A modified Ranson score to predict disease severity, organ failure, pancreatic necrosis, and pancreatic infection in patients with acute pancreatitis

BackgroundAlthough there are several scoring systems currently used to predict the severity of acute pancreatitis, each of them has limitations. Determine the accuracy of a modified Ranson score in predicting disease severity and prognosis in patients with acute pancreatitis (AP).MethodsAP patients admitted or transferred to our institution were allocated to a modeling group (n = 304) or a validation group (n = 192). A modified Ranson score was determined by excluding the fluid sequestration parameter and including the modified computed tomography severity index (CTSI). The diagnostic performance of the modified Ranson score was compared with the Ranson score, modified CTSI, and bedside index of severity in acute pancreatitis (BISAP) score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection.ResultsThe modified Ranson score had significantly better accuracy that the Ranson score in predicting all four outcome measures in the modeling group and in the validation group (all p < 0.05). For the modeling group the modified Ranson score had the best accuracy for predicting disease severity and organ failure, and second-best accuracy for predicting pancreatic necrosis and pancreatic infection. For the verification group, it had the best accuracy for predicting organ failure, second-best accuracy for predicting disease severity and pancreatic necrosis, and third-best accuracy for predicting pancreatic infection.ConclusionThe modified Ranson score provided better accuracy than the Ranson score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection. Relative to the other scoring systems, the modified Ranson system was superior in predicting organ failure

Hematoporphyrin monomethyl ether-mediated photodynamic effects on THP-1 cell-derived macrophages

a b s t r a c t Photodynamic therapy (PDT) has been shown to attenuate atherosclerotic plaque progression and decrease macrophage-infiltration. The effectiveness of PDT depends strongly on the type of photosensitizers. Hematoporphyrin monomethyl ether (HMME) is a promising second-generation porphyrin-related photosensitizer for PDT. This study is designed to characterize effects of HMME-based PDT on THP-1 cellderived macrophages and define the cell-death pathway. HMME was identified to accumulate in the macrophages by fluorescence microscopy and confocal scanning laser microscope. Our data demonstrated that the intensity of laser-induced HMME fluorescence in macrophages steadily increased with the increasing incubation concentration of HMME. The survival rate of macrophages determined by MTT assay decreased with the increasing HMME concentration and irradiation time. HMME-based PDT induced macrophage apoptosis via caspase-9 and caspase-3 activation pathway detected by caspase fluorescent assay kit and flow cytometer. The PDT increased the number of apoptotic macrophages by 14-fold at 12 h post irradiation by 9 J/cm 2 635 nm diode laser. These results imply that photodynamic therapy with HMME may therefore be a useful clinical treatment for unstable atherosclerotic plaques

AMIP GCM Simulations of Precipitation Variability over the Yangtze River Valley

Analysis of 26 simulations from 11 general circulation models (GCMs) of the Atmospheric Model Intercomparison Project (AMIP) II reveals a basic inability to simultaneously predict the Yangtze River Valley (YRV) precipitation (PrYRV) annual cycle and summer interannual variability in response to observed global SST distributions. Only the Community Climate System Model (CCSM) and L\u27Institut Pierre-Simon Laplace (IPSL) models reproduce the observed annual cycle, but both fail to capture the interannual variability. Conversely, only Max Planck Institute (MPI) simulates interannual variability reasonably well, but its annual cycle leads observations by 2 months. The interannual variability of PrYRV reveals two distinct signals in observations, which are identified with opposite subtropical Pacific SST anomalies in the east (SSTe) and west (SSTw). First, negative SSTe anomalies are associated with equatorward displacement of the upper-level East Asian jet (ULJ) over China. The resulting transverse circulation enhances low-level southerly flow over the South China Sea and south China while convergent flow and upward motion increase over the YRV. Second, positive SSTw anomalies are linked with westward movement of the subtropical high over the west-central Pacific. This strengthens the low-level jet (LLJ) to the south of the YRV. These two signals act together to enhance PrYRV. The AMIP II suite, however, generally fails to reproduce these features. Only the MPI.3 realization is able to simulate both signals and, consequently, realistic PrYRV interannual variations. It appears that PrYRV is governed primarily by coherent ULJ and LLJ variations that act as the atmospheric bridges to remote SSTe and SSTw forcings, respectively. The PrYRV response to global SST anomalies may then be realistically depicted only when both bridges are correctly simulated. The above hypothesis does not exclude other signals that may play important roles linking PrYRV with remote SST forcings through certain atmospheric bridges, which deserve further investigation. © 2011 American Meteorological Society

