OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of seven pediatric patients with Acute myeloid leukemia (AML) positive for the t(16;21)(p11;q22) FUS::ERG fusion gene. METHODS: A retrospective analysis was carried out on the clinical data, treatment, and prognosis of seven AML patients with t(16;21)(p11;q22) FUS::ERG fusion gene admitted to Henan Children's Hospital between June 2015 and November 2024. Relevant literature was also reviewed. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-102-001). RESULTS: Among 297 pediatric patients with AML, 7 cases (2.36%) were positive for the t(16;21)(p11;q22) FUS::ERG fusion gene, including 3 males and 4 females, with a median age of 11 years (range: 3 ~ 12 years). According to the FAB classification, these included 1 case of M2, 3 cases of M5, and 3 cases of AML-not otherwise specified (non-M3). All 7 patients were found to harbor the t(16;21)(p11;q22) translocation, with 3 cases showing additional chromosomal abnormalities. Immunophenotyping revealed universal expression of CD13, CD33, CD34, and CD117, with partial expression of CD56, CD4, CD64, CD123, CD15, CD38, CD11b, HLA-DR, cMPO, and CD16. One patient achieved complete remission (CR) after the first course of DAE (cytarabine + daunorubicin + etoposide) induction chemotherapy but relapsed and discontinued the treatment. Six patients received DAH (cytarabine + daunorubicin + homoharringtonine) induction therapy, of whom 2 achieved CR after two courses and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in an overall CR rate of 42.86%. Five children did not receive allo-HSCT and had a median overall survival of 9 months (range: 6 ~ 18 months). Two children who underwent transplantation achieved bone marrow morphological and molecular biological relapse at 6 and 9 months post-transplantation, respectively. After receiving combined chemotherapy and donor lymphocyte infusion, one child failed to achieve remission and died at 22 months post-transplantation, while the other has been followed up to date with positive fusion gene status. Their overall survival was 25 months and 30 months, respectively. CONCLUSION The t(16;21)(p11;q22) FUS::ERG fusion gene is rare in pediatric AML and associated with poor prognosis. Allo-HSCT may mitigate the adverse prognostic impact of the FUS::ERG fusion gene and contribute to prolonged survival.
Humans ; Male ; Child ; Female ; Leukemia, Myeloid, Acute/drug therapy* ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic ; Retrospective Studies ; RNA-Binding Protein FUS/genetics* ; Chromosomes, Human, Pair 16/genetics* ; Adolescent ; Child, Preschool ; Chromosomes, Human, Pair 21/genetics* ; Prognosis ; Treatment Outcome

ObjectiveTo systematically compare the effects of diverse electromagnetic stimulation protocols on hand function and activities of daily living (ADL) in stroke patients using network meta-analysis (NMA), and screen the optimal stimulation strategy for post-stroke hand dysfunction rehabilitation. MethodsNMA was performed in accordance with the PRISMA-NMA statement. Databases of CNKI, Wanfang data, VIP, CBM, PubMed, Web of Science and Embase were searched from database inception to April, 2026 for eligible randomized controlled trials (RCTs) comparing different electromagnetic stimulation protocols for post-stroke hand impairment. The Cochrane Risk of Bias tool and PEDro scale were used to assess methodological quality of included studies, while the GRADE system was adopted to grade evidence quality of primary outcomes of Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI). After literature screening, data extraction and bias evaluation, RevMan 5.4 and Stata 17.0 were used for meta-analysis and NMA. ResultsA total of 22 RCT involving 17 electromagnetic stimulation protocols were finally included. The PEDro scores ranged from six to ten. The top five protocols for improving FMA-UE score were repetitive peripheral magnetic stimulation (rPMS) + repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS) + rPMS, iTBS + transcranial direct current stimulation (tDCS), transcutaneous electrical acupoint stimulation (TEAS) and contralaterally controlled functional electrical stimulation (CCFES). tDCS was the most effective on MBI, followed by TEAS and iTBS+rPMS. Evidence quality for FMA-UE and MBI was moderate. Funnel plots suggested low risk of publication bias, and consistency tests verified good coherence between direct and indirect comparisons in network models. ConclusionElectromagnetic stimulation significantly facilitates upper limb and hand functional recovery, and improves ADL in stroke patients. The combined central-peripheral magnetic stimulation protocol may be the most effective on motor rehabilitation, whereas tDCS on ADL.

