Yan Li

Background: Infectious mononucleosis (IM) is a common disease in children; however, liver injury is its most common complication. However, the pathogenesis of IM complicated with liver injury is ambiguous. Thus, this study aimed to explore the potential mechanism of IM-associated liver injury. Methods: This study was conducted at the Children’s Hospital of Soochow University by collecting peripheral blood of 70 hospitalized children with IM. These patients were categorized into the liver injury (LIG, n = 35) and the non-liver injury groups (NLIG, n = 35), respectively. Subsequently, PBMCs and plasma were separated and obtained. PBMCs transcriptome sequencing was performed in two groups (5 cases in each group), and significantly differentially expressed genes (DEGs) were screened. Additionally, GO function enrichment, KEGG enrichment and GSEA analyses were performed. RT-PCR helped to detect the relative GBP5, NLRP3 and caspase-1 expressions in two groups (30 cases in each group) while the two groups’ caspase-1, IL-1β and IL-18 in plasma levels were measured by ELISA. Thus, clinical and laboratory datas of 60 hospitalized children with IM were evaluated. Results: Transcriptome sequencing results showed that 171 DEGs were screened in the NLIG group, compared with the LIG. Among them, 154 DEGs were up-regulated, and 17 were down-regulated, respectively. KEGG and GSEA analyses showed that IM-associated liver injury is correlated with a NOD-like receptor signaling pathway. Statistically significant differences were observed in the white blood cell and lymphocyte counts, CD3⁺CD4⁺ T cells, CD3⁺CD8⁺T cells, alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) of the two groups (p < 0.05). Compared with NLIG, GBP5, NLRP3 and caspase-1 expressions in PBMCs, as well as the caspase-1, IL-1β and IL-18 in plasma levels, were significantly higher in LIG (p < 0.001). A correlation analysis revealed a positive correlation of GBP5 with LDH, ALT, AST, CD3⁺CD8⁺T cells and NLRP3 (p < 0.05). Conclusions: Our findings demonstrate that GBP5 contributes to liver injury in IM children through the NLRP3-dependent pathway.

Purpose: Histiocytic necrotizing lymphadenitis (HNL), or Kikuchi-Fujimoto disease, is prone to recurrence in children. However, the frequency and risk factors associated with recurrence remain unclear. Patients and Methods: This study included all children with pathology-confirmed HNL from five hospitals over ten years (2013– 2023). This study employed STROBE analysis to investigate the association between clinical characteristics and HNL, which was subsequently verified through in both a derivation group and a validation group. Initial clinical features were collected, and data were randomly divided into derivation and validation sets (3:2 ratio). Cox regression analysis identified risk factors, and receiver operating characteristic curves were used to develop a prediction model. Flow cytometry focused on assessing CD4⁺ T-lymphocytes in lymphoid tissue. Results: Of the 593 HNL cases, 88 (14.8%) experienced recurrence during a median follow-up of 3 years. Cumulative recurrence rates at the first, fifth, and ninth years were 8.7%, 20.0%, and 32.2%, respectively. Factors associated with recurrence included age ≤ 6-year-old (Hazard ratio [HR] 3.6, 95% confident interval [CI], 2.0– 6.4), C-reactive protein > 16 mg/L (HR, 1.9, 95% CI, 1.0– 3.6), blood CD4⁺ T-lymphocytes ≤ 30% (HR, 4.4, 95% CI, 1.0– 18.7), ferritin > 150 μg/L (HR, 2.3, 95% CI, 1.1– 5.3) and platelets ≤ 200× 10⁹/L (HR 1.8, 95% CI, 1.0– 3.2). The prediction model demonstrated areas under the curve of 0.81 for the derivation dataset and 0.77 for the validation dataset, classifying patients into low, medium, and high-risk categories, with corresponding recurrence rates of 5.2%, 19.0%, and 42.9%. Lower lymphoid CD4⁺ T-lymphocyte counts were also observed in the recurrent group. Conclusion: The recurrence of HNL increases over time. Key factors, including C-reactive protein (CRP) levels, CD4⁺ T-lymphocyte counts, ferritin, platelets, and age at diagnosis may contribute to recurrence risk.

