Background With advent of direct-acting antiviral agents (DAA), hepatitis C virus (HCV) treatment is dramatically increasing. Although few studies reported rates of hepatocellular carcinoma (HCC) recurrence following DAA treatment, there have been no studies that followed sufficient number of DAA-treated patients after successful HCC treatment to examine HCC recurrence. Methods We conducted a cohort study of HCV+ patients who had successfully treated HCC before initiating DAAs. We conducted medical record reviews to confirm HCC diagnosis, treatment, and remission prior to DAA initiation, and subsequent HCC recurrence. We calculated HCC recurrence rate and examined the recurrent tumor characteristics. We used Cox proportional hazard model to identify factors associated with HCC recurrence. Results We identified 264 HCV+ patients who received DAAs after an average of 30.9 (20.6) months following HCC treatment. HCC recurred in 26.1% patients during 23.3 (9.8) months follow-up, at a rate of 0.38 [0.30, 0.48] per 1000 personmonth. Most (82.3%) recurrent HCC were early stage. Receiving non-curative treatment for HCC was associated with a higher risk of recurrence than curative treatment (HRadj = 2.06, [1.24, 3.40]). The risk of HCC recurrence decreased with longer duration between HCC treatment completion and DAA initiation (HRadj = 0.97, [0.95, 0.99] per additional month). Compared with patients who achieved sustained virological response (SVR), those without SVR had significantly increased risk of HCC recurrence (HRadj = 4.17, [1.48, 11.75]). Conclusions We conclude that most HCV+ patients with HCC benefit from DAA treatment; however, timing of DAA initiation after HCC treatment should be carefully considered.
Background Insufficient blood supply in the gastric tube is considered as a risk factor for postoperative anastomotic strictures in patients receiving esophagectomy, but the direct evidence is lacking. Aims We aimed to investigate the correlation between perioperative blood supply in the anastomotic area of the gastric tube and the formation of anastomotic strictures in the patients undergoing esophagectomy. Methods This prospective study included 60 patients with esophageal squamous cell carcinoma undergoing Ivor Lewis esophagectomy between March 2014 and February 2016, which were divided into stricture group (n = 13) and non-stricture group (n = 47) based on their severity of anastomotic strictures at 3 months post-operation. The perioperative anastomotic blood supply was measured using a laser Doppler flowmetry. The gastric intramucosal pH (pHi) was measured by a gastric tonometer within 72 h post-operation. The perfusion index and gastric pHi were compared between groups. Results The stricture group had a significantly lower blood flow index (P < 0.001) and gastric pHi values from day 1 to day 3 post-operation than the non-stricture group (all P < 0.001). In addition, Pearson correlation analysis showed that both the perfusion index and gastric pHi were significantly correlated with stricture size and stricture scores, respectively (r = 0.65 - 0.32, all P < 0.05). Furthermore, the multivariate logistic regression analysis showed that perfusion index was an influential factor associated with postoperative anastomotic strictures (OR 0.84. 95% CI 0.72-0.98, P = 0.026). Conclusion These results suggested that poor blood supply in the anastomotic area of the gastric tube in the perioperative period was a risk factor for postoperative anastomotic strictures.
Background The epidemiology of upper gastrointestinal (L4) Crohn's disease in China remains poorly characterized. Aims We aimed to identify the clinical characteristics of L4 disease and clarify the relationship between disease characteristics at diagnosis and early outcomes. Methods We retrospectively enrolled 246 patients diagnosed between 2013 and 2017 and followed up for > 1 year post-diagnosis. Primary outcomes included the 1-year rates of hospitalization and abdominal surgery according to disease location and behavior. Results Of 80 patients with L4 disease (61, 25, and 18 with esophagogastroduodenal, jejunal, and proximal ileal involvement, respectively), none had granuloma, whereas 66.7%, 50%, 46.9%, 75%, and 70% had disease-specific endoscopic lesions in the esophagus, stomach, duodenum, jejunum, and proximal ileum, respectively. Compared to non-L4 disease, L4 disease was associated with higher rates of abdominal surgery (41.3% vs. 11.4%, P < 0.001) but similar rates of hospitalization within 1 year post-diagnosis. In L4 disease, jejunal and proximal ileal involvement was associated with stricturing behavior (P = 0.034, P < 0.001) and higher abdominal surgery rate (both: P < 0.001). Risk factors for abdominal surgery within 1 year post-diagnosis included age >= 40 years (OR 1.920; 95% CI 1.095-3.367), L4 phenotype (OR 6.335; 95% CI 3.862-10.390), stricturing disease (OR 3.162; 95% CI 1.103-9.866), and penetrating disease (OR 11.504; 95% CI 3.409-38.825), whereas the protective factor was female sex (OR 0.214; 95% CI 0.123-0.373). Conclusions Early outcomes are worse for L4 than for non-L4 disease. Jejunoileum involvement predicts stricturing disease and early surgery. More aggressive initial therapy is needed to improve L4-disease prognosis.
