Association of Hearing Status and Cognition With Fall Among the Oldest-Old Chinese: A Nationally Representative Cohort Study.

OBJECTIVES: The oldest-old (aged ≥80 years) are the most rapidly growing population and age is related to hearing impairment (HI) and cognitive decline. We aimed to estimate the association between HI and fall, and the effect of different cognitive states on this association among the oldest-old Chinese population. DESIGN: A total of 6931 Chinese oldest-old were included in the 2018 cross-cohort from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). The presence of HI was identified by using a dichotomized metric of self-reported hearing status. Cognitive function was evaluated by using the modified Mini-Mental State Examination (MMSE). Cognitive impairment was defined as the MMSE score below 24 points. Data on fall history were collected by questionnaires survey from the participants or their relatives. We studied the association of hearing status and cognitive function with fall by using multivariable logistic regressions, upon adjustment of sociodemographic characteristics, lifestyles, and health conditions. RESULTS: Our participants were aged 92 (range 80 to 117) on average, with 60.1% being women. In total, 39.1% of the participants had reported HI, 50.1% had cognitive impairment, and 26.2% had a history of falling. Participants with HI had a higher incidence of cognitive impairment (79.4%), as compared with their counterparts without HI (31.3%). Compared with those without HI, HI patients had a higher risk of falling after full adjustment for potential confounders (OR = 1.16 [95% confidence interval, CI, 1.01, 1.32], p = 0.031). In comparison with HI participants without cognitive impairment, HI patients with cognitive impairment had a higher fall risk (OR = 1.45 [95% CI = 1.23, 1.72], p < 0.001). CONCLUSIONS: Association of hearing status and cognition with fall was, for the first time, examined on the basis of a nationally-representative oldest-old Chinese population. Poor cognitive performance was common in individuals with HI, and those with HI and cognitive impairment further increased the risk of falling.

Discovery and characterization of a novel cGAS covalent inhibitor for the treatment of inflammatory bowel disease.

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, acts as a nucleotidyl transferase that catalyzes ATP and GTP to form cyclic GMP-AMP (cGAMP) and plays a critical role in innate immunity. Hyperactivation of cGAS-STING signaling contributes to hyperinflammatory responses. Therefore, cGAS is considered a promising target for the treatment of inflammatory diseases. Herein, we report the discovery and identification of several novel types of cGAS inhibitors by pyrophosphatase (PPiase)-coupled activity assays. Among these inhibitors, 1-(1-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-2-yl)prop-2-yn-1-one (compound 3) displayed the highest potency and selectivity at the cellular level. Compound 3 exhibited better inhibitory activity and pathway selectivity than RU.521, which is a selective cGAS inhibitor with anti-inflammatory effects in vitro and in vivo. Thermostability analysis, nuclear magnetic resonance and isothermal titration calorimetry assays confirmed that compound 3 directly binds to the cGAS protein. Mass spectrometry and mutation analysis revealed that compound 3 covalently binds to Cys419 of cGAS. Notably, compound 3 demonstrated promising therapeutic efficacy in a dextran sulfate sodium (DSS)-induced mouse colitis model. These results collectively suggest that compound 3 will be useful for understanding the biological function of cGAS and has the potential to be further developed for inflammatory disease therapies.

Vestibular migraine or Meniere's disease: a diagnostic dilemma.

Meniere's disease (MD) represents one of the vertigo disorders characterized by triad symptoms (recurrent vertigo, fluctuating hearing loss, tinnitus or ear fullness). The diagnosis of MD relies on the accurate and detailed taking of medical history, and the differentiation between MD and vestibular migraine (VM) is of critical importance from the perspective of the treatment efficacy. VM is a highly prevalent vertigo condition and its typical symptoms (headache, vestibular symptoms, cochlear symptoms) mimic those of MD. Furthermore, the misdiagnosis in MD and VM could lead to VM patients mistakenly receiving the traumatic treatment protocol designed for MD, and sustaining unnecessary damage to the inner ear. Fortunately, thanks to the advances in examination technologies, the barriers to their differentiation are being gradually removed. These advances enhance the diagnostic accuracy of vertigo diseases, especially VM and MD. This review focused on the differentiation of VM and MD, with an attempt to synthesize existing data on the relevant battery of differentiation diagnosis (covering core symptoms, auxiliary tests [audiometry, vestibular tests, endolymphatic hydrops tests]) and longitudinal follow-up. Since the two illnesses are overlapped in all aspects, no single test is sufficiently specific on its own, however, patterns containing all or at least some features boost specificity.

