Idiopathic pulmonary fibrosis (IPF) is an interstitial pneumonia characterized by chronic progressive fibrosis, ultimately leading to respiratory failure and early mortality. Although not fully explored, the major causative factors in IPF pathogenesis are dysregulated fibroblast proliferation and excessive accumulation of extracellular matrix (ECM) deposited by myofibroblasts differentiated from pulmonary fibroblasts. More signalling pathways, including the PI3K-Akt-mTOR and autophagy pathways, are involved in IPF pathogenesis. Niclosamide ethanolamine salt (NEN) is a highly effective multitarget small-molecule inhibitor reported in antitumor studies. Here, we reported that in an IPF animal model treated with NEN for 14 days, attractive relief of pulmonary function and hydroxyproline content were observed. To further explore, the therapeutic effect of NEN in IPF and pathological changes in bleomycin-challenged mouse lung sections were assessed. Additionally, the effects of NEN on abnormal proliferation and ECM production in IPF cell models established with TGF-β1-stimulated A549 cells or DHLF-IPF cells were studied. In nonclinical studies, NEN ameliorated lung function and histopathological changes in bleomycin-challenged mice, and the lung hydroxyproline content was significantly diminished with NEN treatment. In vitro, NEN inhibited PI3K-mTORC1 signalling and arrested the cell cycle to prevent uncontrolled fibroblast proliferation. Additionally, NEN inhibited TGF-β1-induced epithelial–mesenchymal transition (EMT) and ECM accumulation via the mTORC1-4EBP1 axis. Furthermore, NEN-activated noncanonical autophagy resensitized fibroblasts to apoptosis. The above findings demonstrated the potential antifibrotic effect of NEN mediated via modulation of the PI3K-mTORC1 and autophagy pathways. These data provide strong evidence for a therapeutic role for NEN in IPF.

Background: Mediastinal teratoma is a rare disease, many cases were reported before, but few articles focus on large case analyses. The objective of this article is to summarize the clinical characteristics of benign mediastinal teratoma and the experience of surgical treatment, especially thoracoscopic surgery for benign mediastinal teratoma. Methods: The clinical data of 108 patients with benign mediastinal teratoma confirmed by operation and pathology from January 1992 to January 2018 were analyzed retrospectively. The clinical symptoms, imaging examination, surgical methods and prognosis of all patients were analyzed. We compared the difference of thoracoscopic surgery and thoracotomy surgery using 102 patients underwent only chest surgery. Normally distributed continuous variables were compared by independent sample t test. Categorical variables were analyzed by chi-square test. Results: Imaging examination showed that all 108 cases of mediastinal teratoma were located in the anterior region of mediastinum. All cases underwent surgical resection, postoperative pathology confirmed that all cases were benign. 1 case was taken simple neck collar incision, 5 case was taken median thoracotomy combined with neck incision, other 102 cases were taken thoracoscopic surgery (22) or thoracotomy surgery (80). 4 cases were treated with partial pericardial resection due to adhesions, 12 cases underwent partial pericardial resection, 5 cases underwent lobectomy, 9 cases underwent wedge resection of lobe, and 2 patients underwent anonymous vein angioplasty. 1 case underwent second operation because of postoperative bleeding, 1 case of chylothorax, 1 case of recurrent laryngeal nerve injury, 2 cases of wound infection, 1 case of secondary pulmonary infection. 106 cases were followed up, period from 12 months to 10 years, no recurrence of tumor was found. Comparing to take thoracotomy surgery, patients underwent thoracoscopic surgery has strong advantage on intraoperative blood loss and hospital stay days after surgery (P < 0.05). tumor maximum diameter is larger for thoracotomy surgery group, as well as more patients suffer estimated adhesions from preoperative imaging. so we compared above parameters in patients with tumor diameter less than 10 cm with or without estimated adhesions from preoperative imaging, a strong advantage still can be found in thoracoscopic surgery group, inpatients with estimated adhesions from preoperative imaging, intraoperative blood loss (38.75 ± 15.53 vs 169.17 ± 208.82., P = 0.04) and hospital stay days after surgery (5.50 ± 0.93 vs 9.43 ± 6.54., P = 0.04) were better. In patients without estimated adhesions from preoperative imaging, intraoperative blood loss (46.67 ± 10.00 vs 110.53 ± 123.13., P = 0.06) and hospital stay days after surgery (4.70 ± 1.16 vs 7.53 ± 2.32., P = 0.01) were better. Especially, in thoracoscopic surgery group, hospital stay days after surgery was significantly shorter. Conclusion: The clinical manifestations and imaging performance of benign mediastinal teratoma were complicated, and the surgical treatment was effective. Compared with traditional thoracotomy surgery, thoracoscopic surgery can improve patients’ quality of life, less intraoperative blood loss, and less hospital stay days after surgery, so if condition is permitted, thoracoscopic surgery should be a better choice.

Non-small cell lung cancer (NSCLC) accounts for 85~90% of lung cancer cases, with a poor prognosis and a low 5-year survival rate. Sphingosine kinase-1 (SPHK1), a key enzyme in regulating sphingolipid metabolism, has been reported to be involved in the development of NSCLC, although the underlying mechanism remains unclear. In the present study, we demonstrated the abnormal signature of SPHK1 in NSCLC lesions and cell lines of lung cancers with a potential tumorigenic role in cell cycle regulation. Functionally, ectopic Pre-B cell leukemia homeobox-1 (PBX1) was capable of restoring the arrested G1 phase induced by SPHK1 knockdown. However, exogenous sphingosine-1-phosphate (S1P) supply had little impact on the cell cycle arrest by PBX1 silence. Furthermore, S1P receptor S1PR3 was revealed as a specific switch to transport the extracellular S1P signal into cells, and subsequently activated PBX1 to regulate cell cycle progression. In addition, Akt signaling partially participated in the SPHK1/S1PR3/PBX1 axis to regulate the cell cycle, and the Akt inhibitor significantly decreased PBX1 expression and induced G1 arrest. Targeting SPHK1 with PF-543 significantly inhibited the cell cycle and tumor growth in preclinical xenograft tumor models of NSCLC. Taken together, our findings exhibit the vital role of the SPHK1/S1PR3/PBX1 axis in regulating the cell cycle of NSCLC, and targeting SPHK1 may develop a therapeutic effect in tumor treatment.

Extralobar sequestration is a rare congenital malformation of lung tissue, which can be combined with other foregut and cardiac abnormalities. Our case is the first to report extralobar sequestration, absence of pericardium and atrial septal defect in the same patient. A 22-year-old female with atrial septal defect came for her recent atypical symptom of intermittent palpitation and shortness of breath. Her computed tomography showed a cystic mass located in left superior anterior mediastinum near the pulmonary trunk. With specious of cystic teratoma prior to video-assisted thoracoscopic surgery, she finally was diagnosed as extralobar sequestration, while incidentally found with congenital absence of pericardium during surgery. Extralobar sequestration, absence of pericardium and atrial septal defect can occur in the same patient. The preoperative diagnostic rate of extralobar sequestration and asymptomatic absence of pericardium remains low attributed to atypical imaging features. A cardiac magnetic resonance imaging is highly recommended if necessary. Regular follow-up is essential to asymptomatic absence of pericardium and atrial septal defect patients. To patients with extralobar sequestration, an operation could be performed.