遗传性易栓症与不良妊娠结局的研究进展

近年研究发现妊娠期易栓症的发生呈增加趋势。易栓症分为遗传性易栓症和获得性易栓症,遗传性易栓症主要与凝血基因突变所致的蛋白表达异常有关,包括因子VLeiden(FVL)、凝血酶原基因G20210A、亚甲基四氢叶酸还原酶(MTHFR)基因突变以及蛋白S(PS)、蛋白C(PC)和抗凝血酶(AT)缺乏等。凝血、抗凝及纤溶系统功能失调可引起胎盘灌注不良,不良妊娠结局如子痫前期(PE)、胎盘早剥、胎儿生长受限(FGR)和习惯性流产等可能与此有关。但遗传性易栓症是否是造成不良妊娠结局的直接因素以及预防性抗凝是否可以改善妊娠结局仍需进一步探讨。综述遗传性易栓症与不良妊娠结局的关系,评估预防性抗凝的必要性,为临床诊断和治疗提供思路。     

宫颈原始神经外胚层肿瘤一例及文献复习

为探讨宫颈原始神经外胚层肿瘤[primitive neuroectodermal tumor,PNET;又称尤文氏肉瘤（Ewing sarcoma）]的组织起源、临床特征及诊治进展,提高对该种特殊类型宫颈恶性肿瘤的认识,回顾性分析2016年1月吉林大学第二医院收治的1例PNET患者,该患者体检发现宫颈肿物,无特殊临床表现,经手术病理及免疫组织化学（免疫组化）染色确诊,免疫组化显示人白细胞分化抗原99（cluster of differentiation 99,CD99）、波形蛋白（vimentin,VIM）阳性。提示该类肿瘤极为罕见,生长迅速、恶性程度高、侵袭性强、死亡率高、预后极差,目前尚无标准治疗方案,诊断主要依据病理、免疫组化及细胞遗传学。     

反义Ku80在人肺癌细胞的表达及对放射线的敏感性研究

目的 :研究反义Ku80在人肺癌细胞的表达及对放射线的超敏效应。方法 :采用Western blotting法证明 ,Ku80 LCA中Ku80蛋白的表达情况 ,采用体外放射线敏感实验证明 ,反义Ku80在人肺癌细胞的表达及对放射线的超敏效应 ,用细胞存活克隆率和剂量效应曲线表示。结果 :(1)对照组和导入正义Ku80的LCA细胞可见Ku80蛋白表达印迹 ,导入反义Ku80的LCA细胞未见Ku80蛋白表达印迹。 (2 )导入反义Ku80的LCA细胞对放射线的敏感性明显增强 (P <0 0 1) ,并呈剂量依赖性。结论 :反义Ku80封闭了肿瘤细胞的Ku80蛋白表达后 ,对放射线呈超敏效应 ,为提高肿瘤放疗的特异性和靶向基因治疗奠定了基础。     

p-Cymene Modulates In Vitro and In Vivo Cytokine Production by Inhibiting MAPK and NF-κB Activation

The present study was designed to investigate the effects of p-cymene on lipopolysaccharide (LPS)-induced inflammatory cytokine production both in vitro and in vivo. The production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in LPS-stimulated RAW 264.7 cells and C57BL/6 mice was evaluated by sandwich ELISA. Meanwhile, the mRNA levels of cytokine genes were examined in vitro by semiquantitative RT-PCR. In a further study, we analyzed the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by western blotting. We found that p-cymene significantly regulated TNF-α, IL-1β, and IL-6 production in LPS-stimulated RAW 264.7 cells. Furthermore, the levels of relative mRNAs were also found to be downregulated. In in vivo trail, p-cymene markedly suppressed the production of TNF-α and IL-1β and increased IL-10 secretion. We also found that p-cymene inhibited LPS-induced activation of extracellular signal receptor-activated kinase 1/2, p38, c-Jun N-terminal kinase, and IκBα. These results suggest that p-cymene may have a potential anti-inflammatory action on cytokine production by blocking NF-κB and MAPK signaling pathways.     

