Dalian Maternal and Child Health Hospital

Ovarian tissue cryopreservation (OTC) is essential for fertility preservation in cancer survivors, prepubertal girls, and individuals at high risk of premature ovarian insufficiency (POI). Yet conventional evaluation methods, such as histology and follicle counting, provide limited insight into tissue viability, microenvironmental integrity, molecular injury, and oncologic safety. Recent advances in multi-omics, including transcriptomics, single-cell sequencing, proteomics, and spatial transcriptomics, enable high-resolution characterization of follicular heterogeneity, stromal status, and potential malignant contamination. Concurrently, artificial intelligence (AI) offers automated follicle detection, quantitative tissue assessment, and multimodal prediction models that can support individualized clinical decisions. This review summarizes emerging applications of multi-omics and AI in ovarian tissue quality assessment and highlights their potential to transform fertility preservation strategies. Integrating molecular profiling with AI-based prediction may establish a more precise and intelligent framework for tissue selection, transplantation planning, and reproductive outcome prediction.

Cells constantly experience mechanical forces from their microenvironment, positioning the nucleus as a central integrator of physical cues and gene regulatory programs. This review examines current evidence on how mechanical signals are transmitted from the extracellular matrix to the nucleus and how key nuclear structures respond in a context-dependent manner. The perinuclear cytoskeletal components—such as the actin cap, microtubules, and the Ca2+-INF2 signaling axis—are discussed as key transducers that regulate nuclear morphology and facilitate mechanosensitive nucleocytoplasmic transport. The linker of nucleoskeleton and cytoskeleton (LINC) complex is highlighted as a major conduit for conveying cytoskeletal forces across the nuclear envelope. Within the nucleus, the nuclear pore complex exhibits mechanoresponsive behavior that may modulate molecular flux and contribute to structural resilience. The nuclear lamina acts as a load-bearing scaffold associated with nuclear stiffness regulation and chromatin organization. Chromatin itself undergoes force-associated structural and epigenetic remodeling, and mechanosensitive transcription factors—including, but not limited to, Yes-associated protein and transcriptional co-activator with PDZ-binding motif (YAP/TAZ)—have been implicated in linking mechanically altered nuclear states to gene expression responses. Advances in high-resolution imaging and novel force-probing technologies are further illuminating the dynamics of nuclear mechanics. Together, current findings outline an evolving framework for understanding how extracellular mechanics interface with nuclear structure and gene regulation in health and disease.

[This corrects the article DOI: 10.3389/fmed.2025.1683293.].

Intellectual developmental disorder type 61 (MRD61) is an extremely rare autosomal dominant disorder caused by variants in the MED13 gene. This gene encodes a subunit of the mediator complex, which is also known as TRAP, SMCC, DRIP or ARC. This complex functions as a transcriptional coactivator and is essential for the expression of almost all genes. To date, only 26 cases of MRD61 have been reported worldwide. The main symptoms are intellectual disability (ID) of varying degrees, developmental delay (DD), hypotonia during infancy, facial dysmorphism, language impairment, restricted growth, skeletal and limb abnormalities, and behavioral abnormalities. In this study, we recruited a Chinese family in which two individuals were diagnosed with MRD61. Whole-exome sequencing of the proband revealed a novel heterozygous frameshift variant in the MED13 gene (NM_005121.3): c.5641delinsTC (p.R1882Sfs*9). This variant was inherited from the affected mother and was subsequently confirmed in both the proband and her other family members using Sanger sequencing. The dysmorphology profile of both patients described here is similar to that associated with MRD61. Compared with previously reported cases of MRD61, the proband presented with congenital megacolon, a previously unreported complication. Additionally, skeletal and limb deformities, eye or vision abnormalities, behavioral issues and brain abnormalities were absent in our patients. This is the first report of MED13-associated intellectual developmental disorder-61 in China. This molecular diagnosis expands the known genetic spectrum of MRD61. Furthermore, the specific manifestations observed in these patients with this condition provide valuable additional clinical insight into the syndrome.