Discovery and identification of a novel small molecule BCL-2 inhibitor that binds to the BH4 domain.

The B-cell lymphoma 2 (BCL-2) protein family plays a pivotal role in regulating the apoptosis process. BCL-2, as an antiapoptotic protein in this family, mediates apoptosis resistance and is an ideal target for cell death strategies in cancer therapy. Traditional treatment modalities target BCL-2 by occupying the hydrophobic pocket formed by BCL-2 homology (BH) domains 1-3, while in recent years, the BH4 domain of BCL-2 has also been considered an attractive novel target. Herein, we describe the discovery and identification of DC-B01, a novel BCL-2 inhibitor targeting the BH4 domain, through virtual screening combined with biophysical and biochemical methods. Our results from surface plasmon resonance and cellular thermal shift assay confirmed that the BH4 domain is responsible for the interaction between BCL-2 and DC-B01. As evidenced by further cell-based experiments, DC-B01 induced cell killing in a BCL-2-dependent manner and triggered apoptosis via the mitochondria-mediated pathway. DC-B01 disrupted the BCL-2/c-Myc interaction and consequently suppressed the transcriptional activity of c-Myc. Moreover, DC-B01 inhibited tumor growth in vivo in a BCL­2­dependent manner. Collectively, these results indicate that DC-B01 is a promising BCL-2 BH4 domain inhibitor with the potential for further development.

Diagnostic Value of the Vestibular Autorotation Test in Menière's Disease, Vestibular Migraine and Menière's Disease with Migraine.

(1) Background: Vestibular migraine (VM) and Menière's disease (MD) share multiple features in terms of clinical presentations and auditory-vestibular functions, and, therefore, more accurate diagnostic tools to distinguish between the two disorders are needed. (2) Methods: The study was of retrospective design and examined the data of 69 MD patients, 79 VM patients and 72 MD with migraine patients. Five vestibular autorotation test (VAT) parameters, i.e., horizontal gain/phase, vertical gain/phase and asymmetry were subjected to logistic regression. The receiver operating characteristic (ROC) curves were generated to determine the accuracy of the different parameters in the differential diagnosis of MD and VM. (3) Results: Our results showed that the horizontal gain of VAT significantly outperformed other parameters in distinguishing MD and VM. In addition, the sensitivity, specificity and accuracy of the horizontal gain were 95.7%, 50.6% and 71.6%, respectively, for the differentiation between VM and MD. In most MD patients, the horizontal gain decreased in the range of 3-4 Hz, while in most VM patients, horizontal gain increased in the range between 2-3 Hz. More MD with migraine patients had an increased horizontal gain when the frequency was less than 5.0 Hz and had a decreased horizontal gain when the frequency was greater than 5.0 Hz. (4) Conclusion: Our study suggested the VAT, especially the horizontal gain, as an indicator, may serve as a sensitive and objective indicator that helps distinguish between MD and VM. Moreover, VAT, due to its non-invasive and all-frequency nature, might be an important part of a test battery.

Hearing Impairment With Cognitive Decline Increases All-Cause Mortality Risk in Chinese Adults Aged 65 Years or Older: A Population-Based Longitudinal Study.

