Imbalance of T follicular helper cell subsets trigger the differentiation of pathogenic B cells in idiopathic membranous nephropathy.

OBJECTIVE: This study aims to elucidate the role of T follicular helper (Tfh) cells and their subsets in idiopathic membranous nephropathy (IMN). METHODS: The frequencies of Tfh cell subsets and B cell subsets in peripheral blood (PB) were detected in both IMN patients and healthy controls (HCs). The involvement of Tfh cells in the disease pathogenesis was examined by coculturing human Tfh cells with B cells. The dynamic changes of Tfh cells in PB or spleen were monitored in passive Heymann nephritis (PHN) rats. RESULTS: The frequencies of circulating Tfh (cTfh) cells, cTfh2 cells, and plasmablasts were enriched in the PB of patients with IMN. cTfh cells expressed higher ICOS, and lower BTLA than healthy counterparts. The frequency of ICOS + cTfh2 was associated with the severity of IMN, including 24h urine protein, IgG4 concentration and the IgG4: IgG ratio. Positive correlations were also observed between the frequency of cTfh2 cells with plasmablasts, serum IL-21 and IL-4 levels. Importantly, cTfh cells isolated from IMN patients were able to induce the differentiation of B cells to memory B cells (MBC) and plasmablasts, this process could be substantially attenuated by blocking the IL-21. Similar increases of ICOS + cTfh cells were also detected in spleen of PHN rats, concomitant with elevated urine protein levels. CONCLUSIONS: Collectively, our results demonstrate that the imbalance of cTfh cell subsets play a crucial pathogenic role in IMN by inducing the differentiation of B cells through IL-21, and cTfh2 cells might serve as useful markers to evaluate the progression of IMN.

Peripheral blood lymphocyte subsets predict the efficacy of TACE with or without PD-1 inhibitors in patients with hepatocellular carcinoma: a prospective clinical study.

Background: Although peripheral blood lymphocyte subsets, particularly PD-1+ T cells, are promising prognostic indicators for patients with cancer. However, their clinical significance remains unclear. Methods: We prospectively enrolled 157 patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization combined with or without PD-1 inhibitors. Twenty peripheral lymphocyte subsets and cytokines were analyzed. We analyzed the differences in PD-1+ T cells between patients treated with and without PD-1 inhibitors and their associations with tumor response, survival prognosis, and clinical features. Results: We found that the baseline CD8+PD-1+ and CD4+PD-1+ T-cell frequencies in patients who had received PD-1 inhibitors were lower than those in patients who had not received PD-1 inhibitors (p < 0.001). In the former patients, there were no differences in PD-1+ T-cell frequencies between the responder and non-responder subgroups (p > 0.05), whereas in the latter patients, the levels of CD8+PD-1+ T cells, CD4+PD-1+ T cells, and CD8+PD-1+/CD4+PD-1+ ratio did not predict tumor response, progression-free survival (PFS), or overall survival (OS) (p>0.05). Furthermore, in multivariate analysis of patients treated with or without PD-1 inhibitors revealed that the levels of CD8+CD38+ T cells (OR = 2.806, p = 0.006) were associated with tumor response, whereas those of CD8+CD28+ T cells (p = 0.038, p = 0.001) and natural killer (NK) cells (p = 0.001, p = 0.027) were associated with PFS and OS. Although, these independent prognostic factors were associated with progressive tumor characteristics (p<0.05), with the exception of CD8+CD28+ T cells, changes in these factors before and after treatment were unassociated with tumor response (p > 0.05). Conclusion: Circulating CD8+CD38+ T cells, CD8+CD28+ T cells, and NK cells were identified as potential prognostic factors for tumor response and survival in patients with HCC. Contrastingly, although PD-1 inhibitors can effectively block the T cell PD-1 receptor, the baseline PD-1+ T-cell frequencies and changes in the frequency of these cells have limited prognostic value.

Tanshinone IIA modulates cancer cell morphology and movement via Rho GTPases-mediated actin cytoskeleton remodeling.

