BACKGROUND: Neutrophils present as major inflammatory cells in refractory chronic rhinosinusitis with nasal polyps (CRSwNP), regardless of the endotype. However, their role in the pathophysiology of CRSwNP remains poorly understood. We investigated factors predicting the surgical outcomes of CRSwNP patients with focus on neutrophilic localization. METHODS: We employed machine-learning methods such as the decision tree and random forest models to predict the surgical outcomes of CRSwNP. Immunofluorescence analysis was conducted to detect human neutrophil elastase (HNE), Bcl-2, and Ki-67 in NP tissues. We counted the immunofluorescence-positive cells and divided them into three groups based on the infiltrated area, namely, epithelial, subepithelial, and perivascular groups. RESULTS: On machine learning, the decision tree algorithm demonstrated that the number of subepithelial HNE-positive cells, Lund-Mackay (LM) scores, and endotype (eosinophilic or non-eosinophilic) were the most important predictors of surgical outcomes in CRSwNP patients. Additionally, the random forest algorithm showed that, after ranking the mean decrease in the Gini index or the accuracy of each factor, the top three ranking factors associated with surgical outcomes were the LM score, age, and number of subepithelial HNE-positive cells. In terms of cellular proliferation, immunofluorescence analysis revealed that Ki-67/HNE-double positive and Bcl-2/HNE-double positive cells were significantly increased in the subepithelial area in refractory CRSwNP. CONCLUSION: Our machine-learning approach and immunofluorescence analysis demonstrated that subepithelial neutrophils in NP tissues had a high expression of Ki-67 and could serve as a cellular biomarker for predicting surgical outcomes in CRSwNP patients.

FIG 1: Lung from a dog with a history of epistaxis and respiratory distress. All the lobes are haemorrhagic and moist, with consolidation. Scale=cm

The placement of dental implants in the molar region of the maxilla is often difficult because of insufficient bone volume and the inferior bone quality. In order to avoid these limitations, the pillar of bone, which is composed of the maxillary tuberosity, the pyramidal process of the palatine bone and the pterygoid process of the sphenoid bone, was introduced for implant placement. In fact, the pyramidal process is the posterior structure where implants are placed but until now, there is no available data of the size or shape of the pyramidal process. Therefore, we measured the height, anteroposterior distance and mediolateral distance of the pyramidal process and observed the shape of lateral and posterior surfaces of the pyramidal process of 54 Korean edentulous dry skulls in this study. The height was 13.1 mm (male: 13.6 mm, female: 12.4 mm). The anteroposterior distance was 6.5 mm (male: 6.7 mm, female: 6.1 mm). The mediolateral distance was 9.5 mm (male: 9.9 mm, female: 9.0 mm). The most common type was the right-angled triangle in the lateral surface (44.4%) and in the posterior surface (66.7%). There was no statistical significance between the male and the female in all items (P > 0.05). These results provide anatomical features in relation to placement of dental implants in the molar region of the maxilla and would be useful in treatment planning of partially or completely edentulous patients.

Transcription factors of the RUNX family (RUNXs), which play pivotal roles in normal development and neoplasia, are regulated by various post-translational modifications. To understand the molecular mechanisms underlying the regulation of RUNXs, we performed a large-scale functional genetic screen of a fly mutant library. The screen identified dPias (the fly ortholog of mammalian PIASs), an E3 ligase for the SUMO (small ubiquitin-like modifier) modification, as a novel genetic modifier of lz (the fly ortholog of mammalian RUNX3). Molecular biological analysis revealed that lz/RUNXs are sumoylated by dPias/PIAS1 at an evolutionarily conserved lysine residue (K372 of lz, K144 of RUNX1, K181 of RUNX2 and K148 of RUNX3). PIAS1-mediated sumoylation inhibited RUNX3 transactivation activity, and this modification was promoted by the AKT1 kinase. Importantly, PIAS1 failed to sumoylate some RUNX1 mutants associated with breast cancer. In nude mice, tumorigenicity was promoted by RUNX3 bearing a mutation in the sumoylation site, but suppressed by wild-type RUNX3. Our results suggest that RUNXs are sumoylated by PIAS1, and that this modification could play a critical role in the regulation of the tumor-suppressive activity of these proteins.