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1.
Introduction
The mechanisms of ventilator-induced lung injury (VILI), including the role of MAP kinases, are frequently studied in different mouse strains. A useful model for such studies is the isolated perfused mouse lung. As a further development we present the one-lung method that permits to continue perfusion and ventilation of the right lung after removal of the left lung. This method was used to compare the effect of high pressure ventilation (HPV) on pro-inflammatory signaling events in two widely used mouse strains (C57BL/6, BALB/c) and to further define the role of p38 in VILI.Methods
Lungs were perfused and ventilated for 30 min under control conditions before they were randomized to low (8 cm H2O) or high (25 cm H2O) pressure ventilation (HPV) for 210 min, with the left lung being removed after 180 min. In the left lung we measured the phosphorylation of p38, JNK, ERK and Akt kinase, and in the right lung gene expression and protein concentrations of Il1b, Il6, Tnf, Cxcl1, Cxcl2, and Areg.Results
Lung mechanics and kinase activation were similar in both mouse strains. HPV increased all genes (except Tnf in BALB/c) and all mediators in both strains. The gene expression of mRNA for Il1b, Il6, Cxcl1 and Cxcl2 was higher in BALB/c mice. Backward regression of the kinase data at t = 180 min with the gene and protein expression data at t = 240 min suggested that p38 controls HPV-induced gene expression, but not protein production. This hypothesis was confirmed in experiments with the p38-kinase inhibitor SB203580.Conclusions
The one-lung method is useful for mechanistic studies in the lungs. While C57BL/6 show diminished pro-inflammatory responses during HPV, lung mechanics and mechanotransduction processes appear to be similar in both mouse strains. Finally, the one-lung method allowed us to link p38 to gene expression during VILI. 相似文献2.
Yi-An Ko Ming-Chieh Yang Hung-Tu Huang Ching-Mei Hsu Lee-Wei Chen 《Respiratory research》2013,14(1):69
Background
Although use of the mechanical ventilator is a life-saving intervention, excessive tidal volumes will activate NF-κB in the lung with subsequent induction of lung edema formation, neutrophil infiltration and proinflammatory cytokine/chemokine release. The roles of NF-κB and IL-6 in ventilator-induced lung injury (VILI) remain widely debated.Methods
To study the molecular mechanisms of the pathogenesis of VILI, mice with a deletion of IкB kinase in the myeloid cells (IKKβ△mye), IL-6-/- to WT chimeric mice, and C57BL/6 mice (WT) were placed on a ventilator for 6 hr.WT mice were also given an IL-6-blocking antibody to examine the role of IL-6 in VILI.Results
Our results revealed that high tidal volume ventilation induced pulmonary capillary permeability, neutrophil sequestration, macrophage drifting as well as increased protein in bronchoalveolar lavage fluid (BALF). IL-6 production and IL-1β, CXCR2, and MIP2 expression were also increased in WT lungs but not in those pretreated with IL-6-blocking antibodies. Further, ventilator-induced protein concentrations and total cells in BALF, as well as lung permeability, were all significantly decreased in IKKβ△mye mice as well as in IL6-/- to WT chimeric mice.Conclusion
Given that IKKβ△mye mice demonstrated a significant decrease in ventilator-induced IL-6 production, we conclude that NF-κB–IL-6 signaling pathways induce inflammation, contributing to VILI, and IкB kinase in the myeloid cells mediates ventilator-induced IL-6 production, inflammation, and lung injury. 相似文献3.
