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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). 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 fluorescence 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. 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). 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 μ g/L (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, μ g/L, P

To explore the relationship between the efficacy of realgar for the treatment of myelodysplastic syndromes with multilineage dysplasia (MDS-MLD) and arsenic concentration in the peripheral blood of patients.In this prospective study, a total of 50 MDS-MLD patients were treated with traditional Chinese drugs containing realgar for 3 months in Xiyuan Hospital from March 2018 to January 2019. Routine blood examination as well as liver and kidney function were monitored before and after treatment. The concentration of arsenic in the peripheral blood was measured using an atomic fluorescence spectrometer after treatment. The correlation between clinical effect and arsenic concentration was analyzed by Spearman's method.The treatment response rate was 54%. Two patients (4% ) achieved complete remission, 50% (25 of 50) showed hematologic improvement, and 23 patients had stable disease (23% ). No disease progression was observed. Arsenic concentration in the peripheral blood ranged from 14.60 to 85.96 μg/L. Clinical efficacy was positively correlated with arsenic concentration (P0.05). The incidence of mild adverse reactions was 16%.A relatively high concentration of arsenic in the peripheral blood may improve the clinical efficacy of realgar in MDS-MLD patients.

Traditional Chinese Medicine (TCM) is a practical medicine based on thousands of years of medical practice in China. Arsenic dispensing powder (ADP) has been used as a treatment for MDS patients with a superior efficacy on anemia at Xiyuan Hospital of China Academy of Chinese Medical Sciences. In this study, we retrospectively analyzed MDS patients that received ADP treatment in the past 9 years and confirmed that ADP improves patients’ anemia and prolongs overall survival in intermediate-risk MDS patients. Then, we used the MDS transgenic mice model and cell line to explore the drug mechanism. In normal and MDS cells, ADP does not show cellular toxicity but promotes differentiation. In mouse MDS models, we observed that ADP showed significant efficacy on promoting erythropoiesis. In the BFU-E and CFU-E assays, ADP could promote erythropoiesis not only in normal clones but also in MDS clones. Mechanistically, we found that ADP could downregulate HIF1A in MDS clones through upregulation of VHL, P53 and MDM2, which is involved in two parallel pathways to downregulate HIF1A. We also confirmed that ADP upregulates GATA factors in normal clones. Thus, our clinical and experimental studies indicate that ADP is a promising drug to promote erythropoiesis in both MDS and normal clones with a superior outcome than current regular therapies. ADP promotes erythropoiesis in myelodysplastic syndromes via downregulation of HIF1A and upregulation of GATA factors.

The karyotype is highly important for diagnosis and prognosis in myelodysplastic syndrome (MDS). The objective of the present study was to investigate the cytogenetic characteristics of patients with MDS in China. The karyotypes of 665 Chinese patients with MDS were analyzed, and it was identified that 298 cases (298/665, 44.8%) had abnormal karyotypes. Among the 298 patients with abnormal karyotypes, the 75 patients with trisomy 8 (+8) constituted the most common subset (75/298, 25.2%). The incidence of abnormal karyotypes was significantly higher in patients who were ≥51 years old compared with those

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. 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. 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. 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.

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 As2S2 of 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 As2S2 and the countermeasures against adverse reactions of gastrointestinal tract.

Objective To measure the proportions of blood T cell subsets, Th1, Th2, Th17, Th22, and Treg cells, and other parameters in patients with chronic immune thrombocytopenia (CITP) before and after treatment with Yiqi Tongyang Decoction (益气通阳方, YTD) to explore T cell status of patients with CITP, and to define the mechanism of action of YTD.

A detector setup for the measurement of angular distribution of heavy-ion elastic scattering at energies around Coulomb barrier on the radioactive ion beam line in Lanzhou at the heavy-ion research facility in Lanzhou is designed. The beam profile and the scattering angles on the target are deduced by two parallel plate avalanche counters, and four sets of detector telescopes (including double-sided silicon strip detectors) are placed systematically with the beam line, incorporating with Monte Carlo simulations. The data of $$^{16}\hbox {O}$$ on $$^{89}\hbox {Y}$$ target were analyzed to compare with the simulation results. It is found that the simulated distribution is agreeable with the experimental data. By assuming the pure Rutherford scattering at small scattering angles, the angular distribution of elastic scattering of $${}^{16}\hbox {O} + {}^{89}\hbox {Y}$$ at low energies can be reasonably obtained. It indicates that this set of detector setup can be used for the measurement of angular distributions of heavy-ion elastic scattering at energies around Coulomb barrier.