This study systematically explored the dynamic evolution of bioactive components, flavor metabolites, and microbial communities in citri reticulatae pericarpium (CRP) throughout its processing from fresh materials through drying to controlled aging. Using UPLC, GC–MS, and high-throughput sequencing, we found that during the fresh-to-dry phase (0–7 days), water activity decreased significantly (p < 0.05), while total flavonoids, hesperidin, and volatile oil yield increased by 3.3 %–10.8 %. Drying at 30 °C enhanced microbial diversity (p < 0.05). In the dry-to-aged phase (7–360 days), total flavonoids accumulated, while volatile oil decreased by 50.7 %. Aspergillus emerged as a dominant species from 270 to 360 days. Correlation analysis showed positive links between Aspergillus and flavonoid levels (p < 0.05). This research provides a framework for monitoring CRP processing and highlights the impact of drying methods on quality through microbial diversity.

Endometrial cancer (EC) is a common gynecologic malignancy with limited treatment options. This study aimed to evaluate the potential of itraconazole (ITZ), a widely used antifungal drug, as an anti-tumor agent and an adjuvant to immunotherapy for EC. The effects of ITZ on Ishikawa cells were assessed using proliferation assays, apoptosis assays, and invasion assays. The combination of ITZ and immune checkpoint inhibitors (ICIs) was evaluated to determine their synergistic effects on tumor invasion. Tumor-associated macrophages (TAMs) polarization and cytokine levels were analyzed by flow cytometry and enzyme linked immunosorbent assay (ELISA). Western blotting and Real-time reverse transcription polymerase chain reaction (RT-PCR) were used to investigate the impact of ITZ on the Wnt/β-catenin signaling pathway. Finally, in vivo experiments were conducted using a mice tumor model to validate the anti-tumor effects of ITZ and its combination with ICIs. ITZ inhibits Ishikawa cells proliferation and invasion through apoptosis induction. When combined with ICIs, ITZ significantly enhanced the inhibition of tumor invasion, an effect associated with TAMs polarization. ITZ increased IFN-γ secretion, reduced IL-10 levels, and promoted TAMs polarization from the M2 to the M1 phenotype. Mechanistically, ITZ downregulated Wnt-3a and β-catenin expression while upregulating Axin-1, thereby suppressing Wnt/β-catenin signaling in TAMs. In vivo, ITZ and ICIs synergistically reduced tumor volume and weight, shifted TAMs polarization toward the M1 phenotype, and suppressed Wnt/β-catenin signaling. ITZ demonstrated robust anti-tumor activity against EC by inhibiting Ishikawa cells proliferation, invasion, and enhancing the efficacy of ICIs. Through its dual role in directly targeting tumor cells and modulating the tumor microenvironment, ITZ shows promise as a multitargeted therapeutic agent and a valuable adjuvant to immunotherapy for EC.

Immunotherapy represents a pivotal therapeutic modality in endometrial cancer (EC). Nevertheless, the efficacy of this treatment is limited to a subset of patients. The present investigation endeavors to amalgamate multi-omics data in order to elucidate the determinants impacting individual immune responsiveness and enhance the optimization of immunotherapy for EC. To differentiate EC patients into non-response (NR) and response (R), multi-omics data from publicly available databases were employed in conjunction with the TIDE computational framework. The validity of these findings was further confirmed through the utilization of the EaSIeR and ImmunoPhenoScore algorithms. The study employed functional enrichment and gene set variant analysis to discern noteworthy disparities in biological pathways across various groups. Moreover, three deconvolution algorithms (ESTIMATE, TIMER, and EPIC) were employed to quantify the tumor microenvironment (TME). Somatic mutation and copy number variant (CNV) analyses were also conducted to identify genomic alterations that impact immunotherapy. Integrated bulk and single-cell RNA sequencing (scRNA-seq) data were employed to identify cell populations linked to efficacy and deduce cell-cell interactions. The immunotherapy response rates were found to be greater in elderly EC patients aged 65 years and above. The NR group of patients displayed notable enrichment in cellular differentiation, angiogenesis, and tumor proliferation characteristics, as evidenced by higher tumor purity and lower expression of immune checkpoints. Conversely, the R group exhibited a stronger correlation with immunity, as indicated by pathway enrichment and composition of TME. Patients in the NR group demonstrated higher frequencies of somatic mutations, with a 2- to 6-fold disparity between the groups in genes such as RPRD1B and CTNNB1. Patients in the R group exhibited elevated mutation scores and higher mutation frequencies at the same mutation loci compared to those in the NR group. Moreover, the incidence of mutations was more prevalent among patients in the R group. In independent cohorts, the Scissor algorithm suggests that macrophages may exert a substantial impact on immunotherapy response in patients with EC. Subsequent analysis unveiled an enrichment of M2-like tumor-associated macrophages (TAMs) within the TME of patients in the NR group. These macrophages facilitate angiogenesis and cell proliferation through intercellular communication with subpopulations such as endothelial and epithelial cells. TME of patients in the R group exhibited an enrichment of M1-like TAMs, which primarily engaged with immune cells via diverse immune-activating factors. Furthermore, immunohistochemistry and flow cytometry demonstrated that responders to immunotherapy had significantly increased infiltration of M1-like TAMs. M1-like TAMs were shown to inhibit proliferation and migration of Ishikawa cells in co-culture assays. This research offers a comprehensive insight into the multi-omics level factors influencing the immunotherapy response of EC patients, emphasizing the influence of genomic variants and TAMs on said response. This contributes to an enhanced comprehension of the biological mechanisms underlying EC immunotherapy response and aids in the optimization of EC immunotherapy.

