The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis.

Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has the highest incidence of malignant tumors in the digestive system. We performed a two-sample Mendelian randomization analysis to explore the associations between 19 metabolism-related lifestyle and clinical risk factors and DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, and pancreatic cancer. The causal association was explored for all combinations of each risk factor and each DSC. We gathered information on the instrumental variables (IVs) from various sources and retrieved outcome information from Biobank Japan (BBJ). The data were all from studies of east Asian populations. Finally, 17,572 DSCs cases and 195,745 controls were included. Our analysis found that genetically predicted alcohol drinking was a strong indicator of gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93-0.98) and hepatocellular carcinoma (OR = 1.11; 95% CI: 1.05-1.18), whereas coffee consumption had a potential protective effect on hepatocellular carcinoma (OR = 0.69; 95% CI: 0.53-0.90). Triglyceride was potentially associated with a decreased risk of biliary tract cancer (OR = 0.53; 95% CI: 0.34-0.81), and uric acid was associated with pancreatic cancer risk (OR = 0.59; 95% CI: 0.37-0.96). Metabolic syndrome (MetS) was associated with esophageal and gastric cancer. Additionally, there was no evidence for a causal association between other risk factors, including body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total cholesterol, glycine, creatinine, gout, and Graves' disease, and DSCs. The leave-one-out analysis revealed that the single nucleotide polymorphism (SNP) rs671 from the ALDH2 gene has a disproportionately high contribution to the causal association between alcohol drinking and gastric cancer and hepatocellular carcinoma, as well as the association between coffee consumption and hepatocellular carcinoma. The present study revealed multiple metabolism-related lifestyle and clinical risk factors and a valuable SNP rs671 for DSCs, highlighting the significance of metabolic factors in both the prevention and treatment of DSCs.

Mitochondrial DNA copy number and cancer risks: A comprehensive Mendelian randomization analysis.

Mitochondrial DNA plays a critical role in the pathophysiology of cancer. However, the associations between mitochondrial DNA copy number (mtDNA-CN) and cancer risk are controversial. Mendelian randomization (MR) analyses were performed using three independent instrumental variables (IVs) to explore potential associations between mtDNA-CN and 20 types of cancer. The three sets of IVs were primarily obtained from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium using different methods. The outcome data of cancers were investigated using summary statistics from the FinnGen cohort. The potential causal associations were evaluated using the MR-Egger regression, weighted median, inverse-variance weighted (IVW), and weighted mode methods. The robustness of IVW estimates was validated using leave-one-out sensitivity analysis. Additionally, a meta-analysis was conducted to pool results from three sets of IVs. The results revealed that genetically predicted mtDNA-CN was not associated with cancer risk (odds ratio = 1.02; 95% confidence interval: 0.95-1.10). Subgroup analyses indicated no causal association between mtDNA-CN and breast, lung, prostate, skin, colorectal, gastric, liver, cervical uteri, esophageal, thyroid, bladder, pancreas, kidney, corpus uteri, ovary, brain, larynx, and anus cancers. It was observed that mtDNA-CN was associated with lip, oral cavity, and testis cancers. However, these results should be interpreted with caution because a small number of patients with lip and oral cavity or testis cancers were included. The comprehensive MR analysis demonstrated that mtDNA-CN is not a suitable biomarker for tumor risk assessment.

Mitochondrial DNA copy number is associated with Crohn's disease: a comprehensive Mendelian randomization analysis.

Mitochondrial DNA plays a critical role in the pathophysiological process of inflammation. However, the relationship between mitochondrial DNA copy number (mtDNA-CN) and inflammatory bowel diseases (IBD) remains poorly understood. We conducted a comprehensive Mendelian randomization (MR) using three instrumental variables (IVs) to explore the causal associations between mtDNA-CN and IBD, including Crohn's disease (CD), ulcerative colitis (UC). MR-Egger regression, weighted median, inverse-variance weighted (IVW), and weighted mode methods were used to evaluate the potential causal associations. The robustness of the IVW estimates was determined using the leave-one-out sensitivity test. A meta-analysis was conducted to pool the results from the three sets of IVs. Upon analysis, the findings of the current study revealed that genetically predicted mtDNA-CN was not associated with IBD (CD + UC) and UC. The results of MR analyses between mtDNA-CN and CD risk were inconsistent by using three sets of IVs. After a meta-analysis, we found that genetically predicted mtDNA-CN was associated with CD risk (odds ratio = 2.09; 95% confidence interval: 1.37-3.18). This finding was also confirmed by multivariable MR analyses and remained robust when tested with the leave-one-out sensitivity test. In conclusion, genetically predicted mtDNA-CN was found to be associated with CD risk. Therefore, mtDNA levels in the blood could potentially be used as a marker for CD risk assessment. Further studies are needed to elucidate the underlying mechanisms and validate the results of this study.

