To examine and analyze the barrier factors influencing prescription circulation in Xiangyang City under the outpatient coordination policy and to provide reference evidence for promoting prescription circulation. To assess the practical implementation of prescription circulation under the outpatient coordination policy in retail pharmacy, a targeted questionnaire survey was administered to clinicians from medical institutions at all levels in Xiangyang City. Chi-square tests and structural equation modeling were employed to systematically identify key implementation challenges and to explore the underlying causes within the current electronic prescription circulation process. The findings indicated that clinicians in Xiangyang City possessed a high level of awareness regarding electronic prescription circulation policies. However, the actual circulation rate remained low, and circulation willingness was generally neutral to conservative. Professional title and degree of policy understanding were identified as significant factors influencing circulation willingness. Structural equation modeling further demonstrated that policy incentives and regulatory constraints indirectly affected clinicians' willingness through multiple mediating pathways, including system functional deficiencies and patient cognitive biases. Clinicians in Xiangyang City exhibited high awareness of electronic prescription circulation policies, yet actual circulation rates remained limited, accompanied by neutral to conservative willingness. Complicated system procedures, ambiguous delineation of authority and responsibilities, and insufficient incentive mechanisms constituted the primary barriers to implementation. Policy familiarity and patient misperceptions were confirmed as critical factors influencing clinicians' willingness to participate in prescription circulation.
Flow diversion (FD) requires perfect vessel wall apposition to optimize aneurysm occlusion rates and minimize complications. To elucidate the safety of an off-label technique using the Comaneci device for augmenting vessel wall apposition of distally deployed flow-diverting stents. Over a 20-month period, all FD cases for the treatment of aneurysms beyond the internal carotid artery terminus performed by the senior author were reviewed. Patient demographics, case characteristics, and procedural outcomes were collected and analyzed for cases involving both distal aneurysms and the use of the Comaneci device to augment vessel wall apposition. Of 58 FD cases of distal aneurysms, the Comaneci device was required for vessel wall apposition in 16 cases (27%). Of these cases, the average patient age was 68.8 ± 8.4 years, and 13 (81%) were female. Average aneurysm size was 3.3 ± 1.1 mm. Comaneci device deployment and retrieval was successful in all (100%) cases. Procedures had an average fluoroscopy time of 38 ± 20.9 minutes, average contrast use of 37.9 ± 9.9 mL, and average radiation exposure of 1182 ± 458.3 mGy. This study demonstrates the safety and feasibility of a previously described technique for augmenting stent stenosis in proximal anterior circulation applied in distal anterior circulation aneurysms.Clinical ImpactIncomplete vessel wall apposition of flow-diverting stents increases the risk of thromboembolic complications, in-stent stenosis, and treatment failure. In the distal circulation, techniques for improving apposition are limited due to anatomical tortuosity and vessel size. This series demonstrates the use of the Comaneci device as a safe and effective method for augmenting flow diverter apposition beyond the internal carotid artery terminus. This technique maintains endoluminal flow throughout remodeling, requires no exchange of the existing 0.027" microcatheter, and minimizes device burden, making it an efficient technique for clinicians.
