Roxadustat in treating anemia in dialysis patients (ROAD): protocol and rationale of a multicenter prospective observational cohort study.

BACKGROUND: Roxadustat has been shown effective in treating patients with anemia due to chronic kidney disease. However, its long-term effect on clinical outcomes and socioeconomic burden and safety remains unclear. METHODS/DESIGN: This is a multicenter, prospective, longitudinal observational cohort study assessing if Roxadustat improves prognosis in dialysis patients. Primary outcomes will be major adverse cardiovascular events (MACE), defined as composites of cardiovascular death, myocardial infarction, cerebral infarction, hospitalization because of heart failure; all-cause mortality, and annual economic costs in two years. The data will be collected via Research electronic data capture (REDCap) based database as well as software-based dialysis registry of Sichuan province. The primary outcomes for the ROAD study participants will be compared with those in the dialysis registry cohort. Data at baseline and study follow up will also be compared to assess the association between Roxadustat and long-term clinical outcomes. DISCUSSION: The main objective of this study is to the assess long-term association of Roxadustat on MACE, all-cause mortality, socio-economic burden, safety in dialysis patients, which will provide guidance for designing further large randomized controlled trials to investigate this clinic question. STUDY REGISTRATION: The study has been registered in Chinese Clinical Trials Registry (ROAD, ROxadustat in treating Anemia in Dialysis patients, registration number ChiCTR1900025765) and provincial observational cohort database (Renal disEAse observational CoHort database, REACH, ChiCTR1900024926), registered 07 September 2019, http://www.chictr.org.cn .

Nickel Induces Pyroptosis via the Nrf2/NLRP3 Pathway in Kidney of Mice.

Nickel (Ni) is considered a toxic metal, and excessive exposure can cause kidney damage. This study was designed to explore whether nickel chloride (NiCl2) can induce cell pyroptosis and its possible mechanism. Here, we found that NiCl2 treatment could reduce the kidney index and result in kidney damage. Meanwhile, NiCl2 could obviously induce renal pyroptosis, which was characterized by an increase in IL-18, IL-1ß, NLRP3, and GSDMD expression. Furthermore, NiCl2 induced pyroptosis through the Nrf2/NLRP3 pathway which featured down-regulated protein and mRNA expression levels of Nrf2 and up-regulated protein and mRNA expression levels of Caspase-1, NLRP3, and GSDMD. In summary, excessive Ni exposure can induce renal cell pyroptosis, ultimately leading to kidney tissue damage and hindering normal development, and its possible mechanism may be due to the inhibition of the Nrf2 pathway.

Investigation of kerogen thermal decomposition mechanisms and kinetics via ReaxFF molecular dynamics simulations.

This study investigates the mechanisms and kinetics of kerogen thermal decomposition using molecular dynamics simulations with the ReaxFF force field. The cook-off simulation at the constant heating rate shows that the decomposition of kerogen begins with the cracking at terminals and weaker linkages of kerogen molecule, and the final products are formed by radicals recombination, dehydrogenation, and other reactions. The Flynn-Wall-Ozawa kinetic analysis based on the thermal decomposition simulations at various heating rates shows that the activation energy increases with the conversion of decomposition. These results reveal the thermal decomposition mechanisms and the thermal stability of kerogen in different stages during the process of thermal decomposition.

Initiation mechanisms and kinetic analysis of the isothermal decomposition of poly(α-methylstyrene): a ReaxFF molecular dynamics study.

This study investigates the thermal decomposition initiation mechanisms and kinetics of poly(α-methylstyrene) (PαMS) under isothermal conditions, using molecular dynamics simulations with the ReaxFF reactive force field. The unimolecular pyrolysis simulations show that the thermal decomposition of the PαMS molecule is initiated mainly by carbon-carbon backbone cleavage in two types at random points along the main chain that leads to different intermediates, and is accompanied by depolymerization reactions that lead to the formation of the final products. The time evolution of typical species in the process of PαMS thermal decomposition at various temperatures presents specific evolution profiles and shows a temperature-dependence effect. Isothermal decomposition kinetic analysis based on PαMS pyrolysis shows that the activation energy varies with the degree of conversion during the thermal decomposition processes, which infers that the decomposition process at different conversions may have different reaction mechanisms.

Reactive molecular dynamics simulations on the thermal decomposition of poly alpha-methyl styrene.

Using molecular dynamics simulations with ReaxFF reactive force field, the thermal decomposition mechanism of poly alpha-methyl styrene (PAMS) materials and the effects of heating rate and impurity fluorobenzene on PAMS thermal decompositions are studied. The results show that: 1) Pyrolysis mechanism of PAMS consists of initiation and propagation processes. In the initiation stage, random scissions of C-C backbone produce fragments, and in the propagation stage, depolymerizing reactions generate monomers and other products. 2) Higher decomposition temperature is needed for greater heating rate. 3) The presence of impurity fluorobenzene retards thermal decomposition of PAMS.