A location-based anatomic classification system for acute pancreatic fluid collections: Roadmap for optimal intervention in the step-up era.

Walled-off pancreatic necrosis (WOPN) is a local complication of acute necrotizing pancreatitis frequently requiring intervention. Treatment is typically through the coordinated efforts of a multidisciplinary team. Current management guidelines recommend a step-up approach beginning with minimally invasive techniques (percutaneous or transmural endoscopic drainage) followed by escalation to more invasive procedures if needed. Although the step-up approach is an evidence-based treatment paradigm for management of pancreatic fluid collections, it lacks guidance regarding optimal invasive technique selection based on the anatomic characteristics of pancreatic fluid collections. Similarly, existing cross-sectional imaging-based classification systems of pancreatic fluid collections have been used to predict disease severity and prognosis; however, none of these systems are designed to guide intervention. We propose a novel classification system which incorporates anatomic characteristics of pancreatic fluid collections (location and presence of disconnected pancreatic duct) to guide intervention selection and clinical decision making. We believe adoption of this simple classification system will help streamline treatment algorithms and facilitate cross-study comparisons for pancreatic fluid collections.

Molecular Characterization and Functional Study of Insulin-Like Androgenic Gland Hormone Gene in the Red Swamp Crayfish, Procambarus clarkii.

The androgenic gland (AG) is a male-specific endocrine organ that controls the primary and secondary sexual characteristics in male crustaceans. More evidence indicates that the insulin-like androgenic gland hormone gene (IAG) is the key male sexual differentiation factor, particularly the application of RNA interference (RNAi) technology on IAG. In this study, the full-length cDNA of IAG (termed PcIAG) was isolated from the red swamp crayfish, Procambarusclarkii. Tissue distribution analysis showed that in addition to its expression in the AG of male P. clarkii, PcIAG was widely expressed in female tissues and other male tissues. The PcIAG protein was detected in the reproductive and nervous systems of adult male P. clarkii. Additionally, RNAi results showed that the PcIAG expression could be silenced efficiently, and the male sperm maturation and release possibly present a transient adverse interference at lower doses (0.1 µg/g and 1 µg/g) of PcIAG-dsRNA (PcIAG double-stranded RNA). Dramatically, the expression level of PcIAG increased sharply shortly after the injection of higher doses (5 µg/g and 10 µg/g) of PcIAG-dsRNA, which might accelerate the maturation and release of sperm. Moreover, the expression of PcSxl (P. clarkii Sex-lethal) was detected by Quantitative Real-Time PCR (qPCR) after the injection of PcIAG-dsRNA to explore whether the PcIAG gene regulates the PcSxl gene, and we found that the PcIAG did not directly regulate PcSxl in P. clarkii. The study could help accelerate the progress of PcIAG functional research and provide a useful reference for the single-sex selective breeding of P. clarkii.

KLF15 regulates endobiotic and xenobiotic metabolism.

Hepatic metabolism and elimination of endobiotics (for example, steroids, bile acids) and xenobiotics (for example, drugs, toxins) is essential for health. While the enzymatic (termed phase I-II) and transport machinery (termed phase III) controlling endobiotic and xenobiotic metabolism (EXM) is known, understanding of molecular nodal points that coordinate EXM function in physiology and disease remains incomplete. Here we show that the transcription factor Kruppel-like factor 15 (KLF15) regulates all three phases of the EXM system by direct and indirect pathways. Unbiased transcriptomic analyses coupled with validation studies in cells, human tissues, and animals, support direct transcriptional control of the EXM machinery by KLF15. Liver-specific deficiency of KLF15 (Li-KO) results in altered expression of numerous phase I-III targets, and renders animals resistant to the pathologic effects of bile acid and acetaminophen toxicity. Furthermore, Li-KO mice demonstrate enhanced degradation and elimination of endogenous steroid hormones, such as testosterone and glucocorticoid, resulting in reduced male fertility and blood glucose levels, respectively. Viral reconstitution of hepatic KLF15 expression in Li-KO mice reverses these phenotypes. Our observations identify a previously unappreciated transcriptional pathway regulating metabolism and elimination of endobiotics and xenobiotics.

Ileectomy-induced Bile Overaccumulation in Mouse Intestine.

Intestinal resection is a common therapeutic approach for human diseases such as obesity, inflammatory bowel disease, Crohn's disease, and colon cancer that often results in severe short bowel syndrome-like adverse effects including bile acid diarrhea, dehydration, electrolyte disturbances, and nutrient malabsorption. Here we introduce a murine ileal resection model, termed ileectomy, to evaluate tissue communication and the maintenance of systemic homeostasis. After ileal resection, circulating blood is permanently devoid of the ileum-specific endocrine hormone fibroblast growth factor 15 (FGF15), which releases its endocrinal inhibition of bile acid synthesis in the liver. In combination with the increased production and abolished reabsorption of bile acids after removing the ileum, mice that underwent surgery suffer from bile salt overaccumulation in the intestine and associated diarrhea, morbidity, and mortality. Novel usage of the surgery model introduced in this study may provide mechanistic and functional insights into ileal control of systemic metabolic regulation in physiology and disease.