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Peroral endoscopic myotomy (POEM) is the first-line treatment of achalasia cardia (AC). However, the efficacy of POEM in treating patients with advanced AC remains to be determined. The aim of the present study was to evaluate the feasibility and clinical outcome of POEM in treating patients with advanced AC involving different esophageal morphologies. The study was a single-center, retrospective analysis of patients suffering from advanced AC. The primary endpoint was the Eckardt score at the follow-up examination. Secondary endpoints were procedural-related details, including the operation time and length of myotomy, adverse events (AEs) and hospital stay, as well as post-procedural gastroesophageal reflux disease. The technical success rate was 100%. All 50 patients enrolled underwent successful endoscopic myotomy (conventional POEM, n=20; modified POEM, n=30). AEs were observed in 10 patients. During a 6- to 50-month follow-up period, 41 patients achieved clinical success as evidenced by a decrease in the Eckardt score. Only 3 of 6 patients with a sigmoid-shaped megaesophagus obtained symptomatic relief. Symptomatic reflux occurred in 13 of 46 patients who completed their follow-up. In conclusion, POEM is safe, feasible and effective in treating advanced AC. Patients with a sigmoid-shaped megaesophagus are less likely to report palliation of symptoms.

Aim To investigate the mechanism of hepatoprotection conferred by liver fibrosis through evaluating the activation phenotype of kupffer cells. Methods Control and fibrotic mice were challenged with a lethal dose of D-GalN/lipopolysaccharide (LPS), and hepatic damage was assessed by histology, serum alanine transferase (ALT) levels, and hepatic expression of HMGB1, a potent pro-inflammatory mediator. The localization of F4/80 (a surrogate marker of KCs), HMGB1, and type I collagen (Col-1) was determined by immunofluorescence staining. The phenotype of KCs was characterized by real-time PCR. KCs isolated from control or fibrotic mice were challenged with LPS or HMGB1 peptide, and HMGB1 translocation was analyzed. Results Liver fibrosis protected mice against D-GalN/LPS challenge, as shown by improved hepatic histology and reduced elevation of ALT compared with the normal mice treated in the same way. This hepatoprotection was also accompanied by inhibition of HMGB1 expression in the liver. Co-localization of F4/80, HMGB1, and Col-1 was found in fibrotic livers, indicating the close relationship between KCs, HMGB1 and liver fibrosis. KCs isolated from fibrotic mice predominantly exhibited an M2-like phenotype. In vitro experiments showed that HMGB1 was localized in the nucleus of the majority of M2-like KCs and that the translocation of HMGB1 was inhibited following stimulation with LPS or HMGB1 peptide, while both LPS and HMGB1 peptide elicited translocation of intranuclear HMGB1 in KCs isolated from the control mice. Conclusion M2-like Kupffer cells in fibrotic liver may exert a protective effect against acute insult by inhibiting the translocation of HMGB1.

To explore the effect of down-regulation of astrocyte elevated gene-1 (AEG-1) expression on cell proliferation and cell cycle of gastric carcinoma cells, and its possible molecular mechanism.Control siRNA and AEG-1 siRNA were transfected into gastric carcinoma SGC-7901 cells. 48 h after transfection, the cells were divided into 3 groups including untransfected, siRNA control and AEG-1 siRNA transfection groups. Expressions of AEG-1 mRNA and protein in the 3 group cells were detected by real-time quantitative PCR and Western blot. The changes of cell proliferation were examined using CCK-8 kit, and the cell cycle distribution was detected by flow cytometry. Finally, expressions of cell proliferation and cell cycle related proteins were detected by Western blot.Real-time quantitative PCR and Western blot demonstrated that compared with the untransfected and siRNA control groups, expressions of AEG-1 mRNA and protein were significantly down-regulated in the AEG-1 siRNA transfection group (P0.05), but there was no significant difference between the untransfected and siRNA control groups (P0.05). Furthermore, in vivo experiment confirmed a significant down-regulation of AEG-1 protein in the AEG-1 siRNA transfection group (P0.05). In addition, AEG-1 siRNA obviously inhibited the proliferation of SGC-7901 cells at different time points after transfection with AEG-1 siRNA. The percentage of cells in G0/G1 phase in the AEG-1 siRNA transfection group [(61.26 ± 1.25)%] was significantly higher than those in the untransfected group [(46.17 ± 1.91)%] and siRNA control group [(46.46 ± 1.96)%], and there was a significant difference between them (all P0.001). Furthermore, the result of Western blotting revealed that down-regulation of AEG-1 expression evoked the down-regulation of cdk2 and cyclin D1 expressions and elevation of p21 expression in vitro and in vivo.The inhibition of cell proliferation and cell cycle arrest mediated by down-regulation of AEG-1 expression may be closely associated with the changes of expression of cell cycle related proteins including cdk2, cyclin D1 and p21.

