To elucidate the synergistic mechanism of "Two flowers therapy" - a Behçet's disease (BD) treatment regimen used in China for more than 30 years, namely Total Glucosides of Paeony (TGP)-colchicine - and its efficacy, safety in BD with mucocutaneous involvement.

A retrospective clinical cohort study integrated with computational biology was performed. Five bioactive components were chosen, among which four were from TGP and one was colchicine; 31 overlapping BD-related targets were identified via multi-omics, finally 6 core genes confirmed. 355 BD patients were divided into combination group (CG, n=231) and monotherapy group (MG, n=124).

Four active components of TGP (oxypaeoniflorin, albiflorin, benzoyl paeoniflorin, paeoniflorin) and colchicine constituted five bioactive compounds. A total of 837 BD-related targets were retrieved from GeneCards, with 31 overlapping targets between the five compounds and BD. A PPI network (31 nodes, 197 edges) was constructed, and core targets (MMP9, ICAM1, FGF2, TLR4, EGFR, NOS3) were identified. Molecular docking confirmed their high affinity: colchicine formed hydrogen bonds with EGFR, ICAM1, NOS3 (2.2-3.4 Å) and hydrophobic interactions with TLR4; TGP components formed 2-4 hydrogen bonds with EGFR, FGF2, MMP9 (2.2-3.9 Å). GO analysis involved inflammation- and immune-related biological processes; KEGG identified 10 enriched pathways (including Lipid and atherosclerosis, AGE-RAGE) regulating inflammation, immunity and vascular function. Clinically, CG had superior early (M1-M2) efficacy: oral ulcer prevalence was 0.0% vs. 21.0% (M1) and 0.0% vs. 100.0% (M2), genital ulcer prevalence 0.9% vs. 6.5% (M1) (all p<0.05). Both groups achieved complete ulcer resolution from M3. ESR in CG was significantly lower at M2 (p<0.001), with no CRP difference. CG had transient diarrhea; no drug-associated cytopenia was reported in either group.

TGP combined with colchicine, a regimen used in China for more than 30 years, exerts therapeutic effects on BD by regulating core targets and inflammatory pathways. Clinically, this regimen more effectively controls early mucocutaneous lesion recurrence in BD patients, with good long-term efficacy and safety.

To determine whether circulating soluble Flt-1 (sFlt-1) and soluble Tie-2 (sTie-2) are associated with intraplaque neovascularization (IPN) in human carotid atherosclerotic plaques.

Forty-four patients with ≥50% carotid stenosis underwent conventional carotid ultrasound and superb microvascular imaging (SMI); 29 had plasma collected and 11 provided carotid endarterectomy specimens for histology. IPN was quantified as neovessel counts in 2-minute SMI cine loops and as microvessel counts in excised plaques. Plasma VEGF-A/B/C/D, Ang-2, sFlt-1, and sTie-2 were measured by immunoassays. Public single-cell RNA-seq data from human carotid plaques were interrogated to map FLT1, TEK, VEGFA, ANGPT1, and ANGPT2 expression to specific plaque cell populations.

IPN was detected in 33/44 (75%) patients, with 0-16 neovessels on SMI (median 4). Plasma sFlt-1 correlated with SMI neovessel counts (r=0.42, p=0.030), with a similar trend for sTie-2 (r=0.37, p=0.057), whereas VEGF-A/B/C/D and Ang-2 showed no significant relationships. In the surgical subgroup, histological neovessel counts correlated with sFlt-1 (r=0.65, p=0.030) and SMI neovessel count (r= 0.68, p =0.02) but not sTie-2. sFlt-1 and sTie-2 correlated with BMI (and sTie-2 also with age), yet log-sFlt-1 remained independently associated with SMI-derived neovessel counts after adjustment for age and BMI (B = 13.24, 95% CI 0.17-26.30, p=0.047; R²=0.18), while sTie-2 was not. No significant associations were observed between IPN or sFlt-1/sTie-2 and lipid profile, CRP, leukocyte counts, or other conventional risk factors. Single-cell transcriptomics showed FLT1 and ANGPT2 broadly expressed across endothelial, smooth-muscle, and myeloid clusters, with TEK largely confined to endothelial cells and ANGPT1 to smooth-muscle cells, supporting local activation of VEGF-FLT1 and Ang-TEK/Tie-2 signaling within plaques.

