In the absence of biomarkers, the true biological footprint of migraine remains incompletely understood. It could perhaps be best characterized using machine learning models of multimodal data. The aim of this study was to (1) develop diagnostic models of migraine using multimodal data and (2) identify data-driven migraine phenotypes. This was a cross-sectional machine learning analysis of demographics, self-reported clinical and headache data, and genome-wide genotype data from the Trøndelag Health Study (data collected 1995-1997 and 2006-2008). All participants who were genotyped and completed the headache questionnaire were included. First, predictive machine learning models were developed using genotype data and general clinical data (excluding headache data) to diagnose individuals with migraine vs headache-free controls. Models were optimized on a training set and evaluated on a held-out test set, scored with the area under the receiver operating characteristic curve (AUC). Second, unsupervised models were trained on the headache data and the most predictive features from the diagnostic models to identify subgroups. The subgroups were compared using genome-wide association analyses, conventional polygenic risk scores (PRSs), and machine learning-based genetic risk scores. A total of 43,197 individuals were included in the diagnostic models, and 12,185 individuals were included in the data-driven phenotyping (mean [SD] age 49.1 [16.7] years; 51.7% women). The top-performing diagnostic model was a light gradient boosting machine, with a test set AUC of 0.80 (95% CI 0.78-0.81). Two main clusters were identified, one with 1,425 individuals, 94% of whom met diagnostic criteria for migraine, and another with 10,760 individuals, whereof 71% had nonmigraine headaches. The former was subclustered into 4 relatively distinct groups: one with only men, one with prominent neck pain, one with more musculoskeletal pain, anxiety and depression, and one with "classic" migraine. The groups were better discriminated by machine learning-based genetic risk scores compared with PRSs. Migraine can accurately be diagnosed from nonheadache data, suggesting that it is biologically describable by combinations of clinical, genetic, and environmental data. Data-driven phenotyping with such data identifies migraine subgroups with distinct phenotypic and genotypic signals, possibly not captured by current diagnostic criteria-but with potential implications for management.

The cost and complexity of phase 2 randomized-controlled trials (RCTs) hinder further development of promising treatment candidates for Alzheimer disease (AD). The Simon Two-Stage futility trial design, originally developed for oncology, offers a streamlined approach to evaluate potential disease-modifying therapies by comparing single-arm outcomes with historical controls, but is predicated on identifying outcome measures that reliably worsen with the natural history of the disease, with minimal risk of improvement. We sought to determine the feasibility of such futility trials in AD-associated dementia and mild cognitive impairment (MCI) using a large prospective cohort. We analyzed longitudinal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive decline was assessed using AD Assessment Scale-Cognitive Subscale (ADAS-Cog 11 and ADAS-Cog 13), Clinical Dementia Rating-Sum of Boxes (CDR-SB), and Mini-Mental State Examination (MMSE) at 6, 12, and 24 months using different thresholds for worsening vs improvement. Binary logistic regression models examined baseline factors associated with cognitive worsening using different thresholds of worsening for each outcome of interest to assess what additional selection criteria may be needed for futility trials in AD-associated dementia vs MCI. Sample size estimates were derived based on expected rates of decline. Among 2,665 participants (mean age 73.4 years [SD: 7.5], 1,260 [47.3%] female, 424 with AD-associated dementia), the CDR-SB exhibited the largest percentage of decline in AD-associated dementia and MCI, with 60.6% of patients with AD-associated dementia showing worsening when using a threshold of ≥1.0 points at 12 months vs 6.2% showing improvement. ADAS-Cog 11 and 13 showed similar decline patterns; for example, 41.7% with AD-associated dementia worsened by ≥ 5 points at 12 months on ADAS-Cog 13, whereas 5.8% improved. MMSE exhibited lower sensitivity; 25.8% with AD-associated dementia worsened by ≥ 5 points at 12 months, whereas 2.9% improved. Shorter trials (6-12 months) with 35-62 participants seemed feasible in AD-associated dementia, whereas MCI trials seemed to require 24 months and specific entry criteria based on age, apolipoprotein E ε4 status, and baseline CDR-SB performance. Futility trials seem feasible in AD-associated dementia, offering a faster, cost-effective alternative to traditional phase 2 RCTs. CDR-SB seems to be the optimal primary outcome. Further validation in clinical trial data sets is warranted.

