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 ; Male ; Female ; Prognosis ; Child, Preschool ; Retrospective Studies ; Child ; Leukemia, Erythroblastic, Acute/diagnosis* ; Infant ; Adolescent

Objective:To evaluate the predictive value of the Controlling Nutritional Status (CONUT) score for severe acute pancreatitis (SAP).Methods:A total of 426 patients with acute pancreatitis (AP) admitted to the First Affiliated Hospital of Zhengzhou University between January and December 2024 were retrospectively reviewed. After applying exclusion criteria, 189 patients were included and classified into non-severe AP (NSAP) and SAP groups according to diagnostic criteria. Demographic characteristics (age, sex, underlying diseases), vital signs, CONUT score, Bedside Index for Severity in Acute Pancreatitis (BISAP) score, and laboratory parameters (including complete blood count, blood glucose, liver and kidney function, coagulation profile, amylase, and lipase) on admission were compared between the two groups. Binary logistic regression was used to identify independent risk factors associated with AP severity. Receiver operating characteristic (ROC) curves were generated to assess the predictive performance of each indicator by determining the area under the curve (AUC), sensitivity, specificity, and optimal cutoff values.Results:Compared with the NSAP group, the SAP group had significantly longer hospital stays, higher respiratory rates, and elevated levels of PCT, CRP, absolute neutrophil count, AST, GGT, PT, D-dimer, INR, fibrinogen, FDP, as well as higher CONUT, SIRS, and BISAP scores (all P < 0.05). In contrast, the NSAP group showed significantly higher red blood cell count, hemoglobin, absolute lymphocyte count, serum calcium, albumin, total cholesterol, prothrombin time activity, and PNI score (all P < 0.05). Binary logistic regression analysis identified CONUT score ( OR = 1.623, 95% CI: 1.048–2.512) and BISAP score ( OR = 19.608, 95% CI: 6.585–58.387) as independent risk factors for disease severity. The AUC values for predicting SAP using CONUT score, BISAP score, and their combination were 0.694, 0.815, and 0.864, respectively. Conclusions:The CONUT score is an early independent risk factor for SAP. Combining CONUT with BISAP scores provides better predictive performance for assessing the severity of acute pancreatitis.

Objective To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation(PMV)due to different primary diseases.Methods A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022.According to the primary disease,they were divided into respiratory disease(RD)group,central nervous system(CNS)group,neuromuscular disease(NMD)group,and other disease group.The four groups were compared in terms of general information,treatment,and outcome.Results There were significant differences among the four groups in age,body weight,Pediatric Logistic Organ Dysfunction-2(PELOD-2)score,Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score,analgesic and sedative treatment,nutrition supply,rehabilitation treatment,tracheotomy,successful ventilator weaning,and outcomes(P＜0.05).Compared with the RD group,the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment,and the CNS group had a significantly higher proportion of children receiving tracheotomy(P＜0.008).Compared with the other disease group,the CNS group and the NMD group had significantly lower PELOD-2 and PRISM Ⅲ scores,and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged(P＜0.008).Conclusions There are differences in clinical characteristics among children receiving PMV due to different etiologies.Most children in the RD group have a younger age,and children in the CNS group have a relatively good prognosis.

Objective To investigate the clinical features and prognosis of childhood acute lymphoblastic leukemia (ALL) with CREBBP gene mutation. Methods A retrospective analysis was performed for the clinical data of 14 ALL children with CREBBP gene mutation who were admitted to Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Results The ALL patients with CREBBP gene mutation accounted for 1.5％ (14/963) among all children diagnosed with ALL during the same period of time,among whom there were 4 boys (29％) and 10 girls (71％),with a median age of 4 years and 3.5 months. All children had an immunological type of B-cell ALL and concurrent mutations in other genes including NRAS,KRAS,ETV6,FLT3,PAX5,SH2B3,CDKN2A,and CDKN2B,and 4 children had karyotype abnormality. All 14 children received induction therapy with the VDLP regimen,with a complete remission (CR) rate of 79％ (11/14) after the first course of treatment. Three children experienced bone marrow recurrence alone,with a recurrence rate of 21％ (3/14),among whom 1 child achieved CR after blinatumomab therapy and 2 received bridging hematopoietic stem cell transplantation after chemotherapy for recurrence. Among the 14 children,1 died due to treatment discontinuation and 13 achieved disease-free survival. The 5-year overall survival rate was 92％±7％,and the event-free survival rate was 73％±13％. Conclusions ALL with CREBBP gene mutation is more common in girls and has a low induction remission rate and a high recurrence rate,and it is often accompanied by other types of gene mutations and abnormal karyotypes. Most children with recurrence can achieve long-term survival after immunotherapy or hematopoietic stem cell transplantation.

