Linkage exclusion and mutational analysis of the noggin gene in patients with fibrodysplasia ossificans progressiva (FOP)

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare and disabling genetic disorder characterized by congenital malformation of the great toes and by progressive heterotopic endochondral ossification in predictable anatomical patterns. Although elevated levels of bone morphogenetic protein 4 (BMP4) occur in lymphoblastoid cells and in lesional cells of patients with FOP, mutations have not been identified in the BMP4 gene, suggesting that the mutation in FOP may reside in a BMP4-interacting factor or in another component of the BMP4 pathway. A powerful antagonist of BMP4 is the secreted polypeptide noggin. A recent case report described a heterozygous 42-bp deletion in the protein-coding region of the noggin gene in a patient with FOP. In order to determine if noggin mutations are a widespread finding in FOP, we examined 31 families with 1 or more FOP patients. Linkage analysis with an array of highly polymorphic microsatellite markers closely linked to the noggin gene was performed in four classically-affected multigenerational FOP families and excluded linkage of the noggin locus to FOP (the multipoint lod score was -2 or less throughout the entire range of markers). We sequenced the noggin gene in affected members of all four families, as well as in 18 patients with sporadic FOP, and failed to detect any mutations. Single-strand conformation polymorphism (SSCP) analysis of 4 of these patients plus an additional 9 patients also failed to reveal any mutations. Among the samples analyzed by SSCP and DNA sequencing was an independently obtained DNA sample from the identical FOP patient previously described with the 42-bp noggin deletion; no mutation was detected. Examination of the DNA sequences of 20 cloned noggin PCR products, undertaken to evaluate the possibility of a somatic mutation in the noggin gene which could be carried by a small subset of white blood cells, also failed to detect the presence of the reported 42-bp deletion. We conclude that mutations in the coding region of noggin are not associated with FOP.     

Long-term potentiation deficits and excitability changes following traumatic brain injury

The effects of traumatic brain injury (TBI) on hippocampal long-term potentiation (LTP) and cellular excitability were assessed at postinjury days 2, 7, and 15. TBI was induced using a well-characterized central fluid-percussion model. LTP of the Schaffer collateral/commissural system was assessed in vivo in urethane-anesthetized rats. Significant LTP of the population excitatory postsynaptic potential (EPSP) slope was found only in controls, and no recovery to control levels was observed for any postinjury time point. Four measurement parameters reflecting pyramidal cell discharges (population spike) indicated that TBI significantly increased cellular excitability at postinjury day 2: (1) pretetanus baseline recording showed that TBI reduced population spike threshold and latency; (2) tetanic stimulation (400 Hz) increased population spike amplitudes to a greater degree in injured animals than in control animals; (3) tetanus-induced population spike latency shifts were greater in injured cases; and (4) tetanic stimulation elevated EPSP to spike ratios (E-S potentiation) to a greater degree in injured animals. These parameters returned to control levels, as measured on postinjury days 7 and 15. These results suggest that TBI-induced excitability changes persist at least through 2 days postinjury and involve a differential impairment of mechanisms subserving LTP of synaptic efficacy and mechanisms related to action potential generation     

Traumatic aneurysms of the descending thoracic aorta

From July 1979 to December 1985 we observed 51 patients with traumatic lesions of the descending thoracic aorta. Twenty-nine had acute ruptures, mostly accompanied by multiple injuries, and 27 had to be operated upon immediately. Twenty-two patients (19 males, 3 females) had chronic traumatic aneurysms of the descending thoracic aorta (more than six weeks after trauma). Mean age at the time of trauma was 24 years. Mean age at time of surgery was 36.5 years. Twelve patients were symptomatic. All were treated surgically. At surgery, complete aortic disruption was found in 15 patients and partial rupture in seven. We did not use aortic shunting of any kind, only aortic cross-clamping. Hypertension was controlled by intravenous drug infusion. The ruptured aortic segment was replaced in all cases by prosthetic Dacron graft. There were no operative deaths. One patient (age 77) died 11 weeks after surgery from multiple organ failure. One case of postoperative paraplegia was observed. This patient recovered almost completely from his neurological deficit.     

