Lipid metabolism plays an essential role in nervous system development. Cholesterol deficiency leads to a variety of neurodevelopmental disorders, such as autism spectrum disorder and fragile X syndrome. There have been a lot of efforts to search for biological markers associated with and causal to ADHD, among which lipid is one possible etiological factor that is quite widely studied. We aimed to evaluate the causal relationship between lipids traits, lipid-lowering drugs, and attention deficit hyperactivity disorder (ADHD) outcomes using Mendelian randomization (MR) studies. We used summary data from genome-wide association studies to explore the causal relationships between circulating lipid-related traits and ADHD. Then, quantitative trait loci for the expression of lipid-lowering drug target genes and genetic variants associated with lipid traits were extracted. Summary-data-based MR and inverse-variance-weighted MR (IVW-MR) were used to investigate the correlation between the expression of these drug-target genes and ADHD. After rigorous screening, 939 instrumental variables were finally included for univariable mendelian randomization analysis. However, there is no correlation between lipid profile and ADHD risk. Drug target analysis by IVW-MR method observed that APOB-mediated low-density lipoprotein cholesterol was associated with lower ADHD risk (odds ratio [OR] = 0.90, 95% confidence interval [CI] [0.84, 0.97]; p = .007), whereas LPL-mediated triglycerides levels were associated with a higher risk of ADHD (OR = 1.13, 95% CI [1.06, 1.21]; p < .001). Our results suggest that APOB gene and LPL gene may be candidate drug target genes for the treatment of ADHD.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Due to the complexity and severity, an early diagnosis is crucial to guarantee a good quality of life. Methods The GSE89632 dataset was downloaded from the Gene Expression Omnibus database and then screened for differential genes using different machine learning methodologies. Blood samples from 320 NAFLD patients and livers from 12 mice were collected for experimental validation. Results AP-1 transcriptin factor subunit (FOSB), glycerol-3-phosphate acyltransferase 3 (GPAT3), regulator of the cell cycle (RGCC), and ring finger protein 43 (RNF43) were the key diagnostic genes for NAFLD, and they were further confirmed by a receiver operating characteristic curve analysis. we found that our selected genes when combined together, exhibited a strong ability in identifying NAFLD samples from normal samples (AUC = 0.997) and experimentally examined the expression of these genes in NAFLD patients and NAFLD mice with the same results. Conclusions Data from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People's Hospital in 2021 (ChiCTR1900024415).

Serum 25-hydroxyvitamin D3 [25(OH)D3] concentrations have been associated with diabetic retinopathy (DR) severity. Blood cadmium has also been reported to be associated with the presence of DR. Besides, cadmium can decrease the formation of calcitriol (active vitamin D) in blood. However, the effect of blood cadmium on the association between 25(OH)D3 and DR severity has not been studied comprehensively. Therefore, we designed this cross-sectional study to assess the effect modification of blood cadmium on the association between 25(OH)D3 and DR severity in the U.S. population with type 2 diabetes (T2D). This study was conducted using NHANES from 2005 to 2008. By having stratified participants based on blood cadmium category (low blood cadmium<2.76 nmol/L; high blood cadmium≥2.76 nmol/L), we evaluated the difference (interaction test) between the relationship of 25(OH)D3 with the severity of DR among low blood cadmium and high blood cadmium participants using multivariable logistic regression. In this cross-sectional study, a total of 283 participants were included. In the high blood cadmium group, the odds ratio for severe non-proliferative retinopathy (NPDR)/proliferative retinopathy (PDR) of high 25(OH)D3 (≥50 nmol/L) group was 0.26 (95% CIs: 0.09-0.69, p=0.01) compared with the reference group (low 25(OH)D3 group). Furthermore, there was evidence of interaction between 25(OH)D3 and blood cadmium on decreasing the incidence of severe NPDR/PDR. Our study indicated that blood cadmium might affect the association of 25(OH)D3 with DR severity in participants with T2D. More randomized controlled trials are needed to provide more evidence of such a finding.

