B-cell memory in malaria: Myths and realities

B-cell and antibody responses to Plasmodium spp., the parasite that causes malaria, are critical for control of parasitemia and associated immunopathology. Antibodies also provide protection to reinfection. Long-lasting B-cell memory has been shown to occur in response to Plasmodium spp. in experimental model infections, and in human malaria. However, there are reports that antibody responses to several malaria antigens in young children living with malaria are not similarly long-lived, suggesting a dysfunction in the maintenance of circulating antibodies. Some studies attribute this to the expansion of atypical memory B cells (AMB), which express multiple inhibitory receptors and activation markers, and are hyporesponsive to B-cell receptor (BCR) restimulation in vitro. AMB are also expanded in other chronic infections such as tuberculosis, hepatitis B and C, and HIV, as well as in autoimmunity and old age, highlighting the importance of understanding their role in immunity. Whether AMB are dysfunctional remains controversial, as there are also studies in other infections showing that AMB can produce isotype-switched antibodies and in mouse can contribute to protection against infection. In light of these controversies, we review the most recent literature on either side of the debate and challenge some of the currently held views regarding B-cell responses to Plasmodium infections.     

Plasma-derived mannose-binding lectin shows a direct interaction with C1-inhibitor

MBL-deficiency has been associated with an increased frequency and severity of infection, in particular in children and under immunocompromized conditions. In an open uncontrolled safety and pharmacokinetic MBL-substitution study using plasma-derived MBL (pdMBL) in MBL-deficient pediatric oncology patients, we found that despite MBL trough levels above 1.0 μg/ml MBL functionality was not efficiently restored upon ex vivo testing.     

Prognostic significance of CD20 expression and Epstein‐Barr virus (EBV) association in classical Hodgkin lymphoma in Japan: A clinicopathologic study

To investigate the clinicopathological significance of CD20 expression and Epstein‐Barr virus (EBV) association in Hodgkin and Reed–Sterberg cells of classical Hodgkin lymphoma (CHL), CD20 expression and EBV positivity (by EBER in situ hybridization) were investigated in 389 CHL patients in Japan. They included 74 CD20‐positive cases (19%) and 315 CD20‐negative cases (81%). CD20‐positive cases showed significantly older age at onset (P = 0.018) and higher association with EBV (P = 0.002). Multivariate analysis identified EBV‐positivity (but not CD20‐positivity), presence of B symptoms, thrombocytopenia, elevated serum lactate dehydrogenase and performance status >1 as poor prognostic factors for overall survival (OS). We constructed a new prognostic model with these five factors classifying patients into three groups: low risk, 0–1 adverse factor; intermediate risk, 2–3 factors; high risk, 4–5 factors. This prognostic model could stratify the prognosis of CHL patients (P < 0.0001). For 144 patients (58%) classified into the low‐risk group, the 5‐year OS was 91%. For 92 patients (37%) in the intermediate group, the 5‐year OS was 66%; for 11 patients (5%) in the high‐risk group, the 5‐year OS was 36%. In conclusion, EBV is identified as an independent poor prognostic factor for CHL patients. Therefore, examination of EBV association in CHL is recommended as routine pathologic practice especially in countries where EBV infection prevails.     

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??Abstract??Objective To explore the role of miR-125b in pediatric classical APL?? in order to seek new therapeutic strategies for drug resistant APL. Methods The target genes of miR-125b were predicted online?? validated by Dual-luciferase assay and western blot assay. MiR-125b expression levels were measured in 33 matched-pair APL samples??treated in the First Affiliated Hospital of Sun Yat-sen University and other members of South China Children APL Cooperative Group from March 2007 to September2012??at initial diagnosis and complete remission ??CR?? and in 5 relapsed patients by qRT-PCR. Proliferation and apoptosis were analyzed respectively using the RNA transfection?? MTT assay and flow cytometry. Results The expression of miR-125b was up-regulated in pediatric APL at diagnosis and relapse bone marrow samples?? but returned to normal after complete remission?? miR-125b could promote leukemic cell proliferation and inhibit cell apoptosis by regulating the expression of tumor suppressor Bak1. Remarkably??it was also found to be up-regulated in leukemic drug-resistant cells??NB4-R1??NB4-R2??HL-60/DOX???? and overexpression of exogenous miR-125b could increase their resistance to therapeutic drugs. Conclusion MiR-125b can regulate pediatric classical APL cells proliferation?? apoptosis and drug resistance by repressing BAK1 protein expression.     