Background Delayed colectomy can be life-threatening for patients with acute severe ulcerative colitis (ASUC). However, few biomarkers can predict the outcomes of ASUC patients before treatment. Serum procalcitonin (PCT) has been observed to be increased in ASUC patients. Aim The aim of this study was to estimate the association between serum PCT and short-term outcomes in patients with ASUC. Methods A single-center observational study was conducted at a referral hospital from January 2012 to January 2018. Hospitalized ASUC patients, who were administered intravenous corticosteroids (IVCS), were enrolled and followed up for 6 months. The primary outcome was IVCS failure; the secondary outcome was colectomy. Relationships between indicators and clinical outcomes were assessed. Results Of 152 ASUC patients enrolled in this study, 81 responded to IVCS and 71 failed (62 required short-term colectomy and 9 responded to second-line rescue therapy). Serum PCT on admission was significantly higher in IVCS-failure cases and surgical cases than in medical responders. Serum PCT >= 0.10 mu g/L (OR=4.134, p=0.001) predicted IVCS failure with specificity of 0.741, and the combined measurement with fecal calprotectin (FC) >= 1500 mu g/g improved the sensitivity. Serum PCT correlated significantly with the Ulcerative Colitis Endoscopic Index of Severity (r=0.416, p<0.001) and FC (r=0.384, p<0.001). Conclusion Serum PCT on admission could be a potential early non-invasive predictive biomarker for IVCS failure in ASUC patients, and a combination of PCT and FC could improve the predictive value.
Background We previously reported that there were potentially certain correlations between the high expression of SATB1 and the HBV infection in human hepatocellular carcinoma tissues, and SATB1 promoted tumor growth and metastasis in liver cancer. Hepatitis B virus (HBV) infection is internationally recognized as a contributing factor to metastasis in liver cancer. The anoikis prevention of detached malignant cancer cells is the precondition for metastasis. Aims Our studies aimed to explore the relationship between HBV infection, SATB1 and liver cancer cell anoikis and their specific regulatory mechanisms in HBV-associated liver cancer. Methods HepG2 cell was transiently transfected with pBlue-HBV and seven types of HBV-encoded protein plasmids. Anoikis assay and soft agarose colony formation experiment were analyzed in HepG2.2.15-SATB1 siRNA cells, HBx-overexpressing cells and HepG2-HBx-SATB1 siRNA cells. The inhibitors of signaling molecules were used to treat of HepG2-HBx cells, and then, the SATB1 expression and phosphorylation levels of signaling molecules were evaluated. Results Our data show that the high expression of SATB1 and enhanced anoikis resistance were observed in HBV stably expressing cell line HepG2.2.15 and high metastatic potential cell line SK-HEP-1. HBV can induce SATB1 expression and suppress anoikis of unattached liver cancer cells. Moreover, SATB1 expression and anoikis resistance were mainly regulated by HBV-encoded viral protein HBx through the activation of ERK and p38 MAPK signaling pathways to promote metastasis of liver cancer. Conclusion These data suggest that the HBV-encoded HBx and SATB1 may play an important role in promoting anoikis resistance and metastasis in HBV-associated liver cancer.
Background Vitamin E has been reported to have a beneficial effect on nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanism of action has not yet been clearly defined. Aim We aimed to evaluate the effects and mechanisms of vitamin E on lipid and glucose homeostasis both in vivo and in vitro. Methods An NAFLD model was established in C57BL/6 mice fed a 30% fructose solution for 8 weeks. Subsequently, NAFLD mice were given vitamin E (70 mg/kg) for 2 weeks. In addition, L02 cells were treated with 5 mM fructose and 100 nM vitamin E to explore the potential mechanisms of action. Results Vitamin E reversed the impaired glucose tolerance of fructose-treated mice. Histopathological examination showed that liver steatosis was significantly relieved in vitamin E-treated mice. These effects may be attributed to the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2), carboxylesterase 1 (CES1), and downregulated proteins involved in lipid synthesis by vitamin E treatment. In vivo, vitamin E also significantly reduced lipid accumulation in fructose-treated L02 cells, and the Nrf2 inhibitor ML385 reversed the protective effects of vitamin E. Conclusion These data indicated that the therapeutic effects of vitamin E on lipid and glucose homeostasis may be associated with activation of the Nrf2/CES1 signaling pathway.
