Suppression of lncRNA MALAT1 Reduces LPS- or IL-17A-Induced Inflammatory Response in Human Middle Ear Epithelial Cells via the NF-κB Signaling Pathway.

Otitis media (OM) is a common inflammatory disease of the middle ear cavity and mainly occurs in children. As a critical regulator of inflammation response, the nuclear factor kappa B (NF-κB) pathway has been found to play an essential role in the pathogenesis of various human diseases. The aim of this study was to explore the potential mechanism under the inflammatory response of human middle ear epithelial cells (HMEECs). We established in vitro models of OM by treating HMEECs with lipopolysaccharide (LPS) or interleukin 17A (IL-17A). Enzyme-linked immunosorbent assay and western blot analysis were used to measure the inflammatory response of HMEECs under LPS or IL-17A stimulation. The results revealed that the concentrations of proinflammatory cytokines (p < 0.001) and protein levels of mucin (MUC) (for MUC5AC, p = 0.002, p = 0.004; for MUC8, p = 0.004, p < 0.001) were significantly elevated by LPS or IL-17A stimulation in HMEECs. Moreover, we found that LPS or IL-17A treatment promoted the phosphorylation of IκBα (for p-IκBα, p = 0.018, p = 0.002; for IκBα, p = 0.238, p = 0.057) and the translocation of p65 from cytoplasm to nucleus in HMEECs (for nucleus p65, p = 0.01; for cytoplasm p65, p < 0.001). In addition, RT-qPCR analysis revealed that long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was verified to be upregulated in LPS- or IL-17A-stimulated HMEECs (p < 0.001). Western blot analysis and immunofluorescence staining assay revealed that that MALAT1 knockdown significantly suppressed the activation of the NF-κB pathway by reducing phosphorylated IκBα levels and inhibiting the nuclear translocation of p65 (p < 0.001) in LPS- or IL-17A-stimulated HMEECs (for p-IκBα, p < 0.001; for IκBα, p = 0.242, p = 0.647). Silence of MALAT1 decreased the proinflammatory cytokine production and MUC protein levels (p < 0.001). Furthermore, rescue assays revealed that the increase of proinflammatory cytokine production (for TNF-α, p = 0.002, p = 0.015; for IL-1ß, p < 0.001, p = 0.006; for IL-6, p = 0.002, p < 0.001) and MUC protein levels (for MUC5AC, p = 0.001, p < 0.001; for MUC8, p < 0.001, p = 0.001) induced by MALAT1 overexpression was neutralized by 4-N-[2-(4-phenoxyphenyl) ethyl] quinazoline-4, 6-diamine (QNZ) treatment in LPS- or IL-17A-stimulated HMEECs. In conclusion, MALAT1 promotes inflammatory response in LPS- or IL-17A- stimulated HMEECs via the NF-κB signaling pathway, which may provide a potential novel insight for the treatment of OM.

Artemisia Annua sublingual immunotherapy for seasonal allergic rhinitis: A multicenter, randomized trial.

BACKGROUND: Artemisia annua is the most common outdoor aeroallergen throughout Northern China; however, no multicenter study has investigated sublingual immunotherapy (SLIT) as a treatment option for Artemisia annua-induced allergic rhinitis (AR). The aim of this study was to evaluate the efficacy and safety of an innovative SLIT for Artemisia annua-related AR. METHODS: This was a randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial conducted in China (NCT XXX). A total of 702 Artemisia annua-sensitized eligible patients were randomized in a ratio of 2:1 to receive Artemisia annua-SLIT or placebo. The treatment lasted 32 weeks; including 5-weeks up-dosing phase and 27-weeks maintenance phase. The primary endpoint was the daily combined score of medication and rhinoconjunctivitis symptom (CSMRS), and secondary endpoints were daily total nasal symptom score (dTNSS) and daily rescue medication score (dRMS) during peak pollen period. Safety of treatment was evaluated according to adverse events (AEs) experienced. RESULTS: Mean daily CSMRS was significantly improved during the peak pollen period in the SLIT group compared with the placebo group (1.46 ± 0.47 vs 1.88 ± 0.42, P < 0.0001 in full analysis set [FAS]; 1.49 ± 0.52 vs 1.95 ± 0.46, P < 0.0001 in per protocol set [PPS]); representing a 22.3% and 23.6% reduction, respectively, relative to placebo. In specifically Artemisia annua monosensitized patients, mean daily CSMRS reductions were demonstrated as 24.1% and 27.0% in the FAS and PPS populations, respectively, when comparing the active treatment to placebo treatment. Similarly, SLIT decreased dTNSS in peak pollen period by 19.0% in FAS and 22.3% in PPS, respectively, relative to placebo. In coincidence, dRMS in peak pollen period was reduced by 22.0% in FAS and 26.0% in PPS. 65.8% patients in SLIT group experienced treatment-related AEs, none of which was serious. CONCLUSION: This study indicates that SLIT with Artemisia annua drops is an effective and safe treatment option in Chinese patients with Artemisia Annua-induced AR.

