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Background: Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. Methods: The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF. Results: A total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097–9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792). Conclusions: Early assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis. [ABSTRACT FROM AUTHOR]

The Ten-eleven translocation (TET) family of dioxygenases mediate cytosine demethylation by catalyzing the oxidation of 5-methylcytosine (5mC). TET-mediated DNA demethylation controls the proper differentiation of embryonic stem cells and TET members display functional redundancy during early gastrulation. However, it is unclear if TET proteins have functional significance in mammalian skeletal development. Here, we report that Tet genes deficiency in mesoderm mesenchymal stem cells results in severe defects of bone development. The existence of any single Tet gene allele can support early bone formation, suggesting a functional redundancy of TET proteins. Integrative analyses of RNA-seq, Whole Genome Bisulfite Sequencing (WGBS), 5hmC-Seal and Assay for Transposase-Accessible Chromatin (ATAC-seq) demonstrate that TET-mediated demethylation increases the chromatin accessibility of target genes by RUNX2 and facilities RUNX2-regulated transcription. In addition, TET proteins interact with RUNX2 through their catalytic domain to regulate cytosine methylation around RUNX2 binding region. The catalytic domain is indispensable for TET enzymes to regulate RUNX2 transcription activity on its target genes and to regulate bone development. These results demonstrate that TET enzymes function to regulate RUNX2 activity and maintain skeletal homeostasis. Here the authors investigate the role of the TET family of DNA demethylases in mammalian skeletal development. They find that loss of TETs leads to hypermethylation that results in decreased chromatin accessibility of RUNX2 target genes, repressing osteoblast differentiation and leading to skeletal defects in mouse such as short limbs. [ABSTRACT FROM AUTHOR]