Objective: To draw attention to the diagnosis of active Takayasu arteritis (TAK) in middle-aged and elderly patients and to analyze the clinical characteristics of this population. Methods: Clinical data of 106 patients newly diagnosed with TAK at Beijing Chao-Yang Hospital, Capital Medical University, between 2017 and 2025 were retrospectively collected; 11 patients aged over 50 years (2 men and 9 women) were enrolled in this study. Onset characteristics, medical history, clinical manifestations, laboratory findings, and imaging features were collected and analyzed. Disease activity was evaluated, treatment regimens and prognosis were recorded, and all patients underwent at least one follow-up. Results: Among patients first diagnosed with TAK at this single center, middle-aged and elderly patients with active TAK accounted for 10.40% (11/106) during the same period, with a median age at diagnosis of 61 years. Among them, 6 patients (6/11) were over 60 years old. The median time from symptom onset to diagnosis was 13 months (interquartile range: 12, 36 months). Although all 11 patients had multiple arterial involvements, none underwent complete evaluation of all arteries covered by the international criteria. Among the 8 patients who underwent CT pulmonary angiography (CTPA) or chest contrast-enhanced CT, all showed pulmonary artery luminal stenosis. All 8 patients who underwent contrast-enhanced magnetic resonance pulmonary angiography (MRPA) exhibited pulmonary artery wall thickening with enhancement and luminal stenosis. Of the 9 patients who underwent PET-CT, 7 showed pulmonary artery hypermetabolism. Among the 4 patients with elevated levels of multiple autoantibodies, 2 were male (2/2) and 2 were female (22.2% of female patients, 2/9). Moreover, both male patients had severe TAK-related complications (one with an abdominal aortic aneurysm and the other with pulmonary hypertension). Conclusion: Active TAK can occur in individuals over 60 years of age and the disease may be more severe in middle-aged and elderly male TAK patients. Middle-aged and elderly patients with active TAK require comprehensive evaluation of arterial involvement with modalities such as ultrasound, so as to enhance the capability of clinical differential diagnosis. For patients presenting primarily with respiratory symptoms, CTPA and MRPA should be performed to clarify pulmonary artery involvement in TAK.

Lipid peroxidation marker malondialdehyde is an independent determinant of hepatitis B vaccine response in hemodialysis patients.

Strategies to enhance DNA vaccine efficacy against emerging arboviruses: lessons from ZIKA and Chikungunya viruses.

Since the release of the Evidence-based guidelines for diagnosis and treatment of demyelinating optic neuritis in China (2021), significant progress has been achieved in the diagnostic classification, biomarker detection and targeted therapy of optic neuritis. A quantitative evaluation system combining multimodal imaging and serological antibody testing has been established for clinical application. The updated McDonald criteria have incorporated the optic nerve into the lesion localization of multiple sclerosis. Detection of aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies serves as a key tool for the definitive diagnosis of neuromyelitis optica spectrum disorder and MOG antibody-associated disease. Plasma exchange can improve the prognosis of severe cases, and biological agents represent the first-line therapeutic strategy for AQP4-positive patients. Considering the current domestic status of antibody detection capabilities and drug accessibility, this article proposes implementing routine antibody screening at initial diagnosis, optimizing multidisciplinary collaboration models, and constructing a real-world clinical data system.

To analyze the clinical phenotype and genetic etiology of patients with Dyggve-Melchior-Clausen syndrome (DMC syndrome). A child with DMC syndrome diagnosed at Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University in August 2020 was selected as study subject. A retrospective analysis was carried out to collect the proband's clinical data. Peripheral blood samples was collected from the proband and his parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out. Candidate variants were validated within the family by Sanger sequencing. Pathogenicity of candidate variants was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the center (Ethics No.: SCMCIRB-K2023024-1). The proband, a 5-year-and-7-month-old girl, presented with short stature (height: -5.5 s) and intellectual disability. Physical examination revealed microcephaly (head circumference: -3.5 s), coarse facial features, long philtrum, pigeon chest, and brachydactyly of both hands. Laboratory findings revealed normal serum insulin-like growth factor-1 (IGF-1) levels (168 ng/mL). Imaging analysis demonstrated dysplasia of corpus callosum and spondyloepiphyseal dysplasia in the proband. WES revealed that she has harbored compound heterozygous variants of the DYM gene, namely c.312-313del (p.His104Glnfs*29) and c.1274A>T (p.Tyr425Phe). Both variants were unreported previously and inherited from her parents who were phenotypically normal. Based on guidelines from the ACMG, the DYM gene variant c.312-313del (p.His104Glnfs*29) was classified as pathogenic (PVS1+PM2_Supporting+PP3+PP4_supporting), while the c.1274A>T (p.Tyr425Phe) variant was classified as likely pathogenic (PM2_Supporting+PP3+PP1+PP4_supporting). By following the pre-set literature search strategy, a total of 20 articles were included, which involved a total of 73 cases of DYM gene variants leading to DMC syndrome. Among these, only one family case was documented in China. Together with proband from this study, a total of 74 DMC syndrome patients due DYM gene variants were included for a comprehensive analysis of clinical phenotypes and genetic characteristics. The age at the time of reporting ranged from 1 to 60 years. The main clinical manifestations included intellectual disability, short stature, and spondyloepiphyseal dysplasia, followed by microcephaly and coarse facial features. By genetic testing, c.1877delA variant was the most common mutation at the nucleotide level. The c.312-313del/c.1274A>T compound heterozygous variants of the DYM gene probably underlay the pathogenesis of DMC syndrome in this proband. Above finding has expanded the mutational and phenotypic spectra of the DMC syndrome.

