The aim of this meta-analysis was to evaluate the clinical significance of glutamine in the management of patients with colorectal cancer (CRC) after radical operation. Electronic databases, including PubMed, EMBASE, MEDLINE, Cochrane Library, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), VIP medicine information system (VIP), and Wanfang electronic databases were comprehensively searched from inception to 30, July 2021. Prospective randomized trials with glutamine vs. routine nutrition or blank therapy were selected. The immune function related indicators (including IgA, IgG, IgM, CD4+, CD8+, and the ratio of CD4+/CD8+), post-operative complications [including surgical site infection (SSI), anastomotic leakage, and length of hospital stay (LOS)], and corresponding 95% confidence intervals (CIs) were assessed in the pooled analysis. Subsequently, the heterogeneity between studies, sensitivity, publication bias, and meta-regression analysis were performed. Consequently, 31 studies which contained 2,201 patients (1,108 in the glutamine group and 1,093 in the control group) were included. Results of pooled analysis indicated that glutamine significantly improved the humoral immune function indicators [including IgA (SMD = 1.15, 95% CI: 0.72–1.58), IgM (SMD = 0.68, 95% CI: 0.48–0.89), and IgG (SMD = 1.10, 95% CI: 0.70–1.50)], and the T cell immune function indicators [including CD4+ (SMD = 0.76, 95% CI: 0.53–0.99) and the ratio of CD4+/CD8+ (SMD = 0.92, 95% CI: 0.57–1.28)]. Meanwhile, the content of CD8+ was decreased significantly (SMD = −0.50, 95% CI: −0.91 to −0.10) followed by glutamine intervention. Pooled analysis of SSI (RR = 0.48, 95% CI: 0.30–0.75), anastomotic leakage (RR = 0.23, 95% CI: 0.09–0.61), and LOS (SMD = −1.13, 95% CI: −1.68 to −0.58) were decreased significantly in glutamine group compared with control group. Metaregression analysis revealed that the covariate of small-sample effects influenced the robustness and reliability of IgG outcome potentially. Findings of the present work demonstrated that glutamine ought to be applied as an effective immunenutrition therapy in the treatment of patients with CRC after radical surgery. The present meta-analysis has been registered in PROSPERO (no. CRD42021243327).Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO, Identifier: CRD42021243327.

Aims. The purpose of this study was to explore the biological functions of the mTOR and AMPK signaling pathways in colon cancer (CC). The potential molecular mechanisms by which oleanolic acid (OA) induces autophagy and apoptosis were also investigated. Methods. The biological functions of mTOR were analyzed by GeneCards, the Search Tool for the Retrieval of Interacting Genes (STRING), and the Database for Annotation, Visualization and Integrated Discovery (DAVID). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to obtain prognostic and survival data of CC patients from the Gene Expression Omnibus (GEO) database. The effects of OA on the CC cell lines HCT-116 and SW-480 were analyzed by CCK-8, colony formation assay, and high-content system (HCS) array scan. The apoptosis rate of SW-480 and HCT-116 cells was detected by flow cytometry. The mRNA and protein expression levels in HCT-116 and SW-480 cells and NCM-460 normal colonic epithelial cells were detected by RT-PCR and Western blotting. Results. mTOR was highly expressed in CC patients and acted as an oncogene. The AMPK signaling pathway mediated by mTOR predicted the poor prognosis of CC patients. OA effectively inhibited the proliferation and viability of CC cells. Furthermore, the apoptosis rate of CC cells was clearly increased following OA administration. Regarding the molecular mechanism of OA, the results indicated that mTOR and the antiapoptosis gene Bcl-2 were downregulated by OA. In addition, regulator genes of autophagy and apoptosis, including BAX, caspase-9, caspase-8, and caspase-3, were significantly upregulated by OA. Moreover, OA upregulated AMPK and its downstream proteins, including TSC2, BAX, Beclin 1, LC3B-II, and ULK1, to induce autophagy and apoptosis in CC cells. Conclusion. The findings from this study demonstrate that OA could effectively inhibit the proliferation and viability of CC cells. The anti-CC activity of OA is closely related to the activation of the AMPK-mTOR signaling pathway. Activation of AMPK and inhibition of mTOR are involved in the induction of autophagy and apoptosis by OA. OA induced autophagy and apoptosis mainly in an AMPK activation-dependent manner in CC cells.

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