Deciphering the Mechanism of YuPingFeng Granules in Treating Pneumonia: A Network Pharmacology and Molecular Docking Study.

Objective: YuPingFeng Granules (YPFGs) is an herbal formula clinically used in China for more than 100 years to treat pneumonia. Nevertheless, the mechanism of YPFG in pneumonia treatment has not been established. This network pharmacology-based strategy has been performed to elucidate active compounds as well as mechanisms of YPFG in pneumonia treatment. Methods: First, active compounds of YPFG were identified in the traditional Chinese medicine systems pharmacology (TCMSP) database, and then the targets related to the active compounds were obtained from TCMSP and Swiss Target Prediction databases. Next, using DisGeNET, DrugBank, and GeneCards databases, we got therapeutic targets of pneumonia and common targets between pneumonia targets and YPFG. After that, a protein-protein interaction (PPI) network of pneumonia composed of common targets was built to analyze the interactions among these targets, which focused on screening for hub targets by topology. Then, online software and the ClusterProfiler package were utilized for the enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) data. Finally, the visualization software of Autodock was used for molecular docking among the hub target proteins. Results: 10 hub genes were selected by comparing the GO and KEGG functions of pneumonia targets with those of the common targets of YPFG and pneumonia. By using molecular docking technology, a total of 3 active ingredients have been verified as being able to combine closely with 6 hub targets and contribute to their therapeutic effects. Conclusion: This research explored the multigene pharmacological mechanism of action of YPFG against pneumonia through network pharmacology. The findings present new ideas for studying the mechanism of action of Chinese medicine against pneumonia caused by bacteria.

DNase inhibits early biofilm formation in Pseudomonas aeruginosa- or Staphylococcus aureus-induced empyema models.

Anti-infection strategies against pleural empyema include the use of antibiotics and drainage treatments, but bacterial eradication rates remain low. A major challenge is the formation of biofilms in the pleural cavity. DNase has antibiofilm efficacy in vitro, and intrapleural therapy with DNase is recommended to treat pleural empyema, but the relevant mechanisms remain limited. Our aim was to investigate whether DNase I inhibit the early biofilm formation in Pseudomonas aeruginosa- or Staphylococcus aureus-induced empyema models. We used various assays, such as crystal violet staining, confocal laser scanning microscopy (CLSM) analysis, peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH), and scanning electron microscopy (SEM) analysis. Our results suggested that DNase I significantly inhibited early biofilm formation in a dose-dependent manner, without affecting the growth of P. aeruginosa or S. aureus in vitro. CLSM analysis confirmed that DNase I decreased the biomass and thickness of both bacterial biofilms. The PNA-FISH and SEM analyses also revealed that DNase I inhibited early (24h) biofilm formation in two empyema models. Thus, the results indicated that DNase inhibited early (24h) biofilm formation in P. aeruginosa- or S. aureus-induced rabbit empyema models and showed its therapeutic potential against empyema biofilms.

Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: Combination treatment with erlotinib plus bevacizumab has the potential to become a standard treatment regimen for patients with epidermal growth factor receptor mutation-positive (EGFRm+) advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of erlotinib plus bevacizumab in patients with EGFRm+ advanced NSCLC. DESIGN: Systematic review and meta-analysis. DATA SOURCES: The PubMed, Embase, Web of Science and Cochrane Library databases were searched, from inception to 15 January 2022. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs), reported in English, assessing the efficacy of erlotinib plus bevacizumab versus erlotinib monotherapy in patients with EGFRm + advanced NSCLC. DATA EXTRACTION AND SYNTHESIS: The main objective was to assess overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs). Two independent reviewers extracted data and assessed the risk of bias. A random-effects model was used where there was evidence for homogeneous effects. RESULTS: Four RCTs (reported across six publications) were included in the meta-analysis, with a total of 775 patients included in the pooled analyses of PFS, OS and ORR (387 in the erlotinib plus bevacizumab intervention group and 388 in the erlotinib group). Compared with the erlotinib alone group, the erlotinib plus bevacizumab group achieved a significantly prolonged PFS (HR: 0.59; 95% CI 0.49 to 0.72; p<0.00001; I2=0%), but OS (HR: 0.95; 95% CI 0.78 to 1.15; p=0.59; I2=0%) and ORR (OR: 1.25; 95% CI 0.89 to 1.74; p=0.19; I2=0%) were not significantly prolonged. A total of 776 cases were used for a pooled analysis of AEs. Regarding AEs, combined treatment significantly increased the incidence of diarrhoea (51% vs 43%, 95% CI 1.03 to 1.38; p=0.006), haemorrhagic events (41% vs 20%, 95% CI 1.12 to 6.31; p=0.03), proteinuria (25% vs 3%, 95% CI 4.86 to 17.66; p<0.0001) and hypertension (40% vs 8%, 95% CI 3.66 to 7.88; p<0.0001). CONCLUSIONS: Erlotinib plus bevacizumab for the treatment of patients with EGFRm+ advanced NSCLC was associated with significantly prolonged PFS compared with erlotinib alone, but the combination did not prolong OS.