ABSTRACT:This expert consensus reviews current literature and provides clinical practice guidelines for the diagnosis and treatment of multiple ground glass nodule-like lung cancer. The main contents of this review include the following: ① follow-up strategies, ② differential diagnosis, ③ diagnosis and staging, ④ treatment methods, and ⑤ post-treatment follow-up.

Importance:The benefit of neoadjuvant camrelizumab plus chemotherapy for resectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) remains unknown. Objective:To assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy vs chemotherapy alone for patients with resectable stage IIIA or IIIB NSCLC. Design, Setting, and Participants:In this randomized phase 2 clinical trial conducted at 2 hospitals in China, patients aged 18 to 70 years with resectable stage IIIA or IIIB (T3N2) NSCLC were enrolled between April 7, 2020, and January 12, 2022. Interventions:Patients were randomly assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m2, and platinum [cisplatin, 75 mg/m2; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m2]) or chemotherapy alone, followed by surgery after 4 to 6 weeks. Main Outcomes and Measures:The primary end point was the pathologic complete response (pCR) rate. Secondary end points included the major pathologic response (MPR) rate, objective response rate (ORR), event-free survival (EFS), and safety. Disease-free survival (DFS, defined as the time from surgery to disease recurrence or death from any cause) was analyzed post hoc. Efficacy was assessed on a modified intention-to-treat basis. Results:Ninety-four Chinese patients were randomized, and 88 (93.6%; median age, 61 years [IQR, 54-65 years]; 74 men [84.1%]) received allocated neoadjuvant treatment (43 received camrelizumab plus chemotherapy, and 45 received chemotherapy alone). Among these 88 patients, the pCR rate was 32.6% (14 of 43; 95% CI, 19.1%-48.5%) with camrelizumab plus chemotherapy vs 8.9% (4 of 45; 95% CI, 2.5%-21.2%) with chemotherapy alone (odds ratio, 4.95; 95% CI, 1.35-22.37; P = .008). The MPR rates were 65.1% (95% CI, 49.1%-79.0%) with camrelizumab plus chemotherapy and 15.6% (95% CI, 6.5%-29.5%) with chemotherapy alone. The radiographic ORRs were 72.1% (95% CI, 56.3%-84.7%) with camrelizumab plus chemotherapy and 53.3% (95% CI, 37.9%-68.3%) with chemotherapy alone. With a median follow-up of 14.1 months (IQR, 9.2-20.9 months), the median EFS and DFS were not reached in either group. The most common neoadjuvant treatment-related adverse events of grade 3 or higher were decreased white blood cell count (6 of 43 [14.0%] in the camrelizumab plus chemotherapy group vs 2 of 45 [4.4%] in the chemotherapy group) and decreased neutrophil count (3 of 43 [7.0%] in the camrelizumab plus chemotherapy group vs 5 of 45 [11.1%] in the chemotherapy group). No treatment-related deaths were reported. Conclusions and Relevance:This randomized clinical trial found that among patients with resectable stage IIIA or IIIB (T3N2) NSCLC, camrelizumab plus chemotherapy, compared with chemotherapy alone, significantly improved the pCR rate with manageable toxic effects. Trial Registration:ClinicalTrials.gov Identifier: NCT04338620.

Background Exosomes are known to transmit microRNAs (miRNAs) to affect cancer progression, while the role of M2 macrophages-derived exosomes (M2 exosomes) conveying miR-501-3p in lung cancer (LC) remains unknown. We aim to explore the role of exosomal miR-501-3p in LC development via targeting WD repeat domain 82 (WDR82). Methods Lung cancer tissue and normal tissue specimens were collected, in which tumor-associated macrophages (TAM) were measured by immunohistochemistry. M2 macrophages were induced and treated with altered miR-501-3p, and then the exosomes were extracted and identified. MiR-501-3p and WDR82 expression in LC tissues and cell liens was determined. The predictive role of miR-501-3p in prognosis of LC patients was assessed, and the proliferation, colony formation ability, invasion, migration and apoptosis of the LC cells were determined. Targeting relationship between miR-501-3p and WDR82 was confirmed. Results TAM level was elevated in lung cancer tissues. MiR-501-3p was upregulated while WDR82 was downregulated in LC tissues and cell lines, and the M2 exosomes further upregulated miR-501-3p. M2 exosomes and exosomal miR-501-3p promoted LC cell growth. MiR-501-3p inhibition reversed the effect of M2 exosomes on LC cells. WDR82 was confirmed as a target gene of miR-501-3p. Conclusion M2 macrophages-derived exosomal miR-501-3p promotes the progression of LC via downregulating WDR82.

