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N6-methyladenosine (m6A) is the most common internal modification in mammalian mRNAs while RNA-binding motif protein 15 (RBM15) is an important methyltransferase in m6A modification. Increasing evidences have shown that RBM15 has a close correlation with lung cancer. However, specific functions of RBM15 in lung adenocarcinoma (LUAD) are limited. RBM15 expression was analyzed in human LUAD tissues and matched healthy lung tissue. RBM15 was knocked down via siRNA in A549 and H1734 cells. The relationships between RBM15 with cellular functions characteristics and mRNA m6A levels were explored. We performed functional characterization in A549 and H1734 cells lines to elucidate the molecular role of RBM15. Results found that RBM15 was up-regulated in the LUAD tissue and cells, which was linked to poor survival of LUAD patients. RBM15 can be knocked down via siRNA in A549, which leads to the exploration of the associations between RBM15 with cell characteristics. In vivo, RBM15 knockdown could decrease the methylation level, reduce proliferation, accelerate apoptosis and inhibit tumor growth. Our research shows that RBM15 facilitates LUAC cell progression by m6A demethylation. However, it is necessary to conduct further researches on potential downstream molecular mechanisms and m6A modification of RBM15 activity in LUAC.

Background Although surgery has been widely applied for SPLC therapy, there is still no uniform treatment approach. Whether SPLC and primary lung cancer have similar prognostic characteristics remains controversial. Herein, based on a systematic review and meta-analysis, we aimed to enucleate the influences of diverse surgical strategies and underlying prognostic factors on the prognosis of patients with both the first primary lung cancer and SPLC underwent surgical resection. Methods A comprehensive and systematic literature search was implemented in three databases (MEDLINE, EMBASE, and Cochrane), and eligible studies were screened following inclusion and exclusion criteria. Meanwhile, we extracted the hazard ratios (HR) together with 95% confidence intervals (CI) for each prognostic factor, either directly or indirectly, from the enrolled literature. Results Eleven studies (published between 2000 and 2022) were included in this study, including 1,131 SPLC patients. The overall survival (OS) exhibited no difference between patients with lobectomy and sublobar resection after SPLC (HR: 0.87, 95%CI: 0.62–1.21, P = 0.41). The patients after completion pneumonectomy had a poor prognosis (HR: 1.85, 95% CI: 1.34–2.55, P P 2 cm (HR: 2.44, 95%CI: 1.73–3.44, P P = 0.03), lymph node metastasis (HR: 2.79, 95%CI: 1.40–5.56), and smoking (HR: 2.37, 95%CI: 1.08–26.82, P Conclusions Patients with SPLC, especially those with poor cardiopulmonary function reserve, should be prioritized for sublobar resection for treatment. These patients should also try to avoid completion pneumonectomy. Patients with synchronous SPLC, tumor diameter > 2 cm, solid predominant in CT morphology, lymph node metastasis, and smoking had a poor prognosis. Meanwhile, SPLC has similar prognostic characteristics with single primary lung cancer. However, the study has some limitations and more evidence is warranted to verify the findings.

BackgroundChina’s southwestern region, Qujing, harbors a high incidence of non-small cell lung cancer (NSCLC) and related mortality. This study was designed to reveal the impact of an immune-related prognostic signature (IRPS) on advanced NSCLC in the Qujing.MethodsTissue specimens from an independent cohort of 37 patients with advanced NSCLC were retrospectively evaluated to determine the relationship between the IRPS estimated by next-generation sequencing (NGS) and clinical outcome. To compare the IRPS in tissue and the clinical outcomes between Qujing and non-Qujing populations, we analyzed datasets of 23 patients with advanced NSCLC from The Cancer Genome Atlas (TCGA) database. In addition, an independent cohort (n=111) of blood specimens was retrospectively analyzed to determine the relationship between the IRPS and clinical outcome. Finally, we evaluated the utility of the blood IRPS in classifying 24 patients with advanced NSCLC who might benefit from immunotherapy.ResultsIn cohort 1, the Qujing population with tTMB-H (≥ 10 mutations/Mb) or KRAS mutations had shorter progression-free survival (PFS) (hazard ratio [HR] 0.37, 0.14 to 0.97, P = 0.04; HR 0.23, 0.08 to 0.66, P < 0.01) and overall survival (OS) (HR 0.05, 0.01 to 0.35, P < 0.01; HR 0.22, 0.07 to 0.66, P < 0.01). In cohort 2 of the Qujing population, bTMB-H (≥ 6 mutations per Mb) and KRAS mutations were related to PFS (HR 0.59, 0.36 to 0.99, P = 0.04; HR 0.50, 0.26 to 0.98, P = 0.04) and OS (HR 0.58, 0.35 to 0.96, P = 0.03; HR 0.48, 0.25 to 0.93, P = 0.03). Notably, the Qujing population with bTMB-H had superior PFS (HR 0.32, 0.09 to 1.09, P = 0.01), OS (HR 0.33, 0.10 to 1.13, P < 0.01) and objective response rates (ORRs) (83.3% vs. 14.3% vs. 20.0%, P <0.01) to immunotherapy than other populations.ConclusionsThese findings show that tTMB, bTMB and KRAS mutations appear to be independent validated IRPSs that predict the clinical outcomes of Qujing populations with advanced NSCLC and that bTMB may be used as a reliable IRPS to predict the clinical benefit from anti-PD-1 therapies among populations from Qujing with advanced NSCLC.

Background. Rab8A has been reported as an oncogenic gene in breast and cervical cancer. However, the function and molecular mechanism of Rab8A in esophagus cancer has not been reported. Methods. Rab8A expression was detected by qPCR and western blotting assays, small interference RNA (siRNA) was applied to reduce Rab8A expression, and the biological behaviors of esophagus cancer cells were estimated by cell counting kit-8, colony formation, and transwell and western blotting assays. The transcriptional factor of Rab8A was verified by dual-luciferase assay and chromatin immunoprecipitation assay. The protein expression of key genes in the Wnt/β-catenin signaling pathway was determined by western blotting assay. M435-1279 was used to suppress the Wnt/β-catenin signaling pathway. Results. A significant increase of Rab8A expression has been found in esophagus cancer cells. Knockdown of Rab8A suppressed the viability, colony formation, migration, and invasion abilities of esophagus cancer cells and induced apoptosis. PEA3 transcriptionally regulated Rab8A expression and promoted the viability, colony formation, migration, and invasion abilities of esophagus cancer cells and blocked apoptosis, which were diminished by si-Rab8A transfection. Additionally, the expression levels of key genes related to the Wnt/β-catenin signaling pathway were strengthened by PEA3 overexpression, which were reduced by si-Rab8A transfection. M435-1279 treatment significantly reduced the viability and colony formation of esophagus cancer cells. Conclusions. The data showed that Rab8A was transcriptionally regulated by PEA3 and promoted the malignant behaviors of esophagus cancer cells by activating the Wnt/β-catenin pathway. The above results indicated that Rab8A may be considered as a promising biomarker for diagnosis and precision treatment in esophagus cancer.

Our aim is to establish a model for predicting the aggressiveness of pathological subtypes of multiple primary invasive lung adenocarcinomas based on CT radiomics to provide a reference for preoperative planning in affected patients. Clinical data and CT images of patients who were diagnosed as having multiple primary invasive lung adenocarcinomas through postoperative pathological analysis from January 2016 to December 2020 in the Third Affiliated Hospital of Kunming Medical University were retrospectively analyzed. 3D Slicer software were used to perform the focal segmentation and feature extraction of the CT images. Five classification learners were employed to establish models for predicting the aggressiveness of pathological subtypes of the lung adenocarcinomas, and evaluate the performance of the prediction model based on the area under the Area Under the subject operating characteristic Curve (AUC). 204 patients were enrolled, surgical intervention was applied to 408 nodules. Of them, 36.8% nodules were Acinar-type.The analysis of the CT radiomics-based aggressiveness prediction model demonstrated that the training group showed that the AUC values of logistic regression (LR), random forest (RF), decision tree(DT), support vector machine(SVM), and adaptive boosting(AdaBoost) models were all within 0.7–1, and the testing group showed that the AUC values of the LR and RF models were all within 0.7–0.9. Our results indicate that acinar-type is the main pathological subtype of multiple primary invasive lung adenocarcinomas. LR and RF models presented a certain level of accuracy performance in predicting the aggressiveness of pathological subtypes of multiple primary invasive lung adenocarcinomas and thus facilitate preoperative planning in cancer patients.

