Incidence and influence factors of venous thromboembolism in traumatic rib fracture patient: a multicenter study.

BACKGROUND: This study aimed to determine the incidence and influencing factors of venous thromboembolism (VTE) in patients with traumatic rib fractures. METHODS: The retrospective study analyzed medical records of patients with traumatic rib fractures from 33 hospitals. RESULTS: The overall incidence of VTE in hospitalized patients with traumatic rib fractures was 8.1%. Patients with isolated traumatic rib fractures had a significantly lower incidence of VTE (4.4%) compared to patients with rib fractures combined with other injuries (12.0%). Multivariate analysis identified the number of rib fractures as an independent risk factor for thrombosis. Surgical stabilization of isolated rib fractures involving three or more ribs was associated with a lower VTE incidence compared to conservative treatment. CONCLUSIONS: Patients with rib fractures have a higher incidence of VTE, positively correlated with the number of rib fractures. However, the occurrence of thrombosis is relatively low in isolated rib fractures. Targeted thromboprophylaxis strategies should be implemented for these patients, and surgical stabilization of rib fractures may be beneficial in reducing the risk of VTE.

Arecoline promotes Akt-c-Myc-driven aerobic glycolysis in esophageal epithelial cells.

Aerobic glycolysis is a typical metabolic rearrangement for tumorigenesis. Arecoline is of explicit carcinogenicity, numerous works demonstrate its mutagenicity, genotoxicity, and cytotoxicity. However, the effects of arecoline on aerobic glycolysis of esophageal epithelial cells remain unclear. In the present study, 5 µM arecoline efficiently increased HK2 expression to induce aerobic glycolysis in Het-1A-Are and NE2-Are cells. The mechanistic analysis showed that arecoline activated the Akt-c-Myc signaling pathway and reduced the GSK3ß-mediated phosphorylation of c-Myc on Thr58 to prevent its ubiquitination and destruction, subsequently promoting HK2 transcription and expression. Taken together, these results suggest that arecoline can induce aerobic glycolysis of esophageal epithelial cells and further confirm that arecoline is a carcinogen harmful to human health.

Identification and validation of a 4-extracellular matrix gene signature associated with prognosis and immune infiltration in lung adenocarcinoma.

Background: The extracellular matrix (ECM) plays a crucial role in the development and tumor microenvironment of lung adenocarcinoma (LUAD). This study aimed to establish a risk score of ECM-related genes in LUAD and explore the association between the risk score and patient survival as well as immune cell infiltration, somatic mutations, and therapy response. Methods: Gene expression data from The Cancer Genome Atlas (TGCA) and eight Gene Expression Omnibus (GEO) databases were used to analyze and identify differentially expressed genes (DEGs). Prognostic ECM-related genes were identified and utilized to formulate a prognostic signature. A nomogram was constructed using TCGA dataset and validated in two GEO datasets. Differences between high- and low-risk patients were analyzed for function enrichment, immune cell infiltration, somatic mutations, and therapy response. Finally, Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression of DEGs in LUAD. Results: A risk score based on four ECM-related genes, ANOS1, CD36, COL11A1, and HMMR, was identified as an independent prognostic factor for overall survival (OS) compared to other clinical variables. Subsequently, a nomogram incorporating the risk score and TNM staging was developed using the TCGA dataset. Internal and external validation of the nomogram, conducted through calibration plots, C-index, time-dependent receiver operating characteristics (ROC), integrated discrimination improvement (IDI), and decision curve analyses (DCA), demonstrated the excellent discriminatory ability and clinical practicability of this nomogram. The risk score correlated with the distribution of function enrichment, immune cell infiltration, and immune checkpoint expression. More somatic mutations occurred in the high-risk group. The risk score also demonstrated a favorable ability to predict immunotherapy response and drug sensitivity. Conclusion: A novel signature based on four ECM-related genes is developed to help predict LUAD prognosis. This signature correlates with tumor immune microenvironment and can predict the response to different therapies in LUAD patients.

