地中海贫血脊柱旁髓外造血的影像学特征

目的探讨地中海贫血脊柱旁髓外造血的MRI与cT特征。方法收集5例地中海贫血病例,男3例。女2例,年龄18～31岁,全部病例均经病理证实,2例行MR检查,3例行cT检查,分析脊柱旁髓外造血的MRI与cT表现。结果2例患者MRT。WI、T2WI上椎体及肋骨为普遍性、均匀性低信号,髓外造血表现为脊柱旁边界清晰的肿块,rI弭rI信号不均匀稍高信号,T1WI为稍高信号,增强后强化较明显。3例患者CT上肋骨呈膨胀性改变,肋骨、椎体及其附件骨小梁稀疏、粗大;髓外造血的椎旁肿块平扫为均匀的等密度,增强后中等均匀强化。结论地中海贫血并脊柱旁髓外造血具有较特征性的影像学表现。     

髓外造血的影象学诊断分析及研究

目的:分析髓外造血的影象学诊断的临床意义。方法:选取住院接受治疗的髓外造血患者22例,选取时间为2008年5月-2018年10月,所有患者在治疗前均接受MRI和CT(胸腔、肝、脾、肠管)影像学检查,对MRI和CT影像学资料进行分析(病灶的部位、病变的情况、病灶周围的组织变化),总结该病的影像学的特点和表现。结果:在对患者实施CT平扫时发现,患者的软组织肿块的密度均匀,增强后中度强化。MR表现为T1WI低信号以及T2WI高信号,增强后可见肝脾造血时可见肝脾增大,但缺乏特异性。结论:对髓外造血的CT或MRI表现具有明显的特征性,可以结合典型的影像学特点对患者的疾病做出准确的诊断。     

Heal thyself: Potential applicability of stem cell therapy in the management of heart disease

Acute myocardial infarction results in regional necrotic heart tissue that is considered irreversible. Although angioplasty and thrombolytic therapy can remove the offending atherosclerotic plaque and thrombi, both therapies are dependent upon timely recognition and initiation of treatment and thus have a limited window of opportunity. No currently available therapy has the capability to restore cardiomyocytes or to replace myocardial scar tissue with contractile tissue. In animal models, use of a wide range of cells such as fetal cardiomyocytes, skeletal myoblasts, and bone marrow stem cells have been shown to differentiate into functional cardiomyocytes. In addition, transplantation of adult stem cells directly into the area of infarction has shown clinical promise. This article explores the current data on extramedullary hematopoiesis, stem cell differentiation, and stem cell therapy and its ability to repair injured or ischemic cardiac tissue.     

Physiology of normal bone marrow

The bone marrow is a richly innervated and highly vascularized tissue of the body responsible for hematopoiesis. The major functions include transporting oxygen, defense against foreign invasion, and hemostasis. An uncommitted pluripotent stem cell undergoes proliferation and differentiation in an orderly fashion, producing immature committed progenitors. The progenitors ultimately produce mature committed cells that are released into the circulating blood. Cell production is controlled by a variety of regulatory mechanisms, including growth factors. The availability of recombinant growth factors has stimulated clinical trials of these factors in a wide variety of hematologic diseases.     

剔除成骨细胞特异性基因Smad4不影响小鼠造血稳态的维持

体内证实,成骨细胞作为造血干细胞（HSC）niche的组成部分是随着基因修饰小鼠模型的建立而实现的,成骨细胞构成了HSC自我更新和多向分化的重要微环境。Smad4基因在成骨细胞的特异性剔除可导致小鼠成骨细胞数量的下降和骨内膜面积的减少。为了阐明体内成骨细胞的减少是否影响小鼠骨髓的造血活性,本研究对成骨细胞特异性Smad4基因剔除小鼠的骨髓和髓外造血进行了系统分析,采用流式细胞技术检测骨髓和肝脏、脾脏成熟血细胞的比例;用集落培养技术、脾结节形成实验和LSK细胞分析检测不同阶段造血前体细胞的数量。结果显示,条件剔除小鼠的骨髓造血稳态维持正常,没有髓外造血的表现,特别是其不同阶段的造血前体细胞比例正常,而单位体重的细胞数量反而增加。结论：体内成骨细胞数量的减少不是导致骨髓造血活性下降的决定性因素。     