Abstract Background Tumor differentiation grade has been shown to be an independent prognostic factor in gastric cancer (GC). Here,we report a novel tumor differentiation grade-related genes signature to predict prognosis and provide new biomarkers in GC. Methods ScRNA-seq profiles of GC were analyzed by seurat package. Core modules and key genes related to tumor differentiation grade were identified through a weighted gene co-expression network analysis (WGCNA) from The Cancer Genome Atlas (TCGA) database. A prognostic signature associated with tumor differentiation grade module including COL5A1 was constructed in GC and validated. Results We identified the single-cell expression profiling and revealed the cell differentiation, cell clusters, marker genes in GC. Functional enrichment analysis revealed that common differentially expressed genes (DEGs) from cell transition trajectory were mainly enriched in neutrophil process. Integrating clinical factors in GC, WGCNA analysis indicated that tumor differentiation grade module was the most significant. We established and validated this signature based on ten tumor differentiation grade-related genes (TNFAIP2, MAGEA3, CXCR4, COL1A1, FN1, VCAN, PXDN, COL5A1, MUC13 and RGS2). Cox regression analysis showed that age, TNM stage and the risk score were significantly associated with prognosis. And then, these genes could predict prognosis in GC. Finally, the hub gene COL5A1 was a prognostic factor, and obviously correlated with B cells memory, dendritic cells activated, macrophages M0, macrophages M2, plasma cells, T cells follicular helper in GC. Conclusions This study reveals a novel tumor differentiation grade-related genes signature predicting prognosis in GC, and COL5A1 represents a promising biomarker for GC immunotherapy.

To examine the independent and interactive effects of maternal gestational diabetes mellitus (GDM) and high pre-pregnancy body mass index (BMI) on the risk of offspring adverse growth patterns. One thousand six hundred and eighty onemother-child pairs were followed for 8years in Tianjin, China. Group-based trajectory modelling was used to identify offspring growth patterns. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of GDM and high pre-pregnancy BMI for offspring adverse growth patterns. Restricted cubic spline was used to identify cut-off points. Additive interactions and multiplicative interactions were used to test interactive effects between GDM and high pre-pregnancy BMI for adverse growth patterns. Four distinct growth patterns were identified in offspring, including normal growth pattern, persistent lean growth pattern, late obesity growth pattern (LOGP), and persistent obesity growth pattern (POGP). Maternal high pre-pregnancy BMI was associated with LOGP and POGP (adjusted OR, 95% CI: 2.38, 1.74-3.25 & 4.92, 2.26-10.73). GDM greatly enhanced the adjusted OR of high pre-pregnancy BMI for LOGP up to 3.48 (95% CI: 2.25-5.38). Additive interactions and multiplicative interactions between both risk factors were significant for LOGP but not for POGP. Maternal high pre-pregnancy BMI was associated with increased risk of LOGP and POGP, whereas GDM greatly enhanced the risk of high pre-pregnancy BMI for LOGP.

Based on peripheral blood lymphocyte subsets and common laboratory test indexes, this study aimed to construct a predictive scoring system for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). Children hospitalized in Tianjin Children's Hospital from January 2021 to March 2023 were included in the study (185 cases of IVIG-sensitive KD and 41 cases of IVIG -resistant KD). Forty-six healthy children matched for age and gender were selected as controls. The relative percentage and absolute counts of peripheral lymphocyte subsets were measured by flow cytometry. Multivariate logistic regression was used to identify the predictive factors for IVIG-resistant KD and to construct a predictive scoring system for predicting IVIG-resistant KD. The multivariate logistic regression analysis showed that CD4+ T cell absolute count, natural killer cell absolute count, serum sodium level, globulin level, and total bilirubin level were identified as predictive factors for IVIG-resistant KD (P<0.05). The predictive scoring system based on these factors achieved a sensitivity of 70.7% and a specificity of 83.8% in predicting IVIG-resistant KD. Peripheral blood lymphocyte subsets can serve as predictive indicators for IVIG-resistant KD in children. The introduction of this indicator and the establishment of a scoring system based on it can provide a higher accuracy in predicting IVIG-resistant KD in children.

Introduction: Morganella morganii infection mainly occurred in elderly people and immunocompromised patients.However, the abdominal wall abscess due to Morganella morganii infection in prepubertal children hasn't been documented.Our presented case is a 4-year-old male patient with a 1 month history of left lower quadrant abdominal mass. Preoperative ultrasonography showed a hypoechoic, heterogeneous mass and the mass wasn't just confined to the abdominal wall, mimicking lymphoma. On CDFI, an image of highly vascularized mass was demonstrated. The patient underwent lump resection of abdominal wall.Postoperative process was uneventful except intermittent haematuria, and bladder sludge and urethral calculus on ultrasonography.By symptomatic treatment, haematuria disappeared and urethral calculus and bladder sludge decreased. Then the patient discharged home. Postoperative histopathology and immunohistochemistry were suggestive of abscess formation and Morganella morganii was isolated finally from the aspirated pus. Conclusion: Therefore, although the abdominal wall abscess due to Morganella morganii infection is rare, it should not be absent in the differential diagnosis of abdominal wall masses in children. Imaging features of abdominal wall masses should closely integrate the pertinent clinical history.

