Costimulatory molecule-related lncRNA model as a potential prognostic biomarker in non-small cell lung cancer.

OBJECTIVE: Costimulatory molecules have been demonstrated to exert essential roles in multiple cancers. However, their role in lung cancer remains elusive. Here, we sought to identify costimulatory molecule-related lncRNAs in non-small cell lung cancer (NSCLC) and establish a prognostic signature to predict the prognosis of patients with NSCLC. METHODS: A total of 535 lung adenocarcinoma (LUAD) and 502 lung squamous cell carcinoma (LUSC) patients from the cancer genome atlas (TCGA) database were recruited. A novel costimulatory molecule-based lncRNA prognostic model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm to predict the overall survival. The Homo_sapiens.GRCh38 data set was set as a reference file for probe annotation. RESULTS: A total of 593 costimulatory molecule-related lncRNAs were extracted. After analysis, six costimulatory molecule-related lncRNAs (AC084859.1, AC079949.2, HSPC324, LINC01150, LINC01150, and AC090617.5) were screened. A prognostic model based on the six lncRNAs was established using systematic bioinformatics analyses. The prognostic model had a prognostic value in NSCLC patients. Furthermore, a prognostic nomogram was established based on clinical parameters and a risk-score model. Patients with different risk scores had considerably different tumor-infiltrating immune cells, somatic mutational loading, clinical outcomes, signaling pathways, and immunotherapy efficacy. In addition, LINC01137 was associated with unfavorable disease outcomes and fueled tumor progression in NSCLC. CONCLUSION: Taken together, our study demonstrated that a costimulatory molecule-related lncRNA model could be a potential prognostic biomarker in NSCLC. Moreover, LINC01137 could facilitate the proliferation and invasion of lung cancer.

NEIL3 Mediates Lung Cancer Progression and Modulates PI3K/AKT/mTOR Signaling: A Potential Therapeutic Target.

Background: Nei endonuclease VIII-like 3 (NEIL3) is widely involved in pathophysiological processes of the body; however, its role in lung cancer has not been conclusively determined. Objective: This study is aimed at exploring the role of NEIL3 in lung cancer. Methods: The public data used in this study were downloaded from The Cancer Genome Atlas (TCGA) database. "Limma" in R was used for the analysis of differentially expressed genes. Clinical correlations and prognostic analyses were performed using the survival package in R. The proliferative abilities of lung cancer cells were evaluated by the CCK8 and colony formation assays while their invasive and migration abilities were assessed by the transwell and wound healing assays. Quantitative real-time PCR (qRT-PCR) and western blot analyses were utilized to detect RNA and protein levels. Biological differences between groups were determined by gene set enrichment analysis (GSEA). Tumor Immune Dysfunction and Exclusion (TIDE) as well as Genomics of Drug Sensitivity in Cancer (GDSC) was used for immunotherapeutic and chemotherapeutic sensitivity analyses. Results: NEIL3 was upregulated in NSCLC tissues and cell lines, implying that it is involved in lung cancer initiation and progression. Clinical correlation and prognostic analyses showed that NEIL3 was associated with worse clinical features (stage and T and N classifications) and poor prognostic outcomes. In vitro, NEIL3 significantly enhanced NSCLC proliferation, invasion, and migration. GSEA indicated that NEIL3 might be involved in PI3K/AKT/mTOR, G2/M checkpoints, and E2F target pathways. Inhibition of NEIL3 suppressed cyclinD1 and p-AKT protein levels; however, it had no effects on AKT levels, indicating that NEIL3 can partially activate the PI3K/AKT/mTOR signaling pathway. The predicted result of TIDE indicated that immunotherapeutic nonresponders had elevated NEIL3 levels. Moreover, there was a positive correlation between NEIL3 levels and chemosensitivity to cisplatin and paclitaxel. Conclusion: In general, NEIL3 mediates NSCLC progression and affects sensitivity to immunotherapy and chemotherapy; therefore, it is a potential molecular target for treatment.

circRNA hsa_circ_0018414 inhibits the progression of LUAD by sponging miR-6807-3p and upregulating DKK1.

