More Benefits of Oral Administration of Arsenic-containing Qinghuang Powder Compared with Decitabine for High/Very-high Risk Myelodysplastic Syndrome

OBJECTIVE: To evaluated the benefits of oral administration of arsenic-containing Qinghuang Powder(QHP)compared with decitabine for patients with high/very-high(H/VH) risk myelodysplastic syndrome(MDS) according to the Revised International Prognostic Score System. METHODS: The OS(mOS) rate, annual OS rate and progression to acute myeloid leukemia(AML) in patients with H/VH MDS treated with QHP(QHP group, n = 27) and decitabine(decitabine group, n = 20) were retrospectively analyzed. The effects of prognostic factors of age, proportion of bone marrow blast,peripheral blood cell count, karyotype and Charlson Comorbidity Index(CCI) on OS were further analyzed. RESULTS: The m OS rate of QHP group(29 months) was signi?cantly longer than that of the decitabine group(18 months)(P = 0.043). The OS rates of 1, 2, and 3 years were signi?cantly higher in the QHP group(88.9%, 59.3%, 29.6%) than that in the decitabine group(70%, 25%, and 5%)(P = 0.01). There was no signi?cant difference of 5-year OS rate between the 2 groups(P = 0.133).The effects of prognostic factors on mOS were further analyzed, and it was found that there was no signi?cant difference of m OS rate between the QHP group(29 months) and the decitabine group(21 months) in the patients with age 65 years old(P = 0.673). The mOS rate was signi?cantly longer in QHP group(28.5 months) than that in decitabine group(18 months) in the patients with age of < 65 years old(P = 0.04). The proportions of bone marrow blast cells with 10% or < 10% had no signi?cant effects on the mOS rate of patients in the 2 groups(P = 0.429, P = 0.183). In patients with HGB 80 g/L, mOS rate was signi?cantly longer in the QHP group(57 months) than that in the decitabine group(21 months)(P = 0.047), while in patients with HGB < 80 g/L, there was no signi?cant difference of mOS rate between the 2 groups(P = 0.265). In the patients with PLT < 50×10~9/L, the mOS rate was signi?cantly longer in the QHP group(33 months) than that in the decitabine group(16 months)(P = 0.028). In the patients with PLT 50×10~9/L, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.338). In the patients with ANC < 0.8×10~9/L, the mOS rate was signi?cantly longer in the QHP group(20 months) than that in the decitabine group(7 months)(P = 0.014). In the patients with normal karyotype, the mOS was signi?cantly longer in the QHP group(32 months) than that in the decitabine group(15 months)(P = 0.009). In the patients with abnormal karyotypes, there was no significant difference of the mOS rate between the 2 groups(P = 0.882). In the patients with good karyotypes, the mOS rate was signi?cantly longer in the QHP group(37 months) than that in the decitabine group(20 months)(P = 0.019). In the patients with moderate/poor/very poor karyotype, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.685). In the patients with CCI 3, the mOS rate was signi?cantly longer in the QHP group(34 months) than that in the decitabine group(10.5 months)(P = 0.017). In patients with CCI < 3, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.581). The proportion of progression to AML in the QHP group(18.8%) was signi?cantly lower than that in the decitabine group(25%)(P = 0.03). CONCLUSION: Compared with decitabine, oral administration of arsenic-containing Qinghuang Powder could help patients to survive longer and decrease incidence of progression to acute myeloid leukemia in the treatment of patients with high/very high MDS.

Clinical Observation of the Treatment of Myelodysplastic Syndrome Mainly with Qinghuang Powder(青黄散)

