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Exosome miRNAs profiling in serum and prognostic evaluation in patients with multiple myeloma. 多发性骨髓瘤患者血清外泌体mirna谱分析和预后评估。
Q3 Medicine Pub Date : 2023-07-01 DOI: 10.1097/BS9.0000000000000160
Teng Fang, Hao Sun, Xiyue Sun, Yi He, Peixia Tang, Lixin Gong, Zhen Yu, Lanting Liu, Shiyi Xie, Tingyu Wang, Zhenshu Xu, Shuhua Yi, Gang An, Yan Xu, Guoqing Zhu, Lugui Qiu, Mu Hao

MicroRNAs (MiRNAs) carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment. Our study aimed at identifying the expression profile of exosomal miRNAs (exo-miRNAs) in the serum of multiple myeloma (MM) patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis. Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing. Differential expression of exo-miRNAs was calculated and target genes of miRNAs were predicted. CytoHubba was applied to identify the hub miRNAs and core target genes. The LASSO Cox regression model was used to develop the prognostic model, and the ESTIMATE immune score was calculated to investigate the correlation between the model and immune status in MM patients. The top six hub differentially expressed serum exo-miRNAs were identified. 513 target genes of the six hub exo-miRNAs were confirmed to be differentially expressed in MM cells in the Zhan Myeloma microarray dataset. Functional enrichment analysis indicated that these target genes were mainly involved in mRNA splicing, cellular response to stress, and deubiquitination. 13 core exo-miRNA target genes were applied to create a novel prognostic signature to provide risk stratification for MM patients, which is associated with the immune microenvironment of MM patients. Our study comprehensively investigated the exo-miRNA profiles in MM patients. A novel prognostic signature was constructed to facilitate the risk stratification of MM patients with distinct outcomes.

外泌体携带的MicroRNAs (MiRNAs)在肿瘤微环境中细胞组分之间的串扰中起着关键作用。本研究旨在通过综合生物信息学分析,鉴定多发性骨髓瘤(MM)患者血清中外泌体miRNAs (exo-miRNAs)的表达谱,并研究其调控网络及其潜在功能。从19例新诊断MM患者和9例健康供者的血清中分离出外泌体,并通过小RNA测序研究其miRNA谱。计算外显子mirna的差异表达量,预测mirna的靶基因。应用CytoHubba鉴定中心mirna和核心靶基因。采用LASSO Cox回归模型建立预后模型,计算ESTIMATE免疫评分,探讨模型与MM患者免疫状态的相关性。鉴定出前6个中枢差异表达的血清外显mirna。在詹氏骨髓瘤微阵列数据集中,6个hub外显mirna的513个靶基因在MM细胞中被证实存在差异表达。功能富集分析表明,这些靶基因主要参与mRNA剪接、细胞应激反应和去泛素化。13个核心外显子mirna靶基因被应用于创建一个新的预后标记,为MM患者提供风险分层,这与MM患者的免疫微环境有关。我们的研究全面研究了MM患者的外显mirna谱。构建了一种新的预后特征,以促进具有不同结果的MM患者的风险分层。
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引用次数: 0
Diagnosis and management of adult central nervous system leukemia. 成人中枢神经系统白血病的诊断与治疗。
Q3 Medicine Pub Date : 2023-07-01 DOI: 10.1097/BS9.0000000000000162
Siyu Liu, Ying Wang

Central nervous system leukemia (CNSL) is a prominent infiltration reason for therapy failing in acute leukemia. Recurrence rates and the prognosis have alleviated with current prophylactic regimens. However, the accurate stratification of relapse risk and treatment regimens for relapsed or refractory patients remain clinical challenges yet to be solved. Recently, with hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) cellular therapy showing encouraging effects in some CNSL patients, advances in treating CNSL have already been reported. The development of molecular targeted agents as well as antibody-based drugs will provide patients with more personalized treatment. This article summarized recent research developments about risk factors, diagnosis, prevention, and treatment in adults with CNSL.