Esra' Shishtar John L. Sievenpiper Vladimir Djedovic Adrian I. Cozma Vanessa Ha Viranda H. Jayalath David J. A. Jenkins Sonia Blanco Meija Russell J. de Souza Elena Jovanovski Vladimir Vuksan 《PloS one》2014,9(9)
Importance
Despite the widespread use of ginseng in the management of diabetes, supporting evidence of its anti-hyperglycemic efficacy is limited, necessitating the need for evidence-based recommendations for the potential inclusion of ginseng in diabetes management.Objective
To elucidate the effect of ginseng on glycemic control in a systematic review and meta-analysis of randomized controlled trials in people with and without diabetes.Data sources
MEDLINE, EMBASE, CINAHL and the Cochrane Library (through July 3, 2013).Study selection
Randomized controlled trials ≥30 days assessing the glycemic effects of ginseng in people with and without diabetes.Data extraction
Relevant data were extracted by 2 independent reviewers. Discrepancies were resolved by consensus. The Heyland Methodological Quality Score and the Cochrane risk of bias tool were used to assess study quality and risk of bias respectively.Data synthesis
Sixteen trials were included, in which 16 fasting blood glucose (n = 770), 10 fasting plasma insulin (n = 349), 9 glycated hemoglobin (n = 264), and 7 homeostasis model assessment of insulin resistance (n = 305) comparisons were reported. Ginseng significantly reduced fasting blood glucose compared to control (MD = −0.31 mmol/L [95% CI: −0.59 to −0.03], P = 0.03). Although there was no significant effect on fasting plasma insulin, glycated hemoglobin, or homeostasis model assessment of insulin resistance, a priori subgroup analyses did show significant reductions in glycated hemoglobin in parallel compared to crossover trials (MD = 0.22% [95%CI: 0.06 to 0.37], P = 0.01).Limitations
Most trials were of short duration (67% trials<12wks), and included participants with a relatively good glycemic control (median HbA1c non-diabetes = 5.4% [2 trials]; median HbA1c diabetes = 7.1% [7 trials]).Conclusions
Ginseng modestly yet significantly improved fasting blood glucose in people with and without diabetes. In order to address the uncertainty in our effect estimates and provide better assessments of ginseng''s anti-diabetic efficacy, larger and longer randomized controlled trials using standardized ginseng preparations are warranted.Trial Registration
ClinicalTrials.gov NCT01841229 相似文献4.
Marcus H. Jones Andréa L. Corso Robert S. Tepper Maria I. A. Edelweiss Luciana Friedrich Paulo M. C. Pitrez Renato T. Stein 《PloS one》2013,8(12)
Objective
To explore the relationship between prematurity, gender and chorioamnionitis as determinants of early life lung function in premature infants.Methods
Placenta and membranes were collected from preterm deliveries (<37 weeks gestational age) and evaluated for histological chorioamnionitis (HCA). Patients were followed and lung function was performed in the first year of life by Raised Volume-Rapid Thoracic Compression Technique.Results
Ninety-five infants (43 males) born prematurely (median gestational age 34.2 weeks) were recruited. HCA was detected in 66 (69%) of the placentas, and of these 55(58%) were scored HCA Grade 1, and 11(12%) HCA Grade 2. Infants exposed to HCA Grade 1 and Grade 2, when compared to those not exposed, presented significantly lower gestational ages, higher prevalence of RDS, clinical early-onset sepsis, and the use of supplemental oxygen more than 28 days. Infants exposed to HCA also had significantly lower maximal flows. There was a significant negative trend for z-scores of lung function in relation to levels of HCA; infants had lower maximal expiratory flows with increasing level of HCA. (p = 0.012 for FEF50, p = 0.014 for FEF25–75 and p = 0.32 for FEV0.5). Two-way ANOVA adjusted for length and gestational age indicated a significant interaction between sex and HCA in determining expiratory flows (p<0.01 for FEF50, FEF25–75 and p<0.05 for FEV0.5). Post-hoc comparisons revealed that female preterm infants exposed to HCA Grade 1 and Grade 2 had significant lower lung function than those not exposed, and this effect was not observed among males.Conclusions
Our findings show a sex-specific negative effect of prenatal inflammation on lung function of female preterm infants. This study confirms and expands knowledge upon the known association between chorioamnionitis and early life chronic lung disease. 相似文献5.
6.