In this pilot study, higher plasma sFlt-1, and, to a lesser degree sTie-2, correlated with carotid IPN on SMI and histology, independent of age and BMI. These findings suggest that soluble VEGF- and Ang/Tie-2-receptor pathways may serve as circulating, context-sensitive markers of intraplaque angiogenesis and plaque vulnerability, meriting evaluation in larger longitudinal cohorts.

Stroke impairs functional independence including gait ability. While robot-aided rehabilitation techniques have been developed, there is a need for a robotic system that promotes three-dimensional (3D) movement of the trunk and gait ability while providing automatic function evaluation and individually optimized prescriptions for stroke patients.

To assess the efficacy and safety of a novel trunk and lower limb robotic system for patients with hemiplegia due to chronic stroke.

This study employed a single-arm, before-after trial design conducted in an institutional setting. Twenty individuals (eight males; mean age, 52.3 ± 11.8 years) with hemiplegia resulting from chronic stroke (≥ 12 months postonset) who showed no change in the Functional Ambulation Category (FAC) for at least 2 months prior to baseline were enrolled. Participants underwent robot-assisted training using a system composed of trunk, upright, and lower extremity modules. Each participant received 30-min sessions, 5 days per week, for 4 weeks. The robotic system provided real-time kinematic motion data to support rehabilitation exercises. Primary outcomes included changes in functional evaluation and performance scores from baseline to postintervention. Additionally, a feasibility survey was administered to assess user satisfaction and identify areas for system improvement.

In all patients, the functional scores did not differ significantly between baseline and 1 month after the robotic intervention. However, there were improvements in the performance scores of lateral and forward bending of the trunk while sitting, forward bending ability during sit-to-stand activity, weight transfer, and lateral and forward bending of the trunk while standing 1 month after the intervention (p < 0.05). The user experience survey showed satisfaction in 16 of 20 patients due to the easy and safe operation of the robot.

The proposed robotic system was safe and convenient to use and was associated with improvements in selected kinematic parameters.

Information regarding the signaling axis involving triggering receptor expressed on myeloid cells 1 (TREM-1) and its downstream mediator, signal transducer and activator of transcription 3 (STAT3), remains limited in ischemic stroke. We investigated the plasma levels of TREM-1 in patients with ischemic stroke and compared to controls. Second, we investigated the potential correlation between plasma TREM-1 levels and STAT3 expression in peripheral blood mononuclear cells (PBMCs) and explored their associations with stroke severity and functional outcomes.

In an observational case-control study, plasma and PBMCs from participants were collected to measure TREM-1 and STAT3 expression levels. The National Institutes of Health Stroke Scale (NIHSS) at admission, day 7, and 1 and 3 months, and the modified Rankin Scale (mRS) at 3 months post-discharge were assessed. Plasma TREM-1 levels and STAT3 expression were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (RT-qPCR), respectively. The Inflammation-Related Principal Component Score (IRPCS) was examined for its association with 3-month functional outcome.

TREM-1 and STAT3 were significantly elevated in acute ischemic stroke (AIS) patients (p < 0.05, p < 0.0001) and positively correlated (ρ = 0.432, p < 0.0001). Both biomarkers correlated with the NIHSS at 1 and 3 months and mRS at 3 months (all p < 0.05). The composite IRPCS showed the strongest association with poor 3-month functional outcome among the tested biomarkers (OR = 2.84, 95% CI: 1.32-6.12, p = 0.008).

Plasma TREM-1 levels were positively correlated with STAT3 expression. The TREM-1-STAT3 axis was associated with stroke severity and 3-month functional outcome in AIS patients. These findings should be regarded as exploratory and require validation in larger cohorts.

Timely brain imaging is critical for optimizing stroke treatment outcomes. Delays at the prehospital stage significantly impact acute ischemic stroke management. Computed tomography (CT) plays a vital role in guiding treatment decisions.

We conducted a retrospective observational study using data from the Acute Stroke Statistics System of Taipei City, covering the period from January 1, 2011, to June 30, 2022. The association between prehospital time intervals and door-to-CT time was analyzed in patients with acute ischemic stroke. Logistic regression models were applied, with door-to-CT time <25 min as the dependent variable. Independent variables included patient characteristics, comorbidities, and prehospital time components: decision-making time (symptom onset to emergency medical service [EMS] activation), EMS response time, on-scene time, and transport time.