国医大师张志远治疗中风经验

国医大师张志远教授对中风治疗经验丰富,认为中风病因为内伤积损、情志所伤、气虚邪中,病机关键在于玄府闭塞、气血不通,故以开通玄府,畅行气血为治疗大法,主张分期、分证型论治：针对急性期与恢复期证属痰热腑实采用“三化汤”,恢复期证属气虚血瘀使用“救痪汤”,并自创验方“黄芪愈风汤”治疗恢复期属风痰阻络者。重视风药与虫药,以及黄芪、山楂,丹参、牡丹皮和半夏、橘红的配伍,均收显效。     

基于社会网络分析法的中医药治疗不孕症学术团队挖掘分析

目的 通过社会网络分析法挖掘中医药治疗不孕症学术团队,总结团队治疗经验,归纳不同地域团队间的学术思想异同.方法 检索中国知识资源总库(CNKI)、中国生物医学文献数据库(CBM)、中文科技期刊数据库(维普网)、中国学术期刊数据库(万方数据)自建库至2018年12月31日中医药治疗不孕症的文献,导出文献题录,根据发文数及...     

北京市属医院知名专家团队双向转诊机制探讨

目前我国医联体建设已取得一定成效,但在实践过程中,仍存在医联体内上下转诊不畅的协同困境.北京市医院管理中心在市属医院内部进行分级诊疗制度创新,通过建立知名专家团队层级转诊预约模式,有效解决了疑难病"看专家难"问题.作者通过总结北京市属医院知名专家团队建设经验,探讨了院内知名专家团队层级转诊模式对医联体建设的借鉴意义.     

基于指纹图谱及化学模式识别方法优选经典名方温经汤中莪术药材产地

目的 基于高效液相色谱(HPLC)指纹图谱、聚类分析以及定量分析方法,评价不同产地莪术的质量,优选最佳产地.方法 采用HPLC,流动相为乙腈-水进行梯度洗脱,检测波长为210 nm,对7个不同产地的26批莪术药材进行指纹图谱及3种有效成分含量测定研究,应用聚类分析与显著性差异分析等化学模式识别方法对莪术药材质量进行评价...     

Regional synapse gain and loss accompany memory formation in larval zebrafish

Defining the structural and functional changes in the nervous system underlying learning and memory represents a major challenge for modern neuroscience. Although changes in neuronal activity following memory formation have been studied [B. F. Grewe et al., Nature 543, 670–675 (2017); M. T. Rogan, U. V. Stäubli, J. E. LeDoux, Nature 390, 604–607 (1997)], the underlying structural changes at the synapse level remain poorly understood. Here, we capture synaptic changes in the midlarval zebrafish brain that occur during associative memory formation by imaging excitatory synapses labeled with recombinant probes using selective plane illumination microscopy. Imaging the same subjects before and after classical conditioning at single-synapse resolution provides an unbiased mapping of synaptic changes accompanying memory formation. In control animals and animals that failed to learn the task, there were no significant changes in the spatial patterns of synapses in the pallium, which contains the equivalent of the mammalian amygdala and is essential for associative learning in teleost fish [M. Portavella, J. P. Vargas, B. Torres, C. Salas, Brain Res. Bull. 57, 397–399 (2002)]. In zebrafish that formed memories, we saw a dramatic increase in the number of synapses in the ventrolateral pallium, which contains neurons active during memory formation and retrieval. Concurrently, synapse loss predominated in the dorsomedial pallium. Surprisingly, we did not observe significant changes in the intensity of synaptic labeling, a proxy for synaptic strength, with memory formation in any region of the pallium. Our results suggest that memory formation due to classical conditioning is associated with reciprocal changes in synapse numbers in the pallium.

