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.

K777 promotes functional recovery after spinal cord injury via the PI3K/AKT signaling pathway.

Interstitial deletions involving 3q27.1 define a distinct microdeletion syndrome characterized by prenatal-onset growth restriction, postnatal microcephaly, hypotonia, intellectual disability, and distinctive craniofacial features. While AP2M1 haploinsufficiency has been proposed as the primary driver of this phenotype, the full spectrum of dosage-sensitive genes within the locus remains unclear. Here, we report a patient with a de novo heterozygous 3q27.1 microdeletion and delineate a refined minimal smallest region of overlap (SRO) of approximately 189 kb, representing the narrowest critical interval associated with the 3q27.1 microdeletion phenotype to date. Chromosomal microarray and exome-based CNV analysis confirmed the deletion, which encompasses PSMD2, EIF4G1, and POLR2H but excludes AP2M1 and DVL3. The patient exhibited severe intrauterine growth restriction, microcephaly, global developmental delay, and mild dysmorphism, consistent with the established 3q27.1 phenotype. PSMD2 encodes a non-ATPase regulatory subunit of the 26S proteasome, and its loss may disrupt proteasome-mediated protein turnover and neuronal homeostasis. Comparison with previously published cases and an overlapping ClinVar variant (ID: 60129) with similar features supports the pathogenicity of this minimal deletion. Our findings refine the 3q27.1 critical region, propose PSMD2 haploinsufficiency as a likely molecular mechanism underlying growth and neurodevelopmental defects. Further cases and functional studies are needed to confirm PSMD2 causality and clarify the proteasome-related mechanisms underlying 3q27.1 microdeletion syndrome.

Neuroinflammation plays an important role in the pathophysiology of depression. Interleukin-17A (IL-17A), an inflammatory cytokine, is strongly associated with depression; however, the potential mechanisms through which IL-17A in the brain regulates depressive symptoms remain unknown. Our study aimed at finding out the potential pathway through which IL-17A in the brain regulates depressive-like behaviours. Anti-despair-like behaviours, an important index for evaluating depression in mice, are present in IL-17A knockout mice. Given that the hippocampus is a brain region that is implicated in depression, the level of IL-17A in the hippocampus was evaluated in chronic unpredictable mild stress (CUMS) mice, and the results revealed increased hippocampal IL-17A levels. The expression of IL-17A was subsequently regulated by the stereotactic injection of multivesicular liposomes loaded with IL-17A recombinant protein as a sustained release system, and the AAV-il17a or AAV-shRNA(il17a) into the hippocampus. IL-17A overexpression induced despair-like behaviour, and the anti-despair-like phenotype in IL-17A knockout mice was blocked by the restoration of IL-17A expression in the hippocampus, which demonstrated the role of IL-17A in depression. Gene microarray, UPLC‒MS/MS, Western blot and patch clamp analyses were used to determine the pathway through which IL-17A regulates despair-like behaviours. Enhanced inhibitory synaptic transmission was detected in IL-17A-knockout mice. Furthermore, reducing the expression of the GABAA receptor α2 subunit (GABRA2) abrogated antidespair-like behaviour in IL-17A knockout mice, and hippocampal GABARA2 overexpression alleviated despair-like behaviour in CUMS mice. These results proved that GABRA2-mediated inhibitory synaptic transmission participated in the regulation of depressive-like behaviours by IL-17A. Our results revealed a vital role for IL-17A in depression and suggested that GABRA2 is the key molecule involved in the regulation of depression by IL-17A, indicating its potential as a therapeutic target for depression.

