Middle Ear Meningioma With Recurrence Secretory Otitis Media.

Middle ear meningiomas (MEMs) are rare tumors that can present with nonspecific symptoms, posing challenges in diagnosis and management. This case report focuses on a middle-aged female patient who was misdiagnosed with secretory otitis media for 5 years. However, further evaluation through computed tomography imaging and subsequent pathologic biopsy revealed the presence of a MEM. The patient underwent surgical and gamma knife resection of the tumor and follow-up examination after 1 year showed no signs of recurrence. This case report highlights the importance of considering meningiomas in the differential diagnosis of middle ear pathologies and the need for careful preoperative planning for optimal outcomes. Overall, this case demonstrates that correct diagnosis and appropriate treatment can lead to successful management of MEMs.

Synergistic mechanism of Ni(OH)2/NiMoS heterostructure electrocatalyst with crystalline/amorphous interfaces for efficient hydrogen evolution over all pH ranges.

Designing and fabricating efficient electrocatalysts is a practical step toward the commercial application of the efficient hydrogen evolution reaction (HER) over all pH ranges. Herein, novel Ti@Ni(OH)2-NiMoS heterostructure with interface between crystalline Ni(OH)2 and amorphous NiMoS was rationally designed and fabricated on Ti mesh (denoted as Ti@Ni(OH)2-NiMoS). Acid etching and calcination experiments helped in accurate elucidation of the synergistic mechanism as well as the vital role on crystalline Ni(OH)2 and amorphous NiMoS. In acidic solutions, the HER performance of Ti@Ni(OH)2-NiMoS was mainly attributed to the amorphous NiMoS. In neutral, alkaline, and natural seawater solutions, the HER performance was mainly determined by the synergistic interface behaviors between the Ni(OH)2 and NiMoS. The crystalline Ni(OH)2 accelerated water dissociation kinetics, while the amorphous NiMoS provided abundant active sites and allowed for fast electron transfer rates. To deliver current densities of 10 mA·cm-2 in acidic, neutral, alkaline, and natural seawater solutions, the Ti@Ni(OH)2-NiMoS required overpotentials of 138, 198, 180 and 371 mV, respectively. This paper provides general guidelines for designing efficient electrocatalyst with crystalline/amorphous interfaces for efficient hydrogen evolution over all-pH ranges.

FOXG1 promotes aging inner ear hair cell survival through activation of the autophagy pathway.

Presbycusis is the cumulative effect of aging on hearing. Recent studies have shown that common mitochondrial gene deletions are closely related to deafness caused by degenerative changes in the auditory system, and some of these nuclear factors are proposed to participate in the regulation of mitochondrial function. However, the detailed mechanisms involved in age-related degeneration of the auditory systems have not yet been fully elucidated. In this study, we found that FOXG1 plays an important role in the auditory degeneration process through regulation of macroautophagy/autophagy. Inhibition of FOXG1 decreased the autophagy activity and led to the accumulation of reactive oxygen species and subsequent apoptosis of cochlear hair cells. Recent clinical studies have found that aspirin plays important roles in the prevention and treatment of various diseases by regulating autophagy and mitochondria function. In this study, we found that aspirin increased the expression of FOXG1, which further activated autophagy and reduced the production of reactive oxygen species and inhibited apoptosis, and thus promoted the survival of mimetic aging HCs and HC-like OC-1 cells. This study demonstrates the regulatory function of the FOXG1 transcription factor through the autophagy pathway during hair cell degeneration in presbycusis, and it provides a new molecular approach for the treatment of age-related hearing loss.Abbreviations: AHL: age-related hearing loss; baf: bafilomycin A1; CD: common deletion; D-gal: D-galactose; GO: glucose oxidase; HC: hair cells; mtDNA: mitochondrial DNA; RAP: rapamycin; ROS: reactive oxygen species; TMRE: tetramethylrhodamine, ethyl ester.

Diagnosis and treatment of emergency surgeries in otorhinolaryngology, head and neck surgery during the covid-19 outbreak: A single center experience.

