Cardiometabolic multimorbidity (CMM) is a growing global health challenge. Whether the baseline or cumulative triglyceride glucose and Chinese visceral adiposity index product (TyG-CVAI) can predict incident CMM remains unclear.

We constructed two prospective cohorts from the China Health and Retirement Longitudinal Study (CHARLS): Cohort 1 (n = 8895 patients) to assess the association of the baseline TyG-CVAI with CMM and Cohort 2 (n = 5839 patients) to assess the association of the cumulative TyG-CVAI with CMM. The cumulative TyG-CVAI was calculated as the average TyG-CVAI between baseline and the 2015 wave multiplied by the exposure time. Incident CMM was confirmed via a self-reported physician diagnosis, medication use, and clinical data. Cox regression models were used to estimate hazard ratios (HRs). Nonlinearity was assessed using restricted cubic splines, and predictive performance was evaluated by performing a receiver operating characteristic (ROC) curve analysis.

During follow-up, 875 and 492 incident CMM cases were documented in Cohort 1 and Cohort 2, respectively. Both the baseline and cumulative TyG-CVAI showed graded, positive associations with the CMM risk. Compared with the lowest quartile, the highest quartile was associated with significantly increased risks (baseline: HR = 1.93, 95% CI = 1.46-2.54; cumulative: HR = 1.76, 95% CI = 1.22-2.53). Significant nonlinear relationships with threshold effects were observed for both indices (P for nonlinearity < 0.001). Furthermore, compared with their individual components (TyG or CVAI), both the baseline and cumulative TyG-CVAI demonstrated superior predictive ability for CMM, as indicated by a larger area under the ROC curve.

 Both the baseline and cumulative TyG-CVAI are independent and nonlinear predictors of incident CMM, outperforming TyG or CVAI alone. This easily obtainable metric may enhance risk stratification and help identify high-risk individuals for early preventive intervention.

There is a paucity of data regarding the association between malnutrition and mortality in China. This study aimed to explore the association between the geriatric nutritional risk index (GNRI) and all-cause and cardiovascular mortality in Chinese adults with hypertension.

A total of 14,221 participants with hypertension (mean age, 63.8 ± 9.4 years; 47.2% males) were included in a prospective cohort analysis. GNRI was calculated using the following formula: [1.489 × serum albumin (g/L)]﹢[41.7 × (actual weight/ideal weight)]. The primary outcomes of this study were all-cause and cardiovascular mortalities. Cox regression analysis, restricted cubic spline analysis, and Kaplan-Meier curves were used to evaluate the association between GNRI and mortality.

Over a mean follow-up of 3.9 years, 805 deaths were recorded, of which 397 were due to cardiovascular disease. Overall, GNRI was significantly negatively associated with all-cause and cardiovascular mortality. Compared with participants with normal nutritional status, the hazard ratios for all-cause and cardiovascular mortality were 1.78 (95% CI: 1.41-2.24) and 1.66 (95% CI: 1.17-2.33) among those with mild malnutrition, and 2.13 (95% CI: 1.46-3.11) and 2.38 (95% CI: 1.41-4.02) among those with moderate-to-severe malnutrition, respectively. The association between GNRI and all-cause (P for interaction = 0.004) and cardiovascular mortality (P for interaction = 0.002) was stronger in non-overweight individuals (body mass index (BMI) < 24 kg/m2) than in those who were overweight (BMI ≥ 24 kg/m2).

Malnutrition independently increases the risk of all-cause and cardiovascular mortality in individuals with hypertension.

Management of neonates with hypoplastic left heart syndrome following the Norwood procedure seeks to optimize systemic oxygen delivery while maintaining an appropriate distribution between systemic and pulmonary blood flow. The objective of this study was to quantify actively circulating blood volume, total cardiac output, the pulmonary-to-systemic blood flow ratio (Qp/Qs), and vascular resistance indices at fractions of inspired oxygen (FiO2) of 0.21, 0.5, and 0.9 during the early postoperative period. Measurements were obtained in 16 neonates using an ultrasound dilution technique that determines hemodynamic variables from changes in blood ultrasound velocity following injection of isotonic saline (COstatus, Transonic Systems Inc.). An increase in the Qp/Qs ratio was observed with rising FiO2, which was associated with a reduction in systemic blood flow, while pulmonary blood flow remained statistically unchanged across the FiO2 levels studied. This pattern is consistent with the interpretation that pulmonary blood flow in this setting is mainly influenced by the mechanical properties of the right ventricle to pulmonary artery shunt rather than by FiO2 mediated changes in pulmonary vascular tone. Actively circulating volume index was reduced at baseline and decreased further with increasing FiO2 accompanied by an increase in systemic vascular resistance. These findings indicate that the early postoperative hemodynamics in neonates after the Norwood procedure are more responsive to alterations in systemic circulation than to modulation of pulmonary vascular tone. Therapeutic strategies targeting augmentation of circulating blood volume and reduction of systemic afterload warrant further investigation as potential approaches to optimize postoperative management in this population.

