Bhlhe40 protects cochlear hair cell-like HEI-OC1 cells against H_(2)O_(2) ‑triggered oxidative injury

Background:Cochlear hair cell injury is a common pathological feature of hearing loss.The basic helix-loop-helix family,member e40(Bhlhe40),a gene belonging to the basic helix-loop-helix(bHLH)family,exhibits strong transcriptional repression activity.Methods:Oxidative damage,in House Ear Institute-Organ of Corti 1(HEI-OC1)cells,was caused using hydrogen peroxide(H2O2).The Ad-Bhlhe40 particles were constructed to overexpress Bhlhe40 in HEI-OC1 cells.Various assays including cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay(TUNEL),flow cytometry,immunofluorescence,and corresponding commercial kits were employed to investigate the impacts of Bhlhe40 on cell viability,apoptosis,oxidative stress levels,mitochondrial membrane potential and cellular senescence.Additionally,a dual-luciferase reporter assay was performed to confirm the targeting of the histone deacetylases 2(Hdac2)by Bhlhe40.Results:The results revealed that Bhlhe40 was downregulated in H_(2)O_(2)-treated HEI-OC1 cells,but its overexpression improved cell viability and mitigated H_(2)O_(2)-induced oxidative injury in HEI-OC1 cells with increase of superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GPx)activities and decrease of reactive oxygen species(ROS)levels.Besides,overexpression of Bhlhe40 suppressed H_(2)O_(2)-triggered cell senescence,as evidenced by the fact that the upregulation of P53,P21,and P16 in HEI-OC1 cells treated with H2O2 were all alleviated by Bhlhe40 overexpression.And we further verified that overexpression of Bhlhe40 could inhibit the expression of Hdac2,which may be related to the repression of Hdac2 transcription.Conclusion:This study suggests that Bhlhe40 plays a protective role against senescence and oxidative damage in cochlear hair cells exposed to H2O2.

Inhibitory Effects of 5-Aza-2'-Deoxycytidine and Trichostatin A in Combination with p53-Expressing Adenovirus on Human Laryngocarcinoma Cells

Objective： To investigate the effects of 5-Aza-2＇-deoxycytidine （5-Aza-Cdr） and trichostatin A （TSA） combined with p53-expressing adenovirus （Ad-p53） on Hep-2 cell line in vivo and in vitro, in order to explore its possibility in biological treatment of laryngocarcinoma. Methods： Effects of 5-Aza-Cdr and TSA in combination with Ad-p53 on Hep-2 cell line in vivo were determined by Cell Counting Kit-8 （CCK-8） assay. The effect of drug combination was calculated by Jin＇s formula. Effects on the cell line in vitro were investigated by establishing the nude mice model. Results： 5-Aza-Cdr and TSA showed inhibitory effects on the proliferation of Hep-2 cells in dose- and time-dependent manner. Ad-p53 can inhibit the growth of Hep-2 cells in vivo and in vitro. However, the combination of epigenetic reagents （5-Aza-Cdr/TSA） and Ad-p53 was less effective than individual use of Ad-p53. 5-Aza-Cdr and Ad-p53 inhibited the growth of transplanted tumors and reduced the volume of tumors, and the tumor volume of Ad-p53 group was significantly smaller than that of the control group （P0.05）. Conclusion： Both epigenetic reagents （5-Aza-Cdr/TSA） and Ad-p53 can suppress cell proliferation on Hep-2 in vivo and in vitro and there may be some antagonistic mechanism between Ad-p53 and epigenetic reagents （5-Aza-Cdr/ TSA）.

Effects of IL-17 on Expression of GRO-α and IL-8 in Fibroblasts from Nasal Polyps

Recent studies indicated that interleukin（IL）-17, growth-related oncogene（GRO）-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO-α and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-α and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction（RT-PCR） was used to detect the mRNA expression of GRO-α and IL-8. The mRNA of GRO-α and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-α and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-α and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps.

