BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

OBJECTIVE: To analyze 43 leukemia genes in children with acute lymphoblastic leukemia (ALL) in Yunnan province, and provide the basis for the diagnosis and treatment of children with ALL in this area. METHODS: The clinical data of 428 children with newly diagnosed ALL in Yunnan area from January 2015 to December 2020 were retrospectively analyzed. Multiple nested PCR technology was used to detect 43 common leukemia genes. RESULTS: Among the 428 children with ALL, 159 were positive for leukemia genes, with a positive rate of 37.15% (159/428), and a total of 15 leukemia genes were detected. Among the 159 leukemia gene-positive children, ETV6-RUNX1⁺ accounted for 25.79% (41/159), followed by E2A-PBX1⁺ and BCR-ABL⁺, accounting for 24.53% (39/159) and 23.27% (37/159) respectively. MLL⁺ accounted for 6.29% (10/159), WT1⁺ accounted for 4.40% (7/159), IKZF1 gene deletion and CRLF2⁺ accounted for 3.77% (6/159) respectively. The positive rate of MLL (46.15%) was the highest in ＜1-year old group, the positive rate of ETV6-RUNX1 (10.56%) was the highest in 1-10-year old group, and BCR-ABL⁺ rate (23.65%) was the highest in >10-year old group. The distribution of leukemia genes in different age groups was statistically significant (P <0.05). CONCLUSION The most common fusion gene of children with ALL in Yunnan is ETV6-RUNX1, followed by E2A-PBX1 and BCR-ABL.
Child ; Humans ; Infant ; Child, Preschool ; Oncogene Proteins, Fusion/genetics* ; Fusion Proteins, bcr-abl/genetics* ; Core Binding Factor Alpha 2 Subunit/genetics* ; Retrospective Studies ; China ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Genotype

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Anemia, Iron-Deficiency/epidemiology* ; Sucrose/therapeutic use* ; Ferric Compounds/therapeutic use* ; Retrospective Studies ; Iron/therapeutic use* ; Hemoglobins/therapeutic use*

Objective: To investigate the role and related mechanism of ubiquitin-like protein FAT10 in the angiotensin Ⅱ (AngⅡ)-induced endothelial cell inflammatory responses. Methods: The Western blot was used to detect the protein expression of FAT10 in 16-weeks old WKY rat carotid artery, thoracic aorta artery, renal artery and vascular smooth muscle cells (VSMC), human umbilical vein endothelial cells (HUVEC) and human breast cancer cells (MDA-MB-231). The optimal concentration and stimulation time of AngⅡ on inducing the highest FAT10 in HUVEC were determined. The following plasmids were constructed: control plasmid, overexpression FAT10 plasmid (Flag-FAT10), invalid interference plasmid, and interference FAT10 plasmid (sh-FAT10). These plasmids were then transfected into HUVEC cells and divided into following groups: control group, Flag-FAT10 group, invalid interference group, and sh-FAT10 group. After culturing with 100 nmol/L AngⅡ for 36 h, the control group and the Flag-FAT10 group were treated with reactive oxygen species scavenger N-acetyl-L-cysteine ​​(NAC), the protein expression levels of the inflammatory factor monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) were measured. Laser confocal microscopy was used to detect the generation levels of reactive oxygen species in the cells of vrious groups. Results: FAT10 was expressed in carotid artery, thoracic aorta, and renal artery of normal blood pressure rats and expressed in HUVEC, VSMC, MDA-MB-231. The expression level of FAT10 gradually increased in proportion to the increase of the time and concentration of AngⅡ stimulation in HUVEC, and the expression level of FAT10 was the highest when the HUVEC was treated with 100 nmol/L AngⅡ for 36 h (P<0.01). The protein expression level of MCP-1 (P<0.001) and TNF-α (P<0.01) was higher in AngⅡ treated HUVEC with FAT10 overexpression, while the expression level of MCP-1 and TNF-α protein was lower in AngⅡ treated HUVEC with FAT10 knockdown (all P<0.01). The level of intracellular reactive oxygen species (ROS) production was significantly increased with FAT10 overexpression (P<0.001), and the level of ROS was decreased when the expression of FAT10 was interfered (P<0.05). The increased level of MCP-1 and TNF-α proteins in FAT10 overexpressed HUVEC was reversed by NAC (all P<0.05). Conclusion: FAT10 promotes the release of inflammatory factors induced by AngⅡ in endothelial cells by increasing the level of intracellular ROS production.
Humans ; Rats ; Animals ; Reactive Oxygen Species/pharmacology* ; Cells, Cultured ; Angiotensin II/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Rats, Inbred WKY ; Human Umbilical Vein Endothelial Cells ; Inflammation ; Ubiquitins/pharmacology*

