Combining non-invasive liquid biopsy and a methylation analysis to assess surgical risk for early esophageal cancer.

Background: While the widespread use of endoscopic submucosal dissection (ESD) has significantly reduced the incidence of early esophageal cancer (ESCA), the limited ability of ESD to strip deep infiltrating esophageal lesions results in a considerable risk of intraoperative perforation. Circulating-free DNA (cfDNA) is widely used in modern tumor screening due to its non-invasive detection capabilities. A methylation analysis offers vital insights into the condition and advancement of malignancies due to its unique positioning, such as a marker of cancer. This study investigated the potential of combining a non-invasive liquid biopsy technique, along with a methylation analysis, to assess the surgical perforation risk of ESCA patients. Methods: In this study, we conducted an analysis of gene expression differences between stage I esophageal squamous carcinoma samples and healthy tissue samples using data from The Cancer Genome Atlas (TCGA) database. We also identified the genes associated with progression-free survival (PFS) in esophageal squamous carcinoma. Integrating the framework of the methylation analysis, we explored the methylated sites of these distinct genes. To refine this process, we used the Shiny Methylation Analysis Resource Tool (SMART) to conduct a comprehensive analysis of these sites. We then confirmed the stability of the methylation sites in different lesion conditions using methylation-specific quantitative polymerase chain reaction (MS-qPCR) with paraffin tissue samples collected after ESD. Results: We analyzed RNA-sequencing data from 42 early stage ESCA patients and 17 controls, identifying 1,263 up-regulated and 460 down-regulated genes. Functional analyses revealed involvement in key pathways such as cell cycle regulation and immune responses. Furthermore, we identified 38 differentially expressed genes associated with PFS. Using SMART analysis, we found 217 hyper-methylated regions in 38 genes, suggesting potential early markers for ESCA. Validation experiments confirmed the reliability of 29 hyper-methylated regions in FFPE tissue samples and 6 regions in cfDNA. A LunaCAM model showed high accuracy [area under the curve (AUC) =0.89] in discriminating early ESCA. Integrated assessment of six highly methylated regions significantly improved predictive performance, with 90.56% sensitivity, highlighting the importance of combinatorial biomarker evaluation for early cancer detection. Conclusions: This study established a novel approach that integrates non-invasive testing with a methylation analysis to assess the surgical risk of early ESCA patients. The significance of changes in methylation sites in relation to lesion status should not be underestimated, as they have the potential to offer vital insights for proactive risk assessments before surgery.

MAGED4B is a Poor Prognostic Marker of Stomach Adenocarcinoma and a Potential Therapeutic Target for Stomach Adenocarcinoma Tumorigenesis.

Background: Gastric cancer is the second most common cause of cancer death worldwide with poor overall prognosis. It is important to study the molecular mechanism of stomach adenocarcinoma (STAD). MAGED4B, a member of the melanoma antigen gene (MAGE) family, is highly expressed in many tumor cells and is associated with tumor progression. Its prognostic value in and the function of the encoded protein are still unclear. Methods: The data of 415 STAD tissues was retrieved from TCGA database, and the expression level of MAGED4B mRNA was evaluated. The correlation between the expression of MAGED4B mRNA and the progression free survival (PFS) time of STAD patients was evaluated by Kaplan Meier analysis. The STAD cell lines with overexpressed and silent MAGED4B were constructed, and the effects of MAGED4B on the viability, migration and proliferation were evaluated by the CCK-8, scratch test and EDU test. The flow cytometry was used to detect apoptosis with overexpressed and silent MAGED4B under the cisplatin treatment, and WB was used to detect the expressions of related proteins, such as TNF-α. Results: The expression level of MAGED4B mRNA in the STAD tissues was higher than that in the normal tissues, and its high expression was related to poor PFS. The overexpression of MAGED4B in the STAD cell lines can promote the vitality, motility and proliferation of the STAD cells, while the silencing of MAGED4B can inhibit the above three cell functions of the STAD cells. The overexpression of MAGED4B can reduce the cisplatin induced apoptosis and increase the cisplatin IC50; the silencing of MAGED4B can promote the cisplatin induced apoptosis and reduce the cisplatin IC50. The overexpression of MAGED4B reduced the protein levels of TRIM27 and TNF- α. Conclusion: MAGED4B could be a valuable prognostic biomarker and a therapeutic target for gastric adenocarcinoma of great interest.

Transcriptomic and network pharmacology approaches revealed possible mechanisms underlying the 5-fluorouracil (5-FU)-sensitizing effect of Xuan-Fu-Hua decoction treatment on liver cancer cells.

