Efficacy of Tailor-Made Notched Music Training Versus Tinnitus Retraining Therapy in Adults With Chronic Subjective Tinnitus: A Randomized Controlled Clinical Trial.

OBJECTIVES: Chronic subjective tinnitus can have a serious effect on daily life, even causing serious psychological disorders. Currently there are no specific effective solutions or cures. Tailor-made notched music training (TMNMT) is a recently proposed sound therapy that has simpler processes and a higher compliance rate than tinnitus retraining therapy (TRT), a widely used treatment for chronic subjective tinnitus. This study explores the therapeutic effect of TMNMT in comparison to TRT to highlight its clinical value. DESIGN: The study was a randomized controlled, single-blinded clinical trial. One hundred twenty eligible participants were randomly assigned to receive TMNMT (n = 60) or TRT (n = 60) for 3 mo with concurrent follow-up. It should be noted that the duration of sound treatment in TRT was modified to 2 hr per day for better feasibility in practice. The primary outcome was mean change in tinnitus handicap inventory (THI) measured at baseline ( T0 ), 1 mo ( T1 ) and 3 mo ( T2 ) after intervention. Change in visual analog scale (VAS) was measured as a secondary outcome. A comparison of therapeutic effectiveness between TMNMT and TRT was evaluated by repeated measure analysis of variance. RESULTS: One hundred and twelve (93%) of participants took part in the study, of which 64 were men and 48 women. Mean (SD) age was 42.80 (12.91) years. Fifty-eight were allocated to receive TMNMT and 54 to receive TRT. The between-group difference in primary outcome was -6.90 points (95% confidence interval [CI], -13.53 to -0.27) at T1 and -6.17 points (95% CI, -13.04 to 0.71) at T2 . These results closely reached to clinical significance of tinnitus-related effective relief. For the secondary outcome, the mean value in the TMNMT group was 0.83 points (95% CI, 0.12 to 1.54), significantly lower than the mean value of the TRT group. The differences in THI and VAS between the two groups were statistically significant after intervention. Further analysis showed that age and baseline THI and VAS scores were associated with change in THI and VAS scores after interventions. CONCLUSIONS: Both TMNMT and TRT were able to alleviate chronic subjective tinnitus effectively after a 3 month intervention. When the two forms of therapy were compared TMNMT appeared to be more effective and consequently potentially superior to TRT for reducing tinnitus loudness and functional and emotional disturbance associated with chronic subjective tinnitus.

SRY-related high-mobility group box 9 (SOX9) alleviates cigarette smoke extract (CSE)-induced inflammatory injury in human bronchial epithelial cells by suppressing stromal interaction molecule 1 (STIM1) expression.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a chronic airway disease with airflow limitation and abnormal inflammatory response. It has been verified that SOX9 plays a key role in lung function of various lung diseases and SOX9 is closely associated with COPD. Additionally, literature has reported that STIM1 is involved in lung injury and is highly expressed in neutrophils from COPD patients. This study aimed to characterize the biological roles of SOX9 and STIM1 in the pathogenesis of COPD and to elucidate the regulatory mechanism. METHODS: Human bronchial epithelial cells (BEAS-2B) were treated with CSE to construct in vitro COPD model. The levels of SOX9 and STIM1 in CSE-treated BEAS-2B cells were detected by western blot and RT-qPCR assay. Then, JASPAR datasets were utilized to analyze SOX9 binding sites in the promoter region of STIM1. Besides, luciferase reporter assay and ChIP assay were employed to validate the binding sites in STIM1 promoter region to SOX9. In addition, viability and apoptosis of BEAS-2B cells were assessed by utilizing MTT assay and TUNEL staining. ELISA kits and corresponding commercial kits were applied to measure the levels of TNF-α, IL-6, IL-1ß, SOD, GSH-Px and MDA. RESULTS: CSE treatment dose- and time-dependently reduced SOX9 expression in BEAS-2B cells. SOX9 overexpression enhanced the viability and suppressed the apoptosis of CSE-treated BEAS-2B cells as well as attenuated CSE-induced inflammation and oxidative stress. Then, it was validated that SOX9 bound to the promoter region of STIM1. Moreover, SOX9 overexpression-mediated impacts on cell viability, cell apoptosis, inflammation and oxidative stress in CSE-treated BEAS-2B cells were partially abolished by upregulation of STIM1. CONCLUSION: To sum up, results here suggested that overexpression of SOX9 could mitigate inflammatory injury in CSE-treated bronchial epithelial cells by suppressing STIM1.

