Qingfei Formula Protects against Human Respiratory Syncytial Virus-induced Lung Inflammatory Injury by Regulating the MAPK Signaling Pathway.

OBJECTIVE: Qingfei formula (QF) is an empirical formula that shows good clinical efficacy in treating human respiratory syncytial virus pneumonia (RSVP). However, the underlying mechanism remains unclear. This study explores the possible pharmacological actions of QF in RSVP treatment. METHODS: We used a network pharmacology approach to identify the active ingredients of QF, forecast possible therapeutic targets, and analyze biological processes and pathways. Molecular docking simulation was used to evaluate the binding capability of active ingredients and therapeutic targets. Finally, in vivo experiments confirmed the reliability of network pharmacology-based prediction of underlying mechanisms. RESULTS: The study identified 92 potential therapeutic targets and corresponding 131 active ingredients. Enrichment analysis showed that QF downregulated the MAPK signaling pathway and suppressed the inflammatory injury to the lungs induced by the RSV virus. Molecular docking simulations demonstrated that the core active ingredients of QF could stably bind to genes associated with the MAPK signaling pathway. QF had a protective effect against pneumonia in RSV-infected mice. The QF group exhibited a significant reduction in the levels of inflammatory mediators, interleukin-6 (IL-6), interleukin-8 (CXCL8, IL-8), and P-STAT3, compared to the RSV-induced group. The QF group showed remarkably inhibited MAPK1+3(P-ERK1+2) and MAPK8(P-JNK) protein expression. CONCLUSION: The current study showed that QF downregulated the MAPK signaling pathway, which inhibited pulmonary inflammation triggered by RSV infection. This study recommends the appropriate use of QF in the clinical management of RSVP.

Integrating metabolomics and network pharmacology to assess the effects of quercetin on lung inflammatory injury induced by human respiratory syncytial virus.

Quercetin (QR) has significant anti-respiratory syncytial virus (RSV) effects. However, its therapeutic mechanism has not been thoroughly explored. In this study, a lung inflammatory injury model caused by RSV was established in mice. Untargeted lung tissue metabolomics was used to identify differential metabolites and metabolic pathways. Network pharmacology was used to predict potential therapeutic targets of QR and analyze biological functions and pathways modulated by QR. By overlapping the results of the metabolomics and the network pharmacology analyses, the common targets of QR that were likely to be involved in the amelioration of RSV-induced lung inflammatory injury by QR were identified. Metabolomics analysis identified 52 differential metabolites and 244 corresponding targets, while network pharmacology analysis identified 126 potential targets of QR. By intersecting these 244 targets with the 126 targets, hypoxanthine-guanine phosphoribosyltransferase (HPRT1), thymidine phosphorylase (TYMP), lactoperoxidase (LPO), myeloperoxidase (MPO), and cytochrome P450 19A1 (CYP19A1) were identified as the common targets. The key targets, HPRT1, TYMP, LPO, and MPO, were components of purine metabolic pathways. The present study demonstrated that QR effectively ameliorated RSV-induced lung inflammatory injury in the established mouse model. Combining metabolomics and network pharmacology showed that the anti-RSV effect of QR was closely associated with purine metabolism pathways.

Comparison Between Different Approaches Applied in Pediatric Adenoidectomy: A Network Meta-Analysis.

OBJECTIVE: Adenoidectomy is a surgical procedure most frequently performed by otolaryngologists. However, there are no universally accepted guidelines for the choice of the surgical approach in specific circumstances. Therefore, a network meta-analysis (NMA) is needed to summarize existing studies and provide more evidence-based medical guidelines. METHODS: A systematic search of the literature was conducted in the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE databases from inception to 31 July 2021. A network meta-analysis of operating time, intraoperative blood loss, postoperative pain score, and incidence of postoperative residual tissue was performed. RESULTS: A total of 20 studies with 2329 patients were included. Four common surgical approaches, including powered vacuum shaver adenoidectomy (PVSA), plasma field ablation adenoidectomy (PFAA), curettage adenoidectomy (CUA), and suction diathermy adenoidectomy (SDA), were compared for operative time, intraoperative blood loss, postoperative pain score, and incidence of postoperative residual tissue. There were no significant differences between the surgical techniques for the 3 endpoints, operative time, intraoperative blood loss, and incidence of postoperative residual tissue. The data showed lower postoperative pain scores for PFAA than for CUA (MD = -3.45, 95% CI [-6.01, -0.95]). There were no significant differences in other surgical approaches for postoperative pain scores. CONCLUSION: There were no significant differences between PVSA, PFAA, CUA, and SDA for operative time, intraoperative blood loss, and incidence of postoperative residual tissue. PFAA had advantages over CUA for postoperative pain scores.

Prevalence of pulmonary hypertension in children with adenoid or adenotonsillar hypertrophy: A meta-analysis.

OBJECTIVE: Adenoid or adenotonsillar hypertrophy (AATH) adversely affects cardiovascular function, leading to pulmonary hypertension (PH). This meta-analysis of observational studies aimed to estimate the prevalence of PH in children with AATH. METHODS: A meta-analysis was performed by searching the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases from their inception to 1 July 2021, for all studies that extracted data about PH prevalence in children with AATH. PH prevalence was calculated for each included study and as a pooled estimate with a 95% confidence interval. RESULTS: A total of eight studies were included in this analysis. The pooled prevalence of PH in children with AATH was 35.0% (95% CI [18.0%, 52.0%]). The subgroup analysis demonstrated that the prevalence of PH in children with adenotonsillar hypertrophy was higher than that with adenoid hypertrophy with or without tonsillar hypertrophy (39.0%, 95% CI [14.0%, 65.0%] vs. 22.0%, 95% CI [17.0%, 28.0%], respectively). The prevalence derived from the prospective and cross-sectional studies were 45.0% (95% CI [13.0%, 76.0%]) and 20.0% (95% CI [14.0%, 25.0%]), respectively. America and Africa had lower prevalence rates than Asia (24.0%, 95% CI [1.0%, 46.0%], 27.0%, 95% CI [17.0%, 38.0%], and 48.0%, 95% CI [-2.0%, 98.0%]), respectively. The prevalence of studies with diagnostic criterion (a mean pulmonary artery pressure higher than 20 mmHg) was 50.0% (95% CI [6.0%, 94.0%]). The pooled prevalence of studies with diagnostic criterion (a mean pulmonary artery pressure higher than 25 mmHg) was 25.0% (95% CI [13.0%, 36.0%]). CONCLUSION: The meta-analysis showed a prevalence of PH in children with AATH of 35.0%, demonstrating that this condition is a frequent complication of AATH. To better understand its clinical impact, more prospective evaluations are urgently needed.

Effects of adenoidectomy or adenotonsillectomy on the cardiovascular system in children: a meta-analysis.

OBJECTIVE: Adenoid or adenotonsillar hypertrophy (AATH) causes upper airway obstruction, leading to cardiovascular complications. This meta-analysis was conducted to evaluate the efficacy of adenoidectomy or adenotonsillectomy (AATE) on the cardiovascular system. METHODS: Using the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE databases, we identified studies involving a comparison of preoperative and postoperative cardiovascular function in children with AATH. The Cochrane Collaboration's Review Manager 5.3 software was used for meta-analysis. RESULTS: A total of 13 studies with 706 participants were included. The meta-analysis demonstrated a significant reduction in mean pulmonary artery pressure (mPAP) of patients after AATE compared with preoperative values. The left ventricular myocardial function index (LVMPI) and the right ventricular myocardial function index (RVMPI) showed a significant decrease after the operation. Moreover, AATE prominently increased left ventricular ejection time (LVET) and right ventricular ejection time (RVET) and reduced the left ventricular interventricular septum diameter (LVIVSD) and the right ventricular end-diastolic diameter (RVedD). There was no significant difference in mPAP, LVMPI, RVMPI, LVET, RVET, LVIVSD, and RVedD between postoperative patients and healthy children (P > 0.05). CONCLUSION: AATE can improve cardiovascular function in pediatric patients with AATH. Specifically, it reduces mPAP and LVMPI/RVMPI in pediatric patients. Furthermore, AATE increases LVET and RVET and reduces LVIVSD and RVedD.

Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives.

This work deals with the design and synthesis of 18 barbituric acid derivatives bearing 1,3-dimethylbarbituric acid and cinnamic acid scaffolds to find potent anticancer agents. The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay. Flowcytometry was performed to determine the cell cycle arrest, apoptosis, ROS levels and the loss of MMP. The ratios of GSH/GSSG and the MDA levels were determined by using UV spectrophotometry. The results revealed that introducing substitutions (CF3 , OCF3 , F) on the meta- of the benzyl ring of barbituric acid derivatives led to a considerable increase in the antiproliferative activities compared with that of corresponding ortho- and para-substituted barbituric acid derivatives. Mechanism investigation implied that the 1c could increase the ROS and MDA level, decrease the ratio of GSH/GSSG and MMP, and lead to cell cycle arrest. Further research is needed for structural optimization to enhance hydrophilicity, thereby improve the biological activity of these compounds.

The effectiveness of Chinese herbal medicine for tic disorders in children and adolescents: A protocol for systematic review and meta analysis.

BACKGROUND: The tic disorders are common neuropsychiatric disorders that affects the growth and development of children and adolescents. Chinese herbal medicine is commonly used for the treatment of tic disorders. However, there is no consensus on the difference in clinical efficacy compared with routine treatment. Therefore, we plan to perform a systematic review and meta-analysis to review the clinical efficacy of Chinese herbal medicine for tic disorders. METHODS: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chinese Bio-medical Database, and Wanfang database will be searched from their inception until March 31, 2021. The meta-analysis will be conducted with Review Manager 5.3 software to systematically review the clinical efficacy and safety of Chinese herbal medicine for tic disorders. The primary outcome will include the improvement rate (amount) of tic symptoms using related scales or methods, and the secondary outcome will include adverse events. RESULTS: This analysis will provide useful information about clinical efficacy and safety of Chinese herbal medicine for tic disorders. CONCLUSIONS: Our study will generate strong evidence of Chinese herbal medicine for patients with tic disorders and provide suggestions for clinical practice.

Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation.

Chemotherapeutic agents, which contain the Michael acceptor, are potent anticancer molecules by promoting intracellular reactive oxygen species (ROS) generation. In this study, we synthesized a panel of PL (piperlongumine) analogs with chlorine attaching at C2 and an electron-withdrawing/electron-donating group attaching to the aromatic ring. The results displayed that the strong electrophilicity group at the C2-C3 double bond of PL analogs plays an important role in the cytotoxicity whereas the electric effect of substituents, which attached to the aromatic ring, partly contributed to the anticancer activity. Moreover, the protein containing sulfydryl or seleno, such as TrxR, could be irreversibly inhibited by the C2-C3 double bond of PL analogs, and boost intracellular ROS generation. Then, the ROS accumulation could disrupt the redox balance, induce lipid peroxidation, lead to the loss of MMP (Mitochondrial Membrane Potential), and ultimately result in cell cycle arrest and A549 cell line death. In conclusion, PL analogs could induce in vitro cancer apoptosis through the inhibition of TrxR and ROS accumulation.

The role of Chinese medicine in COVID-19 pneumonia: A systematic review and meta-analysis.

INTRODUCTION: Chinese medicine (CM) has been used to treat Novel Coronavirus 2019 (COVID-19) pneumonia in China. This meta-analysis was conducted to evaluate the clinical efficacy and safety of CM in the treatment of COVID-19 pneumonia. METHODS: Randomized controlled trials (RCTs) involving CM in the treatment of COVID-19 pneumonia were identified from Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Wanfang Database and VIP Information Database. The methodological quality of trials was evaluated with Cochrane Hanadbook criteria, and the Cochrane Collaboration's Review Manager 5.3 software was used for meta-analysis. RESULTS: A total of 7 valid studies involving 681 patients were included. The meta-analysis exhibited in comparison to conventional treatment, CM combined with conventional treatment significantly improved clinical efficacy (RR = 1.21, 95% CI [1.08,1.36]), and significantly increased viral nucleic acid negative conversion rate (RR = 1.49, 95% CI [1.13,1.97]). CM also prominently reduced pulmonary inflammation (RR = 1.27, 95% CI [1.12,1.44]), and improved host immune function (WBC, MD = 0.92, 95% CI [0.07,1.76]; LYM, MD = 0.33, 95% CI [0.08,0.57]; LYM%, MD = 2.90, 95% CI [2.09,3.71]; CRP, MD = -12.66, 95% CI [-24.40, -0.92]). Meanwhile, CM did not increase the incidence of adverse reactions (RR = 1.17, 95% CI [0.39,3.52]). CONCLUSION: According to the allocated data, CM has demonstrated clinical efficacy and safety on COVID-19 pneumonia, which need to be confirmed by high quality, multiple-center, large sample randomized controlled trials.

