Journal of Investigative Medicine

This study aims to investigate the effect of the dopamine D4 receptor (DRD4) gene on violence tendency between athletes and non-athletes. A total of 328 volunteers participated in the study, 214 athletes between the ages of 16 and 32 who have been actively involved in sports for an average of 10.04 years and 114 randomly selected controls (sedentary). A personal information form was used as a data collection tool, and the “Violence Tendency Scale” developed by Göka, Bayat, and Türkçapar was used to determine the participants’ levels of violence. DNA isolation and genotyping methods were used to examine the participants’ DRD4 genotypes and alleles. SPSS 24 package program was used to analyze the data. Our findings reveal significant differences in certain DRD4 variable number tandem repeat genotypes and alleles between athlete and sedentary groups, particularly in the 2/4 and 4/4 genotypes and the 2R and 4R alleles (p < 0.05), while no meaningful differences were observed in other genotypes or alleles (p > 0.05). No significant associations were found between short- and long-repeat genotypes and demographic or background variables such as age, height, weight, gender, type of sport, athletic family history, and chronic illness (p > 0.05). However, a consistent and significant relationship emerged between athletes’ reactions to referee decisions and opponents’ illegal interventions and their history of aggressive behavior, including penalties for unsportsmanlike conduct and violent incidents throughout their sports careers (p < 0.05). The DRD4 gene may play a potential role in the tendency to violence. The results of this study provide important clues for understanding the biological basis of violence and preventing it.

The placebo response represents a significant and complex phenomenon in clinical trials, impacting the interpretation of efficacy and safety outcomes across diverse therapeutic areas. This comprehensive review aims to clarify the mechanisms underlying placebo responses, assess their impact on trial validity, and provide practical strategies for mitigation. We explore psychological and neurobiological drivers, sociocultural influences, and patient–clinician interactions that shape placebo responses. The review also examines design and methodological approaches, including placebo run-in phases, participant selection, and statistical modeling to identify and address placebo effects ethically and effectively. We discuss regulatory and ethical considerations in the context of upholding participant welfare and scientific integrity. By summarizing current evidence, key guidelines, and successful case studies, this guide offers a practical resource for clinical trial designers, sponsors, investigators, and regulators committed to improving trial quality while safeguarding ethical standards. Our recommendations highlight the importance of tailored strategies that balance scientific rigor with participant-centered care, laying the groundwork for more reliable and ethically sound clinical research.

Graphical Abstract

Immunophenotyping via flow cytometry (FC) is a rapid technique for predicting outcomes in acute myeloid leukemia (AML). Cluster of differentiation 25 (CD25) is highly expressed in leukemia stem cells (LSCs), and CD25-positive AML blasts that have an LSC-like gene expression profile. CD200 is consistently overexpressed in AML LSCs when compared with healthy hematopoietic stem cells and their corresponding blast cells. This study aimed to evaluate the impact of CD25/CD200 different expression patterns on newly diagnosed AML patients. For that, 40 AML adult patients were enrolled and assessed using FC to determine CD25 and CD200 surface expression on leukemic blasts. Patients were monitored for clinical features, laboratory findings, response to the induction therapy, overall, and disease-free survival. We reported that the CD25/CD200 double-positive group was significantly associated with unfavorable cytogenetic risk; they also had the poorest response to induction therapy compared to other expression pattern groups. Logistic regression analyses confirmed that CD25/CD200 co-expression is an independent predictor of poor response to induction therapy. Receiver operating characteristic (ROC) curve analysis showed that combining CD25 and CD200 expression provided a better predictive accuracy for treatment response compared to each marker alone. In conclusion, CD25 and CD200 immunophenotypic co-expression was associated with unfavorable cytogenetic risks, lower rates of complete remission following induction therapy, reduced overall survival, disease-free survival, and higher mortality rates. Given the limited sample size, subgroup imbalance, and wide confidence intervals, these findings should be interpreted cautiously as exploratory associations and hypothesis-generating and cannot confirm an independent prognostic role for CD25/CD200 co-expression.