Evaluation of subjective visual vertical and horizontal in patients with acoustic neuroma based on virtual reality.

Objective: To investigate potential differences in absolute deviation values of subjective visual vertical and horizontal between unilateral acoustic neuroma patients and healthy young adults under varying degrees of static head tilt, as well as the impact of proprioception on these values, with the aim of determining the effect of acoustic neuroma on gravity sensory pathway function in patients. Methods: We recruited 22 patients diagnosed with unilateral acoustic neuroma and 25 healthy young adults and employed virtual reality technology to assess the absolute deviation values of subjective visual vertical (SVV) and subjective visual horizontal (SVH) under eight different static tilted head positions (Head centered (0° tilt), PdP, Head tilt 15°, 30°, 45° to the left and right), then compare and analyze intergroup differences. Results: In the Head-centered position, both SVV and SVH absolute deviated values were significantly higher in the AN group compared to healthy young adults. The AN group exhibited significantly higher absolute deviation values of SVV compared to the healthy group when tilting their head 30° left and right. Additionally, when tilting their heads to the right at 15° and 45° the AN group showed significant increases in SVH absolute deviated values compared to healthy adults. The SVV and SVH absolute deviation values of LAN and SAN groups did not reach statistical significance. The results of the SVV test for PDP position did not show any significant differences among all groups. However, the SVH test revealed that the absolute deviation values of the LAN group was significantly higher than that of healthy individuals. Conclusion: Our study shows that the gravity sensing function of patients with unilateral acoustic neuroma is affected to different degrees, however, the degree of gravity sensing function damage of patients has little relationship with tumor size. When acoustic neuroma is larger than 2 cm, the effect of proprioception on patients' SVH outcome is noteworthy. So, we should pay attention to the postoperative follow-up of patients with acoustic neuroma and the evaluation of vestibular rehabilitation effect. Meanwhile, for patients opting for conservative treatment, it is imperative to monitor the dynamic changes in vestibular function and seize timely opportunities for intervention.

Age-related hearing loss accelerates the decline in fast speech comprehension and the decompensation of cortical network connections.

Patients with age-related hearing loss face hearing difficulties in daily life. The causes of age-related hearing loss are complex and include changes in peripheral hearing, central processing, and cognitive-related abilities. Furthermore, the factors by which aging relates to hearing loss via changes in auditory processing ability are still unclear. In this cross-sectional study, we evaluated 27 older adults (over 60 years old) with age-related hearing loss, 21 older adults (over 60 years old) with normal hearing, and 30 younger subjects (18-30 years old) with normal hearing. We used the outcome of the upper-threshold test, including the time-compressed threshold and the speech recognition threshold in noisy conditions, as a behavioral indicator of auditory processing ability. We also used electroencephalography to identify presbycusis-related abnormalities in the brain while the participants were in a spontaneous resting state. The time-compressed threshold and speech recognition threshold data indicated significant differences among the groups. In patients with age-related hearing loss, information masking (babble noise) had a greater effect than energy masking (speech-shaped noise) on processing difficulties. In terms of resting-state electroencephalography signals, we observed enhanced frontal lobe (Brodmann's area, BA11) activation in the older adults with normal hearing compared with the younger participants with normal hearing, and greater activation in the parietal (BA7) and occipital (BA19) lobes in the individuals with age-related hearing loss compared with the younger adults. Our functional connection analysis suggested that compared with younger people, the older adults with normal hearing exhibited enhanced connections among networks, including the default mode network, sensorimotor network, cingulo-opercular network, occipital network, and frontoparietal network. These results suggest that both normal aging and the development of age-related hearing loss have a negative effect on advanced auditory processing capabilities and that hearing loss accelerates the decline in speech comprehension, especially in speech competition situations. Older adults with normal hearing may have increased compensatory attentional resource recruitment represented by the top-down active listening mechanism, while those with age-related hearing loss exhibit decompensation of network connections involving multisensory integration.