Objective
In Malaysia, futsal is a popular sport played by individuals across all ages and genders. Despite its popularity, information on futsal related injury in Malaysia is not available. The purpose of this study is to examine the injury incidence and injury patterns among amateur men and women futsal players in Malaysia.Methods
Players reported injury to the tournament medical team during the FELDA/FAM National Futsal League 2010 were interviewed and assessed by a Sports Medicine registrar. Player''s socio-demographic profiles and information about the injury were documented in the injury report form adapted from medical report form used by FIFA: Medical Assessment and Research Centre (F-Marc).Results
A total of 86 injuries were reported from 141 matches, equivalent to an incidence of 91.5 injuries per 1000 player hours (95% CI 72.2 to 110.8), or 61.0 injuries per 1000 player matches (95% CI 48.1 to 73.9). Most were minor injuries resulted from contact with another player. Injuries often involved the lower extremity (44%) followed by the trunk (14%) and the upper limb (13%). Ankle (n = 7; 39%) and knee (n = 6; 33%) sprains were the most prevalent diagnoses of time-loss injuries. A significant association between time-loss and type of injury was found χ 2 (1,N = 86) = 3.99, p = 0.04. In addition, time-loss injury was significantly associated with playing surface χ 2 (1,N = 86) = 10.11, p = 0.018.Conclusion
The injury rate during the FELDA/FAM National Amateur Futsal Men''s League in Malaysia was lower compared with previous Futsal World Cups competition. Most injuries resulted from contact with another player were minor and did not lead to time-loss from participation. Time-loss injury was significantly associated with type of injury and playing surface. 相似文献7.
Objective
To investigate the association of SOX2 expression in tumor with clinicopathological features and survival of non-small-cell lung carcinoma (NSCLC) patients.Methods
Publications assessing the clinicopathological characteristics and prognostic significance of SOX2 in NSCLC were identified up to May 2013. A meta-analysis of eligible studies was performed using standard statistical methods to clarify the association between SOX2 expression and these clinical parameters.Results
A total of eight studies met the inclusion criteria. Analysis of these data showed that SOX2 expression was positively associated with squamous histology, (pooled OR = 5.26, 95% CI: 1.08–25.6, P = 0.040). Simultaneously, we also found that SOX2 expression was positively associated with overall survival (pooled HR = 0.65, 95% CI: 0.47–0.89, P = 0.007, random-effect).Conclusions
SOX2 expression in tumor is a candidate positive prognostic biomarker for NSCLC patients. 相似文献8.
Tong Qiu Yi Shen Ming-zhao Wang Yao-peng Wang Dong Wang Zi-zong Wang Xiang-feng Jin Yu-cheng Wei 《PloS one》2013,8(7)
Objective
To evaluate whether external suction is more advantageous than water seal in patients undergoing selective pulmonary resection (SPR) for lung neoplasm.Summary of Background Data
Whether external suction should be routinely applied in postoperative chest drainage is still unclear, particularly for lung neoplasm patients. To most surgeons, the decision is based on their clinical experience.Methods
Randomized control trials were selected. The participants were patients undergoing SPR with lung neoplasm. Lung volume reduction surgery and pneumothorax were excluded. Suction versus non-suction for the intervention. The primary outcome was the incidence of persistent air leak (PAL). The definition of PAL was air leak for more than 3–7 days. The secondary outcomes included air leak duration, time of drainage, postoperative hospital stay and the incidence of postoperative pneumothorax. Studies were identified from literature collections through screening. Bias was analyzed and meta-analysis was used.Results
From the 1824 potentially relevant trials, 6 randomized control trials involving 676 patients were included. There was no difference between external suction and water seal in decreasing the incidence of PAL [95% confidence interval (CI) 0.81−2.16; z = 1.10; P = 0.27]. Regarding secondary outcomes, there were no differences in time of drainage (95% CI−0.36−1.56, P = 0.22), postoperative hospital stay (95% CI -.31−.54, P = 0.87) or incidence of postoperative pneumothorax (95% CI 0.18−.02, P = 0.05) between external suction and water seal.Conclusions
For participants, no differences are identified in terms of PAL incidence, drainage time, length of postoperative hospital stay or incidence of postoperative pneumothorax between external suction and water seal. The bias analysis should be emphasized. To the limitations of the bias and methodological differences among the included studies, we have no recommendation on whether external suction should be routinely applied after lung neoplasm SPR. More high-quality randomized controlled trials are needed.Systematic Review Registration
None. 相似文献9.