Actin filaments form unique structures with robust actin bundles and cytoskeletal networks affixed to the extracellular matrix and interact with neighboring cells, which are crucial structures for cancer cells to acquire a motile phenotype. This study aims to investigate a novel antitumor mechanism by which Tanshinone IIA (Tan IIA) modulates the morphology and migration of liver cancer cells via actin cytoskeleton regulation. 97H and Huh7 exhibited numerous tentacle-like protrusions that interacted with neighboring cells. Following treatment with Tan IIA, 97H and Huh7 showed a complete absence of cytoplasmic protrusion and adherens junctions, thereby effectively impeding their migration capability. The fluorescence staining of F-actin and microtubules indicated that these tentacle-like protrusions and cell-cell networks were actin-based structures that led to morphological changes after Tan IIA treatment by retracting and reorganizing beneath the membrane. Tan IIA can reverse the actin depolymerization and cell morphology alterations induced by latrunculin A. Tan IIA down-regulated actin and Rho GTPases expression significantly, as opposed to inducing Rho signaling activation. Preventing the activity of proteasomes and lysosomes had no discernible impact on the modifications in cellular structure and protein expression induced by Tan IIA. However, as demonstrated by the puromycin labeling technique, the newly synthesized proteins were significantly inhibited by Tan IIA. In conclusion, Tan IIA can induce dramatic actin cytoskeleton remodeling by inhibiting the protein synthesis of actin and Rho GTPases, resulting in the suppression of tumor growth and migration. Targeting the actin cytoskeleton of Tan IIA is a promising strategy for HCC treatment.

Triptolide inhibits the proinflammatory potential of myeloid-derived suppressor cells via reducing Arginase-1 in rheumatoid arthritis.

Triptolide (TPT) is widely used in the treatment of rheumatoid arthritis (RA). However, its regulatory mechanisms are not fully understood. This study demonstrated that Myeloid-derived suppressor cells (MDSCs) were expanded in both RA patients and arthritic mice. The frequency of MDSCs was correlated with RA disease severity and T helper 17 (Th17) responses. MDSCs from RA patients promoted the polarization of Th17 cells in vitro, which could be substantially attenuated by blocking arginase-1 (Arg-1). TPT inhibited the differentiation of MDSCs, particularly the monocytic MDSCs (M-MDSCs) subsets, as well as the expression of Arg-1 in a dose dependent manner. Alongside, TPT treatment reduced the potential of MDSCs to promote the polarization of IL-17+ T cell in vitro. Consistently, TPT immunotherapy alleviated adjuvant-induced arthritis (AIA) in a mice model, and reduced the frequency of MDSCs, M-MDSCs and IL-17+ T cells simultaneously. The presented data suggest a pathogenic role of MDSCs in RA and may function as a novel and effective therapeutic target for TPT in RA.

Elevated circulating CD19+CD24hiCD38hi B cells display pro-inflammatory phenotype in idiopathic membranous nephropathy.

CD19+CD24hiCD38hi regulatory B cells exert immunosuppressive functions by producing IL-10, but their role in idiopathic membranous nephropathy (IMN) remains elusive. Here, we investigated the frequency and functional changes of circulating CD19+CD24hiCD38hi B cells and evaluated the correlation of CD19+CD24hiCD38hi B cells with clinical features and T helper cell subsets in IMN patients. Compared with healthy controls (HCs), IMN patients showed an increased frequency of CD19+CD24hiCD38hi B cells, but a significant reduction in the percentage of CD19+CD24hiCD38hi B cells was observed 4 weeks after cyclophosphamide treatment. The frequency of CD19+CD24hiCD38hi B cells was positively correlated with the levels of 24h urinary protein, but negatively correlated with serum total protein and serum albumin, respectively. CD19+CD24hiCD38hi B cells in IMN patients displayed a skewed pro-inflammatory cytokine profile with a higher level of IL-6 and IL-12, but a lower concentration of IL-10 than their healthy counterparts. Accompanied by upregulation of Th2 and Th17 cells in IMN patients, the percentage of CD19+CD24hiCD38hi B cell subset was positively associated with Th17 cell frequency. In conclusion, CD19+CD24hiCD38hi B cells were expanded but functionally impaired in IMN patients. Their altered pro-inflammatory cytokine profile may contribute to the pathogenesis of IMN.

A population-based characterization study of anti-mitochondrial M2 antibodies and its consistency with anti-mitochondrial antibodies.