Neovascular glaucoma (NVG) represents one of the most severe forms of secondary glaucoma and is characterized by an aggressive clinical course, a high risk of irreversible vision loss, and substantial variability in treatment outcomes. At the same time, the roles of systemic inflammation, ocular microcirculation, and neovascularization of the iridocorneal angle (according to the Weiss D. classification, 1978) in determining the long-term prognosis remain insufficiently investigated. To identify clinical, microcirculatory, and systemic inflammatory predictors of long-term treatment effectiveness in secondary NVG and to compare the outcomes of surgical interventions and diode transscleral cyclophotocoagulation depending on the stage of iridocorneal angle neovascularization. A multicenter retrospective cohort study included 87 eyes with ischemic NVG secondary to proliferative diabetic retinopathy or retinal vein occlusion treated between 2018 and 2024 in Ukraine and Moldova. Patients were divided into a surgical group (n=39) and a diode transscleral cyclophotocoagulation group (n=48). Clinical parameters, systemic inflammatory indices (SII, SIRI, AISI), HbA1c, cardiovascular comorbidity, and the rheographic coefficient (RQ), a functional microcirculation marker, were analyzed. Treatment success was defined as intraocular pressure control with stabilization of visual acuity, absence of rubeosis progression, and no need for additional invasive surgery. Multivariable logistic regression and ROC analysis were performed. Treatment effectiveness was strongly associated with the stage of iridocorneal angle neovascularization. In the early stages, both approaches showed high success rates, whereas in the advanced stages, surgical outcomes declined markedly. In multivariable analysis, surgery increased the odds of success more than fivefold (OR=5.4; p=0.003), whereas advanced angle stages reduced it nearly sixfold (OR=0.18; p=0.007). Higher systemic inflammation was associated with poorer prognosis (SII OR=0.76; p=0.009), whereas better microcirculation was associated with improved outcomes (RQ OR=1.42; p=0.023). The combined predictive model demonstrated good discrimination (AUC = 0.84; 95% CI, 0.74-0.92). In the present study, long-term outcomes of neovascular glaucoma were shown to be determined by the complex interaction between the stage of iridocorneal angle neovascularization, systemic inflammation, and ocular microcirculation. Our findings indicated that the Weiss stage is a key morphological factor that modifies treatment effectiveness. In contrast, systemic inflammatory indices (SII, SIRI, AISI) reflect the underlying biological burden of disease and are associated with poorer prognosis. In contrast, higher values of the microcirculatory parameter (RQ) were significantly associated with more favorable treatment outcomes, likely reflecting preserved perfusion capacity and a lower degree of ischemic tissue damage. This observation is consistent with the concept of ischemia-driven progression in NVG. Importantly, integrating these parameters into a multivariable model demonstrated good discriminative performance (AUC = 0.84), supporting the value of a combined clinical-biological approach to risk stratification. Taken together, these results suggest that NVG should be considered not only a localized ocular disorder but also a systemically influenced condition in which the interplay among angiogenesis, inflammation, and microcirculatory dysfunction determines individual treatment response. Long-term outcomes in neovascular glaucoma appear to be determined by the interaction between the stage of iridocorneal angle neovascularization, systemic inflammation, and ocular microcirculation. Surgical treatment provides the greatest benefit in early disease, whereas cyclophotocoagulation remains a stable option in advanced stages. Combined clinical-biological modeling may support personalized treatment selection in NVG.
Carlo Ruini's Dell'Anotomia et dell'infirmità del cavallo (1598) is widely regarded as the first scientific treatise on veterinary anatomy. This paper reviews the historical circumstances of its composition and printing history, the structure and scientific content of its five anatomical books, the long-standing controversy over Ruini's authorship - including the plagiarisms it subsequently suffered - and the disputed attribution of its woodcut illustrations to artists such as Leonardo da Vinci, Titian and Agostino Carracci. Ruini's description of the pulmonary circulation is situated within a comparative chronology running from Vesalius (1543) to Harvey (1628), and a terminological table cross-references Ruini's descriptive language with current veterinary anatomical nomenclature. The paper further considers the nineteenth-century rehabilitation of Ruini's reputation, chiefly through the efforts of Giovan Battista Ercolani, against the background of the broader institutionalization of veterinary medicine in Europe. The analysis situates Ruini's contribution within the broader history of comparative anatomy and of the discovery of blood circulation. It highlights the artistic value of the treatise's iconography alongside its scientific merit.