To investigate the genetic and clinical characteristics of two Chinese pedigrees exhibiting β-thalassemia traits due to variants of SUPT5H gene and conduct a literature review. Two pregnant women and their family members with abnormal thalassemia screening results were selected as study subjects. Clinical data were collected, and peripheral blood DNA was extracted for thalassemia-targeted gene testing and whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Pathogenicity of the candidate variants were rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). A literature review was also carried out on SUPT5H variants associated with thalassemia by searching the PubMed database. This study was approved by the Ethics Committee of Bao'an Women's and Children's Hospital [Ethics No.: LLSC-2025-02-05-15-KS]. Both probands exhibited mild anemia during pregnancy, which was characterized by typical hypochromic microcytic anemia, while no pathogenic variant was detected in the HBB gene. WES and Sanger validation of family members revealed two nonsense variants (SUPT5H: c.1195C>T, p.Gln399*) and (SUPT5H: c.397C>T, p.Arg133*) in the two pedigrees. Carriers from both pedigrees exhibited elevated hemoglobin A2 (Hb A2) and reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Literature review has identified 68 cases of SUPT5H gene variants involving 35 types. Nearly all carriers had elevated Hb A2 levels, 85.2% (58/68) carriers showed decreased MCV or MCH, and 3 cases with concurrent HBB gene variants exhibited significantly lower hemoglobin levels. Loss-of-function variants of the SUPT5H gene may cause β-thalassemia-like phenotypes through a haploinsufficiency mechanism. Routine screening for thalassemia modifier genes, including SUPT5H, is recommended for individuals with unexplained β-thalassemia phenotypes in high-prevalence areas to prevent the birth of children with moderate-to-severe thalassemia.

Advanced therapeutic strategies and drug delivery approaches for management of oral submucosal fibrosis: a comprehensive review.

Model-guided design of lymphatic drug delivery systems using osmotic pressure, viscosity and lymph node size.

To compare the performance of copy number variation sequencing (CNV-seq) and chromosomal microarray analysis (CMA) for the analysis of abortive tissues. Tissue samples were collected from 396 patients with missed abortion who were treated at Yancheng Maternal and Child Health Care Hospital between January 2021 and July 2024. A retrospective analysis method was employed to gather relevant clinical data of the patients. 171 samples were detected by CNV-seq combined with short tandem repeat (STR) analysis, and 225 samples were detected by CMA. Differences between the two techniques, including the detection of chromosomal aneuploidies, structural aberrations [detection of CNVs of various lengths and different CNVs types], the types of chromosomal abnormalities across different ages and gestational weeks were comprehensively compared. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2024-LS-KYLX-010). Among the 396 samples, 256 cases were detected with chromosomal abnormalities, which yielded a detection rate of 64.6%. Among the 171 cases undergoing CNV-seq analysis, 107 (62.6%) were found with chromosomal abnormalities. Among the 225 cases undergoing CMA, 149 (66.2%) were found with chromosomal abnormalities. No significant difference was found between the two groups (Χ2 = 0.566, P > 0.05). Among the autosomal number abnormalities, trisomy 16 was the most common in both groups, followed by trisomy 22, and 45,X was the most common among the abnormal number of sex chromosomes. In cases of chromosomal structural abnormalities, the CNV-seq group detected 36 CNVs, while the CMA group detected 27 CNVs. In the comparison of CNVs between the two groups based on different genome lengths, when the genome length was 100 ~ 500 kb, the CNV-seq group detected more than the CMA group, there was a statistically significant difference (Χ2 = 4.974, P < 0.05). When the genome length was greater than 1 000 kb, the CMA group detected more than the CNV-seq group, there was a statistically significant difference (Χ2 = 5.24, P < 0.05). Compared to different types of detected CNVs, the CMA group detected more pathogenic CNVs than the CNV-seq group, there was a statistically significant difference (Χ2 = 10.176, P < 0.05), while the CNV-seq group detected more variants of uncertain significance (VUS) CNVs, there was a statistically significant difference (Χ2 = 9.625, P < 0.05). The comparison of two groups based on different types of chromosomal abnormalities shows that aneuploidy was the most common in both groups. The proportion of polyploidy abnormalities was higher in the CMA group than in the CNV-seq group, there was a statistically significant difference (Χ2 = 8.106, P < 0.05), and the proportion of chimerism was higher in the CNV-seq group than in the CMA group, there was a statistically significant difference (Χ2 = 6.888, P < 0.05). The comparison of chromosome abnormalities distribution by age group between the CNV-seq group and the CMA group showed no statistical significance in the four age groups of ≤ 24 years, 25 ~ 29 years, 30 ~ 34 years, and ≥ 35 years (P > 0.05). Comparison of chromosomal abnormalities detected in the two groups at different gestational weeks showed that the CNV-seq group had a significantly higher detection rate for the first 8 weeks than the CMA group (Χ2 = 8.419, P < 0.05), though no significant difference was found in the proportion of chromosomal abnormalities between the two groups for the 8 ~ 10 weeks, 10 ~ 12 weeks, and weeks after 12 (all P > 0.05). CNV-seq can detect chromosomal aneuploidies, mosaicisms and more VUS. The combination of CNV-seq and STR analysis can effectively detect chromosomal polyploidy. CNV-seq requires low sample quality and genomic DNA content while achieving high success rates. In the clinics, combined CNV-seq and STR analysis can serve an effective tool for genetic diagnosis of miscarriage tissues.

