Background: Lactate has long been considered an intermediate by-product of glucose metabolism. However, in recent years, accumulating evidence reveals that lactate has unique biological activities. In previous studies, lactate signaling was shown to inhibit inflammation. Furthermore, in vitro experiments have shown that lactate can promote the transformation of pro-inflammatory macrophages into anti-inflammatory macrophages. However, no in vivo studies have shown whether lactate can alleviate inflammation.Methods: RAW 264.7 macrophages were stimulated by LPS to induce an M1 phenotype, and cultured with low and high concentrations of lactate. The cells were then observed for phenotypic transformations and expression of inflammatory mediators and surface markers. The expression of inflammatory factors was also analyzed in the cell-free supernatant fraction. Further, a mouse model of DSS-induced colitis was established and treated with lactate. Colonic tissue injury was monitored by histopathological examinations.Results: The in vitro experiments showed that lactate promoted the transformation of activated macrophages to M2 phenotype and decreased the expression of TLR4-mediated NF-κB signaling proteins and inflammatory factors. In the DSS-induced colitis mouse model, lactate promoted the phenotypic transformation of macrophages in colonic tissue, reduced inflammation and organ damage, inhibited the activation of TLR4/NF-κB signaling pathway, decreased the serum levels of pro-inflammatory factors, increased the expression of anti-inflammatory factors, promoted the repair of the intestinal mucosal barrier and reduced the severity of colitis.Conclusions: Lactate inhibits the TLR/NF-κB signaling pathway and the production of pro-inflammatory factors by promoting polarization of macrophages. In addition, lactate promotesthe repair of the intestinal mucosal barrier and protects intestinal tissue in inflammation. Furthermore, lactate is relatively safe. Therefore, lactate is a promising and effective drug for treating inflammation through immunometabolism regulation.

Evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) are involved in the development and progression of advanced gastric cancer (AGC). Using RNA sequencing data and clinical information obtained from The Cancer Gene Atlas, we combined differential lncRNA expression profiling and weighted gene co-expression network analysis to identify key lncRNAs associated with AGC progression and prognosis. Cancer susceptibility 19 (CASC19) was the top hub lncRNA among the lncRNAs included in the gene module most significantly correlated with AGC's pathological variables. CASC19 was upregulated in AGC clinical samples and was significantly associated with higher pathologic TNM stage, pathologic T stage, lymph node metastasis, and poor overall survival. Multivariable Cox analysis confirmed that CASC19 overexpression is an independent prognostic factor for overall survival. Furthermore, quantitative real-time PCR assay confirmed that CASC19 expression in four human gastric cancer cells (AGS, BGC-823, MGC-803, and HGC-27) was significantly upregulated compared with human normal gastric mucosal epithelial cell line (GES-1). Functionally, CASC19 knockdown inhibited GC cell proliferation and migration in vitro. These findings suggest that CASC19 may be a novel prognostic biomarker and a potential therapeutic target for AGC.

Robot-assisted gastrectomy (RAG), as an alternative minimally invasive surgical technique, is gradually being used for the treatment of gastric cancer (GC). This study aimed to assess the feasibility and safety of RAG over conventional Laparoscopy-assisted gastrectomy (LAG) for the treatment of GC. We retrospectively analyzed all procedures (RAG and LAG) performed by one surgeon between 31 January 2017 and 1 December 2017. The short-term of surgical outcomes were compared between two groups and further subgroup analyses were performed. One hundred patients were enrolled in the RAG group and 135 in the LAG group. The demograghics and clinicopathologic characteristics are well matched between two groups. The RAG group had shorter postoperative hospital stay (11 (interquartile range 9-13) vs. 12 (10-14) day; p < 0.0001), earlier day of first flatus (2 (2-3) vs. 3 (2.3-3) day; p < 0.0001), and larger lymph nodes dissection (40.9 ± 13.1 vs. 35.4 ± 15.8; p = 0.004). Of interest, mean numbers of retrieved lymph nodes from station 6 (p = 0.002), 7 (p = 0.032), 10 (p = 0.025), 11p (p = 0.036), and 14v (p = 0.038) in RAG was significantly larger than LAG. However, no significant differences between two groups were observed in operative time (p = 0.136), operative blood loss (p = 0.434), days of eating liquid diet (p = 0.889), and postoperative complications (p = 0.752). In subgroup analyses, the similar results were observed. RAG for the treatment of GC is a safe and feasible procedure and beneficial for postoperative recovery of GC patients. However, further studies are needed to evaluate long-term and oncologic outcomes of RAG.