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Aims Thrombin is a serine proteinase that is not only involved in coagulation cascade, but also mediates a number of biological responses relevant to tissues repair, and induces bronchoconstriction. TGF-β plays a pivotal role in airway remodeling due to its effects on airway smooth muscle proliferation and extracellular matrix (ECM) deposition. Recently, bronchoconstriction itself is found to constitute a form of strain and is highly relevant to asthmatic airway remodeling. However, the underlying mechanisms remain unknown. Here, we investigated the role of contraction- dependent TGF-β activation in thrombin-induced remodeling in human airway smooth muscle (HASM) cells. Materials and methods Primary HASM cells were treated with or without thrombin in the absence or presence of anti-TGF-β antibody, cytochalasin D and formoterol. CFSE labeling index or CCK-8 assay were performed to test cell proliferation. RT-PCR and Western blotting were used to examined ECM mRNA level and collagen Iα1, α-actin protein expression, respectively. Immunofluorescence was also used to confirm contraction induced by thrombin in HASM cells. Key finding Thrombin stimulation enhanced HASM cells proliferation and activated TGF-β signaling. Thrombin induced ECM mRNA and collagen Iα1 protein expression, and these effects are mediated by TGF-β. Abrogation of TGF-β activation by contraction inhibitors cytochalasin D and formoterol prevents the thrombin-induced effects. Significance These findings suggest that contraction-dependent TGF-β activation could be a mechanism by which thrombin leads to the development of asthmatic airway remodeling. Blocking physical forces with bronchodilator would be an intriguing way in reducing airway remodeling in asthma.

Purpose: To identify the metabolites of gardenin A (GA) in rat liver microsomes (RLMs) using ultra-high performance liquid chromatography coupled with linear ion-trap Orbitrap mass spectrometry (UHPLCLTQ- Orbitrap). Methods : The sample was prepared by incubating GA (100 μg/mL) with RLMs (0.5 mg/mL) for 8 h. Then 5 μL of the sample was injected into UHPLC-LTQ- orbitrap mass spectrometer. The metabolites of GA were tentatively identified based on accurate mass measurements, fragmentation patterns, chromatographic retention times, and bibliography data. Results : A total of 12 metabolites were detected and identified. Based on their structures, the main reactions in the metabolism of GA are de-methoxylation and de-methylation. Conclusion : This is the first report on in vitro metabolites of GA. These results are considered very helpful for better comprehension of the metabolism of GA and its pharmacological effects. Keywords : Gardenin A, Metabolites, UHPLC-LTQ-Orbitrap, Rat Liver microsomes

Endoscopic submucosal tunneling dissection (ESTD) has been proved to be safe and effective for removal of esophageal submucosal tumors (SMTs) and can maintain the mucosal integrity compared with other endoscopic methods. The aim of the study was to estimate the safety and efficacy of ESTD as well as compare its efficacy with thoracoscopic enucleation for esophageal SMTs, which is used increasingly as a minimally invasive approach.We retrospectively collected the clinical data of patients with esophageal SMTs 40 mm who underwent ESTD or thoracoscopic enucleation at Nanfang Hospital between January 2008 and August 2016. Epidemiologic data (sex, age), tumor location, tumor size, en bloc resection rate, adverse events, pathologic results, length of postoperative hospital stay, and cost were compared between ESTD and thoracoscopic enucleation.A total of 126 patients were included. A total of 74 patients underwent ESTD, and the other 52 underwent thoracoscopic enucleation. There was no significant difference between the 2 groups in sex, age, tumor size, hospitalization expense, infection, adverse events, and en bloc resection rate (P .05). However, patients in the ESTD group had a shorter operating time, less estimated blood loss, shorter length of postoperative hospital stay, and lower chest pain level (P .05). Kaplan-Meier curves for disease-free survival also showed no statistically significant difference between ESTD and thoracoscopic enucleation groups during the median follow-up of 19.5 and 42 months, respectively.The treatment efficacy was comparable between the ESTD and thoracoscopic enucleation for esophageal SMTs 40 mm. However, there was a significant advantage in the ESTD group for a shorter operating time, reduced postoperative chest pain, and shorter hospitalization.

