The gut barrier of the rats was seriously damaged at the early phase of ischemic reperfusion injury after hemorrhagic shock, which included the injury and atrophy in intestinal mucosa and the increasing of intestinal permeability. Simultaneously, the intestinal mucosa also showed its great repairing potentiality, such as the improvement of the intestinal permeability and the recovery of the morphology at different phases after ischemic reperfusion injury. The restitution of gut barrier function was obviously slower than that of the morphology and there was no direct correlation between them. Compared with the small intestine, the large intestine had stronger potentiality against injury. The reduction of the amount of intestinal goblet cells by injury did not influence the ability of intestinal mucosal restitution at a certain extent and it appeared to be intimately involved in the restitution of the epithelium.

No abstract

Tumor mutation burden (TMB) is a useful biomarker to predict prognosis and the efficacy of immune checkpoint inhibitors (ICIs). In this study, we aimed to explore the prognostic value of TMB and the potential association between TMB and immune infiltration in lower-grade gliomas (LGGs). Somatic mutation and RNA-sequencing (RNA-seq) data were downloaded from the Cancer Genome Atlas (TCGA) database. TMB was calculated and patients were divided into high- and low-TMB groups. After performing differential analysis between high- and low-risk groups, we identified six hub TMB and immune-related genes that were correlated with overall survival in LGGs. Then, Gene Set Enrichment Analysis was performed to screen significantly enriched GO terms between the two groups. Moreover, an immune-related risk score system was developed by LASSO Cox analysis based on the six hub genes and was validated with the Chinese Glioma Genome Atlas dataset. Using the TIMER database, we further systematically analyzed the relationships between mutants of the six hub genes and immune infiltration levels, as well as the relationships between the immune-related risk score system and the immune microenvironment in LGGs. The results showed that TMB was negatively correlated with OS and high TMB might inhibit immune infiltration in LGGs. Furthermore, the risk score system could effectively stratify patients into low- and high-risk groups in both the training and validation datasets. Multivariate Cox analysis demonstrated that TMB was not an independent prognostic factor, but the risk score was. Higher infiltration of immune cells (B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells) and higher levels of immune checkpoints (PD-1, CTLA-4, LAG-3, and TIM-3) were found in patients in the high-risk group. Finally, a novel nomogram model was constructed and evaluated to estimate the overall survival of LGG patients. In summary, our study provided new insights into immune infiltration in the tumor microenvironment and immunotherapies for LGGs.

Ovarian cancer is one of the most threatening diseases among women in the world. Current detection methods are expensive and lack accuracy. Thus, a fast, non-invasive biomarker for detecting ovarian cancer is urgently needed. Compelling evidences have been demonstrated that microRNAs, a large family of single-stranded and non-protein-coding RNA molecules, can serve as useful biomarkers in cancer detection. In this study, the relative expressions of microRNA-145 (miR-145) in the serum of patients with ovarian cancer and healthy controls were investigated in an independent study. Subsequently, the diagnosis and prognosis value of miR-145 as a biomarker for ovarian cancer were examined. Furthermore, we performed a meta-analysis to summarize all the results from published studies and this study. Relative expressions of miR-145 were investigated in three independent groups (malignant ovarian cancer, benign ovarian tumor, and healthy controls), comprising a total of 270 participants. Receiver operating characteristic (ROC) curves and overall survival (OS) curves were conducted to compare miR-145 level and clinical characteristics among the three groups. The results showed that relative expressions of the serum miR-145 were significantly down-regulated in patients with malignant ovarian cancer and benign ovarian cancer, compared to healthy controls (P < 0.01). Serum miR-145 levels could discriminate patients with malignant ovarian cancer from healthy controls, with a power area under the curve (AUC) of 0.82 (95 % confidence interval (CI) = 0.77-0.88). Furthermore, patients with low serum levels of miR-145 had a significantly shorter median overall survival rate (hazard ratio (HR) = 1.81, 95 % CI = 1.03-3.17, P = 0.039). The meta-analysis yields good diagnostic performances of miR-145 in various cancers, with an AUC of 0.82 (95 % CI, 0.78-0.85). In conclusion, the present study suggested that miR-145 can potentially serve as an outstanding biomarker for ovarian and other human cancers detection.

Dysfunction of microRNAs (miRNAs) is strongly proved to participate in the pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-944 was reported to play either oncogenic or tumor suppressive roles in human cancers. A recent study reported that the levels of miR-944 in recurrent CRC patients were evidently lower than that in non-recurrent cases, suggesting that miR-944 may function as a tumor suppressive miRNA in CRC. Yet, the clinical value and biological function of miR-944 remain rarely known in CRC. In the present study, we present that miR-944 level in CRC tissues is notably reduced compared to matched non-cancerous specimens. Its decreased level is evidently correlated with malignant clinical parameters and poor prognosis of CRC patients. Accordingly, the levels of miR-944 were obviously downregulated in CRC cells. Ectopic expression of miR-944 in CRC cells prominently inhibits the migration and invasion of tumor cells, while miR-944 knockdown increased these effects of CRC cells. Mechanically, miR-944 negatively regulated the metastasis-associated in colon cancer-1 (MACC1) abundance in CRC cells. Herein, MACC1 was found to be a downstream molecule of miR-944 in CRC. An inversely correlation between miR-944 and MACC1 was confirmed in CRC specimens. Furthermore, restoration of MACC1 expression could abrogate the anti-metastatic effects of miR-944 on CRC cells with enhanced cell migration and invasion. MACC1/Met/AKT signaling may be implicated with the function of miR-944 in CRC cells. Altogether, miR-944 potentially act as a prognostic predictor and a drug-target for CRC patients.