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Background and aim: Insulin-like growth factor-1 may be involved in the epithelial-to-mesenchymal transition process. It can mitigate adverse effects when interacting with insulin-like growth factor binding protein 3. This study aimed to explore alterations in the expression of these two factors in the colonic tissue of mice with ulcerative colitis. Method: This study utilized animal models. Mice were randomly allocated into three distinct groups. Disease activity index assessment was performed first, followed by histological grading of colitis. Protein and mRNA expression levels were determined using Western blotting and RT-qPCR. Immunohistochemical detection was used to determine histochemistry scores. Pearson correlation and SPSS 25.0 software were used for data analysis. Results: The findings indicated a reduction in the expression of the two investigated factors as well as in epithelial-to-mesenchymal transition epithelial markers during inflammation, while the expression of noninflammatory factors increased. These effects were notably amplified following treatment. Interestingly, the changes in epithelial-to-mesenchymal transition-inducing factors and mesenchymal markers contradicted this trend. Pearson correlation analysis revealed a correlation between molecular indicators of change and epithelial-to-mesenchymal transition. Conclusion: Insulin-like growth factor-1 and insulin-like growth factor binding protein 3 may play a protective role in the development and progression of ulcerative colitis, potentially through their inhibition of the epithelial-to-mesenchymal transition. These factors hold promise as targets for the clinical diagnosis and treatment of ulcerative colitis.

Abstract Background Dysbiosis of the gut microbiota is closely linked to hyperuricemia. However, the effect of the microbiome on uric acid (UA) metabolism remains unclear. This study aimed to explore the mechanisms through which microbiomes affect UA metabolism with the hypothesis that modifying the intestinal microbiota influences the development of hyperuricemia. Results We proposed combining an antibiotic strategy with protein-protein interaction analysis to test this hypothesis. The data demonstrated that antibiotics altered the composition of gut microbiota as UA increased, and that the spectrum of the antibiotic was connected to the purine salvage pathway. The antibiotic-elevated UA concentration was dependent on the increase in microbiomes that code for the proteins involved in purine metabolism, and was paralleled by the depletion of bacteria-coding enzymes required for the purine salvage pathway. On the contrary, the microbiota with abundant purine salvage proteins decreased hyperuricemia. We also found that the antibiotic-increased microbiota coincided with a higher relative abundance of bacteria in hyperuricemia mice. Conclusions An antibiotic strategy combined with the prediction of microbiome bacterial function presents a feasible method for defining the key bacteria involved in hyperuricemia. Our investigations discovered that the core microbiomes of hyperuricemia may be related to the gut microbiota that enriches purine metabolism related-proteins. However, the bacteria that enrich the purine salvage-proteins may be a probiotic for decreasing urate, and are more likely to be killed by antibiotics. Therefore, the purine salvage pathway may be a potential target for the treatment of both hyperuricemia and antibiotic resistance.

Pancreatic adenocarcinoma (PAAD), one of the most aggressive and lethal malignant tumors, is correlated with increased morbidity and mortality. CC chemokines can modulate the infiltration of immune cells and affect the clinical outcome of cancer patients. However, the therapeutic potential and prognostic value of CC chemokines in PAAD have not yet been elucidated. To do this, we comprehensively explore and analyze large amounts of data base on ONCOMINE, UALCAN, GEPIA2, LinkedOmics, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, DAVID 6.8, TRRUST, TIMER, TISIDB, DGIdb, and TTD. We found the transcriptional levels of CCL5/7/13/15/18/19/20 in PAAD tissues were remarkably increased, whereas the transcriptional level of CCL17 was decreased. CCL20 expression had significantly been correlated with the tumor stage of PAAD patients. High expressions of CCL5, CCL7, CCL13, CCL18, and CCL20 were notably correlated with the prognosis of patients. Moreover, patients with CCL18 and CCL19 alterations showed a poor prognosis in both overall survival (OS) and disease-specific survival (DSS). Patients with CCL5 and CCL15 alterations also presented a poor prognosis in OS. The key transcription factors for CC chemokines are RELA and NF-κB1. The functions of the differentially expressed CC chemokines were mainly correlated the chemokine signaling pathway, cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, and so forth. We also discovered significant associations between the expression levels of CC chemokines and six infiltrating immune cells including, CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells. The drug-gene interactions and related miRNAs of aberrant expression CC chemokines were also explored. Our study indicated the correlation between CC chemokines and PAAD and clarified the value of differentially expressed CC chemokines as potential therapeutic targets and prognostic markers for PAAD.