Background: Hearing impairment (HI), a highly prevalent sensory impairment affecting older adults, is a risk factor for cognitive decline. However, few studies examined the association between HI and all-cause mortality, and the role of different cognitive states on this relationship in Chinese older adults is poorly understood. Methods: A total of 10,744 Chinese older adults aged 65 years or older were included in the 2011/2012 and 2014 cohorts from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), with the longest follow-up period lasting for up to 8 years. The presence of HI was identified by using a dichotomized metric of self-reported hearing status. All-cause mortality data were ascertained from interviews with family members or relatives of the participants. Cognitive function was evaluated by employing the modified Mini-Mental State Examination (MMSE), which consisted of seven subdomains (orientation, naming foods, registration, attention and calculation, copy figure, delayed recall, and speech and language). Kaplan-Meier survival curves were constructed to evaluate the different hearing states on overall survival. The risk of mortality over the follow-up period was estimated by using Cox proportional hazard ratios (HRs) models. Results: A conspicuous probability was revealed in the survival relationship between hearing status and all-cause mortality for the total population (p < 0.001). Participants with HI had a higher risk of all-cause mortality (HR = 2.29, 95% CI: 2.16, 2.42), as compared with their counterparts without HI. The association was robust upon fully adjustment for potential confounders (HR = 1.07, 95% CI: 1.00, 1.14). Compared to HI participants with no cognitive impairment, HI patients with cognitive impairment had a higher mortality risk (HR = 2.31, 95% CI: 2.13, 2.51). Impairment in the subdomains of cognitive function were independently associated with elevated mortality risk in the participants with HI, with an HR ranging from 1.28 (copy figure) to 1.46 (speech and language). Conclusions: Cognitive decline was common in individuals with HI, and those with HI and cognitive impairment further increased mortality risk. Our findings prompt a call for actions to improve the hearing status and cognitive function of older people to minimize health risks and improve longevity.

Is Hearing Impairment Causally Associated With Falls? Evidence From a Two-Sample Mendelian Randomization Study.

Background: Observational studies have suggested that hearing impairment (HI) was associated with the risk of falls, but it remains unclear if this association is of causal nature. Methods: A two-sample Mendelian randomization (MR) study was conducted to investigate the causal association between HI and falls in individuals of European descent. Summary data on the association of single nucleotide polymorphisms (SNPs) with HI were obtained from the hitherto largest genome-wide association study (GWAS) (n = 323,978), and statistics on the association of SNPs with falls were extracted from another recently published GWAS (n = 461,725). MR Steiger filtering method was applied to determine the causal direction between HI and falls. Inverse-variance weighted (IVW) method was employed as the main approach to analyze the causal association between HI and falls, whereas weighted median, simple mode, weighted mode, and MR-Egger methods were used as complementary analyses. The MR-Egger intercept test, the MR-PRESSO test, and Cochran's Q statistic were performed to detect the potential directional pleiotropy and heterogeneity, respectively. The odds ratio (OR) with 95% confidence intervals (CIs) was used to evaluate this association. Results: A total of 18 SNPs were identified as valid instrumental variables in our two-sample MR analysis. The positive causality between HI and risk of falls was indicated by IVW [OR 1.108 (95% CI 1.028, 1.194), p = 0.007]. The sensitivity analyses yielded comparable results. The "leave-one-out" analysis proved that lack of a single SNP did not affect the robustness of our results. The MR-Egger intercept test exhibited that genetic pleiotropy did not bias the results [intercept = -2.4E-04, SE = 0.001, p = 0.832]. Cochran's Q test revealed no heterogeneity. Conclusion: Our MR study revealed a causal association between genetically predicted HI and falls. These results provide further evidence supporting the need to effectively manage HI to minimize fall risks and improve quality of life.

Developing a pyroptosis-related gene signature to better predict the prognosis and immune status of patients with head and neck squamous cell carcinoma.

Chronic inflammation may promote the incidence and development of neoplasms. As a pro-inflammatory death pathway, pyroptosis could induce normal cells to transform into cancerous cells, but the potential effect of pyroptosis in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study developed and evaluated a pyroptosis-related gene signature to predict the prognosis and immune status of patients with HNSCC. The gene expression, mutation information, and clinical characteristics of HNSCC were extracted from TCGA to establish a comprehensive genome database (GEO). Based on LASSO Cox regression model, nine pyroptosis-related genes (TTLL1, TRIML2, DYNC1I1, KLHL35, CAMK2N1, TNFRSF18, GLDC, SPINK5, and DKK1) were used to construct a pyroptosis-related gene signature, which had good ability to predict the prognosis of HNSCC. Furthermore, the expression of nine pyroptosis-related genes in HNSCC and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR). The potential immunotherapeutic features and drug sensitivity prediction of this signature were also explored. Because pyroptosis regulators play an important role in HNSCC development and prognoses, further exploration might assist in identifying new biomarkers and predictors of prognosis to benefit clinical identification and management.