Among 2351 acute ischemic stroke patients, 1734 patients with complete documentation were included in the final analysis. Factors associated with a door-to-CT time >25 min included age ≥85 years (OR: 1.387; 95% CI: 1.025-1.878; p = 0.034), hypertension (OR: 1.412; 95% CI: 1.047-1.905; p <0.001), decision-making delay (OR: 1.001; 95% CI: 1.001-1.002; p <0.001), and decision-making delay ≥160 min (OR: 2.340; 95% CI: 1.766-3.099; p <0.001). Prehospital notification was associated with a lower likelihood of delayed imaging (OR: 0.371; 95% CI: 0.266-0.517; p < 0.001). In multivariable analysis, decision-making delay ≥160 min (OR: 2.279; 95% CI: 1.711-3.036; p <0.001) remained significant determinants of delayed CT imaging, whereas prehospital notification (OR: 0.382; 95% CI: 0.272-0.536; p <0.001) served as a significant protective factor against delayed imaging. A two-stage pooled analysis across nine advanced emergency responsibility hospitals in Taipei City confirmed these findings with low heterogeneity.

Decision-making delays and prehospital notification appear to be key determinants of door-to-CT time in the management of acute ischemic stroke.

Health care systems have a key role in improving hypertension control in large populations, a global challenge, through the implementation of modern multicomponent programs. The impact of such programs in at-risk minority populations, nonetheless, remains to be better characterized. Additionally, the extent to which hypertension control based on a single time-point blood pressure (BP) measurement (LAST-BP), the approach typically used in health system performance assessment, agrees with time-averaged BP (AVG-BP) has not been well studied. Leon Medical Centers (LMC), a major integrated health care system serving Medicare beneficiaries predominantly of Hispanic origin in Miami-Dade County, Florida, implemented a hypertension control program in 2011. We conducted longitudinal data analysis evaluating hypertension control before and after program implementation, and compared annual rates derived from AVG-BP versus LAST-BP. During 2008-2018, the analytic sample increased from 4,710 to 21,540, mean age rose from 73.4 to 77.1 years, and the proportion of Hispanics remained stable (>98%). Adjusted odds of hypertension control were 5.7 (95% CI: 5.4-6.0) times higher after full program implementation. Improvements were comparable in women and men. Trends based on LAST-BP paralleled those of AVG-BP, although rates were consistently lower. Kappa agreement between AVG-BP and LAST-BP metrics was only fair. The LMC program was associated with a meaningful, sustained increase in hypertension control to high levels (crude rates based on AVG-BP ∼ 90%). LAST-BP-based control rates underestimated those derived from AVG-BP. Research is warranted to determine how longitudinal BP metrics can be optimally incorporated into patient care and health system performance assessment. Practical Applications: This study has two practical implications. First, it shows that a coordinated, multicomponent hypertension control program with modern core elements, including team-based care, standardized blood pressure measurement, and promotion of guideline-based management supported by a robust EHR system and enhanced pharmacy and transportation services, and culturally tailored patient engagement, can achieve and sustain high levels of hypertension control in the understudied population of Hispanic Medicare beneficiaries in South Florida. These findings provide a strong foundation for real-world primary care settings, while highlighting the need for continued program refinement as the science of blood pressure (BP) control in large populations evolves. Second, the study shows that a single annual "snapshot" BP value underestimates true hypertension control compared with the average of readings obtained throughout the year. This finding supports the value of longitudinal BP metrics and highlights the need for research to determine how best to incorporate them into performance assessment.

Atrial fibrillation (AF) is the predominant arrhythmia. Growing evidence indicates that immunological diseases may play a role in its development. This study combined observational and genetic analyses to investigate how T-lymphocyte subsets and immunomodulatory drug targets influenced AF risk.

This study retrospectively analyzed T lymphocyte subsets in 302 AF patients and 183 healthy controls. After balancing covariates via 1:1 propensity score matching, multivariate regression revealed AF patients had significantly higher absolute counts of Th1 and Th17 cells, and higher Th1/Th2 and Th17/Treg ratios (p < 0.05). A subsequent two-sample Mendelian randomization (MR) analysis, which assessed 731 immune traits and included drug-target MR, established causal relationships. It showed that increased counts of CD4⁺CD8dim T cells (OR = 1.03, p = 0.002) and IgD^-CD38dim B cells (OR = 1.06, p = 0.0003) elevated AF risk. Furthermore, IL-6R-mediated CRP elevation increased AF risk (OR = 1.33, p = 5.18E-7), whereas higher IL-18 gene expression was protective (OR = 0.95, p = 0.036).

Immune dysfunction, especially T lymphocyte subsets, is a risk factor for the development of AF. The IL-6R signaling pathway may be a potential target for AF prevention, whereas the use of IL-18 inhibitors may increase the risk of AF.