Lyme disease (LD) is caused by a bacterial genospecies complex named Borrelia burgdorferi sensu lato (s.l.), which includes B. burgdorferi sensu stricto (B.b.s.s). Originally described in North America, LD has also been described in other parts of the Northern Hemisphere, and in Eurasia. Different B.b.s.l. species, transmitted through geographically diverse tick vectors, are associated with different clinical presentations of the disease. In recent years, the incidence and the endemic range of LD have steadily expanded to include areas of the world with tropical climate, including Latin American countries. Challenges in serological diagnosis. Inconsistent confirmatory results, despite clinical diagnosis, could be explained by antigenic differences between these new species in these countries, with American strains used in the elaboration of commercial tests. This could explain indeterminate Western blots and polymerase chain reactions in detecting suspected LD cases. Novel Borrelia taxons may impact the reservoir host spectrum, including mammals, birds, and other animals. Different species of Ixodes ticks are found in Latin America, where I. scapularis is absent, and they could serve as vectors. New genospecies of B.b.s.l. and the scarce information about its pathogenicity, reservoirs, and vectors, highlights the importance of further studies tp elucidate their genetic differences in the context of the development of innovative diagnostic and clinical approaches. Knowledge gaps and the need for prospective and rigorous studies, to determine the presence, or not, of LD in this region, warrant call for research providing new insights into the basic biology and epidemiology, and clinical manifestations in this region.

This study reports one case of Kabuki syndrome (KS) accompanied by a new mutation in the KMT2D gene and concurrent congenital pulmonary airway malformation (CPAM). After birth, the child demonstrated delayed physical growth and neurological, psychological, and intellectual development. Notable facial features included arched eyebrows and elongated eyelids toward the lower side. Chest computed tomography revealed pulmonary airway malformation. Whole-exome high-throughput sequencing revealed a novel heterozygous missense mutation in the KMT2D gene, Exon38c.10481C>T (p.Pro3494Leu), a possible pathogenic mutation that has not been previously reported. Both parents were wild-type. The clinical manifestations of KS are complex; however, cases with concomitant CPAM have rarely been reported. This study elucidates the mutation spectrum of the KS gene and the clinical characteristics of KS patients.

Remnant cholesterol (RC) is a non-traditional lipid parameter that reflects residual risk of cardiovascular disease. The purpose of the present study was to explore the relationship between RC and abdominal aortic calcification (AAC) in the U.S. general population. Data were obtained from the 2013–2014 National Health and Nutrition Examination survey. The severity of AAC was assessed using the Kauppila scoring system. Multivariable linear and logistic regression analyses were used to assess the associations of RC with AAC score and severe AAC (score ≥ 5), respectively. In addition, subgroup analyses and mediated effects analysis were performed. A total of 1062 participants were enrolled for analysis. The results of regression analysis demonstrated a positive relationship between RC and both AAC score and severe AAC (β = 0.23, 95% CI 0.04–0.42, p = 0.017; OR = 1.44, 95% CI 1.12–1.85, p = 0.004, per 1-SD increase). Compared with the lowest RC tertile, the AAC score of tertile 3 significantly increased 0.66-unit (β = 0.66, 95% CI 0.19–1.12, p = 0.006), and the risk of severe AAC increased by 165% (OR = 2.65, 95% CI 1.35–5.18, p = 0.005). The results of subgroup analyses showed that no statistically significant interaction across variables. Furthermore, mediation analysis revealed that type 2 diabetes mellitus (T2DM) accounted for 6.76% of the association between RC and AAC, whereas insulin resistance (HOMA-IR) explained 23.4% of this relationship, both showing significant indirect effects. RC was positively associated with AAC score, and higher RC levels were related to higher risk of severe AAC, with both T2DM and insulin resistance acting as mediators.

This meta-analysis systematically evaluates the clinical efficacy and safety of microcatheter-assisted trabeculotomy in glaucoma treatment. We searched databases including PubMed, Embase, Web of Science, Wiley Library, China National Knowledge Infrastructure, Wanfang, and VIP. Four randomized controlled trials and 3 case–control studies, totaling 460 patients, were included. Data were analyzed using Stata/MP18 (StataCorp LLC, College Station, TX, USA) to calculate risk ratio, standardized mean difference (SMD), and 95% confidence interval (CI). It showed a significant short-term (3–6 months) reduction in intraocular pressure (IOP) with microcatheter-assisted trabeculotomy compared to control procedures (SMD = −0.39, 95% CI: −0.72 to −0.05, p = 0.01). Subgroup analysis suggested a significant short-term benefit in adults (SMD = −0.71, 95% CI: −1.37 to −0.05, p = 0.04), but not in pediatric patients. For long-term IOP (>1 year), the overall reduction was statistically significant (SMD = −0.46, 95% CI: −0.89 to −0.04, p = 0.03), with a significant benefit observed in adults (SMD = −1.03, 95% CI: −1.41 to −0.64, p < 0.01) but not in pediatric patients. No significant differences were found in postoperative success rates, number of antiglaucoma medications, or the incidence of ciliary detachment. Current evidence suggests that microcatheter-assisted trabeculotomy provides significant IOP-lowering effects in both the short and long-term overall, with a significant benefit in adults, whereas the benefit in children remains unclear. Its effects on surgical success rates and medication burden remain inconclusive. These findings support its potential as an effective surgical option, but highlight the need for further high-quality, long-term studies.

