Objective Guidelines from different areas on the use of non-invasive ventilation in COVID-19 have generally been inconsistent. The goals were to appraise the quality and availability of guidelines stated and whether non-invasive ventilation in the early stage of the pandemic is of importance. Design and Method Databases including PubMed, Web of Science, Cochrane Library, and websites of international organizations and gray databases were searched up to June 23, 2020. We also hand-searched the reference lists of eligible papers. Results A total of 26 guidelines met the inclusion criteria. Regarding the appraisal by the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, the guidelines’ methodological quality was low. Among six domains, Rigour. of Development and Editorial Independence were of the lowest quality. Given the lack of evidence from randomized clinical trials and the great differences between different regions, non-invasive ventilation’s recommendations generated a considerable debate at the early stage of COVID-19. Conclusions Improving the methodological quality of the guidelines should be a goal in future pandemics. Additionally, more well-designed randomized clinical trials are needed to solve the controversy on the impact of non-invasive ventilation.

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The critical role of phosphoinositide 3-kinase ␥ (PI3K␥) in inflammatory cell activation and recruitment makes it an attractive target for immunomodulatory therapy. 5-Quinoxilin-6-methylene-1,3-thiazolidine-2,4-dione (AS605240), a potent PI3K␥ inhibitor, has been reported to ameliorate chronic inflammatory disorders including rheumatoid arthritis, systemic lupus erythematosus, and atherosclerosis. However, its in vivo effect on intestinal inflammation remains unknown. Here we evaluated the protective and therapeutic potentials of AS605240 in mice with dextran sodium sulfate (DSS)-induced acute and chronic colitis. Our results showed that AS605240 improved survival rate, disease activity index, and histological damage score in mice administered DSS in both preventive and therapeutic studies. AS605240 treatment also significantly inhibited the increase in myeloperoxidase levels, macrophage infiltration, and CD4ϩ T-cell number in the colon of DSS-fed mice. The DSS-induced overproduction of colonic proinflammatory cytokines including interleukin (IL)-1␤, tumor necrosis factor-␣, and interferon-␥ was significantly suppressed in mice undergoing AS605240 therapy, whereas colonic anti-inflammatory cytokines such as IL-4 were up-regulated. The downregulation of the phospho-Akt level in immunological cells from the inflamed colon tissue and spleen of AS605240-treated mice was detected both by immunohistochemical analysis and Western blotting. These findings demonstrate that AS605240 may represent a promising novel agent for the treatment of inflammatory bowel disease by suppressing leukocyte infiltration as well as by immunoregulating the imbalance between proinflammatory and anti-inflammatory cytokines.The intestinal bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract. Despite extensive efforts, the etiology and pathogenesis of IBDs remain unclear and effective therapies with limited side effects are still lacking (Bouma and Strober, 2003;Baert et al., 2004). Therefore, development of new effective and well tolerated drugs for IBD therapy is necessary.Chemokines, as detected in the inflamed colon of humans and in murine IBD models, are responsible for recruitment of leukocytes into the lamina propria (LP) of the intestine, which in most cases results in focal crypt damage and epithelial ulceration, the markers in the pathogenesis of IBD (MacDermott et al., 1998;Danese and Gasbarrini, 2005). Many studies have convincingly demonstrated that antagonists targeted against chemokine or receptor function can effectively inhibit acute and chronic inflammation via prevention of leukocyte chemotaxis and activation in animal models of IBD (Onuffer and Horuk, 2002). Recent studies have illustrated the fact that PI3K␥ acts as a key downstream signaling component that relays chemokine receptor signals (Curnock et al., 2002;Rü ckle et al., 2006).

Background Little is known about the quality and potential impacts of the guidelines for COVID-19 management. Methods We systematically searched PubMed, Web of Science, Cochrane Library, guideline databases and specialty society Web sites to evaluate the quality of the retrieved guidelines using the Appraisal of Guidelines for Research and Evaluation II. Results A total of 66 guidelines were identified. Only 24% were categorized as “recommended” for clinical practice. The 211 identified recommendations for COVID-19 management were classified into four topics: respiratory support(27), ARDS management(31), anti-viral or immunomodulatory therapy(95), or other medicines(58). Only 63% and 56% recommendations were supported by, respectively, assessment of the strength of recommendation or level of evidence. There were notable discrepancies between the different guidelines regarding the recommendations on COVID-19 management. Conclusions The quality of the guidelines for COVID-19 management is heterogeneous, and the recommendations are rarely supported by evidence.