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Infected pancreatic necrosis (IPN) is a highly morbid complication of acute necrotising pancreatitis (ANP). Since there is evidence of early-onset immunosuppression in acute pancreatitis, immune enhancement may be a therapeutic option. This trial aimed to evaluate whether early immune-enhancing Thymosin alpha 1 (Tα1) treatment reduces the incidence of IPN in patients with predicted severe ANP.We conducted a multicentre, double-blind, randomised, placebo-controlled trial involving ANP patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and a computed tomography (CT) severity score ≥ 5 admitted within 7 days of the advent of symptoms. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebos (normal saline). The primary outcome was the development of IPN during the index admission.A total of 508 patients were randomised, of whom 254 were assigned to receive Tα1 and 254 placebo. The vast majority of the participants required admission to the intensive care unit (ICU) (479/508, 94.3%). During the index admission, 40/254(15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95% CI - 7.4 to 5.1%]; p = 0.48). The results were similar across four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%).The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.

Background Optimal non-invasive biomarkers for diagnosis and treatment of nonalcoholic fatty liver disease (NAFLD) remain to be identified. Aims To identify potential DNA methylation biomarkers for NAFLD. Methods Genome-wide DNA methylation profiling was performed to identify differentially methylated CpG sites in peripheral blood leukocytes. Differentially methylated regions were validated using the MassCLEAVE assay. The expression levels of candidate genes were explored by Gene Expression Omnibus database. Results The hypomethylation of PRKCE CpG 4.5 and CpG 18.19 was associated with nonalcoholic fatty liver (NAFL), the odds ratio (OR) and 95% confidence interval (CI) were 0.129 (0.026–0.639) and 0.231 (0.069–0.768). The methylation level of CpG 1.2 and average methylation level of SEC14L3 were correlated with NAFL, with OR (95% CI) being 0.283 (0.093–0.865) and 0.264 (0.087–0.799). PRKCE CpG 4.5 and cg17802464 of SEC14L3 were correlated with body mass index, waist circumference, total triglyceride, high-density lipoprotein cholesterol, alanine aminotransferase and aspartate aminotransferase. All selected datasets showed high expression levels of PRKCE and SEC14L3 in patients with NAFLD. Conclusions Our findings suggest that the hypomethylation of PRKCE and SEC14L3 promoters represent attractive biomarkers for NAFLD. Further studies are warranted to validate these biomarkers as molecular tools for diagnosis of NAFLD and therapeutic targets.

Aortic sinus aneurysms are mainly congenital malformations that can involve the left, right, and noncoronary sinus. Rupture of the noncoronary sinus aneurysms is rare, and its mechanisms and complications are still imperfectly known due to the rarity of this condition. A case of multiple organ dysfunction caused by a ruptured noncoronary sinus aneurysm has been reported.

Objectives The present study aims to identify the underlying mechanisms of ferroptosis and lncRNA-miRNA-mRNA network in AP by bioinformatics tools.Methods The ferroptosis genes interacted with data obtained from the Gene Expression Omnibus to identify differentially expressed genes (DEGs). Gene ontology, KEGG pathway enrichment analysis, protein-protein interaction network construction, hub genes association analysis, and transcription factor prediction were used to select and analyze the differentially expressed genes. lncRNA-miRNA-mRNA interaction network were constructed by integrating the lncRNA-miRNA pairs and miRNA-mRNA pairs.Results We identified 38 differentially expressed genes from the datasets. The function enrichment and pathway enrichment analysis of the DEGs were mostly implicated in stress response and the MAPK signaling pathway. The lncRNA-miRNA-mRNA network contained 145 lncRNA nodes, 4 miRNA nodes, 18 mRNA nodes and 235 edges. SQSTM1, KRAS, NFE2L2, HMOX1, SLC7A11, EGFR and ATF3 were identified as hub DEGs, and hub gene-related main TF MYC was discovered to have critical positive associations with these hub genes in pancreatic tissues. Conclusion The results of this study indicated that hub genes and the lncRNA-miRNA-mRNA network may play an important role in the mechanisms of ferroptosis in AP and provide treatment targets for AP.

Iron overload is frequently observed in non-alcoholic fatty liver disease (NAFLD). Transferrin receptor 2 (TFR2) is an important key factor in iron regulation. We aimed to investigate whetherFive tag SNPs (rs10247962, rs4434553, rs2075672, rs1052897, and rs3757859) in theLogistic regression analyses suggested that subjects with the rs4434553 GA or GG genotype had a lower risk of NAFLD than those carrying the AA genotype (odds ratio = 0.630, 95% confidence interval = 0.504-0.788). Moreover, the rs4434553 GA or GG genotype was negatively correlated with body mass index, hepatic steatosis index, and serum ferritin (In this Chinese Han population, the rs4434553 polymorphism in

BACKGROUND Acute pancreatitis (AP) is a common acute abdominal disease. Rapid evaluation of the severity is important for AP prognosis and treatment. Free triiodothyronine (fT3) level is associated with the prognosis of AP patients. This study aimed to investigate the fT3 level in patients with acute pancreatitis; early warning signs of inflammation, including interleukin-6 (IL-6) and interleukin-10 (IL-10); and the correlation of fT3 level with illness severity. MATERIAL AND METHODS Enrolled AP patients (N=312) were divided into an SAP group (N=92) and a non-SAP group (N=220) according to the Revision of Atlanta classification. Blood or tissue samples and baseline clinical characteristics were recorded. The t test and chi-square test were used to evaluate differences between the 2 groups. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to investigate protective factors. One-way repeated measures analysis of variance was used to evaluate the prognosis of SAP patients. RESULTS In our study, compared with APACHII score (AUC 0.829 [95% CIs 0.769-0.889]) and Ranson score (AUC 0.629 [95% CIs 0.542-0.715]), our predictive model (AUC 0.918 [95% CIs 0.875-0.961]) showed better prognostic performance in predicting poor patient outcomes. In the SAP group, changes in fT3 level were significantly associated with prognosis (P0.05). CONCLUSIONS The predictive model can improve the diagnostic accuracy and prediction of the severity of disease. FT3 level could be used as an independent risk factor to predict the mortality of SAP patients.

