Repressor of GATA-3 can negatively regulate the expression of T cell cytokines through modulation on inducible costimulator / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The transcription factor, repressor of GATA-3 (ROG), can simultaneously suppress the expression of T helper cells (Th1 and Th2) cytokines. Since the suppression of Th2 cytokines by GATA-3 is well understood, it is postulated that there are other molecular targets of ROG that can suppress the expression of the Th1 cytokines. We hypothesized that ROG might suppress the stimulators of T lymphocyte cytokines such as CD3, CD28, and inducible costimulator (ICOS), or indirectly enhance the expression of cytokine suppressors such as T lymphocyte-associated antigen-4 (CTLA-4) and CD45. The objective of this study was to clarify the molecular targets of ROG involved in suppressing Th1 or Th2 cytokines.</p><p><b>METHODS</b>Real-time quantitative PCR (RT-PCR) and Western blotting were performed to evaluate the mRNA and protein levels of CD3, CD28, ICOS, CTLA-4, and CD45 in Th1 and Th2 cells during various levels of ROG expression. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of interferon-γ (IFN-γ) and interleukin (IL)-4 in culture media of Th1 and Th2 cells.</p><p><b>RESULTS</b>The results showed that the mRNA and protein levels of ROG were relatively low in Th1 and Th2 cells (P < 0.01). After ROG-pcDNA3.1 transfection, the mRNA and protein level of ROG was significantly elevated, while the expression of ICOS, IFN-γ, and IL-4 was markedly down-regulated (P < 0.01). Conversely, transfection of ROG-siRNA led to inhibition of ROG expression and up-regulation of ICOS, IFN-γ and IL-4 (P < 0.01). However, the expression levels of CD3, CD28, CTLA-4 and CD45 did not change in either ROG-pcDNA3.1 or ROG-siRNA-transfected Th1 and Th2 cells (P > 0.05).</p><p><b>CONCLUSION</b>It is concluded that ROG can inhibit the expression of Th1 and Th2 cytokines by down-regulating the expression of ICOS, which might be a potential molecular target for asthma treatment.</p>

Budesonide/formoterol maintenance and reliever therapy in Chinese patients with asthma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Many studies have shown the superior efficacy of budesonide (BUD)/formoterol (FORM) maintenance and reliever therapy, but still lack evidence of its efficacy in Chinese asthma patients in a relative large patient-group. We finished this research to compare BUD/FORM maintenance and reliever therapy and high-dose salmeterol (SALM)/fluticasone (FP) maintenance plus an as-needed short-acting β(2)-agonist in Chinese patients with persistent uncontrolled asthma. This was a post hoc analysis based on a 6-month, multicenter, randomized, double-blind study (NCT00242775).</p><p><b>METHODS</b>A total of 222 eligible asthma patients from nine centers in China were randomized to either BUD/FORM+as-needed BUD/FORM (160/4.5 µg/inhalation) (640/18 µg/d; n = 111), or SALM/FP+as-needed terbutaline (0.4 mg/inhalation) (100/1000 µg/d; n = 111). The primary endpoint was time to first severe exacerbation while secondary endpoints included various measures of pulmonary function, symptom control and quality-of-life.</p><p><b>RESULTS</b>Time to first severe exacerbation over six months was lower with the BUD/FORM than with the SALM/FP treatment (risk ratio = 0.52, 95%CI 0.22 - 1.22), but the difference did not achieve statistical significance (P = 0.13). The cumulative number of severe exacerbations in the BUD/FORM group was lower than in the SALM/FP group (7.2% vs. 13.5%; risk ratio = 0.45, P = 0.028). BUD/FORM produced significantly better improvements in reliever use, cumulative mild exacerbations, symptom-free days (%), and morning/evening peak expiratory flow (PEF) than SALM/FP (P < 0.05 in all cases). The two groups achieved similar improvements in their time to first mild exacerbation, forced expiratory volume in one second (FEV(1)), asthma control questionnaire and asthma symptom scores, and percentage of nights with awakening(s). Both treatments were well tolerated.</p><p><b>CONCLUSIONS</b>In Chinese patients with persistent asthma, BUD/FORM decreased severe and mild exacerbations, decreased reliever use, increased symptom-free days, and improved morning/evening PEF compared with SALM/FP. There were no significant differences in time to first severe exacerbation or other assessments regarding daily asthma control between BUD/FORM and SALM/FP. BUD/FORM was more effective in this Chinese sub-group than in the total cohort involved in the original study.</p>

A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC) / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death.</p><p><b>RESULTS</b>The objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05).</p><p><b>CONCLUSIONS</b>Compared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.</p>

