益生菌在腹型过敏性紫癜中临床应用的研究进展

过敏性紫癜(HSP)是儿童最常见的自身免疫性疾病之一,临床表现除皮疹外以消化道症状最为常见,严重影响患儿的生活质量。临床上治疗腹型HSP主要以糖皮质激素和抗组胺药物为主,但只能缓解病情,不能达到根治的目的,同时还存在一定的副作用。最近有学者对腹型HSP患者中肠道微生物区系中的细菌数量进行精确测量,发现腹型HSP可能与肠道菌群失调有关。益生菌是一类在适当摄入数量会对宿主机体带来益处的活的微生物,是调节机体微生态平衡的有效途径,可通过多种途径来增强肠道屏障功能、提高机体自身免疫力和降低变态反应性,从而使其在腹型HSP中具有治疗潜力。本文对益生菌在腹型HSP中的临床应用作一综述。     

左卡尼汀配合复方玄驹胶囊对特发性少弱精子症的疗效观察

目的：观察复方玄驹胶囊联合左卡尼汀口服液治疗不同程度的特发性少弱精症的临床疗效。方法：选择2010年6月．2012年9月就诊于内蒙古医科大学第一附属医院的少弱精症者300例,其中重度少、弱精症者70例（治疗l组）,中度少、弱精症者110例（治疗2组）,轻度少、弱精症者120例（治疗3组）。另选择同期来我院进行健康体检者100例,将其作为对照纽。治疗组口服左卡尼汀口服溶液及复方玄驹胶囊,持续时间3个月。每一位被研究对象都在治疗前后定期进行血常规、尿常规、肝功能和肾功能四个方面的检查,同时观察服药患者在治疗过程中发生的不良反应。并对精液量、精子密度、A级精子等指标进行观察和比较。轻中度患者观察其（A＋B）级精子,重度患者观察其（B＋C）级精子,同时评价其治疗前后的生育能力,并与对照组比较。结果：与治疗前比较,治疗1、2、3组治疗后精液量[（3．7±1．6、3．7±1．1、3．8±1．2）mL]、精子密度[（3．4±1．4、23．2±1．8、39．6±14．2）（mol/L）]、A级精子[（3．6±2．5、15．6±6.3、28．6±9．6）％]、（A＋B）级精子、（B＋C）级精子比例、生育力指数（0．2±0．0、0．8±0．1、1．4±0．1）均升高明显,差异显著（P〈0．05）;与对照组比较,治疗1、2、3组治疗前均有所减少,治疗1、2组治疗后虽有所上升,但还是显著低于对照组（P〈0．05）,治疗3组治疗后与对照组差异不大,提示该方法对轻度少、弱精症者效果较重、中度好。结论：左卡尼汀配合复方玄驹胶囊对特发性少弱精子症效果显著。     

环境因素对儿童特发性矮身材影响的临床研究

目的：探讨环境因素对儿童特发性矮身材的影响。方法：采用病例对照的研究方法,对100例特发性矮身材患者组和100例正常对照儿童组分别进行体格测量,问卷调查家庭基本情况、出生史、饮食习惯、生活方式、生长速率、家庭生活条件、经济状况、父母文化程度等环境因素资料进行Logistic回归分析。结果：家族矮小史、母亲文化程度、家庭经济状况、偏食、运动时间、留守儿童影响特发性矮身材的发生。结论：因素与儿童特发性矮身材有关,为特发性矮身材儿童早期干预提供临床依据。     

Matrix Metalloproteinase (MMP)-1 Induces Lung Alveolar Epithelial Cell Migration and Proliferation,Protects from Apoptosis,and Represses Mitochondrial Oxygen Consumption