Cerebral amyloid angiopathy (CAA) frequently co-occurs with Alzheimer's disease (AD), generating mixed vascular-neurodegenerative phenotypes. Plasma phosphorylated tau (p-tau)217 is a robust biomarker of AD, but its performance in CAA remains unclear.

We studied 231 participants, including 50 patients with CAA (Boston v2.0), 154 with AD, and 27 cognitively unimpaired controls. Plasma p-tau217 was measured on an automated platform and compared to cerebrospinal fluid (CSF)-defined AD status. Associations with magnetic resonance imaging (MRI) markers of CAA burden were evaluated.

Among CAA participants, 29 met CSF criteria for AD co-pathology. Plasma p-tau217 discriminated CAA patients with and without AD co-pathology (area under the curve = 0.920) and showed no association with MRI markers of CAA burden. Predefined cut-offs (≥ 0.27 pg/mL and ≥ 0.34 pg/mL) yielded high accuracy for identifying AD co-pathology within CAA.

Plasma p-tau217 shows high diagnostic accuracy for identifying AD co-pathology in CAA and is not associated with MRI markers of CAA burden, supporting its specificity for AD-related pathology.

The incidence of arrhythmias after transcatheter pulmonary valve replacement (TPVR) beyond the early postprocedural period and their relationship to valve type (balloon-expandable [BEPVR] vs self-expanding [SEPVR] pulmonary valve replacement) have not been well defined.

The goal of this study was to assess the incidence, types, and timing of arrhythmias observed after BEPVR and SEPVR.

We retrospectively reviewed patients undergoing TPVR at our institution from 2012 to 2022 with rhythm monitoring beyond 14 days' postprocedure. The primary outcome was a composite of all-cause mortality and life-threatening arrhythmia. Secondary outcomes included non-life-threatening arrhythmias: nonsustained ventricular tachycardia (NSVT), atrial fibrillation, and other supraventricular tachycardias.

Sixty-eight patients (mean age 40.6 ± 16.4 years) were followed up for a median (IQR) of 4.0 (5.5) years after TPVR. Diagnoses included tetralogy of Fallot (45.6%), congenital pulmonary valve stenosis (23.5%), bicuspid aortic valve status-post Ross procedure (14.7%), and acquired pulmonary valve disease (7.4%). BEPVR was performed in 49 patients (72.1%) and SEPVR in 19 (27.9%). Life-threatening arrhythmias occurred in 13 patients (19.1%), all but one following BEPVR. NSVT was the most frequent non-life-threatening arrhythmia, observed in 47.1% of patients and significantly more common after SEPVR (P = 0.03). NSVT persisted beyond the early postprocedural period but was not associated with life-threatening arrhythmias or mortality.

Arrhythmias are common after TPVR beyond the early postimplantation period. No statistical difference could be determined for incidence of life-threatening arrhythmia or mortality between BEPVR or SEPVR. NSVT was the most observed arrhythmia and occurred significantly more often after SEPVR, independent of preimplantation arrhythmia history. Longer term studies are needed to determine the prognostic implication of NSVT after TPVR and the potential relationship to late life-threatening arrhythmias or mortality.

Two self-expanding transcatheter pulmonary valves (SETPVs), Harmony TPV (Medtronic) and Alterra Adaptive Prestent System with the Sapien 3 Valve (Edwards Lifesciences), treat pulmonary regurgitation in patients with a native or surgically repaired right ventricular outflow tract. Ventricular arrhythmias (VAs) are common after implantation.

The purpose of this study was to identify the incidence of and risk factors for VA in the first 6 months after SETPV implantation.

The multicenter SERVE registry included SETPV implantations at 25 U.S.

VA was defined as nonsustained ventricular tachycardia (VT), sustained monomorphic VT, polymorphic VT, or >1% ventricular ectopy on Holter monitoring.

A total of 513 SETPV implants (359 Harmony, 154 Alterra) were collected, with a median age of 28 years (Q1-Q3: 17-44 years) and no difference in baseline VA by valve type. Alterra patients were more likely (37%) than Harmony patients (26%; P = 0.014) to have VA during the procedural admission. At 6 months, predicted probability of VA burden decreased below baseline for Harmony patients (-6%; 95% CI: -10% to -2%; P < 0.001) and to baseline for Alterra (P = 0.53).

This large multicenter registry study of the natural history of VA after SETPV implantation showed VA to be frequent during the procedural admission, with Alterra patients having more VA than Harmony patients. VA burden decreased to lower than baseline at 6 months in Harmony patients and to baseline in Alterra patients.