Purpose: To characterize and identify metabolites of (-)-epicatechin in microsomal fraction of rat hepatocytes (MFRHs). Methods: A single incubation of (-)-epicatechin (1 mL, 50 µg/mL) in MFRH (0.5 mg/mL) was used for the generation of metabolites. Thereafter, the sample was subjected to protein precipitation prior to analysis with ultra-high performance liquid chromatography coupled to linear ion-trap orbitrap mass spectrometry (UHPLC-LTQ-Orbitap MS). Results: Nine metabolites of (-)-epicatechin were characterized on the basis of high resolution mass measurement, MS spectra and literature data. Based on their structures, the major metabolic routes of (-)-epicatechin in MFRHs were identified as hydroxylation, dihydroxylation and glycosylation. Conclusion: This is the first report on metabolites of (-)-epicatechin in MFRHs, and it is helpful in gaining deeper insight into the metabolism of (-)-epicatechin in vivo. The results will also provide guidance in research on the pharmacokinetics of new drugs. Keywords: (-)-Epicatechin, Metabolites, Hydroxylation, Dihydroxylation, Glycosylation, Rat liver microsomes, Pharmacokinetic studies

To evaluate the outcomes of thoraco laparoscopic esophagectomy venus open esophagectomy for esophageal cancer.Literature search was performed using PubMed, Embase, Cochrane Library, and Google Scholar databases, CBM, and CNKI from inception to July 2011 for comparative studies assessing thoraco laparoscopic esophagectomy and open esophagectomy. Data were extracted and evaluated by two reviewers independently according to the Cochrane Handbook for Systematic Reviews. Meta-analyses were conducted using RevMan 5.1.A total of 10 studies involving 1017 patients were included for the analysis. Four hundred and fifty-five patients underwent thoraco laparoscopic esophagectomy and 562 patients underwent open esophagectomy. There were no significant differences between the two groups in anastomotic leak, 30-day mortality, and number of lymph node retrieved(P0.05). However, thoraco laparoscopic esophagectomy had lower blood loss, less operative time, and reduced respiratory complications(P0.05). There were no significant differences between the two groups in overall complications, cardiac complications, anastomotic stricture, recurrent laryngeal nerve injury, length of stay, ICU stay, and 3-year survival(all P0.05).Thoraco laparoscopic esophagectomy for esophageal cancer is feasible and safe as open esophagectomy.

To evaluate the quality of life (QOL) in patients with esophageal carcinoma after thoracoscopic and laparoscopic esophagectomy and circular stapled cervical esophagogastric anastomosis via retrosternal route or three-incision open surgery.A total of 63 patients with middle-upper esophageal carcinoma who underwent radical surgical resection from January 2009 to October 2010 were enrolled in this study. Thirty-three patients underwent combined laparoscopic and thoracoscopic surgery and 30 three-incision open surgery. The EORTC questionnaire QLQ-C30 and QLQ-OES18 were used to evaluate the QOL.There were no significant differences in the clinical data between the two groups except for anastomosis method(P0.05). In the endoscopy group, there was one patient developed anastomotic leakage(3.0%, 1/33), 1 postoperative wound infection in the neck (3.0%, 1/33), and 1 anastomotic stricture(3.0%, 1/33). In the open group, 8 patients had anastomotic leakage (26.7%, 8/30), 2 had anastomotic stricture (6.7%, 2/30), 1 had wound infection in the neck (3.3%, 1/30), and 6 had pulmonary infection (20.0%, 6/30). All the complications were managed by conservative treatment. The two groups differed in dysphagia, food intake, pain, obstruction, dyspnea, anorexia, fatigue, financial condition, physical function, role function, emotional function, cognitive function, social function and global health level and were more favorable in the endoscopy group(P0.05), while there were no significant differences in the other dimensions.The postoperative complication rate is low after thoracoscopic and laparoscopic esophagectomy. Stapled anastomosis is associated with lower rate of anastomotic leak. QOL is better in patients following thoracoscopic and laparoscopic esophagectomy as compared to those following three-incision open surgery.