To explore the clinical phenotypes and genetic etiology of a child with MRXS34 syndrome due to a variant of NONO gene. A child patient who presented at Shanxi Provincial Maternity and Child Care Hospital on September 28, 2020 was selected as study subject. Clinical data of the child were retrospectively collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing of the family members. Pathogenicity of the variant was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the effect of the NONO gene variant on messenger RNA (mRNA) expression level in the proband, and complementary DNA (cDNA) sequencing was performed to validate the splicing patterns of the NONO gene variant in the proband. Using the keywords "NONO gene" "MRXS34" "developmental delay" "intellectual disability" and "congenital heart disease", a literature search was conducted in databases including the China National Knowledge Infrastructure(CNKI), Wanfang Data and PubMed databases to identify studies on the clinical and genotypic characteristics of children with MRXS34 caused by NONO gene variants. The search period was set from the inception of the databases to April 2025, and a comprehensive analysis of the findings from the identified studies was performed. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: IRB-KYHZ-2019-006). The proband, a 3-year-old male, exhibited global developmental delay, intellectual disability, facial dysmorphism, macrocephaly, corpus callosum dysgenesis, cavum septum pellucidum, atrial septal defect, tricuspid valve insufficiency with regurgitation, cryptorchidism, inguinal hernia, and anal cutaneous fistula. The results of WES and Sanger sequencing validation showed that the proband carried a heterozygous variant of the NONO gene c.577_581del (p.Val193fs), while both parents were wild-type, indicating that this variant was a de novo variant. According to the ACMG guidelines, this variant was classified as pathogenic (PVS1+PS2_Moderate+PM2_Supporting). RT-qPCR results showed that the relative mRNA expression level of the NONO gene in the proband was significantly lower than that in the control group of normal children, and cDNA sequencing results verified that the frameshift variant due to base deletion led to nonsense-mediated mRNA decay (NMD), causing premature termination of transcription without exon skipping at the splice site. Using the literature search strategy established in this study, a total of 15 studies on the clinical and genotypic characteristics of children with MRXS34 caused by NONO gene variants were identified, involving a total of 32 patients. Together with the proband of this study, a total of 33 patients were included in the comprehensive analysis. The results revealed a total of 23 types of variants involving the NONO gene. The main clinical manifestations of MRXS34 included developmental delay/intellectual disability (23/24, 95.8%), cardiovascular abnormalities (23/30, 76.7%), craniofacial/somatic malformations (21/24, 87.5%), and corpus callosum dysgenesis (16/21, 76.2%). The NONO gene variant probably underlay the pathogenesis of MRXS34 in this proband. The findings of this study has expanded of the variant and clinical spectra associated with the NONO gene.