Hiroaki Harada Yoshinori Yamashita Keizo Misumi Norifumi Tsubokawa Junichi Nakao Junko Matsutani Miyako Yamasaki Tomomi Ohkawachi Kiyomi Taniyama 《PloS one》2013,8(3)
Background
To decrease the risk of postoperative complication, improving general and pulmonary conditioning preoperatively should be considered essential for patients scheduled to undergo lung surgery.Objective
The aim of this study is to develop a short-term beneficial program of preoperative pulmonary rehabilitation for lung cancer patients.Methods
From June 2009, comprehensive preoperative pulmonary rehabilitation (CHPR) including intensive nutritional support was performed prospectively using a multidisciplinary team-based approach. Postoperative complication rate and the transitions of pulmonary function in CHPR were compared with historical data of conventional preoperative pulmonary rehabilitation (CVPR) conducted since June 2006. The study population was limited to patients who underwent standard lobectomy.Results
Postoperative complication rate in the CVPR (n = 29) and CHPR (n = 21) were 48.3% and 28.6% (p = 0.2428), respectively. Those in patients with Charlson Comorbidity Index scores ≥2 were 68.8% (n = 16) and 27.3% (n = 11), respectively (p = 0.0341) and those in patients with preoperative risk score in Estimation of Physiologic Ability and Surgical Stress scores >0.3 were 57.9% (n = 19) and 21.4% (n = 14), respectively (p = 0.0362). Vital capacities of pre- and post intervention before surgery in the CHPR group were 2.63±0.65 L and 2.75±0.63 L (p = 0.0043), respectively; however, their transition in the CVPR group was not statistically significant (p = 0.6815). Forced expiratory volumes in one second of pre- and post intervention before surgery in the CHPR group were 1.73±0.46 L and 1.87±0.46 L (p = 0.0012), respectively; however, their transition in the CVPR group was not statistically significant (p = 0.6424).Conclusions
CHPR appeared to be a beneficial and effective short-term preoperative rehabilitation protocol, especially in patients with poor preoperative conditions. 相似文献10.
Adriaan C. G. M. van Es Jeroen van der Grond V. Hester ten Dam Anton J. M. de Craen Gerard J. Blauw Rudi G. J. Westendorp Faiza Admiraal-Behloul Mark A. van Buchem for the PROSPER Study Group 《PloS one》2010,5(3)
Background and Purpose
Although total cerebral blood flow (tCBF) is known to be related to age, less is known regarding the associations between tCBF and the morphologic changes of the brain accompanying cerebral aging. The purpose of this study was to investigate whether total cerebral blood flow (tCBF) is related to white matter hyperintensity (WMH) volume and/or cerebral atrophy. Furthermore, we investigate whether tCBF should be expressed in mL/min, as was done in all previous MR studies, or in mL/100 mL/min, which yielded good results in precious SPECT, PET and perfusion MRI studies investigating regional cerebral blood flow.Materials and Methods
Patients were included from the nested MRI sub-study of the PROSPER study. Dual fast spin echo and FLAIR images were obtained in all patients. In addition, single slice phase contrast MR angiography was used for flow measurements in the internal carotids and vertebral arteries. tCBF was expressed in both mL/min and mL/100 mL/min.Results
We found a significant correlation between tCBF in mL/min and both age (r = −.124; p = p≤.001) and parenchymal volume (r = 0.430; p≤.001). We found no association between tCBF in mL/min and %-atrophy (r = −.077; p = .103) or total WMH volume (r = −.069; p = .148). When tCBF was expressed in mL/100 mL/min the correlation between tCBF and age was no longer found (r = −.001; p = .985). Multivariate regression analyses corrected for age showed a significant correlation between tCBF in mL/100 mL/min and WMH volume (r = −.106; p = .044). No significant association between tCBF in mL/100 mL/min and %-atrophy was found.Conclusion
From this study we conclude that, when evaluating tCBF alterations due to various pathologies, tCBF should in mL/100 mL/min instead of mL/min. Furthermore, changes or differences in WMH volume should be accounted for. 相似文献11.
