Wuhan Third Hospital

Chemoresistance greatly impairs the effectiveness of chemotherapy in gastric cancer (GC) patients. According to our prior results, Cadherin-17 (CDH17) contributes to chemoresistance in GC through activating the Wnt/β-catenin pathway; however, its specific molecular mechanisms require further elucidation. We compared the Wnt/β-catenin pathway activation levels between cisplatin (DDP)-resistant GC cell lines and their parental cell lines. Subsequently, we carried out loss-of-function and gain-of-function tests to investigate CDH17 for its effect on regulating β-catenin expression, nuclear transport, as well as transcriptional activity within DDP-resistant GC cells. Additionally, CDH17 was examined for its role in the expression of four ABC transporters using molecular assays. Finally, rescue experiments were carried out using the Wnt signaling pathway agonist CP21R7 and inhibitor IWR-1 to elucidate the specific mechanism of CDH17 in promoting chemotherapy resistance of GC cells. The results showed that the activation level of the Wnt/β-catenin signaling pathway was significantly elevated in DDP-resistant GC cell lines compared to their parental cell lines. Silencing CDH17 resulted in reduced expression, impaired nuclear translocation, and decreased transcriptional activity of β-catenin, whereas overexpression of CDH17 had the opposite effects. Notably, CDH17 was shown to specifically regulate the expression of ABCB1 (protein name: P-glycoprotein, P-gp) in resistant cells, with no observable impact on the other three ABC transporters (ABCC1, ABCG2, and ABCC2) examined. Importantly, treatment with IWR-1 effectively reversed the enhancing effect of CDH17 overexpression on P-gp protein expression, as well as its suppressive effects on DDP accumulation and chemosensitivity. Conversely, administration of CP21R7 attenuated the inhibitory consequences of CDH17 silencing on P-gp expression, DDP efflux, and drug resistance. In conclusion, CDH17 promotes the expression and nuclear translocation of β-catenin in GC cells, leading to activation of the Wnt/β-catenin signaling pathway, which subsequently upregulates ABCB1/P-gp expression and enhances cellular capacity for DDP efflux. These findings imply that targeting CDH17 could be a potential strategy for overcoming chemotherapy resistance in GC.

Unintended pregnancy leading to induced abortion is a significant public health concern affecting women’s reproductive health globally. In China, a high rate of repeat induced abortion persists, yet the determinants among specific populations like those in Wuhan’s Guanggu area are not fully elucidated. Identifying high-risk groups is crucial for developing targeted interventions to reduce repeat procedures. The study aimed to investigate the factors influencing repeat miscarriage among adult women of reproductive age in Guanggu, Wuhan, China. A retrospective analysis was conducted on the case data of 2,428 women aged 18–49 years who underwent early induced abortion due to unintended pregnancy at the Guanggu Hospital Area of Wuhan Third Hospital from January to December 2022. Data were analyzed using Chi-squared tests and logistic regression model (α = 0.05). Among the 2,428 women with unintended pregnancy who underwent early induced abortion, the average number of induced abortions was 1.77 ± 0.57, and the average number of children was 0.76 ± 0.79. Women aged 20–29 years accounted for the highest proportion of cases (50.95%), while 55.68% of the women had a marriage history (including 53.67% married and 2.02% divorced) and 69.32% had non-Wuhan household registration. The overall rate of repeat induced abortion (defined as having ≥ 2 times of induced abortion) was 49.84%, with 54.41% of women who had children experiencing repeat induced abortion and 45.59% of childless women having repeat induced abortion. Logistic regression analysis showed that married women had a higher rate of repeat induced abortion than unmarried women (OR = 1.80, 95%CI:1.61–2.02, p < 0.001); women who had children had a higher rate of repeat induced abortion than those without children (OR = 1.87, 95%CI:1.67–2.10, p < 0.001); and women with non-Wuhan household registration had a higher rate of repeat induced abortion than those with Wuhan household registration (OR = 1.23, 95%CI:1.07–1.42, p = 0.0005). Additionally, women who had given birth to two boys had a higher risk of early induced abortion due to unintended pregnancy compared with those who had one boy (OR = 11.82, 95%CI:1.11–2.99, p = 0.02). Induced abortion is still very prevalent in the Guanggu area, Wuhan. However, married women of childbearing age without Wuhan household registration and those who have given birth to two boys are high-risk groups for repeat induced abortion. Therefore, repeat induced abortion’s eradication strategies should include patient-centered contraceptive guidance targeting these high-risk groups.

Poly (ADP-ribose) polymerase-(PARP)-1 repairs the damaged DNA to maintain genome integrity, with nicotinamide adenine dinucleotide (NAD)+ being a substrate. Hyperactivation of PARP-1 causes the depletion of NAD+ pool and inhibits ATP production in mitochondria, ultimately leading to mitochondrial dysfunction, energy failure and cell death. These processes are involved in the pathological mechanisms of a range of neurodegenerative diseases. Inhibiting PARP-1 activity may therefore be valuable in the treatment of these diseases. As NAD+ is most highly distributed within mitochondria, direct inhibition of PARP-1 activity in the organelle may be more efficacious. Therefore, three mitochondrial-targeting compounds 4a-4c were synthesized by coupling the triphenylphosphonium (TPP+) moiety with the ─OH derivative of the PARP-1 inhibitor AZD2461 through various linkers. A fourth compound 4d, was synthesized by coupling the ─OH derivative with the enol form of the antioxidant edaravon. The compounds 4a-4d were tested for protective activity in PC12 cells injured by D-galactose (D-gal) at 60mM, and the results showed that compound 4c prevented the PC12 cell impairment. Further assays indicated that 4c could restore the loss of mitochondrial membrane potential triggered by D-gal in PC12 cells. This study demonstrated that a mitochondria-targeting PARP-1 inhibitor could improve mitochondrial function and prevent PC12 cell death caused by excessive oxidative stress induced by D-gal.

