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Stress hyperglycemia has been confirmed as a strong predictor of poor short-term prognosis in acute pancreatitis. However, whether stress hyperglycemia affects the long-term prognosis of patients with acute pancreatitis is unclear. We aimed to investigate the effect of stress hyperglycemia on the long-term prognosis of non-diabetic patients with acute pancreatitis. This retrospective observational study was conducted on 4055 patients with acute pancreatitis from 1 January 2016 to 31 October 2020. The association between stress hyperglycemia and the prognosis was evaluated using regression modeling. There were 935(71.5%) normoglycemic and 373(28.5%) stress hyperglycemia patients. 46(12.3%) patients with stress hyperglycemia had evidence of diabetes compared with 33(3.5%) patients without stress hyperglycemia (P < 0.001). After multivariate adjustment, patients with stress hyperglycemia were more likely to have evidence of diabetes (OR 2.905, 95% CI 1.688–4.999) compared with normoglycemic. However, stress hyperglycemia is not associated with the recurrence of pancreatitis and progression to chronic pancreatitis. Stress hyperglycemia was independently associated with diabetes secondary to acute pancreatitis. Accordingly, a follow-up diabetes-screening program for AP with stress hyperglycemia is an important part of identifying the disease as soon as possible, delaying islet damage, and improving the prognosis of post-acute pancreatitis diabetes mellitus. [ABSTRACT FROM AUTHOR]

Post-acute pancreatitis diabetes mellitus (PPDM-A) is the main component of pancreatic exocrine diabetes mellitus. Timely diagnosis of PPDM-A improves patient outcomes and the mitigation of burdens and costs. We aimed to determine risk factors prospectively and predictors of PPDM-A in China, focusing on giving personalized treatment recommendations. Here, we identify and evaluate the best set of predictors of PPDM-A prospectively using retrospective data from 820 patients with acute pancreatitis at four centers by machine learning approaches. We used the L1 regularized logistic regression model to diagnose early PPDM-A via nine clinical variables identified as the best predictors. The model performed well, obtaining the best AUC = 0.819 and F1 = 0.357 in the test set. We interpreted and personalized the model through nomograms and Shapley values. Our model can accurately predict the occurrence of PPDM-A based on just nine clinical pieces of information and allows for early intervention in potential PPDM-A patients through personalized analysis. Future retrospective and prospective studies with multicentre, large sample populations are needed to assess the actual clinical value of the model. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase-9 (MMP-9) is an attractive target for cancer therapy. In this study, the pharmacophore model of MMP-9 inhibitors is built based on the experimental binding structures of multiple receptor-ligand complexes. It is found that the pharmacophore model consists of six chemical features, including two hydrogen bond acceptors, one hydrogen bond donor, one ring aromatic regions, and two hydrophobic (HY) features. Among them, the two HY features are especially important because they can enter the S1′ pocket of MMP-9 which determines the selectivity of MMP-9 inhibitors. The reliability of pharmacophore model is validated based on the two different decoy sets and relevant experimental data. The virtual screening, combining pharmacophore model with molecular docking, is performed to identify the selective MMP-9 inhibitors from a database of natural products. The four novel MMP-9 inhibitors of natural products, NP-000686, NP-001752, NP-014331, and NP-015905, are found; one of them, NP-000686, is used to perform the experiment of in vitro bioassay inhibiting MMP-9, and the IC value was estimated to be only 13.4 µM, showing the strongly inhibitory activity of NP-000686 against MMP-9, which suggests that our screening results should be reliable. The binding modes of screened inhibitors with MMP-9 active sites were discussed. In addition, the ADMET properties and physicochemical properties of screened four compounds were assessed. The found MMP-9 inhibitors of natural products could serve as the lead compounds for designing the new MMP-9 inhibitors by carrying out structural modifications in the future. [ABSTRACT FROM AUTHOR]