血站免疫血液学实验室信息管理系统的设计与应用

目的按照血站免疫血液学实验室检测业务流程,规划和设计信息管理系统模块,并对应用效果进行评估。方法设计从血站免疫血液学实验室检测标本接收到报告发出过程全覆盖的实验室信息管理系统,连接、整合该系统与血站信息管理系统、医院输血管理系统,实现检验申请、检验过程、血液发放、科室管理等一系列过程的完整性及可追溯性,达到相关信息共享。结果启用该信息管理系统能够满足免疫血液学检测质量和文件控制要求,使实验过程得到了规范,差错发生率明显降低。结论该信息管理系统的设计为狭窄领域实验室信息管理软件设计提供了系统架构及应用上的探索,其启用有效地提高了实验室的工作效率及过程管理水平。     

Generic scheme for independent performance assessment in the molecular biology laboratory

BACKGROUND: A variety of proficiency testing schemes are available for specific molecular analyses, but there is an acute need for more widely accessible schemes to assess and demonstrate general competence in DNA analysis. METHODS: Fifteen laboratories, including academic, clinical, and commercial organizations, were recruited into the prototype assessment exercise. A range of test samples were provided, and participants were required to extract DNA from simple matrices, perform PCR amplification, and score the samples as positive or negative by electrophoretic analysis of the amplification products. Results were requested as both gel images and a completed results table, and the performance of each laboratory was then scored on the submitted analytical results. RESULTS: Overall, laboratories performed the analysis successfully, with participants scoring a high proportion of the samples correctly in the two rounds of the scheme. However, not all of the laboratories were able to achieve amplification for all samples, and the performance of some laboratories was not consistent in the two rounds. In addition, several analytical problems were encountered at all stages of the process, including DNA extraction, PCR amplification, and correct recording of results. CONCLUSIONS: The generic approach described here has enabled effective cross-sectoral benchmarking of laboratories from a variety of analytical sectors. The problems encountered by some participating laboratories highlight the need for quality control and checks at all stages of the process to ensure accuracy of results. A statistical analysis of the results (ANOVA) allowed meaningful comparison of the consistency and sensitivity achieved by laboratories, demonstrating that an effective balance was achieved between the level of data obtained from laboratories and the time expenditure required from participants.     

Discrepancies between red cell phenotyping and genotyping in daily immunohematology laboratory practice

False-positive and false-negative reactions exist for serological and molecular antigen typing methods. If the predicted phenotype is inconsistent with the patient`s known antibodies or serological phenotype, the discrepancy must be investigated. False-negative and false-positive results are clinically problematic in blood donors and patients. In this study, we investigated discrepant results between serology and molecular testing in patients and blood donors that occurred in daily molecular laboratory practice over a two year-period. SCD patients represented a large percentage of our cases of discrepancies but we also observed a high prevalence of discrepancies between phenotypes and genotypes in blood donors. The main reasons that led to discrepancies were recent transfusions and limitations of phenotyping. Discrepancies classified as false positive phenotype/true negative genotype and false negative phenotype/true positive genotype occurred mainly in patients with recent transfusions and individuals with RH variants while those classified as true negative phenotype/false positive genotype involved null phenotypes due to silent genes. Despite the limitations of molecular methods currently employed, we found more false-negative and false-positive phenotypes than genotypes demonstrating that genotyping is more efficient to define the blood types, especially in transfusion dependent patients.     

Clinical pharmacology in the molecular era

The title of this article may raise a smile from colleagues in the field of basic pharmacology. To them, pharmacology has always been about molecular interactions, and this title may simply confirm a suspicion that clinical pharmacology is mainly about semi-quantitative observations that have only a limited foundation in hard science. They are partly right, at least regarding a communication problem. In a discussion about systems biology, an exasperated engineer once remarked that biologists and physicians do not even use the same routine software packages that engineers do. Similarly, a basic pharmacologist might note that, whereas he measures drug concentrations in micromoles, the clinical pharmacologist uses micrograms per milliliters. Nevertheless, as clinical pharmacologists seek to make more quantitative observations at the molecular level in living humans, our colleagues in basic pharmacology are delving into cellular signal transduction systems governed by complex protein-protein interactions and regulated by positive and negative feedback loops. In seeking to understand these systems, they face problems that are similar to the challenge of measurement in intact humans.     