BackgroundLung adenocarcinoma (LUAD) is the most predominant histological subtype of lung cancer. Abnormal lipid metabolism is closely related to the development of LUAD. LncRNAs are involved in the regulation of various lipid metabolism-related genes in various cancer cells including LUAD. Here, we aimed to identify lipid metabolism-related lncRNAs associated with LUAD prognosis and to propose a new prognostic signature.MethodsFirst, differentially expressed lncRNAs (DE-lncRNAs) from the TCGA-LUAD and the GSE31210 dataset were identified. Then the correlation analysis between DE-lncRNAs and lipid metabolism genes was performed to screen lipid metabolism-related lncRNAs. Cox regression analyses were performed in the training set to establish a prognostic model and the model was validated in the testing set and the validation set. Moreover, The role of this model in the underlying molecular mechanisms, immunotherapy, and chemotherapeutic drug sensitivity analysis was predicted by methods such as Gene Set Enrichment Analysis, immune infiltration, tumor mutational burden (TMB), neoantigen, Tumor Immune Dysfunction and Exclusion, chemosensitivity analysis between the high- and low-risk groups. The diagnostic ability of prognostic lncRNAs has also been validated. Finally, we validated the expression levels of selected prognostic lncRNAs by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe prognostic model was constructed based on four prognostic lncRNAs (LINC00857, EP300-AS1, TBX5-AS1, SNHG3) related to lipid metabolism. The receiver operating characteristic curve (ROC) and Kaplan Meier (KM) curves of the risk model showed their validity. The results of Gene Set Enrichment Analysis suggested that differentially expressed genes in high- and low-risk groups were mainly enriched in immune response and cell cycle. There statistical differences in TMB and neoantigen between high- and low-risk groups. Drug sensitivity analysis suggested that patients with low risk scores may have better chemotherapy outcomes. The results of qRT-PCR were suggesting that compared with the normal group, the expressions of EP300-AS1 and TBX5-AS1 were down-regulated in the tumor group, while the expressions of LINC00857 and SNHG3 were up-regulated. The four prognostic lncRNAs had good diagnostic capabilities, and the overall diagnostic model of the four prognostic lncRNAs was more effective.ConclusionA total of 4 prognostic lncRNAs related to lipid metabolism were obtained and an effective risk model was constructed.

This brief presents a new quenching circuit with a metal fuse that aims to protect readout integrated circuit (ROIC) from breakdown due to unexpectedly high voltage from Geiger-mode avalanche photodiode (GmAPD) arrays. Fuse resistances in states of pre-burnout and post-burnout are investigated to satisfy requirements of rapid quenching and high voltage protection, respectively. Several fuse options using commercial mixed-signal CMOS processes, such as metal and polysilicon, are compared in detail. Meander metal fuse is the most suitable candidate according to measurement results. A rapidly quenching circuit integrated with metal fuse is developed using a 0.18 $\mu \text{m}$ CMOS process. After being bonding with GmAPDs and resistors, test results show that this circuit could endure a high voltage of 75 V, demonstrating that this innovative design can contribute in a low-cost and high-reliable way to high-yield large-format GmAPD arrays.

Background: Lung cancer is the most common malignant tumor with the highest mortality all over the world. Among it, Lung Adenocarcinoma owns the highest proportion of pathological classification.Yet, the fuction of MCM4 in the occurrence of Lung Adenocarcinoma is still unknown.In this research, we attempted to disscuss the potential role of MCM4 in LUAD through bioinformatics analysis and hoped to provide a new idea for clinical treatment.Methods: The data of Lung Adenocarcinoma in TCGA and GEO were downloaded.The correlation between MCM4 and immune infiltration were performed by R software packages .Enrichment analysis were underwent to analyze the functions of MCM4. Univariate and multivariate Cox regression analysis were utilized to determine whether MCM4 could be act as an independent prognostic factor for Lung Adenocarcinoma.Lastly,the expression of MCM4 was validated in clinical tissues by immunohistochemistry (IHC), real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and western blotting (WB).Results: The expression of MCM4 was up-regulated in 13 tumors and was significantly correlated with age, gender, stage, T, N and smoke history. Furthermore, the Kaplan-Meier survival curves pointed that LUAD samples with lower MCM4 expression had longer Overall survival (OS) and the Disease-free survival (DFS) in 4 datasets. Univariate Cox regression analysis showed that the p value of MCM4 expression was less than 0.05(P＜0.05) and it appeared in the results of multivariate Cox regression analysis(HR≥1), which indicated that MCM4 can be used as an independent prognostic factor for LUAD.Enrichment Analysis suggested that MCM4 was correlated with the multiple biological functions and involved in vital pathways in GO and KEGG. Furthermore, the MCM4 expression was correlated with immune cells infiltration.Finally,the experimental results were consistent with the bioinformatic analysis.Conclusion: MCM4 might serve as a prognostic biomarker and correlate with immune infiltration in LUAD.

Propose: Autophagy plays a complicated role in cancer progression. This study aims at assessing the function of ATG5-induced autophagy in progression of lung squamous cell carcinoma and its upstream mechanism. Method: TCGA database of lung squamous cell carcinoma was analyzed to explore the differentially expressed miRNAs and mRNAs and relative prognosis. RT-PCR and Western blot were performed to evaluate autophagy relative gene expression level in human lung squamous cell carcinoma cell Lines. Autophagy flux was observed using transmission electron microscopy and immunofluorescence. Meanwhile, binding relationship of potential target miRNA and mRNAs were also confirmed using Dual-luciferase reporter gene assay. Lung metastatic model was established to evaluated the effect of targeting protein and miRNA. Result: High level expression of ATG5 was detected in LUSC patients. Relative experiments confirmed that ATG5 silencing could decrease the autophagy flux in LUSC. In addition, our research revealed that there is a binding sites between hsa-mir-30a-5p and 3′-UTR of ATG5. Mimic miR-30a-5p suppresses ATG5-mediated autophagy in lung squamous cell carcinoma cells. The in vivo experiments confirmed that miR-30a-5p could attenuate lung squamous cell carcinoma progression through the autophagy pathway. Conclusion: Accordingly, the in vivo and in vitro study in our research have demonstrated that miR-30a-5p inhibits lung squamous cell carcinoma progression via ATG5-mediated autophagy.

Background Systematic lymph node dissection is an important part of radical resection for lung cancer. Insufficient incision of the mediastinal pleura results in a tapered or tunnel-like operation surface, which increases the difficulty of uniportal video-assisted thoracoscopic mediastinal lymph node dissection. The objective of this study was to report our concept of broad exposure and investigate the efficacy and safety of this concept in uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection. Methods We retrospectively analyzed the clinical data of the 204 non-small cell lung cancer patients who underwent uniportal video-assisted thoracoscopic surgery for anatomical lobectomy and systematic lymph node dissection following the concept of broad exposure. SPSS 23.0 software was used for statistical analysis. Results All operations were completed under uniportal video-assisted thoracoscopic surgery following the concept of broad exposure. The median surgery time was 102 (range, 76–285) minutes and the median blood loss was 50 (range, 20–900) milliliters. The median chest tube duration time was 2 (range, 1–6) days, the median postoperative hospital duration time was 5 (range, 4–10) days. The median number of dissected lymph node stations and dissected lymph nodes were 8 (range,6–9) and 15(range,12–19), respectively. The median number of dissected mediastinal lymph nodes stations and dissected mediastinal lymph nodes were 5(range,3–6) and 11(range,10–15), respectively. The up-staging rate of N staging was 6.86%. The postoperative complication rate was 10.29% and there was no perioperative death. Conclusions According to our results, it’s effective and safe to perform uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection following the concept of broad exposure. This new concept not only emphasizes sufficient exposure, but also focuses on protection of important tissues.

Surgery is currently the most appropriate treatment for early-stage non-small cell lung cancer (NSCLC). Increasing unilateral or bilateral multiple primary lung cancer being found, segmentectomy has attracted wide attention for its unique advantages in the treatment for such tumors. Ground glass opacity dominant early-stage NSCLC is associated with a good prognosis and can be cured by segmentectomy, however, the treatment of solid-dominant NSCLC remains controversial owing to the invasive nature. With the in-depth study on the lymph node metastasis pathway, radiological characteristics and molecular biology of NSCLC, a large part of solid nodules with certain characteristics can also be cured by segmentectomy. This paper reviews the research status and progress about the indication of segmentectomy.

Background The role of miRNAs in non-small cell lung cancer (NSCLC) has been broadly studied and confirmed, and miR-107 has attracted an ever-growing level of attention. This study set out to research the mechanism of the effect of miR-107 on the malignant biological behavior of NSCLC in vivo and vitro. Methods The expression of miRNAs related to the development of NSCLC was detected by RT-qPCR. Western blotting was carried out to detect expression levels of serine/threonine kinase 33 (STK33) and proteins related to the extracellular regulated protein kinases (ERK) signaling pathway, while cell proliferation was detected using cell counting kit-8 (CCK-8). The cell apoptosis rate was measured using flow cytometry. The invasion ability was detected by Transwell assay. In vivo tumor growth assays were performed on mice. The expression ERK signaling pathway-related proteins in vivo was evaluated by immunohistochemistry staining. The targeted relationship between miR-107 and STK33 was confirmed by the dual luciferase reporter gene. Results In NSCLC cell lines and tissues, miR-107 was downregulated. Overexpression of miR-107 inhibited malignant biological behavior of NSCLC cell lines, and suppressed tumor growth in vivo. In addition, STK33 is one of the target genes of miR-107. Therefore, miR-107 suppressed cell proliferation and invasion and promoted tumor growth in vivo and cell apoptosis of NSCLC in vitro. The mechanism was found to be miR-107 targeting STK33, and a lack of STK33 led to the activation of ERK signaling pathway. Conclusions miR-107 inhibited malignant biological behavior of NSCLC through regulation of the STK33/ERK signaling pathway.

