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Helicobacter pylori (H. pylori) infection is the strongest known risk factor for the development of gastric cancer. DNA damage response (DDR) and autophagy play key roles in tumorigenic transformation. However, it remains unclear how H. pylori modulate DDR and autophagy in gastric carcinogenesis. Here we report that H. pylori infection promotes DNA damage via suppression of Rad51 expression through inhibition of autophagy and accumulation of p62 in gastric carcinogenesis. We find that H. pylori activated DNA damage pathway in concert with downregulation of repair protein Rad51 in gastric cells, C57BL/6 mice and Mongolian gerbils. In addition, autophagy was increased early and then decreased gradually during the duration of H. pylori infection in vitro in a CagA-dependent manner. Moreover, loss of autophagy led to promotion of DNA damage in H. pylori-infected cells. Furthermore, knockdown of autophagic substrate p62 upregulated Rad51 expression, and p62 promoted Rad51 ubiquitination via the direct interaction of its UBA domain. Finally, H. pylori infection was associated with elevated levels of p62 in gastric intestinal metaplasia and decreased levels of Rad51 in dysplasia compared to their H. pylori-counterparts. Our findings provide a novel mechanism into the linkage of H. pylori infection, autophagy, DNA damage and gastric tumorigenesis.

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Objective:Vagus nerve stimulation (VNS) has recently been used in neurorehabilitation and the recovery of consciousness based on its effects on cortical plasticity. The aim of this study was to examine the therapeutic effects of VNS on patients with a minimally conscious state (MCS).Methods:All patients included in the study were assessed more than 5 months after injury and were receiving regular rehabilitation at our hospital from August 2018 to October 2019. Ten patients diagnosed with MCS by Coma Recovery Scale-Revised (CRS-R) test who underwent VNS surgery were enrolled. The scores on CRS-R evaluation at baseline (before VNS implantation) and 1, 3, and 6 months after VNS treatment were recorded. The stimulation parameters were chosen according to a previous study. All clinical rehabilitation protocols remained unchanged during the study. Furthermore, safety was assessed by analyzing treatment-emergent adverse events (TEAEs).Results:No significant improvement in the total CRS-R scores at the end of the 1-month follow-up was observed (p > 0.05). After 3 months of stimulation, a significant difference (p = 0.0078) was observed in the total CRS-R scores compared with the baseline. After 6 months of VNS treatment, CRS-R assessments showed a continuous significant improvement (p = 0.0039); one patient emerged from the MCS and recovered functional communication and object use. Interestingly, one item of CRS-R scores on visual domain was sensitive to VNS treatment (p = 0.0039). Furthermore, no serious adverse event occurred throughout the study.Conclusion:This exploratory study provides preliminary evidence suggesting that VNS is a safe and effective tool for consciousness recovery in patients with MCS.