中枢神经系统白血病(CNSL)是急性白血病治疗失败的重要浸润性原因。复发率和预后已减轻与目前的预防方案。然而,复发或难治性患者复发风险的准确分层和治疗方案仍然是临床有待解决的挑战。最近,随着造血干细胞移植(HSCT)和嵌合抗原受体- t (CAR-T)细胞治疗在一些CNSL患者中显示出令人鼓舞的效果,CNSL治疗的进展已经被报道。分子靶向药物以及基于抗体的药物的发展将为患者提供更加个性化的治疗。本文综述了成人CNSL的危险因素、诊断、预防和治疗方面的最新研究进展。
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引用次数: 0
MXRA7 is involved in megakaryocyte differentiation and platelet production. MXRA7参与巨核细胞分化和血小板产生。
Q3 Medicine Pub Date : 2023-07-01 DOI: 10.1097/BS9.0000000000000167
Zhenjiang Sun, Benfang Wang, Ying Shen, Kunpeng Ma, Ting Wang, Yiqiang Wang, Dandan Lin

Matrix remodeling is a critical process in hematopoiesis. The biology of MXRA7, as a matrix remodeling associated gene, has still not been reported in hematopoietic process. Public databases showed that MXRA7 expressed in hematopoietic stem cells, suggesting that it may be involved in hematopoiesis. We found that the amounts of megakaryocytes were lower in bone marrow and spleen from Mxra7-/- mice compared with that from wild-type mice. Knock-out of MXRA7 also reduced the amount of platelet in peripheral blood and affected the function of platelets. Knock-out of MXRA7 inhibited hematopoietic stem/progenitor cells differentiate to megakaryocytes possibly through down-regulating the expression of GATA-1 and FOG-1. Moreover, knockdown of MXRA7 in MEG-01 cells could inhibit the cell proliferation and cell apoptosis. Knockdown of MXRA7 inhibited the differentiation of MEG-01 cells and proplatelet formation through suppressing the ERK/MAPK signaling pathway and the expression of β-tubulin. In conclusion, the current study demonstrated the potential significance of MXRA7 in megakaryocyte differentiation and platelet production. The novel findings proposed a new target for the treatment of platelet-related diseases, and much more investigations are guaranteed to dissect the mechanisms of MXRA7 in megakaryocyte differentiation and platelet production.

基质重塑是造血过程中的一个关键过程。MXRA7作为基质重塑相关基因在造血过程中的生物学研究尚未见报道。公开数据库显示MXRA7在造血干细胞中表达,提示其可能参与造血。我们发现,与野生型小鼠相比,Mxra7-/-小鼠骨髓和脾脏中巨核细胞的数量较低。敲除MXRA7后,外周血中血小板数量减少,血小板功能受到影响。敲除MXRA7可能通过下调GATA-1和fog1的表达抑制造血干细胞/祖细胞向巨核细胞的分化。此外,MXRA7在MEG-01细胞中表达下调可抑制细胞增殖和细胞凋亡。MXRA7的下调通过抑制ERK/MAPK信号通路和β-微管蛋白的表达,抑制MEG-01细胞的分化和血小板前形成。总之,本研究证明了MXRA7在巨核细胞分化和血小板产生中的潜在意义。这些新发现为血小板相关疾病的治疗提供了新的靶点,并保证更多的研究可以深入探讨MXRA7在巨核细胞分化和血小板产生中的机制。
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引用次数: 0
An investigation of long-term outcome of rabbit anti-thymocyte globulin and cyclosporine therapy for pediatric severe aplastic anemia. 兔抗胸腺细胞球蛋白联合环孢素治疗小儿重度再生障碍性贫血的远期疗效观察。
Q3 Medicine Pub Date : 2023-07-01 DOI: 10.1097/BS9.0000000000000157
Lixian Chang, Mingchen Yan, Jingliao Zhang, Binghang Liu, Li Zhang, Ye Guo, Jing Sun, Yang Wan, Meihui Yi, Yang Lan, Yuli Cai, Yuanyuan Ren, Haihui Zheng, Aoli Zhang, Zhenyu Li, Jian Wang, Yingrui Li, Xiaofan Zhu

Children with severe aplastic anemia (SAA) face heterogeneous prognoses after immunosuppressive therapy (IST). There are few models that can predict the long-term outcomes of IST for these patients. The objective of this paper is to develop a more effective prediction model for SAA prognosis based on clinical electronic medical records from 203 children with newly diagnosed SAA. In the early stage, a novel model for long-term outcomes of SAA patients with IST was developed using machine-learning techniques. Among the indicators related to long-term efficacy, white blood cell count, lymphocyte count, absolute reticulocyte count, lymphocyte ratio in bone-marrow smears, C-reactive protein, and the level of IL-6, IL-8 and vitamin B12 in the early stage are strongly correlated with long-term efficacy (P < .05). Taken together, we analyzed the long-term outcomes of rabbit anti-thymocyte globulin and cyclosporine therapy for children with SAA through machine-learning techniques, which may shorten the observation period of therapeutic effects and reduce treatment costs and time.

