Aplastic anemia (AA) is a common hematologic disease that is characterized by hematopoietic failure of the bone marrow and pancytopenia of the peripheral blood, which can be divided into severe and non-severe aplastic ane-mia, or acute and chronic aplastic anemia according to the severity of the disease and the progress of the clinical course. During the past years, the advantages of Traditional Chinese Medicine (TCM) on the treatment of AA have been well clarified and its theory system has been improved as well. This review is mainly on representing the pathogenesis, therapeutic principle and method, research progression, and advantages of TCM on AA.

Objective. Aplastic anemia (AA) is an uncommon disease, characterized by pancytopenia and hypocellular bone marrow, but it is common in the blood system. The medication rules of traditional Chinese medicine (TCM) in the treatment of AA are not clear, for which it is worth exploring the medication rules by data mining methods. Methods. This study used SPSS Modeler 18.0 and SPSS statistics to analyze the cases of AA from Zhejiang Provincial Hospital of Chinese Medicine (ZJHCM) from March 1, 2019, to March 1, 2022. Data mining methods, including frequency analysis, cluster analysis, and association rule learning, were performed in order to explore the medication rules for AA. Results. (1) A total of 859 prescriptions, which met the inclusion criteria, consisted of 255 herbs. In descending order of the frequency of herbal medicine, we have Danggui, Huangqi, Shudihuang, Fuling, Gancao, Shanyao, Shanzhuyu, Baizhu, Dangshen, and Xianhecao. (2) Frequency analysis of herb properties: the Four Qi of 255 kinds of TCMs are mainly warm and neutral medicines. The Five Flavors are mainly sweet medicines, followed by bitter medicines. The main meridians are the liver, spleen, and kidney. (3) Clustering of medications: TCMs with the top 20 frequencies are classified into 9 groups by cluster analysis. (4) Association rule analysis of high-frequency herbs: using the Apriori algorithm, the results showed that there were 3 herb pairs with support of over 0.3 and 12 herb pairs with confidence above 0.85. Conclusion. The basic pathogenesis of AA (Sui Lao) is spleen and kidney essence deficiency, Qi deficiency, and blood stasis. The main herbs have warm and neutral properties, sweet tastes, and liver, spleen, and kidney meridian tropisms, whose purpose is to tonify the kidney and invigorate the spleen, tonify Qi, and promote blood circulation.

Aplastic anemia (AA) is a disease characterized by hematopoiesis failure, bone marrow aplasia, and pancytopenia. It can be inherited or acquired. Although acquired AA is believed to be immune-mediated and random, new evidence suggests an underlying genetic predisposition. Besides confirmed genomic mutations that contribute to inherited AA (such as pathogenic mutations of TERT and TERC), germline variants, often in heterozygous states, also play an unignorable role in the onset and progression of acquired AA. These variants, associated with inherited bone marrow failure syndromes (IBMFS) and inborn errors of immunity (IEI), contribute to the disease possibly through mechanisms including gene homeostasis, DNA repair, and immune injury. This article explores the nuanced association between acquired AA and germline variants, detailed the clinical significance of germline variants in diagnosing and clinical management of this condition. More works are encouraged to better understand the role of immunogenic pathogenic variants and whether somatic mutation participate as secondary “hit” in the development of bone marrow failure.

Macrophages are pivotal regulators of immunity, with intercellular communication being a central mechanism of their function. Among these communications, chemokines act as critical messengers in macrophage-T cell crosstalk. This review systematically elucidates the notable roles of macrophage-derived chemokines in modulating T cell homeostasis, particularly concentrating on their influence on both CD4 ⁺ and CD8 ⁺ T cell differentiation, proliferation, exhaustion, secretory activity, metabolic reprogramming (involving glycolysis and OXPHOS), chemotaxis, and memory formation. In the tumor microenvironment (TME), the dualistic nature of chemokines was highlighted: tumor-associated macrophages (TAMs) could secrete immunosuppressive factors, such as CCL22 and CCL5, recruiting inhibitory cells and inducing CD8 ⁺ T cell exhaustion. In contrast, M1-like macrophages could produce CXCL9 and CXCL10, activating effector CD8 ⁺ T cells, thereby enhancing anti-tumor immunity. Finally, the promising therapeutic potential of targeting specific chemokine signaling axes, such as CCL2/CCR2 and CXCL10/CXCR3, was discussed as a strategy to improve the efficacy of cancer immunotherapy.

Background/Aims: Although the cure rate of acute promyelocytic leukemia (APL) has exceeded 90%, the relapse/refractory APL that resistant to all-trans retinoic acid (ATRA) or ATO was still serious concern. Matrine (MAT) could improve the differentiation ability of ATRA-resistant APL cells. This study aimed to explore how the APL-specific fusion protein was degraded in ATRA-resistant APL with the application of MAT and ATRA. Methods: ATRA-sensitive (NB4) and ATRA-resistant (NB4-LR1) cell lines were used. Nitroblue tetrazolium reduction assay and flow cytometry were used to detect the differentiation ability. The activity of ubiquitin-proteasome and autophagy-mediated pathways in both cells treated with ATRA with or without MAT were compared in protein and mRNA level (Western blot analysis, qRT-PCR), the Fluorescent substrate Suc-LLVY-AMC detection was used to detect the activity of proteasome, and electron microscope for observing autophagosome. MG 132(proteasome inhibitor), rapamycin (autophagy activator), hydroxychloroquine (lysosomal inhibitor) and STI571 [retinoic acid receptor alpha (RARα) ubiquitin stabilizer] were used as positive controls. The effect of MAT was observed in vivo using xenografts. Results: MAT improved the sensitivity of NB4-LR1cells to ATRA treatment, which was consistent with the expression of PML-RARα fusion protein. MAT promoted the ubiquitylation level in NB4-LR1. MG 132 induced the decrease in RARα in both cell lines, and hampered the differentiation of NB4 cells. MAT also promoted the autophagy in NB4-LR1 cells, with an increase in microtubule-associated protein 1 light chain3 (LC3)-II and LC3-II/LC3-I ratio and exhaustion of P62. The expression of LC3II increased significantly in the MAT and ATRA + MAT groups in combination with lysosomal inhibitors. A similar phenomenon was observed in mouse xenografts. MAT induced apoptosis and differentiation. Conclusions: Autophagy and ubiquitin-mediated proteolytic degradation of PML/RARα fusion protein are crucial in MAT-induced differentiation sensitivity recovery of NB4-LR1 cells.