Repeated implantation failure (RIF) is a major challenge in in vitro fertilization (IVF). Insufficient uterine blood flow and reduced endometrial thickness are important factors contributing to implantation failure. Pelvic physiotherapy, including electrotherapy, manual therapy, and exercise therapy, has shown potential to enhance endometrial thickness and improve local blood flow through pelvic floor exercises. Transfer of Energy Capacitive and Resistive (TECAR) therapy, a novel physiotherapy modality, promotes vasodilation, tissue oxygenation, and blood circulation. This study presents a clinical trial protocol designed to evaluate the effect of pelvic physiotherapy, comprising electrotherapy, exercise therapy, and TECAR therapy, on uterine blood supply in infertile women with RIF. Eligibility criteria include women with a history of at least two RIF events and inadequate uterine blood flow (pulsatility index (PI)> 1.95). The primary aim of this protocol is to evaluate uterine blood flow, endometrial thickness, and endometrial pattern, while secondary outcomes will include sexual function, depression, quality of life, pregnancy and implantation rates, fetal growth up to 12 weeks of gestation, ectopic pregnancy, and miscarriage. Following approval from the relevant ethics committee, this protocol will initially be implemented in a pilot phase involving 22 participants at Al-Zahra Hospital, Tabriz University of Medical Sciences. As of the protocol submission date, the pilot phase is planned but not yet completed. No participant data have been analyzed. Therefore, no results on uterine blood flow, endometrial thickness, implantation rates, or secondary outcomes are available at this stage. Upon completion of the pilot phase and subsequent full-scale trial, the findings will be reported separately. The findings of the forthcoming trial are expected to contribute to establishing evidence-based physiotherapy approaches for improving uterine perfusion and implantation outcomes in infertile women with RIF (registration number: IRCT20230206057338N1).
Large saccular aneurysms of the basilar artery associated with chronic mural ectasia are rare and difficult to manage because of their high risk of thrombus formation and rupture. We present a case that highlights the complexities involved in the diagnosis and treatment decision-making of this condition. A 54-year-old male with hypertension and ischemic cardiomyopathy presented to the Emergency Department via emergency medical services with confusion and unresponsiveness. Neuroimaging revealed a large basilar artery aneurysm with a mural thrombus and posterior circulation infarcts. Despite conservative management and planned angiography, the patient's condition rapidly deteriorated, and he was declared brain dead within 36 h. This case underscores the difficulties associated with managing basilar artery aneurysms, particularly in patients with mural ectasia. It examines the rationale for the initial conservative treatment and evaluates the potential benefits of early endovascular intervention. Literature insights are integrated to explore the implications for vessel integrity, thromboembolic risk, and intervention timing. This case highlights the urgent need for standardized guidelines for the management of basilar artery aneurysms. Future research should focus on comparing surgical and endovascular approaches, assessing long-term aneurysm progression, and developing risk-based treatment protocols.
The COVID-19 pandemic profoundly disrupted respiratory pathogen circulation and reshaped population-level humoral immunity. Using a high-throughput pan-respiratory pathogen protein microarray containing 56 antigens, we profiled serum immunoglobulin G (IgG) responses in 287 individuals across pre-pandemic, COVID-19, and post-pandemic periods, as well as validated the findings in an independent cohort of 175 participants. SARS-CoV-2 exposure induced strong cross-reactivity with SARS-CoV but minimal reactivity to MERS-CoV, while variant-specific immunity progressively shifted from pre-Omicron strains toward Omicron lineages. Spike-specific IgG declined over time, whereas nucleocapsid-specific IgG remained relatively stable. Immune responses to common respiratory pathogens were also broadly reorganized, with decreases in human coronaviruses, influenza B, respiratory syncytial viruses, and human parainfluenza viruses, stable influenza A responses, and increased human metapneumovirus-specific IgG. These findings define a post-pandemic humoral immune landscape and support sustained serological surveillance to identify immunity gaps, anticipate changing infection susceptibility, and strengthen preparedness for future respiratory epidemics.
