Surgical methods influence on the risk of anastomotic fistula after pancreaticoduodenectomy: a systematic review and network meta-analysis.

BACKGROUND: Pancreaticoduodenectomy is the first choice surgical intervention for the radical treatment of pancreatic tumors. However, an anastomotic fistula is a common complication after pancreaticoduodenectomy with a high mortality rate. With the development of minimally invasive surgery, open pancreaticoduodenectomy (OPD), laparoscopic pancreaticoduodenectomy (LPD), and robotic pancreaticoduodenectomy (RPD) are gaining interest. But the impact of these surgical methods on the risk of anastomosis has not been confirmed. Therefore, we aimed to integrate relevant clinical studies and explore the effects of these three surgical methods on the occurrence of anastomotic fistula after pancreaticoduodenectomy. METHODS: A systematic literature search was conducted for studies reporting the RPD, LPD, and OPD. Network meta-analysis of postoperative anastomotic fistula (Pancreatic fistula, biliary leakage, gastrointestinal fistula) was performed. RESULTS: Sixty-five studies including 10,026 patients were included in the network meta-analysis. The rank of risk probability of pancreatic fistula for RPD (0.00) was better than LPD (0.37) and OPD (0.62). Thus, the analysis suggests the rank of risk of the postoperative pancreatic fistula for RPD, LPD, and OPD. The rank of risk probability for biliary leakage was similar for RPD (0.15) and LPD (0.15), and both were better than OPD (0.68). CONCLUSIONS: This network meta-analysis provided ranking for three different types of pancreaticoduodenectomy. The RPD and LPD can effectively improve the quality of surgery and are safe as well as feasible for OPD.

Synergistic chemo-/photothermal therapy based on supercritical technology-assisted chitosan-indocyanine green/luteolin nanocomposites for wound healing.

Despite the success, it is highly challenging to battle against pathogenic biofilms-based chronic bacterial infections by conventional antibiotic therapy. Herein, we report a near-infrared (NIR)/acid-induced nanoplatform based on chitosan (CS)-coated indocyanine green (ICG, photosensitizer)/luteolin (LUT, a natural quorum sensing inhibitor) nanocomposites (ICG/LUT-CS) as antibacterial and antibiofilm agents for skin wound healing. Initially, the ICG/LUT nanoplatforms are prepared by the supercritical antisolvent technology and coated with the CS layer. The obtained ICG/LUT-CS with ultra-high encapsulation efficiency exhibited more favorable photothermal conversion effects and improved NIR laser/acid dual-induced drug release behavior than individual modalities, achieving exceptional bacteria-killing and biofilm elimination effects. Moreover, the ICG/LUT-CS realized the synergetic effects of chemotherapy and photothermal therapy outcomes for wound healing. Together, our findings provided an appealing strategy for the rapid preparation and future translational application of ICG/LUT-CS as an ideal agent for fighting against biofilm infections.

Colchicine Inhibits NETs and Alleviates Cardiac Remodeling after Acute Myocardial Infarction.

PURPOSE: Colchicine, a multipotent anti-inflammatory drug, has been reported to alleviate cardiac remodeling and improve cardiac function after acute myocardial infarction (AMI). However, the underlying mechanism remains incompletely understood. Because neutrophils extracellular traps (NETs) enhance inflammation and participate in myocardial ischemia injury, and colchicine can inhibit NETosis, we thus aimed to determine whether colchicine exerts cardioprotective effects on AMI via suppressing NETs. METHODS: Adult C57BL/6 mice were subjected to permanent ligation of the left anterior descending coronary artery and treated with colchicine (0.1 mg/kg/day) or Cl-amidine (10 mg/kg/day) for 7 or 28 days after AMI. Cardiac function was evaluated by echocardiography, and NETs detected by immunofluorescence. ROS production was detected using 2',7'-dichlorodihydrofluorescein diacetates (DCFH-DA) fluorometry. Intracellular Ca2+ concentration was assessed by a fluorometric ratio technique. RESULTS: We found that colchicine treatment significantly increased mice survival (89.8% in the colchicine group versus 67.9% in control, n = 32 per group; log-rank test, p < 0.05) and improved cardiac function at day 7 (left ventricular ejection fraction (LVEF): 28.0 ± 9.2% versus 12.6 ± 3.9%, n = 8 per group; p < 0.001) and at day 28 (LVEF: 26.2 ± 7.2% versus 14.8 ± 6.7%, n = 8 per group; p < 0.001) post-AMI. In addition, the administration of colchicine inhibited NETs formation and inflammation. Furthermore, colchicine inhibited NETs formation by reducing NOX2/ROS production and Ca2+ influx. Moreover, prevention of NETs formation with Cl-amidine significantly alleviated AMI-induced cardiac remodeling. CONCLUSIONS: Colchicine inhibited NETs and cardiac inflammation, and alleviated cardiac remodeling after acute myocardial infarction.