ObjectiveThis study aimed to investigate whether dexmedetomidine （Dex） alleviates stress-induced mammary tumor progression in mice by inhibiting the TLR4/NF‑κB signaling pathway， and to examine its effects on anxiety‑depression‑like behaviors and stress hormone levels. MethodsAn orthotopic EMT6 mammary tumor model was established in mice， and chronic mild stress （CMS） was applied to induce anxiety‑depression‑like states. The mice were divided into six groups： naive， tumor， CMS， CMS+tumor， CMS+tumor+Dex， and CMS+tumor+Vehicle groups. Behavioral changes were evaluated using the open field test and tail suspension test. Plasma stress hormone levels were measured by high‑performance liquid chromatography. Western blot and RT‑qPCR were performed to detect the expression of TLR4， p‑NF‑κB p65， p‑IκBα， and inflammatory cytokines （IL‑6， IL‑1β， TNF‑α） in tumor tissues. In vitro， EMT6 cells were treated with cortisol to mimic the stress-related microenvironment， and the effects of Dex on the TLR4/NF‑κB pathway were assessed by CCK‑8， Western blot， and RT-qPCR. ResultsTumor‑bearing mice exhibited significant anxiety‑depression‑like behaviors （P＜0.05）， along with markedly elevated plasma levels of norepinephrine， epinephrine， and cortisol （P＜0.05）. Chronic stress further aggravated these behavioral abnormalities and promoted tumor growth （P＜0.05）. Dexmedetomidine intervention significantly improved anxiety‑depression‑like behaviors （P＜0.05） and lowered peripheral stress hormone levels （P＜0.05） in stress‑exposed tumor‑bearing mice. In vitro experiments demonstrated that cortisol treatment activated the TLR4/NF‑κB pathway （P＜0.001） and upregulated the expression of inflammatory cytokines （P＜0.05 in EMT6 cells， whereas dexmedetomidine effectively suppressed this activation （P＜0.001）. In the in vivo model， dexmedetomidine treatment downregulated the expression of TLR4， p‑NF‑κB p65， p‑IκBα， and pro‑inflammatory cytokines in tumor tissues （P＜0.001） and significantly inhibited tumor growth （P＜0.05）. ConclusionDexmedetomidine inhibits the TLR4/NF‑κB signaling pathway， alleviates stress‑induced inflammatory responses， improves anxiety- and depression‑ like behaviors， reduces stress hormone levels， and suppresses mammary tumor progression. These findings provide an experimental basis for understanding anxiety- and depression- associated breast tumor progression and suggest that Dexmedetomidine and the TLR4/NF-κB pathway may serve as potential therapeutic targets.

Objective:To analyze the relationship between social function and family support in young and middle-aged patients undergoing peritoneal dialysis (PD).Methods:In this cross-sectional study, the patients undergoing maintenance PD therapy for more than 3 months at the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University, from May to October 2023 were recruited retrospectively. The social dysfunction screening scale and family support self-rating scale were used to evaluate the social dysfunction and family support of PD patients, respectively. The social demographic and clinical data of the patients were collected. Logistic regression analysis model was used to identify associated factors of social dysfunction in PD patients.Results:A total of 359 PD patients were recruited with age of (42.6±9.5) years old. Among them, 197 patients (54.9%) were males, and 33 patients (9.2%) were complicated with diabetes. The dialysis age was 28.8 (13.5, 56.3) months. The score of social function was 2 (1, 4), and the score of family support was (10.5±2.2). There were 199 patients (55.4%) having social dysfunction. There were 224 patients (62.4%) employed after PD. Compared with the normal social function group, the social dysfunction group had significantly lower score in family support ( Z=-2.613, P=0.009), serum potassium ( t=-2.725, P=0.007), urea clearance index ( Z=-2.346, P=0.019) and proportions of married status ( χ2=6.847, P=0.009), pre-dialysis employment ( χ2=3.996, P=0.046) and post-dialysis employment ( χ2=8.331, P=0.004), and higher serum creatinine ( Z=2.175, P=0.030), and proportions of annual household income < 100 000 yuan ( χ2=6.270, P=0.012) and diabetes mellitus ( χ2=4.400, P=0.036). Multivariate logistic regression analysis revealed that family support ( OR=0.828, 95% CI 0.733-0.935, P=0.002), diabetes mellitus ( OR=3.551, 95% CI 1.456-8.658, P=0.005) and serum potassium ( OR=0.559, 95% CI 0.374-0.835, P=0.005) were independent correlated factors of social dysfunction in young and middle-aged PD patients. Conclusions:The prevalence of social dysfunction is 55.4%, and the employment rate is 62.4% in young and middle-aged PD patients. Poor family support, diabetes mellitus and decreased serum potassium level are independently associated with social dysfunction in young and middle-aged PD patients.

