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Purpose: To investigate predictive risk factors for complications associated with migrating fish bones in the surrounding tissue of upper gastrointestinal tract.Methods: A retrospective analysis over 12 years was conducted of 45 cases of buried fish bones in the surrounding tissue of upper gastrointestinal tract with complications. Meanwhile, a control group, including 39 cases of prolonged buried fish bones in the surrounding tissue of upper gastrointestinal tract without complications, was set. Patient clinical data were collected and analyzed to predict the risk factors for complications.Results: The results of Chi-square test and univariate analysis both showed a significant difference in length of fish bone (> 2 cm), a history of concurrent medical illness (diabetes mellitus and renal hypofunction), symptoms (medium or heavy pain and dysphagia), and duration of significant symptoms (> 7 days) between the complication group and non-complication group. Multivariate analysis further identified length (> 2 cm), diabetes mellitus, medium or heavy pain, dysphagia, and duration of significant symptoms (> 7 days) as independent risk factors for complications.Conclusions: The consequences of fish bones migrating outside the upper gastrointestinal tract are various in different people. Awareness should be raised when encountering a patient ingesting a long fish bone, having a history of diabetes mellitus, presenting with significant discomforts, or these discomforts lasting for a long time. This study will help practitioners counsel their patients on the risks and 'benefits of surgery versus observation of this condition. [ABSTRACT FROM AUTHOR]

Objectives: To present 35 cases of laryngeal foreign bodies (FBs) in pediatric population undergoing misdiagnosis so as to draw on our lessons to improve early diagnosis. Methods: A retrospective analysis over 15 years was conducted of 35 cases of laryngeal FBs undergoing misdiagnosis in children. Meanwhile, a control group, including 42 cases of laryngeal FBs without misdiagnosis in children, was set. These patients’ clinical data were collected and analyzed to identify the risk factors for misdiagnosis. Results: The results of chi-square test and univariate analysis both showed a significant difference in time elapsed between discomforts and admission, witnessed foreign body (FB) aspiration history, biphasic stridor, aphonia, roentgenologic findings, and type and size of FBs between the misdiagnosed group and control group. Multivariate analysis further identified delayed doctor visits, unwitnessed FB aspiration history, nonspecific symptoms, and negative roentgenologic manifestations as independent risk factors for misdiagnosis. Conclusions: Diagnosis of laryngeal FBs, especially small, thin, and radiolucent FBs, remains a challenge. We emphasized the importance of timely doctor visits, careful clinical history inquisition, and prompt performance of radiographic or endoscopic examinations for diagnosis. [ABSTRACT FROM AUTHOR]

Conclusion: The large conductance Ca2+-activated K+ channels (BK) expression is decreased in the cochleae of age-related hearing loss (AHL) mice. BK channel may be associated with AHL. Objective: AHL is the most common among elderly persons. BK channels act as sensors for membrane voltage and intracellular Ca2+ and are essential for hearing. To investigate the distribution of BK channel in the cochleae of C57BL/6J mice, and the relationship between the expression of BK channel and the etiology of AHL. Methods: BK expression was studied in the cochleae of C57BL/6J mice at various ages (4, 12, 26, 52 weeks). The expressions of BK at the protein and mRNA levels were detected by immunofluorescence technique, western blot and quantitative real time PCR. Results: In comparison with 4-week-old mice, BK expressions in the cochleae at 12, 26 and 52 weeks of age were significantly and gradually decreased at both the protein and the mRNA levels. The immunofluorescence technique showed the BK channel was located in the hair cells and cells of the spiral ganglion, spiral ligament and stria vascularis and its expression also decreased with aging. [ABSTRACT FROM AUTHOR]

Conclusions: Na+-K+-2Cl- co-transporter isoform 1 (NKCC1) mRNA and protein decrease with increasing age in the cochlear lateral wall of C57BL/6J (C57) mice. The down-regulation of NKCC1 may influence the K+ transport efficiency and the homeostasis of ion transport cells, and cause the irreversible damage of cochlear cells in old C57 mice. Our results indicate that NKCC1 may play an important role in the pathogenesis of age-related hearing loss (AHL). Objectives: The aim of the present study was to investigate the relationship between the functional expression of NKCC1 transporter and the etiology of AHL. Methods: C57 mice were used and randomly divided into four groups according to age (4 weeks, 14 weeks, 26 weeks, and 52 weeks). Immunofluorescence technique, quantitative real-time PCR, and western blot were applied to detect the expression of NKCC1 in the cochlear lateral wall of C57 mice at the various ages. Results: In all four groups, the expression of NKCC1 was observed in the stria vascularis and type II fibrocytes of the spiral ligament. Also, the expression of NKCC1 appeared to decrease with age at both the transcriptional level and the protein level. [ABSTRACT FROM AUTHOR]