Many natural medicines exert therapeutic effects through multitarget regulation, and using methods that simply evaluate the effects of a chemical drug on several targets to study natural products may not comprehensively reflect their efficacy. This research attempts to explore and establish a new method to evaluate drug efficacy at the gene expression level using natural hepatoprotective drugs. Forty SPF male SD rats were randomly divided into a control group, a liver injury model group, a positive drug group (reduced glutathione), a curcumin treatment group and a puerarin treatment group. Carbon tetrachloride was used to damage liver cells and establish a liver injury model. Gene microarray technology was used to detect gene expression in liver cells. Drug treatments significantly reduced the number of differentially expressed genes in the liver compared with model group and efficacy evaluation of drugs were curcumin > positive control drug > puerarin. The liver function indices and pathological analysis also supported the above results. Our findings demonstrated that the efficacy of different drugs can be evaluated at the level of gene expression.

Copy number variations (CNVs) at the proximal 16p11.2 BP4-BP5 locus are among the most well-characterized genomic regions associated with neurodevelopmental disorders. We aimed to define the clinical and molecular spectrum of these CNVs in a pediatric cohort. A total of 19 patients with pathogenic or likely pathogenic 16p11.2 BP4-BP5 CNVs were identified among 2200 individuals referred for chromosomal microarray analysis (prevalence: 1/116, 0.86%). Deletions were detected in 16/19 (84.2%) patients and duplications in 3/19 (15.8%). Developmental delay/intellectual disability was observed in 12/16 (75%) deletion carriers and 3/3 (100%) duplication carriers. Speech delay was present in 12/16 (75%) and 3/3 (100%), and motor delay in 6/16 (37.5%) and 2/3 (66.6%), respectively. Seizures were identified in 11/16 (68.7%) deletion carriers and 1/3 (33.3%) duplication carriers. Behavioral abnormalities were observed in 6/16 (37.5%) and 2/3 (66.6%), respectively. Neuroimaging data were available in 7/19 patients, with abnormalities detected in 5/7 (71.4%), all of whom had a history of seizures. Structural findings were heterogeneous and included ventricular asymmetry, corpus callosum thinning, and prominence of cerebrospinal fluid spaces. Additional systemic findings included endocrine abnormalities (6/19, 31.6%), skeletal anomalies (4/19, 21.1%), and ophthalmologic findings (3/19, 15.8%). These findings expand the phenotypic spectrum of proximal 16p11.2 BP4-BP5 CNVs and support their early consideration in patients with neurodevelopmental and neurological features, highlighting the need for multidisciplinary evaluation.

Targeting UBE2T by β-elemene inhibits prostate cancer stem cells and bone metastasis by blocking the TRIM28/pGSK3β/β-catenin signaling.

The complex pathophysiological mechanism of end-stage renal disease (ESRD) has not been fully understood. Cuproptosis is a newly discovered type of programmed cell death. Therefore, this study attempts to clarify the relationship between cuproptosis-related genes (CRGs) and the phenotype of ESRD. The National Center for Biological Information Gene Expression Omnibus database was applied to obtain the GSE37171 dataset comprising whole-genome microarray analysis of peripheral blood samples. A 3:1 case-control design was employed with 75 ESRD patients and 20 healthy controls who were frequency-matched for age, sex, and ethnicity. Based on differentially expressed genes (DEGs) and genes related to cuproptosis, CRGs were identified. Thereafter, we explored two different subpopulations based on the cuproptosis gene and analyzed their expression and immune infiltration. Genes specific to the CRG cluster were identified through the weighted gene co-expression network analysis algorithm, and the best prediction model was determined and verified by four machine learning methods. The study identified 14 differentially expressed CRGs, among which ATP7B, SLC31A1, LIAS, LIPT1, DLD, MTF1, CDKN2A, DBT, and DLST had relatively high expression levels in the ESRD samples. Compared with the control group, expression levels of FDX1, DLAT, PDHA1, PDHB, and GLS were significantly lower in the ESRD group, and CRGs played a key role in the regulation of immune infiltration in ESRD. Two cuproptosis-related molecular clusters were identified in the ESRD samples. Cluster2 was more correlated with the immune infiltration of ESRD. By analyzing the intersection points between CRG cluster and key genes of ESRD, a total of 888 specific DEGs were identified. Functional differences related to specific DEGs were further explored using gene set variation analysis. Five significant genes (SMC5, USP47, USP53, AGA, and DMXL1) were identified by the support vector machine model as key predictors for ESRD disease risk, achieving an area under the curve (AUC) of 1.00 in internal validation. However, external validation in independent cohorts is required prior to clinical application. Individual gene analysis showed an AUC >0.81 in discriminating ESRD patients from healthy controls, and the expression of all 5 genes in ESRD patients was significantly lower than in the control group. This study clarified the relationship between CRGs and the phenotype of ESRD, analyzed their specific roles in the immune microenvironment, and obtained a predictive model, providing new insights for the study of its potential therapeutic targets.

