白喉毒素突变体CRM197在大肠杆菌中优化表达及人群血清抗体水平分析

目的 构建白喉毒素突变体CRM197的原核表达载体,在大肠杆菌中表达CRM197蛋白。分析健康人群血清中的CRM197抗体水平。方法 对CRM197基因进行大肠杆菌密码子优化并克隆至pET28a(+)中,经表达条件优化后采用镍柱亲和层析和离子交换层析对重组蛋白CRM197进行纯化,对纯化的CRM197进行Western blot鉴定。最后,经纯化后的CRM197蛋白与健康人群血清进行反应,检测人群血清中针对该蛋白的抗体水平。结果 CRM197蛋白进行了密码子及表达条件优化后,获得了可溶性表达蛋白。经镍柱亲和层析和离子交换层析后其纯度可达95%以上,Western Blot鉴定后能得到单一的特异性条带。经纯化的CRM197蛋白与不同年龄阶段健康人群血清均发生不同程度的抗原抗体反应。结论 利用本研究的策略,CRM197得到高效的可溶性表达,但人群血清中含有高水平的CRM197抗体,这些抗体的存在可能会影响到应用CRM197结合多糖作为抗原进行特异免疫效果的评价以及作为诊断抗原的应用。

雷替曲塞三线治疗转移性结直肠癌62例临床观察

目的目前奥沙利铂、伊立替康及氟尿嘧啶治疗失败的转移性结直肠癌患者没有有效及低价的治疗选择,但许多一般状况良好的患者需进一步治疗。通过回顾性分析雷替曲塞三线治疗转移性结直肠癌化疗疗效,探讨结直肠癌的解救方案。方法回顾性分析2012-01-01-2017-03-31北京市朝阳区三环肿瘤医院34例及中国医学科学院肿瘤医院28例以雷替曲塞为基础化疗方案治疗经奥沙利铂及伊立替康化疗失败的转移性结直肠癌患者合计62例,分析化疗的客观有效率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)、无进展生存(progression-free survival,PFS)及总生存(overall survival,OS)。结果共有62例进展期结肠癌患者接受雷替曲塞为基础联合化疗。在可评价的59例患者中,部分缓解(partial response,PR)9例,稳定(stable disease,SD)27例,进展(progression disease,PD)23例,ORR为15.25%(9/59),DCR为61.02%(36/59)。其OS为7.5个月,95%CI为5.47~10.20;PFS为3.03个月,95%CI为2.28~4.16。雷替曲塞为基础化疗联合贝伐珠单抗27例,联合西妥昔单抗6例,其中有效的9例患者均为联合靶向治疗,联合靶向化疗的患者ORR为27.17%(9/33),高于单纯化疗者的0(0/26),P=0.003;但未延长PFS(3.50个月vs 2.95个月,HR=0.71,95%CI为0.37~1.34,P=0.29)及OS(7.40个月vs 7.90个月,HR=0.72,95%CI为0.19~2.71,P=0.63)。COX分析显示,PS评分为转移性结直肠癌患者的PFS(HR=2.58,95%CI为1.12~5.91,P=0.026)及OS(HR=236.81,95%CI为11.59~4 837.22,P<0.001)的影响因素。结论以雷替曲塞为基础的联合化疗方案三线治疗转移性结直肠癌患者有一定疗效,PS评分为晚期结肠癌的独立预后因素,值得进一步开展临床研究。

A first meningococcal meningitis case caused by serogroup X Neisseria meningitidis strains in China

Neisseria meningitidis is the leading cause of bacterial meningitis and classified into 13serogroups based on the immunological reactivity of the capsular polysaccharide.1 Serogroups A, B, C, W135 and Y are the most common causes of meningitis.2 Among them, serogroup A and C are the major causes of epidemics in Africa and Asia.2 Most of the epidemic outbreaks of meningococcal meningitis are caused by serogroup A Neisseria meningitidis strain from the 1950s to the 1980s in China.3 During the years 2003 and 2005, a new sequence type （ST-4821） of serogroup C was identified in the Anhui and 11 other provinces of China.4

Molecular characterizations of serogroup B Neisseria meningitidis strains circulating in Beijing

Neisseria meningitidis （N. meningitidis） is classified into 13 serogroups based on the immunological reactivity of the capsular polysaccharide.Serogourp-s A,B and C are responsible for over 90% of meningococcal disease.2 In developed countries, endemic disease is generally caused by serogroups B and C.

ST-11 clonal complex serogroup C Neisseria Meningitidis strain in China

To the editor：The serogroups of Neisseria meningitidis （N.meningitidis） strains are distributed with distinct regional characteristic？ Historically,meningococcal diseases in China have mainly been caused by serogroup A.2 Since the outbreaks in the Anhui province in 2003 and 2004,N.meningitidis serogroups A and C have become the major causative agents for most meningococcal diseases and most of serogroup A/serogroup C isolates belong to the ST-7/ST4821 complex,respectively.3 Strains of the serogroup C belonging to the ST-11/ET37 clonal complex which is prevalent in North America,Europe and Africa had previously not been observed in China.However,an isolate from a Kuwaiti case that resulted in the patient＇s death was identified as serogroup C ST-11/ET37 N.meningitidis clonal complex in July,2011,in Beijing.This is the first ST-1 lclonal complex serogroup C N.Meningitidis strain in China.