Artificial intelligence (AI) tools, particularly large language models, are increasingly accessible to medical learners. Early attitudes toward AI may shape how students incorporate these tools into learning and professional development. This study captured first- and second year medical students’ AI familiarity, prior use, and perceptions during orientation week, providing a snapshot of incoming student attitudes. A cross-sectional survey was administered to first- and second year medical students (N = 157) at a single U.S. medical school in August 2024. Data on demographics, AI familiarity, prior use, and perceptions were collected using multiple-choice and five-point Likert scale items. Descriptive statistics, Chi-squared analyses, and Fisher’s exact tests were used to compare responses between cohorts. Of 108 responses, most students reported slight (42.6%) or moderate (37%) AI familiarity. ChatGPT was the most recognized (95.4%) and used (84.3%) tool. First year students were significantly more likely than second year students to have used AI previously, to have used AI during medical school applications, and to plan AI use in medical school (all p < 0.001). Students expressed optimism about AI integration but raised concerns about accuracy (76.9%), clinical thinking (67.6%), and ethics (63%). Over 60% rated ethical AI training as very or extremely important, and 57.4% were uncomfortable with AI-mediated assessment. Pre-clinical students anticipate a growing role for AI in medical education and favor structured, workshop-based ethical training. These findings can inform timely curricular planning as AI technologies continue to evolve.

Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular risk, in part through effects on traditional risk factors such as hypertension. People with chronic kidney disease (CKD) have elevated cardiovascular risk and a unique cardiovascular risk factor profile compared to the general population. We assessed associations of cardiovascular risk factors with PTSD among men and women with CKD. In this cross-sectional study, we identified adults with incident non-dialysis CKD stages 3–5 from 2009 to 2020 in the Veterans Affairs healthcare system. Prevalent PTSD was defined by the use of at least two PTSD diagnosis codes within 12 months prior to incident CKD. Of 1,443,878 Veterans in the cohort, PTSD was prevalent in 18.5% of women and 9.6% of men, p < 0.0001. In multivariable models, younger age, Black race, hypertension, depression, anxiety, alcohol, and/or substance use disorder, the use of antidepressant medications other than selective serotonin reuptake inhibitors (SSRIs), and higher estimated glomerular filtration rate were associated with increased odds of PTSD in both men and women, with significant interactions by sex for each of these (interaction p < 0.001 for each), except for anxiety (interaction p = 0.11). SSRI antidepressant use was associated with PTSD among men but not women. PTSD was differentially associated with cardiovascular risk factors among men and women with CKD. Further studies of the mechanisms of cardiovascular risk in people with CKD should stratify by sex.

Chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, lung cancer and so on, pose a substantial global health challenge. Environmental pollutants such as cigarette smoke, particulate matter (PM), house dust mite (HDM), silicon, and volatile organic compounds (VOCs) are key contributors to these diseases, yet the underlying mechanisms remain not fully elucidated. PANoptosis, a recently identified form of programmed cell death that integrates apoptosis, pyroptosis, and necroptosis, has emerged as a crucial player in various diseases. PANoptosis is orchestrated by the PANoptosome, a multi-protein complex driven by key sensors such as Z-DNA binding protein 1 (ZBP1), absent in melanoma 2 (AIM2), and receptor-interacting protein kinase 1 (RIPK1). Increasing evidence suggests that PANoptosis contributes to lung diseases progression by exacerbating lung tissue damage in response to environmental pollutants. This review consolidates current findings on PANoptosis in pollutant-induced chronic respiratory diseases, which might provide new insights into underlying mechanisms and potential therapeutic targets.

