Changes in type 2 innate lymphoid cells and serum cytokines in sublingual immunotherapy in pediatric patients with allergic rhinitis.

BACKGROUND: Type 2 innate lymphoid cells (ILC2) are upregulated in childhood allergic rhinitis (AR) and are associated with AR severity. This study aimed to investigate changes in the ILC2 milieu in pediatric patients with AR after sublingual immunotherapy (SLIT). METHODS: Forty- pediatric patients with AR received house dust mite (HDM) allergen extract for SLIT group and thirty pediatric patients received placebo in the study, respectively. The levels of ILC2, ILC2-related cytokines (IL-5/IL-13) and their transcription factors (GATA binding protein 3, retinoic acid-related orphan receptor α) in the circulation were assessed after 1- and 2-year SLIT. Moreover, peripheral blood mononuclear cells (PBMCs) in patients were prepared and stimulated by recombinant thymic stromal lymphopoietin, IL-25, and IL-33 after 2-year SLIT. Subsequently, the levels of ILC2, IL-5, and IL-13 were tested. RESULTS: The frequency of ILC2 and the levels of their transcription factors in the circulation were significantly decreased after SLIT in the SLIT group. The levels of ILC2-related cytokines in the SLIT group showed the same trend. The frequency of ILC2 was positively correlated with transcription factors and cytokines after SLIT. SLIT was observed to reduce the ability of HDM sensitization to generate the ILC2 milieu in PBMCs. CONCLUSIONS: Changes in the ILC2 milieu may be correlated with the curative effect and immune regulation function of SLIT. Our results suggested that the regulatory effect on ILC2 is part of the therapeutic mechanism of SLIT.

LncRNA JPX contributes to Treg/Th17 imbalance in allergic rhinitis via targeting the miR-378g/CCL5 axis.

Aim: T-regulatory (Treg)/T-helper (Th) 17 imbalance contributes to the pathogenesis of allergic rhinitis (AR). Long non-coding RNAs (lncRNAs) participate in the progression of AR. Herein, the effect of lncRNA JP X on Treg/Th17 balance in AR was explored.Methods: CD4+ T cells were isolated from patients with AR and healthy control. The percentage of Treg and Th17 cells were examined by flow cytometry. The levels of JP X, miR-378g, CCL5, T GF-ß, and IL-17A were tested using qRT-P CR. The protein expression of Foxp3 and RORγt was measured by western blot.Results: The data showed that an imbalance of Treg/Th17 was associated with AR. Upregulation of JP X was found in AR, and knockdown of which improved the imbalance of Treg/Th17. Furthermore, JP X functioned as a sponge of miR-378g to upregulate CCL5. Inhibition of miR-378g reversed the effects on Treg/Th17 induced by silencing of JP X. Moreover, overexpression of CCL5 reversed miR-378g-induced effects.Conclusion: In conclusion, depletion of JP X promoted Treg/Th17 balance in AR via regulating the miR-378g/CCL5 axis. The findings provided a novel therapeutic insight for AR.

Association Between Sigmoid Sinusoidal Tinnitus and Low-Frequency Sensorineural Hearing Loss: A Retrospective Study at a Single Center.

BACKGROUND We aimed to explore the correlation between patients' sigmoid sinusoidal tinnitus (SST) and low-frequency sensorineural hearing loss (LFSHL) and illustrate the underlying mechanism. MATERIAL AND METHODS Seven healthy volunteers with normal hearing were subjected to 125-, 250-, and 500-Hz pure sound and different white noise-masking intensities. A retrospective analysis was made on the clinical data and postoperative follow-up data of 59 patients with SST in the First Affiliated Hospital of Chongqing Medical University. The patients' sex, age, chief complaints, affected site, concomitant symptoms, course of disease, pure-tone audiometry (PTA) results, tinnitus discomfort loudness scale results, imaging examination, and complications were collected. RESULTS The results of the simulation experiment showed that the threshold of each frequency segment was higher after noise masking than before masking; the intensity of noise masking was positively correlated with hearing loss, and the changes of the hearing threshold of the 3 frequencies before and after masking were statistically significant (P<0.05). Fifty-nine patients with SST were documented between January 2015 and January 2020. After the operation, their low-frequency hearing was recovered to normal; 11 cases had significantly alleviated tinnitus and 9 cases were cured. CONCLUSIONS SST often causes corresponding pseudo-low-frequency hearing loss due to the noise-masking effect. The center frequency of tinnitus appears not to be 250-Hz or 500-Hz octave frequency of PTA, barring the detection of the pseudo-hearing loss in the audiometry chart of most patients. Surgery positively affects patients with SST, and the pseudo-LFSHL can be completely recovered after the operation as a result of tinnitus elimination.