The 2019 Novel Coronavirus (2019-nCoV, SARS-CoV-2) infection has already been assigned as a Class B infectious disease requiring Class A management strategy according to "the Law on the Prevention and Control of Infectious Diseases of the People's Republic of China" and become a global pandemic. The incidence of emergencies in otorhinolaryngology, head and neck surgery such as foreign bodies in the esophagus and the respiratory tract, epistaxis, laryngeal obstruction with dyspnea, and head and neck trauma are relatively high. Emergency surgeries are required as some of these diseases progress rapidly and probably be life-threatening. In this article, we drafted the recommendations for diagnosis and treatment of emergency surgeries in otorhinolaryngology, head and neck surgery in the epidemic area of novel coronavirus pneumonia based on "Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional; 7th Edition Revisions)"and WHO guidelines, combined with the experience of emergency surgeries in the Department of Otorhinolaryngology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, which is at the center outbreak area of the SARS-CoV-2 pneumonia (COVID-19) in China, to improve the success rate of treatment for otorhinolaryngology, head and neck surgery emergency surgeries and to reduce the SARS-CoV-2 infection rate in the perioperative period.

Metformin attenuates the D­galactose­induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways.

Age­related hearing loss, also termed central presbycusis, is a progressive neurodegenerative disease; it is a devastating disorder that severely affects the quality of life of elderly individuals. Substantial evidence has indicated that oxidative stress and associated protein folding dysfunction have a marked influence on neurodegenerative diseases. In this study, we aimed to cells to investigate whether metformin protects against age­related pathologies and to elucidate the underlying mechanisms; specifically, we focused on the role of unfolded protein response (UPR) via the AMPK/ERK1/2 signaling pathways. For this purpose, the biguanide compound, metformin, a medication widely used in the treatment of type 2 diabetes, was administered to rats in a model of mimetic aging. In addition, senescent PC12 were treated with metformin. Although it has been well established that UPR signaling is activated in response to cellular stress and is associated with the pathogenesis of neuronal deterioration, the detailed functions of the UPR in the auditory cortex remain unclear. We found that metformin treatment markedly affected the UPR and the AMPK/ERK1/2 signaling pathway, and maintained the auditory brainstem response (ABR) threshold during the aging process. The results indicated that the regulation of the UPR and AMPK/ERK1/2 signaling pathway by metformin significantly attenuated hearing loss, cell apoptosis and age­related neurodegeneration. Reversing these harmful effects through the use of metformin suggests its involvement in restoring the antioxidant status and protein homeostasis related to the underlying pathology of presbycusis. The findings of this study may provide a better approach for the treatment of age­related neurodegeneration diseases.

The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.

Inflammation is a self-defense response to protect individuals from infection and tissue damage, but excessive or persistent inflammation can have adverse effects on cell survival. Many individuals become especially susceptible to chronic-inflammation-induced sensorineural hearing loss as they age, but the intrinsic molecular mechanism behind aging individuals' increased risk of hearing loss remains unclear. FoxG1 (forkhead box transcription factor G1) is a key transcription factor that plays important roles in hair cell survival through the regulation of mitochondrial function, but how the function of FoxG1 changes during aging and under inflammatory conditions is unknown. In this study, we first found that FoxG1 expression and autophagy both increased gradually in the low concentration lipopolysaccharide (LPS)-induced inflammation model, while after high concentration of LPS treatment both FoxG1 expression and autophagy levels decreased as the concentration of LPS increased. We then used siRNA to downregulate Foxg1 expression in hair cell-like OC-1 cells and found that cell death and apoptosis were significantly increased after LPS injury. Furthermore, we used d-galactose (D-gal) to create an aging model with hair cell-like OC-1 cells and cochlear explant cultures in vitro and found that the expression of Foxg1 and the level of autophagy were both decreased after D-gal and LPS co-treatment. Lastly, we knocked down the expression of Foxg1 under aged inflammation conditions and found increased numbers of dead and apoptotic cells. Together these results suggest that FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.

