Blood&Genomics

Expert consensus on standard operating procedures for autologous ozonized blood transfusion

Jianjun Wu, Yahan Fan, Zhanshan Cha, Shijie Mu, Zhongjun Li, Jiwu Gong, Qiushi Wang, Haiyan Wang, Jiubo Liu, Fenghua Liu, MingChia Yang, Juan Zhang, Xuelian Zhou, Jue Xie, Mei Qin, Zebo Yu, Xianjun Ma, Yanli Bai, Xiaoyu Zhou, Yan Bai, Yongjun Wang, Shouyong Hun, Pu Xu, Jiajin Lin, Chunxia Liu, Jing Chen, Hui Wang, Xiaoning Wang, Liying Xu, Quanli Wang, Shuming Zhao

2022, 6(2): 73-80. doi: 10.46701/BG.2022022022022

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Abstract:
Autologous ozonized blood transfusion (AOBT), an autologous blood transfusion treatment that mixes anticoagulant blood with a certain concentration and volume of medical ozone in vitro, is widely used in clinical medicine. However, there is a lack of country-wide guidelines or other special procedures to follow. The objective of this paper is to provide a general guideline on standard operating procedures for autologous ozonized blood transfusion.

The link between tissue-resident memory T cells and graft-versus-host disease

Qingxiao Song, Qinjian Li, Xiaoqi Wang, Xi Zhang

2022, 6(2): 81-90. doi: 10.46701/BG.2022022022026

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Abstract:
In the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), this review outlines and analyzes recent developments in the understanding of the properties of tissue-resident memory T cells (TRMs). The paper first discusses commonly recognized TRM characteristics and key TRM phenotypic markers and then covers the master transcription factors controlling TRM generation and maintenance. The TRM distribution in graft-versus-host disease (GVHD)-targeted organs and correlations between allo-HSCT outcomes and various GVHD subtypes were also reviewed, mainly focusing on skin and gut GVHD. This review discusses the organ- and tissue-specific characteristics of donor- and recipient-derived TRMs after allo-HSCT. It also highlights investigations using murine GVHD models, nonhuman primates, and cutting-edge technologies to track clonotypes, establish transcriptome profiles, and identify donor- and recipient-derived TRMs. Furthermore, this review discusses significant results for TRM functions in GVHD patients. Moreover, potential advantages of performing GVHD-focused TRM research with "dirty mice" rather than laboratory mice were proposed. Understanding TRMs in allo-HSCT is a rapidly growing field requiring future studies to address unresolved questions regarding TRM heterogeneity, plasticity, longevity, alloreactivity, and roles in GVHD and tolerance after allo-HSCT.

The progress of research on chimeric antigen receptor NK cells

Wenwen Zhao, Weiyu Kong, Yan Peng, Qi Tang, Zhenqing Feng

2022, 6(2): 91-101. doi: 10.46701/BG.2022022022027

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Abstract:
Chimeric antigen receptor-modified T (CAR-T) cells have brought a major breakthrough in tumor immunotherapy. As research continues to develop, CAR-T therapies have shown certain limitations, such as graft-versus-host reaction and the long time required to generate CAR-T cells. Natural killer (NK) cells, as the first line of defense against pathogens and cancer cells, belong to the innate immune system and have the advantage of being able to replace T cells, and can be used to prepare engineered chimeric antigen receptor-modified NK (CAR-NK) cells. The biological characteristics of CAR-NK cells, their sources, and the latest research progress and prospects for tumor treatment in China and worldwide are presented in this review.