Epidemiological studies have indicated a strong link between metabolic disease and an elevated risk of cancer. However, it has not been directly replicated in animal models, nor has its specific underlying mechanism been clarified. From our previous research, liver-specific SIRT1 knockout (LKO) mice developed hyperglycemia within two months and developed fatty liver with whole-body insulin resistance around nine months of age. When the mice's age extended to one year, they presented surprisingly higher lung tumor vulnerabilities in contrast to wild type as determined by macroscopic observation and histological examination. Interestingly, all lung tumors in these mice were classified as lung adenocarcinomas. Microarray analysis revealed elevated levels of MDM2, an oncoprotein, leading to the downregulation of its target genes such as p21 and GADD45. In vitro, the disruption of MDM2 leads to impaired cell cycle checkpoints and increased cell proliferation, which is accompanied by genomic instability, eventually causing full transformation in normal lung epithelia. In addition, the heat shock factor 1 (HSF1) transcription factor was found to regulate MDM2 directly and would decrease in the nucleus under high glucose conditions. Knockdown of HSF1 in the bronchial epithelial cell line (NL20) can increase MDM2 expression and cell proliferation. Human lung adenocarcinomas also displayed elevated MDM2 levels, with a correlation between MDM2 expression and lung cancer survival rates. Collectively, our findings suggest that liver-specific SIRT1 knockout-induced hyperglycemia promotes spontaneous lung adenocarcinomas through the HSF1-MDM2 pathway. Hyperglycemia may represent an underexplored cause of lung adenocarcinomas through impairment of cell cycle checkpoints, providing valuable insights for lung cancer prevention and future precision medicine.

We examined the effects of fucoidan, a sulfated polysaccharide, administered concurrently with the onset of a high-fat diet (HFD) for a short period in C57BL/6N mice to evaluate its immunological effects under obesity-inducing conditions. Numerous genes that were downregulated in the HFD group relative to the control-diet group were restored in the HFD+fucoidan group; these genes were mainly associated with inflammatory responses and cellular functions, including migration and viability, as identified by DNA microarray analysis. Upstream regulator analysis in ingenuity pathway analysis identified numerous cytokines and inflammatory mediators. Quantitative PCR confirmed that the expression of selected inflammatory cytokine genes-particularly Ifn-γ and Il-5-was decreased in the HFD group but restored in the HFD+fucoidan group. Our study suggests that fucoidan administered concurrently with an HFD attenuates HFD-induced downregulation of inflammatory and immune-related functions, including T-cell and B-cell functions, and may improve HFD-induced immune dysfunction and imbalance.

