Circ_100549 promotes tumor progression in lung adenocarcinoma through upregulation of BIRC6.

Lung adenocarcinoma (LUAD) is a subtype of lung cancer with high incidence and mortality globally. Emerging evidence suggests that circular RNAs (circRNAs) exert critical functions in human cancers, including LUAD. CircRNA_100549 (circ_100549) has been reported to be significantly upregulated in non-small cell lung cancer (NSCLC) samples, while its role in modulating LUAD progression remains to be explored. The current study aims at investigating the functional roles of circ_100549 in LUAD and its downstream molecular mechanism. First, we found that the expression of circ_100549 was higher in LUAD cell lines. Loss-of-function assays verified that depletion of circ_100549 repressed LUAD cell proliferation but accelerated cell apoptosis. Furthermore, in vivo experiments demonstrated that silencing of circ_100549 suppressed tumor growth. Subsequently, based on database analysis, we carried out a series of experiments to explore the mechanisms and effects of circ_100549 underlying LUAD progression, including RNA-binding protein immunoprecipitation (RIP), RNA/DNA pull-down, luciferase reporter, and chromatin immunoprecipitation (ChIP) assays. The results indicated that circ_100549 serves as a ceRNA by sponging miR-95-5p to upregulate BPTF expression, thus upregulating BIRC6 expression at a transcriptional level in LUAD. In summary, our study demonstrated that circ_100549 facilitates LUAD progression by upregulating BIRC6 expression.

ITGA9-AS1 up-regulates ITGA9 by targeting miR-4765 and recruiting HNRNPU to affect the proliferation and apoptosis of non-small cell lung cancer cells.

Long non-coding RNAs (lncRNAs) have been regarded as promising biomarkers in the regulation of various biological and pathological processes of non-small cell lung cancer (NSCLC). LncRNAITGA9-AS1 has been reported to be down-regulated in elderly patients with lung cancer, but how it may influence NSCLC remains to be identified. Therefore, we aim to explore the specific mechanism involving ITGA9-AS1 and ITGA9 in NSCLC. A functional assay was conducted to verify ITGA9-AS1's proliferative effects on NSCLC cells. Mechanism experiments with bioinformatics predictions were performed to explore the interaction of ITGA9-AS1 and ITGA9 in NSCLC cells. ITGA9-AS1 inhibited NSCLC cell proliferation while enhancing cell apoptosis. It up-regulated ITGA9 by competitively sponging miR-4765, and it stabilizedITGA9 mRNA by recruiting a RNA-binding protein (RBP)-HNRNPU (heterogeneous nuclear ribonucleoprotein U) in NSCLC cells. ITGA9-AS1 suppressed NSCLC progression by the up-regulation of ITGA9 via targeting miR-4765 and recruiting HNRNPU.

Endobronchial Ultrasound Elastography Combined With Computed Tomography in Differentiating Benign from Malignant Intrathoracic Lymph Nodes.

Objective. This study was to combine endobronchial ultrasound elastography (UE) with computed tomography (CT) to identify benign and malignant thoracic lymph nodes (LNs) more objectively and accurately. Methods. A total of 42 patients with intrathoracic lymphadenopathy required for endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) examination were enrolled. All patients were examined by enhanced chest CT, B-mode ultrasound, and endobronchial ultrasound (EBUS)-guided elastography before EBUS-TBNA. Each lymph node was assessed by describing the characteristics of CT image (short diameter, texture, shape, boundary, and mean CT value), B-mode ultrasound (short diameter, echo characteristic, shape, and boundary), and elastography (image type, grading score, strain rate, and blue area ratio). The pathological results were used as the gold standard. The characteristics were compared alone and in combination between benign and malignant LNs. Results. The blue area ratio of elastography combined with CT had better diagnostic value in differentiating benign and malignant LNs than elastography alone, with the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) being 92%, 96%, 80%, 94%, and 86% vs 81%, 77%, 93%, 97%, and 56%, respectively. Elastography combined with B-mode ultrasound and CT characteristics showed the highest diagnostic value. Accuracy, sensitivity, specificity, PPV, and NPV were all 100%. Conclusions. Endobronchial UE combined with CT and B-mode ultrasound imaging shows a greater diagnostic value in differentiating benign and malignant intrathoracic LNs than either imaging alone.

