5-FU纳米微粒的制备及其释药特性研究

目的 制备一种新型的载氟尿嘧啶(5-FU)纳米微粒并对其体内释药特性进行研究.方法 运用聚合物交联法制备出壳聚糖载氟尿嘧啶纳米粒,通过扫描电镜、激光粒度分析仪对其表征进行检测,紫外分光光度法测定载药量,高效液相色谱法检测体内的释药特性.结果 壳聚糖载氟尿嘧啶纳米粒呈圆形或椭圆形,分散性良好,粒径在120～150nm;载药量为31.000%±0.001%;壳聚糖-5-FU纳米粒注射入兔体内后,初期突释相约在1.5h,峰浓度为5 069.6μg/L,随即进入缓释相,浓度维持在76μg/L,时间长达48h.结论 壳聚糖纳米药物载体可改变5-FU在体内的药代动力学行为,延长其循环时间,具有良好的缓释作用.     

群组对照试验中应用倾向得分匹配法分析数据对干预效果评价的影响

目的 探讨应用倾向评分匹配法（propensity score matching,PSM）处理群组平行对照试验中横断面调查数据对干预效果评估的影响。方法 以某"十二五"国家科技重大专项的子课题"低档暗娼减少性病艾滋病感染干预研究"数据为例,应用PSM法对干预前后两次横断面调查的低档暗娼人群数据进行匹配,对匹配后样本开展结局变量χ2检验并拟合广义线性混合模型（generalized linear mixed models,GLMM）,讨论PSM法对评估结果的影响。结果 以存在显著差别的关键特征变量作为匹配因素进行PSM后,样本量为537,干预前后的两个人群完全可比。GLMM分析结果表明,干预是梅毒感染率降低的主要因素。PSM后数据拟合模型获得的OR值为0.33,与原始数据得到的OR值（0.51）相比降低了0.18,而且前者获得的95%CI（0.16~0.70）比后者（0.27~0.96）更窄,更远离1,将干预措施降低梅毒感染风险的效果从49%提高到了67%。结论 PSM法用于系列横断面调查的群组对照干预试验,可以有效提高不同调查人群之间的可比性,降低人群差异对效果评估的影响,从而提高研究结果的准确性。     

中国10省(市)流感成年人住院病例的临床特征及重症危险因素分析

目的 了解中国10省(市)严重急性呼吸道感染(SARI)住院病例哨点监测纳入的流感成年人住院病例的临床特征及重症危险因素。方法 对2009年12月至2014年6月中国10省(市)SARI哨点监测医院纳入的符合SARI定义的≥15岁病例进行流行病学和临床信息调查,采集呼吸道标本进行流感病毒核酸检测。按检测结果将病例分为流感住院组和非流感住院组,分析两组人口统计学信息、临床和流行病学特征,并分析重症危险因素。结果 10家哨点医院共纳入3 071例SARI成年人病例,其中实验室确诊240例(7.8%),以A(H1N1)pdm2009和A(H3N2)亚型流感病毒为主。病例年龄M为63岁,≥65岁老年人占47.1%。144例(60.0%)患有至少1种慢性基础性疾病,流感病例肺气肿比例(7.9%)高于非流感病例(3.8%),差异有统计学意义(χ²=3.963,P=0.047)。19.4%的流感育龄妇女为孕妇,240例流感病例中仅有1.1%在过去一年接种过流感疫苗。流感住院病例中咽痛、呼吸困难所占比例高于非流感住院病例。17.5%的流感病例收入重症监护室治疗,与非流感住院病例间的差异无统计学意义(P=0.160)。23.1%的流感病例在发病后使用了抗病毒药物治疗,高于非流感住院组(4.8%),差异有统计学意义(P<0.001)。流感住院病例中41.5%出现并发症,病毒性肺炎比例明显高于非流感组(P<0.001)。危险因素分析显示,发病入院时间>7 d(RR=1.673,95%CI:1.071～2.614)、患有哮喘(RR=15.200,95%CI:1.157～199.633)、免疫抑制疾病(RR=5.250,95%CI:1.255～21.960)、怀孕(RR=21.000,95%CI:1.734～254.275)是流感重症的危险因素。结论 成年人流感住院病例主要集中在≥65岁组,流感疫苗接种率极低、抗病毒药物使用不足,应推荐孕妇、老年人、慢性病病例等高危人群每年进行流感疫苗预防接种,流感住院病例应及早应用抗病毒药物。     

Kinetic analysis of the humoral immune response against 3 Toxoplasma gondii-recombinant proteins in infants with suspected congenital toxoplasmosis

The reactivity values of Toxoplasma gondii ROP2, GRA4, and GRA7 recombinant antigens (rAgs) were analyzed by immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) in 23 congenitally infected (I) and 36 noninfected (NI) infants. The reactivity values observed from the serum samples of I versus NI infants for each recombinant protein were 91% versus 67% for rROP2 (P = .05), 86% versus 29% for rGRA4 (P < .001), and 56% versus 11% for rGRA7 (P = .003). The follow-up showed that serum samples from NI infants became negative for specific IgG at 5.8 months (95% confidence interval [CI], 4.9-6.7) using a commercial assay; meanwhile, by specific recombinant protein ELISA, the samples became negative at 3.7 months with rROP2 (95% CI, 2.8-4.6), at 1.3 months with rGRA4 (95% CI, 0.8-1.8), and at 0.9 months with rGRA7 (95% CI, 0.5-1.3). Kinetic analysis also showed that serum samples from group I presented different IgG-profiles among rAgs. The rROP2 IgG profile was similar to that of the commercial assay, whereas rGRA4 and rGRA7 profiles showed a gradual decrease along the period of the study. The potential of the utility of rAgs to develop a diagnostic system that discriminates congenitally I infants from NI is discussed.     

