目的 研究免疫调节剂咪喹莫特对卵蛋白（OVA）致敏大鼠支气管旁淋巴结（PBLN）细胞培养体系中T辅助淋巴细胞（Th）亚群产生细胞因子的影响，并探讨其作用机制。方法 建立PBLN细胞培养体系，并按不同浓度分为A～F组进行干预。在培养0、3、6、12、24、48h后，各组分别取5孔细胞培养液，用酶联免疫吸附法（ELISA）检测各细胞因子的蛋白质水平，用逆转录聚合酶链反应（RT-PCR）检测细胞沉淀中白细胞介素（IL）-4和干扰素（IFN）-γ等细胞因子的mRNA表达。结果 在A组的各时间点PBLN细胞培养液中，仅可检测到少量IFN-γ。随着培养时间的延长，咪喹莫特浓度为1、10μg/ml的E和F组与B组相比，IL-4及相关mRNA水平增加缓慢，IFN-γ水平增长迅速（均P <0.005）。此作用从培养6h开始，12h达峰值，持续至24h。在培养12-48h时，C组IL-4表达与B组比，差异有统计学意义（P<0.05），而IFN-γ表达无差异（P>0.05）。结论 咪喹莫特对致敏大鼠PBLN细胞培养体系中Th亚群产生细胞因子的最佳作用发生在12h时，提示咪喹莫特可能在支气管哮喘等特异性疾病的迟发炎症反应阶段发挥重要作用。

Background; As a result of the finding that the mutation of Arg into Gly at β2-adrenergic receptor(β2-AR)16 loci could promote the downregulation effect triggered by the β2-agonist, it was supposed that Gly16 might be associated with the downregulation of β2-AR in patients with nocturnal asthma. Objective; It was the aim of this study to analyze the association between β2-AR genetic polymorphisms and nocturnal asthmatic patients of Chinese Han nationality. Methods; A polymerase chain reaction allele-specifi c oligonucleotide hybridization assay was used to determine 16 and 27 loci alleles of β2-AR genetic polymorphisms in 25 nocturnal asthmatic patients(nocturnal asthma group), 22 non-nocturnal asthmatic patients(non-nocturnal asthma group), and 72 healthy people(control group). All people investigated were of Chinese Han nationality. Results; The distribution frequency of genotype Arg/Arg, Arg/Gly, and Gly/Gly at β2-AR 16 loci was 12, 16 and 72% in the nocturnal asthma group; and 27, 41 and 32% in the non-nocturnal asthma group. There was a signifi cant increase in the frequency of genotype Gly/Gly and allele Gly in the nocturnal asthma group compared with the non-nocturnal asthma group(p<0.01). However, there was no signifi cant difference in the frequency of genotype Gly/Gly and allele Gly in the non-nocturnal asthma group, compared withthe control group. There was no signifi cance in the frequency of the genotypes and alleles of β2-AR 27 loci among the three groups(p>0.05). Conclusion; The Gly16 polymorphism of β2-AR was overrepresented in nocturnal asthmatic patients, correlated with nocturnal asthma, and therefore appeared to be an important genetic factor in the expression of this asthmatic phenotype.

摘要：目的评价南京药物研究所和上海先药业有限公司联合研制的新药两性霉素B脂质体（锋克松）注射剂，治疗深部真菌的临床疗效和安全性。方法：采用多中心开放阳性药随机平行对照的研究方法；实际入选深部真菌感染患者116例，其中包括试验（T）组30例（给予两性霉素B脂质体注射剂），对照（B）组31例（给予两性霉素B注射剂），开放试验（0）组55例（给予两性霉素B脂质体注射剂）。结果：T组的痊愈率为63.3%，有效率为96.7%，B组痊愈率为50.0%，有效率为86.7%，两组差异无显著性（P>0.05）；中枢神经系统真菌患者中，T组意识障碍消失平均时间（7.75±2.06）d，比B组（21.67±10.4l）d短（P<0.05）；T组和B组真菌清除率分别为93.3%和93.5%，两性霉素B脂质体对临床分离出的112株真菌的MICso为0.5mg/L，MIC90为1mg/L，两性霉素B的MICso和MIC90分别为0.5mg/L和2mg/L；T组不良反应发生率（60.0%）显著低下B组（83.9%，P=0.05）。结论：两性霉素B脂质体治疗深部真菌病的疗效与两性霉素B相似，其不良反应发生率低于两性霉素B。