Lung adenocarcinoma (LUAD) is a subtype of lung cancer with a high incidence and mortality all over the world. In recent years, circular RNAs (circRNAs) have been verified to be a novel subtype of noncoding RNAs that exert vital functions in various cancers. Our research was designed to investigate the role of circ_0018414 in LUAD. We first observed that circ_0018414 was downregulated in LUAD tissues and cells. Also, low expression of circ_0018414 predicted unfavorable prognosis of LUAD patients. Then, upregulation of circ_0018414 repressed cell proliferation and stemness, while promoting cell apoptosis, in LUAD. Moreover, circ_0018414 overexpression enhanced the expression of its host gene, dickkopf WNT signaling pathway inhibitor 1 (DKK1), therefore inactivating the Wnt/ß-catenin pathway. Additionally, circ_0018414 could sponge miR-6807-3p to protect DKK1 mRNA from miR-6807-3p-induced silencing, leading to DKK1 upregulation in LUAD cells. Finally, rescue assays proved that circ_0018414 inhibited the progression of LUAD via the miR-6807-3p/DKK1 axis-inactivated Wnt/ß-catenin pathway. The findings in our work indicated circ_0018414 as a tumor inhibitor in LUAD, which might provide a new perspective for LUAD treatment.

Efficacy of multi-groove silicone drains in single-port video-assisted thoracoscopic lung cancer surgery and their effect on C-reactive protein: a single-center experience.

BACKGROUND: The purpose of this study was to systematically evaluate the effectiveness and safety of a multi-groove silicone drain in single-port video-assisted thoracoscopic lung cancer surgery and its effect on postoperative serum C-reactive protein (CRP) levels. METHODS: We retrospectively analyzed 122 surgical cases who underwent standard lobectomy and lymph node dissection for primary lung cancer between May 2020 and December 2020. A total of 62 patients received 19-F multi-groove silicone drains (experimental group) and 60 patients received 24-F conventional chest drains (control group). According to the different thoracic drainage approaches, the clinical efficacy in the perioperative period, postoperative complications, and postoperative serum CRP levels were compared between the 2 groups. RESULTS: In this study, thoracic drainage volume, the average visual analog scale (VAS) pain scores in incisions, the rate of primary healing at the site of incisions, and the pulmonary infection rate in the multi-groove silicone drain group were significantly lower than those in the conventional chest drain group (P<0.05), but there was no significant difference in the average hospital stay time, arrhythmia rates, and chest tube removal time between the 2 groups. At postoperative day 1, the levels of serum CRP in the 2 groups were further increased (P>0.05), and the comparison between the 2 groups showed that the levels of serum CRP in the multi-groove silicone drain group at 72 h after the operation were significantly lower than those in the conventional drain group (P<0.05). CONCLUSIONS: Our results showed that a multi-groove silicone drain is feasible and relatively safe in single-port video-assisted thoracoscopic lung cancer surgery for most patients. However we should take cautious in those patients with higher susceptibility of postoperative active bleeding. In patients undergoing lung cancer surgery in the clinical treatment process, the use of a multi-groove silicone drain can improve the quality of life of patients. Due to a small number of included studies and unclear bias, the above results should be verified by high-quality, large-sample randomized controlled studies. KEYWORDS: Video-assisted thoracoscopic lung cancer surgery; multi-groove silicone drains; conventional chest drains.

Comparing efficacy and safety of regorafenib versus pemetrexed in lung cancer: A preliminary clinical trial evaluating effect of inflammatory biomarkers on disease progression.