Analysis of bone mass and its relationship with body composition in school-aged children and adolescents based on stage of puberty and site specificity: A retrospective case-control study.

The aim of this study was to better understand the relationship of bone mass with body composition based on different stages of puberty and to illuminate the contribution of site-specific fat mass and lean mass (FM and LM) compared with bone mass in school-aged children and adolescents in Chongqing, China.A total of 1179 healthy subjects of both sexes were recruited. Bone mineral content (BMC), bone mineral density (BMD), bone area, and both FM and LM were measured by dual-energy X-ray absorptiometry (DXA). The fat mass and lean mass indexes (FMI and LMI, respectively) were calculated as the FM (kg) and LM (kg) divided by the height in meters squared, respectively.Most of the bone mass indicators were significantly higher for postpubertal boys than for girls at the same stage (P < .001). The proportion of subjects with normal bone mass increased, while the proportion of subjects with osteopenia and osteoporosis decreased with increased body weight regardless of gender and puberty stage (P < .01). FM and LM were significantly positively related to bone mass regardless of gender and puberty stage (P < .0001). FMI and LMI were significantly positively related to bone mass in most conditions (P < .05 and P < .0001, respectively). Four components of the FM and LM were linearly and significantly associated with BMD and BMC for TB and TBHL. Among them, the head fat mass and head lean mass showed the greatest statistical contribution.In the process of assessing bone status, we recommend measuring fat and lean masses, including the fat and lean masses of the head.

Age-associated decline in Nrf2 signaling and associated mtDNA damage may be involved in the degeneration of the auditory cortex: Implications for central presbycusis.

Central presbycusis is the most common sensory disorder in the elderly population, however, the underlying molecular mechanism remains unclear. NF­E2­related factor 2 (Nrf2) is a key transcription factor in the cellular response to oxidative stress, however, the role of Nrf2 in central presbycusis remains to be elucidated. The aim of the present study was to investigate the pathogenesis of central presbycusis using a mimetic aging model induced by D­galactose (D­gal) in vivo and in vitro. The degeneration of the cell was determined with transmission electron microscopy, terminal deoxynucleotidyl transferase­mediated deoxyuridine 5'­triphosphate nick­end labeling staining, and senescence­associated ß­galactosidase staining. The expression of protein was detected by western blotting and immunofluorescence. The quantification of the mitochondrial DNA (mtDNA) 4,834­base pair (bp) deletion and mRNA was detected by TaqMan quantitative polymerase chain reaction (qPCR) and reverse transcription­qPCR respectively. Cell apoptosis and intracellular ROS in vitro were determined with flow cytometry. The levels of nuclear Nrf2, and the mRNA levels of Nrf2­regulated antioxidant genes, were downregulated in the auditory cortex of aging rats, which was accompanied by an increase in 8­hydroxy­2'­deoxyguanosine formation, an accumulation of mtDNA 4,834­bp deletion, and neuron degeneration. In addition, oltipraz, a typical Nrf2 activator, was found to protect cells against D­gal­induced mtDNA damage and mitochondrial dysfunction by activating Nrf2 target genes in vitro. It was also observed that activating Nrf2 with oltipraz inhibited cell apoptosis and delayed senescence. Taken together, the data of the present study suggested that the age­associated decline in Nrf2 signaling activity and the associated mtDNA damage in the auditory cortex may be implicated in the degeneration of the auditory cortex. Therefore, the restoration of Nrf2 signaling activity may represent a potential therapeutic strategy for central presbycusis.

Metabolic syndrome is associated with hearing loss among a middle-aged and older Chinese population: a cross-sectional study.

