Deguang Mu

Severe Complications of Bronchoscopy

Background: Interventional bronchoscopy is widely used for the diagnosis and therapy of many lung and airway diseases. Concern has been raised about its complications. Objective: To review the severe complications associated with bronchoscopy. Methods: A retrospective review of clinical records of 23,862 patients who underwent bronchoscopic examination or therapy from December 1983 to December 2004 in our department. Severe complications associated with bronchoscopic examination or therapy were analyzed. Results: During the study period, among 23,862 cases, 152 cases experienced severe complications; 3 cases died; the rate of severe complications was 0.637%; mortality rate was 0.013%. The complications included laryngeal, tracheal and bronchial spasm in 68 cases, hematorrhea in 37 cases, arrhythmia in 19 cases, airway obstruction in 8 cases, esophagotracheal fistula in 5 cases, pneumothorax in 4 cases, tracheal perforation in 3 cases, death in 3 cases. Conclusions: Bronchoscopy is a safe procedure. The increased rate of severe complications and death associated with bronchoscopy may be ascribed to the increasingly wide use of bronchoscopy.

Tanshinone IIA ameliorates seawater exposure-induced lung injury by inhibiting aquaporins (AQP) 1 and AQP5 expression in lung

Aquaporins (AQPs), a family of transmembrane water channels, mediate physiological response to changes of fluid volume and osmolarity. It is still unknown what role of AQPs plays in seawater drowning-induced acute lung injury (ALI) and whether pharmacologic modulation of AQPs could alleviate the severity of ALI caused by seawater aspiration. In our study, the results from RT-PCR and Western blotting showed that intratracheal installation of seawater up-regulated the mRNA and protein levels of AQP1 and AQP5 in lung tissues. Furthermore, we found that treatment of tanshinone IIA (TIIA, one of the main active components from Chinese herb Danshen) significantly reduced the elevation of AQP1 and AQP5 expression induced by seawater in rats, A549 cells and primary alveolar type II cells. Treatment of TIIA also improved lung histopathologic changes and blood-gas indices, and reduced lung edema and vascular leakage. These findings demonstrated that AQP1 and AQP5 might play an important role in the development of lung edema and lung injury, and that treatment with TIIA could significantly alleviate seawater exposure-induced ALI, which was probably through the inhibition of AQP1 and AQP5 over-expression in lungs.

Epigallocatechin-3-gallate ameliorates seawater aspiration-induced acute lung injury via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats.

Signal transducers and activators of transcriptions 1 (STAT1) play an important role in the inflammation process of acute lung injury (ALI). Epigallocatechin-3-gallate (EGCG) exhibits a specific and strong anti-STAT1 activity. Therefore, our study is to explore whether EGCG pretreatment can ameliorate seawater aspiration-induced ALI and its possible mechanisms. We detected the arterial partial pressure of oxygen, lung wet/dry weight ratios, protein content in bronchoalveolar lavage fluid, and the histopathologic and ultrastructure staining of the lung. The levels of IL-1, TNF-α, and IL-10 and the total and the phosphorylated protein level of STAT1, JAK1, and JAK2 were assessed in vitro and in vivo. The results showed that EGCG pretreatment significantly improved hypoxemia and histopathologic changes, alleviated pulmonary edema and lung vascular leak, reduced the production of TNF-α and IL-1, and increased the production of IL-10 in seawater aspiration-induced ALI rats. EGCG also prevented the seawater aspiration-induced increase of TNF-α and IL-1 and decrease of IL-10 in NR8383 cell line. Moreover, EGCG pretreatment reduced the total and the phosphorylated protein level of STAT1 in vivo and in vitro and reduced the phosphorylated protein level of JAK1 and JAK2. The present study demonstrates that EGCG ameliorates seawater aspiration-induced ALI via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats.

3,5,4′-tri-O-acetylresveratrol Ameliorates Seawater Exposure-Induced Lung Injury by Upregulating Connexin 43 Expression in Lung

