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isolation, structure elucidation and anticancer activity of two new stigmastane-type steroids (Ia) and (Ib) [ABSTRACT FROM AUTHOR]

Background: To develop a nomogram for predicting the International Study Group of Liver Surgery (ISGLS) grade B/C posthepatectomy liver failure (PHLF) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients.Methods: Patients initially treated with hepatectomy were included. Univariate regression analysis and stochastic forest algorithm were applied to extract the core indicators and reduce redundancy bias. The nomogram was then constructed by using multivariate logistic regression, and validated in internal and external cohorts, and a prospective clinical application.Results: There were 900, 300 and 387 participants in training, internal and external validation cohorts, with the morbidity of grade B/C PHLF were 13.5, 11.0 and 20.2%, respectively. The nomogram was generated by integrating preoperative total bilirubin, platelet count, prealbumin, aspartate aminotransferase, prothrombin time and standard future liver remnant volume, then achieved good prediction performance in training (AUC = 0.868, 95%CI = 0.836-0.900), internal validation (AUC = 0.868, 95%CI = 0.811-0.926) and external validation cohorts (AUC = 0.820, 95%CI = 0.756-0.861), with well-fitted calibration curves. Negative predictive values were significantly higher than positive predictive values in training cohort (97.6% vs. 33.0%), internal validation cohort (97.4% vs. 25.9%) and external validation cohort (94.3% vs. 41.1%), respectively. Patients who had a nomogram score < 169 or ≧169 were considered to have low or high risk of grade B/C PHLF. Prospective application of the nomogram accurately predicted grade B/C PHLF in clinical practise.Conclusions: The nomogram has a good performance in predicting ISGLS grade B/C PHLF in HBV-related HCC patients and determining appropriate candidates for hepatectomy. [ABSTRACT FROM AUTHOR]

In vitro and in vivo metabolism of synthetic cannabinoid, N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluropentyl)-1H-indazole-3-carboxamide (PX-2), has been studied based on human liver microsomes and zebrafish using ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). The dd-MS2 spectra technique is used to analysis metabolic sites and pathway by accurate mass measurement in the research process. An animal model of zebrafish in vivo metabolism is established to verify the in vitro metabolism pathway of PX-2. The results indicated that 20 kinds of metabolites were generated in the zebrafish animal model and human liver microsome model. Biotransformations mainly occurred at the amino of the compound, and minor reaction occurred at the pentyl chain and benzyl. We recommend M1.1 (PX-2 amide hydrolysis metabolites), and M3.1 (PX-2 oxidative defluorination and hydroxylation) combined M1.4 (PX-2 Phenylalanine loss) to be the potential poisoning markers. Metabolism of the synthetic cannabinoid PX-2 in vitro human liver microsomes and in vivo zebrafish. Image 1 • Analysis of in vivo metabolites and metabolic pathways by new experimental animal zebrafish. • Mass spectrometry analysis of PX-2 original drugs and metabolites. • Analysis of in vivo and in vitro metabolites and biotransformations of PX-2. [ABSTRACT FROM AUTHOR]

This study aimed to compare the prognostic value of malnutrition and sarcopenia for mortality in old adults over 80 years. A prospective analysis was performed in 427 hospitalized old adults. Anthropometric measures and biochemical parameters were carried out for each patient. Sarcopenia was defined according to the revised consensus definition of the European Working Group on Sarcopenia in Older People (EWGSOP2). Malnutrition was defined according to the European Society of Clinical Nutrition and Metabolism (ESPEN) criteria. Mortality data were available for up to 32 months of follow-up. The overall prevalence of sarcopenia and malnutrition was 35.1% and 19.4%, respectively. The percentage of coexistence of sarcopenia and malnutrition was 12.2%. Of the 427 participants, 83 deaths were reported during the mean follow-up periods of 24.9 months. Compared with non-sarcopenic subjects with well-nutrition, sarcopenic subjects with well-nutrition and non-sarcopenic subjects with well-nutrition had higher mortality risk (Hazard Ratio (HR), 2.36; 95% confidence interval (CI), 1.31–4.24, P < 0.001; HR, 4.33; 95% CI, 2.12–8.85, P = 0.004; respectively). The patients who coexisted with sarcopenia and malnutrition had the highest risk of mortality (HR, 7.31; 95% CI, 4.21–12.69, P < 0.001). Both sarcopenia and malnutrition could predict mortality separately. Still, from the components of the Cox regression multivariate models, the malnutrition was one of the independent factors influencing the death, sarcopenia was not. When malnutrition and sarcopenia were compared together in a longitude cohort, malnutrition was an independent risk factor for mortality, while sarcopenia was not. The coexistence of malnutrition and sarcopenia showed a synergistically accumulated risk for death. • When compared in a longitude cohort, malnutrition was an independent risk factor for mortality, while sarcopenia was not. • The coexistence of sarcopenia and malnutrition was common in hospitalized old adults over 80 years • The coexistence of malnutrition and sarcopenia showed a synergistically accumulated risk for mortality. • The patients coexisted with sarcopenia and malnutrition had more than seven-fold mortality risk. [ABSTRACT FROM AUTHOR]

Serum interleukin-17 is closely related to inflammatory liver injury after hepatitis B virus (HBV) infection. The objective is to study the expression of interleukin-17 (IL-17) in different immune phases in patients with chronic hepatitis B. Whole venous blood was obtained from normal controls (n = 20) and four patient groups (n = 213): immune tolerance phase (IT, n = 57), immune clearance phase (IC, n = 59), non (low)-replicating phase (LR, n = 44), and reactivation phase (RA, n = 53). We measured IL-17, IL-6, and tumor necrosis factor alpha (TNF-α) levels in serum samples and measured IL-17, IL-6, and TNF-α messenger RNA (mRNA) levels in peripheral blood mononuclear cell (PBMC). Compared to normal controls, IL-17, IL-6, and TNF-α protein levels in serum and mRNA levels in PBMC were significantly higher in the four groups. IL-17 protein levels in serum and mRNA levels in PBMC were positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-6, and TNF-α. Compared to patients in the IT phase and LR phase, patients in the IC phase exhibited the highest serum IL-17 and PBMC mRNA levels. The IL-17 mRNA levels of patients in RA phase were higher than those in patients in IT phase. IL-17 plays an important part in the various immune phases of chronic hepatitis B (CHB). [ABSTRACT FROM AUTHOR]