Construction and validation of a novel prognostic model of neutrophil­related genes signature of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) remains an incurable disease with a poor prognosis. This study aimed to explore neutrophil­related genes (NRGs) and develop a prognostic signature for predicting the prognosis of LUAD. NRGs were obtained by intersecting modular genes identified by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data and the marker genes of neutrophils identified from single-cell RNA-sequencing(scRNA-seq) data. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analyses were run to construct a prognostic signature, follow by delineation of risk groups, and external validation. Analyses of ESTIMAT, immune function, Tumor Immune Dysfunction and Exclusion (TIDE) scores, Immune cell Proportion Score (IPS), and immune checkpoint genes between high- and low-risk groups were performed, and then analyses of drug sensitivity to screen for sensitive anticancer drugs in high-risk groups. A total of 45 candidate NRGs were identified, of which PLTP, EREG, CD68, CD69, PLAUR, and CYP27A1 were considered to be significantly associated with prognosis in LUAD and were used to construct a prognostic signature. Correlation analysis showed significant differences in the immune landscape between high- and low-risk groups. In addition, our prognostic signature was important for predicting drug sensitivity in the high-risk group. Our study screened for NRGs in LUAD and constructed a novel and effective signature, revealing the immune landscape and providing more appropriate guidance protocols in LUAD treatment.

An ensemble deep learning model for risk stratification of invasive lung adenocarcinoma using thin-slice CT.

Lung cancer screening using computed tomography (CT) has increased the detection rate of small pulmonary nodules and early-stage lung adenocarcinoma. It would be clinically meaningful to accurate assessment of the nodule histology by CT scans with advanced deep learning algorithms. However, recent studies mainly focus on predicting benign and malignant nodules, lacking of model for the risk stratification of invasive adenocarcinoma. We propose an ensemble multi-view 3D convolutional neural network (EMV-3D-CNN) model to study the risk stratification of lung adenocarcinoma. We include 1075 lung nodules (≤30 mm and ≥4 mm) with preoperative thin-section CT scans and definite pathology confirmed by surgery. Our model achieves a state-of-art performance of 91.3% and 92.9% AUC for diagnosis of benign/malignant and pre-invasive/invasive nodules, respectively. Importantly, our model outperforms senior doctors in risk stratification of invasive adenocarcinoma with 77.6% accuracy [i.e., Grades 1, 2, 3]). It provides detailed predictive histological information for the surgical management of pulmonary nodules. Finally, for user-friendly access, the proposed model is implemented as a web-based system ( https://seeyourlung.com.cn ).

BACH1 promotes lung adenocarcinoma cell metastasis through transcriptional activation of ITGA2.

BACH1 plays an important role in promoting cancer. This study aims to further verify the relationship between the expression level of BACH1 in lung adenocarcinoma prognosis, as well as the influence of BACH1 expression on lung adenocarcinoma and the potential mechanism. The expression level of BACH1 in lung adenocarcinoma and its relationship with prognosis was evaluated by lung adenocarcinoma tissue microarray analysis combined with bioinformatics approaches. Gene knockdown and overexpression were used to investigate the functions and molecular mechanisms of BACH1 in lung adenocarcinoma cells. The regulatory downstream pathways and target genes of BACH1 in lung adenocarcinoma cells were explored by bioinformatics and RNA sequencing data analysis, real-time PCR, western blot analysis, and cell immunofluorescence and cell adhesion assays. Chromatin immunoprecipitation and dual-luciferase reporter assays were carried out to verify the target gene binding site. In the present study, BACH1 is abnormally highly expressed in lung adenocarcinoma tissues, and high BACH1 expression is negatively correlated with patient prognosis. BACH1 promotes the migration and invasion of lung adenocarcinoma cells. Mechanistically, BACH1 directly binds to the upstream sequence of the ITGA2 promoter to promote ITGA2 expression, and the BACH1-ITGA2 axis is involved in cytoskeletal regulation in lung adenocarcinoma cells by activating the FAK-RAC1-PAK signaling pathway. Our results indicated that BACH1 positively regulates the expression of ITGA2 through a transcriptional mechanism, thereby activating the FAK-RAC1-PAK signaling pathway to participate in the formation of the cytoskeleton in tumor cells and then promoting the migration and invasion of tumor cells.

