慢性脑低灌注大鼠海马Arc低表达与其认知功能障碍的相关性研究

目的 探讨慢性脑低灌注大鼠海马活性调节的细胞骨架相关蛋白(activity-regulated cytoskeletal-associated protein,Arc)的低表达与其认知功能障碍的相关性。方法 大鼠慢性脑低灌注模型使用持久性双颈总动脉结扎术(2-vessel occlusion,2-VO); 大鼠随机分成假手术组和2-VO组,每组各6只。术后第8周行Morris水迷宫评价其认知功能; 实时定量聚合酶链式反应(Real time quantitative polymerase chain reaction,RT-qPCR)及蛋白免疫印迹法检测大鼠海马Arc mRNA及蛋白表达水平。结果(1)2-VO组大鼠第2～5 d的逃逸潜伏期比假手术组明显延长(P<0.01)及其在原平台区域游泳时间明显比假手术组短(P<0.01);(2)2-VO组大鼠海马Arc mRNA水平及免疫反应条带相对灰度值分别比假手术组明显降低(P均<0.01);(3)空间探索实验中2-VO大鼠在原平台区域游泳时间与海马Arc免疫反应条带相对灰度值呈正相关(r=0.7085,P<0.05)。结论 慢性脑低灌注大鼠的认知功能障碍可能与海马Arc的低表达相关。     

Bridges between Nervous and Immune Systems: Their Disconnection and Clinical Consequences

Nervous and immune systems are connected by several mutual links, thus constituting a diffuse functional network in the body. In particular, neurohormones, neuropeptides, and cytokines represent the major mediators of the so-called psychoneuroendocrinoimmune axis. In this review, special emphasis is placed on certain pathologies characterized by a disconnection of the existing bridges between nervous and immune systems. For instance, spinal cord injury (SCI) is a clinical condition in which loss of neurons and very poor axon growth represent the main features. The role played by infiltrating and resident immunocompetent cells is still debated in SCI. However, to enhance axon growth in SCI, current therapeutic attempts are based on the stimulation of the immune response within the central nervous system, thus triggering either cell-mediated or humoral immune responsiveness.     

Leki immunomodulujące – przełom w leczeniu nowotworów hematologicznych

Introduction of new drugs into therapy of multiple myeloma prolonged significantly progression free survival and overall survival of patients. Taking into account pleiotropic effects of these drugs it was shown that immunomodulatory drugs are very effective in other haematological malignancies such as lymphomas, myelodysplastic syndromes, leukemias or chronic myeloproliferative diseases.     

Powikłania infekcyjne i autoimmunologiczne w przewlekłej białaczce limfocytowej

Profound disturbances of different elements of the immune system in chronic lymphocytic leukemia (CLL) lead to impaired elimination of allogeneic antigens, like pathogenic microorganisms, and deficient tolerance of self-antigens, which is responsible for autoimmunological disorders. Susceptibility to infections in CLL patients is due to disease-related immunodeficiency, mainly hypogammaglobulinemia, and aggravated by myelo- and immunosuppressive properties of currently used antileukemic drugs, especially alkylating agents and purine analogues. Severe infections occur in the majority of CLL patients, they may be life-threatening and shortening the patients’ survival. They affect most frequently the respiratory system, and are caused mainly by Gram-positive and Gram-negative bacteria and common viruses like Herpes and Varicella-Zoster. In some patients, especially those treated with purine analogues, opportunistic infections can occur. There are no generally admitted guidelines for the prophylaxis of infections. Vaccinations against influenza and encapsulated bacteria, intravenous immunoglobulins and prophylaxis with cotrimoxazol and antiviral drugs for selected patients under purine analogues or alemtuzumab have been proposed. Autoimmune hemolytic anemia (AIHA) due to the production of anti-erythrocyte autoantibodies is the most common autoimmunological complication of CLL, especially in patients with positive direct antiglobulin test (DAT). It can be also triggered by alkylating agents and purine analogues. The treatment of AIHA includes corticosteroids, rituximab, immunosuppressive agents and splenectomy. Autoimmune thrombocytopenia, pure red cell aplasia, autoimmune neutropenia and non-hematological autoimmune manifestations can also occur.     

CT及MRI多模态参数对鉴别胰头部肿块型慢性胰腺炎与胰头癌的价值

目的分析胰头部肿块型慢性胰腺炎(MFCP)与胰头癌的CT以及MRI定性及定量表现,总结二者有效的影像鉴别特点。方法选取我院16例胰头部MFCP及16例胰头癌临床及影像资料进行回顾性分析。结果胰头部MFCP与胰头癌影像表现:1)肿块形态密度:分叶状(2例,11例),假性囊肿(11例,0例),肿块内钙化(6例,0例);2)DWI高信号:(2例,14例);3)静脉期相对低密度(3例,15例);ROC曲线分析示静脉期CT差值鉴别二者的AUC=0.852;4)胰胆管表现:主胰管扩张(9例,12例),胰管病灶处截断(1例,10例),胆总管扩张(6例,12例),胆总管病灶处截断(2例,10例),双管征(7例,11例),不相交征(1例,12例),肝内胆管扩张(2例,11例);5)周围组织表现:肾周筋膜增厚(9例,3例),胰周血管包绕受侵(1例,2例)。结论胰头部MFCP与胰头癌的影像学表现具有特异性,肿块的形态、DWI信号、胰胆管扩张程度及二者的血供特点有助于二者诊断及鉴别诊断。     