Background: To evaluate the risk of hemophagocytic lymphohistiocytosis (HLH) linked to Epstein-Barr virus (EBV) infection in different lymphocyte subtypes during infectious mononucleosis (IM). Methods: Patients with IM and patients with EBV-HLH were included within the Children's Critical EBV Infection cohort for a nested case-control study. Lymphocytes were isolated into T, B, and natural killer cells using magnetic bead sorting, followed by individual polymerase chain reaction testing. Receiver operating characteristic curve analysis identified subtype-specific cutoffs for EBV-HLH prediction. Kaplan-Meier and Cox regression analyses assessed viral load-HLH risk associations. Results: Patients with EBV-HLH exhibited significantly higher T-cell viral loads than patients with IM (median, 5.1 × 104 vs 6.0 × 102 copies/106 cells). A T-cell viral load >1.5 × 104 copies/106 cells was linked with higher incidences of viral sepsis, renal dysfunction, hepatic dysfunction, coagulation dysfunction, and cardiovascular dysfunction (odds ratios, 10.0, 4.7, 6.5, 15.7, and 6.5). This elevated T-cell viral load was a strong predictor for distinguishing EBV-HLH (AUC 0.815) and increased the risk of developing EBV-HLH (hazard ratio 4.7). Conclusions: High EBV DNA load in T cells can serve as a potential predictor for the development of EBV-HLH.

This case report presents a novel treatment approach for refractory purulent meningitis in a 1-month-old infant caused by penicillin-sensitive group B Streptococcus. Despite initial treatment with intravenous antibiotics, including penicillin and vancomycin, the infant experienced persistent symptoms and bilateral subdural effusions. Conventional therapies failed to resolve these issues, leading to the use of a new technique: subarachnoid puncture via the anterior fontanelle combined with intrathecal vancomycin administration. This minimally invasive procedure allowed for targeted antibiotic delivery, significantly reducing subdural effusions and improving cerebrospinal fluid parameters. The infant showed substantial clinical improvement and was discharged after 68 days with no complications during a 3-month follow-up. This approach offers a promising alternative to more invasive treatments such as craniotomy or subdural external drainage, though further research is needed to confirm its efficacy and safety in broader clinical contexts.

Objective: This study aims to enhance the management of Epstein‐Barr Virus (EBV) infections by analyzing the correlation between laboratory indicators and clinical manifestations in children, thereby proposing more precise diagnostic and treatment strategies.Methods: In this retrospective study included 163 pediatric patients with EBV infections treated at the Children's Hospital of Soochow University from December 2017 to December 2019. Data collected through retrospective analysis included gender, age, clinical symptoms, signs, liver function tests, T‐cell subset distribution, EBV‐DNA copy numbers in plasma, and treatment outcomes. Patients were grouped based on EBV‐DNA copy numbers in plasma and hospital stay duration to compare clinical indicators across different groups.Results: The dichotomous results of EBV‐DNA copy numbers in plasma showed that the two groups of children were significantly different in the number of days of fever (p = .0022), platelet count (p = .0212), ALT (p = .001), immunoglobulin IgM (p = .0039), IgG (p = .0195), TBiL (p = .025), LDH (p = 0.0001), and length of hospital stay (p < .001) were significantly different, indicating that EBV‐DNA copy numbers in plasma may be correlated with these characteristic variables. The dichotomous results of the length of hospital stay showed that the two groups were significantly increased in tonsil enlargement (p = .0024), platelet count (p = .0059), LDH (p = .0394), and ferritin (p = .0106) and EBV‐DNA copy numbers in plasma (p = 0.0361) were significantly different, This suggests a potential correlation between EBV‐DNA copy numbers in plasma and these clinical indicators.Conclusion: Variations in platelet counts and lactate dehydrogenase (LDH) levels in children with EBV infections may serve as indicators of clinical outcomes.