Abstract Background Ulcerative colitis (UC) is considered an immune-mediated disease. The disorder of T-lymphocyte subsets plays an important role in the pathogenesis of UC. The aim of this study was to evaluate the significance of peripheral blood T-lymphocyte subsets in assessing disease severity and predicting clinical outcomes in UC patients. Methods The retrospective case-control study was performed in 116 UC patients with active disease and 90 healthy controls (HC). The UC patients included were followed up for 180 days. Analyses of t-test, Spearman’s correlation coefficient, multivariable Cox regression analysis, receiver operating characteristic (ROC) curves and cumulative survival analysis were done. Results The UC patients had lower proportions of CD4+T cells (42.85%±9.77% vs 45.71%±7.94%, P=0.021) and higher proportion of CD8+T cells (27.88%±8.86% vs 25.00%±6.47%, P=0.008) than HC. The severely active UC patients had higher proportion of CD3+HLA-DR+ T cells (8.83%±6.55% vs 2.80%±1.55%, P5.38% had a shorter time to readmission or surgery (log-rank test, P

BackgroundThe gut microbiota is closely linked to cholesterol metabolism-related diseases such as obesity and cardiovascular diseases. However, whether gut microbiota plays a causal role in cholelithiasis remains unclear.AimsThis study explored the causal relationship between gut microbiota and cholelithiasis. We hypothesize that the gut microbiota influences cholelithiasis development.MethodsA two-sample Mendelian randomization method was combined with STRING analysis to test this hypothesis. Summary data on gut microbiota and cholelithiasis were obtained from the MiBioGen (n=13,266) and FinnGen R8 consortia (n=334,367), respectively.ResultsClostridium senegalense, Coprococcus3, and Lentisphaerae increased the risk of cholelithiasis and expressed more bile salt hydrolases. In contrast, Holdemania, Lachnospiraceae UCG010, and Ruminococcaceae NK4A214 weakly expressed bile salt hydrolases and were implied to have a protective effect against cholelithiasis by Mendelian randomization analysis.ConclusionGut microbiota causally influences cholelithiasis and may be related to bile salt hydrolases. This work improves our understanding of cholelithiasis causality to facilitate the development of treatment strategies.

Introduction Immunothrombosis has recently been used to describe the responses/mechanisms in thrombosis. Systemic inflammatory markers are prognostic markers for a variety of thrombotic conditions; however, their potential value in predicting portal vein thrombosis (PVT) is unknown. This study aimed to establish an easy-to-use nomogram based on systemic inflammatory markers to predict portal vein thrombosis (PVT) in patients with liver cirrhosis. Patients and methods This retrospective study included 478 patients with cirrhosis between January 2013 and January 2021. Reputed systemic inflammatory markers (systemic immune-inflammation index [SII], neutrophil-to-lymphocyte ratio [NLR], monocyte-to-lymphocyte ratio [MLR], and platelet-to-lymphocyte ratio (PLR)) were measured, and the clinical data were recorded. The independent risk factors for PVT were determined using univariate analyses and multivariate logistic regression analyses, and a nomogram to predict the occurrence of PVT was established. The concordance index, receiver operating characteristic curves, and calibration plots were used to evaluate the performance of the model. Results A total of 239 patients with PVT and 239 patients without PVT were selected. In the univariate analysis, high SII, NLR, PLR, and MLR were significantly associated with PVT. NLR and PLR were independent risk factors for PVT (P

Abstract Background T1 colorectal cancers have a low lymph node metastasis rate and good prognosis. Thus, endoscopic resection is an attractive choice. This study aimed to describe the value of poorly differentiated cluster grade in identifying endoscopically curable T1 colorectal cancers. Methods We included 183 T1 colorectal cancer patients who underwent curative resection. Univariate and multivariate logistic regressions were used to identify lymph node metastasis predictors. The Akaike information criterion was used to determine whether poorly differentiated cluster grade was the best predictor. Backward regression was used to screen the variables. Survival analyses were conducted to determine the prognostic predictive power of poorly differentiated cluster grade. Correlations among predictors and concordance between our pathologists were also investigated. Results Poorly differentiated cluster grade was an independent predictor for lymph node metastasis (adjusted odds ratio [OR]G 3 = 0.001; 95% confidence interval [95% CI]G 3 =

BackgroundLymph node status is an important prognostic indicator and it significantly influences treatment decisions for colorectal cancer (CRC). The objective of this study was to evaluate the ability of serum monosaccharides in predicting lymph node metastasis (LNM) and prognosis.MethodsHigh performance anion exchange chromatography coupled with pulsed amperometric detector (HPAEC-PAD) was used to quantify serum monosaccharides from 252 CRC patients. Receiver operating characteristic (ROC) curves were used to evaluate predictive performance of parameters. Predictors of LNM were evaluated by univariate and multivariate analyses. The prognostic role of the factors was evaluated by survival analysis.ResultsThe levels of serum mannose (Man) and galactose (Gal) were significantly increased in patients with LNM (p 5ng/ml) (OR =1.85, p =0.042) and high Man (OR =2.65, p =0.006) to be independent risk factors of LNM. The survival analysis showed that the high serum Man was independent risk factor for poor prognosis in CRC patients (HR=1.75, p =0.004).ConclusionsThe Man is superior to CEA in prediction of LNM for CRC patients. Man is expected to be a predictor for LNM in CRC. High serum Man is associated with poor prognosis of CRC patients.

