Chronic rhinosinusitis with nasal polyps (CRSwNP), one of the most prevalent chronic diseases, is characterized by persistent inflammation of sinonasal mucosa. However, the pathogenesis of CRSwNP remains unclear. Here, we performed next-generation RNA sequencing and a comprehensive bioinformatics analyses to characterize the transcriptome profiles, including mRNAs and long noncoding RNAs (lncRNAs), in patients with eosinophilic and noneosinophilic CRSwNP. A total of 1917 novel lncRNAs and 280 known lncRNAs were identified. We showed eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (non-ECRSwNP) display distinct transcriptome profiles. We identified crucial pathways, including inflammatory, immune response and extracellular microenvironment, connected to the pathogenetic mechanism of CRSwNP. We also discovered key lncRNAs differentially expressed, including lncRNA XLOC_010280, which regulates CCL18 and eosinophilic inflammation. The qRT-PCR and in situ RNA hybridization results verified the key differentially expressed genes. The feature of distinct transcriptomes between ECRSwNP and non-ECRSwNP suggests the necessity to develop specific biomarkers and personalized therapeutic strategies. Our findings lay a solid foundation for subsequent functional studies of mRNAs and lncRNAs as diagnostic and therapeutic targets in CRSwNP by providing a candidate reservoir.

Translocator Protein (18kDa, TSPO) is a mitochondrial outer membrane transmembrane protein. Its expression is elevated during inflammation and injury. However, the function of TSPO in vivo is still controversial. Here, we constructed a TSPO global knockout (KO) mouse with a Cre-LoxP system that abolished TSPO protein expression in all tissues and showed normal phenotypes in the physiological condition. The birth rates of TSPO heterozygote (Het) x Het or KO x KO breeding were consistent with Mendel’s Law, suggesting a normal viability of TSPO KO mice at birth. RNA-seq analysis showed no significant difference in the gene expression profile of lung tissues from TSPO KO mice compared with wild type mice, including the genes associated with bronchial alveoli immune homeostasis. The alveolar macrophage population was not affected by TSPO deletion in the physiological condition. Our findings contradict the results of Papadopoulos, but confirmed Selvaraj’s findings. This study confirms TSPO deficiency does not affect viability and bronchial alveolar immune homeostasis.

Background.Inflammatory myofibroblastic tumor (IMT), as a mesenchymal tumor, is common in the lung and abdomen but rare in the paranasal sinus and nasopharynx.Objective.This study aimed to summarize the clinical characteristics of IMT in the paranasal sinus and nasopharynx and analyze the relationship between the treatment and the overall survival (OS).Method.The clinical features, treatment, and follow-up data of patients diagnosed with IMT of the paranasal sinus or nasopharynx from 2006 to 2017 were retrospectively analyzed, and the previous literature was reviewed.Results.IMT often presents as an ill-defined soft-tissue mass with bone destruction and invasion of surrounding structures. The treatment methods used in this study were different combinations of surgery, prednisone, radiotherapy, and chemotherapy or observation alone. Three of the 13 patients were lost and the follow-up time of the remaining 10 cases ranged from 2 to 87 months (median, 39 months). Two patients died of the disease; the other eight patients were stable. The 5-year survival rate was 72%. Among the four methods of treatment, only treatment with prednisone was significantly correlated with better OS (P= 0.046).Conclusions.IMT is an intermediate tumor that often mimics malignancy. We are not sure if IMTs in the nasal cavity are more aggressive because of the biology or if the location and local therapy in the head region is more complicated. Radiologic findings help know the extent of the lesion. For unresectable nasal IMT, combined therapy with glucocorticoids, chemotherapy, and radiotherapy is sometimes a better choice. Glucocorticoids are especially recommended as a basic part of the integrated therapy. However, the standard treatment needs further research.

MicroRNAs play crucial roles in modulating immune system. miR-146a, a potent feedback suppressor of NF-κB signaling, was shown to limit the innate immune response and myelopoiesis in a knockout mouse model. Here, we observed high lymphopoiesis demonstrated as mild splenomegaly and severe lymphadenopathy in a miR-146a transgenic mouse model. Overexpression of miR-146a resulted in enhanced proliferation and reduced apoptosis of T cells. More activated CD4⁺ T cells or effector memory T cells were observed in transgenic mice even under physiological conditions. Importantly, as one of the key steps to generate central tolerance, the positive selection of thymocytes is impaired in transgenic mice, resulting in more CD4⁺CD8⁺ double-positive thymocytes but fewer CD4⁺CD8⁻ and CD4⁻CD8⁺ single-positive thymocytes. The maturation of selected CD4⁻CD8⁺ thymocytes was also impaired, leading to more severe loss of CD4⁻CD8⁺ than CD4⁺CD8⁻ thymocytes in thymus of transgenic mice. Gene expression profiling analysis identified nine positive selection-associated genes, which were downregulated in transgenic mice, including genes encoding major histocompatibility complex class I/II molecules, IL-7 receptor α chain, and Gimap4, whose downregulation may contribute to the impairment of positive selection. Gimap4 was verified as a novel target of miR-146a. These findings further extend our understanding of the function of miR-146a in T cell biology and identify a novel regulatory mechanism underlying the positive selection during T cell development.