ObjectivesTo evaluate the value of quantitative parameters and radiomic features based on dual-layer spectral detector CT (DLCT) in predicting spread through air spaces (STAS) of lung adenocarcinoma (LUAD).MethodsThis study analyzed 266 patients with pathologically confirmed LUAD from two medical centers. Patients from center 1 were divided into training (n = 131) and internal validation (n = 57) sets, while center 2 (n = 78) formed the external validation set. Clinical data, conventional imaging features, and DLCT quantitative parameters were analyzed to develop a clinical-radiological model. Radiomic features were extracted from venous-phase images, including conventional images, virtual monoenergetic images (VMI) at 40 keV, 65 keV, and 100 keV, along with iodine density maps, effective atomic number (Zeff) maps, and electron density (ED) maps. The best-performing radiomics model was combined with clinical-radiological predictors to create a nomogram. Model performance was evaluated through ROC analysis, calibration curves, and decision curve analysis.ResultsMultivariate analysis revealed that tumor-lung interface and ED values were independent predictive factors in the clinical-radiological model. The optimal radiomics model was constructed based on VMI 40 keV, demonstrating AUCs of 0.899, 0.835, and 0.828 in the training, internal validation, and external validation sets, respectively. The nomogram, which incorporated the VMI 40 keV radiomics signature along with tumor-lung interface and ED values, outperformed the clinical-radiological model in the training set (AUC = 0.910 vs. 0.870; P = 0.018) and the internal validation set (AUC = 0.868 vs. 0.798; P = 0.046). While the improvement in the external validation set was not statistically significant (AUC = 0.848 vs. 0.819; P = 0.184).ConclusionThe nomogram, which integrates conventional imaging features, DLCT quantitative parameters and VMI 40 keV radiomic features, demonstrates promising performance and represents a potential valuable non-invasive tool for the preoperative assessment of STAS in LUAD.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-025-15436-7.

Depression is clinically and biologically heterogeneous, mandating classification strategies for personalized medicine. This study explored depression subtypes using metabolomics data from the UK Biobank and validated the subtypes in the Whitehall II cohort. The five-step analysis included: (1) identification of distinct subtypes using non-negative matrix factorization (NMF) and four machine learning algorithms; (2) genome-wide association studies (GWAS) to examine associations across subtypes and controls; (3) comparison of clinical characteristics across subtypes; (4) development of 24 subtype-specific diagnostic models and validation in an independent cohort; and (5) construction and comparison of metabolic networks across subtypes. Cluster analysis of 249 metabolomic indicators in individuals with current depressive episodes (n = 7,945) identified three metabolic subtypes of depression. Subtype 1 was characterized by fatty acid dysregulation, subtype 3 had a hyperlipidemia phenotype, while subtype 2 displayed an intermediate phenotype. Metabolic subtypes were not associated with SNPs. Diagnostic models built using the 249 metabolic indicators yielded the area under the curve (AUC) of 0.644 for the total depression sample and 0.785, 0.817, and 0.942 for subtypes 1, 2, and 3, respectively. Twenty-three additional diagnostic models based on combinations of metabolic indicators improved performance by 12.8-39.6% over a binary classification model. Metabolic networks significantly differed between each subtype and healthy controls but not between the total depressed group and controls. This study defines distinct metabolic subtypes of depression. Future research should combine high-throughput metabolomics with prospectively established depression cohorts and tailored interventions to explore subtype-specific diagnostic and therapeutic biomarkers.

This study aimed to evaluate the sonographic features of giant fetal hepatic hemangioma (GFHH) as predictors of complications and outcomes. We conducted a retrospective analysis of prenatally diagnosed GFHH cases between 2014 and 2024, reviewing ultrasonographic features, complications, and neonatal outcomes. Among 36 fetuses, 38.9% exhibited homogeneous masses and 61.1% showed heterogeneous masses. Peripheral annular or semi-annular blood flow was observed in 88.9% of cases. Heterogeneous echogenicity was more frequent in the complicated group (93.3%, 14/15) than in the uncomplicated group (38.1%, 8/21) (p<0.01). Significant differences were identified between the complicated and uncomplicated groups regarding the presence of vascularity, arteriovenous fistula (AVF), hepatic artery peak systolic velocity (HAPSV) (> 106cm/s), and hepatic vein dilation (≥ 3 veins) (all p<0.05). The survival rate was 100% among the 21 fetuses in the uncomplicated group, compared with 73.3% among the 15 fetuses in the complicated group. The typical presentation of GFHH is a well-defined hypoechoic mass with peripheral circular or semicircular vascularity. Homogeneous masses are predictive of favorable outcomes, whereas within heterogeneous masses, features such as hypervascularity, AVF, HAPSV > 106cm/s, and dilation of three hepatic veins are closely correlated with an increased risk of complications.