Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria.

BACKGROUND: Multidrug-resistant Gram-negative bacteria, exacerbated by excessive use of antimicrobials and immunosuppressants, are a major health threat. AIM: To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia, and to provide theoretical reference for clinical diagnosis and treatment. METHODS: This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022. After bacteriological culture, the patients' airway secretions were collected to confirm the presence of Gram-negative bacilli. The patients were divided into the experimental and control groups according to the medication used. The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous, nebulization, or intravenous combined with nebulization, with a daily dosage of 1.5-3.0 million units. The control group consisted of 26 patients who received standard dosages of other antibiotics (including sulbactam sodium for injection, cefoperazone sodium sulbactam for injection, tigecycline, meropenem, or vaborbactam). RESULTS: Of the 28 patients included in the research group, 26 patients showed improvement, treatment was ineffective for two patients, and one patient died, with the treatment efficacy rate of 92.82%. Of the 26 patients in the control group, 18 patients improved, treatment was ineffective for eight patients, and two patients died, with the treatment efficacy rate of 54.9%; significant difference was observed between the two groups (P < 0.05). The levels of white blood cell (WBC), procalcitonin (PCT), and C-reactive protein (CRP) in both groups were significantly lower after treatment than before treatment (P < 0.05), and the levels of WBC, PCT, and CRP in the research group were significantly lower than those in the control group (P < 0.05). Compared with before treatment, there were no significant changes in aspartate aminotransferase, creatinine, and glomerular filtration rate in both groups, while total bilirubin and alanine aminotransferase decreased after treatment (P < 0.05) with no difference between the groups. In patients with good clinical outcomes, the sequential organ failure assessment (SOFA) score was low when treated with inhaled polymyxin sulfate, and specific antibiotic treatment did not improve the outcome. Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes. CONCLUSION: Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable. Moreover, the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions, providing new ideas for clinical administration.

Microenvironment-Responsive Metal-Phenolic Nanozyme Release Platform with Antibacterial, ROS Scavenging, and Osteogenesis for Periodontitis.

Periodontitis is a chronic inflammatory disease deriving from dental plaque, characterized by the excessive accumulation of reactive oxygen species (ROS), matrix metalloproteinase (MMP) and other substances, resulting in the destruction of periodontal tissues. At present, the main therapeutic modalities, such as local mechanical debridement and antibiotic delivery, are not only difficult to solve the intractable bacterial biofilm effectively but also tricky to ameliorate the excessive inflammatory response as well as regenerate the impaired periodontal tissues. Herein, we have proposed the TM/BHT/CuTA hydrogel system formed by the self-assembly of the copper-based nanozyme (copper tannic acid coordination nanosheets, CuTA NSs) and the triglycerol monostearate/2,6-di-tert-butyl-4-methylphenol (TM/BHT) hydrogel. The negatively charged TM/BHT/CuTA can retain at the inflammation sites with a positive charge through electrostatic adsorption and hydrolyze in response to the increasing MMP of periodontitis, realizing the on-demand release of the CuTA nanozyme. The released CuTA nanozyme has antibacterial and antiplaque properties. Meanwhile, as a metal-phenolic nanozyme, it can scavenge multiple ROS by simulating the cascade process of superoxide dismutase (SOD) and catalase (CAT). Further, the CuTA nanozyme can modulate the macrophage polarization from M1 phenotype to M2 phenotype through the Nrf2/NF-κB pathway, which reduces the pro-inflammatory cytokines, increases the anti-inflammatory cytokines, and promotes the expression of osteogenetic genes successively, thus relieving the inflammation and accelerating the tissue regeneration of periodontitis. Altogether, this multifunctional nanozyme on-demand release platform (TM/BHT/CuTA) provides a desirable strategy for the treatment of periodontitis.

Chitosan-regulated biomimetic hybrid nanoflower for efficiently immobilizing enzymes to enhance stability and by-product tolerance.

Organic-inorganic hybrid nano-materials have been considered to be promising immobilization matrixes for enzymes due to their significantly enhanced reusability and stability of enzymes. Herein, we constructed a novel organic-inorganic hybrid nanoflower via biomacromolecule-regulated biomimetic mineralization to immobilize sucrose phosphorylase (SPase). It was found that chitosan (CS) effectively regulated the biomimetic mineralization of calcium phosphate (CaP), leading to the formation of flower-like hybrid materials for the entrapment of SPase via self-assembly to establish a nano-biocatalyst (CS-CaP@SPase). Upon immobilization, the obtained CS-CaP@SPase exhibited excellent pH, by-product and organic solvents tolerance, and storage stability. Specifically, at acidic condition (pH 4), CS-CaP@SPase performed over 80 % of initial activity, which was 2.42-folds higher than that of free SPase. The catalytic activity of free SPase was severely inhibited about 30 % in the presence of fructose (1.2 M), but CS-CaP@SPase only lost 5 % relative activity. The CS-CaP@SPase retained over 80 % of its relative activity, while the free SPase maintained <20 % of its relative activity in acetonitrile. The relative activity of CS-CaP@SPase was still retained about 80 % after 10 cycles and maintained 75 % after 15 days. Based on Raman spectra analysis, it was also found that the increased ß-folding component of SPase in the secondary structure after immobilization was the main factor for its enhanced stability. It is reasonable to believe that biomacromolecule-regulated biomimetic mineralization could be potentially used as a promising method to immobilize enzymes with excellent stability and recyclability, thereby facilitating the preparation of highly efficient catalysts for industrial biocatalysts, biosensing, and biomedicine.

Highly Selective Entrapment of His-Tagged Enzymes on Superparamagnetic Zirconium-Based MOFs with Robust Renewability to Enhance pH and Thermal Stability.

Metal-organic frameworks (MOFs), as a kind of poriferous nanoparticle, are promising candidates for enzyme immobilization to enhance their stability and reusability. However, most MOFs could not specifically immobilize enzymes and regenerate easily, which inevitably leads to serious high consumption and environmental pollution. In this study, renewable and magnetic MOFs were first constructed to specially immobilize His-tagged enzymes from the cell lysates without purification. The immobilized ß-glucuronidase exhibited wider pH adaptability and temperature stability. The relative activity of immobilized ß-glucuronidase was still maintained at ∼80% after eight cycles. Importantly, after simple treatment, the immobilization capacity of regenerated MOFs after simple treatment was restored to more than 90% in the first three times. The specific magnetic MOFs were proven to be an efficient and renewable platform for one-step immobilization and purification of His-tagged enzymes, showing great potential in industrial applications of nanotechnology and biocatalysis.

Chemical constituents from Ginkgo biloba leaves and their cytotoxicity activity.

One novel neoligan glucoside, Ginkgoside B (1), and one new glucose ester, 6-O-(4-hydroxyhydrocinnamoyl)-D-glucopyranose (2), along with nine known compounds (3-11) were isolated from the ethanol extract of Ginkgo biloba leaves. Their structures were elucidated by combination of spectroscopic analyses and alkaline methanolysis. The absolute configuration of compound 1 was determined by single-crystal X-ray diffraction. All the isolated compounds were evaluated for their cytotoxicity activities, and compound 11 exhibited IC50 values of 36.20 and 58.95 µM against 5637 and HeLa cell lines, respectively.