LncRNA NEAT-2 regulate the function of endothelial progenitor cells in experimental Sepsis model.

BACKGROUND: Sepsis is a life-threatening disease with a limited effectiveness and the potential mechanism remains unclear. LncRNA NEAT-2 is reported to be involved in the regulation of cardiovascular disease. This study aimed to investigate the function of NEAT-2 in sepsis. METHODS: We built sepsis animal model with Male Balb/C mice induced by cecal ligation and puncture (CLP). A total of 54 mice were randomly assigned into eight groups: sham operation group (n = 18), CLP group (n = 18), CLP plus si-control group (n = 3), CLP plus si-NEAT2 group (n = 3), CLP plus mimic control group (n = 3), CLP plus miR-320 group (n = 3), CLP plus normal saline group (n = 3), and normal control group (n = 3). The number of peripheral endothelial progenitor cells (EPCs), the expression level of NEAT-2 and miR-320 were detected during progression of sepsis, as well as the number of peripheral EPCs and level of TNF-α, IL-6, VEGF, ALT, AST and Cr. In addition, the function of EPCs was evaluated after NEAT-2 knockdown and miR-320 overexpression in vitro. RESULTS: The number of circulating EPCs increased significantly in sepsis. NEAT-2 expression was significantly increased in the progress of sepsis, accompanied with miR-320 downregulated. NEAT-2 knockdown and miR-320 overexpression attenuated hepatorenal function and increased cytokines in sepsis. Moreover, NEAT-2 knockdown and miR-320 overexpression decreased the proliferation, migration and angiogenesis of endothelial progenitor cells in vitro. CONCLUSIONS: LncRNA-NEAT2 regulated the number and function of endothelial progenitor cells via miR-320 in sepsis, which may contribute to the development of novel potential clinical therapy for sepsis.

The value of lymph nodes ratios in the prognosis of resectable remnant gastric cancer through the retrospective propensity score matching analysis.

PURPOSE: Currently, the characteristics and prognosis of remnant gastric cancer (RGC) are not fully understood yet. The present study aimed to describe the details of clinicopathological features of resectable RGC and investigated the factors affecting survival after the curative operation. METHODS: From Jan. 2006 to Dec. 2015, a total of 118 resectable RGC patients (the RGC group) and 236 age-, sex- and TNM stages-matched resectable gastric cancer (GC) patients (the control group) were recruited retrospectively. Clinicopathological characteristics and overall survival were compared between the two groups. RESULTS: The overall survival rate was 46.61% for RGC patients compared to 55.08% for control groups (P < 0.01), and the mean overall survival time of RGC patients was 40.23 ± 32.27 months, compared to 55.06 ± 34.29 months in the control group (P = 0.023 after matching). The overall survival (OS) of RGC patients with stage IIb was much worse than IIa (P < 0.001) and similar to IIIa (P = 0.463) and IIIb (P = 0.014). Multivariate Cox proportional hazards model analysis revealed that TNM stage (HR: 3.899, P < 0.001) and lymph nodes ratio (LNR) (HR: 2.405, P = 0.028) were independent prognostic significance to OS. CONCLUSIONS: The OS of RGC was much worse than GC with similar TNM stages, and LNR might consider a highly reliable indicator to evaluate the prognostic in RGC.

XIST as a valuable biomarker for prognosis and clinical parameters in diverse tumors: a comprehensive meta- and bioinformatics analysis.

Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been found dysregulated in a variety of human tumors and influenced the clinicopathologic characteristics in cancer patients. Therefore, we systematically searched relevant literature that has identified the correlation of lncRNA XIST expression and clinical outcomes of tumor patients and conducted this meta-analysis to elucidate the clinical prognostic value of long noncoding RNA XIST in human tumors. A comprehensive literature search was performed from PubMed, Web of Science, EMBASE, and Cochrane library databases up to August 1, 2019. Pooled hazard ratios (HRs) or odds ratios (ORs) with a 95% confidence interval (95% Cl) were calculated to evaluate the prognosis, as well as the clinicopathological parameters of XIST, respectively. We also further validated this meta-analysis using The Cancer Genome Atlas (TCGA) dataset. The outcome revealed that XIST overexpression in tumor tissue was interacted to a poor overall survival (OS) (HR=0.52, 95% CI: 0.44-0.61, p<0.0001), disease-free survival (DFS) (HR=0.50; 95% CI: 0.36-0.69, p<0.0001), tumor type (digestive system malignancies, HR=0.53; 95% CI: 0.44-0.63, p<0.0001); nondigestive system malignancies, HR=0.48; 95% CI: 0.34-0.67, p<0.0001), lymph node metastasis(LNM) (OR=0.61, 95% CI: 0.37-1.00; p=0.048), differentiation (OR=1.46; 95% CI: 0.94-2.29; p=0.096), distant metastasis (DM) (OR=0.48, 95% CI: 0.31-0.75; p=0.001), tumor size (OR=0.59, 95% CI: 0.38-0.92; p=0.019), and tumor stage (OR=2.36; 95% CI: 1.62-3.43; p<0.001). XIST could have potential value in early diagnosis and result in prediction and provide a novel view for the therapeutic target in clinical application.

Cancer-associated fibroblasts promote malignancy of gastric cancer cells via Nodal signalling.

The roles of cancer-associated fibroblasts (CAFs) in progression of gastric cancer (GC) are far from well illustration. Here, we show that CAFs can trigger the proliferation and decrease the doxorubicin (Dox) sensitivity of GC cells via secretion of Nodal, one embryonic morphogen that can promote malignancy of various cancers. The neutralization antibody of Nodal can attenuate CAFs-induced cell proliferation. Further, CAFs can activate the Smad2/3 signal, which further increase the phosphorylation and nuclear localization of Akt, in GC cells. While anti-Nodal can abolish the CAFs-induced activation of Smad2/3/Akt signals. Further, both inhibitors of Smad2/3 and Akt can attenuate CAFs-induced proliferation of GC cells. All these data suggest that CAFs can increase the malignancy of GC cells via Nodal-induced activation of Smad2/3/Akt signals. It indicates that CAFs/Nodal signals might be a potential new target of clinical interventions for GC patients. SIGNIFICANCE OF THE STUDY: The roles about CAFs in progression of GC are not well illustrated. Our present study reveals that CAFs can increase the proliferation and decrease the Dox sensitivity of GC cells via secretion of Nodal. The secreted Nodal further activated Samd2/3/Akt signals to trigger the GC progression. It suggests that targeted inhibition CAFs/Nodal might be a potential approach for GC therapy.

Analysis of risk factors and prevention strategies for functional delayed gastric emptying in 1243 patients with distal gastric cancer.

BACKGROUND: Analysis of the risk factors associated with functional delayed gastric emptying after distal gastric cancer surgery to provide a basis for further reduction of the incidence of this complication. METHODS: Total of 1382 patients with distal gastric cancer from January 2016 to October 2018 were enrolled. Correlation analysis was performed in 53 patients with FDGE by logistic regression. Subgroup risk analysis was performed in 114 patients with preoperative pyloric obstruction. A Pearson Chi-square analysis was used to compare categorical variables between normal distribution groups. Meanwhile, a t test was used to compare continuous variables between groups. Odds ratio (OR) was used for comparison of the two groups, and it was summarized with its 95% confidence interval (CI) and p value using logistic regression. RESULT: In multivariable analysis, age (OR 1.081, 95% CI, 1.047-1.117), BMI (OR 1.233, 95% CI, 1.116-1.363), preoperative pyloric obstruction (OR 3.831, 95% CI, 1.829-8.023), smaller volume of residual stomach (OR 1.838, 95% CI, 1.325-6.080), and anastomosis in greater curvature perpendicular (OR 3.385, 95% CI, 1.632-7.019) and in greater curvature parallel (OR 2.375, 95% CI, 0.963-5.861) were independent risk factors of FDGE. In the preoperative pyloric obstruction group, higher BMI (OR 1.309, 95% CI, 1.086-1.579) and preoperative obstruction time (OR 1.054, 95% CI, 1.003-1.108) were independent risk factors of FDGE and preoperative gastrointestinal decompression (OR 0.231, 95% CI, 0.068-0.785) was independent protective factor of FDGE. CONCLUSION: Adequate gastrointestinal decompression should be performed before the operation to reduce the incidence of postoperative gastroparesis in patients with preoperative pyloric obstruction. We also could improve the surgical methods to reduce the occurrence of FDGE, such as controlling the size of the residual stomach, ensuring blood supply. Especially selecting an appropriate stapler and anastomosis during the anastomosis process, the occurrence of FDGE can be reduced.