LncRNA expression signature identified using genome-wide transcriptomic profiling to predict lymph node metastasis in patients with stage T1 and T2 gastric cancer.

BACKGROUND: Lymph node (LN) status is vital to evaluate the curative potential of relatively early gastric cancer (GC; T1-T2) treatment (endoscopic or surgery). Currently, there is a lack of robust and convenient methods to identify LN metastasis before therapeutic decision-making. METHODS: Genome-wide expression profiles of long noncoding RNA (lncRNA) in primary T1 gastric cancer data from The Cancer Genome Atlas (TCGA) was used to identify lncRNA expression signature capable of detecting LN metastasis of GC and establish a 10-lncRNA risk-prediction model based on deep learning. The performance of the lncRNA panel in diagnosing LN metastasis was evaluated both in silico and clinical validation methods. In silico validation was conducted using TCGA and Asian Cancer Research Group (ACRG) datasets. Clinical validation was performed on T1 and T2 patients, and the panel's efficacy was compared with that of traditional tumor markers and computed tomography (CT) scans. RESULTS: Profiling of genome-wide RNA expression identified a panel of lncRNA to predict LN metastasis in T1 stage gastric cancer (AUC = 0.961). A 10-lncRNA risk-prediction model was then constructed, which was validated successfully in T1 and T2 datasets (TCGA, AUC = 0.852; ACRG, AUC = 0.834). Thereafter, the clinical performance of the lncRNA panel was validated in clinical cohorts (T1, AUC = 0.812; T2, AUC = 0.805; T1 + T2, AUC = 0.764). Notably, the panel demonstrated significantly better performance compared with CT and traditional tumor markers. CONCLUSIONS: The novel 10-lncRNA could diagnose LN metastasis robustly in relatively early gastric cancer (T1-T2), with promising clinical potential.

Development and validation of metabolic models for predicting survival and immune status of hepatocellular carcinoma patients.

BACKGROUND: Metabolic reprogramming is associated with the carcinogenesis of hepatocellular carcinoma (HCC). The effects of metabolism-related genes on predicting survival and immune status in HCC remain unclear. OBJECTIVES: To develop and validate metabolic models for predicting the survival and immune status of HCC patients. MATERIAL AND METHODS: The metabolic core genes for overall survival (OS) and disease-free survival (DFS) were retrieved. Then, glycolysis and fatty acid metabolism prognostic models were constructed and validated using The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) data. Decision trees based on machine learning were developed for classifying the prognostic risks of HCC patients. The associations between the metabolic signatures, immunotherapy and immune cell infiltration were investigated. Experimental validations were performed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). RESULTS: We identified 30 prognostic core genes for glycolysis metabolism and 12 prognostic core genes for fatty acid metabolism. Subsequently, 2 glycolysis models and 2 fatty acid metabolism models were developed to predict the OS and DFS of HCC patients, respectively. Two decision trees were constructed to classify the low-, intermediateand high-risk groups of HCC patients for OS and DFS. Moreover, the patients in the high-risk groups of glycolysis and fatty acid metabolic models tended to have higher expression of programmed cell death ligand-1 (PD-L1 or CD274), programmed cell death 1 (PDCD1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), and lymphocyte activating 3 (LAG3). Most of the metabolic core genes were significantly associated with immune cell infiltration. In addition, ATP-binding cassette subfamily B member 6 (ABCB6), peptidylprolyl isomerase A (PPIA), uroporphyrinogen decarboxylase (UROD), and non-SMC condensin II complex subunit H2 (NCAPH2) were positively correlated with both tumor mutational burden (TMB) and microsatellite instability (MSI) scores. The expression of ABCB6, PPIA, UROD, and NCAPH2 was validated using RT-qPCR and IHC. CONCLUSIONS: We established novel prognostic models based on metabolism-related genes to better predict the outcome and immune status of HCC patients.