多种特殊状态下关节软骨缺损修复的组织工程技术

文题释义： 生长板：是位于儿童长骨末端的软骨组织结构,生长板中的软骨细胞可不断增生、成熟、肥大并发生骨化过程,使长骨增长。当长骨生长至一定程度,生长板软骨逐渐被成熟骨组织取代,长骨至此也停止生长。 特殊状态：文章提及的特殊状态即指关节软骨缺损的临床治疗中常见的阻碍因素,即全层软骨缺损及骨软骨缺损、生长板缺损、负重区软骨缺损、炎症状态下(骨性关节炎、风湿性关节炎)的软骨缺损。 背景：应用组织工程学技术可获得良好的关节软骨再生,但多为生理状态下小面积缺损的单纯修复。然而临床上的软骨缺损常伴随骨性关节炎、类风湿性关节炎等基础疾病,且缺损的位置、范围、深度均不确定,给软骨组织修复带来了很大挑战。 目的：总结不同位置和炎症状态下软骨缺损的修复方式。 方法：检索PubMed数据库和CNKI数据库,英文检索词为“cartilage defect regeneration,osteochondral,growth plate,weight-bearing area,inflammatory”,中文检索词为“关节软骨缺损,骨软骨,生长板,负重区,炎症”,检索建库至2019年3月发表的相关文献。共检索到相关文献209篇,按照纳入与排除标准,最终纳入86篇文献进行总结。 结果与结论：针对各种特殊状态下的关节软骨缺损,其修复目标和策略是不同的：全层软骨和骨软骨结构缺损多采用具有多层结构的支架,旨在修复软骨特有的分层结构及软骨下骨结构,同时避免新生软骨内异位骨化的问题;生长板缺损的修复关键在于避免长骨成熟后发生畸形,因此在修复支架内应添加胰岛素样生长因子、骨发生形态蛋白7等生长因子,以持续刺激生长板的修复并发挥骨生长的生理功能;负重区软骨修复则需要修复支架具有良好的力学性能,负重时不会发生严重形变及结构破坏,同时新生的软骨组织具有足够的力学强度以支撑持续的纵向压力和磨损;炎症状态下的软骨缺损则要同时治疗炎症与软骨缺损,间充质干细胞的引入可同时发挥免疫调节及组织再生功能,以使疾病达到彻底治疗的目标。ORCID: 0000-0001-9443-8158(陈劲松) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

In vitro synergistic effect of minocycline combined with antifungals against Cryptococcus neoformans

BackgroundCryptococcus neoformans infections occur in immunocompromised patients, especially those with HIV infection, chemoradiotherapy after cancer, and organ transplantation. Infection can cause pneumonia and meningoencephalitis in severe cases with a high mortality rate if not treated. Although fluconazole and amphotericin B are the first-line treatments for cryptococcosis, the rate of fluconazole resistance has increased significantly due to long-term use. Minocycline is a derivative of tetracycline that exerts its antibacterial effect through inhibition of bacterial protein synthesis. It is also able to pass the blood-brain barrier to act on the central nervous system. The present study investigates the effects of minocycline in combination with antifungals in treating C. neoformans.ObjectiveTo determine in vitro interactions of minocycline combined with itraconazole, voriconazole, posaconazole, fluconazole and amphotericin B against C. neoformans.MethodsThe minimum inhibitory concentrations (MIC) of the antifungals were determined by the CLSI Clinical and Laboratory Standards Institute M27-A3 microdilution method. The in vitro synergistic effects of minocycline combined with itraconazole, voriconazole, posaconazole, fluconazole, and amphotericin B on C. neoformans were detected by the broth microdilution checkerboard technique and disk diffusion testing.Results and ConclusionThe working concentration ranges were 0.125–4 µg/mL for itraconazole, 0.03–0.125 µg/ml for voriconazole, 0.03–1 µg/ml for posaconazole, 0.25–16 µg/ml for fluconazole, and 0.125–2 µg/ml for amphotericin B. The synergistic rates of minocycline combinations against C. neoformans were 55% with itraconazole, 10% with voriconazole, 85% with posaconazole, 20% with fluconazole, and 70% with amphotericin B. The effective MIC value of minocycline in the synergistic combination decreased to 2–32 µg/ml, while the MIC of itraconazole decreased to 0.03–0.125 µg/ml, voriconazole 0.03–0.125 µg/ml, posaconazole 0.03–0.125 µg/ml, 0.125–4 µg/ml fluconazole, and 0.06–0.50 µg/ml amphotericin B. The disk diffusion assay showed that the plates containing minocycline and antifungal drugs produced inhibition zones with diameters larger than the single drug plates. Minocycline showed no antagonistic effect in the combinations. In conclusion, the combination of minocycline and azoles or amphotericin B has synergistic effects against C. neoformans in vitro.     

