Objective:To improve the understanding of pediatric acute promyelocytic leukemia with TTMV::RARA fusion gene positive caused by torque teno mini virus (TTMV).Methods:A retrospective analysis was conducted on the clinical data of a patient with relapsed TTMV::RARA fusion gene-positive acute promyelocytic leukemia who was admitted to Children's Hospital Affiliated to Zhengzhou University in July 2024, and literature review was conducted.Results:The patient was a girl with the age of 5 years and 7 months. She presented with joint pain and fever. Combined with bone marrow cell morphology and whole transcriptome sequencing, she was diagnosed with TTMV::RARA fusion gene-positive acute promyelocytic leukemia. After induction therapy with regimens such as retinoic acid +daunorubicin+cytarabine and retinoic acid+venetoclax+homoharringtonine, the joint pain was relieved, but the primary disease did not improve. Subsequently, there was no regular treatment. One year later, the disease recurred and was complicated with severe infection. Her condition improved following anti-infection and induction therapy.Conclusions:TTMV::RARA fusion gene-positive pediatric acute promyelocytic leukemia is a special type of acute promyelocytic leukemia caused by the insertion of viral sequences from TTMV infection. It is rare in clinical practice and difficult to treat, and the overall prognosis may be poor.

Objective To observe the effects of four different modeling method on the hypothalamus-pituitary-adrenal(HPA)axis,blood rheology,platelet aggregation rate,and myocardial ischemia in rats,and to provide new ideas for the establishment of a rat model of"double heart"disease in line with clinical diagnosis and treatment characteristics.Methods Sixty-nine male Sprague-Dawley rats were divided randomly into a Control group(unstimulated),chronic unpredictable mild stimulation(CUMS)group,isoproterenol(ISO)group(intraperitoneal injection of ISO),high-fat diet(HFD)group(fed high-fat chow),and composite model(CUMS+ISO+HFD)group(n=12 rats in the Control and HFD groups;n=15 rats in the other three groups,respectively).Modeling procedures were carried out for a total of 8 weeks,with ISO injection started from week 6 of the experiment for a total of 3 weeks.At the end of modeling,rats in each group were subjected to absent-field and sugar-water preference behavioral tests.Electrocardiography(ECG)was performed to observe changes in ECG lead Ⅱ in each group.Serum levels of adrenocorticotropic hormone(ACTH),cortisol(Cor),corticosterone(CORT),endothelin-1(ET-1),and soluble intercellular adhesion molecule-1(sICAM-1)were detected by enzyme-linked immunosorbent assay.Myocardial histopathological changes were detected by hematoxylin/eosin(HE)staining.Serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured using an enzyme labeling instrument.Whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were assessed using an automatic blood rheology analyzer.The maximum platelet aggregation rate(MAR)and average platelet aggregation rate(AAR)induced by arachidonic acid and adenosine diphosphate were detected using a whole-blood platelet aggregometer.Results Compared with the Control group,all four model groups had significantly lower absenteeism distance and number of entries into the central region in the absent-field test,and a lower sugar-water preference ratio(P＜0.01).ECG revealed ST-segment elevation in the ISO and CUMS+ISO+HFD groups,tachycardia in the CUMS group,and mild ST-segment elevation in the HFD.Serum ACTH,Cor,CORT,ET-1,and sICAM-1 were all significantly elevated in the four model groups(P＜0.01).HE staining showed that myocardial tissue was severely damaged in rats in the ISO and CUMS+ISO+HFD groups,with pathological changes such as localized fibrosis and inflammatory infiltration of the myocardium,while mild cardiomyocyte disarrangement and fracture was seen in the CUMS and HFD groups.Rats in the HFD group had increased serum TC and LDL(P＜0.01)and decreased HDL contents(P＜0.01).Compared with the Control group,whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were all increased in the CUMS,HFD,and CUMS+ISO+HFD groups(P＜0.01,P＜0.05),while whole blood high-cut viscosity(200 V/S),whole blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen levels were decreased in rats in the ISO group(P＜0.01,P＜0.05).MAR and AAR were significantly higher in rats in the CUMS,HFD,and CUMS+ISO+HFD groups(P＜0.01),while the platelet aggregation rate was decreased in the ISO group compared with the Control group(P＜0.01,P＜0.05).Conclusions These result showed that the rat CUMS+ISO+HFD model better reflected the complexity of clinical double heart disease than the other three models.

