Purpose: Pheochromocytomas and paragangliomas (PCPGs) are usually benign neuroendocrine tumors. However, PCPGs with mutations in the succinate dehydrogenase B subunit (SDHB) have a poor prognosis and frequently develop metastatic lesions. SDHBmutated PCPGs exhibit dysregulation in oxygen metabolic pathways, including pseudohypoxia and formation of reactive oxygen species (ROS), suggesting that targeting the redox balance pathway could be a potential therapeutic approach.Experimental design: We studied the genetic alterations of Cluster I PCPGs compared to Cluster II PCPGs, which usually present as benign tumors. By targeting the signature molecular pathway, we investigated the therapeutic effect of ascorbic acid on PCPGs using in vitro and in vivo models.Results: By investigating PCPG cells with low SDHB levels, we show that pseudohypoxia resulted in elevated expression of iron transport proteins, including transferrin (TF), transferrin receptor 2 (TFR2) and the divalent metal transporter 1 (SLC11A2; DMT1), leading to iron accumulation. This iron overload contributed to elevated oxidative stress.Ascorbic acid at pharmacologic concentrations disrupted redox homeostasis, inducing DNA oxidative damage, and cell apoptosis in PCPG cells with low SDHB levels. Besides, through a preclinical animal model with PCPG allografts, we demonstrated that pharmacologic ascorbic acid suppressed SDHB-low metastatic lesions and prolonged overall survival. Conclusions:The data here demonstrate that targeting redox homeostasis as a cancer vulnerability with pharmacologic ascorbic acid is a promising therapeutic strategy for SDHB-mutated PCPGs.

The use of the HybridKnife leads to a significant decrease in POEM procedure time and facilitates reinjection, possibly contributing to a lower rate of minor intra-procedural bleeding.

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Background and aims Making an optimal and lasting submucosal cushion is critical for endoscopic submucosal dissection. The thermo-sensitive binary hydrogels system composed of poloxamer 407 and poloxamer 188 might be an excellent submucosal injection solution considering the unique feature that it remains liquid at room temperature and becomes gelatinous after being injected in the submucosa of the digestive tract. The present study focuses on preparing the thermo-sensitive binary hydrogels system and testing its capacity in mucosal lifting and its role in the endoscopic submucosal dissection procedure. Methods Various concentrations of poloxamer 407 and poloxamer 188 were added to normal saline. The gelation temperature viscosity of the thermo-sensitive binary hydrogels system was measured to choose the best formula. The thermo-sensitive binary hydrogels system and normal saline were first compared in extracted porcine stomach. For in vivo study, the thermo-sensitive binary hydrogels system and normal saline were compared for facilitating the endoscopic submucosal dissection procedure. Results Among the 46 kinds of thermo-sensitive binary hydrogels system, gelation temperatures of the thermo-sensitive binary hydrogels system I (poloxamer 407/poloxamer 188, 17%/0.5%, w/w) and the thermo-sensitive binary hydrogels system II (poloxamer 407/poloxamer 188, 18%/2%, w/w) were among the ideal range of gelation temperature. The injecting pressure in vitro study of thermo-sensitive binary hydrogels system II was significantly higher than that of thermo-sensitive binary hydrogels system I and normal saline ( p < 0.001). Sixteen gastric endoscopic submucosal dissection procedures were performed in a porcine model. The initial volume of normal saline injection (13.88 ± 3.91 ml vs 5.88 ± 3.44 ml, p = 0.001) was significantly larger than the thermo-sensitive binary hydrogels system group. The postoperative wound showed a significant difference in the two groups ( p = 0.023) indicating that the thermo-sensitive binary hydrogels system can create a cleaner wound. Conclusions Considering the gelation temperature, viscosity, injection pressure, and the height of the mucosal elevation, the thermo-sensitive binary hydrogels system I was the better submucosal injection solution.

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Optimal bowel preparation is a prerequisite for a successful colonoscopy; however, the rate of inadequate bowel preparation remains relatively high. In this study, we establish a smartphone app that assesses patient bowel preparation using an artificial intelligence (AI)-based prediction system trained on labeled photographs of feces in the toilet and evaluate its impact on bowel preparation quality in colonoscopy outpatients. We conduct a prospective, single-masked, multicenter randomized clinical trial, enrolling outpatients who own a smartphone and are scheduled for a colonoscopy. We screen 578 eligible patients and randomize 524 in a 1:1 ratio to the control or AI-driven app group for bowel preparation. The study endpoints are the percentage of patients with adequate bowel preparation and the total BBPS score, compliance with dietary restrictions and purgative instructions, polyp detection rate, and adenoma detection rate (secondary). The prediction system has an accuracy of 95.15%, a specificity of 97.25%, and an area under the curve of 0.98 in the test dataset. In the full analysis set (n = 500), adequate preparation is significantly higher in the AI-driven app group (88.54 vs. 65.59%; P < 0.001). The mean BBPS score is 6.74 ± 1.25 in the AI-driven app group and 5.97 ± 1.81 in the control group (P < 0.001). The rates of compliance with dietary restrictions (93.68 vs. 83.81%, P = 0.001) and purgative instructions (96.05 vs. 84.62%, P < 0.001) are significantly higher in the AI-driven app group, as is the rate of additional purgative intake (26.88 vs. 17.41%, P = 0.011). Thus, our AI-driven smartphone app significantly improves the quality of bowel preparation and patient compliance.