A lipid metabolism-related gene signature reveals dynamic immune infiltration of the colorectal adenoma-carcinoma sequence.

BACKGROUND: Lipid metabolism-related genes (LMRGs) have been reported to be correlated with the immune infiltration of colorectal cancer (CRC). This study aimed to investigate the immune infiltration characteristics along the colorectal adenoma-carcinoma sequence (ACS) based on LMRGs. METHODS: Gene expression data of colorectal adenoma and carcinoma samples were obtained from the public databases. The "limma" package was applied to determine the differentially expressed LMRGs. Unsupervised consensus clustering was used to cluster colorectal samples. The features of the tumor microenvironment were analyzed by the "ESTIMATE", "GSVA", and "TIDE" algorithms. RESULTS: The expression of 149 differentially expressed LMRGs was defined as the LMRG signature. Based on this signature, the adenoma and carcinoma samples were divided into three clusters. Unexpectedly, these sequential clusters showed a directional relationship and collectively constituted the progressive course of colorectal ACS. Interestingly, the LMRG signature revealed that adenoma progression was accompanied by a progressive loss of immune infiltration and a stepwise establishment of a cold microenvironment, but carcinoma progression was characterized by a progressive gain of immune infiltration and a gradual establishment of a hot microenvironment. CONCLUSIONS: The LMRG signature reveals dynamic immune infiltration along the colorectal ACS, which substantially changes the understanding of the tumor microenvironment of CRC carcinogenesis and provides novel insight into the role of lipid metabolism in this process.

Probiotics Improve Postoperative Adaptive Immunity in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.

There is no consensus on the effect of the probiotics on postoperative adaptive immunity in patients undergoing surgical resection for CRC. We aimed to systematically evaluate the effect of probiotics on postoperative adaptive immunity in perioperative CRC patients. The main end points were postoperative serum IgG, IgA, IgM, CD4+ T-cells, CD8+ T-cells and CD4+-to-CD8+ ratio. Meta-analysis was performed with a fixed or random effects model. We included six randomized controlled trials (RCTs) with 492 perioperative CRC patients. The use of enteral probiotics significantly increased the levels of peripheral blood IgG (MD: 1.33; 95% CI: 0.88 - 1.77; I2 = 41%), IgA (MD: 0.20; 95% CI: 0.10 - 0.30; I2 = 53%), IgM (MD: 0.18; 95% CI: 0.13 - 0.24; I2 = 41%), CD4+ T-cells (MD: 2.79; 95% CI: 2.34 - 3.24; I2 = 0) and CD4+-to-CD8+ ratio (MD: 0.09; 95% CI: 0.04 - 0.13; I2 = 7%). In conclusion, we report that the use of enteral probiotics improves postoperative humoral and cellular immunity in patients with CRC.

Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection.

OBJECTIVE: To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. DESIGN: We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues. RESULTS: Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients. CONCLUSIONS: GI tract may be a potential transmission route and target organ of SARS-CoV-2.

The association between dietary protein intake and colorectal cancer risk: a meta-analysis.

BACKGROUND: Association between dietary protein intake and colorectal cancer risk has not been fully quantified, while the results were controversial. This study aimed to evaluate the role of protein intake in the development of colorectal cancer. METHODS: PUBMED and EMBASE were searched up to December 2016. Two independent reviewers independently extracted data from eligible studies. Relative risk (RR) with 95% confidence intervals (CI) was pooled using random-effects model to estimate the result. Besides, publication bias and sensitivity analysis were conducted. RESULTS: Thirteen articles involving 21 studies comprising 8187 cases were included in this report. The pooled RR of colorectal cancer was 1.006 (95% CI = 0.857-1.179) indicating that there is no significant association between dietary protein intake and colorectal cancer risk. Furthermore, the pooled RRs for colon cancer and rectum cancer were 1.135(95% CI = 0.871-1.480) and 0.773(95% CI = 0.538-1.111), respectively, with the highest category of dietary protein intake. The association was not significant either in subgroup analysis of study design, protein type (animal protein or vegetable protein), sex, and or geographic locations. CONCLUSIONS: The present study indicated that the highest category compared to the lowest category of protein intake had no significant association on colorectal cancer risk. Dose-response analysis was not conducted due to limited information provided. Therefore, more studies with large cases and participants as well as detailed amounts of dietary protein intake are wanted to confirm this result.

