Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial.

This was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0-not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2-NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC.

A compendium of mitochondrial molecular characteristics provides novel perspectives on the treatment of rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is an autoimmune disease that exhibits a high degree of heterogeneity, marked by unpredictable disease flares and significant variations in the response to available treatments. The lack of optimal stratification for RA patients may be a contributing factor to the poor efficacy of current treatment options. The objective of this study is to elucidate the molecular characteristics of RA through the utilization of mitochondrial genes and subsequently construct and authenticate a diagnostic framework for RA. Mitochondrial proteins were obtained from the MitoCarta database, and the R package limma was employed to filter for differentially expressed mitochondrial genes (MDEGs). Metascape was utilized to perform enrichment analysis, followed by an unsupervised clustering algorithm using the ConsensuClusterPlus package to identify distinct subtypes based on MDEGs. The immune microenvironment, biological pathways, and drug response were further explored in these subtypes. Finally, a multi-biomarker-based diagnostic model was constructed using machine learning algorithms. Utilizing 88 MDEGs present in transcript profiles, it was possible to classify RA patients into three distinct subtypes, each characterized by unique molecular and cellular signatures. Subtype A exhibited a marked activation of inflammatory cells and pathways, while subtype C was characterized by the presence of specific innate lymphocytes. Inflammatory and immune cells in subtype B displayed a more modest level of activation (Wilcoxon test P < 0.05). Notably, subtype C demonstrated a stronger correlation with a superior response to biologics such as infliximab, anti-TNF, rituximab, and methotrexate/abatacept (P = 0.001) using the fisher test. Furthermore, the mitochondrial diagnosis SVM model demonstrated a high degree of discriminatory ability in distinguishing RA in both training (AUC = 100%) and validation sets (AUC = 80.1%). This study presents a pioneering analysis of mitochondrial modifications in RA, offering a novel framework for patient stratification and potentially enhancing therapeutic decision-making.

Chemical speciation and distribution of potentially toxic elements in soilless cultivation of cucumber with sewage sludge biochar addition.

Potentially toxic elements in municipal sewage sludge can be effectively immobilized during biochar production via pyrolysis. However, the bioavailability of these elements when biochar is applied in soilless cultivation to improve substrate quality has yet to be sufficiently established. In this study, we investigated the chemical speciation and cucumber plant uptake of potentially toxic elements in soilless cultivation when the growth substrate was amended with sewage sludge biochar (0, 5, 10, 15, and 20 wt%). It was found that the addition of 10 wt% biochar was optimal with respect to obtaining a high cucumber biomass and achieving low environmental risk considering the occurrence of hormesis. When the substrate was amended with 10 wt% biochar, cucumber fruit contained lower concentrations of As, Cr, and Zn and smaller bioavailable fractions of As, Cd, Cr, Ni, Cu, and Zn compared with the fruit of control plants, thereby meeting national safety requirements (standard GB 2762-2012, China). Most of the As and Cd taken up by cucumbers accumulated in the leaves and fruit, whereas Cr was found primarily in the roots, and most Ni, Cu, and Zn was detected in the fruit. Importantly, only small proportions of the potentially toxic elements in biochar were taken up by cucumber plants (As: 0.0075%; Cd: 0.038%; Ni: 0.0064%; Cu: 0.0016%; and Zn: 0.0015%). Given that the As, Cd, Ni, and Zn speciation in sewage sludge biochar was effectively immobilized after cultivation, the findings of this study indicate that sewage sludge biochar is a suitable substrate amendment in terms of the risk posed by potentially toxic elements.