Zhengzhou Children's Hospital

Platelets are crucial to the development of thrombosis and coagulation abnormalities in sepsis, but the mechanisms by which they contribute to these pathological processes are not fully understood. Here, we identify a key role for platelet-released heat shock protein 90α (HSP90α) in driving neutrophil extracellular trap (NET) formation and supporting thromboinflammation during sepsis. Proteomic analysis of platelets from patients with sepsis showed a significant increase in HSP90α, which we traced back to trafficking pathways originating from megakaryocytes. When activated, platelets translocate HSP90α to their plasma membrane and release it into the extracellular space in both free and exosome-associated forms. Extracellular HSP90α acts as a damage-associated molecular pattern that binds to toll-like receptor 4 (TLR4) on neutrophils. This binding activates a downstream MyD88-Beclin 1 signaling pathway, triggering autophagy and leading to NET formation. Blocking extracellular HSP90α with a neutralizing monoclonal antibody significantly reduced NET formation both in vitro and in vivo, resulting in decreased sepsis-related thrombosis and inflammation. This platelet-HSP90α-TLR4-autophagy-NET pathway not only deepens our understanding of platelet-induced immunothrombosis but also suggests potential targets for therapies aimed at reducing coagulation problems and organ failure in septic patients.

BackgroundMetagenomic next-generation sequencing (mNGS) plays a critical role in the rapid detection of infectious pathogens. We aimed to analyze the clinical characteristics of Pneumocystis jirovecii infection in children without HIV infection and to evaluate the performance of mNGS in distinguishing P. jirovecii colonization from true infection.MethodsA multicenter, retrospective analysis was conducted on critically ill, non-HIV-infected pediatric patients who tested positive for P. jirovecii via mNGS analysis of bronchoalveolar lavage fluid (BALF). Group differences were assessed using Mann–Whitney U-tests (for continuous data) and chi-square tests (for categorical data). Discriminatory performance was evaluated by calculating the area under the receiver operating characteristic curve.ResultsA total of 59 HIV-negative children (age range: 2 months to 14 years) from four children’s hospitals were included and classified into two groups based on P. jirovecii status: P. jirovecii pneumonia (PCP; n = 51) and P. jirovecii colonization (PCC; n = 8). Compared with the PCC group, the PCP group had significantly higher serum C-reactive protein levels and median P. jirovecii read counts in mNGS (both P < 0.05). The optimal threshold value for discriminating P. jirovecii infection from colonization appeared to be 556 reads (sensitivity, 77.6%; specificity, 100.0%). Eighteen patients (35.3%) in the PCP group died. Compared with survivors, these patients were significantly younger, had lower T-cell subset counts (CD3+, CD4+, and CD8+), and a higher prevalence of primary immunodeficiency (all P < 0.05).ConclusionsBALF mNGS analysis may have utility for differentiating between colonization and infection by P. jirovecii, warranting further investigation.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12890-026-04163-9.

EBV-CNS infectionmay bean independent risk factor for poor prognosis in pediatric EBV-HLH, underscoring the importance of CSF EBV-DNA testing, particularly in patients with high blood loads. Although intrathecal therapy effectively reduced CNS viral load and inflammation,its survival benefit requires further validation in large-scale prospective studies. • CNS involvement is a well-established poor prognostic factor in HLH. • EBV-CNS infection is an independent prognostic risk factor in adult EBV-HLH. • EBV-CNS infection is an independent prognostic risk factor in pediatric EBV-HLH. •While intrathecal therapy effectively reduces CSF viral load and inflammation, its survival benefit still requires further validation through large-scale prospective studies.

A novel ultrasound-assisted magnetic sorbent-wrapped stick dip extraction (UA-MSWS-DE) method was developed for the batch-scale determination of seven tyrosine kinase inhibitors (TKIs) in human plasma. The extraction device was fabricated by immobilizing octadecylphosphonic acid-functionalized magnetic nanoparticles onto flame-sealed glass capillaries embedded with magnets. Ultrasonic-assisted dip extraction was used to extract TKIs from diluted plasma, followed by quantification via liquid chromatography-tandem mass spectrometry (LC-MS/MS). Key extraction parameters were systematically optimized, yielding the following optimal conditions: sample pH 5.0 and volume 1.0mL, sorbent particle size 20nm and dosage 10mg, extraction time 20min, and desorption with 150 µL of ethanol for 8min. The method demonstrated excellent linearity (R2 ≥ 0.99), low limits of quantification (0.1-5.0ng/mL), and good intra-/inter-day precision (RSDs < 14.95%). The accuracy in blinded plasma samples, tested at 0.25-25% of the studied concentration range, ranged from 87.13 to 112.33%. Compared to conventional magnetic dispersive solid-phase extraction, the UA-MSWS-DE strategy simplifies handling and is designed to facilitate potential parallel processing using only an ultrasonic bath. Five greenness metrics confirmed the method's high sustainability. Furthermore, the modular design enables adaptation to other analytes by modifying the sorbent coating, making UA-MSWS-DE a sensitive, green, and automation-ready method for therapeutic drug monitoring.