The function and regulatory mechanism of B cells in tumor immunity

Jikai He, Jiaqi Jia, Wenhao Qu, Lizhou Jia, Wei Zhao

2022, 6(2): 103-113. doi: 10.46701/BG.2022022022031

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Abstract:
B cells are important components of the human immune system, and play a role in the process of specific immunity. In recent years, research on B cells and tumor immunity has made rapid progress. Studies have shown that different types of B cells play different roles in the tumor microenvironment (TME) through a variety of mechanisms. Tumor-infiltrating B cells (TIBs) in the TME play an anti-tumor role by secreting antibodies and presenting antigens, while regulatory B cells (Bregs) inhibit the immune response by secreting a variety of cytokines, thereby promoting tumor immune escape. This review introduces the roles and mechanisms of different subtypes of B cells in different types of tumors.

Identification of the transcription factor KLF9 as a key gene during BM-MSCs adipogenic differentiation

Jiuxuan Li, Chun Wu, Weiwei Zhang, Yang Xiang, Lixin Xiang, Xiaoliang Li, Xiaomei Zhang, Lijia Hou, Lanyue Hu, Li Chen, Qian Ran, Zhongjun Li

2022, 6(2): 114-124. doi: 10.46701/BG.2022022022019

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Abstract:
Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent stem cells with the capacity for self-renewal and differentiating into multiple cell types. However, the underlying regulatory mechanism has not been fully clarified. Krüppel-like factors 9 (KLF9), a potential key transcription factor relevant to numerous physiological processes, has been detected during BM-MSCs adipogenic differentiation by bioinformatics (integrated) analyses from four different adipogenic differentiation datasets. Our results indicated that the KLF9 could regulate the adipogenic differentiation of MSCs and the capacity of adipogenic differentiation in BM-MSCs was sharply down-regulated after KLF9 knockdown. Taken together, our findings demonstrate that KLF9 plays an important role in the process of BM-MSCs differentiation and may open up new avenues for the control of adipogenesis to combat obesity and its related diseases.

Clinical and immunological characteristics of coronavirus disease 2019 patients with redetectable viral RNA post-discharge during the quarantine period

Yan Jiang, Yimei Feng, Zheliang Wei, Yuanyuan Zhang, Bo You, Mingdong Hu, Mei Mao, Shiming Yang, Xi Zhang, Cheng Zhang

2022, 6(2): 125-132. doi: 10.46701/BG.2022022022011

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Abstract:
Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. The global pandemic poses a serious challenge to the medical community. Detection of serum immunoglobulin G (IgG) and immunoglobulin M (IgM) is crucial for the diagnosis of COVID-19. IgG is particularly important for antiviral response assessment. Our study divided 51 patients into "persistence" and "non-persistence" groups according to the status of positive RNA, and the clinical and immunological characteristics of two groups of patients with redetectable viral RNA post-discharge during their quarantine period were studied, including the clinical signs, symptoms, hospitalization time and laboratory blood routine tests, biochemical indexes, and IgM/IgG antibodies titers detecting. Overall, the median age was 57.0 (21–90) years, and the median time was 9 days from discharge to redetectable viral RNA. The median titers of IgM and IgG antibodies were 23.19 AU/mL and 170.36 AU/mL (P>0.05), respectively. The median ratio of IgG/IgM was 6.63 and the median ratio of IgG/IgM was 8.02 and 4.03 for persistence and non-persistence groups, respectively (P=0.079). The median length of hospital stays for patients that had reached the composite endpoint was 16.5 and 9 days in the persistence and non-persistence groups. In conclusion, there was a significant difference in hospitalization time between the two groups of patients, but there was no statistical difference in the IgM/IgG titer detection, which required more data to verify.

Clinical effects of CD200 on the outcome of acute myeloid leukemia patients with diverse treatments

Yanfang Zhang, Xi Quan, Guancheng Song, Ying Song, Shifeng Lou, Kang Zhou, Jianchuan Deng

