Chinese expert consensus on interventional diagnosis and management of acquired digestive-respiratory tract fistulas (second edition).

Acquired digestive-respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large-scale evidence-based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive-respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive-respiratory tract fistulas. The guidelines conduct an in-depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.

Application of circulating genetically abnormal cells in the diagnosis of early-stage lung cancer.

PURPOSE: Lung cancer is the leading cause of cancer-related death worldwide. The early detection of lung cancer is crucial for the diagnosis of this disease. Therefore, an effective and noninvasive method for the early diagnosis of lung cancer is urgently needed. METHODS: To evaluate the diagnostic performance of circulating genetically abnormal cells (CACs) in early lung cancer, a total of 63 participants who completed CAC detection by Zhuhai SanMed Biotech Inc. and obtained pathological results from January to December 2020 were included in our study; 50 patients had lung cancer and 13 patients had benign lung disease. The levels of lung cancer-related markers in peripheral blood and the chest computed tomography (CT) imaging characteristics of these patients were collected before pathological acquisition. RESULTS: The positive rate of CAC was 90.0% in the lung cancer group and 23.1% in the benign lung disease group, and the difference was statistically significant (P < 0.01). The area under the receiver operating characteristic (ROC) curve of CAC was 0.837, the sensitivity was 90%, and the specificity was 76.9%. The area under the ROC curve and sensitivity were both higher than those of the combined or single serum tumor marker test. CONCLUSIONS: This study preliminarily concludes that the CAC test, as a noninvasive test, has high sensitivity and specificity for the early diagnosis of lung cancer. This test is expected to help with the early detection of disease in lung cancer patients.

Expert consensus on thermal ablation therapy of pulmonary subsolid nodules (2021 Edition).

The Expert Consensus reviews current literatures and provides clinical practice guidelines for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The main contents include the following: (1) clinical evaluation of GGN; (2) procedures, indications, contraindications, outcomes evaluation, and related complications of thermal ablation for GGN; and (3) future development directions.

[Expert Consensus for Thermal Ablation of Pulmonary Subsolid Nodules (2021 Edition)].

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Suppression of HELLS by miR-451a represses mTOR pathway to hinder aggressiveness of SCLC.

BACKGROUND: Uncovering molecular pathogenesis and mechanisms of small cell lung cancer (SCLC) will contribute to SCLC therapy. Multiple studies demonstrated that miR-451a acts as an anti-tumor miRNA in non-small cell lung cancer. However, the mechanism of miR-451a in SCLC was ambiguous. OBJECTIVE: We aimed to explore the function of miR-451a in SCLC and decipher the underlying mechanisms. METHODS: TargetScan and dual-luciferase reporter assays were used to analyze the target genes of miR-451a. Cell counting kit-8 and colony formation assays were performed to assess the roles of miR-451a on cell growth. Gene set enrichment analysis (GSEA) was utilized to enrich biological pathways. Western blot was used to measure protein expression. RESULTS: MiR-451a expression was reduced dramatically in SCLC tissues and cell lines (NCI-H1688 and NCI-H446). Helicase, Lymphoid Specific (HELLS) was proved to be a target gene of miR-451a. In addition, cell proliferation assays in SCLC cells transfected with miR-451a mimic and/or HELLS revealed that miR-451a inhibited cell proliferation via targeting HELLS. Moreover, the roles of miR-451a/HELLS in expression of key proteins in mTOR and apoptosis signaling pathways suggested that miR-451a inactivated mTOR and activated apoptosis signaling pathway via directly silencing HELLS. CONCLUSIONS: Our study indicated that miR-451a hinders SCLC cell proliferation in vitro through regulating mTOR and apoptosis signaling pathways via silencing HELLS, suggesting that miR-451a could be a promising tumor suppressor in SCLC. And there is a potential for miR-451a to be a drug target and biomarker for SCLC.

Utility of medical thoracoscopy in diagnosis and treatment of hemothorax due to carcinoma: A case report.

