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We aimed to assess the effects of 2 isoenergetic intervention diets (a freshwater fish-based diet [F group] or freshwater fish-based and red meat-based diets alternately [F/M group]) on liver steatosis and their relationship with intestinal flora in patients with nonalcoholic fatty liver disease (NAFLD).In this open-label, 84-day randomized controlled trial, 34 NAFLD patients with hepatic steatosis ≥10% were randomly assigned to the F group or F/M group in a 1:1 ratio using a computer-generated random number allocation by a researcher not involved in the study. Liver fat content and gut microbiota and its metabolites were measured.At the end of intervention, the absolute reduction of hepatic steatosis was significantly greater in the F group than in the F/M group (-4.89% vs -1.83%, P = 0.032). Of the 16 secondary clinical outcomes, the improvement in 7 in the F group was greater compared with the F/M group, including alanine aminotransferase and gamma-glutamyl transferase. Furthermore, dietary freshwater fish and red meat consumption alternately did not exacerbate NAFLD. Moreover, changes in the enrichment of Faecalibacterium, short-chain fatty acids, and unconjugated bile acids and the depletion of Prevotella 9 and conjugated bile acids in the F group were significantly greater compared with the F/M group.Higher intake of freshwater fish may be beneficial to NAFLD by regulating gut microbiota and its metabolites, whereas intake of a similar total of animal protein and fat from the alternating freshwater fish and red meat may not be harmful for NAFLD in the dietary management of patients with NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent hepatic pathology worldwide. However, the precise molecular mechanisms for NAFLD are still not sufficiently explained. Recently, a new mode of cell death (cuproptosis) is found. However, the relationship between NAFLD and cuproptosis remains unclear. We analyzed three public datasets (GSE89632, GSE130970, and GSE135251) to identify cuproptosis-related genes stably expressed in NAFLD. Then, we performed a series of bioinformatics analyses to explore the relationship between NAFLD and cuproptosis-related genes. Finally, 6 high-fat diet- (HFD-) induced NAFLD C57BL/6J mouse models were established to carry out transcriptome analysis. The results of gene set variation analysis (GSVA) revealed that the cuproptosis pathway was abnormally activated to a certain degree ( p = 0.035 in GSE89632, p = 0.016 in GSE130970, p = 0.22 in GSE135251), and the principal component analysis (PCA) of the cuproptosis-related genes showed that the NAFLD group separated from the control group, with the first two principal components accounting for 58.63%-74.88% of the variation. Among three datasets, two cuproptosis-related genes (DLD and PDHB, p < 0.01 or 0.001) were stably upregulated in NAFLD. Additionally, both DLD ( AUC = 0.786 – 0.856 ) and PDHB ( AUC = 0.771 – 0.836 ) had favorable diagnostic properties, and the multivariate logistics regression model further improved the diagnostic properties ( AUC = 0.839 – 0.889 ). NADH, flavin adenine dinucleotide, and glycine targeted DLD, and pyruvic acid and NADH targeted PDHB in the DrugBank database. The DLD and PDHB were also associated with clinical pathology, especially with steatosis (DLD, p = 0.0013 – 0.025 ; PDHB, p = 0.002 – 0.0026 ) and NAFLD activity score (DLD, p = 0.004 – 0.02 ; PDHB, p = 0.003 – 0.031 ). What is more, DLD and PDHB were correlated with stromal score (DLD, R = 0.38 , p < 0.001 ; PDHB, R = 0.31 , p < 0.001 ) and immune score (DLD, R = 0.26 , p < 0.001 ; PDHB, R = 0.27 , p < 0.001 ) in NAFLD. Furthermore, Dld and Pdhb were also significantly upregulated in the NAFLD mouse model. In conclusion, cuproptosis pathways, especially DLD and PDHB, could be potential candidate genes for NAFLD diagnostic and therapeutic options.