To compare the differences in intrapulmonary shunt (Qs/Qt) and arterial oxygenation between selective left lower lobar blockade by Coopdech endobronchial blocker tubes (BB) and one lung ventilation (OLV) by left-sided double-lumen endobronchial tubes (DLT) in patients with normal pulmonary function.Thirty-six patients (aged 32-64 years) scheduled for lower esophageal surgery were allocated randomly into BB and DLT groups (n=18). Anesthesia was induced and maintained with Propofol by target controlled infusion with intravenous administration of sufentanil and cisatracurium if needed. A 35 to 39 French tube was placed in the DLT group, and an 8.0-mm (internal diameter) single-lumen endotracheal tube was used in the BB group where a 9 French Coopdech BB was advanced into the left lower lobar bronchus guided by a fiberoptic bronchoscope. The variables recorded were blood gas analysis data from the venous and arterial blood samples at 20 min after two-lung ventilation in supine position (T(1)), 20 min after initiation of one-lung ventilation or selective left lower lobar blockade by inflating BB balloons in the right lateral decubitus position (T(2)), total collapse of the left lung or the left lower lobe after the pleura was opened (T(3)), and before tracheal extubation (T(4)). Qs/Qt was calculated using a standard formula based on the three-compartment model. Upon pleura opening, the effectiveness of lung collapse was evaluated by the surgeon who performed the surgery. Chest radiograph and arterial blood gas analyses were performed the day after the operation.Both of the groups were similar with regard to rank of the surgical exposure, pH, PaCO(2), hemoglobin from T(1) to T(4), Qs/Qt, PaO(2), PO(2), and oxygenation index at T1. In BB group, a significant reduction of Qs/Qt and greater improvements in PaO(2), PO(2), oxygenation index at T(2), T(3) and T(4) were observed in comparison with those in DLT group (P0.05 or0.01). No lobe collapse was observed postoperatively in BB group, but 2 patients in DLT group showed left lower lobe atelectasis. The patients in BB group showed better postoperative arterial oxygenation and shorter postoperative hospital stay (P0.01).Selective left lower lobar blockade by Coopdech endobronchial blocker tube during lower esophageal surgery provides a lower intraoperative intrapulmonary shunt and a better intra- and postoperative arterial oxygenation..

To investigate the application of flexible bronchoscopy in the postoperative management of lung transplantation.Four male patients with end-stage chronic obstructive pulmonary disease received examination with bronchoscope following the unilateral lung transplant for management of airway complications. One patient developed stenosis at tracheal anastomosis 2 months after transplantation and underwent balloon dilatation and endobronchial metallic stent placement.The 4 patients showed good recovery after transplantation with obviously improved pulmonary function and quality of life.Flexible bronchoscopy provides a valuable means for postoperative management of lung transplantation.

To examine the changes in energy metabolism in the respiratory muscles of canines with unilateral phrenic nerve transection using high-performance liquid chromatography (HPLC).The left phrenic nerve of 8 canines was transected and the contents of adenine nucleotide in respiratory muscles were determined by HPLC before and 1 and 2 months after the operation.In the intercostal muscles, ATP contents remained almost unchanged during the entire course of the observation, while ADP content was elevated 2 months after the operation as compared with that measured before and 1 month after the operation (P0.05). One month postoperatively, the content of total adenylic acid (TAN) decreased to the lowest point, but the difference between the measurements was not statistically significant; also at 1 month after the operation, the content of adenylate energy charge (AEC) was the lowest, with statistically significant difference from the measurements before and 2 months after the operation (P0.05). In the diaphragm, the contents of ATP, ADP, TAN and AEC 2 months postoperatively were 9.05+/-12.70, 2.99+/-2.57, 14.72+/-13.98, 0.57+/-0.29, significantly different from the levels at the other two time points (P0.05).After unilateral phrenic nerve transection in canines, the energy metabolism of the diaphragm declines significantly, whereas that of the intercostal muscle can be compensated to some extent.