严重再生障碍性贫血(SAA)的儿童在免疫抑制治疗(IST)后面临不同的预后。很少有模型可以预测这些患者IST的长期预后。本文旨在基于203例新发SAA患儿的临床电子病历,建立一个更有效的SAA预后预测模型。在早期阶段,使用机器学习技术开发了SAA合并IST患者长期预后的新模型。与远期疗效相关的指标中,早期白细胞计数、淋巴细胞计数、绝对网织细胞计数、骨髓涂片淋巴细胞比例、c反应蛋白、白细胞介素6、白细胞介素8、维生素B12水平与远期疗效有较强相关性(P < 0.05)。总之,我们通过机器学习技术分析了兔抗胸腺细胞球蛋白和环孢素治疗SAA儿童的长期疗效,这可能会缩短治疗效果的观察期,降低治疗成本和时间。
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引用次数: 0
Post-transcriptional regulation of erythropoiesis. 红细胞生成的转录后调控。
Q3 Medicine Pub Date : 2023-07-01 DOI: 10.1097/BS9.0000000000000159
Yanan Li, Haihang Zhang, Bin Hu, Pan Wang, Wei Wang, Jing Liu

Erythropoiesis is a complex, precise, and lifelong process that is essential for maintaining normal body functions. Its strict regulation is necessary to prevent a variety of blood diseases. Normal erythropoiesis is precisely regulated by an intricate network that involves transcription levels, signal transduction, and various epigenetic modifications. In recent years, research on post-transcriptional levels in erythropoiesis has expanded significantly. The dynamic regulation of splicing transitions is responsible for changes in protein isoform expression that add new functions beneficial for erythropoiesis. RNA-binding proteins adapt the translation of transcripts to the protein requirements of the cell, yielding mRNA with dynamic translation efficiency. Noncoding RNAs, such as microRNAs and lncRNAs, are indispensable for changing the translational efficiency and/or stability of targeted mRNAs to maintain the normal expression of genes related to erythropoiesis. N6-methyladenosine-dependent regulation of mRNA translation plays an important role in maintaining the expression programs of erythroid-related genes and promoting erythroid lineage determination. This review aims to describe our current understanding of the role of post-transcriptional regulation in erythropoiesis and erythroid-associated diseases, and to shed light on the physiological and pathological implications of the post-transcriptional regulation machinery in erythropoiesis. These may help to further enrich our understanding of the regulatory network of erythropoiesis and provide new strategies for the diagnosis and treatment of erythroid-related diseases.

红细胞生成是一个复杂的、精确的、终生的过程,对维持正常的身体功能至关重要。它的严格规定是必要的,以防止各种血液疾病。正常的红细胞生成是由一个复杂的网络精确调节的,这个网络涉及转录水平、信号转导和各种表观遗传修饰。近年来,对红细胞生成的转录后水平的研究有了显著的扩展。剪接过渡的动态调控导致了蛋白异构体表达的变化,从而增加了有利于红细胞生成的新功能。rna结合蛋白使转录本的翻译适应细胞对蛋白质的需求,产生具有动态翻译效率的mRNA。非编码rna,如microRNAs和lncRNAs,对于改变靶mrna的翻译效率和/或稳定性以维持红细胞生成相关基因的正常表达是不可或缺的。n6 -甲基腺苷依赖的mRNA翻译调控在维持红系相关基因的表达程序和促进红系谱系确定中起着重要作用。这篇综述旨在描述我们目前对转录后调控在红细胞生成和红细胞相关疾病中的作用的理解,并阐明红细胞生成中转录后调控机制的生理和病理意义。这可能有助于进一步丰富我们对红细胞生成调控网络的认识,并为红细胞相关疾病的诊断和治疗提供新的策略。
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引用次数: 0
Effect of COVID-19 pandemic on blood transfusion service: an experience from a regional blood transfusion center. COVID-19大流行对输血服务的影响:来自区域输血中心的经验。
Q3 Medicine Pub Date : 2023-07-01 DOI: 10.1097/BS9.0000000000000161
Sanjay K Thakur, Anil K Sinha, Dinesh K Negi, Sompal Singh