Auditory characteristics of noise-exposed memberscrossing age-related groups

Objective： To report audiological characteristics in a group of noise-exposed crew members on board ships. Methods and materials： Clinical and audiological measurements including pure-tone thresholds, acoustic immittance results and tinnitus questionnaires were collected from both the ship crew members （study subjects） and their land based colleagues （controls）. Results： 1） Noise exposed crew members showed not only high frequency, but also low frequency hearing loss; 2） Hearing impairment increased with age, with 65.5% of crew members younger than 50 years showing normal hearing while only 14.9% of those older than 50 years had normal hearing; 3） hearing loss gradually increased with the extension of on board career time; and 4） Most study subjects reported high pitch tinnitus, significantly more than the control group although not significantly different among different age groups. Conclusion： Noise induced hearing impairment from working on board ships shows specific frequency and age characteristics. Understanding these characteristics is important for advancing relevant studies and for effective prevention of noise-induced hearing loss in ship crew members.

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.

Late Complication of Tracheostomy: Larynx-Shaped Reorganization of the Tracheal Rings or the True Larynx?

Tracheostomy is a well-established, commonly used surgical procedure, whose early and late complications are widely described in literature. Some of them remain still poorly known, though. One of these rare complications is a peculiar larynx-shaped reorganization of the tracheal rings and cricoid cartilage. This tracheal narrowing seems to be non- symptomatic and not life-threatening, at least as long as the reduction of the lumen is <50% - 75%. Such a finding has never been described so far in the literature, and should be kept in mind as one of late complication of tracheostomy.

The single-cell transcriptomic landscape of the topological differences in mammalian auditory receptors

Mammalian hair cells(HCs)are arranged spirally along the cochlear axis and correspond to different frequency ranges.Serving as primary sound detectors,HCs spatially segregate component frequencies into a topographical map.HCs display significant diversity in anatomical and physiological characteristics,yet little is known about the organization of the cochleotopic map of HCs or the molecules involved in this process.Using single-cell RNA sequencing,we determined the distinct molecular profiles of inner hair cells and outer hair cells,and we identified numerous position-dependent genes that were expressed as gradients.Newly identified genes such as Ptn,Rxra,and Nfe2l2 were found to be associated with tonotopy.We employed the SCENIC algorithm to predict the transcription factors that potentially shape these tonotopic gradients.Furthermore,we confirmed that Nfe2l2,a tonotopy-related transcription factor,is critical in mice for sensing low-tomedium sound frequencies in vivo.the analysis of cell-cell communication revealed potential receptor-ligand networks linking inner hair cells to spiral ganglion neurons,including pathways such as BDNF-Ntrk and PTN-Scd4,which likely play essential roles in tonotopic maintenance.Overall,these findings suggest that molecular gradients serve as the organizing principle for maintaining the selection of sound frequencies by HCs.

Healthcare Algorithms by Wearable Inertial Sensors: A Survey

Wearable smart devices, such as smart watch, wristband are becoming increasingly popular recently. They generally integrate the MEMS-designed inertial sensors, including accelerometer, gyroscope and compass, which provide a convenient and inexpensive way to collect motion data of users. Such rich, continuous motion data provide great potential for remote healthcare and decease diagnosis. Information processing algorithms play the critical role in these approaches, which is to extract the motion signatures and to access different kinds of judgements. This paper reviews key algorithms in these areas. In particular, we focus on three kinds of applications: 1) gait analysis; 2) fall detection and 3) sleep monitoring. They are the most popular healthcare applications based on the inertial data. By categorizing and introducing the key algorithms, this paper tries to build a clear map of how the inertial data are processed; how the inertial signatures are defined, extracted, and utilized in different kinds of applications. This will provide a valuable guidance for users to understand the methodologies and to select proper algorithm for specifi c application purpose.

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.

