Objective: To explore the relationship between folic acid supplementation and the recovery rate of gestational diabetes mellitus (GDM) in women with methylenetetrahydrofolate (MTHFR) 677 TT genotypes in mid-late pregnancy.Methods: 9, 096 pregnant women were recruited with their MTHFR gene genotyped. 5,111 women underwent a 75-g oral glucose tolerance test (OGTT) and 2,097 were confirmed with GDM. The association between MTHFR genotypes and GDM risk was estimated using logistic and log-binomial regression, with age and parity set as the covariates to control their confounding effects. Further assessment of GDM risk on glucose levels was done using the ANCOVA model. As an open-label intervention study, 53 GDM patients with TT genotype were prescribed 800μg/day of folic acid as the high-dose group, while 201 GDM patients were given 400μg/day as the standard-dose group at their 24-28 weeks of pregnancy. A rate ratio (RR) of GDM recovery was estimated at each available time point for both groups. The time-to-GDM persistence events were analyzed with the Kaplan-Meier method and Cox-regression model. The trend of glucose levels over time was estimated using the linear model.Results: MTHFR 677 TT genotype has no significant association with the glucose levels and GDM risk, with an adjusted OR of 1.105 (95% CI 0.853, 1.431; p=0.452) and an adjusted PR of 1.050 (95% CI 0.906, 1.216; p=0.518) compared to the wildtype CC group. Patients in the high-dose group (n=38; 15 drop-outs; 40.69 days (95% CI 33.22, 48.15)) recovered from GDM approximately 27 days faster than those in the standard-dose group (n=133; 68 drop-outs; 68.09 days (95% CI 63.08, 73.11)). Concomitantly, the RR of GDM recovery rose and reached 1.247 (95% CI 1.026, 1.515) at 100 days of treatment with the standard-dose group as reference.Conclusion: High-dose folic acid supplement intake in mid-late pregnancy is associated with faster GDM relief in patients with MTHFR 677 TT genotype compared to the standard dose, which would be served as a novel and low-cost alternative therapy for the treatment of GDM.

Preeclampsia (PE) is characterized by new-onset hypertension after 20 weeks of pregnancy and results in high maternal and fetal mortality worldwide. It has been reported that PE is associated with abnormalities in the umbilical cord and cord blood. However, previous studies were focused primarily on the transcriptomics level, while the underlying gene regulatory landscapes are still unclear. Thus, we performed the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) using the umbilical cord blood samples collected from a patient with superimposed PE and three healthy donors to uncover the chromatin accessibility changes attributed to PE. We have identified genes associated with immunomodulation and hypoxia response that have higher chromatin accessibility close to their transcription start sites. Motif analysis indicated that the GATA family transcription factor binding was enriched in PE and may play an essential regulatory role in the disease progression. Overall, our findings provide an overview of gene regulatory programs and the corresponding downstream pathways associated with PE that may influence the placenta function and fetal growth.

Carcass decomposition is a natural process that is characterized by a series of chemical transformations. During postmortem degradation, macromolecules are broken down into smaller molecules. Because proteins constitute a large proportion of the dry cell mass, protein degradation is the dominant postmortem decomposition process. Currently, the characteristics of protein degradation postmortem are largely unknown. Metabolomics enables the quantitative analysis of all metabolites within organisms or cells and has been used to investigate metabolite changes during physiological and pathological processes. Recently, forensic researchers have also applied metabolomics to postmortem challenges. In this study, we used targeted metabolomics with gas chromatography–mass spectrometry (GC–MS) to quantitatively analyze amino acid changes in rat myocardial tissue and assess protein degradation with the postmortem interval (PMI). First, the GC–MS method was validated and yielded satisfactory results. Quantitative analysis revealed good correlations between the concentrations of 14 amino acids (alanine, glycine, valine, leucine, isoleucine, proline, methionine, phenylalanine, tryptophan, glutamine, tyrosine, glutamic acid, histidine, and arginine) and early PMI. Among the 14 amino acids, the concentrations of nearly all neutral nonpolar amino acids consistently increased during the 0–6 days postmortem, while that of glutamic acid increased up to 10 days postmortem. Higher ambient temperatures increased the rate of protein degradation. A total of 9 amino acids (alanine, glycine, valine, leucine, isoleucine, phenylalanine, tryptophan, tyrosine, and glutamic acid) that exhibit regular increases at different temperatures during specific PMI show potential as biomarkers for PMI estimation.