Recently, nanomaterials with multiple functions, such as drug carrier, MRI and optical imaging, photothermal therapy etc, have become more and more popular in the domain of cancer research. In this study, a C60–IONP nanocomposite is synthesized via decorating iron oxide nanoparticles (IONP) onto fullerene (C60) and then functionalized by polyethylene glycol (PEG2000), giving C60–IONP–PEG with excellent stability in physiological solutions, finally folic acid (FA), a widely used tumor targeting molecule, was linked to C60–IONP–PEG in order to obtain an active tumor targeting effect to MCF-7 cells and malignant tumor in mice models. Herein, a hybrid nanoplatform with multi-functional characteristics for cancer diagnosis, photodynamic therapy (PDT), radiofrequency (RF) thermal therapy (RTT) and magnetic targeting applications was developed and explored its biofunctions in vitro and in vivo. C60–IONP–PEG–FA showed neglectable toxicity, not only served as a powerful tumor diagnostic magnetic resonance imaging (MRI) contrast agent, but also as a strong photosensitizer and powerful agent for photothermal ablation of tumor, furthermore a remarkable synergistic enhancement of PDT combination with RTT was also observed during the treatment both in vitro and in vivo. Moreover, the multi-functional nanoplatform also could selectively kill cancer cells in highly localized regions via the excellent active tumor targeting and magnetic targeted abilities. This work showed the multi-functional C60–IONP–PEG–FA nanoplatform had a great potential for cancer theranostic applications.

In this study, a GO@Ag nanocomposite was synthesized by chemical deposition of Ag nanoparticles onto graphene oxide (GO) through a hydro thermal reaction, and doxorubicin (DOX), one of the most effective drugs against a wide range of cancers, was employed as the model drug and linked to GO@Ag via ester bonds with a very high drug loading efficiency (∼82.0%, weight ratio of DOX/GO@Ag), then GO@Ag-DOX was functionalized by DSPE-PEG2000-NGR, giving GO@Ag-DOX with active tumor-targeting capacity and excellent stability in physiological solutions. The release profiles of DOX from GO@Ag-DOX-NGR showed strong dependences on near-infrared (NIR) laser and the SPR effect of Ag nanoparticles. Compared with free DOX in an in vivo murine tumor model, GO@Ag-DOX-NGR afforded much higher antitumor efficacy without obvious toxic effects to normal organs owing to 8.4-fold higher DOX uptake of tumor and 1.7-fold higher DOX released in tumor with NIR laser than the other tissues. Besides, in this work, GO@Ag-DOX-NGR not only served as a powerful tumor diagnostic X-ray contrast agent, but also as a strong agent for photothermal ablation of tumor, the ability of GO@Ag-DOX-NGR nanoparticles to combine the local specific chemotherapy with external photothermal therapy (PTT) significantly improved the therapeutic efficacy. GO@Ag-DOX-NGR showed excellent chem-photothermal therapeutic efficacy, tumor-targeting property, NIR laser-controlled drug releasing function and X-ray imaging ability, demonstrating that there is a great potential of GO@Ag-DOX-NGR for cancer diagnosis and therapy.

Acute myeloid leukemia progressed from myelodysplastic syndrome (MDS/AML) is generally incurable with poor prognosis for complex karyotype including monosomy 7 (-7). Qinghuang Powder (, QHP), which includes Qing Dai (Indigo naturalis) and Xiong Huang (realgar) in the formula, is effective in treating MDS or MDS/AML even with the unfavorable karyotype, and its therapeutic efficacy could be enhanced by increasing the Xiong huang content in the formula, while Xiong huang contains90% arsenic disulfide (As2S2). F-36p cell line was established from a MDS/AML patient with complex karyotype including -7, and was in cytokine-dependent. The present study was to investigate the effects of As2S2 on F-36p cells.Cell proliferation was measured by an 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was identified by Annexin V-staining. Cell viability was determined by a propidium iodide (PI) exclusion. Erythroid differentiation was evaluated by the expression of cell surface antigen CD235a (GpA).After treatment with As2S2 at concentrations of 0.5 to 16 μmol/L for 72 h, As2S2 inhibited the proliferation of F-36p cells. The 50% inhibitory concentrations (IC50) of As2S2 against the proliferation of F-36p cells was 6 μmol/L. The apoptotic cells significantly increased in a dose-dependent mannar (P0.05). The cell viabilities were significantly inhibited by As2S2 dose-dependent in a dose-dependent manner (P0.05). Significant increases of CD235a-positive cells were concurrently observed (P0.05) also in a dose-dependent manner.As2S2 could inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation dose-dependently in F-36p cells. As2S2 can inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation in cytokine-dependent MDS-progressed human leukemia cell line F-36p with complex karyotype including -7. The data suggest that QHP and/or As2S2 could be a potential candidate in the treatment of MDS or MDS/AML even with unfavorable cytogenetics.