Chinese patent medicine Bailing capsule for treating lupus nephritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Treatment of lupus nephritis (LN) remains challenging. LN remains the primary source of morbidity and mortality in patients with systemic lupus erythematosus. Chinese patent medicine Bailing capsule is commonly used for the treatment of LN. However, there is no consensus on the difference in clinical efficacy compared with routine treatment. Therefore, we plan to perform a systematic review and meta-analysis to review the clinical efficacy and safety of Bailing capsule for LN. METHODS: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Wanfang database, and VIP information database will be searched from their inception until January 2019. The meta-analysis will be conducted with Review Manager 5.3 software to systematically review the clinical efficacy and safety of Bailing capsule for LN. The primary outcome will include clinical effective rate, and the secondary outcomes will include Systemic Lupus Erythematosus Disease Activity Index, serum creatinine, 24-hour urine protein quantity, complement 3, and adverse effects. RESULTS: This analysis will provide useful information about clinical efficacy and safety of Bailing capsule for LN. CONCLUSIONS: Our study will generate strong evidence of Bailing capsule for patients with LN and provide suggestions for clinical practice.

Effectiveness and safety of Chinese herbal medicine for pediatric adenoid hypertrophy: A meta-analysis.

OBJECTIVE: Chinese herbal medicine has been gradually used to treat pediatric adenoid hypertrophy. This meta-analysis were conducted to evaluate the clinical efficacy and safety of Chinese herbal medicine in the treatment of pediatric adenoid hypertrophy. METHODS: Randomized controlled trials involving Chinese herbal medicine in the treatment of pediatric adenoid hypertrophy were identified from Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Wanfang Database and VIP Information Database. The methodological quality of trials was evaluated with Cochrane Handbook criteria, and the Cochrane Collaboration's Review Manager 5.3 software was used for Meta-analysis. RESULTS: A total of 13 valid articles involving 1038 patients were included. The meta-analysis showed that: Compared with western medicine treatment, Chinese herbal medicine significantly improved clinical efficacy (RR = 1.33, 95% CI [1.24,1.43]), and significantly decreased A/N ratio (MD = -0.04,95%CI [-0.05,-0.03]). Chinese herbal medicine also prominently improved the quality of life (MD = -4.77,95%CI [-8.35,-1.20]). Meanwhile, it dramatically improved snoring (MD = -0.46,95%CI [-0.62,-0.30]); mouth breathing (MD = -0.52,95%CI [-0.66,-0.39]); nasal obstruction (MD = -0.56,95%CI [-0.68,-0.45]). CONCLUSION: Chinese herbal medicine has good clinical efficacy and safety on pediatric adenoid hypertrophy, which need to be confirmed by high quality, multiple-centre, large sample randomized controlled trials.

4-(N,N-dimethylamino)pyridine-embedded nanoporous conjugated polymer as a highly active heterogeneous organocatalyst.

We report herein for the first time the incorporation of a versatile organocatalyst, 4-(N,N-dimethylamino)pyridine (DMAP), into the network of a nanoporous conjugated polymer (NCP) by the "bottom-up" approach. The resulting DMAP-NCP material possesses highly concentrated and homogeneously distributed DMAP catalytic sites (2.02 mmol g(-1)). DMAP-NCP also exhibits enhanced stability and permanent porosity due to the strong covalent linkage and the rigidity of the "bottom-up" monomers. As a result, DMAP-NCP shows excellent catalytic activity in the acylation of alcohols with yields of 92-99 %. The DMAP-NCP catalyst could be easily recovered from the reaction mixture and reused in at least 14 consecutive cycles without measurable loss of activity. Moreover, the catalytic acylation reaction could be performed under neat and continuous-flow conditions for at least 536 h of continuous work with the same catalyst activity.