Effect of Warm-Water Retting Pretreatment on the Physical Properties of Banana Stem and Its Fibre

In this paper, warm-water flax retting was used as a pretreatment method for banana-fibre extraction. To determine the optimum conditions for flax retting, the physical properties of various parts of stems and fibres in the process of flax retting were analysed. By studying the tensile strength, elongation at break, diameter, moisture regain, and other characteristics of the fibres, the influences of bacteria and enzymes in the retting liquor on the fibre characteristics in different retting stages were determined. Through mechanical-property tests and microscopic observation of the stem skin, the change rules of the mechanical properties and degumming state of the stems were examined. The results showed that the fibre tensile strength of banana stems reached the maximum value of 45 ± 16 cN·tex−1 after 11 days of retting. As most resins had not been hydrolysed, fibre extraction was difficult. After 21–25 days of retting, the tensile strength of fibres was about 34 ± 10 cN·tex−1, elongation at break was about 1.71%, and moisture regain was about 13.56%. The fibre characteristics met the process requirements, and the tensile separation stress of the stem was small, about 0.034 MPa. This time point could be used as the optimum endpoint for retting flax in warm water, which could provide theoretical support and research basis for the recycling of banana straw. The functional groups of the extracted fibres were studied by FTIR, which confirmed the observed change rule of each component during degumming. The experimental results showed that a longer retting time corresponded with a lower content of fibre impurities, more thorough degumming, and less difficult extraction; however, strength and toughness decreased

Extracellular vesicles of Fusobacterium nucleatum compromise intestinal barrier through targeting RIPK1-mediated cell death pathway

Microbial factors that mediate microbes-host interaction in ulcerative colitis (UC), a chronic disease seriously affecting human health, are not fully known. The emerging oncobacterium Fusobacterium nucleatum (Fn) secretes extracellular vesicles carrying several types of harmful molecules in the intestine which can alter microbes-host interaction, especially the epithelial homeostasis in UC. However, the mechanism is not yet clear. Previously, we isolated EVs by the ultracentrifugation of Fn culture media and characterized them as the potent inducer of pro-inflammatory cytokines. Here, we examined the mechanism in detail. We found that in macrophage/Caco-2 co-cultures, FnEVs significantly promoted epithelial barrier loss and oxidative stress damage, which are related to epithelial necroptosis caused by the activation of receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3). Furthermore, FnEVs promoted the migration of RIPK1 and RIPK3 into necrosome in Caco2 cells. Notably, these effects were reversed by TNF-α neutralizing antibody or Necrostatin-1 (Nec-1), a RIPK1 inhibitor. This suggested that FADD-RIPK1-caspase-3 signaling is involved in the process. Moreover, the observed effects were verified in the murine colitis model treated with FnEVs or by adoptive transfer of FnEVs-trained macrophages. In conclusion, we propose that RIPK1-mediated epithelial cell death promotes FnEVs-induced gut barrier disruption in UC and the findings can be used as the basis to further investigate this disease

Machine learning-based solution reveals cuproptosis features in inflammatory bowel disease

