To evaluate the efficacy and safety of injectable cefoperazone sodium and tazobactam sodium (6∶1) for the treatment of moderate to severe acute respiratory bacterial infections.

Totally 237 patients with respiratory tract infections were enrolled in a randomized, double blind, multi-centerand, parallel controlled study, in which 179 in experimental group and 58 in control group ([injectable cefoperazone sodium and tazobactam sodium (4∶1)]. During the screening period, cefoperazone sodium was uniformly injected for 3 d. During the treatment period, the experimental group was given the test drug 3.0 g by intravenous drip twice a day, and the control group was given 2.0 g of control drug by intravenous drip 3 times a day. The results of symptoms, signs, laboratory examination, chest X-ray examination and sputum bacterial culture were observed before and after treatment.

In experiment group and control group, the clinical cure rates were 87.65% and 78.85%, respectively. The bacterial clearance rates were 97.89% and 97.06%. Comprehensive efficacies were 86.32% and 73.53%. Incidences of adverse reaction were 13.79% (24/174 patients) in the test group and 14.29% (8/56 patients) in the control group. The main manifestations were elevated transaminase, leucopenia, eosinophilia and so on. All patients returned to normal after follow-up.

Injectable cefoperazone sodium and tazobactam sodium (6∶1) is proved to be safe and effective in the treatment of moderate to severe acute bacterial infection of respiratory system after large-scale phase Ⅲ clinical trial, providing an effective drug for the control of drug-resistant bacterial infection.

To investigate the in vivo antibacterial activity of fosfomycin combined with imipenem by using the infection model of Galleria mellonella with Klebsiella pneumonia.

Four strains of carbapenem resistant Klebsiella pneumonia (CRKP) and four strains of carbapenem sensitive Klebsiella pneumonia (CSKP) isolated from patients with bloodstream infection were collected from Wuxi Second People's Hospital Affiliated Nanjing Medical University on January to December 2020. The serotypes of Klebsiella pneumoniae capsule were typed by wzi gene sequencing. The virulence model of wax moth was used to calculate the 80% lethal dose of different strains in 96 h, then the antimicrobial susceptibility test of wax borer was carried out to analyze the antibacterial activity of fosfomycin combined with imipenem in vivo. Finally, the bacterial load was detected by the hemolymph test of wax borer.

Wzi gene sequencing showed that the serotypes of all the four CRKP strains were k64. The serotypes of four CSKP strains were K1, K2, K50 and k26, respectively. The in vivo antibacterial activity result of combined drugs showed that when the MIC value of imipenem was ≤8 mg·L^-1 and fosfomycin ≤32 mg·L^-1 in CRKP group, the antibacterial effect of the combination on two strains was significantly better than that of single drug, and the load clearance rate of hemolymph bacteria was higher. The antibacterial effect of the combination on K1-KP531 and K2-KP532 from high virulence in CSKP group was better than imipenem or fosfomycin alone, with the load clearance rate of hemolymph bacteria lower than that of low virulence strains in CSKP group.

When imipenem MIC≤8 mg·L^-1 and fosfomycin was sensitive, fosfomycin and imipenem showed synergistic effect in the Klebsiella pneumoniae infection model of Galleria mellonella.

Network pharmacology and molecular docking technology were used to explore the possible mechanism of Compound Shuanghua oral liquid in the treatment of influenza.

The active ingredients of the compound Shuanghua oral liquid were searched through the literature, and the target points of the active ingredients were predicted based on the data platform, after which a compound-target network was constructed. The intersection of the active ingredient targets of the compound Shuanghua oral liquid and the influenza disease targets were taken to obtain the key targets to construct a drug-active ingredient-key target-disease network. Protein interaction analysis was conducted through shared core targets. The protein interaction core (PPI) moderate centrality (DC), intermediate centrality (BC), compact centrality (CC), eigenvector centrality (EC), network centrality (NC) and local average connectivity (LAC) parameters were analyzed to screen the core target genes. The selected main active components of the Compound Shuanghua oral liquid are molecularly docked with the influenza virus neuraminidase target.

Totally 80 active ingredients were obtained corresponding to the targets of Compound Shuanghua oral liquid; 616 action targets, 2 574 influenza-related genes, 243 key targets of Compound Shuanghua oral liquid were predicted in the treatment of influenza, and 23 key core targets were screened from protein interaction core (PPI) analysis, including proto-oncogene tyrosine protein kinase Src (SRC), tyrosine protein kinase JAK1 (JAK1), etc. Enrichment analysis showed the common biological process of compound Shuanghua oral liquid and influenza, which is related to inflammation, cell proliferation and apoptosis. The main pathways of action are tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, apoptosis signaling pathway, Toll-like receptor signaling pathway, and C-type lectin receptor signaling Access, etc. The results of molecular docking show that the main active ingredients have good binding activity with influenza virus neuraminidase.

The mechanism of action for Compound Shuanghua oral liquid may mainly be inhibiting neuraminidase activity, inflammatory response and apoptosis related factors and pathways, acting against influenza, reducing the inflammatory response caused by influenza, so as to achieve the purpose of treating influenza.

To explore the effects of histone deacetylase inhibitor chidamide on the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of murine triple-negative breast cancer 4T-1 cells.

CCK-8 method was performed to analyze the effects of chidamide on the proliferation of 4T-1 cells; flow cytometry to detect the effects of chidamide on the cell cycle and apoptosis of 4T-1 cells; Western Blot to detect intracellular histone deacetylase 5, lysine-specifc demethylase 1 and EMT-related proteins E-cadherin, Vimentin, MMP-9, MMP-2 expression; Transwell method to analyze the effect of chidamide on the migration and invasion of 4T-1 cells; HE staining method to observe the pulmonary metastasis of tumor tissues and the toxicity of chidamide on mice; ELISA method to analyze the effect of chidamide on the immune system in mice.

The results of CCK-8 method showed that chidaniline had the ability to prominently inhibit the proliferation of 4T-1 cells, and its 24 h IC₅₀ value was 43.42 μmol·L^-1. Chidamide could induce G₂/M phase arrest and apoptosis of 4T-1 cells. At the same time, it was found that chidamide distinctly down-regulated the mRNA and protein expression of HDAC5 in 4T-1 cells, but only down-regulated the protein expression of LSD1; in addition, the expressions of EMT-related factors E-cadherin, vimentin, MMP-9, MMP-2 were notably down-regulated. Transwell experiments found that chidamide obviously inhibited the migration and invasion of 4T-1 cells. In vivo, chidamide of 10 mg·kg^-1 showed an outstanding suppression effect on the proliferation and pulmonary metastasis of 4T-1 cells in tumor-bearing mice, but did not affect the body weight and the morphology of heart, liver, and kidney tissues.

Chidamide can depress the expression of HDAC5, LSD1 and EMT-related proteins E-cadherin, Vimentin, MMP-9, MMP-2, and inhibit the proliferation and migration of 4T-1 cells both in vivo and in vitro, indicating that chidamide has a great potential for clinical anti-triple-negative breast cancer treatment.