BACKGROUND&AIMSInfected pancreatic necrosis (IPN) is a highly morbid complication of acute pancreatitis (AP). Since there is evidence of immunosuppression in the early phase of AP, immune enhancement using Thymosin alpha 1 (Tα1), which stimulates both innate and adaptive immunity, may be a therapeutic strategy to prevent IPN. Our aim was to assess the efficacy of early Tα1 treatment on the development of IPN.METHODSWe conducted a multicenter, randomized, double-blind, placebo-controlled trial in patients with predicted severe acute necrotizing pancreatitis (ANP). ANP patients with an APACHE II score≥8 admitted within seven days of the advent of symptoms were considered eligible. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg, every 12 hours for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebo (normal saline). The primary outcome was the development of IPN during the index admission.RESULTSFrom Mar 2017 through Dec 2020, 508 patients were randomized at 16 hospitals, of whom 254 were assigned to receive Tα1 and 254 placebo. During the index admission, 40/254 (15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95%CI -7.4% to 5.0%]; p=0.47). The results were similar in four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15.0%; p=0.15), bleeding (6.3% vs. 3.5%; p=0.15), and gastrointestinal fistula (2.0% vs. 2.4%; p=0.75) during the index admission.CONCLUSIONSThe immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.Trial registrationClinicaltrials.gov registry: NCT02473406.

Objectives: We aimed to evaluate the associations between body iron stores and the risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese population and explore whether this effect may be modified by other factors. Methods: A 1: 1 frequency-matched case–control study was conducted, including 482 NAFLD cases and 490 gender- and age-matched controls. Serum levels of ferritin, hepcidin, and C-reactive protein were measured. Results: Multivariate logistic regression analysis showed that hepcidin was not associated with NAFLD risk; however, elevated serum ferritin was significantly associated with increased risk of NAFLD (adjusted OR 1.619, 95% CI 1.158–2.267), and hepcidin:ferritin ratio was significantly associated with decreased risk of NAFLD ­(OR­adjusted 0.702, 95% CI 0.501–0.984). When stratified by gender, a significant association was found between elevated serum ferritin and hepcidin:ferritin ratio and NAFLD only for women (ORadjusted 2.131, 95% CI 1.151–3.944 and ORadjusted 0.414, 95% CI 0.219–0.781, respectively). A significant multiplicative interaction between central obesity and elevated serum hepcidin was observed (p < 0.05). Conclusions: Elevated serum ferritin and hepcidin:ferritin ratio are associated with NAFLD in a Chinese population. Although serum hepcidin is not associated with NAFLD, it may augment the risk effect of central obesity on NAFLD.

To investigate the function of gasdermin D (GSDMD) in intestinal damage of mice with severe acute pancreatitis (SAP).The healthy C57BL/6 mice were divided into four groups randomly, including normal saline (NS) group, small interfering RNA (siRNA)-NS group, SAP model group and siRNA-SAP group, with 6 mice in each group. The SAP mouse model was reproduced by intraperitoneal injection of caerulein 50 μg/kg combined with lipopolysaccharide (LPS) 10 mg/kg; the NS group was given the same amount of NS; in the siRNA-SAP group and siRNA-NS group, siRNA 50 mg/kg was injected through the tail vein three times before modeling or injection of NS. The blood of mice eyeball in each group was taken 12 hours after modeling, and serum interleukins (IL-1β, IL-18) levels were detected by enzyme linked immunosorbent assay (ELISA). The mice were sacrificed to observe the general changes in abdominal cavity, the pancreas and ileum tissues were taken to observe the pathological changes under a light microscope. The expression of long-chain non-coding RNA uc.173 (lnc uc.173) was detected by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect the expression of tight junction proteins zonula occluden-1 (ZO-1) and Occludin in intestinal mucosal epithelial cells. Western blotting was used to detect the GSDMD protein expression level in the intestinal tissue.The serum levels of IL-1β and IL-18 in the SAP model group were significantly higher than those in the NS group and the siRNA-NS group [IL-1β (ng/L): 146.66±1.40 vs. 44.48±5.76, 81.49±10.75, IL-18 (ng/L): 950.47±177.09 vs. 115.43±16.40, 84.84±21.90, all P0.05]; and the levels of IL-1β and IL-18 in the siRNA-SAP group were significantly lower than those in the SAP model group [IL-1β (ng/L): 116.26±15.54 vs. 146.66±1.40, IL-18 (ng/L): 689.96±126.08 vs. 950.47±177.09, both P0.05]. General observation showed that there were no obvious abnormalities in the abdominal cavity of the mice in the NS and siRNA-NS groups; the mice in the SAP model group and the siRNA-SAP group had different degrees of edema and congestion in the intestine; compared with the SAP model group, the abnormalities in the siRNA-SAP group was significantly reduced. Under light microscope, there were no obvious changes in the pancreas and intestinal mucosa in the NS group and the siRNA-NS group; the pancreatic tissue of the SAP model group and the siRNA-SAP group had different degrees of edema, inflammatory cell infiltration, and lobular structure damage, and the intestinal mucosa was damaged to a certain degree, and the villi were broken to varying degrees, but the damage in the siRNA-SAP group was lighter. The results of RT-PCR showed that the expression of lnc uc.173 in the intestinal tissues of the model SAP group was significantly lower than that of the NS group and the siRNA-NS group (2The systemic inflammatory response and intestinal mucosal barrier damage of SAP mice may be related to the increase of GSDMD expression in intestinal tissues. GSDMD mediates cell pyrolysis to promote the release of inflammatory factors, cause intestinal injury, and down-regulate the expression of intestinal epithelial cell tight junction proteins such as ZO-1 and Occludin, resulting in intestinal mucosal damage.