N6-methyladenosine modification and metabolic reprogramming of digestive system malignancies.

N6-methyladenosine (m6A) is a eukaryotic post-transcriptional modification involved in cell growth and developmental processes, including RNA transcription, alternative splicing, degradation, and translation. It is also involved in the development of various cancers. Metabolic reprogramming enables cancer cells to obtain nutrition from the tumor microenvironment, which is a hallmark of cancer. Numerous studies have shown that m6A modification induces metabolic reprogramming in cancer by regulating the expression of metabolic core genes or activation of metabolic signaling pathways. Digestive system malignancies include esophageal, gastric, colorectal, liver, pancreatic, and other cancers, all of which are associated with poor outcomes. This review summarizes the role of m6A modification in the metabolic reprogramming of digestive system malignancies, with the aim of identifying therapeutic strategies.

Effects of aquatic nitrogen pollution on particle-attached ammonia-oxidizing bacteria in urban freshwater mesocosms.

Ammonia-oxidizing bacteria (AOB) attached to aquatic particles are important participants in ammonia oxidation within hypereutrophic urban river systems. To explore the effects of aquatic nitrogen pollution on particle-attached AOB in urban river, we utilized laboratory mesocosms to investigate the responses of abundances and community structure of particle-attached AOB to ammonium (NH4+) and glycine (C2H5NO2) amendments. The abundance and community structure of particle-attached AOB were determined with quantitative real-time polymerase chain reaction (qRT-PCR) analysis and high-throughput sequencing based on the AOB amoA gene, respectively. Most of the bacterial amoA sequences from different treatments were affiliated with uncultured Nitrosomonadaceae bacterium, uncultured Nitrosomonadales bacterium, and uncultured Nitrosomonas sp., which are closely associated with organic pollution. The species richness and diversity of particle-attached AOB communities increased with increasing NH4+ and glycine concentrations. Treatment effects contributed significantly to the variance in particle-attached AOB communities. Although, glycine was completely transformed to ammonium within a few days and ammonium amendments would change the community structure of particle-attached AOB, the effect of glycine on the particle-attached AOB community was regulated by both the resulting ammonium concentration, as well as organic matter availability to the heterotrophic bacteria. Results suggested that high anthropogenic nitrogen loadings appeared to promote higher particle-attached AOB richness and diversity in the hypereutrophic urban river, but the effect of organic nitrogen on the particle-attached AOB community was different from the effect of inorganic nitrogen. This study informs ammonia oxidization mechanisms in the hypereutrophic urban rivers, which contributes to remediation/restoration strategies.

Single-Incision Laparoscopic Intragastric Surgery for Gastric Submucosal Tumors Located Near the Esophagogastric Junction.

Background: Laparoscopic local resection of the stomach for gastric submucosal tumors (SMTs) is widely accepted by surgeons. For SMTs located near the esophagogastric junction (EGJ), simple laparoscopic wedge resection is rarely performed owing to concerns of causing cardia deformities or stenosis. Single-incision laparoscopic intragastric surgery (sLIGS) has been used to treat SMTs located near the EGJ in carefully selected cases. Methods: We modified sLIGS using a subxiphoid incision. Thirteen consecutive patients with intraluminal or intramural growth type gastric SMTs located near the EGJ underwent sLIGS at our institution from July 2018 to April 2020. Results: Thirteen operations were successfully performed using sLIGS, including eight full-thickness resections and five submucosal resections. There were no conversions to an open procedure and all tumors were confirmed to have negative margins on pathology. The mean operation time was 100 ± 10 minutes (range, 85-160 minutes). The mean blood loss was 50 ± 10 mL (range, 50-100 mL). The mean length of postoperative hospital stay was 7 ± 1.5 days (6-10 days). One patient was found to have oozing of blood confirmed by gastroscopy postoperatively and recovered after stopping antiplatelet therapy. Ten cases were gastrointestinal stromal tumor (GIST), two cases were leiomyoma, and one case was neuroendocrine neoplasm. Of the 10 GISTs, 9 were classified as low risk; 1 showed medium risk and the patient received adjuvant imatinib therapy. There were no tumor recurrences during a mean follow-up of 14 ± 4 months (range, 5-25 months). Conclusions: This modified sLIGS for the treatment of the gastric SMTs located near the EGJ is simple and safe. This can be used as an alternative treatment for gastric SMTs near the EGJ.

