Diagnostic efficacy and safety of radial probe endobronchial ultrasound-guided transbronchial needle aspiration for adjacent lesions in segmental or subsegmental bronchi: a single-center retrospective study.

BACKGROUND: Peripheral lung lesions can be sampled using various techniques, including computer tomography-guided transthoracic needle aspiration, electromagnetic navigation bronchoscopy, virtual navigation bronchoscopy, and radial probe endobronchial ultrasound transbronchial lung biopsy. Mediastinal lesions can be sampled using techniques like convex probe endobronchial ultrasound-guided transbronchial needle aspiration (CEBUS-TBNA) and endoscopic ultrasound-fine-needle aspiration. However, effective, safe techniques for lesions adjacent to the segmental or subsegmental bronchi are lacking. Herein, we retrospectively evaluated the diagnostic yield and safety of radial probe endobronchial ultrasound-assisted transbronchial needle aspiration (REBUS-TBNA) for lesions adjacent to the segmental bronchi, and explored the factors related to diagnostic yield. METHODS: We retrospectively analyzed the diagnostic yield and safety of REBUS-TBNA cases performed in our department from January 2019 to December 2022. Observation group patients had undergone REBUS-TBNA for lesions adjacent to the segmental bronchi; control group patients had undergone CEBUS-TBNA for mediastinal or hilar lesions. Patient characteristics and lesion sizes, diagnostic yield, adverse events, and relations between diagnostic yield and clinical characteristics were analyzed. RESULTS: There were not statistically significant between-group differences in sex, age, diagnostic yield, or rate of adverse events. The observation group (n = 25; 17 male, 8 female) had a mean age of 64.76 ± 10.75 years. The average lesion size was 4.66 ± 1.07 cm, and lesions were predominantly in the upper lobes (80%). REBUS-TBNA diagnostic yield was 84%, with no adverse events reported. Diagnostic yield was not associated with lesion size or extent of bronchial stenosis; however, it was positively correlated with number of punctures. Patients with > 3 punctures had a significantly higher diagnostic yield than those with ≤ 3 punctures. CONCLUSIONS: REBUS-TBNA is a safe, effective diagnostic technique, particularly for lesions adjacent to the segmental or subsegmental bronchi of the upper lobe. Performing more than three punctures during the procedure improves the diagnostic yield. Larger-scale studies are warranted to confirm these results, and to further explore the clinical value of REBUS-TBNA.

A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs.

The transcription factor, sterol regulatory element binding protein 1 (SREBP-1), plays important roles in modulating the proliferation, metastasis, or resistance to antitumor agents by promoting cellular lipid metabolism and related cellular glucose-uptake/Warburg Effect. However, the underlying mechanism of SREBP-1 regulating the proliferation or drug-resistance in lung squamous cell carcinoma (LUSC) and the therapeutic strategies targeted to SREBP-1 in LUSC remain unclear. In this study, SREBP-1 was highly expressed in LUSC tissues, compared with the paired non-tumor tissues (the para-tumor tissues). A novel small-molecule inhibitor of SREBP-1, MSI-1 (Ma's inhibitor of SREBP-1), based on natural product monomers, was identified by screening the database of natural products. Treatment with MSI-1 suppressed the activation of SREBP-1-related pathways and the Warburg effect of LUSC cells, as indicated by decreased glucose uptake or glycolysis. Moreover, treatment of MSI-1 enhanced the sensitivity of LUSC cells to antitumor agents. The specificity of MSI-1 on SREBP-1 was confirmed by molecular docking and point-mutation of SPEBP-1. Therefore, MSI-1 improved our understanding of SREBP-1 and provided additional options for the treatment of LUSC.

Selective inhibition of JNK located on mitochondria protects against mitochondrial dysfunction and cell death caused by endoplasmic reticulum stress in mice with LPS­induced ALI/ARDS.