BACKGROUND: Although the association of metabolic syndrome (MetS) and hearing loss has been evaluated, findings are controversial. This study investigated this association in a Chinese population. METHODS: A cross-sectional study including a total of 18,824 middle-aged and older participants from the Dongfeng-Tongji Cohort study was conducted. Hearing loss was defined as the pure-tone average (PTA) of frequencies 0.5, 1.0, 2.0, and 4.0 kHz >25 decibels hearing level (dB HL) in the better ear and graded as mild (PTA 26-40 dB HL), moderate (PTA >40 to ≤60 dB HL), and severe (PTA >60 dB HL). MetS was defined according to the International Diabetes Foundation (IDF) criteria of 2005. Association analysis was performed by logistic regression. RESULTS: After adjustment for potential confounders, participants with MetS showed higher OR of hearing loss (OR, 1.11; 95% CI: 1.03-1.19). The MetS components including central obesity (OR, 1.07; 95% CI: 1.01-1.15) and hyperglycemia (OR, 1.12; 95% CI: 1.04-1.20) were also positively associated with hearing loss. Low HDL-C levels were also associated with higher OR of moderate/severe hearing loss (OR, 1.21; 95% CI: 1.07-1.36). CONCLUSIONS: The MetS, including its components central obesity, hyperglycemia, and low HDL-C levels were positively associated with hearing loss. Key messages Studies indicated that cardiovascular disease and diabetes might be risk factors of hearing loss. However, few efforts have been made to establish a direct relationship between metabolic syndrome and hearing loss, especially in Chinese population. In the present study, a cross-sectional design using data from the Dongfeng-Tongji Cohort study was conducted to assess the association between metabolic syndrome and hearing loss. The metabolic syndrome, as well as its components central obesity, hyperglycemia, and low HDL-C levels were positively associated with hearing loss.

Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR-ULK1 signaling pathway.

Presbycusis is the most common sensory impairment associated with aging; however, the underlying molecular mechanism remains unclear. Autophagy has been demonstrated to serve a key role in diverse diseases; however, no studies have examined its function in central presbycusis. The aim of the present study was to investigate the changes of autophagy in the physiological processes of the auditory cortex and its role in the degeneration of the auditory cortex, as well as the related mechanisms using naturally aging rats and a D­galactose (D­gal)­induced mimetic rat model of aging. The present study demonstrated that autophagy increased from 3 months to 15 months in the normal saline (NS) control group, while it decreased in the D­gal group. Compared with the age­matched NS group, the D­gal group demonstrated significantly increased levels of the autophagy­related proteins, LC3 and Beclin 1 (BECN1) and the anti­apoptotic proteins B­cell lymphoma (BCL)2 and BCL­extra large (BCL­xL) at 3 months, with no obvious changes in cell apoptosis level and neuron ultrastructural morphology. However, LC3, BECN1, BCL2 and BCL­xL were decreased at 15 months in the D-gal group, with cell apoptosis significantly increased and substantial neuron degeneration. Additionally, 5' AMP­activated protein kinase (AMPK) activity was enhanced, and mechanistic target of rapamycin (mTOR) and ULK1 phosphorylation (Ser 757) activities were inhibited at 3 months compared with those of the NS group, while the opposite was observed at 9 and 15 months. The present results suggested that autophagy increases from young to adult and decreases at old age in the physiological processes of the auditory cortex, and has anti­apoptotic as well as anti­aging functions in the degeneration of the auditory cortex. Additionally, autophagy was regulated through AMPK activation and mTOR suppression, and impairment of autophagy may serve a key role in the degeneration of the auditory cortex, even in the pathogenesis of central presbycusis.

Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents.

Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9-guide RNA-lipid complexes targeting the Tmc1Bth allele into the cochlea of neonatal Tmc1Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+ mice. These findings suggest that protein-RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.

The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and CaMKKß/AMPK pathways.