The Value of Subjective Visual Vertical in Diagnosis of Vestibular Migraine.

OBJECTIVE: To study the value of the subjective visual vertical (SVV) in the diagnosis of vestibular migraine (VM). METHODS: This study recruited 128 VM patients and 64 age-matched normal subjects. We detected the SVV during the interval between attacks in both groups, in sitting upright, and the head tilted at 45° to the left or right. We then examined the correlation between the SVV results with the vestibular evoked myogenic potential (VEMP) and canal paresis (CP). RESULTS: It was found there was a significant difference in SVV at the upright position between VM patients and normal controls (P=0.006) and no significant difference was found at the tilts of 45° to the left or right between the two groups. The SVV results at the upright position were significantly correlated with cervical VEMP (P=0.042) whereas not significantly correlated with CP and VEMP. There existed no significant difference in the conformity to the Müller effect (M effect) between the two groups. ROC analysis exhibited that the sensitivity, specificity of SVVs at the upright were 67.200% and 62.500% respectively. The diagnostic value of SVV at the upright position was significantly higher than that at tilts of 45° to the left and right (P=0.006). Nonetheless the diagnostic accuracy was relatively low. CONCLUSION: Abnormality in SVV possibly stems from the lasting functional disorder of cerebellar or high-level cortical centers in VM patients or is linked to the vestibular compensation. The SVV is of low diagnostic value for VM and the value of SVV in VM warrants further study.

Multisensory Exercise Improves Balance in People with Balance Disorders: A Systematic Review.

OBJECTIVE: To examine the effect of multisensory exercise on balance disorders. METHODS: PubMed, Scopus and Web of Science were searched to identify eligible studies published before January 1, 2020. Eligible studies included randomized control trials (RCTs), non-randomized studies, case-control studies, and cohort studies. The methodological quality of the included studies was evaluated using JBI Critical Appraisal Checklists for RCTs and for Quasi-Experimental Studies by two researchers independently. A narrative synthesis of intervention characteristics and health-related outcomes was performed. RESULTS: A total of 11 non-randomized studies and 9 RCTs were eligible, including 667 participants. The results supported our assumption that multisensory exercise improved balance in people with balance disorders. All of the 20 studies were believed to be of high or moderate quality. CONCLUSION: Our study confirmed that multisensory exercise was effective in improving balance in people with balance disorders. Multisensory exercises could lower the risk of fall and enhance confidence level to improve the quality of life. Further research is needed to investigate the optimal strategy of multisensory exercises and explore the underlying neural and molecular mechanisms of balance improvement brought by multisensory exercises.

Light Cupula: To Be Or Not to Be?

Benign paroxysmal positional vertigo (BPPV) represents the most common form of positional vertigo. It is caused by dislodged otoconia that freely float in the semicircular canals (canalolithiasis) or attach to the cupula (cupulolithiasis). A cupulolithiasis-type (or a heavy cupula-type) of BPPV implicating the lateral semicircular canal (LSCC) exhibits persistent ageotropic direction-changing positional nystagmus (DCPN) in a head-roll test. However, in some cases, unlike any type of BPPV, persistent geotropic DCPN cannot be explained by any mechanisms of BPPV, and don't fit the current classifications. Recently, the notion of light cupula has been introduced to refer to the persistent geotropic DCPN. In this study, we looked at the clinical features of light cuplula and discussed the possible mechanisms and therapeutic strategies of the condition. The notion of light cupula is a helpful addition to the theory of peripheral positional vertigo and nystagmus.

Mechanism of Cross-modal Information Influencing Taste.

Studies on the integration of cross-modal information with taste perception has been mostly limited to uni-modal level. The cross-modal sensory interaction and the neural network of information processing and its control were not fully explored and the mechanisms remain poorly understood. This mini review investigated the impact of uni-modal and multi-modal information on the taste perception, from the perspective of cognitive status, such as emotion, expectation and attention, and discussed the hypothesis that the cognitive status is the key step for visual sense to exert influence on taste. This work may help researchers better understand the mechanism of cross-modal information processing and further develop neutrally-based artificial intelligent (AI) system.

