Sun P.,Beijing Chao Yang Hospital |
Sun P.,Peking University |
Tong Z.,Beijing Chao Yang Hospital
Medical Mycology | Year: 2014
Pneumocystis carinii pneumonia (PcP) is a common and potentially fatal opportunistic infection in immunosuppressed patients, and the standard trimethoprim-sulfamethoxazole (TMP-SMZ) treatment has serious side effects. The cell wall of the causative fungal pathogen is enriched in 1-3-β-D-glucan, providing an alternative therapeutic target. We directly compared the efficacy of the 1,3-β-D-glucan synthase inhibitor caspofungin to TMP-SMZ for promoting survival and reducing lung cyst number during the early phase of treatment in a rat model of PcP. Rats were immunosuppressed using dexamethasone for 8 weeks and PcP infection confirmed in test animals by lung print smear. The remaining rats were randomly divided into three control groups, a baseline group and two observed for 7 or 14 days, two caspofungin groups treated intravenously for 7 or 14 days (1 mg/kg/d), and 2 TMP-SMZ positive control groups treated by oral gavage for 7 or 14 days (300 mg/kg/d). Mortality was markedly reduced by both caspofungin and TMP-SMZ after 14 days (caspofungin: 20.0%, TMP-SMZ: 13.3%, Control: 40.0%). Body weight gain in caspofungin-treated rats after 7 (3.04 ± 3.54%) and 14 (4.27 ± 2.79%) days was similar to that in TMP-SMZ-treated rats (3.35 ± 1.88% and 5.85 ± 2.78%, respectively), whereas untreated controls showed weight loss. Lung weight to body weight ratio, and mean cyst number per 50 microscopic fields were significantly lower (all P < 0.05) in caspofungin-treated rats than untreated controls at both 7 and 14 days, and similar to those in the TMP-SMZ-treated rats (all P > 0.05vs. caspofungin). Caspofungin exhibited similar efficacy to TMP-SMZ for enhancing survival and reducing lung edema and cyst load in a rat model of PcP, suggesting potential clinical utility against PcP. © The Author 2014.
Shi Y.,Peking Union Medical College |
Shi Y.,Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs |
Zhang L.,Sun Yat Sen University |
Zhang L.,Peking Union Medical Hospital |
And 30 more authors.
The Lancet Oncology | Year: 2013
Background: Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods: In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings: 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033). Interpretation: Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Funding: Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program. © 2013 Elsevier Ltd.
Simonneau G.,University Paris - Sud |
D'Armini A.M.,University of Pavia |
Ghofrani H.-A.,Justus Liebig University |
Ghofrani H.-A.,Imperial College London |
And 10 more authors.
European Respiratory Journal | Year: 2015
Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit-risk profile and improved several clinically relevant end-points in patients with CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from CHEST-1 received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was the safety and tolerability of riociguat; exploratory efficacy endpoints included 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC). Overall, 237 patients entered CHEST-2 and 211 (89%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±SD 6MWD had changed by +51±62 m (n=172) versus CHEST-1 baseline (n=237), and WHO FC had improved/stabilised/worsened in 47/50/3% of patients (n=176) versus CHEST-1 baseline (n=236). Long-term riociguat had a favourable benefit-risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year. Copyright © ERS 2015.
You L.,Wuhan University |
Li L.,Mu Dan Jiang Medical College |
Xu Q.,Mu Dan Jiang Medical College |
Ren J.,Wuhan University |
Zhang F.,Beijing Chao Yang Hospital
Molecular Biology Reports | Year: 2011
Brief intermittent episodes of ischemia and reperfusion could reduce infarct size, a phenomenon called "postconditioning" at the onset of reperfusion after a prolonged period of ischemia. To investigate whether the opioid receptors and signaling factor JAK-STAT might be responsible for the cardioprotection in ischemic postconditioning, and the possible molecular machinery of cardioprotection. Hundred and twenty healthy New Zealand rabbits were divided into six groups. The myocardial infarct size, cardiac myocyte apoptosis, BCL-2 and P-Stat3 protein expression were tested in the current study. The results suggested that ischemic postconditioning might increase BCL-2 protein expression by activating the opioid receptors and JAK-STAT signaling pathway, and also to reduce ischemia-reperfusion-induced cardiomyocyte apoptosis and to play a key role in myocardial protection. However, further research still needs to be done to unravel the underlying mechanisms. © 2010 Springer Science+Business Media B.V.