Objective： To observe the clinical effectiveness of Qinghuang Powder （青黄散, QHP） combined with Bupi Yishen Decoction （补脾益肾汤 BPYS） in treating myelodysplastic syndrome （MDS）, and its relationship with France, America, and Britain （FAB） type, international prognosis scaling system （IPSS） risk, and chromosome karyotype. Methods： There were 124 MDS patients subjected to the tests. By FAB typing, 91 patients were typed as refractory anemia （RA） type and 33 as refractory anemia with excess of blasts （RAEB） type; by IPSS scale, 21 were sorted to low risk, 77 to moderate risk I, 20 to moderate risk ]], and 6 to high risk; 78 of them had normal chromosome and 46 with abnormal chromosome, including 26 of trisomy 8. All patients were treated with QHP＋BPYS, and the changes of peripheral blood figure and bone marrow were observed. Results： After treatment, the general effective rate was 72.58% （90/124）, which in the patients of RA type was 80.22% （73/91） and in RAEB type 51.52% （17/33）. The former was better than that in the later （P〈0.01）. For the analysis in the patients of different IPSS risk degrees, the effective rate was 95.24% （20/21） in the low- risk group, 72.73% （56/77） in moderate risk I, 65.00% （13/20） in moderate-risk 11, and 16.67% （1/6） in high- risk group. Those in the first two groups were superior to that in the latter two （P〈0.01）. The effective rate was 79.49% （61/78） in the patients with normal chromosome and was 60.87% （28/46） in the patients with abnormal chromosome, showing a significant difference between them. While in the patients of trisomy 8, it was 73.08% （19/26）, which was parallel to that in the patients with normal chromosome. Conclusion： The effectiveness of QHP＋BPYS comprehensive therapy for MDS is unquestionably good, and it is markedly correlated with the FAB type and IPSS risk degree of the disease, as well as the normality of chromosome in the patient.

Oral Arsenic-Containing Qinghuang Powder:A Potential Drug for Myelodysplastic Syndromes

Qinghuang Powder(QHP),an oral arsenic,has become an effective drug in the treatment of myelodysplastic syndromes(MDS)in Xiyuan Hospital,China Academy of Chinese Medical Sciences for many years,and the action mechanism of the compound or active ingredient AsSof QHP has been elucidated.Considering the relatively safety,chemotherapy-free and convenient oral profile,QHP is widely used in the clinical treatment for MDS patients,especially for elderly patients.In this review,the authors document the efficacy and safety of oral arsenic-containing compound QHP in the treatment of MDS,with a special focus on the association of efficacy of QHP with the cytogenetics,prognostic risk,DNA methylation,gene mutation,blood arsenic concentration,mechanism of action of AsSand the countermeasures against adverse reactions of gastrointestinal tract.

Comparing Arsenic-Containing Qinghuang Powder and Low-Intensity Chemotherapy in Elderly Patients with Acute Myeloid Leukemia

Objective To compare the clinical effect of arsenic-containing Qinghuang Powder(QHP)and low-intensity chemotherapy(LIC)in treatment of elderly acute myeloid leukemia(eAML)patients.Methods Clinical data of 80 eAML patients treated at Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2015 to December 2020 were retrospectively analyzed.The treatment scheme was designed by real world study according to patients’preference,and patients were divided into a QHP group(35 cases)and a LIC group(45 cases).The median overall survival(mOS),1-,2-,and 3-year OS rates,and incidence of adverse events were compared between the two groups.Results The mOS of 80 patients was 11 months,and the 1-,2-,and 3-year OS rates were 45.51%,17.96%,and 11.05%,respectively.The QHP and LIC groups demonstrated no significant difference in mOS(12 months vs.10 months),1-(48.57%vs.39.65%),2-(11.43%vs.20.04%),and 3-year OS rates(5.71%vs.13.27%,all P>0.05).Moreover,the related factors of mOS demonstrated no significant difference in patients with age>75 years(11 months vs.8 months),secondary AML(11 months vs.8 months),poor genetic prognosis(9 months vs.7 months),Eastern Cooperative Oncology Group performance status score≥(10 months vs.7 months)and hematopoietic stem cell transplant comorbidity index≥4(11 months vs.7 months)between the QHP and LIC groups(all P>0.05).However,the incidence of myelosuppression was significantly lower in the QHP group than that in the LIC group(28.57%vs.73.33%,P<0.01).Conclusions QHP and LIC had similar survival rates in eAML patients,but QHP had a lower myelosuppression incidence.Hence,QHP can be an alternative for eAML patients who do not tolerate LIC.