Activation of YAP1 by N6-Methyladenosine-Modified circCPSF6 Drives Malignancy in Hepatocellular Carcinoma.

Circular RNAs (circRNA) and N6-methyladenosine (m6A) modification are extensively involved in the progression of diverse tumors, including hepatocellular carcinoma (HCC). However, the cross-talk between circRNAs and m6A remains elusive in the pathogenesis of HCC. Here we investigated m6A-mediated regulation of circRNAs in HCC. m6A-related circRNAs were identified by integrating information from two published studies, revealing circular cleavage and polyadenylation specific factor 6 (circCPSF6) as a novel m6A-modified circRNA. circCPSF6 was dominated by ALKBH5-mediated demethylation, followed by the recognization and destabilization by YTHDF2. Meanwhile, circCPSF6 was upregulated in HCC specimens, and elevated circCPSF6 expression served as an independent prognostic factor for worse survival of patients with HCC. Loss-of-function assays demonstrated that circCPSF6 maintained cell proliferation and tumorigenicity and reinforced cell motility and tumor metastasis. circCPSF6 triggered expression of YAP1, further activating its downstream cascade. Mechanistically, circCPSF6 competitively bound PCBP2, blunting its binding to YAP1 mRNA, thereby sustaining the stability of YAP1. Functionally, removal of YAP1 reversed the effects of circCPSF6 in vitro and in vivo. Aberrant activation of the circCPSF6-YAP1 axis promoted HCC malignancy. These findings offer novel insights into the regulation of circRNAs by m6A modifications and the role of this epigenetic reprogramming in HCC. SIGNIFICANCE: This study advances the understanding of the interplay between m6A methylation and circRNAs in hepatocellular carcinoma, highlighting the potential of circCPSF6 as a therapeutic target.

RBM15 promotes hepatocellular carcinoma progression by regulating N6-methyladenosine modification of YES1 mRNA in an IGF2BP1-dependent manner.

The function of the N6-methyladenosine (m6A) methyltransferase RNA-binding motif protein 15 (RBM15) in hepatocellular carcinoma (HCC) has not been thoroughly investigated. Here we determined the clinical value, biological functions, and potential mechanisms of RBM15 in HCC. Expression of RBM15 was identified using tissue microarrays and online databases. A risk-prediction model based on RBM15 was developed and validated. We determined the biological role of RBM15 on HCC cells in vitro and in vivo. RNA sequencing was used to screen candidate targets of RBM15. Subsequently, the m6A dot blot assay, methylated RNA immunoprecipitation qPCR, dual-luciferase reporter assays, RNA decay assay, and RNA immunoprecipitation qPCR were employed to explore the mechanisms of RBM15. Our study showed that RBM15 was highly expressed in HCC, and overexpression of RBM15 indicated a worse outcome. A new nomogram combining RBM15 with age and TNM stage was developed and validated to predict the outcome of HCC patients; our nomogram increased the prediction accuracy of the TNM system. Functionally, RBM15 facilitates the proliferation and invasiveness of HCC. RBM15-mediated m6A modification contributed to a post-transcriptional activation of YES proto-oncogene 1 (YES1) in an insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)-dependent manner. In addition, YES1 was confirmed as an oncogene in HCC cells by activating the mitogen-activated protein kinase (MAPK) pathway. In conclusion, RBM15-mediated m6A modification might facilitate the progression of HCC via the IGF2BP1-YES1-MAPK axis. RBM15 may be a promising biomarker in the outcome prediction of HCC.

Vitamins and Helicobacter pylori: An Updated Comprehensive Meta-Analysis and Systematic Review.