Recently, fullerene and fullerene derivatives owning to their highly enriched physical and chemical properties have been widely explored for applications in many different fields including biomedicine. In this study, iron oxide nanoparticles (IONPs) were decorated onto the surface of fullerene (C60), and then PEGylation was performed to improve the solubility and biocompatibility of C60-IONP, obtaining a multi-functional C60-IONP-PEG nanocomposite with strong superparamagnetism and powerful photodynamic therapy capacity. Hematoporphyrin monomethyl ether (HMME), a new photodynamic anti-cancer drug, was conjugated to C60-IONP-PEG, forming a C60-IONP-PEG/HMME drug delivery system, which demonstrated an excellent magnetic targeting ability in cancer therapy. Compared with free HMME, remarkably enhanced photodynamic cancer cell killing effect using C60-IONP-PEG/HMME was realized not only in a cultured B16-F10 cells in vitro but also in an in vivo murine tumor model due to 23-fold higher HMME uptake of tumor and strong photodynamic activity of C60-IONP-PEG. Moreover, C60-IONP-PEG could be further used as a T2-contrast agent for in vivo magnetic resonance imaging. Our work showed C60-IONP-PEG/HMME had a great potential for cancer theranostic applications.

To explore the effect of Qinghuang Powder (QHP,()combined with Bupi Yishen Decoction (BPYS, ) 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.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.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.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.

To measure the proportions of blood T cell subsets, Th1, Th2, Th17, Th22, and Treg cells, and other parameters in patients with chronic immune thrombocytopenia (CITP) before and after treatment with Yiqi Tongyang Decoction (, YTD) to explore T cell status of patients with CITP, and to defifine the mechanism of action of YTD.The changes in peripheral blood T lymphocyte subsets, and those of Th1, Th2, Th17, Th22, and Treg cells in 30 patients with CITP (22 females and 8 males) were analyzed using multiparametric flflow cytometry before and after treatment with YTD for 6 months, and 26 healthy volunteers (14 males and 12 females) acted as a control. T-box expressed in T-cells (T-bet) and GATA binding protein 3 (GATA-3) mRNA levels in patients and controls were analyzed using real-time reverse transcription-polymerase chain reaction.The proportions of Th1, Th17, Th22, Th1/Th2, and Th17/Treg cells increased in the peripheral blood of patients with CITP compared to those in controls before YTD therapy (P0.05). Th1 cell numbers and the Th1/Th2 ratio fell in the treated patients with CITP to approximate the values of the control group (P0.05). Th17 cell numbers and the Th17/Treg ratio also decreased in the treatment group (P0.05), but not to the levels of the controls. The number of Treg cells in the peripheral blood of patients with CITP before treatment was lower than that in the control group (P0.05), but increased after YTD treatment P0.05), but not to the level of controls. T-bet and GATA-3 mRNA levels in peripheral blood were initially higher in patients before treatment than controls (P0.05), but decreased after YTD therapy (P0.05).Imbalances in T lymphocyte levels, particularly those of Th1/Th2 and Th17/Treg cells, play important roles in the pathogenesis of CITP. YTD effificiently regulated the dynamics of Th1/Th2 and Th17/Treg equilibria.

