Autophagy inhibition has been demonstrated to increase the efficacy of conventional chemotherapy. In this study, we identified hederagenin, a triterpenoid derived from Hedera helix, as a potent inhibitor of autophagy and then hypothesized that hederagenin might synergize with chemotherapeutic drugs (e.g., cisplatin and paclitaxel) to kill lung cancer cells. Firstly, we observed that hederagenin induced the increased autophagosomes in lung cancer cells concomitantly with the upregulation of LC3-II and p62, which indicated the impairment of autophagic flux. The colocalization assay indicated hederagenin could not block the fusion of lysosomes and autophagosomes, whereas the lysosomal acidification might be inhibited by hederagenin as revealed by the reduced staining of acidity-sensitive reagents (i.e., Lysotracker and acridine orange). The aberrant acidic environment then impaired the function of lysosome, which was evidenced by the decrease of mature cathepsin B and cathepsin D. Lastly, hederagenin, in agree with our hypothesis, promoted pro-apoptotic effect of cisplatin and paclitaxel with the accumulation of reactive oxygen species (ROS); while the synergistic effect could be abolished by the ROS scavenger, N-acetyl-L-cysteine. These data summarily demonstrated hederagenin-induced accumulation of ROS by blocking autophagic flux potentiated the cytotoxicity of cisplatin and paclitaxel in lung cancer cells.

Current recommendations for warning criteria during intraoperative evoked potential monitoring are empirically derived. Until a threshold that predicts spinal cord injury can be accurately determined, it remains difficult to define the clinical utility of intraoperative neurophysiologic monitoring.

Objective: Tie-over dressing is the most frequently used technique of skin grafting. However, many deficiencies affecting the outcome have been reported. We hereby introduce a modified method, termed the ‘extra-wound fixation technique’, for skin dressing, and evaluate the complications and clinical outcomes. Method: In this retrospective cross-sectional study we analysed the medical records of patients treated between January 2012 and December 2017. All patients received full thickness skin grafts. Patients were divided equally into to groups: patients were treated using the extra-wound fixation technique, and the remaining, randomly selected patients treated using the traditional tie-over method. The extra-wound fixation technique uses the traditional tie-over dressing method followed by additional stitches made in healthy skin locating 0.5-1.0 cm laterally to the wound edge. The follow-up outcomes between the two groups were compared using the Chi-square test. Results: A total of 38 patients took part (19 patients in each group). The follow-up duration was 1–6 months. No raised edges were observed in any of the patients. Prolonged follow-up demonstrated that the grafted skin texture became soft with a thin layer of adipose tissue, and elasticity was gradually improved along with the regeneration of dermoelastic fibre. The colour was similar to the normal skin with a smooth surface. Compared with the traditional method, the extra-wound fixation technique significantly improved the survival of the grafted skin (p=0.008), reduced the risk of laceration of the skin (p=0.001), and eliminated crater rim-like appearances (p=0.020). Conclusion: The extra-wound fixation technique could be used for different skin grafts and improve clinical outcomes compared with the traditional tie-over dressing method.

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