Diagnostic value of tumor-associated autoantibodies panel in combination with traditional tumor markers for lung cancer.

Introduction: The diagnostic value of 7 tumor-associated autoantibodies (AABs) including p53, PGP9.5, SOX2, GAGE7, GBU4-5, MEGEA1, and CAGE for the detection of lung cancer has shown inconsistency in several studies. This study aimed to confirm the diagnostic value of 7AABs and to explore whether the diagnostic value would be improved by combining them with 7 traditional tumor-associated antigens (CEA, NSE, CA125, SCC, CA15-3, pro-GRP, and CYFRA21-1) in clinical settings. Methods: The plasma levels of 7-AABs were detected by enzyme-linked immunosorbent assay (ELISA) in 533 lung cancer cases and 454 controls. The 7 tumor antigens (7-TAs) were measured by Electrochemiluminescence immunoassay with Cobas 6000 (Roche, Basel, Switzerland). Results: The positive rate of 7-AABs in the lung cancer group (64.00%) was significantly higher than that of healthy controls (47.90%). The 7-AABs panel was able to discriminate lung cancer from controls with a specificity of 51.50%. After combining the 7-AABs with 7-TAs, the sensitivity showed a significantly enhancement compared with 7AABs panel alone (92.09% vs 63.21%). In patients with resectable lung cancer, the combination of 7-AABs and 7-TAs improved the sensitivity from 63.52% to 97.42. Discussion: In conclusion, our study found that the diagnostic value of 7-AABs was enhanced when combined with 7-TAs. This combined panel could be used as promising biomarker to detect resectable lung cancer in clinical settings.

A Classifier for Improving Early Lung Cancer Diagnosis Incorporating Artificial Intelligence and Liquid Biopsy.

Lung cancer is the leading cause of cancer-related deaths worldwide and in China. Screening for lung cancer by low dose computed tomography (LDCT) can reduce mortality but has resulted in a dramatic rise in the incidence of indeterminate pulmonary nodules, which presents a major diagnostic challenge for clinicians regarding their underlying pathology and can lead to overdiagnosis. To address the significant gap in evaluating pulmonary nodules, we conducted a prospective study to develop a prediction model for individuals at intermediate to high risk of developing lung cancer. Univariate and multivariate logistic analyses were applied to the training cohort (n = 560) to develop an early lung cancer prediction model. The results indicated that a model integrating clinical characteristics (age and smoking history), radiological characteristics of pulmonary nodules (nodule diameter, nodule count, upper lobe location, malignant sign at the nodule edge, subsolid status), artificial intelligence analysis of LDCT data, and liquid biopsy achieved the best diagnostic performance in the training cohort (sensitivity 89.53%, specificity 81.31%, area under the curve [AUC] = 0.880). In the independent validation cohort (n = 168), this model had an AUC of 0.895, which was greater than that of the Mayo Clinic Model (AUC = 0.772) and Veterans' Affairs Model (AUC = 0.740). These results were significantly better for predicting the presence of cancer than radiological features and artificial intelligence risk scores alone. Applying this classifier prospectively may lead to improved early lung cancer diagnosis and early treatment for patients with malignant nodules while sparing patients with benign entities from unnecessary and potentially harmful surgery. Clinical Trial Registration Number: ChiCTR1900026233, URL: http://www.chictr.org.cn/showproj.aspx?proj=43370.

Inflammation characteristics and anti-inflammation treatment with tocilizumab of severe/critical COVID-19 patients: A retrospective cohort study.

The efficacy of tocilizumab on the prognosis of severe/critical COVID-19 patients is still controversial so far. We aimed to delineate the inflammation characteristics of severe/critical COVID-19 patients and determine the impact of tocilizumab on hospital mortality. Here, we performed a retrospective cohort study which enrolled 727 severe or critical inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China), among which 50 patients received tocilizumab. This study confirmed that most recovered patients manifested relatively normal inflammation levels at admission, whereas most of the deceased cases presented visibly severe inflammation at admission and even progressed into extremely aggravated inflammation before their deaths, proved by some extremely high concentrations of interleukin-6, procalcitonin, C-reactive protein and neutrophil count. Moreover, based on the Cox proportional-hazards models before or after propensity score matching, we demonstrated that tocilizumab treatment could lessen mortality by gradually alleviating excessive inflammation and meanwhile continuously enhancing the levels of lymphocytes within 14 days for severe/critical COVID-19 patients, indicating potential effectiveness for treating COVID-19.