Development and validation of a pulmonary complications prediction model based on the Yang's index.

Background: Blunt chest trauma patients with pulmonary contusion are susceptible to pulmonary complications, and severe cases may develop respiratory failure. Some studies have suggested the extent of pulmonary contusion to be the main predictor of pulmonary complications. However, no simple and effective method to assess the severity of pulmonary contusion has been available yet. A reliable prognostic prediction model would facilitate the identification of high-risk patients, so that early intervention can be given to reduce pulmonary complications; however, no suitable model based on such an assumption has been available yet. Methods: In this study, a new method for assessing lung contusion by the product of the three dimensions of the lung window on the computed tomography (CT) image was proposed. We conducted a retrospective study on patients with both thoracic trauma and pulmonary contusion admitted to 8 trauma centers in China from January 2014 to June 2020. Using patients from 2 centers with a large number of patients as the training set and patients from the other 6 centers as the validation set, a prediction model for pulmonary complications was established with Yang's index and rib fractures, etc., being the predictors. The pulmonary complications included pulmonary infection and respiratory failure. Results: This study included 515 patients, among whom 188 developed pulmonary complications, including 92 with respiratory failure. Risk factors contributing to pulmonary complications were identified, and a scoring system and prediction model were constructed. Using the training set, models for adverse outcomes and severe adverse outcomes were developed, and area under the curve (AUC) of 0.852 and 0.788 were achieved in the validation set. In the model performance for predicting pulmonary complications, the positive predictive value of the model is 0.938, the sensitivity of the model is 0.563 and the specificity of the model is 0.958. Conclusions: The generated indicator, called Yang's index, was proven to be an easy-to-use method for the evaluation of pulmonary contusion severity. The prediction model based on Yang's index could facilitate early identification of patients at risk of pulmonary complications, yet the effectiveness of the model remains to be validated and its performance remains to be improved in further studies with larger sample sizes.

NOD2 inhibits the proliferation of esophageal adenocarcinoma cells through autophagy.

AIM: To study the regulatory mechanism of NOD2 in the inhibition of esophageal adenocarcinoma cell proliferation. METHODS: Cell experiments: after confirming the decrease in NOD2 expression in esophageal adenocarcinoma, we overexpressed NOD2 in esophageal adenocarcinoma cells via lentivirus, compared and verified the changes in esophageal adenocarcinoma cell proliferation before and after NOD2 overexpression, and compared the overexpression group with the control group by mRNA sequencing to identify pathways that may affect cell proliferation. Then, the autophagy level of multiple groups were assessed, and the results were verified by rescue experiments. In vivo experiments: we administered esophageal adenocarcinoma cells to nude mice to form tumors under their skin and then injected the tumors with NOD2 overexpression lentivirus and negative control lentivirus. After a period of time, the growth curve of the tumor was generated, and the tumor was removed to generate sections. Ki67 was labeled with immunohistochemistry to verify cell proliferation, and the protein was extracted from the tissue to detect the molecular indices of the corresponding pathway. RESULTS: Upregulation of NOD2 expression inhibited the proliferation of esophageal adenocarcinoma cells. Upregulation of NOD2 expression increased the autophagy level of esophageal adenocarcinoma cells via ATG16L1. After ATG16L1 was inhibited, NOD2 had no significant effect on autophagy and proliferation of esophageal adenocarcinoma cells. Enhanced autophagy in esophageal adenocarcinoma cell lines inhibited cell proliferation. In vivo, the upregulation of NOD2 expression improved the autophagy level of tumor tissue and inhibited cells proliferation. CONCLUSION: NOD2 can activate autophagy in esophageal adenocarcinoma cells through the ATG16L1 pathway and inhibit cell proliferation.