Backfill of mined-out areas in Carlin-type gold mines always encounters the challenges of ultra-fine tailings, low backfill strength and difficult slurry transportation caused by fine tailings. To understand the influence of slurry mass concentration, waste rock content, and cement-sand ratio on the cemented backfill strength and fluidity, influential factors were determined by range analysis of orthogonal proportion experiments. Response surface methodology (RSM) was used to analyze the influence of each factor on response, and the backfill strength and slump were optimized using a robust optimization desirability function method. The results show that the cement-sand ratio has the highest effect on the backfill strength, and the slurry slump is dominated by the slurry mass concentration. The interaction between waste rock content and the cement-sand ratio significantly impacts the slump, while the interaction between the slurry mass concentration and the cement-sand ratio has a positive correlation with the backfill strength. The ultra-fine tailings cemented backfill proportion was optimized by using multi-response robust parameters as 68.36% slurry mass concentration, 36.72% waste rock content and 1:3 cement-sand ratio. The overall robust optimal desirability was 0.8165, and the validity of multi-response robust parameter optimization was verified by laboratory tests.

Objective. The consumption of dairy is associated with decreased risk of colorectal cancer (CRC), but few studies have assessed the relationship between dairy consumption and precursors of CRC. Therefore, we performed the first meta-analysis to further evaluate this association. Methods. PubMed, Embase, Scopus, and Web of Science databases were searched through July 2020 for observational studies. Study-specific risk estimates for the highest versus lowest category were pooled using the random-effects and fixed-effects model. The methodological quality of included studies was assessed using the ROBINS-I Scale. Results. A total of 12 studies were included (3 cohort studies and 9 case-control studies). Compared with the lowest level consumption, fermented dairy products had a decreased risk of precursors of CRC in both cohort (RR = 0.92 95% CI: 0.87–0.97) and case-control studies (RR = 0.98 95% CI: 0.96–0.99). Total dairy (RR = 0.80 95% CI: 0.68–0.96) and cheese (RR = 0.96 95% CI: 0.93–0.99) consumption was inversely associated with the risk in case-control studies whereas yogurt consumption was inversely associated with the risk in cohort studies (RR = 0.91 95%CI: 0.86–0.96). No significant associations were found for consumption of total milk and non/low-fat milk. For dose-response analyses, evidence of linear association was found in total dairy and yogurt consumption. The risk decreased by 12% for an increment of 200 g/d total dairy consumption (RR = 0.88 95% CI: 0.81–0.95) and decreased by 8% for an increment of 50 g/d yogurt consumption (RR = 0.92 95% CI: 0.85–0.99). Conclusions. Fermented dairy products, specifically yogurt and cheese, were significantly associated with decreased risk of conventional and serrated precursors of colorectal cancer.

Purpose The previous analysis of systematic reviews and meta-analyses have illustrated that obstructive sleep apnea (OSA) is correlated with multiple health outcomes. In the present research, our main aim was to execute an umbrella review to assess the available evidence for the associations between OSA and health outcomes. Methods Herein, a meta-analysis of previous observational investigations that have reported associations between OSA and health outcomes in all human populations and settings was performed. We used these studies to execute an umbrella review of available meta-analyses and systematic reviews. Results Sixty-six articles comprising 136 unique outcomes were enrolled in this analysis. Of the 136 unique outcomes, 111 unique outcomes had significant associations (p Conclusion Among the 66 meta-analyses exploring 136 unique outcomes, only 7 statistically significant outcomes were rated as high quality of evidence. OSA may correlate with an increased risk of coronary revascularization after PCI, postoperative respiratory failure, steatosis, ALT elevation, MS, psoriasis, and Parkinson’s disease.