OBJECTIVE: This study aims to estimate the prevalence of anti-mitochondrial antibody subtype M2 (AMA-M2) and assess its consistency with AMA in a general population. METHODS: A total of 8954 volunteers were included to screen AMA-M2 using enzyme-linked immunosorbent assay. Sera with AMA-M2 >50 RU/mL were further tested for AMA using an indirect immunofluorescence assay. RESULTS: The population frequency of AMA-M2 positivity was 9.67%, of which 48.04% were males and 51.96% were females. The AMA-M2 positivity in males had a peak and valley value of 7.81% and 16.88% in those aged 40 to 49 and ≥70 years, respectively, whereas it showed a balanced age distribution in females. Transferrin and immunoglobulin M were the risk factors for AMA-M2 positivity and exercise was the only protective factor. Of 155 cases with AMA-M2 >50 RU/mL, 25 cases were AMA-positive, with a female-to-male ratio of 5.25:1. Only 2 people, with very high AMA-M2 of 760 and >800 RU/mL, met the diagnostic criteria of primary biliary cholangitis (PBC), making the prevalence of PBC 223.36 per million in southern China. CONCLUSION: We found that AMA-M2 has a low coincidence rate with AMA in the general population. A new decision-making point for AMA-M2 is needed to improve consistency with AMA and diagnostic accuracy.

Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in Daboia siamensis and Agkistrodon halys Envenomation-Induced Thrombocytopenia.

Venom-induced thrombocytopenia (VIT) is one of the most important hemotoxic effects of a snakebite, which is often associated with venom-induced consumptive coagulopathy (VICC). Refractory thrombocytopenia without significant coagulation abnormalities has also been reported after envenomation by some viperid snakes; however, the mechanisms are not well understood and therapeutic strategies are lacking. Here, we found that patients injured by Daboia siamensis or Agkistrodon halys snakes, who were resistant to standard antivenom treatment, had developed coagulopathy-independent thrombocytopenia. Venoms from these viperid snakes, rather than from the elapid snake (Bungarus multicinctus), induced platelet surface expression of neuraminidase-1 (NEU-1), and significantly increased the desialylation of the glycoproteins on human platelets. The desialylated platelets caused by viperid snake venoms were further internalized by macrophages, which resulted in reduced platelet numbers in peripheral blood. Importantly, neuraminidase inhibitor significantly decreased viper venom-induced platelet desialylation, therefore inhibiting platelet phagocytosis by macrophages, and alleviating venom-induced thrombocytopenia. Collectively, these findings support an important role for desialylated platelet clearance in the progression of viper envenomation-induced, coagulopathy-independent thrombocytopenia. Our study demonstrates that the neuraminidase inhibitor may be a potential therapy or adjuvant therapy to treat snakebite-induced thrombocytopenia.

Performance Evaluation of Antiphospholipid Antibodies on INOVA Quanta Flash System.

BACKGROUND: The diagnosis of antiphospholipid syndrome (APS) relies predominantly on the laboratory measurement of antiphospholipid antibodies (aPLs). We attempt to verify the analytical performance of anticardiolipin antibodies (aCL) IgA/IgG/IgM and anti-ß2-glycoprotein I antibodies (aß2GPI) IgA/IgG/IgM on a high-throughput automated immunoassay platform. METHODS: Limit of blank (LOB), limit of detection (LOD), imprecision, and linearity were calculated according to the corresponding Clinical and Laboratory Standards Institute (CLSI) guidelines protocols. The biological reference intervals (RIs) were verified in healthy individuals. RESULTS: The LoB of aCL IgA/IgG/IgM and aß2GPI IgA/IgG/IgM were 0.000, 1.200, 0.200, and 0.400, 1.250, 0.100, respectively. The LoD were 0.093, 1.715, 0.337 and 0.547, 2.174, 0.185 CU, respectively. All the within-run CVs and total CVs were less than the criterion at 10%. The linear analysis showed a good correlation between the predictive values and observed values with correlation coefficients greater than 0.99. CONCLUSIONS: The BIO-FLASH automated chemiluminescent analyzer performed well in measuring aPLs.

Clinical relevance of serum α-l-fucosidase activity in the SARS-CoV-2 infection.