Development and validation of a nomogram for preoperative prediction of lymph node metastasis in early gastric cancer.

BACKGROUND: The status of lymph nodes in early gastric cancer is critical to make further clinical treatment decision, but the prediction of lymph node metastasis remains difficult before operation. This study aimed to develop a nomogram that contained preoperative factors to predict lymph node metastasis in early gastric cancer patients. METHODS: This study analyzed the clinicopathologic features of 823 early gastric cancer patients who underwent gastrectomy retrospectively, among which 596 patients were recruited in the training cohort and 227 patients in the independent validation cohort. Significant risk factors in univariate analysis were further identified to be independent variables in multivariable logistic regression analysis, which were then incorporated in and presented with a nomogram. And internal and external validation curves were plotted to evaluate the discrimination of the nomogram. RESULTS: Totally, six independent predictors, including the tumor size, macroscopic features, histology differentiation, P53, carbohydrate antigen 19-9, and computed tomography-reported lymph node status, were enrolled in the nomogram. Both the internal validation in the training cohort and the external validation in the validation cohort showed the nomogram had good discriminations, with a C-index of 0.82 (95%CI, 0.78 to 0.86) and 0.77 (95%CI, 0.60 to 0.94) respectively. CONCLUSIONS: Our study developed a new nomogram which contained the most common and significant preoperative risk factors for lymph node metastasis in patients with early gastric cancer. The nomogram can identify early gastric cancer patients with the high probability of lymph node metastasis and help clinicians make more appropriate decisions in clinical practice.

Potential Role of Caveolin-1 in Regulating the Function of Endothelial Progenitor Cells from Experimental MODS Model.

Multiple organ dysfunction syndrome (MODS) remains a great challenge in critical care because of its common occurrence, high cost of care, and high mortality. Vascular endothelial injury is the initiation step in the development of MODS, and EPCs are essential for the process of organ repair. It is unclear whether and how caveolin-1 (Cav-1) in EPCs contributes to the pathogenesis of MODS. The present study is aimed at investigating the potential role of Cav-1 in EPCs during MODS. We established a MODS model in pigs, isolated and characterized EPCs from the MODS model, and tracked Cav-1 expression and various in vitro behaviors of EPCs from the MODS model. Then, we knockdown Cav-1 expression with siRNA or induce Cav-1 expression with proinflammatory factors to evaluate potential effects on EPCs. Our results suggest that Cav-1 expression correlated with EPC functions during MODS and Cav-1 regulates the function of endothelial progenitor cells via PI3K/Akt/eNOS signaling during MODS. Thus, Cav-1 in EPCs could be an attractive target for the treatment of MODS.

Influence of ERCC1 and ERCC4 polymorphisms on response to prognosis in gastric cancer treated with FOLFOX-based chemotherapy.

Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1)-excision repair cross-complimentary group 4 (ERCC4) genes have been implicated in the prognosis of various cancers. We conducted a cohort study to investigate the role of ERCC1-ERCC4 gene polymorphisms on the response to chemotherapy and the role of these two gene polymorphisms on the clinical outcomes of gastric cancer. Four hundred forty-seven patients with newly diagnosed and histopathologically confirmed primary gastric cancer were collected in our study and were followed up until March 2012. ERCC1 (rs11615, rs3212986C>A, and rs2298881) and ERCC4 (rs226466C>G, rs2276465, and rs6498486) were selected and genotyped. The overall chemotherapy response rate for treatment was 68 %. Carriers of the rs11615 TT and T allele and ERCC1 rs2298881 CC and C allele had a marginally significantly higher response rate to the chemotherapy. In the Cox proportional hazard model, the hazard ratios (HRs) for overall survival (OS) in patients carrying ERCC1 rs11615 TT genotype and T allele were 0.53 (0.29-0.95) and 0.63 (0.42-0.94), respectively. Similarly, we found a significant decreased risk of death from gastric cancer among patients carrying ERCC1 rs2298881 CC genotype and C allele when compared with CC genotype, and HRs (95% confidence interval (CI)) of OS were 0.50 (0.24-0.98) and 0.62 (0.40-0.96), respectively. Moreover, individuals carrying ERCC1 rs11615 T allele and rs2298881 C allele could decrease a 0.62-fold risk of death from gastric cancer. This study reported a carriage of ERCC1 rs11615, and rs2298881 polymorphism can be used as a predictor of response to folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX)-based chemotherapy in gastric cancer patients.

The necroptosis-related signature and tumor microenvironment immune characteristics associated with clinical prognosis and drug sensitivity analysis in stomach adenocarcinoma.

PURPOSE: Necroptosis plays an important role in the tumorigenesis, development, metastasis, and drug resistance of malignant tumors. This study explored the new model for assessing stomach adenocarcinoma (STAD) prognosis and immunotherapy by combining long noncoding RNAs associated with necroptosis. METHODS: Patient clinical data and STAD gene expression profiles were curated from The Cancer Genome Atlas (TCGA). Immune-related genes were sourced from a specialized molecular database. Perl software and R software were used for data processing and analysis. Necroptosis-related lncRNAs in STAD were pinpointed via R's correlation algorithms. These lncRNAs, in conjunction with clinical data, informed the construction of a prognostic lncRNA-associated risk score model using univariate and multivariate Cox regression analyses. The model's prognostic capacity was evaluated by Kaplan-Meier survival curves and validated as an independent prognostic variable. Further, a nomogram incorporating this model with clinical parameters was developed, offering refined individual survival predictions. Subsequent analyses of immune infiltration and chemosensitivity within necroptosis-related lncRNA clusters utilized an arsenal of bioinformatic tools, culminating in RT-PCR validation of lncRNA expression. RESULTS: Through rigorous Cox regression, 21 lncRNAs were implicated in the risk score model. Stratification by median risk scores delineated patients into high- and low-risk cohorts, with the latter demonstrating superior prognostic outcomes. The risk model was corroborated as an independent prognostic indicator for STAD. The integrative nomogram displayed high concordance between predicted and observed survival rates, as evidenced by calibration curves. Differential immune infiltration in risk-defined groups was illuminated by the single sample GSEA (ssGSEA), indicating pronounced immune presence in higher-risk patients. Tumor microenvironment (TME) analysis showed that cluster-C3 had the highest score in the analysis of the three TMEs. Through the differential analysis of immune checkpoints, it was found that almost all immune checkpoint-related genes were expressed differently in various tumor clusters. Among them, CD44 expression was the highest. By comparing all drug sensitivities, we screened out 29 drugs with differences in drug sensitivity across different clusters. Risk score gene expression identification results showed that these lncRNAs were abnormally expressed in gastric cancer cell lines. CONCLUSIONS: This investigation provides a robust methodological advance in prognosticating and personalizing immunotherapy for STAD, leveraging quantitatively derived tumor cluster risk scores. It posits the use of necroptosis-related lncRNAs as pivotal molecular beacons for guiding therapeutic strategies and enhancing clinical outcomes in STAD.

Genetic polymorphisms of XRCC1 gene and susceptibility to gastric cancer in Chinese Han population.

This study aims to evaluate whether the c.1471G > A and c.1686C > G genetic polymorphisms of XRCC1 gene influencing gastric cancer susceptibility. A total of 813 subjects with Chinese Han ethnicity were enrolled. Our data suggest that the allele and genotype frequencies are significantly different from gastric cancer patients with cancer-free controls. We find that c.1471G > A and c.1686C > G genetic polymorphisms statistically increase the risk of gastric cancer. Our findings indicate these two genetic polymorphisms are related with the susceptibility to gastric cancer, and could be used as molecular markers for detecting gastric cancer in Chinese Han ethnicity.

