Preoperative sarcopenia combined with prognostic nutritional index predicts long-term prognosis of radical gastrectomy with advanced gastric cancer: a comprehensive analysis of two-center study.

PURPOSE: This study aims to investigate the predictive value of the combined index smni(skeletal muscle index (SMI)-prognostic nutrition index(PNI)) for the postoperative survival of patients with advanced gastric cancer(AGC). METHODS: 650 patients with AGC from two centers (290 cases from the First Affiliated Hospital of Dalian University and 360 points from the Fujian Medical University Union Hospital) were selected as the study subjects based on unified screening criteria. Clinical data, preoperative abdominal CT images, results of hematology-related examinations, tumor-related characteristics, and surgical and follow-up data of the patients were collected and organized. The L3 vertebral level muscle area was measured using computer-assisted measurement techniques, and the skeletal muscle index(SMI) was calculated based on this measurement. The prognostic nutrition index (PNI) was calculated based on serum albumin and lymphocyte count indicators. The Kaplan-Meier survival analysis of data from the First Affiliated Hospital was used to determine that SMI and PNI are significantly correlated with the postoperative survival rate of patients with advanced gastric cancer. Based on this, a novel combined index smni was fitted and stratified for risk. Cox proportional hazards regression analysis was used to determine that the index smni is an independent prognostic risk factor for patients with AGC after surgery. The ROC curve was used to describe the predictive ability of the new combined index and its importance and predictive power in predicting postoperative survival of patients with AGC, which was verified in the data of Fujian Medical University Union Hospital. RESULT: The Kaplan-Meier curve analysis of the combined indicator smni Is clearly associated with long-term survival(3-year OS (P < 0.001) and DSS (P < 0.001)), univariate analysis and multivariate analysis showed that smni was an independent prognostic risk factor, The ROC curve for the first center 3-year OS(AUC = 0.678), DSS(AUC = 0.662) show good predictive ability and were validated in the second center. CONCLUSION: The combined index smni has a good predictive ability for the postoperative survival rate of patients with AGC and is expected to provide a new reference basis and more accurate and scientific guidance for the postoperative management and treatment of patients with AGC.

Adenovirus-mediated overexpression of sST2 attenuates cardiac injury in the rat with severe acute pancreatitis.

AIMS: Severe acute pancreatitis (SAP) is a serious disease associated with systematic inflammation and multiple organs dysfunction. Soluble ST2 (sST2), a member of the Toll interleukin (IL)-1 receptor (TIR) superfamily, has been demonstrated to exert immune-regulatory and anti-inflammatory properties in several inflammation-related diseases. In this study, we investigated whether transfer of sST2 gene by adenovirus vector could attenuate sodium taurocholate-induced SAP and associated cardiac injury. MAIN METHODS: A rat model of SAP was induced by retrograde injection of 5% sodium taurocholate (1 ml/kg) into the biliopancreatic duct. Rats in the treatment groups were intravenously injected with adenovirus expressing sST2 (Ad-sST2, 1 × 109 particles/rat) or green fluorescent protein (Ad-GFP) via the tail vein 48 h before SAP induction. Histological changes in the pancreatic and heart tissues, and parameters for evaluating SAP and associated cardiac injury were determined at 24 h after SAP. KEY FINDINGS: Sodium taurocholate induced obvious pathological changes in pancreas and elevated serum levels of amylase and lipase. Furthermore, SAP animals exhibited significant cardiac impairment, evidenced by decreased cardiac function, increased myocardial apoptosis and cardiac-related enzymes including creatine kinase isoenzyme, lactate dehydrogenase, and Troponin T. Administration of Ad-sST2 markedly improved the structure of pancreas and heart tissues, and reversed the alterations in serum amylase, lipase and cardiac-related enzymes. In addition, Ad-sST2 treatment downregulated pro-inflammatory cytokines production, demonstrating the anti-inflammatory property of sST2. SIGNIFICANCE: Our results suggest that administration of Ad-sST2 significantly attenuated the severity of SAP and associated cardiac damage, and the cardioprotective effect is associated with its anti-inflammatory action.

MicroRNA-337 regulates the PI3K/AKT and Wnt/ß-catenin signaling pathways to inhibit hepatocellular carcinoma progression by targeting high-mobility group AT-hook 2.

