Mucosal loss as a critical factor in esophageal stricture formation after mucosal resection: a pilot experiment in a porcine model.

BACKGROUND AND AIM: Esophageal stricture is a major complication of large areas endoscopic submucosal dissection (ESD). Until now, the critical mechanism of esophageal stricture remains unclear. We examined the role of mucosal loss versus submucosal damage in esophageal stricture formation after mucosal resection using a porcine model. MATERIALS AND METHODS: Twelve swine were randomly divided into two groups, each of 6. In each group, two 5-cm-long submucosal tunnels were made to involve 1/3rd of the widths of the anterior and posterior esophageal circumference. The entire mucosal roofs of both tunnels were resected in group A. In group B, the tunnel roof mucosa was incised longitudinally along the length of the tunnel, but without excision of any mucosa. Stricture formation was evaluated by endoscopy after 1, 2, and 4 weeks, respectively. Anatomical and histological examinations were performed after euthanasia. RESULTS: Healing observed on endoscopy in both groups after 1 week. Group A (mucosa resected) developed mild-to-severe esophageal stricture, dysphagia, and weight loss. In contrast, no esophageal stricture was evident in group B (mucosa incisions without resection) after 2 and 4 weeks, respectively. Macroscopic examination showed severe esophageal stricture and shortening of esophagus in only group A. Inflammation and fibrous hyperplasia of the submucosal layer was observed on histological examination in both groups. CONCLUSION: The extent of loss of esophageal mucosa appears to be a critical factor for esophageal stricture. Inflammation followed by fibrosis may contribute to alteration in compliance of the esophagus but is not the main mechanism of postresection stricture.

RBM39 is a potential prognostic biomarker with functional significance in hepatocellular carcinoma.

Background: RNA-binding motif protein 39 (RBM39) is a well-known RNA-binding protein involved in tumorigenesis; however, its role in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the role of RBM39 in HCC. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the differential expression of RBM39 in HCC and normal tissues. The prognostic and diagnostic value of RBM39 in HCC was accessed by Kaplan-Meier analysis, Cox regression, and receiver operating characteristic (ROC) curve analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to validate the mRNA and protein expression of RBM39 in HCC. Moreover, gene set enrichment analysis (GSEA) was performed to identify key pathways related to RBM39. The correlation between RBM39 expression and immune cell infiltration was evaluated using a single-sample gene set enrichment analysis (ssGSEA). CCK8 and wound healing assays were performed to investigate the proliferation and migration abilities of HCC cells with RBM39 knockdown. Results: RBM39 expression was upregulated in the HCC tissues. High RBM39 expression was significantly associated with advanced T stage, histological grade, and pathological stage and predicted poor overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) in HCC patients. The upregulation of RBM39 expression was an independent prognostic factor for OS. Moreover, GSEA enrichment analysis indicated that RBM39 was functionally involved in pathways associated with the cell cycle, DNA replication, the p53 signaling pathway, and primary immunodeficiency. RBM39 expression was associated with infiltration of Th2 cells and dendritic cells (DC). RBM39 knockdown significantly inhibited the proliferation and migration of HCC cells. Conclusions: These findings suggest that high RBM39 expression is associated with poor prognosis and promotes HCC cell proliferation and migration. Based on these results, RBM39 is a promising prognostic biomarker with functional significance for HCC.

LncRNA AK142643 promotes hepatic lipid accumulation by upregulating CD36 via interacting with IGF2BP2.

Excessive lipid accumulation in hepatocytes is a defining feature of non-alcoholic fatty liver disease (NAFLD), a condition that is becoming increasingly prevalent worldwide. While long non-coding RNAs (LncRNAs) have been implicated in hepatic lipid metabolism, the precise regulatory mechanisms they employ remain poorly understood. In this study, we investigate the role of AK142643, a previously uncharacterized LncRNA, in hepatic lipid metabolism and the development of NAFLD. Our results demonstrate that AK142643 is upregulated in the livers of ob/ob and high fat diet (HFD)-fed mice, and that it promotes hepatic lipid accumulation both in vivo and in vitro. Furthermore, we reveal that AK142643 acts through the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) to enhance the expression of fatty acid translocase (FAT)/CD36, a key regulator of lipid metabolism. Specifically, AK142643 facilitates the binding of IGF2BP2 to CD36 mRNA, thereby increasing its stability and promoting its expression. Taken together, these findings shed new light on the complex interplay between LncRNAs and hepatic lipid metabolism, and provide insights into the mechanisms underlying the development of NAFLD.

Apatinib in the treatment of gastric cancer in Henan Province: a multicenter prospective real-world observational study (Ahead-HAP01).

Background: Apatinib is approved in China for the treatment of advanced gastric adenocarcinoma that had progressed or relapsed after standard systemic chemotherapy treatments. However, the effectiveness of Apatinib under real-world condition has not been evaluated and the drug performance under ideal and controlled circumstances has not been validated. In fact, genetic factors, poor healthcare access, social economic status, comorbidities compliance and other factors play significant role in drug performance under "real-world" conditions. Real-world experience can help validate the safety and efficacy of apatinib. Methods: In this observational, prospective study we evaluated the safety and efficacy of Apatinib in patient treated in China. Between March 2018 and March 2019, a total of 943 patients with gastric cancer treated with Apatinib were enrolled. Response Evaluation Criteria in Solid Tumors, version 1.1 and Common Terminology Criteria for Adverse Events, version 4.0 were used to evaluate efficacy and adverse effects. Results: The median progression-free survival (PFS) was 5.65 months (5.22-6.05 months), and the median overall survival (OS) was 11.47 months (10.41-12.52 months). Apatinib in combination with more than two agents was superior to single agent apatinib in overall response rate (ORR) [18.18% vs. 9.43%, 95% confidence interval (CI): 1.03-5.90] and disease control rate (DCR) (82.82% vs. 77.87%, 95% CI: 1.21-2.59). Apatinib in combination with single agent chemotherapy was also superior to apatinib alone with DCR (86.29% vs. 77.87%, 95% CI: 1.47-2.99) irrespective of the dose (250 or 500 mg). In the patient cohort who received a starting dose of 250 mg, the DCRs of the combined treatment and monotherapy groups were 86.22% vs. 80.00% (95% CI: 1.18-3.09), respectively. The most common treatment-emergent adverse events were anemia, anorexia and thrombocytopenia (66.28%, 37.75%, 36.06%, respectively). Conclusions: Efficacy of Apatinib in this observational study is promising and toxicities are manageable. Combination of Apatinib with chemotherapy agents has a higher response rate and better disease control at the expense of increased serious adverse events. Better OS can be achieved by receiving apatinib treatment earlier. As a supplement and further validation of explanatory randomized controlled trials, the real-world study reflects the real efficacy of apatinib in practical application.