Activation of the insulin-like growth factor 1 receptor (IGF-1R)-mediated Janus kinase (JAK)1/2-Stat3 pathway contributes to hepatocarcinogenesis. Specifically, a previous study showed that IGF-1R inhibition downregulated Midkine expression in hepatocellular carcinoma (HCC). The present study investigated the role of IGF-1R-JAK1/2-Stat3 and Midkine signaling in HCC, in addition to the molecular link between the IGF-1R-Stat3 pathway and Midkine. The expression levels of IGF-1R, Stat3, and Midkine were measured using reverse transcription-quantitative PCR, following which the association of IGF-1R with Stat3 and Midkine expression was evaluated in HCC. The molecular link between the IGF-1R-Stat3 pathway and Midkine was then investigated in vitro before the effect of IGF-1R-Stat3 and Midkine signaling on HCC growth and invasion was studied in vitro and in vivo. IGF-1R, Stat3, and Midkine mRNA overexpressions were all found in HCC, where the levels of Stat3 and Midkine mRNA correlated positively with those of IGF-1R. In addition, Midkine mRNA level also correlated positively with Stat3 mRNA expression in HCC tissues. IGF-1R promoted Stat3 activation, which in turn led to the upregulation of Midkine expression in Huh7 cells. Similarly, Midkine also promoted Stat3 activation through potentiating JAK1/2 phosphorylation. Persistent activation of this Stat3-Midkine-Stat3 positive feedback signal loop promoted HCC growth and invasion, the inhibition of which resulted in significant antitumor activities both in vitro and in vivo. Constitutive activation of the IGF-1R-mediated Stat3-Midkine-Stat3 positive feedback loop is present in HCC, the inhibition of which can serve as a potential therapeutic intervention strategy for HCC.

Purpose The previous analysis of systematic reviews and meta-analyses have illustrated that multiple sclerosis (MS) is correlated with multiple health outcomes. We designed an umbrella review to evaluate the breadth, validity and presence of biases of the associations of MS with diverse health outcomes. Methods We searched three databases (PubMed, We of Science and Embase) to recalculate the summary effect sizes, 95%CI, heterogeneity and small-study effects in the included meta-analyses. For each meta-analysis, we assessed the quality with AMSTAR2 and graded the epidemiologic evidence. Results A total of 28 articles comprising 84 unique meta-analyses were included in this study. Among the 84 unique outcomes, 52 unique outcomes had significant associations (p Conclusion In our umbrella review, MS seems to increase the risk of IBD, UC, CD, herpes simplex virus type 2-IgG and hypothyroidism while decrease the risk of atrial fibrillation, with high epidemiological evidence. In order to verify our results, more prospective observational studies are needed.

Background: Several epidemiological studies have assessed the association of sugary drinks consumption with cancer, but the results remain controversial. Objective: We performed this analysis to evaluate possible causal relationship between sugary drinks consumption and cancer risk and mortality. Methods: We searched PubMed, Embase, and Web of Science databases in English. Observational studies evaluating the association of sugary drinks intake with cancer were included. Random-effects meta-analysis was used to calculate the risk estimates. Results: A total of 71 observational articles with 32 case-control and 39 cohort studies were included in the meta-analysis. 60 addressed cancer risk, and 11 reported cancer mortality. Compared with the lowest level, the highest level of sugar-sweetened beverages (SSB) consumption showed an increased overall cancer risk (RR=1.12 95% CI: 1.06-1.19, P=0.000) and mortality (RR=1.07 95% CI: 1.01-1.14, P=0.029), and fruit juice intake showed a positive association with cancer risk in cohort studies (RR=1.06 95% CI: 1.01-1.11, P=0.013). Subgroup analyses based on cancer type indicated that risk of breast cancer, hepatocellular carcinoma, colorectal cancer, and prostatic cancer mortality had a positive association with SSB consumption. For dose-response analysis, evidence of a linear association was found between overall cancer risk and SSB or fruit juice consumption, and the risk increase by 4% for one servings/d increment in SSB intake and 14% in fruit juice. Conclusions: Our findings suggest the consumption of sugary beverages may increase the risk and mortality of cancer, especially risk of breast cancer, hepatocellular carcinoma, colorectal cancer, and prostatic cancer, and mortality of breast cancer, though the evidence was limited.