MicroRNAs (miRNAs) serve as major regulators during the tumorigenesis and tumor development of hepatocellular carcinoma (HCC). In addition, miRNAs may serve as new promising biomarkers for the diagnosis and prognosis and as effective therapeutic targets for patients with this malignancy. Therefore, understanding the association between miRNAs and HCC may be beneficial to discover novel therapeutic approaches towards diagnosis and treatments. Results of this study showed that miRNA-337 (miR-337) was markedly downregulated in HCC tissues and cell lines. Decreased miR-337 expression was significantly associated with the TNM stage and lymph node metastasis of HCC. Ectopic expression of miR-337 prohibited the proliferation, colony formation, migration, and invasion of HCC cells. It also promoted the apoptosis in vitro and reduced the tumor growth in vivo of these cells. High-mobility group AT-hook 2 (HMGA2) was identified as a direct target gene of miR-337 in HCC through a series of experiments. HMGA2 was significantly overexpressed in HCC tissues and negatively correlated with miR-337 expression. Moreover, the functions of HMGA2 inhibition were similar to those induced by miR-337 in HCC. Restored HMGA2 expression rescued the tumor-suppressive roles of miR-337 overexpression in HCC. Furthermore, miR-337 overexpression inhibited the activation of PI3K/AKT and Wnt/ß-catenin signaling pathways in HCC both in vitro and in vivo. This study demonstrated that miR-337 may play tumor-suppressing roles in HCC, at least partly, via directly targeting HMGA2 and inhibiting the PI3K/AKT and Wnt/ß-catenin signaling pathways. Therefore, miR-337 may be a novel and effective target for the therapeutic treatment of patients with HCC.

Emodin alleviates severe acute pancreatitis-associated acute lung injury by decreasing pre-B-cell colony-enhancing factor expression and promoting polymorphonuclear neutrophil apoptosis.

The present study aimed to evaluate the protective effects of emodin on severe acute pancreatitis (SAP)­associated acute lung injury (ALI), and investigated the possible mechanism involved. SAP was induced in Sprague­Dawley rats by retrograde infusion of 5% sodium taurocholate (1 ml/kg), after which, rats were divided into various groups and were administered emodin, FK866 [a competitive inhibitor of pre­B­cell colony­enhancing factor (PBEF)] or dexamethasone (DEX). DEX was used as a positive control. Subsequently, PBEF expression was detected in polymorphonuclear neutrophils (PMNs) isolated from rat peripheral blood by reverse transcription­quantitative polymerase chain reaction and western blotting. In addition, histological alterations, apoptosis in lung/pancreatic tissues, apoptosis of peripheral blood PMNs and alterations in the expression of apoptosis­associated proteins were examined by hematoxylin and eosin staining, terminal deoxynucleotidyl­transferase­mediated dUTP nick end labeling assay, Annexin V/propidium iodide (PI) assay and western blotting, respectively. Serum amylase activity and wet/dry (W/D) weight ratios were also measured. An in vitro study was also conducted, in which PMNs were obtained from normal Sprague­Dawley rats and were incubated with emodin, FK866 or DEX in the presence of lipopolysaccharide (LPS). Apoptosis of PMNs and the expression levels of apoptosis­associated proteins were examined in cultured PMNs in vitro by Annexin V/PI assay and western blotting, respectively. The results demonstrated that emodin, FK866 and DEX significantly downregulated PBEF expression in peripheral blood PMNs. In addition, emodin, FK866 and DEX reduced serum amylase activity, decreased lung and pancreas W/D weight ratios, alleviated lung and pancreatic injuries, and promoted PMN apoptosis by regulating the expression of apoptosis­associated proteins: Fas, Fas ligand, B­cell lymphoma (Bcl)­2­associated X protein, cleaved caspase­3 and Bcl­extra­large. In addition, the in vitro study demonstrated that emodin, FK866 and DEX significantly reversed the LPS­induced decrease of apoptosis in PMNs by regulating the expression of apoptosis­associated proteins. In conclusion, the present study demonstrated that emodin may protect against SAP­associated ALI by decreasing PBEF expression, and promoting PMN apoptosis via the mitochondrial and death receptor apoptotic pathways.