OBJECTIVES: To observe the therapeutic effect of spermine in neonatal mouse models of severe hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) infection and explore its therapeutic mechanism in light of regulation of macrophage GBP5/NLRP3 inflammasome pathway. METHODS: Neonatal BALB/c mice (3-5 days old) were divided into control group, EV71 infection group and Spermine treatment group. The mice in the latter two groups received an intraperitoneal injection of 50 μL EV71 suspension (1×10⁶ TCID50 of EV71), followed 3 days later by intraperitoneal injection of 50 μL PBS or 100 μmol/L spermine. GBP5, NLRP3, CXCL10, and TNFSF10 expressions in heart, liver, lung and kidney tissues of the mice were detected using Western blotting and qPCR, and tissue pathologies and macrophage infiltration were assessed with HE staining and immunohistochemistry. In cultured THP-1 and RAW264.7 cells, the effects of EV71 infection, GBP5 siRNA transfection and treatment with spermine or eflornithine on GBP5, NLRP3, CXCL10, and TNFSF10 mRNA expressions were investigated using qPCR. RESULTS: In the neonatal mice, EV71 infection resulted in multiple organ damage, macrophage infiltration and activation of the GBP5/NLRP3 pathway, and spermine treatment significantly improved tissue injuries, reduced macrophage infiltration, and down-regulated the expressions of GBP5, NLRP3 and the inflammatory factors in the infected mice. In THP-1 and RAW264.7 cells, EV71 infection caused significant upregulation of GBP5, NLRP3, CXCL10, and TNFSF10 expressions, which were obviously lowered by spermine treatment. In THP-1 cells, treatment with eflornithine significantly suppressed the reduction of GBP5, NLRP3, CXCL10, and TNFSF10 expressions induced by GBP5 siRNA transfection. CONCLUSIONS Spermine suppressed EV71 infection-induced inflammatory responses by inhibiting GBP5-mediated NLRP3 inflammasome activation, suggesting a new strategy for treatment of severe HFMD.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Mice ; Macrophages/metabolism* ; Enterovirus A, Human ; Mice, Inbred BALB C ; Inflammasomes/metabolism* ; Spermine/therapeutic use* ; Animals, Newborn ; Humans ; Enterovirus Infections ; Hand, Foot and Mouth Disease/drug therapy* ; RAW 264.7 Cells ; Chemokine CXCL10/metabolism*

OBJECTIVES: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

OBJECTIVES: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect. METHODS: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability. RESULTS: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential. CONCLUSIONS Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glucosides/pharmacology* ; Animals, Newborn ; Benzyl Alcohols/pharmacology* ; Amino Acid Transport System y+/metabolism*

INTRODUCTION: Paediatric patients admitted to the inpatient units from the emergency department (ED) are increasing, but the mean length of stay has fallen significantly. We aimed to determine the reasons behind paediatric one-day admissions in Singapore and to assess their necessity. METHODS: A retrospective study involving paediatric patients who were admitted from a general ED of an adult tertiary hospital to a paediatric tertiary hospital between 1 August 2018 and 30 April 2020. One-day admission was defined as an inpatient stay of less than 24 h from the time of admission to discharge. An unnecessary admission was defined as one with no diagnostic test ordered, intravenous medication administered, therapeutic procedure performed or specialty review made in the inpatient unit. Data were captured in a standardised form and analysed. RESULTS: There were 13,944 paediatric attendances - 1,160 (8.3%) paediatric patients were admitted. Among these, 481 (41.4%) were one-day admissions. Upper respiratory tract infection (62, 12.9%), gastroenteritis (60, 12.5%) and head injury (52, 10.8%) were the three most common conditions. The three most common reasons for ED admissions were inpatient treatment (203, 42.2%), inpatient monitoring (185, 38.5%) and inpatient diagnostic investigations (32, 12.3%). Ninety-six (20.0%) one-day admissions were unnecessary. CONCLUSION Paediatric one-day admissions present an opportunity to develop and implement interventions targeted at the healthcare system, the ED, the paediatric patient and their caregiver, in order to safely slow down and perhaps reverse the trend of increased hospital admissions.
Humans ; Retrospective Studies ; Singapore ; Child ; Emergency Service, Hospital/statistics & numerical data* ; Patient Admission/statistics & numerical data* ; Female ; Male ; Child, Preschool ; Length of Stay/statistics & numerical data* ; Infant ; Adolescent ; Tertiary Care Centers ; Hospitalization/statistics & numerical data* ; Infant, Newborn ; Gastroenteritis/therapy* ; Respiratory Tract Infections