Purpose: The goal of this study was to examine the role of sodium butyrate in preserving the intestinal mucosal barrier and reducing hyperuricemia (HUA). Methods: First, we established a mouse model of HUA via intraperitoneal injection of potassium oxonate together with a yeast-rich diet to detect the levels of serum uric acid (UA) and fecal short-chain fatty acids (SCFAs). Then, in vitro, different concentrations of UA and sodium butyrate (NaB) were used to treat LS174T and Caco2 cells. The effects of UA and NaB on the gut barrier were determined based on the expression levels of MUC2, ZO-1, and Occludin.Finally, C57BL/6 mice were used to model HUA, and these mice were administered 200 mg·kg−1·d−1 NaB by gavage to counter the HUA. The effect of NaB on HUA in the intestinal tract was elucidated by determining serum UA levels, inflammatory parameters, epithelial barrier integrity, and via histological analysis. Results: The data showed that the content of fecal SCFAs in HUA mice decreased. Additionally, in LS174T and Caco2 cells, NaB reversed the decrease of ZO-1, Occludin, and MUC2 protein expression caused by high UA levels. Furthermore, NaB decreased serum UA of HUA mice, and reversed both the decreased expression of MUC2, ZO-1, Occludin, and ABCG2 proteins and the increased level of inflammatory factors in the intestinal tissues of these mice. Conclusion: The HUA mouse model showed intestinal barrier damage. NaB protected the intestinal barrier of HUA mice and reduced the serum UA level.

Background and aimsCompared with self-prepared LRD, a prepackaged low-residue diet (LRD) can improve patient compliance, but whether it can further improve the quality of bowel preparation is uncertain. The study aimed to compare the application of the prepackaged formula LRD with self-prepared LRD in bowel preparation for colonoscopy.MethodsA multicenter randomized controlled trial was conducted in 15 centers. The eligible subjects were randomly assigned to one of two groups: the formula LRD group and the self-prepared LRD group. On the day before the colonoscopy, subjects in the self-prepared LRD group were instructed to consume a restricted LRD prepared by themselves, while subjects in the formula LRD group were given six bags of prepackaged formula LRD and instructed to consume them according to their individual need. The primary outcome was an adequate bowel preparation rate. Secondary outcomes mainly included Boston Bowel Preparation Scale (BBPS) scores, dietary restriction compliance rate, tolerance, satisfaction, adenoma detection rate (ADR), and adverse reactions. The trial was registered at ClinicalTrials.gov under the identifier NCT03943758.ResultsA total of 550 subjects were recruited. Compared with the self-prepared LRD group, the formula LRD group showed a higher adequate bowel preparation rate (94.5 vs. 80.4%; P < 0.01), BBPS scores (7.87 ± 1.13 vs. 6.75 ± 1.47; P < 0.01), dietary compliance rate (92.4 vs. 78.9%; P < 0.01), tolerance (P < 0.01 in degree of hunger, intensity of physical strength, and negative influence on daily activities), satisfaction (8.56 ± 1.61 vs. 7.20 ± 2.02; P < 0.01), and ADR (25.6 vs. 16.0%; P < 0.01). There was no significant difference in adverse reactions.ConclusionCompared with self-prepared LRD, the formula LRD showed similar safety and higher bowel preparation quality, compliance, and tolerance in bowel preparation. More formula LRDs could be designed according to different dietary habits and ethnic populations, and further researches are warranted to confirm their effect.Clinical trial registrationhttps://register.clinicaltrials.gov, identifier: NCT03943758.

Background: Ultrasound (US)- or computed tomography-guided drainage for abdominal abscess is currently the first-line options for drainage, but both options have disadvantages. Patients without adequate windows for drainage mostly undergo surgical drainage. However, surgical drainage is invasive and expensive. Endoscopic US (EUS)-guided drainage is a minimally invasive alternative for abdominal abscess, but there is less consensus on its efficacy, safety and complications. This meta-analysis aims to evaluate EUS-guided drainage for abdominal abscess. Materials and Methods: We retrieved relevant papers on EUS-guided drainage for abdominal abscess from the PubMed, Cochrane Library, Web of Science and EMBASE databases. Each paper was reviewed, and data were extracted. We used R software version 3.6.3 to perform the meta-analysis. Fixed effects models were used for merging data. Results: A total of 11 papers met the inclusion criteria, with a total sample population of 264 patients. The meta-analysis showed that the pooled clinical success rate was 90% (95% confidence interval [CI], 0.85–0.95), the technical success rate was 99% (95% CI, 0.97–1.00) and the recurrence rate was 1% (95% CI, 0.00–0.03). Three studies reported the complications, including perforation, bleeding and stent migration; none of the other eight studies reported complications. There were no significant differences between subgroups. There was no publication bias in either the clinical or the technical success rates. Conclusions: This meta-analysis showed that EUS-guided drainage for abdominal abscess was effective and safe, with an excellent technical success rate. In addition, EUS-guided drainage could be used for abscesses with complex anatomy. Nevertheless, complications and stent type should be considered.

