ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

The clinical data and genetic characteristics of one child with mental retardation-56 (MRD56) diagnosed at the Department of Neonatology, Foshan Fosun Chancheng Hospital in October 2021 were retrospectively analyzed.The patient was admitted to the hospital with " 34 + 2 weeks of preterm birth, shortness of breath, and dyspnea for 0.5 hours". In the neonatal period, the patient had special facial features, hypotonia, weaning and feeding difficulties, laryngeal stridor.In infancy, the patient showed global psychomotor development delay, intellectual disability, epilepsy, etc.Magnetic resonance imaging of the brain showed delayed myelination and dysplasia of the cerebellum and corpus callosum.Whole-exome sequencing showed that the CLTC gene had a new missense mutation c.3334T>C (p.Trp1112Arg), and MRD56 was confirmed.A total of 32 cases of MRD56 were reported worldwide, with special facial features, intellectual disability, and psychomotor retardation as the main clinical manifestations.The cause is a mutation in the CLTC gene, which leads to abnormality in the structure of the clathrin encoded, thus affecting neurotransmitter transmission.This is the first report of MRD56 caused by the CLTC gene mutation in China, and a new clinical phenotype has been discovered.The finding enriches the phenotypic spectrum of the disease and provides a basis for clinicians to understand and study the disease.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective:To investigate the feasibility and safety of high-speed railway (HSR) transport for critically ill pediatric patients.Methods:A single-center retrospective analysis was conducted.A total of 39 children transported via HSR (HSR group) and 420 children transported via ambulance (ambulance group) from May 2019 to December 2024 at the Seventh Medical Center of the PLA General Hospital were included.Demographic data,disease types,transport distances,and outcomes were compared between the two groups,and the vital signs,blood gas analysis,mechanical ventilation parameters,and vasoactive drug usage before and after HSR transport were also compared.Results:Over the five-year period,39 HSR transports and 420 ambulance transports were completed.No significant differences were observed in gender,age,or weight between HSR group and ambulance group( P>0.05).The proportion of circulatory system diseases was significantly higher in the HSR group (74.4% vs.55.1%, P = 0.020).HSR transports covered longer distances [855(855,1 075)km vs.84(23,273) km, P<0.001] and achieved faster speeds [150(150,216) vs.80(79,80)km/h, P<0.001].No significant differences were found in heart rate,body temperature,or diastolic pressure before and after HSR transport ( P>0.05).However,systolic blood pressure and partial pressure of oxygen increased slightly post-HSR transport [(82.97±15.44) vs.(85.15 ± 14.82)mmHg, P=0.003；(84.22±25.45)mmHg vs.(88.95±28.70)mmHg, P=0.029].Mechanical ventilation parameters remained stable during HSR transport ( P>0.05). Conclusion:HSR transport is feasible and safe for critically ill children and represents a promising option for long-distance interhospital transfers of pediatric patients.

Objective To investigate the incidence of ipsilateral upper urinary tract stones after partial nephrectomy and its risk factors.Methods We retrospectively analyzed baseline patient characteristics(age,gender,and body mass index),smoking,alcohol consumption,comorbidities(hypertension,diabetes,hypertriglyceridemia,hyperuricemia,and cardiovascular diseases),preoperative tumor conditions(tumor diameter,multiple foci,location,hemorrhage,necrosis,cystic changes,and endophytic growth),preoperative glomerular filtration rate and intraoperative factors(renal collecting system damage,ischemia time,operation time,surgical approach,and estimated intraoperative blood loss)to identify the risk factors for ipsilateral upper urinary tract stones following partial nephrectomy in our center.Results The overall incidence of upper urinary tract stones following partial nephrectomy was 7.80%(112/1435).The incidence of ipsilateral upper urinary tract stones was significantly higher than those of contralateral stones(4.95%vs 1.46%,P<0.001)and bilateral stones(4.95%vs 1.39%,P<0.001).Intraoperative damage to the renal collecting system was identified as a significant risk factor for ipsilateral upper urinary tract stones(OR=4.550,95%CI:2.237-9.252,P<0.001).Diabetes was a probable risk factor for secondary ipsilateral upper urinary tract stones after partial nephrectomy(OR=2.419,95%CI:0.973-6.012,P=0.057).Conclusions The incidence of ipsilateral upper urinary tract stones after partial nephrectomy is higher than that of contralateral and bilateral stones.Intraoperative renal collecting system damage is a risk factor for secondary ipsilateral upper urinary tract stones after partial nephrectomy.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

