Beyond coronavirus disease 2019 (COVID-19) vaccines, messenger RNA (mRNA)-based therapeutics have increasingly demonstrated potential across other treatment areas. To summarize the clinical research landscape for such products and provide valuable references for researchers working in related fields, mRNA clinical trials registered on ClinicalTrials.gov (CTg) and the Chinese Clinical Trial Registry (ChiCTR) up to June 7, 2025, were analyzed. Twelve key items, including registration number, study title, target disease, interventions, blinding, sponsor, phases, enrollment, funder type, study type and start date, and locations, were analyzed to describe trial characteristics. A total of 557 clinical trials of mRNA-based therapeutics were identified. Most of these studies were conducted in phases 0-3 (n = 412, 73.97%), primarily focusing on infectious diseases (n = 410, 73.61%), and predominantly open-label designs (n = 338, 60.68%). Interventional studies accounted for 85.82% (n = 478) of all registered trials. Industry sponsors were the primary source of funding (n = 299, 53.68%). Approximately 45.06% of the projects (n = 251) aimed to enroll 0-100 participants. Most of the studies involved mRNA vaccines (n = 507, 91.02%). Further, 22 trials investigated mRNA-based therapeutics for rare diseases. Among the newly registered projects in 2024 and 2025, the proportion of phase 0-1 trials significantly increased, accounting for 61.67% and 78.13%, respectively. The top three regions that conducted mRNA clinical studies were North America (n = 186; primarily the United States [n = 178]), Asia (n = 184; China [n = 72]), and Europe (n = 90), based on studies registered in both CTg and ChiCTR. Most mRNA products remain in preapproval clinical trials. Further phase 3 clinical evidence will be essential to support its broader application.

This study investigated whether previous resistance exercise training (RT) affects the progression of right ventricular dysfunction and remodeling in rats with severe pulmonary artery hypertension (PAH). Male Wistar rats were submitted to a RT protocol (i.e., ladder-climbing) for 8 weeks, while controls remained in cages without exercising. Then, exercised rats were randomly divided into trained monocrotaline discontinued (TMD), and trained monocrotaline continued (TMC) groups. Subsequently, they received a single monocrotaline injection (i.e., 60 mg/kg) and the TMD group stopped RT, while the TMC group exercised for an additional 6-week period. After euthanasia, right ventricle (RV) was dissected and processed for histological and single RV myocyte analyses. Previous RT increased physical effort tolerance, prevented pulmonary artery resistance augment (i.e., AT/ET) and mitigated the reduction in RV systolic function (i.e., TAPSE). RT also lessened impairments in single RV myocyte contractility and intracellular calcium transient (i.e., amplitude, and times to peak and relaxation) in the TMC group only. Moreover, RT inhibited adverse RV remodeling (i.e., hypertrophy and collagen deposition) in both trained groups. In conclusion, previous RT attenuates the progression of RV dysfunction and remodeling in rats with severe monocrotaline-induced PAH, being the extension of protective effects dependent on the exercise training continuity.

DiGeorge syndrome (DGS), also known as 22q11.2 deletion syndrome, is the most prevalent chromosomal microdeletion syndrome. It presents with a heterogeneous phenotype and diverse clinical manifestations, which may include, but are not limited to, cardiovascular, endocrine, neurodevelopmental and immune function abnormalities. The immune defects seen in individuals with DGS arise from impairment in thymus development, resulting in immune dysregulation. This thymic dysfunction impairs T-cell development and maturation, leading to a spectrum of T-cell lymphopenia, a restricted T-cell receptor repertoire and defects relating to regulatory T cells. Consequently, patients exhibit increased susceptibility to recurrent infections, particularly of the respiratory tract and a higher prevalence of autoimmune conditions and atopic diseases. The present literature review synthesises current knowledge on the immunopathogenic mechanisms, clinical manifestations and treatment approaches for the immune dysregulation in DGS.

As part of its role in the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received 12,180 human influenza-positive samples during 2024. Viruses were analysed for their antigenic, genetic, and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or embryonated hens' eggs for potential use in seasonal influenza virus vaccines. During 2024, influenza A(H1N1)pdm09 and A(H3N2) viruses predominated, accounting for 33% and 42%, respectively, of all viruses received, compared to 5% for influenza B/Victoria. Of note, one influenza A(H5N1) virus was also received in 2024. The majority of A(H1N1)pdm09 (98%), A(H3N2) (88%) and influenza B (100%) viruses analysed at the Centre were found to be antigenically and genetically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2024. Of 4,007 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, twelve A(H1N1)pdm09 viruses and one B/Victoria virus showed highly reduced inhibition against oseltamivir or zanamivir. Of 3,294 total samples sequenced for baloxavir susceptibility, 18 of the 1,825 A(H3N2) samples were identified with genetic evidence of reduced susceptibility to baloxavir marboxil in the PA gene.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. Menopause is associated with increased hepatic fat deposition and thus metabolic dysfunction, contributing to heightened risk of progressive liver and cardiovascular disease. Hormone replacement therapy (HRT), supported by pre-clinical data, may be associated with a lower risk.

