中性粒细胞胞外诱捕网在系统性红斑狼疮相关间质性肺病中的作用

中性粒细胞参与病原体清除与早期炎症反应,是免疫系统的重要组成部分。但近年来越来越多的研究表明,中性粒细胞通过形成中性粒细胞胞外诱捕网(NETs)介导炎症反应并促进纤维化的形成,在自身免疫性疾病和间质性肺病(ILD)的发病机制中的作用逐渐受到重视。本文首先介绍NETs的结构、功能和形成过程,并结合NETs在其他自身免疫病中的作用,总结NETs参与系统性红斑狼疮(SLE)相关ILD针对NETs的发病机制,最后提出了自身免疫性疾病相关ILD针对NETs的潜在治疗靶点。     

桓台县1983～2004年肾综合征出血热监测资料分析

[目的]进一步掌握HERS的流行动态,为制定有效防治措施提供科学依据.[方法]对桓台县1983～2004年HFRS监测资料进行分析.[结果]1983～2004年发病率波动较大,2002年以后有所下降.历年合计发病1 781例,死亡18例.其中,果里镇、索镇、耿桥镇合计发病801例（占44.97%）;20～50岁发病928例;男性1089例,女性692例;农民1 368例;3～6月发病836例.野外黑线姬鼠为优势鼠种,室内褐家鼠为优势鼠种;家鼠带毒率为9.50%,野鼠带毒率为13.17%.[结论]桓台县是以家鼠型为主的HFRS混合型疫区,20～50岁男性农民是高发人群.     

单纯髓核摘除治疗脱垂移位型腰椎间盘突出症

目的:探讨小切口椎板间开窗单纯髓核摘除术治疗脱垂移位型腰椎间盘突出症的临床疗效.方法:2016年2月至2018年2月,对35例单节段脱垂移位型腰椎间盘突出症患者在全身麻醉下采用小切口椎板间开窗单纯髓核摘除术进行治疗,其中男21例,女14例;年龄(42±17)岁;L4,5节段27例,L5S1节段6例,L3,4节段2例;左...     

腹腔镜精索静脉高位结扎术治疗亚临床型精索静脉曲张性不育

目的探讨腹腔镜精索静脉高位结扎术对亚临床型精索静脉曲张性不育的治疗价值。方法回顾性分析2003年1月～2007年12月于我院行腹腔镜下精索静脉高位结扎术治疗的33例亚临床型精索静脉曲张性不育患者的临床资料。结果33例患者平均手术时间37min(25～70min),平均出血量5ml(3～10ml),平均住院3.5天(1～5天),所有患者术后恢复顺利。术后精液分析精子密度较术前明显改善,25例(75.7%)在术后18个月内配偶成功妊娠。结论腹腔镜精索静脉高位结扎术治疗亚临床型精索静脉曲张性不育安全有效。     

Discovery of a highly specific 18F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination

As a member of cyclic nucleotide phosphodiesterase (PDE) enzyme family, PDE10A is in charge of the degradation of cyclic adenosine (cAMP) and guanosine monophosphates (cGMP). While PDE10A is primarily expressed in the medium spiny neurons of the striatum, it has been implicated in a variety of neurological disorders. Indeed, inhibition of PDE10A has proven to be of potential use for the treatment of central nervous system (CNS) pathologies caused by dysfunction of the basal ganglia–of which the striatum constitutes the largest component. A PDE10A-targeted positron emission tomography (PET) radioligand would enable a better assessment of the pathophysiologic role of PDE10A, as well as confirm the relationship between target occupancy and administrated dose of a given drug candidate, thus accelerating the development of effective PDE10A inhibitors. In this study, we designed and synthesized a novel ¹⁸F-aryl PDE10A PET radioligand, codenamed [¹⁸F]P10A-1910 ([¹⁸F]9), in high radiochemical yield and molar activity via spirocyclic iodonium ylide-mediated radiofluorination. [¹⁸F]9 possessed good in vitro binding affinity (IC₅₀ = 2.1 nmol/L) and selectivity towards PDE10A. Further, [¹⁸F]9 exhibited reasonable lipophilicity (logD = 3.50) and brain permeability (P_app > 10 × 10⁻⁶ cm/s in MDCK-MDR1 cells). PET imaging studies of [¹⁸F]9 revealed high striatal uptake and excellent in vivo specificity with reversible tracer kinetics. Preclinical studies in rodents revealed an improved plasma and brain stability of [¹⁸F]9 when compared to the current reference standard for PDE10A-targeted PET, [¹⁸F]MNI659. Further, dose–response experiments with a series of escalating doses of PDE10A inhibitor 1 in rhesus monkey brains confirmed the utility of [¹⁸F]9 for evaluating target occupancy in vivo in higher species. In conclusion, our results indicated that [¹⁸F]9 is a promising PDE10A PET radioligand for clinical translation.KEY WORDS: Phosphodiesterase 10A, PET radioligand, ¹⁸F, Spirocyclic iodonium ylide, Nonhuman primate, Target occupancy     

The clinical relevance of ultra-widefield angiography findings in patients with central retinal vein occlusion and macular oedema receiving anti-VEGF therapy

