BackgroundThe diagnosis of associated choledocholithiasis prior to cholecystectomy for patients with gallstones is important for the surgical decision and treatment efficacy. However, whether ultrasound is sufficient for preoperative diagnosis of choledocholithiasis remains controversial, with different opinions on whether routine magnetic resonance cholangiopancreatography (MRCP) is needed to detect the possible presence of common bile duct (CBD) stones.MethodsIn this study, a total of 413 patients with gallstones who were admitted to the Department of General Surgery of the First Affiliated Hospital of Harbin Medical University in China for a period of 3 years and underwent both ultrasound and MRCP examinations were retrospectively analysed. After reviewing and screening these cases according to the literature, 11 indicators including gender, age, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, γ-aminotransferase, CBD diameter, and concurrent acute cholecystitis were selected and comparatively analysed.ResultsAmong the 413 patients, a total of 109 cases showed concurrent gallstones and choledocholithiasis, accounting for 26.39 % of all cases. Among them, 60 cases of choledocholithiasis were revealed by ultrasound examination, accounting for 55.05 %, while 49 cases of choledocholithiasis were not detected by ultrasound examination but were confirmed by MRCP instead (the missed diagnosis rate of ultrasound was 44.95 %). The results of statistical analysis suggested that alanine aminotransferase, acute cholecystitis, and CBD diameter were the three most relevant factors for missed diagnosis by ultrasound.ConclusionThe accuracy of preoperative ultrasonography for the diagnosis of associated CBD stones for patients with gallstones is not high. However, elevated alanine aminotransferase, concurrent acute cholecystitis, and CBD diameter were identified as key factors that may affect the accuracy of the diagnosis. Thus, routine preoperative MRCP examination is suggested for patients with gallstones to rule out possible concomitant CBD stones.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy that is associated with high levels of mortality. CRCs are often associated with an aberrant wingless-type mouse mammary tumor virus integration site family (Wnt) signaling pathway known to be responsible for tumorigenesis and cancer progression. Other factors that contribute to CRC pathology include hypoxia, extracellular matrix and cellular microenvironment. In the present study, modulation of Wnt, a common molecular progenitor for CRC-associated pathology was evaluated. CRC tissues and specific cell lines were found to exhibit increased expression levels of prolyl 4-hydroxylase subunit α1 (P4HA1). P4HA1 expression was found to stabilize hypoxia inducible factor-1α (HIF1α). The silencing of P4HA1 resulted in decreased cell proliferation, cell cycle arrest in the G 1 phase, decreased tumorsphere formation, decreased tumorsphere volume, increased susceptibility to 5-fluorouracil and increased caspase-3 activity. However, P4HA1 silencing resulted in the activation and thus proteasomal degradation of β-catenin, indicative of the abrogation of Wnt signaling pathway. Wnt is a critical signaling pathway and is activated in most CRCs. HIF1α is a poor prognostic marker in CRC. The present study provided preliminary evidence that HIF1α and the Wnt signaling pathway in CRC are modulated through P4HA1. P4HA1 may serve not just as a biomarker for CRC prognosis but may also be targeted for potential therapeutic intervention.

Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including “immune response” as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma.

BackgroundStudies suggest an important role of autophagy as a target for cancer therapy. We constructed a "disease-gene-drug" network using the modular approach of bioinformatics and screened herbal monomers demonstrating functions related to autophagy regulation.MethodsBased on the microarray results of the gene expression omnibus (GEO) database (GSE2435 and GSE31040, starvation-induced autophagy model), we used the human protein reference database (HPRD) to obtain the protein-protein interaction (PPI) network. In addition, we used the CFinder software to identify several functional modules, performed gene ontology-biological process (GO-BP) functional enrichment analysis using the DAVID software, constructed a herbal monomer-module gene regulatory network using literature search and the Cytoscape software, and then analyzed the relationships between autophagy, genes, and herbal monomers.ResultsWe screened 544 differentially expressed genes related to autophagy, 375 pairs of differentially expressed genes, and 7 gene modules, wherein the functions of module 3 (composed of 7 genes) were enriched in "cell death". Using the constructed herbal monomer-module gene regulatory network, we found that 30 herbal monomers can simultaneously regulate these 7 genes, indicating a potential regulatory role in autophagy.ConclusionsDatabase screening using the disease-gene-drug network can provide new strategies and ideas for the application of herbal medicines in cancer therapy.

Bile acid causes trypsinogen activation in pancreatic acinar cells through a complex process. Additional research is required to further elucidate which signaling pathways affect trypsinogen activation when activated. the changes in the whole‑genome expression profile of AR42J cells under the effect of taurolithocholic acid 3‑sulfate (TLC‑S) were investigated. Furthermore, gene groups that may play a regulatory role were analyzed using the modular approach of biological networks. The aim of the present study was to improve our understanding of the changes in TLC‑S‑stimulated AR42J cells through a genetic functional modular analysis. whole‑genome expression profile chip arrays were applied to detect genes that were differentially expressed in pancreatic acinar AR42J cells treated with TLC‑S for 20 min. Based on the human protein reference database, a protein‑protein interaction network was obtained, which was then processed by CFinder software to derive 14 modules. Among these 14 modules, the gene ontology biological processes enrichment analysis identified two as modules of interest. Kyoto encyclopedia of genes and genomes map analysis revealed that MAP2K4, MAPK8 and FLNA are part of the c-Jun N-terminal kinase (JNK) pathway. The JNK signaling pathway is involved in regulating trypsinogen activation in rat pancreatic AR42J cells. Next, a regulatory network of seven kinase inhibitors was constructed. SP600125 is an ATP‑competitive, efficient, selective and reversible inhibitor of JNK. the results were verified by four sets of experiments and demonstrated that trypsinogen activation is mediated by the JNK signaling pathway in the pathogenesis of acute pancreatitis (AP). The present study provided a useful reference for better understanding the pathogenesis of AP and identifying new targets to regulate trypsinogen activation, in addition to providing valuable information for the treatment of AP.