Liang-Ge-San: a classic traditional Chinese medicine formula, attenuates acute inflammation via targeting GSK3ß.

Sepsis is a serious life-threatening health disorder with high morbidity and mortality rates that burden the world, but there is still a lack of more effective and reliable drug treatment. Liang-Ge-San (LGS) has been shown to have anti-inflammatory effects and is a promising candidate for the treatment of sepsis. However, the anti-sepsis mechanism of LGS has still not been elucidated. In this study, a set of genes related to inflammatory chemotaxis pathways was downloaded from Encyclopedia of Genes and Genomes (KEGG) and integrated with sepsis patient information from the Gene Expression Omnibus (GEO) database to perform differential gene expression analysis. Glycogen synthase kinase-3ß (GSK-3ß) was found to be the feature gene after these important genes were examined using the three algorithms Random Forest, support vector machine recursive feature elimination (SVM-REF), and least absolute shrinkage and selection operator (LASSO), and then intersected with possible treatment targets of LGS found through the search. Upon evaluation, the receiver operating characteristic (ROC) curve of GSK-3ß indicated an important role in the pathogenesis of sepsis. Immune cell infiltration analysis suggested that GSK-3ß expression was associated with a variety of immune cells, including neutrophils and monocytes. Next, lipopolysaccharide (LPS)-induced zebrafish inflammation model and macrophage inflammation model was used to validate the mechanism of LGS. We found that LGS could protect zebrafish against a lethal challenge with LPS by down-regulating GSK-3ß mRNA expression in a dose-dependent manner, as indicated by a decreased neutrophils infiltration and reduction of inflammatory damage. The upregulated mRNA expression of GSK-3ß in LPS-induced stimulated RAW 264.7 cells also showed the same tendency of depression by LGS. Critically, LGS could induce M1 macrophage polarization to M2 through promoting GSK-3ß inactivation of phosphorylation. Taken together, we initially showed that anti-septic effects of LGS is related to the inhibition on GSK-3ß, both in vitro and in vivo.

A global bibliometric analysis on Kawasaki disease research over the last 5 years (2017-2021).

Background: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that mainly affects children. We aim to conduct a bibliometric analysis to explore the latest research hotspots and trends of KD. Method: By using the keywords "Kawasaki disease," "Kawasaki syndrome", and "Mucocutaneous Lymph Node Syndrome," the Web of Science (WOS) and Scopus databases were searched for publications related to KD from 2017 to 2021. Author, country and journal submissions were classified and evaluated using Biblioshiny software (using R language). VOSviewer (version 1.6.18) was used to visualize the relevant network relationships. Result: According to the search strategy, 5,848 and 6,804 KD studies were published in WOS and Scopus, respectively. The results showed an overall increasing trend in the number of publications and citations during the study period. The three most influential institutions in the WOS were St. Marianna University, Kawasaki Medical School and The University of Tokyo in Japan, while in Scopus, Harvard Medical School, University of California and Tehran University of Medical Sciences were the most influential institutions. The most influential authors of the two databases are Goodman SG, Kazunori Kataoka, and Takeshi Kimura of the WOS and Marx Nikolau and Wang Y, Burns JC, and Newburger JW of the Scopus, respectively. And Scientific Reports and Frontiers in Pediatrics were the most critical journals. The most cited documents were the WOS document by McCrindle et al. and the Scopus document by Benjamin et al. published in 2017, while the keywords in the last few years were focused on "COVID-19," "multisystem inflammatory syndrome," and "pandemic." Conclusion: This bibliometric analysis summarizes for the first time the research progress in KD (2017-2021), providing a qualitative and quantitative assessment of KD research bibliometric information. In the field, researchers mainly from Japan and USA are dominant, followed by China. It is recommended to pay close attention to the latest hot spots, such as "COVID-19" and "multisystem inflammatory syndrome." These results provide a more intuitive and convenient way for researchers to obtain the latest information on KD.

Lactobacillus rhamnosus GG for Cow's Milk Allergy in Children: A Systematic Review and Meta-Analysis.

Objective: Cow's milk allergy (CMA) is a common allergic disease. Probiotics have been suggested as a treatment for CMA, with Lactobacillus rhamnosus GG (LGG) being one of the important predominant choices. Despite reports on this topic, the effectiveness of application in CMA remains to be firmly established. Methods: To assess the effects of LGG on CMA in children, the PubMed/Medline, Embase, Cochrane Library, and Web of Science databases were searched for studies on LGG in treatment of CMA, which were published in the English language. Results: Ten studies were finally included. Significantly higher tolerability rates favoring LGG over controls were observed [risk ratio (RR), 2.22; 95% confidence interval (CI), 1.86-2.66; I 2 = 0.00; moderate-quality evidence]. There were no significant differences in SCORAD values favoring LGG over the placebo (mean difference, 1.41; 95% CI, -4.99-7.82; p = 0.67; very low-quality evidence), and LGG may have improved fecal occult blood (risk ratio, 0.36; 95% CI, 0.14-0.92; p = 0.03; low-quality evidence). Conclusion: We found that LGG may have moderate-quality evidence to promote oral tolerance in children with CMA and may facilitate recovery from intestinal symptoms. However, this finding must be treated with caution, and more gpowerful RCTs are needed to evaluate the most effective dose and treatment time for children with CMA. Registration number: CRD42021237221.