A prediction model for risk of low oxygen saturation in patients with post-tuberculosis tracheobronchial stenosis during bronchoscopy.

BACKGROUND: Low oxygen saturation (LOS) is a frequent occurrence for patients with post-tuberculosis tracheobronchial stenosis (PTTS) during bronchoscopic procedures. However, there are currently no systematic assessment tools to predict LOS risk in PTTS patients during bronchoscopy. OBJECTIVES: This study aimed to develop an effective preoperative predictive model to guide clinical practice. DESIGN: Retrospective cohort study. METHODS: Data was retrospectively collected from PTTS patients who underwent bronchoscopic interventions between January 2017 and December 2022. Among all patients included in this study, patients between January 2017 and December 2021 were used as training cohort for the logistic regression model, and patients between January 2022 and December 2022 were utilized as validation cohort for internal validation. We used consistency index (C-index), goodness-of-fit test and calibration plot to evaluate the model performance. RESULTS: A total of 465 patients who met the inclusion criteria were enrolled in the study. The overall incidence of LOS was 26.0% (121/465). Comorbidity, degree of stenosis, bronchoscopist level, thermal ablation therapy, balloon dilation, and airway stenting, as independent risk factors for the presence of LOS, were used to construct the nomogram prediction model. The C-index of training cohort was 0.827 (95% CI, 0.786-0.869), whereas that of validation cohort was 0.836 (95% CI, 0.757-0.916), combining with the results of the calibration plot and goodness-of-fit test, demonstrating that this model had good predictive ability. CONCLUSION: The predictive model and derived nomogram with good predictive ability has been developed to preoperatively predict the risk of LOS in PTTS patients during bronchoscopy, allowing for individualized interventions for high-risk patients.

PLEKHG2 Promotes NSCLC Cell Growth by Increasing Glycolysis via Activated PI3K/AKT Pathway.

Purpose: PLEKHG2 is a member of the diffuse B-cell lymphoma family. The function of PLEKHG2 in NSCLC was still unclear. This study aimed to investigate the relationship between the upregulated expression of PLEKHG2 and the prognosis of NSCLC and to revealed its mechanisms. Materials and methods: The expression of PLEKHG2 in NSCLC patients and its relationship with prognosis were first determined by analyzing public databases. Validation was performed in NSCLC cell lines and patient`s tumor tissues. PLEKHG2-silenced H1299 cells and PLEKHG2 overexpressing PC9 cells were constructed and used to validate its function. Glycolysis was evaluated by assaying cellular metabolites, glucose uptake and the expression levels of biomarkers of glycolysis. The relationship of PLEKHG2 and the PI3K/Akt pathway was demonstrated by small molecule inhibitors. The function of PLEKHG2 was evaluated in vivo by a H1299 cell derived xenograft (CDX) model. Results: PLEKEHG2 was highly expressed in NSCLC tissues and associated with poor prognosis. In PLEKHG2 knockdown H1299 cells, ATP and lactate production and glucose uptake were significantly inhibited. The opposite results were observed in PC9 cells with PLEKHG2 overexpression. The increased glycolysis following PLEKHG2 overexpression was abolished by adding the PI3K/AKT pathway inhibitor LY294002, suggesting that PLEKHG2 promotes glycolysis in NSCLC cells via activation of the PI3K/AKT pathway. Finally, we found that PLEKHG2 knockdown inhibited the tumor growth in the H1299 CDX model. Conclusion: PLEKHG2 contributed to NSCLC development by promoting glycolysis via activation of the PI3K/AKT pathway. PLEKHG2 was a potential therapeutic target and biomarker for poor prognosis of NSCLC.

Predictive value of the resistance of the probe to pass through the lesion in the diagnosis of peripheral pulmonary lesions using radial probe endobronchial ultrasound with a guide sheath.

Background: Transbronchial lung biopsy guided by radial probe endobronchial ultrasonography with a guide sheath (EBUS-GS-TBLB) is becoming a significant approach for diagnosing peripheral pulmonary lesions (PPLs). We aimed to explore the clinical value of the resistance of the probe to pass through the lesion in the diagnosis of PPLs when performing EBUS-GS-TBLB, and to determine the optimum number of EBUS-GS-TBLB. Methods: We performed a prospective, single-center study of 126 consecutive patients who underwent EBUS-GS-TBLB for solid and positive-bronchus-sign PPLs where the probe was located within the lesion from September 2019 to May 2022. The classification of probe resistance for each lesion was carried out by two bronchoscopists independently, and the final result depended on the bronchoscopist responsible for the procedures. The primary endpoint was the diagnostic yield according with the resistance pattern. The secondary endpoints were the optimum number of EBUS-GS-TBLB and factors affecting diagnostic yield. Procedural complications were also recorded. Results: The total diagnostic yield of EBUS-GS-TBLB was 77.8%, including 83.8% malignant and 67.4% benign diseases (P=0.033). Probe resistance type II displayed the highest diagnostic yield (87.5%), followed by type III (81.0%) and type I (61.1%). A significant difference between the diagnostic yield of malignant and benign diseases was detected in type II (P = 0.008), whereas others did not. Although most of the malignant PPLs with a definitive diagnosis using EBUS-GS-TBLB in type II or type III could be diagnosed in the first biopsy, the fourth biopsy contributed the most sufficient biopsy samples. In contrast, considerably limited tissue specimens could be obtained for each biopsy in type I. The inter-observer agreement of the two blinded bronchoscopists for the classification of probe resistance was excellent (κ = 0.84). Conclusion: The probe resistance is a useful predictive factor for successful EBUS-GS-TBLB diagnosis of solid and positive-bronchus-sign PPLs where the probe was located within the lesion. Four serial biopsies are appropriate for both probe resistance type II and type III, and additional diagnostic procedures are needed for type I.

Anoikis-related genes combined with single cell sequencing: Insights into model specification of lung adenocarcinoma and applicability for prognosis and therapy.

Background: Anoikis has therapeutic potential against different malignancies including lung adenocarcinoma. This study used anoikis and bioinformatics to construct a prognostic model for lung adenocarcinoma and explore new therapeutic strategies. Methods: Several bioinformatic algorithms (co-expression analysis, univariate Cox analysis, multivariate Cox analysis, and cross-validation) were used to screen anoikis-related genes (ARGs) to construct a risk model. Lung adenocarcinoma patients were divided into training and testing groups at a ratio of 1:1. The prognostic model was validated by risk score comparison between high- and low-risk groups using receiver operating characteristic curve (ROC), nomograms, independent prognostic analysis and principal component analysis. In addition, two anoikis-related genes patterns were classified utilizing consensus clustering method and were compared with each other in survival time, immune microenvironment, and regulation in pathway. Single cell sequencing was applied to analyze anoikis-related genes constructed the model. Results: This study demonstrated the feasibility of the model based on seven anoikis-related genes, as well as identifying axitinib, nibtinib and sorafenib as potential therapeutic strategies for LUAD. Risk score based on this model had could be used as an independent prognostic factor for lung adenocarcinoma (HR > 1; p < 0.001) and had the highest accuracy to predict survival compared with the clinical characteristics. Single cell sequencing analysis discovered Keratin 14 (KRT14, one of the seven anoikis-related genes) was mainly expressed in malignant cells in various cancers. Conclusion: We identified seven anoikis-related genes and constructed an accurate risk model based on bioinformatics analysis that can be used for prognostic prediction and for the design of therapeutic strategies in clinical practice.

5-methyladenosine regulators play a crucial role in development of chronic hypersensitivity pneumonitis and idiopathic pulmonary fibrosis.

5-methyladenosine (m5C) modification regulates gene expression and biological functions in oncologic areas. However, the effect of m5C modification in chronic hypersensitivity pneumonitis (CHP) and idiopathic pulmonary fibrosis (IPF) remains unknown. Expression data for 12 significant m5C regulators were obtained from the interstitial lung disease dataset. Five candidate m5C regulators, namely tet methylcytosine dioxygenase 2, NOP2/Sun RNA methyltransferase 5, Y-box binding protein 1, tRNA aspartic acid methyltransferase 1, and NOP2/Sun RNA methyltransferase 3 were screened using random forest and nomogram models to predict risks of pulmonary fibrosis. Next, we applied the consensus clustering method to stratify the samples with different m5C patterns into two groups (cluster A and B). Finally, we calculated immune cell infiltration scores via single-sample gene set enrichment analysis, then compared immune cell infiltration, related functions as well as the expression of programmed cell death 1 (PD-1, PDCD1) and programmed death protein ligand-1 (PD-L1, CD274) between the two clusters. Principal component analysis of m5C-related scores across the 288 samples revealed that cluster A had higher immune-related expression than B. Notably, T helper cell (Th) 2 type cytokines and Th1 signatures were more abundant in clusters A and B, respectively. Our results suggest that m5C is associated with and plays a crucial role in development of pulmonary fibrosis. These m5C patterns could be potential biomarkers for identification of CHP and IPF, and guide future development of immunotherapy or other new drugs strategies for pulmonary fibrosis.

A narrative review of progress in airway stents.

Background and Objective: Airway stents, used to restore airway patency, are mostly utilized by patients with malignant airway strictures, and are occasionally used in a range of other airway related diseases, including conditions which result in benign stenosis, malacia, and fistula. There has been an increasing number of airway stents that are being developed thanks to improvements in interventional therapy. However, the method of promoting airway stents for clinical application remains undetermined. Herein, we describe the recent advances in airway stents by reviewing the published studies, providing the reference for clinical decision-making and further research on airway stents. Methods: Relevant articles between January 1964 and November 2021 were obtained from PubMed, Web of Science, and EMBASE databases. The terms "metallic", "silicone", "drug-eluting", "biodegradable", "radioactive", "three-dimensional (3D)", and "stents" were searched in different combinations.Key Content and Findings: In this review, we focus on the latest evidence in terms of the application of various stents with novel materials and designs including novel metallic, novel silicone, drug-eluting, biodegradable, radioactive, and 3D stents for airway stenosis. Despite reducing the well-known complications of all current commercially available stents, novel stents are still in their infancy without a long track record of utility and safety, and remain some limitations. There are more steps to be taken before such stents enter routine clinical practice. Conclusions: A combination of 3D-printing method and biodegradable material may present a promising avenue of solving the existing problems pertaining to "classic" stents and has potential to become the main trend in the future.

Priority of PET-CT vs CT Thorax for EBUS-TBNA 22G vs 19G: Mesothorax Lymphadenopathy.

Introduction: Lung lesions and undiagnosed mesothorax lymphadenopathy is an issue that several doctors face in the everyday clinical practice. PET-CT and CT of the thorax are usually the first examinations to identify characteristics of the lesions before biopsy. Patients and Methods: We performed a retrospective study with 450 patients that had EBUS-TBNA with 22G, Upgraded 22G and 19G needles with and without PET-CT in order to identify the cost effeteness of performing EBUS-TBNA before or after PET-CT. All centers used the same PET-CT equipment and EBUS-TBNA system. Three types of needle were used for the endoscopy in order to identify similarities and differences for the cost-effectiveness. The costs in every center for every examination and materials were the same. Results: There were more block slices for 19G>22Gupgraded>21G>22G and there was cost-effectiveness when in general PET-CT was performed prior to biopsy of any lesion. 19G needle was more effective for lymphomas, while 22Gupgraded and 21G needles were more cost-effective when used for smaller lesions for primary lung cancer of metastatic disease. Conclusions: We have been using PET-CT and EBUS-TBNA in the everyday clinical practice according to the current guidelines for initial disease staging and re-staging. However; we can also use both in a cost effective method based on the initial radiologic findings.

Application of a Simulator-Based Teaching Method in the Training of the Flexible Bronchoscope-Guided Intubation.

BACKGROUND: The study aimed to explore the effect of a bronchoscopic simulator-based comprehensive teaching method in the training of flexible bronchoscope-guided intubation for suspected lung cancer patients for doctors without bronchofibroscopic operation background. METHODS: We designed a prospective self-control study involved in 35 trainees from the Navy Military Medical University's affiliated hospital to evaluate flexible bronchoscope-guided intubation's training outcome. Before and after the practice training, we recorded the flexible bronchoscope passing time from nasal to visible glottis and carina, tracheal placement tube, and ventilation. RESULTS: All 35 trainees could complete flexible bronchoscope-guided intubation independently after training. CONCLUSIONS: The bronchial diagnosis for suspected lung cancer patients and treatment-based model can be widely applied in tracheal intubation training.

Inflammation accelerates copper-mediated cytotoxicity through induction of six-transmembrane epithelial antigens of prostate 4 expression.

Copper is an essential trace metal, but imbalance in copper homeostasis can induce oxidative damage. Inflammation is a fundamental element of various pulmonary diseases. Although a positive relationship between copper and chronic pulmonary diseases has been reported, the underlying reasons are still not clear. The copper level in the sputum of patients with various pulmonary diseases was measured. An inflammatory model was established to evaluate the impact of inflammation on copper uptake in the lung. We found that the level of sputum copper was increased in patients with various pulmonary diseases, especially chronic obstructive pulmonary disease and asthma. Then, we confirmed that mice with pulmonary inflammation were susceptible to copper-mediated oxidative damage because of copper overload in lung tissue. Further investigation demonstrated that interleukin (IL)-17 and tumor necrosis factor (TNF)-α exerted synergistic effects in airway epithelial cells by upregulating the expression of six-transmembrane epithelial antigens of prostate 4 (STEAP4), a metalloreductase that reduces extracellular copper ions from the cupric state to the cuprous state and facilitates copper uptake. Inhibition of STEAP4 decreased the copper uptake of cells and inhibited copper-mediated oxidative damage. Moreover, we demonstrated that the upregulation of STEAP4 by IL-17 and TNF-α was largely dependent on TNF receptor-associated factor 4 (TRAF4). Traf4-/- mice were resistant to copper-mediated oxidative damage. Our data suggest a novel IL-17/TNF-α-TRAF4-STEAP4 axis that regulates copper homeostasis.

The development of bronchoscopy in China: a national cross-sectional study.

Objective: To investigate the development of bronchoscopy in China and compare it with its application in the early 21st century. Methods: The data collection was based on questionnaires. Three hundred and nineteen hospitals, which distributed across 30 provinces and 130 cities, were included in the study. Data about the application of bronchoscopy in Shanghai and Hunan province in the early 21st century are also involved for comparison. Results: The median period of performing diagnostic and therapeutic bronchoscopy was 19.7±11.0 and 7.4±7.0 years, respectively. On average, about 155.2 cases and 28.4 cases received diagnostic and therapeutic bronchoscopy in each hospital per month. The average area and number of the examination room was 122.7m2 and 2.2m2, respectively. More examination items were performed in specialty hospitals than those in general hospitals (P<0.05) and specialty hospitals owned more rooms exclusively for bronchoscopy (P<0.05), while no difference of the number of allocated doctors was found (P>0.05). On the other side, the whole amount of diagnosis and therapeutic items in teaching hospitals was slightly higher than that in non-teaching hospitals (P<0.01). Comparison of diagnosis and therapeutic endoscopy in Shanghai and Hunan province shows that the number of flexible bronchoscopy increased by 5.8 times in Shanghai from 2002 to 2017, while that increased by 3.4 times in Hunan province from 2005 to 2017. Furthermore, the average number of allocated doctors increased by 0.85 times in Shanghai, which was more rapidly compared with that of Hunan province (0.66 times) (P<0.05). Besides, the development rate of the diagnosis and therapeutic projects in Shanghai was significantly higher than that in Hunan province (P<0.05). Conclusion: All different classes of hospitals in China are capable of carrying out conventional bronchoscopy diagnosis and therapeutic projects, and newly developed bronchoscopy technology has gradually spread in high-level hospitals since 21st century. The higher class the hospital was, the earlier bronchoscopy was performed. Respiratory endoscopy in China has developed rapidly since the early 21st century and the construction of respiratory endoscopy center and the personnel training are on the right track, but it is also faced with inadequate equipment, unbalanced regional development and insufficient personnel allocation.

A case report of tongue metastasis from lung squamous cell carcinoma and literature review.

RATIONALE: Tongue metastasis from lung cancer is extremely rare, and the prognosis of these patients is rather poor. PATIENT CONCERS: A 56-year-old man was found a 4-cm cavity lesion in the left upper lobe, which was initially misdiagnosed as tuberculosis. DIAGNOSES: A case of lung squamous cell carcinoma that metastasized to the base of a patient's tongue. INTERVATIONS: We send the biopsy of the lung and the tongue lesions for gene sequencing. OUTCOMES: He received systemic chemotherapy, but continued to have pain at the base of his tongue and died 7 months later. LESSONS: From sequencing data, mutations in KRAS proto-oncogene, GTPase (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and tumor protein p53 (TP53) were found in the tumor biopsy of the patient. All of these were indicators of poor prognosis.

Underexpression of LKB1 tumor suppressor is associated with enhanced Wnt signaling and malignant characteristics of human intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a rare and highly aggressive malignancy. In this study, we identified the presence of gene deletion and missense mutation leading to inactivation or underexpression of liver kinase B1 (LKB1) tumor suppressor and excluded the involvement of LKB1 gene hypermethylation in ICC tissues. Immunohistochemical analysis showed that LKB1 was underexpressed in a portion of 326 ICC tissues compared to their adjacent normal tissues. By statistical analysis underexpression of LKB1 in ICC tissues significantly correlated with poor survival and malignant disease characteristics in ICC patients. Moreover, we showed that knockdown of LKB1 significantly enhanced growth, migration, and invasion of three LKB1-competent ICC cell lines. Global transcriptional profiling analysis identified multiple malignancy-promoting genes, such as HIF-1α, CD24, Talin1, Vinculin, Wnt5, and signaling pathways including Hedgehog, Wnt/ß-catenin, and cell adhesion as novel targets of LKB1 underexpression in ICC cells. Furthermore, knockdown of LKB1 gene expression dramatically enhanced Wnt/ß-catenin signaling in ICC cells, while an inverse correlation between LKB1 and nuclear ß-catenin was observed in ICC tissues. Our findings suggest a novel mechanism for ICC carcinogenesis in which LKB1 underexpression enhances multiple signaling pathways including Wnt/ß-catenin to promote disease progression.

Malignant pleural effusion supernatants are substitutes for metastatic pleural tumor tissues in EGFR mutation test in patients with advanced lung adenocarcinoma.

BACKGROUND: Though the possibility of using malignant pleural effusions (MPEs) as alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth factor receptor (EGFR) mutation test has been examined, due to the lack of studies comparing the results in matching MPEs and MPTTs, the clinical value of MPEs for advanced adenocarcinoma patients with pleural effusions is not confirmed. METHODS: EGFR mutation statuses in matching MPTTs, MPE supernatants and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by thoracoscopy were analyzed using amplification refractory mutation system (ARMS). RESULTS: EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis. Generally, the same EGFR statuses were identified in both MPTTs and matching MPE cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19), specificity was 90.9% (20/22). CONCLUSIONS: The high concordance of EGFR mutation statuses between MPEs and MPTTs in lung adenocarcinoma patients with pleural metastasis as determined by ARMS analysis suggests that MPEs, particularly MPE supernatants, may be substitutes for MPTTs in EGFR mutation test.

Anticancer activity of oncolytic adenoviruses carrying p53 is augmented by 11R in gallbladder cancer cell lines in vitro and in vivo.

Gallbladder cancer (GBC) is a rare disease associated with an extremely poor patient prognosis, and occasionally, aberrant expression of p53 is present. Considering that p53 is one of the most widely studied tumor­suppressor genes, we used a cell-penetrating peptide, 11R, to enhance the transferring efficiency of the oncolytic adenovirus carrying the p53 gene by constructing SG7605-11R-p53, a gene-viral therapy system which has higher specificity, enhanced safety, and efficacy. After infection with SG7605-11R-p53 at a multiplicity of infection (MOI) of 1 PFU/cell in vitro, the survival rate of EH-GB1 cells was lower than 50%, and that of EH-GB2 cells was lower than 40%, while the survival rate was higher than 90% for BJ human fibroblast cells, demonstrating that SG7605-11R-p53 has potent specific cytotoxicity against GBC cells. The tumor growth was greatly inhibited in nude mice bearing EH-GB2 xenografts when the total dose of SG7605-11R-p53 was 1x109 PFU, and terminal dUTP nick end-labeling (TUNEL) revealed that the apoptotic rate of cancer cells was 66.75±6.702%. Compared with existing gene therapy with long-standing shortcomings, our new system offers an additional option for patients with advanced GBC and other cancers who may not be suitable for chemotherapy, radiotherapy or who are not indicated for surgical treatment.

Gemcitabine plus oxaliplatin for the treatment of leptomeningeal metastases of non-small cell lung cancer: A case report and review of the literature.

A 62-year-old male presented with stage IV lung adenocarcinoma with leptomeningeal metastases (LM). Gemcitabine (1000 mg/m2 i.v.) was administered on days 1 and 8 while oxaliplatin (100/m2 i.v.) was administered on day 1 and repeated for 4 cycles every 3 weeks. Computerized tomography (CT) and cerebrospinal fluid (CSF) were used to evaluate the response of the LM and the primary tumor to drug therapy. Following the administration of chemotherapy, headaches were observed to be notably reduced 6 days later and absent after 14 days. The symptoms of coughing and chest pain were alleviated. Subsequent to 4 cycles of treatment, the patient had a partial response (PR) and the CSF pressure was normal. Analysis of the CSF revealed that it was colorless, positive for protein, had a total cell number of 0/l and contained no cancer cells. However, the primary lung tumor progressed for 1 year. This may suggest that first-line therapies, including the use of gemcitabine and oxalipaltin, may be appropriate for the treatment of non-small cell lung carcinoma (NSCLC) with LM involvement.

Identification of novel mutations of TP53, ALK and RET gene in metastatic thymic squamous cell carcinoma and its therapeutic implication.

Thymic tumors are epithelial tumors of the thymus for which multimodal therapies are often ineffective because of a lack of standardized regimens. Due to the low incidence, the molecular pathology and genomic abnormalities of thymic epithelial tumors are largely unknown. In this study, we report our comprehensively genomic study on a case of metastatic thymic tumor. Using next generation deep DNA sequencing technology, we sequenced 190 segments of 46 cancer genes of the cancer genome to cover 739 COSMIC mutations in 604 loci. Among these sequenced cancer genes, we identified that three low frequency (~10% of cells) mutations in the TP53 gene (c.782+1G>T), ALK gene (c.3551C>T), and RET gene (c.2651A>T). To the best of our knowledge, this is the first study to show those mutations in thymic tumor. Of note, our study further indicates comprehensive molecular analysis may facilitate development of novel diagnostic and therapeutic strategies for thymic tumors.

Characterization of two novel cell lines with distinct heterogeneity derived from a single human bile duct carcinoma.

