Uncertainty persists regarding the optimal systolic blood pressure (SBP) target after thrombectomy, as systemic blood pressure may affect the penumbra and associated microcirculatory perfusion. We evaluated the impact of different SBP targets on outcomes and the dose-response relationship between actual 24-hour mean SBP and functional outcomes.

We systematically reviewed studies comparing SBP targets after thrombectomy. Bayesian network meta-analysis assessed functional independence and safety. Multi-threshold sensitivity analyses tested the proportional odds assumption across disability levels. Study-level meta-regression explored the association between 24-hour mean SBP and functional outcomes.

Eight studies were included. The < 180 mmHg target ranked highest for functional independence (SUCRA = 87.3% (50.0%-100.0%)), while < 140 mmHg (SUCRA = 26.3%, OR = 1.65 (1.03-2.54)) and < 120 mmHg (SUCRA = 17.7%, OR = 1.75 (1.14-2.71)) were associated with worse outcomes, and the certainty of the evidence was high. No significant differences in symptomatic intracranial hemorrhage or 90-day mortality were observed. Among six study-level comparisons, five violated the proportional odds assumption, indicating effect heterogeneity across disability levels.An exploratory group-level meta-regression showed that, within the observed range of 117-139 mmHg, higher actual SBP was associated with a higher odds ratio for functional independence at the study group level (OR = 1.028 (1.015-1.041)).

After successful recanalization, clinicians should avoid excessive SBP reduction. Future studies should consider reperfusion status, the burden of ischemic injury, and tissue perfusion to determine individualized blood pressure targets.

ObjectiveVascular dementia is the second most common cause of cognitive impairment in older adults, yet effective pharmacological treatments remain limited. Agnuside, a naturally occurring compound with antioxidant and anti-inflammatory properties, has shown vascular-protective potential; however, its role in vascular dementia remains unclear.MethodsA mouse model of permanent bilateral common carotid artery occlusion was established to evaluate the effects of Agnuside. Cognitive function was assessed using the Morris water maze. Cerebral blood flow, tissue injury, and hippocampal cornu ammonis 1 neuronal apoptosis were evaluated using laser speckle imaging, triphenyltetrazolium chloride staining, Nissl staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Transcriptomic and pathway enrichment analyses were performed, and key targets were validated using quantitative real-time polymerase chain reaction and Western blotting.ResultsAgnuside improved spatial learning and memory, increased cerebral blood flow, reduced histopathological damage, and decreased neuronal apoptosis. Angiogenesis-related genes (Mmp3, IL1RN, and ALAS2) were differentially expressed, and selected genes were validated using quantitative real-time polymerase chain reaction. The PI3K-AKT and MAPK pathways were significantly enriched, and Agnuside restored AKT and ERK1/2 phosphorylation.ConclusionsAgnuside exerts neurovascular protective effects in mice with vascular dementia, likely through modulation of angiogenesis-related genes and activation of AKT/ERK signaling. These findings provide evidence that Agnuside serves as a potential therapeutic candidate for vascular dementia.

Meteorin-like (Metrnl) is a newly discovered multifunctional secreted protein widely expressed in various tissues such as adipose tissue, skeletal muscle, and epithelial barrier tissues. This review systematically summarizes current knowledge of Metrnl, detailing its molecular characteristics, structure, cellular sources, inducers, receptors, and the complex signaling pathways and network. Metrnl has been identified as a pleiotropic protein with multiple effects, including enhancing insulin sensitivity, modulating lipid metabolism, promoting neurogenesis, reducing inflammation and oxidative stress, regulating tumor immunity, and potentiating angiogenesis and tissue repair. In metabolic and endocrine disorders, cardiovascular and cerebrovascular diseases, respiratory diseases, gastrointestinal diseases, skin diseases, autoimmune diseases, and nervous system diseases, and other pathological processes, the expression of Metrnl shows tissue-specific and disease stage-dependent changes, underscoring its potential as a biomarker or novel therapeutic target. However, the expression characteristics and biological functions of Metrnl in some diseases are controversial, and its tissue-specific role has not been fully elucidated. This review integrates clinical cohort studies and animal model results targeting Metrnl and its receptors. On this basis, we propose that Metrnl should be regarded as a stress-responsive immunometabolic molecule rather than a static disease biomarker. The research on targeted intervention in Metrnl is currently in the preclinical stage and has not yet progressed to clinical trials, and its clinical application value in specific diseases needs to be verified by large-scale stratified cohort analysis. This article aims to provide theoretical clues and novel insights for understanding Metrnl as a potential biomarker and therapeutic target.