Long noncoding RNA CDKN2B-AS1 silencing protects against esophageal cancer cell invasion and migration by inactivating the TFAP2A/FSCN1 axis.

Esophageal cancer (EC) is the most aggressive malignancy in the gastrointestinal tract. Long noncoding RNA cyclin-dependent kinase inhibitor 2 B antisense RNA 1 (CDKN2B-AS1) is implicated in EC development. However, the specific mechanisms involved remain poorly defined. Therefore, this research aimed to explore the mechanism of action of CDKN2B-AS1 in EC. Quantitative real-time polymerase chain reaction was conducted to measure CDKN2B-AS1 expression in EC cells and western blotting was utilized to evaluate transcription factor AP-2 alpha (TFAP2A) and fascin actin-bundling protein 1 (FSCN1) expression. After gain-of-function and loss-of-function assays, cell proliferation, migration, invasion, apoptosis, and apoptosis-related protein expression were assessed using cell counting kit-8, scratch tests, Transwell assays, flow cytometry, and western blotting, respectively. The binding relationship between CDKN2B-AS1 and TFAP2A was assessed by RNA immunoprecipitation and RNA pull-down assays. The binding relationship between TFAP2A and FSCN1 was evaluated using dual-luciferase reporter and chromatin immunoprecipitation assays. Tumor xenografts from nude mice were used for in vivo verification. CDKN2B-AS1, TFAP2A, and FSCN1 were upregulated in EC cells. Mechanistically, CDKN2B-AS1 transcriptionally activated FSCN1 by recruiting TFAP2A to the FSCN1 promoter. Silencing CDKN2B-AS1 or TFAP2A suppressed EC cell proliferative, migrating, and invasive properties and augmented apoptosis. TFAP2A was bound to CDKN2B-AS1 and the FSCN1 promoter. Overexpression of TFAP2A or FSCN1 abolished the effects of CDKN2B-AS1-silencing on EC cell function. CDKN2B-AS1 silencing curtailed tumorigenesis in nude mice, which was nullified by the upregulation of TFAP2A or FSCN1. Our findings demonstrated the antioncogenic effects of silencing CDKN2B-AS1 in EC through inactivation of the TFAP2A/FSCN1 axis.

Xanthohumol inhibits non-small cell lung cancer by activating PUMA-mediated apoptosis.

Deregulation of apoptosis signaling is an important feature of cancer cells and plays an essential role in tumorigenesis. Xanthohumol is an active ingredient in Traditional Chinese Medicines Hops (Humulus lupulus L.). Recently studies have shown the profound anti-tumor activities of Xanthohumol in multiple cancer models. However, its potency in non-small cell lung cancer (NSCLC) and the underlying mechanisms are still elusive. Here, we have investigated the potency of Xanthohumol against NSCLC cells in vitro and xenograft mouse models. Xanthohumol suppressed cell viability, colony formation and induced apoptosis in A549, H520, and H358 cells. Xanthohumol activated mitochondrial apoptosis through upregulation of (p53-upregulated modulator of apoptosis) PUMA expression. After Xanthohumol treatment, the Akt activity was inhibited, which resulted in dephosphorylation of FOXO3a and PUMA induction. Silent PUMA or FOXO3a impaired Xanthohumol-induced apoptosis in NSCLC cells. In nude mice, Xanthohumol administration suppressed NSCLC xenograft tumor growth and increased PUMA expression in tumor tissues. Briefly, our studies revealed a novel mechanism by which Xanthohumol exerted its anti-tumor activity in a PUMA-dependent manner in NSCLC cells.

Long non-coding RNA terminal differentiation-induced non-coding RNA regulates cisplatin resistance of choroidal melanoma by positively modulating extracellular signal-regulated kinase 2 via sponging microRNA-19b-3p.

