Objective To explore the causal relationship between DNA copy number and the risk of Alzheimer disease (AD) using Mendelian randomization (MR) methods, as well as to investigate the potential mediating effects of immune cells. Methods The data related to 731 immune cell types, DNA copy number and AD from the Genome-Wide Association Study database were collected. A bidirectional MR analysis was conducted to explore the causal relationship between DNA copy number and AD, primarily using the inverse-variance weighted method and MR-Egger method. Additionally, a two-step mediation analysis was performed to identify potential mediating immune cells. Results A total of 134 single-nucleotide polymorphisms were included for bidirectional MR analysis. The MR methods results showed a negative causal relationship between DNA copy number and the risk of AD (P<0.05), while the reverse analysis showed no statistical significance. Sensitivity analysis confirmed the robustness of these results. The mediation analysis indicated that the immune cell phenotype (HVEM on CD45RA-CD4+) partially mediated the causal relationship between DNA copy numbers and the risk of AD, with a mediation effect proportion of 4.6%. Conclusion An increase in DNA copy numbers may reduce the risk of AD, and immune cells partially mediate this causal relationship.
ObjectiveTo explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. MethodsWe employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. ResultsOur research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ may play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. ConclusionPD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.
Objective To investigate the impact of COVID-19 infection on the early clinical outcomes of patients undergoing valve replacement. MethodsPerioperative data of patients who underwent single valve replacement at the Second Affiliated Hospital of Chinese People's Liberation Army Medical University from January to February 2023 were consecutively collected. Based on COVID-19 infection status, patients were divided into a COVID-19 group and a non-COVID-19 group. General characteristics, comorbidities, operative time, aortic cross-clamp time, postoperative mechanical ventilation duration, ICU stay, myocardial enzyme profiles, and respiratory-related complications were compared between the two groups. The primary endpoint was the incidence of postoperative respiratory and circulatory complications, and the secondary endpoint was the postoperative myocardial enzyme profiles. ResultsA total of 136 patients were included, comprising 53 males and 83 females, with a mean age of (53.4±10.2) years. There were 32 aortic valve replacements, 102 mitral valve replacements, and 2 tricuspid valve replacements. No statistical difference was observed in the incidence of postoperative complications between the two groups [9.09% (6/66) vs. 11.43% (8/70), P=0.654]. However, the COVID-19 group had longer postoperative mechanical ventilation duration [1 201.00 (1 003.75, 1 347.75) min vs. 913.50 (465.50, 1 251.00) min, P=0.001] and ICU stay [3 (2, 3) days vs. 2 (2, 3) days, P<0.001] compared to the non-COVID-19 group. Additionally, troponin I [4.76 (2.55, 7.93) ng/mL vs. 2.66 (1.19, 5.65) ng/mL, P=0.001] and B-typenatriuretic peptide [608.50 (249.75, 1 150.00) pg/mL vs. 192.00 (100.93, 314.75) pg/mL, P<0.001] levels were significantly higher in the COVID-19 group. ConclusionFor patients with single valve disease undergoing elective surgery, short-term outcomes after recovery from COVID-19 infection are favorable, with no significant increase in in-hospital mortality or postoperative complication rates.