Objective To explore the effect of antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) plus kidney-nourishing Chinese medicinal (KNCM) on severe aplastic anemia (SAA). Methods Twenty-five subjects of severe aplastic anemia were treated with ATG/ALD plus KNCM between 1992 and 2009, and the clinical data before and after treatment were collected and analyzed. Results Of the 25 patients, 9 were nearly cured, 6 were improved, 5 were in remission, and 5 failed. The overall effective rate was 80.0%. The 3-year, 5-year, 10-year, 15-year survival rate were respectively 98.6%, 97.3%, 97.3%, 67.5%, and median survival time was 180 months. Compared to the conditions before administering the medication of ATG/ALG plus KNCM, after 2 weeks, reticulocyte was first improved ( P =0.001); one month later, followed by palette ( P =0.037); two months later, by neutrophil cell in peripheral blood ( P =0.001); three months later, then by the hemoglobin ( P =0.012). By conducting 1-year follow-up, 1 case of complication–paroxysmal nocturnal hemoglobinuria (PNH) was identified and the patient still alive today. Conclusion ATG/ALG plus KNCM had better effect on SAA and could improve patients' survival rate.

To explore the prognostic factors for very severe aplastic anemia (VSAA) patients treated mainly with Chinese Kidney (Shen)-invigorating drugs (CKID) combined with anti-lymphocyte globulin (ALG) or anti-thymocyte globulin (ATG).Twenty-seven VSAA patients were treated with CSID+ALG/ATG therapy in conjunction with cyclosporine A, androgen, hemopoietic growth factor, etc. The relationship of the effectiveness and some factors (age of patients, course of illness, blood and bone marrow figures, etc.) were analyzed.In the 25 evaluated VSAA patients who had been followed up for over 1 year, 9 patients (36.0%) were basically cured, 5 (20.0%) remitted, 6 (24.0%) were markedly improved, and 5 (20.0%) were treated in vain, with the total effective rate of treatment being 80.0% (20/25). Better clinical therapeutic effects were shown in patients newly diagnosed with VSAA, of male sex (P=0.037),20 years old (P=0.045), with an illness course [Symbol: see text] month (P=0.048), with peripheral neutrophil count0.1 × 10(9)/L (P=0.023), and with reticulocyte count10 × 10(9)/L (P=0.002). Platelet count (P=0.620) and bone marrow lymphocyte percentage (P=0.736) showed no correlation with the therapeutic effectiveness. Multi-factor analysis by the Kaplan-Meier procedure on the factors influencing survival showed that rather longer survival times occurred in patients20 years old, with peripheral neutrophil count [Symbol: see text] 0.1 × 10(9)/L, reticulocyte count [Symbol: see text]10 × 10(9)/L, and platelet count10 × 10(9)/L (all P=0.0001). Bone marrow lymphocyte percentage and the initiation time of ALG/ATG application (from onset of the illness) showed no significant influence on patients' survival time (P=0.085 and P=0.935, respectively).CSKD+ALG/ATG therapy for treatment of VSAA could enhance the current clinical therapeutic effects and elevate patients' survival rate. Conditions including male sex, age20 years, illness course [Symbol: see text]1 month, neutrophil count0.1 × 10(9)/L, and reticulocyte count10 × 10(9)/L are the likely effective indices for predicting favorable therapeutic effectiveness in newly diagnosed VSAA patients.

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.

Chinese arsenic drugs have been applied in Chinese medicine for several centuries. Beginning from 1970s, arsenic containing drugs have been generally used for the treatment of malignant hematologic diseases including acute promyelocytic leukemia, myelodysplastic syndrome, and multiple myeloma. No matter what ingredients of arsenic drugs were applied, either arsenic trioxide, arsenic disulfide, or arsenic containing Chinese herbal compositions including Qinghuang Powder and Realgar-Indigo naturalis formula, they all provided the distinct approaches for the management of malignant hematologic diseases, and good clinical efficacy was obtained with mild adverse reactions. Moreover, the mechanisms of action have been continually elucidated.