The epidemiology of pneumococcal pneumonia can be influenced by vaccine implementation, serotype replacement, and viral circulation. We aimed to investigate 15-year trends in the epidemiological and clinical characteristics of severe pneumococcal pneumonia patients requiring intensive care unit (ICU) admission. We analyzed data from a prospective cohort of adult patients with severe pneumonia admitted to the 28-bed medical ICU of a 2,700-bed tertiary hospital in South Korea between 2010 and 2024. Temporal changes in incidence, resistance to antimicrobial agents, frequency of co-infections, and mortality were evaluated across three 5-year periods. Among 2,511 ICU patients with severe pneumonia, 140 (5.6%) had pneumococcal infections. The proportion of pneumococcal cases decreased from 9.9% in 2010-2014 to 4.2% in 2015-2019, and further to 2.2% in 2020-2024 (p<0.001 for trend). Conversely, ceftriaxone non-susceptibility rates rose sharply from 4.8% to 16.7% and 45.5% across the same periods (p<0.001). Co-infections were frequent and increased significantly, largely due to respiratory viruses, with rates of 48.9%, 61.8%, and 77.8%, respectively (p=0.02). Influenza was the predominant co-pathogen during 2015-2019, whereas SARS-CoV-2 was most frequent in 2020-2024. The 90-day mortality rates remained stable over time (29.5%, 38.2%, and 27.8%, p=0.64). In this single-center ICU cohort, the proportion of severe pneumococcal pneumonia cases decreased over the 15-year period, whereas ceftriaxone non-susceptibility and viral co-infections became more frequent. These trends should be interpreted cautiously given the lack of serotype and individual vaccination data and incomplete susceptibility results. Continued surveillance of pneumococcal disease, antimicrobial resistance, and respiratory co-infections is warranted.
A residual false lumen after type A aortic dissection repair may rarely serve as an embolic route to the cerebral circulation. A woman in her 60s underwent ascending aortic replacement for Stanford type A aortic dissection, leaving a residual patent dissection involving the supra-aortic branches and the descending aorta. Despite receiving anticoagulant and antiplatelet therapies, the patient developed recurrent multifocal cerebral infarctions. Transesophageal echocardiography (TEE) demonstrated an entry tear in the descending aorta communicating from the true lumen to the false lumen. Flow became markedly stagnant toward the proximal false lumen, with thrombus-like echogenic material. Four-dimensional computed tomography (4DCT) confirmed delayed retrograde flow ascending within the false lumen toward the arch. Total arch replacement was performed to eliminate the suspected embolic route. Intraoperative findings confirmed thrombotic material within the false lumen. No recurrent cerebral infarctions were observed postoperatively.
Commensal small mammals, such as rats and shrews, are recognized reservoirs for numerous zoonotic pathogens; however, their role in pathogen circulation at transport hubs remains underexplored. This study employs shotgun metagenomic sequencing to characterize microbial communities and assess zoonotic potential in tissue samples from commensal small mammals captured at Bangkok Port, an international cargo shipping hub in Thailand between June and August 2025. Following host read depletion, taxonomic profiling was performed to identify bacterial taxa of public health relevance, including sequences assigned to Bordetella spp., Yersinia pestis, Bartonella elizabethae, and Acinetobacter baumannii. The virulence factor and antibiotic resistance gene profiles revealed that some of these pathogens have pathogenic potential and are related to drug-resistant bacteria. In addition, Y. pestis was identified as a shared taxon among rats, shrews, and their associated fleas. The findings support the ecological roles of mammalian hosts and their ectoparasites as reservoirs for pathogens of public health concern. These results emphasize the need to strengthen surveillance programs for commensal small mammals to monitor and mitigate the spread of transboundary pathogens at international maritime gateways.
This study aimed to encapsulate lutein in high internal phase emulsions (HIPEs) stabilized by quinoa protein isolate (QPI), tannic acid (TA), and high-methoxy pectin (HMP) particles at varying concentrations to address its low delivery efficiency and bioavailability. High concentrations (3%-4%) of QPI-TA-HMP particles demonstrated strong interfacial adsorption, forming thick viscoelastic films around oil droplets. These interfacial properties imparted controllable rheological behaviors, textural characteristics, and stable 3D-printing scaffolds to the lutein-loaded HIPEs, achieving an encapsulation efficiency of 81.65 ± 2.36%. In vitro tests indicated that HIPEs enhanced lutein's resistance to storage, heat, and UV exposure while facilitating sustained intestinal release, resulting in a lutein bioaccessibility of 43.73 ± 1.44%. In vivo experiments further demonstrated that the HIPEs delivery system maintained high lutein concentrations in the small intestine, cecum, and colon, thereby significantly enhancing lutein accumulation in systemic circulation. These findings provide new insights into enhancing lutein's stability, delivery performance, and bioavailability.
