Pollution level and risk assessment of pesticide residues in ready-to-drink tea beverages.

Advances in the management of lipid disorders have expanded therapeutic options for hypercholesterolemia and beyond. We review the current advances in RNA interference (RNAi) therapies as small interfering RNA (siRNA) drugs, critically assess their clinical positioning, and explore their potential role in reshaping lipid management over the next years. RNAi enables targeted, durable suppression of key lipid-regulating proteins at the mRNA level. Inclisiran, the first approved RNAi therapy for hypercholesterolemia, achieves about 50% sustained LDL-c reduction with long-interval maintenance dosing, offering an alternative to monoclonal antibodies. Beyond LDL-c lowering, multiple RNAi drugs are in advanced development targeting lipoprotein(a), apolipoprotein C-III, and angiopoietin-like protein 3, aiming to address residual cardiovascular risk. Early safety and adherence data are encouraging, yet pivotal outcome trials and cost-effectiveness analyses are still pending. RNAi is a naturally occurring gene-silencing mechanism that can be harnessed therapeutically through siRNA molecules. In lipidology, siRNA-based therapies represent a disruptive technology with the potential to transform both prevention and treatment of atherosclerotic cardiovascular disease. If ongoing trials confirm cardiovascular benefit and safety, RNAi agents could become foundational in personalized lipid management, moving the field toward long-acting, target-specific, and potentially combination-based regimens. The coming years will determine whether RNAi fulfills its promise as the future standard of care in lipid disorders.

Hypertriglyceridemia is a common lipid disorder linked to residual cardiovascular risk and acute pancreatitis despite standard therapy. Olezarsen, an antisense oligonucleotide targeting apolipoprotein C-III (ApoC-III), offers a novel triglyceride-lowering strategy. We performed an updated meta-analysis to evaluate its efficacy and safety. We performed a meta-analysis of randomised controlled trials (RCTs) identified through PubMed, Cochrane, Scopus and Web of Science up to December 2025. Random-effects models were used to pool mean percentage changes (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs). CRD420261279110. Six RCTs with 2676 participants were analysed. Olezarsen significantly reduced triglycerides at 50 mg (MD -46.61%, 95% CI -49.59 to -43.64) and 80 mg (MD -54.37%, 95% CI -61.26 to -47.48), both p < 0.0001. ApoC-III was markedly reduced (50 mg: MD -63.51%, 95% CI -74.18 to -52.84; 80 mg: MD -66.88%, 95% CI -77.91 to -55.85; both p < 0.0001). Non-HDL-C also decreased significantly (50 mg: MD -21.41%, 95% CI -25.12 to -17.70; p < 0.0001; 80 mg: MD -25.28%, 95% CI -33.99 to -16.58; p = 0.001). LDL-C increased modestly at 50 mg (MD 17.58%, 95% CI 0.24 to 34.93; p = 0.047). Olezarsen reduced acute pancreatitis risk (50 mg: RR 0.16, 95% CI 0.05-0.48; p = 0.001; 80 mg: RR 0.33, 95% CI 0.14-0.76; p = 0.009). Overall adverse events were comparable to placebo, while ALT/AST ≥ 3 × ULN increased with 80 mg (RR 2.56, 95% CI 1.20-5.44; p = 0.01). Olezarsen provides substantial triglyceride reduction with favourable effects on atherogenic lipoproteins and a tolerable short-term safety profile. Longer-term trials are needed to confirm cardiovascular outcomes and safety.

Beyond cholesterol: targeting inflammatory biomarkers in cardiovascular disease.

