Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease characterized by inflammation, intestinal barrier injury, and imbalance of gut microbiota. Excess accumulation of reactive oxygen species (ROS) is closely correlated with the development and reoccurrence of IBD. Previous researches demonstrate that procyanidin, as a natural antioxidant, exhibits strong ability of eliminating ROS, thus showing good therapeutic effects in the inflammation-related diseases. Non-etheless, its poor stability and solubility always limits the therapeutic outcomes. Here, we typically designed an antioxidant coordination polymer nanoparticle using the engineering of procyanidin (Pc) and free iron (Fe), named Pc-Fe nanozyme, for effectively scavenging ROS and further inhibiting inflammation while altering the gut microbiome for the treatment of colitis. Furthermore, in vitro experiments uncover that Pc-Fe nanoparticles exert strong multi biomimic activities, including peroxidase, and glutathione peroxidase, for the scavenging of ROS and protecting cells from oxidative injury. In addition, the colon accumulation of Pc-Fe nanozyme effectively protects the intestinal mucosa from oxidative damage while significantly downregulates pro-inflammatory factors, repairs the intestinal barriers and alternates gut microbiome after orally administrated in sodium dextran sulfate (DSS) induced colitis mice. The results collectively illustrate that the multienzyme mimicking Pc-Fe nanozyme owns high potential for treating IBD through scavenging ROS, inhibiting inflammation, repairing gut barriers and alternating gut microbiome, which further promising its clinical translation on IBD treatment and other ROS induced intestinal diseases.

Purpose: Immune-related pneumonitis (IRP) has attracted extensive attention, owing to its increased mortality rate. Conventional chemotherapy (C) has been considered as an immunosuppressive agent and may thus reduce IRP’s risk when used in combination with PD-1/L1 inhibitors. This study aimed to assess the risk of IRP with PD-1/L1 inhibitors plus chemotherapy (I+C) versus PD-1/L1 inhibitors alone (I) in solid cancer treatment. Method: Multiple databases were searched for RCTs before January 2021. This NMA was performed among I+C, I, and C to investigate IRP’s risk. Subgroup analysis was carried out on the basis of different PD-1/L1 inhibitors and cancer types. Results: Thirty-one RCTs (19,624 patients) were included. The I+C group exhibited a lower risk of IRP in any grade (RR, 0.60; 95% CI, 0.38–0.95) and in grade 3–5 (RR, 0.44; 95% CI, 0.21–0.92) as opposed to the I group. The risk of any grade IRP with PD-1 plus chemotherapy was lower than that with PD-1 monotherapy (RR, 0.50; 95% CI, 0.28–0.89), although grade 3–5 IRP was similar. There was no statistically meaningful difference in the risk of any grade IRP between PD-L1 plus chemotherapy and PD-L1 inhibitors monotherapy (RR, 0.95; 95% CI, 0.43–2.09) or grade 3–5 IRP (RR, 0.71;95% CI, 0.24–2.07). In addition, compared with the I group, the I+C group was correlated with a decreased risk in IRP regardless of cancer type, while a substantial difference was only observed in NSCLC patients for grade 3–5 IRP (RR, 0.39; 95% CI, 0.15–0.98). Conclusion: In comparison to PD-1/L1 inhibitor treatment alone, combining chemotherapy with PD-1/L1 inhibitors might reduce the risk of IRP in the general population. Furthermore, PD-1 inhibitors in combination with chemotherapy were correlated with a decreased risk of IRP compared to PD-1 inhibitor treatment alone. In contrast to the I group, the I+C group exhibited a lower risk of IRP, especially for NSCLC patients.