Effect of Qinghuang Powder(青黄散) Combined with Bupi Yishen Decoction(补脾益肾方) in Treating Patients with Refractory Cytopenia with Multilineage Dysplasia through Regulating DNA Methylation

Objective: To explore the effect of Qinghuang Powder(QHP, 青黄散) combined with Bupi Yishen Decoction(BPYS, 补脾益肾方)on myelodysplastic syndromes(MDS) patients with refractory cytopenia with multilineage dysplasia(RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula. Methods: All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count(ANC), hemoglobin(Hb), platelets(PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation.Gene Ontology(GO) and Pathway analysis were applied to analyze the methylation data. Results: The overall MDS response rate to QHP was 61.68%(190/360) including hematologic improvement-neutrophil(HI-N) or hematologic improvement-erythroid(HI-E) or hematologic improvement-platelet(HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia(55.88% vs 31.54% or 55.88%vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions. Conclusions: QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement(HI-N, HI-P or HI-E)and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.

Relation of Blood Arsenic Concentration with Effect and Safety of Arsenic-Containing Qinghuang Powder (青黄散) in Patients with Myelodysplastic Syndrome

Objective: To investigate the relation of blood arsenic concentration (BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder (青黄散,QHP) in patients with myelodysplastic syndrome (MDS). Methods: Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluoresce nee spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed. Results: After 2 courses of treatment, the total effective rate was 89.6%(146/163), with 31.3%(51/163) of hematological improvement and 58.3%(95/163) of stable disease. The hemoglobin increased from 73.48 ± 19.30 g/L to 80.39 ± 26.56 g/L (P<0.05), the absolute neutrophil count increased from 0.81 ±0.48 × 10^9/L to 1.08 ±0.62 × 1O^9/L (P<0.05), and no significant changes were observed in platelet counts (P>0.05). Among 46 patients previously depended on blood transfusion, 28.3%(13/46) completely got rid of blood transfusion and 21.7%(10/46) reduced the volume of blood transfusion by more than 50% after treatment. The BACs were significantly increased in patients treated for 1 month with 32.17 ± 18.04 jig/L (P<0.05), 3 months with 33.56 ±15.28 μg/L (P<0.05), and 6 months with 36.78 ±11.92 μg/L (P<0.05), respectively, as compared with those before treatment (4.08 ±2.11 ag/L). There were no significant differences of BACs among the patients treated for 1, 3 and 6 months (P>0.05). The adverse reactions of digestive tract during the treatment were mild abdominal pain and diarrhea in 14 cases (8.6%), and no patients discontinued the treatment. The BACs of patients with gastrointestinal adverse reactions were significantly lower than those without gastrointestinal adverse reactions (22.39 ±10.38 vs. 37.89 ± 11.84,μg/L, P<0.05). The BACs of patients with clinical effect were significantly higher than those failed to treatment (40.41 ± 11.69 vs. 23.84 ± 12.03,μg/L, P<0.05). Conclusion: QHP was effective and safe in the treatment of patients with MDS and the effect was associated with BACs of patients.

含砷中药青黄散方案治疗超高龄伴TP53突变高危骨髓增生异常综合征1例并文献复习

骨髓增生异常综合征(MDS)是起源于造血干细胞的克隆性、髓系肿瘤性疾病,其伴原始细胞增多亚型及伴肿瘤蛋白53(TP53)基因突变均与高危疾病预后分层相关,其中TP53基因突变还与治疗耐药相关。高龄MDS患者的器官功能下降,合并症多,移植不可行,且多数不能耐受化疗、去甲基化药物治疗。患者为超高龄男性,确诊MDS伴原始细胞增多Ⅰ型,初诊时全血细胞进行性下降且需输血支持,修订版国际预后评分系统极高危,伴TP53基因突变。与同类患者比较,应用含砷中药青黄散方案治疗后中位生存期延长,血象三系有不同程度改善,生活质量提高,未发生治疗相关不良反应,耐受性良好,达到高龄MDS患者提高生活质量、延长生存期的治疗目标。本文回顾患者病历资料及应用含砷中药青黄散方案治疗过程,并结合国内外相关文献对高龄MDS的临床特点、治疗方法及相关基因突变特征进行分析,以期为高龄或超高龄预后不良MDS患者的治疗提供借鉴。

