BackgroundDysregulated miR-7 and aberrant NF-κB activation were reported in various human cancers. However, the expression profile, clinical relevance and dysregulated mechanism of miR-7 and NF-κB RelA/p65 in human gastric cancers (GC) metastasis remain largely unknown. This study is to investigate the expression profile, clinical relevance and dysregulated mechanism of miR-7 and NF-κB RelA/p65 in GC and to explore the potential therapeutic effect of miR-7 to GC distant metastasis.MethodsTCGA STAD and NCBI GEO database were used to investigate the expression profile of miR-7 and NF-κB RelA/p65 and clinical relevance. Lentivirus-mediated gene delivery was applied to explore the therapeutic effect of miR-7 in GC. Real-time PCR, FACS, IHC, IF, reporter gene assay, IP, pre-miRNA-7 processing and binding assays were performed.ResultsLow miR-7 correlated with high RelA/p65 in GC with a clinical relevance that low miR-7 and high RelA/p65 as prognostic indicators of poor survival outcome of GC patients. Moreover, an impaired pre-miR-7 processing caused by dysregulated Dicer1 expression is associated with downregulated miR-7 in GC cells. Functionally, delivery of miR-7 displays therapeutic effects to GC lung and liver metastasis by alleviating hemangiogenesis, lymphangiogenesis as well as inflammation cells infiltration. Mechanistically, miR-7 suppresses NF-κB transcriptional activity and its downstream metastasis-related molecules Vimentin, ICAM-1, VCAM-1, MMP-2, MMP-9 and VEGF by reducing p65 and p-p65-ser536 expression. Pharmacologic prevention of NF-κB activator LPS obviously restored miR-7-suppressed NF-κB transcriptional activation and significantly reverted miR-7-inhibited cell migration and invasion.ConclusionsOur data suggest loss of miR-7 in GC promotes p65-mediated aberrant NF-κB activation, facilitating GC metastasis and ultimately resulting in the worse clinical outcome. Thus, miR-7 may act as novel prognostic biomarker and potential therapeutic target for aberrant NF-κB-driven GC distant metastasis.Electronic supplementary materialThe online version of this article (10.1186/s13046-019-1074-6) contains supplementary material, which is available to authorized users.

To investigate whether gut microbiota is associated with vitamin A nutritional levels in children with persistent diarrhea, a total of 59 pediatric patients with persistent diarrhea aged 1–12 months were selected from the Department of Gastroenterology at the Children’s Hospital of Chongqing Medical University, China. Subjects were hospitalized and divided into VA-deficient (n = 30) and VA-normal (n = 29) groups according to their venous serum retinol levels. Fecal samples from all 59 subjects were collected immediately after admission and analyzed by Illumina MiSeq for 16S rRNA genes to characterize the overall microbiota of the samples. The gut microbiota of the VA-deficient and VA-normal groups were compared using a bioinformatic statistical approach. The Shannon index (p = 0.02), Simpson index (p = 0.01) and component diagram data indicated significantly lower diversity in the VA-deficient than the VA-normal group. A metagenome analysis (LEfSe) and a differentially abundant features approach using Metastats revealed that Escherichia coli and Clostridium butyricum were the key phylotypes of the VA-normal group, while Enterococcus predominated the VA-deficient group. In conclusion, the diversity of gut microbiota and the key phylotypes are significantly different in children with persistent diarrhea at different VA nutritional levels.

Aberrant STAT3 activation occurs in most human gastric cancers (GCs) and contributes to the malignant progression of GC, but mechanism(s) underlying aberrant STAT3 remain largely unknown. Here we demonstrated that the gene associated with retinoid interferon-induced mortality 19 (GRIM-19) was severely depressed or lost in GC and chronic atrophic gastritis (CAG) tissues and its loss contributed to GC tumorigenesis partly by activating STAT3 signaling. In primary human GC tissues, GRIM-19 was frequently depressed or lost and this loss correlated with advanced clinical stage, lymph node metastasis, H. pylori infection and poor overall survival of GC patients. In CAG tissues, GRIM-19 was progressively decreased along with its malignant transformation. Functionally, we indentified an oncogenic role of GRIM-19 loss in promoting GC tumorigenesis. Ectopic GRIM-19 expression suppressed GC tumor formation in vitro and in vivo by inducing cell cycle arrest and apoptosis. Moreover, we revealed that GRIM-19 inhibited STAT3 transcriptional activation and its downstream targets by reducing STAT3 nuclear distribution. Conversely, knockdown of GRIM-19 induced aberrant STAT3 activation and accelerated GC cell growth in vitro and in vivo, and this could be partly attenuated by the blockage of STAT3 activation. In addition, we observed subcellular redistributions of GRIM-19 characterized by peri-nuclear aggregates, non-mitochondria cytoplasmic distribution and nuclear invasion, which should be responsible for reduced STAT3 nuclear distribution. Our studies suggest that mitochondrial GRIM-19 could not only serve as an valuable prognostic biomarker for GC development, but also as a potential therapeutic target for STAT3-dependent carcinogenesis of GC.