In the present study, we aimed to investigate the role of long non-coding RNA terminal differentiation-induced non-coding RNA (TINCR) in cisplatin (DDP) resistance of choroidal melanoma (CM) and the potential molecular mechanisms. CM and non-CM tissues were collected from 60 CM patients. DDP-resistant CM cells were obtained by selection with linearly increased DDP treatment. The expression levels of TINCR, microR-19b-3p (miR-19b-3p), and extracellular signal-regulated kinase 2 (ERK-2) were detected by quantitative real-time PCR. Cholecystokinin octapeptide (CCK-8) assay was utilized to detect chemosensitivity and cell viability. Flow cytometry analysis was performed to detect apoptotic cells. The protein levels of Bax, Bcl-2, cleaved-caspase-3, ERK-2, and nuclear factor-kappa B p65 were measured by Western blot. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were performed to determine the relationship among TINCR, miR-19b-3p, and ERK-2. The results showed that the levels of TINCR and ERK-2 were markedly increased in DDP-resistant CM tissues and cells, while miR-19b-3p level was significantly reduced. TINCR knockdown reduced DDP resistance and cell viability and promoted cell apoptosis, while TINCR overexpression exhibited opposite effects. TINCR and ERK-2 were direct targets of miR-19b-3p. Further experiments revealed that TINCR enhanced DDP resistance in CM cells by regulating the miR-19b-3p/ERK-2/NF-kb axis. Taken together, our study revealed a critical role of TINCR in regulating DDP resistance in CM and suggested that TINCR is a potential cisplatin-resistant CM therapeutic target.

PTBP3 regulates proliferation of lung squamous cell carcinoma cells via CDC25A-mediated cell cycle progression.

BACKGROUND: The roles of Polypyrimidine tract-binding protein 3 (PTBP3) in regulating lung squamous cell carcinoma (LUSC) cells progression is unclear. The aim of this study was to investigate the role of PTBP3 in LUSC. METHODS: Expression and survival analysis of PTBP3 was firstly investigated using TCGA datasets. Quantitative reverse transcription PCR and Western blot were performed to detect PTBP3 expression in clinical samples. Moreover, cell counting kit 8 (CCK-8) assays, colony formation assays and in vivo tumor formation assays were used to examine the effects of PTBP3 on LUSC cell proliferation. RNA-sequence and analysis explores pathways regulated by PTBP3.Flow cytology was used analyzed cell cycle. Cell cycle-related markers were analyzed by Western blot. RESULTS: PTBP3 was found to be overexpressed in LUSC tissues compared with normal tissues. High PTBP3 expression was significantly correlated with poor prognosis. In vitro and vivo experiments demonstrated that PTBP3 knockdown caused a significant decrease in the proliferation rate of cells. Bioinformatics analysis showed that PTBP3 involved in cell cycle pathway regulation in LUSC. Furthermore, PTBP3 knockdown arrested cell cycle progression at S phase via decreasing CDK2/Cyclin A2 complex. In addition, downregulation of PTBP3 significantly decreased the expression of CDC25A. CONCLUSIONS: Our results suggest that PTBP3 regulated LUSC cell proliferation via cell cycle and might be a potential target for molecular therapy of LUSC.

Hsa_circ_0005576 promotes osimertinib resistance through the miR-512-5p/IGF1R axis in lung adenocarcinoma cells.

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for lung adenocarcinoma (LUAD) harboring activating mutations, but patients ultimately develop acquired resistance. Circular RNAs are involved in EGFR-TKI resistance, while the role of hsa_circ_0005576 in the osimertinib resistance of LUAD remains unknown. In this study, we demonstrated that hsa_circ_0005576 could facilitate osimertinib-resistant LUAD cells. Briefly, knockdown of hsa_circ_0005576 not only suppressed the proliferation and promoted the apoptosis of resistant LUAD cells, but also increased their sensitivity to osimertinib. Mechanistically, hsa_circ_0005576, serving as an miRNA sponge, could directly interact with miR-512-5p and subsequently upregulate the miR-512-5p-targeted insulin-like growth factor 1 receptor. Rescue assays indicated that miR-512-5p inhibition could reverse the effects of hsa_circ_0005576 knockdown in LUAD cells resistant to osimertinib. Overall, our study revealed that hsa_circ_0005576 regulates proliferation and apoptosis through miR-512-5p/IGF1R signaling, which contributes further to the resistance of LUAD cells to osimertinib. In addition, this study provides a novel insight into the mechanisms underlying osimertinib resistance of LUAD.