Graphical abstract

End-stage renal disease (ESRD) is characterized by irreversible loss of kidney function requiring dialysis or a kidney transplant to maintain fluid homeostasis. The integumentary system is known to be affected, and nail changes, such as Terry’s nails and half-and-half nails, are frequently observed. However, the prognostic significance of nail manifestations in this population remains poorly defined. This study sought to determine whether a diagnosis of changes in nails was associated with an increased risk of all-cause mortality. A retrospective cohort analysis was performed using the United States Renal Data System (USRDS), which contains medical claims of all ESRD patients in the United States. Patients in the USRDS database with no missing data and enrolled between 2005 and 2018, allowing for at least a 1-year follow-up, were included. A nail change diagnosis and several clinical covariates were determined using International Classification of Disease (ICD)-9 and ICD-10 codes. Mortality risk was evaluated using Cox Proportional Hazards (CPH) models controlling for various demographic and clinical parameters. Of the 1,028,817 ESRD subjects included in this analysis, 66,704 (6.5%) subjects had a nail change diagnosis. In the final CPH model, a nail change diagnosis was independently associated with an increased risk of all-cause mortality (hazard ratio = 1.22; 95% confidence interval = 1.20–1.23) after controlling for demographic and clinical risk factors. Despite this association, nail changes are likely underdiagnosed in the ESRD population. Our findings underscore the importance of a comprehensive dermatological evaluation of ESRD patients and recognition of nail changes as a possible prognostic indicator.

Atrial arrhythmias (AA), including atrial fibrillation (AF) and atrial flutter, are a significant clinical problem in oncological patients. The effect of AA on clinical outcome of patients with non-small cell lung cancer (NSCLC) is not well-known. We assessed the impact of AA on overall survival (OS) in patients with NSCLC. All consecutive NSCLC patients with baseline FDG–PET/CT in our institutional cancer registry from 2004 to 2017 were included. The incidence and prevalence of AA were determined. Cox regression models and Kaplan–Meier survival curves were used for the analysis. A total of 998 NSCLC patients (mean age 67 years, 54.3% female, 45.5% African American) were enrolled. AA were documented in 142 patients (14.2%); 6.9% had baseline AA and 7.3% had new-onset AA during the treatment of NSCLC. Baseline AA was more common in older, male, White, and comorbid patients. Univariate analysis showed baseline AA was associated with worse OS compared to no AA (hazard ratio (HR) 1.48, p = 0.004), whereas new-onset AA did not significantly impact OS (HR 1.02, p = 0.875). Baseline AA was associated with worse OS compared to new-onset AA (HR 1.45, p = 0.044). In multivariate analysis, baseline AA remained an independent predictor of worse OS (HR 1.59, p = 0.001) after adjusting for nine prognostic variables, including TNM stage, treatment, whole-body metabolic tumor volume, and performance status. New-onset AA did not affect OS (HR 1.16, p = 0.30). In conclusion, baseline AA is an independent prognostic marker for worse OS in NSCLC patients, while new-onset AA does not have an impact on OS.

Early identification of gram-negative bacteremia (GN-BSI) in intensive care units (ICUs) remains challenging at the time of blood culture sampling, when clinical signs are often nonspecific and existing diagnostic approaches typically rely on single-timepoint measurements. We conducted a retrospective cohort study of adult ICU patients admitted between July 2022 and January 2024 to investigate whether short-term longitudinal patterns in routinely collected clinical and laboratory data contain diagnostically relevant information for GN-BSI. Clinical and laboratory variables were extracted at three consecutive timepoints (Day −2, −1, and 0 relative to blood culture collection), and diagnostic models incorporating this temporal information were developed using complementary statistical and machine-learning approaches. Model performance was evaluated on a held-out test set using discrimination, calibration, and decision curve analysis. Among 568 patients, models incorporating short-term longitudinal data demonstrated good and consistent discrimination for GN-BSI (AUC range 0.81–0.83). A parsimonious logistic regression model of the mean values of seven predictors achieved an AUC of 0.81, which was not significantly different from the best-performing machine learning model (MILD-SVM, AUC 0.83; bootstrap test, p = 0.728). Diagnostic performance was stable across modeling approaches, indicating robustness of the underlying signal rather than dependence on a specific algorithm. Decision curve analysis suggested a higher net benefit of model-based risk stratification compared with treat-all or treat-none strategies across clinically relevant threshold probabilities. Central venous catheter presence, prior antibiotic use, hemoglobin, creatinine, and albumin consistently emerged as influential predictors. These findings indicate that short-term longitudinal clinical trajectories contain diagnostically meaningful information for GN-BSI at the time of blood culture sampling and support further external validation and prospective evaluation prior to clinical implementation.