Abstract Background Prognostic indicators in lung adenocarcinoma (LUAD) have been seeking under database analysis, and remarkable advance is on the way. Methods This study calculated the scores of stromal and immune components of the tumor microenvironment (TME) in 551 LUAD samples using the ESTIMATE algorithm on The Cancer Genome Atlas (TCGA) database. R package ''limma'' was used to selected differentially expressed genes (DEG). We have analyzed the DEGs by means of Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments. The protein‐protein network, univariate Cox analysis, and Lasso regression analysis were performed to selected survival‐related genes. Gene Set Enrichment Analysis (GSEA) represented the enriched pathway of CC chemokine receptor 2 (CCR2). The ratios of immune cells in the TME of each LUAD sample were obtained using the R package "limma" and CIBERSORT algorithm in R 4.0.2. Results The ImmuneScore was positively correlated with prognosis regarding survival rate, T classification of TNM stages, and clinicopathological staging characteristics. GO and KEGG enrichments showed DEGs were associated with immune‐related activities. Three genes of LUAD were selected from the PPI network and Cox proportional hazards regression analysis. CCR2 was the most survival correlated gene by Lasso regression analysis. GSEA results showed that C2 kegg gene sets in the CCR2 high‐expression group were mainly enriched in the B cell or T cell receptor signaling pathway and natural killer cell‐mediated cytotoxicity. Correlation of CCR2 expression with prognosis was conducted, implicating a positive correlation with the prognosis of survival rate and M classification, negative correlation with the prognosis of T and N classifications. The correlation between CCR2 and tumor‐infiltrating immune cells (TICs) was analyzed, and 14 kinds of TICs were found closely correlated with CCR2 expression through difference analysis. Conclusion Therefore, CCR2 has prognostic value as an immune indicator in LUAD.

PurposeSystemic inflammatory markers may be predictors of the survival rate of patients with pancreatic cancer (PC). The aim of this work was to investigate the prognostic value of markers, mainly the systemic immune inflammation index (SII), in patients with metastatic and unresectable PC and to explore the relationship between markers and liver metastasis.MethodsRecords of patients with metastatic and unresectable PC at the Affiliated Hospital of Qingdao University from January 2000 to December 2019 and who were followed until December 2020 were retrospectively analyzed. Clinical data and laboratory indexes were collected, and cut-off values for inflammatory markers were determined using median values. The Cox proportional hazard model was used to analyze the prognostic value of the markers through univariate and multivariate survival analysis.ResultsAll 253 patients met the inclusion criteria, and 102 (42.0%) patients had liver metastasis. The patients were divided into a high SII group and a low SII group, and the cut-off value was 533. In the multivariate analysis, high SII (HR = 2.151; p

Emerging evidence has shown that long non-coding RNAs (lncRNAs) play an important role in colorectal cancer (CRC) carcinogenesis, so more specific mechanisms of key lncRNAs in CRC initiation and development are needed. Here, we evaluated the expression profiles of lncRNAs in CRC tissues and identified a novel lncRNA generated from the pseudogene Wiskott-Aldrich syndrome protein (WASP) family homolog 5, termed lncRNA WASH5P. However, the role and potential molecular mechanism of this novel lncRNA in diseases, including CRC carcinogenesis, is unknown. Our present study found that WASH5P was significantly downregulated in CRC cell lines and tissues compared with normal controls. The ectopic expression of WASH5P in CRC cells could significantly inhibit CRC cell proliferation, invasion, and migration. In addition, WASH5P could increase the expression of E-cadherin and decrease Vimentin expression. WASH5P-overexpressing CRC cells developed tumors more slowly in different mouse models. Meanwhile, the overexpression of WASH5P could significantly inhibit AKT activation via suppressing AKT phosphorylation. The treatment of PI3K/AKT (phosphatidlinositol 3-kinase /protein kinase B) signaling agonist 740Y-P rescued WASH5P-reduced AKT phosphorylation and abolished the inhibitory effects of WASH5P on cell viability, migration, and invasion. Moreover, 740Y-P restored the WASH5P-induced downregulation of p-AKT and vimentin and the upregulation of E-cadherin via Western blot. In summary, our findings suggested that the novel lncRNA WASH5P might be a potential candidate biomarker and therapeutic target that could inhibit CRC by repressing the AKT signaling pathway.

IntroductionEarly diagnosis could lead to a cure of colorectal cancer (CRC). Since CRC is related to aging and lifestyles, we tested if the environmental information-enriched monosaccharide composite (MC) of circulating glycans could serve as an early diagnostic biomarker for CRC. Meanwhile, we evaluated its role in predicting prognosis.MethodsHPAEC-PAD was used to quantify glycan monosaccharide compositions from a total of 467 serum samples including CRC patients, colorectal adenoma (CRA) patients and healthy individuals. Two diagnostic model was constructed by logistic regression analysis. The diagnostic performance of the two models was verified in the retrospective validation group and the prospective validation group. The prognostic performance of the model was assessed by survival analysis.ResultsThe concentrations of monosaccharides in serum were significantly higher in CRA and CRC patients than in healthy individuals. Two diagnostic models were constructed: MC1 was used to distinguish between healthy individuals and CRC; MC2 was used to distinguish between healthy individuals and CRA. Area under receptor operating characteristic curve (AUC) of MC2 and MC1 was 0.8025 and 0.9403 respectively. However, the AUC of CEA between healthy individuals and CRC was 0.7384. Moreover, in early stage of CRC (without lymph node metastasis), the positive rates of CEA and MC1 were 28% and 80%, respectively. The follow-up data showed that the increased MC1 value was associated with poor survival in patients with CRC (p=0.0010, HR=5.30).DiscussionThe MC1 model is superior to CEA in the diagnosis of CRC, especially in the early diagnosis. MC1 can be used for predicting prognosis of CRC patients, and elevated MC1 values indicate poor survival.