Objective: This study aims to enhance the management of Epstein-Barr Virus (EBV) infections by analyzing the correlation between laboratory indicators and clinical manifestations in children, thereby proposing more precise diagnostic and treatment strategies. Methods: In this retrospective study included 163 pediatric patients with EBV infections treated at the Children’s Hospital of Soochow University from December 2017 to December 2019. Data collected through retrospective analysis included gender, age, clinical symptoms, signs, liver function tests, T-cell subset distribution, EBV-DNA copy numbers in plasma and whole blood, and treatment outcomes. Patients were grouped based on EBV copy numbers and hospital stay duration to compare clinical indicators across different groups. Results: The dichotomous results of EBV plasma level showed that the two groups of children were significantly different in the number of days of fever (p= 0.0373), platelet count (p= 0.018), ALT (p= 0.0299), immunoglobulin IgM (p= 0.0323), IgG (p= 0.0299), TBiL (p= 0.0037), LDH (p< 0.001), number of CD19+ cells (p= 0.0204) and length of hospital stay (p< 0.001) were significantly different, indicating that EBV plasma levels may be correlated with these characteristic variables.The dichotomous results of the length of hospital stay showed that the two groups were significantly increased in tonsil enlargement (p= 0.0024), platelet count (p= 0.00449), LDH (p= 0.0394), CD3+ cell count (p= 0.0383), and ferritin (p= 0.0106) and EBV plasma levels (p< 0.001) were significantly different, This suggests a potential correlation between EBV plasma levels and these clinical indicators. Conclusion: Variations in platelet counts and lactate dehydrogenase (LDH) levels in children with EBV infections may serve as indicators of clinical outcomes.

Background: This study aimed to analyze the clinical features of children with lobar pneumonia caused by Mycoplasma pneumoniae (MP) infection, to explore the independent risk factors for bronchoscopic intervention in children with lobar pneumonia caused by MP infection. There is a lack of objective assessment tools to guide the use of bronchoscopy in clinical practice. For children with lobar pneumonia caused by MP infection, whether line shall be actively bronchoscope intervention therapy remains to be further defined. We also aimed to construct an early warning model of bronchoscopic intervention to provide an objective evaluation tool for clinicians. Methods: We collected the clinical data of 533 children with lobar pneumonia caused by MP infection. The patients were divided into three groups according to the interventional indications for bronchoscopy and whether they were treated with bronchoscopic intervention, and the clinical features and prognosis of the three groups were compared. A binary logistic regression analysis was performed on the indicators with a significance value of PResults: Children with lobar pneumonia caused by MP infection who demonstrated absolute indications for bronchoscopy exhibited more severe clinical manifestations, and children without absolute indications for bronchoscopy had a better prognosis even without bronchoscopic intervention. To establish our early warning model of bronchoscopic intervention for children with lobar pneumonia caused by MP infection, we used the following indices: C-reactive protein ≥20.94 mg/L (β₁=2.253) received 3 points, while a fever duration before bronchoscopy ≥6.5 d (β₂=1.424), lactate dehydrogenase ≥461.5 U/L (β₃=1.246), or fever (β₄=1.223) each received 2 points, and the complication of pleural effusion (β₅=0.841) received 1 point, for a total possible score of 10 points. Conclusions: When the score for the children with lobar pneumonia caused by MP infection was ≥6, the possibility of bronchoscopic intervention for treatment was >80%. The higher the score, the greater the possibility of bronchoscopic intervention.

Background: Three-dimensional (3D) culture has been reported to increase the therapeutic potential of mesenchymal stem cells (MSCs). The present study assessed the therapeutic efficacy of extracellular vesicles (EVs) from 3D cultures of human placental MSCs (hPMSCs) for acute kidney injury (AKI). Methods: The supernatants from monolayer culture (2D) and 3D culture of hPMSCs were ultra-centrifuged for EVs isolation. C57BL/6 male mice were submitted to 45 min bilateral ischemia of kidney, followed by renal intra-capsular administration of EVs within a 72 h reperfusion period. Histological, immunohistochemical, and ELISA analyses of kidney samples were performed to evaluate cell death and inflammation. Kidney function was evaluated by measuring serum creatinine and urea nitrogen. The miRNA expression profiles of EVs from 2D and 3D culture of hPMSCs were evaluated using miRNA microarray analysis. Results: The 3D culture of hPMSCs formed spheroids with different diameters depending on the cell density seeded. The hPMSCs produced significantly more EVs in 3D culture than in 2D culture. More importantly, injection of EVs from 3D culture of hPMSCs into mouse kidney with ischemia-reperfusion (I/R)-AKI was more beneficial in protecting from progression of I/R than those from 2D culture. The EVs from 3D culture of hPMSCs were more efficient against apoptosis and inflammation than those from 2D culture, which resulted in a reduction in tissue damage and amelioration of renal function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in EVs from 3D culture of hPMSCs, especially miR-93-5p. Conclusion: The EVs from 3D culture of hPMSCs have therapeutic potential for I/R-AKI.