Objective:To explore effect of Glioma-associated oncogene family zinc finger 1(GLI1)on hypoxia induced trans-formation of NR8383 to M1 phenotype and development of pulmonary hypertension(PH).Methods:Fifteen adult male Wistar rats were randomly divided into control group,hypoxia PH model group and hypoxic PH with GANT61 treatment group,with 5 rats in each group.PH related indexes of rats were detected by small animal ultrasound and right cardiac catheter experiment to determine effect of GLI1 specific inhibitor GANT61 on progression of PH.Pulmonary arterial thickness was measured by HE staining.α-SMA and M1 polarization markers TNF-α and IL-1β expressions were determined by immunohistochemistry.M1 polarization markers CD86 and TNF-α expressions were determined by immunofluorescence.GLI1 expression and NF-κB protein were detected by Western blot.mRNA expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 were detected by qRT-PCR.CHIP-PCR verified that GLI1 regulates NF-κB promoter activity.IL-12 content was detected by ELISA.Rat pulmonary artery smooth muscle cells proliferation was detected by CCK-8.Results:GLI1 inhibitor GANT61 could alleviate symptoms of PH in hypoxic rats(P<0.05).Compared with hypoxic group,inhibition of GLI1 reduced expressions of TNF-α and IL-1β in rat lung tissue(P<0.05).In cell experiments,hypoxia induced M1 polarization of NR8383 by up-regulating GLI1 to activate NF-κB pathway,GLI1 overexpression increased expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 in M1 macrophages(P<0.05).NR8383 culture supernatants could stimulate pulmonary artery smooth muscle cell proliferation(P<0.05)and contribute to development of PH.Conclusion:Hypoxia activates NF-κB pathway by up-regulating GLI1 to induce M1 polarization of macrophages contributes to development of PH.

Objective:To investigate the value of fibrinogen to albumin ratio (FAR), creatinine to albumin ratio (CAR) and platelet to lymphocyte ratio (PLR) in predicting the poor prognosis of hyperlipidemic acute pancreatitis (HLAP).Methods:Clinical data of HLAP patients admitted to the hospital from January 2021 to January and December 2023 were retrospectively collected. According to the prognosis, the patients were divided into two groups: good prognosis group and poor prognosis group.The independent risk factors of HLAP in different prognostic groups were obtained by multivariate Logistic regression analysis. Receiver operating characteristic (ROC) curves were plotted to evaluate the prognostic value of FAR, CAR and PLR alone and in combination.Results:A total of 118 patients with HLAP were included, including 69 patients with good prognosis and 49 patients with poor prognosis.The difference of heart rate, lymphocyte, triglyceride, albumin, creatinine, urea nitrogen, blood calcium, blood glucose, C-reactive protein, procalcitonin, fibrinogen, FAR, CAR, PLR, Bedside indicator of acute pancreatitis Severity score, Acute Physiology and Chronic Health status score, hospitalization time assessment between the two groups was statistically significant ( P<0.05). Multivariate Logistic regression analysis showed that FAR (odds ratio ( OR) = 25.949, 95% confidence interval (95% CI):3.190 ~ 211.080, P = 0.002), CAR ( OR = 1.453, 95% CI:1.095 ~ 1.928, P = 0.010) and PLR ( OR = 1.005, 95% CI: 1.001 ~ 1.009, P = 0.020) were independent risk factors for poor prognosis in HLAP patients. ROC curve analysis showed that the area under the ROC curve (AUC) of FAR, CAR and PLR to predict poor prognosis of HLAP patients were 0.823, 0.781 and 0.652, respectively.The AUC of FAR combined with CAR, FAR combined with PLR and CAR combined with PLR were 0.840, 0.845 and 0.849, respectively.The combined ability of FAR, CAR and PLR to predict poor prognosis in HLAP patients was (AUC=0.875,95% CI:0.814 ~ 0.937). When the cut-off value was 0.387, the sensitivity was 83.7%, and the specificity was 79.7%. Conclusions:The prognostic value of FAR, CAR and PLR in HLAP patients is better than that of single or pairwise combination.

