Table1_Identification of effective diagnostic biomarker and immune cell infiltration characteristics in acute liver failure by integrating bioinformatics analysis and machine-learning strategies.xls

Background: To determine effective biomarkers for the diagnosis of acute liver failure (ALF) and explore the characteristics of the immune cell infiltration of ALF.Methods: We analyzed the differentially expressed genes (DEGs) between ALF and control samples in GSE38941, GSE62029, GSE96851, GSE120652, and merged datasets. Co-expressed DEGs (co-DEGs) identified from the five datasets were analyzed for enrichment analysis. We further constructed a PPI network of co-DEGs using the STRING database. Then, we integrated the two kinds of machine-learning strategies to identify diagnostic biomarkers of top hub genes screened based on MCC and Degree methods. And the potential diagnostic performance of the biomarkers for ALF was estimated using the AUC values. Data from GSE14668, GSE74000, and GSE96851 databases was performed as external verification sets to validate the expression level of potential diagnostic biomarkers. Furthermore, we analyzed the difference in the protein level of diagnostic biomarkers between normal and ALF mice models. Finally, we used CIBERSORT to estimate relative infiltration levels of 22 immune cell subsets in ALF samples and further analyzed the relationships between the diagnostic biomarkers and infiltrated immune cells.Results: A total of 200 co-DEGs were screened. Enrichment analyses depicted that they are highly enriched in metabolism and matrix collagen production-associated processes. The top 28 hub genes were obtained by integrating MCC and Degree methods. Then, the collagen type IV alpha 2 chain (COL4A2) was regarded as the diagnostic biomarker and showed excellent specificity and sensitivity. COL4A2 also showed a statistically significant difference and excellent diagnostic effectiveness in the verification set. In addition, there was a significant upregulation in the COL4A2 protein level in ALF mice models compared with the normal group. CIBERSORT analysis showed that activated CD4 T cells, plasma cells, macrophages, and monocytes may be implicated in the progress of ALF. In addition, COL4A2 showed different degrees of correlation with immune cells.Conclusion: In conclusion, COL4A2 may be a diagnostic biomarker for ALF, and immune cell infiltration may have important implications for the occurrence and progression of ALF.</p

Table2_Identification of effective diagnostic biomarker and immune cell infiltration characteristics in acute liver failure by integrating bioinformatics analysis and machine-learning strategies.xlsx

Background: To determine effective biomarkers for the diagnosis of acute liver failure (ALF) and explore the characteristics of the immune cell infiltration of ALF.Methods: We analyzed the differentially expressed genes (DEGs) between ALF and control samples in GSE38941, GSE62029, GSE96851, GSE120652, and merged datasets. Co-expressed DEGs (co-DEGs) identified from the five datasets were analyzed for enrichment analysis. We further constructed a PPI network of co-DEGs using the STRING database. Then, we integrated the two kinds of machine-learning strategies to identify diagnostic biomarkers of top hub genes screened based on MCC and Degree methods. And the potential diagnostic performance of the biomarkers for ALF was estimated using the AUC values. Data from GSE14668, GSE74000, and GSE96851 databases was performed as external verification sets to validate the expression level of potential diagnostic biomarkers. Furthermore, we analyzed the difference in the protein level of diagnostic biomarkers between normal and ALF mice models. Finally, we used CIBERSORT to estimate relative infiltration levels of 22 immune cell subsets in ALF samples and further analyzed the relationships between the diagnostic biomarkers and infiltrated immune cells.Results: A total of 200 co-DEGs were screened. Enrichment analyses depicted that they are highly enriched in metabolism and matrix collagen production-associated processes. The top 28 hub genes were obtained by integrating MCC and Degree methods. Then, the collagen type IV alpha 2 chain (COL4A2) was regarded as the diagnostic biomarker and showed excellent specificity and sensitivity. COL4A2 also showed a statistically significant difference and excellent diagnostic effectiveness in the verification set. In addition, there was a significant upregulation in the COL4A2 protein level in ALF mice models compared with the normal group. CIBERSORT analysis showed that activated CD4 T cells, plasma cells, macrophages, and monocytes may be implicated in the progress of ALF. In addition, COL4A2 showed different degrees of correlation with immune cells.Conclusion: In conclusion, COL4A2 may be a diagnostic biomarker for ALF, and immune cell infiltration may have important implications for the occurrence and progression of ALF.</p

