Dega骨盆截骨术后最佳中心边缘角的三维有限元分析

目的:应用三维有限元技术评估发育性髋关节脱位(developmental dysplasia of the hip,DDH)患儿在Dega骨盆截骨术后不同中心边缘角(center-edge angle,CEA)状态下髋臼的应力分布,为术前的手术规划提供有参考价值的生物力学结果。方法:使用已建立的DDH患者髋关节三维有限元模型,以术后CEA27°为中间值,每3°为一个变量,在Mimics誖10.0软件的模拟手术模块分别构建7组髋臼截骨术后的模型。在单腿站立和双腿站立状态下测量不同CEA状态下髋臼的应力分布。结果:单腿站立情况下,CEA为24°、27°、30°和33°的术后模型患侧髋臼的峰值应力接近正常侧。双腿站立情况下,CEA为24°时双侧髋臼的峰值应力最为接近。结论:对于该患者而言,在7组术后CEA中,24°时患侧髋臼的峰值应力与健侧最为接近,可以认为是最佳的术后CEA。有限元技术能够为Dega手术的术前规划提供个性化的指导方案。     

Monostotic fibrous dysplasia in the temporal bone: A late prehistoric occurrence

Fibrous dysplasia, characterized by benign osteolytic and osteoblastic lesions may involve one or several bones. Recent investigators have suggested that it may be merely a phase of what have previously been thought to be several different bone disease. Isolated fibrous dysplasia in the temporal bone is infrequent. Several reports of this disease have appeared in the literature of paleopathology, but none involved only the temporal bone. Monostotic involvement of the right temporal bone was discovered in the skull of an adult male recovered from an archeological site dating from the Late Mississippian period (A. D. 1,350–A. D. 1,650). It will provide an opportunity for preliminary documentation of the antiquity of this disease in the southeastern portion of the United States.     

Mechanisms of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a chronic lung disease affecting premature infants with long term effect on lung function into adulthood. Multiple factors are involved in the development of BPD. This review will summarize the different mechanisms leading to this disease and highlight recent bench and clinical research targeted at understanding the role of the mesenchyme (both its cellular and extracellular components) in the pathogenesis of BPD.     

A Japanese child with geleophysic dysplasia caused by a novel mutation of FBN1

Geleophysic dysplasia (GD) is a rare disorder characterized by severe short stature, short hands and feet, limited joint mobility, skin thickening, characteristic facial features (e.g., a “happy” face), and cardiac valvular disorders that often result in an early death. The genes ADAMTSL2 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif-like 2) and FBN1 (fibrillin 1) were recently identified as causative genes for GD. Here, we describe a 10-year-old Japanese female with GD who was born to non-consanguineous parents. At the age of 11 months, she was referred to our hospital because of very short stature for her age (− 4.4 standard deviations of the age-matched value) and a “happy” face with full cheeks, a shortened nose, hypertelorism, and a long and flat philtrum, characteristic of GD. Her hands and feet were small, her skin was thickened, and her joint mobility was generally limited. She had cardiac valvular disorders and history of recurrent respiratory failure. Mutation analysis revealed no abnormalities in ADAMTSL2. However, analysis of FBN1 revealed a novel heterozygous mutation (c.5161T > T/G) in exon 41, which encodes transforming growth factor-β-binding protein-like domain 5 (TB5). GD is an extremely rare disorder and, to our knowledge, only one case of GD with an FBN1 mutation has been reported in Japan. Similar to the previously reported cases of GD, the mutation in the current patient was located in the TB5 domain, which suggests that abnormalities in this domain of FBN1 are responsible for GD.     

Selective inactivation of LGI1 in neuronal precursor cells leads to cortical dysplasia in mice

Constitutional mutations in Leucine‐rich glioma inactivated 1 (LGI1) predispose to an autosomal dominant epilepsy syndrome in humans and germline inactivation of LGI1 in mice leads to early onset seizures. LGI1 is highly expressed in the regions involved in neuronal stem cell generation and migration and detailed analysis of the brains in these mice reveals a subtle cortical dysplasia characterized by hypercellularity in the outer cortical layers. To investigate the cellular origin for this cortical dysplasia, we created mice that allow cell‐specific, conditional inactivation of LGI1. Exons 3–4, which contain critical motifs for LGI1 function, were targeted for deletion and, using a CMV‐cre mouse strain, global inactivation of LGI1 led to early onset seizures and the same cortical dysplasia seen in the constitutionally null mice. Similarly, inactivation of LGI1 in cells expressing Nestin, expressed primarily in neuronal precursor cells, led to early onset seizures and cortical dysplasia. In contrast, targeting inactivation of LGI1 in cells expressing Gfap, Camk2a, and parvalbumin, did not lead to cortical dysplasia. This strain of mouse, therefore, allows for a more refined investigation of the cell types involved in the cortical dysplasia seen following inactivation of LGI1 and potentially a better understanding of the molecular mechanisms behind LGI1‐induced epilepsy.     

