Genomic signatures and gene networking: challenges and promises

This is an editorial report of the supplement to BMC Genomics that includes 15 papers selected from the BIOCOMP'10 - The 2010 International Conference on Bioinformatics & Computational Biology as well as other sources with a focus on genomics studies

The Oncogenic Roles of Nuclear Receptor Coactivator 1 in Human Esophageal Carcinoma

Nuclear receptor coactivator 1 (NCOA1) plays crucial roles in the regulation of gene expression mediated by a wide spectrum of steroid receptors such as androgen receptor (AR), estrogen receptor α (ER α), and estrogen receptor β (ER β). Therefore, dysregulations of NCOA1 have been found in a variety of cancer types. However, the clinical relevance and the functional roles of NCOA1 in human esophageal squamous cell carcinoma (ESCC) are less known. We found in this study that elevated levels of NCOA1 protein and/or mRNA as well as amplification of the NCOA1 gene occur in human ESCC. Elevated levels of NCOA1 due to these dysregulations were not only associated with more aggressive clinic-pathologic parameters but also poorer survival. Results from multiple cohorts of ESCC patients strongly suggest that the levels of NCOA1 could serve as an independent predictor of overall survival. In addition, silencing NCOA1 in ESCC cells remarkably decreased proliferation, migration, and invasion. These findings not only indicate that NCOA1 plays important roles in human ESCC but the levels of NCOA1 also could serve as a potential prognostic biomarker of ESCC and targeting NCOA1 could be an efficacious strategy in ESCC treatment

Detection of Exosomal PD-L1 RNA in Saliva of Patients With Periodontitis

Periodontitis is the most prevalent inflammatory disease of the periodontium, and is related to oral and systemic health. Exosomes are emerging as non-invasive biomarker for liquid biopsy. We here evaluated the levels of programmed death-ligand 1 (PD-L1) mRNA in salivary exosomes from patients with periodontitis and non-periodontitis controls. The purposes of this study were to establish a procedure for isolation and detection of mRNA in exosomes from saliva of periodontitis patients, to characterize the level of salivary exosomal PD-L1, and to illustrate its clinical relevance. Bioinformatics analysis suggested that periodontitis was associated with an inflammation gene expression signature, that PD-L1 expression positively correlated with inflammation in periodontitis based on gene set enrichment analysis (GSEA) and that PD-L1 expression was remarkably elevated in periodontitis patients versus control subjects. Exosomal RNAs were successfully isolated from saliva of 61 patients and 30 controls and were subjected to qRT-PCR. Levels of PD-L1 mRNA in salivary exosomes were higher in periodontitis patients than controls (P < 0.01). Salivary exosomal PD-L1 mRNA showed significant difference between the stages of periodontitis. In summary, the protocols for isolating and detecting exosomal RNA from saliva of periodontitis patients were, for the first time, characterized. The current study suggests that assay of exosomes-based PD-L1 mRNA in saliva has potential to distinguish periodontitis from the healthy, and the levels correlate with the severity/stage of periodontitis

The association between a body shape index and elevated urinary albumin–creatinine ratio in Chinese community adults

BackgroundObesity, especially visceral obesity, seems to be one of the most decisive risk factors for chronic kidney disease. A Body Shape Index (ABSI) is an emerging body size measurement marker of visceral obesity. This study aimed to explore whether ABSI is associated with albuminuria in Chinese community adults.MethodsThis cross-sectional study enrolled 40,726 participants aged 40 or older from seven provinces across China through a cluster random sampling method. ABSI was calculated by body mass index, waist circumference, and height. Increased albuminuria was defined as urinary albumin–creatinine ratio (UACR) ≥ 30 mg/g, indicating kidney injury. For ABSI, we divided it by quartile cutoff points and tried to determine the association between ABSI levels and UACR by multiple regression analysis. DAG (Directed Acyclic Graph) was plotted using literature and expert consensus to identify potential confounding factors.ResultsThe average age of subjects with elevated UACR was 61.43 ± 10.07, and 26% were men. The average age of subjects with normal UACR was 57.70 ± 9.02, and 30.5% were men. Multiple logistic regression analysis was conducted and demonstrated that the ABSI quartiles were related to elevated UACR positively (OR [95% CI] Q2 vs. Q1: 1.094 [1.004, 1.197]; OR [95% CI] Q3 vs. Q1: 1.126 [1.030, 1.231]; OR [95% CI] Q4 vs. Q1: 1.183 [1.080, 1.295], p for trend < 0.001) after adjustments for confounding factors. The stratified analysis further showed that with the mounting for ABSI levels, elevated UACR more easily occurred in the people characterized by the elderly, men, and hypertension.ConclusionsIn Chinese community adults, people with higher ABSI levels can be deemed as high-risk individuals with UACR elevation, and it will be beneficial for them to lose weight and significantly reduce visceral fat

