Xiaoling Gu

The plasma mitochondrial DNA is an independent predictor for post-traumatic systemic inflammatory response syndrome.

Background and Purpose Mitochondrial DNA (mtDNA), a newly identified damage-associated molecular pattern, has been observed in trauma patients, however, little is known concerning the relationship between plasma mtDNA levels and concrete post-traumatic complications, particularly systemic inflammatory response syndrome (SIRS). The aim of this study is to determine whether plasma mtDNA levels are associated with injury severity and cloud predict post-traumatic SIRS in patients with acute traumatic injury. Patients and Methods Eighty-six consecutive patients with acute traumatic injury were prospectively enrolled in this study. The plasma mtDNA concentration was measured by a real-time, quantitative PCR assay for the human ND2 gene. The study population’s clinical and laboratory data were analyzed. Results The median plasma mtDNA was higher in trauma patients than in healthy controls (865.196 (251.042-2565.40)pg/ml vs 64.2147 (43.9049-80.6371)pg/ml, P<0.001) and was independently correlated with the ISS score (r=0.287, P<0.001). The plasma mtDNA concentration was also significantly higher in patients who developed post-traumatic SIRS than in patients who did not (1774.03 (564.870-10901.3)pg/ml vs 500.496 (145.415-1285.60)pg/ml, P<0.001). Multiple logistic regression analysis revealed that the plasma mtDNA was an independent predictors for post-traumatic SIRS (OR, 1.183 (95%CI, 1.015-1.379), P=0.032). Further ROC analysis demonstrated that a high plasma mtDNA level predicted post-traumatic SIRS with a sensitivity of 67% and a specificity of 76%, with a cut-off value of 1.3185 µg/ml being established, and the area under the ROC curves (AUC) was 0.725 (95% CI 0.613-0.837). Conclusions Plasma mtDNA was an independent indictor with moderate discriminative power to predict the risk of post-traumatic SIRS.

Intratracheal administration of mitochondrial DNA directly provokes lung inflammation through the TLR9-p38 MAPK pathway

An increasing number of studies have focused on the phenomenon that mitochondrial DNA (mtDNA) activates innate immunity responses. However, the specific role of mtDNA in inflammatory lung disease remains elusive. This study was designed to examine the proinflammatory effects of mtDNA in lungs and to investigate the putative mechanisms. C57BL/6 mice were challenged intratracheally with mtDNA with or without pretreatment with chloroquine. Changes in pulmonary histopathology, cytokine concentrations, and phosphorylation levels of p38 MAPK were assayed at four time points. In in vitro experiments, THP-1 macrophages were pretreated or not pretreated with chloroquine, TLR9 siRNA, p38 MAPK siRNA, or SB203580 and then incubated with mtDNA. The levels of cytokines and p-p38 MAPK were detected by ELISA and Western blot, respectively. The intratracheal administration of mtDNA induced infiltration of inflammatory cells, production of proinflammatory cytokines (including IL-1β, IL-6, and TNF-α), and activation of p38 MAPK. The chloroquine pretreatment resulted in an abatement of mtDNA-induced local lung inflammation. In vitro experiments showed that the exposure of THP-1 macrophages to mtDNA also led to a significant upregulation of IL-1β, IL-6, and TNF-α and the activation of p38 MAPK. And these responses were inhibited either by chloroquine and TLR9 siRNA or by SB203580 and p38 MAPK siRNA pretreatment. The intratracheal administration of mtDNA induced a local inflammatory response in the mouse lung that depended on the interactions of mtDNA with TLR9 and may be correlated with infiltrating macrophages that could be activated by mtDNA exposure via the TLR9-p38 MAPK signal transduction pathway.

A Serum Vitamin D Level <25nmol/L Pose High Tuberculosis Risk: A Meta-Analysis

Background Low serum Vitamin D is considered to be associated with tuberculosis while the “dangerous” level was not clear. The aim of this study was to identify the association between tuberculosis and serum Vitamin D levels via synthesis of available evidence. Methods A search of EMBASE, Medline, ISI Web of knowledge, and Pubmed was conducted. The number of subjects of tuberculosis and no-tuberculosis groups in four Vitamin D range. Meta-analyses were performed and presented by odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results A total of 15 studies involving 1440 cases and 2558 controls were included. A significantly increased risk of tuberculosis was found in two ranges: ≤ 12.5 nmol/L: pooled OR = 4.556, 95% CI = 2.200-9.435; 13-25 nmol/L: pooled OR = 3.797, 95% CI = 1.935-7.405. No statistically significant risk of tuberculosis was found in the range of 26–50 nmol/L (pooled OR = 1.561, 95% CI =0.997-2.442). In range 51–75 nmol/L, no positive association was found (pooled OR =1.160, 95% CI = 0.708-1.900). Conclusions This study found that a serum Vitamin D level ≤ 25 nmol/L was significantly associated with an increased risk of tuberculosis while the range of 51–75 nmol/L was not. The range 26-50nmol/L posed potential high tuberculosis risk. Future large-scale, well-designed studies are needed to verify these results.

Combination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced non-small cell lung cancer patients.

The neutrophil to lymphocyte ratio (NLR) was recently shown to be a remarkable prognostic factor in tumors. Moreover, some studies have indicated that the combination of NLR and platelet to lymphocyte ratio (PLR) could be a better prognostic factor. As the combined prognostic value of NLR and PLR in non‐small cell lung cancer (NSCLC) is not clear, we conducted this study to explore this further.

Hormone Replacement Therapy in Females Can Decrease the Risk of Lung Cancer: A Meta-Analysis

The purpose of the present meta-analysis was to determine the relationship between hormone replacement therapy (HRT) and lung cancer risk in females. Publications were reviewed and obtained through a PubMed, EMBASE database and Cochrane Library literature search up to May, 2012. The detailed numbers of patients in different groups, odd ratios (ORs) and corresponding 95% confidence intervals (CIs) were collected and estimated using a random-effects model. Twenty five studies entered into the meta-analysis. The total number of participates and lung cancer patients was 656,403 and 11,442, respectively. The OR of all 25 studies was 0.91 (95%CI  = 0.83 to 0.99) and P value was 0.033. In stratified analyses, the positive association between HRT use and decreased lung cancer risk was also found in the patients with BMI<25 kg/m2 (OR = 0.65, P = 0.000), and never smokers patients (OR = 0.86, P = 0.042). However, HRT use in patients with artificial menopause could increase the lung cancer risk, OR = 1.51(P = 0.001). The result of Eggers test did not show any evidence of publican bias (P = 0.069). In conclusion, our meta-analysis on HRT and lung cancer risk suggests that HRT use is correlated with decreased lung cancer risk in female, especially in female with BMI<25 kg/m2 and never smokers.

Upregulation of long intergenic noncoding RNA 00673 promotes tumor proliferation via LSD1 interaction and repression of NCALD in non-small-cell lung cancer

Despite improvements in diagnostics and treatment of non-small cell lung cancer (NSCLC), it remains the leading causes of cancer-related mortality worldwide. In more recent years, mutiple lines of evidence have highlighted long noncoding RNAs (lncRNAs) serve as novel class of regulators of cancer biological processes, including proliferation, apoptosis and metastasis. LncRNAs serve as a novel class of regulators of cancer biological processes in cancer, but little is known of their expression and potential functions in NSCLC. We identified an oncogene, linc00673, whose expression level was upregulated by bioinformatics analyses and qRT-PCR analyses in NSCLC. The effects of linc00673 on tumor progression were investigated in vitro and in vivo. Linc00673 knockdown significantly inhibited cell proliferation and colony-forming ability, and suppressed S-phase entry in vitro and shRNA linc00673 mediated knockdown significantly inhibit tumor growth in vivo, meanwhile, linc00673 overexpression increased tumor cell growth. Analysis of RNAseq data revealed linc00673 could modulate the transcription of a large amount of genes including oncogene and tumor suppressor gene, so we investigated the role and regulatory mechanism of linc00673 in NSCLC proliferation. Further mechanistic analyses indicated that the oncogenic activity of linc00673 is partially attributable to its repression of NCALD through association with the epigenetic repressor LSD1. Taken together, these findings suggested that linc00673 could play crucial role in NSCLC progression and might be a potential therapeutic target for patients with NSCLC.

The effect of P2X7 receptor 1513 polymorphism on susceptibility to tuberculosis: A meta-analysis

Studies of the association between the purinergic receptor P2X, ligand-gated ion channel 7 (P2X7 receptor) gene 1513A/C polymorphism and susceptibility to tuberculosis have yielded inconsistent results. We performed this meta-analysis to help clarify these inconsistencies. After systematically searching PUBMED, MEDLINE, EMBASE and ISI Web of knowledge, two of the authors independently extracted relevant data and a meta-analysis was performed by using STATA11.0 software. A total number of nine studies involving 2195 cases and 2036 controls were identified. The results indicated that P2X7 receptor gene 1513C allele (OR 1.389, 95% CI 1.161-1.660, p<0.001) and CC genotype (1.582, 95% CI 1.129-2.217, p=0. 012) were significantly associated with increased susceptibility to tuberculosis. Subgroup analysis indicated that this SNP greatly contributed to susceptibility to tuberculosis in Asians. The C allele of P2X7 receptor gene 1513A/C polymorphism was also associated with increased susceptibility to pulmonary tuberculosis in Asians (C vs. A: OR 1.420, 95% CI 1.163-1.733, p=0.001; (CC+AC) vs. AA: OR 1.522, 95% CI 1.186-1.953, p=0.001). Greater association between P2X7 receptor gene 1513A/C polymorphism and susceptibility to extra-pulmonary tuberculosis with bigger ORs were found (C vs. A, OR 2.035, 95% CI 1.236-3.352, p=0.005; CC vs. AA, OR 3.788, 95% CI 1.434-10.009, p=0.007; AC vs. AA, OR 2.148, 95% CI 1.252-3.684, p=0.005; (CC+AC) vs. AA, OR 2.386, 95% CI 1.302-4.374, p=0.005; CC vs. (AC+AA), OR 2.692, 95% CI 1.242-5.836, p=0. 012). This meta-analysis indicates that the C allele of P2X7 receptor gene 1513A/C polymorphism is a risk factor for pulmonary tuberculosis in Asians, while not in Africans or Latinos and a risk for extra-pulmonary tuberculosis. Further well-designed, large scale studies are required to confirm this conclusion.