Single-nucleotide polymorphism rs4142441 and MYC co-modulated long non-coding RNA OSER1-AS1 suppresses non-small cell lung cancer by sequestering ELAVL1.

Single-nucleotide polymorphisms (SNP) and long non-coding RNAs (lncRNAs) have been involved in the process of lung cancer. Following clues given by lung cancer risk-associated SNP, we aimed to find novel functional lncRNAs as candidate targets in lung cancer. We identified a lncRNA Oxidative Stress Responsive Serine Rich 1 Antisense RNA 1 (OSER1-AS1) through a lung cancer risk-associated SNP rs4142441. OSER1-AS1 was down-regulated in tumor tissue and its low expression was significantly associated with poor overall survival among non-smokers in non-small cell lung cancer (NSCLC) patients. Gain- and loss-of-function studies showed that OSER1-AS1 acted as a tumor suppressor by inhibiting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays and a metastasis mouse model confirmed that OSER1-AS1 suppressed tumor growth and metastasis in vivo. The promoter of OSER1-AS1 was repressed by MYC, and the 3'-end of OSER1-AS1 was competitively targeted by microRNA hsa-miR-17-5p and RNA-binding protein ELAVL1. Our results indicated that OSER1-AS1 exerted tumor-suppressive functions by acting as an ELAVL1 decoy to keep it away from its target mRNAs. Our findings characterized OSER1-AS1 as a new tumor-suppressive lncRNA in NSCLC, suggesting that OSER1-AS1 may be suitable as a potential biomarker for prognosis, and a potential target for treatment.

Circulating Long Noncoding RNAs Act as Diagnostic Biomarkers in Non-Small Cell Lung Cancer.

Identification of novel effective early diagnostic biomarkers may provide alternative strategies to reduce the mortality for non-small cell lung cancer (NSCLC) patients. Circulating long non-coding RNAs (lncRNAs) have emerged as a new class of promising cancer biomarkers. Our study aimed to identify circulating lncRNAs for diagnosing NSCLC. A total 528 plasma samples were continuously collected and allocated to four progressive phases: discovery, training, verification, and expansion phases. The expression of candidate lung cancer related lncRNAs were detected using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We identified a 4-lncRNA panel (RMRP, NEAT1, TUG1, and MALAT1) that provided a high diagnostic value in NSCLC (AUC = 0.86 and 0.89 for training and verification phase, respectively). Subgroup analyses showed that the 4-lncRNA panel had a sensitivity of 78.95% [95% confidence interval (CI) = 62.22%-89.86%] in stage I-II patients and 75.00% (95% CI = 52.95%-89.40%) in patients with small tumor size (≤3cm). Notably, the sensitivity of 4-lncRNA panel was significantly higher than that of routine protein panels in adenocarcinoma (CEA, CA125, and CYFRA21-1, 86.30% vs. 73.96%). Adding 4-lncRNA to protein markers significantly improved the diagnostic capacity in both adenocarcinoma (AUC=0.85, 95% CI = 0.78-0.91) and squamous cell carcinoma (AUC=0.93, 95% CI = 0.86-0.97). In conclusion, we identified a plasma 4-lncRNA panel that has considerable clinical value in diagnosing NSCLC. The 4-lncRNA panel could improve the diagnostic values of routine tumor protein markers in diagnosing NSCLC. Circulating lncRNAs could be used as promising candidates for NSCLC diagnosis.

Hypoxia-sensitive LINC01436 is regulated by E2F6 and acts as an oncogene by targeting miR-30a-3p in non-small cell lung cancer.

