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BackgroundRecent clinical trials of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in human lung adenocarcinoma (LUAD) have not achieved satisfactory results. The disappointing results of single-drug treatments have prompted studies about synergistic therapies of CDK4/6i with other drugs. We aimed to test the anti-tumor effect of ribociclib (a CDK4/6i) combined with pemetrexed on LUAD and the potential mechanisms.MethodsCell lines were exposed to ribociclib and pemetrexed at different doses. Antitumor effects were measured using growth inhibition. Cell cycle distribution and apoptosis were evaluated using flow cytometry. Cell migration and invasion were measured using wound healing and transwell invasion assays, respectively. The expression levels of proteins were analyzed using western blotting. Mice xenograft models were used for validation in vivo.ResultsSynergism was associated with a combination of cell cycle effects from both agents. Cell cycle analysis revealed that pemetrexed blocked cells in the S phase, whereas ribociclib arrested cells in the G1 phase. Concomitant treatment with pemetrexed and ribociclib resulted in a significantly stronger antitumor ability than treatment alone. We also found that ribociclib strongly enhanced the pro-apoptotic activity of pemetrexed via the caspase/bcl-2 signaling pathway. In addition, we report for the first time that combination treatment with ribociclib and pemetrexed significantly inhibits the migration and invasion of LUAD cells.ConclusionsCombining ribociclib and pemetrexed showed a powerful ability to inhibit cancer proliferation, invasion, and metastasis, and it holds potential as a novel effective combinative therapy for patients with LUAD.

Objective: It is revealed that circulating fibrocytes are elevated in patients/animals with cardiac fibrosis, and this review aims to provide an introduction to circulating fibrocytes and their role in cardiac fibrosis. Data Sources: This review is based on the data from 1994 to present obtained from PubMed. The search terms were “circulating fibrocytes “ and “cardiac fibrosis “. Study Selection: Articles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected. Results: Circulating fibrocytes, which are derived from hematopoietic stem cells, represent a subset of peripheral blood mononuclear cells exhibiting mixed morphological and molecular characteristics of hematopoietic and mesenchymal cells (CD34+/CD45+/collagen I+). They can produce extracellular matrix and many cytokines. It is shown that circulating fibrocytes participate in many fibrotic diseases, including cardiac fibrosis. Evidence accumulated in recent years shows that aging individuals and patients with hypertension, heart failure, coronary heart disease, and atrial fibrillation have more circulating fibrocytes in peripheral blood and/or heart tissue, and this elevation of circulating fibrocytes is correlated with the degree of fibrosis in the hearts. Conclusions: Circulating fibrocytes are effector cells in cardiac fibrosis.

Objective: To evaluate the effect of integrated schistosomiasis control measures in Honghu City during the period from 2008 through 2018., Methods: The data pertaining to schistosomiasis control measures and the endemic situation of schistosomiasis in Honghu City were collected from 2008 to 2018, and the effect of integrated schistosomiasis control measures implemented was evaluated., Results: The resources from agriculture, water resources, forestry, land, education and communication sectors were integrated to implement the integrated schistosomiasis control strategy with the focus on the control of source of Schistosoma japonicum infection in Honghu City from 2008 to 2018. The prevalence of S. japonicum infection reduced from 3.03% in 2008 to 0 in 2018 in humans in the city, and no acute infection was detected since 2009. In addition, the prevalence of S. japonicum infection in cattle reduced from 2.85% in 2008 to 0 in 2018, and no snail infection was found since 2012. Transmission control of schistosomiasis was achieved in the city in 2013, and transmission interruption was achieved in 2018., Conclusions: The integrated schistosomiasis control measures achieve remarkable effects in Honghu City; however, there is still a risk of schistosomiasis transmission.