To explore the clinical phenotype and genetic etiology of a fetus with autosomal dominant intellectual disability type 72 (MRD72) resulting from a variant of the SRRM2 gene. A Chinese pedigree with MRD72 (fetus) who had visited the Affiliated Women and Children's Hospital of Ningbo University in November 2024 was selected as study subject. Clinical data of the pedigree were collected. Amniotic fluid and peripheral blood samples were collected from the fetus and its parents for genomic DNA extraction. Whole-exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing of the family members and rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature on MRD72 were searched in domestic and international databases for a review. This study was approved by the hospital (Ethics No.: EC2023-094). The proband was a fetus of 25 weeks of gestation. Fetal echocardiography revealed a relatively small left atrium and left ventricle, along with a diminished aortic-to-pulmonary artery ratio. WES revealed that the fetus has harbored a heterozygous nonsense variant of the SRRM2 gene. Sanger sequencing confirmed both parents carried the wild-type alleles. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PVS1+PM2_Supporting) and has not been recorded in public databases. Bioinformatic analysis predicted amino acid 512 to be highly conserved across various species. According to the pre-set literature search strategy, 4 publications were retrieved, which involved 30 MRD72 patients from 27 pedigrees, In addition to this study, a total of 31 cases were included. Analysis of clinical features and genetic etiology showed that patients with MRD72 presented mainly with clinical manifestations such as mental and motor development delay, special facial features, speech/intellectual development delay, and obesity. The genetic etiology was all variants at relevant loci of the SRRM2 gene. The SRRM2 variant identified in this study is implicated as the genetic cause of MRD72 in the proband. Above results have expanded the mutational and phenotypic spectra of the SRRM2 gene.

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular features, and differential diagnosis of low-grade eosinophilic renal tumors associated with FLCN mutations. Methods: Clinical and pathological data from 18 cases of FLCN-mutation-associated low-grade eosinophilic renal tumors were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histological morphology and immunophenotyping were performed, and high-throughput targeted gene mutation sequencing was performed on all 18 cases. Results: Among the 18 patients, 13 were male and 5 were female, aged 55 (43, 62) years. Twelve cases were diagnosed with hereditary Birt-Hogg-Dubé (BHD) syndrome. Among patients with BHD syndrome, 10 had multifocal tumors and 7 had bilateral tumors. Of the 18 patients, 10 had typical hybrid eosinophilic/chromophobe tumors (HOCT), and 8 had unclassified eosinophilic tumors. Histologically, 10 cases of typical HOCT showed a characteristic "mosaic" pattern. The 8 cases of unclassified eosinophilic cell tumors were morphologically heterogeneous, including 4 cases resembling chromophobe renal cell carcinoma (ChRCC), 1 case resembling succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC), 2 cases rich in "histiocytic lakes," and 1 case with eosinophilic cell; all lacked the hybrid cell components and "mosaic" morphological features typical of HOCT. Immunophenotypically, in the 10 typical HOCT cases, L1CAM, E-cadherin, CD117, and CK7 predominantly showed "mosaic" -like immunohistochemical features, consistent with the histological morphology; Cathepsin K was diffusely moderate positive in 2 cases and focally positive in 3 cases; CD10 was positive in 2 cases. Eight cases of unclassified eosinophilic tumors partially lacked typical immunohistochemical features, and their immunophenotypes were inconsistent. Other commonly used immunohistochemical markers vimentin, CK20, Melan A, TFE3, and TFEB were all negative. Despite their heterogeneity, non-metastatic glycoprotein B (GPNMB) showed diffusely, strongly positive in both typical HOCT and unclassified eosinophilic cell tumors (18/18). Next-generation sequencing (NGS) confirmed the presence of pathogenic or likely pathogenic FLCN mutations in all 18 cases. Conclusions: FLCN-mutation-associated low-grade eosinophilic renal tumors show distinct histological morphology, immunophenotype, and molecular genetic characteristics. It is necessary to make differential diagnosis from morphologically similar renal tumors in clinical practice. GPNMB serves as an important auxiliary marker for diagnosis of FLCN-mutation-associated low-grade eosinophilic renal tumors. Clinical, molecular, and genetic testing should be integrated to assess potential association with BHD syndrome, for making a precise diagnosis.