Prognostic value of pretreatment platelet counts in lung cancer: a systematic review and meta-analysis.

BACKGROUND: The prognostic value of elevated pretreatment platelet counts remains controversial in lung cancer patients. We performed the present meta-analysis to determine its precise role in these patients. METHODS: We employed a multiple search strategy in the PubMed, EMBASE and Cochrane Library databases to identify eligible studies. Disease-free survival (DFS)/progression-free survival (PFS)/time to progression (TTP) and overall survival (OS) were used as outcomes with hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity among the studies and publication bias were also evaluated. RESULTS: A total of 40 studies including 16,696 lung cancer patients were eligible for the analysis. Overall, the pooled analysis showed that compared with normal platelet counts, elevated pretreatment platelet counts were associated with poorer OS (HR = 1.54, 95% CI: 1.37-1.72, P < 0.001) and poorer DFS/PFS/TTP (HR = 1.62, 95% CI: 1.33-1.98, P < 0.001) in patients with lung cancer. In subgroup analyses, elevated pretreatment platelet counts were also associated with poorer OS and DFS/PFS/TTP in most subgroups. There was no evidence of publication bias. CONCLUSIONS: This meta-analysis revealed that elevated pretreatment platelet counts were an independent predictor of OS and DFS/PFS/TTP in lung cancer patients. Large-scale prospective studies and a validation study are warranted.

Inhibition of FASN suppresses the malignant biological behavior of non-small cell lung cancer cells via deregulating glucose metabolism and AKT/ERK pathway.

BACKGROUND: Fatty acid synthase (FASN) is overexpressed in most human carcinomas, including non-small cell lung cancer (NSCLC), and contributes to poor prognosis. An increasing number of studies have highlighted the potential function of FASN as both a biomarker and therapeutic target for cancers. However, the underlying molecular mechanisms of FASN in glucose metabolism and the malignant biological behavior of NSCLC remain the subjects of intensive investigation. METHODS: FASN expression was depleted by FASN-siRNA in A549 and NCI-H1299 cell lines to detect the function of glucose metabolism and the malignant biological behavior of NSCLC cells. Western-blot and qPCR were applied to determine the expressions of FASN, t-AKT, p-AKT, t-ERK, p-ERK, PKM2, HK2 and AZGP1. ATP and lactate were detected to determine the activation of glucose metabolism. CCK8 and transwell assays were used to detect the proliferation, invasion, and migration capacity of the two types of NSCLC cells. The xenograft mouse model was used to evaluate tumor weights after suppression of FASN. RESULTS: LV-FASN-siRNA and its control lentiviral vector were successfully transfected into the two types of NSCLC cells (A549 and NCI-H1299). LV-FASN siRNA significantly suppressed FASN expression in both NSCLC cell types, and expressions of p-AKT, p-ERK, PKM2, and AZGP1 were also significantly decreased. Notably, the levels of ATP and lactate were significantly decreased after transfection with LV-FASN siRNA. The proliferation of both NSCLC cell types was decreased after suppression of FASN. The invasion and migration capacity of A549, but not NCI-H1299, were inhibited following down-regulation of FASN. In vivo, inhibition of FASN caused a marked animal tumor weight loss. CONCLUSIONS: FASN was involved in glucose metabolism via down-regulation of the AKT/ERK pathway and eventually altered the malignant phenotype in lung cancer cells.

Serum Romo1 is significantly associated with disease severity in patients with obstructive sleep apnea syndrome.

PURPOSE: We aim to evaluate reactive oxygen species modulator 1 (Romo1) levels in obstructive sleep apnea syndrome (OSAS) and analyze its possible relationships to OSAS severity, reactive oxygen species (ROS), and C-reactive protein (CRP). Additionally, we also investigated the effects of nasal continuous positive airway pressure (nCPAP) on serum Romo1. METHODS: One hundred and five patients diagnosed with OSAS were classified into the OSAS group, and 41 subjects without OSAS were recruited for the control group. The OSAS group was further divided into mild, moderate, and severe OSAS subgroups. Fifteen patients with moderate and severe OSAS were treated with nCPAP. Serum levels of Romo1, ROS, and CRP were also measured. RESULTS: Serum Romo1, ROS, and CRP were the lowest in normal subjects and increased across OSAS severities (P < 0.05). Univariate analysis showed that serum Romo1 was positively correlated with apnea-hypopnea index (AHI), oxygen desaturation index (ODI), time spent below 90% oxygen saturation (Ts90%), arousal index, ROS, and CRP, and was negatively correlated with minimal oxygen saturation (miniSaO2) (all P < 0.05). Multiple linear regression analysis showed that serum Romo1 level was significantly associated with AHI and ODI, after adjusting for age, gender, BMI, and CRP. After 6 months of nCPAP therapy, serum Romo1, ROS, and CRP were significantly decreased (P < 0.05). CONCLUSIONS: The increase of serum Romo1 in OSAS patients was positively correlated with disease severity. Serum Romo1 may be an important parameter for monitoring the severity of OSAS and treatment efficiency.

Liver X receptors agonist T0901317 downregulates matrix metalloproteinase-9 expression in non-small-cell lung cancer by repressing nuclear factor-κB.

The liver X receptors (LXRs) is an important component of the nuclear receptor (NR) superfamily. Previous studies have shown that the LXRs possessed antitumor activity in various types of tumor cells. However, the complicated mechanisms underlying the antitumor activity remain largely unexplored. In this study, we incubated A549 cells with the compound T0901317, a specific LXRs agonist, for 24 h. The MTT assay was used to assess cell viability. Transwell assays were used to evaluate cell migration and invasion. The shRNA was utilized for RNA interference. The target gene and protein expression levels were assessed using reverse transcription-PCR and western blot assay. The DNA-binding activity of nuclear factor κB (NF-κB) was examined using electrophoretic mobility shift assays. Luciferase reporter assay was used to detect the binding of NF-κB to the matrix metalloproteinase-9 (MMP-9) promoter. We found that T0901317 inhibited the invasion and migration of A549 cells in a dose-dependent manner. Meanwhile, we further indicated that activation of LXRß, one subtype of LXRs, can downregulate MMP-9 expression. More importantly, activation of LXRß triggered by T0901317 inhibited the invasion and metastasis of A549 cells by repressing NF-κB/MMP-9 signaling pathway. Taken together, our study shows that activation of LXRs triggered by T0901317 inhibits the invasion and metastasis of human non-small-cell lung cancer by repressing the NF-κB/MMP-9 signaling pathway.

Identification of an Exosome-relevant SNHG6-hsa-miR-429- CHRDL1/CCNA2 Axis for Lung Adenocarcinoma Prognosis Evaluation.

AIM: To explore an exosome-relevant molecular classification in lung adenocarcinoma (LUAD). BACKGROUND: Exosome genes or relevant non-coding RNAs are regulators of cancer treatment and prognosis, but their function in LUAD has not yet been determined. OBJECTIVE: Unraveling a molecular classification applying exosome-related RNA networks for LUAD prognosis evaluation. METHODS: MicroRNA sequencing data (miRNAs-seq) and RNA sequencing data (RNA- seq) were derived from The Cancer Genome Atlas (TCGA). The ConsensusCluster- Plus package was used for molecular typing in LUAD based on 121 Exosome-related genes. Then, a limma package was conducted to explore differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in molecular typing for constructing an Exosome-driven competing endogenous RNA network (ceRNA). Dominant miRNAs, as well as target mRNAs, were identified by COX modeling and Kaplan-Meier survival analysis. RESULTS: Two Exosome-associated molecular clusters classified in LUAD. The C2 cluster favored high clinicopathology and showed a trend toward poor prognosis. 29 lncRNA- miRNA and 12 miRNA-mRNA interaction pairs were identified. The hsa-miR-429 was the pivotal miRNA in the network that affected the prognosis of LUAD. According to the interaction relationship and LUAD prognostic role, SNHG6-hsa- miR-429-CHRDL1/CCNA2 was identified. SNHG6-hsa-miR-429-CHRDL1 exerts oncogenic effects, and SNHG6-hsa-miR-429- CCNA2 exerts pro-oncogenic effects. CONCLUSION: Overall, our study identified an Exosome-driven ceRNA network in LUAD, and the SNHG6-hsa-miR-429-CHRDL1/CCNA2 axis could be a new therapeutic target for LUAD and our study provides new insights into the molecular mechanisms of LUAD.

Sub-femtomolar vertical graphene field effect immunosensor for detection of lung tumor markers.