Aim Some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rapidly develop to critical condition. Here, we investigated the clinical features of critically ill SARS-CoV-2 patients with and without diabetes and identified risk factors for death of these patients. Methods The medical records including epidemiological, demographic, clinical, and laboratory data from 49 critically ill SARS-CoV-2 patients were collected and analyzed in Huanggang City and Xiaogan City, Hubei Province, outside Wuhan. Results Sixty-seven percent (33) of patients survived and 33% (16) of patients died in 49 critically ill patients (32 men, 17 women), with a median age of 63 years (IQR 53–73). Univariate analyses indicated that the deceased patients were more often associated with two or more comorbidities, one or more gastrointestinal symptoms, high neutrophil percentage, low lymphocytes and lymphocyte percentage, high C-reactive protein, high procalcitonin, high fasting blood glucose (FBG), and high lactate dehydrogenase (LDH) compared with the survivors; moreover, the patients with T2DM had the higher neutrophil percentage, the lower lymphocyte percentage, and the higher levels of FBG and LDH compared with the patients without T2DM. Multivariable logistic regression analyses indicated that gastrointestinal symptoms (≥ 1 symptoms), decreased lymphocytes (

Dietary habits have been implicated in the development and severity of non-alcoholic fatty liver disease (NAFLD). Several epidemiological studies attempted to assess the relationship between food groups and the likelihood of NAFLD, but these results were conflicting. The present meta-analysis was conducted to assess the association between food groups and the likelihood of NAFLD. Published literature was retrieved and screened from MEDLINE, Embase and Web of Science. Out of 7892 retrieved articles, twenty-four observational studies (fifteen cross-sectional studies and nine case-control studies) met our eligibility criteria and were finally included in this systematic review and meta-analysis. Consumption of both red meat and soft drinks contributed to a positive association with NAFLD. Inversely, nut consumption was negatively associated with NAFLD. There were no significant influences on the likelihood of NAFLD about consuming whole grains, refined grains, fish, fruits, vegetables, eggs, dairy products and legumes. This meta-analysis suggests that individuals who consumed more red meat and soft drinks may have a significantly increased likelihood of NAFLD, whereas higher nut intake may be negatively associated with NAFLD. Further prospective studies are required to assess the association between food patterns and NAFLD.

Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer mortality worldwide and nonalcoholic fatty liver disease (NAFLD)-related HCC is related to poorer survival than viral hepatitis-related HCC. However, the pathogenetic process of NAFLD to HCC is still poorly understood. Material and methods: A series of bioinformatics analyses were performed in two public datasets (GSE164760, GSE37031), The Cancer Genome Atlas (TCGA) database, and the International Cancer Genome Consortium (ICGC) database to explore potential hub genes in NAFLD-related HCC. Results: Weighted Gene Co-Expression Network Analysis (WGCNA) and LASSO logistic regression were performed to filter out 8 hub genes, then TMEM126A was selected for further analysis for its better diagnostic, stratification, and prognostic value in HCC. The results of Gene Set Enrichment Analysis (GSEA) indicated that TMEM126A was highly enriched in lipid metabolism. Next, TMEM126A was significantly correlated with the fatty acid biosynthesis and oxidation pathways. Further validation in other datasets confirmed our results. Conclusion: TMEM126A is firstly screened out for a hub gene in the pathogenesis of NAFLD-related HCC. Although further experiments are supposed to verify these results, we provide useful and novel information to explore the underlying mechanism in NAFLD-related HCC.

Objective. To assess the effects of dietary white meat (grass carp and chicken) and red meat (pork and beef) on metabolic parameters, including the intestinal microbiota and its metabolites (SCFAs and bile acids) in NAFLD rats induced by high-fat diet. Methods. NAFLD rats were randomly assigned to five groups: NAFLD group, grass carp group, chicken group, pork group, and beef group (10 rats in each group), and these rats were fed for 8 weeks using the high-fat diet, grass carp-based diet, chicken-based diet, pork-based diet, and beef-based diet, respectively. At the end of the intervention, NAFLD-related metabolic indexes, intestinal flora, and its metabolites were measured. Results. The grass carp-based diet significantly improved hepatic pathological changes and glycolipid metabolism, and the chicken-based diet only partially improved the metabolic parameters. However, NAFLD progression was observed in the pork group and the beef group. What is more, the white meat-based diet-mediated changes in the enrichment of beneficial bacteria (such as Lactobacillus or Akkermansia), SCFAs, and unconjugated BAs (such as UDCA) and the depletion of pathogenic bacteria (such as Bilophila and Prevotella_9) and conjugated BAs were observed, while the red meat-based diet-induced changes in the enrichment of pathogenic bacteria (Prevotella_9 or Lachnospiraceae_UCG-010) and conjugated BAs and the depletion of SCFAs and unconjugated BAs were found. Conclusion. The dietary white meat and red meat modulating gut microbiota and its metabolites may favor and aggravate NAFLD in rats, respectively.

