不同浆细胞病分型患者骨髓浆细胞的流式特征分析

目的探讨根据国际骨髓瘤工作组(International Myeloma Working Group,IMWG)标准不同浆细胞病分型患者骨髓浆细胞数量及免疫表型的差异。方法回顾性分析2019年6月12日至2023年9月5日在复旦大学附属中山医院厦门医院诊治的浆细胞病患者血清学及骨髓流式结果。结果纳入102例浆细胞病患者,男性63例,女性39例,发病年龄22~85岁,其中意义未明的单克隆丙种球蛋白血症46例,冒烟型骨髓瘤5例,多发性骨髓瘤39例,轻链淀粉样变性12例。所有患者均伴有M蛋白,包含IgG型58例、非IgG型44例。所有患者骨髓均可检测到浆细胞,其中79例患者骨髓检测到异常浆细胞,63例患者骨髓检测到正常浆细胞,40例患者骨髓同时检测到正常及异常浆细胞。52例患者骨髓的异常浆细胞表达CD56,12例患者骨髓异常浆细胞表达CD117。不同疾病组间的性别、年龄差异无统计学意义。不同疾病组间的M蛋白类型及浓度、血清受累/非受累游离轻链、骨髓总浆细胞(包括正常及异常浆细胞)/有核细胞、骨髓异常浆细胞/有核细胞、骨髓异常浆细胞/骨髓总浆细胞、骨髓正常浆细胞/骨髓总浆细胞的差异均有统计学意义(P均<0.05)。不同疾病组中异常浆细胞CD56的表达存在统计学差异(P=0.009),而CD117的表达差异无统计学意义。结论轻链淀粉样变性患者骨髓克隆性浆细胞的比例、克隆性浆细胞/骨髓总浆细胞、异常浆细胞CD56表达比例与意义未明单克隆丙种球蛋白血症相仿,而与多发性骨髓瘤患者有显著差异。

应用FISH及细胞遗传学技术检测101例浆细胞疾病的基因异常

目的:探讨荧光原位杂交技术(fluorescence in situ hybridization,FISH)检测多发性骨髓瘤(multiple myeloma,MM)、意义未明单克隆免疫球蛋白增多症(monoclonal gammopathy of undetermined significance,MGUS)及反应性浆细胞增多症(reactive plasmacytosis,RP)的几种常见的异常基因,提高对几种常见浆细胞疾病的诊断及鉴别诊断水平。方法:回顾性分析2012年8月至2015年8月在中南大学湘雅医院初诊的61例MM、20例MGUS及20例RP患者的临床表现、影像学、实验室检查及FISH检测结果。结果:FISH检测61例MM患者中50例患者出现基因异常,FISH阳性检出率为81.9%,其中1q21扩增19例(31.1%)、D13S319缺失18例(29.5%)、RB1缺失10例(16.4%)、IGH易位10例(16.4%)、p53缺失7例(11.4%),出现两种或多种基因异常的阳性率为12例(19.8%);20例MGUS中FISH阳性检出率为30%,其中1q21扩增4例(20%)、IGH易位2例(10%),未发现两种或多种基因异常;而RP患者仅1例出现D13S319缺失,阳性率仅为5%。三组两两比较差异具有统计学意义(P<0.05)。结论:MM患者中FISH的阳性检出率为81.9%,明显高于MGUS及RP的患者,应用FISH可检测MM中的多种异常基因,对MM,MGUS及RP的鉴别诊断、预后判断有重要的临床参考价值。

基于CNN-MGU的侧信道攻击研究

基于深度学习的侧信道攻击对密码算法的安全性具有严重威胁,是学术界研究的热点之一。目前神经网络模型存在准确率低、鲁棒性差、收敛速度慢等问题,针对这些问题,文章结合卷积神经网络(Convolutional Neural Network,CNN)和最小门控单元(Minimal Gated Unit,MGU),提出基于CNN-MGU的神经网络模型。该模型首先通过CNN层提取轨迹上的局部关键信息,然后利用MGU层充分学习局部关键信息在时间上的相互依赖关系恢复密钥,最后在完全同步与非同步的轨迹上对模型的性能进行验证。实验结果表明,与基于CNN、长短期记忆(Long Short-Term Memory,LSTM)网络的攻击方法相比,基于CNN-MGU模型的训练准确率分别提高了约5.6%、3.4%。当数据集中加入的抖动量从0增大至50、100时,基于CNNMGU的神经网络模型的准确率仍达90%,鲁棒性强、收敛速度快。

