Objective To explore the therapeutic effect of Yiqi Tongyang Granule in the treatment of immune thrombocytopenia mice and the underlying mechanism.Methods BALB/c mice were treated with anti-mouse platelet serum from guinea pig to establish an immune thrombocytopenia mouse model. Model mice were randomly devided into the model group, the prednisone group, the Yiqi Tongyang Granule group, and the Jinshuye group; 10 unmodeled mice as the control group. The mice were treated with Yiqi Tongyang Granule（17.4 g/kg）, prednisone（9.1 mg/kg）, and Jinshuye Styptic Mixture（3.9 mL/kg） by gavage for 11 days, and the platelets（PLT）, white blood cells（WBC）, and hemoglobin（Hb） counts in the mice were measured. Bone marrow megakaryocyte counts were compared by bone marrow smears and bone marrow pathology, and the proportions of different types of megakaryocytes in bone marrow were analyzed. The organ coefficients and pathological changes of the spleen and thymus were observed in mice. Lymphocyte subsets were detected using a flow cytometer.Results Compared with the control group, the number of PLT in immune thrombocytopenia mice was reduced（P＜0.05）, and after treatment with Yiqi Tongyang Granule, prednisone, and Jinshuye Styptic Mixture, the number of PLT was increased（P＜0.05）. Compared with the control group, the number of bone marrow megakaryocytes was increased and the proportion of PLT-producing megakaryocytes was decreased in immune thrombocytopenia mice（P＜0.05）. The number of megakaryocytes was decreased after treatment with Yiqi Tongyang Granule（P＜0.05）, the ratio of primitive and naive megakaryocytes was decreased, and the proportion of PLT-producing megakaryocytes was increased in the immune thrombocytopenia mice（P＜0.05）. The spleen was observed to be enlarged in the immune thrombocytopenia mice based on the spleen organ coefficient and pathology, and extramedullary hematopoiesis was found to be common in the spleens of immune thrombocytopenia mice. Thymus atrophy was very obvious in immune thrombocytopenia mice treated with prednisone based on the thymus organ coefficient and pathology. The percentages of Tc, Th, and Treg cells of immune thrombocytopenia mice were reduced, and these percentages were increased after treatment with Yiqi Tongyang granules（P＜0.05）.Conclusion Yiqi Tongyang Granule could regulate the immune state of immune thrombocytopenia mice by regulating the lymphocyte subpopulations and increase the PLT levels in peripheral blood by affecting the number of bone marrow PLT-producing megakaryocytes. The therapeutic effect of Yiqi Tongyang Granule was similar to that of prednisone and clearly superior to that of Jinshuye Styptic Mixture.

Objective To explore the potential molecular target and mechanism of Qinghuang Powder in the treatment of myelodysplastic syndrome（MDS）.Methods Fifteen MDS patients were enrolled in this study.Bone marrow samples were extracted before treatment and 6 months after treatment with Qinghuang Powder, and RNA-seq was performed to detect the differentially expressed genes（DEGs）in bone marrow mononuclear cells before and after treatment.Gene ontology（GO）annotation and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment were performed for the DEGs.Cytoscape 3.9.1 was employed to build the protein-protein interaction（PPI）network of DEGs.Furthermore, the MDS cell line MUTZ-1 was treated with arsenic sulfide, the main effective component of Qinghuang Powder, and then real-time quantitative PCR was employed to verify the RNA-seq results.Results A total of 2 841 DEGs were identified by RNA-seq in bone marrow nucleated cells of MDS patients treated with Qinghuang Powder for 6 months, including 1 892 up-regulated genes and 949 down-regulated genes.GO annotation showed that these DEGs were mainly involved in histone modification highly associated with MDS.KEGG pathway enrichment indicated that Qinghuang Powder treated MDS via the hypoxia-inducible factor-1（HIF-1）,tumor necrosis factor-alpha（TNF-α）,and vascular endothelial growth factor（VEGF）signaling pathways.According to GO annotation results, the DEGs associated with histone modification were used to construct the PPI network, from which the core genes were screened out.The MDS cells treated with arsenic sulfide showed significantly up-regulated expression of E1A binding protein p300（EP300）,histone deacetylase 7（HDAC7）,and SET domain-containing protein 2（SETD2）and down-regulated expression of HDAC6,which was consistent with the sequencing results.Conclusion Histone modification is an important step of Qinghuang Powder in the epigenetic regulation of MDS patients.EP300,HDAC6,HDAC7,and SETD2 may be the key targets of Qinghuang Powder in the treatment of MDS.