It is disputed about optimal bowel preparation for small bowel capsule endoscopy (SBCE). This meta-analysis aimed to investigate the role of simethicone in intestinal preparation for SBCE.We searched four databases (PubMed, web of science, Embase, and Scopus databases) for relevant studies. Studies evaluating the effect of simethicone as an adjunct to SBCE bowel preparation were included. The random-effects model was applied to calculate the risk estimates. Primary outcomes include the degree of gas bubbles and small bowel visualization quality (SBVQ). Secondary outcomes include diagnostic yield (DY), gastric transit time (GTT), small bowel transit time (SBTT), and completion rate (CR).A total of 10 studies were included (8 RCTs, 1 prospective, and 1 retrospective study). Compared with the control group, the simethicone group showed significant improvements in the degree of gas bubbling (RR = 2.05, 95%CI:1.56-2.71, P 0.001, ISimethicone for bowel preparation is useful to improve visualization and reduce the gas bubbling of SBCE.

This study evaluated the relationship between grain consumption and the risk of gastric cancer. A total of 19 studies met the inclusion criteria. For whole grain consumption, there was a 13% reduction in the risk of gastric cancer (

Background: Moderate cases account for the majority in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and can also progress to severe/critical condition. Here, we investigated the clinical course and management of hospitalized moderate SARS-CoV-2 patients.Methods: The medical records and follow-up data were analyzed from the SARS-CoV-2 patients outside Wuhan.Results: A total of 73 moderate patients (38 men, 35 women) were included, with median age of 47.0 (38.5-57.5) years. Among them, only one patient (1.4%) died using active treatment to improve symptoms. The median duration of the four main symptoms cough, fever, chest tightness, and fatigue were about 1-2 weeks; the median duration of the positive nucleic acid test (NAT) results for SARS-CoV-2 was slightly more than 2 weeks; the median hospitalization time was almost four weeks in 72 moderate survivors. The duration of cough and fever was positively correlated with the duration of the positive NAT results. On admission, 50% had lymphopenia; less than 30% had abnormal blood biochemistry findings involving hyperglycemia, liver function and myocardial enzymes. At discharge, the laboratory indexes were substantially improved. Two weeks after discharge, 5.6% survivors experienced a recurrence of the positive NAT results. Conclusions: Moderate SARS-CoV-2 patients have a good prognosis by the active treatment. After discharge, it is necessary that moderate survivors undergo at least a 2-week collective medical observation in quarantine places, which can identify and treat a proportion of patients with re-positive NAT results and to prevent the spread of the potential sources of infection.

Background: Several studies have assessed the relationship between long non-coding RNA five prime to Xist (FTX) expression, clinicopathological features, and survival outcomes in patients with cancer with conflicting results. This meta-analysis synthesized existing data to clarify the association between FTX with cancer prognosis. Methods: PubMed, Embase, Cochrane library, Web of Science, Chinese CNKI, and the Chinese WanFang databases were used to search for relevant studies. The role of FTX in cancers was evaluated by pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Eleven studies comprising 1210 participants including colorectal cancer (CRC), hepatocellular carcinoma (HCC), gastric cancer (GC), renal cell carcinoma (RCC), osteosarcoma (OSC), and glioma were enrolled in this analysis. The meta-analysis showed that high FTX expression was significantly associated with several clinicopathological characteristics, including lymph node metastasis in patients with CRC, GC, HCC, and RCC, distant metastasis in patients with CRC, GC, HCC, and OSC, larger tumor size in patients with CRC, GC, HCC, RCC, and OSC, and subsequently TNM/clinical stage in patients with CRC, GC, HCC, OSC, and glioma. The pooled results from the survival analysis revealed a significant correlation between high FTX expression and shorter OS in patients with HCC, CRC, GC, OSC, and glioma. Further, FTX overexpression could be an independent predictive marker for shorter OS in patients with CRC, HCC, OSC, and glioma. Conclusions: FTX may be a potential oncogene, with high FTX expression being associated with a poorer prognosis in patients with CRC, HCC, OSC, and glioma.

