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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 HEMATOLOGY 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 HEMATOLOGY 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 HEMATOLOGY 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 HEMATOLOGY 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 HEMATOLOGY 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 HEMATOLOGY 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 HEMATOLOGY 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
Development of Auer bodies from giant inclusions associated with rough endoplasmic reticulum in acute promyelocytic leukemia. 急性早幼粒细胞白血病与粗内质网相关的巨包涵体发育成小体。
Q3 HEMATOLOGY Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000145
Yong-Xin Ru, Shu-Xu Dong, Jing Liu, Brian Eyden

Giant inclusions and Auer bodies in promyeloblasts were investigated in a study which included transmission electron microscopy (TEM) for morphology and ultrastructural cytochemistry for myeloperoxidase in 10 patients with acute promyelocytic leukemia (APL). Ultrastructural cytochemistry demonstrated positive myeloperoxidase reactivity in giant inclusions, expanded rER cisternae, Auer bodies and primary granules. TEM revealed that giant inclusions were adorned by degenerated rER membrane, some of them sharing features with Auer bodies. We hypothesize a novel origin for Auer body development in promyeloblasts of APL, namely that they originate from peroxidase-positive and expanded rER cisternae, and that primary granules were directly released from these expanded rER elements, bypassing the Golgi apparatus.

本文用透射电镜观察了10例急性早幼粒细胞白血病(APL)患者幼幼粒细胞中巨包涵体和奥尔小体的形态,并对其超微结构细胞化学进行了研究。超微结构细胞化学显示,在巨大包涵体、扩大的内质网池、奥尔体和原生颗粒中,髓过氧化物酶反应阳性。透射电镜显示,巨大的包裹体由退化的rER膜包裹,其中一些与Auer体具有相同的特征。我们假设APL早幼粒细胞的er体发育有一个新的起源,即它们起源于过氧化物酶阳性和扩大的rER池,并且初级颗粒直接从这些扩大的rER元素中释放出来,绕过高尔基体。
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引用次数: 1
Intravenous-oral itraconazole versus oral posaconazole in preventing invasive fungal diseases for acute leukemia patients. 静脉-口服伊曲康唑与口服泊沙康唑预防急性白血病侵袭性真菌疾病的比较。
Q3 HEMATOLOGY Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000155
Li Liu, Xiaolei Pei, Runzhi Ma, Yi He, Rongli Zhang, Jialin Wei, Qiaoling Ma, Weihua Zhai, Aiming Pang, Erlie Jiang, Mingzhe Han, Donglin Yang, Sizhou Feng

Invasive fungal diseases (IFDs) are major and lethal infectious complications for patients with neutropenia after chemotherapy. Prophylaxis with intravenous and oral suspended itraconazole (200 mg Q12h intravenously × 2 days followed by 5 mg/kg·d orally in twice) or oral suspension of posaconazole (200 mg Q8h) was administered for preventing IFDs. The only 2 episodes of proven IFDs were not included after propensity-score matching (PSM), while the incidence of possible IFDs was 8.2% (9/110) in itraconazole group and 1.8% (2/110) in posaconazole group, respectively (P = .030). In clinical failure analysis, the failure rate of posaconazole group was lower as compared to the itraconazole group (2.7% vs 10.9%, P = .016). Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs, while posaconazole suspension seems more tolerable.

侵袭性真菌病(IFDs)是中性粒细胞减少患者化疗后主要的致死性感染性并发症。预防方法:静脉滴注和口服伊曲康唑悬浮液(200 mg Q12h静脉滴注× 2天,随后5 mg/kg·d口服2次)或泊沙康唑口服悬浮液(200 mg Q8h)。经倾向评分匹配(PSM)后,仅有2例确诊IFDs未被纳入,而伊曲康唑组和泊沙康唑组的可能IFDs发生率分别为8.2%(9/110)和1.8% (2/110)(P = 0.030)。在临床失败分析中,泊沙康唑组的失败率低于伊曲康唑组(2.7% vs 10.9%, P = 0.016)。静脉-口服伊曲康唑和泊沙康唑混悬液均可有效预防ifd,泊沙康唑混悬液的耐受性更强。
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引用次数: 0
Big stride in gene therapy for hemophilia B in China. 血友病B基因治疗在中国取得重大进展。
Q3 HEMATOLOGY Pub Date : 2023-04-01 DOI: 10.1097/BS9.0000000000000150
Jianmin Wang, Dan Yang
In a recent issue of Lancet Haematology , Xue et al 1 reported an adeno-associated virus (AAV)-based gene therapy in 10 patients with hemophilia B (HB) from China. BBM-H901, a novel vector comprised of an engineered liver-tropic AAV cap- sid (AAV843), synthesized liver-specific promoter and CpG reduced factor IX (FIX) Padua coding sequence, was infused in 10 patients (baseline FIX coagulation activity [FIX:C] were less than 2 IU/dL) after 1 week of prophylactic prednisone pretreat- ment (1 mg/kg per day). After a median follow-up of 58 weeks, mean FIX:C reached 36.9 ± 20·5 IU/dL. No FIX inhibitors or serious adverse events were observed. All patients developed high titer neutralizing antibodies against vector capsid. The concentrations of alanine aminotransferase and aspartate aminotransferase in plasma were below the upper limit of normal range in 8 patients. No FIX concentrate infusion was needed after gene therapy for these patients. This is a huge step forward in the treatment of HB in China.
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引用次数: 1
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血液科学(英文)
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