Overexpression of p-4ebp1 in Chinese gastric cancer patients and its correlation with prognosis.

BACKGROUND/AIMS: We sought to reveal the status of phosphorylated 4E-binding protein 1 (p-4ebp1) expression in Chinese gastric cancer patients and its correlation with tumor prognosis. METHODOLOGY: Tissue microarray blocks containing gastric cancer tissue and matched noncancerous gastric tissue specimens from 286 patients were constructed. The expression of 4E-binding protein 1 (4ebp1) and p-4ebp1 of these specimens was analyzed using immunohistochemical studies. RESULTS: The expression rates of 4ebp1 and p-4ebp1 in gastric cancer were 68.5% (196 of 286) and 49.7% (142 of 286) respectively. The expression of 4ebp1 was correlated with node metastasis and poor differentiation, while the expression of p-4ebp1 was correlated with tumor size, node metastasis and TNM stage. p-4ebp1 overexpression has a significant inverse correlation with median survival time. CONCLUSIONS: p-4ebp1 expression is correlated with later TNM stage and is a prognostic factor of survival time after surgery.

Endothelial-Related Biomarkers in Evaluation of Vascular Function During Progression of Sepsis After Severe Trauma: New Potential Diagnostic Tools in Sepsis.

Purpose: This study aimed to investigate the changes in endothelial-related biomarkers and their relationship with the incidence and prognosis of patients with sepsis after severe trauma. Methods: A total of 37 severe trauma patients admitted to our hospital from Jan. to Dec. 2020 were enrolled in our research. All enrolled patients were divided into the sepsis and the non-sepsis groups. Endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), and endothelial microparticles (EMPs) were detected on admission time; 24-48 hours and 48-72 hours after admission respectively. Demographic data, Acute Physiology, Chronic Health Evaluation (APACHE) II, and Sequential Organ Failure Assessment (SOFA) score were calculated every 24 h of admission to assess the severity of organ dysfunction. Receiver operating characteristic (ROC) curves were drawn to compare the areas under the curve (AUC) of endothelial-related biomarkers for the diagnosis of sepsis. Results: The incidence rate of sepsis was 45.95% in all patients. The SOFA score in the sepsis group was significantly higher than that in the non-sepsis group (2 points vs 0 points, P<0.01). The number of EPCs, CECs, and EMPs all rose quickly in the early phase after trauma. The number of EPCs was similar in both groups, but the number of CECs and EMPs in the Sepsis Group was much higher than in the non-Sepsis Group (all P<0.01). Logistic regression analysis showed that the occurrence of sepsis was closely related to the expression of 0-24h CECs and 0-24h EMPs. The AUC ROC for CECs in different time periods were 0.815, 0.877, and 0.882, respectively (all P<0.001). The AUC ROC for EMPs in 0-24h was 0.868 (P=0.005). Conclusion: The expression of EMPs was higher in early severe trauma, and high levels of EMPs were significantly higher in patients with early sepsis and poor prognosis.

Fructose-1,6-bisphosphatase 1 dephosphorylates IκBα and suppresses colorectal tumorigenesis.