青黄散灌胃对骨髓增生异常综合征小鼠骨髓细胞凋亡、周期的影响及机制

目的探讨青黄散灌胃对骨髓增生异常综合征(MDS)小鼠骨髓细胞凋亡、周期的影响及机制。方法用Tg(Vav1-NUP98/HOX D13)G2Apla/J转基因MDS小鼠模型进行取精扩繁,将40只模型小鼠随机分为模型组和青黄散低、中、高剂量组及阿扎胞苷组,每组8只,取8只C57BL/6J小鼠作为空白组。空白组、模型组给予生理盐水100μL灌胃,均每天1次;青黄散低、中、高剂量组分别给予青黄散36.4、72.8、145.6 mg/kg灌胃,均每天1次;阿扎胞苷组给予1 mg/kg阿扎胞苷注射液100μL于颈部皮下注射,3天1次。干预4周,处死小鼠,采集外周血,并提取骨髓细胞。检测各组血常规[白细胞(WBC)、红细胞(RBC)、血红蛋白(HGB)、血小板(PLT)],用流式细胞术检测骨髓细胞凋亡率、周期,用荧光定量PCR法检测骨髓细胞内DNA-甲基转移酶1(DNMT-1)、受体酪氨酸激酶(c-KIT)、GATA结合蛋白1(GATA-1)mRNA,用Western blotting法检测骨髓细胞内DNMT-1、c-KIT、GATA-1蛋白。结果与空白组比较,模型组WBC、RBC、HGB、PLT低(P均<0.05),说明建模成功;与模型组比较,青黄散低、中剂量组及阿扎胞苷组WBC、RBC、HGB、PLT高(P均<0.05);青黄散低、中、高剂量组及阿扎胞苷组WBC、RBC、HGB、PLT比较差异无统计学意义(P均>0.05)。与空白组比较,模型组骨髓细胞凋亡率低(P<0.05);与模型组比较,青黄散低、中、高剂量组及阿扎胞苷组骨髓细胞凋亡率高(P均<0.05)。与空白组比较,模型组骨髓细胞周期变化差异有统计学意义(P均<0.05);与模型组比较,青黄散低、中、高剂量组及阿扎胞苷组S期骨髓细胞少,G1期骨髓细胞多(P均<0.05)。与空白组比较,模型组DNMT-1、c-KIT、GATA-1 mRNA表达低(P均<0.05);与模型组比较,青黄散低、中、高剂量组及阿扎胞苷组DNMT-1、GATA-1 mRNA表达低(P均<0.05),青黄散低、中剂量组c-KIT mRNA表达高(P均<0.05)。与空白组比较,模型组DNMT-1、c-KIT、GATA-1蛋白表达低(P均<0.05);与模型组比较,青黄散低、中、高剂量组及阿扎胞苷组c-KIT蛋白表达低(P均<0.05),GATA-1蛋白表达高(P均<0.05),青黄散低、中、高剂量组DNMT-1蛋白表达低(P均<0.05)。结论青黄散灌胃可促进MDS小鼠骨髓细胞凋亡,阻滞其细胞周期,其作用机制可能与调控DNMT-1、c-KIT、GATA-1表达有关。

青黄散加补肾健脾中药治疗骨髓增生异常综合征的临床观察

目的观察青黄散加补肾健脾中药治疗骨髓增生异常综合征(MDS)的临床疗效。方法55例MDS患者给予青黄散、补肾健睥汤药及雄性激素等治疗。结果55例MDS患者中,完全缓解11例(20.0%),总有效41例(74.5%)。根据FAB分型,RA/RAS型34例,完全缓解9例(26.5%),总有效28例(82.4%);RAEB型21例,完全缓解2例(9.5%),总有效13例(61.9%),两型间疗效比较差异无统计学意义。按国际预后积分系统(IPSS)评定标准,中危Ⅰ组36例,有效25例(其中完全缓解10例),无效11例。中危Ⅱ组7例,完全缓解1例,有效4例,无效2例。高危组6例,完全缓解0例,有效3例,无效3例。3组疗效比较差异无统计学意义。有效者41例,治疗后白细胞、血红蛋白和血小板计数均较治疗前升高(P<0.05);染色体异常组16例,有效11例(68.8%);染色体正常组33例,有效24例(72.7%);染色体异常与否间疗效比较,差异无统计学意义。结论化瘀补肾为主综合治疗MDS具有确切的临床疗效,疗效与FAB分型、IPSS积分及染色体异常与否无明显相关性。