Prevalence of allergic rhinitis comorbidity with asthma and asthma with allergic rhinitis in China: A meta-analysis.

BACKGROUND: Allergic rhinitis (AR) and asthma are the most common inflammatory diseases of the airways. The relationship between asthma and AR is widely and clinically recognised. The concept "one airway, one disease" has been gradually accepted. However, in China, we could not find any systematic review and meta-analysis on the prevalence of AR with asthma and asthma with AR. OBJECTIVE: The aim of this research was to carry out a meta-analysis on the results of all conducted studies to present valid information about the co-occurrence rate of AR with asthma and asthma with AR in China. METHODS: Pubmed/Medline, Science, Springer, Elsevier, Embase, Wanfang data, VIP, CBM, and CNKI were searched systemically and data were extracted from eligible studies by two independent reviewers. Meta-analysis, study quality assessment, and publication bias assessments were all done using Stata 12.1 software. RESULTS: The results of this meta-analysis showed that pooled prevalence estimates of AR with asthma ranged from 6.69% to 14.35%, asthma with AR from 26.67% to 54%. Furthermore, an overall prevalence of 10.17% (95% CI 9.08-11.27%) was ascertained for AR with asthma, and 38.97% (95% CI 34.42-43.53%) for asthma with AR. CONCLUSIONS: The present meta-analysis comprehensively provided the first quantitative summary of the prevalence of AR with asthma and asthma with AR in China. Our study demonstrated that, in China, asthma and AR are often comorbid diseases and co-exist in the same patients. There is a close correlation between AR and asthma from an epidemiological standpoint.

Knockdown of NFBD1/MDC1 enhances chemosensitivity to cisplatin or 5-fluorouracil in nasopharyngeal carcinoma CNE1 cells.

Nasopharyngeal carcinoma (NPC) is a rare but highly invasive cancer that is prevalent among people of southern Chinese ancestry in southern China and Southeast Asia. Radiotherapy and cisplatin (CDDP)-based chemotherapy are the main treatment options. Unfortunately, disease response to concurrent chemoradiotherapy varies among patients with NPC, and many cases are resistant to CDDP and radiotherapy. NFBD1 functions in cell cycle checkpoint activation and DNA repair following DNA damage. In this study, we identified the NFBD1 as a tractable molecular target to chemosensitize NPC cells. NFBD1 expression in NPC CNE1 cell lines was depleted using lentivirus-mediated short hairpin RNA, and the elevated sensitivity of these NFBD1-inhibited NPC cells to therapeutic reagent CDDP and 5-fluorouracil (5-FU) was evaluated using MTS assays. Flow cytometry analysis also showed that NFBD1 knockdown led to an obvious induction of apoptosis in CDDP- or 5-FU-treated CNE1 cells. Furthermore, we implicated the involvement of NFBD1 in Rad51 and DNA-PKcs foci formation following CDDP or 5-FU chemotherapy. In conclusion, NFBD1 knockdown improves the chemosensitivity of NPC cells by inhibiting cell growth and promoting apoptosis through the impairment of DNA damage repair, suggesting NFBD1 as a novel therapeutic target for NPC.

Genetic risk of TNFSF4 and FAM167A-BLK polymorphisms in children with asthma and allergic rhinitis in a Han Chinese population.

BACKGROUND: Asthma and allergic rhinitis (AR) frequently occur as comorbid diseases of the upper airways. Single-nucleotide polymorphisms (SNPs) in the TNFSF4 and FAM167A-BLK genes have recently been shown to be associated with various immune-related disorders. OBJECTIVE: Our aim was to determine whether TNFSF4 or FAM167A-BLK polymorphisms confer genetic susceptibility to asthma and AR in a Han Chinese population. METHODS: We performed a case-control study of 290 asthmatic children and 252 healthy controls. Nine SNPs in the TNFSF4 region (rs1234313, rs1234314, rs1234315, rsl 2039904, rs844648 and rsl 0912580) and the FAM167A-BLK region (rs2254546, rs13277113 and rs1600249) were detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: This study revealed that three SNPs in TNFSF4 (rsl 234313, rsl 234314 and rsl 234315) and two SNPs in FAM167A-BLK (rs2254546 and rsl 600249) were significantly correlated with asthma and AR, while SNP rsl600249 was associated with asthma without allergic rhinitis as a risk factor. Further, we demonstrated synergistic effects between the TNFSF4 and FAM167A-BLK SNPs. CONCLUSION: This study supports that the SNPs in TNFSF4 and FAM167A-BLK may be involved in asthma and AR gene risk in the Han Chinese cohort.

