted out in the ENT department and cervicofacial surgery of Gabriel Toure University Hospital in Bamako, we made an exhaustive sampling of all the patients who consulted for hearing loss, tinnitus, vertigo, hiring report, medical expertise and whose deafness was confirmed to tonal audiometry with an age greater than or equal to 15 years. It was spread over 10 months (June 2016 to March 2017). A total of 200 patients were collected. Exclusion criteria were all patients under 15 years of age as well as deafness related to earwax or foreign bodies, and refusal to participate in the study Results: During our study period, 6055 outpatients were admitted out of which 734 patients underwent audiometric testing and 200 patients (3.30%) met our criteria. The male sex was the most represented with a rate of 60%. The sex ratio was 1.5 or 3 men for 2 women. The 15 to 25 age group was the most represented at 37.5%. The average age was 37.18 years old with extremes ranging from 15 to 83 years old. Pupils/students were the most represented with a rate of 29.5%, followed by housewives in 23%, farmers in 10.5% and military in 10%. As antecedent 26% of our patients had a chronic otitis media (OMC), against 23% who had no antecedent otological and 17% had a traumatic antecedent. Bilateral deafness was the most common with a rate of 64.5%. The mode of progressive appearance was the most frequent in 74.5%. As functional signs 46.22% of our patients had a hearing loss associated with tinnitus. Otoscopic examination was pathological in 34.5% of our patients. Mixed deafness was the most common in 43.35%, followed by perception deafness in 32.19% and transmission deafness 24.46%. Mean deafness was the most common with a rate of 48.91%, was severe in 20.22%, mild in 18.31%, deep in 11.47% and cophotic in 01.09%. Asymmetrical curves were the most found in 65.89% of our patients. Conclusion: Deafness is a sensory disability responsible for communication disorder, sometimes disabling. Audiometry, although subjective, remains essential in the diagnosis of deafness.

Fine Mapping of a Deafness Mutation hml on Mouse Chromosome 10

Objective To map a mouse deafness gene, identify the underlying mutation and develop a mouse model for human deafness. Methods Genetic linkage cross and genome scan were used to map a novel mutation named hypoplasia of the membranous labyrinth (hml), which causes hearing loss in mutant mice. Results ① hml was mapped on mouse Chr 10 (～43 cM from the centromere) suggests that the homologous human gene is on 12q22-q24, which was defined on the basis of known mouse-human homologies (OMIM, 2004). ② This study has generated 25 polymorphic microsatellite markers, placed 3 known human genes in the correct order in a high-resolution mouse map and narrowed the hml candidate gene region to a 500 kb area.

PALMAR RIDGE COUNTS IN FAMILIAL DEAFNESS

The present study was undertaken to measure a-b, a-d and td ridge counts of deaf patients and to compare the dermatoglyphic differences among deaf individuals. The data consists of 208 heredo-familial Punjabi Khatri and Arora deaf subjects, including 118 males and 90 femeles. The control sample consists of 228 Punjabis, comprising of 128 males and 100 females. The present study indicates lower incidence of ’a-b’, ’a-d’ and ’td’ ridge counts in deaf groups when compared to the corresponding normal groups.

Polymorphism of the 86th amino acid in CX26 protein and hereditary deafness

Objective:To investigate the membrane localization function of the CX26 protein when its 86th amino acid is Thr, Ser or Arg, and its relations to deafness. Methods:CX26-GFP protein with either Thr, Ser or Arg as the 86th amino acid was expressed in mouse SGN cells via the GFP fusion type lenti-virus expression system. The membrane localization of the fusion protein was observed under a fluorescence microscope. Results:The mutated protein of CX26 T86S was localized to cell membrane and form gap conjunction structures, showing no difference to the wild type CX26 protein (with Thr as the 86th amino acid). However, the gap conjunction structure disappeared when the mutation was CX26 T86A. Conclusion:These results indicate that the CX26 T86R mutation may be a cause of hearing loss, but CX26 T86S as a non-pathogenic poly-morphism mutation does not affect functions of the CX26 protein. The results are in accordance with the results of clinical screening.

Diuretic Agents in Treatment of Sudden Deafness

Objective To study the role of diuretic agents in treating sudden deafness (SD) and explore the possibility of endolymphatic hydrops as a potential cause of SD. Methods Twenty-eight SD cases were reviewed. In 23 cases, treatment was initiated with routine agents. Diuretic agents were later added in 8 of these cases that failed to respond to routine treatment agents. Diuretic agents were included in the initial treatment in the rest 5 cases. In total, 13 cases received diuretics in addition to routine treatment agents and 15 cases received conventional treatment only. Results In the 8 cases who received diuretics after failed conventional treatments, 4 showed hearing improvement, whereas all 5 cases in which diuretics were included in the initial treatment demonstrated hearing improvement. Conclusion These results suggest a possible role of endolymphatic hydrops in the pathophysiologic course of SD. Diuretics should be considered when clear indications exist with no conflicts to other medical conditions.

COMBINATIONAL ADMINISTRATION OF AMINOGLYCOSIDES AND LOOP DIURETICS AS AN EFFICIENT STRATEGY TO ESTABLISH DEAFNESS MODELS IN RATS

It is known that aminoglycoside antibiotics can damage the vestibular and auditory sensory epithelia, and the loop diuretics can enhance the ototoxic effect of aminoglycosides. Previous studies on the synergistic effect of these two types of drugs have used mice, guinea pigs and cats, but not rats. The aim of this study was to determine this synergistic effects in rat cochleae. Rats received intravenous injections of different doses of furosemide and/or intramuscular injections of kanamycin sulfate. Au- ditory brainstem response （ABR）, scanning electron microscopy （SEM） and immunocytochemistry were used to determine the effects of drug administration. In the group receiving combined administration of furosemide and kanamycin, the ABR thresh- old showed significant elevation 3 days after drug administration, greater than single drug administration. The hair cells showed various degrees of injury from the apical turn to the basal turn of the cochlea and from the outer hair cells to the inner hair cells. Neuron fibers of the hair cells showed significant loss 7 days after the drug administration, but the number of spiral ganglia did not decrease and supporting cells showed no signs of injury. Our study suggest that combined administration of fu- rosemide and kanamycin has an synergistic ototoxic effect, and can result in hair cell loss and hearing loss in rats.