Rheumatoid arthritis (RA) is a systemic immune-mediated disease in which persistent synovial inflammation contributes not only to joint destruction but also to cardiovascular, pulmonary, metabolic, and other extra-articular complications. This review focuses specifically on the translational potential of emerging receptor-directed pro-resolving therapeutics in targeting persistent inflammation, a common mechanism driving RA and its systemic comorbidities. Although contemporary disease-modifying antirheumatic drugs (DMARDs) have substantially improved disease control and structural outcomes, a complementary therapeutic question remains: can the endogenous biological program that terminates inflammation and restores tissue homeostasis be therapeutically engaged? Resolution pharmacology addresses this question by targeting endogenous pro-resolving pathways involving specialized pro-resolving mediators (SPMs), annexin A1 (AnxA1), melanocortin receptors, the formyl peptide receptor 2 (FPR2/ALX), and related signalling networks. This review examines the evidence linking defective resolution with RA and critically evaluates the therapeutic potential of resolution-directed interventions across articular disease and major RA-associated comorbidities. Rather than treating resolution pharmacology as a uniform therapeutic class, we distinguish anti-inflammatory effects from demonstrated pro-resolving activities and evaluate evidence ranging from in vitro and animal studies to observational human studies and clinical trials. This review particularly emphasizes receptor selectivity, biased agonism, and their use in combination with established DMARD therapies. We propose that the principal opportunity for resolution pharmacology is not to replace effective DMARD therapy but to complement it, promoting inflammatory termination and tissue recovery. Thus, resolution pharmacology should currently be considered a promising translational framework requiring future clinical validation rather than an established therapeutic paradigm for RA and its comorbidities. CHEMICAL COMPOUNDS IN THIS ARTICLE: Lipoxin A4; Resolvin D1; Resolvin D2; Resolvin D5; Maresin 1; Resomelagon (AP1189); BMS-986235.

In maintenance hemodialysis (MHD), serum uric acid (UA) is influenced by nutritional, inflammatory, and dialysis-related factors. Whether the prognostic association of soluble suppression of tumorigenicity 2 (sST2) differs according to UA remains uncertain.

This retrospective secondary analysis included 358 MHD patients with baseline UA and sST2 measurements. UA was evaluated continuously and by rank-based quartiles; sST2 was evaluated continuously and in exploratory sample-median combined groups. Cardiovascular death was the primary outcome and major adverse cardiovascular events (MACE) was secondary. Cox and Fine-Gray models were used, and UA Q4 × sST2-high was the main categorical interaction analysis.

During follow-up, 193 all-cause deaths, 76 cardiovascular deaths, and 91 MACE occurred. Higher log10(sST2) per standard deviation was associated with cardiovascular death (HR 1.73, 95% CI 1.34-2.23) and MACE (HR 1.59, 95% CI 1.26-2.01), whereas UA alone was not associated with these outcomes after adjustment. Q1-Q3/sST2-high had higher risk than Q1-Q3/sST2-low, but categorical interactions were non-significant for cardiovascular death (P = 0.192) and MACE (P = 0.151), and Q4 estimates were imprecise.

Higher sST2 was consistently associated with adverse cardiovascular outcomes, whereas UA was not a stable independent prognostic marker. Exploratory subgroup differences do not establish UA-dependent effect modification and require external validation.

Whether periprocedural myocardial infarction (PMI) differs between focal and diffuse coronary physiology in the treated vessel remains unclear.

To compare the incidence and prognostic impact of PMI after PCI for vessels with focal versus diffuse diseases defined by pullback pressure gradient (PPG).

We analyzed 855 patients undergoing PCI in the PPG Global registry. Physiological patterns of treated vessels were classified as focal or diffuse using PPG. PMI in the original registry was defined according to the Fourth Universal Definition of Myocardial Infarction (UDMI). The primary outcome of the current analysis was 1-year target vessel failure (TVF), a composite of cardiac death, spontaneous target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization.

Fourth UDMI PMI was higher in patients with diffuse compared with focal physiology in the treated vessel (9.8% vs 5.9%; p=0.048). Troponin elevation ≥70 × URL(8.5% vs 4.8%; p=0.041) and PMI with flow-limiting angiographic complications (2.0% vs 0.2%; p=0.015) occurred more frequently after PCI for vessels with diffuse disease, whereas PMI with ischemic electrocardiographic changes was infrequent and similar between groups (0.8% vs 0.7%; p=1.000). 17 TVF occurred within 1 year; only troponin elevation ≥35 × URL accompanied by angiographic complications was associated with 1-year TVF.

PMI occurred more frequently after PCI for vessels with diffuse than focal coronary physiology, particularly phenotypes with higher troponin elevation or angiographic complications. Associations with 1-year TVF were observed only for PMI phenotypes incorporating angiographic complications; however, findings should be interpreted cautiously because TVF events were sparse.

Cholesteryl ester transfer protein (CETP) inhibitors have shown cardiovascular benefits, but genetically proxied CETP inhibition may increase age-related macular degeneration (AMD) risk. We evaluated this association in European- and East Asian-ancestry populations.

Drug-target Mendelian randomization (MR) and observational genetic association analyses in the UK Biobank and the Singapore Epidemiology of Eye Diseases (SEED) study.