Age-related dysfunction of the central auditory system, known as central presbycusis, is characterized by defects in speech perception and sound localization. It is important to determine the pathogenesis of central presbycusis in order to explore a feasible and effective intervention method. Recent work has provided fascinating insight into the beneficial function of H2S on oxidative stress and stress-related disease. In this study, we investigated the pathogenesis of central presbycusis and tried to explore the mechanism of H2S action on different aspects of aging by utilizing a mimetic aging rat and senescent cellular model. Our results indicate that NaHS decreased oxidative stress and apoptosis levels in an aging model via CaMKKß and PI3K/AKT signaling pathways. Moreover, we found that NaHS restored the decreased activity of antioxidants such as GSH, SOD and CAT in the aging model in vivo and in vitro by regulating CaMKKß and PI3K/AKT. Mitochondria function was preserved by NaHS, as indicated by the following: DNA POLG and OGG-1, the base excision repair enzymes in mitochondrial, were upregulated; OXPHOS activity was downregulated; mitochondrial membrane potential was restored; ATP production was increased; and mtDNA damage, indicated by the common deletion (CD), declined. These effects were also achieved by activating CaMKKß/AMPK and PI3K/AKT signaling pathways. Lastly, protein homeostasis, indicated by HSP90 alpha, was strengthened by NaHS via CaMKKß and PI3K/AKT. Our findings demonstrate that the ability to resist oxidative stress and mitochondria function are both decreased as aging developed; however, NaHS, a novel free radical scavenger and mitochondrial protective agent, precludes the process of oxidative damage by activating CaMKKß and PI3K/AKT. This study might provide a therapeutic target for aging and age-related disease.

Role of the Ubiquitin C-Terminal Hydrolase L1-Modulated Ubiquitin Proteasome System in Auditory Cortex Senescence.

BACKGROUND/AIMS: According to recent studies, central auditory impairments are closely related to neurodegenerative diseases. However, the mechanism of central presbycusis remains unclear. Ubiquitin C-terminal hydrolase L1 (UCHL1) is important in maintaining proteasomal activity; however, the detailed mechanism has not yet been fully elucidated. This study aims to investigate the molecular alterations involved in UCHL1 regulation during auditory cortex aging. METHODS: D-Galactose (D-gal) induces oxidative stress and senescence in the auditory cortex, as reported in our previous studies. Primary auditory cortex cells were treated with D-gal for 72 h or 5 days. The proteins related to the ubiquitin proteasome system (UPS) and proteasomal activities were evaluated. UCHL1 was overexpressed, and the effects of UCHL1 on the UPS and proteasomal activity were analyzed. RESULTS: Proteasomal activity was elevated at 72 h and decreased at 5 days in D-gal-treated primary auditory cortex cells. We also found that overexpression of UCHL1 increased the UPS-related proteins UBE1, PSMA7, ubiquitinated proteins, and monoubiquitin, and proteasomal activity. CONCLUSION: The results suggest that UCHL1 may modify the aging process in the auditory cortex by regulating UPS- related proteins.

Sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation will increase in lipopolysaccharide-induced inflammation in vitro model.

BACKGROUND: With the increasing popularity of mobile phones, the potential hazards of radiofrequency electromagnetic radiation (RF-EMR) on the auditory system remain unclear. Apart from RF-EMR, humans are also exposed to various physical and chemical factors. We established a lipopolysaccharide (LPS)-induced inflammation in vitro model to investigate whether the possible sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation (at specific absorption rates: 2, 4 W/kg) will increase. METHODS: Spiral ganglion neurons (SGN) were obtained from neonatal (1- to 3-day-old) Sprague Dawley® (SD) rats. After the SGN were treated with different concentrations (0, 20, 40, 50, 100, 200, and 400 µg/ml) of LPS, the Cell Counting Kit-8 (CCK-8) and alkaline comet assay were used to quantify cellular activity and DNA damage, respectively. The SGN were treated with the moderate LPS concentrations before RF-EMR exposure. After 24 h intermittent exposure at an absorption rate of 2 and 4 W/kg, DNA damage was examined by alkaline comet assay, ultrastructure changes were detected by transmission electron microscopy, and expression of the autophagy markers LC3-II and Beclin1 were examined by immunofluorescence and confocal laser scanning microscopy. Reactive oxygen species (ROS) production was quantified by the dichlorofluorescin-diacetate assay. RESULTS: LPS (100 µg/ml) induced DNA damage and suppressed cellular activity (P < 0.05). LPS (40 µg/ml) did not exhibit cellular activity changes or DNA damage (P > 0.05); therefore, 40 µg/ml was used to pretreat the concentration before exposure to RF-EMR. RF-EMR could not directly induce DNA damage. However, the 4 W/kg combined with LPS (40 µg/ml) group showed mitochondria vacuoles, karyopyknosis, presence of lysosomes and autophagosome, and increasing expression of LC3-II and Beclin1. The ROS values significantly increased in the 4 W/kg exposure, 4 W/kg combined with LPS (40 µg/ml) exposure, and H2O2 groups (P < 0.05, 0.01). CONCLUSIONS: Short-term exposure to radiofrequency electromagnetic radiation could not directly induce DNA damage in normal spiral ganglion neurons, but it could cause the changes of cellular ultrastructure at special SAR 4.0 W/kg when cells are in fragile or micro-damaged condition. It seems that the sensitivity of SGN to damage caused by mobile phone electromagnetic radiation will increase in a lipopolysaccharide-induced inflammation in vitro model.

Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP-Trx2-ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: changes to Trx2 in the auditory cortex.

Age-associated degeneration in the central auditory system, which is defined as central presbycusis, can impair sound localization and speech perception. Research has shown that oxidative stress plays a central role in the pathological process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin family, plays a key role in regulating the homeostasis of cellular reactive oxygen species and anti-apoptosis. The purpose of this study was to explore the association between Trx2 and the phenotype of central presbycusis using a mimetic aging animal model induced by long-term exposure to d-galactose (d-Gal). We also explored changes in thioredoxin-interacting protein (TXNIP), apoptosis signal regulating kinase 1 (ASK1) and phosphorylated ASK1 (p-ASK1) expression, as well as the Trx2-TXNIP/Trx2-ASK1 binding complex in the auditory cortex of mimetic aging rats. Our results demonstrate that, compared with control groups, the levels of Trx2 and Trx2-ASK1 binding complex were significantly reduced, whereas TXNIP, ASK1 p-ASK1 expression, and Trx2-TXNIP binding complex were significantly increased in the auditory cortex of the mimetic aging groups. Our results indicated that changes in Trx2 and the TXNIP-Trx2-ASK1 signal pathway may participate in the pathogenesis of central presbycusis.

[The study on 235delC mutation of GJB2 gene in patients with idiopathic sudden hearing loss].

OBJECTIVE: To analyze the rate of 235delC mutation in GJB2 gene in patients with idiopathic sudden hearing loss, and to explore its possible correlation with pathogenesis of idiopathic sudden hearing loss. METHOD: Two hundred and thirty-four patients with diagnosis of idiopathic sudden hearing loss in otolaryngology department were recruited as experimental group. Eighty people with normal hearing level were enrolled as control group. Their peripheral blood samples were obtained and genomic DNA was extracted. Using polymerase chain reaction, the coding region of GJB2 gene was amplified, and 235delC mutation is screened for in GJB2 gene by restriction endonuclease. At same time the clinical data of 234 patients was collected to analyze. RESULT: In 234 cases of idiopathic sudden hearing loss, 5 cases were found to have heterozygous 235delC mutation, none of them harbored homozygous 235delC mutation, the 235delC mutation rate was 2.1% (5/234). No 235delC mutation was found in control group. The rate of 235delC mutation in two group showed no statistically significant difference (P > 0.05). CONCLUSION: This research shows that the rate of 235delC mutation in GJB2 is low in patients with idiopathic sudden hearing loss, and suggest that 235delC mutation possible has no correlation with idiopathic sudden hearing loss.

[DNA microarray screening analysis in children with profound hearing impairment in Hubei province].