A prospective study of the use of antibiotics in the Emergency Department of a Chinese University Hospital

Background: Antibiotics are one of the most widely misused group of medicines. The aim of this study was to investigate the use of antibiotics in one of the paediatric emergency departments in China. Methods: We performed a prospective, cross-sectional study of antibiotic use in the paediatric emergency room of West China Second University Hospital. A total of 500 consecutive patients from March 25 to April 3 2013 were included. Clinical details of the patients were also collected in order to analyse antibiotic use. Key findings: The median age of patients was 2 years 2 months. The five most common conditions seen in the emergency department were wheezy bronchitis, upper respiratory tract infections, tonsillitis, pneumonia and diarrhoea. A total of 311 children (62%) received antibiotics. The antibiotics prescribed were predominantly cephalosporins and penicillins. More than one antibiotic was used in 51 patients. In total, 75% of the antibiotics prescribed were cephalosporins. More than three-quarters of the young children with wheezy bronchitis received antibiotics. Antibiotic use for children with an upper respiratory tract infections or tonsillitis was greater than the 20% maximum recommended by the European Surveillance of Antimicrobial Consumption. Conclusions: The majority of children attending the emergency department received antibiotics. For many of the conditions, the use of antibiotics was inappropriate

Modification effect of changes in cardiometabolic traits in association between kidney stones and cardiovascular events

BackgroundsWhether longitudinal changes in metabolic status influence the effect of kidney stones on cardiovascular disease (CVD) remains unclarified. We investigated the modification effect of status changes in metabolic syndrome (MetS) in the association of kidney stones with risk of incident CVD events.MethodsWe performed a prospective association and interaction study in a nationwide cohort including 129,172 participants aged ≥ 40 years without CVDs at baseline and followed up for an average of 3.8 years. Kidney stones information was collected by using a questionnaire and validated by medical records. The repeated biochemical measurements were performed to ascertain the metabolic status at both baseline and follow-up.Results4,017 incident total CVDs, 1,413 coronary heart diseases (CHDs) and 2,682 strokes were documented and ascertained during follow-up. Kidney stones presence was significantly associated with 44%, 70% and 31% higher risk of CVDs, CHDs and stroke, respectively. The stratified analysis showed significant associations were found in the incident and sustained MetS patients, while no significant associations were found in the non-MetS at both baseline and follow-up subjects or the MetS remission ones, especially in women. For the change status of each single component of the MetS, though the trends were not always the same, the associations with CVD were consistently significant in those with sustained metabolic disorders, except for the sustained high blood glucose group, while the associations were consistently significant in those with incident metabolic disorders except for the incident blood pressure group. We also found a significant association of kidney stone and CVD or CHD risk in the remain normal glucose or triglycerides groups; while the associations were consistently significant in those with incident metabolic disorders except for the incident blood pressure group. We also found a significant association of kidney stone and CVD or CHD risk in the remain normal glucose or triglycerides groups.ConclusionsA history of kidney stones in women with newly developed MetS or long-standing MetS associated with increased risk of CVD. The mechanisms link kidney stones and CVD risk in the metabolic and non-metabolic pathways were warranted for further studies

The Relative Body Weight Gain From Early to Middle Life Adulthood Associated With Later Life Risk of Diabetes: A Nationwide Cohort Study