Irinotecan plus cisplatin for the treatment of advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and adverse events of irinotecan (CPT-11) combined with cisplatin (DDP) in the treatment of patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Of 36 NSCLC patients consisting of 23 males and 13 females with a medium age of 52 years included, there were 26 adenocarcinomas, 7 squamous cell carcinomas, 1 adeno-squamous cell carcinoma and 2 unclassified types; 13 stage III B and 23 stage IV; 24 chemonaive and 12 previously treated by chemotherapy with a medium Karnofsky status of 90. All patients had measurable or evaluable parameters. The regimen was administered as following: CPT-11 60 mg/m2, IV, D1, 8 and 15; DDP 80 mg/m2, IV, D1; every 28 days as a cycle.</p><p><b>RESULTS</b>Totally, 97 cycles were carried out in these 36 patients with a medium cycles of 3. Of 35 evaluable patients, 22.9% (8/35) achieved partial response, 60.0% (21/35) had stable disease and 17.1% (6/35) progressive disease. The response rate was 29.2% (7/24) for chemonaive patients and 9.1% (1/11) for these previously treated. The 1-year survival rate was 45.4% with a medium time to tumor progression (TTP) of 199 days for the responders. The incidence rate of grade III/IV adverse events were: 16.7% for neutropenia, 13.9% alopecia, 5.6% diarrhea, 2.8% nausea and vomiting, respectively.</p><p><b>CONCLUSION</b>Irinotecan plus cisplatin is effective with tolerable adverse events in treating patients with advanced non-small cell lung cancer, but further investigation trials are needed.</p>

Worldwide trends in epidemiology and control of tuberculosis / 第二军医大学学报

Tuberculosis (TB) is a global burden disease and is being resurrected as a major worldwide public health problem after two decades of neglect.In 1993,the World Health Organization (WHO) declared that TB had been a global emergency because of the scale of the epidemic and the urgent need to improve global tuberculosis control.China is one of the countries with the largest population,and also the top of the 22 TB high-burden countries in the world.In the United States,the longstanding downward trend in TB incidence was interrupted in the mid-to-late 1980s,where the national TB incidence peaked in 1992.Sub-Saharan Africa is one of the three regions to dominate the worldwide distribution of notified TB cases.Of the 15 countries with the highest estimated tuberculosis incidence rates in the world,13 are in sub-Saharan Africa,where HIV is the most important single predictor of tuberculosis incidence.The largest share of the global burden of HIV-related tuberculosis falls on this region.The reasons for the persisting global tuberculosis burden include increased poverty in some regions,immigration from countries with high tuberculosis prevalence,the impact of HIV,and most importantly,the failure to maintain the necessary public health infrastructure under the mistaken belief that tuberculosis was a problem of the past.Relying on currently available methods of diagnosis and treatment,the DOT strategy promoted by the WHO for global tuberculosis control is effective,affordable,and adaptable in different settings.

Worldwide trends in epidemiology and control of tuberculosis / 第二军医大学学报

Tuberculosis (TB) is a global burden disease and is being resurrected as a major worldwide public health problem after two decades of neglect.In 1993,the World Health Organization (WHO) declared that TB had been a global emergency because of the scale of the epidemic and the urgent need to improve global tuberculosis control.China is one of the countries with the largest population,and also the top of the 22 TB high-burden countries in the world.In the United States,the longstanding downward trend in TB incidence was interrupted in the mid-to-late 1980s,where the national TB incidence peaked in 1992.Sub-Saharan Africa is one of the three regions to dominate the worldwide distribution of notified TB cases.Of the 15 countries with the highest estimated tuberculosis incidence rates in the world,13 are in sub-Saharan Africa,where HIV is the most important single predictor of tuberculosis incidence.The largest share of the global burden of HIV-related tuberculosis falls on this region.The reasons for the persisting global tuberculosis burden include increased poverty in some regions,immigration from countries with high tuberculosis prevalence,the impact of HIV,and most importantly,the failure to maintain the necessary public health infrastructure under the mistaken belief that tuberculosis was a problem of the past.Relying on currently available methods of diagnosis and treatment,the DOT strategy promoted by the WHO for global tuberculosis control is effective,affordable,and adaptable in different settings.

Effects of Pulmicort Respules on airway resisitance and airway remodeling in rats with asthma / 上海第二医科大学学报

Objective To investigate the effects of Pulmicort Respules on the airway resistance and airway remodeling in rats with allergic asthma. Methods Thirty-two SD rats were randomly divided into blank control group,asthma model group,Pulmicort Respules group and normal saline control group,with 8 rats in each group.On the 14th day of allergization,rats were challenged by ovalbumin inhalation and were treated correspondingly.On the 28th day,airway resistance was determined,HE staining was conducted in lung tissues of each group,and airway remodeling related parameters were also measured. Results The airway resistance of Pulmicort Respules group was significant lower than that of blank control group,asthma model group and normal saline control group(P