Effect of surgery on survival in patients with stage III N2 small cell lung cancer: propensity score matching analysis and nomogram development and validation.

BACKGROUND: The standard treatment of stage III N2 small cell lung cancer (SCLC) is concurrent chemoradiation, and surgery is not recommended. This study was aimed to evaluate whether surgery has survival benefits in patients with stage III N2 SCLC and investigate the factors influencing survival of surgery. METHODS: Patients diagnosed with stage T1-4N2M0 SCLC from 2004 to 2015 were selected from the Surveillance Epidemiology End Results database. Propensity score matching (PSM) was used to balance confounders between patients who underwent surgery and those treated with radiation and/or chemotherapy. We compared overall survival (OS) of the two groups using Kaplan-Meier curves and a Cox proportional hazard model. We also identified prognostic factors in patients with surgical resection, and a nomogram was developed and validated for predicting postoperative OS. RESULTS: -A total of 5576 patients were included in the analysis; of these, 211 patients underwent surgery. PSM balanced the differences between the two groups. The median OS was longer in the surgery group than in the non-surgery group (20 vs. 15 months; p = 0.0024). Surgery was an independent prognostic factor for longer OS in the multivariate Cox regression analysis, and subgroup analysis revealed a higher survival rate in T1 stage patients treated with surgery (hazard ratio = 0.565, 95% confidence interval: 0.401-0.798; p = 0.001). In patients who underwent surgery, four prognostic factors, including age, T stage, number of positive lymph nodes, and radiation, were selected into nomogram development for predicting postoperative OS. C-index, decision curve analyses, integrated discrimination improvement, and time-dependent receiver operating characteristics showed better performance in nomogram than in the tumor-node-metastasis staging system. Calibration plots demonstrated good consistency between nomogram predicted survival and actual observed survival. The patients were stratified into three different risk groups by prognostic scores and Kaplan-Meier curves showed significant difference between these groups. CONCLUSIONS: These results indicate that surgery can prolong survival in patients with operable stage III N2 SCLC, particularly those with T1 disease. A nomogram that includes age, T stage, number of positive lymph nodes, and radiation can be used to predict their long-term postoperative survival.

Comparison of Clinical Efficacy of Alectinib Versus Crizotinib in ALK-Positive Non-Small Cell Lung Cancer: A Meta-Analysis.

OBJECTIVE: To systematically evaluate the efficacy and safety of alectinib versus crizotinib in the treatment of anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer. METHODS: Studies about the efficacy of alectinib versus crizotinib in the treatment of ALK-positive non-small cell lung cancer were searched in PubMed, Scopus, Embase and the Cocharane Library from inception to February 15, 2020. Two reviewers independently screened these studies, extracted the data, assessed the risk of bias in the included studies by using the Cochrane risk assessment tool, and then used review manager 5.3 software for meta-analysis. RESULTS: Three studies comprising a total of 697 patients with ALK-positive non-small cell lung cancer were included, 380 in the alectinib group and 317 in the crizotinib group. The dose of alectinib (300 mg) in J-ALEX were lower than the approved dose (600 mg), however the crizotinib group in all three studies received the recommended dose (250 mg). Performance bias was high in all three studies whereas, and the attrition bias was high in two studies (Toyoaki Hida 2017 and Solange peters 2017). The results of meta-analysis showed that: the overall response rate [OR = 2.07, 95% CI (1.41, 3.06), P = 0.0002], the progression free survival [HR = 0.34, 95% CI (0.21, 0.55), P <0.0001], the partial response [OR = 1.71, 95% CI (1.19, 2.46), P = 0.003], P = 0.001], in alectinib group were higher than that of crizotinib group. Though the total number of events in complete response and the disease control rate were more in alectinib group than that of crizotinib group, the meta-analysis results shows no significant differences between two drugs in the disease control rate [OR = 2.24, 95% CI (0.56, 8.88), P = 0.25], the complete response [OR = 1.82, 95% CI (0.75, 4.45), P = 0.19]. In addition, the number of events in the stable disease [OR = 0.45, 95% CI (0.28, O.74), P = 0.001], and the adverse events [OR = 0.50, 95% CI (0.23, 0.81), P = <0.0001] in alectinib group were lower than that of crizotinib group. CONCLUSION: Alectinib in terms of overall response rate, progression-free survival and partial response is superior to crizotinib in the treatment of ALK-positive non-small cell lung cancer and is well tolerated. Compared with crizotinib, alectinib is more effective than crizotinib and has a lower incidence of total adverse reactions. Meta-analysis results confirm the strong base for alectinib as a first-line treatment for ALK-positive NSCLC.