Sorting Nexin 10 Mediates Metabolic Reprogramming of Macrophages in Atherosclerosis Through the Lyn-Dependent TFEB Signaling Pathway.

RATIONALE: SNX10 (sorting nexin 10) has been reported to play a critical role in regulating macrophage function and lipid metabolism. OBJECTIVE: To investigate the precise role of SNX10 in atherosclerotic diseases and the underlying mechanisms. METHODS AND RESULTS: SNX10 expression was compared between human healthy vessels and carotid atherosclerotic plaques. Myeloid cell-specific SNX10 knockdown mice were crossed onto the APOE-/- (apolipoprotein E) background and atherogenesis (high-cholesterol diet-induced) was monitored for 16 weeks. We found that SNX10 expression was increased in atherosclerotic lesions of aortic specimens from humans and APOE-/- mice. Myeloid cell-specific SNX10 deficiency (Δ knockout [KO]) attenuated atherosclerosis progression in APOE-/- mice. The population of anti-inflammatory monocytes/macrophages was increased in the peripheral blood and atherosclerotic lesions of ΔKO mice. In vitro experiments showed that SNX10 deficiency-inhibited foam cell formation through interrupting the internalization of CD36, which requires the interaction of SNX10 and Lyn-AKT (protein kinase B). The reduced Lyn-AKT activation by SNX10 deficiency promoted the nuclear translocation of TFEB (transcription factor EB), thereby enhanced lysosomal biogenesis and LAL (lysosomal acid lipase) activity, resulting in an increase of free fatty acids to fuel mitochondrial fatty acid oxidation. This further promoted the reprogramming of macrophages and shifted toward the anti-inflammatory phenotype. CONCLUSIONS: Our data demonstrate for the first time that SNX10 plays a crucial role in diet-induced atherogenesis via the previously unknown link between the Lyn-Akt-TFEB signaling pathway and macrophage reprogramming, suggest that SNX10 may be a potentially promising therapeutic target for atherosclerosis treatment.

Protective effects of a traditional Chinese herbal formula Jiang-Xian HuGan on Concanavalin A-induced mouse hepatitis via NF-κB and Nrf2 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiang-Xian HuGan (JXHG) formulated by five natural products including Freshwater clam (Corbicula fluminea), Curcuma longa L., Ligustrum lucidum, Eclipta prostrata (L.) L. and Paeonia lactiflora Pall., has exhibited a great hepatoprotective effect. AIM OF THIS STUDY: We investigated the effect of JXHG on concanavalin A (ConA)-induced acute live injury in mice, and to elucidate its underlying molecular mechanisms. MATERIALS AND METHODS: Jiangkanling Capsule (900 mg/kg), low-dose JXHG (LJXHG, 700 mg/kg), high-dose JXHG (HJXHG, 1400 mg/kg) were administered to mice by oral gavage daily for 20 days prior to a single intravenous injection of ConA (20 mg/kg). Liver injury was evaluated by measuring the serum levels of enzymes and cytokines as well as liver histological analysis. We also measured the hepatic expression of cytokines at mRNA levels and the proteins related to NF-κB and Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways. RESULT: Our results showed that JXHG pretreatment significantly alleviated ConA-induced live injury as evidenced by decreased serum levels of glutamic-pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST), and reduced hepatocyte apoptosis and mortality. Furthermore, JXHG was able to significantly reduce the serum levels of proinflammatory cytokines, down-regulate the mRNA expression of interleukin-6 (IL-6) and interferon-γ (IFN-γ), and up-regulate IL-10 as well as superoxide-dimutase-1 (SOD1), glutathione reductase (GSR) and Glutathione peroxidase 2 (GPX2) mRNA in the liver tissues after Con A injection. In addition, JXHG pretreatment dramatically suppressed the phosphorylation of NF-κB p65 (p65), increased Nrf2 expression, and decreased the expression ratio of cleaved caspase-3/caspase-3 in liver tissues. CONCLUSION: These results suggest that JXHG protects against ConA-induced acute live injury through inhibiting NF-κB mediated inflammatory pathway and promoting Nrf2 mediated anti-oxidative stress signaling pathway.

Foam pad of appropriate thickness can improve diagnostic value of foam posturography in detecting postural instability.