Objective: To investigate the role and related mechanism of ubiquitin-like protein FAT10 in the angiotensin Ⅱ (AngⅡ)-induced endothelial cell inflammatory responses. Methods: The Western blot was used to detect the protein expression of FAT10 in 16-weeks old WKY rat carotid artery, thoracic aorta artery, renal artery and vascular smooth muscle cells (VSMC), human umbilical vein endothelial cells (HUVEC) and human breast cancer cells (MDA-MB-231). The optimal concentration and stimulation time of AngⅡ on inducing the highest FAT10 in HUVEC were determined. The following plasmids were constructed: control plasmid, overexpression FAT10 plasmid (Flag-FAT10), invalid interference plasmid, and interference FAT10 plasmid (sh-FAT10). These plasmids were then transfected into HUVEC cells and divided into following groups: control group, Flag-FAT10 group, invalid interference group, and sh-FAT10 group. After culturing with 100 nmol/L AngⅡ for 36 h, the control group and the Flag-FAT10 group were treated with reactive oxygen species scavenger N-acetyl-L-cysteine ​​(NAC), the protein expression levels of the inflammatory factor monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) were measured. Laser confocal microscopy was used to detect the generation levels of reactive oxygen species in the cells of vrious groups. Results: FAT10 was expressed in carotid artery, thoracic aorta, and renal artery of normal blood pressure rats and expressed in HUVEC, VSMC, MDA-MB-231. The expression level of FAT10 gradually increased in proportion to the increase of the time and concentration of AngⅡ stimulation in HUVEC, and the expression level of FAT10 was the highest when the HUVEC was treated with 100 nmol/L AngⅡ for 36 h (P<0.01). The protein expression level of MCP-1 (P<0.001) and TNF-α (P<0.01) was higher in AngⅡ treated HUVEC with FAT10 overexpression, while the expression level of MCP-1 and TNF-α protein was lower in AngⅡ treated HUVEC with FAT10 knockdown (all P<0.01). The level of intracellular reactive oxygen species (ROS) production was significantly increased with FAT10 overexpression (P<0.001), and the level of ROS was decreased when the expression of FAT10 was interfered (P<0.05). The increased level of MCP-1 and TNF-α proteins in FAT10 overexpressed HUVEC was reversed by NAC (all P<0.05). Conclusion: FAT10 promotes the release of inflammatory factors induced by AngⅡ in endothelial cells by increasing the level of intracellular ROS production.
Humans ; Rats ; Animals ; Reactive Oxygen Species/pharmacology* ; Cells, Cultured ; Angiotensin II/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Rats, Inbred WKY ; Human Umbilical Vein Endothelial Cells ; Inflammation ; Ubiquitins/pharmacology*

Anemia, Aplastic ; Bone Marrow Diseases ; Bone Marrow Failure Disorders ; Humans ; Pancytopenia

Objective: To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia (SAA/VSAA) who failed to respond to immunosuppressive therapy (IST) at 3 months. Methods: We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months. Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months. Results: Univariate analysis showed that the 3-month hemoglobin (HGB) level (P=0.017) , platelet (PLT) level (P=0.005) , absolute reticulocyte count (ARC) (P<0.001) , trough cyclosporine concentration (CsA-C0) (P=0.042) , soluble transferrin receptor (sTfR) level (P=0.003) , improved value of reticulocyte count (ARC(△)) (P<0.001) , and improved value of soluble transferrin receptor (sTfR(△)) level (P<0.001) were related to the 6-month response. The results of the multivariate analysis showed that the PLT level (P=0.020) and ARC(△) (P<0.001) were independent prognostic factors for response at 6 months. If the ARC(△) was less than 6.9×10(9)/L, the 6-month hematological response rate was low, regardless of the patient's PLT count. Survival analysis showed that both the 3-year overall survival (OS) [ (80.1±3.9) % vs (97.6±2.6) %, P=0.002] and 3-year event-free survival (EFS) [ (31.4±4.5) % vs (86.5±5.3) %, P<0.001] of the nonresponders at 6 months were significantly lower than those of the response group. Conclusion: Residual hematopoietic indicators at 3 months after IST are prognostic parameters. The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery. A second treatment could be performed sooner for patients with a very low ARC(△).
Anemia, Aplastic/drug therapy* ; Antilymphocyte Serum/therapeutic use* ; Cyclosporine/therapeutic use* ; Humans ; Immunosuppression Therapy ; Immunosuppressive Agents/therapeutic use* ; Prognosis ; Receptors, Transferrin/therapeutic use* ; Retrospective Studies ; Treatment Outcome