Renal involvement in juvenile idiopathic arthritis (JIA) is uncommon (observed in 8.5% of our cohort) and may arise from either the disease itself or its medications. However, differences in renal manifestations across JIA subtypes remain poorly characterized. To investigate the prevalence, risk factors, and prognostic implications of renal involvement, and to characterize the nature of renal manifestations across JIA subtypes. A retrospective cohort study was conducted involving 376 JIA patients treated from May 2015 to May 2022. Data on medications, laboratory findings, subtypes, and disease activity were analyzed. Renal involvement rates by subtype were as follows: systemic JIA (SJIA, 16.2%), rheumatoid factor (RF)-positive polyarticular JIA (9.5%), enthesitis-related arthritis (ERA, 8.5%), oligoarticular JIA (OJIA, 6.3%), and RF-negative polyarticular JIA (3.4%). SJIA patients with renal involvement all had proteinuria and high serum amyloid A levels. All non-systemic JIA patients had hematuria (two with proteinuria). Only polyarticular JIA patients with renal involvement showed elevated interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels. In contrast, ERA and OJIA patients had no IL-6/TNF-α changes, regardless of renal involvement. ERA cases also had elevated serum IgA. Cox regression analysis revealed that elevated C-reactive protein (HR 1.039, p < 0.001), higher Juvenile Arthritis Disease Activity Score in 27 joints (HR 1.160, p < 0.001), and longer duration of active disease (HR 1.052, p = 0.008) independently predicted renal involvement, whereas biologics were protective (HR 0.394, p = 0.043). All patients were followed up for at least 24months. At final follow-up, renal involvement resolved in 81.3% of JIA patients, including all SJIA and OJIA cases, but only 25% of RF-positive polyarticular JIA patients. This study provides preliminary evidence of distinct patterns of renal involvement across JIA subtypes. The findings support the hypothesis that controlling active disease is important for renal outcomes. Future studies are needed to validate these subtype-specific mechanisms. Key Points • Renal involvement occurred in 8.5% of JIA patients, strongly associated with disease activity. • In SJIA with renal involvement, proteinuria is commonly observed and may be associated with amyloidosis. • ERA patients with renal involvement often present with hematuria, possibly due to IgA nephropathy. •RF-positive polyarticular JIA with renal involvement demonstrates elevated IL-6/TNF-α. Anti-CCP positivity predicts poorer outcomes, mandating intensified renal surveillance and aggressive inflammation control.

ObjectiveTo summarize the pathogen distribution, imaging features, radiologic outcomes, and risk factors for poor prognosis in children with infection-associated plastic bronchitis (PB).MethodsThis retrospective study included 86 hospitalized children diagnosed with infection-associated PB at Henan Children's Hospital from January 2021 to December 2023. Patients were grouped based on radiologic findings and outcomes into favorable prognosis, poor prognosis, and indeterminate outcome groups. Clinical data and laboratory results were compared between the favorable and poor prognosis groups to identify potential risk factors for adverse outcomes.ResultsAmong 86 children with infection-associated PB, 81 (94.2%) were caused by Mycoplasma pneumoniae (MP), including 29 (35.8%) co-infections. Of the MP-associated cases, 65 (80.2%) showed a good outcome, and 10 (12.3%) had unclear outcomes, while 6 (7.4%) developed adverse outcomes. These included 1 case requiring surgery, 3 with persistent atelectasis, 1 with both atelectasis and bronchiectasis, and 1 with persistent bronchiectasis. Patients with adverse outcomes exhibited significantly higher levels of LDH (788.5 U/L vs. 408 U/L, p = 0.01) and D-dimer (2.20 μg/mL vs. 0.81 μg/mL, p = 0.01) compared to the good-outcome group. The adverse-outcome group also required more bronchoscopic interventions (median 3.5 vs. 2, p < 0.01), higher glucocorticoid doses (methylprednisolone 20 mg/kg/day vs. 5 mg/kg/day, p = 0.01), and more frequent use of low molecular weight heparin (100% vs. 21.5%, p < 0.01) and intravenous immunoglobulin (50% vs. 9.2%, p = 0.02).ConclusionMycoplasma pneumoniae is the predominant pathogen in infection-associated PB. All patients with poor outcomes were infected with M. pneumoniae. Although most children responded well to treatment, a subset developed long-term complications such as bronchiectasis and atelectasis, even requiring lobectomy. Elevated LDH and D-dimer levels may serve as early biomarkers for predicting unfavorable outcomes.