Background Non-alcohol fatty liver disease (NAFLD) is the most common liver disease and an unhealthy lifestyle can lead to an increased risk of NAFLD. The present study aims to evaluate the association of meat consumption with NAFLD risk and liver-related biochemical indexes in middle-aged and elderly Chinese. Methods A cross-sectional study was conducted in individuals who were 45 years or older and underwent a physical examination from April 2015 to August 2017 in Southeast China. To evaluate associations between meat intake and NAFLD risk, inverse probability of treatment weighting and subgroup analyses were performed with logistic regressions. Spearman’s rank correlation was carried out to examine the relationship between meat consumptions and liver-related biochemical indexes. Results High consumptions of red meat (28.44–49.74 and > 71.00 g/day) (ORadjusted = 1.948; P ORadjusted = 1.714; P = 0.002) was positively associated with NAFLD risk on inverse probability of treatment weighting analysis, adjusting for smoking, tea intake, weekly hours of physical activity and presence of hypertension, dyslipidemia and diabetes. Exposure–response relationship analysis presented that red meat intake was positively associated with NAFLD risk. Significant associations of red meat intakes with serum levels of γ-glutamyl transferase, alanine transaminase, aspartate aminotransferase, total triglyceride and high-density lipoprotein cholesterol were found (rs = 0.176; P rs = 0.128; P rs = 0.060; P = 0.016; rs = 0.085; P = 0.001; rs = − 0.074; P = 0.003). Conclusions These findings suggest that the reduction of meat consumption may decrease NAFLD risk and should warrant further investigations.

Background: High meats intake contributes to unhealthy status. The present study aims to evaluate the association of meat consumption with non-alcohol fatty liver disease (NAFLD) risk and liver-related biomarkers in middle-aged and elderly Chinese.Methods: A cross-sectional study was conducted in individuals who were 45 years or older and underwent physical examination from April 2015 to August 2017 in Southeast China. NAFLD was evaluated by abdominal ultrasonography. Results: High consumptions of red meat (28.44-49.74 and >71.00 g/day) was positively associated with NAFLD risk on inverse probability of treatment weighting analysis, adjusting for smoking, tea intake, weekly hours of physical activity and presence of hypertension, dyslipidemia and diabetes (ORadjusted=1.948 and 1.1.716, respectively). Exposure-response relationship analysis presented that red meat intake was positively associated with NAFLD risk. Significant associations of red meat intakes with serum levels of γ-glutamyl transferase, alanine transaminase, aspartate aminotransferase, total triglyceride and high-density lipoprotein cholesterol were found (rs=0.176, 0.128, 0.060, 0.085 and -0.074, respectively). Conclusions: These findings suggest that reduction of meat consumption may decrease NAFLD risk and should warrant further investigations. Meat consumptions were measured by a semi-quantitative food frequency questionnaire.

Background: A recent genome-wide copy number variations (CNVs) scan identified a 16q12.2 deletion that included the carboxylesterase 1 (CES1) gene, which is important in the metabolism of fatty acids and cholesterol. We aimed to investigate whether CES1 CNVs was associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in a Chinese Han population. Methods: A case-control study was conducted among 303 patients diagnosed with NAFLD and 303 age (± 5) and sex-matched controls from the Affiliated Nanping First Hospital of Fujian Medical University in China. The copy numbers of CES1 were measured using TaqMan quantitative real-time polymerase chain reaction (qPCR) and serum CES1 was measured using enzyme-linked immunosorbent assays. The Chi-squared test and a logistic regression model were used to evaluate the association between CES1 CNVs and NAFLD susceptibility. Results: The distribution of CES1 CNVs showed a higher frequency of CNVs loss (< 2) among patients; however, the difference was not significant (P = 0.05). After controlling for other known or suspected risk factors for NAFLD, CES1 CNVs loss was significantly associated with greater risk of NAFLD (adjusted OR = 2.75, 95% CI: 1.30–5.85, P = 0.01); while CES1 CNVs gain (>2) was not. There was a suggestion of an association between increased CES1 serum protein levels and CNVs losses among cases, although this was not statistically significant (P=0.07). Conclusions: Copy number losses (< 2) of CES1 contribute to susceptibility to NAFLD in the Chinese Han population.

Disorders of bile acids (BAs) are closely related to the development of liver and intestinal diseases, including acute pancreatitis (AP). However, the mechanism underlying the involvement of BAs in AP development remains unclear. We used intraperitoneal injection of cerulein to construct AP mouse models. These mice had significantly reduced tauroursodeoxycholic acid (TUDCA) and an imbalance of intestinal microbiota, based on 16S rDNA gene sequencing. To explore the role of AP-induced intestinal microbiota changes in the development of AP, we transplanted stool obtained from AP mice to antibiotic-treated, microbiota-depleted healthy mice. Microbiota-depleted mice presented injury to the intestinal barrier function and pancreas. Additionally, microbiota depletion reduced AP-associated pancreatic injury. This indicated that the gut microbiota may worsen AP. As TUDCA was deficient in AP mice, we gavaged AP mice with it, and evaluated subsequent expression changes in the bile acid signaling receptors farnesoid-x-receptor (FXR) and its target gene fibroblast growth factor (FGF) 15. These were downregulated, and pancreatic and intestinal barrier function injury were mitigated. Similar results were found in microbiota-depleted AP without BA treatment. However, we did not observe further downregulation of the FXR signaling pathway in microbiota-depleted AP mice given TUDCA, indicating that improvement of pancreatitis by TUDCA may be associated with gut microbiota. Our analysis of changes to the gut microbiota in AP indicated that Lactobacilli may be the key contributors. Taken together, our study shows that supplementation with BAs could improve bile acid-FXR-FGF15 signaling, and reduce pancreatic and intestinal injury, and that this effect may be associated with the gut microbiota.

In our previous study, advanced glycosylation end-product specific receptor (RAGE) was observed to bind to S100A8/A9 and cause epithelial mesenchymal transition (EMT). The results from target gene prediction revealed that microRNA (miR)-185-5p had a RAGE binding site. However, the function of miR-185-5p in the invasion and migration of breast cancer remains ambiguous. In the present study, the expression of miR-185-5p was examined in breast cancer tissues and cells. Clinical features revealed a negative correlation between miR-185-5p and tumor size, as well as in tumor differentiation and lymph node metastasis in breast cancer. In addition, miR-185-5p was negatively associated with RAGE, and this miRNA reversed the EMT of breast cancer by modulating RAGE in vitro. In addition, miR-185-5p inhibited the S100A8/A9-induced EMT of breast cancer cells by the nuclear factor-κB/Snail signaling pathway. Notably, miR-185-5p upregulation inhibited the F-actin polymerization induced by S100A8/A9 in breast cancer. Furthermore, overexpression of miR-185-5p and reduction of RAGE inhibited lung metastasis node in vivo. Thus, miR-185-5p represents a potential therapeutic target in breast cancer by modulating RAGE.

BACKGROUND MicroRNAs can act as both tumor suppressor genes and oncogenes and participate in cell proliferation, metastasis, and apoptosis. Low levels of miR-577 are found in several cancers, for example, thyroid carcinoma, glioblastoma, and hepatocellular carcinoma. The aim of this study was to investigate the effect of miR-577 on breast cancer (BC). METHODS The relative level of miR-577 in 120 BC tissues and cells was detected by real-time PCR. MDA-MB-231 cells with upregulated miR-577 and MCF-7 cells with downregulated miR-577 were established. Transwell invasion assays were used to examine the invasiveness of cells. Epithelial-mesenchymal transition (EMT) markers were evaluated by immunofluorescence and Western blot. Targeted combinations of miR-577 and Rab25 were analyzed by luciferase assays. Xenograft models were used to examine the effect of miR-577 on BC metastasis. RESULTS MiR-577 expression was significantly suppressed in BC tissues. Tumor size, tumor stage, and lymphatic metastasis were attributed to miR-577 expression. Moreover, miR-577 overexpression strongly inhibited the invasiveness and EMT of BC cells in vitro. MiR-577 directly regulated Rab25 in BC. Rab25 upregulation by miR-577 decreased the levels of E-cadherin and increased the levels of Vimentin. Notably, Rab25 knockdown inhibited BC invasion; however, an increase in Rab25 counteracted the invasive effect of miR-577 in BC. CONCLUSION Results indicated that miR-577 suppressed EMT by inhibiting Rab25 expression in BC. MiR-577 and Rab25 are considered potential targets of BC treatment.

Background Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease nowadays. Changes in diet and lifestyle have led to a dramatic increase in the prevalence of NAFLD around the world. This meta-analysis is to investigate the efficacy of physical activity intervention on liver-specific endpoints in the population with NAFLD, including hepatic enzyme, serum lipid, glucose metabolism and intra-hepatic lipid. Methods PubMed and China National Knowledge Infrastructure (CNKI) databases were searched for randomized clinical trials of physical activity intervention on NAFLD patients through April 20th, 2019. Effect sizes were reported as standardized mean difference (SMD) and 95% confidence intervals (CI). Quality of included studies was assessed according to the Cochrane risk of bias tool. Meta-analyses were conducted using random-effect or fixed-effect models depending on the significance of heterogeneity. Subgroup analyses according to types and duration of physical activity were conducted to investigate clinical variability. Results Nine studies with a cumulative total of 951 participants met selection criteria. Physical activity was found associated with small reductions in hepatic enzyme parameters: ALT (SMD -0.17, 95% CI:-0.30 to − 0.05), AST (SMD -0.25, 95% CI: − 0.38, − 0.13) and GGT (SMD -0.22, 95% CI: − 0.36, − 0.08). Significant small improvements were also found in serum lipid parameters including TC (SMD = − 0.22, 95% CI: − 0.34, − 0.09), TG (SMD = − 0.18, 95% CI: − 0.31 to − 0.06) and LDL-C (SMD = − 0.26, 95% CI: − 0.39 to − 0.13). Significant improvement was also found in intra-hepatic lipid content (SMD = − 0.21, 95% CI: − 0.36 to − 0.06) There was no difference between physical intervention group and control group in HDL and three glucose metabolism parameters. Subgroup analysis suggested both aerobic exercise alone and resistance exercise alone can improve most liver function and longer period of exercise generally had better improvement effect. Conclusions Our findings suggest that physical activity alone can only slightly improve hepatic enzyme levels, most serum lipid levels and intra-hepatic lipid content in non-diabetic patients with NAFLD.

