Breast cancer (BC) is the most frequently diagnosed malignancy worldwide and a leading cause of death in women. Machine learning (ML) enables data-driven risk stratification and outcome prediction, potentially improving screening, treatment choices, and overall care. This scoping review cataloged ML models used to predict BC risk and post-treatment outcomes. A PubMed search using MeSH terms (“breast neoplasms,” “breast cancer,” “machine learning,” and “predictive value of tests”) retrieved 44 records, with 9 added by manual searching; 24 studies were included. We excluded 29 reports limited to imaging/radiomics or biomolecular/omics, plus other ineligible items. Model usage among included studies: 13 random forest (RF); 13 support vector machine; 7 decision tree; 5 k-nearest neighbors; 4 deep learning; 3 naïve Bayes; 2 artificial neural networks. Average RF accuracy surpassed 90% in most reports, indicating RF is both common and consistently strong for predictive modeling, supporting targeted clinical translation.
breast neoplasm ; machine learning ; predictive value of tests

BACKGROUND : Endometrial cancer (EC) ranks as the 6th most common cancer among women worldwide. Despite early detection often yielding favorable outcomes, approximately 13% of early-stage EC patients still experience recurrence. This study aimed to identify prognostic factors for EC recurrence. METHODS : A systematic review and meta-analysis were conducted following preferred reporting items for systematic reviews and meta-analyses guidelines (International Prospective Register of Systematic Reviews ID: CRD42024501501). PubMed, Scopus, and Cochrane Library were searched for cohort and case-control studies published on January 1, 2018–January 1, 2024. The primary outcome was disease recurrence (any, locoregional, or distant). Inclusion criteria included adult women with histologically confirmed EC after primary surgery, ≥12-month follow-up, and sample size ≥100. Risk of bias was assessed using Quality in Prognosis Studies; certainty was rated using Grading of Recommendations Assessment, Development and Evaluation. RESULTS : 8 studies met inclusion criteria from 5,633 records screened. Significant prognostic factors included lymphovascular space invasion (LVSI) (relative risk [RR]: 4.83, 95% confidence interval [CI]: 3.49–6.69), cancer grade (RR: 2.15, 95% CI: 1.86–2.48), histology type (RR: 0.46, 95% CI: 0.34–0.61), cancer stage (RR: 2.58, 95% CI: 2.13–3.12), cervical stromal invasion (RR: 3.36, 95% CI: 1.30–8.73), myometrial invasion (RR: 2.60, 95% CI: 2.03–3.32), and chemotherapy history (RR: 1.81, 95% CI: 1.41–2.31). High heterogeneity was observed for chemotherapy history (I² = 92%) and cancer stage (I² = 77%). CONCLUSIONS Various clinicopathological factors, particularly LVSI, grade, stage, histology, and myometrial invasion, significantly influence EC recurrence. These findings support the need for individualized risk stratification and treatment planning.
endometrial cancer ; meta-analysis ; neoplasm recurrence ; prognostic factors ; systematic review

OBJECTIVE: To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2). METHODS: Three children who were diagnosed with ILFS2 at the Children's Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). RESULTS: The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c.3596G>A and c.1181A>T in child 1, c.2617C>T and c.2T>C in child 2, and c.3596G>A and c.2817_2818insT in child 3. Among these, the c.1181A>T and c.2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+PM3+PP3) and pathogenic (PVS1+PM2_Supporting+PM3). CONCLUSION Combined with the patient's clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c.1181A>T and c.2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.
Humans ; Exome Sequencing ; Genetic Testing/methods* ; Liver Failure, Acute/etiology* ; Mutation ; Child ; Adult ; Neoplasm Proteins

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree with recurrent Joubert syndrome with negative results by whole-exome sequencing in the prior proband. METHODS: Chinese pedigree which opted elective abortion at the Women and Children's Hospital Affiliated to Chongqing Medical University in December 2024 was selected as the study subject. Whole-genome sequencing was carried out on fetal tissue after termination of pregnancy. Candidate variants were validated by Sanger sequencing and interpreted, while non-coding variant was analyzed using in silico prediction tools. RNA sequencing and cDNA sequencing were conducted on fetal brain tissue. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.2024YL045-02). RESULTS: Both the fetus and the affected child were found to harbor compound heterozygous variants of the CEP290 gene, namely c.7341dup (p.Leu2448fs*8) (pathogenic, maternally inherited) and c.1523-408G>A (likely pathogenic, paternally inherited). Both in silico analysis and fetal brain RNA sequencing confirmed aberrant RNA splicing caused by the intronic variant. CONCLUSION This case has highlighted the value of combining whole-genome sequencing with RNA functional validation. Above results not only enriched the spectrum of CEP290 gene mutations but also underscored its diagnostic value in resolving complex prenatal cases, providing critical clues for the prenatal diagnosis and recurrence risk assessment in genetic counseling.
Female ; Humans ; Pregnancy ; Abnormalities, Multiple/genetics* ; Antigens, Neoplasm/genetics* ; Cell Cycle Proteins/genetics* ; Cerebellum/abnormalities* ; Cytoskeletal Proteins/genetics* ; Eye Abnormalities/genetics* ; Introns/genetics* ; Kidney Diseases, Cystic/diagnosis* ; Pedigree ; Retina/abnormalities* ; Sequence Analysis, RNA/methods* ; Whole Genome Sequencing/methods* ; Child