Allergic asthma is an inflammatory disease of the airways that causes great distress to the patient's normal life. Astragalus Polysaccharide (APS) is the main active ingredient in the traditional Chinese medicine Astragalus mongholicus Bunge, which has the effect of regulating immune function. This study aimed to evaluate the effect of APS on allergic asthma and investigate its potential mechanism of action. This study utilized network pharmacology to predict the relevant targets and signaling pathways of APS treatment for allergic asthma. Subsequently, an animal model was established using Ovalbumin (OVA) induction. The efficacy of APS was verified using histopathologic staining and Airway Hyperresponsiveness (AHR) assay. Signaling pathways were examined using Western Blot (WB). Finally, bioinformatics analysis was utilized to explore the correlation between the progression of allergic asthma and signaling pathways. Network pharmacology analysis identified 15 intersection targets significantly enriched in the PI3K/AKT signaling pathway. The results of molecular docking showed that small molecule drugs have a strong binding ability to target proteins. The experiments confirmed APS successfully suppressed the pathological symptoms in allergic asthma model mice. Subsequently, WB provided evidence supporting that APS has potential therapeutic effects mediated through the PI3K/AKT signaling pathway. The bioinformatics results confirmed that disease progression in allergic asthma patients does correlate with the PI3K/AKT signaling pathway. Our study suggests that APS may treat allergic asthma by targeting the PI3K/AKT signaling pathway. This provides a basis for preliminary research on the clinical application of APS for treating allergic asthma.

Telemedicine uses videoconferencing technology to enable real-time audio and visual communication, linking on-site healthcare providers with specialists at remote locations. Over the past decade, telemedicine has grown significantly within the field of neonatology. This study seeks to deepen the understanding of telemedicine applications for newborns and neonatal intensive care units (NICUs) through a detailed bibliometric analysis. Publications on telemedicine in newborns and NICUs from January 1, 2004, to October 22, 2024, were retrieved from the Web of Science Core Collection. Using Microsoft Excel, CiteSpace, the R package "bibliometrix," and VOSviewer, we analyzed the data to examine the number of publications, contributing countries/regions, institutions, authors, journals, references, and keywords. Since 2004, 1177 publications have been included, reflecting a rapid increase in research on telemedicine in newborns and NICUs over the past decade. These studies originated from 55 countries/regions and 139 institutions. The United States, the United Kingdom, and India were the primary contributors in terms of publication volume. Among the 405 authors analyzed, Jennifer L. Fang had the highest number of publications, while James P. Marcin received the most co-citations. BMC Pregnancy and Childbirth published the most articles, and Pediatrics had the highest citation count. The most frequently used keywords included "accuracy," "depression," "digital health," "mobile health," and "parents," highlighting key research areas. Emerging research frontiers such as "palliative care," "low-income populations," "artificial intelligence," and "parents with high-risk infants" indicate rapidly advancing topics in this field. This study is the first to perform a comprehensive bibliometric analysis of publications on telemedicine in newborns and NICUs. In the previous 20 years, global interest in teleneonatology research has significantly increased. Our bibliometric findings offer valuable insights for researchers, helping them understand essential information, recognize current research hotspots, identify potential collaborators, and explore future research frontiers in this field.