BACKGROUND AND AIMS: The reduced fucosylation in the spike glycoprotein of SARS-CoV-2 and the IgG antibody has been observed in COVID-19. However, the clinical relevance of α-l-fucosidase, the enzyme for defucosylation has not been discovered. MATERIALS AND METHODS: 585 COVID-19 patients were included to analyze the correlations of α-l-fucosidase activity with the nucleic acid test, IgM/IgG, comorbidities, and disease progression. RESULTS: Among the COVID-19 patients, 5.75% were double-negative for nucleic acid and antibodies. All of them had increased α-l-fucosidase, while only one had abnormal serum amyloid A (SAA) and C-reactive protein (CRP). The abnormal rate of α-l-fucosidase was 81.82% before the presence of IgM, 100% in the presence of IgM, and 66.2% in the presence of IgG. 73.42% of patients with glucometabolic disorders had increased α-l-fucosidase activity and had the highest mortality of 6.33%. The increased α-l-fucosidase was observed in 55.8% of non-severe cases and 72.9% of severe cases, with an odds ratio of 2.118. The α-l-fucosidase mRNA was irrelevant to its serum activity. CONCLUSION: The change in α-l-fucosidase activity in COVID-19 preceded the IgM and SAA and showed a preferable relation with glucometabolic disorders, which may be conducive to virus invasion or invoke an immune response against SARS-CoV-2.

MIL-1, a novel antitumor agent derived from natural product millepachine, acts as tubulin polymerization inhibitor for the treatment of hepatocellular carcinoma.

Natural products are a large source of clinically effective antitumor drugs. Millepachine, a natural product derived from leguminous plants, was reported to display antitumor activity. In this study, the novel compound, (1H-indol-5-yl) (5-methoxy-2,2-dimethyl-2H-chromen-8-yl)methanone (MIL-1), was designed and synthesized by fusing millepachine and indole rings. MIL-1 exerted much better antitumor activity than millepachine, manifesting as a 24- to 201-fold increase in vitro cytotoxicity and a 2.4-fold increase in in vivo antitumor activity in hepatocellular cell lines-derived models. The immunofluorescence and HPLC detection revealed that MIL-1 was a potent microtubule targeting agent by interfering with the equilibrium of tubulin-microtubule dynamics and irreversibly binding to tubulin. MIL-1 displayed remarkable antitumor activity with an IC50 of 31-207 nM towards various human cancer cell lines derived from various organs and tissues, and it exerted no evidence of toxicity against normal cells. Mechanistic studies showed that MIL-1 arrested the cell cycle at G2/M phase and induced apoptosis by activating caspase-3 activity and reactive oxygen species (ROS) accumulation. Moreover, the superior antitumor effect of MIL-1 is worthy of further detailed study for the treatment of hepatocellular carcinoma (HCC).

Differential diagnosis and prospective grading of COVID-19 at the early stage with simple hematological and biochemical variables.

We evaluated simple laboratory variables to discriminate COVID-19 from bacterial pneumonia or influenza and for the prospective grading of COVID-19. Multivariate logistic regression and receiver operating characteristic curve were used to estimate the diagnostic performance of the significant discriminating variables. A comparative analysis was performed with different severity. The leukocytosis (P = 0.017) and eosinopenia (P = 0.001) were discriminating variables between COVID-19 and bacterial pneumonia with area under the curve (AUC) of 0.778 and 0.825. Monocytosis (P = 0.003), the decreased lymphocyte-to-monocyte ratio (P < 0.001), and the increased neutrophil-to-lymphocyte ratio (NLR) (P = 0.028) were predictive of influenza with AUC of 0.723, 0.895, and 0.783, respectively. Serum amyloid protein, lactate dehydrogenase, CD3+ cells, and the fibrinogen degradation products had a good correlation with the severity of COVID-19 graded by age (≥50) and NLR (≥3.13). Simple laboratory variables are helpful for rapid diagnosis on admission and hierarchical management of COVID-19 patients.

[Thrombopoietin Prevents CoCl2-inducing Apoptosis of HUVEC through the PI3K/AKT Pathway].

