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Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events.

Detection and treatment of lung cancer still remain a clinical challenge. This study aims to validate exosomal microRNA‐96 (miR‐96) as a serum biomarker for lung cancer and understand the underlying mechanism in lung cancer progression. MiR‐96 expressions in normal and lung cancer patients were characterized by qPCR analysis. Changes in cell viability, migration and cisplatin resistance were monitored after incubation with isolated miR‐96‐containing exosomes, anti‐miR‐96 and anti‐miR negative control (anti‐miR‐NC) transfections. Dual‐luciferase reporter assay was used to study interaction between miR‐96 and LIM‐domain only protein 7 (LMO7). Changes induced by miR‐96 transfection and LMO7 overexpression were also evaluated. MiR‐96 expression was positively correlated with high‐grade and metastatic lung cancers. While anti‐miR‐96 transfection exhibited a tumour‐suppressing function, exosomes isolated from H1299 enhanced cell viability, migration and cisplatin resistance. Potential miR‐96 binding sites were found within the 3′‐UTR of wild‐type LMO7 gene, but not of mutant LMO7 gene. LMO7 expression was inversely correlated with lung cancer grades, and LMO7 overexpression reversed promoting effect of miR‐96. We have identified exosomal miR‐96 as a serum biomarker of malignant lung cancer. MiR‐96 promotes lung cancer progression by targeting LMO7. The miR‐96‐LMO7 axis may be a therapeutic target for lung cancer patients, and new diagnostic or therapeutic strategies could be developed by targeting the miR‐96‐LMO7 axis.

The roots and rhizomes of Nardostachys chinensis have neuroprotection and cardiovascular protection effects. However, the specific mechanism of N. chinensis is not yet clear. Nardochinoid C (DC) is a new compound with new skeleton isolated from N. chinensis and this study for the first time explored the anti-inflammatory and anti-oxidant effect of DC. The results showed that DC significantly reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated RAW264.7 cells. The expression of pro-inflammatory proteins including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were also obviously inhibited by DC in LPS-activated RAW264.7 cells. Besides, the production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also remarkably inhibited by DC in LPS-activated RAW264.7 cells. DC also suppressed inflammation indicators including COX-2, PGE2, TNF-α, and IL-6 in LPS-stimulated THP-1 macrophages. Furthermore, DC inhibited the macrophage M1 phenotype and the production of reactive oxygen species (ROS) in LPS-activated RAW264.7 cells. Mechanism studies showed that DC mainly activated nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, increased the level of anti-oxidant protein heme oxygenase-1 (HO-1) and thus produced the anti-inflammatory and anti-oxidant effects, which were abolished by Nrf2 siRNA and HO-1 inhibitor. These findings suggested that DC could be a new Nrf2 activator for the treatment and prevention of diseases related to inflammation and oxidative stress.

Immune checkpoint inhibitors (ICIs) that target cytotoxic T lymphocyte antigen 4, programmed cell death-1, and PD-ligand 1 have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. ICIs are increasingly being used in early cancer settings and in combination with various other types of therapies, including targeted therapy, radiotherapy, and chemotherapy. However, despite the excellent therapeutic effect of ICIs, these medications typically result in a broad spectrum of toxicity reactions, termed immune-related adverse events (irAEs). Of all irAEs, cardiotoxicity, uncommon but with high mortality, has not been well recognized. Herein, based on previous published reports and current evidence, we summarize the incidence, diagnosis, clinical manifestations, underlying mechanisms, treatments, and outcomes of ICI-associated cardiotoxicity and discuss possible management strategies. A better understanding of these characteristics is critical to managing patients with ICI-associated cardiotoxicity.