1.Ameliorative Effect of Wendantang Combined with Danshenyin and Dushentang on Ischemic Heart Disease with Phlegm-stasis Syndrome in Mice Based on Circulating Monocytes
Fenghe YANG ; Ziqi TIAN ; Zhiqian SONG ; Shitao PENG ; Wenjie LU ; Tao LIN ; Chun WANG ; Zhangchi NING
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):22-32
ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang (WDD) on mice with ischemic heart disease (IHD) presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group, WDD low-dose group (WDD-L), WDD medium-dose group (WDD-M), WDD high-dose group (WDD-H), and atorvastatin calcium tablet group, with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91, 17.81, 35.62 g·kg-1, and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg-1, twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration, the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin (HE) staining. Serum N-terminal pro-B-type natriuretic peptide (pro-BNP) content was measured by enzyme-linked immunosorbent assay (ELISA). Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group, model serum group, WDD-L drug-containing serum group, WDD-M drug-containing serum group, and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group, the model group showed a significantly increased cardiac index (P0.01), significantly decreased fractional shortening (FS) (P0.01), and significantly increased left ventricular end-diastolic internal diameter (LVDD) and left ventricular end-systolic internal diameter (LVDS) (P0.01). Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated (P0.01), and whole-blood viscosity (BV) at high, medium, and low shear rates was significantly increased (P0.01). Compared with the model group, the WDD groups showed significantly reduced cardiac index (P0.05, P0.01), significantly increased FS (P0.05, P0.01), significantly decreased LVDD and LVDS (P0.01), markedly improved cardiomyocyte morphology, significantly reduced inflammatory infiltration, significantly decreased serum pro-BNP levels (P0.01), and significantly decreased BV at high, medium, and low shear rates (P0.01), with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group, TC, TG, and LDL levels were significantly increased in the model group (P0.05, P0.01), while HDL levels were significantly decreased (P0.05). After WDD-H treatment, TC, TG, and LDL levels were significantly reduced and HDL levels were significantly increased in mice (P0.05, P0.01). Compared with the sham-operation group, classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group (P0.01), whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased (P0.01). After WDD administration, all circulating monocyte subsets in blood and bone marrow were significantly alleviated (P0.05, P0.01), with the WDD-M group showing the optimal effect. In vitro, compared with the blank group, CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group (P0.01), and CD36 expression was significantly upregulated on RAW264.7 cells (P0.01). Compared with the model serum group, all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation (P0.01). WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines (P0.05, P0.01), with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.
2.Ameliorative Effect of Wendantang Combined with Danshenyin and Dushentang on Ischemic Heart Disease with Phlegm-stasis Syndrome in Mice Based on Circulating Monocytes
Fenghe YANG ; Ziqi TIAN ; Zhiqian SONG ; Shitao PENG ; Wenjie LU ; Tao LIN ; Chun WANG ; Zhangchi NING
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):22-32
ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang (WDD) on mice with ischemic heart disease (IHD) presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group, WDD low-dose group (WDD-L), WDD medium-dose group (WDD-M), WDD high-dose group (WDD-H), and atorvastatin calcium tablet group, with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91, 17.81, 35.62 g·kg-1, and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg-1, twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration, the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin (HE) staining. Serum N-terminal pro-B-type natriuretic peptide (pro-BNP) content was measured by enzyme-linked immunosorbent assay (ELISA). Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group, model serum group, WDD-L drug-containing serum group, WDD-M drug-containing serum group, and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group, the model group showed a significantly increased cardiac index (P<0.01), significantly decreased fractional shortening (FS) (P<0.01), and significantly increased left ventricular end-diastolic internal diameter (LVDD) and left ventricular end-systolic internal diameter (LVDS) (P<0.01). Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated (P<0.01), and whole-blood viscosity (BV) at high, medium, and low shear rates was significantly increased (P<0.01). Compared with the model group, the WDD groups showed significantly reduced cardiac index (P<0.05, P<0.01), significantly increased FS (P<0.05, P<0.01), significantly decreased LVDD and LVDS (P<0.01), markedly improved cardiomyocyte morphology, significantly reduced inflammatory infiltration, significantly decreased serum pro-BNP levels (P<0.01), and significantly decreased BV at high, medium, and low shear rates (P<0.01), with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group, TC, TG, and LDL levels were significantly increased in the model group (P<0.05, P<0.01), while HDL levels were significantly decreased (P<0.05). After WDD-H treatment, TC, TG, and LDL levels were significantly reduced and HDL levels were significantly increased in mice (P<0.05, P<0.01). Compared with the sham-operation group, classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group (P<0.01), whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased (P<0.01). After WDD administration, all circulating monocyte subsets in blood and bone marrow were significantly alleviated (P<0.05, P<0.01), with the WDD-M group showing the optimal effect. In vitro, compared with the blank group, CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group (P<0.01), and CD36 expression was significantly upregulated on RAW264.7 cells (P<0.01). Compared with the model serum group, all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation (P<0.01). WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines (P<0.05, P<0.01), with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.