The aim of the present study was to examine the effects of 3,5,4′-tri-O-acetylresveratrol on connexin 43 (Cx43) in acute lung injury (ALI) in rats induced by tracheal instillation of artificial seawater. Different doses (50, 150, and 450 mg/kg) of 3,5,4′-tri-O-acetylresveratrol were administered orally for 7 days before modeling. Four hours after seawater inhalation, histological changes, contents of TNF-α, IL-1β and IL-10, and the expression of Cx43 in lungs were detected. Besides, the gap junction communication in A549 cells and human umbilical vein endothelial cells (HUVECs) challenged by seawater was also evaluated. Histological changes, increased contents of inflammatory factors, upregulation in gene level, and deregulation in protein level of Cx43 in lungs stimulated by seawater were observed. On the other hand, pretreatment with 3,5,4′-tri-O-acetylresveratrol significantly inhibited infiltration of inflammation, development of pulmonary edema, and contents of inflammatory mediators in lungs. Above all, 3,5,4′-tri-O-acetylresveratrol upregulated the expression of Cx43 in both gene and protein levels, and its intermediate metabolite, resveratrol, also enhanced the gap junction communication in the two cell lines. The results of the present study suggested that administration of 3,5,4′-tri-O-acetylresveratrol may be beneficial for treatment of inflammatorycellsin lung.

Tanshinone IIA suppresses lung injury and apoptosis, and modulates protein kinase B and extracellular signal-regulated protein kinase pathways in rats challenged with seawater exposure.

1. Tanshinone IIA (TIIA) is one of the main active components of the Chinese herb, Danshen. In the present study, we investigated the role of apoptosis in seawater exposure‐induced acute lung injury (ALI), and explored the effects of TIIA on lung injury, apoptosis, and protein kinase B (Akt) and etracellular signal‐regulated protein kinase (ERK) pathways in seawater‐challenged rats. The rats were randomly divided into four groups: (i) naive group, no drug was given; (ii) TIIA control group, TIIA (50 mg/kg) was given intraperitoneally; (iii) seawater (SW) group, seawater (4 mL/kg) was given; and (iv) TIIA/SW group, TIIA (50 mg/kg) was injected intraperitoneally 10 min after seawater instillation.

17β-Estradiol administration attenuates seawater aspiration-induced acute lung injury in rats

There is very little evidence on the value of administering estrogen in cases of seawater drowning which can induce acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Therefore, this study aimed to investigate whether 17β-estradiol (E2) treatment can attenuate seawater aspiration-induced ALI in rats. In the experiment, ALI was induced by endotracheal instillation of seawater (4mL/kg) and the rats were then given intraperitoneal injection of E2 (5mg/kg) 20min after seawater instillation. Finally, the changes of arterial blood gases which contained hydrogen ion concentration (pH), arterial oxygen tension (PaO(2)) and arterial carbon dioxide tension (PaCO(2)) were measured and the measurement of extravascular lung water (EVLW) was observed. The pulmonary histological changes were evaluated by hematoxylin-eosin stain. The expression of aquaporins (AQPs) 1, AQP5, and estrogen receptor-β (ERβ) was measured by western blotting and immunohistochemical methods. The results showed that compared with normal saline water, seawater aspiration induced more serious ALI in rats which was markedly alleviated by E2 treatment. Meanwhile, the ERβ in lung tissues was activated after E2 administration. The seawater aspiration group also presented with severe pulmonary edema which was paralleled with over expressed AQP1 and AQP5. However, the up-regulation of AQP1 and AQP5 was suppressed by the administration of E2, resulting in an attenuation of lung edema. In conclusion, E2 treatment could effectively attenuate seawater aspiration-induced acute lung injury in rats by the down-regulation of AQP1 and AQP5.

Efficacy and safety of bronchoscopic cryotherapy for granular endobronchial tuberculosis.

Background: The most important sequela of endobronchial tuberculosis (EBTB) is bronchial stenosis, which causes wheezing, dyspnea and obstructive pneumonia. But there have been no reports about applying cryotherapy for granular EBTB that did not show luminal narrowing of the bronchus at diagnosis. Whether this technique is useful for preventing granular EBTB from progressing into stenosis needs to be clarified. Objective: To investigate the efficacy and safety of bronchoscopic cryotherapy for granular endobronchial tuberculosis. Methods: In this study, we analyzed the records of 76 patients with granular EBTB. Diagnosis of TB was confirmed by microbiology or histopathology. Bronchoscopic examinations revealed that the patients had granular endobronchial tuberculosis. Thirty-eight patients received bronchoscopic cryotherapy plus routine anti-tuberculosis chemotherapy and the other 38 patients received routine anti-tuberculosis chemotherapy alone. We compared the treatment effect of these 2 groups. The outcome measures were the changes of lesions, the rate of disappearance of lesions and complications of bronchoscopic cryotherapy. Results: The complete removal rate was 100% in patients with bronchoscopic cryotherapy plus routine anti-tuberculosis chemotherapy; the complete removal rate was 78.9% in patients with anti-tuberculosis chemotherapy alone; the rate of disappearance of lesions in the bronchoscopic cryotherapy plus routine anti-tuberculosis chemotherapy group was faster than that of the anti-tuberculosis chemotherapy alone group. There were no severe complications from bronchoscopic cryotherapy. Conclusions: Bronchoscopic cryotherapy can accelerate the healing of granular EBTB and help to prevent progressive bronchial stenosis due to granular EBTB and is a very safe method.

