Significance of paroxysmal nocturnal hemoglobinuria clone in immunosuppressive therapy for children with severe aplastic anemia. / é˜µå‘æ€§ç¡çœ æ€§è¡€çº¢è›‹ç™½å°¿å ‹éš†åœ¨å„¿ç«¥é‡åž‹å†ç”Ÿéšœç¢æ€§è´«è¡€å ç–«æŠ‘åˆ¶æ²»ç–—ä¸­çš„æ„ä¹‰.

OBJECTIVES: To study the association between paroxysmal nocturnal hemoglobinuria (PNH) clone and immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA). METHODS: A retrospective analysis was performed on the medical data of 151 children with SAA who were admitted and received IST from January 2012 to May 2020. According to the status of PNH clone, these children were divided into a negative PNH clone group (n=135) and a positive PNH clone group (n=16). Propensity score matching was used to balance the confounding factors, and the impact of PNH clone on the therapeutic effect of IST was analyzed. RESULTS: The children with positive PNH clone accounted for 10.6% (16/151), and the median granulocyte clone size was 1.8%. The children with positive PNH clone had an older age and a higher reticulocyte count at diagnosis (P<0.05). After propensity score matching, there were no significant differences in baseline features between the negative PNH clone and positive PNH clone groups (P>0.05). The positive PNH clone group had a significantly lower overall response rate than the negative PNH clone group at 6, 12, and 24 months after IST (P<0.05). The evolution of PNH clone was heterogeneous after IST, and the children with PNH clone showed an increase in the 3-year cumulative incidence rate of aplastic anemia-PNH syndrome (P<0.05). CONCLUSIONS: SAA children with positive PNH clone at diagnosis tend to have poor response to IST and are more likely to develop aplastic anemia-PNH syndrome.

[Prevalence and risk factors of obesity in children with Diamond-Blackfan anemia]. / å ˆå¤©æ€§çº¯çº¢ç»†èƒžå†ç”Ÿéšœç¢æ€§è´«è¡€æ‚£å„¿è‚¥èƒ–å‘ç”Ÿæƒ å†µåŠå½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the distribution of body mass index (BMI) and risk factors for obesity in children with Diamond-Blackfan Anemia (DBA). METHODS: The children with DBA who attended National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from January 2003 to December 2020 were enrolled as subjects. The related clinical data and treatment regimens were recorded. The height and weight data measured within 1 week before or after follow-up time points were collected to calculate BMI. The risk factors for obesity were determined by multivariate regression analysis in children with DBA. RESULTS: A total of 129 children with DBA were enrolled, among whom there were 80 boys (62.0%) and 49 girls (38.0%), with a median age of 49 months (range 3-189 months). The prevalence rate of obesity was 14.7% (19/129). The multivariate logistic regression analysis showed that the absence of ribosomal protein gene mutation was closely associated with obesity in children with DBA (adjusted OR=3.63, 95%CI: 1.16-11.38, adjusted P=0.027). In children with glucocorticoid-dependent DBA, obesity was not associated with age of initiation of glucocorticoid therapy, duration of glucocorticoid therapy, and maintenance dose of glucocorticoids (P>0.05). CONCLUSIONS: There is a high prevalence rate of obesity in children with DBA, and the absence of ribosomal protein gene mutation is closely associated with obesity in children with DBA.

[Clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes].