Biocompatible Shape Memory Blend for Self-Expandable Stents with Potential Biomedical Applications

Biocompatible poly­(propylene carbonate) (PPC)/polycaprolactone (PCL) shape memory blends were fabricated using melt blending. The shape memory performance of these blends was found to depend remarkably on their components. On addition of 25 vol % PCL, one blend (PL-25) achieved an optimal shape-fixing ratio (<i>R</i>_f) and -recovery ratio (<i>R</i>_r). Specifically, its <i>R</i>_r considerably increased by 24.1 and 50.0% compared with those of pure PPC and PCL, respectively, because of the restricted irreversible deformation of the amorphous chains cross-linked by tiny crystals. After undergoing three thermomechanical cycles, <i>R</i>_f and <i>R</i>_r reached 97.0%. The PL-25 blend was further melt-processed into a stent, which showed a fast response and self-expansion at 37 °C. These results, along with those obtained from evaluating the material’s blood compatibility, in vitro degradation and drug release behavior, demonstrated the great potential of PL-25 for biomedical applications

Table1_Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis.XLSX

Hepatitis B virus (HBV) infection remains the leading cause of liver fibrosis (LF) worldwide, especially in China. Identification of decisive diagnostic biomarkers for HBV-associated liver fibrosis (HBV-LF) is required to prevent chronic hepatitis B (CHB) from progressing to liver cancer and to more effectively select the best treatment strategy. We obtained 43 samples from CHB patients without LF and 81 samples from CHB patients with LF (GSE84044 dataset). Among these, 173 differentially expressed genes (DEGs) were identified. Functional analysis revealed that these DEGs predominantly participated in immune-, extracellular matrix-, and metabolism-related processes. Subsequently, we integrated four algorithms (LASSO regression, SVM-RFE, RF, and WGCNA) to determine diagnostic biomarkers for HBV-LF. These analyses and receive operating characteristic curves identified the genes for phosphatidic acid phosphatase type 2C (PPAP2C) and versican (VCAN) as potentially valuable diagnostic biomarkers for HBV-LF. Single-sample gene set enrichment analysis (ssGSEA) further confirmed the immune landscape of HBV-LF. The two diagnostic biomarkers also significantly correlated with infiltrating immune cells. The potential regulatory mechanisms of VCAN underlying the occurrence and development of HBV-LF were also analyzed. These collective findings implicate VCAN as a novel diagnostic biomarker for HBV-LF, and infiltration of immune cells may critically contribute to the occurrence and development of HBV-LF.</p

Image1_Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis.tif

Hepatitis B virus (HBV) infection remains the leading cause of liver fibrosis (LF) worldwide, especially in China. Identification of decisive diagnostic biomarkers for HBV-associated liver fibrosis (HBV-LF) is required to prevent chronic hepatitis B (CHB) from progressing to liver cancer and to more effectively select the best treatment strategy. We obtained 43 samples from CHB patients without LF and 81 samples from CHB patients with LF (GSE84044 dataset). Among these, 173 differentially expressed genes (DEGs) were identified. Functional analysis revealed that these DEGs predominantly participated in immune-, extracellular matrix-, and metabolism-related processes. Subsequently, we integrated four algorithms (LASSO regression, SVM-RFE, RF, and WGCNA) to determine diagnostic biomarkers for HBV-LF. These analyses and receive operating characteristic curves identified the genes for phosphatidic acid phosphatase type 2C (PPAP2C) and versican (VCAN) as potentially valuable diagnostic biomarkers for HBV-LF. Single-sample gene set enrichment analysis (ssGSEA) further confirmed the immune landscape of HBV-LF. The two diagnostic biomarkers also significantly correlated with infiltrating immune cells. The potential regulatory mechanisms of VCAN underlying the occurrence and development of HBV-LF were also analyzed. These collective findings implicate VCAN as a novel diagnostic biomarker for HBV-LF, and infiltration of immune cells may critically contribute to the occurrence and development of HBV-LF.</p

Associations between cytokine gene polymorphisms and susceptibility to Helicobacter pylori infection and Helicobacter pylori related gastric cancer, peptic ulcer disease: A meta-analysis