A significant residual risk of myocardial infarction (MI) persists in hypertensive patients treated with angiotensin receptor blockers (ARBs). Conventional risk models often fail to capture the complex, nonlinear interactions among clinical phenotypes, comorbidities, and pharmacogenetic factors. This retrospective cohort study included 1229 hospitalized hypertensive patients treated with ARBs. We analyzed 26 clinical variables and two key genetic polymorphisms: AGTR1 rs5186 and CYP2C9 rs1057910. A hybrid downsampling technique was employed to address severe class imbalance. Ten machine learning models were developed, with a focus on the interpretable deep learning model, TabNet. The TabNet model demonstrated superior predictive performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.887 and a recall of 0.795 in the validation cohort. Model interpretation using Shapley Additive Explanations (SHAP) identified pre-existing coronary heart disease, hypertension stage, chronic heart failure, sex, hyperlipidemia, and the AGTR1 rs5186 polymorphism as the most significant predictors of MI. The CYP2C9 rs1057910 variant showed a risk-modifying interaction effect in patients with pre-existing coronary heart disease. An interpretable deep learning model integrating clinical and pharmacogenetic data effectively predicts MI risk in ARB-treated hypertensive patients. The AGTR1 rs5186 polymorphism is an independent predictor of MI, highlighting its potential as a prognostic biomarker. This clinico-pharmacogenetic approach offers a powerful tool for personalized risk stratification and may guide more targeted preventive interventions.

Emergence delirium (ED) is a common complication in pediatric anesthesia. Although intranasal dexmedetomidine (DEX) is widely used, its application is constrained by a slow onset, residual risk of ED in some patients, and risks such as bradycardia and hypotension. Esketamine (ESK), an NMDA receptor antagonist, may provide a faster onset and reduce these side effects. This study compared the efficacy and safety of intranasal DEX-ESK combination versus DEX alone as premedication for anesthesia induction in pediatric patients undergoing surgery. Electronic databases (PubMed, Web of Science, Scopus, CINAHL, and Embase) were systematically searched for randomized controlled trials (RCTs). The primary outcomes included the ED incidence and the onset of sedation. Secondary outcomes included mask acceptance score, FLACC pain score, post-anesthesia care unit (PACU) length of stay, and adverse events. A random-effects model generated pooled effect estimates-risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. Prediction intervals were also reported to reflect the expected range of effects in future similar studies. Trial Sequential Analysis was performed. The certainty of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Five RCTs encompassing 466 pediatric patients were included in the quantitative synthesis. The DEX-ESK combination was associated with a reduction in ED incidence (RR = 0.58; 95% CI: 0.35-0.97; p = 0.04) and a shorter time to sedation onset (MD = -3.95 min; 95% CI: -4.77 to -3.14; p < 0.01). Secondary analyses demonstrated improved mask acceptance (MD = -0.77; 95% CI: -1.27 to -0.27; p < 0.01), reduced FLACC pain scores (MD = -0.36; 95% CI: -0.70 to -0.02; p = 0.04), and shorter PACU length of stay (MD = -1.83 min; 95% CI: -2.75 to -0.91; p < 0.01). Adverse event incidence did not differ significantly between groups. The intranasal DEX-ESK combination was associated with improved outcomes compared with DEX monotherapy for pediatric premedication including reductions in ED incidence, a modest acceleration in sedation onset, improved mask acceptance, and slightly shorter PACU length of stay, without an increased risk of adverse events. This combination may represent a feasible and safe premedication option for pediatric patients. PROSPERO: CRD420251236740.

The best management of coronary artery disease in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) is debated. We investigated the clinical impact of the residual extent of myocardium at risk in patients undergoing TAVI. Patients enrolled in the REVASC-TAVI (Management of Myocardial Revascularization in Patients Undergoing TAVI With Coronary Artery Disease) international multicenter registry were stratified according to the myocardium jeopardized by coronary artery disease using the British Cardiovascular Intervention Society Jeopardy Score (BCIS-JS) after a planned coronary revascularization. A planned revascularization included percutaneous coronary interventions performed before TAVI, during TAVI, or within 1 month after TAVI. The study population was divided according to the residual BCIS-JS (rBCIS-JS): patients with extensive residual myocardial at risk (rBCIS-JS >4 group) and patients without extensive residual myocardial at risk (rBCIS-JS ≤4 group). The primary study end point was the composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and rehospitalization for heart failure at 2 years. Among the 2407 patients enrolled, 294 pairs of patients were selected by propensity matching and compared. At 2-year follow-up, the incidence of the primary end point was higher in patients with rBCIS-JS >4 compared with patients with rBCIS-JS ≤4 (37.5% versus 23.0%, P=0.004). A significantly lower rate of myocardial infarction was reported in patients with BCIS-JS ≤4 (8.2% versus 2.6%, P=0.011). At multivariate analysis, rBCIS-JS >4 (hazard ratio, 1.43 [95% CI, 1.11-1.84]; P=0.005) independently predicted 2-year major adverse cardiac and cerebrovascular events. In patients with concomitant coronary artery disease and severe aortic stenosis, the residual myocardial risk significantly affects TAVI outcomes. In particular, a rBCIS-JS >4 is associated with higher rates of major adverse cardiac and cerebrovascular events at 2 years.