Bencycloquidium bromide nasal spray is effective and safe for persistent allergic rhinitis: a phase III, multicenter, randomized, double-blinded, placebo-controlled clinical trial.

PURPOSE: To investigate the efficacy and safety of bencycloquidium bromide nasal spray (BCQB) in patients with persistent allergic rhinitis (PAR). METHODS: We enrolled 720 patients from 15 hospitals across China and randomly assigned them into BCQB group or placebo group (90 µg per nostril qid) to receive a 4-week treatment. Visual analog scale (VAS) for rhinorrhea, sneezing, nasal congestion, itching and overall symptoms were recorded by patients every day. Anterior rhinoscopy scoring was completed by doctors on every visit. Adverse events were recorded in detail. RESULTS: A total of 354 and 351 patients were included in BCQB group and in placebo group. Baseline information was comparable. At the end of the trial, the decrease of VAS for rhinorrhea from baseline was 4.83 ± 2.35 and 2.46 ± 2.34 in BCQB group and placebo group, respectively (P < 0.001). The change ratio from baseline of VAS for rhinorrhea in BCQB group was 72.32%, higher than 31.03% in placebo group (P < 0.001). VAS for other symptoms and overall symptoms also improved significantly in the BCQB group, while no inter-group difference was found in anterior rhinoscopy scoring. The incidence of adverse reaction was similar between the two groups. Most reactions were mild and no severe reactions happened. CONCLUSION: 90 µg BCQB per nostril four times daily is effective and safe in the treatment of rhinorrhea as well as sneezing, nasal congestion and itching for patients with PAR. RETROSPECTIVELY REGISTERED: ChiCTR2000030924, 2020/3/17.

[Study of the level of adiponectin in obstructive sleep apnea-hypopnea syndrome patients].

OBJECTIVE: To investigate the change of fasting serum adiponectin in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. METHOD: Forty males with OSAHS and forty age-matched male normal controls were included in the study. Subjects in OSAHS group were divided into two sub-groups according to body mass index (BMI): obese OSAHS group (BMI > or =25, n=26) and non-obese group OSAHS (BMI <25, n=14). All subjects underwent an overnight sleep study. The serum adiponectin levels were measured by ELISA. RESULT: (1) Except for BMI,compared with control subjects, levels of fasting adiponectin level were significantly lower in OSAHS subjects (P < 0.05). (2) In obese OSAHS sub-group, serum adiponectin level was negatively correlated with BMI and AHI. However, serum adiponectin level was positively correlated with the minimum oxygen saturation. There were similar correlations between serum adiponectin level and sleep parameters in non-obese OSAHS sub-group. CONCLUSION: Despite age and BMI, fasting adiponectin level was significantly lower in OSAHS patients than that in control subjects. And fasting adiponectin level was correlated with BMI, AHI and the minimum oxygen saturation. OSAHS is one of the main reasons of the decreased adiponectin.

[Expression of transforming growth factor-beta 1 matrix metalloproteinase-1 and its inhibitor in human middle ear cholesteatoma].

OBJECTIVE: To investigate the expression of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and transforming growth factor-beta 1 (TGF-beta 1) in human middle ear cholesteatoma. METHODS: Immunohistochemical staining was used to detect the expression of TGF-beta 1, MMP-1 and TIMP-1 in the cholesteatoma (41 cases) and the skin of external auditory meatus (15 cases). RESULTS: The percent of positive expression of TGF-beta 1, MMP-1 and TIMP-1 in cholesteatoma was 95.12%, 85.37% and 9.76%, respectively. There was significant difference of the expression of MMP-1 and TGF-beta 1 between cholesteatoma and external auditory meatus skin (P < 0.05). But there was no statistic significance for TIMP-1 (P > 0.05). There was correlation between the expression of TGF-beta 1 and MMP-1, but no correlation between TGF-beta 1 and TIMP-1. CONCLUSION: The imbalance between the expression of MMP-1 and TIMP-1 in cholesteatoma may cause directly proteolytic activity involved in pathologic osteolytic mechanisms.

[Significens of blood platelet CD62p in treating sudden deafness].

OBJECTIVE: To compare different treatment methods for sudden deafness of different blood platelet CD62p levels. METHODS: Blood platelet was measured with flow cytometer. Patients with platelet CD62p over or less than 2% were treated with routine treatment (low molecular weight dextran, ATP, CoA and dexamethasone) or routine treatment plus batroxobin (thrombolysis) separately. RESULTS: In the group with platelet CD62p > or = 2%, the effective rates of routine treatment was 60.5%, and that of routine treatment plus thrombolysis was 84.6%. There was significant difference between them. In the group with platelet CD62p < 2%, the effective rates of two methods were 65.0% and 71.8% respectively(no significant difference between them). CONCLUSIONS: Detecting CD62p in sudden deafness patients makes sense for deciding treatment project.