Application of ultrasound markers measured at different time points of COH cycle in the prediction of ovarian response for individualised ovulation induction.

The purpose of this study was to evaluate the predictive value of ultrasound markers measured at different time points of the controlled ovarian hyperstimulation (COH) cycle on ovarian response and outcome indicators in the IVF-ET cycle. According to the oestrogen level and the number of retrieved oocytes, patients who planned for COH treatment were separated into low-response group, normal and high-response group. The ovarian stromal artery flow parameters on the day of pituitary down-regulation, day 1, day 7, day 10, and the day of hCG injection were collected prospectively. We also have collected the data of cumulus oophorus count on the day of hCG injection by transvaginal sonography. Compared with the low-response group, on the first day of the COH cycle PI, RI, and S/D were lower in the high-response group than they were in the low-response group (p < .05). PSV and EDV were significantly higher in the high-response group than they were in the low-response group (p < .01), and the PSV on the first day of the COH cycle have statistical significance in predicting the number of high-quality embryos. The number of cumulus oophorus on the day of hCG injection has statistical significance in predicting the number of oocytes retrieved and fertilised oocytes. We conclude that the ovarian stromal artery flow parameters on the first day of the COH cycle and cumulus oophorus count on hCG injection day can serve as efficient indicators for an early assessment of ovarian response and individualised ovulation induction.IMPACT STATEMENTWhat is already known on this subject? AMH, AFC, and the age of the patient are well-known effective parameters for the evaluation of ovarian response, but these are insufficient and full of individual differences. Some researchers have investigated the value of colour Doppler ultrasound and cumulus oophorus in assessing ovarian response, but no definitive conclusion has been reached.What do the results of this study add? The hemodynamic parameters of ovarian stromal artery on the first day of the COH cycle and the number of cumulus oophorus on the day of hCG injection detected by Transvaginal Colour Doppler Sonography (TV-CDS) could be used to predict the ovarian response.What are the implications of these findings for clinical practice and/or further research? Ovarian stromal artery flow parameters and cumulus oophorus detected by TV-CDS can potentially be offered as a complementary parameter for ovarian reserve.

Construction and Analysis of a ceRNA Network in Cardiac Fibroblast During Fibrosis Based on in vivo and in vitro Data.