Factors contributing to lymph node occult metastasis in supraglottic laryngeal carcinoma cT2-T4 N0M0 and metastasis predictive equation

Objective： To investigate factors that contribute to lymph node metastasis（LNM） from clinical cT2-T4 N0M0（cN0） supraglottic laryngeal carcinoma（SLC）, and to predict the risk of occult metastasis before surgery.Methods： A total of 121 patients who received surgery were retrospectively analyzed. Relevant factors regarding cervical LNM were analyzed. Multivariate analyses were conducted to predict the region where the metastasis occurred and prognosis. Results： The overall metastatic rate of c N0 SLC was 28.1%. Metastatic rates were 15.4%, 32.5% and 35.7% for T2, T3 and T4, respectively. Metastatic rates for SLC levels II, III and IV were 19.6%, 17.2% and 3.6%, respectively. A regression equation was formulated to predict the probability of metastasis in cN0 SLC as follows： Pn=e（–3.874＋0.749T3＋1.154T4＋1.935P1＋1.750P2）/[1＋e（–3.874＋0.749T3＋1.154T4＋1.935P1＋1.750P2）]. Approximately 0.2% of patients experienced LNM with no recurrence of laryngeal cancer. Comparison of the intergroup survival curves between patients with and without LNM indicated a statistically significant difference（P=0.029）.Conclusions： Cervical lymph node metastatic rates tended to increase in tandem with T stage in patients with LNM in cN0 SLC, and neck dissection is advised for these patients. Moreover, cervical LNM in cN0 SLC showed a sequential pattern and may be predicted.

RECENT ADVANCES OF OTORHINOLARYNGOLOGY IN CHINA

In recent years, great advances of otorhino-laryngology have been achieved in China, in the following three aspects chiefly:

FDG-PET AS A ROUTINE SURVEILLANCE TOOL IN HEAD AND NECK CARCINOMA SIX MONTHS AFTER TREATMENT

Objective To evaluate prospectively the impact of fluorodeoxyglucose-fluorine-18 positron emission tomography (FDG-PET) in the detection of recurrence, second primary cancers, and distant metastases in head and neck squamous cell carcinoma (HNSCC) 6 months after treatment. Methods A total of 41 patients without any clinical element for recurrence, second primary cancer, or distant metastases received a whole-body FDG-PET as a routine surveillance tool 6 months after initial combined curative therapy for HNSCC. Results There were 35 negative PET results and 6 positive. One patient with abnormal FDG-PET did not have recurrent HNSCC (false positive). Five had true positive results: proven recurrence in 2 patients, second primary cancer in 2, and distant metastasis in 1. The sensitivity and specificity of FDG-PET for the diagnosis of HNSCC recurrence, second tumor, and distant metastases were 100% (5/5) and 97.2% (35/36), respectively. The positive predictive value was 83.3% (5/6). The negative predictive value was 100% (35/35). The overall accuracy was 97.6% (40/41). FDG-PET had a therapeutic impact in 5 of 41 patients (12.2%). There was no impact of FDG-PET on management in other 36 patients. Conclusion FDG-PET is useful as primary method for detecting nodal recurrence and distant metastases in HNSCC as well as second cancer in subclinical patients as it had a high effectiveness. But systematic FDG-PET performed at 6 months in patients without any clinical suspicion of local recurrence was scarcely useful.

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.

