临床诊疗
目的 探讨不同剂量右美托咪定(Dex)对腰硬联合麻醉下经皮肾镜碎石术患者的镇静效应和安全性。方法 腰硬联合麻醉下行俯卧位经皮肾镜碎石术患者80例,随机分成4组。D1组、D2组、D3组俯卧位后静脉泵注负荷剂量DEX 0.5 μg/kg,输注的时间为10min,随后分别静脉泵注DEX 0.3 μg/(kg·h)、0.5 μg/(kg·h)、 0.7 μg/(kg·h)至术毕;C组俯卧位后静脉泵注生理盐水10 mL/h至术毕。记录T0~T6共7个时点的HR、MAP、p(O2)和BIS值;在T0、T3~T6等时点对患者静息Ramesay镇静评分;观察患者不良反应发生情况;询问综合满意度。结果 D2组和D3组的HR、MAP、BIS、Ramesay镇静评分在T3~T6等时点明显慢于C组(P<0.05);D3组心动过缓和头晕等不良反应的发生率明显高于D1组、D2组和C组(P<0.05),D2组和D3组术中躁动的发生率明显低于D1组和C组(P<0.05),D1组、D2组和D3组高血压、寒战和恶心呕吐的发生率明显低于C组(P<0.05),且综合满意度明显高于C组。结论 DEX本药物用于该类手术的镇静疗效及安全性均优于对比的药物。建议临床使用剂量为DEX负荷剂量0.5 μg/kg,随后以0.5 μg/(kg·h)维持。
临床诊疗
目的 探讨Reversine对人肝星状细胞系LX-2凋亡的影响。方法 设对照组和Reversine干预组,其中Reversine干预组分为7个浓度,分别为1,5,10,20,40,80,120 μg/mL,CCK-8法检测Reversine对LX-2增殖的影响,选取最佳浓度。将细胞重悬在加入5 μL FITC-Annexin V和5 μL PI,用流式细胞仪进行了凋亡率分析,免疫荧光检测凋亡蛋白bcl-2及caspase 3。结果 Reversine可促进LX-2细胞凋亡,随着Reversine浓度增加,LX-2的凋亡可呈剂量依赖关系,其中10 μg/mL为最佳浓度,LX-2细胞的bcl-2蛋白的表达显著下降而cleaved-caspase 3的表达显著上升。结论 Reversine可通过促进caspase-3蛋白活化、抑制bcl-2蛋白表达的方式诱导LX-2凋亡。
临床诊疗
目的 探究彩色多普勒超声在乳腺良恶性肿瘤鉴别诊断中的应用价值。方法 抽取2012年2月—2016年6月我院门诊、社区普查中的病例中选取符合研究标准的298例乳腺肿瘤疾病患者,所有患者均行彩色多普勒超声检查。通过SPSS 19.0软件对数据进行分析,以病理检查结果作金标准,分析彩色多普勒超声诊断结果,对比良性肿瘤与恶性肿瘤血流分级情况及良性肿瘤与恶性肿瘤收缩期流速峰值(PSV)及(阻力指数)RI水平。结果 经病理检查证实,298例患者中恶性肿瘤32例,良性肿瘤266例;超声诊断恶性肿瘤42例,良性肿瘤256例;超声诊断灵敏度为93.75%(30/32)、特异度为95.49%(254/266)、准确度为95.30%(284/298)。良性肿瘤血流信号检出率为55.26%(147/266),恶性肿瘤血流信号检出率为96.87%(31/32),其中良性肿瘤以0~I级血流为主,为83.83%(223/266),恶性肿瘤以I~III级血流为主,为96.87%(31/32),各分级情况对比,差异有统计学意义(P<0.05)。恶性肿瘤PSV(20.11±6.76)cm/s、RI(0.65±0.07)均明显高于良性肿瘤[(15.30±9.21)cm/s、(0.56±0.09)],差异有统计学意义(P<0.05)。结论 彩色多普勒超声在乳腺良恶性肿瘤临床鉴别诊断中具有较高准确度、特异度及灵敏度,可结合血流分级和RI水平提高乳腺良恶性肿瘤鉴别准确度。
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目的 探讨两种不同手法复位治疗向地性眼震水平半规管良性阵发性位置性眩晕的临床效果。方法 选取水平半规管良性阵发性位置性眩晕患者50例,分组进行不同手法复位治疗,短期治疗效果不佳者结合强迫长时间健侧卧位法治疗。结果 初次治疗360-Barbecue复位法组治愈率80%,Gufoni复位法组患者治愈率72%;两组患者结合强迫长时间健侧卧位法,第二天复查治愈率分别为92%和88%,两组比较差异无统计学意义(P>0.05)。结论 两种手法复位均能有效治疗向地性眼震水平半规管良性阵发性位置性眩晕,近期疗效相近,对于无效者结合FPP可增加治愈率。
Objective To study the effects of two different manual reduction of geotropic nystagmus horizontal semicircular canal benign paroxysmal positional vertigo. Methods 50 cases of patients with two different groups, treated with different manual reduction. Patients with short term treatment but ineffective were treated in combination with forced prolonged lateral position FPP. Results The cure rate of initial treatment in the 360-Barbecue manual reduction groups was 80%, the Gufoni manual reduction groups was 72%. As the patients combined with FPP, the cure rate was 92% and 88% respectively in the second day treatment. There was no significant difference between the two groups(P>0.05). Conclusion Both of the different manual reduction may effectively treat HC-BPPV. Their recent curative effect is similar. For ineffective cases may increase the cure rate combined with FPP.