The stimulatory effects of interleukin (IL)-12 on hematopoiesis are antagonized by IL-12-induced interferon gamma in vivo

Interleukin (IL)-12 synergizes with other cytokines to stimulate the proliferation and differentiation of early hematopoietic progenitors in vitro. However, in vivo administration of IL-12 decreases peripheral blood counts and bone marrow hematopoiesis. Here, we used interferon (IFN) gamma receptor-deficient (IFN gamma R-/-) mice to investigate whether the in vivo inhibition of hematopoiesis by IL-12 is indirectly mediated by IL-12-induced IFN-gamma. IL-12 administered for 4 d (1 microgram/mouse per day) resulted in lower peripheral blood counts and a 2-fold decrease in bone marrow cellularity in wild-type mice, but not in IFN gamma R-/- mice. Bone marrow hematopoietic progenitors were decreased after IL-12 treatment in wild-type mice, but rather increased in IFN gamma R-/- mice. Splenic cellularity was 2.3-fold higher after IL-12 administration in wild-type mice, largely due to natural killer (NK) cell and macrophage infiltration together with some extramedullary hematopoiesis. In IFN gamma R-/- mice, spleen cellularity was less increased, there were fewer infiltrating NK cells, but a strong extramedullary hematopoiesis. Thus, alterations mediated by IL-12- induced IFN-gamma include reduction in bone marrow cellularity and hematopoietic progenitors, as well as pronounced splenomegaly, largely caused by NK cell infiltration. In the absence of IFN-gamma signaling, IL-12 promotes hematopoiesis, consistent with its in vitro activities.     

Chronic inflammation impairs hematopoiesis and survival after irradiation

Our studies show that the induction of a chronic inflammatory lesion in the left hind legs of mice by administration of 5000 rad produced distinct abnormalities of the hematopoietic system. A peripheral neutrophilia accompanied reduced numbers of total nucleated cells, stem cells, stromal cells, erythroblasts, and lymphocytes in the unirradiated femoral marrow, and the spleen was enlarged. Mice with these hematopoietic abnormalities promptly succumbed with bone marrow failure to a sublethal dose of total body irradiation (600 rad TB). Acute inflammation associated with a sterile abscess also impaired survival after 600 rad TB. Hematopoietic abnormalities resembling those in mice with inflammation had been reported in mice bearing a solid extramedullary tumor of sarcoma-180. Concomitant studies showed that bone marrow failure and impaired survival after 600 rad TB administered to mice bearing sarcoma-180 occurred at the same time as that in mice with chronic inflammation. We concluded that chronic inflammation or tumor produced similar abnormalities in the bone marrow and spleen that led to markedly impaired survival and death from bone marrow failure after a sublethal dose of total body irradiation. Although the extramedullary hematopoiesis in the enlarged spleen indicated that its microenvironment supported hematopoiesis, whereas that in marrow was reduced, it was insufficient to compensate for a total body deficit of functional stem cells.     

急性白血病髓外复发的18F-FDG PET/CT特点

目的 探讨急性白血病（AL）髓外复发的¹⁸F-FDG PET/CT影像特点。方法 回顾分析30例AL髓外复发患者的PET/CT,观察髓外受累的器官或组织类型、最大标准化摄取值（SUV_max）及骨髓FDG摄取,比较急性淋巴细胞白血病（ALL）和急性髓系白血病（AML）的差异。结果 16例ALL累及45个髓外器官或组织,14例AML累及29个髓外器官或组织;前者髓外病灶的平均SUV_max为7.38±4.46,高于后者的4.87±2.66（t=3.022,P=0.003）。ALL患者累及淋巴结及软组织的病例数均为10例,平均SUV_max分别为6.38±3.55和10.12±5.48;AML患者累及淋巴结及软组织的病例数均为6例,平均SUV_max分别为4.82±1.43和6.60±4.58（P均>0.05）。5例ALL髓内复发者骨髓均为多灶性摄取,5例AML髓内复发者3例为弥漫性摄取,2例为多灶性摄取。结论 AL髓外复发的¹⁸F-FDG PET/CT影像表现有一定特点;ALL及AML的常见髓外复发部位均为淋巴结和软组织;ALL复发病灶FDG代谢活性较高;骨髓多灶性摄取对髓内复发有提示意义。     