目的 探讨骨髓增生异常综合征伴多系病态造血(MDS-MLD)外周血常规和骨髓象特点,并分析T淋巴细胞亚群情况,为临床诊疗提供依据.方法 选取中国中医科学院西苑医院2021-01-01-10-30确诊的MDS-MLD患者27例和健康体检者8名,用流式细胞仪检测外周血常规中Th1、Th2、Th17和Treg淋巴细胞比例,采用独立样本t、单因素方差和非参数检验分析2组之间T淋巴亚群差异,并收集MDS-MLD患者入组时骨髓形态学和细胞遗传学信息.结果(1)MDS-MLD患者外周血三系减少,平均红细胞体积(MCV)和红细胞分布宽度(RDW-CV)增高,骨髓粒系24例(88.89％)、红系18例(66.67％)和巨核细胞改变9例(33.33％)均可见形态异常,有3例(11.11％)染色体异常;(2)MDS-MLD患者Th1细胞(t=2.931,P=0.006)、Th17细胞(Z=-2.848,P=0.004)和Th1/Th2水平(Z=-2.556,P=0.011)均高于健康人群;(3)MDS-MLD较低危组Th1细胞(Hc=9.169,P=0.007)、Th17细胞(Hc=8.171,P=0.027)和Th1/Th2水平(Hc=7.484,P=0.019)高于健康人群,较高危组Th17细胞(Hc=8.171,P=0.033)高于健康人群,而2个危度层相比各T淋巴亚群间差异均无统计学意义;(4)MDS-MLD患者中有输血依赖的10例(37.04％),较其他患者这类患者Th17细胞(t=-2.870,P=0.008)和Th17/Treg水平(Z=-3.616,P<0.001)增高,Treg细胞水平减低,t=2.503,P=0.019;(5)低增生性MDS 5例(18.52％),较其他患者Th17细胞(Z=-3.059,P=0.002)和Th17/Treg水平(Z=-2.466,P=0.014)增高;(6)再生障碍性贫血(AA)继发MDS-MLD 13例(48.15％),较原发性MDS-MLD Th17细胞增高,Z=2.241,P=0.034.结论 MDS-MLD患者中T淋巴细胞亚群失衡,免疫亢进在疾病发病中具有重要作用.此外,对于输血依赖性MDS、低增生性MDS及AA继发MDS的临床诊疗,Th17细胞淋巴亚群具有一定意义.

目的 观察以血砷浓度≥30μg/L作为目标值调整青黄散方案中青黄散剂量治疗骨髓增生异常综合征伴多系病态造血(MDS-MLD)的有效性和安全性.方法 采用前瞻性病例系列研究方法,纳入2018年3月—2019年5月就诊于中国中医科学院西苑医院血液科门诊MDS-MLD患者60例.所有患者均接受青黄散联合补肾健脾方和司坦唑醇片治疗,3个月为1个疗程,共治疗2个疗程.分析每个疗程后患者的血砷浓度和疗效,并记录治疗期间发生的不良反应.结果 60例患者完成第1个疗程治疗和检测,总有效率48.3％(29/60);血砷浓度≥30 μg/L患者有效率显著高于血砷浓度＜30 μg/L患者(62.8％vs11.8％,P＜0.01).57例患者完成了第2个疗程治疗和检测,总有效率64.9％(37/57);血砷浓度≥30 μg/L患者的有效率显著高于血砷浓度＜30 μg/L患者(69.8％vs0.0％,P＜0.05);患者外周血细胞HGB和PLT计数的提升先于WBC和中性粒细胞计数(ANC).不良反应发生率21.7％(13/60),包括轻度消化道不良反应、下肢水肿和轻度肝功能异常.结论 以血砷浓度≥30 μg/L作为目标值调整青黄散方案中青黄散剂量治疗MDS-MLD有一定的疗效优势和较好的安全性.

目的 探讨含砷中药青黄散治疗前后骨髓增生异常综合征(Myelodysplastic Syndromes,MDS)患者的线粒体DNA(Mitochondrial DNA,mtDNA)拷贝数的变化,并对其作用机理进行初步研究.方法 收集2016年4月至2018年7月中国中医科学院西苑医院血液科门诊的MDS患者40例为治疗组,以青黄散为主联合补肾健脾方治疗6个月.以RT-PCR方法检测青黄散治疗前后MDS患者骨髓单个核细胞的mtDNA拷贝数,同时以9例健康体检者的外周血有核细胞mtDNA拷贝数为正常对照组;以试剂盒检测青黄散治疗前后MDS患者骨髓上清液中超氧化物歧化酶(Superoxide Dismutase,SOD)、谷胱甘肽(Glutathione,GSH)和丙二醛(Malondialdehyde,MDA)的变化.结果 与正常对照组比较,治疗组治疗前MDS患者的mtDNA拷贝数明显增高(P<0.05);治疗组经青黄散治疗后mtDNA拷贝数与治疗前比较明显减低(P<0.05).治疗组MDS患者经青黄散治疗后MDA的表达增加与治疗前比较,差异有统计学意义(P<0.05).结论 含砷中药青黄散治疗MDS的机理之一是改变mtDNA的拷贝数,而这种拷贝数的改变可能与砷制剂引起的氧化应激有关.

目的:分析小剂量青黄散及补肾健脾方联合雄激素对儿童难治性血细胞减少(refractory cytopenia of children,RCC)患儿的疗效及安全性.方法:回顾分析2012年1月至2018年1月就诊于中国中医科学院西苑医院血液科门诊被诊断为RCC,且首次接受小剂量青黄散及补肾健脾方联合雄激素治疗3个月及以上的27例患儿资料.比较治疗前及治疗6、12个月后外周血白细胞(white blood cell,WBC)计数、中性粒细胞(neutrophile granulocyte,ANC)计数、血红蛋白(hemoglobin,HGB)计数、血小板(platelet,PLT)计数及骨髓原始细胞数的变化,分析患儿治疗反应及外周血三系细胞的改善情况,并记录期间发生的不良反应及相应处理方案.结果:小剂量青黄散及补肾健脾方联合雄激素治疗RCC患儿6、12个月时有效率分别为70.4％和81.5％ (P ＞0.05).治疗6个月时,总体外周血三系细胞的获效率HGB＞ PLT＞ ANC (P＜ 0.05);治疗12个月时,三者获效率比较,差异无统计学意义(P＞0.05).治疗12个月内,HGB计数持续且显著升高(P＜0.01),PLT、ANC计数仅在治疗前6个月时较治疗前升高(P ＜0.01,P＜0.05).治疗12个月内,轻度不良反应发生率为11.1％.结论:小剂量青黄散及补肾健脾方联合雄激素可作为RCC患儿一种行之有效的治疗方案;本方案治疗RCC患儿可使外周血HGB获效率更早,计数提升也更显著.