Hip and knee muscle torque and its relationship with dynamic balance in chronic ankle instability,copers and controls

ObjectivesWe compared hip and knee isometric muscle torque between individuals with chronic ankle instability (CAI), those who have sustained one ankle sprain with no ongoing problems (copers) and healthy controls. Our secondary objective was to compare balance between groups and investigate the relationship between muscle torque and balance.DesignCross-sectional study.Methods22 CAI, 20 copers and 22 uninjured participants were tested. Isometric torque (normalised to body mass (Nm/kg)) was measured using a rigidly-fixated hand-held dynamometer. Balance was assessed with the Y-balance test.ResultsKnee and hip flexor and extensor, and hip adductor and abductor muscle torque was less in individuals with CAI compared to controls (standardised mean difference (SMD) >1.2). Hip and knee flexor and extensor muscle torque was less in CAI participants than copers (SMD: 0.69–1.1). Hip external and internal rotator torque did not differ between groups. There was no difference in hip or knee muscle torque between controls and copers (SMD: 0.01–0. 54). Balance was impaired in CAI participants compared to copers and controls in all directions. There was a strong positive correlation between posterolateral Y-balance test performance and torque of the hip adductors (r = 0.53), flexors (r = 0.52) and extensors (r = 0.50).ConclusionsIndividuals with CAI have weak knee and hip muscles compared to copers and controls. Hip strength was shown to be related to posterolateral balance performance. Future studies may investigate the effect of hip and knee strengthening exercise on ongoing ankle problems, such as episodic giving way in individuals with CAI.     

Effects of mild chronic cerebral hypoperfusion and early amyloid pathology on spatial learning and the cellular innate immune response in mice

Understanding the contribution of cerebrovascular factors in the progression of cognitive decline in Alzheimer's disease (AD) is a key step for the development of preventive therapies. Among these factors, chronic cerebral hypoperfusion is an early component of AD pathogenesis that can predict the progression from mild cognitive impairment to AD. Here, we investigated the effects of a protocol of mild chronic cerebral hypoperfusion in the APPswe/PS1 transgenic mouse model of AD. We observed that the permanent occlusion of the right common carotid artery induced spatial learning impairments in young APPswe/PS1 mice, but not in their wild type littermates. Furthermore, the extent of learning deficits strongly correlated with the number of cortical β-amyloid plaques, with the mobilization of monocytes into the blood and with the number of bone marrow-derived microglia in the brain. These results indicate that a mild reduction of cerebral blood flow can selectively induce cognitive deficits at an early stage of amyloid pathology, eliciting a cellular innate immune response, even without causing neuronal death.     

DSC perfusion-based collateral imaging and quantitative T2 mapping to assess regional recruitment of leptomeningeal collaterals and microstructural cortical tissue damage in unilateral steno-occlusive vasculopathy

Leptomeningeal collateral supply is considered pivotal in steno-occlusive vasculopathy to prevent chronic microstructural ischaemic tissue damage. The aim of this study was to assess the alleged protective role of leptomeningeal collaterals in patients with unilateral high-grade steno-occlusive vasculopathy using quantitative (q)T2 mapping and perfusion-weighted imaging (PWI)-based collateral abundance. High-resolution qT2 was used to estimate microstructural damage of the segmented normal-appearing cortex. Volumetric abundance of collaterals was assessed based on PWI source data. The ratio relative cerebral blood flow/relative cerebral blood volume (rCBF/rCBV) as a surrogate of relative cerebral perfusion pressure (rCPP) was used to investigate the intravascular hemodynamic competency of pial collateral vessels and the hemodynamic state of brain parenchyma. Within the dependent vascular territory with increased cortical qT2 values (P = 0.0001) compared to the contralateral side, parenchymal rCPP was decreased (P = 0.0001) and correlated negatively with increase of qT2 (P  < 0.05). Furthermore, volumetric abundance of adjacent leptomeningeal collaterals was significantly increased (P < 0.01) and negatively correlated with changes of parenchymal rCPP (P = 0.01). Microstructural cortical damage is closely related to restrictions of antegrade blood flow despite increased pial collateral vessel abundance. Therefore, increased leptomeningeal collateral supply cannot necessarily be regarded as a sign of effective compensation in patients with high-grade steno-occlusive vasculopathy.     

Skewing of the B cell receptor repertoire in myalgic encephalomyelitis/chronic fatigue syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterized by fatigue and post-exertional malaise, accompanied by various signs of neurological and autonomic dysfunction. ME/CFS is often triggered by an infectious episode and associated with an aberrant immune system. Here we report that ME/CFS is a disorder characterized by skewed B cell receptor gene usage. By applying a next-generation sequencing to determine the clone-based IGHV/IGHD/IGHJ repertoires, we revealed a biased usage of several IGHV genes in peripheral blood B cells from ME/CFS patients. Results of receiver operating characteristic (ROC) analysis further indicated a possibility of distinguishing patients from healthy controls, based on the skewed B cell repertoire. Meanwhile, B cell clones using IGHV3-30 and IGHV3-30-3 genes were more frequent in patients with an obvious infection-related episode at onset, and correlated to expression levels of interferon response genes in plasmablasts. Collectively, these results imply that B cell responses in ME/CFS are directed against an infectious agents or priming antigens induced before disease onset.