Humans ; Ductus Arteriosus, Patent/therapy* ; Infant, Newborn ; Infant, Very Low Birth Weight ; Cardiac Catheterization/adverse effects* ; Consensus ; Infant, Extremely Low Birth Weight ; Hemodynamics

Humans ; Infant, Premature ; Patient Discharge ; Infant, Newborn ; Consensus ; Quality of Life ; Aftercare ; Infant, Premature, Diseases/therapy* ; Follow-Up Studies

Humans ; Pulmonary Valve Stenosis/therapy* ; Infant, Newborn ; Perioperative Care/standards* ; Consensus ; Balloon Valvuloplasty/methods* ; Pulmonary Valve/surgery*

OBJECTIVES: To study the clinical characteristics, efficacy, and prognosis of pediatric Langerhans cell histiocytosis (LCH). METHODS: A retrospective analysis was conducted on 72 children with newly diagnosed LCH. RESULTS: The median age of the 72 children was 5 years (range: 0-14 years), with skull involvement being the most common (56 cases, 77.8%). The BRAF-V600E mutation was not associated with clinical characteristics, efficacy, or prognosis (P>0.05). The 5-year overall survival rate was 91.6%±4.2%, and the 5-year event-free survival (EFS) rate was 67.5%±5.8%. The 6-week chemotherapy response rate and 5-year EFS rate were lower in the risk organ involvement group compared to the no risk organ involvement group (P<0.05). The five-year overall survival rates for the group with multi-system involvement and the group with platelet count ≥450×10⁹/L were respectively lower than those for the single-system involvement group and the group with platelet count <450×10⁹/L (P<0.05). Risk organ involvement is an independent risk factor for 5-year EFS (P<0.05). CONCLUSIONS Skull is the most commonly affected site in pediatric LCH. The BRAF-V600E mutation is not related to clinical characteristics, efficacy, or prognosis. Elevated platelet count, risk organ involvement, and multisystem involvement are associated with poor prognosis, with risk organ involvement being an independent risk factor for 5-year EFS.
Humans ; Histiocytosis, Langerhans-Cell/therapy* ; Child, Preschool ; Child ; Male ; Infant ; Female ; Adolescent ; Retrospective Studies ; Proto-Oncogene Proteins B-raf/genetics* ; Prognosis ; Infant, Newborn ; Mutation

OBJECTIVES: To summarize the clinical characteristics, diagnosis, and treatment outcomes of neonatal venous thrombosis. METHODS: A retrospective analysis was conducted on the clinical data of 11 neonates with venous thrombosis admitted to the Department of Neonatology of Anhui Children's Hospital from January 2019 to September 2024. The clinical characteristics, diagnostic approaches, treatments, and outcomes were analyzed. RESULTS: Among the 11 neonates diagnosed with venous thrombosis, 5 were male, and 6 were preterm infants, with a median gestational age of 35⁺⁶ weeks, birth weight of (2 322±1 069) g, and admission temperature of (36.6±0.4)°C. The median age at symptom onset was 6 days. Of the 11 cases, 8 limb venous thromboses and 1 portal vein thrombosis were confirmed by vascular ultrasound, and 2 cases of intracranial venous sinus thrombosis were confirmed by magnetic resonance imaging. Ten cases received low molecular weight heparin for anticoagulation, with a treatment duration of (24±15) days; 2 cases were treated with urokinase thrombolysis, and 4 cases received fresh frozen plasma transfusion. Thrombosis resolved in 7 cases before discharge. Partial resolution occurred in 2 cases before discharge (1 continued outpatient treatment until resolution and 1 resolved during follow-up). One case was transferred to another hospital after 1 day of treatment and was discharged after thrombosis reduction. No adverse reactions such as bleeding were observed. One neonate with cerebral infarction at admission did not receive heparin anticoagulation and was followed up as an outpatient. CONCLUSIONS Vascular ultrasound is the most commonly used diagnostic method for neonatal venous thrombosis. Heparin anticoagulation is the recommended treatment. The overall prognosis of neonatal venous thrombosis is favorable.
Humans ; Male ; Venous Thrombosis/drug therapy* ; Infant, Newborn ; Female ; Retrospective Studies

In order to effectively assist primary healthcare providers in promptly identifying neonatal pertussis and administering effective treatment to reduce the incidence of severe neonatal pertussis, the Subspecialty Group of Neonatology, Society of Pediatrics, Chinese Medical Association organized a panel of experts to develop the "Guideline for the diagnosis and treatment of common neonatal diseases in primary healthcare institutions: neonatal pertussis (2025)", based on the latest clinical evidence and expert consensus. This guideline provides primary healthcare providers with 14 recommendations addressing nine common clinical questions in neonatal pertussis.
Humans ; Whooping Cough/drug therapy* ; Infant, Newborn ; Primary Health Care