Tinnitus Affects Endogenous But Not Exogenous Auditory Attention Orienting.

PURPOSE: Previous studies have demonstrated that people with tinnitus show attention dysfunctions. In this study, we investigated the influence of tinnitus on attention orienting, especially whether the ability of attention orienting could be modulated by the degree of tinnitus. METHOD: Fifty-nine and 54 unilateral tinnitus participants were included in Experiment 1 and Experiment 2, respectively. All participants reported subjective tinnitus for at least 3 months and were divided into a mild tinnitus group (Tinnitus Handicap Inventory [THI] < 37) or a moderate to severe tinnitus group (THI ≥ 37) according to the THI score. An auditory exogenous attention task and an auditory endogenous attention task were adopted. In the exogenous task, a target sound following a cue sound was presented on either the left or right side. Participants were required to discriminate whether the target was pure tone or white noise. In the endogenous task, participants were required to pay attention to the stimuli on one side and judge the pitch of a target sound. Mixed-design analyses of variance were conducted for the mean reaction times and accuracy across the experimental conditions. RESULTS: Our results showed that in the endogenous attention task, compared with the mild tinnitus group, moderate to severe tinnitus participants had better performance for stimuli presented on the tinnitus side but not on the nontinnitus side. In contrast, in the exogenous attention task, no differences were found between mild and moderate to severe tinnitus groups. CONCLUSION: The results suggest that the degree of tinnitus influences the performance of auditory endogenous attention but not auditory exogenous attention orienting.

Downregulation of DBN1 is related to vincristine resistance in colon cancer cells.

OBJECTIVE: This study was aimed to investigate the relationship between the expression of drebrin (DBN1) gene and resistance in colon cancer to reveal the mechanism of tumor drug resistance and provide a basis for the reversal of this drug resistance in tumor cells. MATERIALS AND METHODS: The human colon carcinoma cell line HCT-8 was used, and vincristine (VCR)-resistant colon cancer cell line HCT-8/V was established by gradually increasing the concentration of VCR. Polymerase chain reaction (PCR) primers were designed for DBN1 gene. The DBN1 differential expression in colon cancer sensitive and resistant cell lines was detected by fluorescence quantitative PCR. Western blot analysis was used to study DBN1 expression in the resistant cells further. RESULTS: VCR resistance of HCT-8/V cell line was established. Quantitative PCR and Western blot results showed that DBN1 expression in the resistant cell line was significantly lower, the difference being statistically significant (P < 0.05). CONCLUSION: Low DBN1 gene expression may be associated with colon cancer cell resistance to VCR.

Reliability and validity of the mandarin version of the tinnitus primary function questionnaire: A preliminary observational study.

Tinnitus is a prevalent condition among different populations. As the nature of tinnitus is subjective, self-reported measures have been validated and utilized to assess psychometric properties of tinnitus patients. Without exception, Chinese clinicians have administered these measures to patients in mainland China after cross-cultural adaptation. However, shortcomings of these Mandarin measures limited the widespread use of them. Measures which can be fully adapted to the context of Chinese tinnitus patients are still needed. The objective of this study was to evaluate the reliability and validity of the Mandarin Tinnitus Primary Function Questionnaire (TPFQ-M) in a Chinese population.In this observational questionnaire study, we recruited 350 subjects with primary tinnitus from hearing clinics of West China Hospital and administered the TPFQ-M, Mandarin Tinnitus Handicap Inventory (THI-M), and a systematic hearing test battery.The subjects finished the TPFQ-M within 3 minutes. Exploratory and confirmatory factor analyses demonstrated that a 4-factor model was close to fit. The Cronbach alpha of TPFQ-M was 0.925, and test-retest reliability was reasonable with a 7-day test interval (ICC = 0.857, P < .001; 95% CI: 0.764-0.915). Test-retest reliabilities of subdomains were not parallel to each other, with 0.612 for Emotion, 0.766 for Sleep, 0.860 for Concentration, and 0.897 for Hearing. The convergent validity of TPFQ-M compared to the THI-M was moderate (r = 0.705, P < .001; 95% CI: 0.647-0.754).The TPFQ-M, which shows high internal consistency and good factor structure, is simple and relatively easy to administer in busy clinics. Additional in-depth research involving multiple centers in mainland China is warranted.