The aim of this study was to systematically examine the annual, seasonal, age-specific, and gender-specific epidemiological trends of human metapneumovirus (hMPV) infections, utilizing extensive real-world data collected over 18 years through a consistent testing methodology and analytical protocol. Real-time reverse transcription polymerase chain reaction assay results of patients admitted to Dankook University Hospital (2007 - 2024) were retrospectively analyzed. Descriptive statistics were used to assess annual, age-specific, and seasonal trends in hMPV positivity rates. We further evaluated the feasibility of using these data to establish robust epidemiological surveillance systems and standardized monitoring metrics. Among 23,284 specimens, 991 (4.2%) were positive for hMPV. The highest annual positivity rates were recorded in 2007 (7.7%) and 2011 (8.1%). Children aged 2 - 11 years exhibited the highest positivity rate (6.0%), with positivity rates declining with increasing age, except for a slight increase in individuals aged ≥ 65 years. Seasonally, infections peaked in spring (11.1%), followed by summer (2.8%), winter (1.4%), and autumn (0.8%). Since the onset of the coronavirus disease 2019 (COVID-19) pandemic (2020 - 2024), the overall positivity rate dropped to 1.6% from 4.7% before the pandemic, accompanied by notable changes in seasonal patterns. This study revealed significant shifts in hMPV epidemiology following the COVID-19 pandemic, including reduced overall circulation, disrupted spring seasonality, and persistent impacts on high-risk pediatric populations. These findings provide evidence to optimize diagnostic testing for hMPV while providing actionable evidence to adjust optimal diagnostic testing windows, enhance infection prevention strategies, and implement focused monitoring of high-risk populations. Specifically, hMPV testing should be prioritized for pediatric patients during the typical peak months (March - May) and expanded to include atypical winter peaks (December - February) in the post-pandemic era. For older adults (≥ 65 years), targeted testing during winter months may enhance diagnostic yield and support timely clinical management.
Underlying atherosclerotic stenosis is more common in acute basilar artery occlusion than in anterior circulation, and often necessitates additional procedures such as balloon angioplasty or stent placement during endovascular revascularization. Preoperative recognition of underlying basilar artery stenosis may be clinically relevant, but reliable imaging indicators remain unclear. This study aimed to identify preoperative magnetic resonance imaging findings associated with underlying basilar artery stenosis in patients undergoing acute endovascular revascularization. We retrospectively analyzed patients at three institutions between 2018 and 2023. Patients were divided into stenosis and non-stenosis groups based on post-recanalization angiographic findings. Stenosis was identified in 13 patients and was found to be absent in 35 patients. Pontine hyperintensity on diffusion-weighted imaging was more frequent in the stenosis group and remained independently associated with preexisting basilar artery stenosis after adjustment for preoperative National Institutes of Health Stroke Scale score. Non-visualization of the proximal basilar artery on magnetic resonance angiography was also more frequent in the stenosis group, but did not remain independently associated after adjustment. Additional endovascular procedures were more frequently required in the stenosis group, whereas recanalization was achieved with mechanical thrombectomy alone in the non-stenosis group. Functional outcomes at discharge were comparable between the groups. In acute basilar artery occlusion, pontine hyperintensity on diffusion-weighted imaging was independently associated with preexisting basilar artery stenosis. Its absence may help exclude underlying stenosis, whereas concordant positivity of pontine hyperintensity and proximal basilar artery non-visualization may support suspicion of stenosis before treatment.
The pulsation of blood in the umbilical artery and the feto-placental circulation has been a focus for computational modelling because of the important association between the patterns of pulsation and placental pathology. This review examines different approaches that have been used to study this relationship and the insights that can be drawn from these computational models. Wave reflection in the umbilical artery is presented both to aid in the interpretation of these patterns and as an example of how modelling approaches can be used to unify disparate hemodynamic measurements. The linkage between modelling and measurement methodologies is examined along with the considerations for model selection when approaching a new research question.