[Retracted] MicroRNA­138 inhibits migration and invasion of non­small cell lung cancer cells by targeting LIMK1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Figs. 3C and 5A were strikingly similar to data appearing in different form in another article by different authors, which had already been published elsewhere at the time of the present article's submission. Furthermore, cell Transwell assay data in the article (featured in Fig. 4B) were strikingly similar to data appearing in different form in other articles by different authors, which were either already under consideration for publication or had already been published elsewhere at the time of the present article's. Owing to the fact that the contentious data in the above article were either already under consideration for publication, or had already been published elsewhere, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 14: 4422­4428, 2016; DOI: 10.3892/mmr.2016.5769].

Identifying and Validating Potential Biomarkers of Early Stage Lung Adenocarcinoma Diagnosis and Prognosis.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. At present, most patients with LUAD are diagnosed at an advanced stage, and the prognosis of advanced LUAD is poor. Hence, we aimed to identify novel biomarkers for the diagnosis and treatment of early stage LUAD and to explore their predictive value. METHODS: The microarray datasets GSE63459, GSE27262, and GSE33532 were searched, and the differentially expressed genes (DEGs) were obtained using GEO2R. The DEGs were subjected to gene ontology (GO) and pathway enrichment analyses using METASCAPE. A protein-protein interaction (PPI) network was plotted with STRING and visualized by Cytoscape. Module analysis of the PPI network was performed using MCODE. Overall survival (OS) analysis and analysis of the mRNA expression levels of genes identified by MCODE were performed with UALCAN. Western blot analysis of hub genes in LUAD patients, MTS assays, and clonogenic assays were performed to test the effects of the hub genes on cell proliferation in vitro. RESULTS: A total of 341 DEGs were obtained, which were mainly enriched in terms related to blood vessel development, growth factor binding, and extracellular matrix organization. A PPI network consisting of 300 nodes and 1140 edges was constructed, and a significant module including 15 genes was identified. Elevated expression of ASPM, CCNB2, CDCA5, PRC1, KIAA0101, and UBE2T was associated with poor OS in LUAD patients. In the protein level, the hub gene was overexpressed in LUAD patients. In vitro experiments showed that knockdown of the hub genes in the LUAD cell lines could promote cell proliferation. CONCLUSIONS: DEGs are potential biomarkers for early stage lung adenocarcinoma and could have utility for the diagnosis and predicting treatment efficacy.

Sutureless Transplantation of Amniotic Membrane Using a Visible Light-Curable Protein Bioadhesive for Ocular Surface Reconstruction.

