Translational pediatrics最新文献

{"title":"Central nervous system post-transplant lymphoproliferative disorder relapse after pediatric liver transplantation: a case report and literature review.","authors":"Cheng Wang, Yilin Wang, Yunjia Xu, Zicong Li, Jian Jiang, Lingzhen Wang","doi":"10.21037/tp-2025-644","DOIUrl":"https://doi.org/10.21037/tp-2025-644","url":null,"abstract":"<p><strong>Background: </strong>Post-transplant lymphoproliferative disorder (PTLD) represents a potentially life-threatening and grave complication that can arise following solid organ transplantation (SOT). Clinically, extranodal involvement in PTLD is frequent, whereas involvement of the central nervous system (CNS) is relatively rare and frequently associated with a poor prognosis. Currently, there is no standardized therapeutic approach for CNS-PTLD.</p><p><strong>Case description: </strong>We report a pediatric patient who suffered from multiple recurrences of CNS-PTLD after liver transplantation. The patient was Epstein-Barr virus (EBV)-negative before transplantation but developed PTLD involving lymph node, liver, and multiple bones 2 years after liver transplantation, accompanied by elevated EBV-DNA in peripheral blood (PB). As the lesion was systemic and CD20-positive, we chose to use rituximab (RTX) monotherapy and achieved remission. However, after 3 cycles of RTX, the child developed neurological symptoms such as facial nerve palsy and mouth deviation. Brain magnetic resonance imaging (MRI) revealed a mass in the inner ear and thickening of the facial nerve, suggesting that the disease had invaded the CNS. Therefore, we upgraded the treatment plan to R-CHOP chemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), and achieved a complete remission (CR). Following 2 cycles of R-CHOP, the patient experienced facial nerve palsy again, and brain MRI indicated a lesion in the left cerebellopontine angle region, suggesting disease recurrence. Re-treatment with 4 cycles of R-CHOP provided minimal symptomatic relief, and follow-up MRI demonstrated progressive multiple intracranial lesions. Brain biopsy confirmed CNS-PTLD [EBV-positive Burkitt's lymphoma (BL)]. Due to the patient's resistance to standard chemotherapy (R-CHOP) and the limited location of the lesion in the CNS, we switched to a more central-permeable treatment regimen. Then the patient achieved CR following treatment with high-dose methotrexate (HD-MTX) combined with intrathecal methotrexate (IT-MTX), and subsequently underwent timely chimeric antigen receptor T-cell (CAR-T) therapy to consolidate the therapeutic effect and prevent recurrence. The patient currently maintains sustained CR.</p><p><strong>Conclusions: </strong>We observe that the combination of HD-MTX and intrathecal chemotherapy exhibits remarkable efficacy in managing post-transplant CNS-PTLD that is resistant to conventional R-CHOP chemotherapy. CAR-T therapy emerges as a potential option for patients suffering from relapsed or refractory CNS-PTLD.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"89"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a novel interpretable machine learning model integrating immune-inflammatory indicators for intravenous immunoglobulin resistance in Kawasaki disease.","authors":"Tongtong Shi, Fei Wang, Xinjiang An, Zhenzhou Wang, Yongmao Xu, Ling Niu, Yan Wang","doi":"10.21037/tp-2025-1-907","DOIUrl":"https://doi.org/10.21037/tp-2025-1-907","url":null,"abstract":"<p><strong>Background: </strong>Children with Kawasaki disease (KD) who are resistant to intravenous immunoglobulin (IVIG) therapy face a substantially increased risk of developing coronary artery lesions (CALs). Developing a robust predictive model to identify pediatric patients at high risk of IVIG resistance is crucial for optimizing clinical decision-making and improving prognosis. This study aimed identify risk predictors for IVIG resistance in children with KD and to establish and validate an interpretable machine learning (ML)-based predictive model for clinical application.</p><p><strong>Methods: </strong>Retrospective analysis was carried out on clinical data sourced from 1,584 KD patients who received initial IVIG treatment during their first hospitalization at Xuzhou Children's Hospital between January 2019 and December 2024. This cohort was randomly allocated into the training (70%) and test (30%) sets. Six distinct ML algorithms-Light Gradient Boosting Machine (LightGBM), Random Forest, eXtreme Gradient Boosting (XGBoost), Neural Network (NeuralNet), Support Vector Machine (SVM), and ElasticNet Logistic Regression-were employed to develop predictive models. Comparative performance was evaluated employing the area under the receiver operating characteristic curve (AUC). Then, SHapley Additive exPlanations (SHAP) were applied to quantify each variable's contribution to the optimal model.