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.

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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-1β, 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.