Although ischemic heart disease (IHD) mortality has declined overall due to advances in prevention and acute care, adults with both chronic atherosclerotic heart disease and diabetes mellitus—who face a twofold increased risk of coronary events—may not have benefited equally. National trends and disparities in acute ischemic event mortality within this dual-risk population remain underexamined.To quantify age-adjusted mortality trends and identify demographic and geographic disparities in acute ischemic event mortality among U.S. adults with both diabetes and chronic atherosclerotic heart disease from 1999 to 2020, we conducted a cross-sectional analysis using CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) (1999–2020). Adults aged ≥25 years were included if the underlying cause of death was an acute ischemic event, with both diabetes and chronic atherosclerotic heart disease listed as contributing causes. Age-adjusted mortality rates (AAMRs) were calculated using the 2000 U.S. standard population. Joinpoint regression was used to assess trends. Among 201,980 deaths identified, AAMRs declined from 1999 to 2009 (−6.15% per year), slowed from 2009 to 2018 (−3.16%), and rose slightly from 2018 to 2020 (+4.39%; not statistically significant). Men, Black and Hispanic individuals, older adults, and residents of micropolitan counties had the highest mortality. State-level AAMRs varied nearly fourfold. Women had steeper declines than men; Black adults bore the highest burden throughout. While mortality declined overall in this high-risk group, progress has slowed and significant disparities persist. Targeted, equity-focused interventions are urgently needed.

Endoplasmic Reticulum Stress (ERS), as a core mechanism of cellular response to protein homeostasis imbalance, plays a dual regulatory role in tumorigenesis and development. In this study, we aimed to analyze the regulatory network of endoplasmic reticulum stress-associated genes (ERSAGs) in oral squamous cell carcinoma (OSCC). By screening differentially expressed genes through the TCGA database, we explored the potential associations between ERS and OSCC across various aspects. We constructed an OSCC prognostic risk scoring model based on ERSRGs and validated the model’s reliability using the GEO dataset as a validation set. In total, 43 differentially expressed ERSAGs were screened as well as 9 prognostic genes. Six genes (KLHL14, SLC25A4, STC2, TRIB3, ALG3, and CCNA2) were screened by Lasso regression to construct a prognostic risk score model. Further analysis suggested that KLHL14 may suppress OSCC progression by modulating tumor-infiltrating immune cells, specifically activated B cells and mast cells. Concurrently, experimental validation demonstrated that overexpression of CCNA2 significantly promotes the proliferation of OSCC. The results indicated that CCNA2 promotes the proliferation of OSCC cells cultured in vitro. This study is the first to construct a prognostic risk model for OSCC based on ERSAGs, which may assist in predicting prognosis of OSCC patients. The identified ERSAGs may contribute to the development of new therapeutic strategies, highlighting the potential clinical application value of ERS-related genes in predicting OSCC prognosis.

The cardiometabolic benefits of caloric restriction (CR) often overlap with those of intermittent fasting (IF), creating clinical uncertainty. This meta-analysis updates and refines the evidence on the effects of a monotherapeutic CR diet (MCRD) on cardiometabolic parameters in adults at high cardiovascular risk, compared with a usual diet. A systematic search of four databases through May 2025 identified 17 randomized controlled trials (1066 participants) with low to moderate risk of bias, all involving populations with a mean baseline body mass index ≥ 30 kg/m². The results indicate that MCRD significantly reduced body weight (MD: −6.29 kg; 95% CI: −7.51 to −5.06), waist circumference (MD: −5.09 cm; 95% CI: −6.48 to −3.70), body fat (MD: −4.89 kg; 95% CI: −5.92 to −3.87), central abdominal fat (MD: −0.7 kg; 95% CI: −0.97 to −0.43), and lean body mass (MD: −1.34 kg; 95% CI: −2.14 to −0.53). Significant metabolic improvements were observed, with reductions in fasting insulin (MD: −2.22 μIU/L; 95% CI: −3.83 to −0.61), HbA1c (MD: −0.31%; 95% CI: −0.61 to −0.01), HOMA-IR (MD: −0.97; 95% CI: −1.86 to −0.09), and both systolic (MD: −6.06 mmHg; 95% CI: −9.46 to −2.65) and diastolic blood pressure (MD: −3.79 mmHg; 95% CI: −6.34 to −1.25). No significant effects were observed on lipid profiles, glucose levels, or high-sensitivity C-reactive protein. Meta-regression showed that caloric intake reduction, longer intervention duration, and older age significantly covariate with weight reduction. While beneficial, MCRD requires complementary strategies for optimal health. Further research is needed to clarify its unique mechanisms and distinguish them from the overlapping effects of IF.