Abstract Background Gastric carcinoma (GC) is currently one of the most common malignant tumors of the digestive system, and gastric precancerous lesions play a vital role in studying the mechanism of GC. Multiple microRNAs (miRNAs) have been documented to be potential biomarkers to indicate progression of gastric precancerous lesions. In this study, we explained the anti-cancer effect of miR-365 in gastric precancerous lesions via regulation of the TLR4/IRF3/YAP/CDX2 axis. Methods miR-365, TLR4, CDX2 and IPF3 expression was determined in GC and atrophic gastritis tissues and cells. After transfection of shRNA and overexpression plasmids, in vitro experiments detected the alteration of cell viability, apoptosis and inflammatory factors. Bioinformatics analysis, Co-IP and dual luciferase reporter gene assay were conducted to evaluate the binding between miR-365 and TLR4 as well as IRF3 and YAP. Rat models were established to explore the effect of the miR-365 and TLR4 on gastric precancerous lesions. Results miR-365 was poorly expressed in GC and atrophic gastritis tissues and GC cell lines, while TLR4, CDX2 and IRF3 were overexpressed. Of note, miR-365 was indicated to target TLR4 and thereby suppressed cancer progression and increased hemoglobin content. Interestingly, silencing of TLR4 was accompanied by decreased IRF3 phosphorylation and reduced expression with less binding between CDX2 and IRF3. Downregulation of YAP resulted in declined CDX2 expression in cancer cells. Moreover, the inhibitory role of miR-365 was further confirmed in animal models. Conclusion Taken together, miR-365-mediated TLR4 inhibition reduces IRF3 phosphorylation and YAP-mediated CDX2 transcription to impede progression of gastric precancerous lesions.

Abstract Background Globally, colorectal cancer (CRC) affects more than 1 million people each year. In addition to non-modifiable and other environmental risk factors, Fusobacterium nucleatum infection has been linked to CRC recently. In this study, we explored mechanisms underlying the role of Fusobacterium nucleatum infection in the progression of CRC in a mouse model. Methods C57BL/6 J-Adenomatous polyposis coli (APC) Min/J mice [APC (Min/+)] were treated with Fusobacterium nucleatum (109 cfu/mL, 0.2 mL/time/day, i.g., 12 weeks), saline, or FadA knockout (FadA−/−) Fusobacterium nucleatum. The number, size, and weight of CRC tumors were determined in isolated tumor masses. The human CRC cell lines HCT29 and HT116 were treated with lentiviral vectors overexpressing chk2 or silencing β-catenin. DNA damage was determined by Comet assay and γH2AX immunofluorescence assay and flow cytometry. The mRNA expression of chk2 was determined by RT-qPCR. Protein expression of FadA, E-cadherin, β-catenin, and chk2 were determined by Western blot analysis. Results Fusobacterium nucleatum treatment promoted DNA damage in CRC in APC (Min/+) mice. Fusobacterium nucleatum also increased the number of CRC cells that were in the S phase of the cell cycle. FadA−/− reduced tumor number, size, and burden in vivo. FadA−/− also reduced DNA damage, cell proliferation, expression of E-cadherin and chk2, and cells in the S phase. Chk2 overexpression elevated DNA damage and tumor growth in APC (Min/+) mice. Conclusions In conclusion, this study provided evidence that Fusobacterium nucleatum induced DNA damage and cell growth in CRC through FadA-dependent activation of the E-cadherin/β-catenin pathway, leading to up-regulation of chk2.

Abstract Fucoidan is a kind of the polysaccharide, which comes from brown algae and comprises of sulfated fucose residues. It has shown a large range of biological activities in basic researches, including many elements like anti-inflammatory, anti-cancer, anti-viral, anti-oxidation, anticoagulant, antithrombotic, anti-angiogenic and anti-Helicobacter pylori, etc. Cancer is a multifactorial disease of multiple causes. Most of the current chemotherapy drugs for cancer therapy are projected to eliminate the ordinary deregulation mechanisms in cancer cells. Plenty of wholesome tissues, however, are also influenced by these chemical cytotoxic effects. Existing researches have demonstrated that fucoidan can directly exert the anti-cancer actions through cell cycle arrest, induction of apoptosis, etc., and can also indirectly kill cancer cells by activating natural killer cells, macrophages, etc. Fucoidan is used as a new anti-tumor drug or as an adjuvant in combination with an anti-tumor drug because of its high biological activity, wide source, low resistance to drug resistance and low side effects. This paper reviews the mechanism by which fucoidan can eliminate tumor cells, delay tumor growth and synergize with anticancer chemotherapy drugs in vitro, in vivo and in clinical trials.