457,242 UK Biobank participants without AMD at baseline and 7,058 SEED participants.

In drug-target MR, CETP inhibition was instrumented using a CETP protein quantitative trait locus (pQTL) instrument in Europeans and a high-density lipoprotein (HDL)-weighted CETP-region instrument in East Asians. Outcomes included advanced and early AMD in Europeans and exudative AMD, typical neovascular AMD (nAMD), and polypoidal choroidal vasculopathy (PCV) in East Asians. In observational analyses, a CETP pQTL score was evaluated against incident AMD in the UK Biobank, and an HDL-weighted CETP genetic score against prevalent AMD in SEED.

Risk of AMD RESULTS: In drug-target MR, greater genetically proxied CETP inhibition was associated with higher risks of advanced AMD (OR, 1.45; 95% CI, 1.25, 1.67) and early AMD (OR, 1.29; 95% CI, 1.19, 1.41) in Europeans, and exudative AMD (OR, 3.14; 95% CI, 2.16, 4.57), typical nAMD (OR, 2.84; 95% CI, 1.69, 4.79), and PCV (OR, 3.18; 95% CI, 2.05, 4.93) in East Asians (all P<0.001). In UK Biobank, each 1-SD decrease in the CETP pQTL score, representing greater genetically proxied CETP inhibition, was associated with higher incident AMD risk (HR,1.03; 95% CI, 1.01, 1.06; P=0.008). In SEED, the HDL-weighted CETP genetic score showed a U-shaped association with prevalent early AMD. Compared with the midrange group, higher odds were observed in the highest decile, representing greater genetically proxied CETP inhibition (OR, 1.74; 95% CI, 1.07, 2.72; P=0.019), and the lowest tertile, representing weaker inhibition (OR, 1.50; 95% CI, 1.13, 1.99; P=0.005).

Greater genetically proxied CETP inhibition was associated with higher AMD risk across genetic analyses in European- and East Asian-ancestry populations. These findings raise a potential retinal safety signal requiring validation in clinical trials and longitudinal observational studies in clinical practice.

Fine particulate matter (PM_2.5) has been linked with adverse pregnancy events. However, the effects of PM_2.5 on pregnant women with pulmonary hypertension (PH) remain poorly understood.

We conducted a retrospective multicenter study of pregnant women with PH hospitalized at 24 tertiary hospitals in China between January 2016 and August 2022. Monthly PM_2.5 exposure was estimated and the average PM_2.5 concentrations during the 3-year exposure proceeding the end of pregnancy was used as the primary exposure metric. Generalized linear models with binomial distributions were applied to assess associations between PM_2.5 exposure and adverse maternal events (maternal death and/or heart failure) and adverse fetal/neonatal events (non-live birth, neonatal death, preterm birth and low birth weight). Pregnancy-specific exposure windows and two-pollutant models were also examined.

Among the 751 participants, 198 (26.4%) experienced adverse maternal events, and 449 (59.8%) had adverse fetal/neonatal events. Three-year median PM_2.5 concentration before the end of pregnancy was 32.8 (26.2-44.0) μg/m³. In the fully adjusted model, each 10 μg/m³ increase in PM_2.5, the odds ratio (OR) was 1.169 (95% CI: 1.014-1.349) for the adverse maternal events and 1.169 (95% CI: 1.018-1.348) for adverse fetal/neonatal events. These associations remained robust in two-pollutant models. Furthermore, when exposure assessment was shifted from long-term levels to pregnancy-specific windows, the strongest trimester-specific association was observed during late pregnancy.

Long-term PM_2.5 exposure was associated with increased risk of adverse pregnancy events among pregnant women with PH, emphasizing the importance of reducing air pollution exposure in this high-risk population.

The clinical utility of streptokinase, a widely used and cost-effective thrombolytic agent, has gained importance post COVID-19 due to increase in cardiovascular diseases globally. But the strong humoral immunogenicity exhibited by it, restricts its usage. Building upon our prior work of developing truncated streptokinase variants and their plasminogen activation study, we report here the results of immunogenicity studies for identification of variants with reduced immunogenicity. A panel of ten rationally truncated and recombinantly expressed streptokinase fragments were screened for antibody recognition and immunogenicity potential. Out of the ten fragments, two N-terminal constructs (amino acid residues 1-300 and 1-173) exhibited approximately 40-45% lower ELISA immunoreactivity compared with full-length streptokinase during initial in vitro screening. These fragments were also already reported to retain >85% of native plasminogen activation activity. In vivo evaluation of the fragments in rabbits demonstrated significantly attenuated humoral responses over a 28-day immunization period, confirmed by longitudinal antibody titration and cumulative area-under-the-curve analysis when compared to the full-length streptokinase. Fragment 1-173 emerged as a promising lower-immunogenic thrombolytic candidate, and this work demonstrates that rational domain minimization can decouple functional competence from immunodominant regions in streptokinase establishing a broadly applicable framework for engineering improved therapeutic proteins.