Trace amine-associated receptor 1 (TAAR1) is a novel target for antipsychotic and potentially mood-stabilizing and anti-addictive drugs, offering a new mechanism by modulating dopaminergic, serotonergic, and glutamatergic neurotransmission. TAAR1 agonists from a prior amino oxazolines series were studied preclinically and clinically, but development of partial agonist RO5263397 was halted due to poor metabolization by N-glucuronidation in individuals with UGT2B10 splice site mutations. A medicinal chemistry program subsequently identified new potent and selective TAAR1 ligands from the morpholine series. Two selective partial agonists, RO6799477 and RO6889450, were advanced and showed antipsychotic, stress-response-modulating, and anti-addictive-like activity in rodent models. They reduced PCP- and cocaine-induced hyperlocomotion, potentiated olanzapine's effect, partially reversed cocaine-induced facilitation of intracranial self-stimulation and demonstrated anxiolytic-like properties in the stress-induced hyperthermia test. Neural activation profiles, measured by pharmacological MRI, differed from first and second-generation antipsychotics. Non-clinical drug abuse liability studies with RO6889450 indicated a favorable low abuse liability profile and suggested a lack of reinforcing effects. Preclinical safety studies indicated a favorable profile with clinically monitorable and reversible findings. Both compounds progressed into Phase I single and multiple ascending dose studies in healthy volunteers. RO6799477 was well tolerated, with rapid absorption and dose-proportional pharmacokinetics, though higher doses led to nervous system and cardiovascular adverse events. RO6889450 was well tolerated up to 300 mg; at 450 mg, dose-limiting adverse events included postural tachycardia and erythema. Together, these results indicate the translational potential and support further clinical exploration of TAAR1 agonists as a novel therapeutic option for neuropsychiatric disorders, particularly schizophrenia and substance use disorder.

Chemotherapy-induced immunosuppression compromises therapeutic outcomes in oncology, particularly in non-small cell lung cancer (NSCLC). While natural polysaccharides have emerged as promising candidates to counteract drug-related immunosuppression, the therapeutic potential of riclin remains unexplored in chemotherapeutic contexts. Here, we systematically evaluated riclin's immunoadjuvant efficacy in a murine NSCLC model treated with gemcitabine (GEM). Oral riclin modulated gut microbiota diversity and metabolite profiles while activating the immune-hematopoietic axis, thereby boosting immunity and hematopoiesis. Mechanistically, riclin counteracted GEM-induced immunosuppression through coordinated NF-κB and JAK-STAT activation, as evidenced by the restoration of circulating immune cells and splenic architecture, expansion of bone marrow mononuclear cells (BMNCs) and Lineage⁻Sca-1⁺Kit⁺ (LSK) cells, and suppression of apoptosis. Notably, riclin demonstrated synergistic effects with GEM, achieving 98% tumor burden reduction while concurrently alleviating systemic immunosuppression. We propose that riclin, a novel oral immunoadjuvant capable of enhancing chemotherapeutic efficacy in NSCLC, supports its clinical development as a promising combination strategy.

Helminth infections are consistently associated with reduced cardiovascular disease (CVD) risk, yet the biological mechanisms underlying this relationship remain unclear. The gut microbiome and metabolome are key regulators of cardiometabolic health and may mediate infection-associated effects on host physiology. Here we show that Schistosoma mansoni infection associates with distinct gut microbial and metabolic profiles linked to CVD risk in people living in Uganda. In a cross-sectional study of 209 individuals living in communities with contrasting S. mansoni endemicity, we profile the gut microbiome using 16S rRNA gene sequencing and the faecal metabolome using liquid chromatography-mass spectrometry. S. mansoni infection associates with increased gut microbial diversity and distinct taxonomic signatures, including enrichment of taxa such as Treponema and depletion of Prevotella and Streptococcus. Several infection-associated microbial taxa statistically mediate the relationships between S. mansoni infection and cardiovascular disease risk. Faecal metabolomic profiling identifies infection-associated metabolites, and integrative analyses showed linked microbe-metabolite networks associated with cardiovascular risk.These findings identify gut microbiome and metabolome signatures associated with S. mansoni infection and cardiovascular disease risk in Uganda. Although causality cannot be inferred, this work provides insight into host-parasite-microbiome interactions and highlights microbial and metabolic pathways relevant to cardiometabolic health.

Early identification of individuals at elevated cardiovascular risk using routine health examination data is essential for preventive cardiology. Machine learning (ML) offers a scalable and non-invasive approach to enhance risk stratification.

This retrospective study analyzed 899 asymptomatic adults (mean age: 57.3 ± 11.8 years; 608 men) who underwent coronary artery calcium (CAC) scanning or coronary computed tomography angiography (CCTA) at a health management center in Taiwan between 2018 and 2021. Participants were classified into four CAC-based risk categories (0, 1-99, 100-299, ≥300). Nineteen demographic and clinical variables were used to train decision tree (DT), random forest (RF), and support vector machine (SVM) classifiers. Model performance was evaluated using accuracy and AUC, with AUC differences assessed by DeLong's test.

The RF model demonstrated the best performance (accuracy: 76 %, AUC: 0.78), followed by SVM (accuracy: 70 %, AUC: 0.78) and DT (accuracy: 74 %, AUC: 0.75). All models showed clinically meaningful discrimination using readily accessible, non-laboratory health examination data.

ML models incorporating routine health examination variables can effectively predict CAC-defined cardiovascular risk and may serve as practical, scalable pre-screening tools within preventive healthcare workflows, particularly in settings where laboratory testing or advanced imaging resources may be limited.