Lung cancer is the main cancer that endangers human life worldwide, with the highest mortality rate. The detection of lung tumor markers is of great significance for the early diagnosis and subsequent treatment of lung cancer. In this study, a vertical graphene field effect transistor (VGFET) immunosensor based on graphene/C60 heterojunction was created to offer quantitative detections for the lung tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1), and neuron-specific enolase (NSE). The experimental results showed that the sensitive range for standard antigen is between 1 pg/ml to 100 ng/ml, with a limit of detection (LOD) of 5.6 amol/ml for CEA, 33.3 amol/ml for Cyfra 21-1 and 12.8 amol/ml for NSE (1 pg/ml for all). The detection accuracy for these tumor markers was compared with the clinically used method for clinical patients on serum samples. Results are highly consistent with clinically used immunoassay in its efficient diagnosis concentration range. Subsequently, the mesoporous silica nanospheres (MSNs) with an average size of 90 nm were surface modified with glutaraldehyde, and a second antibody was assembled on MSNs, which fixes nanospheres on the antigen and amplified the field effect. The LODs for three markers are 100 fg/ml (0.56 amol/ml for CEA) under optimal circumstances of detection. This result indicates that specific binding to MSNs enhances local field effects and can achieve higher sensing efficiency for tumor marker detection at extremely low concentrations, providing effective assistance for the early diagnosis of lung cancer.

Clinic significance of microRNA-99a expression in human lung adenocarcinoma.

BACKGROUND: The purpose of this study was to investigate the clinical significance of microRNA-99a expression in lung adenocarcinoma. METHODS: qRT-PCR assay was performed to detect miR-99a expression in lung adenocarcinoma cells or tissues. The correlations of miR-99a expression with clinicopathological factors and prognosis of lung adenocarcinoma patients were analyzed. The effects of miR-99a expression on growth and apoptosis of lung adenocarcinoma cell line and its potential target gene were determined by MTT, flow cytometry, luciferase reporter, and Western blot assays. RESULTS: The relative miR-99a expression in lung adenocarcinoma cells was significantly lower than that in normal lung bronchial epithelium cell line. Also, miR-99a expression in lung adenocarcinoma tissues was significantly lower than that in corresponding nontumor tissues. Low miR-99a expression was found to be closely correlated with advanced clinical stage and lymph node metastasis. Kaplan-Meier survival and Cox regression analyses showed that the status of miR-99a expression was an independent prognosis factor for lung adenocarcinoma patients. Functional analyses showed that upregulation of miR-99a could inhibit growth and induce apoptosis in lung adenocarcinoma cells by targeting mTOR. CONCLUSION: Low MiR-99a expression was a poor prognostic factor for patients with lung adenocarcinoma, and miR-99a functions as a tumor suppressor by targeting mTOR.

A lung squamous cell carcinoma-associated membranous nephropathy patient free of tumor and membranous nephropathy after the treatment of surgery and radiochemotherapy following pembrolizumab: A rare case report.

RATIONALE: Membranous nephropathy (MN) is an autoimmune disease, which is classified into primary and secondary MN. Malignancy-associated MN (M-MN) accounts for about 10% of secondary MN cases. Lung cancer is the most common type of malignancy among M-MN patients. Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) have showed promising efficacy and good safety in many types of solid tumors, including non-small cell lung cancer. To date, whether ICIs could be a treatment option for M-MN patients with PD-L1 expression and or high tumor mutation burden (TMB) level has not been documented. PATIENT CONCERNS: A 68-year-old male patient presented with edema of the lower limbs with increased urine foam in August 2018. Biopsy on the right kidney showed MN at stage I with subepithelially localized immune deposits. DIAGNOSIS: Lung squamous cell carcinoma (LSCC)-associated MN with PD-L1 expression (20%) and high TMB level (26.2 mutations/Mb). INTERVENTIONS: The patient received immunosuppressive therapy targeting the initially diagnosed primary MN as first-line treatment plus surgery and radiochemotherapy following pembrolizumab targeting the definitively diagnosed lung cancer as second-line treatment. OUTCOMES: The patient benefited from radiochemotherapy following pembrolizumab (lasting more than 38 months) rather than immunosuppressive therapy. LESSONS: Our work suggests that combined ICIs might be an effective treatment option for M-MN patients who harbor PD-L1 expression. Our work highlights that the presence of malignancy should not be neglected at the initial diagnosis of MN.