Gastric cancer (GC) as a serious global health problem is a threat to human longevity. Plasmacytoma variant translocation 1 (PVT1) participates in the formation and progression of various cancers, including GC. The aim of this study is to investigate the mechanism underlying the functions of PVT1 and explore a novel target for the diagnosis and treatment of GC. Analysis of the TCGA dataset using the R software identified that the lncRNA PVT1 was greatly upregulated in GC tissues. Twenty pairs of GC and adjacent normal tissues were acquired from patients with GC, and the expression of PVT1 was evaluated using RT-qPCR. Furthermore, PVT1 expression was knocked down in GC cells using siRNA, and the GC cells were divided into control, negative control (NC), and siRNA groups. Cell proliferation ability was analyzed using Cell Counting Kit-8 (CCK8) and colony formation assays, whereas cell migration and invasion ability were investigated through wound healing and Transwell assays. Moreover, Western blotting was used to analyze the expression of Yes-associated protein (YAP) and epithelial-to-mesenchymal transition (EMT) proteins. We also found that PVT1 and YAP expressions were upregulated in the GC tissues compared with those in the adjacent nontumor tissues. Knockdown of PVT1 was found to inhibit the proliferation, invasion, and migration and promote apoptosis of GC cells. Furthermore, knockdown of PVT1 downregulated YAP and promoted phosphorylation of YAP, suggesting that PVT1 exerts actions on GC cells by targeting YAP and inhibits cell apoptosis in vitro. The EMT process was also inhibited by the knockdown of PVT1. In summary, lncRNA PVT1 facilitated cell proliferation, invasion, and migration and suppressed cell apoptosis by targeting YAP. This study suggests that the expressions of PVT1 and YAP could be used for the early detection of GC and the occurrence and development of GC could be inhibited by interfering the interaction of PVT1 and YAP, which will provide new insights for the diagnosis, treatment, and prognosis of GC.

Salidroside is an active ingredient extracted from Rhodiola rosea that has anti-tumor activities. The current paper attempted to assess the impact of Salidroside on gastric cancer (GC) and explore the potential mechanism. GC cell lines (SNU-216 and MGC803) and gastric epithelial cell line GES-1 were treated with Salidroside. CCK-8 assay, colony formation assay, flow cytometry and Transwell assay were respectively performed to evaluate GC cells phenotype. qRT-PCR and western blot were conducted to reveal the downstream genes and signaling of Salidroside. We found that 800 μM Salidroside was capable of reducing GC cells viability, while has no such impacts on GES-1 cells. Salidroside inhibited GC cells proliferation, migration, invasion and promoted apoptosis, which coupled with the down-regulation of p21, Bcl-2, MMP2, RhoA, p-ROCK1, Vimentin and the up-regulations of CyclinD1, Bax, cleaved caspases. miR-99a was found to be highly expressed in response to Salidroside treatment. Besides, the inhibition of MAPK/ERK and PI3K/AKT signaling induced by Salidroside was attenuated by miR-99a silence and in this process, IGF1R worked as a target of miR-99a. The anti-GC effect of Salidroside was also confirmed in a mouse model of GC. The promoting effect of Salidroside on miR-99a expression was also verified in vivo. Furthermore, Salidroside promoted the cisplatin-sensitivity of SGC7901/DDP cells. In conclusion, this study demonstrated that Salidroside possessed anti-GC effects through regulating miR-99a/IGF1R axis and inhibiting MAPK/ERK and PI3K/AKT pathways.

Human cytomegalovirus (HCMV) infection is very common in the human population all around the world. Although the majority of HCMV infections are asymptomatic, they can cause neurologic deficits. Previous studies have shown that immediate early protein 2 (IE2, also known as UL122) of HCMV is related with the cognitive disorder mechanism. Due to species isolation, a HCMV-infected animal model could not be established which meant a study into the long-term effects of IE2 on neural development could not be carried out. By establishing HCMV-UL122-Tg mice (UL122 mice), we explored the cognitive behavior and complexity of neuron changes in this transgenic UL122 mice that could consistently express IE2 protein at different ages (confirmed in both 6- and 12-month-old UL122 mice). In the Morris water maze, cognitive impairment was more pronounced in 12-month-old UL122 mice than in 6-month-old ones. At the same time, a decrease of the density of dendritic spines and branches in the hippocampal neurons of 12-month-old mice was observed. Moreover, long-term potentiation was showed to be impaired in 12-month-old UL122 mice. The expressions of several synaptic plasticity-regulated molecules were reduced in 12-month-old UL122 mice, including scaffold proteins postsynaptic density protein 95 (PSD95) and microtubule-associated protein 2 (MAP2). Binding the expression of IE2 was increased in 12-month-old mice compared with 6-month-old mice, and results of statistical analysis suggested that the cognitive damage was not caused by natural animal aging, which might exclude the effect of natural aging on cognitive impairment. All these results suggested that IE2 acted as a pathogenic regulator in damaging synaptic plasticity by downregulating the expression of plasticity-related proteins (PRPs), and this damage increased with aging.

