Inhibition of the VEGF/VEGFR-2 pathway is a validated strategy to suppress tumor angiogenesis and progression; however, long-term use of several VEGFR-2 tyrosine kinase inhibitors is limited by resistance and systemic toxicity. Here, a series of novel indolinone-matrine hybrids were designed and synthesized via a molecular hybridization strategy. The antiproliferative activities were evaluated against human hepatocellular carcinoma (HCC) cell lines (HepG-2, HuH7, and MHCC97H). Among them, J9 showed the most potent activity with IC₅₀ values of 5.81, 2.14, and 3.03 μM, respectively, and relatively low cytotoxicity toward HEK-293 cells (IC₅₀ = 27.90 μM) and HL7702 cells (IC50 = 52.23 μM). In HuH7 cells, J9 significantly inhibited colony formation and migration, induced G1-phase arrest, and promoted apoptosis in a dose-dependent manner. Western blot analysis indicated that J9 treatment was associated with downregulation of VEGFR-2 and activation of caspase-dependent apoptosis (increased cleaved caspase-3 and cleaved PARP). Moreover, J9 inhibited VEGFR-2 kinase in vitro (IC₅₀ = 253.51 ± 1.21 nM), and docking/MD simulations suggested stable binding within the VEGFR-2 ATP-binding pocket. Collectively, J9 represents a promising matrine-derived antitumor candidate with potential VEGFR-2-targeting activity.

Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are key differential diagnoses in parathyroid hormone (PTH)-mediated hypercalcemia. While PHPT often arises from single-gland parathyroid adenomas, CaSR mutations are typically associated with FHH. However, the coexistence of CaSR mutations and PHPT represents an unusual presentation, and the variability in their clinical impact remains underexplored. This report highlights two distinct cases of heterozygous CaSR mutations, including a novel mutation, shedding light on their potential roles in disease pathogenesis and management.

The first case involves a 54-year-old Caucasian female with a heterozygous Ala986Ser CaSR mutation, PHPT due to a parathyroid adenoma, and autoimmune Graves' disease. She presented with recurrent sicca syndrome, fatigue, hypercalcemia, elevated PTH, and hypercalciuria. Post-parathyroidectomy, persistent hypercalcemia and abnormal laboratory findings, alongside TRAK and TG antibodies, suggested a multifactorial pathogenesis. Imaging showed patchy hypoechoic thyroid parenchyma and recurrent adenoma. DXA revealed mild osteopenia, while calcimimetic therapy with cinacalcet was initiated but subsequently discontinued due to gastrointestinal intolerance. This unusual overlap of autoimmune and genetic factors emphasizes the complexity of managing PHPT with coexisting CaSR mutations. The second case describes a 52-year-old Caucasian male with a heterozygous Glu1011Gln CaSR mutation. He presented with severe hypercalcemia, elevated PTH, nausea, and diffuse musculoskeletal pain. Imaging revealed no adenomas, but sonography later identified a hypoechoic lesion with central vascularization, suggestive of a potential adenoma. Initial symptomatic improvement occurred despite persistently elevated biochemical markers; however, clinical worsening with recurrent abdominal symptoms and progressive bone mineral density loss was observed during follow-up. This case highlights a possible association between CaSR variants and sporadic adenomas, underscoring diagnostic complexity rather than direct causality.

These cases highlight the complex clinical presentations in patients carrying CaSR variants and autoimmune components, suggesting a broader spectrum of clinical phenotypes and pathogenesis than previously understood. The findings emphasize the importance of genetic analysis in atypical cases and underscore the need for further research into the role of CaSR mutations in PHPT, which may inform future diagnostic and therapeutic strategies.

Colorectal cancer (CRC) and its associated treatments cause significant psychological distress for both patients and their spousal caregivers. Traditional psychosocial interventions often focus on individuals rather than dyads, despite the interconnectedness of patient and caregiver wellbeing. While dialectical behavior therapy (DBT) provides evidence-based skills for emotion regulation and interpersonal effectiveness, it has not been systematically adapted for dyadic cancer care.

To evaluate the effectiveness of Better Together, a DBT-informed dyadic intervention, in improving psychological and relational outcomes for CRC patient-spouse dyads. The study also explored whether these effects differed by role (patient vs. caregiver) and assessment time point (active intervention period vs. follow-up period).