Hemothorax cannot always be treated by thoracic surgeon. Rapidly improved interventional pulmonology broadens the application of medical thoracoscopy. We attempt to share our experiences of medical thoracoscopy for hemothorax and discuss the value of medical thoracoscopy in pleural diseases. We reported a 76-year-old male with hemothorax who was cured by medical thoracoscopy under local anesthesia together with argon plasma coagulation. Moreover, final pathological diagnosis was acquired as pleural sarcomatoid carcinoma. The unusual manifestation under medical thoracoscopy of such a relative rare disease was also described in this paper. The medical thoracoscopy could be used successfully for hemothorax instead of treating with surgeon, especially for those who cannot tolerate procedure of operation or surgical thoracoscopy.

Role of pulmonary function and FeNO detection in early screening of patients with ACO.

Measurement of fractional exhaled nitric oxide (FeNO) is a quantitative and non-invasive approach to examine airway inflammation, which is a powerful aid in diagnosing chronic disorders of airways like asthma. Diagnostic value of FeNO and relevant indices on pulmonary function in the patients with asthma and chronic obstructive pulmonary disease (COPD) was evaluated. A total of 164 patients [58 asthma, 49 COPD and 57 asthma-COPD overlap (ACO)] were randomly recruited. FeNO, pulmonary ventilation function, and bronchial diastolic function were performed. Eight indicators including FeNO, vital capacity percentage (VC%), forced vital capacity percentage (FVC%), forced expiratory volume in one second percentage (FEV1%), forced expiratory volume in one second to forced vital capacity percentage (FEV1/FVC%), maximum independent ventilation volume percentage (MVV%), the increased percentage of FEV1 after bronchial diastolic test, the increased absolute value of FEV1 after bronchial diastolic test were examined. Significant difference in VC%, FVC%, FEV1%, FEV1/FVC%, MVV%, the increased absolute value of FEV1 after bronchial diastolic test and FeNO were significantly different between patients with asthma and patients with COPD (P<0.05). There were significant differences of VC%, FVC%, FEV1%, FEV1/FVC%, MVV% and the increased percentage of FEV1 after bronchial diastolic test in cases of patients with asthma compared to ACO patients (P<0.05). There was no statistical significance on VC%, FVC%, FEV1%, FEV1/FVC%, MVV% between COPD patients and ACO patients (P>0.05). However, more importantly, the increased percentage of FEV1 after bronchial diastolic test, the increased absolute value of FEV1 after bronchial diastolic test and the alterations on FeNO were found significantly different in ACO group compared with COPD alone (P<0.05). We compared the results from pulmonary ventilation function, bronchial diastolic function examination as well as FeNO detection among 3 groups of asthma, COPD and ACO. The examination of pulmonary ventilation function and bronchial diastolic function combined with FeNO detection is helpful in the early screening of ACO.

Clinical efficacy of treatment for primary tracheal tumors by flexible bronchoscopy: Airway stenosis recanalization and quality of life.

The aim of the present study was to evaluate the effectiveness of interventional treatment of primary tracheal tumors through flexible bronchoscopy. The clinical data of 38 patients with primary tracheal tumours who underwent flexible bronchoscopy intervention therapy between January 2011 and January 2017 were retrospectively analyzed. The average time interval from onset of symptoms to the appearance of actual clinical manifestations in the 38 patients ranged from 0 to 60 months, with an average of 8.1±11.6 months and a median of 4.2 months. The rate of misdiagnosis at the first visit was 36.8% (14/38). After interventional treatment, the overall efficiency (complete + partial response) of airway stenosis recanalization in the 38 patients was 89.5%. In 3 patients with benign tumors, the anhelation score was reduced following treatment (1.00±0.77 vs. 3.13±1.21 at the pre-treatment stage; P<0.001). The overall survival rates of the 35 patients at 1, 3 and 5 years were 69.3, 48.7 and 20.3%, respectively. Therefore, flexible bronchoscopic intervention may effectively smoothen the airways of patients and relieve the symptoms of anhelation. Combining radiotherapy and chemotherapy may improve patient prognosis and safety.

Safety and complications of medical thoracoscopy in the management of pleural diseases.

