No abstract

We aimed to elucidate the differences in genomic methylation patterns between ADLI and non-ADLI patients to identify DNA methylation-based biomarkers. Genome-wide DNA methylation patterns were obtained using Infinium MethylationEPIC (EPIC) BeadChip array to analyze 14 peripheral blood samples (7 ADLI cases, 7 non-ADLI controls). Changes in the mRNA and DNA methylation in the target genes of another 120 peripheral blood samples (60 ADLI cases, 60 non-ADLI controls) were analyzed by real-time polymerase chain reaction and pyrosequencing, respectively. A total of 308 hypermethylated CpG sites and 498 hypomethylated CpG sites were identified. Significantly, hypermethylated CpG sites cg06961147 and cg24666046 in TANC1 associated with ADLI was identified by genome-wide DNA methylation profiling. The mRNA expression of TANC1 was lower in the cases compared to the controls. Pyrosequencing validated these two differentially methylated loci, which was consistent with the results from the EPIC BeadChip array. Receiver operating characteristic analysis indicated that the area under the curve of TANC1 (cg06961147, cg24666046, and their combinations) was 0.812, 0.842, and 0.857, respectively. These results indicate that patients with ADLI have different genomic methylation patterns than patients without ADLI. The hypermethylated differentially methylated site cg06961147 combined with cg24666046 in TANC1 provides evidence for the diagnosis of ADLI.

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Tuberculosis (TB) is a chronic infectious disease caused byMycobacterium tuberculosis. It is a preventable and treatable disease mainly transmitted from person to person through the air. Globally, China has a high burden of TB and the third-highest incidence behind India and Indonesia. According to the global tuberculosis report (2019) by the World Health Organization (WHO), there were about 866,000 TB cases and 40,000 TB deaths in China. 1 One of the health-related goals of sustainable development is to curb the TB epidemic by 2030. The World Health Assembly passed the resolution with ambitious targets, but it is not an easy promise. Standardized chemotherapy is a crucial means to achieve this goal. However, the adverse effects of chemotherapeutic drugs such as anti-tuberculosis

Lipoprotein-associated phospholipase A2 (Lp-PLA2) and high-sensitivity C-reactive protein (hs-CRP) have been reported to be associated with cardiovascular disease (CVD). However, whether the combination of these two markers can improve the prediction of CVD is unknown.A total of 1,921 participants without CVD, aged 40 years or older, were enrolled from 2010 to 2011. Plasma Lp-PLA2 and hs-CRP were measured at baseline. Participants were subsequently followed until December 2015. We identified a total of 148 cardiovascular events (myocardial infarction, stroke, and all-cause death). Cox proportional-hazard models were used to determine the association between two independent markers and cardiovascular outcomes. The C statistic, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI) were used to determine the utility of the two markers in predicting cardiovascular risk.After adjustment for potential confounders, compared with the first quartile, hazard ratios (HRs) with 95% confidence interval (CI) for the third and fourth quartiles for Lp-PLA2 were 2.09 (1.17-3.73) and 2.62 (1.48-4.67), respectively, and HRs with 95%CI for the fourth quartile for hs-CRP was 1.78 (1.08-4.67). Compared with conventional risk factors, the combination of hs-CRP and Lp-PLA2 provided greater incremental information, and the C statistic increased by 0.013. The NRI and IDI were also statistically significant for cardiovascular events (P = 0.004 and P < 0.001, respectively).Hs-CRP and Lp-PLA2 have complementary effects in predicting cardiovascular outcomes in adults aged 40 years or older.