Dysregulation of long noncoding RNA (lncRNA) is known to be involved in numerous human diseases, including lung cancer. However, the precise biological functions of most lncRNA remain to be elucidated. Here, we identified a novel up-regulated lncRNA, LINC01436 (RefSeq: NR_110419.1), in non-small cell lung cancer (NSCLC). High expression of LINC01436 was significantly associated with poor overall survival. Notably, LINC01436 expression was transcriptionally repressed by E2F6 under normoxia, and the inhibitory effect was relieved in a hypoxic microenvironment. Gain- and loss-of-function studies revealed that LINC01436 acted as a proto-oncogene by promoting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays in nude mice confirmed that LINC01436 promoted tumor growth and metastasis in vivo. Mechanistically, LINC01436 exerted biological functions by acting as a microRNA (miR)-30a-3p sponge to regulate the expression of its target gene EPAS1. Our findings characterize LINC01436 as a new hypoxia-sensitive lncRNA with oncogenic function in NSCLC, suggesting that LINC01436 may be a potential biomarker for prognosis and a potential target for treatment.

Effects of patient-controlled analgesia with hydromorphone or sufentanil on postoperative pulmonary complications in patients undergoing thoracic surgery: a quasi-experimental study.

OBJECTIVE: To compare the analgesic effects of patient-controlled intravenous analgesia (PCA) with hydromorphone and sufentanil after thoracic surgery on postoperative pulmonary complications (PPCs). METHODS: A total of 142 patients who were scheduled for thoracic surgery were randomly allocated to receive PCA with hydromorphone (group A: experimental group): hydromorphone 0.2 mg/kg + dezocine 0.5 mg/kg + ramosetron 0.6 mg diluted with normal saline to 200 mL; or with sufentanil (group B: control group): sufentanil 3.0µg/kg + dezocine 0.5 mg/kg + ramosetron 0.6 mg diluted with normal saline to 200 mL. The parameters of intravenous analgesia pump were set as background dose 4 ml/h, PCA dose 1 mL, locking time 15 min. Pain NRS (numerical rating scale), Ramsay sedation score, nausea or vomiting score were evaluated at 0 h, 6 h, 12 h, 24 h, 48 h after operation. The cases of PPCs (atelectasis, pulmonary infection, respiratory failure), CRP (C-reaction protein) and inflammatory cells (white cell count and percentage of neutrophils) and blood gas analysis at 12 h after operation, length of ICU and postoperative stay were recorded for each patient. RESULTS: Data of 136 patients were analyzed. Compared with group B (4[IQR:2,2]), the pain NRS in group A (2[IQR:4,4]) was significantly lower at 6 h after operation (P = 0.000). The CRP in group A (69.79 ± 32.13 mg/L) were lower than group B (76.76 ± 43.42 mg/L) after operation, but the difference was not significant (P = 0.427). No difference of nausea or vomiting was found between group A (7.3%) and group B (5.8%) postoperatively (P = 0.999). The PPCs were happened in 11 patients in group A (16.2%) and 22 patients in group B (32.4%) and the difference between two groups was significant (P = 0.027). Seven patients in group A (10.3%) and eighteen patients in group B (26.5%) had clinical evidence of pneumonia and the difference between two groups was significant (P = 0.014). The length of ICU and postoperative stay in group A were 2.73 h and 1.82 days less than group B respectively but the differences were not significant (P = 0.234, P = 0.186 respectively). CONCLUSION: Compared with sufentanil, hydromorphone may provide better postoperative analgesic effect with less pulmonary complications for patients undergoing thoracic surgery, and it may accelerate patients' rehabilitation. TRIAL REGISTRATION: Randomized Controlled Trials ChiCTR1800014282c . Registered 3 January 2018.

Dichloroacetate enhances the antitumor efficacy of chemotherapeutic agents via inhibiting autophagy in non-small-cell lung cancer.

