OBJECTIVES: To investigate the expression of soluble factor-related apoptosis ligand (sFasL) in peripheral blood and microRNA-147b (miR-147b) in monocytes in children with sepsis and their value in assessing prognosis. METHODS: A prospective study was conducted on 124 children with sepsis (sepsis group), 60 children with common infections (infection group), and 60 healthy children undergoing physical examinations (healthy control group). The independent risk factors for poor prognosis in children with sepsis were analyzed, and the value of serum sFasL and monocyte miR-147b in predicting poor prognosis in children with sepsis was assessed. RESULTS: The serum level of sFasL and the relative expression of miR-147b in monocytes were highest in the sepsis group, followed by the infection group and the healthy control group (P<0.05). The multivariate logistic regression analysis showed that the serum level of sFasL and the relative expression of miR-147b in monocytes were closely associated with the poor prognosis of children with sepsis (P<0.05). The receiver operating characteristic curve analysis showed that the combination of serum sFasL level and relative expression of miR-147b in monocytes had a larger area under the curve compared to each indicator alone in predicting the prognosis of children with sepsis (P<0.05). CONCLUSIONS There are significant increases in the level of sFasL in peripheral blood and the relative expression of miR-147b in monocytes in children with sepsis. The combined use of these two indicators has relatively high clinical value in assessing the prognosis of children with sepsis.
Humans ; Sepsis/diagnosis* ; MicroRNAs/blood* ; Male ; Female ; Monocytes/metabolism* ; Prognosis ; Child, Preschool ; Prospective Studies ; Child ; Infant ; TNF-Related Apoptosis-Inducing Ligand/blood* ; Logistic Models

OBJECTIVES: To study the clinical and genetic characteristics of osteopetrosis (OPT) in children. METHODS: A retrospective analysis was performed on the clinical data of 14 children with OPT. Whole-exome sequencing was used to detect pathogenic genes, and clinical phenotypes and genotypic features were summarized. RESULTS: Among the 14 children (10 males and 4 females), the median age at diagnosis was 8 months. Clinical manifestations included systemic osteosclerosis (14 cases, 100%), anemia (12 cases, 86%), infections (10 cases, 71%), thrombocytopenia (9 cases, 64%), hepatosplenomegaly (8 cases, 57%), and developmental delay (5 cases, 36%). Malignant osteopetrosis (MOP) cases had lower platelet counts, creatine kinase isoenzyme, and serum calcium levels, but higher white blood cell counts, lactate dehydrogenase, and alkaline phosphatase levels compared to non-MOP cases (P<0.05). Genetic testing identified 15 variants in 12 patients, including 8 variants in the CLCN7 gene (53%), 6 in the TCIRG1 gene (40%), and 1 in the TNFRSF11A gene (7%). Three novel CLCN7 variants were identified: c.2351G>C, c.1215-43C>T, and c.1534G>A. All four patients with TCIRG1 variants exhibited MOP clinical phenotypes. Of the seven patients with CLCN7 variants, 4 presented with intermediate OPT, 2 with benign OPT, and 1 with MOP. CONCLUSIONS Clinical phenotypes of OPT in children are heterogeneous, predominantly involving CLCN7 and TCIRG1 gene variants, with a correlation between clinical phenotypes and genotypes.
Humans ; Osteopetrosis/genetics* ; Male ; Female ; Infant ; Child, Preschool ; Retrospective Studies ; Vacuolar Proton-Translocating ATPases/genetics* ; Child ; Chloride Channels/genetics* ; Mutation ; Receptor Activator of Nuclear Factor-kappa B