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目的 对信息协作平台的社区结直肠癌三级防治及干预体系进行探索与实践。方法 对纳入本次研究的2 492名社区人群进行问卷调查,包括健康人群1 118人,1 374例肿瘤患者。分析健康人群和肿瘤患者关于肿瘤防治知识及途径的认知情况,比较健康人群和肿瘤患者就诊首选医院,了解肿瘤患者就诊流向和行为以及发现患癌的途径。结果 在肿瘤患者中知道癌前病变、早期肿瘤症状、高危人群的比例显著高于健康人群[26.93%(370/1 374)、39.96%(549/1 374)、46.00%(632/1 374)比14.49%(162/1 118)、21.91%(245/1 118)、26.92%(301/1 118)]。健康人群认为肿瘤三级防治网络可行、会参加三级防治网、有必要开展癌症筛查、会参加筛查的比率显著高于肿瘤患者[98.83%(1 105/1 118)、91.95%(1 028/1 118)、98.12%(1 097/1 118)、98.03%(1 096/1 118)比81.95%(1 126/1 374)、79.98%(1 099/1 374)、80.93%(1 112/1 374)、85.95%(1 181/1 374)],差异均有统计学意义(P<0.05)。健康人群把三甲医院视为就诊首选医院的比率显著低于肿瘤患者[32.56%(364/1 118)比86.97%(1 195/1 374)](P<0.05)。肿瘤患者中发现肿瘤及确诊医院、肿瘤复诊、康复医院的选取主要以三甲综合医院为主。在肿瘤患者中因身体不适到医院就诊发现患癌的比率显著高于单位员工体检、自检发现、社区卫生服务中心体检发现的比率。结论 我国目前肿瘤发病率和死亡率正处在快速上升的阶段,利用网络优势,加大肿瘤防治知识的宣传力度,建立社区、区域二级医院、三级医院优势互补的三级肿瘤防控体系,是当前我国肿瘤防治的迫切需求。
Objective To explore and practice the community tertiary prevention and intervention system for colorectal cancer based on information collaboration platform. Methods A questionnaire survey was conducted among 2 492 community residents which were included in this study, including the healthy crowd of 1 118 people, 1 374 cases of tumor patients. The study was to analyze the knowledge of cancer prevention and treatment in healthy people and cancer patients, to contrast the preferred hospital by healthy people and cancer patients, to acquaint the flow direction in seeking medical service, behavior and way to diagnosis cancer of tumor patients. Results In patients with cancer, the understanding proportion of patients with precancerous lesions, early tumor symptoms, and high risk groups was significantly higher than that in healthy people [26.93% (370/1 374), 39.96% (549/1 374), 46.00% (632/1 374) vs 14.49% (162/1 118), 21.91% (245/1 118), 26.92% (301/1 118)]. In healthy people, the proportion of identification of tumor three-grade prevention and control network, willing to participate in the tertiary prevention and control network, necessity to carry out cancer screening, willing to participate in screening was significantly higher than that in patients with cancer [98.83% (1 105/1 118), 91.95% (1 028/1 118), 98.12% (1 097/1 118), 98.03% (1 096/1 118) vs 81.95% (1 126/1 374), 79.98% (1 099/1 374) and 80.93% (1 112/1 374), 85.95% (1 181/1 374)]. There were significantly differences (P<0.05). Healthy people preferred to choose common hospital instead of 3A hospital as the first choice [32.56% (364/1 118) vs 86.97% (1 195/1 374)] (P<0.05). Discovery and diagnosis of cancer, further consultation, and rehabilitation were mainly carried out in 3A hospital. In patients with cancer, the cancer discovery ratio because of physical discomfort for medical attention was significantly higher than that in unit staff physical examination, self-inspection found, and physical examination in community health service center. Conclusion At present, the incidence and mortality of cancer in our country is in a stage of rapid rising. It's an urgent need for cancer prevention and control in China that making use of the advantage of network to improve the propaganda of the knowledge of cancer prevention and control, and establishing complementary advantages of the tertiary cancer prevention and control system by community, regional hospitals, and 3A hospitals.