To enhance the diagnosis, management, and monitoring of Chinese children with chromosome 15q11-q13 duplication syndrome (dup15q) by analyzing their genetic and clinical characteristics. In this study, one Chinese prenatal case and 21 postnatal cases genetically diagnosed with dup15q syndrome underwent a detailed assessment of genetic and clinical characteristics. Most patients had normal prenatal (12/22, 54.5%) and neonatal (14/21, 66.7%) histories. Most symptoms were developmental delays (motor: 18/21, 85.7%; cognition: 13/21, 61.9%; language: 12/21, 57.1%). Other common features included autism spectrum disorder (ASD)-related behaviors (10/21, 47.6%) and seizures (7/21, 33.3%). Trisomy microduplications accounted for 54.5% (12/22), and tetrasomy microduplications accounted for 40.9% (9/22) of cases. We compared the phenotypic differences between the two groups using a composite score. One rare case of paternal duplication presented with early-onset obesity and tapered fingers resembling Prader-Willi syndrome (PWS). In addition, non-invasive prenatal testing (NIPT) detected int dup(15) in prenatal cases. Some patients with epilepsy were well controlled without anti-seizure drugs or monotherapy (3/7, 42.8%), while others had refractory epilepsy. Chinese children with dup15q exhibited high clinical heterogeneity, including multisystem developmental delays, ASD-related symptoms, and seizures. Phenotypic severity is influenced by multiple factors. NIPT may show positive findings, and chromosomal microarray analysis (CMA) combined with methylation analysis is important.

Paternal finasteride exposure and its impact on offspring testicular histopathology and intracellular junctions: the role of occludin and N-cadherin.

Insulinoma is a functional pancreatic neuroendocrine tumor that usually causes fasting hypoglycemia through inappropriate autonomous insulin secretion. However, some insulinomas show postprandial or stimulus-induced hypoglycemia, suggesting that some tumors retain the ability to respond to physiological stimuli. We examined four patients with confirmed insulinoma who showed different clinical patterns of hypoglycemia and integrated clinical stimulation tests with DNA microarray analysis. Insulin secretory dynamics were assessed using an oral glucose tolerance test, meal tolerance test, and glucagon stimulation test, as clinically indicated. Among the four cases, Case 1 showed no clear fasting hypoglycemia but developed hypoglycemia after meals and oral glucose loading, accompanied by marked insulin secretion. In this case, insulin or C-peptide increased markedly after glucose, meal, and glucagon stimulation. In contrast, the other three cases showed relatively weak insulin secretory responses to stimulation. During the fasting test, Cases 3 and 4 developed hypoglycemia early, whereas Case 2 showed a prolonged time to hypoglycemia. Transcriptomic analysis showed that, by hierarchical clustering, Case 1 was clearly separated from Cases 3 and 4, whereas Case 2 was relatively close to Case 1. Case 1 showed relatively preserved expression of genes involved in glucose sensing, ATP-sensitive potassium channel function, incretin/cAMP signaling, exocytosis, and β-cell differentiation. In contrast, cases with predominant fasting hypoglycemia showed higher expression of hexokinase 1 and stress-response genes. These findings suggest that clinical heterogeneity in insulinoma may reflect differences in β-cell-like stimulus-response mechanisms, glucose sensing, stress responses, and differentiation status.

MicroRNAs (miRNA) are considered promising biomarkers for inflammatory and neoplastic diseases in fecal samples, but despite reproducible miRNA detection, there is no consensus on appropriate normalization in fecal samples. In this study, we aimed to explore an endogenous normalizer for miRNA analysis in fecal samples. For this purpose, we performed a multistep study with 3 independent cohorts. In the first step, we investigated miRNA profiling using serial dilutions of blood and fecal samples from healthy subjects. In the second part, we tested the analysis using a cohort of IBD patients (n = 30) with active disease and in remission and 59 patients with different liver pathologies or healthy subjects. Finally, the data were validated using an independent cohort of patients with liver disease (n = 360). After extraction, miRNAs were analyzed using Affymetrix GeneChip microarray technology in the screening and confirmation cohorts, and TaqMan qPCR was performed for validation. Analysis of the blood stool mixture cohort revealed 5 miRNAs that were stable in all three subgroups. Among them, miR-638 was found to have a Log2FC of 0.0004 and was selected for further analysis as one of the best studied miRNAs from previous reports. The stability of miR-638 in microarray analysis was demonstrated in two independent cohorts of patients with IBD and liver disease. We observed no effect of age or other factors on miR-638 levels in fecal samples. Furthermore, its relatively high concentration in feces and its stability against potential blood contamination may offer great advantages over the previously used miR-16, suggesting miR-638 as a potential endogenous fecal normalizer.