以工学结合为主线构建临床医学专业MGU(1+2m)人才培养模式

我国现行的三年制医学高职教育"2+1"模式是在20世纪80年代以来与五年制医学本科教育"4+1"模式同期产生的,学校学习2年,医院实习1年,理论与实践教学严重脱节,不能适应新形势下高职医学教育的需要。MGU(1+2m)人才培养模式是近年来我校深化教学改革,突出实践能力培养,在"以就业为导向、以能力培养为核心,大力推行工学结合"的职教理念指导下,根据专业培养目标和基层医疗卫生岗位对人才知识、能力、素质的需求,对三年教学进行全程设计、分段实施,在校学习1年,医院学习2年,其中第3年实习期间到乡镇卫生院实习1个月(mouth,简写"m"),适合面向基层(Meet the Grass-roots Units,简称"MGU")培养高素质应用型卫生人才的培养模式,简称"MGU(1+2m)"人才培养模式。

Two cases of chronic myelomonocytic leukemia combined with monoclonal gammopathy of undetermined significance and a literature review

To describe myelodysplastic syndrome(MDS)/myeloproliferative neoplasm(MPN) combined with monoclonal gammopathy of undetermined significance(MGUS) in order to investigate the potential association between these 2 diseases. Two cases of confirmed chronic myelomonocytic leukemia(CMML) combined with MGUS were reported. In addition, prior publications of cases with combined MDS or MPN with MGUS were reviewed. The first case was of a 77-year-old man whose routine blood tests showed abnormal hemogram results. The diagnosis was CMML combined with Ig M monoclonal gammopathy, and the disease course was 4 years. The CMML gradually progressed and the patient presented with anemia, thrombocytopenia, autoimmune hemolysis, and an increase in the number of immature cells in the bone marrow. Although the MGUS caused fluctuations in the concentrations of Ig M, no Ig M-associated organ damage was observed. Eventually, this patient died from a lung infection. The second case was of a 78-year-old man who sought treatment because of fever and a cough. An increase in the number of monocytes was discovered in the peripheral blood. Bone marrow smear results suggested obvious active granulocytes and an increase in the percentages of promyelocytes, myelocytes, and metamyelocytes. Unhealthy granulocytes and immature monocytes could also be observed, and the percentage of monocytes was increased. In addition, serum Ig G levels were increased, and immunofixation electrophoresis results showed Ig G-κ type M proteins. The diagnosis was CMML combined with Ig G monoclonal gammopathy. These diseases were stable and follow-up was conducted for 1 year after diagnosis. The cases in this study combined with those that were reviewed in the relevant literature indicate that the presence of these 2 diseases in the same patient might not be a coincidence. The development of the 2 diseases in case 1 was different, and we speculate that they might have had different clonal origins. Whether CMML is a risk factor for MGUS and the role of clonal plasma cells in the occurrence and development of MDS and MDS/MPN requires further studies on a larger number of cases.

Typing of Four Cases of Monoclonal Gammopathy: A Revival of Immunosubstraction Role

Monoclonal gammopathy of undetermined significance (MGUS) is characterized by increased production of an immunoglobuling (Ig) from a clone of plasma cells and is a pre-malignant disorders in subjects older than 50 years. The prevalence of MGUS in Caucasian population is still not determined. MGUS is characterized by the presence of a monoclonal-protein(M-protein) (IgG and IgA) lower than 30 g/L, bone marrow plasma cell percentage lower than 10%, and absence of clinical signs related to multiple myeloma (MM). MGUS can be responsible for damage to organs through the production of toxic M proteins that may have autoantibody activity or deposit pathologically in the organ tissues. Many techniques are available for the characterization of M-proteins. These techniques can involve different expenses, skills, labor time, and sensitivity in detecting monoclonal proteins also at low-level. Detection of M-proteins needs of assays based on high-resolution electrophoresis and im-munofixation (or immunosubtraction). We show suggestive clinical cases where the subjects involved had not an apparent disease but they showed an interesting pattern in electrophoresis. All cases were investigated by capillary’s electrophoresis and immunofixation to confirm or not the clinical suspect, and then if the immunofixation is not exhaustive, additionally immunosubstraction is done. However in some cases, the interpretation of the peaks is not so easy. Clinical and scientific data provided evidences that immunofixaction technique can fail the identification of monoclonal components. In that cases, we opted for the immunosubtraction method as a third level test, in that cases when immunofixation failed the identification of a monoclonal protein.

