BackgroundTranscription Factors (TFs), essential for many cellular processes, generally work coordinately to induce transcriptional change in response to internal and external signals. Disrupted cooperation between TFs, leading to dysregulation of target genes, contributes to the pathogenesis of many diseases, including cancer. Although the aberrant activation of individual TFs and the functional effects have been widely studied, the perturbation of TF cooperativity in cancer has rarely been explored.ResultsWe used TF co-expression as proxy as cooperativity and performed a large-scale study on disrupted TF cooperation across seven cancer types. While the connectivity of downstream effectors, like metabolic genes and TF targets, were more or similarly disrupted than/with non-TFs, the cooperativity of TFs (upstream regulators) were consistently less disturbed in all studied cancer types. Highly coordinated TFs in normal, however, generally lost that cooperation in cancer. Although different types of cancer shared very few TF pairs with highly disrupted cooperation, the cooperativity of interferon regulatory factors (IRF) was highly disrupted in six cancer types. Specifically, the cooperativity of IRF8 was highly perturbed in lung cancer, which was further validated by two independent lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) datasets. More interestingly, the cooperativity of IRF8 was markedly associated with tumor progression and even contributed to the patient survival independent of tumor stage.ConclusionsOur findings underscore the far more important role of TF cooperativity in tumorigenesis than previously appreciated. Disrupted cooperation of TFs provides potential clinical utility as prognostic markers for predicting the patient survival.

BackgroundThe rapid spread of Clostridium difficile NAP1/BI/027 (C. difficile 027) has become one of the leading threats of healthcare-associated infections worldwide. However, C. difficile 027 infections have been rarely reported in Asia, particularly in China.ResultsIn this study, we identified a rare C. difficile bloodstream infection (BSI) from three isolates of a patient during repeated hospital admission. This finding triggered a retrospective epidemiological study to scan all cases and strains emerged from this ward during the past three years. Using medical personnel interviews, medical record reviews and the genomic epidemiology, two outbreaks in 2012 and 2013–2014 were identified. Through using whole genome sequencing, we succeeded to trace the origin of the BSI strain. Surprisingly, we found the genome sequences were similar to C. difficile 027 strain R20291, indicating the occurrence of a rare C. difficile 027 strain in China. Integrated epidemiological investigation and whole genome sequencing of all strains, we constructed a nosocomial transmission map of these two C. difficile 027 outbreaks and traced the origin of the infection.ConclusionsBy genome sequencing, spatio-temporal analysis and field epidemiology investigation, we can estimate their complex transform network and reveal the possible modes of transmission in this ward. Based on their genetic diversity, we can assume that the toilets, bathroom, and janitor’s equipment room may be contaminated area, which may be suggested to improve infection control measures in the following health care.

BackgroundACFP is an anti-cancer fusion peptide derived from bovine milk protein. This study was to investigate the anti-cancer function and underlying mechanisms of ACFP in ovarian cancer.MethodsFresh ovarian tumor tissues were collected from 53 patients who underwent initial debulking surgery, and primary cancer cells were cultured. Normal ovarian surface epithelium cells (NOSECs), isolated from 7 patients who underwent surgery for uterine fibromas, were used as normal control tissue. Anti-viabilities of ACFP were assessed by WST-1 (water-soluble tetrazolium 1), and apoptosis was measured using a flow cytometry-based assay. Gene expression profiles of ovarian cancer cells treated with ACFP were generated by cDNA microarray, and the expression of apoptotic-specific genes, such as bcl-xl, bax, akt, caspase-3, CDC25C and cyclinB1, was assessed by real time PCR and western blot analysis.ResultsTreatment with ACFP inhibited the viability and promoted apoptosis of primary ovarian cancer cells but exhibited little or no cytotoxicity toward normal primary ovarian cells. Mechanistically, the anti-cancer effects of ACFP in ovarian cells were shown to occur partially via changes in gene expression and related signal pathways. Gene expression profiling highlighted that ACFP treatment in ovarian cancer cells repressed the expression of bcl-xl, akt, CDC25C and cyclinB1 and promoted the expression of bax and caspase-3 in a time- and dose-dependent manner.ConclusionsOur results suggest that ACFP may represent a potential therapeutic agent for ovarian cancer that functions by altering the expression and signaling of cancer-related pathways in ovarian cancer cells.