A right single lung transplantation was performed in a 17-year-old female patient with end-stage cystoid pulmonary fibrosis and without cardiopulmonary bypass in June 2003. The donor lung was perfused with cold UW solution with a cold ischemic time of 280 min. The patient weaned from ventilator on the next day of operation (18 h later) and was able to walk at the fourth day postoperatively. Immunosuppression included methylprednisolone used before FK 506, mycophenolate mofetil and prednisone dosed after operation. The patient remains well a month after operation with significant improvement of the lung function and enjoys normal life.

To evaluate the diagnosis and treatment of tracheobronchial ruptures due to thoracic trauma.The clinical data of 17 cases of bronchial rupture caused by chest trauma was analyzed retrospectively. The surgical approaches and post-trauma complications were described.End-to-end anastomosis was performed in 14 cases. Among the other 3 patients, one received lobectomy after bronchial repair, another had tracheal repair, and resection of the stenosed segment along with end-to-end anastomosis during thoracotomy was necessitated in the last case. Anastomotic stricture occurred early after the operation in 2 of all these cases, while 2 months postoperatively, all the patients were free from such strictures.Early diagnosis and operation in such cases can be life-saving, and may warrant early recovery of the pulmonary function. Accurate diagnoses of bronchial rupture can be obtained by bronchoscopy, with which the surgeons can easily locate the rupture during surgery.

OBJECTIVE: To explore the possible mechanisms for the occurrence of diaphragm fatigue induced by diaphragm pacing. METHODS: The phrenic nerve of 8 dogs were exposed and subjected to stimulation with electric pulses emitted by a diaphragm pacemaker to induce diaphragm fatigue models, and the contents of ATP, ADP, AMP and AXP in the diaphragm muscles before and after diaphragm pacing were determined by high-performance liquid chromatography (HPLC). The contents of SOD and MDA were also measured and the morphological alteration of the mitochondria observed with transmission electron microscope. RESULTS: The contents of ATP, ADP, AXP and SOD were found significantly lower but MDA was higher during fatigue than those in normal conditions, while AMP content manifested no obvious change. Some mitochondria in the diaphragm muscles swelled and in a few cases, vacuolar degeneration was observed. CONCLUSIONS: The exhaustion and synthesis disturbance of ATP may explain the generation of diaphragm fatigue, and the reduction of dynamophore and ultrastructural injuries of the cells induced by oxygen free radicals may also contribute to this result.

To investigate the structural changes in canine lungs perfused with modified Euro-Collins solution (mECS), thus providing insight into the preservation of the donor lung tissue for transplantation.Six dogs were anesthetized and pulmonary perfusion with mECS (4 degrees Celsius) was performed before the lungs were isolated thereafter and stored at 4 to 8 degrees Celsius for 30, 60, 120, 180, 240 min respectively, after which tissue samples of the donor lung were taken for morphological observation with both light and transmission electron microscope.Immediately after reperfusion, the pulmonary tissues exhibited clear and intact structures,showing that mitochondrion swelled slightly in the alveolar epithelial cells (AECs). Mild edema occurred in the alveolar wall and the tissues around the veins at 30 min after preservation, which exacerbated to dilapidation of the alveolar wall and obvious tumefaction of the mitochondrion in the AECs at 60 min. At 180 min, rupture of alveolar wall and emergence of the alveolus was observed at 120 min, and a few pulmonary bullae were formed, the AECs (I) of which presented vacuolar changes in the cytoplasma and mitochondrion, with disappearance of the tiny villus of the AECs (II) at 240 min.Within 4 h of preservation in mECS, the pulmonary tissues do not undergo obvious changes as signs of injury, which, however, may not be the case after longer preservation.