BACKGROUND: Over recent decades, epidemiological studies have shown relationships between vitamins and Helicobacter pylori (H. pylori) infection and eradication, but the results are controversial. METHODS: A comprehensive meta-analysis and systematic review were conducted to clarify the relationships between common types of vitamins and H. pylori. We applied meta-regression, subgroup analysis and sensitivity analysis to obtain available evidence. Articles published from January 1991 to June 2021 in PubMed, EMBASE, and the Cochrane Library were searched. RESULTS: In total, we identified 48 studies. The results indicate that H. pylori -positive patients had lower serum vitamin B12 [standardized mean difference (SMD) = -0.30; 95% confidence interval (CI): -0.53 - -0.08], folate (SMD = -0.69; 95% CI: -1.34 - -0.04), vitamin C (SMD = -0.37; 95%CI: -0.57 - -0.18) and vitamin D (SMD = -0.34; 95% CI: -0.49 - -0.18) levels than H. pylori-negative patients. Patients in which H. pylori had been successfully eradicated had higher serum vitamin D levels (SMD = 1.37; 95% CI: 0.37-2.38) than in patients in which eradication had been unsuccessful. The serum vitamin B12 levels of H. pylori-positive patients improved after successful H. pylori eradication therapy (SMD = 1.85; 95% CI: 0.81-2.90), and antioxidant vitamin supplementation to an H. pylori eradication regimen improved the eradication rate (risk ratio = 1.22; 95% CI: 1.02-1.44 for per-protocol analysis; risk ratio = 1.25; 95% CI: 1.06-1.47 for intention-to-treat analysis). CONCLUSIONS: H. pylori infections decrease the serum levels of several types of vitamins, eradication of H. pylori could rescue its adverse effects, and antioxidant vitamin supplementation may improve the H. pylori eradication rate. SYSTEMATIC REVIEW REGISTRATION: identifier: CRD42021268127.

Influence of a biofilm bioreactor on water quality and microbial communities in a hypereutrophic urban river.

Biofilms play an important role in degradation, transformation and assimilation of anthropogenic pollutants in aquatic ecosystems. In this study, we assembled a tubular bioreactor containing a biofilm substrate and aeration device, which was introduced into mesocosms to explore the effects of bioreactor on physicochemical and microbial characteristics of a hypereutrophic urban river. The biofilm bioreactor greatly improved water quality, especially by decreasing dissolved inorganic nitrogen (DIN) concentrations, suggesting that biofilms were the major sites of nitrification and denitrification with an oxygen concentration gradient. The biofilm bioreactor increased the abundance of planktonic bacteria, whereas diversity of the planktonic microbial community decreased. Sequencing revealed that Proteobacteria, Bacteroidetes, Planctomycetes, and Actinobacteria were the four predominant phyla in the planktonic microbial community, and the presence of the biofilm bioreactor increased the relative abundance of Proteobacteria. Variations in microbial communities were most strongly affected by the presence of the biofilm bioreactor, as indicated by principal component analysis (PCA) and redundancy analysis (RDA). This study provides valuable insights into changes in ecological characteristics associated with self-purification processes in hypereutrophic urban rivers, and may be of important for the application of biofilm bioreactor in natural urban river.

Low-residue versus clear liquid diet before colonoscopy: An updated meta-analysis of randomized, controlled trials.

Great value in the early identification and treatment of adenomatous polyps or early canceration using colonoscopy has been recognized. A clear colonoscopic vision brought by good intestinal preparation will become crucial. Several studies have completed using the low-residue diet (LRD) versus a clear liquid diet (CLD) the day before colonoscopy that presenting contradictory results. Therefore, a more comprehensive and updated meta-analysis is needed to summarize the findings on the effects of LRD and CLD on intestinal preparation and the quality of coloscopy.The comprehensive search was performed in PubMed/MEDLINE, Scopus, Cochrane databases (February 2020). LRD vs CLD before colonoscopy were included in this study. Mantel-Haenszel or DerSimonian and Laird models with the relative risk (RR) to evaluate differences in intestinal preparation, tolerance, readiness to repeat preparation, detected of a polyp, and overall adverse reactions.Total 16 studies (N = 3413) were eligible. Patients with LRD compared with CLD indicated significantly better of tolerability (RR 0.92;95% CI,0.85-0.99; P < .05) and willingness to repeat intestinal preparation (RR 0.86; 95% CI 0.79-0.93; P < .05), but no differences with adequate intestinal preparations, detected polyp or overall adverse reactions (all P > .05).Patients with LRD the day before colonoscopy show better tolerance and willingness to repeat intestinal preparation, and no difference with adequate intestinal preparations compared with CLD, but the recommended level of evidence is weak. However, in terms of the detection rate of intestinal adenomas, the LRD group is not weaker than the CLD group, for its evidence level is high, and can significantly reduce the hunger experience of patients.