In a randomized controlled trial, 254 post-treatment CRC patient-spouse dyads were randomly assigned to the intervention group (7-week DBT-informed sessions plus usual care) or a control group (usual care only). Outcomes (psychological distress, perceived stress, relationship satisfaction, and distress disclosure) were assessed at baseline (T1), post-intervention (T2), and 3-month follow-up (T3). Linear mixed-effects models analyzed intervention effects.

Intervention effects varied significantly by role and time point. Patients showed greater improvements in psychological distress (Δ = -5.13, p < 0.001) and perceived stress (Δ = -5.30, p < 0.001) from T1 to T2, and these effects were sustained at T3. Caregivers demonstrated no immediate improvements at T2 but significant delayed gains in relationship satisfaction (Δ = 4.75, p < 0.001) and distress disclosure (Δ = 6.27, p < 0.001) during follow-up (T2 to T3). Patterns of change differed significantly between patients and caregivers across outcomes and over time.

The BT program effectively improved both individual and dyadic outcomes, with patients benefiting immediately in psychological domains and caregivers exhibiting delayed improvements in relational outcomes during the follow-up period. These findings support implementing phased, role-sensitive dyadic interventions that address the distinct temporal needs of patients and caregivers in cancer care.

Obstructive sleep apnoea (OSA) and excessive daytime sleepiness (EDS) are recognized contributors to road traffic accidents (RTAs). However, the association between OSA, EDS, and RTAs remains underexplored among Nigerian truck drivers.

A cross-sectional study was conducted among 306 adult male long-distance truck drivers in Ado-Ekiti, Nigeria. The Berlin Questionnaire was used to assess the risk of OSA while the Epworth Sleepiness Scale evaluated excessive daytime sleepiness (EDS), and self-reported previous RTAs were adapted in the questionnaire.

The mean age (SD) of the truck drivers was 42.3±9.1 years. The prevalence of snoring, excessive daytime sleepiness and dozing off while driving among the participants was 57%, 46.7% and 21% respectively. Overall, 43.5% of truck drivers were identified as having high risk for OSA. The risk factors associated with OSA were advanced age (50 years and above), self-reported systemic hypertension, obesity and increased neck circumference. In the three years preceding the study, approximately one-third of truck drivers reported being involved in RTAs which was associated with the use of stimulants aOR 11.63(95%CI 3.73 to 36.24, p=0.001), sleeping pills aOR 5.26(95%CI 1.50 to 18.40, p=0.001), high OSA risk aOR 2.21 (95%CI 1.60 to 4.80, p=0.03), EDS aOR 2.75(1.60 to 4.80, p=0.001) and extended working hours aOR 1.02(95%CI 1.00 to 1.04, p=0.03). More than 90% of the drivers were unaware that EDS constitutes a medical concern.

The high prevalence of excessive daytime sleepiness, and obstructive sleep apnoea among truck drivers highlights the underrecognized contributors to road traffic accidents. This underscores the need for targeted sleep disordered screening and regulatory interventions by policymakers to improve road safety in Nigeria.

The links between periodontal disease and a number of systemic diseases including respiratory diseases have been widely reported in the literature. The burden and prevalence of periodontal disease and chronic obstructive pulmonary disease (COPD) is increasing globally. Periodontitis is now recognised as an independent risk factor for COPD. In addition, these two chronic diseases have similar pathogenic mechanisms. Despite these facts, the role of prevention of periodontitis in the management of COPD had not been fully explored. The aim of the study was to look at the effect of non-surgical periodontal therapy on the control of symptoms of Chronic Obstructive Pulmonary Disease (COPD) in our resource-limited settings.

Sixty-nine COPD patients with concurrent periodontitis, who were at least 40 years old, were recruited from the Chest clinic of a tertiary institution in Ile Ife, Osun State, Nigeria between July 2021 and January 2023. Using GraphPad software, the participants were randomly categorised into two groups (control and intervention). The intervention group received non-surgical periodontal therapy (NSPT) and oral hygiene instructions (OHI) while the control group received oral hygiene instruction (OHI) only after the initial determination of the aMMP-8 assay and oral examinations. However, they had their non-surgical periodontal therapy after the three months follow-up. Clinical parameters such as COPD Assessment Test (CAT) scores, probing pocket depths (PPD), clinical attachment level (CAL) and a biomarker active matrix metalloproteinase-8 (aMMP-8) were recorded at baseline and after 3 months. Independent t-test was used for normally distributed variables for the two groups while Mann-Whitney U test was used for non-normally distributed variables. Paired t-test was used for the intra-group comparisons of the mean values and p value set at <0.05.