It is widely believed that memories are formed as a result of alterations in synaptic connections between axons and dendrites, an idea first proposed by Ramon y Cajal (1–4). Although synapse changes have been extensively studied in brain slices in the context of long-term potentiation (5, 6), less is known about how synapses in a living vertebrate are modified when a memory is formed.Memory formation has been widely studied using classical conditioning (CC), a robust and straightforward form of learning in which an animal is exposed to a neutral stimulus (conditioned stimulus, CS) paired with an appetitive or aversive stimulus (unconditioned stimulus, US) that evokes a specific behavioral response (UR, unconditioned response) (7, 8). As a result of the pairing, animals learn to associate the CS with the US, causing them to respond to the CS with a conditioned response (CR) identical to the UR, signifying memory retrieval (9, 10). Memory retrieval is also evoked by activating a cellular engram, a group of neurons active during memory formation and retrieval (11–18). The central locus of CC in mammals, the amygdala (19), is located in a relatively inaccessible area beneath the cortex (20). Thus, although numerous longitudinal imaging studies have documented experience-dependent changes in the structure of spines of cortical and hippocampal neurons (21, 22), few imaging studies have directly examined synaptic changes that occur in the amygdala during associative memory formation.Instead, synaptic changes that occur in the amygdala during CC (23) have been studied primarily using indirect measures of synaptic strength, such as the ratio of α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor/N-methyl D-aspartate (AMPA/NMDA) currents in excitatory postsynaptic currents (EPSCs). Increases in AMPA/NMDA ratio in amygdalar neurons following auditory fear conditioning (FC), a type of CC (24–27), indicate that associative memory formation coincides with increases in synaptic strength. In addition, imaging experiments in brain regions beyond the amygdala have shown diverse effects following CC. For example, following contextual fear conditioning, engram neurons in the CA1 region of the hippocampus that receive inputs from CA3 engram neurons displayed spines that were larger and more densely packed than nonengram cells (28). Furthermore, experiments in which neuronal morphology was directly observed before and after FC found that neurons in the frontal association (29) and primary motor cortex (30) showed a decrease in the number of spines, whereas neurons in the auditory cortex showed an increase in spine number with memory formation (31).To obtain previously unavailable insight into memory formation within the central locus of associative memory storage, we developed a paradigm combining in vivo labeling and imaging with informatics and analysis tools. We used this paradigm to map synaptic changes that occur over time in the intact brain of a living vertebrate during memory formation. We imaged the pallium of teleost fish, which contains the putative homolog of the mammalian amygdala based on anatomy (32), gene expression (33), and function (34). The pallium is on the surface of the brain (35), and zebrafish larvae are highly transparent, allowing for intact, whole-brain imaging using selective plane illumination microscopy (SPIM) without the need for invasive intervention (36). In addition, while most studies of learning in zebrafish have used adults (37–40), at least one study showed that larval zebrafish can learn to associate a place with a positive valence US (41). These attributes suggest that larval zebrafish may be an ideal model organism for studying synaptic changes during memory formation due to CC. We have engaged this challenge by combining purpose-built experimental tools with data management software that enables transparent analyses of large and heterogeneous datasets. All data were characterized and stored at the time of creation in a customized data management system designed to conform to findability, accessibility, interoperability, and reusability (i.e., FAIR principles) (see Materials and Methods) (42).     

范金茹教授治疗颈性眩晕经验举隅

范金茹教授为首批全国优秀中医临床人才,在诊治眩晕类疾病方面积累了丰富经验。颈性眩晕多表现为眩晕、头颈部疼痛、恶心、呕吐、耳鸣等,严重影响了人们的生活质量。范师认为颈性眩晕为本虚标实之证,病位在头颈,肝肾亏虚为本,病性因素多为痰瘀。强调分急性期、缓解期治疗,注重气之升降--引痰饮血瘀下行而出,津气上行以荣脑。自拟颈痹眩晕方,为升降散合泽泻汤加减而成,组方精当,临床运用每获良效。