Idiopathic pulmonary fibrosis is a devastating lung disorder of unknown etiology. Although its pathogenesis is unclear, considerable evidence supports an important role of aberrantly activated alveolar epithelial cells (AECs), which produce a large variety of mediators, including several matrix metalloproteases (MMPs), which participate in fibroblast activation and lung remodeling. MMP-1 has been shown to be highly expressed in AECs from idiopathic pulmonary fibrosis lungs although its role is unknown. In this study, we explored the role of MMP-1 in several AECs functions. Mouse lung epithelial cells (MLE12) transfected with human Mmp-1 showed significantly increased cell growth and proliferation at 36 and 48 h of culture (p < 0.01). Also, MMP-1 promoted MLE12 cell migration through collagen I, accelerated wound closing, and protected cells from staurosporine- and bleomycin-induced apoptosis compared with mock cells (p < 0.01). MLE12 cells expressing human MMP-1 showed a significant repression of oxygen consumption ratio compared with the cells with the empty vector. As under hypoxic conditions hypoxia-inducible factor-1α (HIF-1α) mediates a transition from oxidative to glycolytic metabolism, we analyzed activation of HIF-1α. Ηigher activation of this factor was detected in MMP-1-transfected cells under normoxia and hypoxia. Likewise, a significant decrease of both total and mitochondrial reactive oxygen species was observed in MMP-1-transfected cells. Paralleling these findings, attenuation of MMP-1 expression by shRNA in A549 (human) AECs markedly reduced proliferation and migration (p < 0.01) and increased the oxygen consumption ratio. These findings indicate that epithelial expression of MMP-1 inhibits mitochondrial function, increases HIF-1α expression, decreases reactive oxygen species production, and contributes to a proliferative, migratory, and anti-apoptotic AEC phenotype.     

Excess type I interferon signaling in the mouse seminiferous tubules leads to germ cell loss and sterility

Type I (α and β) interferons (IFNs) elicit antiproliferative and antiviral activities via the surface receptor IFNAR. Serendipitous observations in transgenic mice in 1988 strongly suggested that IFNα/β overexpression in the testis disrupts spermatogenesis. Here, we compare a new mouse strain transgenic for IFNβ (Tg10) and a sister strain lacking the IFNAR1 subunit of IFNAR (Tg10-Ifnar1(-/-)), both strains expressing the transgene in the testis. The main source of IFNβ RNA was the spermatid population. Importantly, the Tg10 mice, but not the double mutant Tg10-Ifnar1(-/-), showed altered spermatogenesis. The first IFNAR-dependent histological alteration was a higher apoptosis index in all germ cell categories apart from non-dividing spermatogonia. This occurred 3 weeks after the onset of IFNβ production at postnatal day 20 and in the absence of somatic cell defects in terms of cell number, expression of specific cell markers, and hormonal activities. Several known interferon-stimulated genes were up-regulated in Tg10 Sertoli cells and prepachytene germ cells but not in pachytene spermatocytes and spermatids. In concordance with this, pachytene spermatocytes and spermatids isolated from wild-type testes did not display measurable amounts of IFNAR1 and phosphorylated STAT1 upon IFNβ challenge in vitro, suggesting hyporesponsiveness of these cell types to IFN. At day 60, Tg10 males were sterile, and Sertoli cells showed increased amounts of anti-Mullerian hormone and decreased production of inhibin B, both probably attributable to the massive germ cell loss. Type I interferon signaling may lead to idiopathic infertilities by affecting the interplay between germ cells and Sertoli cells.     

Octaploidy in idiopathic thrombocytopenic purpura

We report a case of an elderly 68-year-old male who presented in our hospital with chief complaints of petechial rashes and ecchymosis over extremities and bleeding from the oral cavity since 3-4 days prior to hospitalization. He saw a physician before coming to our hospital and received one dose of IV methylprednisolone and oral wysolone. He had come to our hospital for further management. Bone marrow karyotyping was done and chromosomal analysis revealed two cell lines. Eighty percent of the cells analyzed revealed apparently normal male karyotype. However, 20% cells analyzed revealed a total of 184 chromosomes, suggesting octaploidy.     

