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Tinnitus is associated with increased social costs and reduced quality of life through sleep disorders or psychological distress. The pathophysiology of chronic subjective tinnitus, which accounts for most tinnitus, has not been clearly elucidated. This is because chronic subjective tinnitus is difficult to evaluate objectively, and there are no objective markers that represent the diagnosis or therapeutic effect of tinnitus. Based on the results of studies on patients with chronic subjective tinnitus, objective and measurable biomarkers that help to identify the pathophysiology of tinnitus have been summarized. A total of 271 studies in PubMed, 303 in EMBASE, and 45 in Cochrane Library were found on biomarkers related to chronic subjective tinnitus published until April 2021. Duplicate articles, articles not written in English, review articles, case reports, and articles that did not match our topic were excluded. A total of 49 studies were included. Three specimens, including blood, saliva, and urine, and a total of 58 biomarkers were used as indicators for diagnosis, evaluation, prognosis, and therapeutic effectiveness of tinnitus. Biomarkers were classified into eight categories comprising metabolic, hemostatic, inflammatory, endocrine, immunological, neurologic, and oxidative parameters. Biomarkers can help in the diagnosis, measure the severity, predict prognosis, and treatment outcome of tinnitus.

Although hearing loss may be caused by various factors, it is also a natural phenomenon associated with the aging process. This study was designed to assess the contributions of diabetes mellitus (DM) and hypertension, both chronic diseases associated with aging, as well as aging itself, to hearing loss in health screening examinees. This study included 37,773 individuals who underwent health screening examinations from 2009 to 2012. The relationships between hearing threshold and subject age, hearing threshold at each frequency based on age group, the degree of hearing loss and the presence or absence of hypertension and DM were evaluated. The prevalence of hearing loss increased with age, being 1.6%, 1.8%, 4.6%, 14.0%, 30.8%, and 49.2% in subjects in their twenties, thirties, forties, fifties, sixties, and seventies, respectively (p<0.05). Hearing value per frequency showed aging-based changes, in the order of 6000, 4000, 2000, 1000 and 500 Hz, indicating greater hearing losses at high frequencies. The degree of hearing loss ranged from mild to severe. Aging and DM were correlated with the prevalence of hearing loss (p<0.05). There was no statistically significant association between hearing loss and hypertension after adjusting for age and DM. The prevalence of hearing loss increases with age and the presence of DM. Hearing loss was greatest at high frequencies. In all age groups, mild hearing loss was the most common form of hearing loss.

Acute otitis media (AOM) can persist or lead to various complications in individuals in which the innate immune system is impaired. In this context, impaired expression of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR), an intracellular pathogen-recognition receptor (PRR), is involved in the etiology of OM in humans and animals, affecting its development, severity, chronicity, recurrence, and associated complications. To assess this relationship, we reviewed literature reports relating NLR expression patterns with the pathophysiology and clinical features of OM in the larger context of impaired innate immunity. We summarized the results of published studies on the expression of NLRs in animals and humans in acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with cholesteatoma, and COM without cholesteatoma. NLRs were expressed mainly in association with bacterial infection in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. In addition, expression of NLRs was affected by the presence or absence of bacteria, fluid characteristics, disease recurrence, tissue type, and repeated surgery. Various factors of the innate immune system are involved in the pathogenesis of OM in the middle ear. NLRs are expressed in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. Impaired NLR expression induced the development, chronicity and recurrence of OM and exacerbated associated complications, indicating that NLRs have important roles in the pathogenesis of OM.

Objective The objective is to investigate the factors that can predict early treatment response in patients receiving concurrent chemoradiotherapy (CCRT) for cervical cancer. Methods We assessed clinical factors and treatment response in patients who underwent CCRT for cervical cancer at four time points: initial, 2.5 weeks, 6 weeks after starting CCRT, and 3 months after completing CCRT. The final treatment response was determined by positron emission tomography-computed tomography (PET-CT) 3 months after completion of CCRT. Patients were divided into two groups according to the final treatment response: complete response (CR) group or non-CR group. And the early CCRT response prediction model was developed using stepwise multivariate logistic regression analysis. Results Of the 62 patients who underwent CCRT for cervical cancer, 57 patients who completed all 4 time points examinations were included in the analyses and classified as CR (n = 32) and non-CR (n = 25) group. Tumor volume and serum squamous cell carcinoma antigen (SCC Ag) of the initial, 2.5 weeks, and 6 weeks after CCRT were significantly associated with the final treatment response. For the early treatment response prediction model, we selected patient age, tumor volume, and SCC Ag measured at initial and 2.5 weeks of CCRT as variables, and the equation of the final model was yielded. Using a cutoff of 0.433, this model had a sensitivity of 72.0%, a specificity of 84.4%, and a probability of 0.8225 (P < .0001). Conclusion Short-term (at 2.5 weeks after starting CCRT) measurements of tumor volume and serum SCC Ag were significant predictors of response to CCRT in patients with cervical cancer.