BACKGROUND: Chemotherapy is still the primary adjuvant strategy of cancer therapy; however, the emergence of multi-drug resistance has been a cause for concern. Autophagy has been demonstrated to have a protective role against chemotherapeutic drugs in cancer cells, and autophagy inhibition is generally considered to be a promising therapeutic strategy. However, the paucity of effective and specific autophagy inhibitors limits its application. PURPOSE: The objective of this study was to explore the effect of DCA, small molecular anti-tumor agent, on the autophagy regulation and chemosensitization in NSCLC cells. METHODS: We investigated the autophagy regulation of dichloroacetate (DCA) by laser confocal microscopy and western blotting in A549 and H1975 cell lines. The MTT assay and flow cytometry was performed for explore the chemosensitization effectiveness of DCA. The results were verified with subcutaneous tumor model in nude mice and the immunohistochemistry was applied for assessing the level of cell apoptosis and autophagy in vivo post treatment. RESULTS: We found that DCA, which exhibited antitumor properties in various carcinoma models, induced apoptosis of non-small cell lung cancer cells (NSCLC) by inhibiting cancer cell autophagy. Furthermore, Perifosine, an AKT inhibitor, can greatly weaken the capacity of inducing apoptosis by DCA. The results indicate that the AKT-mTOR pathway, a main negative regulator of autophagy, is involved in the DCA-induced inhibition of autophagy. Then, we detected the effectiveness of autophagy inhibition by DCA. When used in co-treatment with the chemotherapeutic drug paclitaxel (PTX), DCA markedly decreased cell autophagy, enhanced apoptosis and inhibited proliferation in A549 and H1975 cells. The results of the xenograft experiment demonstrate that co-treatment of PTX and DCA can significantly decrease cell proliferation in vivo and prolong the survival of mice. CONCLUSION: Our results suggest that DCA can inhibit cell autophagy induced by chemotherapeutics, providing a new avenue for cancer chemotherapy sensitization.

Plasma exosome levels in non-small-cell lung cancer: Correlation with clinicopathological features and prognostic implications.

BACKGROUND: Biomarker studies revealed important clinical significance of exosome for cancer patients. However, there is currently no consensus on exosome quantification methods. METHODS: Bicinchoninic acid (BCA) method, acetylcholinesterase (AChE) method and nanoparticle tracking analysis (NTA) were utilized to quantify 20 plasma exosome samples, and interrelations between these three methods were explored. Associations of plasma exosome levels with characteristics and prognosis of 208 non-small-cell lung cancer (NSCLC) patients were investigated. RESULTS: Results of the three methods for exosome quantification were significantly correlated with each other. Correlation coefficient between AChE and NTA (r= 0.79, P< 0.001) was greater than that between BCA and NTA (r= 0.64, P= 0.003). Plasma exosome levels of 208 NSCLC patients were then quantified with AChE method. Exosome level was significantly associated with tumour stage (P< 0.001) and the history of chronic obstructive pulmonary disease (P= 0.023). Cox proportional hazard analysis demonstrated that higher exosome level was independently associated with poorer overall survival (P= 0.033; hazard ratio = 1.72, 95% confidence interval: 1.05-2.83). CONCLUSIONS: Plasma exosome level correlates with tumor stage and the history of chronic obstructive pulmonary disease, and may serve as a prognostic factor for NSCLC.

Long non-coding RNA MUC5B-AS1 promotes metastasis through mutually regulating MUC5B expression in lung adenocarcinoma.

Long non-coding RNAs (lncRNAs) have been involved in the process of cancer occurrence, progression, and treatment. Lung cancer-related lncRNAs are still an emerging field, thus we sought to identify novel functional lncRNAs as candidate targets in lung cancer. Here, we identified one novel lncRNA, MUC5B-AS1 (Ensembl: ENST00000532061.2). MUC5B-AS1 was upregulated in lung adenocarcinoma tissues compared with normal lung tissues. Moreover, MUC5B-AS1 promoted lung cancer cell migration and invasion in vitro and promoted lung cancer cell metastasis in vivo. MUC5B-AS1 and its cognate sense transcript MUC5B were highly co-expressed and mutually regulated in lung adenocarcinoma. Mechanistically, MUC5B-AS1 promoted cell migration and invasion by forming an RNA-RNA duplex with MUC5B, thereby increasing MUC5B expression levels in lung adenocarcinoma. The high expression of MUC5B was significantly associated with poor outcomes in lung adenocarcinoma. Our findings highlight MUC5B-AS1 functions as an oncogenic lncRNA in tumor metastasis and implicate MUC5B-AS1 as an attractive candidate target for lung adenocarcinoma treatment.

Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer.

Exosomal miRNAs are proposed as excellent candidate biomarkers for clinical applications. However, little is known about their potential roles as prognostic biomarkers in lung cancer. In this study, we explored the prognostic value of plasma exosomal microRNAs (miRNAs) for non-small-cell lung cancer (NSCLC). Using a quantitative polymerase chain reaction (qPCR) array panel, we analyzed 84 plasma exosomal miRNAs in 10 lung adenocarcinoma patients and 10 matched healthy controls. The qPCR array showed 30 aberrantly expressed exosomal miRNAs. Nine candidate miRNAs were selected based on differential expression and previous reports for further evaluating their prognostic roles in 196 NSCLC patients. Elevated levels of exosomal miR-23b-3p, miR-10b-5p and miR-21-5p were independently associated with poor overall survival (with hazard ratio [95% confidence interval]: 2.42 (1.45 - 4.04), P = 0.001; 2.22 (1.18 - 4.16), P = 0.013; 2.12 (1.28 - 3.49), P = 0.003, respectively). When compared to the clinical prognostic variables only model, adding the three exosomal miRNA signatures significantly improved survival predictive accuracy with an increase of time-dependent area under the receiver operating characteristic curve from 0.88 to 0.91 (P=0.015). Our results indicated that plasma exosomal miR-23b-3p, miR-10b-5p and miR-21-5p are promising non-invasive prognostic biomarkers of NSCLC.

OLA1 contributes to epithelial-mesenchymal transition in lung cancer by modulating the GSK3ß/snail/E-cadherin signaling.

Obg-like ATPase 1 (OLA1) belongs to the Obg family of P-loop NTPases, and may serve as a "molecular switch" regulating multiple cellular processes. Aberrant expression of OLA1 has been observed in several human malignancies. However, the role of OLA1 in cancer progression remains poorly understood. In this study, we used the Kaplan-Meier plotter search tool to show that increased expression of OLA1 mRNA was significantly associated with shorter overall survival in lung cancer patients. By immunohistochemical analysis we discovered that levels of OLA1 protein in lung cancer tissues were positively correlated with TNM stage and lymph node metastasis, but negatively correlated with the epithelial-mesenchymal transition (EMT) marker E-cadherin. Knockdown of OLA1 in a lung adenocarcinoma cell line rendered the cells more resistant to TGF-ß-induced EMT and the accompanied repression of E-cadherin. Furthermore, our results demonstrated that OLA1 is a GSK3ß-interacting protein and inhibits GSK3ß activity by mediating its Ser9 phosphorylation. During EMT, OLA1 plays an important role in suppressing the GSK3ß-mediated degradation of Snail protein, which in turn promotes downregulation of E-cadherin. These data suggest that OLA1 contributes to EMT by modulating the GSK3ß/Snail/E-cadherin signaling, and its overexpression is associated with clinical progression and poor survival in lung cancer patients.

Association between Th17-related cytokines and risk of non-small cell lung cancer among patients with or without chronic obstructive pulmonary disease.