To investigate the expression of succinate dehydrogenase B and its potential as a therapeutic target in pleural mesothelioma (PM). The expression of succinate dehydrogenase B was examined in cell lines using PCR. The expression of succinate dehydrogenase B mRNA was subsequently examined in a series of fresh-frozen primary patient samples using reverse transcription polymerase chain reaction. The expression of succinate dehydrogenase B protein was examined by immunohistochemistry on a pleural mesothelioma tissue microarray derived from Formalin-Fixed and Paraffin-Embedded specimens to determine if succinate dehydrogenase B expression correlated with survival benefit. Using a resazurin-based assay we examined whether targeting the mitochondrial complex II (containing succinate dehydrogenase B) with a chemical inhibitor could have effects on cell proliferation. Total ribonucleic acid was isolated from a panel of mesothelial-derived cell lines (both cancerous and non-cancerous), and expression of succinate dehydrogenase B messenger RNA was assessed by RT-PCR and found to be ubiquitously expressed. Total Ribonucleic acid was isolated from a panel of fresh-frozen surgical specimens, and succinate dehydrogenase B was significantly overexpressed in mesothelioma at the messenger RNA level. Immunohistochemical staining and analysis of a mesothelioma tissue microarray showed that expression did not correlate with any survival benefit, confirmed by in silico analyses of other datasets. However, links between DNA methylation at individual residues of the succinate dehydrogenase B gene and overall survival were identified, along with correlations to immune cell infiltrates. Targeting the mitochondrial complex II with oxaloacetic acid did not show any significant potential for higher efficacy in cell lines derived from malignant tumors compared to those derived from normal mesothelial cells. Our results demonstrate that succinate dehydrogenase B is overexpressed in PM but may not be a suitable candidate for therapeutic targeting in this disease.

Mapping the Molecular Connectivity of Pollen Sensitization: A Multiplex Microarray Analysis of the Turkish Paediatric Cohort.

Pancreatic cancer (PC) is one of the leading causes of cancer-related death worldwide. The lack of effective diagnostic biomarkers and therapeutic targets makes PC difficult to screen and treat. The aim of this study was to develop a diagnostic and survival-related gene signature for PC to construct a prognostic model. An Arraystar RNA microarray was used to identify differentially expressed genes (DEGs) in clinical plasma samples between the PC group and the control group. We performed weighted gene co-expression network analysis (WGCNA) to identify significant modules of DEGs in the Gene Expression Omnibus (GEO) cohort and to obtain potential diagnostic hub genes by intersecting the significant module genes with microarray-derived DEGs. In addition, least absolute shrinkage and selection operator (LASSO) cox regression analysis were performed to construct a prognostic model. Moreover, clinical samples were analyzed to evaluate the expression levels of the independent risk genes. Our microarray data revealed 228 significantly upregulated mRNA in plasma samples. FERMT1, S100A14, KCNN4, PKM, and ITGA3 were identified as robust diagnostic biomarkers. Integrating these hub genes, we constructed a prognostic model, with the nomogram exhibiting prognostic value in TCGA cohort. Univariate and multivariate Cox proportional hazard analyses revealed that the expression of FERMT1, S100A14, and ITGA3 was an independent risk factor for poor prognosis. RT-qPCR validation in clinical plasma sample demonstrated concordant expression patterns of the independent risk gene, further supporting its potential prognostic relevance. Our results revealed the potential biomarkers for the prediction of PC prognosis in addition to clinicopathological factors. Moreover, this study identifies potential biomarkers warranting further functional investigation.