The prevalence of sensorineural hearing loss has increased along with increases in life expectancy and exposure to noisy environments. Metabolic syndrome (MetS) is a cluster of co-occurring conditions that increase the risk of heart disease, stroke and type 2 diabetes, along with other conditions that affect the blood vessels. Components of MetS include insulin resistance, body weight, lipid concentration, blood pressure, and blood glucose concentration, as well as other features of insulin resistance such as microalbuminuria. MetS has become a major public health problem affecting 20–30% of the global population. This study utilized health examination to investigate whether metabolic syndrome was related to hearing loss. Methods: A total of 94,223 people who underwent health check-ups, including hearing tests, from January 2010 to December 2020 were evaluated. Subjects were divided into two groups, with and without metabolic syndrome. In addition, Scopus, Embase, PubMed, and Cochrane libraries were systematically searched, using keywords such as “hearing loss” and “metabolic syndrome”, for studies that evaluated the relationship between the two. Results: Of the 94,223 subjects, 11,414 (12.1%) had metabolic syndrome and 82,809 did not. The mean ages of subjects in the two groups were 46.1 and 43.9 years, respectively. A comparison of hearing thresholds by age in subjects with and without metabolic syndrome showed that the average pure tone hearing thresholds were significantly higher in subjects with metabolic syndrome than in subjects without it in all age groups. (p < 0.001) Rates of hearing loss in subjects with 0, 1, 2, 3, 4, and 5 of the components of metabolic syndrome were 7.9%, 12.1%, 13.8%, 13.8%, 15.5% and 16.3%, respectively, indicating a significant association between the number of components of metabolic syndrome and the rate of hearing loss (p < 0.0001). The odds ratio of hearing loss was significantly higher in subjects with four components of metabolic syndrome: waist circumference, blood pressure, and triglyceride and fasting blood sugar concentrations (p < 0.0001). Conclusions: The number of components of the metabolic syndrome is positively correlated with the rate of sensorineural hearing loss.

Natural compounds are known as a resource of anti-cancer agents. Anti-cancer capacity toward human epithelial lung cancer cell lines (A549, H460) was examined with and without treatment of trypsin on the extract of Anoplophora glabripennis. IC50 values without trypsin treatment were about 21.3 and 25.0 μg/mL for H460 and A549, respectively. When the extract was treated with trypsin, the IC50 values were 16.0 and 15.6 μg/mL for H460 and A549, respectively, indicating that the trypsin treatment increased the anti-cancer capacity. Because trypsin treatment increased the capacity, the extract was treated with trypsin to isolate the peptide W-0803 which has lysin (K) in C-terminal and α-helix structures. With treatment of W-0803, the cell viability decreased dose-dependently for H460 and A549 cells. Apoptosis analysis showed that the cell death with the treatment of peptide W-0803 was mainly by apoptosis. The wound-healing assay also showed that the peptide W-0803 has an inhibitory capability on cell migration of H460 and A549 cells. All these results suggest that the peptide W-0803 is an anti-cancer agent for lung cancer cell treatment.

Introduction We aimed to evaluate the efficacy and toxicity of the combination of 6 cycles of chemotherapy and radiation therapy compared with chemotherapy alone as postoperative adjuvant therapy for patients with stage III endometrial cancer. Methods This retrospective cohort study included patients with stage III endometrial cancer who received postoperative chemoradiotherapy or chemotherapy alone at 6 hospitals between January 2009 and December 2019. The progression-free survival (PFS) and overall survival (OS) for each treatment group were analyzed using the Kaplan–Meier method. We also assessed differences in toxicity profiles between the treatment groups. Results A total of 133 patients met the inclusion criteria. Of these, 80 patients (60.2%) received adjuvant chemoradiotherapy and 53 (39.8%) received chemotherapy alone. The PFS and OS did not differ significantly between the groups. For patients with stage IIIC endometrioid subtype, the chemoradiotherapy group had significantly longer PFS rate than did the chemotherapy alone group (log-rank test, P = .019), although there was no significant difference in the OS (log-rank test, P = .100). CRT was identified as a favorable prognostic factor for PFS in multivariate analysis (adjusted HR, .37; 95% CI, .16-.87; P = .022). Patients treated with chemoradiotherapy more frequently suffered from grade 4 neutropenia (73.8% vs 52.8%; P = .018) and grade 3 or worse thrombocytopenia (36.3% vs 9.4%; P = .001) compared with the chemotherapy alone group. There were no differences between the 2 treatment groups in the frequency of toxicity-related treatment discontinuation or dose reduction. Conclusion We confirmed that chemoradiotherapy yields longer progression-free survival than does chemotherapy alone for patients with stage IIIC endometrioid endometrial cancer, with an acceptable toxicity profile.

