Acteoside attenuates RSV-induced lung injury by suppressing necroptosis and regulating metabolism.

Background: Necroptosis and inflammation are closely related to the pathogenesis of respiratory syncytial virus (RSV). Acteoside (AC), a natural phenylpropanoid glycoside from Kuding Tea, has significant anti-RSV effect. However, the roles of AC on RSV-induced lung necroptosis and inflammation are yet to be elucidated. Methods: The effects of AC were investigated in BALB/c mice and A549 cells. Lung histopathology was observed through H&E staining. The viral titer was assessed via plaque assay. The RSV-F expression was determined by RT-qPCR and immunohistochemistry assay. The levels of cytokines were detected by ELISA and RT-qPCR. The necroptosis rate and mitochondrial membrane potential were evaluated via flow cytometry. The expressions of HMGB1/NF-κB and RIP1/RIP3/MLKL/PGAM5/DRP1 were detected by western blot. Additionally, untargeted metabolomics was conducted to investigate the metabolic profiles and related metabolic pathways via Gas Chromatography-Mass Spectrometry. Results: The results showed that compared with the RSV-infected group, AC treatment significantly attenuated lung pathological damage, virus replication, and cytokines levels. AC also alleviated RSV-induced necroptosis and mitochondrial dysfunction in vitro and in vivo. Moreover, AC treatment down-regulated the expression of HMGB1, p-Iκbα/Iκbα, p-p65/p65, RIP1, RIP3, MLKL, PGAM5, and DRP1. Furthermore, metabolomic analyses suggested that the perturbations in major metabolites of AC therapy were related to variations in amino acid and energy metabolism. Conclusion: Our findings validated the beneficial effects of AC in suppressing necroptosis and regulating metabolism, suggesting AC may be a new drug candidate for RSV infection.

[Network Meta-analysis of 14 oral Chinese patent medicines combined with Azithromycin in treatment of mycoplasma pneumonia in children].

To systematically evaluate the clinical efficacy of 14 oral Chinese patent medicines combined with Azithromycin in the treatment of mycoplasma pneumonia in children with network Meta-analysis. Computer retrieval was performed for such databases as CNKI, VIP, Wanfang, CBM, PubMed, EMbase and Cochrane Library to screen out randomized controlled trials of oral Chinese patent medicines combined with Azithromycin in the treatment of mycoplasma pneumonia in children from the time of database establishment to September 2020. The included studies were evaluated by the Cochrane Risk Assessment tool. Stata 14.0 and Review Manager 5.3 software were used for data statistical analysis. A total of 60 RCTs were included in this study, involving 14 oral Chinese patent medicines. The efficacy ranking based on network Meta-analysis was as follows:(1)in terms of total effective rate, top five Chinese patent medicines in surface under the cumulative ranking curve(SUCRA) were Xiao'er Xiaoji Zhike Oral Liquid, Xiao'er Chiqiao Qingre Granules, Xiao'er Feike Granules, Pudilan Xiaoyan Oral Liquid and Lanqin Oral Liquid;(2)in terms of antifebrile time, top five Chinese patent medicines in SUCRA were Huaiqihuang Granules, Xiao'er Magan Granules, Xiao'er Kechuanling Granules/Oral Liquid, Shuanghuang-lian Oral Liquid for children and Xiao'er Xiaoji Zhike Oral Liquid;(3)in terms of cough disappearance time, top five Chinese patent medicines in SUCRA were Xiao'er Magan Granules, Huaiqihuang Granules, Xiao'er Chiqiao Qingre Granules, Xiao'er Feire Kechuan Oral Liquid and Xiao'er Kechuanling Granules/Oral Liquid;(4)in terms of rale disappearance time, top five Chinese patent medicines in SUCRA were Xiao'er Magan Granules, Huaiqihuang Granules, Xiao'er Feire Kechuan Oral Liquid, Shuanghuanglian Oral Liquid for children and Yupingfeng Granules. The results showed that on the basis of the use of Azithromycin, combined administration with oral Chinese patent medicines could improve the overall clinical efficacy in the treatment of mycoplasma pneumonia in children. However, due to the large differences in the quality and the number of included studies among various therapeutic measures, the ranking results of SUCRA of Chinese patent medicines need to be verified by high-quality multi-center, large-sample, randomized double-blind trials in the future.

Chinese Herbal Medicine for the Treatment of Children and Adolescents With Refractory Mycoplasma Pneumoniae Pneumonia: A Systematic Review and a Meta-Analysis.

Objectives: Chinese herb medicine (CHM) is one of the most popular complementary and alternative therapies, which has been widely used to treat Refractory Mycoplasma Pneumoniae Pneumonia (RMPP). However, the effect and safety of CHM remain controversial. Hence, we conducted this meta-analysis to evaluate whether CHM combination therapy could bring benefits to children and adolescents with RMPP. Methods: Seven databases were used for data searching through November 11, 2020 following the PRISMA checklist generally. Review Manager 5.3, Trial sequential analysis 0.9.5.10 Beta software and Stata16.0 were applied to perform data analyses. Mean difference or risk ratio was adopted to express the results, where a 95% confidence interval (CI) was applied. Results: In general, this research enrolled 17 trials with 1,451 participants. The overall pooled results indicated that CHM was beneficial for children and adolescents with RMPP by improving the clinical efficacy rate [RR = 1.20, 95% CI (1.15, 1.25), p < 0.00001], shortening antipyretic time [MD = -2.60, 95% CI (-3.06, -2.13), p < 0.00001], cough disappearance time [MD = -2.77, 95% CI (-3.12, -2.42), p < 0.00001], lung rale disappearance time [MD = -2.65, 95% CI (-3.15, -2.15), p < 0.00001], lung X-ray infiltrates disappearance time [MD = -2.75, 95% CI (-3.33, -2.17), p < 0.00001], reducing TNF-α level [MD = -5.49, 95% CI (-7.21, -3.77), p < 0.00001]. Moreover, subgroup results suggested that removing heat-phlegm and toxicity therapy had more advantages in shortening antipyretic time, cough disappearance time, lung X-ray infiltrates disappearance time and reducing TNF-α level. Meanwhile promoting blood circulation therapy seemed to be better at relieving lung rale. However, regarding adverse events, the two groups displayed no statistical difference [RR = 0.97, 95% CI (0.60, 1.57), p = 0.91]. Conclusion: Despite of the apparently positive results in relieving clinical symptoms, physical signs and reducing inflammation, it is premature to confirm the efficacy of CHM in treating RMPP because of the limitation of quality and the number of the included studies. More large-scale, double-blind, well-designed, randomized controlled trials are needed in future research.