Xia J.,China Japan Friendship Hospital |
Zhang H.,Beijing Chao Yang Hospital |
Sun B.,Beijing Chao Yang Hospital |
Yang R.,Beijing Chao Yang Hospital |
And 2 more authors.
Anesthesiology | Year: 2014
BACKGROUND:: It has been proved that spontaneous breathing (SB) with biphasic positive airway pressure (BIPAP) can improve lung aeration in acute respiratory distress syndrome compared with controlled mechanical ventilation. The authors hypothesized that SB with BIPAP would attenuate lung injury in acute respiratory distress syndrome compared with pressure-controlled ventilation. METHODS:: Twenty male New Zealand white rabbits with hydrochloric acid aspiration-induced acute respiratory distress syndrome were randomly ventilated using the BIPAP either with SB (BIPAP plus SB group) or without SB (BIPAP minus SB group) for 5 h. Inspiration pressure was adjusted to maintain the tidal volume at 6 ml/kg. Both groups received the same positive end-expiratory pressure level at 5 cm H2O for hemodynamic goals. Eight healthy animals without ventilatory support served as the control group. RESULTS:: The BIPAP plus SB group presented a lower ratio of dead space ventilation to tidal volume, a lower respiratory rate, and lower minute ventilation. No significant difference in the protein levels of interleukin-6 and interleukin-8 in plasma, bronchoalveolar lavage fluid, and lung tissue were measured between the two experimental groups. However, SB resulted in lower messenger ribonucleic acid levels of interleukin-6 (mean ± SD; 1.8 ± 0.7 vs. 2.6 ± 0.5; P = 0.008) and interleukin-8 (2.2 ± 0.5 vs. 2.9 ± 0.6; P = 0.014) in lung tissues. In addition, lung histopathology revealed less injury in the BIPAP plus SB group (lung injury score, 13.8 ± 4.6 vs. 21.8 ± 5.7; P < 0.05). CONCLUSION:: In hydrochloric acid-induced acute respiratory distress syndrome, SB with BIPAP attenuated lung injury and improved respiratory function compared with controlled ventilation with low tidal volume. (Anesthesiology 2014; 120:1441-9) © 2014 The American Society of Anesthesiologists, Inc.
Zhai Z.,Beijing Chao Yang Hospital |
Wang J.,Beijing Chao Yang Hospital |
Wang J.,Capital Medical University |
Zhao L.,Imperial College London |
And 3 more authors.
Chest | Year: 2010
Significant progress has been made in understanding the pathogenesis of pulmonary hypertension (PH) and developing therapeutic approaches for PH in recent years. Most of the currently available data regarding the prevalence, diagnosis, treatment, and prognosis of PH are from American and European populations. Whether these data are also valid in the Chinese population is still controversial. China has a relatively large population of patients with PH for clinical and basic research. However, many medical centers and hospitals in China have limited experience with PH diagnosis and treatment. Given the potential higher prevalence of PH in China than in the United States and European countries, it is critical to develop suitable, effective, and novel therapeutic approaches for Chinese patients. Measures for the detection and prevention of PH need to be put in place urgently for the management of PH in China. ©2010 American College of Chest Physicians.
Mao J.,Beijing Anzhen Hospital |
Yin X.,Beijing Chao Yang Hospital |
Zhang Y.,Capital Medical University |
Yan Q.,Beijing Chao Yang Hospital |
And 3 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2014
Background-Previous studies have suggested that systematic ablation of ganglionated plexi (GP) could increase the shortterm success rate of radiofrequency ablation for atrial fibrillation, but the long-term efficacy of this approach is not fully established. Methods and Results-Twenty-four mongrel dogs were divided into 3 groups: epicardial GP ablation group 1 (n=8), epicardial GP ablation group 2 (n=8), and a sham operation group (n=8). In the 2 epicardial GP ablation groups, the 4 major GP and the ligament of Marshall were systematically ablated. The effective refractory period and inducibility of tachyarrhythmias were measured before and immediately after GP ablation in epicardial GP ablation group 1 and 8 weeks later in the other 2 groups. Tyrosine hydroxylase and choline acetyltransferase expressions were also determined immunohistochemically 8 weeks later in the latter groups. Compared with epicardial GP ablation group 1 and the sham operation group, epicardial GP ablation group 2 had the shortest atrial and ventricular effective refractory period and the highest inducibility of atrial tachyarrhythmias. The inducibility of ventricular tachyarrhythmias among the 3 groups was comparable. The density of tyrosine hydroxylase- and choline acetyltransferase-positive nerves in the atrium was the highest in epicardial GP group 2, whereas there were no significant intergroup differences in the densities of these 2 types of nerves in the ventricle. Conclusions-After 8 weeks of healing, epicardial GP ablation without additional atrial ablation was potentially proarrhythmic, which may be attributable to decreased atrial effective refractory period and hyper-reinnervation involving both sympathetic and parasympathetic nerves. © 2014 American Heart Association, Inc.
Shen Y.-M.,Beijing Chao Yang Hospital |
Sun W.-B.,Capital Medical University |
Chen J.,Beijing Chao Yang Hospital |
Liu S.-J.,Beijing Chao Yang Hospital |
Wang M.-G.,Beijing Chao Yang Hospital
Surgery | Year: 2012
Background: We compared the effectiveness of n-butyl-2-cyanoacrylate (NBCA) and traditional suture for patch fixation in Lichtenstein tension-free herniorrhaphy for inguinal hernias. Methods: A total of 110 patients with primary unilateral inguinal hernia were assigned randomly to either experimental or control groups. In the experimental group, NBCA adhesive was used during Lichtenstein herniorrhaphy; traditional suture was used in the control group. We evaluated operation time, postoperative duration of stay, visual analogue scale (VAS) pain score, incidence of chronic pain and hematoma formation, and hernia recurrence. Results: There was no hernia recurrence or wound infection in either group. In the experimental group, 2 local hematomas occurred while no patients experienced chronic postoperative pain; in the control group, 10 hematomas occurred, and 6 patients experienced chronic pain. There was no difference in postoperative duration of stay between the groups (P >.05), but the experimental group had a lesser operation time and postoperative VAS score (P <.05). Conclusion: The use of NBCA medical adhesive in tension-free inguinal herniorrhaphy is effective and safe. © 2012 Published by Mosby, Inc.
Hu X.,Beijing Chao Yang Hospital |
Lee H.,Capital Medical University
Journal of Cardiothoracic Surgery | Year: 2014
Esophageal leiomyoma is one of the most common types of benign esophagus tumors. Giant leiomyoma of the esophagus is traditionally treated by open thoracotomy, which has large incision. We report a case of complete thoracoscopic enucleation of giant leiomyoma in a chinese patient. © 2014 Hu and Lee; licensee BioMed Central Ltd.
Li J.,Beijing Chao Yang Hospital |
Zhang C.,Beijing Chao Yang Hospital |
Jiang H.,Beijing Chao Yang Hospital |
Cheng J.,Beijing Chao Yang Hospital
OncoTargets and Therapy | Year: 2015
Hypoxia-inducible factor-1 (HIF-1) is a master regulator of the transcriptional response to hypoxia. HIF-1α is one of the most compelling anticancer targets. Andrographolide (Andro) was newly identified to inhibit HIF-1 in T47D cells (a half maximal effective concentration [EC50] of 1.03×10-7 mol/L), by a dual-luciferase reporter assay. It suppressed HIF-1α protein and gene accumulation, which was dependent on the inhibition of upstream phosphatidylinositol 3-kinase (PI3K)/AKT pathway. It also abrogated the expression of HIF-1 target vascular endothelial growth factor (VEGF) gene and protein. Further, Andro inhibited T47D and MDA-MB-231 cell proliferation and colony formation. In addition, it exhibited significant in vivo efficacy and antitumor potential against the MDA-MB-231 xenograft in nude mice. In conclusion, these results highlighted the potential effects of Andro, which inhibits HIF-1, and hence may be developed as an antitumor agent for breast cancer therapy in future. © 2015 Li et al.