The conjunctiva is a thin mucous membrane of the eye. Pterygium, a commonly appearing disease on the ocular surface, requires surgery to excise the conjunctiva to prevent visual deterioration. Recently, transplantation of the amniotic membrane (AM), which is the innermost membrane of the placenta, has been highlighted as an efficient method to cure conjunctiva defects because of its advantages of no side effects compared to mitomycin C treatment and not leaving additional scars on donor site compared to conjunctival autografting. However, to minimize additional damage to the ocular surface by suturing, AM transplantation (AMT) needs to be simplified by using a less invasive, time-saving method. In this work, a visible light-curable protein bioadhesive (named FixLight) for efficient sutureless AMT is applied. FixLight, which is based on bioengineered mussel adhesive protein (MAP), is easily applied between damaged ocular surfaces and transplanted AM, and rapidly cured by harmless blue light activation. Through in vivo evaluation using a rabbit model, the authors demonstrated that FixLight enabled facile, fast, and strong attachment of AM on sclera and promoted ocular surface reconstruction with good biocompatibility. Thus, FixLight can be successfully used as a promising clinical bioadhesive in opthalmological surgeries that require sutureless and rapid operation.

Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-17-3p ameliorates inflammatory reaction and antioxidant injury of mice with diabetic retinopathy via targeting STAT1.

BACKGROUND: Accumulating evidence has reported the role of microRNA (miR) on diabetic retinopathy (DR). Thus, the aim of the study was to investigate the effect of exosomal miR-17-3p targeting signal transducer and activator of transcription 1 (STAT1) on inflammatory reaction and antioxidant injury of DR mice. METHODS: A mouse diabetes model was established and injected with miR-17-3p-containing human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes to ascertain the role of exosomal miR-17-3p. The blood glucose, glycosylated hemoglobin (HbAlc), weight, hemoglobin (Hb) content, inflammatory factors, oxidative stress factors, vascular endothelial growth factor (VEGF), apoptosis index and glutamine synthetase (GS) level in serum and/or retinal tissues of DR mice were measured. miR-17-3p and STAT1 expression in retinal tissues as well as the target relationship between miR-17-3p and STAT1 were tested. RESULTS: miR-17-3p decreased and STAT1 increased in retinal tissues of DR mice, and STAT1 was the target gene of miR-17-3p. Injection of up-regulated exosomal miR-17-3p reduced the blood glucose and HbAlc, increased the weight, Hb content and GS level, decreased contents of inflammatory factors and VEGF, alleviated oxidative injury, and inhibited retinal cell apoptosis in DR mice through inhibiting STAT1. CONCLUSION: Functional studies reveal that hucMSCs-derived exosomes shuffle miR-17-3p to ameliorate inflammatory reaction and oxidative injury of DR mice via targeting STAT1.

Eugenol protects the transplanted heart against ischemia/reperfusion injury in rats by inhibiting the inflammatory response and apoptosis.

The aim of the present study was to investigate the protective effect of eugenol on the transplanted heart and explore its mechanisms of action. Male Sprague-Dawley rats were randomly divided into a sham group (n=10), a eugenol group (n=10 pairs, donors and recipients) and a control group (n=10 pairs, donors and recipients). The recipients in the eugenol group received an intraperitoneal injection of eugenol (20 mg/kg/day). The sham group and the control group received equal volumes of physiological saline by intraperitoneal injection. After 15 days the recipients in the control and eugenol groups underwent abdominal heterotopic heart transplantation, while the sham group received only a coeliotomy. The orthotopic hearts in the sham group and the heterotopic hearts in the eugenol and control groups, as well as the peripheral blood samples from all three groups were taken 3 h post operation for biochemical, histopathological, molecular and apoptosis analyses. Compared with the control group, the eugenol treatment significantly reduced the myocardial malondialdehyde content, serum cardiac troponin I, creatine kinase-MB, tumor necresis factor-α and interleukin-6 levels (P<0.05) and significantly alleviated myocardial injury. Western blot analysis demonstrated that the protein expression of cleaved Poly (ADP-ribose) polymerase 1, BAX and active caspase-3 in the eugenol group were significantly decreased, while B-cell lymphoma 2 expression was significantly increased compared with the control group (P<0.05). The myocardial apoptosis rate of the eugenol group was significantly decreased compared with the control group (P<0.05). In conclusion eugenol treatment significantly reduced myocardial injury and demonstrated protective effects for the transplanted heart.