Gastric cancer (GC) represents a prevalent and malignant neoplasm worldwide, characterized by high morbidity and mortality rates. Traditional Chinese medicine offers distinct advantages in the treatment of GC, with Saikosaponin D (SSD), a natural triterpenoid saponin derived from the herb Bupleurum chinense, exhibiting anti-tumor activity in multiple cancer types. Nonetheless, the precise molecular mechanisms underlying SSD's anti-GC effects remain incompletely elucidated.

This study aims to explore the proliferation-inhibitory, metastasis-inhibitory, and pro-apoptotic effects of SSD on GC cells, while clarifying its potential mechanism involving PKM2-mediated lactylation and metabolic reprogramming.

The effects of SSD on cell viability, invasion, migration and apoptosis in BGC-823 and SGC-7901 cells were assessed using assays such as CCK-8, colony formation, transwell, wound healing, flow cytometry, and Western blot. Proteomic sequencing was employed to identify relevant pathways and molecular targets. Furthermore, molecular docking and molecular dynamics (MD) simulations were performed to investigate the interaction between SSD and PKM2. PKM2 overexpression experiments were also carried out to further clarify the underlying mechanisms. An in vivo gastric cancer xenograft mouse model was established to evaluate the antitumor efficacy of SSD. Collectively, these approaches helped highlight SSD's potential as an anticancer agent, particularly in targeting glucose metabolism in gastric cancer.

In vitro experiments showed that SSD significantly reduced the viability, proliferation, migration, and invasion of BGC-823 and SGC-7901 cells in a dose-dependent manner, while promoting apoptosis by upregulating cleaved caspase-3/9 expression. In vivo, SSD notably inhibited xenograft tumor growth and decreased Ki-67 expression and pan-lactylation. Mechanistically, SSD downregulated PKM2 expression and suppressed glycolysis-related metabolic processes, thereby reducing pan-lactylation and H3 histone lactylation levels in GC cells. Furthermore, PKM2 overexpression abrogated SSD-induced inhibition of GC cell proliferation and reduction in H3 histone lactylation levels.

SSD suppresses GC cell growth, migration, and invasion, while promoting apoptosis both in vitro and in vivo. Its anti-tumor mechanism is associated with the suppression of PKM2-mediated glycolysis, and the regulation of global protein lactylation and H3 histone lactylation. These findings highlight SSD's potential as a candidate anticancer agent for GC, particularly by targeting glucose metabolism.

Primary immunodeficiency diseases (PIDs) are a heterogeneous group of genetic disorders associated with recurrent infections, immune dysregulation, and increased morbidity and mortality when diagnosis is delayed. Primary care physicians (PCPs) play a critical role in early recognition; however, data on PCPs' knowledge and preparedness regarding PID remain limited. This study aimed to evaluate PCPs' knowledge, clinical approaches, and preparedness regarding PIDs across Türkiye.

This nationwide, cross-sectional study included 385 PCPs-general practitioners (GPs), family medicine residents (FMRs), and family medicine specialists (FMSs)- working in Family Health Centers in Türkiye. Participants completed a structured online questionnaire assessing sociodemographic characteristics, educational background, clinical experience, self-perceived PID knowledge, and performance on 15 PID-related multiple-choice questions based on international guidelines. Total knowledge scores (range: 0-15) were calculated. Correct response rates for individual items and total scores were compared across professional groups and according to educational and clinical variables. Multivariable logistic regression analyses were performed to identify factors independently associated with higher knowledge scores.

The mean total knowledge score was 9.09 ± 2.46 (range 0-15). FMSs significantly higher total scores than FMRs and GPs (GPs 8.67 ± 2.47; FMRs 8.82 ± 2.63; FMSs 9.83 ± 2.03; p < 0.001). In multivariable analysis, being an FMS was independently associated with scoring above the mean (OR = 2.02, 95% CI: 1.26-3.23; p = 0.004). Regular participation in general medical educational activities was associated with significantly higher total scores (9.74 ± 2.31 vs. 8.23 ± 2.38; p < 0.001). PCPs who participated in PID-related educational activities within the past five years were also associated with higher total scores (9.43 ± 2.58 vs. 8.87 ± 2.47; p = 0.027). PCPs who reported requesting immunoglobulin testing or referring patients with recurrent lower respiratory tract infections achieved significantly higher total scores (9.18 ± 2.43 vs. 7.52 ± 2.42; p = 0.001). PCPs who self-perceived their PID knowledge as moderate or good had substantially higher total knowledge scores compared to those who self-perceived their knowledge as low (Low: 8.36 ± 2.55; Moderate: 9.41 ± 2.26; Good: 10.09 ± 2.50; p < 0.001).