BACKGROUND: CD4 (+) T helper 17 (Th17) cells play critical roles in inflammation and tumor development. The involvement of Th17 cells in chronic obstructive pulmonary disease (COPD)-type inflammation-associated lung cancer has also been confirmed in animal models. However, to the authors' knowledge, it is unknown whether the role of Th17 cells is different in patients with lung cancer complicated with COPD compared with those without COPD. In the current study, the authors attempted to determine the association between the circulating levels of Th17-related cytokines and the clinical characteristics of non-small cell lung cancer (NSCLC) in patients with or without COPD. METHODS: The authors designed a matched case-control study that included 70 patients with NSCLC with COPD, 148 patients with NSCLC without COPD, and 148 healthy controls. The data regarding the clinicopathological features of these participants were collected. Circulating levels of Th17-related cytokines, including interleukin (IL) 23 (IL-23), IL-17A, IL-17F, IL-22, and tumor necrosis factor-α, were measured. RESULTS: The circulating levels of IL-23, IL-17A, IL-17F, IL-22, and tumor necrosis factor-α were found to be significantly higher in the patients with NSCLC compared with the healthy controls (P<.05). The elevated levels were found to be significantly associated with lung cancer risk (P<.05). However, no significant differences were found between patients with NSCLC with COPD and patients without COPD. It is interesting to note that, among patients with NSCLC without COPD, the levels of these cytokines were consistently higher among patients with stage I to stage IIIA disease compared with those with stage IIIB to stage IV disease (P<.05). In addition, the 5 Th17-related cytokines demonstrated pairwise correlations, with Spearman rank correlation coefficients of 0.646 to 0.888 (P<.05). CONCLUSIONS: The results of the current study indicate a clear association between the Th17-related cytokine profile and the risk of NSCLC complicated by the presence or absence of COPD.

A Comparison of Laparoscopy and Laparotomy for the Management of Abdominal Trauma: A Systematic Review and Meta-analysis.

BACKGROUND: This study aimed to systematically review and compare the perioperative outcomes of laparoscopy with laparotomy for abdominal trauma patients. METHODS: We conducted a systematic review and meta-analysis comparing the perioperative outcomes of laparoscopy with laparotomy for abdominal trauma patients. Clinical endpoints included length of hospital stay, operation time, amount of intraoperative blood loss, time to postoperative exhaust, time to regular diet, time to out of bed, duration of postoperative pain, postoperative complications, perioperative mortality rate, length of intensive care unit (ICU) stay, missed injuries, conversions to laparotomy, and cure rate. RESULTS: Sixty-four studies including 9058 patients with abdominal trauma were included. In these studies, laparoscopy was used as a screening, diagnostic, or therapeutic tool. Meta-analysis showed significant reductions in the incidence of postoperative complications (relative risk [RR] [95 % confidence interval (CI)] 0.37 [0.29-0.46]), perioperative mortality rate (RR 0.64; 95 % CI 0.52-0.80), operation time (mean difference [MD] [95 % CI] -19.93 min [-34.43 to 5.43]), length of hospital stay (MD -5.15 days; 95 % CI -6.80 to 3.50), amount of intraoperative blood loss (MD -141.33 ml; 95 % CI -260.99 to 21.67), time to postoperative exhaust (MD -5.32 h; 95 % CI -8.60 to 2.05), time to regular diet (MD -3.46 h; 95 % CI -6.31 to 0.61), time to out of bed (MD -23.51 h; 95 % CI -24.85 to 22.16), duration of postoperative pain (MD -21.34 h; 95 % CI -22.65 to 20.03), length of ICU stay (MD -1.89 days; 95 % CI -4.05 to 0.27) in patients with abdominal trauma treated with laparoscopy compared with laparotomy. The pooled incidence of postoperative complications, missed injuries, conversions, and perioperative mortality rate of laparoscopy among the case reports were 0.04 (95 % CI 0.03-0.06), 0.01 (95 % CI 0.01-0.02), 0.24 (95 % CI 0.20-0.28), 0.01(95 % CI 0.01-0.02), respectively. Cure rate of laparoscopy ranged from 46 to 95 % and the pooled rate was 0.76 (95 % CI 0.71-0.81). CONCLUSIONS: Laparoscopy is an effective way to improve perioperative outcomes and reduce the complications of hemodynamically stable patients with abdominal trauma. It is worth further popularization in clinical practice.

