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Abstract Background Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterized by irreversible scarring of the lung parenchyma. Despite various interventions aimed at mitigating several different molecular aspects of the disease, only two drugs with limited clinical efficacy have so far been approved for IPF therapy. Objective We investigated the therapeutic efficacy of amifostine, a detoxifying drug clinically used for radiation-caused cytotoxicity, in bleomycin-induced murine pulmonary fibrosis. Methods C57BL6/J mice were intratracheally instilled with 3 U/kg of bleomycin. Three doses of amifostine (WR-2721, 200 mg/kg) were administered intraperitoneally on days 1, 3, and 5 after the bleomycin challenge. Bronchoalveolar lavage fluid (BALF) was collected on day 7 and day 21 for the assessment of lung inflammation, metabolites, and fibrotic injury. Human fibroblasts were treated in vitro with transforming growth factor beta 1 (TGF-β1), followed by amifostine (WR-1065, 1–4 µg/mL) treatment. The effects of TGF-β1 and amifostine on the mitochondrial production of reactive oxygen species (ROS) were assessed by live cell imaging of MitoSOX. Cellular metabolism was assessed by the extracellular acidification rate (ECAR), the oxygen consumption rate (OCR), and the concentrations of various energy-related metabolites as measured by mass spectrum (MS). Western blot analysis was performed to investigate the effect of amifostine on sirtuin 1 (SIRT1) and adenosine monophosphate activated kinase (AMPK). Results Three doses of amifostine significantly attenuated lung inflammation and pulmonary fibrosis. Pretreatment and post-treatment of human fibroblast cells with amifostine blocked TGF-β1-induced mitochondrial ROS production and mitochondrial dysfunction in human fibroblast cells. Further, treatment of fibroblasts with TGF-β1 shifted energy metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) and towards glycolysis, as observed by an altered metabolite profile including a decreased ratio of NAD + /NADH and increased lactate concentration. Treatment with amifostine significantly restored energy metabolism and activated SIRT1, which in turn activated AMPK. The activation of AMPK was required to mediate the effects of amifostine on mitochondrial homeostasis and pulmonary fibrosis. This study provides evidence that repurposing of the clinically used drug amifostine may have therapeutic applications for IPF treatment. Conclusion Amifostine inhibits bleomycin-induced pulmonary fibrosis by restoring mitochondrial function and cellular metabolism.

Introduction Cigarette and tobacco use is a leading cause of chronic obstructive pulmonary disease, lung cancer, and other malignant tumors. In China, people prefer to engage in mental activities (gambling, overtime work, playing video games, or other mental activities) on the weekends or during spare time, especially in the evening before they prepare for bed. In China, smokers frequently consume tea while smoking. The relationship between smokers who consume tea, engage in mental activities after dinner, or both (drinking tea and engaging in cognitive activities after dinner together), and daily cigarette smoking or nicotine addiction must be clarified. Methods A total of 438 smokers were included in the study. Age, gender, body mass index (BMI), smoking habits, Fagerström test for nicotine dependence scores, and behaviors, were recorded. The study excluded smokers with a Fagerström score

ABSTRACT Objective: Transbronchial lung cryobiopsy (TBCB) has developed rapidly and has become one of the research hotspots of lung biopsy technology. The present study sought to evaluate the efficacy of TBCB guided by radial-probe EBUS (RP-EBUS) and a guide sheath (GS) without fluoroscopy for peripheral pulmonary lesions. Methods: In this retrospective study, McNemar’s test was used in order to compare TBCB and transbronchial forceps biopsy (TBFB) in terms of diagnostic performance. A multivariate logistic regression model was designed to explore the association between predictive variables and the diagnostic yield of TBCB. Results: A total of 168 patients underwent GS-guided RP-EBUS. Of those, 157 had lesions that were visible and 11 had lesions that were not. Of those 157 patients, 24 were excluded because of missing data or an unclear final diagnosis. Therefore, 133 patients underwent RP-EBUS-GS-guided TBFB and TBCB. The pooled diagnostic yield of RP-EBUS-GS-guided TBCB without fluoroscopy was 71.5% (103/144). In 133 patients, the diagnostic yield of TBCB was significantly higher than that of TBFB (77.4% vs. 59.4%; p < 0.05). Multivariate analysis indicated that lesion size and site were independently associated with the diagnostic yield of TBCB (OR = 2.8, p = 0.03 and OR = 4.1, p = 0.01, respectively), although cryoprobe size was not. There was no significant difference between the 1.1-mm cryoprobe and the 1.9-mm cryoprobe in terms of diagnostic performance (78.4% vs. 76.8%; p > 0.05). Conclusions: GS-guided RP-EBUS is regarded as a practical option for guiding cryobiopsy, although it may not be able to replace fluoroscopy. Peripheral pulmonary lesions not located in the upper lobes or larger than 30 mm are significantly associated with a higher diagnostic yield of cryobiopsy.

Background: The diagnosis of peripheral pulmonary nodules (PPNs) still is the key and difficult point. Previous studies have demonstrated that the diagnostic yield of radial endobronchial ultrasound (rEBUS) visible nodules is significantly higher than that of invisible nodules. The traditional method of predicting the rEBUS-visibility of nodules is based on the CT-bronchus signs, but its effectiveness may be unsatisfactory. Objective: We innovate a valuable predictive model based on virtual bronchoscopic navigation to identify beforehand which PPNs are likely to be successfully visualized by rEBUS. The innovative predictor is the ratio of the size of lesions (S) to the shortest straight-line distance (D) from the terminal point of the virtual navigation path to the localization point of the nodule. Methods: This is a retrospective study. On the training dataset of 214 patients, a receiver operating characteristic curve was drawn to understand the utility of the predictive model and get the optimal cut-off points. Ninety-two cases were enrolled in the validation dataset to validate the external predictive accuracy of the predictor. Results: The optimal cut-off point of the curve was 1.84 with the Youden index of 0.65, at which point the area under the curve was 0.85 (95% CI: 0.76-0.95). The predictor has a good performance in the validation dataset with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 81%, 100%, 100%, 71%, and 87%, respectively. Conclusion: The S/D ratio is a valuable and innovative method to identify beforehand which PPNs are likely to be successfully visualized by rEBUS. If the S/D ratio of the nodule is greater than 1.84, it will be visualized by rEBUS.

Introduction Nicotine dependence (ND) is a maladaptive pattern of tobacco smoking with withdrawal symptoms similar to other drug addictive disorders. It is very common in clinical practice that smokers always have different degrees of nicotine dependence with the same amount of tobacco consumption. Behaviors may influence daily cigarette consumption or smoking status. Hence it is critical to ascertain the association between concurrent behaviors and high nicotine dependence among smokers. Methods A total of 343 patients who attended a clinic for smoking cessation were recruited, and the information on concurrent behaviors were recorded. Factors associated and not associated with nicotine dependence were recorded. Nicotine dependence was determined by Fagerström test for nicotine dependence (FTND). Results High ND patients (FTND >5) showed significant behaviors distribution compared with mild and moderate ND patients (FTND ≤5). There is no single behavior that was significantly different between high ND and mild and moderate ND smokers. However, the combined effects of nicotine dependence influencing behaviors of caffeine drinking and mental activities after dinner have an association with high ND (OR=1.939; 95% CI: 1.154–3.258, p=0.012). In addition, the combined effects of inadequate sleep time (