OBJECTIVE: To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021. METHODS: Using data from the Global Burden of Disease Study (GBD) 2021, the number of prevalent cases, prevalence rate, disability-adjusted life years (DALYs), and age-standardized DALY rates were analyzed by sex, age group, and province for headache disorders and their subtypes (migraine and tension-type headache [TTH]) between 1990 and 2021. Percentage changes during this period were also estimated. RESULTS: In 2021, approximately 426 million individuals in China were affected by headache disorders, with an age-standardized prevalence rate of 27,582.61/100,000. The age-standardized DALY rate for all headache disorders was 487.15/100,000. Between 1990 and 2021, the number of prevalent cases increased by 37.78%, while the prevalence of all headache disorders, migraine, and TTH increased by 6.92%, 7.57%, and 7.86%, respectively. The highest prevalence was observed in the 30-34 age group (39,520.60/100,000). Migraine accounted for a larger proportion of DALYs attributable to headache disorders, whereas TTH has a greater impact on its prevalence. In 2021, the highest age-standardized DALY rates for headache disorders were observed in Heilongjiang (617.85/100,000) and Shanghai (542.86/100,000). CONCLUSION The prevalence of headache disorders is increasing in China. Effective health education, improve diagnosis and treatment are essential, particularly for middle-aged working populations and women of childbearing age.
Humans ; China/epidemiology* ; Female ; Male ; Adult ; Middle Aged ; Prevalence ; Young Adult ; Adolescent ; Aged ; Child ; Headache Disorders/epidemiology* ; Disability-Adjusted Life Years ; Child, Preschool ; Cost of Illness ; Infant ; Aged, 80 and over

OBJECTIVES: To investigate the incidence of ipsilateral upper urinary tract stones after partial nephrectomy and its risk factors. METHODS: We retrospectively analyzed baseline patient characteristics (age, gender, and body mass index), smoking, alcohol consumption, comorbidities (hypertension, diabetes, hypertriglyceridemia, hyperuricemia, and cardiovascular diseases), preoperative tumor conditions (tumor diameter, multiple foci, location, hemorrhage, necrosis, cystic changes, and endophytic growth), preoperative glomerular filtration rate and intraoperative factors (renal collecting system damage, ischemia time, operation time, surgical approach, and estimated intraoperative blood loss) to identify the risk factors for ipsilateral upper urinary tract stones following partial nephrectomy in our center. RESULTS: The overall incidence of upper urinary tract stones following partial nephrectomy was 7.80% (112/1435). The incidence of ipsilateral upper urinary tract stones was significantly higher than those of contralateral stones (4.95% vs 1.46%, P<0.001) and bilateral stones (4.95% vs 1.39%, P<0.001). Intraoperative damage to the renal collecting system was identified as a significant risk factor for ipsilateral upper urinary tract stones (OR=4.550, 95% CI: 2.237-9.252, P<0.001). Diabetes was a probable risk factor for secondary ipsilateral upper urinary tract stones after partial nephrectomy (OR=2.419, 95% CI: 0.973-6.012, P=0.057). CONCLUSIONS The incidence of ipsilateral upper urinary tract stones after partial nephrectomy is higher than that of contralateral and bilateral stones. Intraoperative renal collecting system damage is a risk factor for secondary ipsilateral upper urinary tract stones after partial nephrectomy.
Humans ; Nephrectomy/methods* ; Retrospective Studies ; Risk Factors ; Male ; Female ; Case-Control Studies ; Middle Aged ; Aged ; Kidney Neoplasms/surgery* ; Adult ; Intraoperative Complications ; Kidney Tubules, Collecting/injuries* ; Propensity Score ; Incidence ; Kidney Calculi/etiology* ; Urinary Calculi/epidemiology*

Infancy is a critical period for children's growth and development. During this period，the reasonable increase of fat mass percentage and fat mass index is very important for children's healthy growth. However，excessive increases in fat mass percentage and fat mass index may increase the risk of metabolic related diseases. In China，the research field of body composition in infants is still in the development stage，and the relevant research results and literature are relatively few. This article summarizes the domestic and foreign research on infant body composition，including application techniques，influencing factors and application significance，so as to provide reference for the formulation of domestic infant body composition reference standards and related clinical and scientific research work.