Objective To investigate the role of Butein on lung adenocarcinoma A549 cells and the role of forkhead box O 3a (FOXO3a)/p27 kinase inhibitor protein 1 (p27kipl) and cell oxidative stress in this process.Methods A549 cells were treaded with 25,50 and 100 μmol/L Butein,then the cell viability,cell migration,Caspase-3 activity,NADPH oxidase activity,Reactive oxygen species (ROS) and total glutathione (GSH) were detected.Further expressions of FOXO3a,p27kip1,B-cell lymphoma-2 (bcl-2) and bcl-2 associated X protein (bax) were detected by Western blotting.In addition,small interference RNA was used to knock down FOXO3a expression in A549 cell.Then the cells were divided into four groups,which were the control group,the FOXO3a siRNA group,the Butein 100 μmol/L group and FOXO3a siRNA + Butein 100 μmol/L group.Expression of FOXO3a,p27kip1,bcl-2 and bax were detected.Results Mter treatment of Butein (25,50,100 μmol/L),cell viability were reduced from 100％ to (78.3 ± 4.6) ％,(63.5 ± 4.8) ％ and (40.1 ± 4.1) ％ (t =10.330,P =0.000) and the distance between cell boundary were increased from 100％ to (120.0 ± 8.4)％,(150.0 ± 10.6) ％ and (175.0 ± 11.1) ％ (t =4.777,P =0.001).In addition,Butein treatment increased Caspase-3 activity,NADPH oxidase activity and ROS production,and reduced total GSH concentration.Furthermore,Butein treatment increased FOXO3a,p27kip1 and bax expression and reduced bcl-2 expression.FOXO3a siRNA treatment blocked FOXO3a expression and p27kip1 transcription,and reversed Butein induced A549 cell apoptosis by increasing bcl-2 and reducing bax expression.Conclusion Butein can induce A549 cell apoptosis via activating FOXO3a/p27kip1 and cell oxidative stress.

Background: Blunt main stem bronchial injuries are rare but potentially life-threatening injuries in clinical.The aim of this study was to sum up the experience on diagnosis and treatment of blunt main stem bronchial injuries.Methods: This report retrospective1y analyzed eight cases of main stem bronchial injuries induced by blunt chest trauma between 2013 and 2016 in Tangdu Hospital, Fourth Military Medical University.Results: There were eight patients, including four men and four women.The definitive diagnosis was confirmed by fibrobronchoscopy.Mean time between injury and treatment in our hospital was 4.25 days (range, 1-12 days).Mean length of airway tear was 1.04 cm (range, 0.5-2 cm).In four patients there was an injury to the left main stem bronchus, in three patients to the right main stem bronchus and in one patient to the ambilateral main stem bronchus.Emergent operation was performed in two patients and elective operation in six patients.End to end bronchial anastomosis was performed via right thoracotomy in two patients and via left thoracotomy in three patients, and primary repair was performed via right thoracotomy in two patients and via left thoracotomy in the remaining one patient.There was no death in this group.Seven patients had no complications and were able to take part in normal activities.One patient suffered from anastomotic stricture after operation was healed by granulation tissue resection and cryotherapy under fibrobronchoscopy.Conclusions: Fibrobronchoscopy is able to define the blunt main stem bronchial injuries precisely and surgical approach is the preferred method for patients with these life-threatening complications.

Alveolar macrophages exist in the lung airspaces, and their differentiation and function are considerably regulated by the microenvironment. In this study, we examine the important role of resident neutrophil/IL-23/granulocyte/macrophage colony-stimulating factor (GM-CSF) axis in the development and preferential phenotype of alveolar macrophages under physiological conditions. Using CD18-deficient (CD18(-/-) ) mice, we show a correlation between increased granulopoiesis and enhanced alveolar macrophage development in an IL-23- and GM-CSF-dependent manner. The apoptotic neutrophils could inhibit the secretion of IL-23 from alveolar macrophages, which is important for the production of GM-CSF, and depletion of neutrophils disrupted the regulation of IL-23 and GM-CSF. This study reveals a mechanism for the regulation of the local alveolar macrophage population and function by neutrophil apoptosis in the circulatory system.