3.The Impairment Attention Capture by Topological Change in Children With Autism Spectrum Disorder
Hui-Lin XU ; Huan-Jun XI ; Tao DUAN ; Jing LI ; Dan-Dan LI ; Kai WANG ; Chun-Yan ZHU
Progress in Biochemistry and Biophysics 2025;52(1):223-232
ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.
4.Guided by National Strategic Needs,Striving to Build a First-Class Forensic Medicine Discipline—The Construction Plan for Forensic Medicine at Southern Medical University
Dong-Fang QIAO ; Ping-Ming QIU ; Qi WANG ; Yun-Chun TAI ; Dong-Ri LI ; Jing-Tao XU ; Qi-Zhi LUO ; En-Ping HUANG ; Bo-Feng ZHU
Journal of Forensic Medicine 2025;41(1):15-19
The 2024 National Education Work Conference pointed out that at the current juncture of the critical period for achieving the goals and tasks of the 14th Five-Year Plan,the implementation of the Education Powerhouse Construction Plan Outline should be taken as the main line of work,and building first-class disciplines is an crucial task for a higher education powerhouse.In 2022,forensic medicine was officially listed as a first-level discipline under the medical category,presenting an un-precedented historical opportunity for the development of forensic medicine.The forensic medicine dis-cipline of Southern Medical University comprehensively improves the quality of talent cultivation and facilitates the construction of first-class disciplines as its main direction.It aims to initiate and imple-ment a high-level faculty team building plan featuring"combining recruitment and cultivation,inter-disciplinary integration";make vigorous efforts to establish a first-level doctoral program,refine advan-tageous second-level disciplines and research directions;and establish an innovative research platform from a high starting point with deep integration.The discipline adheres to moral cultivation and the Five Domains of Education simultaneous development,to build a high-quality talent joint training model.Guided by the construction of the national legal system and industry needs,the discipline will enhance social service capabilities.The forensic medicine construction in our university will continue to contribute to the rule of law in China and educational power.
5.Research progress on risk factors for acute kidney injury following left ventricular assist device implantation
Chun SHEN ; Yunhan BAO ; Yunyan WANG ; Tao ZHANG
Journal of Clinical Medicine in Practice 2025;29(11):144-148
Heart failure,as a severe consequence or late-stage manifestation of various cardiac conditions,is marked by high morbidity,high mortality,and high rates of readmission,significantly compromising patients' quality of life.Despite ongoing advancements in novel drugs and technologies that have improved the clinical efficacy of heart failure,5%to 10%of patients still progress to end-stage heart failure annually.Heart transplantation stands as an effective approach to enhance both the quality of life and survival rates for patients with end-stage heart failure.However,due to the scarcity of donor organs,it falls short of meeting the needs of a large number of patients.In this scenario,left ventricular assist device(LVAD)implantation emerges as a promising alternative therapeutic option for these patients.Acute kidney injury(AKI)represents one of the common complications encoun-tered after LVAD implantation,with notable morbidity and mortality rates.This article synthesized relevant research findings and literature to investigate the risk factors associated with the development of AKI in patients following LVAD implantation.