Central and peripheral neurological involvement in monoclonal gammopathies of undetermined significance

Several studies have suggested a pathogenetic role of paraproteinaemias in PNS damage. Over the few last years, the presence of symptomatic or subclinical PNS lesions in CNS diseases like multiple sclerosis has been described. On the other hand, CNS demyelinating lesions and cervical atrophy have been re- ported in patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Very few cases of MGUS associated with CNS disease alone or with both CNS and PNS disease have been re- ported. Since 1999, we have been studying 16 patients (8 M, 8 F), with a mean age 60.2 ± 13.4, affected by MGUS associated with symptomatic neurological central and/or peripheral diseases. Patients affected with lymphomas, lupus erithematosus and other immunological diseases were excluded. Involvement of both PNS and CNS was not associated to a particular type of paraproteinemia: monoclonal IgM were found in 8 patients;monoclonal IgG in 6 patients and mono- clonal IgA in 1 patient and Igl in 1 patient. High anti- nervous system autoantibodies were found in 10/16 patients and antiMAG antibodies were detected in patients with paraproteinemic demyelinating neuropathy (PDN). High reactivity anti-nervous system might support the hypothesis of a pathogenetic role of MGUS in these neurological diseases. Nevertheless, at present, we cannot exclude that there is only a circumstantial association between MGUS and neurological damages, particularly concerning CNS.

以周围神经病起病的IgG型单克隆丙种球蛋白病1例报告

单克隆丙种球蛋白病是由一组异质性疾病组成,其特征在于B淋巴细胞或浆细胞大量增殖产生免疫球蛋白(M蛋白) [1] 。该疾病谱表现复杂,可侵及心脏、肾脏、皮肤、神经及肝脏等。其中以周围神经病起病的案例,国内外报道较少。本文主要介绍1例由周围神经起病的单克隆丙种球蛋白病。

Utility of Flow Cytometry to Classify Abnormal Plasma Cell Populations in Marrow Samples Collected from Patients with Putative Plasma Cell Neoplasms

Plasma cell neoplasms comprise a spectrum of diseases that include monoclonal gammopathy of undetermined signi-ficance (MGUS) and multiple myeloma (MM). Flow cytometric immunophenotyping has become an invaluable tool as an ancillary and diagnostic test for hematologic malignancies and is being used with increasing frequency in the diag-nosis and monitoring of plasma cell neoplasms. As multiparameter flow cytometry has evolved, faster fluidics and detection systems facilitate the screening of a large number of events and the detection of multiple antigens simultaneously. This review addresses the approaches used to evaluate clonal plasma cell neoplasms and describes different surface and cytoplasmic markers and techniques that are important for the study of these diseases.

单克隆丙种球蛋白病在HIV阳性病人中有不同的特征

多中心的研究发现，在HIV阳性病人中，单克隆丙种球蛋白病（MGUS）发生在一个较年轻的年龄阶段，并且比普通人群更易伴有其它病毒感染。HIV阳性病人比一般人群更易发展成意义未定的MGUS，但其临床特征还没有得到广泛研究。

发动机起停系统的开发与应用

传统发动机起停系统在车辆停车时发动机会进入停机状态,实现了"车不动,油不烧"的状态,从而降低了车辆的油耗和排放。但是传统起动系统存在噪声大,起动慢,价格高和结构复杂等问题。针对上述问题,提出了一整套发动机起停技术解决方案。该方案不仅可以解决传统起停系统的常见问题,而且可以低成本地大规模推广到现有的生产车型中。该方案基于紧凑型MGU(Motor/Generator Unit起动机/发电机总成),通过预测曲轴停机角度,优化发动机点火提前角和MGU发电电压,皮带驱动代替起动机起动等一系列措施来提高起动速度,降低噪声。