</p><p><strong>Results: </strong>The LightGBM model demonstrated superior discriminative performance, attaining an AUC of 0.832 [95% confidence interval (CI): 0.766-0.898] on the independent test set, with a sensitivity of 0.860 and a specificity of 0.639. SHAP summary plots revealed that the five most influential features predicting IVIG resistance were, in descending order: fever duration before initial IVIG, the neutrophil-to-lymphocyte ratio (NLR), interleukin-1β (IL-1β) level, albumin (ALB) level, and aspartate aminotransferase (AST) level.</p><p><strong>Conclusions: </strong>Our analysis identified five pivotal predictors (fever duration before initial IVIG, NLR, IL-1β, ALB, and AST) for IVIG resistance and validated an interpretable LightGBM model with satisfactory performance. This model shows potential for estimating the risk of IVIG resistance, thereby aiding in the personalized therapeutic strategies for children with KD.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"74"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal screening for Duchenne muscular dystrophy in eastern China: a closed prospective study.","authors":"Guling Qian, Rulai Yang, Xinwen Huang, Dingwen Wu, Kexing Fang, Zhengyan Zhao","doi":"10.21037/tp-2025-aw-808","DOIUrl":"https://doi.org/10.21037/tp-2025-aw-808","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD) is a progressive, lethal X-linked neuromuscular disorder with a worldwide incidence of 1:5,000. The early identification of DMD through newborn screening (NBS) has gained increased attention and interest due to the availability of new therapies. The study aimed to determine the analytical and clinical validity of screening for the muscular isoenzyme form of creatine kinase (CK) to identify newborns at risk for DMD using dried blood spots (DBSs) collected from a routine part of NBS. We also collected data on the prevalence of DMD in newborns in Zhejiang, China.</p><p><strong>Methods: </strong>A closed concurrent cohort study for Duchenne was introduced at The Children's Hospital Zhejiang University School of Medicine, China. Over an eight-month period, DBSs from the 42,862 male infants enrolled in the study were collected and tested for elevated CK using a prototype Genetic Screening Platform (GSP^®) Neonatal creatine kinase-muscle isozyme (CK-MM) assay following parental consent.</p><p><strong>Results: </strong>A total of 214 male infants had elevated CK-MM activity >400 ng/mL (~99.5th percentile). Eighty-six percent (184) of infants returned for further testing; 174 infants had normal serum CK, and ten infants had elevated serum CK. DMD was confirmed in eight patients by next-generation sequencing (NGS) of the <i>DMD</i> gene. Among the 30 patients that were lost to follow-up, DMD was confirmed in 3 by NGS. In total, 11 infants were diagnosed with DMD or Becker muscular dystrophy (BMD). Further examination of the cut-off value indicated that a CK-MM >700 ng/mL (~99.9th percentile) correctly identified all confirmed patients. Genetic testing could not be performed on all samples to more accurately verify the detection efficiency of CK-MM assay screening.</p><p><strong>Conclusions: </strong>This study successfully provides preliminary performance data for clinical application of the CK-MM assay as an NBS for DMD.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"72"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors for postoperative recurrence of thyroid cancer patients in children, adolescents, and young adults.","authors":"Mengran Tian, Xing Wan, Chuanxiang Hu, Jingtai Zhi, Linfei Hu, Xianhui Ruan, Ming Gao, Jingzhu Zhao, Xiangqian Zheng","doi":"10.21037/tp-2025-1-871","DOIUrl":"https://doi.org/10.21037/tp-2025-1-871","url":null,"abstract":"<p><strong>Background: </strong>The incidence of pediatric thyroid cancer increases sustainably in the past years. Pediatric thyroid cancer is different from adult thyroid cancer in pathophysiology, clinical characteristics and others, which determines the different treatment methods for pediatric thyroid cancer and adult patients. In order to avoid the overtreatment of younger patients, this study aims to explore the effect of clinically pathological features on postoperative recurrence of thyroid cancer in younger patients.