Emerging evidence demonstrates that some metabolic enzymes that phosphorylate soluble metabolites can also phosphorylate a variety of protein substrates as protein kinases to regulate cell cycle, apoptosis and many other fundamental cellular processes. However, whether a metabolic enzyme dephosphorylates protein as a protein phosphatase remains unknown. Here we reveal the gluconeogenic enzyme fructose 1,6-biphosphatase 1 (FBP1) that catalyzes the hydrolysis of fructose 1,6-bisphosphate (F-1,6-BP) to fructose 6-phosphate (F-6-P) as a protein phosphatase by performing a high-throughput screening of metabolic phosphatases with molecular docking followed by molecular dynamics (MD) simulations. Moreover, we identify IκBα as the substrate of FBP1-mediated dephosphorylation by performing phosphoproteomic analysis. Mechanistically, FBP1 directly interacts with and dephosphorylates the serine (S) 32/36 of IκBα upon TNFα stimulation, thereby inhibiting NF-κB activation. MD simulations indicate that the catalytic mechanism of FBP1-mediated IκBα dephosphorylation is similar to F-1,6-BP dephosphorylation, except for higher energetic barriers for IκBα dephosphorylation. Functionally, FBP1-dependent NF-κB inactivation suppresses colorectal tumorigenesis by sensitizing tumor cells to inflammatory stresses and preventing the mobilization of myeloid-derived suppressor cells. Our finding reveals a previously unrecognized role of FBP1 as a protein phosphatase and establishes the critical role of FBP1-mediated IκBα dephosphorylation in colorectal tumorigenesis.

[Changes in endothelial progenitor cells and their implications in multiple organ dysfunction syndrome caused by trauma in pigs].

OBJECTIVE: To investigate characteristics of changes in bone marrow endothelial progenitor cells (EPCs) and implications on multiple organ dysfunction syndrome (MODS) as a result of trauma. METHODS: Eighteen mini-pigs were randomized into two groups: MODS group (n=9) and control group (n=9). The animal models of MODS were reproduced by "two-hit" injury with hemorrhagic shock and lipopolysaccharide (LPS) injection. Bone marrow and peripheral blood of them were collected at five time points: normal condition (T1), before injection of LPS (T2), and 0 (T3), 24 (T4) and 48 hours (T5) after injection of LPS. Erythrocytic lysate was added to the samples, and the number of leucocytes in every sample was counted. The rate of EPCs in each sample was determined by flow cytometry. Number of EPCs in bone marrow and peripheral blood were calculated, and the results were analyzed statistically. RESULTS: The number of EPCs (x10(6)/L) in bone marrow of control group at T1-5 was 7.64+/-0.68, 7.32+/-0.55, 7.58+/-1.13, 7.77+/-0.70, and 7.88+/-0.84, respectively, and in peripheral blood control group was 3.54+/-0.26, 4.06+/-0.64, 3.74+/-0.55, 3.61+/-0.37, and 3.98+/-0.63, respectively. The number of EPCs (x10(6)/L) in bone marrow in the experimental group was 7.45+/-1.55, 6.58+/-0.80, 11.27+/-1.20, 10.88+/-1.15, and 8.36+/-2.88, respectively. The number of EPCs (x10(6)/L) in peripheral blood in the experimental group was 3.21+/-0.48, 8.71+/-2.04, 5.98+/-0.77, 1.27+/-0.91, and 2.14+/-0.96, respectively. The number of EPCs in bone marrow of experimental group was larger than that of control group at T3, T4, T5. The number of EPCs in the experimental group in peripheral blood was larger than that of control group at T2, T3, T4, T5. The number of EPCs in bone marrow was larger than that in peripheral blood at every time point (all P<0.05). CONCLUSION: The number of EPCs in peripheral blood elevates sharply in the earlier period, then plummeted quickly during MODS after a trauma. While the number of EPCs in bone marrow descends mildly at first, then rises obviously. Along with the aggravation of MODS, a declination of EPCs in bone marrow emerges. The change in bone marrow EPCs plays an important role in recovery of MODS.

Identification of Potential Core Genes Associated With the Progression of Stomach Adenocarcinoma Using Bioinformatic Analysis.