Background. Nasopharyngeal carcinoma (NPC) is one of the most prevalent cancers with a poor prognosis. Immunotherapy, especially immune checkpoint blockade (ICB), is becoming a potential therapeutic choice for NPC patients. Thus, the identification of patients who could benefit from immunotherapy is clinically significant. Methods. The NPC expression profiles from GSE102349 were used to calculate the cell scores of the tumor microenvironment (TME). The consensus clustering method was utilized to identify the potential molecular subtypes among NPC samples. The hub genes were selected from subtype-specific genes by bioinformatics analysis. Machine learning models, including random forest (RF) and support vector machine (SVM) algorithms, were constructed to predict the immune subtype. Results. In the present study, we identified two TME subtypes among NPC patients. Patients with the S1 subtype have higher levels of immune cells, immune checkpoint genes, and prognosis. Using expression data profiles of NPC patients, we constructed machine learning models for predicting TME subtypes of NPC patients. This model consists of 8 genes (LCK, CD247, FYN, ZAP70, SH2D1A, CD3D, CD3E, and CD3G). Among them, LCK, FYN, SH2D1A, and CD3D were associated with better prognoses. Among the two constructed models, SVM exhibited a higher area under curve (AUC) of 0.977, when compared with RF (AUC = 0.966). The web server based on the constructed machine learning models will contribute to the identification of NPC patients likely to benefit from ICB therapies. Conclusions. This study identified NPC subtypes and provided an accurate model to select individuals who are most likely to respond to ICB. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study the expression of plasma membrane Ca2+-ATPase isoform 2 (PMCA2) and its alternative splicing at sites A (the first intracellular loop) and C (the C-terminal region) in the neonatal rat cochlea. Methods: The cochleae from rats postnatal day 3 to postnatal day 4 (P3–P4) were dissected, fixed, embedded, and sectioned. Meanwhile, the cochlear coils from neonatal rats were isolated and fixed. Using immunofluorescence staining, the expression of PMCA2 was respectively examined in the cochlear sections and cochlear coils. In addition, the total RNAs of basilar membrane (BM, including the organ of corti, the same below), spiral ganglion (SG), spiral ligament (SL, including SV, the same below), and the whole cochlea from neonatal rats were respectively extracted and reverse transcribed to cDNAs, then subjected to primers flanking site A or C in the PMCA2 gene using reverse transcription polymerase chain reaction (RT-PCR). Western blot was also applied to detect the expression of PMCA2 isoforms in the cochlear tissues. Results: We found that PMCA2 is strongly expressed in outer hair cell (OHC) bundles, SG, and stria vascularis (SV), weakly expressed in Reissner''s membrane (RM), and occasionally expressed in inner hair cell (IHC) bundles. Moreover, w/a is the major splice form of PMCA2 present in hair cell bundles, z/b and z/c are the major splice forms of PMCA2 present in SG, and w/a and w/c are the major splice forms of PMCA2 present in SV. In the whole cochlea, variants w, y, and z were detected at site A, and variants a, b, and c were detected at site C. Using Western blot, variant a or b was also detectable in the same cochlear tissues mentioned above. Conclusions: PMCA2 and its splice variants at sites A and C are differentially expressed in cochlear tissues of neonatal rat. [Copyright &y& Elsevier]

Abstract: The mechanisms of the response in the murine cochlear lateral wall following sensorineural hearing loss (SNHL) are poorly understood. We focused on comparing the endocochlear potential (EP) with morphological changes in the lateral wall and expression of four important potassium (K+) transporters in a mouse model of SNHL induced by co-administration of aminoglycoside and loop diuretic. The expression of the α1 and α2 isoforms of Na,K-ATPase, Na–K–2Cl-Cotransporter-1 (NKCC1) and potassium channel KCNQ1 was assessed. The EP showed a significant decline at 12h post-treatment followed by complete recovery by 2 days post-treatment. The EP was maintained at near normal levels in animals deafened for periods up to 112 days. Despite this recovery, there was a significant and progressive decrease in the thickness of the stria vascularis, which was predominantly due to atrophy of marginal cells. Both protein and mRNA expression of α1 and α2 isoforms of Na,K-ATPase and NKCC1 in the lateral wall were dramatically reduced following a long-term deafening. KCNQ1 expression remained unchanged. These observations provide insight into the detailed mechanisms of EP modulation following SNHL and may have crucial implications in the future treatment of aminoglycoside-induced hearing loss. [ABSTRACT FROM AUTHOR]

Heat shock protein 70 (Hsp70) has been known to be able to play a protective role in the cochlea. The aim of this study was to investigate whether geldanamycin hydrosoluble derivative 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) has the ability to induce Hsp70 up-regulation to protect hair cells from kanamycin-induced ototoxicity in vitro . The organ of Corti (OC) explants were isolated from mice at postnatal day 3–5. Then, the explants were exposed to kanamycin with or without pre-incubation with 17-DMAG. The expression of Hsp70 was assessed by reverse transcription-quantitative polymerase chain reaction, ELISA, and immunofluorescent staining. The surviving hair cells were examined by phalloidin labeling and were counted. We found that Hsp70 expression in the explants after pre-incubation with 17-DMAG was significantly increased at both mRNA and protein levels. Immunofluorescent staining showed that Hsp70 was mainly located in the auditory hair cells. Compared with kanamycin group, the loss of hair cells was inhibited significantly in 17-DMAG + kanamycin group. Our study demonstrated that 17-DMAG induces Hsp70 in the hair cells, and has a significant protective effect against kanamycin ototoxicity in vitro . 17-DMAG has the possibility to be a safe and effective anti-ototoxic drug. [ABSTRACT FROM AUTHOR]

Excessive oxidative stress of the inner ear as a result of high, intense noise exposure is regarded as a major mechanism underlying the development of noise-induced hearing loss (NIHL). The present study was designed to explore the effect and mechanism of activated transcription factor 3 (ATF3) in reduction/oxidation homeostasis of NIHL. In vitro and in vivo assays were performed to investigate the functional role of ATF3 in the inner ear. Mice hearing was measured using auditory brainstem response. ATF3 short hairpin RNA (shRNA) was transfected into House Ear Institute-Organ of Corti 1 (HEI-OC1) cells to decrease ATF3 expression. Western blotting and quantitative real-time polymerase chain reaction (RT-qPCR) were performed to quantify ATF3, NRF2, HO-1 and NQO1 expression. Glutathione (GSH) assay was performed to detect intracellular GSH levels. ATF3 immunofluorescence analysis was carried out in cochlear cryosectioned samples and HEI-OC1 cells to localize ATF3 expression. Cell counting kit 8 assay and flow cytometry were performed to analyze cell viability. ATF3 was upregulated in noise-exposed cochleae and HEI-OC1 cells treated with H 2 O 2. NRF2 is a key factor regulated by ATF3. NRF2, HO-1, NQO1, and GSH expression was significantly downregulated in shATF3 HEI-OC1 cells. ATF3 silencing promoted reactive oxygen species accumulation and increased apoptosis and necrosis with H 2 O 2 stimulus. ATF3 functions as an antioxidative factor by activating the NRF2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that tinnitus may occur despite normal auditory sensitivity, probably linked to partial degeneration of the cochlear nerve and damage of the inner hair cell (IHC) synapse. Damage to the IHC synapses and deafferentation may occur even after moderate noise exposure. For both salicylate- and noise-induced tinnitus, aberrant N-methyl-d-aspartate (NMDA) receptor activation and related auditory nerve excitation have been suggested as origin of cochlear tinnitus. Accordingly, NMDA receptor inhibition has been proposed as a pharmacologic approach for treatment of synaptopathic tinnitus. Methods: Round-window application of the NMDA receptor antagonist AM-101 (Esketamine hydrochloride gel; Auris Medical AG, Basel, Switzerland) was tested in an animal model of tinnitus induced by acute traumatic noise. The study included the quantification of IHC ribbon synapses as a correlate for deafferentation as well as the measurement of the auditory brainstem response (ABR) to close-threshold sensation level stimuli as an indication of sound-induced auditory nerve activity. Results: We have shown that AM-101 reduced the trauma-induced loss of IHC ribbons and counteracted the decline of ABR wave I amplitude generated in the cochlea/auditory nerve. Conclusion: Local round-window application of AM-101 may be a promising therapeutic intervention for the treatment of synaptopathic tinnitus. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]