含砷中药复方青黄散治疗骨髓增生异常综合征的克隆选择性与砷体内效应的相关性研究

目的探讨含砷中药复方青黄散治疗骨髓增生异常综合征(MDS)的克隆选择性与砷体内效应的相关性。方法对接受口服青黄散(每日雄黄0.16 g)治疗的MDS患者40例(治疗组)进行疗效评价,分析MDS患者口服青黄散后血砷浓度和线粒体膜电位(△Ψm),并与未服用青黄散或其他砷制剂的MDS患者(未治疗组)以及正常人(健康对照组)进行比较。结果治疗组总有效率为75.0%(30/40)。伴随正常克隆与+8异常克隆患者的疗效明显好于其他异常克隆类型(P<0.05)。治疗组全血和血浆砷浓度均明显高于未治疗组及健康对照组(P<0.05)。治疗组有效患者的全血砷浓度明显高于治疗失败者(P<0.05)。治疗组全血砷浓度明显高于血浆砷浓度(P<0.05)。治疗组正常核型和+8患者与其他异常克隆患者的血砷浓度差异无统计学意义(P>0.05)。治疗组线粒体△Ψm与未治疗组比较差异无统计学意义(P>0.05)。治疗组线粒体△Ψm与全血砷浓度没有相关性(P>0.05)。结论口服青黄散治疗MDS,砷被人体少量吸收,并进入细胞内发挥作用。MDS患者对青黄散的治疗反应与全血砷浓度具有相关性。青黄散治疗MDS的克隆选择性与全血砷浓度以及线粒体△Ψm变化没有相关性。

麻柔教授病证结合治疗骨髓增生异常综合征浅谈

在中医学长期发展中,逐渐形成了病证结合的诊疗模式,这一模式适于发挥中西医双方优势,在临床诊疗中广泛应用。麻柔教授是中西医结合血液学专家,"参西而不背中",运用西医方法诊断疾病、中医方法治疗疾病的诊疗思路,在疾病诊疗过程中辨病与辨证相结合,根据骨髓增生异常综合征(myelodysplastic syndromes,MDS)的发病特点,认为此病本在"毒瘀",治以青黄散为主,解毒祛瘀,"去其所害";同时根据患者证候表现,总结出脾肾阳虚、肝肾阴虚两种常见证型,配合培补脾肾中药治疗,取得良好疗效。近年来临床研究与实验研究均取得一定成果,为进一步探讨麻柔教授病证结合治疗MDS学术思想提供了科学依据。

青黄散治疗骨髓增生异常综合征31例临床观察

目的:系统观察中药青黄散治疗骨髓增生异常综合征(MDS)的临床疗效。方法:采用随机对照方法。61例MDS患者随机分为治疗组(青黄散组)31例和对照组(维甲酸组)30例。3个月为1个疗程。结果:青黄散组总缓解率与总有效率分别为9.7%和74.1%,维甲酸组总缓解率与总有效率分别为0与46.7%,青黄散组疗效优于维甲酸组。青黄散毒副作用主要为皮肤色素沉着、角化过度及消化道症状。结论:中药青黄散治疗MDS有确切的临床疗效,能够明显改善红系造血,提高血红蛋白含量,提高白细胞数量,明显提高患者的生活质量,且患者耐受性好,对西药无效的患者仍然有效。

含砷中药青黄散对骨髓增生异常综合征患者线粒体DNA拷贝数的影响

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。

青黄散加解毒化瘀方治疗骨髓增生异常综合征疗效及对患者血清可溶性细胞间黏附分子-1、转化生长因子-β_(1)的影响

目的:探究青黄散加解毒化瘀方对毒瘀阻滞证骨髓增生异常综合征(MDS)的疗效及血清可溶性细胞间黏附分子(sICAM-1)、转化生长因子β_(1)(TGF-β_(1))水平的影响。方法:选取76例MDS患者作为研究对象,随机分为试验组和对照组,各38例,对照组予以西医基础治疗,试验组在对照组基础上联合青黄散加解毒化瘀方治疗。两组患者均于给药4个月后评估临床疗效、中医证候积分、血常规指标水平、血清学免疫因子水平,并记录两组患者不良反应发生率。结果:治疗后两组患者的主症及次症评分均低于治疗前,且试验组均低于对照组(P<0.05)。试验组临床疗效优于对照组(P<0.05)。两组不良反应发生率比较差异无统计学意义(P>0.05)。治疗后,两组患者的血清sICAM-1水平均低于治疗前,且试验组低于对照组(P<0.05);两组治疗后TGF-β_(1)水平较治疗前升高,试验组高于对照组(P<0.05)。治疗后,两组PLT、Hb、WBC水平较治疗前升高,试验组PLT、Hb水平均高于对照组(P<0.05)。结论:青黄散加解毒化瘀方应用于毒瘀阻滞证MDS患者治疗中,有助于促进患者症状恢复,改善血常规指标水平,调节血清免疫因子水平,且安全性良好。