A total of 69 participants comprising 35 participants in the intervention group and 34 participants in the control group were enrolled in this study. The intervention group demonstrated statistically significant improvements in the CAT scores from 18.66 to 15.06 (p<0.04), aMMP-8 from 26.28ng/ml to 18.66ng/ml (p<0.001), mean PPD from 2.78mm to 2.64mm (p<0.05) and mean CAL from 4.64mm to 4.50mm (p<0.001) in comparison to the control group ( CAT scores from 18.91 to 17.59 p=0.07, aMMP-8 from 30.80ng/ml to 27.11ng/ml p=0.11, mean PPD from 2.82mm to 2.84mm p=0.37, and mean CAL from 4.88mm to 4.89mm p=0.69).

The results of this study emphasize the possible advantages of incorporating periodontal care into strategies for managing COPD.

Dietary sodium and potassium intake are key determinants of blood pressure (BP) control in hypertensive patients. However, their associations with longitudinal home BP control in patients with apparent treatment-resistant hypertension (aTRH) remain unclear. In this prospective cohort study, baseline 24-hour urinary sodium and potassium excretion, objective biomarkers of dietary sodium and potassium intake, as well as urinary sodium-to-potassium (Na/K) ratio were evaluated as exposure variables. The primary outcome was longitudinal home BP control during follow-up. Mixed-effects models were used to assess these associations. A total of 172 patients were followed for a median of 39.3 months, contributing 7547 morning and 6640 evening home BP measurements. After multivariable adjustment, each 1-standard deviation (SD) increase in urinary sodium excretion (99.49 mmol) was associated with poorer home systolic BP (SBP) control (morning: odds ratio [OR] 0.59, 95% confidence interval [CI] 0.38-0.89; evening: OR 0.65, 95% CI 0.44-0.96). Each 1-SD increase in the urinary Na/K ratio (1.98 units) was associated with poorer morning (OR 0.68, 95% CI 0.48-0.97) and evening home SBP control (OR 0.69, 95% CI 0.51-0.94). A higher Na/K ratio was also associated with poorer overall evening home BP control (OR 0.73, 95% CI 0.54-0.98). Consistent associations were observed when BP was analyzed as a continuous outcome. Urinary potassium excretion alone was not significantly associated with home BP control. Dietary sodium restriction and maintenance of sodium-potassium balance may represent important strategies for improving home BP control in patients with aTRH. Trial Registration: Not applicable. This study was a prospective observational cohort study with no assignment of participants to any intervention; thereby clinical trial registration was not required.

Abdominal obesity and related cardiometabolic risk (CMR) factors frequently begin in adolescence and contribute to long‑term health burden, yet longitudinal trajectories in U.S. youth are poorly characterized. This study quantifies the prevalence and 2‑ and 4‑year incidence of emerging CMR, with emphasis on excess adiposity, in a diverse adolescent cohort. We analyzed longitudinal data from the Adolescent Brain Cognitive Development Study, collected at three time points: 2018-2020 (mean age, 12.1 years), 2020-2022 (mean age, 14.2 years), and 2022-2024 (mean age, 16.1 years). Adolescents (n = 4788 to 3313) with anthropometric and laboratory data were included. Abdominal obesity was defined as a waist-to-height ratio > 0.5. Additional CMR factors included elevated total cholesterol (≥ 145 mg/dL), glycated hemoglobin (HbA1c ≥ 5.7%), and high blood pressure (≥ 95th percentile for age, sex, and height). Weighted prevalence and 2- and 4-year incidence were calculated. At baseline, abdominal obesity affected 38.4% (95% CI: 36.4%-40.4%), followed by elevated cholesterol (17.6%), HbA1c (8.7%), and blood pressure (3.0%). Over a four-year period, new-onset abdominal obesity occurred in 10.5% of individuals, compared with 15.4% for cholesterol, 4.7% for HbA1c, and 3.1% for blood pressure. The steepest CMR progression was observed for lipid and adiposity markers. Abdominal obesity is highly prevalent by early adolescence, and new cardiometabolic risk develops rapidly, particularly for adiposity and dyslipidemia. These results highlight the need for early obesity screening and interventions to mitigate long‑term cardiometabolic risk in youth.

Left ventricular hypertrophy (LVH) is a serious complication of hypertension. However, the association between the nondipper heart rate (NDHR) and the risk of LVH remains unclear.

A cross-sectional analysis was conducted involving 991 patients with essential hypertension. NDHR was defined as a <10% reduction in nocturnal heart rate assessed by 24-h ambulatory blood pressure monitoring. Propensity score matching (PSM) was used to balance baseline characteristics. The independent association was assessed using multivariable logistic regression, and interactions were evaluated on multiplicative and additive scales.

After exclusions, 991 eligible hypertensive patients were included, with 234 PSM pairs of nondipper and dipper participants achieving balanced baseline characteristics. The NDHR was independently associated with LVH after multivariable adjustment (OR = 1.588 [95%CI: 1.062-2.373]; P = 0.024). A significant synergistic interaction was observed between NDHR and nondipper blood pressure, with the dual nondipper phenotype conferring the highest odds of LVH (OR = 2.52 [95%CI: 1.68-3.78]). Additive interaction measures confirmed biological synergy (RERI = 0.98; AP, 0.39). A nomogram incorporating NDHR demonstrated acceptable discrimination for LVH (AUC = 0.66 [95%CI: 0.61-0.71]) and provided superior net benefit across a wide threshold probability range (20%-80%). Subgroup analyses indicated stronger associations in younger patients and those not using ACEI/ARBs.

NDHR is an independent risk factor for LVH and exhibits significant synergy with NDBP. Assessment of nocturnal heart rate decline, despite its behavioral confounders, may enhance cardiovascular risk stratification in hypertension.

ObjectiveCongestive heart failure (CHF) is a chronic disease marked by impaired cardiac function, and excess visceral fat has been reported to be associated with CHF. While the age-adjusted visceral adiposity index (AVAI) is a novel metric for evaluating visceral fat, its association with CHF has not been well elucidated.MethodsThe association between AVAI and CHF prevalence was assessed using cross-sectional data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES). Logistic regression was used to assess the association between AVAI and CHF prevalence, with sequential adjustment for covariates. Subgroup analyses stratified by demographic variables and lifestyle factors were done to examine the robustness of the results. Lastly, the discriminative ability of VAI and AVAI in distinguishing individuals with and without prevalent CHF was evaluated using receiver operating characteristic (ROC) curve analysis.ResultsA total of 6,695 participants were included in the analysis, comprising 6,470 without CHF and 225 with CHF. Logistic regression revealed a significant positive association between AVAI and CHF prevalence (OR = 1.75, 95% CI: 1.62-2.89), which remained robust after adjusting for confounders (adjusted OR = 1.57, 95% CI: 1.31-1.87). In subgroup studies, AVAI was consistently associated with the prevalence of CHF. ROC analysis indicated that AVAI demonstrated superior discriminative performance compared with VAI in distinguishing individuals with and without prevalent CHF.ConclusionsThis cross-sectional study identified a significant association between AVAI and prevalent CHF. AVAI may represent a clinically relevant marker associated with the prevalence of CHF and may help identify populations with a higher likelihood of prevalent CHF for further prospective investigation.

Heart failure (HF), as the terminal stage of various cardiovascular diseases, remains a global health challenge with persistently high morbidity and mortality rates. Although current therapies-including angiotensin receptor-neprilysin inhibitors, sodium-glucose cotransporter-2 inhibitors, and cardiac resynchronization therapy-have improved outcomes, significant limitations persist. Ginseng, a renowned traditional Chinese medicine, contains bioactive ginsenosides (e.g., Rb1, Rb3, Re, Rg1, and Rg3) that exhibit multitarget cardioprotective effects, offering a promising therapeutic strategy for HF. This review systematically elucidates the mechanisms by which ginsenosides ameliorate HF, including modulation of myocardial energy metabolism, suppression of oxidative stress and inflammation, attenuation of fibrosis, and inhibition of cardiomyocyte apoptosis. We further evaluate the synergistic efficacy of ginsenoside-containing formulations (e.g., YiQiFuMai injection and Qiliqiangxin capsule) in HF management. Although clinical evidence remains limited and heterogeneous, preclinical studies robustly support ginsenosides as pleiotropic natural compounds with therapeutic potential for HF. Future research should prioritize high-quality clinical trials, optimize delivery systems (e.g., nanocarriers), and explore combination therapies with conventional drugs to accelerate clinical translation.