To explore the relationship between different kinds of dietary fatty acids intake and non-alcoholic fatty liver disease(NAFLD).A 1↿ frequency matched case-control study was conducted among 546 NAFLD patients diagnosed by ultrasound as case group, 546 people without NAFLD randomly selected and matched by sex and age(±5) as control group from April 2015 to August 2017 in Nanping first hospital. The data was obtained from participants using structured questionnaires during face-to-face interviews. Information on dietary intake was collected using semi-quantitative food frequency questionnaires. Residual method was used to derive energy-adjusted variable, unconditional Logistic regression was used to estimate odds ratios(OR) and their 95% CI.The NAFLD group consumed a significantly higher amount of fatty acid(FAs), saturated fatty acid(SFAs), mono-unsaturatedfattyacids(MUFAs), poly-unsaturated fatty acids(PUFAs), n-3 PUFAs, n-6 PUFAs, C16↿, C18↿, C16↿, C18↿, C18↿ and C18↿. Multivariate unconditional Logistic regression analysis indicated that daily intake of total fatty acids, MUFAs, n-6 PUFAs, C18↿, C18↿ more than 98. 96 g/d, 38. 83 g/d, 26. 23 g/d, 33. 55 g/d and 24. 91 g/d respectively, were the risk factors for NAFLD. The adjusted ORs and 95% CI were 2. 26(1. 49-3. 44), 1. 93(1. 29-2. 88), 5. 13(3. 40-7. 76), 1. 82(1. 22-2. 79) and 5. 24(3. 40-7. 76). Daily intake of C20↿, C22↿ in 0. 07-0. 09 g/d, 0. 01-0. 02 g/d were the protective factors for NAFLD. The adjusted ORs and 95% CI were 0. 58(0. 39-0. 85) and 0. 64(0. 43-0. 94).Daily intake of total fatty acids, MUFAs, n-6 PUFAs, C18↿, C18↿ more than 98. 96, 38. 83, 26. 23, 33. 55 and 24. 91 g/d respectively, were the risk factors for NAFLD. Daily intake of C20↿, C22↿ in 0. 07-0. 09 g/d, 0. 01-0. 02 g/d respectively, were the protective factors for NAFLD.

ObjectivesNut consumption has been associated with a lower risk of type 2 diabetes, metabolic syndrome and insulin resistance. However, its effect on the risk of non-alcoholic fatty liver disease (NAFLD) is unknown. Therefore, we investigated the relationship between nut consumption and NAFLD risk.Setting and participantsWe conducted a retrospective case-control study including 534 patients diagnosed with NAFLD and 534 controls matched by sex and age (±5 years) from the Affiliated Nanping First Hospital of Fujian Medical University in China.Main outcome measuresInformation on dietary intake was collected using a semiquantitative food frequency questionnaire and nut consumption was calculated. Nut consumption was categorised using quartiles based on the distribution of daily nut intake of the controls. Binary logistic regression models were used to estimate ORs and the 95% CIs for the association between nut consumption and NAFLD risk.ResultsAfter adjusting for potential confounding variables, nut consumption was not associated with NAFLD risk in the overall sample. When the fully adjusted model was stratified by sex, a significant inverse association was found between high nut consumption and NAFLD only among the men in the highest quartile (OR=0.43; 95% CI 0.26 to 0.71;Ptrend =0.01). The inverse association of nut consumption with NAFLD risk in men remained significant after controlling for other known or suspected risk factors for NAFLD.ConclusionsDiets with a higher intake of nuts may be associated with a decreased risk of NAFLD, particularly in men.

BACKGROUND Gut microbiota dysbiosis plays a key role in pathogenesis of severe acute pancreatitis (SAP). In this study, we explored the protective effects of the p38 MAPK inhibitor, SB203580, against gut inflammation and microbiota dysbiosis induced by pancreatic duct injection with 3.5% sodium taurocholate in an SAP rat model. MATERIAL AND METHODS Ninety male Sprague-Dawley rats were randomly assigned to sham-operated, SAP model, and SAP plus SB203580 groups (n=30/group). Histological examination was conducted to assess gut and pancreatitis injury. The levels of amylase, D-lactate, diamine oxidase, tumor necrosis factor alpha, IL-6, IL-1s, and phospho-p38MAPK in the plasma and intestine were evaluated at 3, 6, or 12 h after SAP induction. The gut microbiome was investigated based on16S rDNA gene sequencing at 12 h after SAP induction. RESULTS Histological examination revealed edema and inflammatory infiltrations in the pancreas and distal ileum. The expression of tumor necrosis factor alpha, IL-1s, and IL-6 in plasma and distal ileum was increased in the SAP group, which were restored after treatment with SB203580. Significantly lower bacterial diversity and richness was found in the SAP group. In the SAP group, the abundance of Bacteroidetes and Firmicutes was decreased, and there was a higher proportion of Proteobacteria at the phylum level. The SAP plus SB203580 group exhibited significantly less damage to the gut microbiota, with higher bacterial diversity and a more normal proportion of intestinal microbiota. CONCLUSIONS SB203580 mediated suppression of the p38 MAPK signaling pathway via reduced gut inflammatory response and microbiota dysbiosis.

To find the pathogenies and risk factors related to surgical intensive care unit (SICU) readmission for patients who underwent hepatobiliary-pancreatic surgery, and to develop a predictive model for determining patients who are likely to be readmitted to SICU.The patients who admitted to SICU of the Affiliated Hospital of Qingdao University from January 2013 to August 2018; who first stayed in SICU after hepatobiliary-pancreatic surgery; who were assessed and discharged from SICU by surgeons and SICU physicians after treatment, and then transferred to SICU again because of the change of their condition were enrolled. The unintended return to SICU within 3 days and 7 days were recorded. Patients who returned to SICU within 7 days were studied for the pathogenies, risk factors and predictive model of returning to SICU, and non-returning patients were enrolled according to 1:1 as the controls. A total of 43 indicators were divided into five categories, including general clinical data, medical history, surgical indicators before first admission of SICU, length of first SICU stay, and other indicators on the day of first discharge from the SICU. Logistic regression was used to screen the risk factors associated with SICU readmission, then the Nomogram diagram was drawn by using the R 3.4.1 software for predicting SICU readmission, and the classification performance of Nomogram was evaluated by self-help sampling test.Of the 763 patients discharged from the SICU, 2.10% (16/763) of them were readmitted within 3 days and 3.28% (25/763) were readmitted within 7 days to the SICU unexpectedly. The pathogenies of SICU readmission within 7 days included infection [56.00% (14/25)], heart failure [16.00% (4/25)], infarction [12.00% (3/25)], bleeding [12.00% (3/25)], and sutures splitting [4.00% (1/25)]. The pathogenies of SICU readmission within 3 days included infection [56.25% (9/16)], heart failure [18.75% (3/16)], infarction [12.50% (2/16)], and bleeding [12.50% (2/16)]. Nomogram analysis showed that the risk factors associated with unplanned SICU readmission were length of first SICU stay, history of hypertension, and activity of daily living (ADL) score, white blood cell count (WBC), arterial partial pressure of oxygen (PaOThe common pathogenies of SICU readmission for patients who underwent hepatobiliary-pancreatic surgery were infection, heart failure, infarction and bleeding. Risk factors of readmission after SICU discharge included the length of first SICU stay, history of hypertension, and ADL score, WBC, PaO