Objective To establish a rat model of acclimatization to motion sickness(MS)induced by rotational stimulation.Methods To determine the stimulation conditions of MS,SD rats were divided into a static control group(SCG)and a single rotation stimulation group(SRG)before being subjected to the motion sickness index(MSI)measurement,open-field experiment and Morris water maze experiment after rotational stimulation to verify the feasibility of MS being induced in rats.Morris water maze experiments were performed to find out whether rotational stimulation could be used to induce MS in rats.During experiments on acclimatization,the SD rats were divided into the control group(Ctrl),one day of rotational stimulation group(Day1),three days of continuous rotational stimulation group(Day3),and seven days of continuous rotational stimulation group(Day7)before the changes in the MSI and behavior of these rats were recorded so as to explore the relationship between continuous stimulation and MS acclimatization in rats.Results After rotational stimulation,the rats showed a significant increase in the number of fecal pellets(P<0.0001)and in the MSI(P<0.0001)compared with the SCG.In the open field experiment,the rats showed a significant decrease in the spontaneous activity time(AT)(P<0.0001),total spontaneous activity distance(TD)(P<0.001)and distance moved by the center point per second(DMCPS)(P<0.001).The time taken to climb onto the platform(latency to find the platform,LP)(P<0.0001)and the total distance to the platform(distance to the platform,DP)(P<0.001)were significantly increased during the Morris water maze experiment.Acclimatization experiments revealed a significant increase in MSI and in the number of fecal pellets in the Day1 and Day3 groups of rotational stimulation compared to the Ctrl group(P<0.0001).AT(P<0.01),TD(P<0.05)and DMCPS(P<0.01)were significantly decreased,while LP and DP were significantly increased(P<0.0001),but there was no statistically significant difference in indices compared with the Day7 group(P>0.05).Conclusion Sinusoidal stimulation can induce MS in rats,and twice-a-day,continuous rotational stimulation for seven days can lead to acclimatization.The rat MS model can be assessed via behavioral experiments.

Objective:To investigate the efficacy of Naikan cognitive therapy(NCT)combined with medica-tion in improving depressive symptoms and sleep quality in patients with chronic schizophrenia.Methods:Patients were included if they met the following criteria:diagnosed with schizophrenia based on ICD-10 criteria,a disease course of ≥2 years,stable condition under maintenance antipsychotic medication,presence of depressive symptoms and sleep quality issues,and no use of antidepressants in the past two months.A total of 64 eligible patients were randomly assigned to the NCT group(n=32)or the mental health education(MEC)group(n=32).The interven-tion lasted 6 days,with 2 patients from each group dropping out.The Beck Depression Inventory-Ⅱ(BDI-Ⅱ)and Pittsburgh Sleep Quality Index(PSQI)were used to assess depressive symptoms and sleep quality.Results:After the intervention,the BDI-Ⅱ score difference(post-treatment score minus pre-treatment score)in the NCT group was significantly lower than that in the MEC group(P＜0.001).Similarly,the PSQI total score difference was also lower in the NCT group compared to the MEC group(P＜0.001).Conclusion:Adding Naikan cognitive therapy to routine medication treatment can effectively improve depressive symptoms and sleep quality in patients with chronic schizophrenia.

Objective:To explore the clinical features and risk factors for pediatric severe Mycoplasma pneumoniae pneumonia (SMPP) complicated with pulmonary embolism. Methods:SMPP patients admitted to Department of Pediatrics, Jiaxing First Hospital and Pediatric Intensive Care Unit, Shanghai Children′s Hospital from December 2019 to December 2023 were included in this retrospective case-control study.According to whether they were complicated with pulmonary embolism, SMPP patients were divided into a pulmonary embolism group and a non-pulmonary embolism group.Clinical characteristics of the two groups, including general data, laboratory examination and imaging data were compared and analyzed.The t-test and Mann-Whitney rank-sum test were used to compare the measurement data, and the χ2 test was used to compare the count data.The risk factors of SMPP patients developing pulmonary embolism were analyzed by the univariate method. Results:There were 10 out of 62 SMPP children developing pulmonary embolism, showing an incidence of 16.13%.In the pulmonary embolism group, there were 5 boys and 5 girls, with a median age of 7.50 (5.75, 9.25) years.There were 52 children in the non-pulmonary embolism group, including 29 boys and 23 girls, with a median age of 6.50(5.00, 8.00)years.The hospitalization time, body temperature, total white blood cell count, neutrophil count, C-reactive protein levels, lactate dehydrogenase levels, prothrombin time, activated partial thromboplastin time, D-dimer (D-D) levels, fibrinogen degradation product levels, pleural effusion and atelectasis rates in the pulmonary embolism group were significantly higher than those in the non-pulmonary embolism group (all P<0.05). Fibrinogen levels in the pulmonary embolism group were significantly lower than those in the non-pulmonary embolism group ( P<0.05). Univariate Logistic regression analysis showed that the D-D level was a risk factor for SMPP patient developing pulmonary embolism.The receiver operating characteristic curve analysis revealed that the D-D level had the largest area under the curve for predicting pulmonary embolism of 0.990(95% CI: 0.972-1.000, P<0.001), with a sensitivity of 100%, a specificity of 92%, and a cut-off value of 4.63 mg/L. Conclusions:SMPP children complicated with pulmonary embolism are prone to high inflammation and impaired coagulation function.The increase of D-D levels is a risk factor for the development of pulmonary embolism in SMPP.

OBJECTIVES: To investigate the protective effects of dexmedetomidine (DEX) against heat stress (HS)-induced oncosis in human skeletal muscle cells (HSKMCs) and its underlying mechanisms. METHODS: A HSKMC model of HS-induced oncosis were established by 43 ℃ water bath for 4 h, and the effects of treatments with 30 μmol/L DEX, ML385 (a Nrf2 inhibitor) +DEX, si-Nrf2+HS, and si-Nrf2+DEX prior to modeling on cell viability was assessed using CCK-8 assay. Oncosis characteristics were evaluated using transmission electron microscopy and Annexin V-FITC/PI flow cytometry. The oxidative stress markers (GSH, GSH-Px, MDA, SOD and ROS), mitochondrial membrane potential, energy metabolism, and inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the cells were quantified using standard kits, and the expressions of porimin, caspase-3 and Nrf2 pathway proteins were analyzed using Western blotting and qRT-PCR. RESULTS: HS induced typical oncotic features in HSKMCs including organelle swelling and cytoplasmic vacuolization. DEX pretreatment significantly attenuated these changes, reduced Annexin V⁺/PI⁺ cell ratio and cellular porimin expression, and lowered the levels of ROS and MDA while restoring GSH and SOD levels. DEX pretreatment also significantly increased the mitochondrial membrane potential and ATP level, upregulated the expressions of Nrf2, p-Nrf2, HO-1 and NQO1, and suppressed the expressions of TNF-α, IL-6 and IL-1β. The protective effects of DEX were obviously attenuated by interventions with ML385 or si-Nrf2. CONCLUSIONS DEX mitigates HS-induced HSKMC oncosis by activating the Nrf2/HO-1 pathway to relieve oxidative stress, mitochondrial dysfunction, and inflammatory responses.
Humans ; Dexmedetomidine/pharmacology* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects* ; Heat-Shock Response/drug effects* ; Signal Transduction/drug effects* ; Membrane Potential, Mitochondrial ; Muscle, Skeletal/cytology* ; Heme Oxygenase-1/metabolism* ; Apoptosis/drug effects*