Association between JAK1 gene polymorphisms and susceptibility to allergic rhinitis.

OBJECTIVES: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Janus kinase 1 (JAK1), a member of JAK family, has recently been found to participate in the immune response and the development of allergic airway disease. This study was performed to evaluate the potential association of JAK1 polymorphisms with AR in a Chinese Han population. METHODS: A case-control study was performed in 450 Chinese AR patients and 615 healthy controls. Three SNPs in the JAK1 gene, rs3790532, rs310241 and rs2780815, were analyzed using a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). RESULTS: An association was detected between SNP rs310241 in the JAK1 gene and AR in a Chinese Han population. However, no significant association was observed between the polymorphisms rs3790532 and rs2780815 and AR. For rs310241, the CC genotype and the C allele significantly increased the risk of AR. Furthermore, we found that the ACG haplotype in JAK1 gene was positively correlated with AR, while the GTG haplotype was associated with a significantly decreased risk of AR. CONCLUSION: This study indicates that the JAK1 rs310241 C-related genotype and allele are involved in AR susceptibility, making them potentially useful genetic biomarkers for AR susceptibility in the Chinese Han population.

[Effect of Astragalus membranaceus on Peripheral Blood Th17 in Patients with Allergic Rhinitis].

Objective To observe the effect of Astragalus membranaceus (AM) on expression levels of helper T cell 17 (Th17) and its related factors in patients with allergic rhinitis (AR). Methods Peripheral blood mononuclear cells (PBMCs) were sampled from 31 AR patients (recruited in the AR group) and 22 healthy subjects (recruited in the control group). PBMCs were isolated and in-vitro inter- vened by high and low dose AM injection (2 000 and 500 µg/mL) respectively for 24 h. mRNA expression levels of related orphan receptor C (RORC) were detected by real time quantitative PCR (RT-qPCR). Ex- pression levels of IL-17A and IL-22 in the supernatant were measured by ELISA. Expression levels of Th17 cells were measured by flow cytometry. Results Expression levels of Th17, RORC mRNA, IL- 17A, and IL-22 were higher in the AR group than in the control group (P <0. 01). mRNA expression levels of RORC, Th17 and its cytokines were not changed statistically in the AR group and the control group after PBMCs were intervened by low dose AM (P>0. 05). After intervened by high dose AM,mRNA expres- sion levels of RORC decreased statistically in the AR group and the control group (P <0. 05 for the AR group, P <0. 01 for the control group). Meanwhile,the expression levels of Th-17 and its cytokines de- creased in the AR group and the control group with statistical difference (P <0. 01). Conclusions Ex- cessive activation of Th17 is one of key factors-for AR. AM could further inhibit inflammation of AR and control the inflammation state of AR possibly through inhibiting the differentiation of Th17 cells and promo- ting the release of its cytokines.

Association study between interleukin-12 receptor ß1/ß2 genes and allergic rhinitis in the Chinese Han population.

Interleukin-12 (IL-12) plays a key role in the protection against allergic reaction induced by allergen as well as the differentiation of T helper 1 cells in patients with allergic rhinitis (AR), exerting its biological effects through binding to specific IL-12 receptors (IL-12Rs) termed IL-12Rß1 and IL-12Rß2. In this study, we investigated the relationship between polymorphisms in the IL-12R gene and AR in the Chinese Han population. A total of 543 patients with AR and 749 normal controls were genotyped for IL-12Rß1/rs438421, IL-12Rß2/rs3790565, rs3790567, and rs6679356 using a PCR restriction fragment length polymorphism analysis. The association study of each polymorphism of the IL-12Rß1 and IL-12Rß2 gene and AR showed that a significantly increased prevalence of the homozygous rs438421 GG genotype and G allele appeared in the AR patients compared with healthy controls. A significantly decreased prevalence of AG in rs438421 in AR patients is compared with healthy controls. Our research demonstrated an important association between polymorphisms in IL-12Rß1 and AR in the Chinese Han population. A strong association between rs438421 in a single nucleotide polymorphism of IL-12Rß1 and AR was identified.