AimsTo report, using ultra-widefield angiography (UWFA) the area, distribution, and change in retinal capillary nonperfusion (RCNP) at baseline and 100 weeks in eyes with central retinal vein occlusion (CRVO) receiving anti-VEGF for macula oedema.MethodsProspective longitudinal multi-centre cohort study. Adults with CRVO treated with anti-VEGF therapy for macular oedema underwent UWFA at baseline and week-100. The area, distribution, and change in total, peripheral and posterior pole RCNP were determined.ResultsOf 153 eyes at baseline, mean area of RCNP was 34.3DA and 12 (7.8%) had ≥75DA RCNP. More than 10DA RCNP was present in the temporal periphery in 75.8% of eyes vs. 10.5% in the nasal periphery. At week-100, mean RCNP was 42.1DA with a median change from baseline of 3.3DA 95% CI [0.4, 7.3]; p < 0.01. Of 146 eyes with ≤10DA of posterior pole RCNP at baseline, 16/146 (11.0%) progressed to >10DA at week-100. These eyes had a median increase in total RCNP of 69.7DA [95% CI 27.2–85.4] vs 0DA [0.0–1.4]; p < 0.001 for those who did not, and two developed neovascular glaucoma. Larger baseline area of RCNP and history of glaucoma were risk factors for posterior pole RCNP developing.ConclusionsWith UWFA, significant baseline RCNP was identified in the majority of CRVO patients, notably in the temporal periphery, but large increases over 100 weeks were uncommon. Development of >10DA posterior pole RCNP is a marker for widespread RCNP and in such cases the risk of anterior segment neovascularisation is not abolished by concomitant anti-VEGF therapy.Subject terms: Retinal diseases, Vision disorders     

癌胚抗原阳性CT26结肠癌细胞株的构建及鉴定

目的构建适于普通小鼠的癌胚抗原（CEA）阳性结肠癌细胞株。方法以重组CEACAM5cDNA-Lentivims慢病毒转染小鼠结肠癌CT26细胞．抗生素筛选2周．以有限稀释法获得癌胚抗原阳性细胞CT26CEA,体外培养至第7代和第14代进行鉴定。用RT．PCR法和Western blot法分别检测CEACAM5mRNA及蛋白表达．用荧光显微镜和免疫细胞化学法观察CEACAM5表达位置：并以第14代CT26CEA细胞建立BALB／c鼠皮下种植瘤模型．用活体荧光成像法和免疫组织化学染色观察瘤体CEACAM5表达情况。结果在第7代和第14代CT26CEA细胞内可以检测到CEACAM5mRNA及CEACAM5蛋白表达．荧光显微镜和免疫细胞化学法观察到其表达主要在细胞质,活体荧光成像法和免疫组织化学染色观察到小鼠瘤体有丰富CEACAM5表达。结论成功构建小鼠结肠癌CT26CEA细胞株,能够在体外培养及小鼠体内稳定表达癌胚抗原．为研究正常免疫环境下癌胚抗原对结肠癌进展的影响及作用机制提供了适用工具．     

米非司酮调控乳腺癌细胞增殖的研究

目的研究米非司酮对乳腺癌细胞系MCF-7和T47D的增殖抑制作用。方法采用四甲基偶氮唑盐(MTT)法检测米非司酮对乳腺癌细胞系MCF-7和T47D的半数抑制浓度(IC50)。不同浓度米非司酮(0.25、2.5、25和50μmol/L)分别处理人乳腺癌细胞系MCF-7和T47D1、2、3d后,观察细胞形态变化,以及检测各组细胞生长曲线。结果米非司酮对乳腺癌MCF-7和T47D细胞均有抑制作用,其抑制率均随着米非司酮浓度的增加而变化,存在明显的量效关系。通过对两种细胞抑制率(IR)值直线回归分析,米非司酮对MCF-7细胞的IC50为51.21μmol/L,对T47D细胞的IC50为54.29μmol/L。形态学观察发现,各组细胞体积变小,细胞间的链接消失,细胞内明显有黑色小颗粒聚集。25和50μmol/L浓度米非司酮对MCF-7乳腺癌细胞株生长抑制作用明显,特别是50μmol/L干预24h后在高倍镜下可见明显的核质浓缩。结论米非司酮对病理分型、激素受体型不同的乳腺癌MCF-7和T47D细胞均具有抑制增殖的作用,并呈时间和剂量依赖效应。     

微创食管癌根治术后早期去除胃肠减压管的临床观察

目的 观察微创食管癌根治术后早期去除胃肠减压管对胃肠功能恢复的影响及并发症发生情况,探讨微创食管癌根治术后早期去除胃肠减压管的可行性及安全性.方法 行微创食管癌根治术的胸段食管癌患者120例,随机分为观察组和对照组各60例,分别于术后第2、7天去除胃肠减压管.比较2组手术时间、术中出血量、住院时间、首次排气时间及排便时...     

门静脉、肠系膜上静脉的解剖与临床应用的初步研究

目的 为提高肝门胆管癌和壶腹周围癌的手术切除率,使该区域受肿瘤浸润的血管能同时切除,血管直接重建提供解剖学依据.方法 在实施肝门胆管癌切除术及胰十二指肠切除术中,对病人的肝蒂内门静脉干、胰腺钩突内的肠系膜上静脉干进行解剖学定位并分段测量长度及可以纵向折叠的长度,以此估计可切除的静脉长度及重新再建血管的长度.结果 测量肝蒂内门静脉干104例,男性(5.8±1.99)cm,女性(5.5±O.81)cm,优势长度大于4.5cm者,男性56例占76.7%,女性25例占80.6%.胰腺钩突内段肠系膜上静脉干测量54例,男性(3.7±0.77)cm,女性(3.5±0.64)cm,优势长度大于3.0cm者,男性28例占77.6%,女性14例占77.8%.门静脉纵向折叠移动的范围在1.8～4.2cm,平均折叠2.2(1.8～2.4)cm者占66.3%,平均折叠2.8(2.5～4.2)cm者占33.7%.切除胰十二指肠后胰腺钩突内肠系膜上静脉段纵向折叠范围平均4.0cm,最长达5.2cm.结论 肝门胆管癌和壶腹周围癌切除术合并受浸血管切除在一定范围是可行的.