Triglycerides and Residual Risk, Where Do They Fit Now?

Residual cardiovascular risk persists in many patients despite optimal control of established factors such as low-density lipoprotein cholesterol (LDL-C), blood pressure and glycaemia. Mounting evidence indicates that hypertriglyceridemia (HTG) and triglyceride-rich lipoproteins (TRLs), including their remnant particles, contribute to atherogenesis and therefore constitute actionable targets for risk reduction. This narrative review summarizes current knowledge of TRL metabolism and its role in atherosclerotic cardiovascular disease (ASCVD), drawing on mechanistic studies, observational cohorts and Mendelian-randomization analyses. TRLs display pro-inflammatory and pro-thrombotic properties and are increasingly implicated in plaque initiation and progression. Traditional and emerging therapeutic strategies designed to lower TRL burden are critically examined with particular emphasis on their ability to address residual cardiovascular risk. Conventional interventions, fibrates and mixed omega-3 fatty-acid formulations, have yielded modest and inconsistent cardiovascular benefits. By contrast, icosapent ethyl, a highly purified ethyl ester of eicosapentaenoic acid, is the only TRL-targeted therapy that has demonstrated a significant reduction in major cardiovascular events in a large, randomized trial, irrespective of baseline triglyceride levels. Novel agents such as evinacumab (an ANGPTL3 monoclonal antibody) and antisense oligonucleotides against apolipoprotein C-III (volanesorsen, olezarsen, plozasiran) have produced marked decreases in triglycerides, apoB-containing lipoproteins and remnant cholesterol in recent clinical studies, even though cardiovascular outcome data are not yet available. Therefore, therapies targeting TRL metabolism represent a promising approach to reduce residual cardiovascular risk, particularly in high-risk or statin-treated patients.

BackgroundIn China’s post-transmission-interruption stage of schistosomiasis control, infection signals are often sparse, and conventional surveillance indicators focused on infection detection may not adequately capture residual risk across heterogeneous ecological settings. This study aimed to develop an operational indicator framework for assessing schistosomiasis transmission risk and supporting routine risk assessment and management in this stage.MethodsA county-level indicator framework for schistosomiasis transmission risk assessment was developed through a two-round Delphi consultation and weighted using a combined Delphi-entropy weight method. Using longitudinal data from six pilot counties during 2020–2024, an annual composite risk index (R) was calculated by weighted linear aggregation and classified into risk levels with trapezoidal fuzzy membership functions. Robustness was evaluated by perturbing the subjective preference coefficient (α) and examining the consistency of county-year rankings across scenarios using Spearman’s rank correlation.ResultsThe final framework comprised three first-level, twelve second-level, and thirty-nine third-level indicators spanning biological, environmental, and social domains. Across the six pilot counties, R ranged from 0.18 to 0.44 and the overall risk level was predominantly low. Nonetheless, distinct county-level risk profiles were observed between lake/marshland and mountainous settings. Risk rankings remained highly consistent under α perturbations (ρ = 0.909–0.998), indicating good robustness of the assessment results.ConclusionsThis framework translates multidimensional determinants relevant to the re-establishment of schistosomiasis transmission into interpretable county-level risk profiles. It provides an operational tool to support targeted surveillance and more efficient allocation of control resources in low-endemicity contexts.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40249-026-01453-6.