Molecular mechanism of silymarin-induced apoptosis in a highly metastatic lung cancer cell line anip973.

BACKGROUND Silymarin, the main flavonoid constituent element extracted from Silybum marianum possessing antioxidant activity, is already known to be able to block the NF-κB activation process and result in cell apoptosis, implicating silymarins potential to control cancer cell growth. MATERIALS AND METHODS In this study, based upon the above assumption, silymarin was administered to a highly metastatic lung cancer cell line Anip973 to test silymarins role in cancer cell proliferation. RESULTS Silymarin had significant inhibitory effects on the proliferation of Anip973 cells in a dose-dependent and time-response manner within 48 hours. Silymarin can induce Anip973 apoptosis. CONCLUSIONS Silymarin may in vitro inhibit the proliferation of the human lung adenocarcinoma cell line Anip973 and induce apoptosis via the mitochondria-dependent caspase cascade pathway.

Application of bronchoscopic argon plasma coagulation in the treatment of tumorous endobronchial tuberculosis: Historical controlled trial

OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of bronchoscopic argon plasma coagulation for tumorous endobronchial tuberculosis. METHODS We analyzed the records of 115 patients with tumorous endobronchial tuberculosis who did not show luminal narrowing of the bronchus at diagnosis. Of these 115 patients, 41 patients received bronchoscopic argon plasma coagulation plus routine antituberculosis chemotherapy (argon plasma coagulation group) and the other 74 patients received only routine antituberculosis chemotherapy (chemotherapy group). The treatment effects between these 2 groups were compared based on changes in lesions, rate of lesion disappearance, and complications associated with bronchoscopic argon plasma coagulation. RESULTS The complete removal rate was 100% in patients in argon plasma coagulation group. About 84.6% lesions disappeared completely in patients in the chemotherapy group. The rate of disappearance of lesions in the argon plasma coagulation group was faster than that of the chemotherapy group. There were no severe complications in the argon plasma coagulation group. CONCLUSIONS Bronchoscopic argon plasma coagulation can accelerate the healing of tumorous endobronchial tuberculosis and can help prevent progressive bronchial stenosis resulting from tumorous endobronchial tuberculosis, and it is a very safe method.

Lewis Lung Cancer Cells Promote SIGNR1(CD209b)‐Mediated Macrophages Polarization Induced by IL‐4 to Facilitate Immune Evasion

Tumor‐associated macrophages are a prominent component of lung cancer and contribute to tumor progression by facilitating the immune evasion of cancer cells. DC‐SIGN (CD209) assists in the immune evasion of a broad spectrum of pathogens and neoplasms by inhibiting the maturation of DCs and subsequent cytokines production. However, the expression of DC‐SIGN in macrophages and its role in mediating immune evasion in lung cancer and the underlying mechanism remain unclear. Our study aimed to identify the immunosuppressive role of SIGNR1 in murine macrophage differentiation and lung cancer progression. We found that SIGNR1‐positive RAW264.7 macrophages were enriched in mixed cultures with Lewis lung cancer cells (LLC) (ratio of RAW 264.7 to LLC being 1:1) after stimulation with IL‐4. Moreover, LLC‐educated macrophages exhibited significantly higher levels of IL‐10 but lower IL‐12 in response to IL‐4 treatment as determined by RT‐PCR and ELISA. However, inhibition of SIGNR1 markedly hampered the production of IL‐10, indicating that SIGNR1 was indispensable for IL‐4+LLC induced macrophage polarization towards the M2 subtype. Furthermore, polarized M2 cells immersed in a tumor microenvironment promoted the migration of LLCs, as measured by transwell assays, but migration was suppressed after blockade of SIGNR1 using CD209b antibody. In addition, IL‐4+LLC‐educated macrophages reduced the proliferation of the activated T cells and reduced IFN‐γ‐mediated Th1 response in T cells, while SIGNR1 inhibition rescued Th1 cell functions. In conclusion, murine SIGNR1 expressed in LLC‐educated macrophages appears to mediate IL‐4‐induced RAW264.7 macrophage polarization and thus facilitate lung cancer evasion. J. Cell. Biochem. 117: 1158–1166, 2016.