High frequency of T helper type 9 cells in Chinese patients with allergic rhinitis.

BACKGROUND: T helper type 9 cells (Th9) are the most recently discovered subset of Th cells, and are involved in the pathology of several autoimmune and allergic diseases. The significance of Th9 cells in allergic rhinitis (AR) in Chinese patients is unclear. OBJECTIVE: The aim of this study was to investigate the possible role of Th9 cells in AR in Chinese patients. METHODS: Th9 cells and related factors were assessed by measuring levels of interleukin-9 (IL-9), PU.1, interferon-regulatory factor 4 (IRF4), and numbers of Th9 cells. A Th9-polarized milieu was evaluated by determining the levels of IL-4 and transforming growth factor-ß1 (TGF-ß1). Disease severity was assessed by rhino-conjunctivitis quality of life questionnaires (RQLQ), visual analog scale scores (VAS), and peripheral eosinophils (EOS) count. RESULTS: Levels of IL-4 and TGF-ß1 were elevated in AR groups versus healthy controls (P < 0.05). Levels of IL-9, PU.1, IRF4, and the numbers of Th9 cells were also significantly higher in the AR groups (P < 0.05). Furthermore, positive correlations were identified between IL-9 levels and EOS expression, RQLQ, and VAS scores (P < 0.01). CONCLUSIONS: Th9 cells and their relative factors were elevated in AR patients. Levels of Th9 polarization-related factors were much higher in AR patients, and the severity of disease was associated with a more severe Th9 response. These results suggest that AR patients present a favorable environment for Th9 differentiation, and that Th9 cells may play a crucial role in the pathology of AR in Chinese patients.

An aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress the Th17 response in allergic rhinitis patients.

A predominant Th17 population is a marker of allergic rhinitis (AR). The aryl hydrocarbon receptor (AhR) exhibits strong immunomodulation potential via regulation of the differentiation of T lymphocytes and dendritic cells (DCs) after activation by its ligand, such as 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). The aim of this study was to analyze the effect of AhR on Th17 differentiation by investigating the action of ITE on DCs and CD4(+) T cells from patients with AR. In all, 26 AR patients and 12 healthy controls were included in this study. The expression of interleukin (IL)-1ß, IL-6, IL-10, and IL-17 in the culture supernatant and the presence of Th17 cells in CD4(+) T cells and DC-CD4(+) T-cell co-culture system were measured before and after treatment with ITE. We show that ITE significantly induced cell secretion of IL-10 and inhibited IL-1ß and IL-6 production in DCs, and promoted IL-10 production and suppressed IL-17 expression in CD4(+) T cells in vitro. It also suppressed the expansion of Th17 cells in vitro. Our work demonstrates that ITE acts on DCs and CD4(+) T cells to inhibit the Th17 response that suppresses AR; the AhR-DC-Th17 axis may be an important pathway in the treatment of AR. ITE, a nontoxic AhR ligand, attenuated the Th17 response; thus, it appears to be a promising therapeutic candidate for suppressing the inflammatory responses associated with AR.

Allergen induced Treg response in the peripheral blood mononuclear cells (PBMCs) of patients with nasal polyposis.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of the nasal cavity and sinuses regulated by T cells. Regulatory T (Treg) cells are involved in controlling immune responses and inhibiting the allergen-specific effector cell response. The aim of this study was to evaluate whether NP patients had defects in Treg cells after specific allergen exposure and the possible correlation between atopy and Treg cells. METHODS: Peripheral blood mononuclear cells (PBMCs), isolated from NP patients and controls, were cultured with allergen+phytohemagglutinin (PHA) or PHA stimulation for 48h. The frequency of CD4+CD25+Foxp3+ cells was measured by flow cytometry. The level of Foxp3 was measured by Real-time PCR. Concentrations of Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Interleukin-5 (IL-5), Interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) in culture supernatants were determined by ELISA. RESULTS: Both atopic and non-atopic NP patients had a significantly decreased frequency of Treg cells and Foxp3 level in allergen stimulated PBMCs, also significantly decreased TGF-ß level in culture supernatants. The decrease was even more striking in the atopic group. Also, there were significantly negative correlations between Treg cells and IFN-γ, IL-4, IL-5. Moreover, inthe atopic group, allergen stimulation downregulated Treg cells and increased IFN-γ, IL-4, IL-5 levels, while upregulating Treg cells and decreasing IFN-γ, IL-4, IL-5 levels in controls. CONCLUSIONS: Patients with NP have a defective Treg cell response after allergen stimulation which is related to excessive Th1 and Th2 responses to specific allergens. Atopy may increase the impairment of Treg and exacerbate NP through the defective suppression of Treg on Th1 and Th2.