2022, 6(2): 133-140. doi: 10.46701/BG.2021022022018

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Abstract:
CD200 has been associated with a poor prognosis in acute myeloid leukemia (AML). However, the outcome for AML remains heterogeneous and relies more heavily on treatment procedures received by patients. This study aimed to evaluate the correlations between CD200 expression and its prognostic significance in AML treated using diverse treatments. 160 AML patients treated using different chemotherapeutic approaches were retrospectively reviewed from 2018 to 2021, and the effects of CD200 expression on disease outcomes were evaluated. CD200 expressed in 100/160 (62.5%) cases, defined as the CD200-positive (CD200⁺) group, while the remaining cases were identified as the CD200-negative (CD200⁻) group. The CD200⁺ group had a significantly lower probability of complete remission after the first induction chemotherapy, both in univariate (P=0.002) and multivariate (P=0.023) analyses. In the entire population, CD200 expression exerted no significant effect on disease-free survival (DFS) (P=0.837) nor overall survival (OS) (P=0.155). In the subgroup analysis, CD200 negatively affected OS in patients receiving less-intensive treatments (P=0.005) and those receiving chemotherapy alone (P=0.019). In conclusion, CD200 positive indicates a low remission rate and further reduces long-term survival in patients receiving less-intensive approaches and chemotherapy-alone. Intensive chemotherapy and stem cell transplantation may reduce the adverse effects of CD200 expression on AML patients.

A prediction model of alternative splicing events reveals the prognostic predictors and immune microenvironment signatures in lung adenocarcinoma

Tong Cheng, Manyu Xu, Jiaweng Shi, Hui Zhang, Zhiyuan Tang

2022, 6(2): 141-151. doi: 10.46701/BG.2022022022016

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Abstract:
In tumor development and microenvironment formation, alternative splicing (AS) has become increasingly important. Nevertheless, the clinical significance of AS in lung adenocarcinoma (LUAD) remains unclear. A comprehensive assessment of AS events in 455 LUAD patients was performed using data from The Cancer Genome Atlas (TCGA) database in this study. Lasso and Cox regression analyses were performed to identify survival-related significant AS events. The tumor microenvironment was assessed using CIBERSORT, a single-sample gene set enrichment analysis, and the ESTIMATE software package. Fifteen AS events screened by Lasso regression were constructed to build a risk prediction model. FAXDC2, CDKN2A, and LAMA3 were identified in this study. In addition, immune scores, stromal scores, and tumor purity in different risk groups were assessed. The risk score was also correlated with tumor infiltrating immune cells. This study suggests that AS events are associated with tumor development and the immune microenvironment, and three genes, FAXDC2, CDKN2A, and LAMA3 are identified, which may be potential markers of prognosis in LUAD.

Identification of a novel nonsense mutation (c.618C>G, p.Tyr206Ter) in the ABO gene in a Chinese individual

Yujie Kong, Tong Li, Mingquan Liu, Min Yang, Dongming Wu, Ying Xu

2022, 6(2): 153-155. doi: 10.46701/BG.2022022022029

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Abstract:
The ABO gene is mainly composed of A, B, and O alleles. The most common O alleles share one nucleotide deletion of G at position 261 in the ABO gene. This report found a novel nonsense mutation in an ABO allele which led to group O in a Chinese individual. Forward and reverse typing tests were carried out first using the manual tube method. Weak expression of A or B antigens on red blood cells (RBCs) was confirmed by absorption and elution test. Exons 6 and 7 in the ABO gene were amplified and direct-sequenced. The haplotypes of the ABO gene were identified by clone-sequencing. Serologic results showed that the phenotype of proband was group O. Based on direct sequencing results, the proband was heterozygous for the ABO*A1.01 allele and ABO*O.01.01 allele, except for a heterozygous c.618C>G mutation. The clone sequencing demonstrated that a nonsense C>G mutation at position 618 was identified in exon 7 of the ABO*A1.01-like allele, which caused a p.Tyr206Ter exchange in the ABO glycosyltransferase. Thus, the novel ABO allele was classified as O allele. The study suggested that a novel nonsense mutation in the ABO gene was identified in a Chinese individual with group O, resulting in the truncated, 205-amino-acid ABO glycosyltransferase, which lost its transferase activity.

2022 Vol. 6, No. 2