Concurrent Hearing and Genetic Screening of 180,469 Neonates with Follow-up in Beijing, China.

Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.

An Intrinsically Disordered Motif Mediates Diverse Actions of Monomeric C-reactive Protein.

Most proinflammatory actions of C-reactive protein (CRP) are only expressed following dissociation of its native pentameric assembly into monomeric form (mCRP). However, little is known about what underlies the greatly enhanced activities of mCRP. Here we show that a single sequence motif, i.e. cholesterol binding sequence (CBS; a.a. 35-47), is responsible for mediating the interactions of mCRP with diverse ligands. The binding of mCRP to lipoprotein component ApoB, to complement component C1q, to extracellular matrix components fibronectin and collagen, to blood coagulation component fibrinogen, and to membrane lipid component cholesterol, are all found to be markedly inhibited by the synthetic CBS peptide but not by other CRP sequences tested. Likewise, mutating CBS in mCRP also greatly impairs these interactions. Functional experiments further reveal that CBS peptide significantly reduces the effects of mCRP on activation of endothelial cells in vitro and on acute induction of IL-6 in mice. The potency and specificity of CBS are critically determined by the N-terminal residues Cys-36, Leu-37, and His-38; while the versatility of CBS appears to originate from its intrinsically disordered conformation polymorphism. Together, these data unexpectedly identify CBS as the major recognition site of mCRP and suggest that this motif may be exploited to tune the proinflammatory actions of mCRP.

[Acoustic analysis for 21 patients with amyotrophic lateral sclerosis complaining of dysarthria].

OBJECTIVE: To observe the characteristics of acoustic parameters of 21 patients with amyotrophic lateral sclerosis (ALS) complaining of dysarthria and to explore the possibility and clinical value of Multi-Dimensional Voice Program (MDVP) on aseessing the patient's voice. METHODS: The clinical data and speech intelligibility of each of the 21 patients with ALS complaining of dysarthria were collected. All the 21 patients with ALS and 44 normal subjects were suggested to pronounce the vowel [a:]. The voice samples were collected and analyzed by Multi Dimensional Voice Program. The data were compared to detect the difference between the two groups. RESULTS: Speech intelligibility of 10 in the 21 patients was above 97% including 5 patients whose scores were 100%. It seemed that the speech intelligibility score was not related with the duration of the disease and the on-set part. The values of noise to harmonic ratio (NHR) of both the light and the severe damage to the speech group were higher than those of the control group with significant difference (P<0.05).Significant difference was noticed between the severe damage to the speech group and control group in Jitter. CONCLUSION: Multi Dimensional Voice Program could be used to analyze the characteristics of acoustic parameters of patients with ALS patients complaining of dysarthria. There was more noise composition in the voice of the patients with dysarthria. NHR seemed to be the sensitive and stable parameter. Especially in patients whose speech intelligibility were affected severely, more acoustic parameters were detected with significant difference.

[Echinococcus granulosus infection in dogs and livestock from Xinjiang production and construction corps].

The prevalence of Echinococcus granulosus infection in dogs and livestock was investigated in Xinjiang Production and Construction Corps by stratified random sampling. A total of 5 391 dog feces were detected by double antibody sandwich ELISA, and the positive rate of dog coproantigen was 0.69% (37/5 391). The livestock were subjected to necropsy, inspection and palpation. The prevalence of E. granulosus infection in livestock was 3.88% (431/11 122).

Tinnitus assessment: Chinese version of the Tinnitus Primary Function Questionnaire.

