Background: Immune checkpoint inhibitors (ICIs) have become one of the standard treatment options for advanced lung cancer. However, adverse events (AEs), particularly immune–related AEs (irAEs), caused by these drugs have aroused public attention. The current network meta-analysis (NMA) aimed to compare the risk of AEs across different ICI–based regimens in patients with advanced lung cancer. Methods: We systematically searched the PubMed, EMBASE, and Cochrane Library databases (from inception to 19 April 2021) for relevant randomized controlled trials (RCTs) that compared two or more treatments, with at least one ICI administered to patients with advanced lung cancer. The primary outcomes were treatment–related AEs and irAEs, including grade 1–5 and grade 3–5. The secondary outcomes were grade 1–5 and grade 3–5 irAEs in specific organs. Both pairwise and network meta-analyses were conducted for chemotherapy, ICI monotherapy, ICI monotherapy + chemotherapy, dual ICIs therapy, and dual ICIs + chemotherapy for all safety outcomes. Node–splitting analyses were performed to test inconsistencies in network. Sensitivity analyses were adopted by restricting phase III RCTs and studies that enrolled patients with non–small cell lung cancer. Results: Overall, 38 RCTs involving 22,178 patients with advanced lung cancer were enrolled. Both pooled incidence and NMA indicated that treatments containing chemotherapy increased the risk of treatment–related AEs when compared with ICI-based regimens without chemotherapy. As for grade 1–5 irAEs, dual ICIs + chemotherapy was associated with the highest risk of irAEs (probability in ranking first: 50.5%), followed by dual-ICI therapy (probability in ranking second: 47.2%), ICI monotherapy (probability in ranking third: 80.0%), ICI monotherapy + chemotherapy (probability in ranking fourth: 98.0%), and finally chemotherapy (probability in ranking fifth: 100.0%). In grade 3–5 irAEs, subtle differences were observed; when ranked from least safe to safest, the trend was dual ICIs therapy (60.4%), dual ICIs + chemotherapy (42.5%), ICI monotherapy (76.3%), ICI monotherapy + chemotherapy (95.0%), and chemotherapy (100.0%). Furthermore, detailed comparisons between ICI–based options provided irAE profiles based on specific organ/system and severity. Conclusions: In consideration of overall immune–related safety profiles, ICI monotherapy + chemotherapy might be a better choice among ICI–based treatments for advanced lung cancer. The safety profiles of ICI–based treatments are various by specific irAEs and their severity. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42021268650

This study was to investigate the protective effect of hyperbaric oxygen (HBO) on HT22 and PC12 cell damage caused by oxygen-glucose deprivation/reperfusion-induced ferroptosis. A 2-h oxygen-glucose deprivation and 24-h reperfusion model on HT22 and PC12 cells was used to simulate cerebral ischemia-reperfusion injury. Cell viabilities were detected by Cell Counting Kit-8 (CCK-8) method. The levels of reactive oxygen species (ROS) and lipid reactive oxygen species (Lipid ROS) were detected by fluorescent probes Dihydroethidium (DHE) and C11 BODIPY 581/591. Iron Colorimetric Assay Kit, malondialdehyde (MDA) and glutathione (GSH) activity assay kits were used to detect intracellular iron ion, MDA and GSHcontent. Cell ferroptosis-related ultrastructures were visualized using transmission electron microscopy (TEM). Furthermore, PCR and Western blot analyses were used to detect the expressions of ferroptosis-related genes and proteins. After receiving oxygen-glucose deprivation/reperfusion, the viabilities of HT22 and PC12 cells were significantly decreased; ROS, Lipid ROS, iron ions and MDA accumulation occurred in the cells; GSH contents decreased; TEM showed that cells were ruptured and blebbed, mitochondria atrophied and became smaller, mitochondrial ridges were reduced or even disappeared, and apoptotic bodies appeared. And the expressions of Nrf2, SLC7A11 and GPX4 genes were reduced; the expressions of p-Nrf2/Nrf2, xCT and GPX4 proteins were reduced. Notably, these parameters were significantly reversed by HBO, indicating that HBO can protect HT22 cells and PC12 cells from damage caused by oxygen-glucosedeprivation/reperfusion via the inhibition of Nrf2/System Xc-/GPX4 axis-mediated ferroptosis.

Background: To conduct a meta-analysis to investigate the effects of different nutritional interventions on various serum nutritional indicators and patients’ prognosis during radiotherapy for nasopharyngeal carcinoma, to assess treatment safety and efficacy. Methods: A systematic literature search, mainly randomized controlled trials (RCTs), on the effects of nutritional support on patients undergoing radiotherapy for nasopharyngeal carcinoma was conducted between January 2010 and August 2022 using databases such as China National Knowledge Infrastructure, Wanfang Database, Web of Science, PubMed, Cochrane Library, and Embase. Risk of bias was assessed using the Cochrane Rob2 scale. The meta-analysis was performed using Stata 17.0 software, and the heterogeneity between studies was assessed using the I² test, and funnel plots were used to qualitatively assess publication bias. Results: Overall, 10 RCTs with a total sample size of 879 cases were identified. The meta-analysis results showed that body mass index (BMI) (odds ratio = 0.026, 95% confidence interval^[1]: −0.348 to 0.401, P > .05), albumin (standardized mean difference [SMD] = 0.13, 95% CI: −0.127 to 0.387, P > .05), and total protein levels were not significantly different between the nasopharyngeal cancer (NPC) radiotherapy group with nutritional support group (SMD = −0.262, 95% CI: −1.062 to 0.537, P > .05) and the control group; pre-albumin (SMD = 0.256, 95% CI: 0.022–0.491, P = .032), hemoglobin (SMD = 0.436, 95% CI: 0.26–0.612, P < .000), and lymphocyte count (SMD = 1.125, 95% CI: 0.868–1.381, P < .000) were significantly higher in the nutritional intervention group than in the control group. Conclusion: Compared with conventional diets, nutritional interventions can improve serum nutritional parameters, nutritional status, treatment tolerance, and prognosis of patients undergoing radiotherapy for nasopharyngeal carcinoma.

Background: Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus. This study aims to investigate the efficacy and safety of optional antimicrobial therapy for the treatment of complicated SSTIs (cSSTIs). Methods: We searched PubMed, Medline (Via Ovid SP), Embase (Via Ovid SP), and the Cochrane Central Register of Controlled Trials from their inception to March 22, 2021 for randomized controlled trials (RCTs) that studied the use of optional antimicrobial therapy for cSSTIs. Citations’ screening, study selection, data extraction, and risk of bias assessment were independently performed by 2 authors. The primary outcomes were clinical and microbiological treatment success, and adverse events (AEs) were also assessed. Results: A total of 48 trials covering 24,381 patients assessing 20 types of antimicrobial treatment modalities were included. Overall, omadacycline was associated with the highest beneficial effect on clinical and microbiological treatment success and with the largest rank probability based on surface under the cumulative ranking curve values, avarofloxacin was closely followed. Both had, however, omadacycline was related to moderately safety profiles. Lefamulin ranked as the best option was associated with the lowest risk of severe AEs. Subgroup analysis showed similar results. The quality of primary outcomes was moderate to low. Conclusions: The use of omadacycline was associated with higher rates of clinical and microbiological treatment success for the treatment of cSSTIs, with a relative low risk of AEs. Due to the limitations of the included RCTs, high-quality and well-designed RCTs are needed to further confirm the results.