Practical Experience of Endoscope Reprocessing and Working-Platform Disinfection in COVID-19 Patients: A Report from Guangdong China during the Pandemic.

BACKGROUND: No consensus exists regarding which procedures should be performed to disinfect endoscopes and working platforms after COVID-19 patients have undergone endoscopy. METHODS: We analyzed the disinfection quality of endoscopes and working platforms after 11 COVID-19 patients had undergone endoscopy. CONCLUSIONS: For endoscopic preprocessing at the bedside, a key disinfection step is using a multienzyme stock solution. The nucleic acid tests for endoscopists, washers, endoscopes, and working platforms were all negative. Based on our experience with the 11 COVID-19 patients who had undergone endoscopy, we provide an endoscopic reprocessing method for the bedside endoscopic diagnosis and treatment of COVID-19 patients for reference.

Analysis of Genes Involved in Ulcerative Colitis Activity and Tumorigenesis Through Systematic Mining of Gene Co-expression Networks.

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colon, characterized by continuous mucosal inflammation. Recently, some studies have considered it as part of an inflammatory bowel disease-based global network. Herein, with the aim of identifying the underlying potential genetic mechanisms involved in the development of UC, multiple algorithms for weighted correlation network analysis (WGCNA), principal component analysis (PCA), and linear models for microarray data algorithm (LIMMA) were used to identify the hub genes. The map of platelet activation, ligand-receptor interaction, calcium signaling pathway, and cAMP signaling pathway showed significant links with UC development, and the hub genes CCR7, CXCL10, CXCL9, IDO1, MMP9, and VCAM1, which are associated with immune dysregulation and tumorigenesis in biological function, were found by multiple powerful bioinformatics methods. Analysis of The Cancer Genome Atlas (TCGA) also showed that the low expression of CCR7, CXCL10, CXCL9, and MMP9 may be correlated with a poor prognosis of overall survival (OS) in colorectal cancer (CRC) patients (all p < 0.05), while no significance detected in both of IDO1 and VCAM1. In addition, low expression of CCR7, CXCL10, CXCL9, MMP9, and IDO1 may be associated with a poor prognosis in recurrence free survival (RFS) time (all p < 0.05), but no significant difference was identified in VCAM1. Moreover, the NFKB1, FLI1, and STAT1 with the highest enrichment score were detected as the master regulators of hub genes. In summary, these results indicated the central role of the hub genes of CCR7, CXCL10, CXCL9, IDO1, VCAM1, and MMP9, in response to UC progression, as well as the development of UC to CRC, thus shedding light on the molecular mechanisms involved and assisting with drug target validation.

Relative risk factors associated with the development of fundic gland polyps.

OBJECTIVES: The prevalence of fundic gland polyps (FGPs) is increasing. Some researchers consider this increase to be associated strongly with the long-term use of proton-pump inhibitors (PPIs); however, not all researchers share this belief. There are minimal data on the development of FGPs in China. Therefore, we aimed to investigate the prevalence of FGPs and risk factors associated with the development of this disease. MATERIALS AND METHODS: We studied 10 904 consecutive patients who underwent gastroduodenal endoscopies at our digestive endoscopy center between February 2011 and January 2013. Information on sex, age, Helicobacter pylori infection, PPIs intake, and the pathological results of the polyps were collected in the FGPs group and in the control group. The use of PPIs, sex, and H. pylori infection were statistically evaluated as dichotomous variables using a χ-test; age was evaluated as a continuous variable using a t-test. Finally, these factors were evaluated using a multiple logistic regression analysis. RESULTS: Gastric polyps were found in 759 (7.0%) patients, and 213 (2.0%) of these patients had FGPs. FGPs accounted for 28.1% of the gastric polyps. In the FGPs group, the percentage of H. pylori infection was 66.8% and the percentage of PPIs intake for at least 12 months was 23.1%. In the control group, the percentage of H. pylori infection was 77.4% and the percentage of PPIs intake for at least 12 months was 2.3%. The difference in the long-term use of PPIs was statistically significant between these two groups [χ=33.98, P<0.05, odds ratio (OR)=12.83, 95% confidence interval (CI): 4.47-36.80]. The results of the logistic regression were as follows: long-term use of PPIs (P<0.01, OR=14.11, 95% CI: 4.15-47.93); age (P<0.01, OR=1.69, 95% CI: 1.31-2.18). The P-values for sex and H. pylori infection were higher than 0.05. CONCLUSION: Age and the long-term use of PPIs were risk factors for the presence of FGPs; the long-term use of PPIs was a particularly strong risk factor.

