Next-generation sequencing through multigene panel testing for the diagnosis of hereditary epidermolysis bullosa in Chinese population

Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients with KRT5 mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB.     

基于免疫系统非线性模型对中医正邪相争理论和扶正祛邪治则的一个非线性动力学诠释

文中基于免疫系统有关免疫活性细胞或分子与外来抗原相互作用的非线性的动力学模型对中医学正邪相争理论及其扶正祛邪治则进行了新的诠释,提出了新的研究思路。认为:中医学关于外感邪气致病的六经、卫气营血和三焦辨证在本质上是识别抗原与免疫活性细胞或分子相互作用的三种不同的非线性动力学诊断模式,其证相应于这一过程中不同的非线性动力状态,可以用一个或一组非线性动力学方程进行定量描述。一个证常常对应于抗原与免疫活性的细胞或分子非线性动力学相互作用相空间中的一个稳定或不稳定的极限环和混沌,这可以作为证诊断的图形或形象标识。以中医学扶正祛邪的治疗思想为先导,有可能研制出全新靶向的和更有效的治疗传染性疾病的药物。     

马来西亚寒邪致病及其证治初探

根据第一作者在马来西亚从事中医临床工作50余年的经验,以中医理论为指导,探讨了在炎热的马来西亚,寒邪致病的可能性、客观性以及寒邪致病的病因、病机、临床表现特征及其治疗方法。     

临床医师处方抗菌药物前需思考的几个问题

2001年和2003年卫生部全国医院感染监测网调查结果均显示,医院横断面抗菌药物的平均使用率在54%以上,联合用药较为普遍.国内监测结果也表明细菌耐药性日益严重.针对上述问题,提出临床医师在面对病人开处方抗菌药物之前,须思考的问题:是否有使用抗菌药物的适用症?是否了解选用的抗菌药物,选用何种药物?是否有联合使用抗菌药物的指征?采用何种给药途径、给药剂量、给药时间?是否属于特殊宿主或针对特殊病原体的感染使用抗菌药物?密切观察抗菌药物治疗是否有效?针对局部感染是否需要穿刺或外科手术引流病灶?是否已出现抗菌药物的不良反应?是否存在药物相互作用?是否存在不合理使用抗菌药物情况?并且针对每个问题提出了建议.     

Presence of immunoglobulin M antibodies around the glomerular capillaries and in the mesangium of normal and passive Heymann nephritis rats

Summary Diffuse distribution of small, faintly staining, beaded deposits of rat immunoglobulin M (IgM) around the glomerular capillary blood vessels, and a more intensely staining larger deposition in the mesangium, were observed on the kidney sections of normal rats. As glomerular-fixed nephritogenic antigens are known to be present on the epithelial aspect of the glomerular basement membrane (GBM), especially at the soles of foot processes and at the slit pores, it was assumed that the IgM antibodies were directed against these antigens. Investigation by immunofluorescent antibody double-staining techniques of rat kidney sections obtained from normal and rabbit anti-FX1A-injected rats stained for the nephritogenic antigen showed that a number of antigenic sites in the glomeruli and in the mesangium shared antibody hits by heterologous rabbit IgG and autologous rat IgM antibodies. Most sites in the glomeruli stained specifically for rat IgM or rabbit IgG, but preferentially for the latter. The intensely fluorescent mesangial deposits stained mainly for rat IgM, indicating that at these sites the antigenic material was virtually saturated, while areas at the entry to the mesangial space also stained for rabbit IgG, indicating that at these locations free nephritogenic epitopes were still available for reaction with the anti-FX1A antibody. Western blot analysis have shown that the rabbit anti-rat FX1A IgG and the rat anti-rat KF3 IgM antibodies are directed against the same renal tubular-derived antigen with a molecular weight of 70,000. These experimental findings collectively demonstrate that the heterologous IgG and autologous IgM antibodies are directed against the same nephritogenic antigen, which is found in the glomeruli, the mesangium and the proximal convoluted tubules. Thus, the IgM autoantibody has a possible physiological role but, in addition, there is evidence of active immunophagocytic events, manifested in a rapid and continuous entrapment and expulsion of macromolecules after their processing by the mesangial cells of normal and passive Heymann nephritis rats.     

Fate-Mapping of GM-CSF Expression Identifies a Discrete Subset of Inflammation-Driving T Helper Cells Regulated by Cytokines IL-23 and IL-1β

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The beta1 adrenergic effects of antibodies against the C-terminal end of the ribosomal P2beta protein of Trypanosoma cruzi associate with a specific pattern of epitope recognition

BALB/c mice immunized with recombinant Trypanosoma cruzi ribosomal P2beta protein (TcP2beta) develop a strong and specific antibody response against its 13 residue-long C-terminal epitope (peptide R13: EEEDDDMGFGLFD) that has a concomitant beta1-adrenergic stimulating activity. However, other animals that undergo similar immunizations seem tolerant to this epitope. To evaluate further the antibody response against the ribosomal P proteins, 25 BALB/c and 25 Swiss mice were immunized with TcP2beta. From the 50 animals, 31 developed a positive anti-R13 response, whereas 19 were non-responsive. From the 31 anti-R13 positive mice, 25 had anti-R13 antibodies that recognized the discontinuous motif ExDDxGF, and their presence correlated with the recording of supraventricular tachycardia. The other six had anti-R13 antibodies but with a normal electrocardiographic recording. These anti-R13 antibodies recognized the motif DDxGF shared by mammals and T. cruzi and proved to be a true anti-P autoantibody because they were similar to those elicited in Swiss, but not in BALB/c mice, by immunization with the C-terminal portion of the mouse ribosomal P protein. Our results show that the recognition of the glutamic acid in position 3 of peptide R13 defines the ability of anti-R13 antibodies to react with the motif AESDE of the second extracellular loop of the beta1-adrenergic receptor, setting the molecular basis for their pathogenic beta1 adrenoceptor stimulating activity.