Stenotrophomonas maltophilia complex is an important nosocomial cause of bacteraemia. The complex comprises multiple species, but their relative clinical and genomic significance remains unclear. We examined clinical and genomic differences between S. maltophilia and non-S. maltophilia species to better understand their virulence and implications for patient care. Hospitalized adult patients (≥ 21years) between January 2022 and June 2024 with Stenotrophomonas species bacteraemia were examined. Clinical data were extracted from electronic medical records. Whole-genome sequencing was performed on all isolates, with species assignment confirmed by average nucleotide identity. S. maltophilia and non-S. maltophilia species were compared. Fifty-three S. maltophilia complex isolates were identified, of which 45 had clinical data. S. maltophilia predominated (n = 32), followed by S. pavanii (n = 7), S. sepilia (n = 4), S. muris (n = 1), and S. geniculata (n = 1). S. maltophilia isolates formed multiple clades with diverse sequence types, consistent with both clonal expansion and ongoing diversification. Virulence genes, including stmPr, smoR, and iron acquisition-associated genes were conserved across S. maltophilia lineages, but stmPr1 was less frequently observed in non-S. maltophilia. Most infections were line-related. Pneumonia-associated bacteraemia appeared more frequently among with S. maltophilia infections. Polymicrobial bacteraemia appeared more commonly in non-S. maltophilia infections. Mortality was similar between groups, but recurrence of infection within one year occurred only in S. maltophilia. Compared with non-S. maltophilia, S. maltophilia appeared to be associated with pneumonia and recurrent bacteraemia episodes, although mortality was similar. These exploratory findings suggest potential differences within the complex, but require validation in larger studies.

Objective: To explore the efficacy of the implementation of quality control (QC) program for children with fulminant myocarditis (FM) on improving the survival rate, reducing mortality and complication rates, and to evaluate the feasibility of the QC protocol. Methods: A retrospective cohort study was conducted. A Clinical Medical Quality Control Scoring Scale for Pediatric Fulminant Myocarditis (the QC Scale) was implemented since January 2021. Clinical data and the QC Scale data of 187 children with FM admitted to 8 tertiary hospitals capable of pediatric extracorporeal membrane oxygenation (ECMO) treatment over 6 years were collected, including the pre-QC group (January 2018 to December 2020) and the post-QC group (January 2021 to December 2023). Independent-samples t-test, Mann-Whitney U test, Chi-square test or Fisher's exact test were used for intergroup comparisons; and multivariate Logistic regression was performed for risk factor analysis. The clinical characteristics of pediatric FM and the feasibility and clinical efficacy of the QC protocol were evaluated. Results: A total of 187 children with FM were enrolled, including 82 cases in the pre-QC period and 105 cases in the post-QC period. The age was (8±4) years, and the weight was (28±14) kg. There were 104 female cases (55.5%) and 83 male cases (44.5%). A total of 156 children survived and 31 died, with an overall in-hospital mortality rate of 16.6% (31/187). The completion rates of electrocardiogram or cardiac monitoring and echocardiography or non-invasive hemodynamic monitoring within 30 min after admission were 98.7% (81/82) and 92.6% (72/82) in the pre-QC group, compared with 96.2% (101/105) and 90.5% (95/105) in the post-QC group. The post-QC group showed significantly higher completion rates of blood lactate measurement and Glasgow Coma Scale assessment within 60 min of admission than the pre-QC group (86.5% (71/82) vs. 98.1% (103/105), 62.2% (51/82) vs. 81.9% (86/105), χ²=9.43, 8.72; P=0.002, 0.003). The pre-QC completion rates of reaching blood lactate ≤5 mmol/L, central venous oxygen saturation ≥65%, and urine output≥1 ml/(kg·h) at 12 h after treatment were 82.1%(46/56), 72.1%(31/43) and 72.7%(48/66), respectively, compared with 81.1%(77/95), 69.1%(47/68) and 80.9%(76/94) in the post-QC group. The time from admission to ECMO initiation was shorter in the post-QC group than in the pre-QC group ((11±17) vs. (7±10) h, t=2.09, P=0.037). The mortality rates were 22.0% (18/82) in the pre-QC group and 12.4% (13/105) in the post-QC group. Compared with the pre-QC group, the post-QC group presented decreased rates of pre-ECMO cardiopulmonary resuscitation, cerebral injury and severe renal injury (51.2% (42/82) vs. 28.6% (30/105), 19.5% (16/82) vs. 8.6% (9/105), 19.5% (16/82) vs. 8.6% (9/105); χ²=9.97, 4.76, 4.76, all P<0.05). Conclusions: The implementation of the QC protocol for pediatric FM improves the ability of organ injury identification and standardized treatment, facilitates timely ECMO initiation, reduces the occurrence of cardiac arrest and major complications, and is of great significance for improving long-term quality of life. The pilot hospitals achieves high completion rates of QC indicators, indicating good feasibility of the protocol.