Background/Aims Early assessment is a key factor for adequate and comprehensive treatment of acute pancreatitis (AP). Silent information regulator 1 (SIRT1) plays an important role in inflammation. The aim was to explore the relationship between serum SIRT1 and persistent organ failure (POF) in patients with AP. Methods Thirty-seven healthy controls (HCs) and 113 patients with AP were recruited for this study. All 113 patients whose blood samples were collected on the first morning after admission were within 48 h of the onset of AP symptoms. The concentration of serum SIRT1 protein was determined by enzyme-linked immunosorbent assay. Results The serum SIRT1 protein levels were 1495.7 +/- 185.9, 2098.3 +/- 153.6, 2498.4 +/- 198.2, and 3674.3 +/- 170.8 pg/ml in the HCs, mild AP, moderately severe AP, and severe AP groups, respectively. Obvious differences were observed between HCs and patients with AP (P < 0.05). Significant increases were observed in SIRT1 concentrations in patients with POF compared with non-POF patients (P < 0.05). When the cut-off of the SIRT1 concentration was 4065.4 pg/ml, the serum SIRT1 concentration had an area under the curve (AUC) of the receiver operating characteristic curve of 0.825 (95% CI 0.744-0.906) for predicting POF, with a sensitivity of 61.4% and specificity of 92.8%. Combining serum SIRT1 and bedside index for severity acute pancreatitis (BISAP) achieved 0.931 (95% CI 0.882, 0.980) of AUC for the predication of POF. Conclusions High serum SIRT1 levels may serve as an early predictive marker for POF. Combining the serum SIRT1 concentration with BISAP increased the ability to predict outcomes.
Background The protein tyrosine phosphatase delta (PTPRD) is a tumor suppressor, and its role in gastric cancer (GC) remains poorly understood. Methods The expressions of PTPRD were determined based on public data. In addition, the mRNA expressions of PTPRD in the GC samples, and the expressions of PTPRD in the GC cell lines including HGC27, SGC790, and BGC823, and gastric epithelial cell line GES-1 were determined by western blotting and quantitative real-time PCR. Furthermore, PTPRD siRNA was transfected into the HGC27 cell line, and then, cell proliferation, migration, and invasion were evaluated. The activity of signal transducer and activator of transcription 3 (STAT3) pathways in HGC27 cells transfected with PTPRD siRNA was determined by western blotting. Results PTPRD deletion was found in the GC patients, and this deletion was found to be correlated with poor prognosis in the GC patients. Expression of PTPRD was significantly downregulated in gastric carcinoma specimens and tumor cell lines when compared with those in normal controls. PTPRD also plays a key role in the GC cells proliferation, invasion, and migration. Silencing PTPRD expression by siRNA dramatically promoted GC cells proliferation, invasion, and migration. Mechanism study demonstrated that phosphorylation of STAT3 was inhibited by silencing PTPRD expression and the according changes including inhibition of cell migration and invasion were observed. Conclusion This study supports PTPRD as a tumor suppressor and could be served as a marker for prognostic of GC. Silencing PTPRD could be a potential therapeutic in GC.
