Home The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
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The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis

  • Rui Lian and Xiangmin Zhang EMAIL logo
Published/Copyright: November 4, 2025
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Open Medicine
From the journal Open Medicine Volume 20 Issue 1

Abstract

Background

This meta-analysis evaluates the diagnostic accuracy of machine learning-derived FFRCT (ML-FFRCT) for CAD, using invasive coronary angiography-derived fractional flow reserve (ICA-FFR) as the gold standard to provide evidence for clinical translation.

Methods

We systematically searched PubMed and Embase for relevant studies. Study quality was assessed using QUADAS-2 in RevMan 5.3. Diagnostic performance was evaluated by pooling sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC) using Stata 14.0. Meta-regression and subgroup analyses were conducted based on the publication year, country, study design, sample source, and sample size.

Results

The pooled SEN was 0.84 (95% CI: 0.79–0.87) and SPE was 0.83 (95% CI: 0.77–0.88). The PLR and NLR were 4.95 (95% CI: 3.58–6.84) and 0.20 (95% CI: 0.15–0.26), respectively. The DOR was 25.15 (95% CI: 14.87–42.52) and the AUC was 0.90 (95% CI: 0.87–0.93), indicating high diagnostic accuracy. Deeks’ funnel plot revealed no significant publication bias.

Conclusions

ML-FFRCT demonstrates high SEN and SPE in diagnosing CAD. These findings support its potential as a promising noninvasive tool for CAD assessment.

Keywords: machine learning; FFRCT; CAD; meta

1 Introduction

Coronary artery disease (CAD), the leading cause of cardiovascular mortality worldwide, is pathologically characterized by atherosclerotic plaque-induced luminal stenosis and myocardial microcirculatory dysfunction [1,2]. Invasive coronary angiography-derived fractional flow reserve (ICA-FFR) remains the gold standard for CAD assessment. This technique measures the ratio of distal coronary pressure to aortic pressure under pharmacologically induced maximal hyperemia, with FFR ≤ 0.80 indicating myocardial ischemia [3]. Despite its diagnostic superiority, the requirements of ICA-FFR for invasive procedures and pharmacologic stress testing significantly increase healthcare costs and procedural complexity, limiting its widespread clinical adoption [4]. Coronary computed tomography angiography (CCTA) has emerged as a preferred noninvasive screening modality due to its rapid imaging acquisition and low radiation exposure [5,6].

However, conventional lumen-based stenosis assessment often overestimates lesion severity, and not all anatomical stenoses cause functional ischemia [7,8]. This “anatomical-functional mismatch” prompted the development of computational fluid dynamics-derived FFR (CFD-FFRCT), which simulates hyperemic hemodynamics using CCTA data to provide a combined anatomical and functional evaluation [9]. Nevertheless, reliance on CFD-FFRCT on complex mathematical modeling results in prolonged computation times, often requiring several hours per case [10]. The advent of machine learning in medical imaging has led to the development of ML-derived FFR (ML-FFRCT), which establishes an ML-derived mapping relationship between CCTA image features and CFD results. Through database training, ML-FFRCT optimizes computational performance and simplifies workstation requirements, delivering objectively quantified hemodynamic assessments within minutes while maintaining diagnostic performance comparable to CFD-FFRCT [11].

Although ML-FFRCT demonstrates significantly improved computational performance over traditional CFD methods, there remains a paucity of systematic evidence evaluating its diagnostic concordance with the gold-standard FFR. This study employs meta-analytic methodology to synthesize the most current research data, assessing the diagnostic efficacy of ML-FFRCT for CAD at the vessel level. Our findings aim to provide evidence-derived support for the clinical translation of this innovative technology and its implementation in precision medicine practice.

2 Methods

2.1 Literature search strategy

A systematic computerized search was conducted in the EMbase and PubMed databases to identify clinical studies evaluating the diagnostic performance of ML-FFRCT for CAD, published between January 2014 and December 2024. The search was restricted to English-language publications. Two independent researchers performed study selection and data extraction, with any discrepancies resolved by a third investigator. The search strategy combined Medical Subject Headings (MeSH) terms and free-text keywords, including: “Artificial intelligence” OR “Machine learning,” “fractional flow reserve” “FFR” OR “FFRCT,” “CCTA.” Prospero number: CRD420251046889.