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目的 探讨七氟烷复合静脉诱导在脑动脉瘤栓塞术中的临床效果。方法 分析2013年1月—2015年12月在我院接受脑动脉瘤栓塞术80例患者的临床资料,根据随机数字表法分为研究组(n=40)和对照组(n=40),对照组采用全凭静脉诱导插管方法,研究组采用七氟烷复合静脉诱导插管方法,比较两组患者的应用效果。结果 两组患者血流动力学、血浆E及NE、呛咳反应发生率、阿托品及血管活性药物使用率比较,研究组均明显优于对照组(P<0.05)。结论 七氟烷复合静脉诱导用于脑动脉瘤栓塞术对患者血流动力学和应激反应的影响较小,具有较高的安全性和可靠性,可应用于临床。
Objective To explore the clinical effect of sevoflurane combined with intravenous induction in the treatment of cerebral aneurysm embolization. Methods The clinical data of 80 patients with cerebral aneurysm embolization in our hospital from January 2013 to December 2015 were analyzed and divided into study group (n=40) and control group (n=40) according to the random number table. The control group was treated by intratracheal intubation with total intravenous induction. In the study group, sevoflurane combined intravenous induction with intratracheal intubation was used to compare the effect of the two groups. Results Compared with the control group, the hemodynamics, the plasma E and NE, the incidence of cough reaction, atropine and vasoactive drug use were significantly better than those in the control group (P<0.05). Conclusion Sevoflurane combined with intravenous induction for cerebral aneurysm embolization in patients with less impact on hemodynamics and stress response, with high safety and reliability, can be used clinically.
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目的 研究不同剂量重组人干扰素α1b雾化吸入治疗毛细支气管炎的疗效及安全性。方法 选取2016年1月—2016年9月期间我院儿科收治的年龄≤2 a的毛细支气管炎患儿86例,均符合毛细支气管炎诊断标准,随机分为观察一组(29例)、观察二组(29例)和对照组(28例)。所有患儿均给予综合常规治疗,观察一组患儿雾化吸入生理盐水+质量浓度为0.2 g/L的沙丁胺醇+1 μg/(kg·次)重组人干扰素α1b,观察二组患儿雾化吸入生理盐水+质量浓度为0.2 g/L的沙丁胺醇+2 μg/(kg·次)重组人干扰素α1b。比较三组患儿治疗有效率、临床症状改善和不良反应发生情况。结果 观察一组与观察二组在治愈率和总有效率两个方面均显著高于对照组(P<0.05),但观察一组与观察二组治愈率和总有效率比较差异不显著(P>0.05);观察一组和观察二组患儿临床症状和体征持续时间明显少于对照组(P<0.05),但观察一组和观察二组患儿临床症状和体征持续时间无显著差异(P>0.05);三组患儿不良反应发生率差异不显著(P>0.05)。结论 低剂量与高剂量雾化吸入重组干扰素α1b对于小儿毛细支气管炎临床疗效接近,且均无严重不良反应,综合经济效益和社会效益考虑,在临床上推广低剂量雾化吸入重组干扰素α1b治疗小儿毛细支气管炎更具价值。
Objective To study the effects of different doses of recombinant human interferon α1b inhalation efficacy and safety in the treatment of bronchiolitis. Methods 86 cases of children, who were less than 2 years old were selected in department of pediatrics from January 2016 to September 2016. They were randomly divided into for observation group Ⅰ (29 cases), observation group Ⅱ(29 cases) and control group (28 cases). All the patients were treated with conventional therapy. Group Ⅰ with atomization inhalation of salbutamol and 0.02% with saline+1 μg /kg times of recombinant human interferon α1b were observed and the same as in the two groups Ⅱ with atomization inhalation of salbutamol and 0.02% with saline+2 μg /kg recombinant human interferon α1b. The treatment efficiency, the improvement of clinical symptoms and adverse reactions were compared. Results The cure rate and total effective rate of observation group Ⅰand Ⅱ were significantly higher than those in the control group (P<0.05), there were no significant differences in the cure rate and total effective rate between observation group Ⅰand Ⅱ(P>0.05). The clinical symptoms and signs of the patients of observation group Ⅰand Ⅱ were significantly higher