The incidence of leukemia,a malignant cancer originating from the hematopoietic system,is increasing annually.Although traditional treatment method such as chemotherapy and hematopoietic stem cell transplantation have improved patient survival rates to some extent,serious side effects,drug tolerance,and high recurrence rates remain.In recent years,studies have shown that the gut microbiota and its metabolites play an important role in the occurrence,development,and complications of leukemia.Imbalance of the gut microbiota can lead to decreased immune function and an intensified inflammatory response,which is a key factor driving disease progression.Some metabolites,such as short-chain fatty acids,enhance immune function and improve patient prognosis through intestinal barrier repair,while others,such as hydrogen sulfide and bile acids,show potential anti-tumor effects exerted through regulation of tumor cell apoptosis and immune balance.Traditional Chinese medicine aimed at regulating the structure of the gut microbiota and its metabolites has shown great potential in alleviating the side effects of chemotherapy for leukemia.This review covers the role of the gut microbiota and its metabolites in the occurrence,development,and complications of leukemia,and explores treatment strategies for regulating the microbiota,including fecal microbiota transplantation,probiotics,and traditional Chinese medicine intervention.We anticipate that this review will serve as a reference for improving the treatment and prognosis of leukemia.

Objective To investigate the effects and underlying mechanisms of total flavonoids of sarcandra glabra(TFFSG)on bone marrow mesenchymal stem cells(BMSCs)and their derived exosomes in immune thrombo-cytopenia(ITP),with a focus on promoting megakaryocyte differentiation and maturation.Methods BMSCs induced by rabbit anti-rat platelet serum(APS)were divided into five groups:a blank control group,an ITP-BMSCs model group,and three TFFSG intervention groups with low(1.95 μg/mL),medium(3.90 μg/mL),and high doses(7.80 μg/mL).The apoptosis rates and the expression levels of apoptosis-related proteins-B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(BAX),and Cysteinyl aspartate-specific proteinase-3(Caspase-3)-were assessed.Exosomes were isolated from the blank control group(NC-BMSCs-Exos),the ITP-BMSCs model group(ITP-BMSCs-Exos),and the medium-dose TFFSG group(TFFSG-BMSCs-Exos).Each group's exosomes(5 μg/mL)were co-cultured with megakaryocytic lineage Dami cells for 96 hours.Flow cytometry was employed to evaluate the expression of megakaryocytic differentiation markers(CD41a,CD42b,CD61)and the proportion of polyploid cells(≥4 N)in each group.Western Blot analysis was conducted to examine the expression of p-MEK1/2,MEK1/2,p-ERK1/2,and ERK1/2 across all groups.Results Compared with the ITP-BMSCs model group,the apoptosis rates in all TFFSG intervention groups were significantly reduced(P<0.01).In the medium-and high-dose TFFSG groups,BAX and Caspase-3 expression levels were markedly downregulated,whereas Bcl-2 expression was upregulated(P<0.05,P<0.01).Compared with the ITP-BMSCs-Exos group,the TFFSG-BMSCs-Exos group demonstrated increased expression of CD41a+,CD42b+,and CD61+,a higher proportion of polyploid cells(≥4 N)(P<0.05),as well as elevated ratios of p-MEK1/2 to MEK1/2 and p-ERK1/2 to ERK1/2(P<0.05).Conclusion TFFSG inhibits apopto-sis of ITP-state BMSCs in vitro and promotes megakaryocyte differentiation and polyploidization maturation through BMSC-derived exosomes by activating the MEK1/2-ERK1/2 signaling pathway.

The incidence of leukemia,a malignant cancer originating from the hematopoietic system,is increasing annually.Although traditional treatment method such as chemotherapy and hematopoietic stem cell transplantation have improved patient survival rates to some extent,serious side effects,drug tolerance,and high recurrence rates remain.In recent years,studies have shown that the gut microbiota and its metabolites play an important role in the occurrence,development,and complications of leukemia.Imbalance of the gut microbiota can lead to decreased immune function and an intensified inflammatory response,which is a key factor driving disease progression.Some metabolites,such as short-chain fatty acids,enhance immune function and improve patient prognosis through intestinal barrier repair,while others,such as hydrogen sulfide and bile acids,show potential anti-tumor effects exerted through regulation of tumor cell apoptosis and immune balance.Traditional Chinese medicine aimed at regulating the structure of the gut microbiota and its metabolites has shown great potential in alleviating the side effects of chemotherapy for leukemia.This review covers the role of the gut microbiota and its metabolites in the occurrence,development,and complications of leukemia,and explores treatment strategies for regulating the microbiota,including fecal microbiota transplantation,probiotics,and traditional Chinese medicine intervention.We anticipate that this review will serve as a reference for improving the treatment and prognosis of leukemia.