Few pharmacological interventions are able to improve the mortality rate of acute lung injury and acute respiratory distress syndrome (ALI/ARDS). The aim of this research was to elucidate whether endoplasmic reticulum (ER) stress and c­Jun­N­terminal kinase (JNK)­mitochondria pathways serve important roles in ALI/ARDS and to determine whether the key component Sab is a potential treatment target. The current study investigated the activation of ER stress and the JNK pathway, the content of JNK located on the mitochondria during ER stress and lipopolysaccharide (LPS)­induced ALI/ARDS by western blot analysis. The treatment effects of Tat­SabKIM1, a selective inhibitor of JNK located on mitochondria were explored by multiple methods including histopathological evaluation, lung cell apoptosis tested by TUNEL assay, mitochondrial membrane permeability and survival analysis. The results verified that ER stress was enhanced during LPS­induced ALI/ARDS and could induce activation of the JNK pathway and JNK­mitochondrial localization as well as mitochondrial dysfunction and cell death. Tat­SabKIM1 alleviated LPS injection­induced lung injury and improved mouse survival rates by specifically inhibiting JNK localization to mitochondria and mito­JNK signal activation without affecting cytosolic/nuclear JNK activation. The protective effect of Tat­SabKIM1 against ALI/ARDS was partly caused by inhibition of the excessive activation of mitochondria­mediated apoptosis and autophagy. These results showed the important role of Sab as a treatment target of ALI/ARDS and the potential treatment effect of Tat­SabKIM1. In conclusion, abnormal activation of the JNK­mitochondrial pathway could significantly disrupt the normal physiological function of lung cells, resulting in the occurrence of ALI/ARDS and selective inhibit of JNK located on mitochondria by Tat­SabKIM1 had a protective effect against the mitochondrial dysfunction and cell death caused by endoplasmic reticulum stress in mice with LPS­induced ALI/ARDS.

Complications and safety analysis of diagnostic bronchoscopy in COPD: a systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) often coexists with many diseases that require bronchoscopy. We conducted this systematic review and meta-analysis to assess the safety and complication rate of diagnostic bronchoscopy in patients with COPD. METHODS: We retrieved clinical trials that reporting the complications of conducting diagnostic bronchoscopy on patients with COPD through electronic databases. Analyses of the overall major complication rate of bronchoscopy and potential risk factors in patients with COPD were conducted. RESULTS: 18 trials/arms were evaluated. The overall major complication rate of bronchoscopy was 4.3% (95% CI, 2.2%-8.2%; 18 trials/arms, n = 2000). The major complication rate of the patients with an exacerbation of COPD was higher than that of the stable patients (7.8% vs. 4.5%, Q-value = 11.29, df (Q) = 1, p < 0.01); using of sedative medicine was also related with higher major complication rate (Q-value = 6.303, df (Q) = 2, p = 0.043). Patients with severe COPD who were GOLD stages III and IV (Q = 13.40, df = 1, p < 0.01; R2 = 0.66) or had a high BMI (Q = 30.83, df = 1, p < 0.01; R2 = 0.91) more easily encountered complications during bronchoscopy. CONCLUSIONS: The major complication rate of diagnostic bronchoscopy in patients with COPD was acceptable and low Exacerbations of COPD and using sedative medicine were related with higher major complication rate. EXPERT OPINION: COPD is a major risk factor for lung cancer and infection, so the patients with COPD often required bronchoscopy. Although our results showed diagnostic bronchoscopy might not be more fatal for patients with COPD, further studies are needed to explore the potential risk factors for major complications of bronchoscopy in patients with COPD.

Identification and analysis of urban functional area in Hangzhou based on OSM and POI data.

The accurate identification of urban functional areas is of great significance for optimizing urban spatial structure, rationally allocating spatial elements, and promoting the sustainable development of the city. This paper proposes a method to precisely identify urban functional areas by coupling Open Street Map (OSM) and Point of Interest (POI) data. It takes the central urban area of Hangzhou as a case study to analyze the spatial distribution characteristics of the functional areas. The results show that: (1) The central urban areas of Hangzhou are divided into 21 functional areas (6 single functional areas, 14 mixed functional areas and 1 comprehensive functional area). (2) The single functional areas and the mixed functional areas show the geographical distribution characteristics of the looping stratification, which means "Core-periphery" differentiation is obvious, and the comprehensive functional area is relatively scattered. (3) The mixed degree of regional function with ecological function and production function is low while comprehensive functional areas are usually associated with higher potential and vitality. (4) The identification results are in great agreement with the actual situation of Hangzhou central urban area, and the method is feasible. Therefore, this paper can provide a reference for urban development planning and management.