Humans ; Liver Neoplasms/surgery*

ObjectiveTo explore effect of Huanglian Jiedutang （HLJDT） on autophagy-related protein expression in septic mice with liver injury induced by cecal ligation and puncture （CLP）. MethodSixty eight-week-old C57BL/6 mice were randomly divided into four groups， namely， the sham operation group， model group， and low- （1.44 g∙kg^-1） and high-dose （2.88 g∙kg^-1） HLJDT groups， with 15 in each group. The septic model was established by CLP after the last administration of HLJDT for three successive days. The survival rate of mice with 24 h was observed. The mice were sacrificed 12 h after operation for collecting the serum and liver tissue. The levels of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β） were detected by enzyme-linked immunosorbent assay （ELISA）， and the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum by biochemical method. The pathological changes in liver tissue were observed by hematoxylin-eosin （HE） staining， and the apoptosis index （AI） of hepatocytes by TdT-mediated dUTP-biotin nick end-labeling （TUNEL）. The expression levels of protein high-mobility group box 1 protein （HMGB1）， Beclin1， and microtubule-associated protein 1 light chain 3 （LC3）-Ⅱ/Ⅰ in the liver tissue were assayed by Western blot. ResultCompared with the sham operation group， the model group showed reduced survival rate at 12 and 24 h， elevated IL-6， TNF-α， and IL-1β levels， enhanced AST and ALT activities （P<0.05）， hepatocyte swelling， inflammatory cell infiltration， and apoptosis， and up-regulated HMGB1 （P<0.05）， Beclin1， and LC3-Ⅱ/Ⅰ （P<0.05）. Compared with the model group， each medication group exhibited increased survival rate at 12 and 24 h， lowered IL-6 and TNF-α levels， weakened AST and ALT activities （P<0.05）， alleviated liver injury and apoptosis （P<0.05）， down-regulated HMGB1 expression （ P<0.05）， and up-regulated Beclin1 and LC3-Ⅱ/Ⅰ （P<0.05）. ConclusionHLJDT alleviates the liver injury of septic mice possibly by inducing autophagy and inhibiting apoptosis.

OBJECTIVE: To analyze the risk factors affecting prognosis of children with hemophagocytic lymphohistiocytosis (HLH). METHODS: The clinical manifestations and laboratory data of 143 HLH children who met the HLH-2004 diagnostic criteria in Shenzhen Children's Hospital from January 2009 to May 2017 were retrospectively analyzed, and the independent factors affecting prognosis were also analyzed. RESULTS: The median age of 143 HLH children was 1.9 (0.1-14.3) years old, and the median follow-up time was 6.7 years (1 day - 11.9 years). The overall survival rate of 1 month, 1 year, and 10 years was (87.4±5.5)%, (81.1±6.5)%, and (81.1±6.5)%, respectively. The deaths occurred within 1 year after onset. Multivariate analysis showed that central nervous system (CNS) involvement (P=0.047), low hemoglobin (P=0.002), prolonged activated partial thromboplastin time (APTT) (P<0.001), high triglyceride (P=0.005) were all the independent risk factors affecting survival of the children. Receiver operating characteristic curve indicated that APTT (AUC=0.753, P<0.001) was more valuable than other risk factors in predicting death of the children. The cut-off value of APTT was 56.6 s, and the sensitivity and specificity of which was 55.6% and 89.7%, respectively. CONCLUSION Hypohemoglobinemia, prolonged APTT, hypertriglyceridemia, and CNS involvement the risk factors affecting prognosis of HLH, and prolonged APTT shows a strong predictive value for death.
Adolescent ; Child ; Child, Preschool ; Humans ; Infant ; Lymphohistiocytosis, Hemophagocytic ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Rate