Wei Wang,1,2,&ast; Zaoxiu Hu,3,&ast; Mingsheng Ma,4 Haoyuan Yin,4 Yunchao Huang,1 Guangqiang Zhao,1 Xin Cui,1 Qinling Sun,1 Yantao Yang,1 Yichen Yang,1 Biying Wang,1 Lianhua Ye1 1Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Thoracic Surgery, Taihe Hospital (Hubei University of Medicine), Shiyan, People’s Republic of China; 3Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4Department of Thoracic Surgery, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianhua YeDepartment of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, No. 519 Kunzhou Road, Xishan District, Kunming City, Yunnan Province, People’s Republic of ChinaEmail lhye1204@aliyun.comPurpose: Currently, there is no uniform standard to guide postoperative adjuvant chemotherapy for patients with multifocal non-small cell lung cancers (NSCLCs) ≤ 3 cm. Therefore, there is an urgent need to explore prognostic molecular markers to identify high-risk patients with multifocal NSCLCs ≤ 3 cm. We aimed to explore the potential value of metastasis-associated protein 1(MTA1) expression in risk stratification of patients with multifocal NSCLCs ≤ 3 cm.Methods: We retrospectively analyzed the clinical data and postoperative survival data of patients with multifocal NSCLCs ≤ 3 cm. Paraffin-embedded tissue sections were used for immunohistochemistry. Semiquantitative immunoreactivity scoring (IRS) system was used to evaluate the nuclear expression of MTA1. SPSS software (version 23.0) was used to analyze the data.Results: The IRS of MTA1 nuclear expression in 259 lesions of 119 patients ranged from 2.2 to 11.7 (median: 5.6). Our results showed that MTA1 expression was highest in high-risk pathological subtypes of lung adenocarcinoma. MTA1 expression in multiple primary lung cancers (MPLCs) was lower than that in intrapulmonary metastases (IPMs). The median follow-up duration was 25.97 months. The disease-free survival (DFS) of patients with MPLCs was significantly better than that of patients with IPMs, and the DFS of patients with high MTA1 expression was significantly worse than that of patients with low MTA1 expression. Multivariate Cox analysis showed that high MTA1 expression (hazard ratio: 7.937, 95% confidence interval: 2.433– 25.64, p =0.001) was a statistically significant predictor of worse DFS in patients with multifocal NSCLCs ≤ 3 cm.Conclusion: MTA1 expression can stratify the risk in patients with multifocal NSCLCs ≤ 3 cm. Patients with MTA1 immunohistochemical score > 5.6 are at a high risk of postoperative recurrence, and these patients may benefit from postoperative adjuvant chemotherapy.Keywords: multifocal, non-small cell lung cancer, MTA1, multiple primary lung cancers, intrapulmonary metastases, risk of postoperative recurrence

Distant metastasis is the main cause of death in non-small cell lung cancer (NSCLC) patients. The mechanism of metastasis-associated protein 1(MTA1) in NSCLC has not been fully elucidated. This study aimed to reveal the mechanism of MTA1 in the invasion and metastasis of NSCLC. Bioinformatics analysis and our previous results showed that MTA1 was highly expressed in NSCLC tissues and correlated with tumor progression. Knockout of MTA1 by CRISPR/Cas9 significantly inhibited the migration and invasion of H1299 cells, but enhanced cell adhesion. Stable overexpression of MTA1 by lentivirus transfection had opposite effects on migration, invasion and adhesion of A549 cells. The results of in vivo experiments in nude mouse lung metastases model confirmed the promotion of MTA1 on invasion and migration. Tight junction protein 1 (TJP1) was identified by immunoprecipitation and mass spectrometry as an interacting protein of MTA1 involved in cell adhesion. MTA1 inhibited the expression level of TJP1 protein and weakened the tight junctions between cells. More importantly, the rescue assays confirmed that the regulation of MTA1 on cell adhesion, migration and invasion was partially attenuated by TJP1. In Conclusion, MTA1 inhibits the expression level of TJP1 protein co-localized in the cytoplasm and membrane of NSCLC cells, weakens the tight junctions between cells, and changes the adhesion, migration and invasion capabilities of cells, which may be the mechanism of MTA1 promoting the invasion and metastasis of NSCLC. Thus, targeting the MTA1-TJP1 axis may be a promising strategy for inhibiting NSCLC metastasis.

Objective Although the significance of increased plasma D-dimer levels in activating coagulation and fibrinolysis has been reported, it is still controversial whether it can be used to predict the prognosis of lung cancer patients. This meta-analysis was performed to explore the beneficial role of plasma D-dimer as a prognostic factor in lung cancer patients according to a larger sample capacity. Materials and methods MEDLINE, EMBASE, and Cochrane Central databases were searched from inception to January 2021. The data are mainly hazard ratio(HR) with 95% confidence interval (CI) and Kaplan–Meier survival curves. The publication bias was examined by Egger’s test. Results Finally, a total of 28 studies, enrolling 8452 patients were included in the current meta-analysis. Our results showed that the OS (HR = 1.742, 95%CI:1.542–1.969, P P = 0.003) in the high D-dimer group were significantly lower than those in the low D-dimer group. Subgroup analysis suggested that localization, detection methods and disease stage had an important effect on the prognosis. Conclusion This meta-analysis revealed that the high plasma D-dimer level leads to lower survival than in the low D-dimer level, which might provide an important clue for high plasma D-dimer level as an independent factor of poor prognosis in patients with lung cancer.

Increasing evidence indicated that long noncoding RNAs (lncRNA) play critical roles in the progression of multiple cancers and that dysregulation of lncRNA promotes tumor progression. However, the function and underlying mechanism of lncRNA DLEU2 in biological behaviors of NSCLC cells are still largely unknown. Our studies confirmed that lncRNA DLEU2 was highly expressed in NSCLC tissues and cell lines, which was correlated with shorter overall survival in NSCLC patients. In vitro, knockdown of lncRNA DLEU2 inhibited proliferation, invasion, migration and induced apoptosis of both A549 and LLC cells; In vivo, it suppressed tumor growth and metastasis. lncRNA DLEU2 directly interacted with miR-30c-5p, which further targeted SOX9 and exerted oncogenic functions in NSCLC. Mechanistically, overexpression of lncRNA DLEU2 exhibits tumorigenic effects through downregulating the inhibitory effect of miR-30c-5p on SOX9 expression. In conclusion, Our finding confirmed that lncRNA DLEU2 as a novel oncogenic in NSCLC, which provide a potential novel diagnostic and therapeutic target for NSCLC.

Background: Persisters make biofilm infections difficult to cure, the low content of persisters in biofilm and the difficulty of obtaining them are outstanding problems in research, finding a reliable method to obtain a sufficient amount of persisters is the key to research. Methods: In this study, C.albicans strain ATCC10231 and S.epidermidis ATCC35984 were used to culture mixed biofilms on the surface of a titanium metal coupon. Tetracycline, gentamicin, 5-fluorocytosine(5-Fc), caspofungin, rifampicin, fluconazole and carbonyl cyanide m-chlorophenylhydrazone (CCCP) were used to induce the dormancy of biofilms to produce persisters. Ciprofloxacin and amphotericin B were used to kill the non dormant bacteria, and then the persisters were screened. Results:The study showed that dormancy induced by tetracycline and 5-Fc could significantly increase the persister levels of S.epidermidis and C.albicans, respectively. After the induced persisters were re-cultured, there was no significant change in antibiotic sensitivity compared with before induction.Scanning electron microscope(SEM) observations showed that after dormancy induction, the surface morphology of C.albicans in the mixed biofilm showed convex changes, and the volume of S.epidermidis decreased. Confocal laser scanning microscope (CLSM)observation showed that the mixed biofilm with high content of persisters did not dissolve under the killing of antibiotics, and the biofilm with low content of persisters dissolved in large area. Conclusions: Induction of dormancy is a reliable method for the formation of persistent bacteria in C.albicans-S.epidermidis mixed biofilm.

Background: Thoracic solitary fibrous tumors (TSFT) are a rare disease. We aim to determine the prognostic factors related to survival of TSFT patients through the use of The Surveillance, Epidemiology, and End Results database to analyze demographic and clinical characteristics. This study is intended to determine the prognostic factors associated with TSFT and has clinical value. Patients and Methods: This is a retrospective study of patients who were diagnosed with TSFT in the SEER database from 2001 to 2015. The kaplan-Meier method and Cox regression analysis were used to identify prognostic factors for patient survival. Results: From the SEER database (2001-2015), 227 patients with TSFT were detected. The 5-year survival rate was 82.7%, and the 10-year survival rate was 62.4%. Surgical resection [HR 0.314, 95% CI 0.201-0.491, P

Objective It has been confirmed that the micropapillary (MP) pattern is a poor prognostic factor after resection of lung adenocarcinoma (ADC), but the proportion of the MP component as a prognostic criterion is still controversial. Hence, a meta-analysis was performed to evaluate whether the presence of an MP component has equal prognostic power as the MP predominant subtype. Methods Literature retrieval was performed in the MEDLINE, EMBASE, and Cochrane databases until December 23, 2019. Eligible studies were selected based on the inclusion and exclusion criteria. The included studies were divided into two subgroups, the MP component subgroup and the MP predominant subgroup, according to the proportion of the MP pattern to analyse the effect of this pattern on disease-free survival (DFS) and overall survival (OS). The hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study. Review Manager 5.3 was used for statistical analyses. Results Finally, 10 studies, including a total of 4934 lung ADC patients, were included in this meta-analysis. Our results indicated a significantly worse pooled DFS (HR 1.62, 95% CI 1.20–2.21) and OS (HR 1.53, 95% CI 1.19–1.96) in the subgroup of MP predominant subtype patients. The pooled DFS (HR 1.80, 95% CI 1.45–2.85) and OS (HR 2.26, 95% CI 1.46–3.52) were also poor in the subgroup of patients with the presence of an MP component. Conclusions Both the presence of an MP component and the MP predominant subtype are related to poor DFS and OS after lung ADC resection and represent adverse prognostic factor for lung ADC patients. However, there are some limitations in this meta-analysis, and quantitative stratification based on the proportion of the MP component is needed to explore its effect on prognosis of lung ADC patients in the future.

