ABSTRACT
BACKGROUND: Oncostatin M (OSM) may be involved in the promotion of mucosal epithelial barrier dysfunction in patients with eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) by inducing matrix metalloproteinase (MMP) -1 and -7. The aim was to evaluate the roles and mechanisms of action of OSM on MMP-1 and -7 synthesis from nasal epithelial cells (NECs). METHODS: OSM, OSM receptor (OSMR), MMP-1 and -7 expression was evaluated in nasal mucosa or primary NECs from scrapings by quantitative polymerase chain reaction (qPCR), immunofluorescence and immunohistochemistry. OSM and other cytokines were used to stimulate air-liquid interface (ALI) cultured NECs. qPCR, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence were used to evaluate the expression of OSMR, MMP-1, -7 and occludin in NECs. RESULTS: Elevated levels of OSMRß, MMP-1 and -7 were found in the tissues and scraped NECs of Eos CRSwNP in comparison to them obtained from the inferior turbinate (IT) and control subjects. The levels of OSM and OSMRß mRNA in tissues were positively correlated with the levels of MMP-1 and -7. OSM stimulation of NECs increased the expression of MMP-1 and -7, and the responses were suppressed by a STAT3 inhibitor, and a PI3K inhibitor respectively. In parallel studies, we found that stimulation with OSM disrupted the localization of occludin, a tight junction protein in NECs. The response was suppressed by a pan-MMP inhibitor. CONCLUSION: OSM induces the synthesis and release of MMP-1 and -7 in NECs. Furthermore, MMP-1 and -7 promote mucosal epithelial barrier dysfunction in patients with Eos CRSwNP.
ABSTRACT
As a new variant of COVID-19 with varied mutations, Omicron is more transmissible, more rapidly contagious, and has a greater risk of reinfection. Given those facts, a precise manage strategy needs to be formulated and implemented in designated megacities. Here, the precise COVID-19 prevention and control strategy for a designated hospital in Shenzhen, China is summarized, including implementation of a two-wing "On duty/On standby" approach based on busy and calm periods, an identification, classification, and grading system for the occupational exposure risks of medical staff, classification of patient transmission risks, separate admission, and an innovative treatment (nasal irrigation). The strategy has enabled the efficient and orderly integration of resources, it has resulted in zero infections among medical staff even during the peak hours of the pandemic at the hospital (1,930 patients admitted to both wings in a single day), and it has significantly reduced the initial period of no virus detection when patients infected with Omicron received saline nasal irrigation (P < 0.001). This strategy has provided evidence of precise prevention and control in a hospital, infection control, and efficient patient treatment in an era when Omicron is widespread.