PID-related knowledge scores among PCPs differed across professional groups, with GPs demonstrating lower scores. Higher knowledge scores were significantly associated with being an FMS and with participation in regular general medical education and past 5 year PID-related education. Strengthening targeted educational strategies, particularly for GPs in primary care settings, may improve early recognition and management of PIDs.

Cardiovascular disease is linked to mental health conditions. Patients with cardiovascular disease and comorbid psychiatric illnesses such as major depressive disorder or generalized anxiety disorder often experience greater physical limitations and decreased overall health.

To determine if proactive psychiatric interventions improve staff satisfaction and patient outcomes, such as reducing length of stay and decreasing the 30-day readmission rate, for patients hospitalized on cardiac units with psychiatric comorbidities.

The implementation of a proactive psychiatric consultation-liaison service, which included proactive screening of psychiatric needs among patients hospitalized on cardiac units, targeted support for cardiovascular staff, and supportive interactions for patients.

Comparison between preintervention and postintervention periods indicated a 21% reduction in the 30-day readmission rate for patients hospitalized on cardiac inpatient units with psychiatric comorbidities without adversely affecting hospital length of stay. Staff satisfaction significantly increased with the availability of psychiatric resources.

The implementation of a multi-disciplinary proactive psychiatric consultation-liaison service on inpatient cardiac units was associated with an increase in cardiovascular staff satisfaction with psychiatric services and a decrease in the 30-day readmission rate of patients with psychiatric comorbidities who were hospitalized for cardiovascular services without significantly affecting length of stay.

Hypertension is a key risk factor for type II endoleaks after endovascular aneurysm repair (EVAR), but the biomechanical mechanisms linking blood pressure to outcomes are unclear. This study aimed to elucidate these mechanisms by examining how elevated branching vessel pressure affects sac hemodynamics and wall mechanics. This study constructed a type II endoleak model with a patent inferior mesenteric artery (IMA) and two lumbar arteries (LAs). The non-Newtonian fluid model and a two-way fluid-structure interaction (FSI) method were utilized to simulate the blood flow and vessel wall mechanics for type II endoleak. By setting different inlet pressures for the branching vessels, this study investigated the impact of blood pressure on the biomechanical environment following EVAR. An increase in IMA and LA inlet pressures led to a reversal of blood flow at the branch vessels and resulted in an unstable flow field within the aneurysm sac. This was accompanied by elevated wall shear stress (WSS), energy loss (EL), sac wall displacement, and Von Mises stress. The pressure within the aneurysm sac also rose correspondingly. Elevated inlet pressures in the IMA and LA lead to increased and prolonged retrograde flow into the aneurysm sac, elevate sac pressure, raise WSS and EL, and amplify wall displacement and mechanical stress-collectively intensifying hemodynamic disturbance and structural loading on the aneurysm wall.

Atherosclerosis (AS) serves as the shared pathological substrate for cardiovascular and cerebrovascular diseases. The traditional passive-accumulation model centered on cholesterol no longer explains why lipid targets are met while clinical events persist and has therefore prompted a shift toward a combined anti-inflammatory and lipid-lowering strategy. Inflammasomes-particularly the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-integrate and amplify multiple pro-atherogenic signals and have emerged as a key target. However, no agent targeting NLRP3 has yet gained Food and Drug Administration (FDA) approval, and the unmet clinical need remains pressing. Natural products are considered a promising option for this chronic and multifactorial disease due to their favorable safety profile and multi-target effects. However, a narrative review of intervention strategies at various levels-from traditional Chinese medicine (TCM) formulas and plant extracts to natural compounds-is still lacking. We searched for publications from the past 4 years using PubMed, Web of Science, EMBASE, the Cochrane Library, and Scopus. This narrative review highlights the key role of NLRP3 inflammasome-related signaling pathways in the development of AS and evaluates the evidence for natural products targeting these pathways. Given the limitations of the available evidence, large-scale, high-quality randomized controlled trials are needed to establish clinical efficacy and safety.

