Aim:To investigate the mechanism leading to in vivo carbapenem resistance development in Klebsiella pneumoniae. Methods: Carbapenemase was detected using the modified carbapenem inactivation method. β-lactamases resistant genes were identified by PCR and sequencing. Clonal relatedness was evaluated by random amplified polymorphic DNA and multiple locus sequence typing. The relationship between sequence typing and resistant genes was analyzed by using the chi-squared test. Results: All ST37 carbapenem-resistant isolates were bla OXA-1 positive and all ST37 carbapenem-sensitive isolates were bla OXA-1 negative at Stage I. A significant relationship between carbapenem resistance and bla OXA-1 was observed. The bla OXA-1 -positive rate was significantly higher in ST37 K. pneumoniae than others. Conclusion: This is the first study about the development of carbapenem resistance in vivo potentially mediated by bla OXA-1 in ST37 K. pneumoniae among neonates.

The emergence and spread of bacteria carrying the bla NDM-1 gene has become a worldwide concern. Here, we report eight cases of Klebsiella pneumoniae with bla NDM-1 in the neonatal ward of a teaching hospital in mainland China. Multilocus sequence typing showed that seven isolates were clonally related and confirmed them as sequence type 17 (ST17). One isolate belonged to ST433. These findings suggest continuous spread of bla NDM-1 in mainland China and emphasize the need for intensive surveillance and precautions.

Background and objectives Ubiquitin-specific peptidase 28 (USP28) has been reported to play significant roles in several tumors, but its roles in non-small-cell lung cancer (NSCLC) is still unknown. In this study, we aimed to investigate the biological function and molecular mechanisms of USP28 in NSCLC. Materials and methods Immunoblotting analysis was used to detect relative proteins’ expression. Luciferase assay was performed to explore the activation of signal transducer and activator of transcription 3 (STAT3). Immunoprecipitation was performed to assess whether USP28 interacted with STAT3 or deubiquitinated STAT3. Quantitative real-time PCR was performed to evaluate the relative mRNA levels of STAT3 and USP28. Cycloheximide chase assay was carried out to examine whether USP28 affected the half-life of STAT3 protein. Cell Counting Kit-8 assay and xenograft model were used to assess whether USP28 regulated NSCLC cell growth. Results In this study, the deubiquitinating enzyme USP28 was found to mediate STAT3 signaling in NSCLC cells. USP28 interacted with STAT3, and increased the stability of STAT3 by inducing its deubiquitination. Further studies showed that USP28 was upregulated in both the primary tissues and cell lines of NSCLC. The Kaplan–Meier plotter also indicated that USP28 predicted a poor prognosis of NSCLC patients. Moreover, knockdown of USP28 inhibited cell growth of NSCLC cells in vitro and delayed NSCLC tumor growth in vivo. Conclusion These results demonstrated that USP28 was functional in NSCLC cells, and promoted NSCLC cell growth by inducing STAT3 signaling. This suggests that USP28 could be a novel target for NSCLC therapy.

The present study aimed to develop a rational therapy based on the genetic epidemiology, molecular mechanism evaluation and in vitro antibiotic combinations activity in multidrug-resistant Acinetobacter baumannii (MDRAB). MDRAB was screened by the Kirby-Bauer method. The random amplified polymorphic DNA technique was used to establish genetic fingerprinting, and a series of resistance genes were detected by polymerase chain reaction. Antimicrobial agents including amikacin (AK), cefoperazone/sulbactam (SCF I/II), meropenem (MEM), minocycline (MINO) and ciprofloxacin (CIP) were used to determine the minimum inhibitory concentrations (MICs) and interactions between antibiotics by the broth microdilution method and chequerboard assays. In total, 34 MDRAB strains were isolated and classified into 8 phenotypes A-H, according to their general drug susceptibilities. A total of 4 major genotypes (I–IV) were clustered at 60% a genotypic similarity threshold. High positive rates of β-lactamase TEM-1, topoisomerase IV, oxacillinase (OXA)-23, AdeB family multidrug efflux RND transporter adeB, β-lactamase AmpC, class 1 integrons (Int-1), 16S rRNA methylase rmtA, phosphotransferase aph(3), 16S rRNA methyltransferase armA were presented to exceed 90%, acetylyltransferase aac(3)-I, aac(6′-I, ant(3″)-I, 16S rRNA methylase rmtB, oxacillinase OXA-24 and metallo-β-lactamase IMP-5 genes demonstrated positive rates of 29.4–85.29%, while adeRS two-component system was not observed in any strain. MEM+SCF I or SCF II primarily exhibited synergistic effects. AK+SCF I, AK+SCF II, MINO+SCF I, MINO+SCF II, MINO+CIP and MINO+MEM primarily presented additive effects. AK+CIP demonstrated 70.59% antagonism. The antibacterial activity of SCF I was superior compared with that of SCF II. The results indicated the polyclonal genetic epidemiological trend of MDRAB in the Second Xiangya Hospital, and verified the complexity of genetic resistance. In addition, combinations suggested to be efficacious were MEM+SCF I and MEM+SCF II, which were more effective compared with other combinations for the management of MDRAB infection.