Influence of esophageal morphology on the clinical efficacy of peroral endoscopic myotomy in treating advanced achalasia cardia.

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.

Expression of PC cell-derived growth factor and vascular endothelial growth factor in esophageal squamous cell carcinoma and their clinicopathologic significance.

BACKGROUND: Esophageal carcinoma is a common kind of malignant tumor and about 90% of which is esophageal squamous cell carcinoma (ESCC), and it has a high incidence in China. In recent years it has been argued that angiogenesis plays a key role in tumor growth and metastasis and it is a complex process influenced by many factors. This study was aimed to investigate the expression of PC cell-derived growth factor (PCDGF or progranulin) and vascular endothelial growth factor (VEGF) in ESCC tissue and their relationship with clinical pathological parameters of ESCC, clarify the role of PCDGF and VEGF in the angiogenesis of ESCC. METHODS: The expression of PCDGF and VEGF in 50 surgical specimens from patients with ESCC and 20 with normal esophageal mucosa were detected by immunohistochemistry. The vascular endothelial cells in tumor tissues were labeled by antibody to CD105 for counting microvessel density (MVD). RESULTS: The expression of PCDGF and VEGF in ESCC was significantly higher than that in normal mucosa. Expression correlated with the depth of tumor invasion, lymph node metastasis, and TNM (classification tumor, nodes, metastasis). In ESCC, both the expression level of PCDGF and VEGF had a positive correlation with MVD and the expression of PCDGF had a significant correlation with the expression of VEGF. CONCLUSIONS: These results show that both of PCDGF and VEGE have higher expression in ESCC, which indicate that they have a close relationship with angiogenesis. They may be involved in tumor growth, infiltration and metastasis through promoting tumor angiogenesis and may be an important index reflecting biological behavior and prognosis of ESCC.

Selective Ortho-π-Extension of Perylene Diimides for Rylene Dyes.

A range of ortho-π-extended PDI derivatives are straightforwardly synthesized in good yields through highly regioselective heteroannulations of ortho-alkynyl-substituted PDI derivatives with sulfur, selenium, or nitrogen nucleophiles. Successful synthesis of pyrrole-fused rylene dyes by using primary amines as nucleophiles indicates the great synthetic potential of this facile annulation route. Further opto-electrochemical study of these novel thiophene-, selenophene-, and pyrrole-fused PDIs suggests that effective π-conjugation enlargement combined with distortion of the perylene core renders these PDI derivatives tunable and desirable physical properties.

Direct Synthesis of Large-Scale Ortho-Iodinated Perylene Diimides: Key Precursors for Functional Dyes.

A highly regioselective tetra-ortho-iodination reaction of perylene diimides (PDIs) has been developed, which could be conducted on a multigram scale (>10 g), featuring a column chromatography-free workup and purification. The ortho-iodinated-PDIs serve as key intermediates for the preparation of a variety of ortho-functionalized PDIs and PDI-based conjugated polymers.

2,5,8,11-Tetraalkenyl Perylene Bisimides: Direct Regioselective Synthesis and Enhanced π-π Stacking Interaction.

A series of 2,5,8,11-tetraalkenyl perylene bisimide (PBI) derivatives were synthesized through Ru(II)- or Rh(III)-catalyzed regio- and steroselective oxidative C-H olefination in one step. The optical electronic and self-assembly of the 2,5,8,11-substituted PBIs were investigated, which showed great potential in optoelectronic applications.

Detection of methylated tissue factor pathway inhibitor 2 and human long DNA in fecal samples of patients with colorectal cancer in China.

BACKGROUND: To investigate the feasibility of detecting methylated tissue factor pathway inhibitor (TFPI2) and quantifying human long DNA with fluorescent quantitative Alu PCR in fecal DNA as a non-invasive screening tool for colorectal cancer (CRC). MATERIALS AND METHODS: Methylation-specific PCR (MSP) was performed to analyze TFPI2 gene promoter methylation status in a blinded fashion in stool samples taken from 30 endoscopically diagnosed healthy controls, 20 patients with adenomas, and 60 patients with colorectal cancer. Real-time Alu PCR was used to quantify human long DNA. RESULTS: The specificity of fecal TFPI2 MSP assay and long DNA assay was 100% and 83.3%, respectively. The sensitivity of fecal TFPI2 MSP assay and long DNA assay was 68.3% and 53.3%, respectively. The sensitivity of fecal DNA assay (either marker being positive) was 86.7%, which was high for CRC. CONCLUSIONS: Our results have demonstrated the feasibility of using TFPI2 methylation and quantify human long DNA with fluorescent quantitative Alu PCR in fecal samples as a new noninvasive test for CRC.