Objective: To understand the etiological diagnosis, triggers for disease recurrence and treatment status of diffuse alveolar hemorrhage (DAH) in Chinese children. Methods: A retrospective cohort study was conducted. Clinical data, including baseline information, laboratory findings, chest imaging findings and treatment regimens were collected from 567 children with DAH admitted to 21 hospitals in China from 2002 to 2021. Cases with immune-related etiologies or undetermined etiological diagnosis were included and divided into two groups based on glucocorticoids treatment duration: ≥3 months group and <3 months group. The study period from January 2002 to December 2021 was divided into two time intervals: 2002-2011 and 2012-2021. The two groups were compared in terms of etiological diagnosis rate, initial and overall immunosuppressant use rate, disease recurrence rate and mortality rate. All group comparisons were performed using the χ² test. Results: Among the 567 children with DAH, 333 were male and 234 were female. The age at onset was 4.0 (2.1, 6.5) years and the follow-up duration was 4.4 (2.4, 7.2) years. A definite etiological diagnosis was established in 107 cases (18.9%), while 460 cases (81.1%) remained without a definite etiological diagnosis. Among the 494 cases (including idiopathic pulmonary hemosiderosis and those with undetermined etiological diagnosis), 389 cases (78.7%) were initially treated with glucocorticoids alone and 45 cases (9.1%) with a combination of glucocorticoids and immunosuppressants. Throughout the treatment, immunosuppressants were used in 132 cases (26.7%). Among the 549 cases (including immune-related cases and those with undetermined etiological diagnosis), 303 cases (55.2%) experienced recurrent exacerbation of the disease. The common triggers included respiratory infection in 193 cases (35.2%), glucocorticoid dose reduction in 103 cases (18.8%) and non-adherence to medication in 66 cases (12.0%). Eight cases were lost to follow-up. The mortality rate was 8.7% (47/541), with causes of death including end-stage lung disease with severe infection in 32 cases (5.9%), severe pulmonary hemorrhage in 12 cases (2.2%) and unknown cause in 3 cases (0.5%). Among those receiving glucocorticoids therapy, 373 cases were in the ≥3 months group and 125 cases in the <3 months group. The mortality rate in the ≥3 months group was lower than that in the <3 months group (P<0.01). There were 92 cases in the 2002-2012 group and 457 cases in the 2012-2021 group. The utilization rates of immunosuppressants in both initial treatment and the entire treatment course for children with immune-related and those with undetermined etiological diagnosis were higher in the 2012-2021 group than in the 2002-2012 group (both P<0.01). Conclusions: In China, pediatric DAH has complex etiologies and a definitive etiological diagnosis remains difficult to establish in some cases. Recurrent exacerbation is common and mainly due to the respiratory infection, glucocorticoids dose reduction and non-adherence to medication. Glucocorticoids remain the primary treatment, with combined use of immunosuppressants in some cases.

Objective: To analyze the risk factors for poor prognosis in children with steroid-resistant nephrotic syndrome (SRNS) and to construct and validate a prognostic model. Methods: A retrospective cohort study was conducted. Clinical data of 456 children with SRNS who were initially diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from January 2009 to December 2024 was collected, including general information, laboratory and pathological indicators, gene types, treatment, and prognosis. Follow-up was conducted for more than 12 months. The endpoint event was defined as a decrease in the estimated glomerular filtration rate (eGFR) of more than 30% compared to the baseline for three consecutive times (with an interval of at least one month between each measurement). The patients were divided into the event group and the non-event group based on whether the endpoint event occurred. Independent sample t-test, Mann-Whitney U test, test χ2, or Fisher's exact probability test were used for comparison between groups. Multivariate Logistic regression was used to rank the importance of variables to screen for characteristic variables. The top 6 ranked characteristic variables were used to construct four machine learning models using Python: extreme gradient boosting, random forest, support vector machine, and logistic regression. The area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, and F1 score were used to evaluate the discrimination and performance of the models. Calibration curves and clinical decision curves were drawn to assess the prediction accuracy and clinical net benefit of the models. The Shapley Additive Explanations (SHAP) method was applied to analyze the contribution of features. Results: Among the 456 children, 306 were male and 150 were female. The age of onset was 4.1 (2.3, 8.0) years, and the follow-up time was 2.2 (1.0, 4.0) years. There were 195 cases (42.7%) in the event group and 261 cases (57.3%) in the non-event group. The time of occurrence of the endpoint event in the event group was 1.0 (0.5, 2.5) years. Univariate analysis showed that there were statistically significant differences between the two groups in initial serum creatinine, initial eGFR, eGFR change rate after 3 months of treatment, gender, calcineurin inhibitor (CNI) treatment response, gene variation, white blood cell count, absolute monocyte count, blood urea nitrogen, and urine red blood cells (all P<0.05). The top 6 characteristic variables, including the eGFR change rate after 3 months of treatment, genetic variation, baseline eGFR, CNI treatment responsiveness, gender and baseline serum creatinine (the AUC decrease percentages of 20.1%, 9.4%, 1.6%, 1.0%, 0.3% and 0.1% respectively after permutation test). Among the four machine learning models, the random forest model performed the best (test set AUC was 0.77 (95%CI 0.73-0.81), accuracy 73.9%, specificity 78.5%, sensitivity 71.2%, and F1 score 68.9%). The Hosmer-Lemeshow test showed that the predicted risk and actual risk of the random forest model were in good agreement (χ2=7.72, P=0.461); the clinical decision curve showed that the random forest model performed best and had the highest net benefit within a certain threshold range (0-0.5). Through SHAP, it was determined that the eGFR change rate after 3 months of treatment, initial eGFR, gene variation, and CNI treatment response were important predictors of poor prognosis in SRNS (average SHAP absolute values were 0.18, 0.08, 0.07 and 0.02, respectively). Conclusions: A random forest model was constructed based on machine learning and explained using the SHAP method. The eGFR change rate after 3 months of treatment, initial eGFR, gene variation, and CNI treatment response are important factors affecting prognosis.

