Progression to severe disease is a difficult problem in treating coronavirus disease 2019 . The purpose of this study is to explore changes in markers of severe disease in COVID-19 patients. Sixty-nine severe COVID-19 patients were included. Patients with severe disease showed significant lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, and D-dimer was found in most severe cases. Baseline interleukin-6 (IL-6) was found to be associated with COVID-19 severity. Indeed, the significant increase of baseline IL-6 was positively correlated with the maximal body temperature during hospitalization and with the increased baseline of CRP, LDH, ferritin, and D-dimer. High baseline IL-6 was also associated with more progressed chest computed tomography (CT) findings. Significant decrease in IL-6 and improved CT assessment was found in patients during recovery, while IL-6 was further increased in exacerbated patients. Collectively, our results suggest that the dynamic change in IL-6 can be used as a marker for disease monitoring in patients with severe COVID-19.

A new force field and a hybrid Monte Carlo/molecular dynamics simulation method are developed to investigate the structural transition of zeolitic imidazolate framework-8 (ZIF-8) induced by N2 sorption. At a high loading (approximately 50 N2 molecules per unit cell), ZIF-8 shifts from low-loading (LL) to high-loading (HL) structure. A stepped sorption isotherm is predicted with three distinct regions, which agrees well with experimental data. The orientation of imidazolate rings and the motion of framework atoms exhibit sharp changes upon structural transition. Furthermore, pronounced changes are observed in various contributions to potential energies (including stretching, bending, torsional, van der Waals, and coulombic). The analysis of radial distribution functions between N2 and framework atoms suggests N2 interacts strongly with the imidazolate rings in ZIF-8. The simulation reveals that the structural transition of ZIF-8 is largely related to the reorientation of imidazolate rings, as attributed to the enhanced van der Waals interaction between N2 and imidazolate rings as well as the reduced torsional interaction of framework in the HL structure. This is the first molecular simulation study to describe the continuous structural transition of ZIF-8 and, it provides microscopic insight into the underlying mechanism.

ObjectiveTo assess the efficacy and safety of intradialytic exercise for haemodialysis patients.DesignSystematic review and meta-analysis.Data sourcesDatabases, including PubMed, Embase, the Cochrane Library, China Biology Medicine and China National Knowledge Infrastructure, were screened from inception to March 2017.Eligibility criteriaRandomised controlled trials (RCTs) aimed at comparing the efficacy and safety of intradialytic exercise versus no exercise in adult patients on haemodialysis for at least 3 months. A minimum exercise programme period of 8 weeks.Data extractionStudy characteristics and study quality domains were reviewed. Studies were selected, and data extracted by two reviewers.Data analysisThe pooled risk ratios and mean differences (MDs) with 95% CIs for dichotomous data and continuous data were calculated, respectively.ResultsA total of 27 RCTs involving 1215 subjects were analysed. Compared with no exercise, intradialytic exercise increased dialysis adequacy (Kt/V) (MD 0.07, 95% CI 0.01 to 0.12, p=0.02) and maximum volume of oxygen that the body can use during physical exertion peak oxygen consumption (MD 4.11, 95% CI 2.94 to 5.27, p<0.0001), alleviated depression standardised mean difference (−1.16, 95% CI −1.86 to –0.45, p=0.001) and improved physical component summary-short form-36 (SF-36) level (MD 7.72, 95% CI 1.93 to 13.51, p=0.009). Also, intradialytic exercise could significantly reduce systolic blood pressure (MD −4.87, 95% CI −9.20 to –0.55, p=0.03) as well as diastolic blood pressure (MD −4.11, 95% CI −6.50 to –1.72, p=0.0007). However, intradialytic exercise could not improve mental component summary-SF-36 level (MD 3.05, 95% CI −1.47 to 7.57, p=0.19). There was no difference in the incidence of adverse events between the intradialytic exercise and control groups.ConclusionsIntradialytic exercise resulted in benefits in terms of improving haemodialysis adequacy, exercise capacity, depression and quality of life for haemodialysis.

Inhibition of the human Ether-a-go-go Related Gene (hERG) potassium channel may result in QT interval prolongation, which causes severe cardiac side effects and is a major problem in clinical studies of drug candidates. The development of in silico tools to filter out potential hERG potassium channel blockers in early stages of the drug discovery process is of considerable interest. Here, a diverse set of 806 compounds with hERG inhibition data was assembled, and the binary hERG classification models using naïve Bayesian classification and recursive partitioning (RP) techniques were established and evaluated. The naïve Bayesian classifier based on molecular properties and the ECFP_8 fingerprints yielded 84.8% accuracy for the training set using the leave-one-out (LOO) cross-validation procedure and 85% accuracy for the test set of 120 molecules. For the two additional test sets, the model achieved 89.4% accuracy for the WOMBAT-PK test set, and 86.1% accuracy for the PubChem test set. The naïve Bayesian classifiers gave better predictions than the PR classifiers. Moreover, the Bayesian classifier, employing molecular fingerprints, highlights the important structural fragments favorable or unfavorable for hERG potassium channel blockage, which offers extra valuable information for the design of compounds avoiding undesirable hERG activity.