Connecting aging biology and inflammation in the omics era

Aging is characterized by the accumulation of damage to macromolecules and cell architecture that triggers a proinflammatory state in blood and solid tissues, termed inflammaging. Inflammaging has been implicated in the pathogenesis of many age-associated chronic diseases as well as loss of physical and cognitive function. The search for mechanisms that underlie inflammaging focused initially on the hallmarks of aging, but it is rapidly expanding in multiple directions. Here, we discuss the threads connecting cellular senescence and mitochondrial dysfunction to impaired mitophagy and DNA damage, which may act as a hub for inflammaging. We explore the emerging multi-omics efforts that aspire to define the complexity of inflammaging — and identify molecular signatures and novel targets for interventions aimed at counteracting excessive inflammation and its deleterious consequences while preserving the physiological immune response. Finally, we review the emerging evidence that inflammation is involved in brain aging and neurodegenerative diseases. Our goal is to broaden the research agenda for inflammaging with an eye on new therapeutic opportunities.

Aging has been conceptualized as a continuous duel between damage accumulation — due to a combination of environmental and endogenous processes — and resilience mechanisms that cope with such stressors and resolve damage (1). With aging, resilience mechanisms become less effective at repairing or removing damage and preventing its deleterious effects on health (2). Persistent molecular and cellular damage due to exhausted resilience is ultimately expressed as phenotypes of aging, including inflammaging, susceptibility to chronic diseases, physical and cognitive impairments, and, ultimately, frailty and death.Atop the hierarchy of resilience is the immune system, the aggregate of cells, mediators, and signaling pathways that continuously patrol for pathogens or structural perturbations revealed as “unusual” molecular motifs. The immune system reacts to a variety of threats, such as symbiotic commensal and pathogenic microorganisms, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs) from endogenous and exogenous sources, and orchestrates defense responses aimed at eliminating the specific threat while minimizing damage to the host. While inflammation is important for tissue repair and regeneration, when abnormally intense or persistent, it can drive degeneration and chronic diseases.The immune system undergoes numerous and profound changes with aging, which are extensively reviewed elsewhere (3–5). Hallmarks of immune aging are (a) a state of proinflammatory activation characterized by high circulating levels of proinflammatory cytokines — such as IL-6 and TNF-α — and localized tissue inflammation, and (b) an aberrant response to antigens and pathogens that could either be blunted, such as in flu vaccination, or excessive, such as in response to SARS-CoV-2 (6).Considerable research in both animal models and humans has examined the causes and consequences of inflammaging (4). Although increased levels of inflammatory mediators (mostly IL-1, IL-6, TNF-α, and its receptors) are detected in all elderly individuals, higher levels of these biomarkers are associated with increased risk for many chronic conditions, including dementia, disability, and physical frailty. Inflammation’s causal role in cardiovascular disease was established by the CANTOS trial (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study), which demonstrated that IL-1β inhibition reduced the risk of cardiovascular events versus the placebo, particularly in participants whose IL-6 levels were initially elevated (7).Mechanisms identified as hallmarks of aging biology and immune cell dysfunction have all been hypothesized as causes of inflammation (8). Aging researchers now recognize that measuring a few cytokines in circulation fails to capture the complexity and potential ramifications of inflammaging. Immune cells in tissues, particularly lymphocytes and resident macrophages, show tissue-specific age-related changes likely connected to specific pathological processes (9). By measuring hundreds or thousands of molecules in a few drops of blood, scientists are attempting to identify (a) signatures of accelerated aging that are both informative of the complexity and diversity of the response and predictive of health outcomes and (b) key molecules and molecular mechanisms that can be targeted for intervention (10).Given the extreme complexity of inflammaging, we focus herein on a few topics that have attracted considerable attention and controversy in the field. First, we discuss cellular senescence as a source of local and systemic inflammation. We highlight evidence that mitochondrial dysfunction is a nexus that binds impaired mitophagy with DNA damage and cellular senescence to ultimately foster a chronic inflammatory state. We then summarize efforts to identify circulating signatures of inflammation through “omics.” Finally, we review emerging data indicating that inflammation is involved in brain aging and dementia. Our intent is to discuss the causes and consequences of inflammaging and to enrich the research agenda toward the development of new therapeutic strategies.     

