Objective:To improve the understanding of acute lymphoblastic leukemia (ALL) secondary to Burkitt lymphoma (BL) in children.Methods:The clinical data of a child with ALL secondary to BL who was admitted to Children's Hospital Affiliated to Zhengzhou University in June 2024 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a boy with the age of 8 years and 8 months. He presented with a neck mass at the age of 4 years and 6 months, and pathological examination revealed a diagnosis of BL with clinical stage Ⅲ. The patient was given regular chemotherapy according to the Chinese Children's Lymphoma Group non-Hodgkin lymphoma mature B-cell 2017 protocol-B2 regimen. PET-CT showed recurrence of lymphoma in 6 months after the suspension of treatment. The patient was given with placement of 125I particles, oral etoposide and dexamethasone, and traditional Chinese medicine. The patient was admitted to hospital at the age of 8 years and 8 months with fever and skin hemorrhagic spots, bone marrow morphology, immunology, cytogenetics and molecular biology typing indicated a diagnosis of B-ALL with TCF3::PBX1 fusion gene. The patient received induction chemotherapy according to the Chinese Children's Leukemia Group-ALL 2018 protocol. A review of bone marrow cytology achieved complete remission on the 33rd day of chemotherapy, and minimal residual disease detected by flow cytometry indicated less than 0.01%. TCF3::PBX1 fusion gene was negative. Conclusions:ALL secondary to BL in children is rare, and the ALL treatment regimens are effective.

The clinical data of one child with metanephric stromal tumor (MST) and BRAF V600E gene mutation admitted to the First Affiliated Hospital of Zhengzhou University in June 2022 was analyzed retrospectively.Literature was reviewed.The patient, a 2-year-old girl, was diagnosed with a tumor in the left abdomen.The maximum diameter of the tumor was 10.5 cm.A radical nephrectomy was performed on the left kidney, and postoperative pathology revealed MST.Microscopically, the tumor had no envelope and exhibited expansive growth.The tumor cells were fusiform or stellate, and nuclear division was visible in the cell-rich region.Dysplastic blood vessels were seen inside the tumor.The tumor cells around the blood vessels and invaginated renal tubules were arranged like onion skin.CD34 was detected positive by immunohistochemical staining, and BRAF V600E mutation was also detected positive by fluorescent polymerase chain reaction.A total of 21 relevant case reports were retrieved, including 16 in English and 5 in Chinese.Fifty-eight MST patients, including the one in this report were analyzed.These patients were aged 2 days to 15 years, with a median age of 2 years.Except for 2 patients with unknown sex, the ratio of male to female was about 1.4∶1.0.Most MST patients were asymptomatic, with an average tumor size of 5.3 cm.The tumor cell CD34 showed positive expression in different degrees.Eight patients received the BRAF V600E mutation detection, and the results were all positive.Fifty-eight patients underwent nephrectomy and were followed up for 0-156 months, of which 7 patients were assisted with radiotherapy and chemotherapy.During the follow-up, 1 patient died, and 1 patient had a relapse.MST is a rare benign renal stromal tumor. BRAF V600E mutations are detected in a variety of malignancies.This paper is the first to report MST with BRAF V600E mutation in China and points out the importance of molecular detection of BRAF mutation for accurate diagnosis of MST.

Objective:To explore the clinical features and genetic etiology of a child with Central core disease (CCD).Methods:A child with CCD who was treated at the Children′s Hematology Department of the First Affiliated Hospital of Zhengzhou University in February 2022 was selected as the study subject. Muscle biopsy was performed. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. The child was subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing.Results:The child, a 12-year-old boy, had manifested motor retardation, facial weakness, ptosis, pectus carinatum, scoliosis, etc. Muscle biopsy showed that the central nucleus muscle fibers and atrophic muscle fibers were mainly type I. WES revealed that the child has harbored c. 10561G>A (p.G3521S) and c. 3448T>C (p.C1150R) compound heterozygous variants of the RYR1 gene. Sanger sequencing confirmed that they were inherited from his mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were considered as likely pathogenic (PS4+ PM1+ PM2_Supporting+ PP3; PM1+ PM2_Supporting+ PM3+ PP3). Conclusion:By combining his clinical manifestation and results of muscle pathology and genetic testing, the child was diagnosed with CCD, which may be attributed to the c. 10561G>A (p.G3521S) and c.3448T>C (p.C1150R) compound heterozygous variants of the RYR1 gene.