BACKGROUND: Medical thoracoscopy is considered an overall safe procedure, whereas numbers of studies focus on complications of diagnostic thoracoscopy and talc poudrage pleurodesis. We conduct this study to evaluate the safety of medical thoracoscopy in the management of pleural diseases and to compare complications in different therapeutic thoracoscopic procedures. METHODS: A retrospective study was performed in 1926 patients, 662 of whom underwent medical thoracoscopy for diagnosis and 1264 of whom for therapeutic interventions of pleural diseases. Data on complications were obtained from the patients, notes on computer system, laboratory and radiographic findings. Chi-square test was performed to compare categorical variables and Fisher's exact test was used for small samples. RESULTS: The mean age was 51 ± 8.4 (range 21-86) years and 1117 (58%) were males. Diagnostic procedure was taken in 662 (34.4%) patients, whereas therapeutic procedure was taken in 1264 (65.6%) patients. Malignant histology was reported in 860 (44.6%) and 986 (51.2%) revealed benign pleural diseases. Eighty patients (4.2%) were not definitely diagnosed and they were considered as unidentified pleural effusion. One patient died during the creation of artificial pneumothorax, and the causes of death were supposed as air embolism or an inhibition of phrenic motoneurons and circulatory system. Complication of lung laceration was found in six patients (0.3%) and reexpansion pulmonary edema was observed in two patients (0.1%). Higher incidence of prolonged air leak was observed in bulla electrocoagulation group, in comparison with pleurodesis group. Moreover, pain and fever were the most frequently complications in pleurodesis group and cutaneous infection in entry site was the most frequently reported complication in pleural decortication of empyema group. CONCLUSIONS: Medical thoracoscopy is generally a safe and effective method, not only in the diagnosis of undiagnosed pleural effusions, but also in the management of pleural diseases. Mastering medical thoracoscopy well, improving patient management after the procedure and attempts to reduce the occurrence of post-procedural complications are the targets that physicians are supposed to achieve in the future.

Medical thoracoscopy for tuberculous pleurisy: A retrospective analysis of 575 cases.

OBJECTIVE: The objective of this retrospective study was to assess the efficacy of medical thoracoscopy in diagnosing of tuberculous pleurisy and characterize tuberculous pleurisy with medical thoracoscopy. METHODS: A total of 575 patients with tuberculous pleurisy who underwent medical thoracoscopy were included in the study. Demographic data, clinical manifestations, and routine and biochemical tests on pleural fluid, cultures of pleural fluid, sputum, and pleural biopsy for the detection of Mycobacterium tuberculosis and pathological findings were evaluated. RESULTS: Sputum, pleural fluid, and pleural biopsy cultures were positive for M. tuberculosis in 12.5%, 19.2%, and 41.9% of patients, respectively. Furthermore, there were significant differences in total positive tuberculosis (TB) tests in the pleural cavity according to patient's age (<18 years old, 50.0%; 18-34 years old, 50.2%; 35-59 years old, 34.8%; >60 years old, 18.6%; and all groups vs. >60 years old, P < 0.001). Patients with 18-34 years old were more likely to have granuloma in pleural biopsy specimens when compared to patients >60 years old (77.0% vs. 37.9%). The percentage of patients with high adenosine deaminase (ADA) levels in pleural fluid (>40 U/L), who were <18, 18-34, 35-59, and > 60 years old, was 83.3% (15/18), 72.8% (193/265), 51.2% (88/172), and 34.7% (17/49), respectively (all groups vs. >60 years old, P < 0.001). CONCLUSION: Medical thoracoscopy is effective for diagnosing tuberculous pleurisy. Younger patients with tuberculous pleurisy have a higher number of positive TB tests in the pleural cavity, are more likely to have granuloma in pleural biopsy specimens, and have higher ADA levels in the pleural fluid.

Retracted Article: Structural characterization of centipede oligopeptides and capability detection in human small cell lung carcinoma: inducing apoptosis.

Lung cancer is the most frequent cause of cancer deaths in the world, and smoking is considered as one of the major causes. Small cell lung carcinoma (SCLC) represents a highly malignant and particularly aggressive form, with properties of widespread metastases and poor prognosis. Herein, twenty-five Scolopendra subspinipes mutilans L. Koch Oligopeptides (SSMOs) were isolated and their structures were identified, and the anti-proliferative activity against lung cancer cell lines was evaluated. Results showed that SSMO-5 induced the production of reactive oxygen species (ROS) markedly in NCI-H446 cells. Furthermore, SSMO-5 decreased the mitochondrial membrane potential (MMP) and enhanced the mitochondria-related apoptosis. These results demonstrate that in NCI-H446 cells, the apoptotic and cytotoxic effects of SSMO-5 are mediated by the intrinsic mitochondria-mediated apoptotic pathway, which in turn causes the activation of caspases and increases Bax expression, while decreases Bcl-2 and Bcl-xL expressions and regulates the interaction of p53/MDM2. In conclusion, a ROS-mediated mitochondrial pathway plays an important role in the process of SSMO-5-induced apoptosis against SCLC.

Berberine induces mitochondrial­mediated apoptosis and protective autophagy in human malignant pleural mesothelioma NCI­H2452 cells.

Increasing evidence shows that berberine has antitumor effects against a number of tumor cells. In the present study, we evaluated the effect of berberine on the proliferation of the human malignant pleural mesothelioma (MPM) cell line NCI­H2452, and explored the therapeutic potential and underlying mechanisms of this agent. Our results showed that berberine inhibited the proliferation of NCI­H2452 cells in a dose­ and time­dependent manner and could induce apoptosis, possibly through a caspase­9­dependent intrinsic mitochondrial pathway. In addition, autophagy was induced by berberine, which was characterized by the accumulation of LC3­II and decreased p62 expression. We used inhibitors of apoptosis and autophagy, and an inducer of autophagy, to evaluate the significance of autophagy in berberine­induced cell death. The results demonstrated that apoptosis is the primary route through which berberine induces NCI­H2452 cell death. Berberine­induced autophagy may be an adaptive response to antitumor agents and have a protective role in MPM cells. Inhibition of autophagy enhanced berberine­induced apoptosis. Therefore, inhibition of autophagy may be an effective treatment strategy in the management of MPM. In conclusion, berberine is a potent antitumor agent for treating MPM, and it induces mitochondrial­mediated apoptosis and protective autophagy in human NCI­H2452 MPM cells.

Chinese expert consensus on diagnosis and management of acquired respiratory-digestive tract fistulas.

Acquired respiratory-digestive tract fistulas occur with abnormal communication between the airways and digestive tract, causing the interflow of gas and liquid. Despite advances in surgical methods and the development of multimodal therapy in recent years, patients with acquired respiratory-digestive tract fistulas continue to exhibit unfavorable clinical outcomes. Therefore, in order to guide clinical practice in China, the Respiratory and Cancer Intervention Alliance of the Beijing Health Promotion Association organized a group of experienced experts in the field to develop this consensus document. Based on a study of clinical application and expert experience in the diagnosis and management of acquired respiratory-digestive tract fistulas at home and abroad, an Expert Consensus was developed. The panelists recruited comprised experts in pulmonology, oncology, thoracic surgery, interventional radiology, and gastroenterology. PubMed, Chinese Biology Abstract, Chinese Academic Journal, and Wanfang databases were used to identify relevant articles. The guidelines address etiology, classification, pathogenesis, diagnosis and management of acquired respiratory-digestive tract fistulas. The statements on treatment focus on the indications for different procedures, technical aspects, and preprocedural, post-procedural and complication management. The proposed guidelines for the diagnosis and management of acquired respiratory-digestive tract fistulas are the first to be published by Chinese experts. These guidelines provide an in-depth review of the current evidence and standard of diagnosis and management.

Overexpression of OCT4 is associated with gefitinib resistance in non-small cell lung cancer.

Epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs) have emerged as first-line drugs for non-small cell lung cancers (NSCLCs). However, the resistance to TKIs represents the key limitation for their therapeutic efficacy. We found that the difference of OCT4 expression between NSCLC and the adjacent non-tumourous tissues was statistically significant. Knockdown of OCT4 in NSCLC cells could decrease cell proliferation, and potentiate apoptosis induced by gefitinib, suggesting OCT4 may contribute to gefitinib resistance in NSCLC.

Construction of protein interaction network involved in lung adenocarcinomas using a novel algorithm.

