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.

Non-exosomal non-coding RNAs (non-exo-ncRNAs) and exosomal ncRNAs (exo-ncRNAs) have been associated with the pathological development of myocardial infarction (MI). Accordingly, this analytical review provides an overview of current MI studies on the role of plasma non-exo/exo-ncRNAs. We summarize the features and crucial roles of ncRNAs and reveal their novel biological correlations via bioinformatics analysis. The following contributions are made: (1) we comprehensively describe the expression profile, competing endogenous RNA (ceRNA) network, and "pre-necrotic" biomarkers of non-exo/exo-ncRNAs for MI; (2) functional enrichment analysis indicates that the target genes of ncRNAs are enriched in the regulation of apoptotic signaling pathway and cellular response to chemical stress, etc.; (3) we propose an updated and comprehensive view on the mechanisms, pathophysiology, and biomarker roles of non-exo/exo-ncRNAs in MI, thereby providing a theoretical basis for the clinical management of MI.
Humans ; RNA, Untranslated/genetics* ; RNA ; Myocardial Infarction/genetics* ; Biomarkers ; Computational Biology ; MicroRNAs/genetics*

OBJECTIVE: To generate a new strain of HBeAg transgenic mice using CRISPR/Cas9 technique. METHODS: Hepatitis B virus (HBV) HBeAg gene was cloned and inserted in the pliver-HBeAg expression frame at the site of Rosa26 gene using CRISPR/Cas9 and homologous recombination techniques to construct the pliver-HBeAg expression vector containing HBeAg gene. The linear DNA fragment containing HBeAg gene was obtained by enzyme digestion. Cas9 mRNA, gRNA and the donor vector were microinjected into fertilized eggs of C57BL/6J mice, which were then transplanted into the uterus of C57BL/6J female surrogate mice to obtain F0 generation mice. The F0 generation mice were identified by long fragment PCR to obtain F0 transgenic mice with HBeAg gene. The positive F0 generation mice were bred with wild-type C57BL/6J mice to produce the F1 mice, which were identified by PCR and sequencing. The positive F1 transgenic mice carrying HBeAg gene were backcrossed until the homozygous offspring transgenic mice were obtained. The genotypes of the offspring mice were identified. The expressions of HBeAg and HBeAb in the heterozygous and homozygous HBeAg transgenic mice were detected by automatic chemiluminescence immunoassay, immune colloidal gold technique and immunohistochemistry method. RESULTS: A total of 56 F0 mice were obtained, and 2 of them carried homologous recombined HBeAg gene. Six positive F1 mice were obtained, from which 22 homozygous and 29 heterozygous F2 generation HBeAg transgenic mice were obtained. High concentration of HBeAg protein was detected in the peripheral blood of all the positive HBeAg transgenic mice without HBeAb expression. HBeAg expression was detected in the hepatocytes of HBeAg transgenic mice. CONCLUSIONS We obtained a new strain of HBeAg transgenic mice with stable expression of HBeAg in the hepatocytes and immune tolerance to HBeAg using CRISPR/Cas9 technique, which provide a new animal model for studying HBV.
Animals ; CRISPR-Cas Systems ; Female ; Genetic Vectors ; Hepatitis B e Antigens ; genetics ; Hepatitis B virus ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic