Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major cause of nosocomial infections and hospital outbreaks worldwide, remaining a critical clinical concern. Here we characterized and investigated the phylogenetic relationships of 105 CRAB isolates from an intensive care unit from one hospital in China collected over six years. All strains carried bla_OXA-23, bla_OXA-66 genes for carbapenem resistance, also had high resistance gene, virulence factor, and insertion sequence burdens. Whole-genome sequencing revealed all strains belonged to ST2, the global clone CC2. The phylogenetic analysis based on the core genome showed all isolates were dominated by a single lineage of three clusters and eight different clones. Two clones were popular during the collection time. Using chi-square test to identify the epidemiologically meaningful groupings, we found the significant difference in community structure only existed in strains from separation time. The haplotype and median-joining network analysis revealed genetic differences appeared among clusters and changes occurred overtime in the dominating cluster. Our results highlighted substantial multidrug-resistant CRAB burden in the hospital ICU environment demonstrating potential clone outbreak in the hospital.

Background. N6-methyladenosine (m6A) modification plays an essential role in diverse key biological processes and may take part in the development and progression of hepatocellular carcinoma (HCC). Here, we systematically analyzed the expression profiles and prognostic values of 13 widely reported m6A modification-related genes in HCC. Methods. The mRNA expression of 13 m6A modification-related genes and clinical parameters of HCC patients were downloaded from TCGA, ICGC, GSE109211, and GSE78220. Univariate and LASSO analyses were used to develop risk signature. Time-dependent ROC was performed to assess the predictive accuracy and sensitivity of risk signature. Results. FTO, YTHDC1, YTHDC2, ALKBH5, KIAA1429, HNRNPC, METTL3, RBM15, YTHDF2, YTHDF1, and WTAP were significantly overexpressed in HCC patients. YTHDF1, HNRNPC, RBM15, METTL3, and YTHDF2 were independent prognostic factors for OS and DFS in HCC patients. Next, a risk signature was also developed and validated with five m6A modification-related genes in TCGA and ICGC HCC cohort. It could effectively stratify HCC patients into high-risk patients with shorter OS and DFS and low-risk patients with longer OS and DFS and showed good predictive efficiency in predicting OS and DFS. Moreover, significantly higher proportions of macrophages M0 cells, neutrophils, and Tregs were found to be enriched in HCC patients with high risk scores, while significantly higher proportions of memory CD4 T cells, gamma delta T cells, and naive B cells were found to be enriched in HCC patients with low scores. Finally, significantly lower risk scores were found at sorafenib treatment responders and anti-PD-1 immunotherapy responders compared to that in nonresponders, and anti-PD-1 immunotherapy-treated patients with lower risk scores had better OS than patients with higher risk scores. Conclusion. A risk signature developed with the expression of 5 m6A-related genes could improve the prediction of prognosis of HCC and correlated with sorafenib treatment and anti-PD-1 immunotherapy response.

Background: Carbapenem-resistant Klebsiella pneumoniae infections have caused major concern and posed a global threat to public health. As bla_KPC-2 and bla_NDM-1 genes are the most widely reported carbapenem resistant genes in K. pneumonia, it is crucial to study the prevalence and geographical distribution of these two genes for further understanding of their transmission mode and mechanism. Purpose: Here, we investigated the prevalence and distribution of bla_KPC-2 and bla_NDM-1 genes in carbapenem-resistant K. pneumoniae strains from a tertiary hospital and from 1579 genomes available in the NCBI database, and further analyzed the possible core structure of bla_KPC-2 or bla_NDM-1 genes among global genome data. Materials and Methods: K. pneumoniae strains from a tertiary hospital in China during 2013– 2018 were collected and their antimicrobial susceptibility testing for 28 antibiotics was determined. Whole-genome sequencing of carbapenem-resistant K. pneumoniae strains was used to investigate the genetic characterization. The phylogenetic relationships of these strains were investigated through pan-genome analysis. The epidemiology and distribution of bla_KPC-2 and bla_NDM-1 genes in K. pneumoniae based on 1579 global genomes and carbapenem-resistant K. pneumoniae strains from hospital were analyzed using bioinformatics. The possible core structure carrying bla_KPC-2 or bla_NDM-1 genes was investigated among global data. Results: A total of 19 carbapenem-resistant K. pneumoniae were isolated in a tertiary hospital. All isolates had a multi-resistant pattern and eight kinds of resistance genes. The phylogenetic analysis showed all isolates in the hospital were dominated by two lineages composed of ST11 and ST25, respectively. ST11 and ST25 were the major ST type carrying bla_KPC-2 and bla_NDM-1 genes, respectively. Among 1579 global genomes data, 147 known ST types (1195 genomes) have been identified, while ST258 (23.6%) and ST11 (22.1%) were the globally prevalent clones among the known ST types. Genetic environment analysis showed that the ISKpn7-dnaA/ISKpn27 -bla_KPC-2-ISkpn6 and bla_NDM-1-ble-trpf-nagA may be the core structure in the horizontal transfer of bla_KPC-2 and bla_NDM-1, respectively. In addition, DNA transferase (hin) may be involved in the horizontal transfer or the expression of bla_NDM-1. Conclusion: There was clonal transmission of carbapenem-resistant K. pneumoniae in the tertiary hospital in China. The prevalence and distribution of bla_KPC-2 and bla_NDM-1 varied by countries and were driven by different transposons carrying the core structure. This study shed light on the genetic environment of bla_KPC-2 and bla_NDM-1 and offered basic information about the mechanism of carbapenem-resistant K. pneumoniae dissemination.