Studies that only assess differentially-expressed (DE) genes do not contain the information required to investigate the mechanisms of diseases. A complete knowledge of all the direct and indirect interactions between proteins may act as a significant benchmark in the process of forming a comprehensive description of cellular mechanisms and functions. The results of protein interaction network studies are often inconsistent and are based on various methods. In the present study, a combined network was constructed using selected gene pairs, following the conversion and combination of the scores of gene pairs that were obtained across multiple approaches by a novel algorithm. Samples from patients with and without lung adenocarcinoma were compared, and the RankProd package was used to identify DE genes. The empirical Bayesian (EB) meta-analysis approach, the search tool for the retrieval of interacting genes/proteins database (STRING), the weighted gene coexpression network analysis (WGCNA) package and the differentially-coexpressed genes and links package (DCGL) were used for network construction. A combined network was also constructed with a novel rank-based algorithm using a combined score. The topological features of the 5 networks were analyzed and compared. A total of 941 DE genes were screened. The topological analysis indicated that the gene interaction network constructed using the WGCNA method was more likely to produce a small-world property, which has a small average shortest path length and a large clustering coefficient, whereas the combined network was confirmed to be a scale-free network. Gene pairs that were identified using the novel combined method were mostly enriched in the cell cycle and p53 signaling pathway. The present study provided a novel perspective to the network-based analysis. Each method has advantages and disadvantages. Compared with single methods, the combined algorithm used in the present study may provide a novel method to analyze gene interactions, with increased credibility.

SIRT5 prevents cigarette smoke extract-induced apoptosis in lung epithelial cells via deacetylation of FOXO3.

Cigarette smoking plays an important role in increased incidence of chronic obstructive pulmonary disease (COPD). The underlying mechanism in which cigarette smoking induced impairment of lung epithelial cells is still unknown. SIRT5 is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, which has been implicated in the regulation of metabolism, stress responses, and aging. Forkhead box O3 (FOXO3) belongs to the O subclass of the forkhead family of transcription factors. It is also involved in protection from oxidative stress by upregulating antioxidants in epithelial cells. Here, we show that cigarette smoke extract (CSE) induces SIRT5 to deacetylate FOXO3 at K271 and K290. Deacetylation of FOXO3 promotes its nuclear localization. Notably, transfection with FOXO3 K271R- or K290R-attenuated CSE-induced apoptosis in SIRT5 knocked down cells, suggesting the protective effects of SIRT5, is mediated by FOXO3. In contrast, CSE stress upregulates SIRT5, which activates FOXO3α leading to rescuing apoptosis. Thus, SIRT5 constitutes a determinant of apoptosis by CSE in lung epithelial cells.

Efficacy of medical thoracoscopic talc pleurodesis in malignant pleural effusion caused by different types of tumors and different pathological classifications of lung cancer.

The aim of this study was to assess the efficacy and complications and compare the efficacy of medical thoracoscopic talc pleurodesis among patients with different types of tumors and different pathological classifications of lung cancer as well as to evaluate the role of postoperative negative pressure chest tube drainage. A total of 1061 patients with malignant pleural effusion who underwent thoracoscopic pleurodesis were analyzed retrospectively. The complications, postoperative drainage time, and efficacy of pleurodesis among patients with different types of tumors and different pathological classifications of lung cancer were assessed. The overall response rate (ORR) was 88.03%. Major complications included chest pain (68%) and fever (47%). The postoperative drainage time was 4.74 ± 1.56 days. Postoperative negative pressure chest tube drainage significantly shortened the drainage time (negative vs. non-negative: 4.56 ± 1.49 days vs. 4.81 ± 1.59 days, P = 0.037). Pleurodesis was less effective in treating effusion caused by lung cancer (72.3%) and mesothelioma (68.2%) than that caused by breast cancer (84.4%) and other tumors (87.8%) (P = 0.009). The efficacy in the treatment of effusion caused by adenocarcinoma (66.7%) was slightly less than that caused by other types of lung cancer (P = 0.311). In conclusion, medical thoracoscopic talc pleurodesis is a palliative and effective treatment for malignant pleural effusion. In addition, postoperative simple negative pressure chest tube drainage significantly shortens the drainage time. However, thoracoscopic pleurodesis is less effective for the treatment of effusion caused by lung cancer and pleural mesothelioma compared with that caused by other types of cancers.

Serum albumin as a significant prognostic factor in patients with malignant pleural mesothelioma.