The safety and efficacy profile of the combined "one-stop" catheter ablation (CA) and left atrial appendage occlusion (LAAO) procedure in atrial fibrillation (AF) patients with a prior history of cerebral infarction requires further validation. In this retrospective, single-center study, 242 consecutive AF patients undergoing the one-stop procedure were categorized into Stroke (n = 103) and Non-Stroke (n = 139) groups. A 1:1 propensity score matching (PSM) was performed, yielding 57 balanced pairs. The primary efficacy endpoint was procedural success. Key safety endpoints included post-procedural residual shunt assessed at 45 days, device-related thrombosis (DRT), and stroke recurrence. After PSM, baseline characteristics were well-balanced. Procedural success (91.2%vs. 87.7%, p = 0.484) and freedom from AF recurrence (88.6%vs. 89.3%, p = 0.979) were comparable between Stroke and Non-Stroke groups. However, the incidence of residual shunt was significantly higher in the Stroke group (5.3%vs. 0%, p = 0.028). No significant differences were observed in DRT or stroke recurrence rates. Notably, a significant interaction was found between prior stroke and LAAO device type on residual shunt risk (p-for-interaction = 0.045), indicating the risk varied substantially depending on the occluder used. A history of prior stroke does not impair the procedural success or mid-term rhythm control of the one-stop CA+LAAO strategy. However, it is associated with an increased risk of residual shunt, a relationship significantly modified by the type of occluder device. These findings highlight the potential need for individualized device selection in stroke survivors.

Atherosclerosis is recognized as a chronic inflammatory disease, with high-sensitivity C-reactive protein (hs-CRP) serving as a biomarker of cardiovascular risk that persists despite optimal control of traditional risk factors. Landmark trials, like JUPITER (Justification for the Use of Statins in Prevention) and PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy), demonstrate the effect of lipid-lowering medications on inflammation. This can have further implications for comprehensive cardiovascular risk reduction. Statins lower hs-CRP alongside low-density lipoprotein cholesterol (LDL-C), with greater effects from high-intensity regimens. Nonstatin medications have variable effects; for example, the addition of ezetimibe to statin therapy enhances hs-CRP reduction. Bempedoic acid exerts direct anti-inflammatory effects, producing significant hs-CRP lowering. Omega-3 fatty acids also demonstrate favorable effects on inflammatory markers. However, fibrates offer only marginal benefits, and PCSK9 inhibitors (Proprotein Convertase Subtilisin/Kexin type 9) have minimal impact. Residual inflammatory risk persists despite LDL-C control, supporting dual-target strategies. The evidence supports therapeutic strategies targeting both lipid and inflammatory pathways, with hs-CRP serving as a complementary marker to refine cardiovascular risk stratification and guide treatment intensification in primary and secondary prevention. Future studies should evaluate inflammation-targeted adjunctive therapies to address discordance between lipid control and residual inflammatory risk.

Background Diabetic kidney disease (DKD) remains a leading cause of end-stage renal disease worldwide. Despite advances in renin–angiotensin–aldosterone system (RAAS) inhibitors, sodium–glucose cotransporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRAs), substantial residual renal risk persists. Endothelin-1 (ET-1), primarily via endothelin A (ETA) receptor activation, plays a central role in glomerular injury, inflammation, and fibrosis. Methodology This narrative review summarizes current evidence on the mechanistic basis and clinical translation of ETA receptor antagonists (ERAs) in DKD. Relevant preclinical and clinical studies were identified through structured literature searches of PubMed, Embase, and Web of Science, focusing on mechanistic insights, therapeutic efficacy, and safety profiles. Results Preclinical studies across diabetic models (e.g., streptozotocin-induced and db/db mice) demonstrate that ETA antagonism reduces glomerular hypertension, preserves podocyte integrity, and attenuates inflammatory and fibrotic signaling pathways. In clinical settings, the SONAR trial showed that atrasentan significantly reduced the risk of renal events (hazard ratio ~0.65) and achieved approximately 30–40% reduction in urinary albumin-to-creatinine ratio (UACR) in selected responders. However, ERA therapy is associated with fluid retention and increased heart failure risk. Notably, a biomarker-guided enrichment strategy, based on early albuminuria response during a run-in phase, improved patient selection and benefit–risk balance. Conclusion ETA receptor antagonists represent a promising mechanism-based adjunctive therapy for DKD. Their future role is likely to be integrated within combination regimens alongside SGLT2 inhibitors and MRAs, guided by biomarker-driven precision medicine approaches to optimize efficacy while minimizing adverse effects.