The lysine(K)-specific methyltransferase 2A gene (KMT2A), previously known as mixed lineage leukemia (MLL), frequently rearranged in acute leukemia, belongs to one of the most promiscuous genes and has been found fused to more than 80 different partners. KMT2A::SEPTIN6 fusion is a relatively uncommon rearrangement observed in pediatric acute myeloid leukemia (AML) patients, some of which may harbor other mutations. We herein report a case of AML-M4-infant with KMT2A::SEPTIN6 fusion and DIS3 variant. The 8-month-old girl presented with leukocytosis, anemia and thrombocytopenia. A bone marrow smear disclosed that 64% of the total nucleated cells were blasts. Karyotype analysis showed 46,X,t(X;11)(q24;q23)[10]/46,XX[10]. Fluorescence in situ hybridization analysis suggested a possible break in the KMT2A gene. After whole transcriptome sequencing, Exon 9 of KMT2A was fused in-frame with Exon 2 of SEPTIN6. This is a typical type of chromosomal rearrangement leading to the KMT2A::SEPTIN6 fusion. Meanwhile, DIS3 variant [c.2065C>T, p.R689X, variant allele frequency (VAF): 39.8%] was identified. KMT2A::SEPTIN6 fusion has been associated with the pathogenesis of AML, whereas DIS3 variants are relatively rare genetic events in pediatric AML. Regrettably, the relatives disagreed with the combination chemotherapy, and the patient eventually died of progressive disease. In conclusion, our findings provide a foundation for a better understanding of the genotypic profile of KMT2A::SEPTIN6 associated AML, and the co-existence of KMT2A::SEPTIN6 and DIS3 variant might contribute to the disease progression and transformation of AML.

Abstract Purpose of the study: In this study, our objective was to discover and immunologically profile clusters of molecules associated with copper-induced cell death in biliary atresia (BA) by employing a bioinformatics approach. We conducted an analysis of the GSE46960 dataset, sourced from the Gene Expression Omnibus (GEO), to gain insights into the involvement of copper-related molecular clusters in the development of BA. Study design: We conducted our study using liver samples collected from 64 children diagnosed with biliary atresia and compared them with 14 age-matched children suffering from other cholestatic diseases. Our investigation revolved around the identification of molecular clusters based on cuproptosis-related genes, while also examining the associated immune cell infiltration. To pinpoint genes specific to each cluster, we employed the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm. Results: We identified dysregulated cuproptosis-related genes and observed activated immune responses in the comparison between biliary atresia and non-biliary atresia control groups. Within biliary atresia, we categorized two distinct cuproptosis-related molecular clusters. Our analysis of immune infiltration indicated notable differences in immune profiles between these two clusters, with Cluster2 displaying relatively higher levels of immune infiltration. Functional analysis further revealed that the cluster-specific Differentially Expressed Genes (DEGs) in Cluster2 were closely associated with a variety of immune responses. Conclusions: Our study provides a comprehensive depiction of the intricate relationship between copper-induced cell death and biliary atresia. Previous research has suggested a potential link between the activation of the HIF-1alpha pathway and the development of biliary atresia, and the findings presented in this paper lend support to this hypothesis.

Background: We aimed to establish and validate diagnostic models for distinguishing bacterial/viral infections among sepsis neonates and also a model for prognostic evaluation. Methods: Training data sets (cohorts) of neonatal sepsis patients were derived retrospectively from 2017 to 2019, and the verifying sets were followed up from 2019 to 2021. The backward elimination method of logistic regression was used in identifying the optimum feature combination by adding all potential factors to the regression equation. Results: The current study established 3 models. For distinguishing bacterial sepsis patients and bacterial culture-negative patients, we found Y=1.930+0.105X1+0.891X2-1.389X3-0.774X4 (Y symbolizes the status of bacterial infectious sepsis, X1 is age increase, X2 is intra-amniotic infection (mother), X3 is vomiting sign, and X4 is cough sign). Similarly, for distinguishing bacterial infectious sepsis patients and bacterial/viral double-positive patients, we found Y=2.918+1.568X1+1.882X2-0.113X3-2.214X4-2.255X5-2.312X6 (Y means the bacterial/viral double-positive status, X1 is IL-6 increase, X2 means CRP increase, X3 means age increase, X4 means high fever sign, X5 is cyanotic sign, and X6 is HGB increase). For predicting hospital days as one of the prognoses, we found Y=-1.993+0.073X1+1.963X2+0.466X3-0.791X4-0.633X5 (Y means worse prognosis, which is hospital days longer than 7 days, X1 means age increase, X2 means intra-amniotic infection (mother), X3 is IL-6 increase, X4 is convulsion with unconsciousness, and X5 is cough sign). Then, the ROC curves of the models from the verifying cohort indicated that all of the 3 models had good performance among sepsis children. Conclusions: Two diagnostic models and one prognostic model were established for clinical reference from the current first-step analysis with excellent model performance, which could be suggested as new useful diagnostic tools and a therapeutic strategy guiding marker for neonatal sepsis in the future.