特发性骨髓纤维化的发病机制研究进展

特发性骨髓纤维化（idiopathic myelofibrosis，IMF）是一种慢性骨髓增殖性疾病（chronic myeloproliferative disorders，CMPD），以脾增大，幼粒一幼红细胞性贫血，泪滴状红细胞以及不同程度的骨髓纤维化和髓外造血（extr—amedullary haematopoiesis）为特点。本文对特发性骨髓纤维化的生物学特性以及发病机制，诸如酪氨酸激酶受体突变、γ-氨基丁酸转运蛋白1（GATAl）突变，JAK2基因突变，C—MPl受体突变和与特发性骨髓纤维化有关的其他发病机制加以综述，     

Hepatocyte growth factor ameliorates acute graft-versus-host disease and promotes hematopoietic function

Acute graft-versus-host disease (GVHD) is a major complication of bone marrow transplantation (BMT) and is characterized by hematopoietic dysfunction, immunosuppression, and tissue injury in the skin, liver, and intestinal mucosa. Hepatocyte growth factor (HGF), originally identified and cloned as a potent mitogen for hepatocytes, induces mitogenic and antiapoptotic activity in various epithelial cells and promotes hematopoiesis. Working in a murine model of acute GVHD, we performed repeated transfection of the human HGF cDNA into skeletal muscle and showed that this treatment inhibited apoptosis of intestinal epithelial cells and donor T-cell infiltration into the liver, thereby ameliorating the enteropathy and liver injury caused by acute GVHD. HGF also markedly suppressed IFN-gamma and TNF-alpha expression in the intestine and liver and decreased the serum IL-12. Furthermore, extramedullary hematopoiesis by donor cells was increased, and the survival rate was improved. These results suggest that HGF may be useful for controlling acute GVHD after allogeneic BMT.     

Tumefactive extramedullary hematopoiesis of the stomach

A 3×4 cm submucosal gastric mass of extramedullary hematopoietic tissue occurred in a patient with chronic myelogenous leukemia. Such stomach masses have been misinterpreted as malignant tumor. Tumefactive extramedullary hematopoiesis of the stomach is an infrequent occurrence in patients with extramedullary hematopoiesis but should be considered in the differential diagnosis of patients known to have this condition.     

Expression of IL-5 alters bone metabolism and induces ossification of the spleen in transgenic mice

We have developed a transgenic mouse line, NJ.1638, which expresses high levels of IL-5 from T cells, with profound hematological consequences. Eosinophils comprise more than 60% of circulating white blood cells in these animals, with the total peripheral white blood cell counts increasing more than 40-fold relative to wild-type littermates. This extraordinary proliferative capacity is sustained by expanded sites of extramedullary hematopoiesis and is accompanied by multifocal, ectopic bone formation in the spleen. Histology of the splenic nodules revealed the presence of osteoid matrices and osteocytes trapped within mineralized trabecular plates. In addition, polarized light microscopy of calcified tissue sections revealed both woven bone and areas of organized lamellar bone. Morphometric assessments demonstrated that both the growth and mineralization of splenic bone occurred at rates nearly an order of magnitude higher than in skeletal bone. Skeletal bone metabolic parameters were also perturbed. We also observed heterotopic ossification of the spleen and perturbation of skeletal bone homeostasis following adoptive engraftment of transgenic marrow to wild-type recipients. These data suggest that IL-5 overexpression mediates bone formation through the mobilization of marrow-derived osteogenic progenitors and/or the inhibition of recruited osteoclasts.     

