Radiogenomics, an extension of radiomics, explores the relationship between imaging features and underlying gene expression patterns. This field is instrumental in providing reliable imaging surrogates, thus potentially representing an alternative to genetic testing. The rapidly growing area of radiogenomics that utilizes ultrasound (US) imaging seeks to elucidate the connections between US image characteristics and genomic data. In this review, the authors outline the radiogenomics workflow and summarize the applications of US-based radiogenomics. These include the prediction of gene variations, molecular subtypes, and other biological characteristics, as well as the exploration of the relationships between US phenotypes and cancer gene profiles. Although the field faces various challenges, US-based radiogenomics offers promising prospects and avenues for future research.

Radiogenomics, an extension of radiomics, explores the relationship between imaging features and underlying gene expression patterns. This field is instrumental in providing reliable imaging surrogates, thus potentially representing an alternative to genetic testing. The rapidly growing area of radiogenomics that utilizes ultrasound (US) imaging seeks to elucidate the connections between US image characteristics and genomic data. In this review, the authors outline the radiogenomics workflow and summarize the applications of US-based radiogenomics. These include the prediction of gene variations, molecular subtypes, and other biological characteristics, as well as the exploration of the relationships between US phenotypes and cancer gene profiles. Although the field faces various challenges, US-based radiogenomics offers promising prospects and avenues for future research.

Radiogenomics, an extension of radiomics, explores the relationship between imaging features and underlying gene expression patterns. This field is instrumental in providing reliable imaging surrogates, thus potentially representing an alternative to genetic testing. The rapidly growing area of radiogenomics that utilizes ultrasound (US) imaging seeks to elucidate the connections between US image characteristics and genomic data. In this review, the authors outline the radiogenomics workflow and summarize the applications of US-based radiogenomics. These include the prediction of gene variations, molecular subtypes, and other biological characteristics, as well as the exploration of the relationships between US phenotypes and cancer gene profiles. Although the field faces various challenges, US-based radiogenomics offers promising prospects and avenues for future research.

Radiogenomics, an extension of radiomics, explores the relationship between imaging features and underlying gene expression patterns. This field is instrumental in providing reliable imaging surrogates, thus potentially representing an alternative to genetic testing. The rapidly growing area of radiogenomics that utilizes ultrasound (US) imaging seeks to elucidate the connections between US image characteristics and genomic data. In this review, the authors outline the radiogenomics workflow and summarize the applications of US-based radiogenomics. These include the prediction of gene variations, molecular subtypes, and other biological characteristics, as well as the exploration of the relationships between US phenotypes and cancer gene profiles. Although the field faces various challenges, US-based radiogenomics offers promising prospects and avenues for future research.

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective To investigate the relationship between the expression of serum solute carrier family member 11 (SLC7A11) and acyl CoA synthase long-chain family member 4 (ACSL4) and the degree of neurological impairment and prognosis in patients with acute cerebral infarction (ACI). Methods 60 ACI patients admitted to the Department of Neurology,Suzhou Jiulong Hospital,School of Medicine,Shanghai Jiaotong University from October 2019 to December 2022 were selected as the ACI group,and 60 healthy people in the same period were taken as a control group. Serum SLC7A11 and ACSL4 levels were detected by enzyme-linked immunosorbent assay(ELISA). According to the degree of neurological impairment[assessed by the National Institutes of Health Stroke Scale (NIHSS)],60 patients with ACI were divided into a mild group(n=41) and a severe group (n=19). According to the prognosis of patients 3 months after discharge[assessed by the modified Rankin scale (mRS) score],60 patients with ACI were divided into good group(n=47) and bad group(n=13),and the serum SLC7A11 and ACSL4 levels of ACI patients in different groups were compared. Pearson correlation was used to analyze the correlation between serum SLC7A11 and ACSL4 levels and the degree of neurological impairment and prognosis,and receiver operating characteristic(ROC) curve was used to analyze the value of serum SLC7A11 and ACSL4 levels in predicting poor prognosis of ACI patients.Results The serum SLC7A11 (16.88±3.19ng/ml)level in ACI group was lower than that in the control group(25.13±5.61ng/ml),and the ACSL4(40.01±4.23ng/ml)level was higher than that in the control group(23.29±5.72ng/ml),with statistical significance (t=9.902,18.205,all P<0.05).Serum SLC7A11(15.16±3.91ng/ml)level in ACI patients in the severe group was lower than that in the mild group(17.68±2.41ng/ml),and ACSL4 (42.08±5.02ng/ml) level was higher than that in a mild group(39.05±3.40ng/ml),the serum SLC7A11(14.25±2.95 ng/ml)level of ACI patients in the bad group was lower than that in the good group(17.61±2.85 ng/ml),and the ACSL4 (43.54±3.87 ng/ml)level was higher than that in the good group(39.03±3.78 ng/ml),and the differences were statistical significance (t=3.070,2.747;3.735,3.789,all P<0.05). Pearson correlation analysis showed that serum SLC7A11 level was negatively correlated with NISS and mRS scores of ACI patients (r=-0.416,-0.378,all P<0.05). The serum ACSL4 level was positively correlated with NISS and mRS scores (r=0.351,0.415,all P<0.05). The AUC (95％ CI) of serum SLC7A11 and ACSL4 in predicting the poor prognosis of ACI patients was 0.810 (0.688～0.900),and the sensitivity and specificity were 68.09％ and 92.31％,respectively,which were better than those of individual detection (Z=2.176,1.977,P=0.030,0.048). Conclusion The combination of serum SLC7A11 and ACSL4 has a high predictive efficiency for the poor prognosis of ACI patients.

Objective:To integrate the best available evidence regarding the management of perinatal intraventricular hemorrhage (IVH) in preterm infants.Methods:Using keywords such as "intracranial hemorrhage", "intraventricular hemorrhage", "germinal matrix hemorrhage", and their Chinese equivalents, we systematically searched for clinical decisions, guidelines, expert consensuses, evidence summaries, group standards, systematic reviews, and meta-analyses related to IVH management in preterm infants. Data sources included BMJ Best Practice, UpToDate, World Health Organization website, Guidelines International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, Registered Nurses' Association of Ontario, National Guideline Clearinghouse, American Academy of Pediatrics, Canadian Paediatric Society, European Foundation for the Care of Newborn Infants, British Association of Perinatal Medicine, Yiigle, Cochrane Library, Joanna Briggs Institute, PubMed, Web of Science, CINAHL, MEDLINE, Embase, China National Knowledge Infrastructure, Wanfang Data, and SinoMed. The search period spanned from January 2015 to December 2024. Literature screening, quality appraisal, evidence extraction, and synthesis were performed independently according to uniform standards.Results:A total of 12 publications were included, comprising three clinical decisions, three evidence-based guidelines, and six expert consensuses. Thirty-seven best evidence statements were synthesized across four domains: risk factor identification, diagnosis and monitoring, antenatal and delivery room management, and neonatal intensive care unit management. These included 28 strong recommendations (Grade A) and nine weak recommendations (Grade B).Conclusion:The 37 summarized best evidence statements provide an evidence-based foundation for developing clinical management protocols for perinatal IVH in preterm infants.

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*