OBJECTIVE: The present study investigated the effect of foam thickness on postural stability in patients with unilateral vestibular hypofunction (UVH) during foam posturography. METHODS: Static and foam posturography were performed in 33 patients (UVH group) and 30 healthy subjects (control group) with eyes open (EO) and closed (EC) on firm surface and on 1-5 foam pad(s). Sway velocity (SV) of center of pressure, standing time before falling (STBF) and falls reaction were recorded and analyzed. RESULTS: (1) SVs had an increasing tendency in both groups as the foam pads were added under EO and EC conditions. (2) STBFs, only in UVH group with EC, decreased with foam thickness increasing. (3) Significant differences in SV were found between the control and UVH group with EO (except for standing on firm surface, on 1 and 2 foam pad(s)) and with EC (all surface conditions). (4) Receiver operating characteristic curve analysis showed that the SV could better reflect the difference in postural stability between the two groups while standing on the 4 foam pads with EC. CONCLUSION: Our study showed that diagnostic value of foam posturography in detecting postural instability might be enhanced by using foam pad of right thickness.

Sensory organization test principally reflects utricular function.

CONCLUSION: Our study showed that sensory organization test (SOT) could principally reflect utricular function, and our cut-score of VEST ratio (the indicator of inputs from the vestibular system in balance performance) in SOT could help to screen patients with unilateral peripheral vestibular dysfunction in non-fallers. OBJECTIVES: We aimed to know SOT reflects the function of which vestibular end organs and to assess the possibility of screening patients with peripheral vestibular dysfunction in non-fall population by means of SOT. METHODS: A total of 75 patients with unilateral peripheral vestibular dysfunction underwent SOT, ocular vestibular-evoked myogenic potential (oVEMP), cervical vestibular-evoked myogenic potential (cVEMP) and caloric tests. RESULTS: Regression model indicated that oVEMP, as an independent variable, exerted the greatest influence on VEST ratio, followed by age and cVEMP. There were no significant differences in VEST ratio among groups with different extents of peripheral vestibular involvement (p > .05). VEST ratio in the vestibular impairment groups was significantly lower than in the control group and significantly higher than in fall group (p < .01). VEST ratio in group with normal oVEMP was significantly higher than in group with abnormal oVEMP (p = .013). The cut-score between populations with functional and dysfunctional vestibule was 0.649.

Assessment of balance and vestibular functions in patients with idiopathic sudden sensorineural hearing loss.

This study investigated the relationship among the severity of hearing impairment, vestibular function and balance function in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). A total of 35 ISSNHL patients (including 21 patients with vertigo) were enrolled. All of the patients underwent audiometry, sensory organization test (SOT), caloric test, cervical vestibular-evoked myogenic potential (cVEMP) test and ocular vestibular-evoked myogenic potential (oVEMP) test. Significant relationship was found between vertigo and hearing loss grade (P=0.009), and between SOT VEST grade and hearing loss grade (P=0.001). The abnormal rate of oVEMP test was the highest, followed by the abnormal rates of caloric and cVEMP tests, not only in patients with vertigo but also in those without vertigo. The vestibular end organs were more susceptible to damage in patients with vertigo (compared with patients without vertigo). Significant relationship was found between presence of vertigo and SOT VEST grade (P=0.010). We demonstrated that vestibular end organs may be impaired not only in patients with vertigo but also in patients without vertigo. The cochlear and vestibular impairment could be more serious in patients with vertigo than in those without vertigo. Vertigo does not necessarily bear a causal relationship with the impairment of the vestibular end organs. SOT VEST grade could be used to reflect the presence of vertigo state in the ISSNHL patients. Apart from audiometry, the function of peripheral vestibular end organs and balance function should be evaluated to comprehensively understand ISSNHL. Better assessment of the condition will help us in clinical diagnosis, treatment and prognosis evaluation of ISSNHL.

Repeated courses of intratympanic dexamethasone injection are effective for intractable Meniere's disease.