MAPKAPK5-AS1/miR-515-5p/CAB39 Axis Contributes to Non-small Cell Lung Cancer Cell Proliferation and Migration.

Several studies have elucidated the pivotal function that long noncoding RNAs (lncRNAs) exerted on the initiation and development of various human carcinomas, encompassing non-small cell lung cancer (NSCLC). In spite of the fact that lncRNA MAPKAPK5 antisense RNA 1 (MAPKAPK5-AS1) has already been investigated by researchers and confirmed to play oncogenic roles in colorectal cancer, the underlying regulatory function of MAPKAPK5-AS1 in NSCLC cells still remain unclear. In our research, we found that MAPKAPK5-AS1 was expressed at high levels in NSCLC cells. Biological functional assays unclosed that downregulation of MAPKAPK5-AS1 repressed proliferative and migratory capacities whereas promoted apoptotic level in NSCLC cells. Molecular mechanism experiments confirmed that, in NSCLC cells, MAPKAPK5-AS1 combined with miR-515-5p and negatively modulated miR-515-5p expression level. Besides, calcium-binding protein 39 (CAB39) expression level was verified to be negatively modulated by miR-515-5p whereas positively modulated by MAPKAPK5-AS1 in NSCLC cells. Furthermore, rescued-function assays disclosed that inhibited miR-515-5p expression or overexpressed CAB39 could restore the suppressive influence of MAPKAPK5-AS1 silence on NSCLC progression. In summary, MAPKAPK5-AS1 upregulates CAB39 expression level to facilitate NSCLC progression by sequestering miR-515-5p, providing promising biomarkers for NSCLC treatment.

Exosome-mediated transfer of SNHG7 enhances docetaxel resistance in lung adenocarcinoma.

Long noncoding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) has been widely reported in various cancers, including lung adenocarcinoma (LUAD). However, it is largely unknown whether SNHG7 is involved in docetaxel resistance of LUAD. In the current study, we identified the high expression of SNHG7 in docetaxel-resistant cells. Through functional assays, we determined that silencing of SNHG7 decreased IC50 value of LUAD cells to docetaxel and suppressed proliferation and autophagy in LUAD cells, and reversed M2 polarization in macrophages. Mechanistically, we uncovered that SNHG7 promoted autophagy via recruiting human antigen R (HuR) to stabilize autophagy-related genes autophagy related 5 (ATG5) and autophagy related 12 (ATG12). Moreover, exosomal SNHG7 was transmitted from docetaxel-resistant LUAD cells to parental LUAD cells and thus facilitated docetaxel resistance. Additionally, exosomal SNHG7 activated the phosphatidylinositol 3-kinase (PI3K)/AKT pathway to promote M2 polarization in macrophages via recruiting cullin 4A (CUL4A) to induce ubiquitination and degradation of phosphatase and tensin homolog (PTEN). Taken together, we concluded that exosomal SNHG7 enhances docetaxel resistance of LUAD cells through inducing autophagy and macrophage M2 polarization. All findings in the study suggested that SNHG7 may be a promising target for relieving docetaxel resistance in LUAD.

The Molecular Mechanism of Metabolic Remodeling in Lung Cancer.

Metabolic remodeling is a key phenomenon in the occurrence and development of tumors. It not only offers materials and energy for the survival and proliferation of tumor cells, but also protects tumor cells so that they may survive, proliferate and transfer in the harsh microenvironment. This paper attempts to reveal the role of abnormal metabolism in the development of lung cancer by considering the processes of glycolysis and lipid metabolism, Identification of the molecules that are specifically used in the processes of glycolysis and lipid metabolism, and their underlying molecular mechanisms, is of great clinical and theoretical significance. We will focus on the recent progress in elucidating the molecular mechanism of metabolic remodeling in lung cancer.

Lipoprotein-associated phospholipase A2 predicted cardiovascular disease in obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular disease (CVD). As a new inflammatory biomarker of CVD, rare attention has been paid to the roles of lipoprotein-associated phospholipase (Lp-PLA2) in OSAS studies. In this study, we aimed to investigate the correlation between Lp-PLA2 and concomitant CVD in OSAS patients. METHODS: In this prospective study, 152 OSAS patients were further divided into mild, moderate, and severe OSAS subgroups. They presented heart failure, coronary artery disease, or arrhythmia were confirmed with CVD. Thirty-one subjects without OSAS were recruited for the control group. The relationship between Lp-PLA2 and concomitant CVD in OSAS patients was analyzed. RESULTS: Serum Lp-PLA2 values were significantly higher in the severe and moderate OSAS group compared with mild OSAS and OSAS negative groups (P = 0.025). Significant increase was noticed in serum Lp-PLA2 levels in CVD patients compared with those without in severe-moderate-mild OSAS (P < 0.05). In logistic regression analysis, the level of Lp-PLA2 was proved as a significant independent predictor for CVD (OR = 1.117, P = 0.008). The ROC analysis indicated that the best cut-off value of Lp-PLA2 for predicting CVD in OSAS patients was 238.09 ng/ml. The positive and negative predictive values were 72.5% and 70.5%, respectively. The sensitivity was 46.8% and the specificity was 87.8%. CONCLUSIONS: Lp-PLA2 might be associated with the severity of OSAS and the occurrence of CVD in OSAS patients. Lp-PLA2 is expected to be a promising biomarker candidate in predicting CVD in patients with OSAS due to test convenience.

Increased Serum Romo1 Was Correlated with Lung Function, Inflammation, and Oxidative Stress in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammation and high oxidative stress. Studies suggest that reactive oxygen species modulator 1 (Romo1) involve in diseases associated with oxidative stress and inflammation. However, the relationship between COPD and Romo1 is still not clear. In this study, we compared serum Romo1 in 49 COPD patients and 34 health controls, and their correlation with lung function, systematic inflammation, and oxidative stress. In addition, serum levels of Romo1, C-reactive protein (CRP), and oxidative stress (measured by reactive oxygen species, ROS) were analyzed using commercial kits. Serum Romo1 was significantly higher in COPD patients than that of control (132.24 ± 10.34 vs. 93.26 ± 7.75 pg/ml, P < 0.05). Serum CRP and ROS were also significantly higher in COPD patients. Serum Romo1 was correlated inversely with FEV1% predicted in COPD patients (푟 = - 0.347, 푃 = 0.016), while it was correlated positively with CRP and ROS levels, respectively. These results suggest that serum Romo1 increase in COPD patients and that these levels are associated with lung function, inflammation, and oxidative stress in COPD.

Prognostic Value of Plasma Fibrinogen in Lung Cancer Patients: A Meta-Analysis.

Background: The prognostic role of plasma fibrinogen in lung cancer remains controversial. The aim of this meta-analysis was to assess the prognostic value of plasma fibrinogen in lung cancer. Methods: We performed a systematic literature search to identify eligible studies in PubMed, Embase and the Cochrane Library database. The hazard ratios (HR) and their 95% confidence intervals (CI) were collected from these eligible studies and were used to assess the relationship between plasma fibrinogen and lung cancer. Results: A total of 16 studies including 6,881 patients were selected in this meta-analysis. The results showed that elevated plasma fibrinogen in lung cancer patients was correlated with poor overall survival (OS) (HR = 1.38, 95% CI: 1.22-1.55, P < 0.001) and disease-free survival (DFS) / progress-free survival (PFS). (HR = 1.29, 95% CI: 1.01-1.65, P = 0.042). When stratified by cut-off value for OS and DFS/PFS, there was no significant heterogeneity. And the results of "cut-off value ≥ 400mg/dl" group showed that the high level of fibrinogen in serum was associated with worse OS and DFS/PFS of lung cancer. In further subgroup analysis by tumor histology, high plasma fibrinogen was also associated with worse OS in non-small cell lung cancer (NSCLC) (HR = 1.32, 95% CI: 1.14-1.53, P < 0.001). However, there was no significant association between high plasma fibrinogen and poor DFS in NSCLC patients (HR = 1.24, 95% CI: 0.97-1.57, P = 0.08). The Egger's regression test indicated evidence of publication bias for DFS/PFS. Conclusions: Elevated plasma fibrinogen, particularly defined as a plasma fibrinogen concentration of ≥ 400mg/dl, could be a promising indicator for worse OS in lung cancer patients, including NSCLC.

[Clinical analysis of the rare causes of hemoptysis: a report of 4 cases].

