Subcutaneous fat thickness and abdominal depth are risk factors for surgical site infection after gastric cancer surgery.

BACKGROUND: Surgical site infection (SSI) is one of the most common complications after gastric cancer (GC) surgery. The occurrence of SSI can lead to a prolonged postoperative hospital stay and increased medical expenses, and it can also affect postoperative rehabilitation and the quality of life of patients. Subcutaneous fat thickness (SFT) and abdominal depth (AD) can be used as predictors of SSI in patients undergoing radical resection of GC. AIM: To explore the potential relationship between SFT or AD and SSI in patients undergoing elective radical resection of GC. METHODS: Demographic, clinical, and pre- and intraoperative information of 355 patients who had undergone elective radical resection of GC were retrospectively collected from hospital electronic medical records. Univariate analysis was performed to screen out the significant parameters, which were subsequently analyzed using binary logistic regression and receiver-operating characteristic curve analysis. RESULTS: The prevalence of SSI was 11.27% (40/355). Multivariate analyses revealed that SFT [odds ratio (OR) = 1.150; 95% confidence interval (95%CI): 1.090-1.214; P < 0.001], AD (OR = 1.024; 95%CI: 1.009-1.040; P = 0.002), laparoscopic-assisted surgery (OR = 0.286; 95%CI: 0.030-0.797; P = 0.017), and operation time (OR = 1.008; 95%CI: 1.001-1.015; P = 0.030) were independently associated with the incidence of SSI after elective radical resection of GC. In addition, the product of SFT and AD was a better potential predictor of SSI in these patients than either SFT or AD alone. CONCLUSION: SFT and AD are independent risk factors and can be used as predictors of SSI in patients undergoing radical resection of GC.

Sphingosine kinase 1 knockout alleviates hepatic ischemia/reperfusion injury by attenuating inflammation and oxidative stress in mice.

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1 (SphK1) phosphorylates sphingosine to sphingosine-1-phosphate (S1P) which participates in multiple bioactive processes. However, little is known about the role of SphK1 in hepatic I/R injury. This study aimed to investigate the effect of SphK1 knockout on liver I/R injury and to explore underlying mechanisms. METHODS: SphK1 knockout and wild type mice were subjected to 70% partial hepatic I/R. Serum alanine aminotransferase was determined to indicate the degree of liver damage. Hematoxylin-eosin staining and TUNEL assay were used to assess histological changes and hepatocellular apoptosis, respectively. Immunohistochemistry was performed to detect the expression and translocation of phosphorylated p65 and signal transducer and activator of transcription 3 (STAT3). Western blotting was used to determine the expression of S1P receptor 1 (S1PR1), phosphorylated p65 and STAT3. Real-time PCR was used to demonstrate the changes of proinflammatory cytokines. Oxidative stress markers were also determined through biochemical assays. RESULTS: SphK1 knockout significantly ameliorated I/R-induced liver damage, mitigated liver tissue necrosis and apoptosis compared with wild type control. I/R associated inflammation was alleviated in SphK1 knockout mice as demonstrated by attenuated expression of S1PR1 and reduced phosphorylation of nuclear factor kappa B p65 and STAT3. The proinflammatory cytokines interleukin-1ß, interleukin-6 and tumor necrosis factor-α were also inhibited by SphK1 genetic deletion. The oxidative stress markers were lower in SphK1 knockout mice after I/R injury than wild type mice. CONCLUSIONS: Knockout of SphK1 significantly alleviated damage after hepatic I/R injury, possibly through inhibiting inflammation and oxidative stress. SphK1 may be a novel and potent target in clinical practice in I/R-related liver injury.

Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy.

PURPOSE: FTY720, known as fingolimod, is a new immunosuppressive agent with effective anticancer properties. Although it was recently confirmed that FTY720 inhibits cancer cell proliferation, FTY720 can also induce protective autophagy and reduce cytotoxicity. Blocking autophagy with Beclin 1 siRNA after treatment with FTY720 promotes apoptosis. The objective of this study was to enhance the anticancer effect of FTY720 in hepatocellular carcinoma (HCC) by targeted co-delivery of FTY720 and Beclin 1 siRNA using calcium phosphate (CaP) nanoparticles (NPs). MATERIALS AND METHODS: First, the siRNA was encapsulated within the CaP core. To form an asymmetric lipid bilayer structure, we then used an anionic lipid for the inner leaflet and a cationic lipid for the outer leaflet; after removing chloroform by rotary evaporation, these lipids were dispersed in a saline solution with FTY720. The NPs were analyzed by transmission electron microscopy, dynamic light scattering and ultraviolet-visible spectrophotometry. Cancer cell viability and cell death were analyzed by MTT assays, fluorescence-activated cell sorting analysis and Western blotting. In addition, the in vivo effects of the NPs were investigated using an athymic nude mouse subcutaneous transplantation tumor model. RESULTS: When the CaP NPs, called LCP-II NPs, were loaded with FTY720 and siRNA, they exhibited the expected size and were internalized by cells. These NPs were stable in systemic circulation. Furthermore, co-delivery of FTY720 and Beclin 1 siRNA significantly increased cytotoxicity in vitro and in vivo compared with that caused by treatment with the free drug alone. CONCLUSION: The CaP NP system can be further developed for co-delivery of FTY720 and Beclin 1 siRNA to treat HCC, enhancing the anticancer efficacy of FTY720. Our findings provide a new insight into HCC treatment with co-delivered small molecules and siRNA, and these results can be readily translated into cancer clinical trials.

Exosome-Mimetic Nanovesicles from Hepatocytes promote hepatocyte proliferation in vitro and liver regeneration in vivo.

The liver has great regenerative capacity after functional mass loss caused by injury or disease. Many studies have shown that primary hepatocyte-derived exosomes, which can deliver biological information between cells, promote the regenerative process of the liver. However, the yield of exosomes is very limited. Recent studies have demonstrated that exosome-mimetic nanovesicles (NVs) can be prepared from cells with almost 100 times the production yield compared with exosomes. Thus, this study investigated the therapeutic capacity of exosome-mimetic NVs from primary hepatocytes in liver regeneration. Exosome-mimetic NVs were prepared by serial extrusions of cells through polycarbonate membranes, and the yield of these NVs was more than 100 times that of exosomes. The data indicated that the NVs could promote hepatocyte proliferation and liver regeneration by significantly enhancing the content of sphingosine kinase 2 in recipient cells. To the best of our knowledge, this is the first time that exosome-mimetic NVs from primary hepatocytes have been prepared, and these NVs have components similar to exosomes from primary hepatocytes and, in some respects, biofunctions similar to exosomes. Strategies inspired by this study may lead to substitution of exosomes with exosome-mimetic NVs for biofunctional purposes, including utilization in tissue repair and regeneration.