FCGR2C genotyping by pyrosequencing reveals linkage disequilibrium with FCGR3A V158F and FCGR2A H131R polymorphisms in a Caucasian population

The FCGR3A-V158F and FCGR2A-H131R polymorphisms are associated with clinical responses to therapeutic mAbs and with immune thrombocytopenic purpura (ITP). The FCGR2C-ORF/STOP polymorphism, controlling FcγRIIC expression on natural killer cells and therefore FcγRIIC-mediated antibody dependent cell-mediated cytotoxicity, is also associated with ITP. Using a new pyrosequencing assay to determine this polymorphism in a control population, we observed the expected allele frequencies (ORF:12.6%) and percentages of individuals with a single copy (10.0%) or 3 copies (12.1%) of FCGR2C, or with at least one FCGR2C-ORF allele (20.1%). No association of FCGR2C copy number variations with the FCGR3A-V158F or FCGR2A-H131R genotype was detected. More importantly, our results demonstrate a strong and a weaker linkage disequilibrium associating the FCGR2C-ORF allele with the FCGR3A-158V and the FCGR2A-131H allele, respectively.     

Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature

Neisseria meningitidis causes a severe, frequently fatal sepsis when it enters the human blood stream. Infection leads to extensive damage of the blood vessels resulting in vascular leak, the development of purpuric rashes and eventual tissue necrosis. Studying the pathogenesis of this infection was previously limited by the human specificity of the bacteria, which makes in vivo models difficult. In this protocol, we describe a humanized model for this infection in which human skin, containing dermal microvessels, is grafted onto immunocompromised mice. These vessels anastomose with the mouse circulation while maintaining their human characteristics. Once introduced into this model, N. meningitidis adhere exclusively to the human vessels, resulting in extensive vascular damage, inflammation and in some cases the development of purpuric rash. This protocol describes the grafting, infection and evaluation steps of this model in the context of N. meningitidis infection. The technique may be applied to numerous human specific pathogens that infect the blood stream.     

Integrated analyses identify the involvement of microRNA-26a in epithelial–mesenchymal transition during idiopathic pulmonary fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and highly lethal fibrotic lung disease with poor treatment and unknown etiology. Emerging evidence suggests that epithelial–mesenchymal transition (EMT) has an important role in repair and scar formation following epithelial injury during pulmonary fibrosis. Although some miRNAs have been shown to be dysregulated in the pathophysiological processes of IPF, limited studies have payed attention on the participation of miRNAs in EMT in lung fibrosis. In our study, we identified and constructed a regulation network of differentially expressed IPF miRNAs and EMT genes. Additionally, we found the downregulation of miR-26a in mice with experimental pulmonary fibrosis. Further studies showed that miR-26a regulated HMGA2, which is a key factor in the process of EMT and had the maximum number of regulating miRNAs in the regulation network. More importantly, inhibition of miR-26a resulted in lung epithelial cells transforming into myofibroblasts in vitro and in vivo, whereas forced expression of miR-26a alleviated TGF-β1- and BLM-induced EMT in A549 cells and in mice, respectively. Taken together, our study deciphered the essential role of miR-26a in the pathogenesis of EMT in pulmonary fibrosis, and suggests that miR-26a may be a potential therapeutic target for IPF.     

Idiopathic pulmonary fibrosis: new insights in its pathogenesis

Idiopathic pulmonary fibrosis (IPF) is a unique type of chronic fibrosing lung disease of unknown etiology. The sequence of the pathogenic mechanisms is unknown, but the disease is characterized by epithelial injury and activation, the formation of distinctive subepithelial fibroblast/myofibroblast foci, and excessive extracellular matrix accumulation. These pathological processes usually lead to progressive and irreversible changes in the lung architecture resulting in progressive respiratory insufficiency and an almost universally terminal outcome in a relatively short period of time. While research has largely focused on inflammatory mechanisms for initiating the fibrotic response, recent evidence strongly suggests that disruption of the alveolar epithelium is an underlying pathogenic event. Although treatment to date has proved largely ineffective, this new approach has opened up several promising therapeutic avenues.