Clinical classification and treatment of leukokeratosis of the vocal cords

Background Leukokeratosis of the vocal cords is a clinical descriptive diagnosis, which includes a group of squamous intraepithelial lesions of the vocal cord mucosa. We investigated the clinical classification and treatment efficacy of leukokeratosis of the vocal cords. Methods We conducted a retrospective analysis of the medical history, laryngoscopic examinations, morphological features under a surgical microscope, and pathology results of 360 cases of leukokeratosis of the vocal cords to examine correlations among treatment modalities, therapeutic effects, and clinical features. Results All cases were divided into four types based on symptoms, examination results, and treatment efficacies as follows： 21 patients had type I inflammatory leukoplakia and their vocal cord morphology and voice quality recovered after conservative therapies; 76 patients had type II frictional polyps and received CO2 laser submucosal cordectomy; 68 patients had type III sulcus vocalis and received mucosal slicing with dredging; and 195 cases had type IV simple leukokeratosis and received partial subligamental cordectomy with CO2 lasers or transmuscular cordectomy. Our treatment achieved a surgical cure rate of 90.9% （308/339）, with a recurrence rate of 9.1% （31/339） and malignant transformation rate of 6.5% （22/339）. All cancerous transformations occurred in type IV patients. Conclusion Choosing conservative or C02 laser surgery based on the morphological characteristics of squamous epithelial lesions of keratinized vocal cord mucosa can maximally protect voice quality, reduce complications, and improve the cure rate.

Risk factors of juvenile onset recurrent respiratory papillomatosis in the lower respiratory tract

Background Juvenile onset recurrent respiratory papillomatosis （JORRP） is a relatively rare disease. It affects the larynx in most cases. Because reports on JORRP to the lower respiratory tract （LRT） are few, we investigated clinical features of patients with a history of JORRP to analyze the risk factors of this disease. Methods Data from 208 JORRP patients admitted to Beijing Tongren Hospital from January 2008 to December 2010 were reviewed. Gender, age at onset of symptoms, age at first surgery, duration of symptoms before the first surgical procedure, the number of surgical procedures, mean interval between surgical interventions, and the number of tracheotomies in patients with and without LRT spread of JORRP were analyzed. The data from patients with and without tracheotomy were recorded and compared. Two cases of primary tracheal papillomatosis were reviewed. Results Papillomas extension down to the LRT was observed in 46 children （22.1%）. Patients with LRT papillomatosis had a shorter time from the onset of the symptoms until the first surgery, required significantly more surgical procedures, and had a shorter mean surgical interval. Tracheotomy was performed in 13/162 （8.0%） children with laryngeal papillomatosis vs. 36/46 （78.3%） children with LRT papillomatosis. After tracheotomy, 36/49 （73.5%） children developed LRT papillomatosis and 10/157 （6.4%） children who did not have a tracheotomy developed LRT papillomatosis. Patients with tracheotomy required a significantly higher number of surgical procedures. The younger the patient had a tracheotomy, the longer the duration of cannulation was. Conclusions JORRP patients with LRT spread are prone to develop more aggressive disease. Tracheotomy resulted in a significant increase of LRT involvement.

Three-dimensional Evaluation of Nasal Surgery in Patients with Obstructive Sleep Apnea

Background： Obstructive sleep apnea （OSA） is a common sleep disorder and is characterized by airway collapse at multiple levels of upper airway. The effectiveness of nasal surgery has been discussed in several studies and shows a promising growing interest. In this study, we intended to evaluate the effects of nasal surgery on the upper airway dimensions in patients with OSA using three-dimensional （3D） reconstruction of cone-beam computed tomography （CT）. Methods： Twelve patients with moderate to severe OSA who underwent nasal surgery were included in this study. All patients were diagnosed with OSA using polysomnography （PSG） in multi sleep health centers associated with Massachusetts General Hospital, Massachusetts Eye and Ear Infirmary and the Partners Health Care from May 3 I, 2011 to December 14, 2013. The effect of nasal surgery was evaluated by the examination of PSG, subjective complains, and 3D reconstructed CT scan. Cross-sectional area was measured in eleven coronal levels, and nasal cavity volume was evaluated from anterior nasal spine to posterior nasal spine. The thickness of soft tissue in oral pharynx region was also measured. Results： Five out of the 12 patients were successfully treated by nasal surgery, with more than 50% drop of apnea-hypopnea index. All the 12 patients showed significant increase of cross-sectional area and volume postoperatively. The thickness of soft tissue in oral pharynx region revealed significant decrease postoperatively, which decreased from 19.14 ± 2.40 cm2 and 6.11± 1.76 cm2 to 17.13 ±1.91 cm2 and 5.22 ± 1.20 cm2. Conclusions： Nasal surgery improved OSA severity as measured by PSG, subjective complaints, and 3D reconstructed CT scan. 3D assessment of upper airway can play an important role in the evaluation of treatment outcome.