BACKGROUND: The role of miRNAs in non-small cell lung cancer (NSCLC) has been broadly studied and confirmed, and miR-107 has attracted an ever-growing level of attention. This study set out to research the mechanism of the effect of miR-107 on the malignant biological behavior of NSCLC in vivo and vitro. METHODS: The expression of miRNAs related to the development of NSCLC was detected by RT-qPCR. Western blotting was carried out to detect expression levels of serine/threonine kinase 33 (STK33) and proteins related to the extracellular regulated protein kinases (ERK) signaling pathway, while cell proliferation was detected using cell counting kit-8 (CCK-8). The cell apoptosis rate was measured using flow cytometry. The invasion ability was detected by Transwell assay. In vivo tumor growth assays were performed on mice. The expression ERK signaling pathway-related proteins in vivo was evaluated by immunohistochemistry staining. The targeted relationship between miR-107 and STK33 was confirmed by the dual luciferase reporter gene. RESULTS: In NSCLC cell lines and tissues, miR-107 was downregulated. Overexpression of miR-107 inhibited malignant biological behavior of NSCLC cell lines, and suppressed tumor growth in vivo. In addition, STK33 is one of the target genes of miR-107. Therefore, miR-107 suppressed cell proliferation and invasion and promoted tumor growth in vivo and cell apoptosis of NSCLC in vitro. The mechanism was found to be miR-107 targeting STK33, and a lack of STK33 led to the activation of ERK signaling pathway. CONCLUSIONS: miR-107 inhibited malignant biological behavior of NSCLC through regulation of the STK33/ERK signaling pathway.

Because the segmental bronchi and vessels are commonly variable and complicated, it is difficult to correctly identify them. Misidentification of the segmental anatomy could result in the failure of segmentectomy and conversion to other surgical procedures such as bisegmentectomy or lobectomy. We describe a novel method to identify the target segmental vessels and bronchi by exposing the adjacent segmental anatomy during uniportal video-assisted thoracoscopic segmentectomy, which could help to reduce the chance of misidentification.

In this study, we attempted to find out the underlying mechanism of Benzoapyrene and metastasis of lung cancer cells. We also did experiments to testify the connection between BaP and its potential target, TNF-α. Cell median lethal dose (IC50 ) of both cells was measured by crystal violet method. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot were employed to detect the expression of TNF-α. Wound healing assay and transwell assay were utilized to testify the impacts of BaP and TNF-α on the metastasis of lung cancer cells. Cell death rate was elevated with the increase of BaP concentration. BaP increased the number of metastatic cells of lung cancer. The expressions of TNF-α pathway-associated protein (TNF-α, NF-kB [P65], Caspase3, and Caspase8) were enhanced by overexpressed BaP. TNF-α shRNA suppressed the positive effects of BaP on migration and invasion of lung cancer cells. Our study validated the positive effects of BaP on the metastasis of lung cancer cells. We also revealed the instrumental role of TNF-α in helping the development of lung cancer cells induced by BaP.

Additional file 1: Table S1. The quality evaluation results of the included studies.

Objective Whether segmentectomy can be used to treat radiologically determined pure solid or solid-dominant lung cancer remains controversial owing to the invasive pathologic characteristics of these tumors despite their small size. This meta-analysis compared the oncologic outcomes after lobectomy and segmentectomy regarding relapse-free survival (RFS) and overall survival (OS) in patients with radiologically determined pure solid or solid-dominant clinical stage IA non-small cell lung cancer (NSCLC). Methods A literature search was performed in the MEDLINE, EMBASE, and Cochrane Central databases for information from the date of database inception to March 2019. Studies were selected according to predefined eligibility criteria. The hazard ratio (HR) and associated 95% confidence interval (CI) were extracted or calculated as the outcome measure for data combining. Results Seven eligible studies published between 2014 and 2018 enrolling 1428 patients were included in the current meta-analysis. Compared with lobectomy, segmentectomy had a significant benefit on the RFS of radiologically determined pure solid or solid-dominant clinical stage IA NSCLC patients (combined HR: 1.46; 95% CI, 1.05–2.03; P = 0.024) and there were no significant differences on the OS of these patients (HR: 1.52; 95% CI, 0.95–2.43; P = 0.08). Conclusions Segmentectomy leads to lower survival than lobectomy for clinical stage IA NSCLC patients with radiologically determined pure solid or solid-dominant tumors. Moreover, applying lobectomy to clinical stage IA NSCLC patients with radiologically determined pure solid or solid-dominant tumors (≤2 cm) could lead to an even bigger survival advantage. However, there are some limitations in the present study, and more evidence is needed to support the conclusion.

OBJECTIVE: To investigate the effect of accessory gene regulator C (agr C) specific binding peptides (named N1) on the biofilm formation of Staphylococcus epidermidis on the surface of polyvinyl chloride (PVC) materials in vitro. METHODS: Firstly, the two strains (ATCC35984, ATCC12228) were cultured with N1 at concentrations of 100, 200, 400, 800, and 1 600 μg/mL, respectively. The control group was cultured with agrC specific binding unrelated peptides (named N0) at the same concentrations and the absorbance (A) value was measured after 24 hours to determine the optimal bacteriostatic concentration of N1. The two strains were cultured with N1 and N0 of the optimal concentration, respectively. The A values were measured at 6, 12, 18, 24, 30, and 48 hours to observe the effect of N1 on the biofilm formation ability ofStaphylococcus epidermidis. On this basis, the surface structure of the biofilm on the surface of PVC material was observed by scanning electron microscopy after 6, 12, 18, 24, and 30 hours of incubation with PVC material sheet. The thickness of the biofilm was observed by laser confocal microscopy after 6, 12, 18, and 24 hours of incubation with ATCC35984 strain. RESULTS: The optimal bacteriostatic concentration of N1 was 800 μg/mL. ATCC 12228 strain did not form obvious biofilm after being cultured with N1 and N0. When ATCC35984 strain was cultured with N1 and N0 for 12 hours, the difference in biofilm formation ability between groups N1 and N0 was statistically significant (P0.05). Scanning electron microscopy examination showed that mature biofilm structure was observed in ATCC35984 strain and was not observed in ATCC12228 strain. Laser confocal microscopy observation showed that the number of bacteria in the group N1 was significantly lower than that in the group N0 at 12 hours, and the most of bacteria were dead bacteria. There was no significant difference in the number of bacteria at 6, 18, and 24 hours, and the most of them were live bacteria. The biofilm thickness of group N1 was significantly lower than that of group N0 at 12 and 18 hours (P

Background Apelin plays an important role in many types of tumors. We aimed to identify the effects of miR-195 on inhibiting apelin and clarify the regulating mechanism of miR-195-apelin in lung adenocarcinoma cells. Methods We detected the expression levels of apelin and miR-195 in lung adenocarcinoma tissues and lung cancer cell lines using Western blotting and quantitative reverse transcription PCR assay, respectively. Luciferase reporter assay was used to confirm the target gene of miR-195. The effects of miR-195 and apelin on the proliferation and cell cycle of lung adenocarcinoma cells were assessed by methyl thiazolyl tetrazolium and colony formation assays, and flow cytometry. Wound-healing and transwell invasion experiments were employed to examine cellular migration and invasion. A tumor xenograft model was then used to investigate the role of miR-195 on tumor growth in vivo. Results The expression level of apelin and miR-195 showed an inverse correlation in lung adenocarcinoma tissues and cell lines. Luciferase reporter assay suggested that miR-195 directly targets apelin messenger RNA. Overexpression of miR-195 significantly inhibited the proliferation, migration, and invasion of lung adenocarcinoma cells in vitro and suppressed tumor growth in vivo. Further analysis revealed that apelin is one of the functional target genes of miR-195, and the overexpression of apelin efficiently inhibits the promotion of cell proliferation and invasion mediated by miR-195 mimics in lung adenocarcinoma cells. Conclusions Our data constitute evidence that miR-195 inhibits lung adenocarcinoma cell proliferation and invasion though targeting apelin and provides novel insight into the mechanism underlying the development of lung adenocarcinoma.

Background Considering the wide-spread misuse of antibiotics, the development of new antibacterial drugs may effectively prevent the emergence of antibiotic resistance in bacteria. The understanding of the mechanism underlying the Staphylococcus epidermidis agrC-specific binding polypeptide-mediated inhibition of S. epidermidis biofilm formation may supply ideas for the development of new antibacterial drugs. Methods S. epidermidis cells were cultured with different concentrations (0, 100, 200, 400, 800, and 1,600 µg/mL) of agrC-specific binding polypeptide (N1) and blank (N0). Crystal violet staining was performed to test the formation of biofilms and to determine the best concentration of agrC-specific binding polypeptides, and the bacterial inhibitory concentration was also determined. At different time points (6, 12, 18, 24, and 30 h), XTT assay was used to measure bacterial viability, and the real-time quantitative polymerase chain reaction was performed to measure the expression of atlE, icaA, fbe, and icaR genes. The sulfuric acid-phenol method was used to determine polysaccharide intercellular adhesin (PIA) levels. Results The biofilm formation ability of S. epidermidis was the lowest after treatment with 800 µg/mL agrC-specific binding polypeptide. After 6 h of culture, agrC-specific binding polypeptide upregulated the expression of atlE, icaA, fbe, and icaR and increased the bacterial viability. However, the polypeptide downregulated the expression of atlE, icaA, fbe, and icaR and inhibited S. epidermidis growth and PIA formation after 12 h of culture. Although agrC-specific binding polypeptide upregulated the expression of atlE, icaA, fbe, and icaR after 18 h, they inhibited bacterial growth and PIA formation. Conclusions Thus, agrC-specific binding polypeptide could downregulate the expression of atlE, icaA, fbe, and icaR and inhibit PIA formation by S. epidermidis after 12 h, demonstrating its transient inhibitory effects on the biofilm formation ability of S. epidermidis. Its effective concentration was 800 µg/mL.

To investigate the effect of the estradiol hormones on biofilm formati on and structure of Staphylococcus epidermidis after breast implant surgery.?The concentration of Staphylococcus epidermidis strains ATCC35984 was adjusted to 1×10?According to the results of semi quantitative detection of crystal violet stain and XTT methods, the bacterial suspension of 1×10?High level estradiol can promote bacteria growth, biofilm formation, and biofilm maturity of Staphylococcus epidermidis.探讨雌二醇对乳腺癌术后假体表面表皮葡萄球菌生长以及生物膜形成能力及其结构的影响。.取表皮葡萄球菌标准株ATCC35984，调整浓度至1×10根据XTT法及结晶紫染色半定量检测结果，选择浓度为1×10高浓度雌二醇可促进表皮葡萄球菌生长、生物膜形成和生物膜的成熟。.

Animal models play a key role in identifying treatments for various types of cancer, including lung cancer. The aim of the present study was to develop a new animal model for lung cancer induction using tree shrews from the Yunnan region in China. Tree shrews are suitable for a full simulation of human disease because their structure, function and metabolism are adequately close to human. This animal may offer a new experimental animal model to be used in the study of lung cancer. In the present study, 80 healthy tree shrews were distributed in experimental and control groups. Animals in the experimental group received different concentrations of iodized oil suspension of 3-methylcholanthrene (3-MC) and diethylnitrosamine (DEN) while animals in the control groups received saline or lipiodol solvent via endotracheal instillation. In the 3rd, 5th, 7th, 9th and 11th weeks the body weights of the animals were measured and chest X-ray examinations were conducted. Pathological studies on the lung tissues were also performed and the pathological changes occurring in bronchial epithelium in all the groups were examined. Animals in the experimental group gradually lost their body weight. For tree shrews in the blank control and solvent control groups the survival rates were 100 and 80%, respectively while the survival rate for the experimental group was 0%. Results from the chest X-ray conducted on animals in the blank control and solvent control groups revealed no obvious abnormalities while in the experimental group high-density shadow spots within the perfusion sites were observed. Pathological studies performed on these high-density areas confirmed changes in the bronchial epithelium. In the experimental groups we also detected bronchial epithelial atypical hyperplasia, and apparent changes in carcinoma in situ. In conclusion, lung cancer was successfully induced in tree shrews by a one-time endotracheal introduction of iodized oil suspension of 3-MC and DEN.

Background and objective Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor κB (NF-κB)-inducible nitric oxide synthase (iNOS) signaling pathway of lung tissue in Xuanwei lung cancer patients. Methods From December 2013 to November 2014, 48 cases Xuanwei patients with lung cancer who underwent surgical treatment from the Third Affiliated Hospital of Kunming Medical University were enrolled in this study and compared with lung cancer patients from other regions. The ultrastructure of postoperative specimens was observed by transmission electron microscopy (TEM) to explore the occurrence of inorganic particles. Serum cytokines were analyzed. Then, the expression levels of NF-κB-p65 protein and iNOS protein in postoperative specimens was explored by immunohistochemistry and Western blot. Finally, 8-OHdG accumulation in lung cancer tissues and urine was measured. Results A large number of nanoscale inorganics were observed in alveolar type II cells and macrophages located in adjacent tissues of lung cancer with Xuanwei patients. Silicon (Si) content was found in inorganic elemental analysis. The serum interleukin (IL)-1β levels (31.50±19.16) pg/mL of Xuanwei lung-cancer patients were remarkably higher than those from other regions (11.33±6.94) pg/mL (P

Background and objective The high incidence of lung cancer in Xuanwei, China, has become an important restricting factor for livelihood development, thus exerting local social and economic impacts. Coal is the main fuel of the local community and also the main source of indoor pollution. This study aims to explore the coal combustion inhalable fine particulate matter (PM2.5) and its component output differences in different areas of Xuanwei, Yunnan. Moreover, the aim of this study is to investigate the relationship between inhalation of fine particles and high incidence of local lung cancer. Methods For combustion test, coal mines designated as C1, K7 and M30 were collected from LaoLin Colliery of Laibing Town, Huchang Colliery of Baoshan Town, and Taiping Colliery of Wenxing Town in Xuanwei, respectively. PM2.5 of indoor air was weighed, analyzed for elemental composition, and morphologically compared. The pathological specimen of lung cancer patients in Xuanwei who underwent operation was observed through electron microscope. Results The PM2.5 concentrations in indoor air were (8.244 ±1.460) mg/m3 (C1), (5.066±0.984) mg/m3 (K7), and (5.071±1.460) mg/m3 (M30). The differences among pairwise comparisons were statistically significant (P=0.029). The filter impurities of C1 coal seam primarily include Si- and O-enriched compounds. Moreover, three membranes that comprised other elements, including C, S, and Si, were observed. These membranes were evident from the aggregation of silica and a Ca-Al membrane. Compared with that of other coal seams, C1 coal generated a mass of impurities, in which several particles have irregular shape. We found nanoscale fine particles in some specimens of Xuanwei lung cancer patients. Conclusion The produced combustion of C1 coal was different from that of K7 and M30 coal. PM2.5 composition may be associated with the high local incidence of lung cancer.

The objective of the study was to establish an in vitro model of Candida albicans-Staphylococcus epidermidis mixed species biofilm (BF) on polyvinyl chloride (PVC) material, and to investigate the formation and the structure of mixed species BF formation using a combined approach of confocal laser scanning microscope (CLSM), scanning electron microscope (SEM), and 3D image reconstruction technique. Mixed species BF is achieved by co-incubating Staphylococcus epidermidis bacteria (ATCC35984) and Candida albicans fungal (ATCC10231) with PVC pieces in Tris-buffered saline. BF formation was examined at 2, 6, 12, 24, 48, and 72 h of co-culture. Thickness of these BFs and the number, and percentage of viable cells in BFs were measured. CT scan images of BFs were obtained using CLSM and SEM and reconstructed 3D images of mixed species BF were acquired, in an effort to examine structure of the BF. Staphylococcus epidermidis attached to various forms of candida albicans (spores, pseudohyphae, and hyphae), formed complex and dense mesh arrays. The BF is constituted of a large number of viable and dead pathogens, the surface of mixed species BF is uneven, with living pathogens predominating protrusive portions and dead pathogens aggregating in concaves. Mixed species BF formation on the surface of PVC material was found to be a dynamic process, with rapid growth being at 24 h of co-culture, maximal thickness peaked at 48 h. These mixed species BF matured at 48-72 h. Significant differences were observed in the proportion of viable cells between interior, middle, and outer layers of BFs (p

In the tumor progression, transforming growth factor β1 (TGFβ1) plays a critical role in tumorigenesis as well as metastasis. It is known that high plasma level of TGFβ1 in patients with advanced non-small cell lung cancer (NSCLC) is correlated with poor prognostics. In addition, the generation of cancer stem-like cells is associated with metastasis, drug resistance, and tumor recurrence, which also lead to poor outcomes in NSCLC patients. However, it remains unclear how TGFβ1 promotes NSCLC cells to acquire stem-like properties and accelerate tumor metastasis. In our study, we found that short term TGFβ1 treatment resulted in a significant epithelial-mesenchymal transition (EMT) morphological change in TGFβ1–sensitive NSCLC cells but not in insensitive cells. Western blotting confirmed increased Vimentin and reduced E-Cadherin protein expression after TGFβ1 treatment in A549, NCI-H1993, and NCI-H358 cells. TGFβ1 incubation dramatically decreased in vitro cell proliferation and increased cell invasion in TGFβ1–sensitive NSCLC cells but not in NCI-H1975, NCI-H1650, and HCC827 cells. Moreover, TGFβ1 was able to enhance the mRNA expression of Oct4, Nanog and Sox2 and drastically increased anchorage-independent colony formation in TGFβ1–sensitive NSCLC cells, suggesting the acquisition of cancer stem-like properties. Interestingly, we found that vascular endothelial growth factor receptor 3 (VEGFR3) mRNA expression was significantly elevated in TGFβ1–sensitive NSCLC cells compared to insensitive cells. And TGFβ1 was capable of inducing VEGF-C gene expression. Pharmacological blocking TGFβ type I receptor kinase (ALK5) significantly inhibited TGFβ1-induced VEGF-C expression. Silencing of ALK5 by siRNA also dramatically reduced TGFβ1-induced VEGF-C expression in TGFβ1–sensitive NSCLC cells. Therefore, TGFβ1 contributes for NSCLC metastasis through promoting EMT, generation of high invasive cancer cells with stem-like properties, and increasing VEGF-C expression. Blocking TGFβ pathway is a potential therapeutic target in human non-small cell lung cancer.

