Peroral endoscopic myotomy (POEM) has been widely applied to the treatment of achalasia. The aim of this study is to retrospectively investigate the long-term outcome of POEM in patients with achalasia. Patients undergoing POEM at our center with a minimum follow-up of 3 years were enrolled in this study. Relief of patients' symptom was defined as the primary outcome. Secondary outcomes included lower esophageal sphincter pressure, esophageal emptying, symptoms relapse, and clinical reflux adverse events. The Chi-square test was performed to determine the potential predictors of surgical failure. Sixty-seven patients (aged 40.7 ± 15.3 years) were recruited in the study, with a mean follow-up period of 40.1 ± 2.8 months. At the final follow-up, the median Eckardt score reduced from 7.6 ± 2.3 preoperatively to 1.9 ± 1.7 (P < 0.001), the lower esophageal sphincter pressure was reduced from 35.4 ± 13.7 mmHg preoperatively to 8.9 ± 4.1 mmHg (P < 0.001), and the height of the barium column at 5 min after barium swallowed was reduced from 9.7 ± 1.6 cm preoperatively to 2.9 ± 2.1 cm (P < 0.001). Eight patients had symptoms relapse and nine patients developed reflux esophagitis. Type III achalasia was found to be indicative of surgical failure. POEM was a promising treatment for patients with achalasia, which can yield a long-term relief of the symptom and a low rate of clinical reflux adverse events.

Cucurbitacin-I (Cu-I, also known as Elatericin B or JSI-124) is developed to inhibit constitutive and abnormal activation of STAT3 in many cancers, demonstrating a potent anticancer activity by targeting disruption of STAT3 function. Here, we for the first time systematically studied the underlying molecular mechanisms of Cu-I-induced gastric cancer cell death both in vitro and in vivo. In our study, we show that Cu-I markedly inhibits gastric cancer cell growth by inducing G2/M phase cell cycle arrest and apoptosis at low nanomolar concentrations via a STAT3-independent mechanism. Notably, Cu-I significantly decreases intracellular GSH/GSSG ratio by inhibiting NRF2 pathway to break cellular redox homeostasis, and subsequently induces the expression of GADD45α in a p53-independent manner, and activates JNK/p38 MAPK signaling. Interestingly, Cu-I-induced GADD45α and JNK/p38 MAPK signaling form a positive feedback loop and can be reciprocally regulated by each other. Therefore, the present study provides new insights into the mechanisms of antitumor effects of Cu-I, supporting Cu-I as an attractive therapeutic drug in gastric cancer by modulating the redox balance.