<div><p>Objectives</p><p>The aim of this study is to clarify the associations between IL-1B31C/T, IL-1B-511C/T, IL-8-251T/A gene polymorphisms and the risk of Helicobacter pylori (<i>H</i>. <i>pylori</i>) infection together with <i>H</i>. <i>pylori</i>-related gastric cancer (GC), peptic ulcer disease (PUD).</p><p>Methods</p><p>All eligible literature published up to July 2016 were identified by searching Pubmed, Embase, Web of Science and CNKI. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using a fixed or random effects model.</p><p>Results</p><p>29 case-control studies were eligible, and each of them may focus on more than one gene polymorphism. Ultimately, there were 21 studies (3159 cases and 2816 controls) for IL-1B-31C/T, 16 studies (2486 cases and 1989 controls) for IL-1B-511C/T polymorphisms, 9 studies (1963 cases and 1205 controls) for IL-8-251T/A polymorphisms. Overall, an increased risk of <i>H</i>. <i>pylori</i> infection was found for IL-1B-31C/T polymorphisms in total population [OR = 1.134, 95%CI = 1.008–1.275 for recessive model; OR = 1.145, 95%CI = 1.007–1.301 for TT <i>vs</i> CC model]. While, for IL-1B-511C/T and IL8-251T/A polymorphisms, no evidence indicated that they were associated with the risk of <i>H</i>. <i>pylori</i> infection in all genetic models. Furthermore, we found an increased risk of <i>H</i>. <i>pylori</i>-related GC with IL-1B-511C/T polymorphisms [OR = 1.784, 95%CI = 1.289–2.469 for recessive model; OR = 1.772, 95%CI = 1.210–2.594 for TT <i>vs</i> CC model] and IL8-251A/T polymorphisms [OR = 1.810, 95%CI = 1.229–2.667 for recessive model; OR = 1.717, 95%CI = 1.143–2.580 for TT <i>vs</i> AA model], an increased risk of H. pylori-related PUD with IL8-251T/A polymorphisms [OR = 1.364, 95%CI = 1.010–1.843 for recessive model; OR = 1.427, 95%CI = 1.039–1.959 for AA <i>vs</i> TT model].</p><p>Conclusions</p><p>IL-1B-31C/T gene polymorphisms might increase <i>H</i>. <i>pylori</i> infection risk. IL-1B-511-C/T and IL-8-251T/A gene polymorphisms might act as a risk factor to H. pylori-related diseases including GC or PUD</p></div

Table2_Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis.XLSX

Hepatitis B virus (HBV) infection remains the leading cause of liver fibrosis (LF) worldwide, especially in China. Identification of decisive diagnostic biomarkers for HBV-associated liver fibrosis (HBV-LF) is required to prevent chronic hepatitis B (CHB) from progressing to liver cancer and to more effectively select the best treatment strategy. We obtained 43 samples from CHB patients without LF and 81 samples from CHB patients with LF (GSE84044 dataset). Among these, 173 differentially expressed genes (DEGs) were identified. Functional analysis revealed that these DEGs predominantly participated in immune-, extracellular matrix-, and metabolism-related processes. Subsequently, we integrated four algorithms (LASSO regression, SVM-RFE, RF, and WGCNA) to determine diagnostic biomarkers for HBV-LF. These analyses and receive operating characteristic curves identified the genes for phosphatidic acid phosphatase type 2C (PPAP2C) and versican (VCAN) as potentially valuable diagnostic biomarkers for HBV-LF. Single-sample gene set enrichment analysis (ssGSEA) further confirmed the immune landscape of HBV-LF. The two diagnostic biomarkers also significantly correlated with infiltrating immune cells. The potential regulatory mechanisms of VCAN underlying the occurrence and development of HBV-LF were also analyzed. These collective findings implicate VCAN as a novel diagnostic biomarker for HBV-LF, and infiltration of immune cells may critically contribute to the occurrence and development of HBV-LF.</p

Meta-analysis of the association between IL-1B-511C/T polymorphisms and susceptibility to <i>H</i>. <i>pylori</i>-related GC.

<p>(a). Recessive model. (b) TT vs CC model.</p

Charateristics of studies included in the meta-analysis.

<p>Charateristics of studies included in the meta-analysis.</p

Summary of ORs of IL-1B-511C/T, IL-8-251T/A gene polymorphisms and H. pylori-related GC and PUD risk.

<p>Summary of ORs of IL-1B-511C/T, IL-8-251T/A gene polymorphisms and H. pylori-related GC and PUD risk.</p