Previous research has shown that p-EGFR (particularly mutated EGFR) may activate fibroblast growth factor-inducible 14 (Fn14) expression in non-small cell lung cancer (NSCLC), and the JAK/STAT signaling pathway may participate in this process. Thus, in order to verify this hypothesis, correlations among the expression levels of EGFR Del 19, Fn14 and JAK/STAT were detected and analyzed. The expression and location of these molecules were assessed using IHC, immunohistofluorescence, RT-qPCR and western blotting. The differences and correlations in the expression of these molecules and clinical pathological characteristics were statistically analyzed using Mann-Whitney U, Kruskal‑Wallis H and cross-table tests. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of EGFR Del 19 and Fn14 expression on survival. Data showed that EGFR Del 19, Fn14 and JAK1/STAT1 expression was significantly related with differentiation, pTNM stage and lymphatic metastasis (P<0.01) and there was a marked correlation of EGFR Del 19, Fn14 and JAK1/STAT1 expression with histological type, differentiation, pTNM stage of NSCLC (P<0.05; rs>0.3). Immunohistofluorescence showed that there was a co-localization phenomenon between EGFR Del 19 and Fn14 expression. NSCLC patients with higher EGFR Del 19/Fn14 expression had a significantly worse prognosis than those with lower EGFR Del 19/Fn14 expression (P=0.0155/P=0.001; log-rank test). The multivariate analysis indicated that Fn14 expression may be an independent prognostic factor in NSCLC with EGFR Del 19 [hazard ratio (HR), 0.326; P=0.042]. Therefore, our results indicate that EGFR Del 19 may promote Fn14 and JAK1/STAT1 expression in NSCLC and Fn14 may serve as a prognostic biomarker in NSCLC with EGFR Del 19.

BACKGROUND:As radioresistance of non-small cell lung cancers (NSCLC) is one of the main causes of failure in radiotherapy, we examined whether micro ribonucleic acid (miR-451) could function as a potential radiosensitizer of NSCLC and the related mechanism.METHODS:Radioresistant NSCLC cell line A549 was transfected with pre-miR-451 or a scrambled control. The miR-451 messenger RNA level, colony-forming ability, apoptosis, and phosphatase and tensin homolog (PTEN) protein level of 549 cells were examined by real-time polymerase chain reaction, clonogenic assay, flow cytometry analysis, and Western blot.RESULTS:Upregulation of miR-451 enhanced the suppressive effects of irradiation on the colony-forming ability of A549 cells. The apoptosis and PTEN expression of A549 cells post-irradiation were also enhanced by upregulation of miR-451.CONCLUSIONS:Upregulation of miR-451 sensitized radioresistant NSCLC A549 cells to irradiation through the enhancement of apoptosis. The activation of PTEN post-irradiation was possibly correlated with the radiosensitization of A549 cells induced by miR-451 overexpression.

Objective: Radiofrequency ablation (RFA) has been recently applied as an alternative option of pulmonary surgery in the treatment of pulmonary malignancies. In this study, we assessed the risk associated with percutaneous RFA, and discussed its safety and efficacy. Methods: The clinical data of 329 consecutive patients with primary (n = 237) and metastatic (n = 92) lung tumor treated with RFA from 1999 to 2006 in this hospital were considered for this study, and the character and clinical data of these patients were analyzed. Complications, local progression, and overall survival at 1, 2 and 5 years of these patients were evaluated. Results: Following the procedure 63 (19.1%) patients presented with pneumothorax, 14 (4.2%) with hemoptysis (one death), 10 (3.0%) hemothorax, 15 (4.5%) pneumonia, and three (0.9%) pericardial tamponade (one death); the 30-day mortality after the procedure was 0.6%. Needle-track implantation was observed in six (1.8%) patients. Median progression-free interval was 21.6 months. The overall survival at 1, 2 and 5 years was 68.2%, 35.3%, and 20.1%, respectively. A total of 78 (23.7%) patients developed local progression during the follow-up. Significant difference in the risk of local progression was found in tumors more than 4 cm; however, no significant difference was found in tumors less than 3 cm and 3-4 cm in our group. Conclusion: RAF is a safe and well-tolerated procedure with satisfied efficacy in the treatment of malignant lung nodules. To avoid complications with potential fatal outcome, adequate training and careful patient selection by a multidisciplinary team might be helpful. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.