6.Effects of esketamine-mediated opioid-free anesthesia on postopera-tive gastrointestinal function in patients undergoing laparoscopic rad-ical resection of distal gastric cancer
Yidong XU ; Siqi YANG ; Tao WANG ; Liuyan WU ; Ting PAN ; Sen WANG ; Zhenhui ZHOU ; Shasha YOU ; Xingzi CHEN ; Saifu WANG ; Linjun WANG ; Cunming LIU ; Chun YANG ; Di WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1297-1304
AIM:To investigate the impact of es-ketamine-mediated opioid-free anesthesia(OFA)on postoperative gastrointestinal function in patients undergoing laparoscopic distal gastrectomy for gas-tric cancer.METHODS:A total of 150 pa-tients,scheduled for elective laparoscopic distal gas-trectomy for gastric cancer and meeting the inclu-sion and exclusion criteria,were randomly assigned to either the OFA group or the opioid-based anes-thesia(OBA)group using a random number ta-ble,with 75 patients in each group.The OFA group was administered an anesthesia regimen pri-marily consisting of esketamine,while the OBA group received conventional opioid anesthesia,pri-marily consisting of sufentanil and remifentanil.The primary outcome measure was postoperative flatus time,defined as the interval from the end of sur-gery to the first passage of gas.RESULTS:The OFA group exhibited a shorter postoperative flatus time compared to the OBA group(P<0.01).Intraopera-tive blood loss and norepinephrine consumption were significantly less in the OFA group compared to the OBA group(P<0.05);the postoperative HADS-D score was better in the OFA group than in the OBA group,and both the OFA and OBA groups showed significantly lower postoperative HADS-A and HADS-D scores compared to their preoperative levels(P<0.05);the incidence rate of abdominal distension was significantly lower in the OFA group compared to the OBA group(P<0.05).CONCLUSION:The use of esketamine-mediated opioid-free anesthesia can expedite gastrointestinal function recovery,reduce hospital stay duration,and decrease postoperative adverse reactions in patients undergoing laparo-scopic distal gastrectomy for gastric cancer.
7.Multicenter randomized controlled trial of Yiqi Huoxue formula() for the treatment of ruptured lumbar disc herniation.
Yu ZHU ; Zhi-Qiang WANG ; Shun LIN ; Ying-Ying YAO ; Xue-Qiang SHEN ; Xiao-Chun LI ; Feng YU ; Xiao-Yang XIONG ; Yi SONG ; Meng-Fei CHEN ; Peng-Fei YU ; Hong JIANG ; Jin-Tao LIU
China Journal of Orthopaedics and Traumatology 2025;38(11):1112-1118
OBJECTIVE:
To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease.
METHODS:
A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment.
RESULTS:
A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group.
CONCLUSION
After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans
;
Male
;
Female
;
Intervertebral Disc Displacement/drug therapy*
;
Adult
;
Drugs, Chinese Herbal/adverse effects*
;
Middle Aged
;
Lumbar Vertebrae
8.Interposition of acellular amniotic membrane at the tendon to bone interface would be better for healing than overlaying above the tendon to bone junction in the repair of rotator cuff injury.
Jiang-Tao WANG ; Chun-Bao LI ; Jia-Ting ZHANG ; Ming-Yang AN ; Gang ZHAO ; Yu-Jie LIU
Chinese Journal of Traumatology 2025;28(3):187-192
PURPOSE:
The retear rate of rotator cuff (RC) after surgery is high, and the rapid and functional enthesis regeneration remains a challenge. Whether acellular amniotic membrane (AAM) helps to promote the healing of tendon to bone and which treatment is better are both unclear. The study aims to investigate the effect of AAM on the healing of RC and the best treatment for RC repair.