AimTo determine the effect of decade-based body weight gain from 20 to 50 years of age on later life diabetes risk.Methods35,611 non-diabetic participants aged ≥ 50 years from a well-defined nationwide cohort were followed up for average of 3.6 years, with cardiovascular diseases and cancers at baseline were excluded. Body weight at 20, 30, 40, and 50 years was reported. The overall 30 years and each 10-year weight gain were calculated from the early and middle life. Cox regression models were used to estimate risks of incident diabetes.ResultsAfter 127,745.26 person-years of follow-up, 2,789 incident diabetes were identified (incidence rate, 2.18%) in 25,289 women (mean weight gain 20-50 years, 7.60 kg) and 10,322 men (7.93 kg). Each 10-kg weight gain over the 30 years was significantly associated with a 39.7% increased risk of incident diabetes (95% confidence interval [CI], 1.33-1.47); weight gain from 20-30 years showed a more prominent effect on the risk of developing diabetes before 60 years than that of after 60 years (Hazard ratio, HR = 1.084, 95% CI [1.049-1.121], P <0.0001 vs. 1.015 [0.975-1.056], P = 0.4643; PInteraction=0.0293). It showed a stable effect of the three 10-year intervals weight gain on risk of diabetes after 60 years (HR=1.055, 1.038, 1.043, respectively, all P < 0.0036).ConclusionsThe early life weight gain showed a more prominent effect on developing diabetes before 60 years than after 60 years; however, each-decade weight gain from 20 to 50 years showed a similar effect on risk developing diabetes after 60 years

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4–15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for pathological neonatal jaundice.Methods: Databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) were searched and the deadline is December 2016. Randomized controlled trials (RCTs) of probiotics supplementation for pathological neonatal jaundice in publications were extracted by two reviewers. The cochrane tool was applied to assessing the risk of bias of the trials. The extracted information of RCTs should include efficacy rate, serum total bilirubin level, time of jaundice fading, duration of phototherapy, duration of hospitalization, adverse reactions. The main outcomes of the trials were analyzed by Review Manager 5.3 software. The relative risks (RR) or mean difference (MD) with a 95% confidence interval (CI) was used to measure the effect.Results: 13 RCTs involving 1067 neonatal with jaundice were included in the meta-analysis. Probiotics supplementation treatment showed efficacy [RR: 1.19, 95% CI (1.12, 1.26), P < 0.00001] in neonatal jaundice. It not only decreased the total serum bilirubin level after 3day [MD: −18.05, 95% CI (−25.51, −10.58), P < 0.00001], 5day [MD: -23.49, 95% CI (−32.80, −14.18), P < 0.00001], 7day [MD: −33.01, 95% CI (−37.31, −28.70), P < 0.00001] treatment, but also decreased time of jaundice fading [MD: −1.91, 95% CI (−2.06, −1.75), P < 0.00001], as well as the duration of phototherapy [MD: −0.64, 95% CI (−0.84, −0.44), P < 0.00001] and hospitalization [MD: −2.68, 95% CI (−3.18, −2.17), P < 0.00001], when compared with the control group. Additionally, no serious adverse reaction was reported.Conclusion: This meta-analysis shows that probiotics supplementation therapy is an effective and safe treatment for pathological neonatal jaundice

Efficacy and safety of tacrolimus in myasthenia gravis: A systematic review and meta-analysis

Aims: This study was designed to determine whether treatments with tacrolimus would provide benefit for patients with myasthenia gravis (MG). Materials and Methods: The databases of Medline, EMBASE, the Cochrane Library, and four Chinese databases were searched for eligible studies. Weighted mean differences and standardized mean differences (SMD) with corresponding 95% confidence intervals (CIs) were used to summarize the primary outcome, namely, steroid-sparing effect of tacrolimus in maintaining minimal manifestations, and the secondary outcome, namely, the effect of tacrolimus in reducing the severity of MG, respectively. Results: After systematic retrieval, 13 researches with two randomized controlled trials (RCTs) and 11 prospective open-label single-arm clinical trials were included in the study. For the primary outcome of two RCTs, one RCT which was followed up for 1 year showed a positive effect and the other RCT which was associated with treatment duration of 28 weeks showed a negative result. For the secondary outcome, meta-analyses of other 11 trials showed a benefit effect, overall. For the quantitative MG (QMG) score, there were significant differences with high heterogeneity (SMD: 2.93; 95% CI: 1.14–4.73; I2 = 86%). In contrast, for MG activities of daily living (MGADL) score, it was reduced by tacrolimus with significant SMD and less heterogeneity (SMD: 0.59; 95% CI: 0.33–0.85; I2 = 7%). Adverse effects were mentioned as mild. Discussion: The opposite results of two RCTs showed that tacrolimus with enough treatment duration might have positive steroid-sparing effect. The most possible cause of heterogeneity in the outcome of QMG score between trials was the baseline severity of MG. Conclusion: The above finding suggests that there might be a potential beneficial role with no serious side effects of tacrolimus, and additional better RCTs including larger sample sizes and long-term study are needed to confirm or refute the results