Alterations in the microbiome are associated with the development of gastric cancer. Our study aimed to identify dysbiotic features in early gastric cancer (EC). The gastric microbiome was assessed in EC (n = 30), advanced gastric cancer (AC) (n = 30), and chronic gastritis (CG) (n = 60). The results demonstrated significant differences in the microbial profile and composition between EC and AC, suggesting alterations associated with gastric cancer progression. Linear discriminant analysis (LDA) effect size (LEfSe) analyses identified 32 bacterial genera that were associated with EC. Functional analyses of the gastric microbiome showed that the production of urease and synthesis of bacterial flagella were weakened in EC, while the glycolysis of fructose and hydrolysis of glycosides were enhanced. A classifier based on a random forest (RF) machine learning algorithm identified a microbial signature that distinguished EC from CG or AC with high accuracy. The correct identification of the signature was further validated in independent cohorts. This signature enriched of bacteria with varied abundance, high degree of bacterial interactions and carcinogenic potentials. Constrained principal coordinate analyses revealed that the presence of Helicobacter pylori and the cagA and vacA virulence genotypes influenced the structure of the gastric microbiome. To determine the impacts of host genetic variations on the gastric microbiome, six previously reported single nucleotide polymorphisms (SNPs) were examined. The minor allele of MUC1 rs4072037 was associated with an increased abundance of Ochrobactrum. The gastric microbiome altered in EC, which might be attributed in part to host genetic variations, H. pylori infection, bacterial virulence and environmental adaptations. The identified microbial signature could serve as biomarkers for clinical assessment of gastric cancer risk in high-risk patients.

Background/Aims: The up-regulation of hepatocyte growth factor/receptor, HGF/Met, signal transduction is observed in most of human cancers. Specific heparan sulfate structures enhance the HGF/Met signaling at both cell and animal-based model systems. Biochemical studies indicate that heparan sulfate interacts with HGF and a natural occurring splicing variant NK1 of HGF with similar affinity. However, it is currently unknown if cell surface heparan sulfate binds to Met at physiological conditions and if specific cell surface heparan sulfate structures are required for effective HGF/Met or NK1/Met signaling. Methods: An established flow sorting strategy was used to isolate a soluble Met recombinant protein-binding positive or negative CHO cell clones different only in specific heparan sulfate structures. The cell surface bindings were imaged by confocal microscopy and flow cytometry analysis. Glucosamine vs. galactosamine contents from media-, cell surface-, and cell association glycosaminoglycans were quantified by HPLC. 35S-sulfate labeled glycosaminoglycans were characterized by anion exchange and size-exclusion HPLC. Heparan sulfate disaccharide compositions were determined by HPLC-MS analysis. Western blot analyses of MAPK-p42/44 were used to monitor HGF- and NK1-facillated Met signaling. Results: CHO-Positive but not CHO-Negative cell surface heparan sulfate bound to Met recombinant protein and HGF/NK1 further promoted the binding. Overall glycosaminoglycan analysis results indicated that the CHO-Negative cells had reduced amount of heparan sulfate, shorter chain length, and less 6-O-sulfated disaccharides compared to that of CHO-Positive cells. Moreover, CHO-Negative cells were defective in NK1/Met but not HGF/Met signaling. Conclusions: This study demonstrated that soluble Met recombinant protein bound to cell surface HS at physiological conditions and a Met /HGF or NK1/HS ternary signaling complex might be involved in Met signaling. Shorter HS chains and reduced 6-O-sulfation might be responsible for reduced Met binding and the diminished NK1-initiated signaling in the CHO-Negative cells. The unique CHO-Positive and CHO-Negative cell clones established in current study should be effective tools for studying the role of specific glycosaminoglycan structures in regulating Met signaling. Such knowledge should be useful in developing glycosaminoglycan-based compounds that target HGF/Met signaling.

Background and Aims. Endoscopic removal of GISTs (gastrointestinal stromal tumors) is recently recognized, but less is known about its efficacy and safety. This study is aimed at assessing the feasibility, clinical efficacy, and safety of the endoscopic removal of gastric GISTs. Patients and Methods. Endoscopic removal (ER) of GISTs was performed in 134 patients at our hospital between January 2015 and January 2019. The clinical features, surgical outcomes, complications, pathological diagnosis, and risk classification were evaluated retrospectively. Results. ER was successful in 131 cases (98%), including 58 by ESD (endoscopic submucosal dissection), 43 by ESE (endoscopic submucosal excavation), 25 by EFTR (endoscopic full-thickness resection), and 5 by STER (submucosal tunneling endoscopic resection). In addition, GISTs of two cases were resected using LECS (laparoscopic and luminal endoscopic cooperative surgery) for the extraluminal and intraluminal growth pattern. The average tumor size was 1.89±1.25 cm (range: 0.5-6.0 cm). Of these patients, 26 cases had a large tumor size (range: 2.0-6.0 cm), and endoscopic removal was successful in all of them. During the procedure, endoclips were used to close the perforation in all cases, without conversion to open surgery. The average length of hospital stay was 5.50±2.15 days (range: 3-10 days). In the risk classification, 106 (79.7%) were of a very low risk, 25 (18.8%) of a low risk, and 2 (1.5%) of a moderate risk. The moderate-risk cases were treated with imatinib mesylate after ER. No recurrence or metastasis was observed during the follow-up period of 23±8 months (range: 3-48 months). Conclusions. The endoscopic treatment is feasible, effective, and safe for gastric GISTs, and individualized choice of approaches is recommended for GISTs.

