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The activation of mast cells (MCs) and mediator release are closely related to the pathophysiology of irritable bowel syndrome (IBS). However, the exact underlying mechanisms are still not completely understood. The nuclear receptor subfamily 4a (Nr4a) is a family of orphan nuclear receptors implicated in regulating MC activation, degranulation, cytokine/chemokine synthesis and release. Acute and chronic stress trigger hypothalamic-pituitaryadrenal axis (HPA) activation to induce the release of corticotropin-releasing hormone (CRH), resulting in MC activation and induction of the Nr4a family. Our newest data showed that Nr4a members were specially over-expressed in colonic MCs of the chronic water-avoidance stress (WAS)-induced visceral hyperalgesia mice, suggesting that Nr4a members might be involved in the pathophysiology of visceral hypersensitivity. In this review, we highlight the present knowledge on roles of Nr4a members in the activation of MCs and the pathophysiology of IBS, and discuss signaling pathways that modulate the activation of Nr4a family members. We propose that a better understanding of Nr4a members and their modulators may facilitate the development of more selective and effective therapies to treat IBS patients.

Non-small-cell lung cancer (NSCLC) is one of the most common malignancies, and specific molecular targets are still lacking. Angiogenesis plays a central regulatory role in the growth and metastasis of malignant tumor. Angiogenic factors (AFs) are involved. Although there are many studies comparing AFs and cancer, a prognostic risk model for AFs and cancer in humans has not been reported in the literature. This study aimed to identify the key AFs closely related to the process of NSCLC development, and four genes have been found, C1QTNF6, SLC2A1, PTX3, FSTL3. Then we constructed a novel prognostic risk model based on these four genes in non-small-cell lung cancer (NSCLC) and fully analyzed the relationship with clinical features, immune infiltration, genomes and predictors. This model had good discrimination and calibration and will perform well for predicting the prognosis of treatment in clinical practice.