Hypoxia induces sorafenib resistance mediated by autophagy via activating FOXO3a in hepatocellular carcinoma.

Sorafenib, a multikinase inhibitor, is considered as the only approved drug to cure the advanced hepatocellular carcinoma (HCC); however, the acquired chemoresistance caused by intratumoral hypoxia through sorafenib long term therapy induces sorafenib inefficacy. We demonstrated here that hypoxia significantly attenuated sensitivity of HCC cells to sorafenib treatment and reduced its proliferation. Autophagy was observed in sorafenib-treated HCC cells in hypoxia, and inhibition of autophagy by 3-MA eliminated hypoxia-induced sorafenib resistance. Further study revealed hypoxia-activated FOXO3a, an important cellular stress transcriptional factor, via inducing its dephosphorylation and nuclear location; and FOXO3a-dependent transcriptive activation of beclin-1 was responsible for hypoxia-induced autophagy in HCC cells. Knockout of FOXO3a inhibited the autophagy induced by sorafenib itself in normoxia and significantly enhanced the cytotoxicity of sorafenib in HCC cells; and it also inhibited the hypoxia-induced autophagy and achieved the same effect in sorafenib sensitivity-enhancement in HCC cells as it in normoxia. Finally, knockout of intratumoral FOXO3a significantly enhanced curative efficacy of sorafenib via inhibition of autophagy in xenograft tumors in nude mice. Collectively, our study suggests that FOXO3a plays a key role in regulating hypoxia-induced autophagy in sorafenib-treated HCC, and FOXO3-targeted therapy may serve as a promising approach to improve clinical prognosis of patients suffering from HCC.

High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma.

Exosomes play an important role in intercellular communication and metastatic progression of hepatocellular carcinoma (HCC). However, cellular communication between heterogeneous HCC cells with different metastatic potentials and the resultant cancer progression are not fully understood in HCC. Here, HCC cells with high-metastatic capacity (97hm and Huhm) were constructed by continually exerting selective pressure on primary HCC cells (MHCC-97H and Huh7). Through performing exosomal miRNA sequencing in HCC cells with different metastatic potentials (MHCC-97H and 97hm), many significantly different miRNA candidates were found. Among these miRNAs, miR-92a-3p was the most abundant miRNA in the exosomes of highly metastatic HCC cells. Exosomal miR92a-3p was also found enriched in the plasma of HCC patient-derived xenograft mice (PDX) model with high-metastatic potential. Exosomal miR-92a-3p promotes epithelial-mesenchymal transition (EMT) in recipient cancer cells via targeting PTEN and regulating its downstream Akt/Snail signaling. Furthermore, through mRNA sequencing in HCC cells with different metastatic potentials and predicting potential transcription factors of miR92a-3p, upregulated transcript factors E2F1 and c-Myc were found in high-metastatic HCC cells promote the expression of cellular and exosomal miR-92a-3p in HCC by directly binding the promoter of its host gene, miR17HG. Clinical data showed that a high plasma exosomal miR92a-3p level was correlated with shortened overall survival and disease-free survival, indicating poor prognosis in HCC patients. In conclusion, hepatoma-derived exosomal miR92a-3p plays a critical role in the EMT progression and promoting metastasis by inhibiting PTEN and activating Akt/Snail signaling. Exosomal miR92a-3p is a potential predictive biomarker for HCC metastasis, and this may provoke the development of novel therapeutic and preventing strategies against metastasis of HCC.

Endoscopic or laparoscopic resection for small gastrointestinal stromal tumors: a cumulative meta-analysis.