骨髓增生异常综合征患者应用青黄散临床疗效及对QOL评分的影响

目的:探讨骨髓增生异常综合征患者应用青黄散临床疗效及对生活质量(QOL)评分的影响。方法:选取2016年1月-2018年1月本院收治的52例骨髓增生异常综合征患者,按随机数字表法分为对照组与研究组,各26例。对照组进行常规治疗,研究组进行青黄散治疗。比较两组治疗效果、外周血象、免疫功能及QOL评分。结果:研究组治疗总有效率高于对照组(χ^2=5.421,P<0.05);治疗前,两组血小板、血红蛋白与骨髓原始细胞百分比比较,差异均无统计学意义(P>0.05)。治疗后,研究组血小板、血红蛋白均高于对照组(P<0.05)。治疗后,两组骨髓原始细胞百分比比较,差异无统计学意义(P>0.05)。治疗后,研究组免疫功能各相关指标均优于对照组(P<0.05);研究组各项QOL评分均高于对照组(P<0.05)。结论:对骨髓增生异常综合征患者进行青黄散治疗,可有效改善临床症状,改善免疫功能和外血象,有利于病情恢复,提高生活质量,具有非常高的临床应用价值,应进一步推广和应用。

蛋白质相互作用网络指导下青黄散治疗慢性粒细胞白血病的机制探究

目的：通过慢性粒细胞白血病（chronic myelogenous leukemia,CML）蛋白质相互作用网络的构建、分析与体外实验验证两部分,探讨青黄散治疗CML的有效分子学机制。方法：筛选在线人类孟德尔遗传数据库（OMIM）获得CML相关基因,STRING用于进一步文本挖掘并构建CML蛋白质相互作用网络,互作数据读入Cytoscape后,插件Centi Sca Pe和Cluster Viz用于实现拓扑和聚类分析,DAVID数据库富集关键通路信息。然后针对关键基因c-myc设计体外实验,制备青黄散含药血清,MTT法检测阴性对照组（无药血清）与实验组（5%、10%和20%青黄散含药血清）在24、48、72 h对K562细胞的增殖抑制率,Western Blot法检测c-myc蛋白的表达情况。结果：构建了由416个节点（蛋白质）和2792条边（相互作用）组成的蛋白质相互作用网络,分析得出关键基因c-myc。实验结果表明,与阴性对照组相比,实验组能有效的抑制K562细胞增殖,且青黄散含药血清能有效抑制c-myc的表达,两者具有统计学意义（P〈0.05）。结论：CML是一个受多基因调控、多信号通路传导的复杂疾病,c-myc很可能是关键节点,而青黄散对K562细胞增殖的抑制作用机制之一是降低c-myc的表达。