To observe the clinical efficacy of Chinese drugs combined with chemotherapy in the treatment of acute myeloid leukemia (AML) and to investigate the prognostic relevance of the main parameters in AML treated with integrative medicine.Forty AML patients hospitalized at the authors hospital were treated with Chinese drugs and chemotherapy. The routine examination, immunophenotype and karyotype analyses were carried out. The clinical efficacy was observed and the prognostic factors were analyzed.(1) Clinical efficacy: Twenty patients had complete remission (CR), with the CR rate being 50.0%. Among these patients, the CR rate was 73.9% (17/23) in de novo AML and 17.6% (3/17) in secondary or refractory AML, respectively. The median disease free survival (DFS) was 6 months (2-32 months) and median overall survival (OS) was 7 months (1-36 months). (2) Analysis of prognostic factors: Aging (60 years) and hepatosplenomegaly or extramedullary leukemia did not affect the treatment outcome. Patients with lower white blood cell (WBC) counts (4.0x10(9)/L) had a significantly higher CR rate (P0.01). Secondary or refractory AML was associated with a lower CR rate and shorter OS (P0.01,P0.05). Expression of CD34 was an adverse factor for obtaining CR (P0.05) and survival in both DFS and OS (P0.05,P0.01). The expression of CD56 was significantly associated with a lower CR rate (P0.05), but did not affect DFS and OS. Twenty-three (57.5%) out of 40 cases had chromosomal abnormalities. The CR rate was decreased and both DFS and OS shortened stepwise from the cases with favorable cytogenetics to those with intermediate and unfavorable cytogenetics (P0.01).The combined treatment of Chinese drugs with chemotherapy has a predominant effect in de novo AML. Secondary or refractory AML, expression of CD34 and CD56, and unfavorable cytogenetics were the main factors of poor prognosis in AML.

To observe the clinical efficacy of a low dose Qinghuang Powder (QP) combined with Chinese drugs for Shen supplementing and Pi invigorating (CDSSPI) in treatment of hypocellular myelodysplastic syndromes (hypo-MDS).Totally 33 hypo-MDS patients enrolled in this study came from outpatient clinics between November 2011 and December 2012. A self-control method was used in this study. Patients took QP (0.4 g per day) combined with CDSSPI (one dose per day), and Stanozolol Tablet (2 mg each time, three times per day), 3 months as one therapeutic course, a total of 2 courses. The clinical efficacy was evaluated timely at the end of each therapeutic course. The venous blood was withdrawn before treatment, at month 3 and 6 after treatment. Changes of neutrophils (ANC), hemoglobin (Hb), and platelet (PLT) were mainly observed.Totally 31 patients in this study finished the treatment. Three months after treatment ANC, Hb, and PLT increased more than before treatment (P0.05). Six months after treatment Hb and PLT increased (P0.01, P0.05), but with no statistical difference in ANC (P0.05). Hb increased higher at month 6 after treatment than at month 3 after treatment (P0.01), but with no statistical difference in ANC or PLT (P0.05). After 3-month treatment the number of hematologic progress, stability, disease progression were: 13 cases (41.9%), 15 cases (48.4%), and 3 cases (9.7%), respectively; after 6-month treatment the number of hematologic improvement, stability, and disease progression were: 18 cases (58.1%), 7 cases (22.6%), 6 cases (19.3%), respectively. There was no significant difference between 3-month efficacy and 6-month efficacy (P0.05). There was no correlation between the efficacy and ages of hypo-MDS patients or the efficacy and courses of hypo-MDS patients (P0.05).A low dose QP combined with CDSSPI showed confirmative efficacy in treatment of hypo-MDS. But the efficacy had little correlation with ages and courses of hypo-MDS patients.

To study the effect of Qinghuang Powder (QHP) combined Chinese herbs for Pi-strengthening and Shen-reinforcing (CHPSSR) on hypoxia-inducible factor 1alpha (HIF-1alpha) in bone marrow mononuclear cells of myelodysplastic syndrome (MDS) patients.Changes of HIF-1alpha in bone marrow mononuclear cells of MDS patients were detected in 25 MDS patients treated by QHP combined CHPSSR using flow cytometry. Meanwhile, 13 healthy subjects were recruited as the control group. Changes HIF-1alpha levels in various serial bone marrow mononuclear cells were detected.(1) Among the 25 patients in the treatment group, there were 19 patients effective and 6 patients ineffective, with the total effective rate being 76%. (2) Compared with before treatment, levels of peripheral blood WBC, Hb, PLT, and ANC significantly increased in the treatment group after treatment, showing statistical difference (P0.05, P0.01). (3) Compared with before treatment, the HIF-1alpha mean fluorescence intensity was enhanced in bone marrow lymphocytes, monocytes, granulocytes, and nucleated red blood cells of the treatment group after treatment (P0.05, P0.01). Compared with the control group, the HIF-1alpha mean fluorescence intensity was weakened in bone marrow lymphocytes, monocytes, and nucleated red blood cells of the treatment group before treatment; while it was obviously enhanced in granulocytes (P0.01). But after treatment the HIF-1alpha mean fluorescence intensity increased more in the granulocytes of the treatment group than in those of the control group (P0.01), but there was no statistical difference in bone marrow lymphocytes, monocytes, or nucleated red blood cells.QHP combined CHPSSR could improve HIF-1alpha levels in bone marrow lymphocytes, monocytes, granulocytes, and nucleated red blood cells of MDS patients, thus improving Hb levels of MDS patients, and improving their anemia and correlated symptoms.