No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this research, autophagy is being investigated for its role in nerve regeneration. Here, we review the existing literature regarding the involvement and significance of autophagy in peripheral nerve injury and regeneration. A comprehensive literature review was conducted to assess the induction and role of autophagy in peripheral nerve injury and subsequent regeneration. Studies were included if they were prospective or retrospective investigations of autophagy and facial or peripheral nerves. Articles not mentioning autophagy or the facial or peripheral nerves, review articles, off-topic articles, and those not written in English were excluded. A total of 14 peripheral nerve studies that met these criteria, including 11 involving sciatic nerves, 2 involving facial nerves, and 1 involving the inferior alveolar nerve, were included in this review. Studies conducted on rats and mice have demonstrated activation of autophagy and expression of related factors in peripheral nerves with or without stimulation of autophagy-inducing factors such as rapamycin, curcumin, three-dimensional melatonin nerve scaffolds, CXCL12, resveratrol, nerve growth factor, lentinan, adipose-derived stem cells and melatonin, basic fibroblast growth factor, and epothilone B. Among the most studied of these factors in relation to degeneration and regeneration of facial and sciatic nerves are LC3II/I, PI3K, mTOR, Beclin-1, ATG3, ATG5, ATG7, ATG9, and ATG12. This analysis indicates that autophagy is involved in the process of nerve regeneration following facial and sciatic nerve damage. Inadequate autophagy induction or failure of autophagy responses can result in regeneration issues after peripheral nerve damage. Animal studies suggest that autophagy plays an important role in peripheral nerve degeneration and regeneration.

Otitis media is mainly caused by upper respiratory tract infection and eustachian tube dysfunction. If external upper respiratory tract infection is not detected early in the middle ear, or an appropriate immune response does not occur, otitis media can become a chronic state or complications may occur. Therefore, given the important role of Toll-like receptors (TLRs) in the early response to external antigens, we surveyed the role of TLRs in otitis media. To summarize the role of TLR in otitis media, we reviewed articles on the expression of TLRs in acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with cholesteatoma, and COM without cholesteatoma. Many studies showed that TLRs 1–10 are expressed in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. TLR expression in the normal middle ear mucosa is absent or weak, but is increased in inflammatory fluid of AOM, effusion of OME, and granulation tissue and cholesteatoma of COM. In addition, TLRs show increased or decreased expression depending on the presence or absence of bacteria, recurrence of disease, tissue type, and repeated surgery. In conclusion, expression of TLRs is associated with otitis media. Inappropriate TLR expression, or delayed or absent induction, are associated with the occurrence, recurrence, chronicization, and complications of otitis media. Therefore, TLRs are very important in otitis media and closely related to its etiology.

Aquaporins (AQPs) are water-specific membrane channel proteins that regulate cellular and organismal water homeostasis. The nose, an organ with important respiratory and olfactory functions, is the first organ exposed to external stimuli. Nose-related topics such as allergic rhinitis (AR) and chronic rhinosinusitis (CRS) have been the subject of extensive research. These studies have reported that mechanisms that drive the development of multiple inflammatory diseases that occur in the nose and contribute to the process of olfactory recognition of compounds entering the nasal cavity involve the action of water channels such as AQPs. In this review, we provide a comprehensive overview of the relationship between AQPs and rhinologic conditions, focusing on the current state of knowledge and mechanisms that link AQPs and rhinologic conditions. Key conclusions include the following: (1) Various AQPs are expressed in both nasal mucosa and olfactory mucosa; (2) the expression of AQPs in these tissues is different in inflammatory diseases such as AR or CRS, as compared with that in normal tissues; (3) the expression of AQPs in CRS differs depending on the presence or absence of nasal polyps; and (4) the expression of AQPs in tissues associated with olfaction is different from that in the respiratory epithelium.