This pilot clinical trial was designed to compare the efficacy and safety of regorafenib versus pemetrexed in Chinese patients with early stage of lung cancer. Also, the effect of inflammatory biomarkers on disease progression among Lung cancer patients who received regorafenib versus pemetrexed was evaluated in the present study. The patients who were diagnosed with early stage of lung cancer were enrolled. The eligible participants were randomized to receive regorafenib 160 mg (orally once daily for the first 21 days of each 28-day cycle) plus BSC or pemetrexed 500 mg/m2 intravenously (Day 1 of each 21-day cycle in combination with cisplatin 75 mg/m2 i.v. beginning 30 minutes after pemetrexed administration) plus BSC in a 1:1 ratio. Efficacy measures such as overall survival, progression-free survival and overall response were assessed after regorafenib and pemetrexed treatment. Safety of after regorafenib and pemetrexed treatment was also assessed. Blood was collected into a test tube pre-washed with chilled EDTA tubes, and then centrifuged to collect plasma sample for estimation of inflammatory biomarkers of interest. Survival time in respect to disease progression was also assessed. Also, biomarker assessments were made at each visit, to see whether inflammatory biomarker has any specific role on survival or in predicting progression of lung cancer. The present study results show that the safety and efficacy profile of regorafenib and pemetrexed was found similar in Chinese patients with early stage lung cancer. In general, regorafenib and pemetrexed treatment was well tolerated in Chinese patients with early stage Lung cancer. The results of this pilot study showed that inflammatory biomarkers such as interleukin 6 and interleukin 17A play an important role predicting progression of early stage lung cancer among Chinese patients.

CircRNA has_circ_0001946 promotes cell growth in lung adenocarcinoma by regulating miR-135a-5p/SIRT1 axis and activating Wnt/ß-catenin signaling pathway.

Circular RNAs (circRNAs) are involved in the tumorigenesis and progression of human cancers. However, little is known about the biological role and mechanism of circRNAs in lung adenocarcinoma (LAC). In the present study, we applied microarray analysis to screen for LAC-specific circRNAs. Top ten upregulated circRNAs were chosen for qRT-PCR analysis. Among them, circ_0001946 was significantly overexpressed in both LAC tissues and cell lines. In addition, the expression level of circ_0001946 was positively correlated with TNM stage and tumor size. Using Kaplan-Meier analysis, we found that circ_0001946 expression was negatively related with the overall survival of LAC patients. Next, we treated LAC cells with circ_0001946-specific shRNAs and found that knockdown of circ_0001946 inhibited LAC cell growth in vitro and in vivo. Mechanism investigation revealed that circ_0001946 was located in the cytoplasm of LAC cells and acted as a molecular sponge of miR-135a-5p to upregulate Sirtuin 1 (SIRT1) expression. Rescue assays further validated the role of circ_0001946-miR-135a-5p-SIRT1 axis in LAC progression. Additionally, SIRT1 has been demonstrated to be a positive regulator of Wnt/ß-catenin signaling pathway. Western blot analysis revealed that circ_0001946 regulated SIRT1/Wnt/ß-catenin signaling pathway. In conclusion, our findings suggested that circ_0001946 might be a potential biomarker for the diagnosis or treatment of LAC.

CircRNA has_circ_0006427 suppresses the progression of lung adenocarcinoma by regulating miR-6783-3p/DKK1 axis and inactivating Wnt/ß-catenin signaling pathway.

Recently, circular RNAs (circRNAs) are identified as a novel class of noncoding RNAs playing important roles in human malignant tumors. However, the regulatory function of circRNA in lung adenocarcinoma (LUAD) is still largely unknown. Present study aimed to explore the role of circ_0006427 in LUAD progression. Firstly, the downregulation of circ_0006427 in LUAD tissues and cell lines was revealed by microarray analysis and qRT-PCR analysis. And we also confirmed the circ_0006427 as a prognostic target in LUAD patients. Functionally, overexpression of circ_0006427 effectively suppressed cell proliferation, migration and invasion. Mechanistically, circ_0006427 was found to be predominantly located in the cytoplasm of LUCA cell, and was further revealed to positively regulate DKK1 in LUAD by sponging miR-6783-3p. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and western blot analysis revealed that circ_0006427 inactivated Wnt/ß-catenin signaling pathway by upregulating DKK1. At last, rescue assays proved the function of circ_0006427/miR-6783-3p/DKK1 axis in LUAD progression. In conclusion, our study revealed that circ_0006427 suppressed lung adenocarcinoma progression through regulating miR-6783-3p/DKK1 axis.

Tracheal Compression Caused by a Mediastinal Hematoma After Interrupted Aortic Arch Surgery.

