Clinical characteristics and prognosis of liver injury induced by immune checkpoint inhibitors in patients with malignancies: A real-world retrospective study.

AIMS: Programmed cell death receptor (ligand)-1 inhibitors (PD-(L)1), as the preferred immunotherapy, have been widely used in the Chinese mainland and drug-induced liver injury (DILI) has been reported. The study aimed to investigate the clinical features or risk factors for immunotherapy-related DILI. METHODS: Patients who received PD-(L)1 inhibitors from January 2020 to July 2021 were retrospectively reviewed. The likelihood of DILI was adjudicated by the Roussel-Uclaf causality assessment. RESULTS: A total of 1175 patients were included in the study and 89 patients (7.6%) developed DILI, of which 12 (13.5%) progressed to acute liver failure (ALF) and three (3.4%) died. Among the DILI population, 56 (62.9%) had a cholestatic pattern and exhibited a prolonged treatment course and duration for resolution compared to the hepatocellular and mixed patterns. Hepatocellular carcinoma (HCC), hepatitis B virus (HBV) and abnormal baseline of alkaline phosphatase (ALP) had increased risks of DILI by 2.1-fold (95% confidence interval [CI], 1.231-3.621), 1.9-fold [95% CI, 1.123-3.325] and 2.1-fold [95% CI, 1.317-3.508], respectively. The model for end-stage liver disease (MELD) score had a c-statistic of 0.894 (95% CI, 0.778-1.000) with a sensitivity of 67% and a specificity of 95% for poor outcomes. COX analysis showed that the MELD ≥ 18 was predictive of immunotherapy-related ALF or death. CONCLUSIONS: PD-(L)1 inhibitor-related liver injury manifests primarily as a cholestatic pattern, on which corticosteroid treatment has minimal effect compared to hepatocellular and mixed patterns. MELD score ≥ 18 at the time of liver injury performed best in the prediction of ALF or death in immune checkpoint inhibitor (ICI)-related DILI.

A Cost-Effective and Chemical-Recycling Approach for Facile Preparation of Regenerated Cellulose Materials.

Cellulose is difficult to melt or dissolve. The dissolution and regeneration process paves the way to convert cellulose into diverse forms but still suffers from high costs and environmental pollution. Here, we developed a method that uses aqueous alkali to efficiently dissolve cellulose at a temperature above 0 °C in minutes for fabricating regenerated cellulose. Cellulose was modified with minimal carboxymethyl groups to weaken the intermolecular interaction and improve its dissolution. The modified cellulose can be commercially obtained from carboxymethyl cellulose manufacturing with low cost and high quality. The use of only aqueous alkali reduces pollution and facilitates chemical recycling, and the moderate dissolving temperature reduces energy consumption. The regenerated cellulose materials display excellent mechanical properties and can be recycled or biodegraded after use. The method allows the use of diverse raw materials and modifications to broaden its applicability. The study develops a low-cost and eco-friendly method to fabricate regenerated cellulose.

Investigation on the interaction mechanism during co-combustion of sewage sludge and coal slime: The effect of coal slime type and pretreatment method.

Co-combustion of sewage sludge (SS) and coal slime (CS) is the preferred method for mitigating their environmental impact and increasing their added value. However, the interaction mechanism between SS and CS during the co-combustion process has not yet developed a unified understanding. This work aims to obtain the effect of CS types on SS-CS co-combustion and reveal the interaction mechanism between SS and CS based on the influence of pretreatment methods on the interaction. The results showed that during co-combustion, SS reduced the ignition and burnout temperatures, and CS with high fixed carbon content (e.g., XCS) improved the comprehensive combustion characteristics. Principal component analysis showed that the effect of CS on co-combustion was more significant. The interaction between SS and CS mainly occurred within 100-700 °C, in which inhibition and synergism coexisted. The large differences in the interactions before and after de-volatilization and pickling treatments revealed that the volatiles and ash in SS were the main interaction factors. The analysis of the interaction mechanisms showed that the free radicals and heat released from the SS volatiles combustion accelerated the weight loss of CS, but the formation of tars from its incomplete combustion may inhibit the decomposition of CS. The interaction in the fixed carbon combustion stage was mainly caused by SS ash, which can catalyze the combustion of CS fixed carbon, but for the high ash CS (e.g., QCS), the combustion of fixed carbon was hindered by the addition of SS ash higher than 10 %. The final manifestation (synergy or inhibition) of SS and CS interactions was the result of the competitive balance of the above interactive behaviors. This work provides a more comprehensive understanding of the interaction between SS and CS during co-combustion.

The Adsorption of Pb(II) from Aqueous Solution Using KOH-Modified Banana Peel Hydrothermal Carbon: Adsorption Properties and Mechanistic Studies.

Adopting banana peel as a raw material, the adsorption properties of banana peel hydrothermal carbon modified with a KOH solution for lead ions in aqueous solution were studied. The surface structure and functional groups of the modified hydrothermal carbon were analyzed by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR) spectroscopy, the Brunner-Emmet-Teller (BET) method, element analysis, and Raman spectroscopy. The results showed that an adsorption capacity of 42.92 mg/g and a removal rate of 86.84% were achieved when the banana peel hydrothermal carbon was modified with a KOH solution of 0.5 mol/L, with a pH of 6 and a solid-liquid ratio of 1 g/L. The equilibrium adsorption time for lead ions in solution being adsorbed using KOH-modified hydrothermal carbon was 240 min, the adsorption process satisfied the quasi-second-order kinetic model and the Redlich-Peterson isotherm equation, and the equilibrium removal efficiency was 88.62%. The adsorption of lead ions using KOH-modified hydrothermal carbon is mainly chemical-physical adsorption.

Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.