BACKGROUND Intestinal injury plays a key role in the pathogenesis of severe acute pancreatitis (SAP). In this study, we investigated the protective function of downregulated Gasdermin D (GSDMD) in intestinal damage in a mouse model of severe acute pancreatitis (SAP). MATERIAL AND METHODS Twenty-four healthy male C57BL/6 mice were randomly divided into 4 groups - the NS group, the siRNA-NS group, the SAP group, and the siRNA-SAP group - with 6 mice in each group. SAP was induced in mice by intraperitoneal injection of caerulein and lipopolysaccharide. The pathological changes of pancreatic and the intestinal mucosa and the relative gene and protein expressions in each group were compared, and the levels of GSDMD and serum IL-1s and IL-18 were evaluated after induction of the SAP model. RESULTS The mice in the SAP group were in more serious condition than those in the siRNA-SAP group, with various degrees of edema and hemorrhage in the intestinal tract. Under an optical microscope, the pathological changes of pancreatic tissue such as edema, inflammatory cell infiltration, and the damage of lobular structural were gradually increased in the SAP group and the siRNA-NS group. In addition, intestinal mucosal damage and intestinal villus breakage were found in the SAP group and the siRNA-NS group, and the latter was lighter than the former. Compared with the SAP group, the level of GSDMD protein expression in the siRNA-SAP group was lower, and the serum levels of IL-1s and IL-18 were higher in the SAP group and siRNA-SAP group (P

IntroductionInfected pancreatic necrosis (IPN) and its related septic complications are the major causes of death in patients with acute necrotising pancreatitis (ANP). Therefore, the prevention of IPN is of great clinical value, and immunomodulatory therapy with thymosin alpha 1 may be beneficial. This study was designed to test the hypothesis that the administration of thymosin alpha 1 during the acute phase of ANP will result in a reduced incidence of IPN.Methods and analysisThis is a randomised, multicentre, double-blind, placebo-controlled study. 520 eligible patients with ANP will be randomised in a 1:1 ratio to receive either the thymosin alpha 1 or the placebo using the same mode of administration. The primary endpoint is the incidence of IPN during the index admission. Most of the secondary endpoints will be registered within the index admission including in-hospital mortality, the incidence of new-onset organ failure and new-onset persistent organ failure (respiration, cardiovascular and renal), receipt of new organ support therapy, requirement for drainage or necrosectomy, bleeding requiring intervention, human leucocyte antigens-DR(HLA-DR) on day 0, day 7, day 14, and so on and adverse events. Considering the possibility of readmission, an additional follow-up will be arranged 90 days after enrolment, and IPN and death at day 90 will also be served as secondary outcomes.Ethics and disseminationThis study was approved by the ethics committee of Jinling Hospital, Nanjing University (Number 2015NZKY-004-02). The thymosin alpha 1 in the prevention of infected pancreatic necrosis following acute necrotising pancreatitis(TRACE) trial was designed to test the effect of a new therapy focusing on the immune system in preventing secondary infection following ANP. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberClinicalTrials.gov Registry (NCT02473406).

Background MicroRNAs can act as both tumor suppressor genes and oncogenes and participate in cell proliferation, metastasis, and apoptosis. Low levels of miR‐577 are found in several cancers, for example, thyroid carcinoma, glioblastoma, and hepatocellular carcinoma. The aim of this study was to investigate the effect of miR‐577 on breast cancer (BC). Methods The relative level of miR‐577 in 120 BC tissues and cells was detected by real‐time PCR. MDA‐MB‐231 cells with upregulated miR‐577 and MCF‐7 cells with downregulated miR‐577 were established. Transwell invasion assays were used to examine the invasiveness of cells. Epithelial‐mesenchymal transition (EMT) markers were evaluated by immunofluorescence and Western blot. Targeted combinations of miR‐577 and Rab25 were analyzed by luciferase assays. Xenograft models were used to examine the effect of miR‐577 on BC metastasis. Results MiR‐577 expression was significantly suppressed in BC tissues. Tumor size, tumor stage, and lymphatic metastasis were attributed to miR‐577 expression. Moreover, miR‐577 overexpression strongly inhibited the invasiveness and EMT of BC cells in vitro. MiR‐577 directly regulated Rab25 in BC. Rab25 upregulation by miR‐577 decreased the levels of E‐cadherin and increased the levels of Vimentin. Notably, Rab25 knockdown inhibited BC invasion; however, an increase in Rab25 counteracted the invasive effect of miR‐577 in BC. Conclusion Results indicated that miR‐577 suppressed EMT by inhibiting Rab25 expression in BC. MiR‐577 and Rab25 are considered potential targets of BC treatment.

