BACKGROUND:Numerous studies have demonstrated the existence of stable regulatory RNAs, microRNAs (miRNAs), in the circulation and have shown that the spectrum of these extracellular miRNAs is affected by various pathologic conditions including cancers.CONTENT: Circulating miRNAs have been the focus of numerous cancer biomarker discovery efforts over the past few years; however, a considerable number of these studies have yielded inconsistent and irreproducible findings. Here, we have summarized and compared the results of studies covering 8 different cancer types to address key questions, including the possibility of using circulating miRNA to detect cancers and what factors may affect miRNA signatures. Although identifying circulating miRNA signatures to detect specific types of early stage cancers can be challenging, study results suggest that it may be possible to use miRNAs to detect cancers in general.

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MicroRNAs (miRNAs) are short regulatory RNAs that modulate the transcriptome and proteome at the post-transcriptional level. To obtain a better understanding on the role of miRNAs in the progression of cervical cancer, meta-analysis and gene set enrichment analysis were used to analyze published cervical cancer miRNA studies. From 85 published reports, which include 3,922 cases and 2,099 noncancerous control tissue samples, 63 differentially expressed miRNAs (DEmiRNAs) were identified in different stages of cervical cancer development (CIN 1-3 and CC). It was found that some of the dysregulated miRNAs were associated with specific stages of cervical cancer development. To illustrate the impact of miRNAs on the pathogenesis of cervical cancer, a miRNA-mRNA interaction network on selected pathways was built by integrating viral oncoproteins, dysregulated miRNAs and their predicted/validated targets. The results indicated that the deregulated miRNAs at the different stages of cervical cancer were functionally involved in several key cancer related pathways, such as cell cycle, p53 and Wnt signaling pathways. These dysregulated miRNAs could play an important role in cervical cancer development. Some of the stage-specific miRNAs can also be used as biomarkers for cancer classification and monitoring the progression of cancer development.Cervical cancer is the second leading cause of female cancer deaths worldwide, with an estimated annual global incidence of more than half a million new cases and about 270,000 deaths. 1,2 Most cervical cancers are caused by infection with high risk (HR) human papilloma virus (HPV), which disrupts the normal proliferation and differentiation of cervical squamous epithelium cells via two viral-encoded oncoproteins: E6 and E7. The E6/E7 protein tumorgenesis is mediated through the interaction with cellular tumor suppressor proteins, TP53 and RB1 (Retinoblastoma 1), respectively. 3 Besides the misregulated host proteins, E6 and E7 oncoproteins also interact with host noncoding transcripts such as microRNAs (miRNAs). [4][5][6] MiRNAs are short (19-25 nucleotides in length) regulatory RNAs that modulate gene expression level by partial base pairing with the 3' untranslated region of their target messenger RNAs (mRNAs). 7 There are currently over 2,500 human miRNAs recorded in miRBase (www.mirbase.org), and it has been estimated that roughly two third of human transcripts are regulated by miRNAs. 8 One of the most important features of miRNAs is the partial nucleotide sequence paring between the miRNA and its mRNA target, which results in promiscuous interactions: one miRNA often interacts with more than one mRNAs, and one transcript can be targeted by multiple miRNAs. 9 The first cervical cancer

Summary Background The results of various studies attempting to assess the risks of venous thromboembolism in liver cirrhosis have been conflicting. Furthermore, although the incidence of venous thromboembolism is thought to be low in Asians, the relationship between venous thromboembolism and liver cirrhosis has not been investigated in Asian countries. Objective We investigated the risks of venous thromboembolism in cirrhotic patients in Taiwan to evaluate whether the risk is higher than in the general population. Methods The data from 1 000 000 National Health Insurance beneficiaries were utilized. All adult beneficiaries were followed from 1 January 2007 to 31 December 2010 to identify those who developed venous thromboembolism. Each identified patient with liver cirrhosis was matched with 10 non‐cirrhotic patients on the basis of high‐dimensional propensity score. Cox regression models were applied to compare the hazards of venous thromboembolism in the matched cohorts. Results A total of 757 940 patients were enrolled. After matching, 2223 cirrhotic patients and 22 230 non‐cirrhotic patients were selected. The adjusted hazard ratio of venous thromboembolism was significantly increased by having cirrhosis (1.71; 95% confidence interval [CI] 1.05–2.78). A subgroup analysis revealed a much higher hazard ratio of venous thromboembolism in an advanced cirrhosis subgroup (n = 293) than in a matched non‐cirrhosis subgroup (n = 2930) (4.36; 95% CI 1.36–14.01). Conclusion The risk of venous thromboembolism may be higher in Asian patients with cirrhosis than in the general Asian population, especially in those with advanced cirrhosis.