高职高专临床医学专业MGU(1+2m)人才培养模式下的教材建设探析

根据我校临床医学专业以就业为导向、以能力培养为核心、以工学结合的高职高专教育为宗旨,从MGU(1+2m)人才培养模式的实质出发,探讨了新的人才培养模式下教材建设的具体实施措施。

基于MGU的μC/OS实现

嵌入式系统的应用已经越来越广泛。μC/OS是一个简单有效的嵌入式操作系统,并且很容易移植到不同的处理器上,我们在使用MGU保护内存的情况下,实现了将μC/OS移植到CK520处理器上。通过MGU的保护,可以增强嵌入式系统的稳定性。

浅析人工智能中的归结方法

本文探讨归结方法在人工智能领域的应用。给出使用反演推理方法的步骤,并通过证明一个实际命题来说明归结推理过程。

无症状多发性骨髓瘤诊治的若干问题

无症状性多发性骨髓瘤（asymptomaticmultiplemyeloma，AMM），也称为冒烟型多发性骨髓瘤（smolderingmultiplemyeloma，SMM），与意义未明的单克隆免疫球蛋白血症（MGUS）相似，后者被认为是MM发展过程中的早期阶段，而SMM则是处于MGUS和多发性骨髓瘤（MM）之间的阶段。MGUS每年进展为有症状MM的发生率约为1％，而SMM进展为MM的概率逐年降低，诊断后最初5年内为10％，第2个5年内降至3％，而在随后10年内降至1％。随着MM研究的进展，目前对SMM的认识更加深入。

Subepidermal Autoimmune Bullous Disease Associated With Monoclonal Gammopathy of Unknown Significance and Unexpected Positive Direct Nikolsky Phenomenon:A Case Report

Introduction:Numerous dermatoses associated with monoclonal gammopathy have been reported in the literature.Subepidermal autoimmune bullous diseases(SABD)are one of them which were not common.Case presentation:A 68-year-old male patient was admitted to our clinic with erosions on the oral mucosa,tense blisters,erosions,and ulcers on the trunk and extremities.Subepidermal vesicle formation was detected in the skin biopsy.Clinical examination revealed positivity for the Nikolsky phenomenon.The disease was unresponsive to conventional treatments and dysphagia and hoarseness occurred.The patient was screened for malignancy due to his unresponsiveness to the treatments and his severe oral mucosal involvement.Ig-G MGUS was detected in the patient.Discussion:The Nikolsky sign is an indicator of acantholysis and is known as a specific finding for pemphigus.However,when we look at gammopathy-associated autoimmune bullous dermatoses,skin fragility has been reported in cases.However,the meaning of fragility is not explained.The diagnosis of all these patients was Ig-M MGUS.Our patient was presented because of non-IgM MGUS,direct Nikolsky positivity,and severe mucosal involvement.Conclusion:Nikolsky positivity may be a clue for gammopathy-related subepidermal autoimmune bullous diseases.

基于MGU的大规模IP骨干网络实时流量预测

为克服长短时记忆网络(long short-term memory, LSTM)计算成本相当大的弊端,提出基于最小门控单元(minimal gated unit, MGU)的大规模IP骨干网络实时流量预测方法。试验结果表明,与基于LSTM的流量预测方法相比,该方法以较少的模型训练时间获得了相当甚至略优的流量预测性能,在流量预测精度和实时性方面也优于已有的前馈神经网络(feed forward neural network, FFNN)和门控循环单元神经网络(gated recurrent unit, GRU)方法。

Minimal Gated Unit for Recurrent Neural Networks

Recurrent neural networks （RNN） have been very successful in handling sequence data. However, understanding RNN and finding the best practices for RNN learning is a difficult task, partly because there are many competing and complex hidden units, such as the long short-term memory （LSTM） and the gated recurrent unit （GRU）. We propose a gated unit for RNN, named as minimal gated unit （MCU）, since it only contains one gate, which is a minimal design among all gated hidden units. The design of MCU benefits from evaluation results on LSTM and GRU in the literature. Experiments on various sequence data show that MCU has comparable accuracy with GRU, but has a simpler structure, fewer parameters, and faster training. Hence, MGU is suitable in RNN＇s applications. Its simple architecture also means that it is easier to evaluate and tune, and in principle it is easier to study MGU＇s properties theoretically and empirically.