OBJECTIVES: To summarize the clinical and genetic characteristics of end-stage renal disease caused by PLCE1 gene mutations. METHODS: A retrospective analysis of the clinical and genetic features of three children from a family with PLCE1 gene mutations was conducted, along with a literature review of hereditary kidney disease cases caused by PLCE1 gene mutations. RESULTS: The proband was an 8-year-old male presenting with nephrotic syndrome stage 4 chronic kidney disease. Renal biopsy showed focal segmental glomerulosclerosis. Two years and five months after kidney transplantation, the patient had persistent negative proteinuria and normal renal function. Whole-exome sequencing identified two pathogenic heterozygous variants: c.961C>T and c.3255_3256delinsT, with c.3255_3256delinsT being a novel mutation. Family screening revealed no renal involvement in the parents, but among five siblings, one brother died at age of 4 years from end-stage renal disease. A 7-year-old sister presented with proteinuria and bilateral medullary sponge kidney, with proteinuria resolving after one year of follow-up. A 3-year-old brother died after kidney transplantation due to severe pneumonia. The literature review included 45 patients with hereditary kidney disease caused by PLCE1 gene mutations. The main clinical phenotype was nephrotic syndrome (87%, 39/45), and renal pathology predominantly showed focal segmental glomerulosclerosis (57%, 16/28). No mutation hotspots were identified. CONCLUSIONS Compound heterozygous mutations in the PLCE1 gene can lead to rapid progression of the disease to end-stage renal disease, with favorable outcomes following kidney transplantation. Family screening is crucial for early diagnosis, and medullary sponge kidney may be a novel phenotype associated with these gene mutations.
Humans ; Male ; Proteinuria/genetics* ; Kidney Failure, Chronic/etiology* ; Child ; Mutation ; Female ; Child, Preschool ; Retrospective Studies ; Phosphoinositide Phospholipase C

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

OBJECTIVES: To investigate the clinicopathological characteristics and prognostic factors of pediatric Hodgkin lymphoma (HL). METHODS: A retrospective analysis was conducted on the clinical data of children with newly diagnosed HL from January 2011 to December 2023 at four hospitals: Fujian Medical University Union Hospital, Fujian Medical University Zhangzhou Hospital, First Affiliated Hospital of Xiamen University, and Fujian Children's Hospital. Patients were categorized into low-risk (R1), intermediate-risk (R2), and high-risk (R3) groups based on HL staging and pre-treatment risk factors. The patients received ABVD regimen or Chinese Pediatric HL-2013 regimen chemotherapy. Early treatment response and long-term efficacy were assessed, and prognostic factors were analyzed using the Cox proportional hazards regression model. RESULTS: The overall complete response (CR) rates after 2 and 4 cycles of chemotherapy were 42% and 68%, respectively. Compared with the ABVD regimen group, patients treated with the HL-2013 regimen in the R1 group showed significantly higher CR rates after both 2 and 4 cycles (P<0.05). However, no statistically significant differences in CR rates were observed between the two regimens in the R2 and R3 groups (P>0.05). The 5-year event-free survival (EFS) rate, overall survival rate, and freedom from treatment failure rate were 83%±4%, 97%±2%, and 88%±4%, respectively. Cox analysis indicated that the presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy were independent risk factors for lower EFS rates (P<0.05). CONCLUSIONS Pediatric HL generally has a favorable prognosis. The presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy indicate poor prognosis.
Humans ; Hodgkin Disease/pathology* ; Male ; Child ; Female ; Adolescent ; Retrospective Studies ; Child, Preschool ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Infant

OBJECTIVE: To analyze two families with inherited dysfibrinogenemia, and explore the molecular pathogenic mechanisms. METHODS: The coagulation indexes of the probands and their family members were detected. The FGA, FGB, and FGG exons and their flanking sequences were amplified by PCR, and the mutation sites were identified by sequencing. SIFT, PolyPhen2, LRT, ReVe, MutationTaster, phyloP, and phastCons bioinformatics software were used to predict the functional impact of the mutation sites. Protein structure and amino acid conservation analysis of the variant were conducted using PyMOL and Clustal X software. RESULTS: The thrombin time (TT) of the proband in family 1 was prolonged to 37.00 s, and Fg∶C decreased to 0.52 g/L. The TT of the proband in family 2 was 20.30 s, and Fg∶C was 1.00 g/L, which was lower than the normal range. Genetic analysis revealed that the proband in family 1 had a heterozygous mutation c.80T>C in FGA, resulting in the substitution of phenylalanine 27 with serine (Phe27Ser). The proband in family 2 had a heterozygous mutation c.1007T>A in FGG, resulting in the substitution of methionine 336 with lysine (Met336Lys). Bioinformatics software prediction analysis indicated that both mutations were deleterious variants. PyMOL mutation models revealed that the Aα chain mutation (Phe27Ser) in family 1 and γ chain mutation (Met336Lys) in family 2 resulted in alterations in spatial structure and reduced protein stability. Clustal X results showed that both Aα Phe27 and γMet336 were highly conserved across homologous species. CONCLUSION Heterozygous mutations of FGA gene c.80T>C and FGG gene c.1007T>A are both pathogenic variants, causing inherited dysfibrinogenemia.
Female ; Humans ; Male ; Afibrinogenemia/genetics* ; Fibrinogen/genetics* ; Heterozygote ; Mutation ; Pedigree

