Prior exposure to ciprofloxacin disrupts intestinal homeostasis and predisposes ayu ( Plecoglossus altivelis) to subsequent Pseudomonas plecoglossicida-induced infection.

With the rapid development of intensive farming, the aquaculture industry uses a great many antibiotics for the prevention and treatment of bacterial diseases. Despite their therapeutic functions, the overuse and accumulation of antibiotics also pose a threat to aquaculture organisms. In the present study, ayu ( Plecoglossus altivelis) was used as a fish model to study the impacts of ciprofloxacin (CIP) overuse on intestinal homeostasis and immune response during subsequent Pseudomonas plecoglossicida infection. Based on 16S rRNA gene amplification and Illumina sequencing, we found that CIP pre-exposure caused significant variation in intestinal microbiota, including increased species richness, altered microbiota composition and interaction networks, and increased metabolic dysfunction. Furthermore, immunohistochemical analysis indicated that CIP pre-exposure resulted in severe mucosal layer damage, goblet cell reduction, and epithelial cell necrosis of the intestinal barrier in infected ayu. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that disruption of intestinal homeostasis impaired systemic anti-infection immune responses in the intestine, gill, spleen, and head kidney, while inhibiting IL-1ß, TNF-α, and IL-10 expression and promoting TGF-ß expression. Our findings indicated that CIP administration can directly affect intestinal microbiota composition and intestinal integrity in ayu fish. This perturbation of intestinal homeostasis is likely responsible for the lower survival rate of hosts following subsequent infection as the capacity to mount an effective immune response is compromised. This study also provides preliminary clues for understanding the effects of antibiotic overuse on higher vertebrates through trophic transfer.

RGD-binding integrins mediated phagocytosis involved in the entry of Edwardsiella tarda into mudskipper MO/MФ.

The versatile fish pathogen Edwardsiella tarda is an intracellular pathogen with the ability to invade and replicate in host phagocytes. However, the mechanism mediating the uptake of E. tarda in fish monocytes/macrophages (MO/MΦ) is not yet understood. Generating mudskipper kidney-derived MO/MФ transcriptomic resources from mudskipper challenged by E. tarda is crucial for understanding the molecular mechanisms underlying the mudskipper invasion process. In the present study, a total of 1185 up-regulated and 885 down-regulated differentially expressed genes (DEGs) were identified using RNA-seq. Enrichment and pathway analysis of DEGs revealed the centrality of the phagosome and regulation of actin cytoskeleton pathways in pathogen entry. The progress of phagosome formation was observed by transmission electron microscopy. Eight conserved integrin (ITG) subunit genes, belonging to the phagocytic receptors, were found in the transcriptomic sequence data. Additionally, quantitative real-time PCR showed that the mRNA expressions of most ITG subunit genes were related to the different infection times of E. tarda and the different bacterial pathogens. Further assays demonstrated that phagocytosis of FITC-labeled E. tarda by mudskipper MO/MФ was significantly reduced by the tetrapeptide Asp-Gly-Arg-Ser (RGDS). In summary, phagocytosis is one of the entry pathways into mudskipper MO/MΦ, and RGD-binding ITGs are involved in the phagosome formation process.

Intrahepatic portosystemic shunt assisted by percutaneous transhepatic approach for treatment of portal vein thrombosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the safety and efficacy of mechanical thrombectomy combined with pharmacologic thrombolysis to treat non-acute and symptomatic portal vein thrombosis (PVT) using an intrahepatic portosystemic shunt (IPS) assisted by percutaneous transhepatic approach.</p><p><b>METHODS</b>From April 2006 to May 2012, 18 patients with non-acute and symptomatic PVT were treated with balloon dilation, sheath-directed thrombus aspiration and continuous infusion of urokinase using the IPS assisted by percutaneous transhepatic approach. The significance of differences in the portosystemic gradient measured before and after therapy was assessed by paired samples t-test, and survival analysis was made by the Kaplan-Meier method.</p><p><b>RESULTS</b>IPS was successfully created in all patients. The mean duration of the thrombolytic therapy was 65.3 +/- 29.5 h, and the mean concentration of urokinase used for the thrombolysis was 2324000 +/- 945000 U. Comparison of the mean portosystemic gradients showed a significant improvement in response to the therapy (before: 33.8 +/- 4.9 mm Hg vs. after: 15.4 +/- 2.1 mm Hg; P less than 0.001). The overall rate of clinical improvement was 94.4%. One patient died on day 2 post-therapy and another two patients experienced mild hepatic encephalopathy or right hemothorax, respectively, on day 5 post-therapy, with conservative medical management achieving complete recovery for both. The mean follow-up time was 18.6 +/- 17.5 months, during which only one patient died and five others experienced shunt dysfunction; all remaining patients showed maintenance of shunt patency without symptoms of recurrence.</p><p><b>CONCLUSION</b>Mechanical thrombectomy combined with pharmacologic thrombolysis via the IPS assisted by percutaneous transhepatic approach is a safe and effective therapeutic option for patients with non-acute and symptomatic PVT.</p>

Comparative study of portal vein stent and TACE combined therapy with or without endovascular implantation of iodine-125 seeds strand for treating patients with hepatocellular carcinoma and main portal vein tumor thrombus / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare the efficacies of portal vein stenting and transcatheter arterial chemoembolization (TACE) combined therapy performed with or without endovascular implantation of iodine-125 (125I) seeds strand in patients with hepatocellular carcinoma (HCC) and main portal vein tumor thrombus (MPVTT).</p><p><b>METHODS</b>One-hundred-and-six patients with HCC complicated by MPVTT who were treated with portal vein stents and TACE, either with (Group A, n=56) or without (Group B, n=50) endovascular implantation of 125I seeds strand, between July 2005 and April 2011, were retrospectively analyzed. Overall survival, stent patency, and procedure-related adverse events were compared between the two groups.</p><p><b>RESULTS</b>The technical success rate was 100% for placement of 125I seeds strands and stents in the obstructed main portal vein. No serious procedure-related adverse events were recorded. Group A had significantly higher median survival (335 days vs. group B: 146 days; P=0.001, hazard ratio (HR)=2.244). Additionally, group A had significantly higher median stent patency (400 days vs. group B: 190 days; P=0.005, HR=2.479).</p><p><b>CONCLUSION</b>The combination therapeutic strategy of portal vein stenting and TACE with endovascular implantation of 125I seeds strands improves the survival of HCC patients with MPVTT complication.</p>