BackgroundTuberculosis remains a major public health problem in China. The Hebei province is located in the Beijing-Tianjin-Hebei integration region; however little information about the genetic diversity of Mycobacterium tuberculosis was available in this area. This study describes the first attempt to map the molecular epidemiology of MTB strains isolated from Hebei.MethodsSpoligotyping and 15-locus MIRU-VNTR were performed in combination to yield specific genetic profiles of 1017 MTB strains isolated from ten cities in the Hebei province in China during 2014. Susceptibility testing to first line anti-TB drugs was also conducted for all strains using the L-J proportion method.ResultsBased on the SpolDB4.0 database, the predominant spoligotype belonged to the Beijing family (90.5 %), followed by T family (6.3 %). Using 15-locus MIRU-VNTR clustering analysis, 846 different patterns were identified, including 84 clusters (2–17 strains per cluster) and 764 individual types. Drug susceptibility pattern showed that 347 strains (34.1 %) were resistant to at least one of the first line drugs, including 134 (13.2 %) multi-drug resistance strains. Statistical analysis indicated that drug resistance was associated with treatment history. The Beijing family was associated with genetic clustering. However, no significant difference was observed between the Beijing and non-Beijing family in gender, age, treatment history and drug resistance.ConclusionsThe Mycobacterium tuberculosis strains in Hebei exhibit high genetic diversity. The Beijing family is the most prevalent lineage in this area. Spoligotyping in combination with 15-locus MIRU-VNTR is a useful tool to study the molecular epidemiology of the MTB strains in Hebei.

BackgroundWe sought to understand the multilevel syndemic factors that are concurrently contributing to the HIV epidemic among women living in the US. We specifically examined community, network, dyadic, and individual factors to explain HIV vulnerability within a socioecological framework.MethodsWe gathered qualitative data (120 interviews and 31 focus groups) from a subset of women ages 18–44 years (N = 2,099) enrolled in the HPTN 064 HIV seroincidence estimation study across 10 US communities. We analyzed data from 4 diverse locations: Atlanta, New York City (the Bronx), Raleigh, and Washington, DC. Data were thematically coded using grounded theory methodology. Intercoder reliability was assessed to evaluate consistency of team-based coding practices.ResultsThe following themes were identified at 4 levels including 1) exosystem (community): poverty prevalence, discrimination, gender imbalances, community violence, and housing challenges; 2) mesosystem (network): organizational social support and sexual concurrency; 3) microsystem (dyadic): sex exchange, interpersonal social support, intimate partner violence; and 4) individual: HIV/STI awareness, risk taking, and substance use. A strong theme emerged with over 80 % of responses linked to the fundamental role of financial insecurity underlying risk-taking behavioral pathways.ConclusionsMultilevel syndemic factors contribute to women’s vulnerability to HIV in the US. Financial insecurity is a predominant theme, suggesting the need for tailored programming for women to reduce HIV risk.Trial registrationClinicaltrials.gov, NCT00995176

BackgroundTranscutaneous acupoint electrical stimulation (TAES) as a needleless acupuncture has the same effect like traditional manual acupuncture. The combination of TAES and anesthesia has been proved valid in enhancing the anesthetic effects but its mechanisms are still not clear.MethodsIn this study, we investigated the effect of TAES on anesthesia with an electroencephalogram (EEG) oscillation analysis on surgery patients anesthetized with propofol, a widely-used anesthetic in clinical practice. EEG was continuously recorded during light and deep propofol sedation (target-controlled infusion set at 1.0 and 3.0 μg/mL) in ten surgery patients with pituitary tumor excision. Each concentration of propofol was maintained for 6 min and TAES was given at 2–4 min. The changes in EEG power spectrum at different frequency bands (delta, theta, alpha, beta, and gamma) and the coherence of different EEG channels were analyzed.ResultsOur result showed that, after TAES application, the EEG power increased at alpha and beta bands in light sedation of propofol, but reduced at delta and beta bands in deep propofol sedation (p < 0.001). In addition, the EEG oscillation analysis showed an enhancement of synchronization at low frequencies and a decline in synchronization at high frequencies between different EEG channels in either light or deep propofol sedation.ConclusionsOur study showed evidence suggested that TAES may have different effects on propofol under light and deep sedation. TAES could enhance the sedative effect of propofol at low concentration but reduce the sedative effect of propofol at high concentration.