Drugs with anticholinergic properties are commonly used in older adults for various medical conditions, but the long-term cardiovascular consequences of cumulative exposure have not been well established. This study aims to examine whether cumulative anticholinergic drug burden is associated with incident cardiovascular events.

The large population-based cohort study included 508,273 Stockholm residents aged ≥ 45 years on January 1, 2008, who had no history of major cardiovascular diseases, with follow-up until December 31, 2021. Anticholinergic burden was assessed using the Anticholinergic Cognitive Burden scale and quantified as annual consumption in defined daily doses (DDDs). Inverse probability-weighted Cox proportional hazards models were used to estimate the weighted hazard ratio (HR) and 95% confidence interval (CI) for the associations between both baseline and time-varying exposure and incident cardiovascular events, overall and by disease subtypes.

A total of 118,266 incident cardiovascular events were recorded during a median follow-up of 14.0 years. Higher levels of anticholinergic drug exposure were significantly associated with an increased risk of cardiovascular events after adjusting for sociodemographic, lifestyle, and clinical risk factors in both baseline and time-updated models, with stronger associations observed in the latter. In the time-updated model, the HR (95% CI) increased with annual cumulative exposure: 1.16 (1.13, 1.20) for 1-89 DDDs, 1.31 (1.28, 1.34) for 90-364 DDDs, and 1.71 (1.67, 1.76) for ≥ 365 DDDs. A significant dose-response relationship was observed across event subtypes. In the highest exposure group, the HR (95% CI) was 2.70 (2.57, 2.84) for heart failure, 2.17 (2.08, 2.27) for arrhythmias, 1.48 (1.34, 1.63) for artery disease, 1.32 (1.21, 1.43) for venous thromboembolism, 1.46 (1.37, 1.55) for myocardial infarction, and 1.32 (1.25, 1.39) for cerebrovascular disease. Results were consistent in subgroups and sensitivity analyses.

These findings highlight the potential cardiovascular harms of anticholinergic drug burden in middle-aged and older adults and underscore the need for careful prescribing and monitoring of such medications.

Cardiovascular diseases are the leading cause of death globally. Consequently, metabolomics studies have in recent years aimed at identifying relevant biomarkers, yet no studies have been performed in twin populations, which reduce confounding due to genetic and environmental factors. We included 11,217 twins (age at intake, 47-94 years (mean = 65)) from the Swedish Twin Registry, holding data on 173 nuclear magnetic resonance metabolomic biomarkers and nationwide register-based data on diagnoses of ischemic stroke, ischemic heart disease, myocardial infarction, angina pectoris, and coronary artery disease. Only incident cases (i.e., exclusively holding diagnosis after blood sampling) were included for statistical analyses, which were performed at the individual level and the twin-pair level by Cox regression analyses. Lastly, biomarkers significant in both analyses were inspected, hence conditioning on the twin pair design. Fifty-one biomarkers were found to be associated with myocardial infarction after correction for multiple testing, all showing a hazard ratio above 1. LASSO regression analysis of these biomarkers identified four biomarkers, all related to ApoB lipoprotein biology, potentially reflecting a pro-atherogenic effect. Investigation of biomarkers with p-values < 0.05 identified 20 biomarkers for ischemic heart disease, all showing hazard ratios below 1 and primarily related to ApoA1 lipoprotein biology, potentially reflecting an anti-atherogenic effect. Lastly, three biomarkers, i.e., acetoacetate, bOHbutyrate, and isoleucine, were found for ischemic stroke, all showing a hazard ratio above 1. Taken together, different biomarkers associated with the disease phenotypes indicate that their molecular profiles are different, despite their common basis. The ApoB stands out as a promising biomarker for myocardial infarction.

