Prospective findings from the Dongfeng-Tongji cohort: Exposure to various metals, the expression of microRNA-4286, and the incidence of acute coronary syndrome.

Mounting evidence suggests that metal/metalloid exposure is related to the adverse health effects. Our prior investigation revealed a positive relation between the plasma level of microRNA-4286 (miR-4286) and an increased risk of developing acute coronary syndrome (ACS). However, it is a lack of studies evaluating the connection between metal/metalloid exposure and miRNA expression on ACS. In the prospective Dongfeng-Tongji cohort, we performed a nested case-control study. A total of 480 ACS and 480 controls were carefully selected based on similar age, sex, and blood collection time. Using inductively coupled plasma mass spectrometry, we assessed the plasma concentrations of 24 different metals. Quantitative real-time polymerase chain reaction was used to analyze the plasma miR-4286. We examined the relations of plasma metals with miR-4286 levels, the incidence of ACS, and the potential interactions. Using the multivariate conditional logistic regression models, we observed that the adjusted odds ratios (95% confidence intervals [CI]) for incident ACS were 1.79 (1.03, 3.12; P-trend = 0.03), 0.60 (0.41, 0.87; P-trend = 0.008), and 0.66 (0.46, 0.93; P-trend = 0.02), when comparing the extreme tertiles of aluminum, rubidium, and selenium, respectively. There was a relation between the concentration of rubidium in plasma and a decrease in the level of plasma miR-4286 (percent difference [95% CI]: -13.36% [-22.74%, -2.83%]; P-trend = 0.01). Both multiplicative (P interaction = 0.009) and additive interactions (relative excess risk due to interaction [95% CI]: 0.82 [0.59, 1.06]) were noted in our observation regarding the relationship between plasma aluminum and miR-4286 in incident ACS. The findings indicated that plasma aluminum was positively while plasma rubidium and selenium were negatively linked to an increased risk of developing ACS. Plasma aluminum exposure and plasma miR-4286 expression might synergistically affect the incident ACS risk. Controlling aluminum exposure was important for ACS prevention, especially for individuals with high expression of plasma miR-4286.

RNA-binding motif 4 promotes angiogenesis in HCC by selectively activating VEGF-A expression.

Increased angiogenesis in the liver plays a critical role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism underlying increased angiogenesis in HCC is not well understood. Current study was designed to identify the potential angiogenic effect of RNA-binding motif 4 (RBM4)through a small-scale overexpression screening, followed by comparison of the expression level of RBM4 in cancer and adjacent tissues in multiple malignancies to explore the relationship between RBM4 and CD31 protein expression level and related clinical indicators, and understand the role of RBM4 in the hepatocellular carcinoma. To understand the specific mechanism of RBM4 in detail, transcriptome sequencing, mass spectrometry and multiple molecular cytological studies were performed. These cellular level results were verified by experiments in animal models of nude mice. The increased expression of RBM4 in cancer tissues, suggested its use as a prognostic biomarker. The RBM4 expression was found to be strongly correlated with tumor microvessel density. Mechanistically, RBM4 mediated its effects via interaction with HNRNP-M through the latter's WDR15 domain, which then stabilized RelA/p65 mRNA. Consequently, RBM4 induced the activation of the NF-kB signaling pathway, upregulating the expression of proangiogenic factor VEGF-A. The results confirmed the mechanism by which RBM4 promotes angiogenesis in hepatocellular carcinoma suggesting RBM4 as a crucial promoter of angiogenesis in HCC, helping understand regulation of NF-kB signaling in HCC.

Exploring the Potential of Pyroptosis-Related Genes in Predicting Prognosis and Immunological Characteristics of Pancreatic Cancer From the Perspective of Genome and Transcriptome.

Objective: To probe into the role of pyroptosis-related genes in pancreatic carcinoma. Methods: Herein, we conducted a comprehensive bioinformatics analysis to evaluate tumor-immune infiltration and tumor mutation burden, the correlations between PRGs, and microsatellite instability and found that 33 PRGS were up- or down-regulated in PC. Then we built the PPI network, which was downloaded from the STRING database. Using TCGA cohort median risk score, PC subjects from the Gene Expression Composite cohort (GEO) data resource were stratified into two risk categories, with the low-PC risk group harboring a higher overall survival (OS) (P = 0.011). We employed the ssGSEA approach to quantify immune cell abundance in separate risk groups separated by risk signature while assessing variations in immune cell invasion. Chemotherapeutic drugs were retrieved from the Genomics of Drug Sensitivity in Cancer (GDSC) data resource. Results: Eight prognostic PRG models (CASP4, GSDMC, IL-18, NLRP1, NLRP2, PLCG1, TIRAP, and TNF) were established via LASSO Cox regression to estimate the OS of PC subjects with medium-to-high accuracy. Conclusion: Our study is the first to identify a pyroptotic-related prognostic gene feature for PC, providing more options for the prognostic prediction of PC.

Past Shift Work and Incident Coronary Heart Disease in Retired Workers: A Prospective Cohort Study.

