Objective:To explore the associations between red blood cell distribution width and cysteine-rich 61(Cyr61)with efficacy and prognosis of luspatercept in the treatment of myelodysplastic syndrome.Methods:From August 2020 to August 2023,140 patients with myelodysplastic syndrome who received luspatercept treatment were selected.They were divided into effective group(104 cases)and ineffective group(36 cases)based on clinical efficacy,and into survival group(118 cases)and death group(22 cases)based on prognosis.Logistic regression analysis was used to investigate the correlation between red blood cell distribution width and Cyr61 with prognosis.Kaplan-Meier method was employed to plot survival curves,and receiver operating characteristic(ROC)curves were used to analyze the value of red blood cell distribution width and Cyr61 in evaluating the efficacy and prognosis of luspatercept treatment for myelodysplastic syndrome.Results:Compared with the ineffective group,the platelet count,neutrophil count,and hemoglobin level were significantly lower(P<0.05)in the effective group,while the platelet distribution width,red blood cell distribution width,and Cyr61 level were significantly higher(P<0.05).Compared with the ineffective group,the red blood cell distribution width and Cyr61 level were significantly lower(P<0.05)in the effective group as the efficacy improved.The red blood cell distribution width and Cyr61 level were positively correlated with ineffectiveness.Especially when the red blood cell distribution width was>20.86%and Cyr61 was>61.65 pg/mL,the risk of treatment non-response in patients with myelodysplastic syndrome increased significantly with the increase in red blood cell distribution width and Cyr61 level.Compared with the survivors,the platelet count,neutrophil count,and hemoglobin level were significantly lower(P<0.05),while the platelet distribution width,red blood cell distribution width,and Cyr61 level were significantly higher(P<0.05).The logistic regression analysis results showed that the red blood cell distribution width[odds ratio:0.694(95%confidence interval:0.504-0.812);P<0.05]and Cyr61[odds ratio:0.543(95%confidence interval:0.405-0.653);P<0.05]were independent risk factors for prognosis.The Kaplan-Meier analysis results showed that the survival rate significantly decreased with the increase in red blood cell distribution width and Cyr61 level(P<0.05).The receiver operating characteristic curve analysis results showed that both red blood cell distribution width and Cyr61 had certain significance for predicting the efficacy and prognosis of luspatercept treatment for myelodysplastic syndrome(P<0.05,area under the curve>0.75),and the combination of the two had the highest accuracy in predicting efficacy and prognosis(P<0.05,area under the curve>0.90).Conclusion:With the increase in red blood cell distribution width and Cyr61 levels,the risk of treatment ineffectiveness and death in patients with myelodysplastic syndrome receiving luspatercept therapy significantly increases.Clinically,the combination of red blood cell distribution width and Cyr61 can effectively evaluate the efficacy and prognosis of luspatercept in the treatment of myelodysplastic syndrome.