Despite optimal lipid-lowering treatment, numerous older adults with atherosclerotic cardiovascular disease continue to experience progression driven by inflammation, referred to as residual inflammatory risk. Cellular senescence and the senescence-associated secretory phenotype (SASP) significantly contribute to vascular inflammaging; however, pharmacological interventions in aging populations are still inadequately investigated. This review synthesizes evidence regarding the role of SASP in atherosclerosis and critically evaluates senotherapeutic strategies, emphasizing mechanisms, preclinical efficacy, and translational potential. Senescent endothelial cells, vascular smooth muscle cells, and foam cells aggregate in plaques, secreting pro-inflammatory cytokines (IL-1α, IL-6, MCP-1) and matrix metalloproteinases that enhance plaque susceptibility. Two complementary pharmacological strategies have emerged. Senolytics (dasatinib combined with quercetin, fisetin, and lanatoside C) specifically eradicate senescent cells by inhibiting anti-apoptotic pathways (BCL-2, PI3K/AKT, and HSP90). Senomorphics (rapamycin, metformin, JAK/STAT inhibitors, NF-κB inhibitors) attenuate SASP expression through modulation of mTOR, NF-κB, and JAK/STAT pathways. Preclinical studies indicate that senolytics diminish the burden of senescent cells, reduce plaque area, and limit necrotic core expansion, while simultaneously improving plaque stability. Senomorphics provide comparable advantages with profiles appropriate for prolonged utilization. Targeting SASP constitutes a rational strategy to alleviate residual inflammatory risk. Nonetheless, significant knowledge deficiencies persist concerning patient selection, dosing protocols, drug-drug interactions with cardiovascular treatments, and long-term safety. Translation necessitates stringent clinical trials in geriatric cardiovascular patients. This review offers an extensive pharmacological framework for senotherapeutics in atherosclerosis.

A probabilistic framework for risk-bounded patient-specific quality assurance in volumetric modulated arc therapy based on measured and calculated gamma pass rates.

ABSTRACT This article examines how residual risk persists inside strong digital controls in Indonesia’s public-sector Integrated Financial Management Information Systems. Focusing on Sistem Perbendaharaan dan Anggaran Negara and Sistem Aplikasi Keuangan Tingkat Instansi, the study analyzes why vulnerability persists despite validation rules, approval sequencing, role-based access, and audit trails having become routine. Using an interpretive qualitative case design, the study draws on interviews with 14 informants from treasury service, supervisory, and system-management units, and is supported by regulatory documents. The findings show that strong digital controls do not abolish risk; they reorganize it. Audit trails improve reconstructability, but they do not guarantee prevention. Residual risk persists through weak access recertification, credential-use discipline, synchronization delays, revision–execution timing conflicts, and procedural workarounds under service pressure. The article contributes to IT audit and public-sector control research by conceptualizing residual risk as a post-control phenomenon. It argues that assurance should move beyond feature verification toward active log review, access governance, data lineage testing, exception analytics, and workaround escalation.

Lipoprotein(a) [Lp(a)] is a genetically determined, independent risk factor for atherosclerotic cardiovascular disease (ASCVD). While it contributes significantly to residual cardiovascular risk, it remains under-recognized in clinical practice. In recent years, several novel drugs have been developed to lower Lp(a) levels, with multiple therapies currently under investigation. This narrative review provides a summary of the structure and pathophysiological role of Lp(a) and current therapeutic approaches for its reduction. The primary focus is a critical analysis of published Phase 1 and Phase 2 clinical trial data on Zerlasiran, a GalNAc-conjugated siRNA developed to silence the LPA gene. Zerlasiran has shown promising results in early clinical trials. In the Phase 1 trial, it achieved up to a 98% reduction in Lp(a) levels. In the Phase 2 trial, after a 36-week follow-up, Zerlasiran reduced Lp(a) levels by 80% or more in patients with cardiovascular disease, along with modest reductions in LDL-C and ApoB, and demonstrated a favorable safety profile. These findings suggest that Zerlasiran and similar siRNA therapies may address a significant unmet need in cardiovascular prevention by targeting a key component of residual risk. However, the long-term impact of Lp(a) lowering on clinical outcomes, such as Major Adverse Cardiovascular Events (MACE), remains to be determined. Zerlasiran represents a novel and highly targeted approach to managing elevated Lp(a), with the potential to shift future ASCVD prevention strategies. Pending Phase 3 trial results will be critical in establishing its role in clinical practice.

