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.

This meta-analysis assessed the clinical significance of omega-3 polyunsaturated fatty acids (PUFAs) in the management of patients with colorectal cancer (CRC) after radical resection. We comprehensively searched electronic databases, such as EMBASE, PubMed, MEDLINE and Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Database (CBM), Wanfang Electronic Database, and VIP Medical Information System (VIP) from inception to 10 April 2022. Randomized controlled trials (RCTs) of omega-3 PUFAs and conventional nutrition or blank treatments were selected. The following were evaluated in the pooled analysis: immune function-related indices (IgA, IgG, IgM, CD3+, CD4+, CD8+, and ratio of CD4+/CD8+), nutritional status-related indices [total protein (TP), albumin (ALB), and prealbumin (PA)], and their corresponding 95% confidence intervals (CIs). Next, we conducted heterogeneity detection, sensitivity analysis, contour-enhanced funnel plot to detect possible publication bias, and meta-regression analysis. In all, 20 studies, including 1,613 patients (809 in the omega-3 PUFAs group and 804 in the control group), were selected in the final analysis. The results of the pooled analysis showed that omega-3 PUFAs significantly increased the humoral immune function indices, including IgA [standardized mean difference (SMD) = 0.54, 95% CI 0.10–0.99], IgM (SMD = 0.52, 95% CI 0.05–0.99), IgG (SMD = 0.65, 95% CI 0.47–0.84); T cell immune function indices, including CD3+ (SMD = 0.73, 95% CI 0.54–0.92), CD4+ (SMD = 0.76, 95% CI 0.53–0.98), and ratio of CD4+/CD8+ (SMD = 0.66, 95% CI 0.39–0.92). However, CD8+ was markedly reduced after intervention of omega-3 PUFAs (SMD = –0.28, 95% CI –0.66–0.09). In addition, pooled analysis indicated that omega-3 PUFAs markedly improved the nutritional status indicators, including TP (SMD = 0.53, 95% CI 0.17–0.88), ALB (SMD = 0.43, 95% CI 0.15–0.70), and PA (SMD = 0.46, 95% CI 0.01–0.90). The meta-regression analysis revealed that the covariates of the small sample affected the robustness and credibility of the CD4+ results. Conclusively, this study suggested that omega-3 PUFAs have the potential to be used as a valid immunonutritional therapy/support for treating patients with CRC postoperatively. This meta-analysis protocol was registered in PROSPERO (no. CRD42021288487).Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021288487], identifier [CRD42021288487].

Purpose This study aimed to develop and validate a prognostic model for metastasis-free survival (MFS) based on genes that may functionally interact with cytotoxic T lymphocytes (CTLs) and M2 macrophages in patients with triple-negative breast cancer (TNBC) who underwent adjuvant radiotherapy.Methods The transcriptional pro les and phenotypical les of TNBC and other subtypes of breast cancer were downloaded from the Gene Expression Omnibus (GEO). The abundance of in ltrated immune cells was evaluated through CIBERSORTx or MCP-counter. A weighted linear model, the score for MFS (SMFS), was developed by using least absolute shrinkage and selection operator (LASSO) in GSE58812 and validated in GSE2034 and GSE12276. The biological implication of SMFS was explored by evaluating its associations with TNBC molecular subtypes and other radiosensitivity-or immune-related signatures.Results A model consisting of the gene expression ratios of PCDH12/ELP3, PCDH12/MSRA and FAM160B2/MSRA with nonzero coe cients nally selected by LASSO was developed in GSE58812. In GSE2034 (treatment with adjuvant radiotherapy), SMFS was signi cantly associated with MFS in TNBC patients (HR=8.767, 95% CI: 1.856-41.408, P=0.006) and, to a lesser extent, in non-TNBC patients (HR=2.888, 95% CI: 1.076-7.750, P=0.035). However, the interaction of subtype (TNBC vs non-TNBC) and SMFS tended to be signi cant (P interaction =0.081). In contrast, SMFS was not signi cantly associated with MFS in either TNBC patients (P=0.499) or non-TNBC patients (P=0.536) in GSE12276 (treatment without radiotherapy). Among the four TNBC molecular subtypes, the c1 and c4 subtypes exhibited higher CTL in ltration and lower SMFS values than the c2 and c3 subtypes. In addition, SMFS was positively correlated with the abundance of endothelial cells (r=0.413, P<0.001). ConclusionsThe proposed model has the potential to predict MFS in TNBC patients after adjuvant radiotherapy. SMFS may represent a measurement of tumor immune suppression.

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.