Familial hypercholesterolemia (FH) is a common inherited condition resulting in elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary artery disease. Despite its clinical significance, FH remains underdiagnosed in South Asia. This study aims to determine the prevalence and demographic distribution of FH in Sri Lanka, using data from a country-wide laboratory network. The study is a cross-sectional and observational study. Retrospective collection of lipid panels from a laboratory network, covering October 2024–March 2025 was done. Patients with LDL-C >190 mg/dl were recruited for the study, and Make Early Diagnoses to Prevent Early Deaths criteria were used for FH diagnosis. Statistical analysis calculated the prevalence with 95% confidence interval (CI); subgroup analyses were done by age, sex, and district. A total of 219,653 individuals had done a lipid profile test, of which 13,592 individuals had an LDL-C >190 mg/dl. FH was prevalent in 0.57%, equivalent to a ratio of 1:177 (95% CI: 0.54–0.60), accounting for 1243 cases. Most cases were male (n = 703); highest prevalence in >40 age group (n = 524, 3.9%) and in the Western Province of the country (Colombo, Gampaha). Males <20 years had higher LDL-C than females, but females >40 had higher LDL-C. Males had higher triglycerides and lower HDL across ages. LDL/HDL and CHOL/HDL ratios were consistently higher in males. This study reveals that FH is more prevalent in Sri Lanka than previously recognized, with notable differences by age, sex, and geographic region. The findings highlight a significant burden of undiagnosed FH and emphasize the importance of implementing nationwide screening.

This study aimed to compare the effectiveness of augmented reality (AR)-assisted teaching versus traditional methods in enhancing clinical core competencies among postgraduate medical students. Fifty postgraduate medical students were randomly assigned to either an experimental group (AR-assisted teaching, n = 25) or a control group (traditional teaching, n = 25). Following an identical instructional curriculum, participants underwent objective theoretical and case analysis assessments, completed self-evaluation surveys, and responded to standardized teaching satisfaction questionnaires. Competency evaluations were based on the six Accreditation Council for Graduate Medical Education (ACGME) core competencies: patient care, medical knowledge, system-based practice, practice-based learning and improvement, professionalism, and interpersonal and communication skills. Students in the experimental group outperformed the control group in theoretical knowledge and case analysis (p < 0.05). They also reported significantly greater improvements in self-directed learning ability, learning efficiency, clinical reasoning, and concentration. The experimental group showed higher satisfaction across teaching dimensions, including spatial visualization, interactivity, curriculum design, and perceived learning outcomes. Additionally, scores across all six ACGME core competencies were significantly higher in the experimental group compared to the control group (p < 0.05). AR-assisted teaching offers significant advantages over traditional methods in medical education, leading to enhanced knowledge acquisition, clinical reasoning, learner engagement, and competency development, thereby providing a promising approach for advancing postgraduate clinical training.

Rheumatoid arthritis (RA) is characterized by persistent synovitis. Conventional inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) inadequately reflect synovial inflammation, particularly under interleukin-6 pathway inhibition. Pentraxin 3 (PTX3), an extrahepatic acute-phase protein produced in inflamed tissues, may better reflect local inflammation and angiogenesis in RA joints. We enrolled 80 RA patients and 80 age-sex-matched healthy controls. Clinical data, inflammatory markers, and disease activity scores (DAS28) were collected. Serum PTX3 levels were quantified by ELISA. Musculoskeletal ultrasound assessed bilateral wrists and metacarpophalangeal/proximal interphalangeal joints for synovial hypertrophy, effusion, color Doppler flow, and bone erosion. Eight patients received tocilizumab at baseline and week 12. PTX3 levels were significantly higher in RA patients than in controls. Serum PTX3 concentrations showed a progressive increase from remission to moderate-to-high disease activity groups. PTX3 showed no significant reduction after tocilizumab treatment. PTX3 correlated positively with CRP, ESR, DAS28-CRP, and rheumatoid factor, but not with anti-cyclic citrullinated peptide antibodies. PTX3 levels were elevated in patients with ultrasound-detected synovial blood flow compared to those without. Receiver operating characteristic analysis demonstrated superior diagnostic performance of PTX3 for predicting synovial blood flow compared to CRP and ESR. In multivariable logistic regression, PTX3 was the only significant predictor of synovial blood flow positivity. PTX3 demonstrates superior diagnostic performance over traditional inflammatory markers in detecting synovial vascularity and independently correlates with disease activity. PTX3 may serve as a valuable complementary biomarker for assessing local synovial inflammation and angiogenesis, particularly when conventional markers are inadequate.