OBJECTIVE: To explore the clinical and genetic characteristics of fetuses with Kabuki syndrome (KS) and their genotype-phenotype correlation. METHODS: A retrospective analysis was carried out on the prenatal manifestations and results of genetic testing of six KS fetuses diagnosed by whole-exome sequencing (WES). The findings were compared with 28 prenatally diagnosed KS cases reported in the literature to summarize the prenatal features of KS. This study has been approved by the Ethics Committee of Maternal and Child Health Care Hospital of Hubei Province (Ethics No.: 2025-141-01). RESULTS: Prenatal ultrasound findings in KS fetuses showed high heterogeneity. The most common abnormalities were cardiac (23/35, 65.7%) and renal (20/35, 57.1%), which are often accompanied by amniotic fluid abnormalities (5/35, 14.3%), single umbilical artery (5/35, 14.3%), and fetal hydrops (4/35, 11.4%). Among the six fetuses from our center, all were identified by WES to harbor pathogenic variants of the KMT2D gene, and all of which were de novo. These included 3 frameshift variants, 2 nonsense variant, and 1 missense variant, among which 4 were unreported previously. CONCLUSION This study has expanded the mutational spectrum of the KMT2D gene. Prenatal ultrasound findings of KS lack specificity, though multi-system anomalies or specific soft markers may indicate KS. WES is an effective tool for the diagnosis, and KS should be included in the differential diagnosis list for prenatal cardiac and renal abnormalities.
Humans ; Hematologic Diseases/diagnostic imaging* ; Face/diagnostic imaging* ; Female ; Vestibular Diseases/diagnostic imaging* ; Abnormalities, Multiple/diagnostic imaging* ; Pregnancy ; Ultrasonography, Prenatal ; Adult ; Neoplasm Proteins/genetics* ; Retrospective Studies ; DNA-Binding Proteins/genetics* ; Male ; Exome Sequencing ; Fetus/diagnostic imaging* ; Genetic Association Studies ; Mutation

Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

Our previous research demonstrated that the Wenxia Changfu Formula (WCF), as a neoadjuvant therapy, inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (CD163) expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. In vivo, WCF inhibited recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.
Epithelial-Mesenchymal Transition/drug effects* ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Humans ; Animals ; Lung Neoplasms/metabolism* ; Chemokines, CC/antagonists & inhibitors* ; Mice ; Mice, Nude ; Drugs, Chinese Herbal/administration & dosage* ; Cell Line, Tumor ; Neoplasm Metastasis ; Tumor-Associated Macrophages/drug effects* ; Mice, Inbred BALB C ; Signal Transduction/drug effects*

Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics* ; Wnt Signaling Pathway/drug effects* ; Animals ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neoplasm Metastasis/prevention & control* ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Neutrophil Infiltration/drug effects* ; Down-Regulation/drug effects* ; Cell Movement/drug effects* ; beta Catenin/genetics* ; Apoptosis/drug effects* ; Mice, Inbred C57BL ; Male ; Neoplastic Cells, Circulating/drug effects*

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Objective To elucidate the molecular mechanism by which exosomes (Exo) derived from cancer-associated fibroblasts (CAF) carrying HOX transcript antisense intergenic RNA (lncRNA HOTAIR) promote the metastasis of esophageal squamous cell carcinoma (ESCC). Methods CAFs were collected from tumor tissues, and non-cancer associated fibroblasts (NFs) were obtained from adjacent normal tissues at least 5 cm away from the tumor. Exosomes (CAFs-Exo and NFs-Exo) were isolated from conditioned media collected from CAFs or NFs. CAFs-Exo and NFs-Exo were incubated with human ESCC cell line TE-1 for 24 hours, and CCK-8 was used to determine the cell proliferation ability. Scratch test and Transwell test were performed to determine the cell migration and invasion ability. TE-1 cells were divided into the following two groups: NC group and KD group. The NC group and KD group were transfected with control siRNAs or siRNAs targeting HOTAIR respectively. The effects of HOTAIR knock-down on cell proliferation, migration, invasion and glycolysis were determined. Results CAFs-Exo promoted the proliferation of TE-1 cells more significantly than NFs-Exo. Compared with NFs-Exo group, the migration and invasion ability of TE-1 cells treated with CAFs-Exo were improved significantly. In addition, CAFs-Exo treatment inhibited the expression of E-cadherin and enhanced the expression of N-cadherin. The expression of HOTAIR in CAFs was significantly higher than that in NFs. Compared with NFs-Exo, the expression level of HOTAIR in CAFs-Exo increased significantly. Compared with NC group, the proliferation, migration and invasion of TE-1 cells in KD group decreased significantly. Compared with NC group, hexokinase 2 (HK2), extracellular acidification rate (ECAR) and ATP/ADP ratio of TE-1 cells in KD group decreased significantly. Conclusion HOTAIR, an exosome derived from CAFs, may be involved in metastasis and EMT by regulating glycolysis in ESCC cells.
Humans ; RNA, Long Noncoding/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Esophageal Squamous Cell Carcinoma ; Exosomes/genetics* ; Neoplasm Metastasis ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; Glycolysis/genetics* ; Cancer-Associated Fibroblasts/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Cadherins/genetics*