温抗体型自身免疫性溶血性贫血的诊治进展

自身免疫性溶血性贫血(AIHI)按照自身抗体作用于红细胞时所需的温度分为温抗体型AIHI(WAIHI)和冷抗体型AIHI(CAIHI),以WAIHI居多,并且多为继发性。WAIHI的发病与温度没有显著的相关关系,其发病是由各种原因引起的免疫机制变异,主要包括基因遗传因素、自身免疫调节异常及免疫因素等,导致针对自身红细胞的抗体产生,再与红细胞膜表面抗原结合,它是一种会使自身红细胞破坏或者缩短寿命的比较难以治疗的贫血,目前治疗AIHI首选疗法为肾上腺皮质激素(激素),有效率可达80%,大剂量静脉注射丙种球蛋白(IVIG)、输血、切除脾等方法的使用也在实践中逐渐增多,并且疗效可观。近年来对温抗体型自身免疫性溶血性贫血的诊治进展的研究越来越多。     

颗粒溶素的研究进展

颗粒溶素具有溶细胞作用和杀菌活性,其作用对象包括肿瘤细胞、细菌、真菌和寄生虫。颗粒溶素是T淋巴细胞、单核细胞和其他炎性细胞的化学刺激物,可以激活许多细胞因子的表达,包括调节激活T细胞表达和分泌(RANTES)、单核细胞化学引诱物蛋白(MCP)1、MCP3、巨噬细胞炎性蛋白1(MIP)、白介素(IL)-10、IL-1、IL-6和干扰素(IFN)-α。颗粒溶素与感染、癌症、移植、自身免疫、皮肤和生殖疾病等多种疾病相关。基于颗粒溶素的多功能性,本文针对其作用机制和与临床常见疾病关系做一综述。     

内毒素耐受的机制研究

内毒素是革兰阴性菌细胞壁的成分,能够激发机体的免疫反应。当细菌释放大量的内毒素到血液,即可引起内毒素血症,内毒素血症可以伴随多种疾病出现,引起致死性感染性休克,循环功能衰竭,其病死率极高。内毒素耐受是指机体接受小剂量内毒素刺激后对后续内毒素刺激的反应性降低,表现为促炎因子释放减少而抗炎因子释放增加,机体发热,缺氧,低血压,休克的症状减轻。内毒素耐受的发生机制极其复杂,受机体内多种因素的调节,但目前尚无明确的结论。近年来,有关其机制的研究有许多报道,其中,对内毒素耐受的信号机制的研究最为广泛,大量的研究表明内毒素的主要受体,细胞内的信号蛋白,负调控因子以及转录因子可能在内毒素耐受的发生过程中起重要作用。也有报道表明免疫细胞的凋亡,染色体修饰和基因重排以及小RNA的参与可能诱导内毒素耐受的发生。本文从细胞、分子水平对内毒素耐受的发生机制进行综述,拟对炎症性疾病如内毒素血症的预防和治疗提供理论依据。     

巨噬细胞凋亡对结核分枝杆菌感染的机制研究进展

结核病是一种严重危害人类健康的慢性传染性疾病,主要由结核分枝杆菌感染导致,结核分枝杆菌进入人体后,与免疫防御的第一道屏障—巨噬细胞发生反应,部分菌株在细胞内长期生存、繁殖,是导致结核病转归的决定性因素。感染早期,结核分枝杆菌的繁殖受到巨噬细胞凋亡的抑制,随着高效价、高毒力菌株繁殖速度的增加,抗巨噬细胞凋亡作用不断增强,使自身繁殖得到有效保护,为菌株的生长提供了充足、适宜的胞内环境。因此,调控结核分枝杆菌对巨噬细胞凋亡进程的抑制作用,是预防和治疗结核病的关键。     

糖尿病足治疗新进展

糖尿病足溃烂是糖尿病的常见慢性并发症,以高发生率、高致残率、经济负担重,治疗时间长及高死亡率严重影响病人的生活质量甚至威胁生命,我国糖尿病协会于2010年11月14公布我国糖尿病的患病者已达9240万,除此之外糖尿病前期患者已达1.482亿。而在糖尿病患者中糖尿病足的发病率达到1.7%-11.9%;糖尿病患者中有15%的患者一生中有患糖尿病足的倾向,因此对于糖尿病足的治疗显得尤为重要,本文从糖尿病足的病因、机制,微环境变化着手,重点阐述糖尿病足传统的中西医疗法及目前的手术、介入及干细胞治疗方法的近况,旨在探讨各种方法的优点和不足及可开拓的空间,为进一步治疗糖尿病足提供一定的理论依据,为糖尿病足新方法的研究提供一些新的思维方式。     