PURPOSE: Stomach adenocarcinoma (STAD) is one of the most frequently diagnosed cancer in the world with both high mortality and high metastatic capacity. Therefore, the present study aimed to investigate novel therapeutic targets and prognostic biomarkers that can be used for STAD treatment. MATERIALS AND METHODS: We acquired four original gene chip profiles, namely GSE13911, GSE19826, GSE54129, and GSE65801 from the Gene Expression Omnibus (GEO). The datasets included a total of 114 STAD tissues and 110 adjacent normal tissues. The GEO2R online tool and Venn diagram software were used to discriminate differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) enriched pathways were also performed for annotation and visualization with DEGs. The STRING online database was used to identify the functional interactions of DEGs. Subsequently, we selected the most significant DEGs to construct the protein-protein interaction (PPI) network and to reveal the core genes involved. Finally, the Kaplan-Meier Plotter online database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to analyze the prognostic information of the core DEGs. RESULTS: A total of 114 DEGs (35 upregulated and 79 downregulated) were identified, which were abnormally expressed in the GEO datasets. GO analysis demonstrated that the majority of the upregulated DEGs were significantly enriched in collagen trimer, cell adhesion, and identical protein binding. The downregulated DEGs were involved in extracellular space, digestion, and inward rectifier potassium channel activity. Signaling pathway analysis indicated that upregulated DEGs were mainly enriched in receptor interaction, whereas downregulated DEGs were involved in gastric acid secretion. A total of 80 DEGs were screened into the PPI network complex, and one of the most important modules with a high degree was detected. Furthermore, 10 core genes were identified, namely COL1A1, COL1A2, FN1, COL5A2, BGN, COL6A3, COL12A1, THBS2, CDH11, and SERPINH1. Finally, the results of the prognostic information further demonstrated that all 10 core genes exhibited significantly higher expression in STAD tissues compared with that noted in normal tissues. CONCLUSION: The multiple molecular mechanisms of these novel core genes in STAD are worthy of further investigation and may reveal novel therapeutic targets and biomarkers for STAD treatment.

Delivery of TSPAN1 siRNA by Novel Th17 Targeted Cationic Liposomes for Gastric Cancer Intervention.

Several studies focus on the relationship between immune cells in the tumor microenvironment and tumor cells. Th17 cells, a naïve CD4+ T cell subtype, secrete IL-17 cytokines that further the progression and metastasis of tumors, such as gastric cancer, which is a leading cause of cancer-related death worldwide. Moreover, previous studies have demonstrated that the polarization ratio of CD4+ T cells to Th17 cells is closely related to the Tetraspanin 1 (TSPAN1) protein. Therefore, in this study, we designed a novel Th17 antibody-modified liposome polycation-DNA complex (LPD) encapsulated with TSPAN1 small interfering RNA (siRNA) (Th17-LPDT), to decrease the polarization of CD4+ T cells, and thereby inhibit the development of gastric cancer. Our in vitro results demonstrated the decrease in CD4+ T cells polarization to Th17 cells follwing Th17-LPDT treatment. Furthermore, in vivo data proved that Th17-LPDT treatment significantly inhibits the formation of gastric tumors. We believe that Th17-LPDT is a promising targeted nanoparticle drug for the clinical treatment of gastric cancer and this study provides a new strategy for tumor intervention.

[Influences of the phosphorylation of p38 mitogen activated protein kinase on gene expression of tumor necrosis factor-alpha in multiple organ dysfunction syndrome in pigs].

OBJECTIVE: To investigate that the phosphorylation of the p38 mitogen activated protein kinase (p38MAPK) influences gene expression of tumor necrosis factor-alpha (TNF-alpha) in multiple organ dysfunction syndrome (MODS) in pigs. METHODS: Thirty pigs were divided into MODS group and control group, and an animal model of MODS of "two-hit" injury, including hemorrhagic shock and endotoxemia, was reproduced. The content of p38MAPK's phosphorylation was assessed with Western blotting. TNF-alpha mRNA in peripheral blood monocytes was assayed with real time-polymerase chain reaction (RT-PCR). TNF-alpha was monitored in the peripheral blood plasma with enzyme linked immunosorbent assay (ELISA). RESULTS: Phosphorylation of p38MAPK was obviously increased in extent, which enhanced gene expression of TNF-alpha and then secretion of TNF-alpha by the peripheral blood mononuclear cell in MODS, and the differences were statistically significant compared with that of control group (P<0.05 or P<0.01). CONCLUSION: p38MAPK's phosphorylation is important in pathogenesis of MODS, and phosphorylation of p38MAPK can enhance TNF-alpha mRNA transcription and secretion of TNF-alpha from peripheral blood mononuclear cells, which is the mechanism of increased TNF-alpha in MODS.

