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Background: We demonstrated that postoperative mesenchymal circulating tumor cell (mCTC) in peripheral blood were independent risk factors for the recurrence of hepatocellular carcinoma (HCC) after radical resection. However, few studies have been conducted on the efficacy and survival benefit of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) for patients with mCTC-positive HCC. We evaluated the effect of PA-TACE on the prognosis of mCTC-positive/mCTC-negative HCC patients. Methods: A total of 261 HCC patients from February 2014 to December 2017 undergoing curative hepatectomy were included in this study. Recurrence-free survival (RFS) rates, overall survival (OS) rates, and prognostic factors were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazard model. Results: The results showed that 57.8% (59/102) mCTC-positive and 43.4% (69/159) mCTC-negative patients underwent PA-TACE. Multivariate analyses demonstrated that PVTT (HR 2.370; 95% CI, 1.535–3.660; P < 0.001), BCLC stage (B+C) (HR 3.871; 95% CI, 2.544–5.892; P < 0.001), mCTC (HR 1.414; 95% CI, 1.276–1.622; P < 0.001), and without PA-TACE (HR 1.724; 95% CI, 1.152–2.580; P = 0.008) were independent risk factors for poor RFS. Meanwhile, PVTT (HR 1.744; 95% CI, 1.261–2.412; P = 0.001), multinodularity (HR 1.416; 95% CI, 1.069–1.876; P = 0.015), mCTC (HR 1.612; 95% CI, 1.471–1.796; P < 0.001), and without PA-TACE (HR 1.311; 95% CI, 1.010–1.701; P = 0.042) were independent risk factors for poor OS. Both RFS (P = 0.004) and OS (P = 0.045) in mCTC-positive patients who received PA-TACE were significantly improved relative to those who underwent hepatic resection alone. Among 102 mCTC-positive patients, the mCTC-positive rate was significantly lower in patients treated with PA-TACE than in those treated with liver resection alone (46.4% vs. 88.4%, P = 0.031). No differences were observed in DFS and OS among the mCTC-negative patients with or without PA-TACE. Early recurrence was more likely to occur in patients without PA-TACE (P = 0.006). Conclusions: PA-TACE was a safe intervention and could effectively prevent tumor recurrence and improve the survival of mCTC-positive HCC patients. [ABSTRACT FROM AUTHOR]

Background: A growing body of research indicates that the monitoring of circulating tumor cells (CTCs) may have great significance to the diagnosis of malignant tumors, assessment of condition, selection of treatment methods, and evaluation of prognosis and has a broad range of potential applications. However, the value of CTCs with different phenotypes in the diagnosis of hepatocellular carcinoma (HCC) and assessment of patient condition remains unclear.Methods: We collected 5 ml of peripheral blood from 176 patients who were found to have space-occupying lesions in the liver via B-ultrasound diagnosis at Zhujiang Hospital affiliated with Southern Medical University between August 2015 and October 2017 and used CanPatrol™ CTCs assay technology to isolate and count CTCs with different phenotypes in the patients' peripheral blood. This allowed analysis of the value of CTCs with different phenotypes in the diagnosis of HCC and assessment of BCLC stage.Results: We used CanPatrol™ CTCs assay technology to isolate different types of CTCs: epithelial CTCs (only stained for epithelial markers), mesenchymal CTCs (only stained for mesenchymal markers), mixed CTCs (stained for epithelial markers and mesenchymal markers), and total CTCs (all of the foregoing CTC phenotypes). Of 176 observed patients, 6 patients were finally diagnosed as other malignant tumor liver metastasis, 113 were diagnosed as having hepatocellular carcinoma, and 57 were diagnosed as having nonmalignant liver diseases. Furthermore, we intend to evaluate the diagnostic value of different phenotype CTCs count in discrimination between hepatocellular carcinoma and nonmalignant liver diseases. We found that CTCs of all types were significantly more numerous in the peripheral blood of the HCC group patients than in the NLD group patients (P < 0.05). Furthermore, of the different types of CTCs, total CTCs had the greatest diagnostic value (AUC 0.774; 95% CI, 0.704-0.834). A further discovery was that the AUC values for total CTCs, AFP, and a combined model (combined use of total CTCs and AFP) were 0.774 (95%CI, 0.704-0.834), 0.669 (95%CI, 0.587-0.750), and 0.821 (95%CI, 0.756-0.886). Late-stage HCC patients (BCLC stage B-C) had a higher peripheral blood mesenchymal CTC count than early-stage patients (BCLC stage 0-A) (median:1 vs 0), and mesenchymal CTCs ≥ 1 was the cut-off value for the diagnosis of BCLC stage in HCC patients (sensitivity: 66.67%, specificity: 59.46%, Youden index: 0.26).Conclusions: Total CTCs are more effective than AFP in the diagnosis of HCC; combined use of total CTCs and AFP can enhance the sensitivity of HCC diagnosis. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cells (CTCs) have been actively studied for their functions in hepatocellular carcinoma (HCC) recurrence. However, the relationship between circulating tumor cells subtypes and hepatocellular carcinoma recurrence is still unclear.Methods: CTCs were collected from the peripheral blood of 62 postoperative HCC patients. The CTCs were isolated with a filtration-based method. Multiplex fluorescence in situ hybridization was used to characterize the CTCs based on mRNA expression levels of epithelial and mesenchymal markers.Results: Of the 62 HCC patients, 26 were diagnosed with early recurrence (ER) and 36 did not experience recurrence. Comparison between the recurrence group and the non-recurrence group showed the total number of CTCs, mesenchymal CTCs, and mixed CTCs in the recurrence group was significantly higher than in the non-recurrence group. Receiver operator characteristic (ROC) curve analysis was performed to define the positive cutoff values as follows: total number of CTCs ≥ 4, mesenchymal CTCs ≥ 1, and mixed CTCs ≥ 3. Analysis showed that portal vein tumor thrombus (hazard ratio [HR] = 2.905, P = 0.023) and mesenchymal CTC positivity (HR = 3.453, P = 0.007) were independent risk factors for ER. The correlation between the presence of mesenchymal CTCs and time to recurrence was further examined, and the results showed significantly shortened postoperative disease-free survival in patients positive for mesenchymal CTCs (P < 0.001).Conclusions: HCC patients with positive peripheral mesenchymal CTCs have a more serious risk of ER, which could be a potential biomarker in HCC prognosis monitoring. [ABSTRACT FROM AUTHOR]