BackgroundCuproptosis, a new cell death mode, is majorly modulated by mitochondrial metabolism and protein lipoylation. Nonetheless, cuproptosis-related genes (CRGs) have not yet been thoroughly studied for their clinical significance and relationship with the immune microenvironment in inflammatory bowel disease (IBD).MethodsWe screened CRGs that had a significant correlation with immune status, which was determined utilizing single-sample GSEA (ssGSEA) and Gene Expression Omnibus datasets (GSE75214). Furthermore, utilizing the R package “CensusClusterPlus”, these CRGs’ expression was used to obtain different patient clusters. Subsequently, gene-set enrichment analysis (GSEA), gene set variation analysis (GSVA), and CIBERSORT assessed the variations in the enrichment of gene function and the abundance of immune cell infiltration and immune functions across these clusters. Additionally, weighted gene co-expression network analysis (WGCNA) and analysis of differentially expressed genes (DEGs) were executed, and for the purpose of identifying hub genes between these clusters, the construction of protein-protein interaction (PPI) network was done. Lastly, we used the GSE36807 and GSE10616 datasets as external validation cohorts to validate the immune profiles linked to the expression of CRG. ScRNA-seq profiling was then carried out using the publicly available dataset to examine the CRGs expression in various cell clusters and under various conditions.ResultsThree CRGs, PDHA1, DLD, and FDX1, had a significant association with different immune profiles in IBD. Patients were subsequently classified into two clusters: low expression levels of DLD and PDHA1, and high expression levels of FDX1 were observed in Cluster 1 compared to Cluster 2. According to GSEA, Cluster 2 had a close association with the RNA processes and protein synthesis whereas Cluster 1 was substantially linked to environmental stress response and metabolism regulations. Furthermore, Cluster 2 had more immune cell types, which were characterized by abundant memory B cells, CD4+ T memory activated cells, and follicular helper T cells, and higher levels of immune-related molecules (CD44, CD276,CTLA4 and ICOS) than Cluster 1. During the analysis, the PPI network was divided into three significant MCODEs using the Molecular Complex Detection (MCODE) algorithm. The three MCODEs containing four genes respectively were linked to mitochondrial metabolism, cell development, ion and amino acid transport. Finally, external validation cohorts validated these findings, and scRNA-seq profiling demonstrated diverse intestinal cellular compositions with a wide variation in CRGs expression in the gut of IBD patients.ConclusionsCuproptosis has been implicated in IBD, with PDHA1, DLD, and FDX1 having the potential as immune biomarkers and therapeutic targets. These results offer a better understanding of the development of precise, dependable, and cutting-edge diagnosis and treatment of IBD

Presentation8_Gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signaling.PPTX

Backgroud and aims: Ductular reaction (DR) is a common pathological change and thought to have a key role in the pathogenesis and progression of liver fibrosis. Our previous study reported Gypenosides (GPs) ameliorated liver fibrosis, however, the anti-fibrotic mechanisms of GPs are still unclear.Methods: Liver fibrosis was induced in rats by carbon tetrachloride combining with 2-acerylaminofluorene (CCl4/2-AAF), and Mdr2 knockout (Mdr2−/−) mice to evaluate the anti-fibrotic role of GPs. In vitro, WB-F344 cells, a hepatic progenitor cells (HPCs) line, with or without Gli1 overexpressing lentiviral vectors, were induced by sodium butyrate (SB) to validate the mechanism of GPs and NPLC0393, the main ingredient of GPs.Results: Both in CCl4/2-AAF-treated rats and Mdr2−/− mice, GPs obviously reduced the deposition of collagen and hydroxyproline content, inhibited the activation of hepatic stellate cells and inflammatory cell infiltration. Notably, GPs reduced the expressions of Epcam, CK19, CK7, Dhh, Smo, Ptch2, Gli1 and Gli2. Furthermore, CK19+ cells co-expressed Gli1, while the number of CK19+/Gli1+ cells was decreased by GPs. In vitro, GPs and NPLC0393 inhibited the differentiation of WB-F344 cells toward a biliary phenotype. Mechanistically, GPs and NPLC0393 protected against DR by inhibiting hedgehog signaling, which was supported by the results that DR, triggered directly by Gli1 overexpressing lentiviral vector was blocked by administration with GPs or NPLC0393.Conclusion: GPs attenuated DR and liver fibrosis by inhibiting hedgehog signaling, which provided more evidences and a novel mechanism of anti-fibrotic effect of GPs.</p