BACKGROUND: Despite the recent large number of studies comparing endoscopic and laparoscopic resection for small gastrointestinal stromal tumors (GISTs) (diameter ≤ 5 cm), the results remain conflicting. The objective of this work was to perform a cumulative meta-analysis to assess the advantages and disadvantages of endoscopic resection vs. laparoscopic resection. METHODS: The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched medical databases up to January 2020. Meta-analytical random or fixed effects models were used in pooled analyses. Meta-regression, cumulative meta-analyses, and subgroup analyses were performed to improve the accuracy of the conclusion. Sensitivity analyses were applied to assess the robustness of the results. RESULTS: A total of 12 cohort studies with 1383 participants comparing endoscopic resection and laparoscopic resection were identified, while three cohort studies with 167 participants comparing endoscopic resection and laparoscopic and endoscopic cooperative surgery were found. We found that endoscopic resection had shorter operation times (weighted mean difference [WMD] = -27.1 min, 95% confidence interval [CI]: -40.8 min to -13.4 min) and lengths of hospital stay (WMD = -1.43 d, 95% CI: -2.31 d to -0.56 d) than did laparoscopic resection. The results were stable and reliable. There were no significant differences in terms of blood loss, hospitalization costs, incidence of complications or recurrence rates. For tumor sizes 2 - 5 cm, endoscopic resection increased the risk of positive margins (relative risk [RR] = 5.78, 95% CI: 1.31 - 25.46). Although operation times for endoscopic resection were shorter than those of laparoscopic and endoscopic cooperative surgery (WMD = -41.03 min, 95% CI: -59.53 min to -22.54 min), there was a higher incidence of complications (RR = 4.03, 95% CI: 1.57 - 10.34). CONCLUSIONS: In general, endoscopic resection is an alternative method for gastric GISTs ≤ 5 cm. Laparoscopic and endoscopic cooperative surgery may work well in combination. Further randomized controlled trials are recommended to validate or update these results.

Delayed gastric emptying after Pancreaticoduodenectomy: a propensity score-matched analysis and clinical Nomogram study.

BACKGROUND: Delayed gastric emptying (DGE) is a common and frustrating complication of pancreaticoduodenectomy (PD). Studies suggest that surgical methods and other clinical characteristics may affect the occurrence of DGE. Nevertheless, the results of such studies are conflicting. The objective of this work was to perform a propensity score matching analysis to compare the differences between pylorus-preserving pancreaticoduodenectomy (PPPD) and pylorus-removing pancreaticoduodenectomy (PrPD) and to develop and validate a nomogram to predict the probability of severe DGE (SDGE). METHODS: This retrospective study enrolled patients who underwent PD at our institution from December 2009 to December 2018. Propensity score matching was applied at a ratio of 1:1 to compare PPPD and PrPD groups. We compared incidence of complications, DGE, lengths of hospital stay, hospitalization costs, and mortality. Univariate and multivariate logistic regression analysis were performed to identify potential risk factors of severe DGE. Finally, a nomogram was developed and validated to predict severe DGE. RESULTS: The PPPD group had a significantly higher rate of postoperative pancreatic fistula (29.9% versus 17.4%, P < 0.05) and less blood loss (463.7 ml versus 694.9 ml, P < 0.05). After propensity score matching, the PPPD group had a significantly higher rate of postoperative DGE (19.2% versus 3.8%, P < 0.05), especially severe DGE (17.3% versus 0%) than the PrPD group. There were no significant differences in terms of lengths of hospital stay, hospitalization costs or mortality between the groups. Surgical method, biliary leakage, abdominal infection, and diabetes were independent risk factors for SDGE. The nomogram predicted SDGE with a training C - index of 0.798 and a validation C - index of 0.721. CONCLUSION: PPPD increases the risk of DGE than PrPD, especially SDGE. Our prediction nomogram gives good prediction of SDGE after pancreaticoduodenectomy.

INHBA is a prognostic predictor for patients with colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is one of the most lethal cancers. It is particularly important to accurately predict prognosis and to provide individualized treatment. Several lines of evidence suggest that genetic factors and clinicopathological characteristics are related to cancer onset and progression. The aim of this study was to identify potential prognostic genes and to develop a nomogram to predict survival and recurrence of COAD. METHODS: To identify potential prognostic genes in COAD, microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained from GEO2R. Venn diagram was drawn to select those genes that were overexpressed in all datasets, and survival analyses were performed to determine the prognostic values of the selected genes. New nomograms were developed based on the genes that were significantly associated with prognosis. Clinicopathological data were obtained from The Cancer Genome Atlas (TCGA). Finally, the new nomograms were compared head-to-head comparison with the TNM nomogram. RESULTS: From GSE21510, GSE110223, GSE113513 and GSE110224, a total of 834, 218, 236 and 613 overexpressed DEGs were screened out, respectively. The Venn diagram revealed that 12 genes appeared in all four profiles. After survival analyses, only INHBA expression was associated with both overall survival (OS) and disease-free survival (DFS). Multivariate analyses revealed that age, pathological N and pathological M were significant independent risk factors for OS. Age, pathological N, pathological M and INHBA were significant independent risk factors for DFS. Two prediction models predicted the probability of 3-year survival and 5-year survival for OS and DFS, respectively. The concordance indexes were 0.785 for 3-year overall survival, 0.759 for 5-year overall survival, 0.789 for 3-year disease-free survival and 0.757 for 5-year disease-free survival. The head-to-head comparison according to time-dependent ROC curves indicated that the new models had higher predictive accuracy. Decision curve analyses (DCA) indicated that the clinical value of the new models were higher than TNM models for predicting disease-free survival. CONCLUSION: The combination of INHBA expression with a clinical nomogram improves prognostic power in colon adenocarcinoma, especially for predicting recurrence.