Objective: To investigate the distribution of IgM anti-A/B titers among group O whole blood donors in Jiangsu, establish a low-titer threshold, and analyze the demographic characteristics of low-titer donors, so as to provide data for recruiting low-titer group O whole blood (LTOWB) donors. Methods: Plasma samples from 1 009 group O whole blood donors were tested for IgM anti-A and anti-B titers using the microplate technique. The distribution of antibody titers was analyzed to establish a low-titer threshold. The distribution trends of titers across different demographic groups were also analyzed. Results: The peak titer for anti-A, anti-B were 64 (31.5%), 4 (23.8%), respectively, The proportion of donors with both anti-A and anti-B titers below 64 was 97.3% (982/1 009). The mean anti-A titer was higher than anti-B titer. Anti-A titers were higher in female donors than in male donors (P<0.05). The anti-A titers differed significantly among different age groups (P<0.05). However, no significant difference in titers was observed based on the number of donations (P>0.05). Conclusion: A titer of 64 can be used as the reference threshold of LTOWB in Jiangsu. Male donors of appropriate age are more suitable than female donors for establishing an emergency panel of LTOWB mobile donors.

Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.

ObjectiveTo clarify whether epigallocatechin gallate （EGCG） is involved in the clearance of amyloid β-protein （Aβ） and autophagy induction by microglia， so as to explore the potential mechanisms of EGCG in the prevention and treatment of Alzheimer's disease （AD）. MethodsSix-month-old APP/PS1 mice were randomly divided into model and EGCG groups， with some additional wild type （WT） mice as the control group， each group consisting of 15 mice. The EGCG group received continuous gavage administration［5 mg/（kg·d）］ for 8 weeks， followed by the open field test and Y-maze to assess the learning and memory abilities of the mice. Thioflavin-S staining was used to evaluate the content and distribution of amyloid β-protein （Aβ）in the brain parenchyma of the mice， and immunofluorescence was employed to detect the expression levels of Aβ_1-42， glial fibrillary acidic protein （GFAP）， and ionized calcium-binding adapter molecule 1 （Iba1） in the hippocampal tissue of the mice. Additionally， N9 mouse microglial cells were induced with 20 µmol/L Aβ_1-42， and the cell viability was measured after treatment with different concentrations of EGCG （5 µmol/L， 10 µmol/L， 20 µmol/L）. Western blotting was used to detect the levels of Aβ_1-42， low density lipoprotein receptor-related protein 1（LRP1）， receptor for advanced glycation endproducts （RAGE）， amyloid precursor protein （APP）， insulin degrading enzyme （IDE）， neprilysin （NEP）， microtubule associated protein 1 hydrogen chain 3（LC3）-Ⅱ/LC3-Ⅰ， phosphatidylinositol 3-hydroxy kinase（PI3K）， p-PI3K， protein kinase B （AKT）， p-AKT， mammalian target of rapamycin （mTOR）， p-mTOR， and histone deacetylase 6（HDAC6）. Finally， through the co-culture of microglial cells and neuronal SH-SY5Y cells， cell viability and Caspase-3 levels were measured to verify the protective effect of EGCG-mediated Aβ clearance on neurons. ResultsEGCG increased the activity time and frequency of APP/PS1 mice in the central area of the open field （P<0.05）， and enhanced the percentage of alternation in the Y-maze test （P<0.01）； EGCG reduced Aβ deposition in the hippocampal tissue of APP/PS1 mice and increased the number of microglia； in vitro experiments showed that EGCG improved the survival rate of Aβ-induced N9 cells （P<0.01）， upregulated RAGE activity （P<0.05）， and promoted the internalization and phagocytosis of Aβ （P<0.01）. ECGC activated microglial autophagy by downregulating the level of HDAC6 （P<0.05）， inhibiting the phosphorylation of PI3K， AKT， mTOR （P<0.001）， and increasing the LC3-Ⅱ/LC3-I ratio （P<0.001）； EGCG improved the survival rate of SH-SY5Y cells （P<0.05） and reduced the activity of Caspase-3 （P<0.01） by clearing Aβ_1-42 through microglia， and had a protective effect on neurons. ConclusionEGCG activates microglial autophagy to clear Aβ by targeting and inhibiting the HDAC6-PI3K/AKT/mTOR axis.