Presentation7_Gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signaling.PPTX

Backgroud and aims: Ductular reaction (DR) is a common pathological change and thought to have a key role in the pathogenesis and progression of liver fibrosis. Our previous study reported Gypenosides (GPs) ameliorated liver fibrosis, however, the anti-fibrotic mechanisms of GPs are still unclear.Methods: Liver fibrosis was induced in rats by carbon tetrachloride combining with 2-acerylaminofluorene (CCl4/2-AAF), and Mdr2 knockout (Mdr2−/−) mice to evaluate the anti-fibrotic role of GPs. In vitro, WB-F344 cells, a hepatic progenitor cells (HPCs) line, with or without Gli1 overexpressing lentiviral vectors, were induced by sodium butyrate (SB) to validate the mechanism of GPs and NPLC0393, the main ingredient of GPs.Results: Both in CCl4/2-AAF-treated rats and Mdr2−/− mice, GPs obviously reduced the deposition of collagen and hydroxyproline content, inhibited the activation of hepatic stellate cells and inflammatory cell infiltration. Notably, GPs reduced the expressions of Epcam, CK19, CK7, Dhh, Smo, Ptch2, Gli1 and Gli2. Furthermore, CK19+ cells co-expressed Gli1, while the number of CK19+/Gli1+ cells was decreased by GPs. In vitro, GPs and NPLC0393 inhibited the differentiation of WB-F344 cells toward a biliary phenotype. Mechanistically, GPs and NPLC0393 protected against DR by inhibiting hedgehog signaling, which was supported by the results that DR, triggered directly by Gli1 overexpressing lentiviral vector was blocked by administration with GPs or NPLC0393.Conclusion: GPs attenuated DR and liver fibrosis by inhibiting hedgehog signaling, which provided more evidences and a novel mechanism of anti-fibrotic effect of GPs.</p

DataSheet1_Gypenosides ameliorate ductular reaction and liver fibrosis via inhibition of hedgehog signaling.docx

Backgroud and aims: Ductular reaction (DR) is a common pathological change and thought to have a key role in the pathogenesis and progression of liver fibrosis. Our previous study reported Gypenosides (GPs) ameliorated liver fibrosis, however, the anti-fibrotic mechanisms of GPs are still unclear.Methods: Liver fibrosis was induced in rats by carbon tetrachloride combining with 2-acerylaminofluorene (CCl4/2-AAF), and Mdr2 knockout (Mdr2−/−) mice to evaluate the anti-fibrotic role of GPs. In vitro, WB-F344 cells, a hepatic progenitor cells (HPCs) line, with or without Gli1 overexpressing lentiviral vectors, were induced by sodium butyrate (SB) to validate the mechanism of GPs and NPLC0393, the main ingredient of GPs.Results: Both in CCl4/2-AAF-treated rats and Mdr2−/− mice, GPs obviously reduced the deposition of collagen and hydroxyproline content, inhibited the activation of hepatic stellate cells and inflammatory cell infiltration. Notably, GPs reduced the expressions of Epcam, CK19, CK7, Dhh, Smo, Ptch2, Gli1 and Gli2. Furthermore, CK19+ cells co-expressed Gli1, while the number of CK19+/Gli1+ cells was decreased by GPs. In vitro, GPs and NPLC0393 inhibited the differentiation of WB-F344 cells toward a biliary phenotype. Mechanistically, GPs and NPLC0393 protected against DR by inhibiting hedgehog signaling, which was supported by the results that DR, triggered directly by Gli1 overexpressing lentiviral vector was blocked by administration with GPs or NPLC0393.Conclusion: GPs attenuated DR and liver fibrosis by inhibiting hedgehog signaling, which provided more evidences and a novel mechanism of anti-fibrotic effect of GPs.</p