Elevated pretreatment serum globulin albumin ratio predicts poor prognosis for advanced non-small cell lung cancer patients

BACKGROUND The aim of the present study was to explore the association between the pretreatment globulin albumin ratio (GAR) and the survival of advanced non-small cell lung cancer (NSCLC) patients. METHODS Patients hospitalized between January 2007 and December 2010 were enrolled and eliminated according to the inclusion and exclusion criteria. GAR was defined as the absolute globulin value divided by the absolute albumin value. Chi-squared test was performed to compare clinical characteristics in different groups. Kaplan-Meier and Cox regression model were used to determine independent prognostic factors. A P value of ≤0.05 was considered to be statistically significant. RESULTS Total 316 patients were finally enrolled. The median progression free survival (PFS) and overall survival (OS) were 210.0 and 430.0 days, respectively. The statistical analyses indicated that pretreatment GAR >0.58 [hazard ratio (HR) =1.52, 95% confidence interval (95% CI): 1.12-2.08, P=0.008 for PFS, HR =1.65, 95% CI: 1.20-2.26, P=0.002 for OS], and pretreatment albumin ≤35 g/L (HR =2.09, 95% CI: 1.20-3.65, P=0.003 for PFS, HR =1.92, 95% CI: 1.10-3.36, P=0.022 for OS) were independent prognostic factors for both PFS and OS. CONCLUSIONS Our study first established a connection between pretreatment GAR and advanced NSCLC patients, suggesting that GAR was an independent prognostic factor and could be the biomarker for prognosis.

The role of serum carcinoembryonic antigen in predicting responses to chemotherapy and survival in patients with non-small cell lung cancer.

BACKGROUND Previous studies indicated that carcinoembryonic antigen (CEA) could predict the therapeutic objective response (OR) and overall survival (OS) of patients with cancers, including non-small cell lung cancer (NSCLC). However, the role it could play in evaluating therapeutic responses and OS in patients with NSCLC requires further elucidation. Herein, we investigated the potential role of CEA in predicting OR and OS in patients with NSCLC. MATERIALS AND METHODS For this retrospective study, the medical records of 689 patients with NSCLC who were treated at Nanjing Jinling Hospital between January 2000 and August 2011 were reviewed. Serum levels of CEA of these patients were measured before and after chemotherapy. The relatedness between CEA levels and OR, and between CEA and OS were investigated for correlations via a series of statistical analyses. RESULTS The baseline serum CEA level of 689 patients was 54.18 ± 143.45 ng/mL. Serum CEA significantly decreased after two cycles of chemotherapy (t = 2.196, P = 0.031). The receiver operator characteristic (ROC) curve analysis showed that a 5.28% reduction in CEA level was an appropriate cut-off value for predicting the OR to chemotherapy, with a sensitivity of 61.3% and a specificity of 62.4%. The Kaplan-Meier survival analysis indicated no significant correlation between baseline CEA and OS (P = 0.079). CONCLUSION Our study shows that while the baseline level of CEA was not a prognostic factor, the post-treatment reduction of CEA can predict the OR in patients with NSCLC.

Activated Protein C Induces Endoplasmic Reticulum Stress and Attenuates Lipopolysaccharide-Induced Apoptosis Mediated by Glycogen Synthase Kinase-3β

This study investigated the relationship between antiapoptotic activities induced by activated protein C and endoplasmic reticulum stress. In this study, it was observed that activated protein C elicited a rise in glucose-regulated protein 78 and glycogen synthase kinase-3β and inhibited apoptosis in human umbilical vein endothelial cells induced by lipopolysaccharide. Calcium inhibition did not alter the antiapoptotic effect of activated protein C. The antiapoptotic efficiency of activated protein C was reduced in human umbilical vein endothelial cells following treatment with glycogen synthase kinase-3β-siRNA. In summary, activated protein C induced endoplasmic reticulum stress and attenuated lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis mediated by glycogen synthase kinase-3β.