Objective To compare the effects of dulaglutide and liraglutide combined with metformin on serum C1q/TNF-related protein 3(CTRP3)and vascular cell adhesion molecule 1(VCAM-1)in obese patients with type 2 diabetes mellitus(T2DM).Methods A total of 89 obese T2DM patients who were admitted to Affiliated Nantong Hospital of 3 Nantong University from March 2019 to September 2022 were selected as research subjects.They were randomly divided into liraglutide group(n=45,liraglutide+metformin)and dulaglutide group(n=44,dulaglutide+metformin).Body mass index(BMI),obesity degree,waist circumference,hip circumference,glucolipid metabolism related indexes,insulin resistance related indexes,CTRP3,and VCAM-1 were compared between the two groups.Results Compared with those before treatment,BMI,obesity degree,hip circumference,waist circumference,glucolipid metabolism related indexes,insulin resistance related indexes,CTRP3,and VCAM-1 were significantly changed after treatment(all P<0.05).Mean amplitude of glucose fluctuation(MAGE)and VCAM-1 in the dulaglutide group were significantly lower than those in the liraglutide group after treatment,while time in target glucose range(TIR)and CTRP3 in the dulaglutide group were significantly higher than those in the liraglutide group after treatment(all P<0.05).There was no statistically significant difference in the other indexes between the two groups after treatment(all P>0.05).Conclusion Both dulaglutide and liraglutide combined with metformin can control blood glucose levels and improve glucolipid metabolism in obese T2DM patients.But dulaglutide is more effective in controlling MAGE and TIR than liraglutide,which may be related to the ability of dulaglutide to regulate the levels of CTRP3 and VCAM-1.

BACKGROUND: Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. METHODS: Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. RESULTS: Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. CONCLUSION PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Rats ; Male ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Connexin 43/genetics* ; Sumoylation ; Down-Regulation ; Rats, Sprague-Dawley ; Arrhythmias, Cardiac/drug therapy* ; Myocardial Ischemia/metabolism* ; RNA, Small Interfering/metabolism*

Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.

Objective:To investigate the clinical features and long-term prognosis of pediatric acute lymphoblastic leukemia (ALL) with renal involvement as the initial manifestation, thus enhancing the diagnostic and therapeutic efficacy.Methods:Twenty-four cases of pediatric ALL with renal involvement as the initial manifestation treated in the First Affiliated Hospital of Zhengzhou University from March 2013 to March 2019 were analyzed retrospectively, and their clinical characteristics were analyzed.According to renal imaging examination findings, they were divided into abnormal group and normal group.The differences in clinical features between the two groups were compared, and the cumulative survival rate was evaluated by Kaplan-Meier method.Results:Among 1 030 newly treated cases of pediatric ALL, 24 cases(2.33%) had renal involvement as the initial manifestation, involving 20 males and 4 females, with a male/female ratio of 5∶1 and the median age of 4.3 years (1.3-14.0 years). There were 16 cases of superficial lymph node enlargement and 21 cases of hepatosplenomegaly.Immature cells in peripheral blood were found in 15 cases.Nine cases were examined with abnormal renal imaging, involving 8 cases returned normal after chemotherapy, and 1 died of renal failure.At the end of follow-up on August 1, 2020, there were 9 cases of bone marrow relapse, 11 survival cases, 10 death cases and 3 cases of loss to follow-up.There were no significant differences in the sex, age, immunophenotype, organ infiltration and urinary protein between the two groups (all P>0.05). The proportion of high creatinine level and intramedullary recurrence rate in the abnormal group were significantly higher than those in the normal group [55.6%(5/9 cases) vs.0(0/15 cases), P=0.003; 66.7%(6/9 cases) vs.20.0%(3/15 cases), P=0.036]. The survival analysis indicated that the 3-year cumulative survival in the abnormal group was significantly lower than that of normal group (17.3% vs.72.7%, χ2=4.047, P< 0.05). Conclusions:For children with unexplained renal involvement as the initial manifestation, clinicians should consider the possibility of leukemic renal infiltration or nephrogenic lymphoma.Physical examinations of the liver, spleen and lymph nodes, morphological analysis of peripheral blood cells, bone marrow examination and renal biopsy are important to make a definite diagnosis in time.Children with imaging abnormalities caused by leukemic renal infiltration are more likely to relapse and have a lower survival rate, which may be a poor prognostic factor for ALL.