OBJECTIVE: To improve the diagnosis of hemoptysis caused by rare lung diseases. METHODS: Four cases of hemoptysis caused by rare diseases which were diagnosed by angiography or operation were reported and related literature were reviewed. RESULTS: The 4 cases of hemoptysis were caused by intercostal-to-pulmonary arterial fistula (IPAF), pulmonary hamartoma (PH), congenital unilateral absence of the left pulmonary artery (ALPA) and primary pulmonary hypertension (PPH). Bronchial arteriography and bronchial artery embolization were performed for IPAF. For PH, a benign tumor, the diagnosis was based on the history and radiography examination, and operation was the choice for therapy. ALPA was confirmed by radiography, if massive hemoptysis occurred, surgical intervention was the best choice. The diagnosis of PPH was firstly evaluated by chest film and echocardiogram, and the final diagnosis relied on right cardiac catheter examination. CONCLUSIONS: Hemoptysis is a common symptom of respiratory diseases, including some rare cases which are easy to be misdiagnosed. The correct diagnosis and therapy rely on comprehensive thinking, careful history collection and reasonable examinations.

HE4 expression in lung cancer, a meta-analysis.

BACKGROUND: The prognostic role of Human epididymis protein 4 (HE4) expression in lung cancer remains controversial. We performed this meta-analysis to assess the prognostic value of HE4 expression in lung cancer. METHODS: A systematic literature search was conducted to identify eligible studies in PubMed, Embase and Wanfang databases. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to assess the relationship. RESULTS: A total of 1412 patients from 8 studies were included in this meta-analysis. The results of univariate analysis (HR=1.73, 95% CI: 1.19-2.52, P=0.004) and multivariate analysis (HR=2.49, 95% CI: 1.89-3.28, P<0.001) demonstrated that high HE4 expression in lung cancer patients was correlated with poor overall survival (OS). We observed through further stratified analysis of the results of the univariate analysis that high HE4 expression was associated with worse OS in Asian lung cancer patients (HR=2.48, 95% CI: 1.88-3.26, P<0.001). However, there was no significant association between high HE4 expression and poor OS in Caucasian patients (HR=1.12, 95% CI: 0.80-1.55, P=0.513). CONCLUSION: High serum HE4 level was a marker of poor prognosis in lung cancer patients, particularly in Asian patients with lung cancer.

Proanthocyanidin from grape seed extract inhibits airway inflammation and remodeling in a murine model of chronic asthma.

Asthma is characterized by airway inflammation and airway remodeling. Our previous study revealed that grape seed proanthocyanidin extract (GSPE) could inhibit asthmatic airway inflammation and airway hyper-responsiveness by down-regulation of inducible nitric oxide synthase in a murine model of acute asthma. The present study aimed to evaluate GSPE's effects on airway inflammation and airway remodeling in a chronic asthmatic model. BALB/c mice were sensitized with ovalbumin (OVA) and then were challenged three times a week for 8 weeks. Airway responsiveness was measured at 24 h after the last OVA challenge. HE staining, PAS staining, and Masson staining were used to observe any airway inflammation in the lung tissue, airway mucus secretion, and subepithelial fibrosis, respectively. The cytokines levels in the lavage fluid (BALF) in addition to the total serum immunoglobulin E (IgE) levels were detected by ELISA. Furthermore, lung collagen contents, α-smooth muscle actin (α-SMA), and transforming growth factor-ß1 (TGF-ß1) expression in the airway were assessed by hydroxyproline assay, immunohistochemistry, and Western blot analysis, respectively. GSPE administration significantly suppressed airway resistance as well as reduced the amount of inflammatory cells, especially the eosinophil count, in BALF. Additionally, the GSPE treatment markedly decreased interleukin (IL)-4, IL-13, and vascular endothelial growth factor (VEGF) levels in BALF in addition to the total serum IgE levels. A histological examination demonstrated that GSPE significantly ameliorated allergen-induced lung eosinophilic inflammation and decreased PAS-positive epithelial cells in the airway. The elevated hydroxyproline contents, lung α-SMA contents, and TGF-ß1 protein expression that were observed in the OVA mice were also inhibited by GSPE. In conclusion, GSPE could inhibit airway inflammation and airway remodeling in a murine model of chronic asthma, thus providing a potential treatment for asthma.