Nature:研究发现与肝硬化相关肠道菌群的遗传特征

<正>近日,浙江大学医学院附属第一医院传染病诊治国家重点实验室、感染性疾病诊治协同创新中心主任李兰娟院士及其科研团队,找到了汉族人和肝硬化相关的肠道菌群的遗传特征,为检测晚期肝疾病提供了方法。该研究成果在学术期刊《自然》发表。目前,部分病毒性肝炎及脂肪性、酒精性、药物性、免疫性肝病患者会经历肝炎、肝硬化、肝癌"三部曲"。尽管有些研究表明,肠道微生物的改变在终末期肝硬化并发症中起重要作用,但一直缺乏肠道菌群和肝脏病变的确切关联证据。李兰娟院士及其科研团队通过收集181个来自于中国人肠道菌群的样本,其中包括98个中国肝硬化患者及83个健康中国志愿者的粪便样本,用宏基因组学的研究方法,开展了肝硬化肠道菌群的深度测序及关联分析研究,从中获得269万个非冗余的人体肠道微生物菌群的基因集,     

棕榈酸促进肝癌细胞侵袭转移的分子机制

目的:探讨棕榈酸(Palmiticacid,PA)对人肝癌细胞系SMMC-7721侵袭转移能力的影响,并通过检测肝癌细胞系中CD147-MMPs信号通路在PA影响下的变化,初探PA影响肝癌细胞侵袭转移的分子机制。方法:PA(0、20、50、100μM)作用SMMC-7721细胞后(8、16、24h),MTT法检测细胞增殖,划痕及Transwell实验评价细胞迁移侵袭能力,Western-blot及real-time PCR检测CD147蛋白及其mRNA的水平,ELISA检测基质金属蛋白酶(MMP-2,MMP-9)的水平。结果:与对照组相比,PA作用SMMC-7721细胞后,细胞存活率无显著差异(P0.05);细胞迁移和侵袭能力显著增高(P0.05);CD147蛋白及其mRNA的表达显著增高(P0.05);培养上清中MMP-9的浓度显著增高(P0.05),MMP-2的水平则无变化。不同的梯度组之间相比较,细胞迁移和侵袭能力、CD147的表达水平(蛋白及其mRNA)以及培养上清中MMP-9的浓度均随PA作用时间和作用剂量的增大而产生更显著的增高。结论:PA通过活化CD147-MMPs信号通路促进SMMC-7721细胞的迁移侵袭。     

嗜水气单胞菌致病性研究进展

嗜水气单胞菌(Aeromonas hydrophila,AH)是我国养殖鱼类的重要病原,对其侵袭机制和毒力因子的研究有重要的意义。本文对嗜水气单胞菌的生物学特性、致病机制、毒力因子及其防治措施进行了综述。     

Methylation Modifications in Eukaryotic Messenger RNA

RNA methylation modifications have been found for decades of years, which occur at different RNA types of numerous species, and their distribution is species-specific. However, people rarely know their biological functions. There are several identified methylation modifications in eukaryotic messenger RNA （mRNA）, such as NT-methylguanosine （mVG） at the cap, Nr-methyl-2＇-O-methyladenosine （m6Am）, 2＇-O-methylation （Nm） within the cap and the internal positions, and internal N6-methyladenosine （m6A） and 5-methylcytosine （mSC）. Among them, mTG cap was studied more clearly and found to have vital roles in several important mRNA processes like mRNA translation, stability and nuclear export, m6A as the most abundant modification in mRNA was found in the 1970s and has been proposed to function in mRNA splicing, translation, stability, transport and so on. mrA has been discovered as the first RNA reversible modification which is demethylated directly by human fat mass and obesity associated protein （FRO） and its homolog protein, alkylation repair ho- molog 5 （ALKBH5）. b-TO has a special demethylation mechanism that demethylases m6A to A through two over-oxidative intermediate states： N6-hydroxymethyladenosine （hm6A） and Nr-formyladenosine （frA）. The two newly discovered m6A demethylases, bTO and ALKBH5, significantly control energy homeostasis and spermatogenesis, respectively, indicating that the dynamic and reversible mrA, analogous to DNA and histone modifications, plays broad roles in biological kingdoms and brings us an emerging field ＂RNA Epige- netics＂. 5-methylcytosine （5mC） as an epigenetic mark in DNA has been studied widely, but mSC in mRNA is seldom explored. The bisulfide sequencing showed mSC is another abundant modification in mRNA, suggesting that it might be another RNA epigenetic mark. This review focuses on the main methylation modifications in mRNA to describe their formation, distribution, function and demethylation from the current knowledge and to provide future 19erspectives on functional studies.     

Meiotic Chromosome Behavior in a Human Male t（8;15） Carrier

Reciprocal translocation is one of the most common structural chromosomal rearrangements in human beings; it is widely recognized to be associated with male infertility. This association is mainly based on the abnormal chromosome behavior of the translocated chromosomes and sex chromosomes during meiosis prophase I in reciprocal translocation carriers. However, the underlying mechanisms are not completely known. Here we report a reciprocal translocation carrier of t（8;15）, who is oligozoospermic due to apoptosis of primary spermatocytes and to premature germ cell desquamation from seminiferous tubules. Further analysis showed abnormal synapsis and recombination frequency in this patient, indicating a connection between chromosome behavior and apoptosis of primary spermatocytes. We also compared these observations with recently reported findings on spermatogenesis defects in reciprocal translocation carriers, and discuss the possible mechanisms underlying both common and unique phenotypes of reciprocal translocations involving different chromosomes with the aim of further understanding the regulation of human spermatogenesis.