大鼠液压脑损伤后bax和bcl—XL的表达改变在mRNA和蛋白水平的相关性

目的探讨脑创伤后bax和bcl-XL在mRNA和蛋白水平的变化规律及其与神经细胞凋亡发生、发展的关系.方法在液压脑损伤模型中,应用逆转录聚合酶链反应、免疫组化分别检测大鼠脑创伤后不同时程bax和bcl-xL的表达;采用凋亡原位末端标记、电镜超微结构、DNA凝胶电泳观察脑创伤后细胞凋亡的形态和生化特征.结果伤后6h,bcl-xL.mRNA下调[伤侧半球为对侧的(67.42±7.54)%],bcl-xL蛋白水平下降[伤侧为对侧的(85.85±5.72)%].伤后3d,bcl-xLmRNA和bd-xL蛋白表达分别为对侧的(39.97±3.61)%和(57.50±6.21)%;baxmRNA和bax蛋白分别为对侧半球的(203.95±17.53)%和(189.02±7.23)%.伤后bax/bclxL比率升高比细胞凋亡提前出现,早期由于bcl-xL.的表达下降,后期主要是由于bax的升高所致.结论细胞凋亡及其调节基因的表达间具有一致性;脑创伤对bax和bcl-xL的调节发生在转录水平以前的某一环节.bax/bcl-xL平衡体系的维持或紊乱影响脑创伤后神经细胞生存或死亡.     

Current updates in management of extremity injuries in polytrauma

Injury-related morbidity and mortality have been one of the most common causes of loss in productivity across all geographic distributions. It remains to be a global concern despite a continual improvement in regional and national safety policies. The establishment of trauma care systems and advancements in diagnostics and management have improved the overall survival of severely injured. A better understanding of the physiopathological and immunological responses to injury led to a significant shift in trauma care from “Early Total Care” to “Damage Control Orthopedics.” While most of these algorithms were tailored to the philosophy of “life before limb,” the impact of improper fracture management on disability and societal loss is increasingly being recognized. Recently, “Early Appropriate Care” of extremities has gained importance; however, its implementation is influenced by regional health care policies, available resources, and expertise and varies between low and high-income countries. A review of the literature was performed using PubMed, Embase, Web of Science, and Scopus databases on articles published from 1990 to 2020 using the Mesh terms “Polytrauma,” “Multiple Trauma,” and “Fractures.” This review aims to consolidate on guidelines and available evidence in the management of extremity injuries in a polytraumatized patient to achieve better clinical outcomes of these severely injured.     

创伤性脑损伤患者脑脊液中嗜中性白细胞碱性磷酸酶-1的表达及意义

目的探讨炎性体蛋白嗜中性白细胞碱性磷酸酶-1(NALP-1)在创伤性脑损伤患者脑脊液中表达水平及其与预后相关性。方法选取2017年2月至2018年9月来自首都医科大学附属北京同仁医院的120例创伤性脑损伤患者,选取同期健康体检者30例作为对照组,采用免疫印迹化学发光法检测研究对象脑脊液中炎性体蛋白NALP-1表达水平,根据格拉斯哥预后评分(GOS)将创伤性脑损伤患者分为预后良好组(GOS>3分)和预后不良组(GOS≤3分)。χ²检验和t检验分析预后良好组和预后不良组NALP-1和临床资料差异,采用多因素Logistic回归模型分析创伤性脑损伤后患者预后影响因素。结果创伤性脑损伤患者脑脊液中NALP-1表达(1.64±0.52)高于对照组(0.94±0.28,t=7.108,P<0.05),差异有统计学意义。NALP-1高表达组急性生理与慢性健康状况评分Ⅱ(APACHEⅡ)得分(26.4±5.4)分、脑挫伤比例(76.62%)、蛛网膜下腔出血比例(77.27%)高于低表达组[(22.3±4.5)分、23.38%、22.73%],差异有统计学意义(χ²/t=4.135、9.586、7.424,P<0.05)。年龄[比值比(OR):2.175,95%可信区间(CI):1.167~8.767,P<0.05]、蛛网膜下腔出血(OR:1.241,95%CI:1.101~3.794,P<0.05)、NALP-1(OR:2.841,95%CI:1.675~10.717,P<0.05)、纤维蛋白原水平(OR:1.215,95%CI:1.056~3.627,P<0.05)、APACHEⅡ得分(OR:1.615,95%CI:1.314~5.485,P<0.05)是预后不良独立影响因素,差异均有统计学意义。结论创伤性脑损伤脑脊液中NALP-1表达增加,且表达量升高与预后不良相关。     