The unforeseen and uncertain life-threatening situation of the COVID-19 pandemic dramatically affected all areas of the human daily work schedule. This study was designed to assess the impact of the COVID-19 pandemic on blood transfusion services and discuss the adopted confrontation measures for uninterrupted blood supply during the pandemic situation. The data on blood donation, blood component preparation, and issue from January 2019 to December 2022 were collected from the inventory registers of the RBTC, Delhi, India. Compared to the non-pandemic year 2019, during the year 2020, all variables decreased gradually. The observed maximum decrease in variables such as blood collection (-79.16%) in the month of October, blood issue (-71.61%) in the month of August, random donor platelets (RDP) preparation (-98.09%) in the month of October, RDP issue (-86.08%) in the month of September, fresh frozen plasma (FFP) preparation (-100%) in the month of October, and FFP issue (-96.08%) in the month of July with an annual decrease of -45.52%, -42.87%, -33.00%, -59.79%, -40.98%, and -54.48%, respectively, as compared to year 2019. Compared to year 2020, in year 2021, the annual increase in blood collection, blood issue, FFP preparation, FFP issue, RDP preparation, and RDP issue was +50.20%, +21.68%, +65.31%, +78.52%, +116.23%, and +213.30%, respectively. Our study results show that the COVID-19 pandemic has significantly affected blood transfusion services at our blood bank. The adopted coping strategies to maintain the safe and uninterrupted blood transfusion chain at our blood bank gave us lessons for future preparedness if faced with a similar situation.

COVID-19大流行的不可预见和不确定的危及生命的局势极大地影响了人类日常工作安排的所有领域。本研究旨在评估新冠肺炎大流行对输血服务的影响,探讨疫情期间采取的不间断供血对抗措施。2019年1月至2022年12月期间的献血、血液成分制备和发放数据收集自印度德里RBTC的库存登记册。与2019年非大流行年份相比,2020年所有变量均逐渐下降。10月采血(-79.16%)、8月供血(-71.61%)、10月随机捐献血小板(RDP)制备(-98.09%)、9月随机捐献血小板(RDP)制备(-86.08%)、10月新鲜冷冻血浆(FFP)制备(-100%)、7月FFP制备(-96.08%)等指标降幅最大,年降幅分别为-45.52%、-42.87%、-33.00%、-59.79%、-40.98%和-54.48%。与2019年相比。与2020年相比,2021年采血、供血、FFP准备、FFP准备、RDP准备、RDP发放的年增长率分别为+50.20%、+21.68%、+65.31%、+78.52%、+116.23%、+213.30%。我们的研究结果表明,COVID-19大流行严重影响了我们血库的输血服务。为维护血库安全不间断输血链所采取的应对策略,为我们今后面对类似情况时的防范提供了借鉴。
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引用次数: 0
Erratum: Benefit of rituximab maintenance is associated with Follicular Lymphoma International Prognostic Index in patients with follicular lymphoma. 在滤泡性淋巴瘤患者中,利妥昔单抗维持的获益与滤泡性淋巴瘤国际预后指数相关。
Q3 Medicine Pub Date : 2023-07-01 DOI: 10.1097/BS9.0000000000000164

[This corrects the article DOI: 10.1097/BS9.0000000000000144.].

[这更正了文章DOI: 10.1097/BS9.0000000000000144.]。
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引用次数: 0
Erratum: Development of Auer bodies from giant inclusions associated with rough endoplasmic reticulum in acute promyelocytic leukemia. 勘误:急性早幼粒细胞白血病中与粗内质网相关的巨包涵体的发育。
Q3 Medicine Pub Date : 2023-07-01 DOI: 10.1097/BS9.0000000000000163

[This corrects the article DOI: 10.1097/BS9.0000000000000145.].