Objective:To illustrate the effectiveness of Micro-Teachermate platform combined with problem-based learning (PBL) in gynecology and obstetrics teaching.Methods:Students from different classes were randomly divided into experimental group and control group, and the general data of the two groups were compared. The two groups respectively adopted Micro-Teachermate platform combined with PBL and traditional lecture teaching methods. The class attendance rate and the scores of relevant chapters in the final examination were analyzed through statistical methods for assessing the enthusiasm of students and teaching quality in class in terms of the same content and the same class hours. A questionnaire survey was conducted to know students' evaluation of this teaching mode, evaluating its teaching effect and satisfaction comprehensively. SPSS 17.0 was used for t test and chi-square test. Results:There was no difference in general information between the two groups. The class attendance rate of the experimental group (274/279) was significantly higher than that of the control group (61/90), while the scores of the relevant chapters in the final exam were also significantly higher ( P<0.01). Questionnaire survey results among 93 students in the experimental group were taken back 93 valid questionnaires (the effective rate, 100%), showing that most of the students were very satisfied with this teaching mode (90/93) and hoped to apply it to more subjects teaching (89/93). Conclusion:The application of Micro-Teachermate platform combined with PBL in gynecology and obstetrics class teaching contributes to improve students' participating enthusiasm and can effectively improve the quality and efficiency of teaching. Most students highly recognize the teaching method, which is worth applying and popularizing.

Objective:To discuss whether platelet distribution width (PDW) can effectively predict the prognosis of neuroblastoma (NB).Methods:The clinical data of 67 NB patients in the First Affiliated Hospital of Zhengzhou University between January 2014 and January 2018 were retrospectively analyzed.They were divided into low PDW group and high PDW group according to the PDW level, and the differences in clinical indicators between the 2 groups were compared.The prognostic effects of PDW were assessed by using the Kaplan- Meier method and Cox regression model. Results:Among the 67 patients, 41 cases were male, 26 cases were female, with the ratio of male to female being 1.58∶1.00, and the average age was 44 months (2-156 months). Five cases were in stage Ⅰ, 1 case in stage Ⅱ, 15 cases in stage Ⅲ and 46 cases in stage Ⅳ.At the first time of diagnosis, there were 14 cases with age ≤ 18 months, 53 cases with age > 18 months, 47 cases with neuron specific enolase (NSE) level ≥ 100 μg/L, 20 cases with NSE level<100 μg/L.The median follow-up time was 20.4 months.At the end of follow-up, 35 cases died and 32 cases survived.There was no statistical difference in age, gender, primary site of tumor, tumor stage and mean platelet volume between the low PDW group and the high PDW group (all P>0.05). The proportion of high-risk patients, the level of NSE, bone marrow metastasis rate, MYCN gene amplification rate and the red blood cell distribution width in the high PDW group were significantly higher than those in the low PDW group, but the high PDW group had a lower level of thrombocytocrit than the low PDW group, and the differences were statistically significant(all P<0.05). Survival analysis revealed that the 2-year overall survival of the low PDW group was significantly higher than that of the high PDW group (69.8% vs.25.3%, χ2=15.761, P<0.05). Univariate analysis showed that NSE ( HR=6.606, 95% CI: 2.018-21.620), MYCN gene ( HR=1.977, 95% CI: 0.794-4.919), tumor risk stratification ( HR=5.926, 95% CI: 1.416-24.794), PDW ( HR=4.036, 95% CI: 1.957-8.322), and red blood cell distribution width ( HR=1.120, 95% CI: 1.005-1.249) were the adverse factors affecting the overall survival, and thrombocytocrit was a protective factor for the prognosis of NB.Multivariate analysis indicated that PDW was an independent risk factor of NB ( HR=2.524, 95% CI: 1.017-6.264, P=0.046). Conclusions:There is a good consistency between the increase of PDW and the known prognostic risk factors, elevated tumor markers and bone marrow metastasis.Increased PDW is associated with poor prognosis in NB patients, and PDW is an independent risk factor for the poor prognosis of NB.

Objective:To illustrate the effectiveness of Teachermate platform combined with problem-based learning (PBL) in gynecology and obstetrics teaching.Methods:Students from different classes were randomly divided into experimental group and control group, and the general data of the two groups were compared. The two groups respectively adopted Teachermate platform combined with PBL and traditional lecture teaching methods. The class attendance rate and the scores of relevant chapters in the final examination were analyzed through statistical methods for assessing the enthusiasm of students and teaching quality in class in terms of the same content and the same class hours. A questionnaire survey was conducted to know students' evaluation of this teaching mode, evaluating its teaching effect and satisfaction comprehensively.Results:There was no difference in general information between the two groups. The class attendance rate of the experimental group (274/279) was significantly higher than that of the control group (61/90) ( P=0.00), while the scores of the relevant chapters in the final exam were also significantly higher ( P=0.00). Questionnaire survey results among 93 students in the experimental group were taken back 93 valid questionnaires (the effective rate, 100%), showing that most of the students were very satisfied with this teaching mode (90/93) and hoped to apply it to more subjects teaching (89/93). Conclusion:The application of Teachermate platform combined with PBL in gynecology and obstetrics class teaching contributes to improve students' participating enthusiasm and can effectively improve the quality and efficiency of teaching. Most students highly recognize the teaching method, which is worth applying and popularizing.