</p><p><strong>Methods: </strong>A total of 234 patients ≤25 years and 311 patients >25 years of age with papillary thyroid carcinoma from Medical University Cancer Institute and Hospital were enrolled in the retrospective study. We retrospectively analyzed thyroid cancer patients, stratified by age (<18, 18-25, >25 years). Clinicopathological features were compared using log-rank tests; multivariable Cox regression identified recurrence predictors, and Kaplan-Meier analyses assessed recurrence-free survival (RFS).</p><p><strong>Results: </strong>Patients aged <18 and 18-25 years showed comparable clinical characteristics (only sex distribution differed, P=0.02), supporting a unified children, adolescents, and young adult (CAYA) cohort (≤25 years). CAYA patients exhibited higher rates of bilateralism, multifocality, papillary thyroid microcarcinoma, extrathyroidal extension, lymphatic metastasis, and recurrence. Lymphatic metastasis [Exp(B) =6.818, P=0.009] and lateral cervical lymph node (LN) dissection [Exp(B) =3.044, P=0.005] were independent recurrence predictors. Lymphatic metastasis (presence, ≥5 nodes, or lateral location) correlated with poorer RFS (P≤0.006).</p><p><strong>Conclusions: </strong>LN metastasis is an important risk factor for postoperative recurrence in CAYA patients, suggesting that preoperative attention should emphasize the assessment of LN metastasis, including the number and area.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"69"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome with aplasia cutis congenita due to PIK3R2 mutations: case report.","authors":"Yixuan Liu, Jing Zhang, Jie Leng, Peng Gou, Xinran Cheng","doi":"10.21037/tp-2025-aw-698","DOIUrl":"https://doi.org/10.21037/tp-2025-aw-698","url":null,"abstract":"<p><strong>Background: </strong>Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a rare congenital developmental disorder characterized by megalencephaly, polymicrogyria, posterior polydactyly, and hydrocephalus and driven by PI3K-AKT-mTOR pathway dysregulation. This report presents a case of genetically confirmed MPPH in which the patient also exhibited aplasia cutis congenita (ACC), a cutaneous phenotype rarely described in this syndrome.</p><p><strong>Case description: </strong>We describe a full-term female infant with macrocephaly [head circumference > +2 standard deviations (SDs)] and distinctive craniofacial features, including a prominent forehead, hypertelorism, and a low nasal bridge. Neuroimaging revealed bilateral perisylvian polymicrogyria, while developmental assessment indicated mild-to-moderate delay across multiple domains. Genetic testing identified a heterozygous c.1117G>A (p.G373R) mutation in PIK3R2 and confirmed it to be MPPH syndrome. Notably, a well-demarcated area of ACC was observed on the anterior neck. The patient was also found to have a patent ductus arteriosus (PDA). Such clinical findings have infrequently been described in the existing medical literature.</p><p><strong>Conclusions: </strong>This report highlights the co-occurrence of ACC and PDA in a patient with PIK3R2-related MPPH, suggesting a potential expansion of the phenotypic spectrum associated with this syndrome and may provide valuable reference for early diagnosis and genetic counseling. Continued systematic documentation and synthesis of the phenotypic spectrum are vital to strengthening diagnostic consensus for this rare disease.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"90"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of elective discontinuation, retreatment, and alternatives to surgery in childhood fibrosarcoma.","authors":"Adrián Ibáñez-Navarro, Angélica Villanueva Freije, Cristina Aguirre-Portolés, Antonio Pérez-Martínez","doi":"10.21037/tp-2025-aw-801","DOIUrl":"https://doi.org/10.21037/tp-2025-aw-801","url":null,"abstract":"","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"65"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transfer learning prediction of surgical necrotizing enterocolitis in preterm infants without pneumoperitoneum on abdominal X-ray.","authors":"Dayan Sun, Chuanping Xie, Yong Zhao, Junmin Liao, Yanan Zhang, Kaiyun Hua, Yichao Gu, Jingbin Du, Shuangshuang Li, Dingding Wang, Jinshi Huang","doi":"10.21037/tp-2025-1-867","DOIUrl":"https://doi.org/10.21037/tp-2025-1-867","url":null,"abstract":"<p><strong>Background: </strong>Necrotizing enterocolitis (NEC) remains a leading cause of mortality in preterm infants, with 30-39% requiring surgical intervention. However, existing models for predicting surgical NEC lack accuracy and clinical utility, especially for infants without pneumoperitoneum on abdominal X-ray (AXR). In this study, we aimed to develop a prediction model to earlier identify NEC requiring surgical intervention.</p><p><strong>Methods: </strong>All preterm infants diagnosed with NEC (modified Bell's stage ≥ II) without pneumoperitoneum on AXR from Beijing Children's Hospital between January 2016 to December 2022 were retrospectively reviewed. Demographic, perinatal, clinical, laboratory, and imaging findings were analyzed. Six machine learning (ML) algorithms-logistic regression, decision tree, random forest, support vector machine, multilayer perceptron, and extreme gradient boosting-were trained and optimized via ten-fold cross-validation. The best-performing support vector machine model was further enhanced using transfer learning. The optimal algorithm was deployed into a web-based graphical user interface (GUI) for real-time risk stratification.</p><p><strong>Results: </strong>A total of 144 preterm infants with NEC without pneumoperitoneum on AXR were included in our study, including the surgical NEC group (n=31) and the medical NEC group (n=113). Multivariate analysis identified lower gestational age (P=0.010), pregnancy vaginitis (P=0.014), respiratory support (P=0.005), positive abdominal examinations (P<0.001), elevated C-reactive protein (P=0.003), and turbid peritoneal fluid on abdominal ultrasonography (P<0.001), as independent risk factors for surgical NEC. Then we constructed six ML models to predict surgical NEC by utilizing five variables derived from clinical, laboratory, and imaging findings in NEC-afflicted infants. Of all the models, support vector machine achieved perfect discrimination and superior reproducibility across training and validation sets. The transfer-learning model, built on the support vector machine base, achieved superior performance in the training set [area under the receiver operating characteristic curve (AUC) =0.964, 95% confidence interval (CI): 0.921-0.995] and validation set (AUC =0.937, 95% CI: 0.829-1.000). SHapley Additive exPlanations analysis highlighted positive abdominal examinations, turbid fluid on abdominal ultrasound, and bowel sounds grades as the top predictors. Furthermore, we developed a transfer-learning based GUI for the predictive model to facilitate clinical application.</p><p><strong>Conclusions: </strong>This study pioneered an interpretable ML framework integrating multimodal data to predict surgical NEC with near-perfect discrimination. Furthermore, the transfer-learning based GUI represented a transformative approach to optimizing surgical timing.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"68"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Before biliary atresia is claimed as a phenotypic manifestation of the m.3243A>G variant, the causal relationship must be proven.","authors":"Josef Finsterer","doi":"10.21037/tp-2026-1-0033","DOIUrl":"https://doi.org/10.21037/tp-2026-1-0033","url":null,"abstract":"","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"93"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity and perioperative outcomes in pediatric laparoscopic appendectomy: a retrospective, propensity score-matched cohort study.","authors":"Jie Li, Jiandong Lu","doi":"10.21037/tp-2026-1-0023","DOIUrl":"https://doi.org/10.21037/tp-2026-1-0023","url":null,"abstract":"<p><strong>Background: </strong>The global surge in childhood obesity introduces new complexities to pediatric surgical management. While obesity correlates with adverse outcomes in adult appendectomy, its impact on pediatric laparoscopic appendectomy remains poorly defined due to methodological limitations in existing studies. This study aimed to isolate the independent effect of obesity on perioperative outcomes in children undergoing laparoscopic appendectomy using propensity score matching (PSM) that rigorously controls for confounding variables.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed 549 pediatric patients (aged 2-18 years) with acute appendicitis treated at a tertiary center [2021-2025]. Patients were stratified into two groups based on body mass index (BMI): the normal weight group (NW, BMI <85th percentile) and the overweight/obesity group (OW/OB, BMI ≥85th percentile). A 3:1 PSM balanced key covariates (age, perforation status, surgical approach, etc.), yielding 448 matched patients (327 NW; 121 OW/OB). Primary outcomes included operative time, blood loss, surgical site infection (SSI), and hospitalization duration.