BACKGROUND: Intratumoral heterogeneity reflects subclonal diversity and accounts for a variety of clinically defined phenotypes including the development of drug resistance and recurrence. However, intratumoral heterogeneity of bile duct carcinoma (BDC) is rarely studied. METHODS: Two highly heterogeneous cell lines named EH-CA1a and EH-CA1b were established from a primary tumor tissue of a pathologically proven BDC. Distinct heterogeneity and underlying mechanisms of two cell lines in karyotype, colony formation, tumorgenicity, and sensitivity to chemoradiotherapy were intensively studied. RESULTS: Both cell lines showed typical morphology of cancer cells. EH-CA1a cells grew as free-floating aggregates, while EH-CA1b cells grew adherently as a monolayer. EH-CA1a cells had higher cloning efficiencies and were able to keep proliferating under hypoxic condition. Coincidentally, hypoxia-induced factor-1α (HIF1α) and vascular endothelial growth factor (VEGF) mRNA were significantly higher in EH-CA1a cells than in EH-CA1b cells. Both cell lines were tumorigenic in nude mouse, however, EH-CA1a cells showed more aggressive characteristics. Most importantly, the EH-CA1a cells showed much more resistance against radiation and chemotherapy with gemcitabine. Metastasis-related genes including matrix metalloproteinase 2 (MMP-2), MMP-9, epithelial-mesenchymal transition (EMT) markers such as Vimentin, Snail, and Twist, are more highly expressed in EH-CA1a cells than in EH-CA1b cells. Moreover, the percentage of cells expressing cancer stem cell-like marker, CD133, in EH-CA1a cells is much higher than that in EH-CA1b cells. Moreover, knockdown of CD133 in both EH-CA1a and EH-CA1b cells significantly reduced their invasive potential and increased their sensitivities to radiation and gemcitabine, suggesting the differential expression of CD133 protein may partially account for the difference in malignancy between these two cancer cells. CONCLUSION: Establishment of these two cell lines will not only shed light on intratumoral heterogeneities of BDC, but also potentially facilitate the development of novel therapeutic approaches of BDC.

In vitro study of safety and co-efficiency of the transbronchial coagulation techniques.

BACKGROUND: The usual transbronchial coagulation techniques include microwave, argon plasma coagulation (APC), electrocautery and cryotherapy. However, there are serious clinical problems in the safety of each. By analyzing the experimental data and clinical observations, we observed the variable effects of different coagulation techniques via bronchofibroscopy, to look for an optimal interventional management of luminal bronchus diseases, and evaluate the safety and the equivalent point. METHODS: Four kinds of coagulation techniques under bronchoscopy were performed on the fresh bronchus of healthy sheep, and the pathologic changes in all groups were observed under the microscope. The different treatment parameters were as follows: microwave 60 W×1 second, 3 seconds, 5 seconds and 40 W×1 second, 3 seconds, 5 seconds; APC 40 W×1 second, 3 seconds, 5 seconds; electrocautery 40 W×1 second, 3 seconds, 5 seconds; cryotherapy 100 Ω×60 seconds, 120 seconds. RESULTS: After treatment, ovine bronchial mucosa in all groups showed pathologic changes such as local necrosis and amotio of the mucosa lining epithelium, local submucosa coagulative necrosis or tissue defects, while inflammation in the surrounding tissue was not obvious. Under the same output power and action time, different methods had different outcomes. The damage by APC was the most superficial, microwave was the second, and electrocautery caused the worst damage. The study also found that effects of electrocautery at 40 W×3 seconds, microwave at 40 W×5 seconds or 60 W×3 seconds, APC at 40 W×5 seconds and cryotherapy at 100 Ω×120 seconds were the equivalent point conditions. The appearance included mucosa absence, partial submucosa absence, and collagen fiber coagulation in treatment areas. CONCLUSIONS: Each coagulation technique has its own characteristic. It is very important to choose the appropriate power and action time of the suitable method according to the therapy requirement.

Salmeterol attenuates the inflammatory response in asthma and decreases the pro-inflammatory cytokine secretion of dendritic cells.

Salmeterol is a long-acting ß2-agonist that activates adenylate cyclase, causing long-lasting bronchodilation and has been used for many years to control asthma. However, little information is available about the immunoregulatory effects of salmeterol. We found that salmeterol decreases the production of pro-inflammatory cytokines in a model of allergen-challenged mice that expressed tumor-necrosis factor-alpha, interleukin-1 and interleukin-6. Dendritic cells (DCs) are antigen-presenting cells and act as sentinels in the airway. We found that salmeterol (10(-5) mol/l) reduced the inflammation caused by lipopolysaccharide (0.1 µg/ml) in activated murine bone marrow-derived DCs. Moreover, western blots demonstrated that this protective effect was mediated partially by inhibiting signaling through the nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) pathways and dramatically decreased levels of p-ERK. We suggest that salmeterol regulates the inflammation of allergen-induced asthma by modulating DCs. In conclusion, we provide evidence that DCs are the target immune cells responsible for the action of salmeterol against asthma.