青黄散联合低强度化疗对老年急性髓系白血病患者生存期及预后因素的分析

目的探讨青黄散为主与低强度化疗治疗老年急性髓系白血病(Acute Myeloid Leukemia,AML)患者的临床疗效及预后影响因素。方法回顾性分析2015年1月—2020年12月期间于中国中医科学院西苑医院接受治疗的80例老年AML患者的临床资料,分为青黄散组35例和低强度化疗组45例,比较两组患者的中位生存期、年生存率以及不良反应发生率,并分析预后影响因素。结果80例患者的中位生存期为11个月,1年、2年和3年生存率分别为45.51%、17.96%和11.05%。影响中位生存期的单因素分析显示,遗传学、体能状况评分(PS评分)以及并发症指数评分(HCT-CI评分)是影响预后的主要因素,差异有统计学意义(P<0.05);多因素分析显示,PS评分是影响预后的独立因素(P<0.05)。青黄散组与低强度化疗组比较,中位生存期(12个月vs 10个月,χ^(2)=0.061,P=0.806)、1年生存率(48.6%vs 40.0%,χ^(2)=0.588,P=0.443)、2年生存率(11.4%vs 20.0%,χ^(2)=1.063,P=0.303)和3年生存率(5.7%vs 13.3%,χ^(2)=0.564,P=0.453)差异无统计学意义(P>0.05)。两组患者中位生存期影响因素分析显示,青黄散组与低强度化疗组继发性AML(11个月vs 8个月,χ^(2)=1.097,P=0.295)、遗传预后不良(9个月vs 7个月,χ^(2)=0.037,P=0.847)、PS评分≥3分(10个月vs 7个月,χ^(2)=1.035,P=0.309)、HCT-CI评分≥4分(11个月vs 7个月,χ^(2)=0.455,P=0.500)患者中位生存期比较,差异均无统计学意义(P>0.05)。两组患者不良反应发生率比较,青黄散组骨髓抑制发生率明显低于低强度化疗组,差异有统计学意义(P<0.05)。结论遗传学、PS评分以及HCT-CI评分是影响老年AML患者的预后因素。青黄散为主与低强度化疗方案治疗老年AML生存期相当,但青黄散为主方案骨髓抑制发生率较低,该方案可作为不耐受低强度化疗老年AML患者的替代方案。

青黄散组分抑制BCL-2、XIAP-1、c-IAP协同诱导KG1a细胞凋亡的实验研究

目的研究中药砷复合制剂青黄散(由青黛和雄黄二药组成)组分靛玉红(Indirubin,青黛的有效成分)和二硫化二砷(Arsenic Disulfide,As_2S_2,雄黄的有效成分)对非M3型急性髓系白血病(AML)KG1a细胞株的单独和联合杀伤作用,并探讨相关杀伤作用机制。方法采用瑞氏姬姆沙染色法观察靛玉红与As_2S_2作用于KG1a细胞的形态,采用流式细胞术检测靛玉红与As_2S_2作用于KG1a细胞凋亡率,采用CCK-8检测靛玉红与As_2S_2作用于KG1a细胞抑制率,进一步用Western blot检测KG1a细胞Bcl-2、Smac、XIAP-1、c-IAP、Caspase-3蛋白的表达。结果青黄散组分靛玉红与As_2S_2单独对KG1a细胞均具有增殖抑制作用,联合用药的增殖抑制率、凋亡率作用更明显(P<0.05),Compu Syn软件分析靛玉红和As_2S_2以1∶1组合对KG1a细胞株的联合指数(CI)<0.9。联合用药在形态学上能明显促进细胞的凋亡变化,增加细胞的Caspase-3和Smac蛋白表达,抑制BCL-2、XIAP-1、c-IAP蛋白的表达。结论青黄散组分靛玉红与As_2S_2能联合抑制KG1a细胞增殖和诱导其凋亡,其机制与抑制BCL-2、XIAP-1、c-IAP蛋白表达,促进Caspase-3、Smac蛋白表达相关。本药可用于治疗常规药物抵抗的AML并为非M3型AML的治疗提供相关实验依据。

青黄散治疗骨髓增生异常综合症的网络药理学研究

目的:本研究拟利用网络药理学方法探讨青黄散治疗骨髓增生异常综合症(MDS)的潜在活性成分和作用机制。方法:通过BATMAN-TCM平台收集雄黄、青黛的活性成分和作用靶点信息,GeneCards和PALM-IST平台收集MDS疾病靶点基因;采用Cytoscape 3.2.1构建“药物-活性成分-靶点”网络并利用network analyzer插件进行拓扑结构分析,采用STRING数据库进行基因互作分析,采用Metascape数据库进行基因本体论(GO)分析及KEGG信号通路富集分析。结果:共获得青黄散治疗MDS的潜在活性成分4个,其中自由度≥2的重要靶基因54个;基因富集分析显示青黄散主要通过调控氧化应激、炎症反应、能量代谢和细胞凋亡等生物学过程发挥治疗MDS的作用。结论:本研究从网络药理学角度初步阐释了青黄散治疗MDS的潜在活性成分和作用机制,揭示了其多成分、多靶点、多途径调节的特点,为后续机制研究的开展提供了基础和依据。