</p><p><strong>Results: </strong>After PSM, OW/OB patients had significantly longer operative time (median 45 <i>vs.</i> 41 min, P=0.02), higher absolute estimated blood loss (median 5 <i>vs.</i> 3 mL, P=0.001), and increased SSI rates (6.6% <i>vs.</i> 2.7%, P=0.04). However, blood loss per kilogram was similar (P=0.64), and no differences were found in overall complications (14.1% <i>vs.</i> 15.6%, P=0.89), Clavien-Dindo severity, length of stay (median 5.5 days both, P=0.93), or 30-day readmissions (0.8% <i>vs.</i> 0.9%, P>0.99).</p><p><strong>Conclusions: </strong>Obesity independently increases technical challenges (prolonged surgery and bleeding) and SSI risk in pediatric laparoscopic appendectomy but does not affect overall complication rates or recovery metrics such as hospitalization duration.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"80"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the expression and regulatory mechanisms of platelet miR-223-3p in hand, foot, and mouth disease (HFMD) complicated by encephalitis.","authors":"Chun-Yu Lu, Meng-Lu Cao, Dan-Dan Jin, Zhao-Fang Hui, Wen-Xin Shi, Wen-Hua Yan, Jian-Mei Tian, Fang-Fang Cheng","doi":"10.21037/tp-2025-aw-802","DOIUrl":"https://doi.org/10.21037/tp-2025-aw-802","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hand, foot, and mouth disease (HFMD) complicated by encephalitis is a severe condition with an acute onset, yet its pathogenesis remains incompletely understood. This study aimed to investigate the role of platelet miR-223-3p in HFMD complicated by encephalitis. We sought to determine its expression dynamics, verify its direct target F-box and WD repeat domain containing 7 (&lt;i&gt;FBXW7&lt;/i&gt;), and elucidate its functional impact on neuronal apoptosis, thereby exploring a novel microRNA (miRNA) mediated mechanism in the pathogenesis of this severe complication.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We initially enrolled 20 children with HFMD complicated by encephalitis and 20 with uncomplicated HFMD. Platelet miRNA expression profiles were analyzed by high-throughput sequencing. Bioinformatics tools predicted key target genes, which were validated in a larger cohort (n=70) using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Gain- and loss-of-function models were established in SK-N-SH neuroblastoma cells by transfecting with an miR-223-3p mimic or inhibitor. A dual-luciferase reporter assay confirmed the direct targeting of &lt;i&gt;FBXW7&lt;/i&gt;. The effects on apoptosis were assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and by measuring the protein levels of B-cell lymphoma 2 (Bcl-2), BCL2-associated X protein (Bax), and cleaved cysteinyl aspartate specific proteinase-3 (caspase-3) via Western blot. Rescue experiments with an &lt;i&gt;FBXW7&lt;/i&gt; overexpression plasmid (OE-&lt;i&gt;FBXW7&lt;/i&gt;) were performed to confirm the specific pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Platelet miR-223-3p was identified as the most significantly upregulated miRNA in the encephalitis group. Its expression was elevated in the acute phase but decreased during recovery (P&lt;0.05). A significant negative correlation was observed between acute-phase miR-223-3p and whole-blood &lt;i&gt;FBXW7&lt;/i&gt; expression. Both messenger RNA (mRNA) and protein levels of &lt;i&gt;FBXW7&lt;/i&gt; were reduced by the miR-223-3p mimic and increased by its inhibitor (P&lt;0.05). The dual-luciferase assay confirmed &lt;i&gt;FBXW7&lt;/i&gt; as a direct target. Functionally, miR-223-3p overexpression suppressed apoptosis, as evidenced by decreased TUNEL-positive cells, increased Bcl-2, and decreased Bax and cleaved caspase-3 (P&lt;0.05). Conversely, both miR-223-3p inhibition and &lt;i&gt;FBXW7&lt;/i&gt; overexpression promoted apoptosis, and &lt;i&gt;FBXW7&lt;/i&gt; overexpression effectively reversed the anti-apoptotic effect of the miR-223-3p mimic.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our study demonstrates that platelet miR-223-3p is significantly upregulated in HFMD complicated by encephalitis. It promotes the pathogenesis of this condition by directly targeting &lt;i&gt;FBXW7&lt;/i&gt; and inhibiting mitochondrial pathway-mediated apoptosis. These findings highlight a novel role for platelet miRNAs in the neuropathogenesis of HFMD and suggest the miR-223-3p/&lt;i&gt;FBXW7&lt;/i&gt; axis as a potential t","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 3","pages":"78"},"PeriodicalIF":1.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}