Present shift work has been associated with coronary heart disease (CHD) among employed workers, but it remains unclear whether shift work performed in the past is still associated with CHD in retired workers. We recruited 21,802 retired workers in Shiyan, China, in 2008-2010 and 2013 and followed them for CHD events occurring up to December 31, 2018. Retired workers with longer durations of past shift work (rounded to 0.25 years) had higher CHD risks (for those with ≤5.00, 5.25-10.00, 10.50-20.00, and >20.00 years of past shift work, hazard ratios were 1.05 (95% confidence interval (CI): 0.94, 1.16), 1.08 (95% CI: 0.94, 1.25), 1.23 (95% CI: 1.07, 1.42), and 1.28 (95% CI: 1.08, 1.51), respectively). The association was substantially higher among service or sales workers than among manufacturing or manual-labor workers (for every 5-year increase in past shift work, hazard ratio = 1.11 (95% CI: 1.05, 1.16) vs. hazard ratio = 1.02 (95% CI: 0.98, 1.06)). Moreover, the risk was lower among those who were physically active than among their inactive counterparts (P for interaction = 0.019). Longer duration of past shift work was associated with higher risk of incident CHD among these retired workers, especially those from the service or sales sectors. Physical exercise might be beneficial in reducing the excess risk.

Prospective Study on Plasma MicroRNA-4286 and Incident Acute Coronary Syndrome.

Background Mounting evidence suggests that circulating microRNAs (miRNAs) are critical indicators of cardiovascular disease. However, prospective studies linking circulating miRNAs to incident acute coronary syndrome (ACS) are limited, and the underlying effect of associated miRNA on incident ACS remains unknown. Methods and Results Based on a 2-stage prospective nested case-control design within the Dongfeng-Tongji cohort, we profiled plasma miRNAs from 23 pairs of incident ACS cases and controls by microarray and validated the candidate miRNAs in 572 incident ACS case-control pairs using quantitative real-time polymerase chain reaction. We observed that plasma miR-4286 was associated with higher risk of ACS (adjusted odds ratio according to an interquartile range increase, 1.26 [95% CI, 1.07-1.48]). Further association analysis revealed that triglyceride was positively associated with plasma miR-4286, and an interquartile range increase in triglyceride was associated with an 11.04% (95% CI, 3.77%-18.83%) increase in plasma miR-4286. In addition, the Mendelian randomization analysis suggested a potential causal effect of triglyceride on plasma miR-4286 (ß coefficients: 0.27 [95% CI, 0.01-0.53] and 0.27 [95% CI, 0.07-0.47] separately by inverse variance-weighted and Mendelian randomization-pleiotropy residual sum and outlier tests). Moreover, the causal mediation analysis indicated that plasma miR-4286 explained 5.5% (95% CI, 0.7%-17.0%) of the association of triglyceride with incident ACS. Conclusions Higher level of plasma miR-4286 was associated with an increased risk of ACS. The upregulated miR-4286 in plasma can be attributed to higher triglyceride level and may mediate the effect of triglyceride on incident ACS.

Identification and Genotypic Characterization of Potentially Pathogenic Acanthamoeba Isolated from Tap Water in Wuxi, China.

Members of genus Acanthamoeba are widely distributed in the environment. Some are pathogenic and cause keratitis and fatal granulomatous amoebic encephalitis. In this study, we isolated an Acanthamoeba CJW/W1 strain from tap water in Wuxi, Jiangsu Province, China. Its 18S rDNA was sequenced and a phylogenetic tree was constructed. The isolated cysts belonged to morphologic group II. Comparison of 18S rDNA sequences of CJW/W1 strain and other isolates showed high similarity (99.7%) to a clinical isolate Asp, KA/E28. A phylogeny analysis confirmed this isolate belonged to the pathogenic genotype T4, the most common strain associated with Acanthamoeba-related diseases. This is the first report of an Acanthamoeba strain isolated from tap water in Wuxi, China. Acanthamoeba could be a public health threat to the contact lens wearers and, therefore, its prevalence should be monitored.

Event-tree analysis with imprecise probabilities.

Novel methods are proposed for dealing with event-tree analysis under imprecise probabilities, where one could measure chance or uncertainty without sharp numerical probabilities and express available evidence as upper and lower previsions (or expectations) of gambles (or bounded real functions). Sets of upper and lower previsions generate a convex set of probability distributions (or measures). Any probability distribution in this convex set should be considered in the event-tree analysis. This article focuses on the calculation of upper and lower bounds of the prevision (or the probability) of some outcome at the bottom of the event-tree. Three cases of given information/judgments on probabilities of outcomes are considered: (1) probabilities conditional to the occurrence of the event at the upper level; (2) total probabilities of occurrences, that is, not conditional to other events; (3) the combination of the previous two cases. Corresponding algorithms with imprecise probabilities under the three cases are explained and illustrated by simple examples.

[Endoscopic treatment of urethra stenosis by super-impulse plasma electrode].

OBJECTIVE: To evaluate the effect of internal urethrotomy with Super-impulse plasma electrode (SIPE) method on urethral stricture. METHODS: A total of 48 patients clinically diagnosed as having urethral stricture were hospitalized and treated with SIPE under the endoscope from February 2005 to August 2006. The patients' symptoms and clinical signs were compared before and after the treatment. In addition, techniques in operating SIPE were discussed. RESULTS: Of the 48 patients, 46 were cured and 2 experienced recurrence after the operation. A 3-18 months follow-up revealed no complications. CONCLUSION: SIPE under the endoscope is safe and effective in the treatment of urethra stenosis. It is easy to handle and the results are satisfactory.