Background. Quantification of extracellular volume (ECV) fraction by cardiovascular magnetic resonance (CMR) has emerged as a noninvasive diagnostic tool to assess myocardial fibrosis. Secreted frizzled-related protein 2 (SFRP2) appears to play an important role in cardiac fibrosis. We aimed to evaluate the association between SFRP2 and myocardial fibrosis and the prognostic value of ECV fraction in patients with heart failure (HF). Methods. In this prospective cohort study, 72 hospitalized adult patients (age≥18 years) with severe decompensated HF were included. CMR measurements and T1 mapping were performed to calculate ECV fraction. Serum SFRP2 level was detected by an enzyme-linked immunosorbent assay kit. All patients were followed up, and the primary outcomes were composite events including all-cause mortality and HF hospitalization. Results. During the median follow-up of 12 months, 27 (37.5%) patients experienced primary outcome events and had higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), SFRP2, and ECV fraction compared with those without events. In Pearson correlation analysis, levels of SFRP2 (r=0.33), high-sensitivity C-reactive protein (r=0.31), and hemoglobin A1c (r=0.29) were associated with ECV fraction (all P<0.05); however, in multivariate linear regression analysis, SFRP2 was the only significant factor determined for ECV fraction (rpartial=0.33, P=0.02). In multivariate Cox regression analysis, age (each 10 years, hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.04–1.22), ECV fraction (per doubling, HR 1.68, 95% CI 1.03–2.74), and NT-proBNP (per doubling, HR 2.46, 95% CI 1.05–5.76) were independent risk factors for primary outcomes. Conclusions. Higher ECV fraction is associated with worsened prognosis in HF. SFRP2 is an independent biomarker for myocardial fibrosis. Further studies are needed to explore the potential therapeutic value of SFRP2 in myocardial fibrosis.

Background. Serum gamma-glutamyltransferase (GGT) is a biomarker of hepatic disease. Recent studies have shown that GGT may also associate with the risk of coronary artery disease. However, the underlying mechanisms of this association are still unclear. Methods. This study included 216 young patients with acute coronary syndrome (aged ≤55years) and 227 age-matched controls with normal findings by coronary angiography or coronary computed tomography angiography. We use standard colorimetric techniques and sandwich enzyme-linked immunosorbent assay to measure the levels of GGT and oxidized low-density lipoprotein (ox-LDL), respectively. Traditional risk factors of coronary artery disease, including smoking, diabetes mellitus, hypertension, dyslipidemia, and obesity/overweight, were evaluated according to the current guidelines. Results. The levels of GGT were significantly correlated with body mass index and levels of triglyceride, fasting plasma glucose, aspartate aminotransferase, and ox-LDL (all P<0.05). Multivariate logistic regression analysis showed that GGT was significantly associated with the risk of acute coronary syndrome in young Chinese patients (OR = 1.53, 95% CI = 1.09–2.15) after adjusting for traditional risk factors, including sex, age, quantity of smoking, hypertension, diabetes, body mass index, dyslipidemia, and high-sensitivity C-reactive protein. However, this association was significantly attenuated (OR = 1.20, 95% CI = 0.91–1.58) after further adjusting for the levels of ox-LDL. Conclusions. GGT was associated with the risk of ACS in relatively young patients. The link between GGT and the risk of ACS may be dependent on ox-LDL levels, indicating that the prooxidant action is an important pathway for GGT in the development of cardiovascular disease.