Procalcitonin (PCT) elevation has been observed in non-infectious conditions. This study aimed to investigate the relationship between early-stage PCT levels and prognosis of acute necrotizing encephalopathy (ANE) in children. We enrolled children diagnosed with ANE who were admitted to the pediatric intensive care unit of Beijing Children's Hospital and Henan Children's Hospital between January 1, 2018 and December 31, 2023. Patients were categorized into survival and non-survival groups based on their 28-day outcomes. The optimal early PCT cutoff value was determined using receiver operating characteristic (ROC) curve analysis. A total of 74 children with ANE were included. Viral pathogens accounted for 79.7% (59/74) of infections. Antimicrobial therapy was initiated in 17 patients (23.0%, 17/74) at admission. The 28-day mortality rate was 55.4% (41/74). The optimal cutoff value of PCT was 3.55 ng/mL (area under the curve =0.689). The proportion of patients with shock at admission was significantly higher in the PCT >3.55 ng/mL group than the PCT ≤3.55 ng/mL group (45.7% vs. 21.4%, P=0.04). Multivariate logistic regression analysis revealed that PCT >3.55 ng/mL and shock at admission were independent risk factors for 28-day mortality (odds ratio =4.414, 95% confidence interval: 1.193-16.333, P=0.03; odds ratio =52.741, 95% confidence interval: 6.224-446.925, P<0.001). Early PCT >3.55 ng/mL was identified as an independent risk factor for 28-day mortality in children with ANE, and this should alert clinicians to the possibility of concurrent shock. The majority of PCT elevations were not attributable to bacterial infections in ANE patients.

AimTo analyze the clinical characteristics, antimicrobial therapies, and outcomes of neonates with carbapenem‐resistant Enterobacteriaceae (CRE) bloodstream infections.MethodsThis single‐center retrospective study included 22 neonates with CRE bloodstream infections at a tertiary children’s hospital in China (September 1, 2019–August 31, 2024). Data of clinical characteristics, risk factors, pathogens, carbapenemase testing, antimicrobial therapy, and outcomes were analyzed.ResultsAll 22 neonates had hospital‐acquired late‐onset infections (males, 77.3%; preterm infants, 81.8%). Prior to onset, 72.7% of the neonates had a history of broad‐spectrum antibiotic exposure. Klebsiella pneumoniae was the predominant pathogen (91.9%). Eighteen isolates underwent carbapenemase testing, with KPC being the most prevalent carbapenemase (66.7%). The antimicrobial agents were changed for 8 infants based on the carbapenemase testing results. Six neonates with KPC‐producing CRE infections received ceftazidime‐avibactam (CAZ‐AVI), and two neonates with NDM‐producing CRE infections were treated with CAZ‐AVI plus aztreonam. All 20 neonates who completed full treatment achieved clinical cure, while two neonates succumbed to infection before effective therapy initiation. The all‐cause mortality rate was 13.6%.ConclusionNeonates with immature immunity are more susceptible to CRE bloodstream infections, but clinical cure could be achieved after effective antimicrobial therapy. Carbapenemase testing plays a crucial role in the decision making on treatment of neonatal CRE infections.

Keratoconus (KC) is an intricate disease involving multiple factors. It is widely accepted that the pathogenesis of KC is linked to oxidative stress (OS). Nevertheless, the precise causal relationship between OS and KC remains uncertain due to the presence of confounding factors. This study aims to ascertain whether there was a potential causal effect between OS and KC. A bidirectional 2-sample Mendelian randomization (MR) analysis was conducted, utilizing genetic instrumental variables as substitutes for 12 oxidative stress injury biomarkers (OSIBs). The available summarized data for OSIBs were obtained through the published genome-wide association study. Data for KC was collected from the FinnGen cohort, comprising 311 cases and 209,287 controls of European population. The primary MR analysis employed the inverse variance weighted (IVW) method. To evaluate the reliability of the observed associations, sensitivity analysis and reverse MR analysis were performed. The MR analysis revealed significant associations. The IVW method suggested that elevated genetically predicted glutathione peroxidase levels were correlated with the diminished KC risk (odds ratio [OR]: 0.660, 95% confidence interval [CI]: 0.500–0.873, P = .004). Total bilirubin was also found to be associated with a decreased risk of KC through the IVW method (OR: 0.912, 95% CI: 0.845–0.984, P = .017), which was consistent with the result from the MR-Egger method (OR: 0.910, 95% CI: 0.835–0.992, P = .034). Reverse MR analysis did not suggest causal relationship of KC on OSIBs. These findings provide a robust support for the causal link between OSIBs and the development of KC, indicating that targeting OS pathways may become a potential therapeutic approach for KC.