阵发性睡眠性血红蛋白尿症临床缓解患者仍可查出异常血细胞

目的观察临床完全缓解的阵发性睡眠性血红蛋白尿症（ＰＮＨ）患者体内是否仍有异常造血细胞并探讨其临床意义。方法用免疫荧光标记及流式细胞术检测患者骨髓有核细胞、外周血红细胞ＣＤ５９抗原表达及骨髓ＣＤ３４＋造血干／祖细胞数。结果２例临床完全缓解的ＰＮＨ患者体内仍呈正常造血细胞与异常克隆并存状态,但与未缓解ＰＮＨ患者相比,完全缓解患者外周血红细胞、骨髓单个核细胞及ＣＤ３４＋细胞中均以正常的ＣＤ５９＋细胞为主,表明体内异常克隆造血优势已经消失。结论临床完全缓解的ＰＮＨ患者仍可有残存的异常克隆;ＰＮＨ达到临床完全缓解并不一定需要体内异常克隆的彻底消灭;ＰＮＨ患者体内异常克隆的造血优势在一定条件下是可以消失的。     

Transforming growth factor beta 1 selectively regulates early murine hematopoietic progenitors and inhibits the growth of IL-3-dependent myeloid leukemia cell lines

Transforming growth factor beta 1 (TGF-beta 1) has been shown to be associated with active centers of hematopoiesis and lymphopoiesis in the developing fetus. Therefore, the effects of TGF-beta 1 on mouse hematopoiesis were studied. TGF-beta 1 is a potent inhibitor of IL-3-induced bone marrow proliferation, but it does not inhibit the proliferation induced by granulocyte/macrophage, colony-stimulating factor (CSF), granulocyte CSF, and erythropoietin (Epo). TGF-beta 1 also inhibits IL-3-induced multipotential colony formation of bone marrow cells in soft agar, which includes early erythroid differentiation, while Epo-induced terminal differentiation is unaffected. In addition, IL-3-induced granulocyte/macrophage colonies were inhibited; however, small clusters of differentiated myeloid cells were consistently seen in cultures containing IL-3 and TGF-beta 1. Thus, TGF-beta 1 selectively inhibits early hematopoietic progenitor growth and differentiation but not more mature progenitors. TGF-beta 1 is also a potent inhibitor of IL-3-dependent and -independent myelomonocytic leukemic cell growth, while the more mature erythroid and macrophage leukemias are insensitive. Therefore, TGF-beta 1 functions as a selective regulator of differentiating normal hematopoietic cells, and suppresses myeloid leukemic cell growth.     

川芎嗪促进放射损伤小鼠骨髓微环境修复VEGF/flk-1途径作用的研究

目的:探讨川芎嗪对放射损伤小鼠骨髓基质细胞(BMSCs)中血管内皮生长因子(VEGF)表达的影响及其意义.方法:采用蛋白免疫印迹(Western blot)法、免疫组化法及流式细胞术,对放射损伤小鼠BMSCs中VEGF蛋白表达水平、骨髓组织中VEGF受体胎肝激酶-1(flk-1)表达变化、BMSCs凋亡率及细胞周期改变进行分析,同时观察川芎嗪的影响.结果:放射损伤后小鼠BMSCs中VEGF和骨髓组织中flk-1表达均明显低于正常水平,随时间推移而逐渐升高,但照射后第14 d仍未恢复正常;而川芎嗪组在第14 d时已接近正常水平.放射损伤后BMSCs停滞于G0/G1期,S期合成减少,凋亡率明显增加;随时间推移G0/G1期细胞比例呈由高到低变化,凋亡率也逐渐降低,但第14 d时仍未恢复正常;用川芎嗪治疗后,BMSCs的S期合成活跃,凋亡率明显下降,第14 d时恢复更明显,接近正常水平.骨髓切片苏木素-伊红(HE)染色也证实川芎嗪组小鼠造血恢复明显较对照组快.结论:川芎嗪促进BMSCs中VEGF的表达,通过VEGF/flk-1途径改善放射损伤小鼠骨髓微环境,是其促进造血功能恢复的机制之一.     