OBJECTIVE: To investigate the effect of thrombopoietin (TPO) on chemical hypoxia-induced apoptosis of human umbilical vein endothelial cells (HUVEC), and to explore its potential mechanism. METHODS: The experiment was divided into 4 groups. The untreated HUVECs were used as normal control group. HUVECs treated with CoCl2 was CoCl2 group, and TPO was added into the culture medium 48 h before CoCl2 treatment as TPO + CoCl2 group. The cells was treated with TPO alone as TPO group. The cell viability and apoptosis of each groups were tested by Cell Counter Kit 8 (CCK-8) assay and flow cytometry. The expression of Caspase-3 and mitochondrial membrane potential (MMP) were then determined by flow cytometry with Caspase-3-PE and JC-1. The effect of TPO in PI3K/AKT pathway was detected by using Western blot. RESULTS: CoCl2 significantly inhibited the growth of HUVECs. The cell viability of HUVECs decreased gradually with enhancement of CoCl2 at a gradient of chemical concentrations (r= -0.997). CoCl2 dramatically increased apoptosis of HUVECs, whereas pre-treatment with TPO rescued cell apoptosis induced by CoCl2 (P<0.001). Further investigation found that TPO decreased the expression of Caspase-3 and inhibited the reduction of MMP induced by CoCl2 (P<0.05). TPO could increased the activation of PI3K/AKT pathway in HUVECs. CONCLUSION: TPO has a protective effect against CoCl2-induced apoptosis of HUVECs through activating the PI3K/AKT pathway, thus decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.

Thrombopoietin protects H9C2 cells from excessive autophagy and apoptosis in doxorubicin-induced cardiotoxicity.

Cardiac toxicity has been the major concern when using doxorubicin (DOX) in cancer therapy. Thrombopoietin (TPO) protects cardiac cells from DOX-induced cell damage; however, its molecular mechanism remains exclusive. The anti-autophagic and anti-apoptotic effects of TPO upon DOX treatment were studied in the cardiac H9C2 cell line, with bafilomycin A1 treatment as a positive control for autophagy inhibition. Cell viability was measured by Cell Counting Kit-8 assay in different treatment groups. The mRNA and/or protein levels of apoptotic markers and autophagy-associated factors were detected. The mean number of microtubule-associated protein 1A/1B-light chain 3 (LC3) puncta per cell was quantified to indicate autophagosomes and autolysosomes, of which the ones co-stained with lysosomal-associated membrane protein 1 were considered as autolysosomes. DOX treatment (5 µg/ml, 24 h) significantly impaired H9C2 cell viability compared with the control, while TPO pretreatment (10 ng/ml, 36 h) improved cell viability upon DOX treatment. DOX exposure markedly increased LC3 puncta in H9C2 cells, and TPO pretreatment reduced the number of autophagosomes, but showed no significant inhibitory effect on autolysosome formation. The autophagy inhibition by TPO upon DOX treatment was confirmed according to protein quantification of LC3-II and nucleoporin 62. TPO also suppressed autophagy-promoting protein Beclin-1, and elevated the anti-autophagic factors GATA-binding protein-4 and B cell lymphoma-2. Furthermore, TPO reduced DOX-induced apoptosis in H9C2 cells, as reflected by the amount changes of caspase-3. Taken together, these results revealed that TPO has a protective role in H9C2 cells from DOX-induced autophagy as well as apoptosis, and indicated that TPO may act as a cardioprotective drug in DOX-treated patients.

[PDGF-BB Promotes CFU-GM and CFU-MK Formation and Its Possible Mechnism].

OBJECTIVE: To investigate the effect of platelet-derived growth factor (PDGF-BB) on the formation of granulocyte-monocyte colony forming unit (CFU-GM) and megakaryocyte colony forming unit (CFU-MK) and its anti-apoptotic effect on CHRF cells. METHODS: The CFU-GM and CFU-MK of murine and human bone marrow cells were cultured in vitro by using plasma clot culture system. The anti-apoptotic effect of PDGF-BB on CHRF cells and its mechanism were clarified by flow cytometry. RESULTS: PDGF-BB 0-100 ng/ml stimulated the proliferation of murine and human CFU-GM and CFU-MK in a dose-dependent manner. The maximal stimulation effect was obtained at 50 ng/ml of PDGF-BB (P<0.01). Furthermore, PDGF-BB had an anti-apoptotic effect on CHRF cells as shown by the flow cytometry with AnnexinV/PI double staining, Caspase-3 expression and JC-1 detection (P<0.05). CONCLUSION: PDGF-BB significantly stimulates the proliferation of CFU-GM and CFU-MK in vitro, and has an anti-apoptotic effect on CHRF cells.

[Role of PDGF/PDGFR Pathway in Essential Thrombocythemia and Its Action Mechanism].