High Centromere Protein-A (CENP-A) Expression Correlates with Progression and Prognosis in Gastric Cancer.

PURPOSE: Recent studies have established the ability of centromere protein-A (CENP-A) to perform as an oncogene, regulating tumor progression. The aim of this research was to explore the relationship between CENP-A expression and clinical significance in gastric cancer (GC) patients. MATERIALS AND METHODS: Experiments with a microarray were conducted using the Affymetrix U133 plus 2.0 GeneChip Array. Upregulated differentially expressed genes (DEGs) were identified via the GEO2R and intersected using a Venn diagram. Bioinformatic databases Omcomine, GEPIA, and Ualcan were applied to investigate the expression level of CENP-A in GC. The real-time quantitative RT-PCR (qRT-PCR) was used to validate the level of CENP-A mRNA in GC. Immunohistochemistry (IHC) was employed to verify the protein levels of CENP-A, while the relationship between CENP-A expression and patients' clinical parameters in GC was explored through the use of IHC. Kaplan-Meier analysis was conducted to evaluate the prognostic significance of CENP-A. Additionally, the Kaplan-Meier plotter database (KM plotter) was used to verify the prognostic function of CENP-A in GC patients. RESULTS: The results indicated that CENP-A was significantly overexpressed, both in protein and mRNA levels of GC tissues, compared to adjacent noncancerous tissues (P<0.05). Furthermore, we observed that CENP-A expression was positively associated with TNM stage, tumor classification, lymph node metastasis, distant metastasis, and Lauren type (P<0.05). Kaplan-Meier analysis showed that patients with an overexpression of CENP-A had significantly poorer overall survival (OS) times (P<0.05). Multivariate analysis suggested CENP-A may serve as an independent predicting factor for the poor outcome of GC patients. CONCLUSION: Our results show that CENP-A upregulation is significantly correlated with advanced tumor progression and poor prognosis. CENP-A may function as a novel potential biomarker for predicting the clinical outcomes of GC patients.

Particle-attached microorganism oxidation of ammonia in a hypereutrophic urban river.

To elucidate the importance and mechanisms of particle-attached microorganisms on ammonia oxidation, we conducted a controlled simulation experiment with samples collected from the Shunao River, an ammonia-rich hypereutrophic urban river in eastern China. The effects of particle concentration, ammonia concentration, organic carbon source and concentration, dissolved oxygen concentration, and pH were investigated on ammonia transformation rate (ammonia removal rate and NO2 - + NO3 - accumulation rate) and abundance of particle-attached ammonia-oxidizing bacteria (AOB) and archaea (AOA). All these factors significantly influenced ammonia transformation rates. Our results provided direct evidence that microorganisms attached on riverine suspended particles were associated with ammonia oxidation. Sequencing revealed that the AOA genus Nitrososphaera, and the AOB genus Nitrosomonas were the most dominant in particle-attached ammonia-oxidizing microbial communities. Further analysis showed that AOB communities had higher species richness and diversity compared with AOA communities. Additionally, AOB amoA genes were ~10-100 times more abundant than AOA amoA genes, and AOB abundance was more strongly correlated with ammonia transformation rates than AOA abundance in most experiments, indicating that particle-attached AOB were more important than AOA in the hypereutrophic urban river. This study adds to our knowledge of particle-attached microorganism oxidation of ammonia.