Background and objective The mismatch between pleural space and remnant lung after bilobectomy has been considered as the main reason for the high incidence of postoperative complications in non-small cell lung cancer (NSCLC) patients. The aim of this study is to analyze the differences in postoperative complications between bilobectomy and lobectomy in the right lung of NSCLC patients. Method This study included 528 NSCLC patients who underwent right pulmonary lobectomy. A total of 352 cases that underwent upper or lower right lobectomy (108 upper and 244 lower) were the control group, and 176 cases that underwent bilobectomy (57 upper and middle and 119 lower and middle) were the observation group. A retrospective case-control study was performed on a series of matched NSCLC patients. Cases and controls were matched by age, ppoFEV1%, LEVF%, operation method, cardiac comorbidity, type of postoperative management, and pathological type at a ratio of 1:2. The prevalence of 30-day death, occurrence of cardiac-respiratory complications (hospital-acquired pneumonia, low oxygen concentration, pulmonary embolism, cerebral apoplexy, arrhythmia, myocardial ischemia or infarction, and cardiac insufficiency) and occurrence of space-related complications (atelectasis, air leak more than 5 days, and pneumothorax) were compared between the bilobectomy and lobectomy groups. Result The prevalence of 30-day death was 3.4% (6/176) in the bilobectomy group and 2.3% (8/352) in the lobectomy group. No statistical significance was observed between the two groups. The cardiac-respiratory complication rate in bilobectomy group (23.8%; 42/176) was higher than that in lobectomy group (10.7%; 38/352). The cardiac-respiratory complication rate of the lower and middle pulmonary lobectomy patients in the bilobectomy group (26.5%; 31/119) was significantly higher than that in the lower pulmonary lobectomy patients (4.9%; 12/244). The space-related complications in bilobectomy group and lobectomy group were 20.4% (36/176) and 17.3% (61/352), respectively. No statistically significant difference between the two groups was observed. Conclusion The postoperative cardiac-respiratory complications of NSCLC patients with right bilobectomy are higher than those of the right lobectomy patients, but the prevalence of 30-day death and space-related complication was not statistically different between the two groups.

Background and objective This study was conducted to evaluate the effects of the accumulation-associated protein (Aap) gene and transform growth factor-beta 1 (TGF-β1) on the biofilm formation of lung cancer-related Staphylococcus epidermidis (SE). Methods Species identification was performed to isolate SE strains from clinically implanted materials in lung cancer patients. Stable genetic aggregated proteins, which are associated with negative and positive isolates, were obtained. The biofilm-formation ability of the SE Aap gene was determined by PCR. Density gradient method was used to extract peripheral blood mononuclear cells from patients with non-small cell lung cancer. After 30 h, these cells were co-cultured with A549 at different TGF-β1 concentrations. The supernatant was then combined with SE Aap+ and SE Aap- strains and co-cultured with a medical silicone rubber. A semi-quantitative adhesion test was performed for each bacterial biofilm formation. Scanning electron microscopy was also conducted to observe the microcosmic condition of this material on the bacterial biofilm surface. Results The Aap gene was closely related to SE biofilm formation. At 10 ng/mL, 20 ng/mL, and 40 ng/mL, SE Aap+ biofilm on the medical silicone rubber surface was thicker in the TGF-β1 group than in the control group. No significant differences were found between TGF-β1 groups. For the SE Aap- strains, no evident biofilm was formed in TGF-β1 and control groups. Conclusion In plant material-related infection of lung cancer patients, SE Aap+ strain easily forms biofilm. Furthermore, TGF-β1 was conducive for the biofilm formation of SE Aap+ strains.

To study the influence of brominated furanones on the formation of Staphylococcus aureus (SA) biofilm on PVC thus providing new avenues of research on the surface modification of materials and clinical treatment of biomaterial-centered infection. Three brominated furanones (furanone-1, furanone-2, and furanone-3) were coated on the surface of PVC material. Both the modified PVC materials and SA were co-cultivated together. To assess the thickness of bacterial biofilm and bacterium colony unit area on PVC materials, confocal laser scanning microscopy and scanning electron microscopy (SEM) were used to observe the surface structure of SA biofilm formation. All treatments were compared with the control group which was not coated with furanones. PVC materials coated with furanone-1 had an increase in bacterial biofilm as well as SA colony area when compared with control. However, there was no significant difference between treating with furanone-1 and furanone-3 (P > 0.05). The impact of different brominated furanones on SA biofilm formation on the surface of PVC materials is different, furanone-1 can promote the SA biofilm formation on the surface of PVC material.

Xuanwei district in Yunnan Province of China has pretty high incidence of lung cancer in China, even a- round the world. Studies have shown that there exists a close relationship between lung cancer and local indoor air pollution caused by Bituminous coal. Considering that the indoor air pollution in Xuanwei District is caused by "open fireplace", an indoor air pollution simulation system was designed, and an F344 rats lung damage model was estab- lished for this indoor air pollution fireplace. The model is based on indoor air pollution simulation system with signal multiplexer control and multi-channel acquisition, and mining PID algorithm was used for polynomial fitting to each test point, and a relatively constant PM2. 5 air pollution status was simulated. The results showed that the system could simulate a variety of states of air pollution, provide a new test method for evaluation of human injury caused by indoor air pollution and a new idea for the study of the incidence of lung cancer in Xuanwei district and other places.

The aim of the study was to investigate the effects of Survivin antioligonucleotide on the proliferation, apoptosis and cell cycle of Xuanwei lung adenocarcinoma cell XWLC-05. Specific targeting Survivin ASODN was composed firstly. XWLC-05 would be divided into 4 groups: Group Sham (blank), Group Lip (simple liposome), Group Lip-SODN (transfected sense oligonucleotide) and Group Lip-ASODN (transfected ASODN). All groups had been transfected under the same condition for 48 hours. Then West blotting was used to check the expression of Survivin in cells from different groups and flow cytometer was used to find out the apoptosis rate of cells in different groups. The expression of XWLC-05 Survivin in Group Lip-ASODN decreased obviously and apoptosis rate was significantly higher than that of other groups (P < 0. 05). XWLC-05 transfected by Survivin ASODN could down regulate the expression of Survivin and lower expression of Survivin might lead to the apoptosis of XWLC-05 and restrain the proliferation of cancer cells.

Objective The interaction of cell and medical biomaterial is one of the significant factors to affect clinical application of medical biomaterial. This research is to investigate three of suture lines how to affect the proliferation and cell cycle of lung adenocarcinoma cell A549 in vitro.

Background and objective Xuanwei is an area of the highest incidence and mortality with lung cancer in China. The aim of this study is to determine serum selenium concentrations in lung cancer patients from Xuanwei as well as selenium levels of cancerous tissues, cancer-adjacent pulmonary tissues, and normal pulmonary lung tissues from lung cancer patients, and the relationship between selenium and the high incidence of lung cancer in Xuanwei. Methods One hundred and twenty female adults from Xuanwei were enrolled in the study (60 lung cancer patients and 60 with non-tumor and non-respiratory diseases, respectively) and blood samples were collected. Sixty fresh cancerous tissues and their adjacent as well as normal tissues were collected (31 samples from lung cancer patients living in Xuanwei for more than 2 years and 29 from patients in other regions of Yunnan Province outside of Xuanwei, respectively). Serum and tissue selenium concentrations were assayed using a fluorometric method. Results Women with lung cancer had a mean serum selenium value (55.22 μg/L±13.34 μg/L) of averagely 8.47%, significantly lower than that in subjects with non-tumor and non-respiratory disease controls (60.33 μg/L±13.82 μg/L)(P < 0.05). Selenium concentrations in the tumor tissues (0.105 μg/g±0.034 μg/g) were statistically lower than that of normal ones (0.140 μg/g±0.048 μg/g)(P < 0.05) from lung cancer patients in Xuanwei. Statistical differences had not been found between the cases from Xuanwei and non-Xuanwei district, adenocarcinoma and squamous cell carcinoma, among Stage I, Stage II, stage III groups. Conclusion Lower serum selenium state was negatively related to the incidence of lung cancer in Xuanwei. It was likely that lower selenium level of lung tissues was potential risk factor to lead to lung cancer.

