The sensitivities and maximum responses to each agent differed between the clasp fibers and sling fibers. This suggests that the two kinds of fiber have different roles in establishing tension in the lower esophageal sphincter, with implications for the medical and surgical treatment of disorders in this region.

Esophageal myotomy for achalasia can reduce the resting pressures of the esophageal body and LES and improve esophageal transit and dysphagia. Myotomy in combination with antireflux procedure can prevent gastroesophageal reflux to a certain extent, but further randomized studies should be carried out to demonstrate its efficacy.

310 Background: Taxane is one of the commonly used chemotherapy drugs for ESCC. Nab-paclitaxel, a small particle albumin-bound form of paclitaxel, showed potentially efficacy in metastatic ESCC. This randomized, controlled, multi-center study is conducted to evaluate the efficacy and safety of nab-paclitaxel plus cisplatin in neoadjuvant treatment of ESCC. Methods: Two hundred and two patients with resectable locally advanced ESCC which was located in the middle or lower third of the esophagus were enrolled and randomly assigned in a 1:1 ratio to receive neo-adjuvant chemotherapy or surgery alone. Patients were treated with either two 3-week cycles of nab-paclitaxel (125mg/m2, iv, d1, 8) and cisplatin (75mg/m2, iv, d1), followed by esophagectomy 4-6 weeks after neoadjuvant (the treatment arm) or directly underwent esophagectomy (the control arm). The primary endpoint was overall survival (OS), the secondary endpoints included 1-, 2-, and 3-year OS rate, 1-, 2-, and 3-year disease-free survival (DFS) rate, R0 resection rate, reduction stage rate, chemotherapy-related adverse events. Results: Between April 2019 and June 2021, we randomly assigned 67 patients, of whom 31 in the treatment arm and 33 in the control arm were analyzed. There was no difference in baseline characteristics between the two arms. In the treatment arm, 24 patients underwent R0 resection, and 2 did not undergo surgery although chemotherapy was completed. All patients in control arm underwent R0 resection. In the treatment arm, the pathological complete response (pCR) rate was 20.83%, the major pathological response (mPR) rate was 33.33%, and the down-staging rate was 58.33%. No difference in survival benefit was observed between the two arms. The 1- and 2-year DFS rates of the treatment arm and the control arm were 88.99% vs 75.58% (HR = 0.421, 95%CI: 0.087̃2.032, P = 0.281) and 88.99% vs 66.13% (HR = 0.387, 95%CI: 0.082̃1.833, P = 0.231), respectively. The 1-year and 2-year OS rates of the treatment arm and control arm were 93.21% vs 75.32% (HR = 0.293, 95%CI: 0.061̃1.409, P = 0.125) and 86.56% vs 75.32% (HR = 0.444, 95%CI: 0.115̃1.716, P = 0.239). The neoadjuvant chemotherapy was well tolerated. According to NCI-CTC AE V.5.0, the most common adverse events were hematological toxicity, including neutropenia (16.13%), anemia (3.23%) and hypoproteinemia (3.23%), no grade IV adverse events occurred. Conclusions: Nab-paclitaxel plus cisplatin for ESCC reveals a promising efficacy and safety, and has a tendency to prolong DFS and OS compared with surgery alone. The long-term results are worthy of further exploration. Clinical trial information: NCT03964753.

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PBX/knotted 1 homeobox 2 (PKNOX2) has been implicated in tumorigenesis; however, its role in lung cancer (LC) remains unknown. The present study thus aimed to examine the expression, regulation, function and clinical implication of PKNOX2 in LC. A series of experiments were performed, including Cell Counting Kit-8 assay, cell cycle analysis, wound-healing assay, Transwell assay, methylation-specific PCR and western blotting. Bioinformatics analysis revealed that PKNOX2 was a LC-related gene, and a decrease in its expression was found in LC tissues from three public datasets. The results of reverse transcription-quantitative PCR assays also confirmed that PKNOX2 mRNA expression was markedly downregulated in LC tissues (n=60, P<0.01) and in five types of LC cell lines, and this was associated with the promoter methylation of PKNOX2. In addition, PKNOX2 expression was significantly associated with tumor invasion (P<0.0001), lymph node metastasis (P=0.0057) and TNM stage (P=0.0003); however, it was not associated with sex, age, pathological type or distant metastasis. The data obtained in vitro demonstrated that PKNOX2 silencing promoted LC cell proliferation and inhibited cell cycle arrest, accompanied by an increase in the expression levels of cell cycle-related proteins (cyclinD1, cyclinE1, CDK2 and CDK4), whereas PKNOX2 overexpression exhibited the opposite trend. In addition, PKNOX2 inhibited the migration and invasion of LC cells. Mechanistically, PKNOX2 knockdown activated the PI3K/AKT/mTOR signaling pathway by accelerating the phosphorylation of PI3K, AKT and mTOR, whereas PKNOX2 overexpression inactivated this signaling pathway. In conclusion, the findings of the present study suggested that PKNOX2 may suppress LC cell proliferation by inhibiting the PI3K/AKT/mTOR axis.