Our aim was to evaluate the prognostic role of the pretreatment serum albumin level in patients with malignant pleural mesothelioma (MPM) receiving platinum-based systemic chemotherapy. From 1995 to 2013, a total of 97 patients receiving platinum-based systemic chemotherapy for newly diagnosed MPM were enrolled. All clinical information and laboratory results were retrospectively collected from the medical records. The Kaplan-Meier method was used to calculate survival. The Cox proportional hazards model was used to identify significant independent prognostic factors for predicting survival. In total, 34 of the 97 patients (35.1 %) had hypoalbuminaemia (albumin ≤ 35 g/l). The 1-year overall survival rate was 44.1 % for patients with hypoalbuminaemia and 72.0 % for patients with a normal albumin level. Multivariate analysis indicated that pretreatment albumin was an independent prognostic factor in MPM. Patients with hypoalbuminaemia had a greater risk of death than those with a normal albumin level [hazard ratio (HR) 1.778; 95 % confidence interval (CI) 1.504-2.998; P = 0.031]. When albumin was entered as a continuous variable in the Cox regression model, the HR of death was significantly decreased by 9.8 % (95 % CI 0.851-0.956) for each 1-g/l increment. The pretreatment serum albumin level is a simple, inexpensive and easily measurable marker with prognostic significance in MPM patients treated with platinum-based systemic chemotherapy.

Prognostic nutritional index predicts outcomes of malignant pleural mesothelioma.

PURPOSE: Nutritional status has been associated with long-time outcomes in cancer patients. We investigated whether the prognostic nutritional index (PNI), an indicator of nutritional status, affects overall survival in patients with malignant pleural mesothelioma (MPM). METHODS: We enrolled 121 patients with histologically confirmed MPM, who had successfully undergone biopsy by medical thoracoscopy in this study. Demographic, clinical and laboratory data were collected retrospectively. The PNI was calculated as 10× serum albumin value (g/dl) + 0.005 × total lymphocyte count (per mm(3)) in peripheral blood. Univariate and multivariate analyses were used to identify prognostic factors. RESULTS: Mean pretreatment PNI was 44.6. PNI was significantly associated with age (P = 0.031), smoking habits (P = 0.039) and weight loss (P = 0.029). Survival analysis showed PNI to be an independent prognostic factor in MPM. Patients with lower PNIs (PNI < 44.6) had greater risk of death than those with higher PNIs (PNI ≥ 44.6; hazard ratio: 2.290; 95 % confidence interval: 1.415-3.706; P = 0.001). These analyses were adjusted for patient age, gender, smoking habits, dyspnea, chest pain, weight loss, primary site of tumor, histology, platinum-based systemic chemotherapy, hospital and stage. CONCLUSIONS: Pretreatment PNI is a novel independent prognostic factor in MPM.

Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in rats.

BACKGROUND: Recent evidence has demonstrated the role of angiogenesis in the pathogenesis of pulmonary fibrosis. Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis. The aim of our study was to assess whether endostatin has beneficial effects on bleomycin (BLM)-induced pulmonary fibrosis in rats. METHODS: The rats were randomly divided into five experimental groups: (A) saline only, (B) BLM only, (C) BLM plus early endostatin treatment, (D) BLM plus late endostatin treatment, and (F) BLM plus whole-course endostatin treatment. We investigated the microvascular density (MVD), inflammatory response and alveolar epithelial cell apoptosis in rat lungs in each group at different phases of disease development. RESULTS: Early endostatin administration attenuated fibrotic changes in BLM-induced pulmonary fibrosis in rats. Endostatin treatment decreased MVD by inhibiting the expression of VEGF/VEGFR-2 (Flk-1) and the activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). Endostatin treatment also decreased the number of inflammatory cells infiltrating the bronchoalveolar lavage fluid during the early inflammatory phase of BLM-induced pulmonary fibrosis. In addition, the levels of tumour necrosis factor-α (TNF-α) and transforming growth factor ß1 (TGF-ß1) were reduced by endostatin treatment. Furthermore, endostatin decreased alveolar type II cell apoptosis and had an epithelium-protective effect. These might be the mechanism underlying the preventive effect of endostatin on pulmonary fibrosis. CONCLUSIONS: Our findings suggest that endostatin treatment inhibits the increased MVD, inflammation and alveolar epithelial cell apoptosis, consequently ameliorating BLM-induced pulmonary fibrosis in rats.