Mouse models of the laminopathies

The A and B type lamins are nuclear intermediate filament proteins that comprise the bulk of the nuclear lamina, a thin proteinaceous structure underlying the inner nuclear membrane. The A type lamins are encoded by the lamin A gene (LMNA). Mutations in this gene have been linked to at least nine diseases, including the progeroid diseases Hutchinson-Gilford progeria and atypical Werner's syndromes, striated muscle diseases including muscular dystrophies and dilated cardiomyopathies, lipodystrophies affecting adipose tissue deposition, diseases affecting skeletal development, and a peripheral neuropathy. To understand how different diseases arise from different mutations in the same gene, mouse lines carrying some of the same mutations found in the human diseases have been established. We, and others have generated mice with different mutations that result in progeria, muscular dystrophy, and dilated cardiomyopathy. To further our understanding of the functions of the lamins, we also created mice lacking lamin B1, as well as mice expressing only one of the A type lamins. These mouse lines are providing insights into the functions of the lamina and how changes to the lamina affect the mechanical integrity of the nucleus as well as signaling pathways that, when disrupted, may contribute to the disease.     

胃癌发展相关阶段中E-cadherin基因启动子甲基化及蛋白表达的研究

为了研究E cadherin基因启动子甲基化在胃癌发生及发展阶段中的作用 ,我们采用甲基化特异性PCR和免疫组化的方法对异型增生 (2 3例 )、早期胃癌 (2 0例 )和进展期胃癌 (2 0例 )石蜡标本进行启动子甲基化状态及蛋白表达的分析。结果表明E cadherin基因启动子在异型增生、早期胃癌和进展期胃癌中均有甲基化 ,其阳性率分别为78 3% ,80 %和 90 % ,经χ2 检验各病例组与正常组 (30 % )比较均有差异 (P <0 0 5 ) ,但各病例组间没有差异 (P >0 0 5 ) ;进展期胃癌E cadherin蛋白表达全部阴性 ,早期胃癌 70 %阴性 ,异型增生中无蛋白阴性 ,在早期胃癌和进展期胃癌 34例蛋白表达阴性的标本中 31例有启动子甲基化 (91 2 % ) ,蛋白表达与启动子甲基化呈明显负相关 (P <0 0 1)。表明E cadherin启动子甲基化是胃癌发生的早期事件 ,也是胃癌发生、进展的重要事件     

异型增生上皮和口腔鳞癌组织EGFR和PCNA表达意义及相关性研究

采用免疫组化S－P法研究表皮生长因子受体（EGFR）、增殖核抗原（PCNA）在口腔粘膜上皮异型增生及口腔鳞癌组织中的表达意义及其相互关系。结果表明,EGFR及PCNA的正常口腔粘膜上皮为阴性或仅在上皮基底层有少量阳性表达。上皮异型增生时,随病变程度加重,阳性表达呈递增趋势（P＜0.01）,至重度异型增生时,PCNA表达与鳞癌无显性差异（P＞0.05）,EGFR表达甚至超过高分化鳞癌。口腔鳞癌组织随分化程度降低,阳性表达率相应增加（P＜0.01）。EGFR表达与PCNA表达有明显相关性（P＜0.01）。EGFR和PCNA可作为评估和监测口腔粘膜上皮恶变潜能,判断口腔鳞癌恶性度的有用标记物。     

Solution structure of NEMO zinc finger and impact of an anhidrotic ectodermal dysplasia with immunodeficiency-related point mutation

The regulatory NEMO (NF-κB essential modulator) protein has a crucial role in the canonical NF-κB signaling pathway notably involved in immune and inflammatory responses, apoptosis and oncogenesis. The regulatory domain is located in the C-terminal half of NEMO and contains a classical CCHC-type zinc finger (ZF). We have investigated the structural and functional effects of a cysteine to phenylalanine point mutation (C417F) in the ZF motif, identified in patients with anhidrotic ectodermal dysplasia with immunodeficiency. The solution structures of the wild type and mutant ZF were determined by NMR. Remarkably, the mutant adopts a global ββα fold similar to that of the wild type and retains thermodynamic stability, i.e., the ability to bind zinc with a native-like affinity, although the last zinc-chelating residue is missing. However, the mutation induces enhanced dynamics in the motif and leads to an important loss of stability. A detailed analysis of the wild type solution structure and experimental evidences led to the identification of two possible protein-binding surfaces that are largely destabilized in the mutant. This is sufficient to alter NEMO function, since functional complementation assays using NEMO-deficient pre-B and T lymphocytes show that full-length C417F pathogenic NEMO leads to a partial to strong defect in LPS, IL-1β and TNF-α-induced NF-κB activation, respectively, as compared to wild type NEMO. Altogether, these results shed light onto the role of NEMO ZF as a protein-binding motif and show that a precise structural integrity of the ZF should be preserved to lead to a functional protein-recognition motif triggering full NF-κB activation.