Endothelial PAS domain protein 1 (EPAS1) is a hypoxia-inducible protein that contributes to tumor progression. Hypoxia is involved in tumor aggressiveness and resistance to chemotherapy and ionizing radiation. In this study, we aimed to assess the effects of EPAS1 silencing using polyethylenimine-poly(lactide-coglycolide) (PLGA)/poloxamer nanoparticles loaded with EPAS1 siRNA on BxPC-3 pancreatic cancer cells and in a mouse model of ectopic pancreatic cancer. PLGA/poloxamer nanoparticles loaded with EPAS1 siRNA or scramble siRNA were prepared using the emulsion/solvent evaporation method. BxPC-3 pancreatic cancer cells were cultured under hypoxic conditions and treated with or without the nanoparticles. MTT and apoptosis assays were then performed. A xenograft nude mouse model of pancreatic cancer was established and the mice were treated with or without the nanoparticles. The mRNA and protein expression levels of EPAS1 in the tumor tissues were determined by semi-quantitative RT-PCR and western blot analysis, respectively. Vascular endothelial growth factor (VEGF) and tumor microvessel density indicated by CD34 were determined by immunohistochemistry. The in vitro release of EPAS1 siRNA from the nanoparticles exerted a sustained-release effect. EPAS1 siRNA nanoparticles inhibited BxPC-3 cell proliferation, and induced cell apoptosis under hypoxic conditions, compared with the nanoparticles loaded with scramble siRNA (all P

Objectives Pancreatic cancer is one of the most common malignancies of the digestive system, and remains a clinical challenge. This study aimed to assess the effects of bovine serum albumin (BSA) nanoparticles carrying the hMDA-7 gene (BSA-NP-hMDA-7) in the treatment of pancreatic cancer. Methods BSA-NP-hMDA-7 was generated by nanotechnology and gene recombination technology. A total of 5 BXPC-3 or PANC-1 pancreatic cancer cell groups were examined, including Control, BSA-NPs, Empty vector, hMDA-7 plasmid, and hMDA-7 BSA-NPs groups, respectively. Proliferation and apoptosis of cultured cells were assessed by the MTT method and flow-cytometry, respectively. In addition, pancreatic cancer models were established with both cell lines in nude mice, and the expression profiles of hMDA-7 and VEGF in cancer tissues were measured by Western blot and immunohistochemistry. Results BSA-NP-hMDA-7 nanoparticles were successfully generated, and significantly inhibited the proliferation of BXPC-3 and PANC-1 cells; in addition, apoptosis rates were higher in both cell lines after treatment with BSA-NP-hMDA-7 (P

Background/Aims: This study aimed to report the clinical efficacy of continuous renal replacement therapy (CRRT) in combination with ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD) (CRRT+PTGD) in the treatment of acute severe biliary pancreatitis (ASBP). Methods: Between January 2010 and January 2016, 40 cases of patients with ASBP who received routine CRRT (CRRT group) and 40 of those who received CRRT+PTGD (CRRT+PTGD group) at the Affiliated Hospital of Qingdao University (Qingdao, China) were retrospectively reviewed. Clinical (including abdominal pain remission time, gastrointestinal decompression time, Intensive Care Unit (ICU) hospital stay, respirator treatment time, and mortality rate), laboratory (white blood cells [WBC], platelet [PLT], procalcitonin [PCT], C-reactive protein [CRP], total bilirubin [TBIL], alanine aminotransferase [ALT], albumin [ALB], and blood lactic acid [Lac]) parameters, various critical disease scores, and incidence of complications after the treatment were compared between the two groups. Results: Compared with those in the routine CRRT group, patients in the CRRT+PTGD group exhibited significant remission of clinical symptoms (i.e. shorter abdominal pain remission time, gastrointestinal decompression time, respirator treatment time and ICU hospital stay) (all PConclusion: CRRT in combination with PTGD is more effective in the treatment of ASBP than CRRT alone.

To explore the factors associated with delayed defecation in long-term ventilated patients in intensive care unit (ICU) and their potential effect on prognosis.A prospective observational cohort study was conducted. The patients admitted to general ICU of the Affiliated Hospital of Qingdao University from October 1st in 2013 to September 30th in 2015 who underwent mechanical ventilation (MV) for ≥6 days were enrolled, and they were divided into early defecation group (6 days) and late defecation group (≥6 days). At admission, clinical nutritional support were given as usual, and gender, age, acute physiology and chronic health evaluation II (APACHEII) score, admission reasons, MV reasons, the usage of morphine and epinephrine/norepinephrine, the highest positive end-expiratory pressure (PEEP), the lowest oxygenation index (PaOTotally 189 patients were enrolled, 39 patients did not satisfied the inclusion criteria and 13 patients gave up treatment or referrals were excluded. Finally 137 patients were enrolled in the analysis, 83 patients in late defecation group and 54 in early defecation group. There were no significant differences in the baseline characteristics such as gender, age, APACHE II score, LOD score at 1 day of MV, admission reasons, MV reasons, disgorging and gastric residual volume per day during the first 5 days of MV, enteral nutrition, lactulose treatment in patients with hepatic encephalopathy during the first 5 days of MV, and blood purification treatment between the two groups (all P0.05). Compared with the early defecation group, late defecation group had less patients with loose stools or watery stool at first time [15.7% (13/83) vs. 33.3% (18/54)], more patients using morphine and the usage of epinephrine/norepinephrine more than 24 hours [48.2% (40/83) vs. 40.7% (22/54), 42.2%(35/83) vs. 29.6% (16/54)], higher the maximum PEEP level [cmHPaO

Many studies have shown that LPS mainly activates four signal transduction pathways to induce inflammation, namely the p38, ERK1/2, JNK and IKK/NF-κB pathways. Studies have demonstrated that 5'-AMP-induced hypothermia (AIH) exhibits high anti-inflammatory capabilities. In this study, we explore that how AIH inhibits the inflammatory response. Wistar rats were divided into five groups: a control group, an LPS group, a 5'-AMP pre-treatment group, a 5'-AMP post-treatment group and a 5'-AMP group. For each group, plasma and lung were collected from the rats at 6h and 12h after LPS injection. ELISA assays were used to detect plasma levels of CD14, CRP and MCP-1. Inflammatory pathway activation and TLR4 expression were assayed separately by Western blot analysis and immunohistochemistry. Our results showed that rats treated with AIH either before or after an LPS-challenge had a significant decrease in plasma levels of CD14, CRP and TLR4 compared with rats that received LPS only. Western blot analysis showed that AIH inhibited the activation of extracellular signal-regulated kinases (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) and NF-κB in inflammatory rats. Our study concluded that AIH attenuated LPS-induced inflammation mainly by inhibiting activation on the ERK1/2, p38, JNK and NF-κB signaling pathways.