Objective: The aim of this study is to evaluate the Chinese Version of the Tinnitus Primary Function Questionnaire (TPFQ). Methods: One hundred and sixteen patients who had been suffering from tinnitus for over 3 months were included in this study. Those tinnitus patients were administered the TPFQ, the Tinnitus Handicap Inventory (THI), the Beck Anxiety Inventory (BAI), the Beck Depression Inventory (BDI), and the Pittsburgh Sleep Quality Index (PSQI). Additionally, the magnitude estimate of tinnitus loudness, pure tone audiogram, and tinnitus matching was obtained. The factor structure was measured using the Kaiser-Meyer-Olkin test. The internal consistency was examined using Cronbach's α coefficient. The relationships between the TPFQ scores and other measurements were compared using Spearman's rank correlation coefficient. Results: The Cronbach's α of the 20-item version of TPFQ was 0.94, and that of the 12-item version of TPFQ was 0.92. Both the 20- and 12-item versions of TPFQ were significantly correlated with magnitude estimation of tinnitus loudness, THI, PSQI, BDI, and BAI. The average pure tone hearing threshold was significantly correlated with the hearing subscale. Conclusion: The 20- and 12-item Chinese versions of TPFQ are reliable and valid measures of tinnitus. The TPFQ can be applied to the assessment and management of tinnitus among the Chinese-speaking population.

Role of the caudate-putamen nucleus in sensory gating in induced tinnitus in rats.

Tinnitus can be described as the conscious perception of sound without external stimulation, and it is often accompanied by anxiety, depression, and insomnia. Current clinical treatments for tinnitus are ineffective. Although recent studies have indicated that the caudate-putamen nucleus may be a sensory gating area involved in noise elimination in tinnitus, the underlying mechanisms of this disorder are yet to be determined. To investigate the potential role of the caudate-putamen nucleus in experimentally induced tinnitus, we created a rat model of tinnitus induced by intraperitoneal administration of 350 mg/kg sodium salicylate. Our results revealed that the mean spontaneous firing rate of the caudate-putamen nucleus was increased by sodium salicylate treatment, while dopamine levels were decreased. In addition, electrical stimulation of the caudate-putamen nucleus markedly reduced the spontaneous firing rate of neurons in the primary auditory cortex. These findings suggest that the caudate-putamen nucleus plays a sensory gating role in sodium salicylate-induced tinnitus. This study was approved by the Institutional Animal Care and Use Committee of Peking University Health Science Center (approval No. A2010031) on December 6, 2017.

Monomeric C-reactive protein regulates fibronectin mediated monocyte adhesion.

The acute phase reactant C-reactive protein (CRP) binds with high affinity to fibronectin (FN), but this binding occurs only at pH 6.5 or lower, and the binding is inhibited by calcium ions at physiological pH. Since CRP in the circulating blood exists in a calcium-binding form, the interaction between CRP and FN in vivo has been uncertain. CRP can undergo a conformational rearrangement in the absence of calcium or in the local microenvironment (e.g., acidic pH) of inflamed tissue to dissociate into monomeric CRP (mCRP). Therefore, we tested whether these discrepancies can be explained by the different isoforms and locations of CRP. Surface plasmon resonance and ELISA assays showed that mCRP binds with high affinity to FN, and the binding of mCRP to FN was unaffected by calcium or pH. Peptide competition assay, deletion mutant binding assay and protein docking analyse verified that the binding site of mCRP to FN is residues a.a.35-47. Furthermore, mCRP can significantly enhance the adhesion of monocytes to FN as well as upregulate the adhesion molecules expression on endothelial cell. Colocalization of mCRP with FN was observed in mice with DSS-induced colitis, whereas there was very little signal orcolocalization of CRP. These results provide in vitro and in vivo evidence that mCRP formed by local dissociation from circulating CRP is the major isoform that interacts with FN and regulates FN-mediated monocyte adhesion, which is involved in the pro-inflammatory process.

Change of extracellular ascorbic acid in the brain cortex following ice water vestibular stimulation: an on-line electrochemical detection coupled with in vivo microdialysis sampling.

BACKGROUND: Ascorbic acid (AA) represents one of the most important enzyme co-factors, antioxidants and neuromodulators and plays an important role in the cerebral system. Increasing evidence has suggested that AA could treat certain kinds of vertigo diseases such as Meniere's disease. To elucidate the neurochemical functions associated with AA in vertigo, the change of extracellular AA in the brain cortex following caloric vestibular stimulation (CVS) was evaluated. METHODS: An on-line electrochemical detection was coupled with in vivo microdialysis to continuously monitor the change of extracellular AA in the primary somatosensory (SI) area of guinea pigs following a caloric vestibular stimulation. Sixteen guinea pigs were divided into three groups, i.e., experimental group with irrigation of the ear canal with ice water (0 degrees C) (n = 8), and two control groups, one with irrigation of the ear canal with warm water (38 degrees C) (n = 4) and the other with irrigation of the auricle with ice water (n = 4). RESULTS: In the experimental group, the ice water irrigation of the left external ear canal induced a horizontal nystagmus towards the right side lasting about 45 seconds. No nystagmus was induced by warm water irrigation of the external ear canal or by ice water irrigation of the auricle. The extracellular AA concentration significantly increased following the ice water vestibular stimulation, reaching a maximum of (130 +/- 20)% (n = 8) of the basal dialysate level (2.61 +/- 0.92) micromol/L (n = 8), lasting at least for an hour. AA level did not change distinctly after the irrigation of the left external ear canal with warm water or the irrigation of the auricle with ice water. CONCLUSIONS: The concentration of extracellular AA in the brain cortex of the SI area increased following the ice water vestibular stimulation. This demonstration may be useful for the investigation of the neurochemical processes associated with AA in the process of vertigo.

Effect of Neuronal Excitability in Hippocampal CA1 Area on Auditory Pathway in a Rat Model of Tinnitus.

BACKGROUND: Tinnitus is a common disorder that causes significant morbidity; however, the neurophysiological mechanism is not yet fully understood. A relationship between tinnitus and limbic system has been reported. As a significant component of the limbic system, the hippocampus plays an important role in various pathological processes, such as emotional disturbance, decreased learning ability, and deterioration of memory. This study was aimed to explore the role of the hippocampus in the generation of tinnitus by electrophysiological technology. METHODS: A tinnitus model was established in rats through intraperitoneal injection of salicylate (SA). Subsequently, the spontaneous firing rate (SFR) of neurons in the hippocampal CA1 area was recorded with in vivo multichannel recording technology to assess changes in excitability induced by SA. To investigate the effect of excitability changes of hippocampus on the auditory pathway, the hippocampus was electrically stimulated and neural excitability in the auditory cortex (AC) was monitored. RESULTS: Totally 65 neurons in the hippocampal CA1 area were recorded, 45 from the SA group (n = 5), and 20 from the saline group (n = 5). Two hours after treatment, mean SFR of neurons in the hippocampal CA1 area had significantly increased from 3.06 ± 0.36 Hz to 9.18 ± 1.30 Hz in the SA group (t = -4.521, P < 0.05), while no significant difference was observed in the saline group (2.66 ± 0.36 Hz vs. 2.16 ± 0.36 Hz, t = 0.902, P > 0.05). In the AC, 79.3% (157/198) of recorded neurons showed responses to electrical stimulation of the hippocampal CA1 area. Presumed pyramidal neurons were excited, while intermediate neurons were inhibited after electrical stimulation of the hippocampus. CONCLUSIONS: The study shows that the hippocampus is excited in SA-induced tinnitus, and stimulation of hippocampus could modulate neuronal excitability of the AC. The hippocampus is involved in tinnitus and may also have a regulatory effect on the neural center.

Effects of caloric vestibular stimulation on serotoninergic system in the media vestibular nuclei of guinea pigs.

BACKGROUND: Anatomic and electrophysiological studies have revealed that the neurons located in the media vestibular nuclei (MVN) receive most of the sensory vestibular input coming from the ipsilateral labyrinth and the responses of MVN neurons to caloric stimulation directly reflect changes in primary vestibular afferent activity. The aim of this study was to clarify the intrinsic characteristics of serotonin (5-hydroxytryptamine, 5-HT) release in the MVN during the period of vertigo induced by caloric stimulation. METHODS: We used an in vivo microdialysis technique to examine the effects of caloric stimulation on the serotoninergic system in MVN. Twenty four guinea pigs were randomly divided into the groups of irrigation of the ear canal with hot water (n = 6), ice water (n = 6) and 37 degrees C water (n = 4), and the groups of irrigation of the auricle with hot water (n = 4) and ice water (n = 4), according to different caloric vestibular stimulation. We examined the animal's caloric nystagmus with a two-channel electronystagmographic recorder (ENG), and meanwhile examine serotonin (5-hydroxytryptamine, 5-HT) level in the MVN with microdialysis technique after caloric stimulation. RESULTS: In the caloric test the hot water (44 degrees C) irrigation of the right external auditory canal induced horizontal nystagmus towards the right side lasting about 60 seconds and the ice water irrigation of the right external auditory canal induced it towards the left side lasting for about 90 seconds. No nystagmus was induced by 37 degrees C water irrigation of the external ear canal. Therefore, it was used as a negative control stimulation to the middle ear. The MVN 5-HT levels significantly increased in the first 5-minute collecting interval and increased to 254% and 189% of the control group in the second collecting interval in response to caloric vestibular stimulation with ice water and hot water respectively. The serotonin release was not distinctly changed by the irrigation of the auricle with ice water or hot water. CONCLUSIONS: Neither somato-sensory stimulation of the middle ear nor nonspecific cold or hot stress affects the serotonin release. The rise of 5-HT in MVN may be involved in the mechanism of vertigo induced by caloric stimulation.

[Expression of desmoglein 3 in nasopharyngeal carcinoma: research of 22 cases].

OBJECTIVE: To investigate the expression of desmoglein 3 (DSG3), a candidate target gene in the antisense RNA (aRNA) from the purified nasopharyngeal tissues in nasopharyngeal carcinoma (NPC). METHODS: Specimens of nasopharyngeal tissues were harvested from 22 NPC patients, aged 44 +/- 11 (NPC group), and 12 normal persons or patients with nasopharyngeal infectious diseases, aged 46 +/- 14. Microdissection technique was used to get homogenous tissue cells from which total RNA was isolated (control group). aRNA was amplified from the total RNA by "in vitro transcription" (IVT). The expression of DSG3 gene was identified using these aRNA by semi-quantitative reverse transcriptase polymerase chain reaction (sqRT-PCR). RESULTS: The average expression level of DSG3 in the NPC group was 3.536 +/- 2.689, significantly higher than that of the control group (0.95 +/- 0.23, df = 32, t = 3.307, P = 0.002). The expression level of DSG3 in the whole expression profiling of the NPC group was 1.06 +/- 1.60, significantly higher than that of the control group (0.48 +/- 0.23, df = 16, t = 2.145, P = 0.048). CONCLUSION: The whole genome expression profiling detected by sqRT-PCR can be used to shift the marker genes from biopsy tissue samples. DSG3 may be a tumor candidate gene in NPC.

Minimally Invasive Cochlear Implantation Assisted by Bi-planar Device: An Exploratory Feasibility Study in vitro.

BACKGROUND: A single drilled tunnel from the lateral mastoid cortex to the cochlea via the facial recess is essential for minimally invasive cochlear implant surgery. This study aimed to explore the safety profile of this kind of new image-guided and bi-planar device-assisted surgery procedure in vitro. METHODS: Image-guided minimally invasive cochlear implantations were performed on eight cadaveric temporal bone specimens. The main procedures were: (1) temporal bone specimens were prepared for surgery and fiducial markers were registered. (2) computed tomography (CT) scans were performed for future reference. (3) CT scan images were processed and drill path was planned to minimize cochlear damage. (4) bi-planar device-assisted drilling was performed on the specimens using the registration. (5) surgical safety was evaluated by calculating the deviation between the drill and the planned paths, and by measuring the closest distance between the drilled path and critical anatomic structures. RESULTS: Eight cases were operated successfully to the basal turn of the cochlear with intact facial nerves (FNs). The deviations from target points and entrance points were 0.86 mm (0.68-1.00 mm) and 0.44 mm (0.30-0.96 mm), respectively. The angular error between the planned and the drilled trajectory was 1.74° (1.26-2.41°). The mean distance from the edge of the drilled path to the FN and to the external canal was 0.60 mm (0.35-0.83 mm) and 1.60 mm (1.30-2.05 mm), respectively. In five specimens, the chorda tympani nerves were well preserved. In all cases, no injury happened to auditory ossicles. CONCLUSIONS: This exploratory study demonstrated the safety of the newly developed image-guided minimally invasive cochlear implantation assisted by the bi-planar device and established the operational procedures. Further, more in vitro experiments are needed to improve the system operation and its safety.

[Effectiveness of voice training for professional voice users with voice disorders].

OBJECTIVE: To explore the effectiveness of voice training on professional voice users with voice disorders. METHODS: Thirty one professional voice users suffering from voice symptoms without organic disorder were treated with a four-week voice training program, including vocal hygiene education, respiratory training and resonant therapy. Voice handicap index, maximum phonation time, noise to harmonic ratio, jitter and shimmer were compared before and after the training. RESULTS: The voice handicap index (x(-) ± s) decreased from 33.7 ± 19.2 to 18.8 ± 18.4 after the training and the difference was significant (t = 6.14, P < 0.05). Maximum phonation time (x(-) ± s) increased significantly from (15.5 ± 5.8) s to (18.6 ± 6.0) s (t = -3.43, P < 0.05). jitter (M [P(25); P(75)]) decreased significantly after the training from 0.42% [0.36%; 0.62%] to 0.35% [0.29%; 0.47%] (Z = -2.51, P < 0.05), while there was no significant change in shimmer and noise to harmonic ratio. CONCLUSION: Voice training can effectively reduce the vocal symptoms in professional voice users, decrease the handicap degree and increase the respiratory support during phonation, thus improve the voice quality.

[Significance of maxillary septa in endoscopic nasal surgery].

OBJECTIVE: To explore the significance of maxillary septa in endoscopic nasal surgery. METHODS: Five hundred and ninety-two patients (both inpatients and outpatients) encountered in our hospital during May 2006 and December 2006 were included in this study. Computer tomography images of sinuses from scheduled axial and coronal or saggital scan were analyzed by using digital imaging and communication in medicine. RESULTS: The incidence of the coronal complete maxillary septa was 3.2% (19/592), 16 cases on bilateral sides and 3 cases on unilateral side. The cavity anterior to the coronal complete maxillary septa drainage into the middle meatus, whereas the antrum posterior drainage into the superior meatus. The incidence of chronic sinusitis was 36.8% (7/19) in patients with coronal complete maxillary septa. CONCLUSIONS: The optimum method to observe maxillary coronal septa was axial CT. The diseases in the cavity posterior to the coronal complete maxillary septa and in pterygopalatine fossa should be operated via the superior meatus.

Alteration of gene expression during nasopharyngeal carcinogenesis revealed by oligonucleotide microarray after microdissection of tumor tissue and normal epithelia from nasopharynx.

BACKGROUND: Microarray and microdissection techniques were being used for many applications to study the carcinogenesis of some human tumors. But seldom studies had hitherto combined these two techniques to study carcinogenesis mechanism of nasopharyngeal carcinoma (NPC). To identify a set of genes involved in the carcinogenesis and development of NPC, we used the microdissected homogeneous NPC tissue cells and the pure normal epithelium pillar cells to construct the whole human genome expression profiles. METHODS: We preserved the tissue samples from nasopharynx of 18 patients (including 13 samples of NPC and 5 samples of normal or inflammatory mucous tissue samples from nasopharynx) in RNAlater Stabilization Reagent. The tissue samples were microdissected to harvest the homogeneous tissue cells, then total RNA was isolated from them. The sufficient antisense RNA (aRNA) was amplified from these total RNA. HG-U133.Plus.2.0 GeneChip was used to construct the human whole genome expression profiling of each sample. Differential patterns of expression of genes correlated with the carcinogenesis, classification and progression of NPC were identified with comparing the expression profiling data respectively in leave one out cross-validation analysis. Correlation between aRNA expression measured by the microarrays and semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) were also ascertained, and found that hybridization results were validated in all of the 18 patients. RESULTS: Differential patterns of expression of 127 genes correlated with the carcinogenesis (A P value less than 0.001 with the 2-fold differentiated expression between case group and control group) of the NPC were filtered. The top most up-regulated and down-regulated 8 genes by the way of permutation test were also selected and listed in the paper. Expression of genes E2F6 and TSPAN-1 was identified using aRNA by sqRT-PCR and showed that there was significant difference between the average value of case groups and that of control group respectively (t = 2.170, df = 16, P = 0.045 and t = -2.946, df = 16, P = 0.009). CONCLUSIONS: We had identified some genes which could be the molecular marker during the carcinogenesis and the development of the NPC. The genes which selected from the different subgroups seemed to be implicated for the diagnosis,classification, and progression of NPC, and provided important insights into their underlying biology.

[Anatomy of locating the internal auditory canal through the middle fossa approach with the assistance of high resolution CT].

OBJECTIVE: To evaluate the feasibility of localizing the internal auditory canal (IAC) and the facial nerve through the root of the zygoma, foramen spinosum and the head of the malleus in middle fossa approach with the assistance of high resolution computerized tomography (HRCT). METHODS: Eighteen human cadaveric temporal bones were scanned and measured by HRCT. Cadaver specimen were divided into two groups. Group A was studied first through a middle fossa approach to find out the relationship between the HRCT measurements and the anatomic measurements. Then 4 whole human cadaveric heads (8 temporal bones) of group B were dissected using a HRCT oriented middle fossa approach to localize IAC with the root of the zygoma, foramen spinosum and the head of the malleus as landmarks. The two measurement methods were analysed with the Paired-Sample T test, and the difference was thought to be statistical significant when P < 0.05. RESULTS: In Group A, there were no statistical significant differences between the CT measurements and the anatomic measurements from the head of the malleus to other important anatomic structures. In group B, the operation was guided with CT measurements: the distance between the head of the malleus and the root of the zygoma, and the distance between the head of the malleus and foramen spinosum. Within the range 1.5 mm to 3.7 mm, the head of malleus was correctly localized. In seven out of the eight cases, the root of the zygoma, the head of the malleus and the internal auditory canal were in a straight line, whereas, in one case, there was an angle of 15 degrees between the root of zygoma -head of malleus line and head of malleus -internal auditory canal line. CONCLUSIONS: HRCT would provide more information on the distance relationship between the head of malleus and the root of the zygoma, foramen spinosum and the internal auditory canal. The head of the malleus could be localized through the root of the zygoma and foramen spinosum with HRCT and therefore the IAC could be exposed with the head of the malleus as a landmark in middle fossa approach when other landmarks were not recognizable.

[Efficacy of Betahistine Mesilate combined with Flunarizine Hydrochloride for treating tinnitus].

OBJECTIVE: To determine whether Betahistine mesilate is effective in treating tinnitus. METHODS: Randomized, prospective, double-blind, controlled trial was used in our study. The study group consisted of 60 adult patients who consulted our outpatient clinic complaining of subjective tinnitus, excluded objective tinnitus and the patients who had tinnitus caused by obvious diseases, such as outer and middle ear diseases. Thirty patients were given Betahistine mesilate and Flunarizine Hydrochloride as an experimental group, 30 patients were given Vitamin B6 and Flunarizine Hydrochloride as a control group. After a week of treatment the efficacy of the medicines in two groups was observed. Tinnitus questionnaire was performed before the treatment, and pure tone audiogram, tinnitus pitch and loudness matching were performed both in the beginning and at the end of the treatment. RESULTS: Completion of treatment, tinnitus loudness matching assessment showed that the efficacy of the Betahistine mesilate group was better then the control group. The efficacy of treatment was respectively 65.5% by per protocol (PP) and 63.3% by intend to treat (ITT) in the Betahistine mesilate group and 39.3% by PP and 36.7% by ITT in the control group. The difference of tinnitus loudness improvement rate between the experimental group and control group was statistically significant. But the subjective tinnitus improvement rate showed no difference between two groups. There were not serious side effects in the two groups. CONCLUSIONS: Betahistine mesilate can be a choice for tinnitus treatment clinically. Further studies of larger series and placebo-controlled trial are needed.