Background: Cardiovascular disease (CVD) remains the leading cause of global mortality, necessitating a largescale bioimaging database to advance personalized precision medicine strategies. Objectives: The Dongzong Cardiovascular Bio-imaging Registry (DAILY) study was designed to establish a largescale Chinese cardiovascular bioimaging database (NCT06894095). It aims to address ethnic disparities in genetics and imaging, and to elucidate crucial driving mechanisms and effects of genetic biology and exposure factors on imaging-derived intermediate phenotypes and CVD. Methods: This prospective, multicenter study plans to enroll 50,000 adults from six medical centers across China. It employs a comprehensive data framework, systematically collecting information on exposure factors, highthroughput multiomics (blood and saliva samples), and cardiopulmonary computed tomography (CT) imaging (chest CT, cardiac CT) for cardiac, coronary and pulmonary phenotypes assessment. The primary outcome is a composite major adverse cardiovascular event, including all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Results: To September 10, 2025, the study has recruited 8699 participants in Nanjing, China. Standardized biospecimen collection was performed, obtaining blood samples from 8632 participants and saliva specimens from 8621 individuals, and cardiopulmonary CT scans have been completed in 8699 participants. The cohort maintains a 1-year follow-up rate of 98.9%. Conclusions: The DAILY study will deepen our understanding of ethnic disparities in CVD, help elucidate the effects of genetic and exposure factors on cardiopulmonary intermediate phenotypes, and decipher the pathophysiological mechanisms underlying CVD.
RATIONALE AND OBJECTIVES:To evaluate the predictive value of the lesion-specific preoperative pericoronary fat attenuation index (FAI) for in-stent restenosis (ISR) after stent placement. MATERIALS AND METHODS:This retrospective multicenter study, conducted between January 2016 and December 2023, included patients with coronary artery disease who underwent coronary CT angiography (CCTA) within 30 days before percutaneous coronary intervention (PCI). Patients who subsequently underwent invasive coronary angiography (ICA) were identified and stratified into ISR-positive and ISR-negative groups based on the angiographic findings. Lesion-specific pericoronary FAI was measured from preoperative CCTA. The optimal FAI threshold was determined using the Youden index. Kaplan-Meier analysis and Cox regression were used to assess ISR risk. Predictive models were evaluated using area under receiver operating characteristic curves (AUC). RESULTS:A total of 223 patients (263 lesions) were included, with 68.2% male and a median age of 65.0 years. ISR occurred in 14.7% patients during a median follow-up of 17.0 months. The optimal FAI threshold for predicting ISR was -83.5 HU. Kaplan-Meier survival analysis demonstrated that lesions with FAI ≥ -83.5 HU had a significantly higher cumulative incidence of ISR than those with FAI < -83.5 HU (P < 0.001). Lesion-specific pericoronary FAI was identified as independent risk factor of ISR (HR: 8.09, 95% CI: 1.93-33.96, P = 0.004). A model including FAI showed improved predictive performance (AUC: 0.78, 95% CI: 0.72-0.83) compared to models without FAI. CONCLUSION:Lesion-specific pericoronary FAI measured before stent placement is an independent risk factor for ISR. Incorporating FAI into clinical risk models may improve risk stratification and support individualized management after stent placement.
Objective:The objective of this study was to examine the utility of combining the detection of serum prostate-specific antigen (PSA), prostate cancer antigen 3 (PCA3), and apparent diffusion coefficient (ADC) of magnetic resonance imaging for predicting bone metastases in prostate cancer. Methods:We looked back at 67 men with prostate cancer who were admitted to our hospital between December 2015 and December 2022. Based on the results of bone metastasis in ECT, men with prostate cancer were split into two groups: those with metastasis (26 cases) and those without (41 cases). The Gleason score, the levels of serum PSA and PCA3, and the difference between ADCmean and the difference between ADCmax and ADCmin (ADCdiff) were compared between the two groups. Results:Patients with bone metastases of prostate cancer exhibited significantly higher levels of PSA, PCA3, ADCmean, and ADCdiffer compared to the control group (P < .05). ADCmean and ADCdiffer were statistically significant (P < .05) greater in the metastatic group compared to the control group. Prostate cancer bone metastasis risk variables were shown to be elevated PSA, PCA3, ADCmean, and big ADCdiffer by logistic regression analysis (P < .05). ROC analysis showed that the AUC curves of PSA, PCA3, ADCmean, ADCmean, and their combination had certain predictive value. Conclusion:Patients with bone metastases of prostate cancer will have drastically different PSA and PCA3 serum values. Risk factors for prostate cancer bone metastases include elevated PSA and PCA3 levels as well as elevated ADCmean and big ADCdiffer. The combination of PSA, PCA3, and MRI ADC values demonstrated a strong predictive value for bone metastasis in prostate cancer patients.