Background Continuous positive airway pressure(CPAP)treatment has been proven to be effective in improving the symptoms of coexisting coronary heart disease(CHD)in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). However, it is still unclear whether such improvements are linked to changes in vascular endothelial function. This research was carried out to investigate the effects of CPAP treatment on vascular endothelial function in patients with OSAHS and CHD. Methods Thirty-six patients with moderate or severe OSAHS and CHD undergoing three months of CPAP treatment were recruited for this study. The changes in their morning plasma nitric oxide(NO)and endothelin(ET) levels, NO/ET ratio, total ischemic burden(TIB)of the myocardium, apnea hypopnea index (AHI), and minimal and mean pulse oxygen saturation(SpO2)were compared and analyzed before and during CPAP treatment. Results Compared with the plasma levels of ET[(51.39±11.69)ng/L] and NO[(36.67±11.86)μmol/L], NO/ET(0.71±0.14), AHI(32.4±7.9), minimal SpO2[(68.9±11.4)% ], and myocardial TIB[(66.29±16.37)mm min]before treatment, there were significant decreases in ET [(33.41±10.03)ng/L](P<0.05), increases in NO[(59.89±10.26)umol/L] and NO/ET(1.79±0.38)(P<0.01), decreases in AHI(1.9±0.5), and increases in minimal Sp02[(90.6±1.8)%](all P<0.01)and myocardial TIB[(36.42±10.87)mm min](P<0.05 )after three months of CPAP treatment. Conclusion CPAP treatment may play an vascular endothelial dysfunction and myocardia mportant role in the improvement and protection of ischemia in OSAHS patients with CHD.

Background Corticosteroids remain the most effective therapy available for asthma. They have widespread effects on asthmatic airway inflammation. However, little is known about the effects of corticosteroids on the production of bone marrow inflammatory cells in asthma. This study observed the effects of glucocorticoid and cysteinyl leukotriene 1 receptor antagonist on CD34+ hematopoietic cells, so as to explore the possible effectiveness of a bone marrow-targeted anti-inflammatory strategy. Methods Balb/c mice were sensitized and challenged with ovalbumin(OVA)to establish an asthmatic model. For two consecutive weeks, asthmatic mice were challenged with OVA while being given either prednisone, montelukast, prednisone plus montelukast, or sterile saline solution. The mice were killed 24 hours after the last challenge with OVA, and bronchoalveolar lavage fluid(BALF), peripheral blood, and bone marrow were collected. Eosinophils in peripheral blood and BALF, and nucleated cells in BALF, peripheral blood, and bone marrow were counted. The percentages of CD34+ cells, CD4+T lymphocytes and CD8 + T lymphocytes among nucleated cells in peripheral blood and bone marrow were counted by flow cytometry. Immunocytochemistry and in situ hybridization were employed to detect expression of CD34 and interleukin(IL)-5RαmRNA(CD34+IL-5RαmRNA+cells) among bone marrow hematopoietic cells. Results Compared with the sterile saline solution group, the number of eosinophils in BALF and peripheral blood, CD34+cells in peripheral blood and bone marrow, and CD34+IL-5RαmRNA+cells in bone marrow of mice from the prednisone and prednisone plus montelukast groups were significantly lower(P<0.01). The number of eosinophils in BALF from the montelukast group was also significantly lower(P<0.05). Conclusions The results suggest that, in this asthmatic mouse model, prednisone probably inhibits proliferation, differentiation, and migration of CD34+cells in bone marrow, blocks eosinophilopoiesis in bone marrow, and interferes with eosinophil migration into peripheral blood and subsequent recruitment in the airway. In addition, montelukast may suppress eosinophil infiltration into the lungs of asthmatic mice. However, a significant inhibitory effect of montelukast on the proliferation and migration of CD34+cells and a cooperating effect with prednisone on bone marrow of asthmatic mice were not observed.