IntroductionAntibiotic residues in milk are a growing public health concern, primarily due to their role in fostering antimicrobial resistance. Consuming contaminated milk can pose significant health risks, especially in areas with weak regulatory systems and limited public awareness.Materials and MethodsA cross‐sectional study was conducted from September 2023 to June 2024 to assess antibiotic residues in milk and stakeholder awareness. A total of 324 raw milk samples were randomly collected from dairy farms in Hawassa City (198 samples) and Wondo Genet woreda (126 samples). Samples were initially screened using the Delvotest SP sensor kit, and positives were confirmed by high‐performance liquid chromatography (HPLC). Additionally, structured questionnaires were administered to 60 dairy farmers to evaluate their knowledge and awareness of antibiotic residue.ResultsOut of 324 milk samples tested, 29 (9%) were positive for antibiotic residues using the Delvotest SP kit. (HPLC confirmed oxytetracycline (OTC) in 8 (2.5%) samples and penicillin G (PnG) in 16 (4.9%) samples. The mean OTC concentration was below the Codex Alimentarius maximum residue limit (MRL), although some samples exceeded the limit (up to 122.76 µg/L), while PnG residues (up to 142.38 µg/L) markedly exceeded the MRL, indicating potential public health risks and regulatory noncompliance. Previous treatment history, adherence to the withdrawal period, and owner awareness of drug residues were significantly associated with the prevalence of drug residues. Samples from cows with recent antibiotic treatment showed significantly higher residue levels. Among 60 dairy farmers surveyed, only 8.3% were aware of antibiotic residues in milk. All veterinarians (100%) used broad‐spectrum antibiotics for undifferentiated cases, mostly relying on clinical judgment rather than laboratory diagnosis, increasing the risk of drug residues and antimicrobial resistance.ConclusionThe presence of antibiotic residues in milk and low awareness among dairy farmers in the study areas highlight a critical public health gap. Farmers’ awareness of antibiotic residues was mainly influenced by education level, while veterinarians showed good knowledge of antibiotic risks, but gaps remain in laboratory diagnosis, record keeping, and regulatory understanding, indicating the need for targeted training and stronger residue control.

Hemoglobin glycation index and cardiovascular outcomes in patients with coronary intermediate lesions: insights from a large cohort study.

BackgroundAs of 2023, cardiovascular disease (CVD) affects 626 million people globally, imposing a heavy burden on both society and families. Despite advances in antihypertensive therapy, residual risk persists, underscoring the need for potential biomarkers to optimize risk stratification. Lactate dehydrogenase (LDH), traditionally a marker of tissue injury, may reflect metabolic or inflammatory stress associated with vascular damage. This study investigates the association between annual cumulative LDH exposure and incident major adverse cardiac and cerebrovascular events (MACCE) in hypertensive patients, providing insights for prevention strategies.MethodsIn this retrospective cohort study, we included hypertensive patients treated at a large tertiary hospital in Urumqi, China, from January 2011 to April 2025. Kaplan-Meier curves visualized survival differences, and Cox proportional hazards models assessed the association between annual LDH_AUC and MACCE risk. Stratified and sensitivity analyses evaluated robustness, while C-statistics compared the predictive performance of annual LDH_AUC versus single-timepoint LDH.ResultsDuring a median follow-up period of 47 months, a total of 879 new MACCE were recorded. The research results showed that whether the annual LDH_AUC was used as a continuous variable or a categorical variable, an increase in annual LDH_AUC would increase the risk of MACCE (HR=1.012, 95% CI, 1.007–1.017; HR=1.431, 95% CI, 1.185–1.727). Moreover, the predictive value of annual LDH_AUC for MACCE is superior to that of a single LDH measurement.ConclusionIn hypertensive patients, elevated annual LDH_AUC levels is associated with an elevated risk MACCE.