Objective To observe the effects of Fuzheng Kangbai Granule (FZKBG) on immune function and survival time in minimal residual leukemia (MRL) model mice and explore its mechanism.

To explore the effects of Qinghuang Power (QHP) combined Chinese herbs for Shen reinforcing and Pi strengthening (CHSRPS) on activated T cells of myelodysplastic syndrome (MDS) patients.The percentage and the absolute value of CD3+ CD28+, CD3+ CD28+ CD4+ CD8-, CD3+ CD28+ CD8+ CD4-, CD3+ CD25+, CD3+ CD25+ CD4+ CD8-, CD3+ CD25+ CD8+ CD4-, CD3+ DR+, CD3+ DR+ CD4+ CD8-, and CD3+ DR+ CD8+ CD4- in the peripheral blood of 24 MDS patients were detected by flow cytometry before and after treatment by QHP combined CHSRPS for 9 months. The changes of the differences in the aforesaid indices were analyzed between the effective group and the in-, and CD3 + effective group.The absolute values of CD3+ CD28+, CD3+ CD28+ CD4+ CD8-, and CD3+ CD28+ CD8+ CD4- obviously decreased in the effective group(13 cases)after treatment (P0.05). The percentages of the three indices also obviously decreased in the ineffective group (11 cases, P0.05). After treatment, both the percentage and the absolute value of CD3+ CD25+ and CD3+ CD25+ CD4+ CD8- obviously decreased in the effective group (P0.05). There was no statistical difference in the two indices of the ineffective group between before and after treatment (P0.05).QHP combined CHSRPS could induce second signal loss by decreasing the expressions of in vitro costimulatory molecules, resulting in deactivation of T cells. It also could suppress the hyperfunction of the immune state in MDS patients, thus preventing normal hematopoietic cells from immune attack induced apoptosis.

The diagnosis and treatment pattern using combination of disease and syndrome, fully developing the advantages of both traditional Chinese medicine (TCM) and Western medicine (WM) and being widely used clinically, has been constructed in the long history of TCM. Prof. MA Rou, as a hematology specialist of integrative medicine (IM), uses modern medical equipment to diagnose diseases and takes traditional Chinese medical methods to treat diseases. He is loyal to TCM sciences and refers to the advantages of WM. He holds the essence of MDS lies in toxic stasis according to its pathogenic features. He detoxifies and removes stasis using Qinghuang Powder. Meanwhile, according to patients' clinical manifestations, he summarized two common syndrome types, Pi-Shen yang deficiency syndrome and Gan-Shen yin deficiency syndrome. Better efficacy could be achieved by combining Chinese herbs for tonifying Pi-Shen. In recent years the application of Qinghuang Powder won some achievements in clinical study and experimental study, thus providing scientific reliance for Prof. MA Rou's academic thought on treating MDS.

Jinjin Shi, Zhenzhen Wang, Lei Wang, Honghong Wang, Lulu Li, Xiaoyuan Yu, Jing Zhang, Rou Ma, Zhenzhong ZhangSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People's Republic of ChinaAbstract: Fullerene (C60) has shown great potential in drug delivery. In this study we exploited modified fullerene (diadduct malonic acid-fullerene-Asn-Gly-Arg peptide [DMA-C60-NGR]) as an antitumor drug carrier in order to build a new tumor-targeting drug delivery system. We also investigated the synergistic enhancement of cancer therapy using photodynamic therapy (PDT) induced by DMA-C60-NGR and 2-methoxyestradiol (2ME). Cytotoxicity tests indicated that DMA-C60-NGR had no obvious toxicity, while our drug delivery system (DMA-C60-2ME-NGR) had a high inhibition effect on MCF-7 cells compared to free 2ME. The tumor-targeting drug delivery system could efficiently cross cell membranes, and illumination induced the generation of intracellular reactive oxygen species and DNA damage. Furthermore, DMA-C60-2ME-NGR with irradiation had the highest inhibition effect on MCF-7 cells compared to the other groups. DMA-C60-NGR combined with 2ME showed a good synergistic photosensitization effect for inhibiting the growth of MCF-7 cells, demonstrating that DMA-C60-2ME-NGR may be promising for high treatment efficacy with minimal side effects in future therapy.Keywords: fullerene, drug delivery system, photodynamic therapy, tumor targeting