Background and objective The interaction of cell and medical biomaterial is one of the significant factors to affect clinical application of medical biomaterial. This research is to investigate three of suture lines how to affect the proliferation and cell cycle of Lung Adenocarcinoma cell A549. Methods Three of suture lines are respectively cultivated with Lung Adenocarcinoma cell A549, after of 72 hours, to detect absorptance of each groups by MTT method in order to reflect the proliferation of Lung Adenocarcinoma cell A549 and to detect percentage of G1 period cell and S period cell of each of groups by flow cytometry. Results Different of suture lines have effect differently on the proliferation and cell cycle of Lung Adenocarcinoma cell A549 (P < 0.05). The effect of absorbent suture line on the proliferation and cell cycle of Lung Adenocarcinoma cell A549 is strong, the effect of chorda serica chirurgicalis is medium, the effect of slide wire is poor. Different length of each suture line have effect differently on the proliferation and cell cycle of Lung Adenocarcinoma cell A549 (P < 0.05). Conclusion Three of suture line materials have different effect on the proliferation and cell cycle of Lung Adenocarcinoma cell A549, to reflect dose-effect relation.

Background and objective The therapeutic efficacy of late lung-cancer was very poor, and cytokine-induced killer cells (CIK) were paid more attention to treat non-small cell lung cancer (NSCLC). The aim of this study is to get insight into the role of bronchial arterial infusion bronchial arterial infusion (BAI) plus CIK about NSCLC by comparing therapeutic efficacy among BAI, traditional vein chemotherapy and BAI plus CIK, for late NSCLC. Methods A total of 120 patients were enrolled in this study, dividing randomly into three groups: bronchial arterial infusion (BAI), traditional vein chemotherapy and BAI plus CIK. Clinical effects and side effects were estimated after two period of therapy. Results The effective rate (CR+PR%) of combined group is higher than the traditional vein chemotherapy group (66.67%, n=39) and there are significant differences (χ2=4.721, P=0.03); The side effect of rate of BAI plus CIK group is significantly lower than the traditional vein chemotherapy group, and so did the non-bone marrow inhibition side effects (P < 0.05). The tumor progression rate (PD%) of bronchial arterial infusion (BAI) group is higher than combined group (χ2=4.287, P=0.038). There was no difference between the traditional vein chemotherapy group and combined group (χ2=0.082, P=0.775). Conclusion Bronchial Artery Infusion combined with cytokine-induced killer cells is an ideal, safety, effective comprehensive treatment method for late stage lung cancer.

Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor κB (NF-κB)-inducible nitric oxide synthase (iNOS) signaling pathway of lung tissue in Xuanwei lung cancer patients.From December 2013 to November 2014, 48 cases Xuanwei patients with lung cancer who underwent surgical treatment from the Third Affiliated Hospital of Kunming Medical University were enrolled in this study and compared with lung cancer patients from other regions. The ultrastructure of postoperative specimens was observed by transmission electron microscopy (TEM) to explore the occurrence of inorganic particles. Serum cytokines were analyzed. Then, the expression levels of NF-κB-p65 protein and iNOS protein in postoperative specimens was explored by immunohistochemistry and Western blot. Finally, 8-OHdG accumulation in lung cancer tissues and urine was measured.A large number of nanoscale inorganics were observed in alveolar type II cells and macrophages located in adjacent tissues of lung cancer with Xuanwei patients. Silicon (Si) content was found in inorganic elemental analysis. The serum interleukin (IL)-1β levels (31.50 ± 19.16) pg/mL of Xuanwei lung-cancer patients were remarkably higher than those from other regions (11.33 ± 6.94) pg/mL (P0.01), with statistically significant difference. The pathological tissues of Xuanwei lung-cancer patients express NF-κB-p65, and iNOS expression were significantly higher than those of patients from non-Xuanwei regions. No significant difference was found between cancerous and normal adjacent tissues. Xuanwei lung-cancer tissues and urine 8-OHdG level (40.124 ± 8.597) ng/mgCr were significantly higher than those of patients from other regions (25.673 ± 7.986) ng/mg Cr (P0.05), with statistically significant difference.The accumulation of inorganics and the activation of NF-κB-iNOS signaling pathway may contribute to Xuanwei lung cancer. .背景与目的 室内空气污染不仅会诱发哮喘，也会导致慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD），甚至促进肺癌发生。随着宣威肺癌的病因学研究，发现室内空气污染最终造成肺部无机颗粒物的沉积，这些物质可以造成肺泡细胞损伤、信号通路激活，最终促进肿瘤的发生。本研究旨在探讨宣威肺癌患者肺部中无机杂质的赋存以及核转录因子（nuclear factor κB, NF-κB）-诱导型一氧化氮合成酶（inducible nitric oxide synthase, iNOS）信号通路的激活情况。方法 选取48例2013年12月-2014年11月在昆明医科大学第三附属医院行手术治疗的宣威肺癌患者与其他地区的肺癌患者作为研究对象，用透射电镜（transmission electron microscope, TME）对患者术后标本进行超微结构的观察，探究无机颗粒物的赋存情况；对患者的血清行细胞因子检测；对术后的标本行免疫组化以及蛋白质印迹（Western blot），了解NF-κB-p65蛋白以及iNOS蛋白的表达；对肺癌组织中和尿液中的8-OHdG赋存进行检测。结果 在宣威肺癌患者癌旁组织的肺泡II型细胞、巨噬细胞中可见到大量纳米级无机物赋存；对无机物进行元素分析，含有硅（Silicon, Si）成分；宣威地区患者血清中白介素（interleukin, IL）-1β（31.50±19.16）pg/mL较其他地区肺癌患者（11.33±6.94）pg/mL高，差异有统计学意义（P0.01）；宣威肺癌与其他地区肺癌患者的术后病理组织中癌组织有NF-κB-p65和iNOS表达，较非宣威地区明显升高；癌旁和正常组织之间未见明显差异；宣威肺癌组织和尿液8-OHdG较非宣威地区肺癌患者高，肺癌患者尿液中的8-OhdG（40.124±8.597）ng/mgCr与其他地区患者（25.673±7.986）ng/mgCr相比，差异有统计学意义（P0.05）。结论 肺部无机物的赋存以及NF-κB-iNOS信号通路的激活可能促进了宣威肺癌的发生。.

To explore the function of intercellular adhesion A (icaA), fibrinogen binding protein (fbe), and accumulation-associated protein (aap) genes in formation of Staphylococcus epidermidis-Candida albicans mixed species biofilms.The experiment was divided into 3 groups: single culture of Staphylococcus epidermidis ATCC35984 (S. epidermidis group) or Candida albicans ATCC10231 (C. albicans group), and co-culture of two strains (mixed group) to build in vitro biofilm model. Biofilm mass was detected by crystal violet semi-quantitative adherence assay at 2, 4, 6, 8, 12, 24, 48, and 72 hours after incubation. XTT assay was performed to determine the growth kinetics in the same time. Scanning electron microscopy (SEM) was used to observe the ultrastructure of the biofilms after 24 and 72 hours of incubation. The expressions of icaA, fbe, and aap genes were analyzed by real-time fluorescent quantitative PCR.Crystal violet semi-quantitative adherence assay showed that the biofilms thickened at 12 hours in the S. epidermidis and mixed groups; after co-cultured for 72 hours the thickness of biofilm in mixed group was more than that in the S. epidermidis group, and there was significant difference between 2 groups at the other time (P0.05) except at 72 hours (P0.05). In C. albicans group, the biofilm started to grow at 12 hours of cultivation, but the thickness of the biofilm was significantly lower than that in the mixed group in all the time points (P0.05). XTT assay showed that the overall growth speed in the mixed group was greater than that in the C. albicans group, and it was greater than that in the S. epidermidis group at 48 hours; there was no significant difference in the growth speed between the mixed groups and the S. epidermidis group in the other time points (P0.05) except at 12 hours (P0.05). The absorbance (A) value in the mixed group was lower than that in the S. epidermidis group at 2 and 4 hours, but no significant difference was shown (P0.05); the A value of mixed group was significantly higher than that of the C. albicans group after 6 hours (P0.05). SEM observation showed that mature biofilms with complex structure formed in all groups. The real-time fluorescent quantitative PCR showed the expressions of fbe, icaA, and aap genes in mixed group increased 1.93, 1.52, and 1.46 times respectively at 72 hours compared with the S. epidermidis group (P0.05).Mixed species biofilms have more complex structure and are thicker than single species biofilms of Staphylococcus epidermidis or Candida albicans, which is related to increased expressions of the icaA, fbe, and aap genes of Staphylococcus epidermidis.

