BackgroundThere are no established accurate models that use machine learning (ML) methods to preoperatively predict immediate remission after transsphenoidal surgery (TSS) in patients diagnosed with histology-positive Cushing’s disease (CD).PurposeOur current study aims to devise and assess an ML-based model to preoperatively predict immediate remission after TSS in patients with CD.MethodsA total of 1,045 participants with CD who received TSS at Peking Union Medical College Hospital in a 20-year period (between February 2000 and September 2019) were enrolled in the present study. In total nine ML classifiers were applied to construct models for the preoperative prediction of immediate remission with preoperative factors. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the performance of the models. The performance of each ML-based model was evaluated in terms of AUC.ResultsThe overall immediate remission rate was 73.3% (766/1045). First operation (p<0.001), cavernous sinus invasion on preoperative MRI(p<0.001), tumour size (p<0.001), preoperative ACTH (p=0.008), and disease duration (p=0.010) were significantly related to immediate remission on logistic univariate analysis. The AUCs of the models ranged between 0.664 and 0.743. The highest AUC, i.e., the best performance, was 0.743, which was achieved by stacking ensemble method with four factors: first operation, cavernous sinus invasion on preoperative MRI, tumour size and preoperative ACTH.ConclusionWe developed a readily available ML-based model for the preoperative prediction of immediate remission in patients with CD.

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NF-erythroid 2–related factor 2 (Nrf2) is a major transcription factor to protect cells against reactive oxygen species (ROS) and reactive toxicants. Meanwhile, Nrf2 can inhibit contact dermatitis through redox-dependent and -independent pathways. However, the underlying mechanisms of how Nrf2 mediates irritant contact dermatitis (ICD) are still unclear. In this article, we elucidated the role of Nrf2 in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute ICD. Our study demonstrated that the ear thickness, redness, swelling, and neutrophil infiltration were significantly increased, accompanied by increased expression of inflammatory cytokines (IL-1α, IL-1β, IL-6, etc.) and decreased expression of antioxidant genes (HO-1 and NQO1) in Nrf2 knockout mice. Moreover, ERK phosphorylation was elevated in mouse embryonic fibroblasts (MEFs) from Nrf2 knockout mouse. Inhibition of ERK significantly alleviated TPA-induced cutaneous inflammation and ROS accumulation in MEFs derived from mouse. Conversely, ROS scavenging inhibited the ERK activation and TPA-induced inflammation in MEFs. Taken together, the findings illustrate the key role of the Nrf2/ROS/ERK signaling pathway in TPA-induced acute ICD.