than those in the control group (P<0.05), there were no significant differences in the clinical symptoms and signs of the patients between observation group Ⅰand Ⅱ(P>0.05). There was no significant difference in the incidence of adverse reactions between the three groups (P>0.05). Conclusion There were no serious adverse reactions in low dose and high dose of atomization inhalation of recombinant interferon α1b for close to the clinical curative effect of children with bronchiolitis. Considering comprehensively economic benefits and social benefits, it is worth of promotion low dose of atomization inhalation of recombinant interferon 1b in the treatment of children with bronchiolitis.
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目的 评价鞘内注射雷帕霉素对CCI神经病理性痛大鼠的痛阈及脊髓背角胶质细胞表达的影响。方法 健康雄性SD大鼠30只随机分为6组:①CCI组:CCI术后14天处死;②正常对照组:不做任何处理; ③前对照剂组:鞘内置管3天后行CCI术,术后4小时后鞘内给同体积生理盐水,连给3天; ④前给药组:鞘内置管3天后行CCI术,术后4小时鞘内给雷帕霉素溶液,连给3天; ⑤后对照剂组:鞘内置管3天后行CCI术,术后7天鞘内给同体积生理盐水,连给3天;⑥后给药组:鞘内置管3天后行CCI术,术后7天鞘内给雷帕霉素溶液,连给3天。各组于CCI术前1天和术后第2、4、6、8、10、12、14天测机械痛阈和热痛阈。术后14天测痛后用多聚甲醛灌注大鼠,取L4~5脊髓,免疫组化染色,星形胶质细胞标记蛋白(GFAP)检测星形胶质细胞表达变化,并定量分析。结果 与对照组相比,CCI手术组热痛阈和机械痛阈从CCI手术后第4天开始下降(P<0.05);前后给药对照剂组与CCI组相比,差别无统计学意义(P>0.05)。前给药组痛阈从CCI手术后第4天开始上升并持续至手术后第14天,与CCI组相比,差别有统计学意义 (P<0.05)。与CCI组相比,后给药组痛阈从CCI第8天开始上升并持续至手术后第14天,差别有统计学意义(P<0.05)。 与正常对照组比较,CCI组、前、后对照剂组手术侧脊髓背角GFAP染色阳性区平均光密度与阳性面积均有增加,差别有统计学意义(P<0.05)。前、后给药组手术侧GFAP染色阳性区平均光密度与阳性面积与CCI组比较,均有明显降低,差别有统计学意义(P<0.05)。结论 鞘内注射雷帕霉素可缓解大鼠神经病理性痛,并抑制脊髓背角胶质细胞的激活。
Objective To evaluate the effects of intrathecal injection of rapamycin on pain threshold and spinal cord gliacyte activation in rats of neuropathic pain. Methods Healthy 30 male SD rats were randomly divided into 6 groups(n=5 in each group): ① control group without operation or intrathecal injection. ②CCI group without intrathecal injection. ③ intrathecal injection of rapamycin 10 μg(10 μL) 4 hours after CCI operation and the next 2 days once a day. ④ intrathecal injection of NS10 μL 4 hours after CCI operation and the next 2 days once a day. ⑤ intrathecal injection of rapamycin 10 μg(10 μL) 7 days after CCI operation and the next 2 days once a day.⑥ intrathecal injection of NS10 μL 7 days after CCI operation and the next 2 days once a day. Mechanical and thermal threshold were tested 1 day before the CCI operation and 2th、4th、6th、8th、10th、12th、14th days after the CCI operation for all the rats. Lumbar segment of spinal cords was removed for determination of glial fibrillary acidic protein(GEAP) in spinal cord by immuohistochemistry dyeing and assay in the 14th day after CCI operation for all the rats. Results Mechanical and thermal hyperalgesia emerged on 4th day and maintained till 14th day after CCI operation(P<0.05). After intrathecal injection of rapamycin 4 hours or 7days after CCI, mechanical and thermal threshold significantly increased compared to intrathecal injection of NS(P<0.05). And the sum area of GFAP positive and the mean density of GFAP positive area in the dorsal horn of operation side greatly increased in rapamycin treated groups compared NS treated groups(P<0.05). Conclusion Intrathecal injection of rapamycin may attenuate CCI induced hyperalgesia and inhibit the activation of astrocyte.