We performed a retrospective cohort study using the TriNetX global federated research network. Eligible participants were peri-menopausal women (ICD-10 codes N95/Z78.0, AND age 40-65 years) with pre-existing MASLD (based on ICD-10 codes K76.0/K75.81 or positive modified hepatic steatosis index plus ≥ 1 metabolic syndrome, MetS, trait). Patients initiating HRT (oestrogen ± progesterone) were compared with untreated controls using 1:1 propensity score matching for demographics, comorbidities, biochemistry and medications. The primary outcome was a composite of major adverse liver outcomes (MALO: portal hypertension, varices, ascites, spontaneous bacterial peritonitis, encephalopathy, hepatorenal/pulmonary syndromes, cirrhosis, decompensated liver disease, hepatocellular carcinoma, liver transplant). Secondary outcomes were individual MALO components, type 2 diabetes (T2D), major adverse cardiovascular events (MACE), breast and endometrial cancer, and venous thromboembolism (VTE). Cox regression generated hazard ratios (HRs) with 95% CIs over 5 years. Sensitivity analyses adjusted for geography, hormone type, and degree of obesity.

After matching, 21 639 patients were included in each treatment arm. HRT was associated with a significantly reduced risk of MALO (HR 0.80; 0.71, 0.9), largely driven by reductions in ascites and SBP (0.78; 0.64, 0.95), and liver cirrhosis (0.75; 0.63, 0.90), and reduced risk of cardiometabolic outcomes: T2D (0.90; 0.84, 0.96), and MACE (0.90; 0.83, 0.98). HRT was not associated with increased risk of breast cancer or VTE, whilst endometrial cancer risk was reduced (0.49; 0.40, 0.61). Oestrogen was linked to greater benefits compared to progesterone, and patients with mild-moderate obesity experienced more significant risk reduction.

Treatment of peri-menopausal symptoms with HRT, in patients with pre-existing MASLD, is associated with a lower 5-year risk of major liver and cardiometabolic disease. These findings support early basic science research and should prompt a closer examination through clinical trials.

ANCA-associated vasculitis (AAV) frequently involves the kidneys and may progress to end-stage kidney disease (ESKD). The benefit of plasma exchange (PLEX) in this setting remains uncertain. We conducted a retrospective cohort study of 163 patients with AAV and serum creatinine ≥ 1.5 mg/dL from two tertiary centers in Colombia, comparing PLEX versus no PLEX. The primary outcome was a composite of all-cause mortality or ESKD. Overall, PLEX was not associated with a reduction in the composite outcome (adjusted hazard ratio [HR] 1.04, 95% CI 0.61-1.76). Among patients with baseline creatinine > 5.7 mg/dL, PLEX was associated with a lower risk of ESKD (adjusted HR 0.38, 95% CI 0.14-0.97) and a borderline reduction in the composite outcome (HR 0.45, p = 0.05), with no benefit in those with lower creatinine levels. PLEX was associated with increased in-hospital infections (adjusted risk ratio 4.66, p = 0.001). These findings suggest a potential role for PLEX in selected patients with severe kidney dysfunction.

The objective of this study is to identify preoperative echocardiographic predictors of mitral valve (MV) repair failure in pediatric patients. Pediatric patients with mitral regurgitation (MR) grade ≥ 2 who received MV repair between January 2019 and July 2024 were retrospectively reviewed. MV repair failure was defined as a composite of postoperative functional MV failure, heart transplantation, or death. MV morphology and related parameters were assessed using two- and three-dimensional echocardiography. A total of 309 pediatric patients were included, with a median age of 15.50 (6.00, 52.30) months; 164 (53.1%) were male. During a follow-up of 6.93 (1.37, 14.67) months, 11.97% cases experienced MV repair failure. The underdeveloped chordae tendineae (hazard ratio (HR) = 3.69, 95% confidence interval (CI) = 1.46 to 9.33; P = 0.006) and elevated mitral valve annulus area index (MVAI) (HR = 1.23, 95% CI = 1.07 to 1.40; P = 0.003) were identified as two independent preoperative echocardiographic predictors. The significantly dilated mitral annulus, measured with MVAI exceeding 8.73 cm²/m², was established as the clinically significant threshold for predicting MV repair failure. Sensitivity analyses revealed a more pronounced predictive effect of MVAI in the isolated MR group (HR = 1.84, 95% CI = 1.19 to 2.85; P = 0.006).

 For pediatric patients with MR grade ≥ 2, echocardiography identified underdeveloped chordae tendineae and significantly dilated mitral annulus may serve as crucial preoperative predictors for risk stratification of MV repair failure.