To assess the diagnostic value of Trefoil factor 3 (TFF3) and the correlation between TFF3 expression and clinicopathological features in patients with gastric cancer (GC). PubMed, The Cochrane, EMbase, and Web of Science were retrieved comprehensively to collect relevant literature. The search ended on 31 May 2020. All data were analyzed using PubMed, The Cochrane, EMbase, and Web of Science were retrieved to collect relevant articles. All data from the included studies were subjected to meta-analysis using Stata 12.0 software. Seventeen studies involved 4654 subjects were included. For the diagnostic value of TFF3 for GC, the sensitivity, specificity, and AUC were 0.71, 0.80, and 0.80, respectively. For the clinicopathological value of TFF3, tissue TFF3 expression showed a higher risk of lymph node metastasis (OR 2.20, 95% CI 1.75–2.78, p < 0.001) and muscularis propria invasion (≥T2) (1.51, 1.13–2.03, p = 0.006), as well as worse TNM stage (2.26, 1.63–3.12, p < 0.001) and histological type (1.72, 1.34–2.20, p < 0.001), while no apparent relationship was found for serous membrane invasion (T4), venous invasion, and peritoneal metastasis. TFF3 may be a promising biomarker for GC, and the TFF3 expression is likely to be involved in the invasion, metastasis, and differentiation of GC.

Background Several studies assessed the relationship between FTX expression level and clinicopathological features and survival outcomes in patients with cancer, but these results were conflicting. This meta-analysis aimed to synthesize existing data to clarify the association of FTX with prognosis of cancers. Methods Electronic databases of PubMed, Embase, Cochrane library, Web of Science, Chinese CNKI, and the Chinese WanFang databases were used to search for relevant studies. Role of FTX in cancers was evaluated by pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). Results In total, 11 studies compromising 1210 participants including colorectal cancer (CRC), hepatocellular carcinoma (HCC), gastric cancer (GC), renal cell carcinoma (RCC), osteosarcoma (OSC), and glioma, were enrolled in this analysis. The meta-analysis showed that high FTX expression was associated with lymph node metastasis, distant metastasis, tumor size and TNM/clinical stage. More importantly, the pooled results from survival analysis revealed that there was a significant correlation between high FTX expression and a shorter OS in patients with HCC, CRC, GC, OSC, and glioma, and that FTX overexpression could be an independent predictive marker for shorter OS in patients with CRC, HCC, OSC, and glioma. Conclusions FTX may be a potential oncogene, and high FTX expression be associated with a poor prognosis in patients with CRC, HCC, OSC, and glioma.

The human insulin-like growth factor-II (IGF-II) gene transcribes four mRNAs (P1 mRNA-P4 mRNA), and P3 mRNA overexpression contributes to hepatocarcinogenesis. IGF-II-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in P3 mRNA overexpression regulation and its role in hepatocellular carcinoma. Our results showed that miR-483-5p up-regulated P3 mRNA transcription by targeting the 5'-untranslated region (5'UTR) of P3 mRNA in hepatocellular carcinoma. The mechanism was involved in recruiting of an argonaute 1(Ago1)-argonaute 2 (Ago2) complex to the P3 mRNA 5'UTR and the P3 promoter of IGF-II gene by miR-483-5p, accompanied by increased enrichment of RNA polymerase II and activating histone marks histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 27 acetylation (H3K27ac), and histone 4 lysine 5/8/12/16 acetylation (H4Kac) at the P3 promoter. High miR-483-5p expression was an independent predictor for shorter survival of HCC patients. The findings suggest that miR-483-5p promotes P3 mRNA transcription by recruiting the Ago1-Ago2 complex to the P3 mRNA 5'UTR and is associated with poor prognosis of HCC. Our results display a potential new model for miRNAs to up-regulate gene expression.

