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Background: Epigenetics contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS). We aimed to characterize the DNA methylation profiles associated with clinical heterogeneity in disease progression and survival among patients. Methods: We included a cohort of 41 patients with sporadic ALS, with a median follow-up of 86.9 months, and 27 rigorously matched healthy controls. Blood-based genome-wide DNA methylation analysis was conducted. Results: A total of 948 progression rate-associated differentially methylated positions, 298 progression rate-associated differentially methylated regions (R-DMRs), 590 survival time-associated DMPs, and 197 survival time-associated DMRs (S-DMRs) were identified, using complementary grouping strategies. Enrichment analysis of differentially methylated genes highlighted the involvement of synapses and axons in ALS progression and survival. Clinical analysis revealed a positive correlation between the average methylation levels of the R-DMR in PRDM8 and disease progression rate (r = 0.479, p = 0.002). Conversely, there was an inverse correlation between the average methylation levels of the R-DMR in ANKRD33 and disease progression rate (r = − 0.476, p = 0.002). In addition, patients with higher methylation levels within the S-DMR of ZNF696 experienced longer survival (p = 0.016), while those with elevated methylation levels in the S-DMR of RAI1 had shorter survival (p = 0.006). Conclusion: DNA methylation holds promise as a potential biomarker for tracking disease progression and predicting survival outcome and also offers targets for precision medicine. [ABSTRACT FROM AUTHOR]

AbstractBackground: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Abnormalities in the peripheral immune system in ALS have been paid attention; however, the results of changes in peripheral immune parameters were inconsistent. Methods: A total of 1109 ALS patients were enrolled in the study. All patients received clinical evaluation and peripheral immune parameters measurement. The outcomes were analyzed by correlation analysis, multiple linear regression and cox survival analysis. Results: We found that ALS patients had significantly higher percentage of CD4+ T cells (39.3 vs. 37.1%, p < 0.001) and CD4+/CD8+ ratio (1.88 vs. 1.72, p = 0.011), significantly lower IgG (11.73 vs.12.82, p < 0.001) and IgA (2130.70 vs. 2284.8, p = 0.013) compared with the health controls. In the multivariate linear model, we found that each increase of 1.262, 0.278, and 4.44E-4 in ALSFRS-R scores were significantly associated with each increment of lymphocyte count, IgG, and IgA, respectively. However, each decrease of 0.341, 0.068, and 0.682 in ALSFRS-R score was associated with each increment in neutrophils, CD4+ T cells, and CD4+/CD8+ ratio, respectively. Cox survival regression analysis showed that the death risk of ALS patients was related to the levels of C3 (HR 0.592, 95% CI 0.361–0.973). Conclusion: We found that there were differences in peripheral immune parameters of ALS patients with the severity of the disease, especially neutrophil, lymphocyte, CD4+ T, and IgG; C3 is an independent predictor of survival in ALS patients. More studies are needed to elucidate the mechanisms associated with altered immune parameters in ALS. [ABSTRACT FROM AUTHOR]

Background: The extent of lymphadenectomy during laparoscopic right colectomy can affect the oncological outcome and the safety of surgery. The principle of complete mesocolic excision (CME) has been gradually accepted and increasingly applied by colorectal surgeons. The aim of this study is to investigate whether extended lymphadenectomy (CME) in laparoscopic colectomy could improve the oncological outcomes of patients with right-sided colon cancers, compared with D2 lymphadenectomy.Methods/design: The Radical Extent of lympadenectomy: D2 dissection versus complete mesocolic excision of LAparoscopic Right Colectomy for right-sided colon cancer (RELARC) study is a prospective, multicenter, randomized controlled trial in which 1072 eligible patients with right-sided colon cancers will be randomly assigned to the CME group or the D2 dissection group during laparoscopic right colectomy. Inclusion criteria are locally advanced colon cancers situated from the cecum to the right third of the transverse colon and clinically staged as T2-4aN0M0 or TanyN + M0. The primary endpoint of this trial is 3-year disease-free survival. Secondary endpoints include 3-year overall survival, postoperative complication rates, perioperative mortality rates, and rates of positive central lymph nodes (the station 3 nodes).Discussion: The RELARC trial is a prospective, multicenter, randomized controlled trial that will provide evidence on the optimal extent of lymphadenectomy during laparoscopic right colectomy in terms of better oncological outcome and operation safety.Trial Registration: ClinicalTrials.gov: NCT02619942 . Registered on 29 November 2015. [ABSTRACT FROM AUTHOR]