OBJECTIVE: To elucidate the role and mechanism of microRNA-145-5p (miR-145-5p) in hypoxia-induced pyroptosis of human alveolar epithelial cells. METHODS: In vitro, human alveolar epithelial cell line BEAS-2B was cultured. Cells in the logarithmic growth phase were cultured to 80% confluence and then used for the experiment. (1) BEAS-2B cells were cultured under 1% O₂ hypoxic condition, with a normoxic control group. Western blotting was employed to detect the expressions of pyroptosis marker proteins [NOD-like receptor protein 3 (NLRP3), Gasdermin D N-terminal domain (GSDMD-N), and caspase-1] in cells cultured for 24 hours. Real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of miR-145-5p in cells cultured for 6 hours and 12 hours. (2) Cells were transfected with 30 nmol/L miR-145-5p mimic to overexpress miR-145-5p expression under normoxic condition or 30 nmol/L miR-145-5p inhibitor to suppress miR-145-5p expression under hypoxic condition. Control group and negative control group were respectively set up. After 24 hours of cell culture, Western blotting was used to detect the expressions of pyroptosis marker proteins and nuclear factor-E2-related factor 2 (Nrf2) in cells. Flow cytometry was applied to detect the level of reactive oxygen species (ROS) in cells. The target genes of miR-145-5p were predicted by miR target gene prediction software miRWalk and verified by Western blotting. (3) Under hypoxic condition, cells were transfected with 6.94 ng/μL silent information regulator 5 (Sirt5) overexpression plasmid or pretreated with 12.5 mmol/L N-acetyl-L-cysteine (NAC) as an ROS inhibitor. The empty plasmid group and control group were set up. After 24 hours of cell culture, Western blotting was used to detect the expressions of Sirt5, Nrf2, and pyroptosis marker proteins in cells. Flow cytometry was used to detect the level of ROS in cells. RESULTS: (1) Compared with the normoxic control group, the expression levels of pyroptosis marker proteins in the 24-hour hypoxia group was significantly increased, indicating that hypoxia could induce pyroptosis in BEAS-2B cells. The expression level of miR-145-5p in cells gradually increased with the extension of hypoxia induction time, indicating that hypoxia could cause the increase of miR-145-5p expression level. (2) The expression levels of pyroptosis marker proteins in cells of miR-145-5p mimic group significantly increased under normoxic condition as compared with the control and negative control groups [NLRP3 protein (NLRP3/β-actin): 1.58±0.07 vs. 1.00±0.01, 0.98±0.07, GSDMD-N protein (GSDMD-N/β-actin): 1.71±0.03 vs. 1.01±0.01, 0.85±0.03, caspase-1 protein (caspase-1/β-actin): 2.33±0.04 vs. 1.01±0.01, 1.05±0.04, all P < 0.05], Nrf2 protein expression level was significantly decreased (Nrf2/β-actin: 0.79±0.03 vs. 1.00±0.01, 1.03±0.04, both P < 0.05), ROS level was significantly up-regulated (fluorescence intensity: 1.74±0.03 vs. 1.00±0.01, 0.92±0.03, both P < 0.05). Under hypoxia condition, compared with control group and negative control group, the expression levels of pyroptosis marker proteins in miR-145-5p inhibitor group were significantly decreased [NLRP3 protein (NLRP3/β-actin): 0.21±0.04 vs. 1.70±0.02, 1.63±0.04; GSDMD-N protein (GSDMD-N/β-actin): 1.32±0.02 vs. 2.51±0.02, 2.72±0.03; caspase-1 protein (caspase-1/β-actin): 0.56±0.01 vs. 2.77±0.02, 3.12±0.03; all P < 0.05], Nrf2 protein expression level was significantly increased (Nrf2/β-actin: 1.57±0.04 vs. 1.22±0.01, 1.28±0.04, both P < 0.05), ROS level was significantly down-regulated (fluorescence intensity: 0.64±0.05 vs. 1.87±0.04, 1.70±0.07, both P < 0.05). The results indicated that miR-145-5p could promote cell pyrodeath. The predictive result of miRWalk showed that the 3' untranslated region (3'UTR) of Sirt5 had complementary base binding sites with miR-145-5p. The expression level of Sirt5 protein in cells of miR-145-5p mimic group was significantly lower than that of control group and negative control group under normoxic condition (Sirt5/β-actin: 0.59±0.03 vs. 1.00±0.01, 1.01±0.03, both P < 0.05), which verified that Sirt5 was the target gene of miR-145-5p. (3) The occurrence of pyrodeath could be partially reversed by transfection with Sirt5 overexpression plasmid or adding ROS inhibitor NAC into cells, and Sirt5 overexpression could also up-regulate Nrf2 expression and eliminate intracellular ROS. CONCLUSION In human alveolar epithelial cells, miR-145-5p can down-regulate Nrf2 by targeting Sirt5, thereby increasing ROS expression and inducing pyrodeath.
Humans ; MicroRNAs ; Pyroptosis ; Cell Hypoxia ; Alveolar Epithelial Cells/cytology* ; Cell Line ; NLR Family, Pyrin Domain-Containing 3 Protein ; Caspase 1/metabolism* ; Epithelial Cells/metabolism* ; Gasdermins ; Phosphate-Binding Proteins

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells