Histone modifications play a critical role In the pathological processes of dilated cardiomyopathy (DCM), while the role and expression pattern of histone methyltransferases (HMTs), especially mixed lineage leukemia (MLL) families, in DCM are unclear. To this end, 12 normal and 15 DCM heart samples were included in the present study. A murine cardiac remodeling model was induced by transverse aortic constriction (TAC). Real-time polymerase chain reaction was performed to detect the expression levels of MLL families in the mouse and human left ventricles. The mRNA level of MLL3 was significantly increased in the mouse hearts treated with TAC surgery. Compared with normal hearts, higher mRNA and protein level of MLL3 was detected in the DCM hearts, and its expression level was closely associated with left ventricular end diastolic diameter and left ventricular ejection fraction. However, there was no obvious change in the expression levels of other MLL families (MLL, MLL2, MLL4, MLL5, SETD1A and SETD1B) between control and DCM hearts or remodeled mouse hearts. Furthermore, the dimethylated histone H3 lysine 4 (H3K4me2) but not H3K4me3 was significantly increased in the DCM hearts. The protein levels of Smad3, GATA4 and EGR1, which might be regulated by MLL3, were remarkably elevated in the DCM hearts. Our hitherto unrecognized findings indicate that MLL3 has a potential role in the pathological processes of DCM by regulating H3K4me2 and the expression of Smad3, GATA4 and EGR1.

BackgroundColorectal cancer (CRC) is one of the most common malignancies worldwide with poor prognosis. Studies have showed that abnormal microRNA (miRNA) expression can affect CRC pathogenesis and development through targeting critical genes in cellular system. However, it is unclear about which miRNAs play central roles in CRC’s pathogenesis and how they interact with transcription factors (TFs) to regulate the cancer-related genes.ResultsTo address this issue, we systematically explored the major regulation motifs, namely feed-forward loops (FFLs), that consist of miRNAs, TFs and CRC-related genes through the construction of a miRNA-TF regulatory network in CRC. First, we compiled CRC-related miRNAs, CRC-related genes, and human TFs from multiple data sources. Second, we identified 13,123 3-node FFLs including 25 miRNA-FFLs, 13,005 TF-FFLs and 93 composite-FFLs, and merged the 3-node FFLs to construct a CRC-related regulatory network. The network consists of three types of regulatory subnetworks (SNWs): miRNA-SNW, TF-SNW, and composite-SNW. To enhance the accuracy of the network, the results were filtered by using The Cancer Genome Atlas (TCGA) expression data in CRC, whereby we generated a core regulatory network consisting of 58 significant FFLs. We then applied a hub identification strategy to the significant FFLs and found 5 significant components, including two miRNAs (hsa-miR-25 and hsa-miR-31), two genes (ADAMTSL3 and AXIN1) and one TF (BRCA1). The follow up prognosis analysis indicated all of the 5 significant components having good prediction of overall survival of CRC patients.ConclusionsIn summary, we generated a CRC-specific miRNA-TF regulatory network, which is helpful to understand the complex CRC regulatory mechanisms and guide clinical treatment. The discovered 5 regulators might have critical roles in CRC pathogenesis and warrant future investigation.

BackgroundData to date is far from sufficient to describe the recent epidemiology of ventilator-associated pneumonia (VAP) in mainland China. This study aimed to estimate the overall incidence of VAP, with a special focus on its temporal trend and associated factors.MethodsMeta-analyses of 195 studies published from 2010 to 2015 were conducted, followed by subgroup analyses by methodological quality, pre-defined setting characteristics and attributes of populations.ResultsThe overall cumulative VAP incidence in mainland China was 23.8% (95% confidence interval (CI) 20.6–27.2%), with the results showing high heterogeneity. The pooled incidence densities were 24.14 (95% CI 21.19–27.51) episodes and 22.83 (95% CI 19.88–26.23) patients per 1000 ventilator-days. A decline in the cumulative incidence was observed from 2006 (49.5%, 95% CI 40.0–59.0%) to 2014 (19.6%, 95% CI 10.4–31.0%); differences in the incidence rates were also documented according to Chinese provinces and diagnostic criteria (p < 0.001). Older age (≥60 years), coma, re-intubation, tracheotomy and prolonged ventilation were the factors significantly associated with the occurrence of VAP.ConclusionsThe incidence of VAP remains high in mainland China but has decreased since 2006. The reported rates vary considerably across individual studies, probably due to variations in diagnosis and geographical region. More studies using standard definitions and cut-off points are needed to better clarify the epidemiology of VAP across the country.