The mismatch between pleural space and remnant lung after bilobectomy has been considered as the main reason for the high incidence of postoperative complications in non-small cell lung cancer (NSCLC) patients. The aim of this study is to analyze the differences in postoperative complications between bilobectomy and lobectomy in the right lung of NSCLC patients.This study included 528 NSCLC patients who underwent right pulmonary lobectomy. A total of 352 cases that underwent upper or lower right lobectomy (108 upper and 244 lower) were the control group, and 176 cases that underwent bilobectomy (57 upper and middle and 119 lower and middle) were the observation group. A retrospective case-control study was performed on a series of matched NSCLC patients. Cases and controls were matched by age, ppoFEV1%, LEVF%, operation method, cardiac comorbidity, type of postoperative management, and pathological type at a ratio of 1:2. The prevalence of 30-day death, occurrence of cardiac-respiratory complications (hospital-acquired pneumonia, low oxygen concentration, pulmonary embolism, cerebral apoplexy, arrhythmia, myocardial ischemia or infarction, and cardiac insufficiency) and occurrence of space-related complications (atelectasis, air leak more than 5 days, and pneumothorax) were compared between the bilobectomy and lobectomy groups.The prevalence of 30-day death was 3.4% (6/176) in the bilobectomy group and 2.3% (8/352) in the lobectomy group. No statistical significance was observed between the two groups. The cardiac-respiratory complication rate in bilobectomy group (23.8%; 42/176) was higher than that in lobectomy group (10.7%; 38/352). The cardiac-respiratory complication rate of the lower and middle pulmonary lobectomy patients in the bilobectomy group (26.5%; 31/119) was significantly higher than that in the lower pulmonary lobectomy patients (4.9%; 12/244). The space-related complications in bilobectomy group and lobectomy group were 20.4% (36/176) and 17.3% (61/352), respectively. No statistically significant difference between the two groups was observed.The postoperative cardiac-respiratory complications of NSCLC patients with right bilobectomy are higher than those of the right lobectomy patients, but the prevalence of 30-day death and space-related complication was not statistically different between the two groups.背景与目的 双肺叶切除后剩余肺叶与胸膜腔空间不匹配是右侧非小细胞肺癌（non-small cell lung cancer, NSCLC）患者术后高并发症发病率的主要原因。本研究旨在比较右侧NSCLC双肺叶切除与单肺叶切除患者术后并发症发生率之间的差异。方法 本研究共纳入行右侧肺叶切除NSCLC 528例，右肺单肺叶切除病例352例（108例上叶与244例下叶）为对照组，右肺双肺叶切除病例176例（57例中上叶与119例中下叶）为观察组。两组病例行回顾性病例-对照配对研究。两组病例按照年龄、性别、术前预计FEV1%、LEVF%、手术方式、术前心脏伴随疾病、术后管理方式、病理类型、肿瘤大小等情况进行按1:2进行配对。比较两组患者术后30天内死亡率、空间相关并发症（肺不张、漏气大于5天、气胸）发生率与心肺并发症（院内获得性肺炎、低氧气血症、肺栓塞、脑卒中、心律失常、心肌缺血或梗塞、心功能不全）发生率之间的差异。结果 双肺叶切除组病例术后30天死亡率为3.4%（6/176），单肺叶切除组病例为2.3 %（8/352），两者间差异无统计学意义；双肺叶切除组病例术后心肺并发症总体发病率为23.8%（42/176）高于单肺叶切除组10.7%（38/352），差异具有统计学意义；双肺叶切除组中下叶切除病例的心肺并发症发病率为26.5%（31/119）远高于单肺叶切除组4.9%（12/244）；而空间相关并发症双肺叶切除组与单肺叶切除组分别为20.4%（36/176）和17.3%（61/352），两者间差异无统计学意义。结论 右侧NSCLC双肺叶切除患者术后心肺相关并发症发生率高于单肺叶切除患者， 30天内死亡率与空间相关并发症发生率无明显差异。

In this study, a central venous catheter (CVC)-associated infection model was established in rats to investigate and evaluate the effect of biofilms on the virulence of the pathogens. Twenty-four adult SD rats were randomly divided into biofilm positive (BF+) and biofilm negative (BF-) groups to be challenged with strains of S.epidermidis. Serum levels of inflammatory cytokines were measured and the infection rate and counts of bacteria cells were studied. Compared to rats of BF- group, the serum level of TNF and IL-6 significantly increased in rats of BF+ group (P < 0.01) and the level of IL-10 and IFN-γ significantly decreased (P < 0.01), striking the balance of pro-inflammatory/anti-inflammatory cytokines. The infection rate and bacterial counts in tissues and blood of rats of BF + group were significantly higher than those of rats of BF- group (P < 0.05).Inflammatory cell infiltration in vital organs (heart, lung, liver and kidneys) was more significant in rats of BF+ group than that of rats of BF- group. CVC-associated infection model can be successfully reproduced in rats by injecting 5 × 10(6) CFU of S.epidermidis. Biofilm formation can significantly enhance the virulence of the bacteria, leading to uncontrolled infection. The serum level of inflammatory cytokines, infection rate and the extent of inflammatory cell infiltration are important markers for evaluating the virulence of biofilm.

This study was conducted to evaluate the effects of the accumulation-associated protein (Aap) gene and transform growth factor-beta 1 (TGF-β1) on the biofilm formation of lung cancer-related Staphylococcus epidermidis (SE).Species identification was performed to isolate SE strains from clinically implanted materials in lung cancer patients. Stable genetic aggregated proteins, which are associated with negative and positive isolates, were obtained. The biofilm-formation ability of the SE Aap gene was determined by PCR. Density gradient method was used to extract peripheral blood mononuclear cells from patients with non-small cell lung cancer. After 30 h, these cells were co-cultured with A549 at different TGF-β1 concentrations. The supernatant was then combined with SE Aap+ and SE Aap- strains and co-cultured with a medical silicone rubber. A semi-quantitative adhesion test was performed for each bacterial biofilm formation. Scanning electron microscopy was also conducted to observe the microcosmic condition of this material on the bacterial biofilm surface.The Aap gene was closely related to SE biofilm formation. At 10 ng/mL, 20 ng/mL, and 40 ng/mL, SE Aap+ biofilm on the medical silicone rubber surface was thicker in the TGF-β1 group than in the control group. No significant differences were found between TGF-β1 groups. For the SE Aap- strains, no evident biofilm was formed in TGF-β1 and control groups.In plant material-related infection of lung cancer patients, SE Aap+ strain easily forms biofilm. Furthermore, TGF-β1 was conducive for the biofilm formation of SE Aap+ strains.背景与目的 研究聚集相关蛋白（accumulation-associated protein, Aap）基因及转化生长因子β1（TGF-β1）对肺癌相关生物材料表皮葡萄球菌（SE）生物膜形成的影响。方法 种属鉴定分离临床肺癌患者植入材料感染表皮葡萄球菌株，PCR法检测生物膜形成相关基因Aap，检测表皮葡萄球菌Aap基因株生物形成能力。密度梯度法提取非小细胞肺癌患者外周血单个核细胞，与人肺腺癌细胞A549在不同浓度（10 ng/mL, 20 ng/mL, 40 ng/mL）TGF-β1共培养30 h后，取上清液分别加入SE Aap+株、SE Aap-株下与医用硅橡胶培养30 h，半定量粘附试验测各组细菌生物膜形成的情况，扫描电镜观察材料表面生物膜微观情况。结果 Aap基因的与表皮葡萄球菌生物膜的形成密切相关（P0.01）。在（10 ng/mL, 20 ng/mL, 40 ng/mL）TGF-β1浓度组医用硅橡胶表面SE Aap+生物膜的厚度大于空白组（P0.01）。SE Aap+株在TGF-β1浓度组间生物膜的厚度无明显差异（P0.05）。在不同浓度TGF-β1因子刺激下SE Aap-株均不能形成明显细菌生物膜。结论 在肺癌患者植入材料引起感染中表皮葡萄球菌Aap基因表达阳性株较易形成细菌生物膜，TGF-β1对SE Aap阳性形成细菌生物膜有一定促进作用。

OBJECTIVES: Lymph node involvement is a key feature and an independent prognostic factor of oesophageal squamous cell carcinoma. However, an accurate and robust assay to predict the lymphatic spread of oesophageal squamous cell carcinoma is unavailable. The purpose of this study was to determine whether serum vascular endothelial growth factor-C (VEGF-C) and spleen tyrosine kinase levels are potential markers of lymph node metastasis in patients with oesophageal squamous cell carcinoma. METHODS: In the study, 108 patients with oesophageal squamous cell carcinoma and 24 healthy subjects participated. Serum spleen tyrosine kinase and VEGF-C concentrations were examined by enzyme-linked immunosorbent assays. RESULTS: Patients with oesophageal squamous cell carcinoma had significantly elevated VEGF-C and decreased spleen tyrosine kinase in serum when compared with normal controls (P< 0.05). Pearson’s correlation analysis revealed that serum spleen tyrosine kinase was negatively correlated with the serum VEGF-C level in oesophageal squamous cell carcinoma patients (r = −0.453, P= 0.000). In addition, surgical resections of the oesophageal tumour profoundly brought both serum spleen tyrosine kinase and VEGF-C closer to the normal range at 2 weeks after operation (P< 0.05). Statistical analysis showed that enhanced serum VEGF-C and reduced spleen tyrosine kinase significantly correlated with the stage of regional lymph node metastasis, tumour size and the status of primary tumour extension, but not with other clinicopathological features of the patients (P< 0.05). CONCLUSIONS: Our data suggest that both serum spleen tyrosine kinase and VEGF-C levels are valuable in the preoperative evaluation of lymph node metastasis in patients with oesophageal squamous cell carcinoma.