CONCLUSION: Intra-tympanic dexamethasone injection (ITD) could serve as a first-line intra-tympanic (IT) treatment for Meniere's disease (MD), regardless of hearing level. Even if the response to initial ITD course was unsatisfactory, a repeated course may be beneficial with some patients. OBJECTIVES: This study examined the effect of repeated courses of ITD administered on demand and investigated the possibility of ITD as an initial IT treatment for medically intractable MD patients. METHOD: Fifty-one patients who had been diagnosed with definite MD and given course(s) of ITD treatment were included. Vertigo control, pure tone average and functional disability scores were evaluated against the American Academy of Otolaryngology-Head and Neck Surgery guidelines for MD. RESULTS: Vertigo disappeared or was substantially controlled in 58.8% and 23.5% of the patients, respectively, after the first ITD course. A repeated course further raised the complete vertigo control rate by 15.7% and intra-tympanic gentamycin injection could be postponed or avoided in 78.6% of the patients who required repeated IT treatment. Hearing was unchanged after the first course of ITD (p > .05). No significant differences were detected in the clinical profiles or laboratory findings between patients receiving single course of ITD and those on multiple courses (p > .05).

Assessment of Balance and Vestibular Functions in Patients with Idiopathic Sudden Sensorineural Hearing Loss / 华中科技大学学报（医学）（英德文版）

This study investigated the relationship among the severity of hearing impairment,vestibular function and balance function in patients with idiopathic sudden sensorineural hearing loss (ISSNHL).A total of 35 ISSNHL patients (including 21 patients with vertigo) were enrolled.All of the patients underwent audiometry,sensory organization test (SOT),caloric test,cervical vestibular-evoked myogenic potential (cVEMP) test and ocular vestibular-evoked myogenic potential (oVEMP) test.Significant relationship was found between vertigo and hearing loss grade (P=0.009),and between SOT VEST grade and hearing loss grade (P=0.001).The abnormal rate of oVEMP test was the highest,followed by the abnormal rates of caloric and cVEMP tests,not only in patients with vertigo but also in those without vertigo.The vestibular end organs were more susceptible to damage in patients with vertigo (compared with patients without vertigo).Significant relationship was found between presence of vertigo and SOT VEST grade (P=0.010).We demonstrated that vestibular end organs may be impaired not only in patients with vertigo but also in patients without vertigo.The cochlear and vestibular impairment could be more serious in patients with vertigo than in those without vertigo.Vertigo does not necessarily bear a causal relationship with the impairment of the vestibular end organs.SOT VEST grade could be used to reflect the presence of vertigo state in the ISSNHL patients.Apart from audiometry,the function of peripheral vestibular end organs and balance function should be evaluated to comprehensively understand ISSNHL.Better assessment of the condition will help us in clinical diagnosis,treatment and prognosis evaluation of ISSNHL.

Expression of glycine receptors and gephyrin in rat medial vestibular nuclei and flocculi following unilateral labyrinthectomy.

The medial vestibular nucleus (MVN) and the cerebellar flocculus have been known to be the key areas involved in vestibular compensation (VC) following unilateral labyrinthectomy (UL). In this study, we examined the role of gephyrin and glycine receptor (GlyR) in VC using Sprague-Dawley rats, in an aim to gain deeper insight into the mechanisms responsible for VC. The expression of the α1 and ß subunits of GlyR and gephyrin was immunohistochemically localized in rat MVN and flocculi. The mRNA and protein expression of GlyR (α1 and ß subunits) and gephyrin was quantitatively determined by RT-qPCR and western blot analysis at 8 h, and at 1, 3 and 7 days following UL. It was found that in the ipsilateral MVN, the mRNA and protein expression of the ß subunit of GlyR was significantly increased in comparison to the sham-operated (P<0.01) rats, and in comparison to the contralateral side (P<0.01) at 8 h following UL. In the ipsilateral flocculi, GlyR ß protein expression was significantly elevated (P<0.01 for all), as compared to the sham-operated rats at 8 h, and at 1 and 3 days and to the contralateral side 8 h, 1 and 3 days following UL. No significant differences were observed in the mRNA and protein expression of GlyR α1 and gephyrin in the MVN or flocculi between the two sides (ipsilateral and contralateral) in the UL group, and between the sham-operated group and the UL group at any time point. The findings of our study thus suggest that GlyR plays a major role in the recovery of the resting discharge of the deafferented MVN neurons in the central vestibular system.