糖皮质激素对弥漫增生型狼疮性肾炎血清TGF-β1的影响

目的：通过对弥漫增生型狼疮性肾炎(LN)糖皮质激素治疗前后血中转化生长因子β1(TGF-β1)含量测定，了解糖皮质激素在治疗弥漫增生型LN中的作用。方法：用ELISA方法检测正常对照组(n＝15)及弥漫增生型LN组(n＝18)血清中TGF-β1水平。结果：弥漫增生型LN组糖皮质激素冲击治疗后TGF-β1水平明显降低。结论：弥漫增生型LN及时应用足量的精皮质激素，可能会延续硬化性肾炎的发生。     

子痫前期及子痫期患者联合检测血小板膜糖蛋白及凝血酶原的临床意义

目的研究子痫前期及子痫期患者血管内皮损伤和血小板活化状态及凝血系统活跃程度。方法采用全血流式细胞术分别检测32例重度子痫前期／子痫患者、16例轻度子痫前期患者、22例孕晚期妇女剖宫产术前及剖宫产术后72h内血小板膜糖蛋白Ⅰbα（GPⅠbot）、Ⅱb（GPⅡb）水平变化,采用血凝仪同期检测血浆凝血酶原时间（PT）和活化部分凝血活酶时间（APTT）。结果剖宫产术前,与轻度子痫前期组、正常孕晚期组比较,重度子痫前期及子痫组GPⅠbα和PT明显降低（P〈0．01）,术后两者72h内恢复至正常孕晚期水平,与术前比较差异显著（P〈0．01）;各组间剖宫产术前或术后GPⅡb变化无显著性差异（P〉0．05）;正常孕晚期组、轻度子痫前期组及重度子痫前期子痫组APTT递次延长但无统计学差异（P〉0．05）;术后上述三组APTT递次降低,但无显著性差异（P〉0．05）。GPⅠbα与PT呈正相关（r=0．371,P〈0．01）。结论孕晚期子痫前期及子痫患者存在血管内皮细胞损伤及血小板活化状态,引起外源性凝血系统活跃,而内源性凝血系统由于肝脏产生的凝血因子相对减少而活跃性相对降低。     

肺炎支原体脑炎患儿血清细胞因子干扰素-γ、白细胞介素-4的变化

目的探讨肺炎支原体(MP)脑炎患儿急性期血清干扰素-γ(IFN-γ)和IL-4水平变化及其意义。方法采用酶联免疫吸附(ELISA)双抗体夹心法检测MP脑炎24例急性期和24例健康儿童外周血血清IFN-γ和IL-4水平,并对确诊的MP脑炎患儿予阿奇霉素静脉滴注,10例同时应用地塞米松,15例应用丙种球蛋白治疗。结果健康对照组血清IFN-γ、IL-4为(85.35±6.91)、(26.78±9.89)ng/L;MP脑炎组IFN-γ、IL-4为(98.56±12.93)、(45.55±17.58)ng/L。MP脑炎组患儿IFN-γ、IL-4水平均较健康对照组升高,差异有显著性(Pa<0.05)。结论MP脑炎患儿血清INF-γ、IL-4均升高,提示MP脑炎发病可能与免疫功能紊乱相关,且可引起继发性免疫功能低下。