Impact of nonsteroidal anti-inflammatory drugs on efficacy of anti-PD-1 therapy for primary liver cancer / 南方医科大学学报

OBJECTIVE@#To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma.@*METHODS@#We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups.@*RESULTS@#There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729).@*CONCLUSION@#Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.

Optimization of the Mechanical Properties and the Cytocompatibility for the PMMA Nanocomposites Reinforced with the Hydroxyapatite Nanofibers and the Magnesium Phosphate Nanosheets.

Commercial poly methyl methacrylate (PMMA)-based cement is currently used in the field of orthopedics. However, it suffers from lack of bioactivity, mechanical weakness, and monomer toxicity. In this study, a PMMA-based cement nanocomposite reinforced with hydroxyapatite (HA) nanofibers and two-dimensional (2D) magnesium phosphate MgP nanosheets was synthesized and optimized in terms of mechanical property and cytocompatibility. The HA nanofibers and the MgP nanosheets were synthesized using a hydrothermal homogeneous precipitation method and tuning the crystallization of the sodium-magnesium-phosphate ternary system, respectively. Compressive strength and MTT assay tests were conducted to evaluate the mechanical property and the cytocompatibility of the PMMA-HA-MgP nanocomposites prepared at different ratios of HA and MgP. To optimize the developed nanocomposites, the standard response surface methodology (RSM) design known as the central composite design (CCD) was employed. Two regression models generated by CCD were analyzed and compared with the experimental results, and good agreement was observed. Statistical analysis revealed the significance of both factors, namely, the HA nanofibers and the MgP nanosheets, in improving the compressive strength and cell viability of the PMMA-MgP-HA nanocomposite. Finally, it was demonstrated that the HA nanofibers of 7.5% wt and the MgP nanosheets of 6.12% wt result in the PMMA-HA-MgP nanocomposite with the optimum compressive strength and cell viability.

Investigation of EDTA concentration on the size of carbonated flowerlike hydroxyapatite microspheres.

Ethylenediamine tetraacetic acid (EDTA) is considered an effective crystal growth modifier for template-assisted hydrothermal synthesis of hydroxyapatite (HA) materials. In this work, flowerlike-carbonated HA (CHA) microspheres were synthesized using EDTA via a one-step hydrothermal route. The phase, functional groups, morphology and particle size distribution of the products were examined by X-ray diffraction, Fourier transform infrared spectrometer, field emission scanning electron microscopy as well as laser diffraction particle size analysis. Results show that the morphology of the products can be well controlled by adjusting the EDTA concentration. With an increase of the EDTA concentration, the particle size of flowerlike microspheres decreased from tens of microns down to a few microns. The underlying mechanism for the morphological transition of CHA microspheres with different concentrations of EDTA under hydrothermal conditions is proposed. This work provides a simple way to controllably fabricate CHA microspheres with various sizes using the same synthesis system for biomedical applications, such as cell carriers and drug delivery.

Electrocatalytic oxygen reduction by a Co/Co3O4@N-doped carbon composite material derived from the pyrolysis of ZIF-67/poplar flowers.

Catalysts used for the oxygen reduction reaction (ORR) are crucial to fuel cells. However, the development of novel catalysts possessing high activity at a low cost is very challenging. Recently, extensive research has indicated that nitrogen-doped carbon materials, which include nonprecious metals as well as metal-based oxides, can be used as excellent candidates for the ORR. Here, Co/Co3O4@N-doped carbon (NC) with a low cost and highly stable performance is utilized as an ORR electrocatalyst through the pyrolysis of an easily prepared physical mixture containing a cobalt-based zeolite imidazolate framework (ZIF-67 precursor) and biomass materials from poplar flowers. Compared with the pure ZIF-derived counterpart (Co@NC) and PL-bio-C, the as-synthesized electrocatalysts show significantly enhanced ORR activities. The essential roles of doped atoms (ZIF-67 precursor) in improving the ORR activities are discussed. Depending mainly on the formation of Co-Co3O4 active sites and abundant nitrogen-containing groups, the resulting Co/Co3O4@NC catalyst exhibits good electroactivity (onset and half-wave potentials: E onset = 0.94 V and E 1/2 = 0.85 V, respectively, and a small Tafel slope of 90 mV dec-1) compared to Co@NC and PL-bio-C and follows the 4-electron pathway with good stability and methanol resistance. The results of this study provide a reference for exploring cobalt-based N-doped biomass carbon for energy conversion and storage applications.

Novel PMMA bone cement nanocomposites containing magnesium phosphate nanosheets and hydroxyapatite nanofibers.

Lack of bioactivity and monomer toxicity are limiting factors of polymethyl methacrylate (PMMA) bone cement in orthopedic applications. Herein, we address these shortcomings by proposing two-dimensional magnesium phosphate (MgP) nanosheets and hydroxyapatite (HA) nanofibers as novel fillers in PMMA bone cement nanocomposites. Two-dimensional MgP nanosheets and one-dimensional HA nanofibers were synthesized by tuning the crystallization of the sodium-magnesium-phosphate ternary system and hydrothermal homogeneous precipitation, respectively. We show that MgP nanosheets exhibit antibacterial properties against Escherichia coli (E. coli). In addition, HA nanofibers with high level of bioactivity are the proper choice to induce cell viability in the nanocomposite. Results indicate that the combination of both fillers can act as deformation locks enhancing the compressive strength of the nanocomposites. The synthesized nanocomposite possesses excellent bioactivity, mechanical properties, and cytocompatibility potentially opening new paradigm in the design of next generation bone cement composites.