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目的 研究BAG-1基因与乳腺癌他莫昔芬(TAM)治疗敏感性的相关性。方法 以58例乳腺癌患者为观察组,50例乳腺良性肿瘤患者为对照组。予以观察组患者TAM治疗,检测并统计2组患者肿瘤组织BAG-1基因的阳性率;并根据检测结果将观察组患者分为BAG-1阳性组与阴性组,对比分析观察组BAG-1阳性者与阴性者的临床预后及血清肿瘤标志物水平,包括癌胚抗原(CEA)、糖类抗原153(CA153)。结果 观察组BAG-1基因阳性率为74.14%,对照组为12%,2组比较, P<0.05。观察组BAG-1阳性组患者临床缓解率为46.51%,阴性组为66.67%,2组比较,P<0.05;BAG-1阳性组患者临床控制率为67.44%,阴性组为86.67%,2组比较,P<0.05。观察组BAG-1阳性组患者平均OS为(1.55±0.86)a,PFS为(1.02±0.31)a,阴性组依次为(2.76±0.95)a、(2.06±0.82)a,2组比较,差异均有统计学意义(P<0.05)。治疗后,观察组BAG-1阴性组患者血清CEA、CA153指标值均低于对照组(P<0.05)。结论 BAG-1基因与乳腺癌TAM治疗敏感性密切相关,BAG-1阳性者行TAM治疗的临床效果及预后均较阴性者差。
Objective To study the correlation between BAG-1 gene and the sensitivity of tamoxifen (TAM) in breast cancer. Methods 58 cases of breast cancer patients as the observation group, 50 cases of benign breast cancer patients as the control group.The positive rate of BAG-1 gene in two groups of patients was detected and statistically analyzed by TAM. The patients in the observation group were divided into BAG-1 positive group and negative group according to the test results, and the positive rate of BAG- (CEA), carbohydrate antigens 153 (CA153) and carcinoembryonic antigen (CEA). Results The positive rate of BAG-1 gene was 74.14% in the observation group and 12% in the control group, P<0.05. The clinical response rate of BAG-1 positive group was 46.51% and negative group was 66.67%, P<0.05; The clinical control rate of BAG-1 positive group was 67.44%, negative group was 86.67%. Compared 2 groups , it was P<0.05. The mean OS was (1.55±0.86) years, PFS was(1.02±0.31) years in the BAG-1 positive group and (2.76±0.95) years in the negative group and (2.06±0.82) years in the negative group, (P<0.05). After treatment, the serum CEA and CA153 values in the negative group of BAG-1 were lower than those in the control group (P<0.05). Conclusion BAG-1 gene and breast cancer TAM treatment sensitivity is closely related to BAG-1 positive TAM treatment of clinical efficacy and prognosis were worse than negative.