Objective To observe the effects of four different modeling method on the hypothalamus-pituitary-adrenal(HPA)axis,blood rheology,platelet aggregation rate,and myocardial ischemia in rats,and to provide new ideas for the establishment of a rat model of"double heart"disease in line with clinical diagnosis and treatment characteristics.Methods Sixty-nine male Sprague-Dawley rats were divided randomly into a Control group(unstimulated),chronic unpredictable mild stimulation(CUMS)group,isoproterenol(ISO)group(intraperitoneal injection of ISO),high-fat diet(HFD)group(fed high-fat chow),and composite model(CUMS+ISO+HFD)group(n=12 rats in the Control and HFD groups;n=15 rats in the other three groups,respectively).Modeling procedures were carried out for a total of 8 weeks,with ISO injection started from week 6 of the experiment for a total of 3 weeks.At the end of modeling,rats in each group were subjected to absent-field and sugar-water preference behavioral tests.Electrocardiography(ECG)was performed to observe changes in ECG lead Ⅱ in each group.Serum levels of adrenocorticotropic hormone(ACTH),cortisol(Cor),corticosterone(CORT),endothelin-1(ET-1),and soluble intercellular adhesion molecule-1(sICAM-1)were detected by enzyme-linked immunosorbent assay.Myocardial histopathological changes were detected by hematoxylin/eosin(HE)staining.Serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured using an enzyme labeling instrument.Whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were assessed using an automatic blood rheology analyzer.The maximum platelet aggregation rate(MAR)and average platelet aggregation rate(AAR)induced by arachidonic acid and adenosine diphosphate were detected using a whole-blood platelet aggregometer.Results Compared with the Control group,all four model groups had significantly lower absenteeism distance and number of entries into the central region in the absent-field test,and a lower sugar-water preference ratio(P＜0.01).ECG revealed ST-segment elevation in the ISO and CUMS+ISO+HFD groups,tachycardia in the CUMS group,and mild ST-segment elevation in the HFD.Serum ACTH,Cor,CORT,ET-1,and sICAM-1 were all significantly elevated in the four model groups(P＜0.01).HE staining showed that myocardial tissue was severely damaged in rats in the ISO and CUMS+ISO+HFD groups,with pathological changes such as localized fibrosis and inflammatory infiltration of the myocardium,while mild cardiomyocyte disarrangement and fracture was seen in the CUMS and HFD groups.Rats in the HFD group had increased serum TC and LDL(P＜0.01)and decreased HDL contents(P＜0.01).Compared with the Control group,whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were all increased in the CUMS,HFD,and CUMS+ISO+HFD groups(P＜0.01,P＜0.05),while whole blood high-cut viscosity(200 V/S),whole blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen levels were decreased in rats in the ISO group(P＜0.01,P＜0.05).MAR and AAR were significantly higher in rats in the CUMS,HFD,and CUMS+ISO+HFD groups(P＜0.01),while the platelet aggregation rate was decreased in the ISO group compared with the Control group(P＜0.01,P＜0.05).Conclusions These result showed that the rat CUMS+ISO+HFD model better reflected the complexity of clinical double heart disease than the other three models.

Objective:To explore the association between mouth breathing (MB) and functional speech sound disorders (FSSDs) in children, aiming to establish a novel theoretical basis for FSSD interventions.Methods:Eighty-nine children with an FSSD aged 4-12 years formed the FSSD group, while eighty-five age-matched healthy children served as controls. Their clinical data were processed using independent sample t-tests and chi-square tests to test for any significant differences between the two groups in terms of gender, age, mouth breathing status, post-frenotomy condition, Mandarin exposure before age 4, and delayed speech onset. Multivariate logistic regressions were evaluated to identify risk factors for FSSD in such children and to seek any association between mouth brea-thing and FSSD.Results:The regression analysis identified the following risk factors for childhood FSSD, ranked by odds ratio ( OR) magnitude: mouth breathing (adjusted OR=22.168, 95% CI=7.849-62.608, P≤0.01), delayed speech onset (adjusted OR=20.091, 95% CI=4.812-83.878, P≤0.01), age (a protective effect) (adjusted OR=0.979, 95% CI=0.962-0.997, P≤0.05). Univariate analysis of mouth breathing and associated factors revealed significant associations of FSSD with mouth breathing (χ 2=52.15, P≤0.01) and delayed speech onset (χ 2=25.873, P≤0.01). Conclusions:The significant risk factors for childhood functional speech sound disorders are mouth breathing (showing the highest adjusted OR), delayed speech onset and age. These findings suggest that early screening and therapeutic interventions for mouth breathing should be clinically prioritized to minimize FSSD risk.