A comparison of video-assisted thoracoscopic surgery with open thoracotomy for the management of chest trauma: a systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically review and compare the perioperative outcomes of video-assisted thoracoscopy (VATS) with open thoracotomy for chest trauma patients. METHODS: We conducted a systematic review and meta-analysis of randomized control trials and cohort studies comparing the perioperative outcomes of VATS with open thoracotomy for chest trauma patients. Clinical endpoints included postoperative complications, perioperative mortality rate, chest tube drainage volume, duration of tube drainage, duration of hospitalization, operation time, and amount of bleeding and transfusion volume in operation. A subgroup analysis was performed to explore the potential source of heterogeneity. RESULTS: Twenty-six studies were included. Pooled analyses showed significant reductions in the incidence of postoperative complications (risk ratio [RR] [95% confidence interval (CI)], 0.47 [0.35, 0.64]), chest tube drainage volume (mean difference [MD] [95% CI], -146.88 ml [-196.04, -97.72]), duration of tube drainage (MD, -1.71 days; 95% CI -2.16 to -1.26), duration of hospitalization (MD, -4.67 days; 95% CI -5.19 to-4.14), operation time (MD, -41.18 min; 95% CI -52.85 to -29.51), and amount of bleeding (MD, -119.10 ml; 95% CI -147.28 to -90.92) and transfusion volume (MD, -379.51 ml; 95% CI -521.24 to-237.77) in chest trauma patients treated with VATS compared with open thoracotomy. The perioperative mortality rate was not significantly different between patients received VATS and open thoracotomy (RR, 0.52; 95% CI 0.22-1.21). CONCLUSIONS: Compared to open thoracotomy, VATS is an effective and even better treatment for improving perioperative outcomes of hemodynamically stable patients with chest trauma and reduce the complications. However, caution should also be exercised in certain clinical scenarios.

Prognostic and predictive significance of thymidylate synthase protein expression in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: It remains controversial whether thymidylate synthase (TS) protein expression is associated with survival for patients with non-small cell lung cancer (NSCLC). OBJECTIVE: To evaluate prognostic and predictive significance of tumor TS protein level in NSCLC. METHODS: Electronic searches were performed for relevant studies in PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature Database. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled for meta-analysis. Subgroup and sensitivity analyses were performed. Publication bias was evaluated by funnel plot and Begg's test. RESULTS: Twenty-four studies, including 2280 patients, were eligible. This analysis showed that patients with low TS expression had statistically significantly longer OS and PFS than those with high TS (HR=0.51 and HR=0.49, respectively). Based on TS-targeted drug use status, TS expression was significantly associated with OS in pemetrexed (HR=0.42) and 5-Fluorouracil subgroups (HR=0.34), but not in no TS-targeted drug subgroup. There were similar results for PFS analyses. Sensitivity analysis indicated that the results were robust. Begg's test did not reveal any publication bias. CONCLUSION: Low TS protein expression is a favorable predictive factor for better OS/PFS in NSCLC patients treated with TS-targeted drugs. Prognostic value of TS protein expression needs further validation.

Prognostic value of circulating inflammatory factors in non-small cell lung cancer: a systematic review and meta-analysis.

INTRODUCTION: Inflammation has been recognized as an important contributing factor in the development and progression of lung cancer. However, the relationship between the magnitude of inflammation and prognosis in patients with lung cancer remains unclear. This meta-analysis aimed to investigate the association between levels of circulating inflammatory factors and clinical survival in patients with non-small cell lung cancer(NSCLC). METHODS: We conducted a meta-analysis of cohort studies to evaluate the prognostic effect of circulating inflammatory factors. Twenty-three studies were eligible and included in our meta-analysis. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to assess the predictive ability of circulating inflammatory factors on overall survival (OS) in patients with NSCLC. RESULTS: In overall analysis, high circulating C-reactive protein (CRP) and interleukin-6 (IL-6) level were significantly associated with shorter OS in NSCLC. However, either in CRP or IL-6 subgroup analysis by treatment, significant association with poor prognosis was observed in (radio)chemotherapy group (HR[95% CI]:1.30 [1.09-1.54] and 1.80 [1.32-2.46]; respectively), but not in surgery group. Additionally, there was no significant association between circulating IL-8, IL-10, TNF-α level and OS. CONCLUSION: Increased circulating CRP and IL-6 levels were significantly associated with poor prognosis especially in patients with unresectable NSCLC.