BackgroundIt was previously reported in China that two recent large-scale outbreaks of Streptococcus suis serotype 2 (S. suis 2) infections in human were caused by two highly virulent S. suis 2 strains, from which a novel genomic island (GEI), associated with disease onset and progression and designated 89 K, was identified. Here, an avirulent strain, 05HAS68, was isolated from a clinically healthy pig.ResultsBy comparing the genomes of this avirulent strain with virulent strains, it was found that massive genomic rearrangements occurred, resulting in alterations in gene expression that caused enormous single gene gain and loss. Important virulent genes were lost, such as extracellular protein factor (ef) and suilysin (sly) and larger mutants, such as muramidase-released protein (mrp). Piglets vaccinated with the avirulent strain, 05HAS68, had increased TNF-α and IFN-γ levels in the peripheral blood and were fully protected from challenge infection with the most virulent S. suis 2 strain, 05ZYH33. Transfusion of T cells and plasma from vaccinated pigs resulted in protection of recipient animals against the 05ZYH33 challenge.ConclusionThese results suggest that analysis genome of the avirulent strains are instrumental in the development of vaccines and for the functional characterization of important of genetic determinants.

BackgroundPolyploidy and hybridization are both recognized as major forces in evolution. Most of our current knowledge about differences in gene regulation in polyploid hybrids comes from plant studies. The gene expression of diverged genomes and regulatory interactions are still unclear in lower vertebrates.ResultsWe generated 229 million cleaned reads (42.23 Gbp) from triploid of maternal grass carp (Ctenopharyngodon idellus, Cyprininae, 2n = 48) × paternal blunt snout bream (Megalobrama amblycephala, Cultrinae, 2n = 48) and their diploid parents using next-generation sequencing. In total, 157,878 contigs were assembled and 15,444 genes were annotated. We examined gene expression level changes among the parents and their triploid offspring. The mechanisms of dosage compensation that reduced triploid expression levels to the diploid state were determined in triploid fish. In this situation, novel gene expression and gene silencing were observed. Then, we established a model to determine the extent and direction of expression level dominance (ELD) and homoeolog expression bias (HEB) based on the relative expression level among the parents and their triploid offspring.ConclusionsOur results showed that the genome-wide ELD was biased toward maternal genome in triploid. Extensive alterations in homoeolog expression suggested a combination of regulatory and epigenetic interactions through the transcriptome network. Additionally, the expression patterns of growth genes provided insights into the relationship between the characteristics of growth and underlying mechanisms in triploids. Regulation patterns of triploid state suggest that various expression levels from the initial genomic merger have important roles in adaptation.

BackgroundData to date is far from sufficient to describe the recent epidemiology of ventilator-associated pneumonia (VAP) in mainland China. This study aimed to estimate the overall incidence of VAP, with a special focus on its temporal trend and associated factors.MethodsMeta-analyses of 195 studies published from 2010 to 2015 were conducted, followed by subgroup analyses by methodological quality, pre-defined setting characteristics and attributes of populations.ResultsThe overall cumulative VAP incidence in mainland China was 23.8% (95% confidence interval (CI) 20.6–27.2%), with the results showing high heterogeneity. The pooled incidence densities were 24.14 (95% CI 21.19–27.51) episodes and 22.83 (95% CI 19.88–26.23) patients per 1000 ventilator-days. A decline in the cumulative incidence was observed from 2006 (49.5%, 95% CI 40.0–59.0%) to 2014 (19.6%, 95% CI 10.4–31.0%); differences in the incidence rates were also documented according to Chinese provinces and diagnostic criteria (p < 0.001). Older age (≥60 years), coma, re-intubation, tracheotomy and prolonged ventilation were the factors significantly associated with the occurrence of VAP.ConclusionsThe incidence of VAP remains high in mainland China but has decreased since 2006. The reported rates vary considerably across individual studies, probably due to variations in diagnosis and geographical region. More studies using standard definitions and cut-off points are needed to better clarify the epidemiology of VAP across the country.