Colorectal cancer (CRC) is a growing health problem throughout the world. Strong evidences have supported that gut microbiota can influence tumorigenesis; however, little is known about what happens to gut microbiota following surgical resection. Here, we examined the changes of gut microbiota in CRC patients after the surgical resection. Using the PCoA analysis and dissimilarity tests, the microbial taxonomic compositions and diversities of gut microbiota in post-surgery CRC patients (A1) were significantly different from those in pre-surgery CRC patients (A0) and healthy individuals (H). Compared with A0 and H, the Shannon diversity and Simpson diversity were significantly decreased in A1 (P < 0.05). Based on the LEfSe analysis, the relative abundance of phylum Proteobacteria in A1 was significantly increased than that in A0 and H. The genus Klebsiella in A1 had higher proportions than that in A0 (P < 0.05). Individual variation was distinct; however, 90% of CRC patients in A1 had more abundances of Klebsiella than A0. The Klebsiella in A1 was significantly associated with infectious diseases (P < 0.05), revealed by the correlation analysis between differentiated genera and metabolic pathway. The Klebsiella (Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae) in A1 was significantly linked with lymphatic invasion (P < 0.05). Furthermore, the PCA of KEGG pathways indicated that gut microbiota with a more scattered distribution in A1 was noticeably different from that in A0 and H. The nodes, the links, and the kinds of phylum in each module in A1 were less than those in A0 and H, indicating that gut microbiota in A1 had a relatively looser ecologcial interaction network. To sum up, this pilot study identified the changes of gut microbiota in post-surgery CRC patients, and highlights future avenues in which the gut microbiota is likely to be of increasing importance in the care of surgical patients.

Prevalence of malnutrition is a common and serious issue responsible for the morbidity and mortality rate among hospitalized patients. We aimed to provide an actual and comprehensive situation of the nutritional characteristics, nutritional support and the risk factors for malnutrition among hospitalized patients in China.We analyzed the data from nutritionDay audit 2016 in China. The international daylong cross-sectional survey was performed on November 10th, 2016 via filling out several questionnaires regarding information on patients' illness, food intake history, weight change and nutritional care. Re-assessment of patients' outcome questionnaire was performed 30 days later.Total of 781 patients from 9 hospitals and 8 kinds of departments were enrolled in this report. Of these, malnutrition rate was 29.6%. Parenteral nutrition (251/344, 73.0%) was the primary nutrition support form in Chinese hospitals. However, 41.8% (136/325) of patients at nutritional risk or already diagnosed with malnutrition did not received any form of nutritional support, whereas 34.0% (155/456) well-nourished patients did. Patients with malnutrition had extended length of hospital stay and poor 30-day outcomes compared to well-nourished patients. Nutritional support could benefit nutritional risk or malnutrition patients, rather than well-nourished patients. Moreover, major lesion types, self-related health, food intake last week were independent risk factors of malnutrition (all p

Background: The aim of this study was to explore the relationship between nutritional status and expression of RUNX3 in gastric cancer cells and to investigate the effects of nursing strategies on the nutritional status of elderly patients with advanced gastric cancer. Methods: Forty-eight elderly patients admitted at Affiliated Hospital of Qingdao University with advanced gastric cancer and 30 healthy controls were selected as subjects from 2014-15. The correlation between RNX3 gene expression and nutritional status of the gastric cancer patients was investigated. The patients with advanced gastric cancer who had low expression of RUNX3 gene were treated with holistic nursing while routine nursing was taken for those patients who had normal or high expression of RUNX3 gene. The nutritional statuses of these patients were evaluated after 3 months of nursing. After a follow-up of 1 year, the influence of different nursing methods on the survival time was evaluated. Results: Compared with normal gastric tissue, the expression of RUNX3 gene and protein in tissues of advanced gastric cancer were significantly decreased (P0.05). The survival time of patients with low expression of RUNX3 who received holistic nursing were similar to patients with normal or high expression of RUNX3 who received routine nursing (P>0.05). Conclusion: RUNX3 is correlated with the occurrence and development of advanced gastric cancer. The low nutritional status of elderly advanced gastric cancer patients with low expressions of RUNX3 can be significantly enhanced by holistic nursing, thereby prolonging survival time.

The aim of this study is to identify and consolidate reliable endoscopic features associated with H. pylori infection in gastric mucosa, which is one of the major causes of gastric cancer. A total of 256 Chinese patients with symptomatic stomach disturbances were enrolled. Pathological examination was conducted using a light microscope and biopsy specimens stained with hematoxylin-eosin. Endoscopic examination was performed using a high resolution video endoscope. The association between endoscopic features and pathological H. pylori diagnosis was compared, and endoscopic features significantly associated with H. pylori infection were identified. A total of 14 endoscopic features were observed. Six of the 14 endoscopic features, including mucus on the gastric mucosa, diffuse redness, spotty redness of fundic mucosa, enlarged fold, mucosal edema, and RAC (type D and type I), were highly associated with H. pylori infection and were significantly sensitive and specific predictors for H. pylori diagnosis. The type R RAC was not significantly associated with H. pylori diagnosis. Our results indicate that conventional endoscopy features can be used to diagnose H. pylori in Chinese patients and can help determine the risk factor for gastric cancer.