[Effect of NK4 gene transfection on tumor growth of human pancreatic cancer xenograft in nude mice].

BACKGROUND & OBJECTIVE: NK4 is not only an antagonist of hepatocyte growth factor but also an angiogenesis inhibitor. Studies have confirmed that NK4 can inhibit tumor growth and metastasis, but its effect on pancreatic cancer remains unknown. This study was designed to observe the effect of NK4 gene on human pancreatic cancer in nude mice and the possible mechanisms. METHODS: The nude mouse model of pancreatic cancer was established with human pancreatic cancer cell line SW1990. The eukaryotic expression vector of NK4 gene was constructed and transfected into the tumors. The mice weight, tumor size and volume were measured before and after transfection. The apoptotic cells, microvessel density (MVD), and the expression of proliferating cell nuclear antigen (PCNA) in the tumors were observed using immunohistochemistry and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique. RESULTS: Four weeks after NK4 gene transfection, the tumor volume and weight was significantly smaller in NK4-transfected group than in PBS control group and empty vector group [(1.39+/-0.33) cm(3) vs. (2.06+/-0.55) cm(3) and (1.90+/-0.36) cm(3), P<0.01; (1.30+/-0.81) g vs. (3.45+/-1.88) g and (3.14+/-1.51) g, P<0.01]; the inhibition rate was 62.29%. The tumor cell apoptotic index was significantly higher in NK4-transfected group than in the rest 2 groups (9.34+/-0.91 vs. 4.13+/-0.79 and 3.94+/-1.03, P<0.001); the MVD was significantly lower in NK4-transfected group than in the rest 2 groups (12.24+/-4.63 vs. 20.13+/-7.00 and 19.70+/-6.15, P<0.05); the expression of PCNA in NK4-transfected group was not different from those of the rest 2 groups (53.88+/-4.30 vs. 56.24+/-4.03 and 54.33+/-5.41,P>0.05). CONCLUSION: NK4 gene transfection may inhibit the growth of human pancreatic cancer in mouse model through suppressing angiogenesis and enhancing the apoptosis of pancreatic cancer cells.

[Effect of transferred NK4 gene on biological characteristics of human pancreatic cancer cell line SW1990].

BACKGROUND & OBJECTIVE: Hepatocyte growth factor (HGF) plays an important role in the regulation of migration, invasion,and angiogenesis of cancer via the activation of its receptor, c-Met. NK4 is not only an antagonist of HGF but also an angiogenesis inhibitor. The blockade of HGF/c-Met signal pathway and tumor angiogenesis may be a new strategy for cancer treatment. This study was designed to construct eukaryotic expressing vector of NK4 gene, transfer it into human pancreatic cancer cell line SW1990, and observe the effect of transfected NK4 gene on the biological behaviors of SW1990 cells,and its expression in SW1990 cells. METHODS: The recombinant of pcDNA3/hNK4 plasmid was digested by restrictive enzyme,NK4 gene was cloned into a high effective eukaryotic expressing vector pRC/CMV2, and the recombinant of pRC/CMV2-hNK4 plasmid was transiently introduced into SW1990 cells by lipofectamine. Reverse transcriptase-polymerase chain reaction (RT-PCR),and Western blot were used to detect the expression of NK4 at mRNA, and protein levels,respectively. Migration, and invasion capabilities of the transfected cells were evaluated by Transwall chamber, and Matrigel invasion chamber, respectively. RESULTS: Expressions of NK4 gene after lipofectamine mediated transfection were observed in SW1990 cells, expected fragment of 453 bp has been amplified by RT-PCR, and Western blot analysis showed positive expression of NK4 protein (50 KDa). NK4 gene had no inhibitory effect on the growth of SW1990 cells (2.2x10(5) vs 2.5x10(5), P >0.05), while it had significantly suppressive effect on the migration and invasion of SW1990 cells driven by HGF or fibroblasts (P< 0.01). CONCLUSION: NK4 gene transfection may inhibit spreading and invasion of pancreatic cancer cells, which would play an important role in the anti-metastasis therapy for pancreatic cancer.