• The land use of Xixi wetland region has experienced substantial changes during 1984–2018. • While CS presented an increasing trend, the changes of other services illustrated the overall degradation. • Redundancy analysis revealed the detrimental impacts of impervious cover on the provision of ESs. • Much more efforts need to be taken to enhance the overall services capability of Xixi wetland region. Although extensive studies have investigated changes in regional ecosystem services (ESs) under rapid urbanization, few analyses have used high-resolution image data to investigate urban wetlands. Taking the Xixi wetland region as a case area, this study aimed to investigate the temporal and spatial variation and influencing factors of typical ESs during 1984–2018 using high-resolution images. The results showed that the Xixi wetland region underwent substantial changes of land use as well as in different ESs. While carbon storage presented an increasing trend from 223.25 t/ha to 368.11 t/ha from 1984 to 2018, the changes of other services illustrated an overall degradation in this important urban wetland. Evident trade-off and synergy effects were observed between water yield and carbon storage and between biodiversity protection and recreation and cultural services. Redundancy analysis revealed the detrimental impacts of impervious cover on the provision of ESs in this urban wetland area. The results obtained in this study highlight the great challenges that urban wetland parks face in balancing wetland conservation and sustainable use. [ABSTRACT FROM AUTHOR]

Sorafenib is a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), and reducing sorafenib resistance is an important issue to be resolved for the clinical treatment of HCC. In the current study, we identified that ABCC5 is a critical regulator and a promising therapeutic target of acquired sorafenib resistance in human hepatocellular carcinoma cells. The expression of ABCC5 was dramatically induced in sorafenib-resistant HCC cells and was remarkably associated with poor clinical prognoses. The down-regulation of ABCC5 expression could significantly reduce the resistance of sorafenib to HCC cells. Importantly, activation of PI3K/AKT/NRF2 axis was essential for sorafenib to induce ABCC5 expression. ABCC5 increased intracellular glutathione (GSH) and attenuated lipid peroxidation accumulation by stabilizing SLC7A11 protein, which inhibited ferroptosis. Additionally, the inhibition of ABCC5 enhanced the anti-cancer activity of sorafenib in vitro and in vivo. These findings demonstrate a novel molecular mechanism of acquired sorafenib resistance and also suggest that ABCC5 is a new regulator of ferroptosis in HCC cells. [ABSTRACT FROM AUTHOR]