Hypertrophic cardiomyopathy is the most common form of feline heart disease, and current therapy is largely supportive with no widely available effective treatment to reverse myocardial hypertrophy or attenuate fibrosis. Sacubitril/valsartan (Sac/Val), an angiotensin receptor-neprilysin inhibitor, has antihypertrophic and antifibrotic effects, but its potential in feline hypertrophic cardiomyopathy remains unclear. The objective of this exploratory pilot study was to evaluate the effects of Sac/Val on myocardial hypertrophy and fibrosis in a feline pressure-overload model. Twelve healthy cats were equally randomized to sham surgery (SHAM group), abdominal aortic constriction (AAC group), and AAC plus Sac/Val treatment (AAC+Sac/Val group). Left ventricular (LV) hypertrophy was assessed by transthoracic echocardiography, with computed tomography performed at the study endpoint. Circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) were measured serially using feline-validated ELISA assays. Myocardial fibrosis was evaluated by histology and quantitative reverse-transcription PCR (qRT-PCR) targeting BNP, ACTA, TGF-β, and COL-I. Pressure-overload AAC induced hypertrophic remodeling, with increased circulating cardiac biomarkers and maximal LV wall thickness. At Day 60 (pre-treatment), NT-proBNP and cTnI were higher in AAC (and AAC+Sac/Val) cats than in SHAM cats (P < 0.05). By Day 90, Sac/Val was associated with lower NT-proBNP and cTnI versus untreated AAC (e.g., NT-proBNP 0.241 ± 0.049 vs 0.921 ± 0.115ng/mL; cTnI 0.958 ± 0.519 vs 3.313 ± 0.510ng/mL; P < 0.05). Sac/Val also reduced maximal LV wall thickness compared with AAC on echocardiography and endpoint CT (echo 3.45 ± 0.33 vs 5.88 ± 1.77mm; CT 3.54 ± 0.24 vs 5.68 ± 1.61mm; P < 0.05). Histology showed reduced interstitial collagen deposition with Sac/Val (P < 0.05), accompanied by downregulation of fibrosis-associated transcripts (P < 0.05). In conclusion, sacubitril/valsartan administration was associated with reduced left ventricular hypertrophy and fibrosis in a feline pressure-overload model, suggesting additional benefits for feline hypertrophic cardiomyopathy.
Q fever, caused by Coxiella burnetii, is a globally distributed zoonosis that remains largely underdiagnosed in Algeria. Since its first description in 1935, fragmented data have accumulated across human, animal, and vector hosts without comprehensive synthesis. This systematic review summarizes all available information on the occurrence of C. burnetii in Algeria from 1935 to 2025, across human, animal and ectoparasite compartments, and critically discusses potential reservoirs, vectors and knowledge gaps. Following PRISMA 2020 guidelines, we searched PubMed, Scopus, ScienceDirect and the Algerian national thesis repository. Studies reporting original data on C. burnetii in humans, livestock, pets, wildlife, ticks or lice were included. Data were extracted on study period, location, host species, diagnostic methods, prevalence and molecular typing. Sixty-one studies met the inclusion criteria. Human cases consisted mainly of sporadic acute infections, endocarditis and obstetric complications, often diagnosed abroad, reflecting limited local testing. In livestock, serological and molecular surveys showed infection in cattle, sheep, goats and camels across 30 among 58 wilayas, with apparent seroprevalence ranging from 8 to 27% in cattle, 15-75% in small ruminants and up to 70% in camels. Seventeen studies investigated arthropods: C. burnetii or Coxiella-like endosymbiont DNA was found in 13 tick species from ruminants, camelids and companion or wild animals, though the significance of these detections remains uncertain. Four studies reported on the bacterium in human and animal lice. Molecular typing identified several genotypes, suggesting multiple transmission cycles. Available evidence supports the long-standing and widespread circulation of C. burnetii in Algeria, but the true burden remains underestimated due to limited diagnostic capacity and lack of integrated surveillance. Strengthening local serological and molecular tools, including strain typing, is essential to clarify reservoirs, transmission dynamics and human infection sources within a One Health framework.
