Background The recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) remains a major clinical problem. Cells that survive the sublethal heat stress that is induced by incomplete RFA are the main source of HCC relapse. Heat stress has long been reported to increase intracellular reactive oxygen species (ROS) generation. Although ROS can induce apoptosis, a pro-survival effect of ROS has also been demonstrated. However, the role of ROS in HCC cells exposed to sublethal heat stress remains unclear. Methods HepG2 and HuH7 cells were used for this experiment. Insufficient RFA was performed in cells and in a xenograft model. ROS and antioxidant levels were measured. Apoptosis was analyed by Annexin-V/PI staining and flow cytometry. Protein expression was measured using western blotting. Colocalization of lysosomes and mitochondria was analyzed to assess mitophagy. Corresponding activators or inhibitors were applied to verify the function of specific objectives. Results Here,we showed that sublethal heat stress induced a ROS burst, which caused acute oxidative stress. This ROS burst was generated by mitochondria, and it was initiated by upregulated NOX4 expression in the mitochondria. n-acetylcysteine (NAC) decreased HCC cell survival under sublethal heat stress conditions in vivo and in vitro. NOX4 triggers the production of mitochondrial ROS (mtROS), and NOX4 inhibitors or siNOX4 also decreased HCC cell survival under sublethal heat stress conditions in vitro. Increased mtROS trigger PINK1-dependent mitophagy to eliminate the mitochondria that are damaged by sublethal heat stress and to protect cells from apoptosis. Nrf2 expression was elevated in response to this ROS burst and mediated the ROS burst-induced increase in PINK1 expression after sublethal heat stress. Conclusion These data confirmed that the ROS burst that occurs after iRFA exerted a pro-survival effect. NOX4 increased the generation of ROS by mitochondria. This short-term ROS burst induced PINK1-dependent mitophagy to eliminate damaged mitochondria by increasing Nrf2 expression.

Background: Breast cancer and lung cancer are the leading causes of cancer-related mortality in women. Computed tomography (CT) plays an important role in lung cancer examination but an unidentified role in breast examination. Objectives: To investigate the feasibility of breast composition categorization according to the fifth edition of Breast Imaging-Reporting and Data System (BI-RADS) atlas in low-dose CT screening. Patients and Methods: This was a cross-sectional study completed in The 5th Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. We collected the imaging data of 57 women, who underwent low-dose chest CT scan and mammography within one week from 1st October 2013 to 31st March 2015. Two radiologists independently interpreted the mammograms and chest CT scans and classified the breast composition into categories a, b, c, and d. We also summarized the distribution of breast composition categories by collecting, observing, and classifying the chest CT scans from 1916 female examinees from 1st October 2013 to 31st March 2016. Results: Excellent agreement was observed between the two radiologists, using both low-dose CT scan (κ = 0.91) and mammography (κ = 0.86). Agreement between low-dose chest CT scan and mammography was moderate for radiologist A (κ = 0.50) and radiologist B (κ = 0.43). More breasts were classified in categories a and b on the chest CT scan compared to mammography according to both radiologist A (P < 0.01) and radiologist B (P < 0.01). The proportion of non-dense breast tissues (categories a & b) increased with advancing age, while the proportion of dense breast tissues (categories c & d) decreased (P < 0.05). With advancing age, the probability of non-dense breasts increased, while the probability of dense breasts decreased. Conclusions: Based on the findings, it is feasible to categorize breast composition using low-dose chest CT. In the older age group, the probability of non-dense breasts increased.