Fullerene has shown great potential both in drug delivery and photodynamic therapy. Herein, we developed a doxorubicin (DOX)-loaded poly(ethyleneimine) (PEI) derivatized fullerene (C60-PEI-DOX) to facilitate combined chemotherapy and photodynamic therapy in one system, and DOX was covalently conjugated onto C60-PEI by the pH-sensitive hydrazone linkage. The release profiles of DOX from C60-PEI-DOX showed a strong dependence on the environmental pH value. The biodistributions of C60-PEI-DOX were investigated by injecting CdSe/ZnS (Qds) labeled conjugates (C60-PEI-DOX/Qds) into tumor-bearing mice. C60-PEI-DOX/Qds showed a higher tumor targeting efficiency compared with Qds alone. Compared with free DOX in an in vivo murine tumor model, C60-PEI-DOX afforded higher antitumor efficacy without obvious toxic effects to normal organs owing to its good tumor targeting efficacy and the 2.4-fold greater amount of DOX released in the tumor than in the normal tissues. C60-PEI-DOX also showed high antitumor efficacy during photodynamic therapy. The ability of C60-PEI-DOX nanoparticles to combine local specific chemotherapy with external photodynamic therapy significantly improved the therapeutic efficacy of the cancer treatment, the combined treatment demonstrating a synergistic effect. These results suggest that C60-PEI-DOX may be promising for high treatment efficacy with minimal side effects in future therapy.

In recent years, significant progresses have been got in study on pathogenesis, treatment and prognosis of myelodysplastic syndromes (MDS), especially on use of new technology, that has great importance for cytogenetics of MDS. Recently, the progress of cytogenetic detection in MDS is very remarkable. Based on the metaphase cytogenetics (MC) method, prognostic significance of cytogenetics in MDS was clarified gradually. For example, people have known the prognostic significance of 12 p-, 11 q-, +21, t(11(q23)), although these genetic abnormalities are rare in the MDS. In addition, chromosome mutation emerged in the process of MDS may indicate the poor prognosis. On the other hand, with the use of SNP-A and aCGH in the study of genetics, MDS cytogenetic abnormality detection rate has been further improved and can reach to 78%. At the same time, some of MDS patients with the "normal karyotype" detected by MC have new hidden aberrations through the SNP or CGH detection, and these patients have a poorer prognosis. In this review, the advances of study on cytogenetic detection for MDS based on MC and SNP-A or aCGH methods are summarized.

Professor MA Rou has been engaged in clinical and basic research of hematology for more than 40 years. He is excel in the treatment of refractory hematological diseases under the guidance of holism and syndrome differentiation in Chinese medicine. Application of arsenic-containing Chinese herbal medicine in treating myelodysplastic syndrome (MDS), primary polycythemia vera (CMPD-PV), primary thrombocythemia (CMPD-ET), MDS-U, myeloproliferative disease, acute non lymphocytic leukemia except for promyelocytic leukemia, Prof. MA has made great innovation and exploration. For some diseases, he has obtained much mature experiences. Although some are still in the stage of exploration, ideal clinical effects has been shown primarily.

To observe the clinical effectiveness of Qinghuang Powder (QHP) combined with Bupi Yishen Decoction (, 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.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 II, 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.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 (P0.01). For the analysis in the patients of different IPSS risk degrees, the effective rate was 95.24% (20/21) in the lowrisk group, 72.73% (56/77) in moderate risk I, 65.00% (13/20) in moderate-risk II, and 16.67% (1/6) in high-risk group. Those in the first two groups were superior to that in the latter two (P0.01). 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.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.

To explore the effect of Yiqi Bushen Granule (YBG) on CD4+ CD8high T lymphocyte in patients with minimal residual leukemia (MRL) and to probe its prognosis after treatment.The changes of CD4+ CD8high T lymphocyte subgroup and natural killer (NK) cells in 36 patients (16 males and 20 females) received long-term (3 months) YBG therapy before and after treatment were analyzed using multi-parameter flow cytometry and controlled by those in 34 healthy persons (19 males and 15 females).The 3-year and 5-year complete remission rates in MRL patients were 75.0% and 63.9%; their 3-year and 5-year survival rates were 80.5% and 72.2%, respectively; as compared with the baseline, the absolute value and percentage of CD4+ CD8high T lymphocyte and NK cells were all significantly raised after treatment (P0.05 or P0.01).YBG could prolong the disease-free survival in MRL patients by way of regulating the immune function of organism, elevating the amount of CD4+ CD8high T lymphocyte and NK cells to kill or suppress the residual leukemic cell in body.