To investigate the effect of vitamin A and Zn supplementation on vitamin A status, haemoglobin level and defecation of children with persistent diarrhea, a total of 160 paediatric patients were randomly assigned to one of four intervention groups: daily supplementation of 1,500 IU VA for 14 days; daily Zn supplementation for 14 days; daily supplementation with both VA and Zn for 14 days; no supplementation. One hundred twenty-seven children with persistent diarrhea finished intervention (33 were lost to follow-up). Among the 127 children, 41 (32.28%) had anaemia, 104 (81.89%) had a VA deficiency and 38 (29.92%) had an iron insufficiency. Supplementation with VA or VA + Zn enhanced the serum VA levels and ameliorated anaemia. Supplementation with Zn and VA + Zn for 5 days significantly improved defecation, where the VA + Zn treatment resulted in superior outcomes. After 14 days of intervention, the total effectiveness rates were 93.94%, 96.77% and 96.67% in the three groups, significantly greater than that of the non-supplementation group (72.73%). These results indicate that single VA or concurrent VA + Zn supplementation can improve vitamin A status, haemoglobin level and defecation. However, concurrent VA + Zn supplementation is the optimal option and can shorten the duration of persistent diarrhea and markedly improve nutritional status. (www.clinicaltrials.gov registration number: ChiCTR-IOR-14005498)

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Silicon-bonded silicon carbide (SBSC) porous ceramics had been prepared by mixing two different particle size of SiC powder (coarse and fine) as aggregates for silicon carbide porous ceramics, adding metallic Si as the binder phase and firing at 1450 °C under argon atmosphere. Various combinations of SiC mixtures consisting of two different particle size and packing density were prepared, and the samples were investigated to understand apparent porosity, bending strength, pore size distribution, and microstructure. The result showed that mixing an appropriate proportion of SiC coarse and fine powders could not only improve the pore size distribution of SBSC porous ceramics but also significantly increase the bending strength compared with the single-particle size sample. The system had the highest free packing density when the ratio of coarse to fine SiC size was >2 and the coarse powder content was 60-70 wt%. The optimal bending strength, and apparent porosity were 37.53 MPa and 37.11% respectively when mixing 70 wt% of coarse powder (50.8 μm) and 30 wt% of fine powder (9.5 μm) and sintered at 1450 ℃ in an argon atmosphere. The material created had 100.3% increased bending strength, and 0.99% decreased porosity compared with the single-particle size sample (50.8 μm).

Background: Concerns still exist with respect to unsatisfactory eradication rates and/or therapyassociated side effects for the use of standard triple therapy in the treatment of Helicobacter pylori infection, which prompts considerable interest in new therapy. We systematically reviewed the literature to investigate whether Lactobacillus GG as supplementation to standard triple therapy could improve H. pylori eradication rates and/or reduce therapy-associated side effects. Methods: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched from their inception to August 4, 2015 for randomized controlled trials (RCTs). The language was restricted to English only. Results: Four RCTs involving a total of 305 participants (including 83 children) were included. Lactobacillus GG given along with triple therapy significantly reduced the risk of overall H. pylori therapy-related adverse effects (three RCTs, n = 221, RR 0.59, 95% CI 0.45 -0.78), particularly of diarrhea (four RCTs, n = 285, RR 0.23, 95% CI 0.11 -0.47), bloating (four RCTs, n = 289, RR 0.61, 95% CI 0.41 -0.90), and taste disturbance (four RCTs, n = 288, RR 0.38, 95% CI 0.23 -0.62). There were no significant differences between groups in the risk of other adverse effects. No beneficial effects of Lactobacillus GG were observed for H. pylori eradication rates (four RCTs, n = 284, RR 0.99, 95% CI 0.88 -1.13). Conclusion: Current evidence indicates that Lactobacillus GG administered along with standard triple therapy is a feasible way to reduce therapy-related side effects, particularly diarrhea, bloating, and taste disturbance. However, Lactobacillus GG shows no effects on eradication rates.

Background and AimsResearch on the effect of the coronavirus disease 2019 (COVID-19) pandemic on psychosocial function in patients with pediatric-onset inflammatory bowel disease (PIBD) is limited. This study aimed to evaluate the psychological status of patients with PIBD before and during the pandemic, and the relationship between mental health and disease activity.MethodsThis study was a retrospective cohort study. Statistical analyses were performed to assess the relationship between demographic, clinical data and psychological data (questionnaires) of PIBD patients before and during the epidemic. The anxiety and depression emotional status of the guardians during the pandemic were evaluated.ResultsIn the PIBD follow-up cohort, 42 patients(male 61.9%) were included. Female with PIBD had lower pediatric quality of life inventory(PedsQL) scores (P = 0.007) and higher spence children's anxiety scale(SCAS) scores (P = 0.038) than male. The pandemic did not have a substantial impact on PedsQL, pittsburgh sleep quality index(PSQI), SCAS, or children's depression inventory(CDI) in patients with PIBD. The self-rating anxiety scale(SAS) score, anxiety rate, self-rating depression scale(SDS) score, and depression rate of PIBD guardians were significantly higher than those of healthy controls (SAS, P = 0.008; SDS, P = 0.001).ConclusionsFemale children with PIBD were more vulnerable to decreased QOL and increased anxiety than male children. The anxiety and depression status of PIBD guardians were significantly higher than those of healthy controls during the COVID-19 pandemic. But the COVID-19 pandemic did not significantly affect quality of life(QOL), sleep, anxiety, or depressive mood of patients with PIBD in our study.