论著
目的 观察不同剂量卡介苗核酸(Bacille Calmette-guerin DNA , BCG-DNA)在不同干预时间对哮喘小鼠气道高反应性及气道炎症的干预作用。方法 1.将Balb/c雌鼠随机分为哮喘模型组、NS对照组、BCG- DNA干预组。干预组根据干预的时间和干预制剂剂量的不同分为-7DNA1 μg、-7DNA10 μg、-7DNA100 μg、10DNA1 μg、10DNA10 μg、10DNA100 μg、17DNA1 μg、17DNA10 μg、17DNA100 μg组。2.在末次激发48小时后,测定各浓度级乙酰甲胆碱激发下的增强的呼气间歇 (Enhanced Pause, Penh)值,将其与小鼠激发前吸入NS后的Penh的百分比(Penh%NS),作为其气道反应性评价指标;其次对肺泡灌洗液进行细胞学分析。结果 1.气道反应性:①-7DNA1 μg组从Mch为3.12~50 mg/mL之间的Penh%NS显著低于哮喘组(P<0.05);②-7DNA10 μg组和-7DNA 100 μg组从Mch为6.25~25 mg/mL之间的Penh%NS显著低于哮喘组(P<0.05);③10DNA10 μg组从Mch为12.5~25 mg/mL之间的Penh%NS显著低于哮喘组(P<0.05);④10DNA100 μg组从Mch为3.12、12.5~50 mg/mL之间的Penh%NS显著低于哮喘组(P<0.05);⑤17DNA1 μg组在Mch为3.12、12.5 mg/mL的Penh%NS显著低于哮喘组(P<0.05);⑥17DNA10 μg组在Mch为12.5 mg/mL之间的Penh%NS显著低于哮喘组(P<0.05) 2.气道炎症:10DNA1 μg、-7DNA10 μg、10DNA10 μg和17DNA10 μg组的BALF细胞分类Eos%分别为:35.34±3.81、27.30±6.91、38.20±6.56、42.17±5.17;显著低于哮喘组的Eos%(48.8±6.12)(P<0.05);10DNA1 μg组的Eos%显著低于-7DNA1 μg组的Eos%(P<0.05);-7DNA10 μg组的Eos%显著低于10DNA10 μg、17DNA10 μg、-7DNA1 μg和-7DNA100 μg组的Eos%(P<0.05)。结论 BCG-DNA能降低哮喘小鼠的气道高反应性,减轻哮喘小鼠的气道炎症,早期(-7 d)中小剂量的干预效果较佳。
Objective To investigate the effect of Bacille Calmette-Guerin BCG-DNA on airway hyperresponsiveness and airway inflammation in asthmatic mouse model. Methods 1.According to different intervention, mouse were divided into asthma groups, NS control group, BCG-DNA group. According to different time and dosage intervened with asthma model, the BCG-DNA group were subdivided into -7DNA1 μg、-7DNA10 μg、-7DNA100 μg、10DNA1 μg、10DNA10 μg、10DNA100 μg、17DNA1 μg、17DNA10 μg and 17DNA100 μg group. 2.48 hours after the final incitation, the mice were stimulated with increasing concentrations of methacholine, and the airway resistance was measured. Enhance pause (Penh) was taken for each group. Bronchoalveolar lavage cytology was performed to evaluate the airway inflammation. Results 1.Airway hyperresponsiveness: ① Penh%NS of-7DNA1 μg group was significantly lower than the asthma group when Mch was 3.12~50 mg/mL (P<0.05); ② Penh%NS of -7DNA10 μg group and -7DNA100 μg group were significantly lower than the asthma group when Mch was 6.25~50 mg/mL (P<0.05);③ Penh%NS of 10DNA10 μg group was significantly lower than the asthma group when Mch was 12.5~25 mg/mL (P<0.05); ④ Penh%NS of 10DNA100 μg group was significantly lower than the asthma group when Mch was 3.12,12.5~50 mg/mL (P<0.05); ⑤ Penh%NS of 17DNA1 μg group was significantly lower than the asthma group when Mch was 3.12 or 12.5 mg/mL (P<0.05);⑥Penh%NS of 17DNA10 μg group was significantly lower than the asthma group when Mch was 12.5 mg/mL(P<0.05). 2.Airway inflammation: The Eos% of 10DNA1 μg, -7DNA10 μg,10DNA10 μg and 17DNA10 μg group (35.34±3.81、27.30±6.91、38.20±6.56、42.17±5.17) were lower than the asthma group (P<0.05); The Eos% of 10DNA1 μg group was lower than the -7DNA1 μg group (P<0.05); The Eos% of -7DNA10 μg group was lower than the 10DNA10μg, 17DNA10 μg,-7DNA1 μg and -7DNA100 μg group (P<0.05). Conclusion BCG-DNA can inhibit the airway inflammation and hyperresponsiveness in asthmatic mouse model. Early interventions with middle dose bring better results.