Background
Comatose patients with acute intracerebral hemorrhage (ICH) diagnosed as inoperative due to their severe comorbidity will be treated differently between countries. In certain countries including Japan, aggressive medical care may be performed according to the patients'' family requests although the effects on the outcome are obscure. For respiratory distress in comatose patients with inoperative acute ICH, the role of mechanical ventilation on the outcome is unknown. We speculated that the efficacy of a ventilator in such a specific condition is limited and possibly futile.Methods
We retrospectively evaluated the in-hospital mortality and further outcome of 65 comatose patients with inoperative ICH. Among the patients, 56 manifested respiratory distress, and the effect of the ventilator was evaluated by comparing the patients treated with and without the ventilator.Results
The in-hospital mortality was calculated as 80%. A statistically significant parameter affecting the mortality independently was the motor subset on the Glasgow Coma Scale (P = 0.015). Among the patients who manifested respiratory distress, 7.7% of patients treated with a ventilator and 14.0% of patients not treated with a ventilator survived; an outcome is not significantly different. The mean survival duration of patients treated with a ventilator was significantly longer than the mean survival duration of patients not treated with a ventilator (P = 0.021). Among the surviving 13 patients, 7 patients died 5 to 29 months after onset without significant consciousness recovery. Another 6 patients suffered continuous disablement due to prolonged severe consciousness disturbances.Conclusion
The current results indicate that treating comatose patients resulting from inoperative acute ICH may be futile. In particular, treating these patients with a ventilator only has the effect of prolonging unresponsive life, and the treatment may be criticized from the perspective of the appropriate use of public medical resources. 相似文献12.
Background
The prognostic significance of circulating tumor cells (CTCs) detected in patients with non-small-cell lung cancer (NSCLC) is still inconsistent. We aimed to assess the prognostic relevance of CTCs using a meta-analysis.Methods
We searched PubMed, Web of Science and EMBASE for relevant studies that assessed the prognostic relevance of CTCs in NSCLC. Statistical analyses were conducted to calculate the summary incidence, odds ratio, relative risks (RRs) and 95% confidence intervals (CIs) using fixed or random-effects models according to the heterogeneity of included studies.Results
A total of 20 studies, comprising 1576 patients, met the inclusion criteria. In identified studies, CTCs were not correlated with histology (adenocarcinoma vs squamous cell carcinoma) (odds ratio [OR] = 0.88; 95% confidence interval [CI]: 0.59–1.33; Z = –0.61; P = 0.545). However, pooled analyses showed that CTCs were associated with lymph node metastasis (OR = 2.06; 95% CI: 1.18–3.62; Z = 2.20; P = 0.027) and tumor stage (OR = 1.95; 95% CI: 1.08–3.54; Z = 2.53; P = 0.011). Moreover, CTCs were significantly associated with shorter overall survival (relative risk [RR] = 2.19; 95% CI: 1.53–3.12; Z = 4.32; P<0.0001) and progression-free/disease-free survival (RR = 2.14; 95% CI: 1.36–3.38; Z = 3.28; P<0.0001).Conclusion
The presence of CTCs indicates a poor prognosis in patients with NSCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in lung cancer. 相似文献13.
Ryan M. McAdams Jeroen Vanderhoeven Richard P. Beyer Theo K. Bammler Federico M. Farin H. Denny Liggitt Raj P. Kapur Michael G. Gravett Craig E. Rubens Kristina M. Adams Waldorf 《PloS one》2012,7(10)
Background
Intrauterine exposure to amniotic fluid (AF) cytokines is thought to predispose to bronchopulmonary dysplasia (BPD). We evaluated the effects of GBS exposure on RNA expression in fetal lung tissue to determine early molecular pathways associated with fetal lung injury that may progress to BPD.Methods
Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received choriodecidual inoculation of either: 1) Group B Streptococcus (n = 5) or 2) saline (n = 5). Cesarean section and fetal necropsy was performed in the first week after GBS or saline inoculation regardless of labor. RNA was extracted from fetal lungs and profiled by microarray. Results were analyzed using single gene, Gene Set, and Ingenuity Pathway Analysis. Validation was by RT-PCR and immunohistochemistry.Results
Despite uterine quiescence in most cases, fetal lung injury occurred in four GBS cases (intra-alveolar neutrophils, interstitial thickening) and one control (peri-mortem hemorrhage). Significant elevations of AF cytokines (TNF-α, IL-8, IL-1β, IL-6) were detected in GBS versus controls (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable by culture and PCR in the AF and fetal lungs. A total of 335 genes were differentially expressed greater than 1.5 fold (p<0.05) with GBS exposure associated with a striking upregulation of genes in innate and adaptive immunity and downregulation of pathways for angiogenesis, morphogenesis, and cellular growth and development.Conclusions
A transient choriodecidual infection may induce fetal lung injury with profound alterations in the genetic program of the fetal lung before signs of preterm labor. Our results provide a window for the first time into early molecular pathways disrupting fetal lung angiogenesis and morphogenesis before preterm labor occurs, which may set the stage for BPD. A strategy to prevent BPD should target the fetus in utero to attenuate alterations in the fetal lung genetic program. 相似文献14.
