Alpha-1 antitrypsin protects against phosgene-induced acute lung injury by activating the ID1-dependent anti-inflammatory response (preprint)

Phosgene, a highly dangerous chemical warfare agent, is widely used as an industrial chemical. Phosgene inhalation causes acute lung injury (ALI), which may further progress into pulmonary edema. Currently, there is no known antidote for phosgene poisoning. Alpha-1 antitrypsin (α1-AT) is a protease inhibitor that has been used to treat emphysema patients, who are deficient in α1-AT, for decades. Recent studies have shown that α1-AT has both anti-inflammatory and anti-SARS-CoV-2 effects. In this study, we aimed to investigate the role of α1-AT in phosgene-induced ALI. We observed a time-dependent increase in α1-AT expression and secretion in the lungs of rats exposed to phosgene. Interestingly, α1-AT was derived from neutrophils, but not from macrophages or alveolar type II cells, and α1-AT knockdown aggravated phosgene- and lipopolysaccharide (LPS)-induced inflammation and cell death in human bronchial epithelial cells (BEAS-2B). Conversely, α1-AT administration suppressed the inflammatory response and prevented death in LPS- and phosgene-exposed BEAS-2B cells. Furthermore, α1-AT treatment increased the expression of the inhibitor of DNA binding (ID1) gene, which suppressed NF-κB pathway activation, reduced inflammation, and inhibited cell death. These data demonstrate that neutrophil-derived α1-AT protects against phosgene-induced ALI by activating the ID1-dependent anti-inflammatory response. This study may provide novel strategies for the treatment of patients with phosgene-induced ALI.

The evaluation of learning platforms for experimental teaching of regional anatomy after the COVID-19 pandemic (preprint)

Purpose Based on the dominance of learner-centered active learning after the COVID-19 pandemic, finding suitable platforms is critical for experimental teaching of regional anatomy.Methods We investigated the satisfaction and preference of medical students about selective platforms through a questionnaire. The students were divided into three groups for this teaching experiments. At the end of the semester, their satisfaction and preference about the platforms was investigated through a questionnaire.Results In the satisfaction survey on the Virtual simulation teaching platform of EVDO and Digital Human platforms, differences had been observed between groups and gender. In terms of students’ preference for auxiliary teaching, 96/112 (85.71%) of subjects chose station B, Xuexitong (95/112 (84.82%)), Chinese University MOOCs (61/112 (54.46%)) as the after-school learning platform. Moreover, 32/112 (28.57%) of them chose both of Station B and Xuexitong, and 48/112 (42.86%) of them chose three platforms at the same time.Conclusion Students prefer more than one platforms to assist their learning. The interactive teaching of virtual simulated anatomy teaching platform and cadaveric dissection can improve students’ interest in learning anatomy.

Efficacy and Safety of Tocilizumab in Patients with COVID-19: A Systematic Review and Meta-Analysis. (preprint)

Background Tocilizumab (TCZ) is an anti-interleukin-6 antibody that has been used to treat patients with 2019 coronavirus disease (COVID-19). Numerous retrospective studies have shown beneficial treatment efficacy. Several recent randomized clinical trials have questioned the efficacy of TCZ in patients with COVID-19. Therefore, we performed an updated systematic review and meta-analysis to explore the effectiveness and safety of tocilizumab recently used for treating patients with COVID-19. Methods Randomized clinical trials (RCTs) and comparative studies that compared the outcomes between TCZ and standard of care (SOC) were analysed. PubMed, EMBASE, and the Cochrane Library (inception to November 20, 2020) were systematically searched. Primary outcomes included mortality and the rate of requirement for mechanical ventilation (MV). In addition, several subgroup analyses stratified by disease severity, publication type and TCZ administration were performed. Results Three RCTs, twenty-one cohort studies and nine case-control studies including 11,206 patients were finally included. The TCZ group included 2,794 patients (24.93%) and the SOC group included 8,412 patients (75.07%). The mortality rate (>14 days) of the TCZ group, 29.63% (590/1,991), was lower than the SOC group, 41.51% (2,380/5,734) (OR 0.64, 0.57 to 0.73; p <0.00001). However, no significant difference in-14-day mortality rates was observed between the two groups (13.53% vs 22.92%, p = 0.21). Meanwhile, the rate of MV was significantly decreased in the TCZ group compared with the SOC group (OR 0.42, 0.22 to 0.83; p = 0.01). According to the results of the subgroup analysis stratified by disease severity, TCZ only reduced the mortality rate for critical patients with COVID-19 compared with SOC (OR 0.60, 0.52 to 0.71; P < 0.00001), particularly for patients in the intensive care unit (ICU) or patients requiring MV. No statistically significant increase was recognized in the rates of secondary infections or thrombosis between the two groups. Conclusions This systematic review and meta-analysis found that the addition of tocilizumab to the SOC might reduce mortality after 14 days in patients with COVID-19, particularly critical patients requiring MV. More extensive RCTs with longer follow-up periods are needed to validate these findings.

Efficacy and Safety of Tocilizumab in Patients with COVID-19 : A Systematic Review and Meta-Analysis. (preprint)

Background Tocilizumab (TCZ) is an anti-interleukin-6 antibody that has been used to treat patients with 2019 coronavirus disease (COVID-19). Numerous retrospective studies have shown beneficial treatment efficacy. Several recent randomized clinical trials have questioned the efficacy of TCZ in patients with COVID-19. Therefore, we performed an updated systematic review and meta-analysis to explore the effectiveness and safety of tocilizumab recently used for treating patients with COVID-19. Methods Randomized clinical trials (RCTs) and comparative studies that compared the outcomes between TCZ and standard of care (SOC) were analysed. PubMed, EMBASE, and the Cochrane Library (inception to November 20, 2020) were systematically searched. Primary outcomes included mortality and the rate of requirement for mechanical ventilation (MV). In addition, several subgroup analyses stratified by disease severity, publication type and TCZ administration were performed. Results Three RCTs, twenty-one cohort studies and nine case-control studies including 11,206 patients were finally included. The TCZ group included 2,794 patients (24.93%) and the SOC group included 8,412 patients (75.07%). The mortality rate (>14 days) of the TCZ group, 29.63% (590/1,991), was lower than the SOC group, 41.51% (2,380/5,734) (OR 0.64, 0.57 to 0.73; p <0.00001). However, no significant difference in-14-day mortality rates was observed between the two groups (13.53% vs 22.92%, p = 0.21). Meanwhile, the rate of MV was significantly decreased in the TCZ group compared with the SOC group (OR 0.42, 0.22 to 0.83; p = 0.01). According to the results of the subgroup analysis stratified by disease severity, TCZ only reduced the mortality rate for critical patients with COVID-19 compared with SOC (OR 0.60, 0.52 to 0.71; P < 0.00001), particularly for patients in the intensive care unit (ICU) or patients requiring MV. No statistically significant increase was recognized in the rates of secondary infections or thrombosis between the two groups. Conclusions This systematic review and meta-analysis found that the addition of tocilizumab to the SOC might reduce mortality after 14 days in patients with COVID-19, particularly critical patients requiring MV. More extensive RCTs with longer follow-up periods are needed to validate these findings.