Babaodan controls excessive immune responses and may represent a cytokine-targeted agent suitable for COVID-19 treatment.

It has become evident that the actions of pro-inflammatory cytokines and/or the development of a cytokine storm are responsible for the occurrence of severe COVID-19 during SARS-CoV-2 infection. Although immunomodulatory mechanisms vary among viruses, the activation of multiple TLRs that occurs primarily through the recruitment of adapter proteins such as MyD88 and TRIF contributes to the induction of a cytokine storm. Based on this, controlling the robust production of pro-inflammatory cytokines by macrophages may be applicable as a cellular approach to investigate potential cytokine-targeted therapies against COVID-19. In the current study, we utilized TLR2/MyD88 and TLR3/TRIF co-activated macrophages and evaluated the anti-cytokine storm effect of the traditional Chinese medicine (TCM) formula Babaodan (BBD). An RNA-seq-based transcriptomic approach was used to determine the molecular mode of action. Additionally, we evaluated the anti-inflammatory activity of BBD in vivo using a mouse model of post-viral bacterial infection-induced pneumonia and seven severely ill COVID-19 patients. Our study reveals the protective role of BBD against excessive immune responses in macrophages, where the underlying mechanisms involve the inhibition of the NF-κB and MAPK signaling pathways. In vivo, BBD significantly inhibited the release of IL-6, thus resulting in increased survival rates in mice. Based on limited data, we demonstrated that severely ill COVID-19 patients benefited from BBD treatment due to a reduction in the overproduction of IL-6. In conclusion, our study indicated that BBD controls excessive immune responses and may thus represent a cytokine-targeted agent that could be considered to treating COVID-19.

Attitudes toward the American nutrition guidelines for the critically ill patients of Chinese intensive care physicians.

Nutrition therapy is essential for the management of critically ill patients. Some guidelines have been published to standardize and optimize the nutrition therapy. However, there are still many controversies in nutrition practice and there is a gap between guidelines and clinical nutrition therapy for patients in intensive care units (ICUs). This study aimed to assess attitudes and beliefs toward nutrition therapy of Chinese intensive care physicians by using the American guidelines as a surrogate. A questionnaire was sent to 45 adult ICUs in China, in which surveyed physicians were asked to rate their attitudes toward the American guidelines. A total of 162 physicians from 45 ICUs returned the questionnaires. Physicians were categorized into groups according to their professional seniority, hospital levels and whether they were members of Chinese Society for Parenteral and Enteral Nutrition (CSPEN). Overall, 94% of the respondents thought that nutrition therapy for critically ill patients was very important, and 80% mentioned that they used the American guidelines. There was diversity of opinion on the recommendations pertaining to nutrition assessment, supplemental parenteral nutrition and cutoff values for gastric residual volume, negative or neutral attitudes about these recommendations were 43%, 59% and 41%, respectively. Members of CSPEN were more likely to select a greater strength of recommendation than non-members. In conclusion, the overall attitudes of Chinese intensive care physicians toward the American guidelines were positive. Nevertheless, given the great guideline-practice gap, nutrition-focused education is warranted for many intensive care physicians in China.

Direct factor Xa inhibitors (rivaroxaban and apixaban) versus enoxaparin for the prevention of venous thromboembolism after total knee replacement: A meta-analysis of 6 randomized clinical trials.

OBJECTIVE: A meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy and safety of direct factor Xa inhibitors (rivaroxaban and apixaban) with enoxaparin for the prevention of venous thromboembolism (VTE) after total knee replacement. METHODS: A systematic literature search in Medline, EMBASE, EBSCO, Springer, Ovid and Cochrane library databases was performed to identify RCTs comparing rivaroxaban/apixaban with enoxaparin for the prevention of VTE after total knee replacement. The outcomes including deep vein thrombosis (DVT), pulmonary embolism (PE) and major bleeding were pooled using risk ratios (RRs) with their 95% confidence intervals (95% CIs) as statistic. RESULTS: A total of 6 RCTs with 13,790 patients were included in this meta-analysis. Overall, the incidence of DVT was significantly decreased with the use of direct Xa inhibitors (both twice daily [b.i.d] and once daily [q.d.] regimes) comparing with the enoxaparin treatment (P<0.01); however, there was no significant influencing difference between direct Xa inhibitors (b.i.d. regime) and enoxaparin on the incidence of PE (P=0.06), while significantly lower rate was found for q.d. regime of direct Xa inhibitors (P=0.02). With respect to major bleeding, the pooled analysis did not demonstrate a significant difference between direct Xa inhibitors (b.i.d. and q.d. regimes) and enoxaparin (30mg and 40mg b.i.d.). CONCLUSION: In conclusion, our results confirmed that direct Xa inhibitors (rivaroxaban and apixaban) were more effective for prevention of VTE after total knee replacement as compared with enoxaparin, without increasing major bleeding risk.