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Porcine circovirus type 2 (PCV2) impairs the immune function in pigs and contributes to immunosuppressive disease, causing substantial economic losses worldwide. To isolate and characterize PCV2 strains from two pig farms in China and evaluate pathogenicity in mice. Lymph node tissues suspected of a PCV infection were collected from farms in Heilongjiang Province and Inner Mongolia Autonomous Region. Virus isolation was performed in PK-15 cells and confirmed by a polymerase chain reaction, sequencing, indirect immunofluorescence, and transmission electron microscopy. The genotypes were assigned by phylogenetic analysis. The replication kinetics were evaluated by quantitative polymerase chain reaction, and the pathogenicity was assessed in BALB/c mice. Two isolates were obtained and classified as PCV2d (PCV2-HLJ-92 and PCV2-NMG-103). The capsid amino acid sequences were identical between the isolates. Relative to the vaccine strains (PCV2a-LG and PCV2b-SH), both isolates carried multiple capsid amino acid substitutions. Regarding a PCV2d reference strain (BDH), a single substitution at residue 169 was observed. Differences in replication kinetics and tissue viral loads were observed between the isolates; these differences coincided with a Rep residue 6 substitution. Both isolates infected mice and produced histopathologic lesions primarily in the liver and lung. These PCV2d isolates expand the available genomic and phenotypic data for circulating strains and may inform epidemiologic surveillance and vaccine development.
CD31+ T-cells possess angiogenic properties and have been termed angiogenic T-cells (TANG) and are altered in number with advancing age. We examined circulating TANG subsets and VEGF-A content in young (n = 16, 18-30 years) and older (n = 16, 50-65 years) males by flow cytometry. Cardiorespiratory fitness ( V ̇ O2max) was quantified. Circulating IL-6 and cytomegalovirus (CMV) serostatus were determined by immunoassays. TANG contained more VEGF-A than CD31- T-cells (CD31+: 9374 ± 8587 AU vs. CD31-: 8722 ± 8149 AU, p = 0.021), also evident in CD4+ and CD8+ subsets. Older adults possessed fewer CD4+ TANG cells as a proportion of total CD4+ T-cells than younger adults (young: 35% ± 11%; older: 24% ± 9%, p = 0.004), and all TANG subsets from older adults exhibited higher VEGF-A content than younger adults (CD3+: young: 6081 ± 4001 AU; older: 13426 ± 10,945 AU, p = 0.019; CD31+: young: 6373 ± 3972 AU; older: 15660 ± 12,829 AU, p = 0.011; CD8+: young: 6335 ± 4029 AU; older: 11216 ± 8056 AU, p = 0.043). TANG cells and VEGF-A expression were not independently associated with CMV serostatus, IL-6 or V ̇ O2max. Advancing age is associated with a pathological TANG phenotype which may contribute to age-related inflammation.
Although metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for chronic kidney disease (CKD), validated clinical markers for individualized renal risk stratification remain limited, especially in lean patients. Therefore, we aimed to evaluate an accessible index to predict this risk and explore the underlying pathophysiological mechanisms. We investigated incident CKD risk among UK Biobank participants across a biomarker-based FLI cohort (N = 353,325) and an imaging-based MRI-PDFF cohort (N = 33,155). The participants with MASLD were stratified into lean and non-lean groups. We then evaluated uric acid to HDL ratio (UHR) as a continuous proxy to assess metabolic-related renal risk, and integrated Mendelian randomization (MR), plasma proteomics, and single-cell RNA sequencing to identify circulating mediators. While non-lean MASLD consistently increased CKD risk, the risk in lean MASLD differed by metabolic status. FLI-defined lean MASLD, characterized by severe metabolic abnormalities, predicted a higher incident CKD risk, whereas MRI-defined lean MASLD with milder metabolic traits showed no such association. Furthermore, UHR showed a dose-response relationship with CKD and provided better predictive value than the TyG index. MR analyses revealed that MASLD increases CKD risk indirectly through metabolic burden. Integrative multi-omics analyses suggested AHSG and CPB2 as potential circulating markers of this metabolic-renal axis. In MASLD, the severity of systemic metabolic burden is a key determinant of incident CKD risk across both lean and non-lean individuals. To quantify this burden, UHR serves as a robust continuous proxy that provides better renal risk stratification than the TyG index for both lean and non-lean patients. Furthermore, AHSG and CPB2 represent potential circulating biomarkers for this metabolic-renal link.