This study aimed to systematically study the characterize of retinal damage induced by 525nm laser irradiation at different power densities through multimodal assessment methods, including structural, functional and cytokine analyses. A total of 24 rabbits were exposed to laser irradiation at 0.5, 200, 500, and 1000 mW/cm2 with a single-eye exposure duration of 0.25s. Multimodal evaluations including ERG, OCT/OCTA, histopathology and aqueous humor cytokine microarray analysis were used to evaluate the characteristics of laser-induced injury in rabbit eyes. No visible functional or pathological damage was observed after low-power laser radiation (0.5 mW/cm2). Laser irradiation exceeding 200 mW/cm2 induced transient electroretinographic suppression and persistent laser spots in the fundus. Laser-induced retinal edema and hemorrhage were naturally absorbed within 7days after injury, and cellular damage and structural changes persisted in the form of old plaques (14d). Notably, 1000 mW/cm2 laser exposure caused severe retinal detachment (1d), ultimately leading to a retinal hole (14d). There was no significant difference in the inflammatory array clustering analysis of anterior aqueous humor, but several individual cytokines showed statistically significant differences: ANG-1 was upregulated (500 and 1000 mW/cm2, p < 0.01) while VEGF-A was downregulated (500 mW/cm2, p < 0.05); MIP-1β was significantly increased (200 mW/cm2, p < 0.05), whereas IL-1RA was decreased (500 mW/cm2, p < 0.05). The 525nm laser induced dose-dependent retinal injury, ranging from reversible functional inhibition to irreversible structural damage, and triggered the expression of cytokines related to vascular stability and inflammation regulation.

Lymph node metastasis marks a clinically and biologically important transition in breast cancer, reflecting more aggressive disease and increased risk of recurrence. Expression of the Notch ligand JAG1 is linked to poor breast cancer outcomes, but its role in lymphatic dissemination is unclear. Tumor microarray analysis with multiplex staining was performed on synchronous breast and lymph node metastases from node-positive patients to quantify JAG1 expression and correlate findings with clinical outcomes. Orthotopic implantation of human and murine breast cancer cells was used to assess the impact of JAG1 expression on lymphovascular invasion and lymph node metastasis in vivo. The contribution of VEGFR3 signaling to JAG1-mediated lymphatic dissemination was evaluated using a soluble VEGFR3 antagonist. The cell-specific response of lymphatic endothelial cells to JAG1 was assessed by transendothelial migration assays, barrier examination, and sequencing. Mammary tumor cells expressing JAG1 demonstrated increased lymphovascular and lymph node metastasis in mouse models. Inhibition with a soluble VEGFR3 antagonist attenuated JAG1-dependent lymph node metastasis. Exposure to JAG1 disrupted lymphatic endothelial barrier integrity, promoted tumor cell migration across cultured endothelium, and induced pro-inflammatory and pro-adhesion changes in lymphatic endothelial cells. Tumor microarray analyses revealed enrichment of JAG1 in metastatic tumor cells within lymph nodes relative to matched primary tumors. High JAG1 expression in lymph node metastases was significantly associated with increased risk of recurrence. These findings support a role for tumor cell JAG1 promoting lymphatic dissemination and lymph node metastasis in breast cancer through effects on lymphatic endothelial signaling and barrier function. Enrichment of JAG1 in lymph node metastases and its association with recurrence further support its potential utility as a prognostic biomarker and therapeutic target in node-positive breast cancer.

Objective To explore the role of pathogenicity classification, genetic origin, and clinical decision-making in pregnancy outcomes for copy number variations (CNVs) detected by prenatal chromosome microarray analysis (CMA), and to assess the value of CNV reclassification in dynamic interpretation. Methods This retrospective study analyzed 43 fetuses with confirmed CNVs from 3,726 amniocenteses (2023–2025). CNVs were reclassified via literature and database review. Results Among 43 CNVs, 15 were pathogenic (P)/likely pathogenic (LP) (53.3% de novo) and 28 were variants of uncertain significance (VUS) (71.4% inherited). Reclassification updated 2 to P, 2 to VUS, and 23 to likely benign (LB). Incomplete penetrance and fetal sex influenced interpretation. Conclusion CNV interpretation is dynamic; regular review incorporating updated data improves prenatal counseling accuracy.