[Significance of Lipopolysaccharide Lipid A Gene Mutation of Extensively Drug-resistant Acinetobacter baumanii on Polymyxin Resistance and Its Influence on Treatment].

OBJECTIVE: To explore the significance of the resistance to polymyxin resistance of the extensively drug resistant Acinetobacter baumannii (XDRAB) lipopolysaccharide (LPS) lpx A, lpx C, lpx D and to screen appropriate combination therapy. METHODS: In the past two years, 72 XDRAB in the secretions of our patients were selected as the research object. According to the minimum inhibitory concentration (MIC) of the XDRAB strain on polymyxin, they were included in the drug resistance group and the sensitive group. The gene sequences of strains lpx A, lpx C, lpx D were compared with the standard strains to analyze gene mutations and compared the mutation rates in the drug resistant group and the sensitive group. The efficacy of the combination drugs was evaluated by microcheckerboard dilution method, including polymyxin+imipenem group, polymyxin+meropenem group, polymyxin+cefoperazone/sulbactam group, polymyxin+levofloxacin group, and polymyxin+fosfomycin group. Calculated the fractional inhibitory concentration (FIC) index of the combined medication regimen and compared the percentage of strains that exhibited synergistic, additive, irrelevant, and antagonistic effects. RESULTS: Tentyone were in the drug resistant group, accounting for 21 (29.17%,) and 51 were in the sensitive group, accounting for 70.83%. Some strains had mutations in lpx A, lpx C, lpx D genes. The mutation rate in the drug resistant group was 90.48%, which was significantly higher than 11.76% in the sensitive group, the difference was statistically significant ( P<0.05). The combined drug sensitivity test showed, compared with the polymyxin+fosfomycin group, the mycotin+fosfomycin group had a higher percentage of strains with synergistic FIC index in the polymyxin+imipenem group, the difference was statistically significant ( P<0.01). CONCLUSION: XDRAB is resistant to polymyxin, which is related to mutations in LPS lipid A biosynthesis genes lpx A, lpx C, lpx D. Clinical treatment should adopt a combination of polymyxin+imipenem/meropenem and other drug combination to reduce the secondary infection of drug resistant bacteria.

Preparation, characterization, and application of soluble liquid crystalline molecularly imprinted polymer in electrochemical sensor.

A novel soluble molecularly imprinted polymer (SMIP) without chemical cross-linker was successfully synthesized. The quinine (QN), which the structure was similar to the template, was chosen as the immobile template to improve the affinity of MIP. 4-Methyl phenyl dicyclohexyl ethylene (MPDE) was used as the liquid crystal (LC) monomer to increase the rigid of the composite. The cooperative effect of QN and MPDE was demonstrated by comparing with the conventional MIP, which synthesized without QN and MPDE. The polymerization conditions of SMIP including the ratio of MAA to MPDE, template to functional monomer, and HQN to QN were also optimized. Moreover, the characterizations of the SMIP were investigated by the transmission electron microscopy (TEM), field emission scanning electron microscopy (SEM), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and nitrogen adsorption. In binding behavior, the SMIP presented the maximum adsorption capacity (0.37 ± 0.06 mmol/g) and imprinting factor (3.44 ± 0.25). And above all, the obtained polymer exhibited the solubility in the organic solution. In addition, the proposed SMIP as the electrochemical sensor exhibited a significant conductivity and sensitivity with the detection limit of 0.33 µM for HQN, the recoveries for the sample analysis varied from 97.4 to 100.8%, and the intra-day precision and inter-day precision were within 5.5% and 12.5%, respectively. It turned out that the SMIP had demonstrated more excellent potential than the traditional insoluble MIP in the development of the membrane-based electrochemical sensors.Graphical abstract.

[Effect of paeoniflorin on oxidative stress and energy metabolism in mice with lipopolysaccharide (LPS)-induced brain injury].

Paeoniflorin is the main active ingredient of Chinese herbaceous peony. This study is to investigate the protective effect of paeoniflorin (Pae) on acute brain damage induced by lipopolysaccharide (LPS) in mice. The mice were randomly assigned to the normal control, model control (LPS), as well as groups of paeoniflorin and lipopolysaccharide (Pae + LPS). Then the mice were administered intraperitioneally with normal saline or Pae (10, 30 mg · kg(-1)) once daily for 6 d. One hour after intrapertioneally treatment on the seventh day, each group were injected LPS (5 mg · kg(-1)) to establish the endotoxin lipopolysaccharide inflammation model except the normal group. The mice were sacrificed after 6 h and the brain homogenates were prepared and measured. The malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2), succinatedehydrogenase (SDH), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase were dectected by the colorimetric method. The levels of HO-1 and Nrf2 protein in subcellular fractions of brain tissue were detected by Western blot. The results demonstrated that the administration with paeoniflorin reduced the levels of the MDA production; significantly increase the activities of antioxidant enzyme (SOD and GSH-PX). In addition, paeoniflorin could enhance the total antioxidant capacity, decrease the level of H2O2, and increase the activities of SDH, Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase. Furthermore, paeoniflorin can increase the expression of HO-1 and activate the nuclear transfer of Nrf2. Taking together, these findings suggest that paeoniflorin alleviate the acute inflammation in mice brain damage induced by LPS, which is related with its antioxidant effect and improvement of energy metabolism.