NOD样受体蛋白1炎性小体在创伤性中枢神经损伤中的作用

NOD样受体蛋白1（NOD-like receptor protein 1,NLRP1）炎性小体在人体固有免疫反应中发挥着重要作用,可促进半胱氨酸蛋白水解酶（cysteinyl aspartate specific proteinases,Caspases）的活化,进一步激活白介素-18和白介素-1β,同时介导细胞焦亡,NLRP1炎性小体在创伤性中枢神经损伤中发挥着作用,本文就NLRP1炎性小体的结构、NLRP1炎性小体在创伤性中枢神经损伤中的激活以及以NLRP1炎性小体为靶点的治疗等方面进行了综述。     

Novel approach to an early assessment of a patient’s potential for neurological remission after acute spinal cord injury: Analysis of hemoglobin concentration dynamics

Context/objective: Examining hemoglobin (Hb) dynamics with regard to the potential of neurological remission in patients with traumatic spinal cord injury (TSCI).Design: Prospective Clinical Observational Study.Setting: BG Trauma Centre Ludwigshafen, Department of Paraplegiology, Rhineland-Palatinate, Germany.Methods: From 2011 to 2017 a total of 80 patients with acute spinal injury were enrolled and divided into three groups: initial neurological impairment either with (G1; n = 33) or without subsequent neurological remission (G0; n = 35) and vertebral fractures without initial neurological impairment as control group (C; n = 12). Blood samples were taken for 3 months at 11 time-points after injury. Analyses were performed using routine diagnostics.Outcome measures: Multiple logistic regression was used to determine the prognostic value of Hb regarding neurological remission respecting clinical covariates.Results: Data showed elevated mean Hb concentrations in G1 from the third day to 1 month compared to G0, Hb levels were significantly higher in G1 after 3 days (P = 0.03, G1 > G0). The final multiple logistic regression model based on this data predicting the presence of neurological remission resulted in an AUC (area under the curve) of 80.5% (CI: 67.8%–93.2%) in the ROC (receiver operating characteristic) analysis.Conclusion: Elevated Hb concentrations are associated with a higher likelihood of neurological remission. Elevated concentrations of Hb in G1 compared to G0 over time might be linked to both a better initial oxygen supply response and a decreased ECM (extracellular matrix) degradation highlighting the role of Hb as a valuable biomarker for neural regeneration after TSCI.     

车祸致颅脑损伤患者家属心理健康状况与社会支持相关性研究

目的 了解车祸致颅脑损伤患者家属的心理健康状况和社会支持状况,探讨其相关性。方法 采用自编一般资料调查表、症状自评量表（SCL - 90）和社会支持量表（SSRS）,对225名到精神专科医院就诊的车祸致颅脑损伤患者家属进行问卷调查。结果 车祸致颅脑损伤患家属的SCL - 90总分为（178.45±82.56）分, SCL - 90总分、阳性项目数和9个因子分均显著高于肿瘤患者家属和全国常模(P＜0.05)。社会支持总分为（38.52±8.23）分,社会支持水平与家属的心理健康状况呈显著的负相关（r = - 0.416, P＜0.05）。多元线性回归分析显示,社会支持总分可以负向预测家属的心理健康状况（β = - 0.399,P＜0.05）。结论 车祸致颅脑损伤患者家属的心理问题发生率较高,应从个人、家庭和社会层面为家属提供社会支持资源。     

Inflammatory and non-inflammatory inclusion body myositis

Summary In ten patients with inclusion body myositis (IBM) five muscular biopsies showed profuse inflammatory exudates and three showed a few scattered inflammatory cells with partial invasion in some muscle fibers. No inflammatory cells were seen in two cases. In all patients, histopathological, histomorphometric and immunocytochemical studies were performed. Immunocytochemistry for the class I and class II major histocompatibility complex gene product (MHC) was performed in all cases and in ten control muscles including: normal muscles [3], dermatomyositis [3], polymyositis [3], scleroderma [1]. In the five cases of IBM with inflammatory exudates, subsets of lymphocytes were analyzed with a panel of monoclonal antibodies against B cells, T4 cells, T8 cells, K and natural killer cells and macrophages. Some muscle fibers expressed class I MHC antigens in the inflammatory cases of IBM. These fibers were near the inflammatory exudates and occasionally showed a partial invasion. No expression of class I MHC was found in normal muscles and in non-inflammatory cases of IBM. The antigen which triggers the mononuclear cells in the inflammatory forms of IBM is probably not the filamentous inclusions in rimmed vacuoles. In other inflammatory myopathies, expression of class I MHC was present on all fibers in polymyositis, only in the perifascicular area in dermatomyositis and in scleroderma. It could be suggested that the term inclusion body muscle disease be applied to cases with rimmed vacuoles and IBM-like filaments without inflammatory cells.