OBJECTIVE: To study the role of PDGF/PDGFR in essential thrombocythemia (ET) by investigating the expression of PDGF-BB in bone marrow and the expression of PDGFR-ß in bone marrow cells of patients with ET and explore the new target for treating ET patients through inhibiting the PDGFR of megakaryocytes. METHODS: The expression level of PDGF-BB in bone marrow of ET patients and normal controls were assayed by using ELISA, the expression level of PDGFR-ß (CD140) in bone marrow of ET patients and normal controls were detected by using flow cytometry, the effect of PDGF-BB in JAK2/STAT3 and PI3K/AKT pathway was detected by using flow cytometry or Werstern blot, and the effect of imatinib on the megakaryopoiesis of PDGF was observed. RESULTS: The expression level of PDGF-BB in bone marrow of ET patients was significantly higher than that in normal controls; the expression level of PDGFR-ß in bone marrow of ET patients was significantly higher than that in nornal controls; PDGF-BB could activate JAK2/STAT3 and PI3K/AKT pathway of megakaryocytes, while the imatinib could block the effect of PDGF-BB on megakaryocyte. CONCLUSION: The elevated PDGF-BB and PDGFR-ß may be involved in ET, and the physiopathologic mechanism is that the elevated PDGF-BB activates PDGFR with subsequent activation of the JAK2/STAT3 and PI3K/AKT pathways, stimulating megakaryopoiesis. Imatinib may have a therapeutical effect on ET via blocking of PDGFR.

Association between MTHFR C677T polymorphism and risk of acute lymphoblastic leukemia: a meta-analysis based on 51 case-control studies.

BACKGROUND: Studies and systematic reviews have reached inconsistent conclusions on the role of 5, 10-methylenetetrahydrofolate reductase (MTHFR) polymorphism C677T in acute lymphoblastic leukemia (ALL) risk. MATERIAL AND METHODS: The present meta-analysis comprising of 51 case-control studies, including 7892 cases and 14 280 controls was performed to reevaluate the association between MTHFR C677T polymorphism and ALL risk. RESULTS: Statistical differences were found in the dominant model (TT+CT vs. CC, odd ratio (OR)=0.89, 95% CI, 0.79-1.00, P=0.04) and the CT vs. CC (OR=0.89, 95% CI, 0.80-1.00, P=0.05), but not in the allele contrast model (T vs. C, OR=0.92, 95% CI, 0.84-1.01, P=0.08), additive model (TT vs. CC, OR=0.87, 95% CI, 0.73-1.05, P=0.15), or recessive model (TT vs. CT+CC, OR=0.94, 95% CI, 0.81-1.10, P=0.44) in overall populations. In the subgroup analyses stratified by age (children and adults) and ethnicity (Asian and Caucasian), no significant associations between MTHFR C677T polymorphism and ALL risk were observed. CONCLUSIONS: The current study found no sufficient evidence of a protective role of MTHFR C677T polymorphism in ALL susceptibility.

[Anti-apoptotic effect of Astragalus Polysaccharide on myeloid cells].

This study was aimed to assess the effect of Astragalus Polysaccharide (ASPS) on in-vitro hematopoiesis. CFU-GM assays were used to determine the effect of ASPS and thrombopoietin (TPO) on granulocytic-monocyte progenitor cells. The CFU assays were also used to investigate the effect of ASPS on the proliferation of HL-60 cells.HL-60 cells were cultured with serum-free RPMI 1640 medium and treated with or without of different concentrations of ASPS. After 72 h incubation, the number of cells were counted.In addition, the caspase-3 and JC-1 expression was determined by flow cytometry with Annexin V/PI double staining. The results showed that ASPS (100, 200 µg/ml) and TPO (100 ng/ml) significantly promoted CFU-GM formation in vitro. Various concentrations of ASPS and TPO also promoted the colony formation of HL-60 cells, the largest effect of ASPS was observed at a concentration of 100 µg/ml. There were no synergistic effects between TPO and ASPS on cellular proliferation. The results also showed that ASPS significantly protected HL-60 cells from apoptosis in condition of serum-free medium culture, suppressed caspase 3 activation, and reduced the cell apoptosis. It is concluded that ASPS can significantly promote the formation of bone marrow CFU-GM and the proliferation of HL-60 cells, the optimal concentration of ASPS is at 100 µg/ml. In the absence of serum inducing apoptosis, ASPS also significantly reduced the apoptosis of HL-60 cells via suppressing the activation of caspase-3.