Background Gastric cancer (GC) is one of the most common causes of cancer death. Hypoxia is an important property of the tumor microenvironment of GC. Increasing evidence demonstrates that tumor-associated macrophages are related to the metastasis of GC, while the precise mechanism of how hypoxic macrophages affect tumor progression is still not fully understood. Aims To examine whether the mediators released from hypoxic macrophages contribute to the invasion and proliferation of GC cells. Methods Cell Counting Kit-8 was utilized to determine the proliferation of SGC7901 and MKN45 cells. The invasion of SGC7901 and MKN45 cells was measured by transwell invasion assay. Expression of VEGF mRNA in THP-1-derived macrophages was determined by RT-PCR, and protein level of VEGF in the culture medium was detected by ELISA. Results The proliferation and invasion of SGC7901 and MKN45 cells were dramatically increased after treatment with conditioned medium (CM) collected from THP-1-derived macrophages under hypoxia (H-CM), and the phosphorylation of Akt and p38 in SGC7901 and MKN45 cells was also up-regulated by H-CM stimulation. Notably, blockage of PI3K-Akt or p38 MAP kinase abolished the effects of H-CM on the proliferation and invasion of SGC7901 and MKN45 cells. Furthermore, VEGF was increased in macrophages after hypoxia and administration with nintedanib, an inhibitor of VEGFR, significantly decreases the phosphorylation of Akt and p38, as well as the proliferation and invasion of SGC7901 and MKN45 cells in response to H-CM. Conclusions Our findings suggest that hypoxia-injured macrophages contribute to the proliferation and invasion of GC cells through the release of mediators such as VEGF.
Necrotizing enterocolitis (NEC) is one of the most severe diseases of preterm neonates and has a high mortality rate. With the development of inspection techniques and new biomarkers, the diagnostic accuracy of NEC is constantly improving. The most recognized potential risk factors include prematurity, formula-feeding, infection, and microbial dysbiosis. With further understanding of the pathogenesis, more effective prevention and therapies will be applied to clinical or experimental NEC. At present, such new potential prevention and therapies for NEC are mainly focused on the Toll-like receptor 4 inflammatory signaling pathway, the repair of intestinal barrier function, probiotics, antioxidative stress, breast-feeding, and immunomodulatory agents. Many new studies have changed our understanding of the pathogenesis of NEC and improve our approaches for preventing and treating of NEC each year. This review provides an overview of the recent researches focused on clinical or experimental NEC and highlights the advances made within the past 5 years toward the development of new potential preventive approaches and therapies for this disease.
The original version of the article unfortunately contained an error in funding information. This has been corrected with this erratum.
BackgroundTrophinin-associated protein (TROAP) is a cytoplasmic protein that functions as an adhesion molecule in processes such as embryo implantation, spindle formation, and cancer.ObjectiveTo evaluate the relationship of TROAP expression in hepatocellular carcinoma (HCC) tissue with clinicopathologic parameters and survival time in liver cancer patients based on an analysis of The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data.MethodsRNA-sequencing (RNA-Seq) expression data and clinical information were downloaded for the TCGA-LIHC cohort. Associations between TROAP expression in HCC tissues and clinical parameters were evaluated by Chi-square tests. Differences in survival between high and low expression groups (median expression cutoff) from Cox regression analysis were compared, and P values were calculated by a log-rank test. Kaplan-Meier curves were compared with the log-rank test.ResultsAnalysis of RNA-Seq gene expression data for 373 patients with primary tumors revealed overexpression of TROAP in liver cancer. High TROAP expression was associated with survival status (P=0.015), T stage (P=0.049), clinical stage (P=0.048), and gender (P=0.033). Patients with high TROAP-expressing liver cancers had a shorter median overall survival of 3.83years compared with 5.80years for patients with low TROAP-expressing liver cancers (P=0.00422). Multivariate analysis identified TROAP expression as an independent prognostic variable for overall survival in liver cancer patients.ConclusionTROAP expression is an independent predictor of poor survival in liver cancer.
BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Recent studies have reported that circular RNAs (circRNAs) are important regulators of hepatic steatosis. However, the role and mechanism of circRNA in NAFLD are poorly understood.AimsThis study is to reveal the role and mechanism of circRNA in NAFLD.MethodsThrough NAFLD-related circRNA microarrays, we used real-time quantitative reverse transcription-polymerase chain reaction to screen circScd1 levels in control and test groups of mice fed a high-fat diet. RNA interference and over-expression plasmid vectors were used to manipulate the expression of circScd1, and the biological effects were evaluated by oil red staining, triglyceride detection, and western blot analysis.ResultsCircScd1 expression was significantly lower in NAFLD tissues than in control tissues. Moreover, over-expression of circScd1 significantly inhibited the formation of lipid droplets. Western blot analyses showed that the protein levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) were significantly increased. However, knockdown of circScd1 significantly promoted the degree of hepatocellular lipidosis and reduced the expression levels of JAK2 and STAT5.ConclusionsAberrant expression of circScd1 affects the extent of hepatocellular lipidosis in NAFLD and promotes fatty liver disease via the JAK2/STAT5 pathway.