Polyacetylene carbon materials: facile preparation using AlCl3 catalyst and excellent electrochemical performance for supercapacitors.

Polyacetylene (PA) was synthesized for the first time under mild conditions via polymerization of acetylene in n-octane with AlCl3 as a catalyst, whereby a series of PA-derived carbon materials were obtained. Their composition and structure were characterized and their electrochemical performance was evaluated systematically. It is found that acetylene gas at 1 MPa can polymerize explosively at room temperature under catalysis of AlCl3, forming acetylene black-like PA and a great amount of H2, while in the presence of n-octane solvent, acetylene polymerizes smoothly at higher temperature (30 to 300 °C), forming PA with a H(CH[double bond, length as m-dash]CH) n H structure. A series of PA-derived carbon materials are obtained by treating PA with KOH at 800 °C. The as-synthesizzed PA-100-KOH exhibits a high specific surface area (∼2500 m2 g-1), high specific capacitance (241 F g-1 at a current density of 0.1 A g-1 and 143 F g-1 at 5 A g-1), low AC resistance, and good cycling stability with 91.7% maintenance of capacity after 2000 cycles at a current density of 2 A g-1. This paper provides a new method for the facile synthesis of PA and a novel carbon source for supercapacitor electrode materials with excellent electrochemical performance and practical application.

MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis.

Gastric adenocarcinoma, which originates from the gastric mucosal epithelium, has the highest incidence among various malignant tumours in China. As a crucial long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been suggested to play an important role in many tumours. Here, we aimed to investigate the role and underlying mechanism of MALAT1 in gastric adenocarcinoma. Quantitative reverse transcription polymerase chain reaction was applied to determine the expression levels of MALAT1 in serum and cell lines. A CCK-8 assay and a clonogenic survival assay were used to examine cell proliferation and apoptosis. The protein level of RAC-γ serine/threonine-specific protein kinase (AKT3) was determined by western blot. Our results showed that MALAT1 was highly expressed in the serum of patients with gastric adenocarcinoma and in cell lines. Downregulating MALAT1 inhibited proliferation and promoted apoptosis of MGC-803 cells. In addition, MALAT1 directly targeted and decreased the expression of miR-181a-5p, which in turn upregulated the expression of AKT3. Further, overexpressing miR-181a-5p or directly inhibiting the AKT pathway with the inhibitor ipatasertib exhibited similar effects to MALAT1 knockdown. Our research proposes a novel mechanism where the role of MALAT1 is dependent on the MALAT1/miR-181a-5p/AKT3 axis. MALAT1 competes with AKT3 for miR-181a-5p binding, thereby upregulating the AKT3 protein level and ultimately promoting the growth of gastric adenocarcinoma.

Clinical management of abdominal trauma.

OBJECTIVE: To improve the prognosis of patients with abdominal trauma. METHODS: Between January 1993 and December 2005, 415 patients were enrolled in this research. The patients consisted of 347 males and 68 females with mean age of 36 years (ranging from 3-82 years). All abdominal traumas consisted of closed traumas (360 cases, 86.7%) and open traumas (55 cases, 13.3%). RESULTS: A total of 407 cases (98.1%) were fully recovered from trauma and the other 8 cases (1.9%) died of multiple injuries. The mean injury severity score (ISS) of all patients was 22 while the mean ISS of the patients who died in hospital was 42. Postoperative complications were seen in 9 patients such as infection of incisional wounds (6 cases), pancreatic fistula (2 cases) and intestinal fistula (1 case). All these postoperative complications were cured by the conservative treatment. CONCLUSION: Careful case history inquisition and physical examination are the basic methods to diagnose abdominal trauma. Focused abdominal ultrasonography is always the initial imaging examination because it is non-invasive and can be performed repeatedly with high accuracy. The doctors should consider the severity of local injuries and the general status of patients during the assessment of abdominal trauma. The principle of treatment is to save lives at first, then to cure the injuries. Unnecessary laparotomy should be avoided to reduce additional surgical trauma.