Background: Understanding the molecular basis underlying metastasis of non-small cell lung cancer (NSCLC) may provide a new therapeutic modality for the treatment of NSCLC. However, the mechanisms by which tumor-associated macrophages (TAMs) affect NSCLC metastasis remain undefined. In this study, we aimed to discover a novel regulatory pathway involved in NSCLC metastasis.Methods: Cell Counting Kit-8 (CCK-8), Transwell, western blot assays were used to assess cell viability, migration, invasion and epithelial-mesenchymal transition (EMT). Exosomes from macrophages medium were characterized, and in vitro cell coculture was further conducted to investigate M2 derived exosomes mediated crosstalk between TAMs and tumor cells. Besides, miRNA microarray was used to analyze miRNA expression profiles of M0 and M2 derived exosomes. Luciferase reporter assay was used to verify the potential binding between miRNA and mRNA. Moreover, 6-week-old male BALB/c nude mice were performed to establish transplantation tumor model using tail vein injection. Hematoxylin & eosin staining was used to detect the metastasis of tumor tissues.Results: We found that M2 TAMs were the main TAMs in metastatic tissues of NSCLC patients and exosomes derived from M2 TAMs were able to promote cell viability, cell migration, cell invasion and EMT in NSCLC. We demonstrated that miR-155 and miR-196a-5p were abundant in M2 TAMs and exosomes secreted by M2 TAMs. Functional experiments demonstrated that the deletion of miR-155 and miR-196a-5p in M2 TAMs significantly prevented NSCLC metastasis in vitro and in vivo. To clarify the mechanism governing miR-155 and miR-196a-5p from M2 TAMs, we carried out bioinformatics analysis to predict potential target genes. Mechanistically, miR-155 and miR-196a-5p directly bound to the 3'-UTR of Ras association domain family member 4 (RASSF4), and negatively regulating RASSF4 expression. At last, rescue assays demonstrated that miR-155 and miR-196a-5p exerted its performance by RASSF4.Conclusions: Overall, we revealed a new regulatory pathway that was M2 TAMs secreted exosomal miR-155 and miR-196a-5p to promote NSCLC metastasis. This dynamic and reciprocal cross-talk between NSCLC and macrophages innovatively provided a potential opportunity for diagnosis and treatment of NSCLC.

Intraoperative bleeding is the most crucial safety concern of video-assisted thoracic surgery (VATS) for a major pulmonary resection. Despite the advances in surgical techniques and devices, intraoperative bleeding is still not rare and remains the most common and potentially fatal cause of conversion from VATS to open thoracotomy. Therefore, to guide the clinical practice of VATS lung surgery, we proposed the International Interest Group on Bleeding during VATS Lung Surgery with 65

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To review the clinical evidence for ultrasound-accelerated catheter-directed thrombolysis (UACDT) using the EKOS system in the treatment of deep vein thrombosis (DVT) in terms of case selection, procedural outcomes, clinical outcomes and safety outcomes. A systematic literature search strategy was used to identify the use of the EKOS system in the treatment of DVT using the following electronic databases: MEDLINE, EMBASE, the Cochrane databases and the Web of Science. The references in the relevant literature were also screened. Our literature search identified a total of 16 unique clinical studies. Twelve of the sixteen studies were retrospective case series studies. To date, only one randomised controlled trial (RCT) is available. Overall, UACDT using the EKOS system was performed 548 times in 512 patients. Among all cases, 77-100% achieved substantial lysis (> 50%) based on the different definitions of the individual studies. This treatment modality appears to be safe, as there were no reported procedure-related pulmonary embolisms (PE) and only one procedure-related death was reported. Bleeding events were reported in 14 of the 16 studies, and 3.9% (20/512) of the cases of bleeding were considered major. During the follow-up, post-thrombotic syndrome was observed in 17.1% (20/117) of cases. UACDT using the EKOS system is an effective, safe and promising treatment modality for DVT, but the existing clinical evidence is inadequate to make UACDT using the EKOS system the first-line choice for DVT. Additional prospective large-sample RCTs with long-term follow-ups are warranted to define the role of UACDT using the EKOS system in the treatment of DVT.