OBJECTIVE: To investigate characteristics of molecular etiology of children with profound sensorineural hearing loss in Hubei province, and to provide reference for deafness treatment and genetic counseling. METHOD: Three hundred and six children with profound sensorineural hearing loss in Hubei province were enrolled, their genomic DNA were extracted from peripheral blood and a deafness gene test chip was used to screen nine hot spot mutation in the GJB2, GJB3, SLC26A4, and mitochondria 12SrRNA gene. All patients with SLC26A4 gene mutation were given temporal bone CT scan. RESULT: One hundred and thirty-two (43.14%) out of 306 children were found carrying at least one pathogenic gene mutation. The mutation rates of GJB2, SLC26A4 and mitochondria DNA 12SrRNA gene were 29.41% (90/306), 13.72% (42/306) and 0.65% (2/306), respectively. None out of 306 children was detected GJB3 gene mutation. Thirty-six patients carrying SLC26A4 gene mutation were detected enlarged vestibular aqueduct by CT scan. CONCLUSION: Mutations of GJB2 and SLC26A4 gene are two major pathogenic gene for genetic hearing loss in children. 235delC mutation is the main mutation type, followed by IVS7-2A> G mutation type. The screening of SLC26A4 gene common mutations contribute to the diagnosis of enlarged vestibular aqueduct syndrome.

Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal). We showed that malondialdehyde (MDA) levels were increased and manganese superoxide dismutase (SOD2) activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA) 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS) homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

[Survey on quality of life in children and adolescents with type 1 diabetes].

OBJECTIVE: To survey the quality of life in children and adolescents with type 1 diabetes. METHODS: Ninety-eight children and adolescents with type 1 diabetes who participated in Diabetes Summer Camp held in Chongqing, Wuhan and Cheng during 2012 April and December were recruited in the study. The American juvenile diabetes patients quality of life scale Diabetes Quality of Life for Youths was used to assess the quality of life and SPSS19.0 was used for statistical analysis. RESULTS: The scale had satisfactory reliability and validity with a Cronbach's Alpha score of 0.942 and a validity score of 0.679. All three dimension of scales: scales of impact, scales of worries and scales of satisfaction were significantly correlated with self-health assessment (P<0.01). The scores of impact and worries accounted for >50% of total scores as the same for the self health assessment scores. The score of disease course, diet and blood glucose control were positive correlated with each other. Age and HbA1c were positively correlated with the scale of impact, while gender has negative correlation with satisfaction scale (P<0.05). The diabetes diet had significant effects on the quality of life. CONCLUSION: The quality of life in children and adolescents with type 1 diabetes is decreased, especially for those with longer disease course and female adolescents. The form of Diabetes Quality of Life for Youth used in the study has good reliability and validity, which can reflect the quality of life of Chinese diabetic children and adolescents.

The effect of overexpression of PGC-1α on the mtDNA4834 common deletion in a rat cochlear marginal cell senescence model.

Aging is a natural process usually defined as a progressive loss of function with an accumulation of senescent cells. The clinical manifestations of this process include age-related hearing loss (AHL)/presbycusis. Several investigations indicated the association between a mitochondrial common deletion (CD) (mtDNA 4977-bp deletion in humans, corresponding to 4834-bp deletion in rats) and presbycusis. Previous researches have shown that peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a key regulator of mitochondrial biogenesis and energy metabolism. However, the expression of PGC-1α in the inner ear and the possible effect of PGC-1α on presbycusis are not clear. Our data demonstrated the distribution of PGC-1α and its downstream transcription factors nuclear respiratory factor-1 (NRF-1), mitochondrial transcription factor A (Tfam) and nuclear factor κB (NF-κB) in marginal cells (MCs) for the first time. To explore the role of PGC-1α in cellular senescence, we established a model of marginal cell senescence harboring the mtDNA4834 common deletion induced by d-galactose. We also found that PGC-1α and its downstream transcription factors compensatorily increased in our cell senescence model. Furthermore, the overexpression of PGC-1α induced by transfection largely increased the expression levels of NRF-1 and TFAM and significantly decreased the expression level of NF-κB in the cell senescence model. And the levels of CD, senescent cells and apoptotic cells in the cell model decreased after PGC-1α overexpression. These results suggested that PGC-1α might protect MCs in this cell model from senescence through a nuclear-mitochondrial interaction and against apoptosis. Our study may shed light on the pathogenesis of presbycusis and provide a new therapeutic target for presbycusis.