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DNA methylation, an epigenetic modification, regulates gene transcription and maintains genome stability. DNA methyltransferase (DNMT) inhibitors can activate silenced genes at low doses and cause cytotoxicity at high doses. The ability of DNMT inhibitors to reverse epimutations is the basis of their use in novel strategies for cancer therapy. In this review, we examined the literature on DNA methyltransferase inhibitors. We summarized the mechanisms underlying combination therapy using DNMT inhibitors and clinical trials based on combining hypomethylation agents with other chemotherapeutic drugs. We also discussed the efficacy of such compounds as antitumor agents, the need to optimize treatment schedules and the regimens for maximal biologic effectiveness. Notably, the combination of DNMT inhibitors and chemotherapy and/or immune checkpoint inhibitors may provide helpful insights into the development of efficient therapeutic approaches.

Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

BackgroundAlthough pleural fluid lactate dehydrogenase (LDH) and adenosine deaminase (ADA) levels are often used to distinguish between tuberculous pleural effusion (TPE) and parapneumonic pleural effusion (PPE), this can be challenging as the LDH level may vary from normal to severely increased in PPE and a significantly elevated ADA is frequently measured in both conditions. In this study, we evaluated use of the pleural fluid LDH/ADA ratio as a new parameter to discriminate TPE from PPE.MethodsA retrospective study was conducted in patients with pathologically-confirmed TPE (n = 72) and PPE (n = 47) to compare pleural fluid LDH and ADA levels and LDH/ADA ratios between the 2 groups. A receiver operating characteristic (ROC) curve was constructed for identifying TPE.ResultsThe median pleural fluid LDH and ADA levels and LDH/ADA ratios in the TPE and PPE groups were: 364.5 U/L vs 4037 U/L (P < .001), 33.5 U/L vs 43.3 U/L (P = .249), and 10.88 vs 66.91 (P < .0001), respectively. An area under the ROC curve of 0.9663 was obtained using the LDH/ADA ratio as the indicator for TPE identification, and the sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were, respectively, 93.62%, 93.06%, 13.48, and 0.068 at a cut-off level of 16.20.ConclusionsThe pleural fluid LDH/ADA ratio, which can be determined from routine biochemical analysis, is highly predictive of TPE at a cut-off level of 16.20. Measurement of this parameter may be helpful for clinicians in distinguishing between TPE and PPE.Electronic supplementary materialThe online version of this article (10.1186/s12890-017-0526-z) contains supplementary material, which is available to authorized users.