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Abstract The RNA 5-methylcytosine (m5C) modification has been demonstrated to be an important epigenetic regulator and to impact colorectal cancer (CRC) progression. However, the potential roles of m5C modification in immune cell infiltration in the CRC tumor microenvironment (TME) remain unknown. The m5C modification phenotypes were comprehensively evaluated based on 14 m5C regulators in a meta-CRC cohort of 1792 patients and systematically correlated with the m5C modification phenotypes, immune cell infiltration characteristics and known biological processes. The m5Cscore model was constructed by principal component analysis (PCA) algorithms to quantify the m5C modification phenotypes of individual CRC samples and was used to predict the immunotherapy response. We identified three m5C modification phenotypes associated with distinct clinical outcomes and biological processes among the 1792 meta-CRC patients. Three phenotypes with a highly consistent TME landscape and characteristics were revealed: immune excluded, immune desert and immune inflammation. The meta-CRC patients were divided into high and low m5Cscore subgroups based on the m5Cscore. The m5Cscore was confirmed to have a negative correlation with infiltrating immune cells and PD-L1 expression and a positive correlation with tumor mutation burden (TMB), mutation rate and microsatellite instability (MSI) score. Moreover, patients in the low m5Cscore group had better immunotherapy responses and significant durable survival benefits in independent anti-PD-1/L1 immunotherapy cohorts for the immune checkpoint inhibitor (ICI) therapeutic strategy. This study revealed that m5C modification plays a crucial role in TME composition and complexity. Comprehensive evaluation of the m5C modification phenotypes of individual patients will enhance our understanding of TME characteristics and promote the application of more appropriate and personalized treatment strategies.

Purpose. To compare the antireflux effect, long-term nutritional levels, and quality of life (QoL) between laparoscopy-assisted proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction (LTG-RY) for adenocarcinoma of the esophagogastric junction (AEG). Methods. This multicenter retrospective cohort study collected clinicopathological and follow-up data of AEG patients from January 2016 to January 2021 at five high-volume surgery centers. The study included patients who underwent digestive tract reconstruction with LPG-DTR or LTG-RY after tumor resection. Propensity score matching (PSM) was utilized to minimize confounding factors. The comparison after PSM included postoperative complications, reflux esophagitis, long-term nutritional levels, and QoL. Results. A total of 151 consecutive patients underwent either LPG-DTR or LTG-RY. After PSM, 50 patients from each group were included in the analysis. The frequency of reflux esophagitis and Clavien–Dindo classification did not significantly differ between the two groups (P>0.05). At 1 year after surgery, the LPG-DTR group showed significantly higher weight and hemoglobin levels than the LTG-RY group (P0.05). Conclusion. Both LPG-DTR and LTG-RY are safe and feasible methods for digestive tract reconstruction in patients with AEG. Both methods have similar antireflux effects and postoperative QoL. However, LPG-DTR resulted in superior nutritional levels compared to LTG-RY. Therefore, LPG-DTR is considered a relatively effective method for digestive tract reconstruction in AEG patients.

PurposeLaparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic proximal gastrectomy with tube-like stomach reconstruction (LPG-TLR) are both function-preserving procedures performed for treating AEG. However, there is no clinical consensus on the selection of digestive tract reconstruction after proximal gastrectomy, and the best way to reconstruct the digestive tract remains controversial. This study aimed at comparing the clinical outcomes of LPG-DTR and LPG-TLR to provide some reference to the choice of AEG surgical modalities.MethodsThis was a multicenter, retrospective cohort study. we collected clinicopathological and follow-up data of patients with consecutive cases diagnosed with AEG from January 2016 to June 2021 in five medical centers. According to the way of digestive tract reconstruction after tumor resection, patients who underwent LPG-DTR or LPG-TLR were included in the present study. Propensity score matching (PSM) was performed to balance baseline variables that might affect the study outcomes. The QOL of the patients was evaluated using the Visick grade.ResultsA total of 124 eligible consecutive cases were finally included. Patients in both groups were matched using the PSM method, and 55 patients from each group were included in the analysis after PSM. There was no statistically significant difference between the two groups in terms of the operation time, amount of intraoperative blood loss, days of postoperative abdominal drainage tube placement, postoperative hospitalization days, total hospitalization cost, the total number of lymph nodes cleared, and the number of positive lymph nodes (P>0.05). There was a statistically significant difference between the two groups in terms of time to first flatus after surgery and postoperative soft food recovery time (P0.05).ConclusionThe anti-reflux effect and quality of life of LPG-DTR for AEG were comparable to those of LPG-TLR. Compared with LPG-TLR, LPG-DTR provide better nutrition status for patients with AEG. LPG-DTR is a superior reconstruction method after proximal gastrectomy.