Dual role of TGF-ß1 on Fas-induced apoptosis in lung epithelial cells.

Recent evidence suggests that TGF-ß1 has a dual role in regulating cell response to Fas/Fas ligand (FasL)-induced apoptosis. TGF-ß1 may play a positive or negative role on cell sensitivity to apoptosis via Fas/FasL system, depending on cell types and their specific environment. TGF-ß1 and the Fas/FasL system are also involved in pathological processes of acute lung injury (ALI) and interstitial lung diseases including early lung injury and subsequent tissue repair. However, it is not well understood how TGF-ß1 regulates Fas/FasL mediated apoptotic signaling in lung epithelium. In this study, we found that TGF-ß1 could affect the sensitivity of lung epithelial A549 cells to Fas/FasL mediated apoptosis in a time-dependent manner. Apoptosis of A549 cells could be enhanced significantly by co-treatment with TGF-ß1 and FasL, or pretreatment with TGF-ß1 followed by FasL exposure, as evidenced by markedly increased caspase-8 and JNK activities. However, prolonged exposure to TGF-ß1 could result in an obvious inhibition of the Fas/FasL-induced apoptosis, accompanied by down-regulation of Fas and up-regulation of c-Flip. Our results also showed that the effect of TGF-ß1 on cell sensitivity to Fas-mediated apoptosis was independent of Akt pathway activation. These findings suggest that timely interplay of TGF-ß1 and the Fas/FasL system could determine the final outcomes of cell survival/death signaling, for example, switching cell death signaling to survival signaling during early injury and later repair process of lung epithelium.

Hypoxia-induced SOCS3 is limiting STAT3 phosphorylation and NF-κB activation in congenital heart disease.

Suppressor of cytokine signaling 3 (SOCS3) is a critical attenuator of the JAK-STAT signaling pathway, and it is involved in mediating the intensity and duration of STAT3 activation in the process of myocardial protection. Nuclear factor-κB (NF-κB) has emerged as a decisive transcription factor in cardiac myocyte compensatory responses to stress that enhance survival. However, the expression, activation and regulation of this signaling molecule in response to hypoxic stress have not been elucidated. We investigated 40 infants with cyanotic or acyanotic cardiac defects, as well as H9c2 embryonic rat cardiomyocytes, to examine the effect of hypoxia on the expression or activation of SOCS3, STAT3 and NF-κB in vivo and in vitro. We found an increase in endogenous cardiac SOCS3, p-STAT3 and AC-RelA activation in the myocardium of infants with cyanotic cardiac defects. In hypoxic cultivated H9c2 cells, SOCS3, STAT3 and AC-RelA activity slowly increased and then reached a stable expression. We evaluated the interaction of SOCS3 with STAT3 and NF-κB by transfecting the SOCS3 plasmid to hypoxic cultured H9c2 cells. Forced expression of SOCS3suppressed tyrosine phosphorylation of STAT3 and transcription of the C-myc and interleukin-6 genes. AC-RelA activation was also suppressed by over expression of SOCS3. These findings suggest that the mechanism of a positive transactivation loop that maintains higher levels of NF-κB and p-STAT3 and the negative feedback factor SOCS3, which maintains balanced NF-κB and p-STAT3 activities, is important in the process of myocardial adaptation to chronic hypoxia. SOCS3 is a rapid hypoxia inducible gene and acts to inhibit activation of the cellular signaling pathway in a classical negative feedback loop. Upregulated SOCS3 might play an important role in cardiocytes during chronic hypoxia as SOCS3 regulates cell signaling crosstalking between NF-κB and p-STAT3 under stressful conditions.