• In pediatric populations with mitral regurgitation, MV repair is generally preferred, yet it remains one of the most technically demanding and less predictable congenital cardiac surgeries.

• Preoperative underdeveloped chordae tendineae and enlarged annulus (MVAI > 8.73 cm2/m2) are strong predictors of MV repair failure in pediatric patients, particularly those with isolated MR. These findings support performing repair early, before substantial annular remodeling occurs.

Behçet's disease (BD) is a chronic multisystem vasculitis that may begin in childhood. Microvascular dysfunction is central to its pathogenesis, yet pediatric data are scarce. This study evaluated nailfold videocapillaroscopy (NVC) findings in children with BD using standardized methodology and compared microvascular parameters between complete and incomplete disease phenotypes, as well as with age-matched healthy reference data. In this cross-sectional study, pediatric BD patients fulfilling the pediatric Behçet's disease (PEDBD) criteria underwent NVC following the European Alliance of Associations for Rheumatology (EULAR) microcirculation protocol. Capillary density, morphology, and microhemorrhages were compared between complete and incomplete BD and with age-matched healthy reference data. Associations between NVC parameters and clinical or laboratory findings were analyzed. Complete BD patients (n = 15, 40.5%) had significantly lower capillary density and higher apical loop width, tortuosity, dilatation, abnormal capillaries, and microhemorrhage scores than incomplete BD (n = 22, 59.5%). Compared with healthy peers, BD patients showed significantly lower capillary density, arterial and venous diameters, and capillary length but higher intercapillary distance and width.

 Pediatric BD is associated with distinct NVC abnormalities compared with healthy reference data. Differences in capillary density and morphology were observed between complete and incomplete phenotypes. These findings provide a descriptive overview of phenotype-associated microvascular features in pediatric BD.

• Nailfold videocapillaroscopy (NVC) can detect microvascular abnormalities in adult Behçet's disease, but pediatric data are extremely limited. • Childhood-onset Behçet's disease often evolves over time from incomplete to complete phenotype, and reliable objective markers reflecting vascular involvement are lacking.

• Pediatric Behçet's disease shows measurable NVC abnormalities compared with healthy children, even in the absence of clinically overt vascular involvement. • Microvascular alterations are significantly more pronounced in complete phenotype than incomplete phenotype, suggesting cumulative vascular burden independent of disease activity scores.

ObjectiveEarly and accurate detection of carotid vulnerable plaques is essential for preventing ischemic stroke. This study developed an automated deep learning framework using ultrasound images and compared the performance of various You Only Look Once models.MethodsA retrospective multicenter dataset of 1610 carotid ultrasound images from 368 patients was collected from 17 September 2024 to 17 March 2025. Plaques were classified as stable or vulnerable using standardized ultrasound criteria. The dataset was stratified and divided into training, validation, and test sets at a 6:2:2 ratio, with strict patient-level separation to prevent data leakage. Four You Only Look Once models (versions 7, 8, 9, and 10) were trained under identical conditions. Performance was evaluated using mean average precision at various intersection-over-union thresholds as well as precision, recall, and F1 score.ResultsYou Only Look Once version 9 showed the best overall performance, achieving the highest mean average precision at intersection-over-union thresholds of 0.5 and 0.95 in the validation set. Similar results were observed in the test set, with superior detection accuracy for both stable and vulnerable plaques. You Only Look Once version 9 also achieved the highest precision, recall, and F1 score.ConclusionThe You Only Look Once version 9-based framework enables accurate and efficient carotid plaque detection and classification, supporting real-time assessment of plaque vulnerability and the prevention of ischemic stroke.

Research regarding Custodiol's safety in minimally invasive mitral valve repair remains limited in Asian populations. We compared Custodiol in minimally invasive mitral valve repair to repetitive cold blood cardioplegia in open mitral valve repair.

We retrospectively evaluated 98 consecutive patients who underwent minimally invasive mitral valve repair with Custodiol and 70 consecutive patients who underwent open mitral valve repair with repetitive cold blood cardioplegia at our institution between January 2015 and December 2024. The primary endpoints were creatine kinase-myocardial band (MB) levels and left ventricular ejection fraction determined by echocardiography pre- and post-surgery.

Maximum creatine kinase-MB levels within 48 h post-surgery were significantly lower in the minimally invasive group than in the open repair group, both in the overall cohort (45.0 vs. 60.7 U/L; p <0.001, respectively) and after excluding patients who underwent Maze procedure or pulmonary vein isolation (42.4 vs. 50.0 U/L; p = 0.009, respectively). Left ventricular ejection fraction pre- and post-surgery was comparable between the minimally invasive and open repair groups (72% vs. 69%; p = 0.426 and 59% vs. 60%; p = 0.204, respectively).

Custodiol during minimally invasive mitral valve repair provides myocardial protection comparable to repetitive cold blood cardioplegia in open mitral valve repair.