The Role of Asymmetry Values, Gain, and Pathological Saccades of the Video Head Impulse Test (vHIT) in Sudden Sensorineural Hearing Loss.

OBJECTIVE: The purpose of this study was to evaluate the value of asymmetry values, gain, and pathological saccades of the video head impulse test (vHIT) in sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A total of 226 individuals diagnosed with unilateral definite SSNHL were hospitalized. The assessment included a comprehensive evaluation of medical history, pure-tone test, acoustic impedance, positional test, video nystagmography (VNG), vHIT, vestibular evoked myogenic potentials (VEMPs) and magnetic resonance. INTERVENTIONS: vHIT, VNG, cVEMP, oVEMP. Statistical analysis was performed with SPSS version 22.0 for Windows. MAIN OUTCOME MEASURES: The asymmetry values, gain, and pathological saccades of the vHIT. RESULTS: The abnormal gain of vHIT in anterior, horizontal, and posterior canal in SSNHL patients with vertigo were revealed in 20 of 112 (17.9%), 24 of 112 (21.4%), and 60 of 112 (53.6%), respectively. The vHIT pathological saccades (overt + covert) of anterior, horizontal, and posterior canal in SSNHL patients with vertigo were observed in 5 of 112 (4.6%), 52 of 112 (46.4%), and 58 of 112 (51.8%), respectively. Multivariate analysis indicated that the prognosis of patients with vertigo was correlated with vHIT gain of posterior canal, pathological saccade in horizontal canal, asymmetric ratio of horizontal canal gain, asymmetric ratio of posterior canal gain, Canal paresis (%) on caloric test and spontaneous nystagmus. CONCLUSION: In the vHIT of patients with SSNHL with vertigo, the posterior canal is most easily affected. Reduced gain of posterior canal, pathological saccade of horizontal canal, and larger asymmetric gain of posterior canal and horizontal canal may be negative prognostic factors.

A New Floating Piezoelectric Microphone for Fully Implantable Cochlear Implants in Middle Ear.

OBJECTIVE: Our team designed a long-lasting, well-sealed microphone, which uses laser welding and vacuum packaging technology. This study examined the sensitivity and effectiveness of this new floating piezoelectric microphone (NFPM) designed for totally implantable cochlear implants (TICIs) in animal experiments and intraoperative testing. METHODS: Different NFPM frequency responses from 0.25 to 10 kHz at 90 dB SPL were analyzed using in vivo testing of cats and human patients. The NFPM was tested in different positions that were clamped to the ossicular chains or placed in the tympanic cavity of cats and human patients. Two volunteers' long incus foot and four cats' malleus neck of the ossicular chain were clamped with the NSFM. The output electrical signals from different locations were recorded, analyzed, and compared. The NFPM was removed after the test without causing any damage to the middle-ear structure of the cats. Intraoperative tests of the NFPM were performed during the cochlear implant surgery and the cochlear implant surgery was completed after all tests. RESULTS: Compared with the results in the tympanic cavity, the NFPM could detect the vibration from the ossicular chain more sensitively in cat experiments and intraoperative testing. We also found that the signal output level of the NFPM decreased as the acoustic stimulation strength decreased in the intraoperative testing. CONCLUSION: The NFPM is effective in the intraoperative testing, making it feasible as an implantable middle-ear microphone for TICIs. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:937-944, 2024.

Transforming growth factor-ß1 promotes Treg commitment in nasal polyposis after intranasal steroid treatment.