Objective To explore the relationship between circulating IGFBP-3, IL-6, and bone mineral density and the potential diagnostic role of circulating IGFBP-3 and IL-6 in postmenopausal women with osteoporosis. Methods Eighty-five postmenopausal women at Soochow University's First Affiliated Hospital, Osteoporosis and Menopause Clinics, were recruited. Forty-five of 85 women were diagnosed with osteoporosis. Circulating IL-6, PTH, 1,25(OH)2D3, osteocalcin (OST), IGF-1, IGFBP-3, and bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN) were measured in 40 ordinary and 45 osteoporotic women. A simple regression analysis calculated the correlation between age, BMD, IL-6, and IGFBP-3. Multiple stepwise regression analyses were conducted to determine which variables were independently related to BMD. The potential role of IGFBP-3 and IL-6 in the diagnosis of postmenopausal osteoporosis was predicted using the area under the receiver operating characteristic curve (ROC, AUC). Results Age, years since menopause, and circulating IL-6, PTH, and IGFBP-3 were significantly higher in the osteoporosis group compared to the normal group. Osteoporotic women had substantially lower BMDs of the LS and FN than normal women. Age-related increases were found for IGFBP-3 and IL-6, whereas age-related decreases were observed for LS/FN BMD. IGFBP-3 and IL-6 were both negatively correlated with LS and FN BMD. Stepwise multiple regression analysis showed that IGFBP-3 and IL-6 were strong predictors of BMD in postmenopausal women. AUC cut-off values (IGFBP-3: 3.65, IL-6: 0.205) were best evaluated for the diagnosis of postmenopausal women with osteoporosis, and the AUC for circulating IGFBP-3 and IL-6 were 0.706 (95% CI 0.594–0.818) and 0.685 (95% CI 0.571–0.798), respectively. Conclusion In this cross-sectional study of postmenopausal women, IGFBP-3 and IL-6 were negatively related to BMD. Circulating IGFBP-3 and IL-6 might be essential predictors of postmenopausal osteoporosis and can help predict osteoporotic fracture.
To explore the clinical relevance of stent-specific perivascular fat attenuation index (FAI) in patients with stent implantation. A total of 162 consecutive patients who underwent coronary computed tomography angiography (CCTA) following stent implantation were retrospectively included. The stent-specific FAI at 2 cm adjacent to the stent edge was calculated. The endpoints were defined as target vessel revascularization (TVR) on the stented vessel after CCTA and readmission times due to chest pain after stent implantation. Binary logistic regression analysis for TVR and ordinal regression models were conducted to identify readmission times (0, 1, and ≥ 2) with generalized estimating equations on a per-stent basis. On a per-stent basis, 9 stents (4.5 • Non-invasive stent-specific FAI derived from CCTA was associated with TVR (OR: 1.189 [95 • Stent-specific FAI significantly differed among a subgroup of patients with chest pain after stent implantation and with different readmission times (p = 0.002); the patients with at least one readmission had higher stent-specific FAI than those without readmission (p < 0.001). • Non-invasive stent-specific FAI derived from CCTA could be used as an imaging maker for the functional assessment of patients following stent implantation.
Cholangiocarcinoma (CCA) is an aggressive malignancy originating from the epithelium of the bile duct. The prognosis of patients is poor regardless of radical resection and chemoradiotherapy. The current classification and prognostic model of CCA are unable to satisfy the requirements for predicting the clinical outcome and exploring therapeutic targets. Estrogen signaling is involved in diverse cancer types, and it has long been established that CCA could be regulated by estrogen. In our study, estrogen response was identified to be significantly and stably correlated with poor prognosis in CCA. Employing several algorithms, CCA was classified into ES cluster A and B. ES cluster B was mainly composed of patients with fluke infection and overlapped with CCA cluster 1/2, and ES cluster A was mainly composed of patients without fluke infection and overlapped with CCA cluster 3/4. COMT and HSD17B1 were identified to be responsible for the differential estrogen response between ES clusters A and B, and the estrogen response may be correlated with the differentiation and cancer stemness of CCA at the single-cell level. Complement activation and the expression of C3 and C5, which are mainly expressed by CCA cells, were significantly downregulated in ES cluster B. An estrogen response risk score (ESRS) model was constructed to predict the prognosis of CCA, followed by a nomogram integrating ESRS and clinical features. Finally, altered pathways, applicable drugs and sensitivity to chemical drugs were analyzed specific to the estrogen response. In summary, our results provide insights into the role of the estrogen response in CCA progression as well as applicable drugs and potential therapeutic targets in estrogen metabolism, the complement system and ESRS-related pathways.
Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and P-gp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potentially valuable treatment for gastric cancer.
Increased adipocytes are associated with obesity and many human disorders including cancers. To further understand the molecular mechanisms of adipogenesis, transcriptome sequencing was performed to find genes involved in the adipogenic differentiation of human adipose-derived stem cells (hASCs). The mRNA of taurine transporter (TauT, also known as SLC6A6) was found significantly upregulated in hASCs undergoing differentiation. TauT expression was also markedly increased in fat tissues from obese mice induced by high fat diet or genetic mutations (ob/ob and db/db mice). In vitro, downregulation of TauT attenuated effectively the adipogenic differentiation of hASCs, and TauT overexpression promoted the formation of adipocytes. Among the molecules transported by TauT, hypotaurine and β-alanine promoted adipocyte formation, whereas taurine inhibited the process. Moreover, the inhibitory effect of TauT knockdown on hASCs differentiation was largely reversed by hypotaurine and β-alanine through promoting the downregulation of β-catenin. These results indicated that TauT regulate adipocyte formation through transported amino acids and may serve as a target for therapeutic intervention of obesity.