Objective:To explore the associations between red blood cell distribution width and cysteine-rich 61(Cyr61)with efficacy and prognosis of luspatercept in the treatment of myelodysplastic syndrome.Methods:From August 2020 to August 2023,140 patients with myelodysplastic syndrome who received luspatercept treatment were selected.They were divided into effective group(104 cases)and ineffective group(36 cases)based on clinical efficacy,and into survival group(118 cases)and death group(22 cases)based on prognosis.Logistic regression analysis was used to investigate the correlation between red blood cell distribution width and Cyr61 with prognosis.Kaplan-Meier method was employed to plot survival curves,and receiver operating characteristic(ROC)curves were used to analyze the value of red blood cell distribution width and Cyr61 in evaluating the efficacy and prognosis of luspatercept treatment for myelodysplastic syndrome.Results:Compared with the ineffective group,the platelet count,neutrophil count,and hemoglobin level were significantly lower(P<0.05)in the effective group,while the platelet distribution width,red blood cell distribution width,and Cyr61 level were significantly higher(P<0.05).Compared with the ineffective group,the red blood cell distribution width and Cyr61 level were significantly lower(P<0.05)in the effective group as the efficacy improved.The red blood cell distribution width and Cyr61 level were positively correlated with ineffectiveness.Especially when the red blood cell distribution width was>20.86%and Cyr61 was>61.65 pg/mL,the risk of treatment non-response in patients with myelodysplastic syndrome increased significantly with the increase in red blood cell distribution width and Cyr61 level.Compared with the survivors,the platelet count,neutrophil count,and hemoglobin level were significantly lower(P<0.05),while the platelet distribution width,red blood cell distribution width,and Cyr61 level were significantly higher(P<0.05).The logistic regression analysis results showed that the red blood cell distribution width[odds ratio:0.694(95%confidence interval:0.504-0.812);P<0.05]and Cyr61[odds ratio:0.543(95%confidence interval:0.405-0.653);P<0.05]were independent risk factors for prognosis.The Kaplan-Meier analysis results showed that the survival rate significantly decreased with the increase in red blood cell distribution width and Cyr61 level(P<0.05).The receiver operating characteristic curve analysis results showed that both red blood cell distribution width and Cyr61 had certain significance for predicting the efficacy and prognosis of luspatercept treatment for myelodysplastic syndrome(P<0.05,area under the curve>0.75),and the combination of the two had the highest accuracy in predicting efficacy and prognosis(P<0.05,area under the curve>0.90).Conclusion:With the increase in red blood cell distribution width and Cyr61 levels,the risk of treatment ineffectiveness and death in patients with myelodysplastic syndrome receiving luspatercept therapy significantly increases.Clinically,the combination of red blood cell distribution width and Cyr61 can effectively evaluate the efficacy and prognosis of luspatercept in the treatment of myelodysplastic syndrome.

BACKGROUND:Vocuolar-type ATPase (V-ATPase) is highly expressed in osteoclasts and especial y plays an important role in osteoclastic bone resorption. Tumor necrosis factor-αis a potent stimulator of bone resorption. However, the effect of tumor necrosis factor-αon expression and activity of V-ATPase is stil not clear.
OBJECTIVE:To investigate the mechanism of tumor necrosis factor-αto promote osteoclastic bone resorption by observing expression and activity of V-ATPase.
METHODOsteoclasts cultured in vitro were intervened by different concentrations of tumor necrosis factor-α(5, 10, 30μg/L) in order to observe the changes in expression and enzyme activity of V-ATPase and its effects on bone resorption of osteoclasts. Under an inverted microscope, we observed the formation of resorption lacunas, and bone resorption area was analyzed using Image J software.
RESULTS AND CONCLUSION:The expression and activity of V-ATPase increased significantly after 48 hours of tumor necrosis factor-αintervention and the increase of tumor necrosis factor-αconcentration might enhance this effect. In addition, osteoclastic bone resorption was promoted after intervention with tumor necrosis factor-α. The bone-resorbing capabilities of osteoclasts increased in paral el with the concentration of tumor necrosis factor-α.The results suggested that tumor necrosis factor-α, as a significant inflammatory mediator involved in the pathological process of bone resorption, not only promotes formation of osteoclasts but also enhances bone-resorbing capabilities of osteoclasts by increasing V-ATPase expression and activity.

AIM: To obtain nerve growth factor subunit ?(NGF ?) gene from Chinese fetal hippocampus tissue, prove its sequence, clone the mature peptide sequence, and make it express in E.coli .METHODS: Total RNA was extracted, amplified by RT-PCR method. Its 650 bp DNA sequence was inserted into PCR Ⅱ vector. PCR/NGF ? vector was used as the template to amplfy the C-terminate mature peptide sequence, then subcloned it into PG5 vector. The recombinant was transferred into E.coli BL21. BL21 was cultured and induced by IPTG. The activity of the expressed product was measured after purified and refolded.RESULTS: A complete cDNA sequence was determined as 1 047 nucleotides. The cloned 636 bp encoding 212 amino acids was proved homological to Genbank by sequence analysis. The expressed mature peptide showed an clear band of the prospected 14 kD by SDS-PAGE electrophoresis, and was testified by Western blot. The expression level was about 10% of the total cell lysate. CONCLUSION: The chinese NGF ? gene was homological to the foreigners'. The recombinant NGF ? was efficiently expressed in E.Coli and the recombinant protein has high immunological activities.