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Background Lymph node ratio (LNR) has been suggested to be an effective prognostic tool for stratifying non-small cell lung cancer (NSCLC) cases. In this study, we sought to determine cancer-specific survival (CCS) of NSCLC cases from the SEER registry and used the X-tile method to optimize CCS-based LNR cut-off points for prognostic stratification of node-positive NSCLC. Methods CSS and other clinicopathologic variables were retrieved from the SEER registry. Kaplan-Meier methods were used to calculate CSS. The optimal cut-off points for LNR classification were determined by the X-tile approach. Multivariate Cox regression analysis was performed to identify independent risks of CSS. Results Totally 11,341 lung cancer patients were included. Their median CSS was 22 months (range 0,143). The median LNR was 0.22 (Q1,Q3: 0.11, 0.50). X-tile analysis showed that the optimal LNR cut-off points were 0.28 and 0.81, dividing the cohort into low (LNR1 ≤ 0.28; n = 6580, 58%), middle (0.28 n = 3025, 26.7%), and high (LNR3 > 0.81; n = 1736, 15.3%) subsets. Kaplan-Meier analysis showed that patients with a low LNR had a significantly higher CCS versus patients with middle or high LNR (P P P Conclusions LNR is an independent prognostic factor of node-positive NSCLC and its optimal cut-off values established using the robust x-tile method effectively define subpopulations of node-positive NSCLC cases, which is important in guiding selection of treatment strategies clinically.

Additional file 1: Figure S1. SEM images of (a) Fe2O3 and (b) FP NPs. Figure S2. Colloidal stability of FP NPs. (a) Tyndall effect of Fe2O3 (left) and FP NPs (right). (b) DLS profiles and the optical images of FP NPs in water, PBS and serum (from left to right) after 4 h. Figure S3. The FTIR spectra of mPEG-SH, FP NPs and FP NPs modified with mPEG-SH. Figure S4. The UV���vis spectra of time-dependent DPBF degradation after incubation with (a) blank, (b) Fe2O3, (c) FP + H2O2 (200 ��M) under US irradiation (1.0 MHZ, 1.0 W cm���2). Figure S5. The solid UV���vis spectra of Fe2O3 and FP NPs. Figure S6. TEM image of pure Pt NPs with the same size as that on the surface of FP NPs. Figure S7. ROS fluorescence intensity of 4T1 cells by flow cytometry analysis after incubation with FP NPs under different conditions. Figure S8. The fluorescence images of 4T1 cells staining with DCFH-DA, calcein AM (green, live cells)/ PI (red, dead cells) and RDPP after different treatments. Figure S9. (a) The optical images of O2 generation after incubation with H2O2 (100 mM), FP NPs and FP + H2O2 (100 mM) for 5 min. (b) In vivo US imaging and time-intensity curve analysis of contrast-enhanced ultrasound imaging after intratumoral injection of FP NPs. Figure S10. The representative mice photographs of each groups recorded every 2 days. Figure S11. The immunohistochemistry detection for HIF-1�� of tumor tissues from the mice in different groups. Figure S12. Routine blood analysis including mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and mean corpuscular hemoglobin (MCH). Figure S13. H&E staining of the major organs (heart, liver, spleen, lung and kidney) of mice to examine the pathological changes treated with FP, Fe2O3 + US, Pt + US and Fe2O3/Pt + US.

BackgroundIdentifying novel and actional targets in hepatocellular carcinoma (HCC) remains an unmet medical need. TAK1 was originally identified as a TGF-β-activated kinase and was further proved to phosphorylate and activate numerous downstream targets and promote cancer progression. Although TAK1 depletion leads to early onset of hepatocarcinogenesis in mice, the role of TAK1 in developed HCC progression and targeted therapy resistance is poorly understood. MethodsThe expression of TAK1 and MTDH in HCC cell lines and patients and sorafenib-resistant models was analyzed by in silico analysis, quantitative real-time PCR, western blotting and immunohistochemistry. In vivo and In vitro experiments was introduced to examine the function of TAK1 or MTDH in HCC and sorafenib resistance using small interfering RNA and pharmacological inhibitors in combination with or without sorafenib. Co-immunoprecipitation and RNA immunoprecipitation was carried out to determine the binding between TAK1 and FBXW2 or between MTDH and FBXW2 RNA.ResultsOur findings unraveled the clinical significance of TAK1 in promoting HCC and sorafenib resistance. We identified a novel E3 ubiquitin ligase, FBXW2, targeting TAK1 for K48-linked polyubiquitylation and subsequent degradation. We also found that MTDH contributes to TAK1 upregulation in HCC and sorafenib resistance, through binding to FBXW2 mRNA and accelerate its degradation. Moreover, combination of TAK1 inhibitor and sorafenib suppressed the growth of sorafenib-resistant HCCLM3 xenograft in mouse models.ConclusionThese results revealed novel mechanism underlying TAK1 protein degradation and highlighted the therapeutic value of targeting TAK1 in suppressing HCC and overcoming sorafenib resistance.

Background Laparoscopic anatomical resection (LAR) is a highly challenging procedure. This study aimed to describe our experience of the LAR with an indocyanine green fluorescence negative staining (ICGNS) by the Glissonean pedicle transection (Takasaki) approach. Methods From April 2017 to December 2019, 43 consecutive patients underwent LAR with ICGNS strategy in our medical team. The details of the ICGNS strategy were described. The demographic and clinicopathological data of the included patients were retrospectively analyzed. Results The extent of resections included right hemihepatectomy (n = 12), left hemihepatectom (n = 4), left lateral sectionectomy (n = 3), Right anterior sectionectomy (n = 3), Right posterior sectionectomy (n = 6), central hepatectomy (n = 2), single anterolateral segmentectomy (n = 5), single posterosuperior segmentectomy (n = 6), and bisegmentectomy (n = 2). The mean operation time was 212 ± 53 min, and the median estimated blood loss was 200 (100–300) ml. The overall complication rate was 30.2% (grade I, 14%; grade II, 14%; grade III, 2.3%). The median duration of postoperative hospital stay was 6 (4–7) days. Conclusion ICGNS is a safe and feasible LAR strategy that greatly facilitates selecting the liver transection plane, although its benefits need to be verified by large-sample comparative studies.

Additional file 1.