To investigate the expression of KIAA0101 protein in gastric carcinoma cells, and to explore the effects of its down-regulation on the cell proliferation, cell cycle and invasion.Western blot was used to detect KIAA0101 protein expression in three gastric carcinoma cell lines including MKN-28, SGC-7901 and MKN-45. KIAA0101 siRNA and control siRNA were utilized to transfect MKN-45 cells, respectively. CCK-8 was used to analyze the changes of cell proliferation, and flow cytometry to examine the changes of cell cycle distribution. Finally, Boyden chamber was used to detect the ability of cell invasion.Relative level of KIAA0101 protein in MKN-45 cells was significantly higher than those in MKN-28 and SGC-7901 cells, and there was significant difference among the three cell lines (P0.05). The result of CCK-8 study demonstrated that, compared with untreated group and control siRNA group, the proliferation of MKN-45 cells in KIAA0101 siRNA group was significantly inhibited (P0.05). Additionally, the result of cell cycle analysis revealed that the percentage of cell number in G(0)/G(1) phase in KIAA0101 siRNA group [(61.47 ± 0.89)%] was significantly higher than those in untreated group [(47.43 ± 0.85)%] and control siRNA group [(48.43 ± 0.73)%; F = 271.653, P = 0.000]. Further, Boyden chamber assay showed that the cell numbers migrated to Matrigel in KIAA0101 siRNA group (61.51 ± 4.76) were significantly lower than those in untreated group (138.74 ± 10.16) and control siRNA group (132.93 ± 11.25; F = 65.949, P = 0.000).Down-regulation of KIAA0101 expression leads to an inhibition of cell proliferation, cell cycle and cell invasion. It may provide a novel target for the treatment of patients with gastric carcinoma.

Substantial evidence has demonstrated that platelet-derived growth factor-D (PDGF-D) is tightly associated with the development and progression of tumors. However, its biological functions in esophageal squamous cell carcinoma (ESCC) remain to be delineated. In this study, we found that expressions of PDGF-D mRNA and protein in ESCC tissues and cells were significantly higher than that in normal esophageal epithelial tissues (P0.05), further investigation showed that PDGF-D protein level in EC1 cells was obviously higher than those in EC9706 and Eca109 cells (P0.05). Elevated PDGF-D level was closely associated with TNM staging, tumor differentiation and lymph node metastasis (P0.05), but not related to the patients' age and gender (P0.05). In addition, down-regulation of PDGF-D expression markedly inhibited proliferation, reduced invasion and induced apoptosis in EC1 cells. More importantly, reduced PDGF-D level evoked the down-regulation of p65 and p-IκBα proteins and elevation of IκBα protein of NF-κB pathway, accompanied with the decreases of bcl-2 and MMP-9 protein expressions and increases of bax protein level and caspase-3 activities. Correctively, our data suggest that PDGF-D plays pivotal roles in the development and progression of ESCC, and combinations with PDGF-D and NF-κB pathway may be effective and feasible molecular targets for therapy of ESCC.