造血干细胞与骨髓微环境相互作用的研究进展

造血干细胞移植(HSCT)后,供者造血干细胞(HSC)的归巢和植入直接影响移植的效果.HSC位于骨髓微环境即HSC龛中,并与骨髓微环境相互作用调节其自我更新和多向分化,维持骨髓造血功能动态平衡.近期,研究者们采用不同的创新方法观察移植后骨髓中HSC与骨髓微环境的相互作用关系,发现骨髓微环境对HSC稳态起重要作用,同时HSC也对“龛”的完整性形成必不可少.现就HSC与骨髓微环境的相互作用作一简要综述.     

Anemia in children

Anemia is one of the most common symptoms in children caused by numerous underlying diseases. In majority of patients, these diseases can be correctly diagnosed through physical examination, history taking, and routine laboratory tests. Bone marrow failure syndromes associated with several genetic diseases are rare causes of anemia in childhood. We reviewed the recent progress of molecular mechanisms in bone marrow failure syndromes, such as Shwachman-Diamond syndrome (SDS), Diamond-Blackfan anemia (DBA), and dyskeratosis congenita (DC), which are all predicted to involve defective ribosome synthesis. Delineation of the precise role of each gene product in ribosomal biogenesis and hematopoiesis may have both therapeutic and prognostic significance.     

MR imaging of the hip: osseous lesions

Because of the exquisite soft tissue contrast resolution of MR imaging combined with recent technologic developments, a variety of conditions involving the hip joint and adjacent bony structures can be well evaluated using MR imaging, with or without contrast material. Among the different conditions, hip trauma and avascular necrosis are the most frequent indications. Other entities for which MR imaging has proven its usefulness include subchondral fractures, osteochondritis dissecans, transient osteoporosis, bone tumors, inflammatory and infectious processes, and a variety of bone marrow disorders.     

MDS-RA与CAA骨髓细胞学及组织学活检的实验研究

目的 探讨骨髓增生异常综合征难治性贫血与慢性再生障碍性贫血的鉴别特征，为临床的诊断和治疗提供诊断依据。方法 对15例骨髓异常增生综合征难治性贫血(MDS-RA)与36例慢性再生障碍性贫血(CAA)作血象及骨髓像细胞学检查．并比较和分析其组织病理学结果。结果 CAA组出血及三系减少的发生率明显高于MDS-RA组：骨髓细胞学检查显示，CAA组有核细胞增生程度低下和巨核细胞减少的发生率明照高于MDS-RA组．而MDS-RA组病态造血的发生率则明显高于CAA组。结论 骨髓细胞学检查是骨髓增尘异常综合征难治性贫血与慢性再生障碍性贫血的主要鉴别手段，骨髓组织学活检能提高病态造血的检出率，尤其是幼稚前体细胞异常定位(ALIP)检测不仅为MDS-RA和CAA鉴别的主要指标，而且能为疚病的预后提供参考依据。     

Hematopoietic stem and progenitor cells are present in healthy gingiva tissue

Hematopoietic stem cells reside in the bone marrow, where they generate the effector cells that drive immune responses. However, in response to inflammation, some hematopoietic stem and progenitor cells (HSPCs) are recruited to tissue sites and undergo extramedullary hematopoiesis. Contrasting with this paradigm, here we show residence and differentiation of HSPCs in healthy gingiva, a key oral barrier in the absence of overt inflammation. We initially defined a population of gingiva monocytes that could be locally maintained; we subsequently identified not only monocyte progenitors but also diverse HSPCs within the gingiva that could give rise to multiple myeloid lineages. Gingiva HSPCs possessed similar differentiation potentials, reconstitution capabilities, and heterogeneity to bone marrow HSPCs. However, gingival HSPCs responded differently to inflammatory insults, responding to oral but not systemic inflammation. Combined, we highlight a novel pathway of myeloid cell development at a healthy barrier, defining a gingiva-specific HSPC network that supports generation of a proportion of the innate immune cells that police this barrier.