A randomized, double-blind, multicenter Phase II study comparing the efficacy and safety of oral nemonoxacin with oral levofloxacin in the treatment of community-acquired pneumonia.

BACKGROUND/PURPOSE: To compare the clinical efficacy and safety of nemonoxacin with levofloxacin in treating community-acquired pneumonia (CAP) in a Phase II clinical trial. METHODS: One hundred ninety-two patients with CAP were randomized to receive oral nemonoxacin (500 mg or 750 mg) or levofloxacin (500 mg) once daily for 7-10 days. Clinical and bacteriological responses were determined at the test of cure (TOC) visit in the full analysis set (FAS). RESULTS: The clinical cure rate of nemonoxacin (500 mg), nemonoxacin (750 mg), and levofloxacin (500 mg) was 93.3%, 87.3%, and 88.5%, respectively, in the FAS (n = 168), and 93.0%, 93.9%, and 88.9%, respectively in the per protocol set (n = 152). At the TOC visit, nemonoxacin at 500 mg and 750 mg was proven to be noninferior to levofloxacin at 500 mg in the FAS in terms of clinical efficacy. The overall bacteriological success rate was 83.3% in both nemonoxacin groups and 80.0% in the levofloxacin 500 mg group in the bacteriological FAS. The comprehensive efficacy rate was comparable among the three groups (87.5% for the nemonoxacin 500 mg group, 93.8% for the nemonoxacin 750 mg group, and 81.3% for the levofloxacin 500 mg group). Most drug-related adverse events were mild and transient, mainly gastrointestinal symptoms such as nausea and vomiting, transient neutropenia, and elevated liver enzymes. No drug-related serious adverse events occurred. CONCLUSION: Either 500 mg or 750 mg of oral nemonoxacin taken once daily for 7-10 days demonstrated high clinical and bacteriological success rates in Chinese adult patients with CAP. Nemonoxacin at 500 mg once daily for 7-10 days is recommended for future Phase III clinical trials. ClinicalTrials.gov identifier: NCT01537250.

[Efficacy and Safety of Tiotropium Bromide in the Treatment of Chronic Obstructive Pulmonary Disease--a Multi-center Randomized Clinical Trial].

OBJECTIVE: To investigate the efficacy and safety of domestic tiotropium inhalation capsule in patients with chronic obstructive pulmonary disease (COPD) with multi-center randomized clinical trial. METHODS: Patients with stable slight to moderate COPD were randomized into trial group (n=109) with tiotropium 18 pg Qd or control group (n =111) with ipratropium 40 µg Qid for a treatment of four weeks. The spirometry and scoring questionaire were recorded at different visits during the treatment. Rescue medication consumption and adverse events were recorded. Results Forced expiratory volume in 1 s (FEV1) of both groups increased obviously 30 min and 3 h after first dosing. After four weeks treatments, FEV, and forced vital capacity (FVC) in both groups were improved obviously, and the improvement in tiotropium group was significantly higher than that ipratropium group. COPD symptom scores were significantly reduced in both groups, and the improvement in tiotropium group was significantly better than that in ipratropium group. There was no significant difference in rescue medication consumption between the two groups. The ratios of adverse events were 22. 02% and 15. 32% in tiotropium and ipratropium group, respectively (P=0. 23). CONCLUSION: Domestic tiotropium inhalation capsule is efficient and safe in the treatment of COPD.

Vasohibin attenuates bleomycin induced pulmonary fibrosis via inhibition of angiogenesis in mice.

AIMS: Much evidence suggests that vascular remodelling in the lung plays a crucial role in the development of pulmonary fibrosis. Therefore, anti-angiogenesis therapy may be a promising treatment for pulmonary fibrosis. Recently, a new inhibitor called vasohibin has been discovered to operate as an intrinsic and highly specific feedback inhibitor in the process of angiogenesis. However, to date, the effect of vasohibin on anti-angiogenesis of pulmonary fibrosis has not been examined. METHODS: In this study, we utilised vasohibin to test the potential of pulmonary fibrosis therapy. We examined the role of vasohibin in the pathophysiology of bleomycin-induced pneumopathy in mice by transfection of the vasohibin gene. RESULTS: The results demonstrated that transfection of the vasohibin gene could attenuate pulmonary fibrosis via inhibition of angiogenesis, which markedly decreased lymphocyte infiltration, cytokine secretion and fibroblast proliferation. CONCLUSIONS: This method may be beneficial for treating lung fibrosis and may provide a novel strategy for clinical application in the future.

A novel pseudovirus encoding Diphtheriatoxin A fragment eliminates autoantibody-producing B cells and inhibits lupus in the BWF1 mouse model.

Lupus-associated anti-dsDNA Abs plays an important role in the triggering and development of human systemic lupus erythematosus (SLE). The method of targeting B cells that produce anti-dsDNA Abs has become a promising way to treat autoantibody-mediated SLE in the immunotherapy field. In this study, we reported a novel pseudovirus, which consisted of the peptide DWEYSVWLSN and a plasmid encoding the Diphtheriatoxin A fragment (DTA). Our data demonstrated that vaccination of lupus-prone (BWF1) mice with the pseudovirus could eliminate anti-dsDNA antibody-producing B cells, reduce serum anti-dsDNA antibody levels, impede the development of proteinuria and improve survival. These findings suggested that this novel pseudovirus ablated autoreactive B cells and might represent a promising therapeutic strategy for autoantibody-mediated diseases.