Objective:To explore the association between mouth breathing (MB) and functional speech sound disorders (FSSDs) in children, aiming to establish a novel theoretical basis for FSSD interventions.Methods:Eighty-nine children with an FSSD aged 4-12 years formed the FSSD group, while eighty-five age-matched healthy children served as controls. Their clinical data were processed using independent sample t-tests and chi-square tests to test for any significant differences between the two groups in terms of gender, age, mouth breathing status, post-frenotomy condition, Mandarin exposure before age 4, and delayed speech onset. Multivariate logistic regressions were evaluated to identify risk factors for FSSD in such children and to seek any association between mouth brea-thing and FSSD.Results:The regression analysis identified the following risk factors for childhood FSSD, ranked by odds ratio ( OR) magnitude: mouth breathing (adjusted OR=22.168, 95% CI=7.849-62.608, P≤0.01), delayed speech onset (adjusted OR=20.091, 95% CI=4.812-83.878, P≤0.01), age (a protective effect) (adjusted OR=0.979, 95% CI=0.962-0.997, P≤0.05). Univariate analysis of mouth breathing and associated factors revealed significant associations of FSSD with mouth breathing (χ 2=52.15, P≤0.01) and delayed speech onset (χ 2=25.873, P≤0.01). Conclusions:The significant risk factors for childhood functional speech sound disorders are mouth breathing (showing the highest adjusted OR), delayed speech onset and age. These findings suggest that early screening and therapeutic interventions for mouth breathing should be clinically prioritized to minimize FSSD risk.

Objective:To explore the treatment of the patients with severe phenotype of mucopolysaccharidosis (MPS) type ⅣA by analysing the clinical feature and diagnosis.Methods:Two pediatric patients diagnosed as MPS ⅣA in severe form were enrolled in Children′s Hospital Affiliated to Zhengzhou University from August 2021 to April 2022.Two children from 2 pedigrees with the main manifestations of short stature and bone deformities were retrospectively included.The clinical manifestations, biochemical indexes, and bone imaging findings were retrospectively analyzed.Peripheral blood leukocytes were collected and subjected to the N-acetylgalactosamine-6-sulfatase (GALNS) assay and genetic sequencing.Gene analysis of amniotic fluid cells at the 18 th week of the second pregnancy of the mother of case 2 was performed for prenatal diagnosis.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed in both patients and to explore the treatment of patients with MPS ⅣA. Results:Both cases presented clinical manifestations of short stature, joint laxity, pectus carinatum, and genu valgus.X-ray examination revealed the decreased bone mineral density, ulnar deviation of the radial epiphysis, kyphosis and scoliosis.The respiratory and skeletal systems were affected in both patients, and the optic nerve was suspiciously affected. GALNS gene analysis showed that there were 2 missense mutations of c. 1019G>A (p.G340D) and c. 706C>G (p.H236D) in case 1, and 2 missense mutations of c. 425A>G (p.H142R) and c. 463G>A (p.G155R) were detected in case 2.Mutations in both cases were inherited from their fathers and mothers, which were all newly discovered that have not been reported.Only the c. 463G>A mutation was detected in the amniotic fluid cells of the mother of case 2.It is confirmed that case 2 was the carrier of MPS ⅣA, whose gene mutation was from the mother, and case 2 did not suffer the same disease as the proband.Both cases were treated with allo-HSCT with full donor chimerism and no severe transplant complications were reported.Their GALNS activity was within the normal range, and the scores of activities of daily living were higher than those before transplantation. Conclusions:The MPS ⅣA patients with severe phenotype is a rare autosomal recessive disease caused by GALNS mutations that is difficult to diagnose and poor prognosis.Early detection, diagnosis, and effective treatment contribute to improve the long-term quality of life.The allo-HSCT is an effective therapeutic strategy for MPS ⅣA.

Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the childhood Epstein-Barr virus(EBV)-positive lymphoproliferative diseases(EBV + LPD). Methods:The clinical features, treatment course, and prognosis of 9 children with EBV + LPD who underwent allo-HSCT in Children′s Hospital Affiliated to Zhengzhou University from July 2019 to July 2022 were analyzed retrospectively. Results:All the 9 children underwent histopathological examination, including 6 patients with EBV-positive T-cell lymphoproliferative disease (EBV + T-LPD), 1 with pulmonary lymphomatoid granuloma, and 2 with systemic EBV-positive T-cell lymphoma.There were 6 males and 3 females, with the median age of 5.8 (1.5-13.0) years.At the initial diagnosis, plasma and peripheral EBV-DNA copy at the initial diagnosis was (5.67-865.00)×10 2/mL, and (5.13-1 250.00)×10 2/mL, respectively.The EBV-DNA load of cerebrospinal fluid increased to (5.18-291.00)×10 2/mL in 3 cases.The whole exon sequencing data showed no abnormality in 3 cases, pulmonary lymphomatoid granuloma with the IL2RG mutation in 1 case and EBV + T-LPD with a hemizygous mutation in the SH2D1A gene as the pathogenic mutation in 1 case.Pathogenic mutations were not detected in the remaining 4 cases.The course of disease before transplantation was 5.4(3.0-10.0) months.Disease status before transplantation was as follows: all 3 cases of lymphomas had partial regression; 2 cases of EBV + T-LPD had active disease; and 4 cases had no active disease.Among the donors, there were 5 cases of half-matched relatives, 2 cases of full-matched siblings and 2 cases of unrelated full-matched donors.The median number of mononuclear cells in peripheral blood and/or bone marrow hematopoietic stem cell was 6.60(3.64-12.18)×10 8/kg, while the median implantation time of neutrophils was 18(9-23) days.One month after the transfusion of hematopoietic stem cells, plasma EBV-DNA copy was negative in all cases, and peripheral EBV-DNA copy was negative in 7 cases.The copy number in the other 2 cases was 10 2/mL.At the 3-month evaluation, plasma and peripheral EBV-DNA copy were negative in all cases.In addition, 3 cases of lymphomas achieved radiographic complete remission, and 6 cases of EBV + T-LPD were inactive.All transplant-related complications were effectively controlled after medication.Following the median follow-up of 24 (11-42) months, all patients had disease-free survival.Serious impact on the quality of life due to graft versus host disease was not reported. Conclusions:allo-HSCT is an effective treatment of childhood EBV + LPD, which is able to control transplant-related complications.Children with EBV + LPD can achieve long-term disease-free survival through transplantation.

Objective:To explore the expression of fructose bisphosphate aldolase A (ALDOA) in the bone marrow of patients with acute myeloid leukemia (AML) and the correlation with clinical features and prognosis.Methods:The bone marrow samples of 90 newly diagnosed AML (non-acute promyelocytic leukemia) patients and 18 allogeneic hematopoietic stem cell transplantation donors who were treated from January 2013 to December 2015 in the First Affiliated Hospital of Zhengzhou University and the Children's Hospital Affiliated to Zhengzhou University were collected. The relative expression level of ALDOA mRNA in bone marrow samples was detected by using real-time quantitative polymerase chain reaction (qRT-PCR). Clinical data of these patients were retrospectively analyzed, and the patients were divided into continuous complete remission (CR) group and refractory recurrent (RR) group according to the clinical response and follow-up results. The differences of the relative expression level of ALDOA mRNA between AML group and the normal control group, CR group and RR group were analyzed. Univariate and multivariate Cox regression risk model were used for analysis of factors influencing prognosis of AML patients.Results:The relative expression level of ALDOA mRNA in AML group was higher than that in normal control group [(5.71±0.44) vs. (1.10±0.08), t = 4.74, P<0.001]. The relative expression level of ALDOA mRNA in the RR group was higher than that in the CR group [(6.69±0.67) vs. (4.30±0.36) , t = 2.79, P < 0.001]. In addition, there were statistically significant differences in the proportion of patients with ALDOA mRNA high expression and those with ALDOA mRNA low expression stratified by the number of white blood cell, the proportion of bone marrow blasts and whether complete remission could be achieved or not after 1 course of induction therapy (all P < 0.05). Overall survival in patients with ALDOA high expression was worse than that in patients with ALDOA low expression ( χ2 = 5.59, P = 0.018). Multivariate analysis showed that white blood cell count, prognosis stratification, whether complete remission could be achieved or not after 1 course of induction therapy and ALDOA expression were the independent prognostic factors for the death of AML patients (all P < 0.05). Conclusions:ALDOA may play an important role in the development and progression of AML, and the expression level of ALDOA in the bone marrow can be used as an index for the prognosis assessment of AML patients and may be a potential therapeutic target for AML.

Both spike and local field potential (LFP) signals are two of the most important candidate signals for neural decoding. At present there are numerous studies on their decoding performance in mammals, but the decoding performance in birds is still not clear. We analyzed the decoding performance of both signals recorded from nidopallium caudolaterale area in six pigeons during the goal-directed decision-making task using the decoding algorithm combining leave-one-out and -nearest neighbor (LOO- NN). And the influence of the parameters, include the number of channels, the position and size of decoding window, and the nearest neighbor value, on the decoding performance was also studied. The results in this study have shown that the two signals can effectively decode the movement intention of pigeons during the this task, but in contrast, the decoding performance of LFP signal is higher than that of spike signal and it is less affected by the number of channels. The best decoding window is in the second half of the goal-directed decision-making process, and the optimal decoding window size of LFP signal (0.3 s) is shorter than that of spike signal (1 s). For the LOO- NN algorithm, the accuracy is inversely proportional to the value. The smaller the value is, the larger the accuracy of decoding is. The results in this study will help to parse the neural information processing mechanism of brain and also have reference value for brain-computer interface.

OBJECTIVE:To investigate the correlation between ribonucleotide reductase M1 subunit (RRM1) single nucleo-tide polymorphisms (SNPs) and chemotherapy sensitivity of patients with non-small cell lung cancer (NSCLC) for gemcitabine. METHODS:A total of 96 NSCLC patients receiving primary treatment selected from our hospital during Aug. 2014-Jul. 2016 were all accepted gemcitabine-based two-drug chemotherapy plan,with continuous treatment for at least 2 cycles(28 d as a cycle). Che-motherapy sensitivity rate was calculated by using the ratio of the sum of patients with complete response and partial response to the sum of test patients. RRM1 genotype was tested by PCR and direct sequencing. The correlation between different genotypes and chemotherapy sensitivity was analyzed. RESULTS:Distribution frequency of RRM1-37C>A CC, CA, AA genotype were 35.42％,52.08％,12.50％,respectively;distribution frequency of-524C>T CC,CT,TT genotype were 18.75％,37.50％, 43.75％,respectively. The frequency of each genotype was in the line with Hardy-Weinberg equilibrium(P>0.05). Chemotherapy sensitivity rate of 96 NSCLC patients was 37.50％. The patient's age,sex,ethnicity,smoking or not,TNM stage,pathological type,chemotherapy plan,and the Eastern American Oncology Collaboration score were not associated with chemotherapy sensitivi-ty (P>0.05). Chemotherapy sensitivity rates of RRM1(-37CA)+(-524CT)genotype and (-37CC)+(-524TT) genotype patients (57.14％,39.39％) were significantly higher than those of other genotype patients (10.71％),with statistical significance (P<0.05). There was no statistical significance in chemotherapy sensitivity rate between RRM1(-37CA)+(-524CT) and (-37CC)+(-524TT)genotype patients. CONCLUSIONS:In NSCLC patients,the SNPs of RRM1 can be used as predictive factor for the sen-sitivity of gemcitabine chemotherapy,and RRM1(-37CA)+(-524CT)and(-37CC)+(-524TT)genotype patients have higher sensi-tivity to this type of chemotherapy.