城市血吸虫病综合防治措施的研究

目的探索快速控制城市血吸虫病流行的综合措施。方法在城市血吸虫病流行区选择3个试点现场,南津港、太平桥2个点采取以化疗为主的综合防治措施,小柳叶洲点采取以环境改造灭螺为主的综合防治措施。结果南津港点3年居民血吸虫感染率分别为2.80%、2.60%和2.24%,并发生急性血吸虫病2例;感染螺平均密度分别为0.0009、0.0027、0.0020只/0.1m2。小柳叶洲点3年无居民粪检阳性者,无急性血吸虫病例,哨鼠感染率为0,没有查到感染性钉螺。太平桥点3年居民感染率分别为1.18%、0.20%和0.26%,无急性血吸虫病例,家畜感染率分别为6.35%、3.57%和3.85%,2004年发现感染性钉螺,平均密度为0.0001只/0.1m2。结论在城市血吸虫病流行区,采取以环境改造灭螺为主、人群化疗、健康教育、药物灭螺灭蚴的综合防治措施能快速控制疫情。采取以化疗为主的综合防治措施,难以有效控制疫情。     

阻断血吸虫病传播策略与措施专家共识

2015年全国达到血吸虫病传播控制标准后,进入以全面阻断血吸虫病传播为新目标、开展监测预警为主要干预措施的新时期.“十三五”时期,四川、江苏、云南、湖北等4个血吸虫病防治重点省份先后达到血吸虫病传播阻断标准或通过国家血吸虫病传播阻断技术评估,我国血吸虫病疫情处于历史最低水平,流行程度进一步降低,《“十三五”全国血吸虫病...     

单增李斯特菌质粒研究进展

单增李斯特菌是一种可引起李斯特菌病的重要食源性病原体,质粒在单增李斯特菌中分布广泛,这些质粒对宿主的环境适应能力、毒力以及耐药有一定的促进作用.基因组测序技术的发展为质粒的发现及功能研究提供了很好的基础.本文综述了单增李斯特菌质粒的分类、分布及其生物学功能研究进展.     

中国血吸虫病流行地区农村家庭卫生厕所建造资金状况分析

为了解我国血吸虫病流行地区农村卫生厕所建造资金的管理状况,对目前仍然存在血吸虫病流行的湖南、湖北、江西、安徽、江苏、云南、四川7个省,每省随机抽取2个县,每县分别选取2个完成改厕的村,每村随机抽取30个使用卫生厕所的农户家庭进行现场调查。结果显示:血吸虫病流行地区农村833个不同类型无害化卫生厕所,不同来源投入差异较大,卫生厕所类型、政府投入、家庭收入、施工方式和家庭人口对卫生厕所造价有显著性影响。政府投入是中国血吸虫病流行地区农村卫生厕所建造资金的主要来源,政府主导、个人参与是我国血吸虫病流行地区农村建造卫生厕所的主要模式。应重点加强政府投入资金管理,提高改厕资金的使用效率。     

Immunogenicity and protection induced by recombinant Toxocara canis proteins in a murine model of toxocariasis

Toxocariasis, a natural helminth infection of dogs and cats caused by Toxocara canis and T. cati, respectively, that are transmitted to mammals, including humans. Infection control is based currently on periodic antihelmintic treatment and there is a need for the development of vaccines to prevent this infection. Materials and Methods: Eight potential vaccine candidate T. canis recombinant proteins were identified by in silico (rTcGPRs, rTcCad, rTcVcan, rTcCyst) and larval proteomics (rTES26, rTES32, rMUC-3 and rCTL-4) analyses. Immunogenicity and protection against infectious challenge for seven of these antigens were determined in a murine model of toxocariasis. C57BL/6 female mice were immunized with each of or combinations of recombinant antigens prior to challenge with 500 T. canis embryonated eggs. Levels of specific antibodies (IgG, IgG1, IgG2a and IgE) in sera and cytokines (IL-5, INF-ɣ and IL-10) produced by antigens-stimulated splenocytes, were measured. Presence of specific antibodies to the molecules was measured in sera of T. canis-seropositive dogs and humans. Results: All seven molecules were immunogenic in immunized mice; all stimulated significantly elevated levels of specific IgG, IgG1 or IgG2a and six were associated with elevated levels of specific IgE; all induced elevated production of IFN- ɣ and IL-10 by splenocytes, but only the in silico-identified membrane-associated recombinants (rTcCad, rTcVcan, and rTcCyst) induced significantly increased IL-5 production. Vaccination with two of the latter (rTcCad and rTcVcan) reduced larval loads in the T. canis challenged mice by 54.3% and 53.9% (P < 0.0001), respectively, compared to unimmunized controls. All seven recombinants were recognized by T. canis-seropositive dog and human sera. Conclusion: The identification of vaccine targets by in silico analysis was an effective strategy to identify immunogenic T. canis proteins capable of reducing larval burdens following challenge with the parasite. Two recombinant proteins, rTcCad and rTcVcan, were identified as promising vaccine candidates for canine toxocariasis.