Background
Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin of CorA.Methods
HC-CorA were quantified in paired samples of cord serum from newborns and serum from mothers (n = 69).Results
The CorA-concentration was higher in cord serum (median = 380, range: 41–780 pmol/L) than in serum from the mothers (median = 160, range: 64–330 pmol/L), (p<0.0001). HPLC-analysis showed CorA-peaks with retention times of 13.5, 14,5 and 16.5 min in samples from both the mother and cord serum. The peak with retention time 16.5 min constituted 24% (mother) and 45% (cord serum) of the total amount CorA, and eluted as does dicyanocobinamide.Conclusion
Our results support that CorA in the human body are derived from Cbl. 相似文献15.
Sangbin Han Justin Sangwook Ko Sang-Man Jin Hyo-Won Park Jong Man Kim Jae-Won Joh Gaabsoo Kim Soo Joo Choi 《PloS one》2014,9(10)
Background
Patients undergoing liver resection are at risk for intraoperative hyperglycemia and acute hyperglycemia is known to induce hepatocytes injury. Thus, we aimed to evaluate whether intraoperative hyperglycemia during liver resection is associated with the extent of hepatic injury.Methods
This 1 year retrospective observation consecutively enrolled 85 patients undergoing liver resection for hepatocellular carcinoma. Blood glucose concentrations were measured at predetermined time points including every start/end of intermittent hepatic inflow occlusion (IHIO) via arterial blood analysis. Postoperative transaminase concentrations were used as surrogate parameters indicating the extent of surgery-related acute hepatocytes injury.Results
Thirty (35.5%) patients developed hyperglycemia (blood glucose > 180 mg/dl) during surgery. Prolonged (≥ 3 rounds) IHIO (odds ratio [OR] 7.34, P = 0.004) was determined as a risk factors for hyperglycemia as well as cirrhosis (OR 4.07, P = 0.022), lower prothrombin time (OR 0.01, P = 0.025), and greater total cholesterol level (OR 1.04, P = 0.003). Hyperglycemia was independently associated with perioperative increase in transaminase concentrations (aspartate transaminase, β 105.1, standard error 41.7, P = 0.014; alanine transaminase, β 81.6, standard error 38.1, P = 0.035). Of note, blood glucose > 160 or 140 mg/dl was not associated with postoperative transaminase concentrations.Conclusions
Hyperglycemia during liver resection might be associated with the extent of hepatocytes injury. It would be rational to maintain blood glucose concentration < 180 mg/dl throughout the surgery in consideration of parenchymal disease, coagulation status, lipid profile, and the cumulative hepatic ischemia in patients undergoing liver resection for hepatocellular carcinoma. 相似文献16.
Zhixuan Zhang Ting Wang Jun Zhang Xiaohong Cai Changchuan Pan Yu Long Jing Chen Chengya Zhou Xude Yin 《PloS one》2014,9(8)
Background
The prognostic value of epidermal growth factor receptor (EGFR) mutations in resected non-small cell lung cancer (NSCLC) remains controversial. We performed a systematic review with meta-analysis to assess its role.Methods
Studies were identified via an electronic search on PubMed, Embase and Cochrane Library databases. Pooled hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS) were calculated for meta-analysis.Results
There were 16 evaluated studies (n = 3337) in the meta-analysis. The combined HR evaluating EGFR mutations on disease free survival was 0.96 (95% CI [0.79–1.16] P = 0.65). The combined HR evaluating EGFR mutations on overall survival was 0.86 (95% CI [0.72–1.04] P = 0.12). The subgroup analysis based on univariate and multivariate analyses in DFS and OS showed no statistically significant difference. There was also no statistically significant difference in DFS and OS of stage I NSCLC patients.Conclusion
The systematic review with meta-analysis showed that EGFR mutations were not a prognostic factor in patients with surgically resected non-small cell lung cancer. Well designed prospective study is needed to confirm the result. 相似文献17.