Factors affecting the migration of ILC2s in allergic disease

It is well known that group 2 innate lymphoid cells(ILC2s)are enriched in mucosal tissues and respond to epithelial cell-derived cytokines,initiating and maintaining type 2 inflammation.Although an increased number of ILC2s has been observed at sites of allergic inflammation and during helminth infection,some studies have shown that ILC2s are largely tissue-resident cells seeded in the tissue early in life.

Multifaceted anti-colorectal tumor effect of digoxin on HCT8 and SW620 cells in vitro

Background Colorectal cancer(CRC)is one of the leading causes of cancer death worldwide.Novel drugs for CRC therapy are urgently needed.Digoxin has been in clinical use for treatment of heart failure and atrial arrhythmias for many years.Fragmentary reports suggested that digoxin might have antitumor efficacy on CRC.Here,we aimed to investigate the antitumor effect of digoxin on human CRC cells and the underlying mechanism.Methods Cell viability was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT)assay and plate colony formation assay.The effects of digoxin on cell-cycle distribution and apoptosis were analysed by flow cytometry.The anti-metastatic effect on tumor cells was determined by wound-healing assay and transwell assay.Anti-angiogenic effect was examined by determining the inhibition against proliferation,migration,and tube formation of human umbilical vein endothelial cells(HUVECs).Mechanism study was performed by Western blot,enzyme-linked immunosorbent assay(ELISA),and gelatin-zymography assay.Results Digoxin potently inhibited cell proliferation,induced G1-phase and G2/M-phase arrest in colorectal-cancer HCT8 and SW620 cells,respectively.No obvious apoptosis was observed in the treated cells.Anti-metastatic activities were shown on HCT8 cells by inhibiting the migration and invasion.Meanwhile,the expression of MMP2,MMP9,and phosphorylated Integrinb1 were decreased.Digoxin inhibited the proliferation,migration,and tube formation of HUVECs and reduced HIF1a expression and vascular endothelial growth factor A(VEGF-A)secretion in HCT8 cells,suggesting anti-angiogenic activity.Furthermore,digoxin significantly reversed ABCB1-mediated multidrug resistance on SW620/Ad300 cells.Conclusion Our findings suggest that digoxin has the potential to be applied as an antitumor drug via inhibiting proliferation and metastasis as well as reversing the ABCB1-mediated multidrug resistance of colorectal cancer.

Group 2 innate lymphoid cells can engulf and destroy bacteria

Group 2 innate lymphoid cells(ILC2s)are now known to play prominent roles in many inflammatory responses involving the production of Th2-type cytokines,which contribute to parasitic infections,tissue repair,and metabolic homeostasis[1].More recently,it has emerged that ILC2s may act as antigen-presenting cells,although corresponding evidence of phagocytic activity of these cells is currently scarce[2,3].Herein,we investigated whether ILC2s can phagocytose bacteria,through in vitro experiments.

BRIEF REPORTSCOMBINED ACUPUNCTURE AND MEDICINAL ANESTHESIA FOR NEOLARYNX RECONSTRUCTION

30 cases of carcinoma of the larynx underwent neolarynx reconstruction under combined acupuncture and medicinal anesthesia from 1992 to 1994. Neoglottis was easily readjusted to an optimal degree for the patients in consciousness. An excellent rate of 76.7% of acupuncture anesthesia and a success rate of phonation of 100% were achieved. No complications occurred.