BACKGROUND: A predominant Th17 population and impaired Treg function is the marker of nasal polyposis (NP) in Chinese patients. TGF-ß1, a multifunction cytokine, is a vital factor involved in inducing or restricting specific Th cell development. However, its role in NP has still not been well understood. METHODS: In a double-blind trial, 30 subjects were randomized into 2 groups (15 steroid-treated NP, 15 untreated NP), and 15 normal subjects were allocated as control group. We analyzed the expression of TGF-ß1, p-Smad2, p-STAT3, Smad7, SOCS3, IL-10, IL-17A, Foxp3, and RORc in the NP tissue of Chinese patients using mRNA and protein detection methods. RESULTS: TGF-ß1, p-Smad2, IL-10, SOCS3, and Foxp3 expression was higher in steroid-treated NP patients than in untreated NP patients. Conversely, expression of p-STAT3, Smad7, IL-17A, and RORc was higher in untreated NP patients than in steroid-treated NP patients, demonstrating that TGF-ß1 was more likely to contribute to Treg commitment in Chinese NP patients after intranasal steroid treatment. CONCLUSIONS: TGF-ß1 may be a signature Treg cytokine, which is valuable for obtaining a clear understanding of the pathogenesis of NP. Moreover, intranasal steroid treatment attenuated the chronic inflammatory response in these patients by promoting Smad-dependent Treg functions and reducing STAT3-mediated Th17 reactions.

Quercetin improves the imbalance of Th1/Th2 cells and Treg/Th17 cells to attenuate allergic rhinitis.

Allergic rhinitis (AR) is a common inflammation that affects many people globally. Quercetin has anti-allergic biological activity in AR. Here, we aimed to explore the effects of quercetin on type 1 helper T (Th1)/Th2 and regulatory T cells (Treg)/Th17 balance. We established an ovalbumin (OVA)-induced mouse model and orally administered 20, 35, and 50 mg/kg/day quercetin. The nasal symptoms of mice were observed. The immunoglobulin levels, Treg/Th17-related factors, and pro-inflammatory factors were examined by ELISA. The differentiated inflammation cells were visualized using the diff-quick staining assay. The nasal histopathology was evaluated using H&E, periodic acid Schiff (PAS), and Giemsa staining assay. The results showed that quercetin attenuated OVA-induced rubbing and sneezing. Quercetin reduced IgE, IgG1, histamine, and increased IgG2 in serum. The number of differentiated inflammation cells and goblet cells in tissues that elevated by OVA was reduced by quercetin. Moreover, OVA increased the Treg cell percentage, the levels of IL-17, TGF-ß, IL-6, TNF-α, and decreased Th17 cell percentage, IL-10 and FOXP3 levels, while quercetin abrogated their levels induced by OVA. Additionally, quercetin inactivated the NF-κB pathway. Taken together, quercetin attenuated AR symptoms by balancing the Th1/Th2, Treg/Th17 ratios, and inactivating the NF-κB pathway. The results suggested that quercetin may use for AR treatment.

Considering the protective effect of exendin-4 against oxidative stress in spiral ganglion neurons.

Objectives: The protection of spiral ganglion neurons (SGNs) is crucial for hearing loss. Exendin-4 has been shown to have neuroprotective effects in several neurological disorders. Therefore, this study aimed to investigate the effect of the glucagon-like protein-1 receptor (GLP-1R) agonist exendin-4 on kanamycin-induced injury in mouse SGNs in vitro. Materials and Methods: In this study, GLP-1R expression in SGNs was verified by immunofluorescence and immunohistochemical staining. In vitro-cultured SGNs and the organ of Corti were exposed to kanamycin with or without exendin-4 treatment. The cell survival rate was measured using the cell counting kit-8 assay, and the damage to auditory nerve fibers (ANF) projecting radially from the SGNs was evaluated using immunofluorescence staining. Reactive oxygen species (ROS) content was determined by flow cytometry, and glutathione peroxidase (GSH-Px) content, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content were determined by spectrophotometry. Protein expression of nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) was detected using western blotting. Results: GLP-1R was expressed in SGNs. Treatment with 1 mM kanamycin for 24 hr induced SGN damage. Exendin-4 (100 nM) had a protective effect against kanamycin-induced SGN cell injury, improved cell survival rate, reduced nerve fiber injury, increased SOD activity and GSH-Px level, and reduced MDA and ROS contents. The Nrf2/HO-1 pathway was activated. Conclusion: Exendin-4 alleviates oxidative damage and exerts neuroprotective effects in kanamycin-induced SGN injury through the Nrf2/HO-1 signaling pathway. Exendin-4 has the potential to prevent or treat hearing loss due to SGN damage.

Feasible pickup from intact ossicular chain with floating piezoelectric microphone.