To analyze the changes in peripheral natural killer T-cells (NKT) and gammadelta T-cells (γ δ T-cell) in patients with minimal residual leukemia (MRL) before and after being treated with Yiqi Bushen Granule (益气补肾颗粒, YBG) in order to determine their significance in prognosis of the disease. Granule (益气补肾颗粒, YBG) in order to determine their significance in prognosis of the disease.Before and after treatment, the changes in 36 patients (16 males and 20 females) receiving long-term (more than 3 months) YBG therapy were analyzed using multi-parameter flow cytometry, with 34 healthy persons (19 males and 15 females) acting as controls. males and 15 females) acting as controls.The absolute value and percentage of NKT cells and γ δ T-cells were all significantly raised after treatment, for NKT cells, 0.52%±0.39% to 0.83%±0.66% and 7.25±7.77 cells cell/μL to 12.86±11.99 cell/μL, for γ δ T-cells, 6.08%±3.03% to 7.24%±2.78% and 83.97±48.09 cell/μL 110.53±54.12 cell/μL, respectively (P0.05 or P0.01).YBG could regulate the immune function and elevate the amount of NKT cells and γ δ T-cells, thus to kill or suppress the residual leukemic cell in the body, which might be one of the mechanisms of YBG in prolonging the disease-free survival in MRL patients.

Ginseng contains multiple components, such as saponins and saccharide, etc. The major is ginsenoside, which includes more than 40 kinds of monomers. It has been applied to treat blood-deficiency syndrome, but the action mechanism is still unclear. The fundamental researches on the effect of ginseng and its components on hematopoiesis and their clinical application were reviewed in this article. They were found to have effects on hematopoietic cells, microenvironment and regulatory factors, indicating they are potential for prevention of hemocytopenia, protection from injury of radiotherapy/chemotherapy and even for transplantation of hematopoietic stem cell.

To explore the effects and mechanism of Shuangshen Tongguan (SSTG) serum, a formula composed of the active fractions of Chinese medicine, on calcium overload in cultured cardiomyocytes injured by hypoxia and reoxygenation.The cardiomyocytes were deprived of oxygen and glucose to producl hypoxia reoxygenation injuried models. The changes of intracellular calcium fluorescence intensity induced by K+ and Thapsigargin were measured by fluorospectrophotometry and laster scanning confocal microscope respectively.Intracellular calcium concentration was low in normal cardiomyocytes and was enhanced after hypoxia/reoxygenation (P0.05); SSTC drug serum reduced the intracellular calcium concentration and depressed the increase of calcium fluorescence intensity in singular cardiomyocyte due to K+ and Thapsigargin stimulation.Hypoxia/reoxygenation injury, K+ and Thapsigargin could induce calcium overload in cardiomyocytes. The effects of calcium antagonism of SSTG drug serum were achieved by inhibiting calcium inflow, promoting calcium re-absorption of calcium.

The aim was to investigate the immunophenotypes of NK series leukemia. Immunophenotypes of 297 cases of acute leukemia (AL) were measured by flow cytometry, and these immucopenotypic features were analyzed. The results showed that 43 out of 297 cases of AL (14.5%) were CD56 positive. 6 cases were NK series leukemia and 37 cases were acute myelogenous leukemia with CD56 expressed. One patient has been diagnosed as myeloid/NK cell precursor acute leukemia, two patients were blastic NK cell leukemia, one was supposed to be NK-like T-cell lymphoma/leukemia, while another one was large granular lymphocyte leukemia (LGLL). It is concluded that almost all of CD56 positive leukemia were acute myelogenous leukemia with CD56 expressed. The immunophenotypes of NK series leukemia were antigens from hematopoietic stem cells to T/NK progenitor cells with meyloid antigen positive, and through NK progenitors to mature NK cells. The immunophenotypes of heterogeneous NK leukemia cells are different, that should be carefully distinguished.