Applying molecular immunohematology discoveries to standards of practice in blood banks: now is the time

Lessons from more than 100 years of immunohematology exemplify that many critical discoveries were made serendipitously and their more rapid implementation could have benefited transfusion recipients and pregnancies. Constituents of blood that are not essential for the attempted therapeutic benefit of a transfusion are largely removed from today's blood products. We are now moving on to avoid unnecessary exposure to potentially harmful constituents of the therapeutically required cells, like blood group antigens that are foreign to the patient. Cost efficacy needs to be kept in mind but may eventually prove much better than anticipated, once hidden benefits are captured, as we show by examples from past immunohematologic developments. Here, we detail clinical applications for molecular immunohematology advances including “dry‐matching” that will improve transfusion outcomes and argue for their widespread implementation by rapid timelines through standards of practice.     

Pediatric embryonal brain tumors in the molecular era

ABSTRACT

Introduction: Embryonal brain tumors (EBTs) are highly aggressive malignancies predominantly affecting children. They include medulloblastoma (MB), atypical rhabdoid/teratoid tumors (ATRT), pineoblastoma (PB), embryonal tumor multiple rosettes (ETMR)/C19MC-altered tumors, and newly recognized embryonal tumors with FOXR2 activation or BCOR alteration.

Areas covered: This review will provide a comprehensive overview and updated of the literature on each of these EBTs. The evolution from location- and histopathology-based diagnosis to more specific and robust molecular-based classification schemes, as well as treatment modalities, will be discussed.

Expert commentary: The subgrouping of EBTs with multi-omic profiling has had important implications for risk stratification and discovery of targetable driver pathways. However, these innovations are unlikely to significantly improve survival among high-risk patients until robust preclinical studies are conducted, followed by validation in biology-informed clinical trials.     

The significance of complement in immunohematology

In vitro detection of red cell-bound complement can be important in the differential diagnosis of autoimmune and drug-induced immune hemolytic anemias; it can also be a sensitive test for the detection of complement-binding alloantibodies, e.g., in compatibility testing. Red cell-bound complement can be detected by the antiglobulin test if suitable antiglobulin sera (AGS) are utilized. In 1971, the Federal Standards for AGS were criticized because so-called broad spectrum AGS used routinely in blood banks were shown to often be deficient in anticomplement reactivity. In the new few years commercial regents changed with regard to the quantity and specificity of their anticomplement components. A great deal of controversy developed as to the true importance of detecting red cell-bound complement, the particular fragments of complement that should be detected, and the causes of nonspecific reactions that seemed to be occurring, especially with the increasing usage of new techniques utilizing low ionic strength media. When monospecific anti-IgG and anti-C3 became available commercially, the controversy regarding diagnostic testing was resolved as direct antiglobulin testing could be performed with these reagents rather than the broad spectrum reagents. Two main questions remained: how rare are alloantibodies that are only detectable by the anticomplement component of AGS? How clinically significant are such antibodies? The results of our 3-year study indicated that such antibodies (usually anti-Kidd) occurred with a incidence of 1/8000 sera tested. Some of these antibodies seemed capable of shortening the life span of transfused red cells, as determined by 51Cr survival studies; some showed negligible cell destruction. Severe transfusion reactions due to such antibodies would seem unlikely. Individual laboratories will have to balance the risk of missing some complement-dependent antibodies of possible clinical significance with the increased nonspecificity encountered in their own laboratory with AGS containing anticomplement.     

Chimerism in allogeneic mini-transplantation

The need of quantitation of chimerism is increasing as mini-transplantation has been on trial and they are possibly become the mixed chimeras. FISH method using XY chromosome as a marker is effective in heterosexual transplantation, And STR-PCR method is effective in homosexual transplantation. There is wide range in strength of pre-conditioning in Mini-transplantation; almost all stronger pre-conditioning with fludarabine end up in completely donor-type, and the pre-conditioning with ATG, TBL, L-PAM, M-Pred, 40% became mixed chimera but they all became completely donor type with DLI. There is a report that there are less GVHD with mixed chimera. To decide which pre-conditioning to use, we need to examine the rate of the relapse.     

新时代检验医学发展定位与思考

检验医学作为医学科学的重要支撑学科,在疾病早期诊断、病情监测、预后判断与风险评估等方面发挥着重要作用。21世纪是数字信息时代,高新检测技术、计算机科学及互联网大数据等,为检验医学的发展带来巨大的机遇与挑战,新时代下如何借助信息科技革命实现检验医学新发展是检验工作者面临的重要课题。该文回顾检验医学的发展历程,重点关注检验医学在新时代的发展定位及未来发展方向,以求开创检验医学发展新局面。