Abstract Background Growing evidence has shown that the prognosis for colon cancer depends on changes in microenvironment. The purpose of this study was to elucidate the prognostic value of long noncoding RNAs (lncRNAs) related to immune microenvironment (IM) in colon cancer. Methods Single sample gene set enrichment analysis (ssGSEA) was used to identify the subtypes of colon cancer based on the immune genomes of 29 immune signatures. Cox regression analysis identified a lncRNA signatures associated with immune infiltration. The Tumor Immune Estimation Resource database was used to analyze immune cell content. Results Colon cancer samples were divided into three subtypes by unsupervised cluster analysis. Cox regression analysis identified an immune infiltration-related 5-lncRNA signature. This signature combined with clinical factors can effectively improve the predictive ability for the overall survival (OS) of colon cancer. At the same time, we found that the expression of H19 affects the content of B cells and macrophages in the microenvironment of colon cancer and affects the prognosis of colon cancer. Finally, we constructed the H19 regulatory network and further analyzed the possible mechanisms. We found that knocking down the expression of H19 can significantly inhibit the expression of CCND1 and VEGFA. At the same time, the immunohistochemical assay found that the expression of CCND1 and VEGFA protein was significantly positively correlated with the infiltration of M2 type macrophages. Conclusion The findings may help to formulate clinical strategies and understand the underlying mechanisms of H19 regulation. H19 may be a biomarker for targeted treatment of colon cancer.

Pueraria lobata, an edible food and medicinal plant, is a rich source of bioactive components. In this study, a polyphenol-rich extract was isolated from P. lobata. Puerarin was identified, and the high antioxidant bioactivity of the P. lobata extract was evaluated using the methods of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS), and hydroxyl free radical scavenging ratio. Additionally, the IC50 values of DPPH, ABTS, and hydroxyl radical scavenging activities were 50.8, 13.9, and 100.4 μg/ml, respectively. Then, the P. lobata extract was administered to C57Bl/6J mice and confirmed to have a superior effect on enhancing the antioxidant status including improving superoxide dismutase activity, glutathione peroxidase peroxide activity, total antioxidant capacity activity, and malondialdehyde contents in vivo. Furthermore, the P. lobata extract had beneficial and prebiotic effects on the composition and structure of gut microbiota. Results showed that the P. lobata extract significantly increased the abundance of beneficial bacteria, involving Lactobacillaceae and Bacteroidetes, and decreased the abundance of Ruminococcaceae, Prevotellaceae, and Burkholderiaceae. Overall, our results provided a basis for using the P. lobata extract as a promising and potential functional ingredient for the food industry.

BackgroundThis study aimed to assess the clinical utility of the advanced lung cancer inflammation index (ALI) as a prognostic indicator for patients with cholangiocarcinoma (CCA) and construct a prognostic nomogram based on ALI.MethodsA total of 97 CCA patients who received radical resection were included. The optimal cut-off point for ALI was identified by X-tile analysis. COX regression analysis were used to identify risk factors of overall survival (OS) and disease-free survival (DFS). A predictive nomogram for DFS was constructed.ResultsThe optimal cut-off value for preoperative ALI was 31.8. 35 (36.1%) patients were categorized into the low-ALI group and 62 (63.9%) patients into the high-ALI group. Low ALI was independently associated with hypoproteinemia and lower body mass index (BMI) (all P < 0.05). COX regression analysis revealed that preoperative ALI level (HR = 0.974, P = 0.037) and pathological TNM stage (HR = 7.331, P < 0.001) were independently correlated with OS for patients with CCA, and preoperative ALI level (HR = 0.978, P = 0.042) and pathological T stage (HR = 1.473, P = 0.035) remained to be independent prognostic factors for DFS in CCA patients. Using time-dependent ROC analysis, we found that ALI was better at predicting prognosis than other parameters, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI) in terms of OS and DFS. A nomogram predicting DFS was built (C-index: 0.73 95%CI: 0.67–0.79).ConclusionsALI may be useful for prognosis assessment for patients with CCA.