Recent evidence questioned the overall safety and efficacy of colchicine in patients with coronary artery disease (CAD), as novel evidence focusing on acute coronary syndromes (ACSs) gave neutral results, while trials focusing on chronic coronary syndrome supported colchicine administration to improve long-term outcomes. However, no study has ever explored whether there is a true therapeutic difference across the populations or these discrepancies are due to additional confounders. Against this background, we performed a systematic review and meta-analysis of randomized trials of colchicine in patients with CAD. The primary endpoints were trial-defined major adverse cardiovascular events (MACE) and serious adverse events (SAEs). Secondary endpoints included all-cause death, measures of ischemia (cardiovascular death, myocardial infarction [MI], any revascularization, stroke) and measures of safety (serious infections or sepsis and gastrointestinal adverse events). All analyses included an interaction term for the clinical presentation. Sensitivity analyses were performed to explore sources of heterogeneity. After literature search, 20 trials encompassing a total of 21,486 patients (65.4% ACS) were included. Colchicine significantly reduced MACE (incidence rate ratio [IRR]: 0.70; 95% CI 0.55-0.87) without increasing risk for SAEs. Colchicine also reduced MI (IRR 0.81; 95% CI 0.70-0.94) and any revascularization (IRR 0.71; 95% CI 0.51-0.99), while increasing the risk of gastrointestinal adverse events (IRR 1.68; 95% CI 1.23-2.28). No statistically significant interaction was noted for clinical presentation for any endpoint, but a significant interaction for the drug dosage administered and the relationship with the COVID-19 pandemic was noted. In conclusion, the use of colchicine in patients with CAD reduces MACE without significantly increasing SAEs compared to control, although increasing gastrointestinal adverse events, without interaction by clinical presentation.

Anticoagulation is a critical component in the treatment of cardiovascular diseases. Large randomised controlled trials have demonstrated that direct oral anticoagulants (DOACs) are effective and safe for stroke prevention in patients with atrial fibrillation (AF) and treatment or prevention of venous thromboembolism. Nevertheless, for specific cardiac indications and patient characteristics, vitamin K antagonists (VKAs) rather than DOACs are either preferred, or the benefit of DOACs in comparison to VKAs remains uncertain. These include, among others, mechanical heart valves, AF associated with moderate-to-severe mitral stenosis, left ventricular or atrial thrombus, and older patients with frailty. As VKAs will continue to play a vital role in the management of patients with cardiovascular diseases in the foreseeable future, this review discusses cardiac indications and patient characteristics that necessitate the use of VKAs and general management principles of VKA therapy.

Pulmonary hypertension (PH) associated with lung disease (Group 3 PH) is a serious complication that negatively impacts patient outcomes. This study aimed to assess the epidemiology and disease burden of Group 3 PH in the UK, focusing on interstitial lung disease (ILD-PH).

Retrospective cohort study.

Electronic medical records from the Clinical Practice Research Datalink Aurum, linked to Hospital Episode Statistics.

6690 incident cases of Group 3 PH, including 1561 ILD-PH cases, were identified from a sample of approximately 33 million individuals between January 2017 and December 2019.

Primary outcomes included prevalence and incidence of Group 3 PH and ILD-PH. Secondary outcomes included patient characteristics, overall survival, hospitalisations, outpatient visits and healthcare costs.

Over the 3-year period, prevalence and annual incidence were 139/million (95% CI 134 to 142) and 73/million/year (95% CI 70 to 76) for Group 3 PH and 36/million (95% CI 33 to 37.3) and 17/million/year (95% CI 16 to 19) for ILD-PH. Median overall survival was 19.3 (95% CI 17.77 to 20.8) for Group 3 PH and 15.1 months (95% CI 12.66 to 18.2) for ILD-PH. Following a PH diagnosis, all-cause inpatient visits increased by 33.6% from baseline. The all-cause annual hospitalisation rate was 1.63 (95% CI 1.6 to 1.65) for Group 3 PH and 1.36 (95% CI 1.31 to 1.4) for ILD-PH, with about half linked to PH diagnosis. Pulmonologists were the most consulted specialists, averaging 1.78 (95% CI 1.76 to 1.81) and 2.31 (95% CI 2.25 to 2.37) visits per patient per year for Group 3 PH and ILD-PH, respectively. Annual per-patient costs were £7761 (95% CI 7759 to 7762) for Group 3 PH and £7170 (95% CI 7167.17 to 7173.69) for ILD-PH.

Incidence and prevalence of Group 3 PH in the UK are consistent with other European countries. Patients had poor survival, with PH associated with half of hospital admissions, highlighting the negative impact of PH in chronic lung disease.