Background Several epidemiological studies have assessed the association between the use of antibiotics and cancer risk, but the results were inconsistent. Objective The objective of this study was to perform a meta-analysis to further evaluate possible association between antibiotic exposure and the risk of cancer. Methods We searched PubMed,Embase,Web of Science,and Chinese databases for studies on the association between antibiotic use and cancer without time restrictions. The risk estimates (hazard ratio (HR) or relative risk (RR) or Odds ratio (OR)) with their corresponding 95% confidence interval (CI) were calculated. Results A total of 23 observational studies with 19 case-control and 4 cohort studies were included in the meta-analysis. Exposure to antibiotics significantly increased the risk of cancer with an OR of 1.20 (95%CI 1.13-1.27, P=0.000). Subgroup meta-analysis by gender showed that the effect of antibiotic use on cancer risk was greater in male (34%) compared with that in female (19%). On the other hand, the risk of cancer increased with an increasing number of antibiotic prescriptions and the increasing cumulative days of antibiotic exposure. Moreover, of the 7 antibiotic types included, the six classes of antibiotics (penicillin, macrolides, quinolones, sulfonamides, tetracycline, cephalosporins) were associated with the increased risk of cancer. Further, of the 16 separate cancers included, exposure to antibiotics increased the risk of eight common cancer types (liver cancer, colorectal cancer, stomach and small intestine cancer, lymphomas, breast cancer, lung cancer, prostate cancer, and renal and bladder). Conclusions Exposure to common antibiotic types may increase the risk of the eight common cancer types in the studies population, especially in male, and the cancer risk increases with increasing antibiotic exposure intensity.

A 28-year-old man had a one-month history of fever, mild cough, and abdominal distension. He was started on cephalosporin antibiotic for the suspicion of upper respiratory infections.

Background The dynamic changes of serum circRNAs, which act as a sponge of microRNA, has a great potential in predicting colonic disease, especially in malignant diseases. However, whether the mechanism of circRNA in regulating colonic epithelial mucosa is still unknown. Here, we explore the sponging effects of hsa_circ_0053063 targeting miR-361-3p in colon epithelial cells. Methods According to the ceRNA analysis, the potential target miRNAs of hsa_circ_0053063 were collected. Dual-luciferase reporter gene assays were performed to confirm the circRNA sponge of miRNAs. Then the potential target gene of miR-361-3p was predicted. Dual-luciferase reporter gene assays and real-time PCR were performed to detect the regulation between ncRNAs and target gene in colon epithelial cells HCoEpiC and NCM460. Results According to the ceRNA analysis, we found that miR-361-3p might be a target of hsa_circ_0053063 (figure 1a). Dual-luciferase reporter gene assays demonstrated that hsa_circ_0053063 bound miR-361-3p directly (figure 1b). Then we predicted that ATG13 was a target gene of miR-361-3p. Dual-luciferase reporter gene assays demonstrated that miR-361-3p bound ATG13 directly. Real-time PCR revealed that miR-361-3p decreased expression of ATG13, however, hsa_circ_0053063 reversed the inhibition of expression of ATG13 by miR-361-3p. Conclusions Hsa_circ_0053063 released the inhibition of expression of ATG13 by miR-361-3p. hsa_circ_0053063 may act as a sponge of miR-361-3p targeting ATG13 in colon epithelial cell.

Background & aims Long noncoding RNA 91H is transcribed from the H19/IGF2 locus and contributes to the development of breast and oesophagus cancers by regulating the expression of IGF2, but the regulation mechanism remains poorly characterized. Here, we explored the role of 91H in hepatocellular carcinoma (HCC) and the mechanism of IGF2 expression regulation by 91H. Methods Firstly, the expression of 91H was analysed in HCC by quantitative RT-PCR, the association of 91H with survival was evaluated by the Kaplan-Meier method and the effect of 91H on the growth and invasion of HCC was investigated by the in vitro and in vivo studies. Then, the association of 91H with the expression of IGF2 was evaluated in HCC tissues, and the effect of 91H on the expression of IGF2 was investigated by 91H knockdown. Finally, the binding of RBBP5 to 91H and the binding of RBBP5, activating H3K4me3 mark and repressive H3K27me3 mark to the P3 and P4 promoters of IGF2 gene were studied by RIP and ChIP respectively. Results The overexpression of 91H was found in HCC and in association with the growth, metastasis and shorter survival time of HCC. The knockdown of 91H down-regulated the IGF2 expression in HCC, and the mechanism was correlated with the decreased enrichment of RBBP5 and H3K4me3 and increased enrichment of H3K27me3 at the bivalent P3 and P4 promoters. Conclusions The overexpression of 91H promotes tumour growth and metastasis, and is associated with a poor prognosis of HCC at least partially by positively regulating the expression of IGF2 through bivalent histone modification changes characterized by H3K4me3 and H3K27me3 at the P3 and P4 promoters.