Background: Xuan-Fu-Hua decoction is a traditional Chinese medicine formula widely used for the treatment of inflammation-related disease in the lung and liver. This study aimed to investigate the effect of Xuan-Fu-Hua decoction treatment on liver cancer cells and its mechanism of action. Methods: The impact of Xuan-Fu-Hua decoction treatment on the proliferation and apoptosis of SMMC-7721 liver cancer cells with or without 5-fluorouracil (5-FU) cotreatment was determined in both in vitro and in vivo settings. Alterations in gene expression patterns in SMMC-7721 cells induced by Xuan-Fu-Hua decoction treatment were explored by transcriptomic sequencing. Effective components of Xuan-Fu-Hua decoction and their target proteins were investigated using network pharmacology approaches. Results: Xuan-Fu-Hua decoction alone did not significantly influence SMMC-7721 liver cancer cell growth, but it significantly increased the 5-Fu-induced growth inhibition and apoptosis of SMMC-7721 liver cancer cells in vitro and in vivo. Most differentially expressed genes in SMMC-7721 liver cancer cells with or without Xuan-Fu-Hua decoction treatment were enriched in cell apoptosis-related pathways. Xuan-Fu-Hua decoction treatment significantly increased the transcription levels of DDIT3, PMAIP1, and ZMAT3 genes while decreasing that of WNT4, AXIN2, NFE2L2, TGFBR1, MITF, and IGFBP3 genes. An interaction network between the effective components and their possible target proteins was constructed by predicting compound-target protein and protein-protein interactions. Gene set enrichment analysis revealed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway as well as Bcl-2 and Mcl-1 proteins as potential regulatory targets of Xuan-Fu-Hua decoction in sensitizing SMMC-7721 cells to the cytotoxicity of 5-FU treatment. Conclusions: Xuan-Fu-Hua decoction increased the sensitivity of liver cancer cells to the cytotoxicity of 5-FU treatment, possibly by potentiating cell apoptosis and inhibiting the prosurvival machinery.

Is laryngeal mask airway general anesthesia feasible for minimally invasive esophagectomy?

Minimally invasive esophagectomy (MIE) has been identified as an oncological method with lower mortality and morbidity. This procedure is usually performed under general anesthesia using double endotracheal tube intubation and one-lung ventilation for a good visualization like other video-assisted thoracoscopic surgery (VATS). However, it is difficult to differentiate weather the postoperative hoarseness is caused by intubation or by recurrent laryngeal nerve injury during operation, and some complications related to intubation also are the focus of thoracic surgeons. Recently, VATS without tracheal intubation were reported to be feasible and safe in a series of VATS procedures, including management of pneumothorax, wedge resection of pulmonary tumors, excision of mediastinal tumors, lung reduction surgery and lobectomy. However, there is no report about its use in MIE. In December of 2012, we successfully applied nonintubated laryngeal mask airway (LMA) general anesthesia in MIE for three patients with esophageal cancer. Here, we retrospectively report the tentative results.

Berberine demonstrates anti-inflammatory properties in Helicobacter pylori-infected mice with chronic gastritis by attenuating the Th17 response triggered by the B cell-activating factor.

Berberine (BBR) is an isoquinoline alkaloid derived from various medicinal herbs. Previous studies have suggested that BBR exerts antimicrobial, antitumor, and antidiabetic effects and can be used to treat Helicobacter pylori-induced chronic gastritis. However, the exact mechanism by which BBR inhibits H. pylori infection is not fully understood. We investigated the anti-inflammatory properties and potential mechanism of BBR in H. pylori-infected mice with chronic gastritis. We found that BBR can suppress the expression of pro-inflammatory genes IL-6, TGF-ß, and IL-1ß and upregulate anti-inflammatory gene IL-10 expression in the mucosa and RAW 264.7 macrophages. Exposure to BBR also reduced the expression and accumulation of IL-17 in the mucosa and CD4+ T cells activated by anti-CD3 and anti-CD28, and it decreased the frequency of IL-17-producing CD4+ T cells. B cell-activating factor (BAFF) production was inhibited by BBR and by cultured dendritic and CD4+ T cells. Furthermore, we demonstrated that BAFF can trigger the Th17 response by promoting the production of pro-Th17 cytokines IL-6, TGF-ß, and IL-1ß, which are strongly associated with the anti-inflammatory role of BBR in chronic gastritis caused by H. pylori. In conclusion, we determined that BBR has anti-inflammatory effects on H. pylori-induced chronic gastritis by attenuating the BAFF-triggered Th17 response.

[Clinical therapy of Zisheng decoction recipe for chronic atrophic gastritis with intestinal metaplasia].

To explore the therapeutic effect and security of Zisheng decoction recipein treatment of the chronic atrophic gastritis (CAG) with intestinal metaplasia(IM). A total of 147 eligible cases were randomly divided into the traditional Chinese medicine group, Western medicine group and the combined group,47 cases in each group. Zisheng decoction recipe, famotidine, as well as Zisheng decoction recipe + famotidine were respectively given in the above three groups, with a treatment course of 30 d. The symptoms of traditional Chinese medicine, pathological score of gastric mucosa and the negative rate of Helicobacter pylori before and after treatment were observed in each group.The changes in pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), gastrin-17 (GAS-17) and endothelin-1 (ET-1)were also detected to compare the efficient and safety indexes in the three groups. The combined group was better than the traditional Chinese medicine groupand the Western medicine group in total effective rate (P<0.05), pathological score of gastric mucosa and the negative rate of Helicobacter pylori, and serum indexes improvement (P<0.05). The improvement in TCM symptom score was more obvious in traditional Chinese medicine group and combined group than the Western medicine group (P<0.05). In the comparison ofincidence of complications,heart, liver and renal dysfunction, the traditional Chinese medicine group (2 case,4.8%)< the combined group (7 case,15.2%)