METHODS:
Thirty-three Sprague Dawley rats underwent RC transection and repair using microsurgical techniques and were randomly divided into the suturing repair only (SRO) group (n = 11), the AAM overlaying (AOL) group (n = 11), and the AAM interposition (AIP) group (n = 11), respectively. Rats were sacrificed at 4 weeks, then examined by subsequent micro-CT, and evaluated by histologic and biomechanical tests. The statistical analyses of one-way ANOVA or Kruskal-Wallis test were performed using with SPSS 23.0. A p < 0.05 was considered a significant difference.
RESULTS:
AAM being intervened between tendon and bone (AIP group) or overlaid over tendon to bone junction (AOL group) in a rat model, promoted enthesis regeneration, increased new bone and cartilage generation, and improved collagen arrangement and biomechanical properties in comparison with suturing repair only (SRO group) (AOL vs. SRO, p < 0.001, p = 0.004, p = 0.003; AIP vs. SRO, p < 0.001, p < 0.001, p < 0.001). Compared with the AOL group, the AIP group had better results in micro-CT evaluation, histological score, and biomechanical testing (p = 0 0.039, p = 0.011, p = 0.003, respectively).
CONCLUSION
In the RC repair model, AAM enhanced regeneration of the tendon to bone junction. This regeneration was more effective when the AAM was intervened at the tendon to bone interface than overlaid above the tendon to bone junction.
Animals
;
Rats, Sprague-Dawley
;
Rotator Cuff Injuries/surgery*
;
Amnion/transplantation*
;
Rats
;
Wound Healing
;
Rotator Cuff/surgery*
;
Male
;
X-Ray Microtomography
;
Tendons/surgery*
;
Biomechanical Phenomena
9.Corrigendum to "Interposition of acellular amniotic membrane at the tendon to bone interface would be better for healing than overlaying above the tendon to bone junction in the repair of rotator cuff injury" Chinese J Traumatol 28 (2025) 187-192.
Jiang-Tao WANG ; Chun-Bao LI ; Jia-Ting ZHANG ; Ming-Yang AN ; Gang ZHAO ; Yu-Jie LIU
Chinese Journal of Traumatology 2025;28(6):518-518
10.Clinical characteristics and prognosis of acute erythroleukemia in children.
Ping ZHU ; Wen-Jing QI ; Ye-Qing TAO ; Ding-Ding CUI ; Guang-Yao SHENG ; Chun-Mei WANG
Chinese Journal of Contemporary Pediatrics 2025;27(1):88-93
OBJECTIVES:
To investigate the clinical characteristics and prognosis of acute erythroleukemia (AEL) in children.
METHODS:
A retrospective analysis was conducted on the clinical data, treatment, and prognosis of 8 children with AEL treated at the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023.
RESULTS:
Among the 7 patients with complete bone marrow morphological analysis, 4 exhibited trilineage dysplasia, with a 100% incidence of erythroid dysplasia (7/7), a 71% incidence of myeloid dysplasia (5/7), and a 57% incidence of megakaryocytic dysplasia (4/7). Immunophenotyping revealed that myeloid antigens were primarily expressed as CD13, CD33, CD117, CD38, and CD123, with 4 cases expressing erythroid antigens CD71 and 2 cases expressing CD235a. Chromosomal analysis indicated that 2 cases presented with abnormal karyotypes, including +8 in one case and +4 accompanied by +6 in another; no complex karyotypes were observed. Genetic abnormalities were detected in 4 cases, with fusion genes including one case each of dup MLL positive and EVI1 positive, as well as mutations involving KRAS, NRAS, WT1, and UBTF. Seven patients received chemotherapy, with 6 achieving remission after one course of treatment; 2 underwent hematopoietic stem cell transplantation, and all had disease-free survival. Follow-up (median follow-up time of 6 months) showed that only 3 patients survived (2 cases after hematopoietic stem cell transplantation and 1 case during treatment).
CONCLUSIONS
Children with AEL have unique clinical and biological characteristics, exhibit poor treatment response, and have a poor prognosis; however, hematopoietic stem cell transplantation may improve overall survival rates.
Humans
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Male
;
Female
;
Prognosis
;
Child, Preschool
;
Retrospective Studies
;
Child
;
Leukemia, Erythroblastic, Acute/diagnosis*
;
Infant
;
Adolescent

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