Effect of CEACAM-1 knockdown in human colorectal cancer cells.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) is the major antigen of the CD66 cluster of granulocyte differentiation antigens. The present study aimed to assess the biological function of CEACAM-1 on the growth of human colorectal cancer (CRC) cells in vitro. Treatment of cultured CRC HCT-8 cells with CEACAM-1-specific siRNA successfully downregulated CEACAM-1 expression by 61% compared with control cells. The effects of CEACAM-1 downregulation on HCT-8 cell proliferation and apoptosis were then assessed via Cell Counting kit-8 assay and flow cytometry, respectively. The results demonstrated that siRNA-induced CEACAM-1 downregulation significantly inhibited proliferation and increased apoptosis, but had no significant effect on cell cycle progression in HCT-8 cells. Together, these results suggest that CEACAM-1 activity is critical to CRC growth, and thus, CEACAM-1 may be a promising therapeutic target for the treatment of CRC.

Brain-derived neurotrophic factor gene-modified bone marrow mesenchymal stem cells.

The present study aimed to investigate the effects of human brain-derived neurotrophic factor (hBDNF) on the differentiation of bone marrow mesenchymal stem cells (MSCs) into neuron-like cells. Lentiviral vectors carrying the hBDNF gene were used to modify the bone marrow stromal cells (BMSCs) of Sprague-Dawley (SD) rats. The rat BMSCs were isolated, cultured and identified. A lentivirus bearing hBDNF and enhanced green fluorescent protein (eGFP) genes was subcultured and used to infect the SD rat BMSCs. The expression of eGFP was observed under a fluorescence microscope to determine the infection rate and growth of the transfected cells. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) was used to detect the proliferation rate of cells following transfection. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to detect the expression levels of hBDNF. Differentiation of neuron-like cells was induced in vitro and the differentiation rate of the induced neural-like cells was compared with that in control groups and analyzed statistically. In the cultured cells, flow cytometry demonstrated positive expression of cluster of differentiation (CD)90 and CD44, and negative expression of CD34 and CD45. The proliferation rate of the rat BMSCs increased following gene transfection. The expression of hBDNF-eGFP was detected in the BMSCs of the experimental group. The differentiation rate of hBDNF-modified cells into neuron-like cells in the experimental group was higher compared with that in empty plasmid and untransfected negative control groups. The difference was statistically significant (P<0.05). Thus, BDNF gene transfection is able to promote the differentiation of BMSCs into neuron-like cells. BDNF may play an important role in the differentiation of MSCs into neuron-like cells.

Downregulation of DBN1 is related to vincristine resistance in colon cancer cells

Objective: This study was aimed to investigate the relationship between the expression of drebrin (DBN1) gene and resistance in colon cancer to reveal the mechanism of tumor drug resistance and provide a basis for the reversal of this drug resistance in tumor cells. Materials and Methods: The human colon carcinoma cell line HCT-8 was used, and vincristine (VCR)-resistant colon cancer cell line HCT-8/V was established by gradually increasing the concentration of VCR. Polymerase chain reaction (PCR) primers were designed for DBN1 gene. The DBN1 differential expression in colon cancer sensitive and resistant cell lines was detected by fluorescence quantitative PCR. Western blot analysis was used to study DBN1 expression in the resistant cells further. Results: VCR resistance of HCT-8/V cell line was established. Quantitative PCR and Western blot results showed that DBN1 expression in the resistant cell line was significantly lower, the difference being statistically significant (P < 0.05). Conclusion: Low DBN1 gene expression may be associated with colon cancer cell resistance to VCR.