A novel pseudovirus containing lewis X oligosaccharides with pD-L1 targeting to DCs induces T cells tolerance.

The purpose of this study was to assess the potential of a novel pseudovirus targeting to dendritic cells (DCs) inducing T cells tolerance. To prove it, allogeneic DCs transfected of the novel pseudovirus containing Lewis X oligosaccharides with programmed death-ligand 1 were co-cultured with T cells. After mixed leukocyte reactions were performed, the proliferation, cytokines secretion, and activation marker expression of T cells were analyzed. The results demonstrated that the proliferation, cytokines secretion, and activation marker expression of T cells were suppressed after co-cultured with the pseudovirus transfected DCs. These findings suggested that DCs transfected with pseudovirus could induce T-cells tolerance, which provided a promising therapeutic means to negatively manipulate immune response in organ transplantation.

[The changes of apoptosis and proliferation of pulmonary tissue in chronic obstructive pulmonary disease rats].

OBJECTIVE: To observe the changes of apoptosis and proliferation of pulmonary tissue cells in rats with chronic obstructive pulmonary disease (COPD). METHODS: The rat model of COPD was established by exposure to cigarette smoking. Thirty-three Wistar rats were randomly divided into a normal control (NC) group, a smoking inhalation for 1 month (COPD-1) group and a smoking inhalation for 2 month (COPD-2) group. Pathologic changes of lung tissues and inflammatory cell differentials were studied. Immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) methods were carried out to examine the percentage of positive cells and distribution of apoptotic cells and proliferating cells in the lung tissue. RESULTS: Significant increases in total leukocyte numbers and neutrophils in the bronchoalveolar lavage were found in the COPD groups as compared to NC group. Two months after smoking exposure, enlargement of airspaces distal to the terminal bronchiole, destruction of alveolar walls, and loss of the alveolar unit were observed. The percentage of apoptotic cells of airway epithelium, alveolar wall cell and vascular smooth muscle cells were (36.2 +/- 8.5)%, (32.7 +/- 6.4)%, (16.1 +/- 7.2)% in COPD-1 group; (39.5 +/- 9.3)%, (37.3 +/- 7.6)%, (21.4 +/- 6.5)% in COPD-2 group; the difference being significant (all P < 0.01), as compared with NC group [(5.8 +/- 1.7)%, (6.1 +/- 2.3)%, (4.9 +/- 1.4)%]. The percentage of proliferative cells of airway epithelium, alveolar wall cell and vascular smooth muscle cells were (33.4 +/- 6.3)%, (30.1 +/- 4.6)%, (28.4 +/- 6.3)% in COPD-1 group; (35.5 +/- 9.8)%, (33.2 +/- 7.7)%, (34.5 +/- 6.7)% in COPD-2 group; the difference being significant (all P < 0.01), as compared with NC group [(7.4 +/- 2.3)%, (5.2 +/- 2.1)%, (4.4 +/- 1.8)%]. The numbers of apoptotic and proliferating cells were significantly higher in the COPD-2 group than those in the COPD-1 group (all P < 0.01). The ratio of proliferative index (PI)/apoptotic index (AI) of the pulmonary tissue cells were also different. The ratio of PI/AI of airway epithelium in COPD-1 and COPD-2 group [(0.82 +/- 0.13)%, (0.78 +/- 0.24)%] was much lower than NC group [(1.12 +/- 0.23)%, P < 0.05]; The ratio of PI/AI in small pulmonary vessels in the COPD groups [(1.55 +/- 0.25)%, (1.47 +/- 0.28)%] was significantly higher than NC group [(0.92 +/- 0.05)%, P < 0.05]. CONCLUSION: The changes of apoptosis and proliferation of pulmonary tissue in COPD rats might contribute to the pathogenesis of COPD.

[The mechanisms and effects of panax notoginside and methylprednisolone in a rat model of pulmonary fibrosis].

OBJECTIVE: To study the effects of panax notoginside (PNS) and methylprednisolone (solu-medrol) on the development of pulmonary fibrosis and the possible underlining mechanisms. METHODS: Rats were divided into 3 groups: pulmonary fibrosis group, PNS treated group and solu-medrol treated group. On days 1, 3, 7, 14, and 28 after bleomycin treatment, 5 rats in each group were killed and the lungs and plasma were harvested for histopathological studies, immunohistochemical determination of collagen I and III and ELISA detection of MIP-1alpha and MCP-1. RESULTS: The degrees of fibrosis, the levels of collagen I and III, and the levels of MIP-1alpha and MCP-1 decreased significantly in the PNS and solu-medrol treated groups as compared with the fibrosis group (P < 0.05). CONCLUSION: Both PNS and solu-medrol are effective in modulating the process of pulmonary fibrosis induced by bleomycin in rats.