OBJECTIVE: To study the clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). METHODS: A retrospective analysis was performed on the medical data of 14 children who were diagnosed with AML-MRC from June 2014 to March 2020, including clinical features, laboratory examination results, and prognosis. RESULTS: Among the 14 children with AML-MRC, there were 9 boys and 5 girls, with a median age of 11 years (range: 1-17 years), a median leukocyte count of 8.3×109/L [range: (2.0-191.0)×109/L], a median hemoglobin level of 73 g/L (range: 44-86 g/L), and a median platelet count of 75×109/L [range: (4-213)×109/L] at diagnosis. According to the FAB classification, the children with AML-M5 accounted for 71% (10/14). Among the 14 children, 4 had multi-lineage dysplasia (MLD), 2 had a history of myelodysplastic syndrome (MDS), 5 had MDS-related cytogenetic changes, 2 had MLD with MDS-related cytogenetic changes, and 1 had a history of MDS with MLD. The median follow-up time was 10.6 months (range: 0.4-54.4 months) for 14 children, among whom 2 gave up treatment immediately after diagnosis and 12 had an evaluable treatment outcome. The 2-year overall survival (OS) rate was 50%±15%, and the 2-year disease-free survival (DFS) rate was 33%±13%. Of the 12 children, 7 underwent haploidentical hematopoietic stem cell transplantation (HSCT), among whom 5 achieved DFS and 2 died, with a 2-year OS rate of 71%±17% and a 2-year DFS rate of 43%±19%; 5 children underwent chemotherapy alone, among whom 1 achieved DFS, 3 died, and 1 was lost to follow-up, with a 2-year OS rate of 40%±30% and a 2-year DFS rate of 30%±24%. There was no significant difference in the survival condition between the transplantation and chemotherapy groups (P > 0.05). CONCLUSIONS: Childhood AML-MRC is often observed in boys, and AML-M5 is the most common type based on FAB classification. Such children tend to have a poor prognosis. HSCT is expected to improve the poor prognosis of children with AML-MRC. However due to the small number of cases, it is necessary to increase the number of cases for further observation.

Optimization of GRACE Risk Stratification by N-Terminal Pro-B-type Natriuretic Peptide Combined With D-Dimer in Patients With Non-ST-Elevation Myocardial Infarction.

We aimed to explore the utility of multiple biomarkers with GRACE risk stratification for non-ST-elevation myocardial infarction (NSTEMI). A total of 1,357 patients diagnosed with NSTEMI were enrolled in this study at multiple medical centers in Tianjin, China. The outcomes were 1-year all-cause death and major adverse cardiac events (MACE: all-cause death, hospital admission for unstable angina, hospital admission for heart failure, nonfatal recurrent myocardial infarction, and stroke). C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to verify that the biomarkers improve the predictive accuracy of the GRACE score. A total of 57 participants died, while 211 participants experienced 231 MACEs during follow-up (mean: 339 days). For all-cause death, the combination of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and D-dimer improved the predictive accuracy of GRACE the most, with C-index, IDI, and NRI values of 0.88, 0.085, and 1.223, respectively. For MACE, trigeminal combination of NT-proBNP, fibrinogen, and D-dimer resulted in C-index, IDI, and NRI values of 0.80, 0.079, and 0.647, respectively. As a result, NT-proBNP, D-dimer, fibrinogen, and GRACE comprise a new scoring system for assessing 1-year clinical events. Kaplan-Meier analysis revealed a significant increase in 1-year mortality (score ≥3.85 vs <3.85, p < 0.0001) and 1-year MACE (score ≥1.72 vs <1.72, p < 0.0001) between different score groups. In conclusion, the combination of NT-proBNP and D-dimer added prognostic value to GRACE for all-cause death. Combining NT-proBNP, fibrinogen, and D-dimer increased the prognostic value of GRACE for MACE. This newly developed scoring system is strongly correlated with all-cause mortality and MACE, and can be easily utilized in clinical practice.

A peptide model of insulin folding intermediate with one disulfide.

Insulin folds into a unique three-dimensional structure stabilized by three disulfide bonds. Our previous work suggested that during in vitro refolding of a recombinant single-chain insulin (PIP) there exists a critical folding intermediate containing the single disulfide A20-B19. However, the intermediate cannot be trapped during refolding because once this disulfide is formed, the remaining folding process is very quick. To circumvent this difficulty, a model peptide ([A20-B19]PIP) containing the single disulfide A20-B19 was prepared by protein engineering. The model peptide can be secreted from transformed yeast cells, but its secretion yield decreases 2-3 magnitudes compared with that of the wild-type PIP. The physicochemical property analysis suggested that the model peptide adopts a partially folded conformation. In vitro, the fully reduced model peptide can quickly and efficiently form the disulfide A20-B19, which suggested that formation of the disulfide A20-B19 is kinetically preferred. In redox buffer, the model peptide is reduced gradually as the reduction potential is increased, while the disulfides of the wild-type PIP are reduced in a cooperative manner. By analysis of the model peptide, it is possible to deduce the properties of the critical folding intermediate with the single disulfide A20-B19.