Objective To elucidate the regulatory effects of Glycerol Kinase(GLPK)on the inflammatory response induced by lipopolysaccharide(LPS)in mouse Raw264.7 macrophages.Methods Raw264.7 macrophages were cultured in vitro,and an inflammatory model was established through LPS induction.The transcriptional levels of inflammatory cytokines NF-κB,TNF-α,IL-6,and IL-1β were quantified using RT-qPCR.The expression and localization of GLPK were examined via Western blot and immunofluorescence.Additionally,Western blot analysis was employed to detect the levels of cellular pan-succinylation and H3K23su expression.ChIP-qPCR was utilized to assess the enrichment of H3K23su modification at the IL-10 promoter.The total reactive oxygen species production was measured using DCFH-DA probes,while mitochondrial ROS levels were determined with Mito-SOX probes.Mitochondrial membrane potential changes,indicative of mitochondrial dysfunction,were evaluated using JC-1 fluorescent probes.Furthermore,GLPK overexpression plasmids were transfected into cells to investigate the effects of GLPK on inflammatory responses,mitochondrial function,and epigenetic modifications.Results LPS treatment led to mitochondrial dysfunction,inflammatory responses exacerbation,succinylation modifications reduction,and GLPK protein expression decrease in Raw264.7 cells.Overexpression of GLPK in LPS-treated cells improved mitochondrial function and reduced the transcription of pro-inflammatory cytokines.ChIP-qPCR analysis revealed that GLPK overexpression could reverse the LPS-induced suppression of H3K23su modification at the IL-10 promoter,thereby attenuating the inflammatory response.Conclusion LPS mediates inflammatory responses in Raw264.7 macrophages through a GLPK-dependent H3K23 succinylation modification mechanism.

Objective To elucidate the regulatory effects of Glycerol Kinase(GLPK)on the inflammatory response induced by lipopolysaccharide(LPS)in mouse Raw264.7 macrophages.Methods Raw264.7 macrophages were cultured in vitro,and an inflammatory model was established through LPS induction.The transcriptional levels of inflammatory cytokines NF-κB,TNF-α,IL-6,and IL-1β were quantified using RT-qPCR.The expression and localization of GLPK were examined via Western blot and immunofluorescence.Additionally,Western blot analysis was employed to detect the levels of cellular pan-succinylation and H3K23su expression.ChIP-qPCR was utilized to assess the enrichment of H3K23su modification at the IL-10 promoter.The total reactive oxygen species production was measured using DCFH-DA probes,while mitochondrial ROS levels were determined with Mito-SOX probes.Mitochondrial membrane potential changes,indicative of mitochondrial dysfunction,were evaluated using JC-1 fluorescent probes.Furthermore,GLPK overexpression plasmids were transfected into cells to investigate the effects of GLPK on inflammatory responses,mitochondrial function,and epigenetic modifications.Results LPS treatment led to mitochondrial dysfunction,inflammatory responses exacerbation,succinylation modifications reduction,and GLPK protein expression decrease in Raw264.7 cells.Overexpression of GLPK in LPS-treated cells improved mitochondrial function and reduced the transcription of pro-inflammatory cytokines.ChIP-qPCR analysis revealed that GLPK overexpression could reverse the LPS-induced suppression of H3K23su modification at the IL-10 promoter,thereby attenuating the inflammatory response.Conclusion LPS mediates inflammatory responses in Raw264.7 macrophages through a GLPK-dependent H3K23 succinylation modification mechanism.