Background
The association between NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and lung cancer has been widely evaluated, and a definitive answer so far is lacking. We first conducted a case-control study to assess this association in northeastern Han Chinese, and then performed a meta-analysis to further address this issue.Methodology/Principal Findings
This case-control study involved 684 patients clinically diagnosed as lung cancer and 602 age-matched cancer-free controls from Harbin city, Heilongjiang province, China. Genotyping was conducted using the PCR-LDR (ligase detection reactions) method. Meta-analysis was managed by STATA software. Data and study quality were assessed in duplicate. Our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between lung cancer patients and controls, consistent with the results of the further meta-analysis involving 7286 patients and 9167 controls under both allelic (odds ratio (OR) = 0.99; 95% confidence interval (CI): 0.92–1.06; P = 0.692) and dominant (OR = 0.98; 95% CI: 0.89–1.08; P = 0.637) models. However, there was moderate evidence of between-study heterogeneity and low probability of publication bias. Further subgroup analyses by ethnicity, source of controls and sample size detected no positive associations in this meta-analysis.Conclusions
Our study in northeastern Han Chinese, along with the meta-analysis, failed to confirm the association of NQO1 gene C609T polymorphism with lung cancer risk, even across different ethnic populations. 相似文献18.
Ping Xu Li Liu Jianzhong Wang Kai Zhang Xiaohua Hong Qifei Deng Jingjun Xiang Xiaomin Zhang Meian He Tangchun Wu Huan Guo 《PloS one》2013,8(8)
Objectives
Bcl-2 is a critical apoptosis inhibitor with established carcinogenic potential, and can confer cancer cell resistance to therapeutic treatments by activating anti-apoptotic cellular defense. We hypothesized that genetic variants of BCL2 gene may be associated with lung cancer susceptibility and prognosis.Methods
Three selected tagSNPs of BCL2 (rs2279115, rs1801018, and rs1564483) were genotyped in 1017 paired male Chinese lung cancer cases and controls by TaqMan assay. The associations of these variants with risk of lung cancer and overall survival of 242 male advanced non-small-cell lung cancer (NSCLC) patients were separately investigated.Results
Compared with the BCL2 3′UTR rs1564483GG genotype, the rs1564483GA, AA, and GA+AA genotypes were associated with significantly decreased susceptibilities of lung cancer in male Chinese (adjusted OR = 0.78, 0.73, and 0.76, P = 0.016, 0.038, and 0.007, respectively), while rs1564483A allele has a inverse dose-response relationship with lung cancer risk (P trend = 0.010). These effects were more evident in the elders, smokers, and subjects without family history of cancer (P trend = 0.017, 0.043 and 0.005, respectively). Furthermore, advanced NSCLC males carrying BCL2 rs1564483 GA+AA genotypes had significantly longer median survival time (Long-rank P = 0.036) and decreased death risk (adjusted HR = 0.69, P = 0.027) than patients with rs1564483GG genotype. These effects were more obvious in patients with smoking, stage IIIA, and in patients without surgery but underwent chemotherapy or radiotherapy (adjusted HR = 0.68, 0.49, 0.67, 0.69, 0.50, respectively, all P<0.05).Conclusion
The BCL2 3′UTR rs1564483A allele was associated with a decreased lung cancer risk and better survival for advanced NSCLC in male Chinese, which may offer a novel biomarker for identifying high-risk population and predicting clinical outcomes. 相似文献19.
Edith T. Zemanick J. Kirk Harris Brandie D. Wagner Charles E. Robertson Scott D. Sagel Mark J. Stevens Frank J. Accurso Theresa A. Laguna 《PloS one》2013,8(4)
Background
Pulmonary exacerbations (PEx), frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF). Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood.Objective
To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx.Methods
Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0–3d.) and late treatment (>7d.) for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE); and circulating C-reactive protein (CRP) were measured.Results
Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA) of Pseudomonas (r = −0.67, p<0.001), decreased FEV1% predicted (r = 0.49, p = 0.03) and increased CRP (r = −0.58, p = 0.01). In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV1. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV1 response to treatment than Pseudomonas or Staphylococcus.Conclusions
Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens. 相似文献20.
Wang Zhou Min Zhao Xia Wang Robert F. Schilling Sheng Zhou Hong-Yan Qiu Nian-Hua Xie Man-Qing Liu Han-Sheng Dong Zhong-Zhao Yao Thomas Cai 《PloS one》2014,9(12)