The proposed bidirectional relationship between acute pancreatitis (AP) and diabetes has never been examined with the same source of data. Furthermore, the effects of disease severity on this relationship have not been fully evaluated. The present study employed the findings from a single database to measure the strength of the association between AP and diabetes.Findings from 1 million National Health Insurance beneficiaries were utilized. Two cohort studies with this database were selected to evaluate the linkage between diabetes and AP. The first cohort analysis addressed the risk of AP among diabetic patients and was comprised of 42,080 diabetic patients and 672,146 unexposed subjects. The second cohort analysis considered the risk of diabetes among patients with AP and enrolled 3187 patients with AP and 709259 unexposed subjects. All adult beneficiaries were followed from January 1, 2005 to December 31, 2012 to identify outcomes of interest. Cox regression models were applied to compare hazards adjusted for potential confounders.For the first cohort, the adjusted hazard ratio (HR) of AP was significantly increased by the presence of diabetes (1.72; 95% confidence interval [CI], 1.52–1.96). In diabetic patients with a history of hyperglycemic crisis episodes (HCEs), the HR was even higher (6.32; 95% CI, 4.54–8.81). For the second cohort, the adjusted HR of diabetes in patients with AP was increased compared to the general population (2.15; 95% CI, 1.92–2.41). For patients with severe AP, the HR was also higher (2.22; 95% CI, 1.50–3.29) but did not differ significantly from that for patients with nonsevere AP.The 2 cohort studies provided evidence for the bidirectional relationship between diabetes and AP. Moreover, diabetic patients with history of HCEs may be associated with higher risk of AP.

BackgroundIt is known that the risk of stroke in patients with traumatic brain injury might be increased. However, the relationship between mild traumatic brain injury and ischemic stroke has never been established. We conducted a study of patients in Taiwan with mild traumatic brain injury to evaluate if they had a higher risk of stroke compared with the general population.MethodsWe utilized a sampled National Health Insurance claims database containing one million beneficiaries. We followed all adult beneficiaries older than 18 years from January 1, 2007 to December 31, 2010 to determine if they were diagnosed with ischemic stroke. We further identified patients with mild traumatic brain injury and compared their risk of ischemic stroke with the general population.ResultsWe identified 24,905 patients with mild traumatic brain injury and 719,811 patients without mild traumatic brain injury. After controlling for age, gender, urbanization level, socioeconomic status, diabetes, hypertension, coronary artery disease, hyperlipidemia, history of alcohol intoxication, malignancies, heart failure, atrial fibrillation, smoking, obesity, epilepsy, peripheral artery disease and Charlson Comorbidity Index score, the adjusted hazard ratio for ischemic stroke was 1.46 (95% confidence interval, 1.33—1.62).ConclusionMild traumatic brain injury is an independent significant risk factor for ischemic stroke.

Myocardial remodeling following myocardial infarction (MI) is emerging as key causes of chronic infarct mortality. Interleukin-6 is a classic pro-inflammatory cytokine needed to mount an effective immune response. It seems that interleukin-6 acts as an important role in the dynamic and superbly orchestrated process of innate immunity after MI. Interleukin-6 timely suppresses of innate immune signals to prevent the catastrophic consequences of uncontrolled inflammation on cardiac geometry and function, and thus tunes myocardial remodeling. A comprehensive understanding of biological processes of interleukin-6 in innate immunity leading to inflammatory response and disease-related ventricular remodeling is helpful to find the solution of chronic heart failure. To accomplish this, we reviewed the articles of interleukin-6 regard to inflammation, innate immunity, and cardiac remodeling. This review focuses on the role of interleukin-6 that dominates cell-mediated immunity, especially on neutrophils, monocytes, macrophages, and fibroblasts. In addition, we will also briefly discuss other inflammatory cytokines involved in this process within the paper.