Objective To investigate the effects and underlying mechanisms of total flavonoids of sarcandra glabra(TFFSG)on bone marrow mesenchymal stem cells(BMSCs)and their derived exosomes in immune thrombo-cytopenia(ITP),with a focus on promoting megakaryocyte differentiation and maturation.Methods BMSCs induced by rabbit anti-rat platelet serum(APS)were divided into five groups:a blank control group,an ITP-BMSCs model group,and three TFFSG intervention groups with low(1.95 μg/mL),medium(3.90 μg/mL),and high doses(7.80 μg/mL).The apoptosis rates and the expression levels of apoptosis-related proteins-B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(BAX),and Cysteinyl aspartate-specific proteinase-3(Caspase-3)-were assessed.Exosomes were isolated from the blank control group(NC-BMSCs-Exos),the ITP-BMSCs model group(ITP-BMSCs-Exos),and the medium-dose TFFSG group(TFFSG-BMSCs-Exos).Each group's exosomes(5 μg/mL)were co-cultured with megakaryocytic lineage Dami cells for 96 hours.Flow cytometry was employed to evaluate the expression of megakaryocytic differentiation markers(CD41a,CD42b,CD61)and the proportion of polyploid cells(≥4 N)in each group.Western Blot analysis was conducted to examine the expression of p-MEK1/2,MEK1/2,p-ERK1/2,and ERK1/2 across all groups.Results Compared with the ITP-BMSCs model group,the apoptosis rates in all TFFSG intervention groups were significantly reduced(P<0.01).In the medium-and high-dose TFFSG groups,BAX and Caspase-3 expression levels were markedly downregulated,whereas Bcl-2 expression was upregulated(P<0.05,P<0.01).Compared with the ITP-BMSCs-Exos group,the TFFSG-BMSCs-Exos group demonstrated increased expression of CD41a+,CD42b+,and CD61+,a higher proportion of polyploid cells(≥4 N)(P<0.05),as well as elevated ratios of p-MEK1/2 to MEK1/2 and p-ERK1/2 to ERK1/2(P<0.05).Conclusion TFFSG inhibits apopto-sis of ITP-state BMSCs in vitro and promotes megakaryocyte differentiation and polyploidization maturation through BMSC-derived exosomes by activating the MEK1/2-ERK1/2 signaling pathway.

Leukemia is a critical disease with a high incidence and extremely high fatality rate.Immune escape by leukemia stem cells(LSC)is the main factor for recurrence and progression after remission.Clinical diagnosis and treatment by Traditional Chinese Medicine(TCM)have distinct advantages of syndrome differentiation and treatment.Based on the purpose of diagnosis and treatment,leukemia treatment by TCM emphasizes the harmony of yin and yang to restore human functions,which is conducive to improve autoimmunity and conforms to the mechanism of intervention for tumor cell immune escape.This article discusses the mechanism and research progress of TCM interventions in LSC immune escape based on literature and TCM theory.

Objective Through bibliometrics and visual analysis of the related studies on traditional Chinese medicine (TCM) treatment of immune thrombocytopenia (ITP), this study aims to sort out the overall research progress, hotspots, and trends in this field, and provide reference for further research in ITP. Methods The articles on ITP treated by TCM were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), Web of Science Core Collection (WOSCC), and PubMed. The retrieval time was from the establishment of the databases to July 31, 2022. VOSviewer, CiteSpace, Carrot2, and NoteExpress were used for data analysis of the articles in terms of their quantities, types, and journals, and for visualization of research hotspots, authors, institutions, and keywords. Results 1 493 Chinese articles and 40 English articles were included. The articles in Chinese mainly focus on clinical trial research and clinical experience summary, while the English articles mainly focus on clinical trial research and animal research. The Chinese articles were published in 317 Chinese journals, while English articles were published in 29 English journals. Research hotspots include the clinical syndrome differentiation of ITP, the therapeutic effect of TCM compounds on ITP, and the mechanism of ITP treatment. Keyword analysis shows that there are many research achievements in integrated traditional Chinese and western medicine treatment, clinical research, famous doctors’ experience, TCM treatment, cellular immunity, and humoral immunity. The authors with the most articles in Chinese and English are Professor CHEN Xinyi and Professor MA Rou, respectively, and the research institutions with the most articles are Dongzhimen Hospital of Beijing University of Chinese Medicine and Xiyuan Hospital of China Academy of Chinese Medical Sciences. Chinese herbs often used to treat ITP clinically include Xianhecao (Agrimoniae Herba), Nvzhenzi (Ligustri Lucidi Fructus), Mohanlian (Ecliptae Herba), Zhongjiefeng (Sarcandrae Herba), etc., and the prescription usually used to treat ITP include Guipi Decoction (归脾汤), Xijiao Dihuang Decoction (犀角地黄汤), Bazhen Decoction (八珍汤), Erzhi Pill (二至丸), and Xiaochaihu Decoction (小柴胡汤). The main development trends toward retrospective study, TCM treatment mechanism, and data mining. Conclusion The research on TCM treatment of ITP has progressed steadily, but in-depth studies and close cooperation between research institutions are necessary for the modernization of TCM in treating ITP.

Objective To observe the effect of expelling wind, cooling blood and invigorating kidney prescription on the marrow megakaryocyte differentiation maturity and TGF-β1 in patients with chronic idiopathic thrombocytopenic purpura (CITP). Methods Fifty CITP patients were randomly divided to three groups, including 20 patients administrated with the expelling wind, cooling blood and invigorating kidney prescription as TCM group, 15 patients with the same decoction and prednisone as combine group, and 15 patients with prednisone as western medicine group, 4 weeks as one treatment course. After 3 courses, the change of platelet counts, marrow megakaryocyte amount, platelet-produced megakaryocyte proportion and TGF-β1 level in the marrow were observed. Results The fine efficiency of TCM group (55.0%, 11/20) excelled western medicine group (20.0%, 3/15) significantly and close to that of combine group (60.0%, 9/15). Platelet counts of TCM group was raised obviously after treatment (P<0.01), better than that of western medicine group (P<0.05), and was similar to that of combine group. The marrow megakaryocyte amount of TCM group was effectively decreased and the platelet-produced megakaryocyte proportion was increased greatly (P<0.01), similar to that of combine group, which of western medicine group had no significant difference between pre-therapy and post-therapy. TGF-β1 of TCM group and combine group degraded obviously (P<0.05) compared with that before treatment, and was significant deviation compared with that of western medicine group (P<0.05). Conclusion The expelling wind, cooling blood and invigorating kidney prescription can effectively degrade the value of TGF-β1 of CITP patients, facilitate the maturity of the marrow megakaryocyte amount and raise the platelet counts.