Circular RNAs (circRNAs) play an important regulatory role in a variety of human cancers, including gastric cancer. The mechanisms for the circRNAs in gastric cancers are not fully understood. This study aims to uncover the mechanism by which circRNAs regulate gastric cancer tumorigenesis. Among the microarray data, we screened dysregulated circRNAs and identified an up-regulated circRNA, hsa_circ_0008035. Functionally, the hsa_circ_0008035 silencing by the siRNA transfection inhibited the proliferation and invasion of gastric cancer cells. Mechanically, hsa_circ_0008035 acted as a sponge for the miR-375 and absorbed its expression, and miR-375 was found to target YBX1 3’-UTR, constructing a hsa_circ_0008035/miR-375/YBX1 axis. Taken together, these findings are evidence that circRNA hsa_circ_0008035 promotes gastric cancer cell proliferation and invasion by regulating miR-375/YBX1.

Figure S1. Human GC cells were transfected with miR-632-mimic or inhibitor. (A) miRNA mimic upregulated miR-632 expression compared with the negative control in AGS and BGC823 cells. (B) miRNA inhibitor downregulated miR-632 expression compared with the negative control in MKN45 and MGC803 cells. The experiments were performed at least three times independently. **Pâ

Background Gastric cancer (GC) is a common malignant disease worldwide. Aberrant miRNAs expression contributes to malignant cells behaviour, and in preclinical research, miRNA targeting has shown potential for improving GC therapy. Our present study demonstrated that miR-632 promotes GC progression in a trefoil factor 1 (TFF1)-dependent manner. Methods We collected GC tissues and serum samples to detect miR-632 expression using real-time PCR. A dual-luciferase reporter assay was used to identify whether miR-632 directly regulates TFF1 expression. Tube formation and endothelial cell recruitment assays were performed with or without miR-632 treatment. Western blot and in situ hybridization assays were performed to detect angiogenesis and endothelial recruitment markers that are affected by miR-632. Results Our results showed that miR-632 is highly expressed in GC tissue and serum and negatively associated with TFF1 in GC. miR-632 improves tube formation and endothelial cell recruitment by negatively regulating TFF1 in GC cells. Recombinant TFF1 reversed miR-632-mediated angiogenesis. TFF1 is a target gene of miR-632. Conclusions Our study demonstrated that miR-632 promotes GC progression by accelerating angiogenesis in a TFF1-dependent manner. Targeting of miR-632 may be a potential therapeutic approach for GC patients. Electronic supplementary material The online version of this article (10.1186/s12885-018-5247-z) contains supplementary material, which is available to authorized users.

Hes1 is a transcription factor that influences cell proliferation and differentiation. However, the effect of Hes1 on invasiveness and the underlying mechanism remain unknown. In the current study, we found that Hes1 suppressed cell apoptosis, promoted cell growth, induced EMT phenotype and cytoskeleton reconstruction, and enhanced the metastatic potential of colon cancer cells in vitro and in vivo. Furthermore, we indicated that Bmi-1 mediated Hes1-induced cell proliferation and migration, downregulated PTEN and activated the Akt/GSK3β pathway, consequently induced EMT and cytoskeleton reconstruction, ultimately leading to enhanced invasiveness of cancer cells. In addition, we also found that both Hes1 and Bmi-1 could directly regulate PTEN by associating at the PTEN locus, and played important roles in regulating PTEN/Akt/GSK3β pathway. Our results provide functional and mechanistic links between Hes1 and Bmi-1/PTEN/Akt/GSK3β signaling in the development and progression of colon cancer.