MicroRNA-6077 enhances the sensitivity of patients-derived lung adenocarcinoma cells to anlotinib by repressing the activation of glucose transporter 1 pathway.

Anlotinib is a novel molecular targeted agent targeting the vascular endothelial growth factor receptor, which differs from the other currently available non-small cell lung cancer (NSCLC) molecular targeted drugs targeting this receptor. Although the application of anlotinib may bring new hope for patients with advanced NSCLC, the cost of treatment is high. The results of this study showed that microRNA-6077 (miR-6077) represses the expression of GLUT1 (glucose transporter 1) and enhances the sensitivity of patient-derived lung adenocarcinoma (AC) cells to anlotinib. The miR-6077, which potentially binds to the 3'untranslated region of GLUT1, was identified and screened by miRDB, an online tool; sequences of miR-6077 were prepared as lentivirus particles. A549 cells (a lung adenocarcinoma cell line) and five patient-derived AC cell lines were infected with control miRNA or miR-6077, and subsequently treated with the indicated concentration of anlotinib. The expression of proteins, such as GLUT1, was determined by western blotting. The antitumor effect of anlotinib was identified through in-vitro (e.g., MTT) or in-vivo methods (e.g., subcutaneous tumor model). Overexpression of miR-6077 repressed the expression of GLUT1 and decreased the glucose uptake, lactate production, or ATP generation in AC cells. In addition, MiR-6077 may enhance the antitumor effect of anlotinib on A549 or patient-derived AC cell lines. Therefore, our results indicated that miR-6077 represses the expression of GLUT1 and enhances the sensitivity of patients-derived lung AC cells to anlotinib.

miR­24 may be a negative regulator of menin in lung cancer.

The incidence of lung cancer in China increases annually, and effective targets for the diagnosis and treatment of lung cancer are urgently needed. miRNAs are currently considered to be involved in the regulation of tumor development and growth. miR­24 has been found to contribute to the development of several tumors. Menin is a key tumor suppressor gene, and its expression is generally low in lung cancer. The effects of miR­24 on the biological behavior of lung cancer cells were detected by MTT and Transwell assays. In the present study, miR­24 was found to be associated with menin, affecting the activity of the SMAD3 pathway in lung cancer by inhibiting menin expression. miR­24 may promote the growth and metastasis and inhibit the apoptosis of lung cancer cells by targeting menin. Therefore, the aim of the present study was to provide a new theoretical basis for the targeted therapy of lung cancer.

miR-646 is a key negative regulator of EGFR pathway in lung cancer.

BACKGROUND: As one of the leading cause of cancer-related deaths in the worldwide, lung cancer needs to be understood better. Nowadays, increasing point mutations of specific oncogenes are biomarkers used to predict the therapeutic effect of targeted therapy and lung cancer has entered the age of individual treatment. At present, many relevant researchers have suggested that EGFR is a biomarker used to predict the therapeutic effect of targeted therapy. A large number of evidence indicates that EGFR/Akt pathway plays important role in cancer growth and metastasis. AIM OF THE STUDY: In this paper, we found EGFR was a target of miR-646. RESULTS: Overexpression of miR-646 not only downregulated EGFR/Akt pathway, but also inhibited lung cancer cell proliferation and metastasis. At the same time, miR-646 was a prognosis factor for overall survival. CONCLUSION: Our finding could provide new insights into the molecular therapeutic of lung cancer.

MiR-122 Induces Radiosensitization in Non-Small Cell Lung Cancer Cell Line.

MiR-122 is a novel tumor suppresser and its expression induces cell cycle arrest, or apoptosis, and inhibits cell proliferation in multiple cancer cells, including non-small cell lung cancer (NSCLC) cells. Radioresistance of cancer cell leads to the major drawback of radiotherapy for NSCLC and the induction of radiosensitization could be a useful strategy to fix this problem. The present work investigates the function of miR-122 in inducing radiosensitization in A549 cell, a type of NSCLC cells. MiR-122 induces the radiosensitization of A549 cells. MiR-122 also boosts the inhibitory activity of ionizing radiation (IR) on cancer cell anchor-independent growth and invasion. Moreover, miR-122 reduced the expression of its targeted genes related to tumor-survival or cellular stress response. These results indicate that miR-122 would be a novel strategy for NSCLC radiation-therapy.