Congenital abnormalities of the aortic arch include interrupted aortic arch (IAA), coarctation of the aorta (CoA), and double aortic arch (DAA). Aortic arch repair is difficult and postoperative complications are common. However, postoperative tracheobronchial stenosis with respiratory insufficiency is an uncommon complication and is usually caused by increased aortic anastomotic tension. We report here a case of tracheal compression by a mediastinal hematoma following IAA surgery. The patient underwent a repeat operation to remove the hematoma and was successfully weaned off the ventilator.In cases of tracheobronchial stenosis after aortic arch surgery, airway compression by increased aortic anastomotic tension is usually the first diagnosis considered by clinicians. Other causes, such as mediastinal hematomas, are often ignored. However, the severity of symptoms with mediastinal hematomas makes this an important entity.

Treatment of persistent congenital chylothorax with intrapleural injection of sapylin in infants.

Test the therapeutic efficacy of Sapylin in resolving persistent Congenital Chylothorax (CC) in four infants who failed to respond to conservative medical therapy including Erythromycin and/or Octreotide management. All cases were cured and have no adverse reactions during follow-up. The result shows Sapylin is effective in reducing chylous production.

Resolvin D1 Alleviates the Lung Ischemia Reperfusion Injury via Complement, Immunoglobulin, TLR4, and Inflammatory Factors in Rats.

Lung ischemia-reperfusion injury (LIRI) is still an unsolved medical issue, which negatively affects the prognosis of many lung diseases. The aim of this study is to determine the effects of RvD1 on LIRI and the potential mechanisms involved. The results revealed that the levels of complement, immunoglobulin, cytokines, sICAM-1, MPO, MDA, CINC-1, MCP-1, ANXA-1, TLR4, NF-κBp65, apoptosis index, and pulmonary permeability index were increased, whereas the levels of SOD, GSH-PX activity, and oxygenation index were decreased in rats with LIRI. Except for ANXA-1, these responses induced by LIRI were significantly inhibited by RvD1 treatment. In addition, LIRI-induced structure damages of lung tissues were also alleviated by RvD1 as shown by H&E staining and transmission electron microscopy. The results suggest that RvD1 may play an important role in protection of LIRI via inhibition of complement, immunoglobulin, and neutrophil activation; down-regulation of TLR4/NF-κB; and the expression of a variety of inflammatory factors.

Resolvin D1 mitigates energy metabolism disorder after ischemia-reperfusion of the rat lung.

BACKGROUND: Energy metabolism disorder is a critical process in lung ischemia-reperfusion injury (LIRI). This study was aimed to determine the effects of resolvin D1 (RvD1) on the energy metabolism in LIRI. METHODS: Forty Sprague-Dawley rats were divided into the following groups: Sham group; untreated ischemia-reperfusion (IR) control; IR treated with normal saline (IR-NS); and IR treated with RvD1 (IR-RV) (100 µg/kg, iv). LIRI and energy metabolism disorder were determined in these rats. RESULTS: The results revealed that the levels of interleukin (IL)-1ß, tumor necrosis factor-α, IL-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-2, cytokine-induced neutrophil chemoattractant-1, injured alveoli rate, apoptosis index, pulmonary permeability index, malondialdehyde, ADP, and lactic acid were increased, whereas the levels of ATP, ATP/ADP, glycogen, Na(+)-K(+)-ATPase, superoxide dismutase, glutathione peroxidase activity, pulmonary surfactant associated protein-A, and oxygenation index were decreased in rats with LIRI. Except for IL-10, all these biomarkers of LIRI and its related energy metabolism disorder were significantly inhibited by RvD1 treatment. In addition, histological analysis via hematoxylin-eosin staining, and transmission electron microscopy confirmed that IR-induced structure damages of lung tissues were reduced by RvD1. CONCLUSION: RvD1 improves the energy metabolism of LIRI disturbance, protects the mitochondrial structure and function, increases the ATP, glycogen content and Na(+)-K(+)-ATPase activity of lung tissue, balances the ratio of ATP/ADP and finally decreases the rate of apoptosis, resulting in the protection of IR-induced lung injury. The improved energy metabolism after LIRI may be related to the reduced inflammatory response, the balance of the oxidative/antioxidant and the pro-inflammatory/anti-inflammatory systems in rats.