ROS1 gene rearrangements have been reported in diverse cancer types including non-small-cell lung cancer (NSCLC), and with a notably higher prevalence in lung adenocarcinoma. The tyrosine kinase inhibitors, crizotinib, lorlatinib, and entrectinib, have demonstrated favorable efficacy in treating ROS1-rearranged NSCLCs. Herein, we retrospectively reviewed 17 158 NSCLC patients whose tumor specimen and/or circulating cell-free DNA underwent comprehensive genomic profiling. A total of 258 unique patients were identified with ROS1 rearrangements, representing an overall prevalence of approximately 1.5% of ROS1 fusions in newly diagnosed and relapsed NSCLC patients. CD74 (38%) was the most common fusion partner of ROS1, followed by EZR (13%), SDC4 (13%), SLC34A2 (10%), and other recurrent fusion partners with lower frequencies, including TPM3, MYH9, and CCDC6. Variant breakpoints occurred in ROS1 introns 33 (37%), 31 (25%), 32 (17%), and 34 (11%) with no obvious hotspots. CD74 (63%) and EZR (50%) were more frequently fused to ROS1 intron 33 than other introns, while ROS1 intron 31 was most frequently fused with SDC4 (79%) and SLC34A2 (81%). Crizotinib progression-free survival (PFS) was not significantly different between fusion variants involving breakpoints in different ROS1 introns, nor was there a significant difference in PFS between CD74-ROS1 and non-CD74-ROS1 groups of patients. Furthermore, TP53 was most frequently mutated in patients who progressed on crizotinib, and TP53 mutations were significantly associated with shorter crizotinib PFS. ROS1 mutations, including G2032R, were observed in approximately 33% of post-crizotinib samples. Collectively, we report the prevalence of ROS1 fusions in a large-scale NSCLC population and the efficacy of crizotinib in treating patients with ROS1-rearranged NSCLC.

To explore the immunological mechanisms underlying the effect of exogenous interleukin-34 (IL-34) on collagen-induced arthritis (CIA) in mouse. We established a CIA mouse model and injected exogenous recombination mouse IL-34 (rmIL-34) intraperitoneally. The articular index (AI) was measured according to the amount of erythema, swelling, or joint rigidity. The concentrations of TNF-α, IL-17, and IL-6 in CIA mice sera were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of TNF-α, IL-17, and IL-6 in CIA synovial tissue were detected by reverse transcription PCR. The CIA mice dosed with rmIL-34 exhibited increased AI. Neutralization of endogenous IL-17 with anti-IL-17 antibody reduced the effect of IL-34. TNF-α, IL-17, and IL-6 levels in serum in IL-34-treated CIA mice were increased compared to those in CIA mice. IL-34 increased the expression of TNF-α and IL-17 mRNA in synovial tissues of CIA mice, but the gene expression of IL-6 was not affected. The effects of IL-34 on TNF-α, IL-17, and IL-6 expression were abolished by anti-IL-17 antibody. In conclusion, IL-34 acts as a proinflammatory factor, aggravating the severity of arthritis in CIA mice by inducing the production of IL-17.

Background: Major depressive disorder is associated with inflammation and immune processes. Depressive symptoms correlate with inflammatory markers and alterations in the immune system including cytokine levels and immune cell function. Th17 cells are a T cell subset which exerts proinflammatory effects. Th17 cell accumulation and Th17/Treg imbalances have been reported to be critical in the pathophysiology of major depressive disorder and depressive-like behaviors in animal models. Th17 cells are thought to interfere with glutamate signaling, dopamine production, and other immune processes. Ketamine is a newly characterized antidepressant medication which has proved to be effective in rapidly reducing depressive symptoms. However, the mechanisms behind these antidepressant effects have not been fully elucidated.Method: Literature about Th17 cells and their role in depression and the antidepressant effect of ketamine are reviewed, with the possible interaction networks discussed.Result: The immune-modulating role of Th17 cells may participate in the antidepressant effect of ketamine.Conclusion: As Th17 cells play multiple roles in depression, it is important to explore the mechanisms of action of ketamine on Th17 cells and Th17/Treg cell balance. This provides new perspectives for strengthening the antidepressant effect of ketamine while reducing its side effects and adverse reactions.

Background: Postoperative depression is a common complication after surgery that profoundly affects recovery and prognosis. New research indicates that (R,S)-ketamine is a potent antidepressant that exerts a rapid and sustained antidepressive effect. However, there is no consensus on whether intraoperative low-dose (R,S)-ketamine prevents postoperative depression. Objectives: This study aimed to investigate the safety, feasibility, and short-term complications of intraoperative low-dose (R,S)-ketamine in preventing postoperative depressive symptoms. Methods: The Web of Science, Cochrane, PubMed, and CNKI databases were systematically searched (last search February 28, 2020) to identify studies involving ketamine. Sensitivity and metaregression analyses were performed to identify potential confounders. The meta-analysis was performed using Review Manager 5.3. Results: A total of 13 studies (seven in Chinese and six in English) representing 1,148 cases of patients who were treated with (R,S)-ketamine and 874 cases of patients who received other treatments were included in the meta-analysis. Anesthesia duration and blood loss did not significantly differ between the two groups, demonstrating that (R,S

Epigenetic gene silencing due to promoter methylation is observed in human neoplasia, including lymphoma and certain cancer types. One important target for gene methylation analysis in non-Hodgkin lymphoma (NHL) is inhibitor of DNA binding 4 (ID4). The present study aimed to investigate the gene methylation status of ID4, the expression of ID4 protein and the effect of demethylating agent 5-aza-2'-deoxycytosine (CdR) in the Raji human Burkitt's lymphoma cell line in vitro. Following assessment of the inhibition of Raji cell growth by various concentrations of CdR, the effects of CdR on the expression of ID4 protein were assessed using the immunocytochemical streptavidin-peroxidase method and semi-quantitative analysis, while apoptosis and cell cycle were determined by flow cytometry. The ID4 gene methylation status of Raji cells was tested using methylation-specific polymerase chain reaction analysis. ID4 was methylated and its protein expression was low in the control group, while ID4 was partly or completely demethylated and its protein expression was upregulated in Raji cells treated with CdR. In addition, CdR induced apoptosis and cell cycle arrest in Raji cells in a dose- and time-dependent manner. These results demonstrated that ID4 is hypermethylated and its protein expression is low in Burkitt's lymphoma cells, while CdR reversed the abnormal DNA methylation and induced re-expression of ID4 protein. Hypermethylation of ID4 promotes the proliferation of Burkitt's lymphoma cells; ID4 may function as a tumor suppressor and can be targeted with demethylating compounds such as CdR for the treatment of Burkitt's lymphoma.