BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for cancer chemoimmunotherapy. However, only few drugs or treatment modalities can trigger an ICD response and none of them exert a considerable clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic response are required. In this study, five new cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed and synthesized. Among them, Ir-1 exhibited the highest in vitro cytotoxicity. Mechanistically, Ir-1 could trigger autophagy-dependent ferroptosis and a subsequent ferroptosis-dependent ICD response as well as indoleamine 2,3-dioxygenase (IDO) inhibition via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in MDA-MB-231 cells. When immunocompetent BALB/c mice were vaccinated with Ir-1-treated dying TNBC cells, antitumor CD8⁺ T-cell response and Foxp3⁺ T-cell depletion were induced, resulting in long-lasting antitumor immunity in TNBC cells. Moreover, combination therapy with Ir-1 and anti-PD1 could substantially augment in vivo therapeutic effects. Based on these results, Ir-1 is a promising candidate for chemoimmunotherapy against TNBC and its effects are mediated synergistically via ICD induction and IDO blockage.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/pathology* ; Jumonji Domain-Containing Histone Demethylases/chemistry* ; Gene Expression Regulation, Leukemic ; Oxidoreductases, N-Demethylating/genetics* ; Cell Line, Tumor

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.