Background and Aim This study sought to investigate the effects of hypothermia induced by adenosine 5′-monophosphate (5′-AMP) on L-arginine (L-Arg)-induced acute pancreatitis in rats. Methods The rats were divided into four groups: the control group, the acute pancreatitis group, the 5′-AMP pretreatment group, and the 5′-AMP posttreatment group. Rats in all groups, except for the control group, received two injections of 2.5 g/kg body weight (intraperitoneally) L-Arg, with an interval of 1 h between the injections. Subsequently, the rats were observed to assess whether hypothermia induced by 5′-AMP could effectively inhibit inflammation associated with L-Arg-induced acute pancreatitis in rats. Results Hypothermia induced by 5′-AMP produced protective effects in our acute pancreatitis model. These effects exhibited the following manifestations: (i) a significant reduction in rat mortality rates; (ii) a significant decrease in the occurrence of pancreatic edema; (iii) significant reductions in serum amylase (P

AimPhysical activity plays an important role in the development of non-alcoholic fatty liver disease (NAFLD).However, the optimal intensity and dose of physical activity for the treatment of NAFLD have yet to be found. In the present study, we aimed to provide a dose–response association between physical activity and NAFLD in a Chinese population.MethodsWe recruited 543 patients with NAFLD diagnosed by abdominal ultrasonography, and 543 age-matched and sex-matched controls. The amount of physical activity, sedentary time and energy intake was collected through a structured questionnaire. Logistic regression analyses were performed to investigate the association between physical activity and NAFLD.ResultsAfter adjusting for hypertension, diabetes, body mass index, fasting blood glucose, energy intake and sedentary time, the total amount of physical activity was found to be inversely associated with NAFLD in a dose-dependent manner in men (>3180 metabolic equivalent of energy [MET]-min/week vs ≤1440 MET-min/week: OR 0.60, 95% CI 0.40 to 0.91, p for trend=0.01). In addition, both moderate-intensity and vigorous-intensity physical activity were effective in reducing the risk of NAFLD, independent of confounding variables in men (moderate-intensity physical activity: >684 MET-min/week vs none: OR 0.58, 95% CI 0.40 to 0.86, p for trend=0.01; vigorous-intensity physical activity: >960 MET-min/week vs none: OR 0.63, 95% CI 0.41 to 0.95, p for trend=0.02).ConclusionsPhysical activity was inversely associated with risk of NAFLD in a dose-dependent manner in men. Vigorous-intensity and moderate-intensity physical activity were both beneficial to NAFLD, independent of sedentary time and energy intake.

Hepatocellular carcinoma is one of the most common tumors in the world. The purpose of the present study was to investigate the inhibitory effects of adenoviral transduction of human melanoma differentiation-associated gene-7 (MDA-7) gene on hepatocellular carcinoma, so as to provide a theoretical basis for gene therapy of the disease. The human MDA-7 gene was cloned into replication-defective adenovirus specific to HepG2 cells using recombinant virus technology. RT-PCR and Western blotting assays were used to determine the expression of human MDA-7 mRNA and MDA-7 protein in HepG2 cells in vitro. Induction of apoptosis by overexpression of the human MDA-7 gene was determined by flow cytometry. In-vivo efficacy of adenoviral delivery of the human MDA-7 gene was assessed in nude mice bearing HepG2 cell lines in vivo by determining inhibition of tumor growth, VEGF and CD34 expression, and microvascular density (MVD). The results showed that AdGFP/MDA-7 induced apoptosis of HepG2 cells in vitro and significantly inhibited tumor growth in vivo (P < 0.05). The intratumoral MVD decreased significantly in the treated tumors (P < 0.05). We conclude the recombination adenovirus AdGFP/MDA-7 can effectively express biologically active human MDA-7, which leads to inhibition of hepatocellular carcinoma growth.

Objective to investigate the expression of NF-κB and occludin in intestinal mucosal barrier during severe acute pancreatitis (SAP) and its clinical significance. Method Twenty-four Wistar rats were randomly divided into a normal control group, an SAP group, and a PDTC group. The rats were sacrificed at 24h after modeling, and general appearance of the abdominal cavity, pathological changes of the intestinal mucosa, changes in intestinal mucosal permeability were observed, serum inflammatory factor IL-1 was measured, and expression of tight junction protein occludin in the intestinal epithelial cells were determined by immunohistochemistry. Results Rats of the SAP group showed obvious inflammatory reaction in the abdominal cavity, manifested by enlargement of intestinal tract, intestinal edema, and increased permeability of intestinal barrier, whereas NF-κB inhibitor alleviated intestinal damage and intestinal mucosa edema, upregulated intestinal epithelial tight junction protein occludin, decreased intestinal permeability, and lowered the level of inflammatory factors. Conclusion Impairment of intestinal barrier function during SAP may be associated with increased NF-κB and decreased intestinal tight junction protein occludin; inhibiting NF-kB may alleviate intestinal mucosal barrier dysfunction during SAP.