[这更正了文章DOI: 10.1097/BS9.0000000000000145.]。
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引用次数: 0
Ginsenoside Rg1 improves anti-tumor efficacy of adoptive cell therapy by enhancing T cell effector functions. 人参皂苷Rg1通过增强T细胞效应物功能提高过继细胞治疗的抗肿瘤效果。
Q3 Medicine Pub Date : 2023-07-01 DOI: 10.1097/BS9.0000000000000165
Yue Liu, Lingna An, Chengfei Yang, Xiaoqi Wang, Ruihao Huang, Xi Zhang

Adoptive cell therapy (ACT) has emerged with remarkable efficacies for tumor immunotherapy. Chimeric antigen receptor (CAR) T cell therapy, as one of most promising ACTs, has achieved prominent effects in treating malignant hematological tumors. However, the insufficient killing activity and limited persistence of T cells in the immunosuppressive tumor microenvironment limit the further application of ACTs for cancer patients. Many studies have focused on improving cytotoxicity and persistence of T cells to achieve improved therapeutic effects. In this study, we explored the potential function in ACT of ginsenoside Rg1, the main pharmacologically active component of ginseng. We introduced Rg1 during the in vitro activation and expansion phase of T cells, and found that Rg1 treatment upregulated two T cell activation markers, CD69 and CD25, while promoting T cell differentiation towards a mature state. Transcriptome sequencing revealed that Rg1 influenced T cell metabolic reprogramming by strengthening mitochondrial biosynthesis. When co-cultured with tumor cells, Rg1-treated T cells showed stronger cytotoxicity than untreated cells. Moreover, adding Rg1 to the culture endowed CAR-T cells with enhanced anti-tumor efficacy. This study suggests that ginsenoside Rg1 provides a potential approach for improving the anti-tumor efficacy of ACT by enhancing T cell effector functions.

过继细胞疗法(ACT)在肿瘤免疫治疗中具有显著的疗效。嵌合抗原受体(CAR) T细胞疗法作为一种极具发展前景的act疗法,在治疗恶性血液肿瘤方面取得了显著的效果。然而,T细胞在免疫抑制性肿瘤微环境中的杀伤活性不足和持久性有限,限制了ACTs在癌症患者中的进一步应用。许多研究都集中在改善T细胞的细胞毒性和持久性,以达到更好的治疗效果。在本研究中,我们探讨了人参的主要药理活性成分人参皂苷Rg1在ACT中的潜在功能。我们在T细胞体外激活和扩增阶段引入Rg1,发现Rg1处理上调了两个T细胞激活标记CD69和CD25,同时促进T细胞向成熟状态分化。转录组测序显示Rg1通过加强线粒体生物合成影响T细胞代谢重编程。当与肿瘤细胞共培养时,rg1处理的T细胞比未处理的细胞表现出更强的细胞毒性。此外,在培养物中加入Rg1使CAR-T细胞的抗肿瘤功效增强。本研究提示人参皂苷Rg1通过增强T细胞效应物功能,为提高ACT抗肿瘤疗效提供了一条潜在途径。
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引用次数: 0
CAR-T cell therapy in myeloma: hopes and hurdles. CAR-T细胞治疗骨髓瘤:希望与障碍。
Q3 Medicine Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000148
Jean Luc Harousseau
Immune therapy is a new avenue in the treatment of multiple myeloma (MM). The naked anti-38 antibodies daratumumab and isatuximab are already used in frontline therapy after excellent results have been achieved in relapsed/refractory MM (RRMM).The second step was the development of immune therapies targeting B cell maturation antigen (BCMA). Genetically mod- ified autologous chimeric antigen receptor (CAR)-T cell therapy BCMA-directed were initially tested in heavily pretreated patients with RRMM exposed to the 3 main therapeutic classes, immunomodulatory drugs (iMiDs), proteasome inhibitors, and anti-CD38 antibodies (triple-class exposed). Efficacy results were unprecedented in this context and Idecabtagene vicleucel (ide-cel or Abecma) was the first BCMA-directed CAR-T cell therapy approved in MM by both Federal Drug Administration (FDA) and European Medicines Agency (EMA). This approval was based on the results of the KarMMa Phase 2 study in 128 patients with RRMM who had previously received a median number of 6 lines of therapy (LOT). 1 The response rate (RR) was 73%, including 33% of complete response (CR) or better and 26% negative min- imal residual disease (MRD). However, median progression-free survival (PFS) was only 8.8 months. The Cartitude 1 Phase1b/2 evaluated ciltacabtagene autoleucel (cilta-cel) another CAR-T cell therapy with 2 BCMA-targeting single domain antibodies in 97 heavily pretreated patients with RRMM. 2 Results were recently updated and with a median follow-up of 27.7 months, 3 the results were even more impressive with a 98% RR, including 82.5% CR or better, and 92% negative MRD in evaluable patients. The 27-month PFS was 55%. With these results, Cilta-cel (Carvykti) was
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引用次数: 1
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血液科学(英文)
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