Objective: To summarize the clinical features, endoscopic characteristics, treatment and prognosis of cap polyposis (CP) in children. Methods: In this case series study, clinical data including clinical manifestations, laboratory tests, endoscopic examinations, pathological results, treatment plans and follow-up conditions of 6 CP children diagnosed at Xi'an Children's Hospital from January 2018 to August 2025 were summarized. Results: Among the 6 children, there were 5 males and 1 female, with the age range at diagnosis of 9.2 to 14.3 years. The symptoms included bloody stool in all 6 cases, diarrhea in 4 cases, prolapse of perianal masses in 2 cases, and malnutrition in 2 cases. Among the auxiliary examinations, 3 cases were positive for 13C-urea breath test, and 5 cases were positive for Helicobacter pylori (Hp) in gastric mucosa histopathology. Colonoscopy revealed irregular polyps covered with white mucus, with 3 cases involving the rectum and 3 cases involving both the rectum and sigmoid colon. Histopathology showed inflammatory polyps covered with fibrous purulent exudate. The treatment plan included Hp eradication, mesalazine, hormone enema, thalidomide, and endoscopic polypectomy. The symptoms of all 6 children improved. Five of the children underwent re-examination with colonoscopy. Among them, 3 cases showed small polyp-like protrusions, and 2 cases showed local intestinal mucosa with slight congestion. Conclusions: CP is rare in children, with hematochezia and diarrhea as the main clinical manifestations. Colonoscopy typically reveals polyps with mucus adhering to the surface. Diagnosis requires histopathological examination, and individualized treatment should be formulated based on the specific condition of the child.

Objective: To analyze the clinical diagnosis and treatment strategies for acquired tracheoesophageal fistula (aTEF) and bronchoesophageal fistula (aBEF) in children, and explore the value of interventional bronchoscopy in their management. Methods: A case series study analyzed the clinical data of 9 pediatric patients with aTEF and aBEF admitted to the Department of Respiratory Intervention and Department of Gastroenterology, Children's Hospital Affiliated to Shandong University, from February 2014 to July 2025. The clinical features, diagnostic and therapeutic processes, and treatment outcomes were summarized. Results: Among the 9 patients, 7 were male and 2 were female, the age of onset was 1.7 (1.0, 4.0) years. Etiologies included esophageal corrosive injury due to button battery ingestion (4 cases), and 1 case each of esophageal corrosive injury from caustic alkali ingestion, esophageal perforation by foreign body, fall from height, neck stab wound, and iatrogenic injury.Clinical manifestations: 6 cases of dyspnea, 5 cases of recurrent cough and choking during feeding. There were 6 cases of aTEF and 3 cases of aBEF. Seven patients underwent interventional therapy via bronchoscopy or gastrointestinal endoscopy: 4 cases received covered metallic stent placement via bronchoscopy for fistula occlusion, 1 case underwent titanium clip closure via gastroscopy, 1 case underwent mucosal deepithelialization combined with titanium clip closure via gastroscopy, and 1 case received combined bronchoscopic stent placement, epidermal growth factor injection, and gastroscopic titanium clip closure. Seven patients underwent surgical treatment, including aTEF or aBEF repair in 6 cases, gastric fundoplication with gastrostomy in 2 cases, and jejunostomy in 1 case. Conclusions: The management of aTEF, aBEF in children is challenging. For patients presenting with respiratory symptoms, palliative interventions such as airway-covered stent placement or gastroscopic fistula clip closure can be considered to occlude the fistula. A multidisciplinary collaborative approach is essential for managing children with aTEF, aBEF, improve nutrition and manage complications to enhance the quality of life of the pediatric patients.