OBJECTIVES: Many microphones have been developed to meet with the implantable requirement of totally implantable cochlear implant (TICI). However, a biocompatible one without destroying the intactness of the ossicular chain still remains under investigation. Such an implantable floating piezoelectric microphone (FPM) has been manufactured and shows an efficient electroacoustic performance in vitro test at our lab. We examined whether it pick up sensitively from the intact ossicular chain and postulated whether it be an optimal implantable one. METHODS: Animal controlled experiment: five adult cats (eight ears) were sacrificed as the model to test the electroacoustic performance of the FPM. Three groups were studied: (1) the experiment group (on malleus): the FPM glued onto the handle of the malleus of the intact ossicular chains; (2) negative control group (in vivo): the FPM only hung into the tympanic cavity; (3) positive control group (Hy-M30): a HiFi commercial microphone placed close to the site of the experiment ear. The testing speaker played pure tones orderly ranged from 0.25 to 8.0 kHz. The FPM inside the ear and the HiFi microphone simultaneously picked up acoustic vibration which recorded as .wav files to analyze. RESULTS: The FPM transformed acoustic vibration sensitively and flatly as did the in vitro test across the frequencies above 2.0 kHz, whereas inefficiently below 1.0 kHz for its overloading mass. Although the HiFi microphone presented more efficiently than the FPM did, there was no significant difference at 3.0 kHz and 8.0 kHz. CONCLUSIONS: It is feasible to develop such an implantable FPM for future TICIs and TIHAs system on condition that the improvement of Micro Electromechanical System and piezoelectric ceramic material technology would be applied to reduce its weight and minimize its size.

Reciprocal roles of STAT3 and STAT5 in nasal polyposis.

PURPOSE: Nasal polyposis (NP) is a chronic inflammatory disease that is characterized by increased populations of Th17 cells and impairment of Treg cells function in Chinese patients. Recent studies have shown that signal transducer and activator of transcription 3 (STAT3) and STAT5 are indispensable in the development and maintenance of Th17 and Treg cells. We investigated the roles of STAT3 and STAT5 in the imbalance of Th17 and Treg cells in NP. MATERIALS AND METHODS: The levels of IL-6, IL-2, pSTAT3, pSTAT5, SOCS3, RORc, Foxp3, IL-17A, and TGF-ß1 were measured in patients with atopic NP, patients with nonatopic NP, and controls. We also evaluated the local distribution of Th17 and Treg cells by double immunofluorescence staining and the correlations between activated STAT3/STAT5 and Th17/Treg cell development were assessed. RESULTS: Increased levels of IL-6, pSTAT3, SCOS3, RORc, IL-17A, and CD4(+) RORc(+) cells, and decreased levels of IL-2, pSTAT5, Foxp3, TGF-ß1, and CD4(+) Foxp3(+) cells were detected in both NP groups compared to controls (P < .05). The differences in all expression levels (except for IL-6) were significant between atopic and nonatopic patients (P < .05). There was a positive correlation between pSTAT3/pSTAT5 levels and Th17/Treg development and a negative correlation between SOCS3 and pSTAT3 in NP (P < 0.01). CONCLUSIONS: The results suggest that STAT3 and STAT5 may function through the IL-6 and IL-2 pathways to play a role in the imbalance of Th17/Treg in NP. An even more exaggerated imbalance of Th17/Treg caused by atopy may be correlated to the improper ratio of activated STAT3/STAT5.

Role of leptin/ILC2 axis in allergic rhinitis in obese children.

OBJECTIVES: Since the leptin participates in the upregulation of type 2 innate lymphoid cells (ILC2s). We investigated the role of the leptin/ILC2 axis in AR pathogenesis in Chinese paediatric patients with obesity. METHODS: Seventy AR paediatric patients with or without obesity and 30 healthy obese subjects were enrolled. The levels of leptin, its receptor and ILC2 milieu were measured, and correlations between them and clinical symptom severity and between ILC2 milieu and leptin levels were assessed. Changes of ILC2 milieu in AR patients after leptin stimulation were also detected. RESULTS: Levels of leptin, its receptor and ILC2 milieu levels were significantly higher in the disease than in the controls, and highest in the obese-AR group. The leptin/ILC2 axis and severity of clinical symptoms in obese patients with AR were significantly correlated, similarly to what was observed between leptin/leptin receptors and ILC2 milieu. Recombinant leptin could significantly increased the levels of ILC2 milieu in the obese-AR group. CONCLUSIONS: These findings suggest the unique function ofthe leptin/ILC2 axis in obese paediatric AR patients. The mechanism by which obesity promotes AR in paediatric patients may be related to the leptin/ILC2 axis.