OBJECTIVE: To observe the effects of electroacupuncture (EA) on cardiac function and local field potential (LFP) in sensory and motor cortices in mice with stress cardiomyopathy (SC), and to explore the possible mechanism of EA in improving SC. METHODS: Twenty-seven female C57BL/6 mice were randomized into a blank group, a model group and an EA group, 9 mice in each group. In the model group and the EA group, SC model was established by continuous intraperitoneal injection of isoproterenol (ISO) for 14 days. At the same time of modeling, EA was applied at "Neiguan" (PC 6) and "Shenmen" (HT 7) in the EA group, with disperse-dense wave, in frequency of 2 Hz/15 Hz, 15 min each time, once a day for 14 days. After intervention, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test within 5 minutes were observed; the left ventricular function indexes (left ventricular diameter of end-diastole [LVIDd], left ventricular diameter of end-systole [LVIDs], left ventricular volume of end-diastole [LVEDV], left ventricular volume of end-systole [LVESV], ejection fraction [EF] and fraction shortening [FS]) were detected by echocardiography; the changes in ST-segment amplitude and PR interval of electrocardiogram were observed; the morphology of myocardial tissue was observed by HE staining; the serum levels of cortisol (CORT), cardiac troponin T (cTnT) and brain natriuretic peptide (BNP) were detected by ELISA; the changes of LFP in sensory and motor cortices were recorded by Plexon multi-channel acquisition system. RESULTS: Compared with the blank group, in the model group, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test were decreased (P<0.05); LVIDd, LVIDs, LVEDV and LVESV were increased (P<0.05), EF and FS were decreased (P<0.05); ST-segment amplitude was increased (P<0.05) and PR interval was prolonged (P<0.05); irregular myocardial fiber arrangement, interstitial edema and inflammatory cell infiltration were observed; the serum levels of CORT, cTnT and BNP were increased (P<0.05); in the sensory cortex, the ratios of delta, theta, alpha and beta frequency bands were increased (P<0.05), the maximum energy spectrum of theta and beta frequency bands was increased (P<0.05), the power spectral density (PSD) of delta, theta, alpha, beta and gamma frequency bands was increased (P<0.05); in the motor cortex, the ratios of delta, theta, alpha and beta frequency bands were increased (P<0.05), the maximum energy spectrum as well as PSD of delta, theta, alpha, beta and gamma frequency bands were increased (P<0.05). Compared with model group, in the EA group, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test were increased (P<0.05); LVIDd, LVIDs, LVEDV and LVESV were decreased (P<0.05), EF and FS were increased (P<0.05); ST-segment amplitude was decreased (P<0.05), and the PR interval was shortened (P<0.05); myocardial fiber injury and inflammatory cell infiltration were reduced; the serum levels of CORT, cTnT and BNP were decreased (P<0.05); in the sensory cortex, the ratios of theta, alpha and beta frequency bands were decreased (P<0.05), the ratio of gamma frequency band was increased (P<0.05), the maximum energy spectrum of theta frequency band as well as the PSD of theta, alpha, beta and gamma frequency bands were decreased (P<0.05); in the motor cortex, the ratios of theta, alpha and beta frequency bands were decreased (P<0.05) and the ratio of gamma frequency band was increased (P<0.05), the maximum energy spectrum of delta frequency band was increased (P<0.05), the maximum energy spectrum of theta frequency band as well as the PSD of theta and gamma frequency bands were decreased (P<0.05). CONCLUSION EA can improve cardiac function in mice with stress cardiomyopathy, and its mechanism may be related to the regulation of local field potentials in sensory and motor cortices.
Female ; Mice ; Animals ; Electroacupuncture ; Takotsubo Cardiomyopathy ; Motor Cortex ; Mice, Inbred C57BL ; Myocardium

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
Male ; Child ; Female ; Humans ; Child, Preschool ; Receptors, Tumor Necrosis Factor, Type I/genetics* ; Retrospective Studies ; Hereditary Autoinflammatory Diseases/drug therapy* ; Glucocorticoids/therapeutic use* ; Biological Factors/therapeutic use* ; Immunosuppressive Agents/therapeutic use* ; Autoantibodies ; Familial Mediterranean Fever/diagnosis* ; Mutation