AIMS: Activation of cardiac fibroblasts (CF) is crucial to cardiac fibrosis. We constructed a cardiac fibroblast-related competing endogenous RNA (ceRNA) network. Potential functions related to fibrosis of "hub genes" in this ceRNA network were explored. MATERIALS AND METHODS: The Gene Expression Omnibus database was searched for eligible datasets. Differentially expressed messenger (m)RNA (DE-mRNA) and long non-coding (lnc)RNA (DE-lncRNA) were identified. microRNA was predicted and validated. A predicted ceRNA network was constructed and visualized by Cytoscape, and ceRNA crosstalk was validated. A Single Gene Set Enrichment Analysis (SGSEA) was done, and the Comparative Toxicogenomics Database (CTD) was employed to analyze the most closely associated pathways and diseases of DE-mRNA in the ceRNA network. The functions of DE-mRNA and DE-lncRNA in the ceRNA network were validated by small interfering (si)RNA depletion. RESULTS: The GSE97358 and GSE116250 datasets (which described differentially expressed genes in human cardiac fibroblasts and failing ventricles, respectively) were used for analyses. Four-hundred-and-twenty DE-mRNA and 39 DE-lncRNA, and 369 DE-mRNA and 93 DE-lncRNA were identified, respectively, in the GSE97358 and GSE116250 datasets. Most of the genes were related to signal transduction, cytokine activity, and cell proliferation. Thirteen DE-mRNA with the same expression tendency were overlapped in the two datasets. Twenty-three candidate microRNAs were predicted and the expression of 11 were different. Only two DE-lncRNA were paired to any one of 11 microRNA. Finally, two mRNA [ADAM metallopeptidase domain 19, (ADAM19) and transforming growth factor beta induced, (TGFBI)], three microRNA (miR-9-5p, miR-124-3p, and miR-153-3p) and two lncRNA (LINC00511 and SNHG15) constituted our ceRNA network. siRNA against LINC00511 increased miR-124-3p and miR-9-5p expression, and decreased ADAM19 and TGFBI expression, whereas siRNA against SNHG15 increased miR-153-3p and decreased ADAM19 expression. ADAM19 and TGFBI were closely related to the TGF-ß1 pathway and cardiac fibrosis, as shown by SGSEA and CTD, respectively. Depletion of two mRNA or two lncRNA could alleviate CF activation. CONCLUSIONS: The CF-specific ceRNA network, including two lncRNA, three miRNA, and two mRNA, played a crucial role during cardiac fibrosis, which provided potential target genes in this field.

Optimization and apoptosis induction by RNAi with UTMD technology in vitro.

Apoptosis induction by short hairpin RNA (shRNA) expression vectors may be an efficient and promising strategy for cancer gene therapy. Ultrasound-targeted microbubble destruction (UTMD) is an appealing technique; however, there few data are available to demonstrate the feasibility and to optimize the methodology for this technology. The aim of this study was to optimize this technique and to elucidate the effects on gene inhibition and apoptosis induction in vitro. Human cervical cancer cell lines were obtained and cultured.shRNA vectors were constructed, and the UTMD technique was examined to determine whether or not it was suitable for shRNA transfection into cells. Cells were then examined using flow cytometry. The results revealed that the optimal irradiation parameters obtained higher transfection efficiency and did not affect the integrity of plasmid DNA. We concluded that survivin downregulation with shRNA expression vectors, mediated by the optimal UTMD parameters, markedly induced cell apoptosis and caused cell cycle arrest, laying a foundation for further investigation of this cancer therapy.

Expression profiling of liver cell lines expressing entire or parts of hepatitis C virus open reading frame.

Although hepatitis C virus (HCV) is a causative agent of liver diseases, its mechanism of pathogenesis is still unclear, mainly because of the lack of adequate cell culture systems to support HCV infection and replication. In this report, we describe development and characterization of human hepatoma cell lines constitutively expressing entire (Hep394) or parts (Hep352, Hep3294) of the HCV open reading frame (ORF). The viral and cellular proteolytic machinery involved in the viral precursor processing was consistently functional, and processed HCV proteins were synthesized in these established cell lines. By using a cDNA microarray analysis coupled with semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), we identified 12 genes up-regulated and 4 genes down-regulated in Hep394 cells. With regard to genes related to cell growth regulation, we found up-regulation of forkhead transcription factor FREAC-1, poly (A) binding protein PABP2, and Ras suppressor Rsu-1. Another category of changes in gene expression includes MHC antigens, which play an important role in the T-cell-mediated immune reaction in the liver. In conclusion, functional genomic approaches comparing expression among the different cell lines expressing parts of the HCV genome may promote our understanding of the molecular basis of pathogenicity of HCV infection.