2.2 Inclusion and exclusion criteria

Inclusion criteria: (1) Publication Type: original clinical studies (in English) evaluating ML-FFRCT for CAD diagnosis; (2) Population: patients who underwent CCTA with AI-derived FFRCT assessment; (3) Reference Standard: invasive FFR (ICA-FFR) as the gold standard, with FFR ≤ 0.80 defining hemodynamically significant ischemia; (4) Data Availability: reported or derivable diagnostic metrics – true positive (TP), false positive (FP), false negative (FN), true negative (TN).

Exclusion criteria: (1) reviews, conference abstracts, case reports (<10 patients), or lacked gold-standard validation; (2) provided insufficient data for meta-analysis calculations; (3) duplicate publications (only the most recent was retained).

2.3 Literature screening and data extraction

Two independent investigators (L.R. and Z.X.) performed screening and data extraction using the following protocol: (1) Basic Study Characteristics: author, year, country, study design, sample source, and sample size; (2) Diagnostic Accuracy Data: 2 × 2 contingency tables (TP, FP, FN, TN) and performance metrics (sensitivity, specificity). Discrepancies were resolved via cross-verification, group discussion, or third-party arbitration. Studies with irresolvable ambiguities were excluded. The QUADAS-2 tool (implemented in RevMan 5.3) [12] was used for quality assessment. Disagreements were resolved by consensus.

2.4 Statistical analysis

Meta-analysis was performed using Stata 14.0. Heterogeneity Assessment. Heterogeneity was evaluated via Cochran’s Q test and quantified using the I² statistic, with thresholds defined as follows. 25–49%: low heterogeneity, 50–74%: moderate heterogeneity, ≥75%: high heterogeneity. Random-effects model if I 2 ≥ 50%, while fixed-effects model if I 2 < 50%. Diagnostic Performance Metrics Weighted pooled estimates were calculated for pool sensitivity (SEN) and specificity(SPE), diagnostic score and diagnostic odds ratio (DOR), and positive/negative likelihood ratios (PLR/NLR) with 95% CI. A summary receiver operating characteristic curve, with the area under the curve (AUC), was used to quantify overall diagnostic accuracy. Publication bias was assessed using Deeks’ funnel plot asymmetry test. Sensitivity analysis was used to evaluate the impact of individual studies on the overall meta-analysis. Meta-regression and subgroup analysis were stratified by the following study characteristics: publication year (pre-2020 vs post-2020), country (Asia vs non-Asia), study design (retrospective vs prospective), sample source (single-center vs multi-center), and sample size (<200 vs ≥200).

3 Results

3.1 Studies and selection

The literature search and screening process are shown in Figure 1, with 249 articles initially identified from PubMed/EMBASE. After removing duplicates and applying inclusion/exclusion criteria, 13 eligible studies [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27] were included. Quality assessment was performed using QUADAS-2 for 13 studies (Figure 2 and Table S1), and most studies showed low risk of bias. As shown in Table 1, the analysis comprised four multicenter and nine single-center studies, predominantly retrospective (ten studies) with only three prospective studies. Geographically, studies originated from Asia (China, Japan, South Korea) and non-Asian countries (Romania, Sweden, Germany, USA, Brazil). Temporally, eight studies were published before 2020 and five studies in 2020 or later. Regarding sample size, 5 studies had ≥200 participants while 8 studies included <200 participants.

Figure 1 Flowchart of literature search and study selection.
Figure 1

Flowchart of literature search and study selection.

Figure 2 Quality assessment of included studies based on QUADAS-2 tool criteria.
Figure 2

Quality assessment of included studies based on QUADAS-2 tool criteria.

Table 1

Basic characteristics and diagnostic parameters of the 13 studies

Author Year Country Study design Sample source Sample size Sensitivity Specificity TP FN TN FP
Itu [13] 2016 Romania Retrospective Single center 125 81.6 83.9 31 7 73 14
Coenen [14] 2018 USA Prospective Multi-center 525 81 76 171 41 239 74
Di Jiang [15] 2021 China Retrospective Multi-center 544 83 94 161 33 329 21
Yu [16] 2018 China Retrospective Single center 166 87.5 78.2 49 7 86 24
Koo [17] 2021 South Korea Retrospective Single center 557 63.2 68.1 172 100 194 91
Kurata [18] 2019 Japan Retrospective Single center 91 89 75 42 5 33 11
Zhang [19] 2023 China Retrospective Multi-center 130 92 85 36 3 77 14
De Geer [20] 2019 Sweden Retrospective Multi-center 225 85 72.8 85 15 91 34
Morais [21] 2021 Brazil‌ Retrospective Single center 152 87 86 65 9 67 11
Li [22] 2019 China Prospective Single center 157 88 68 66 9 56 26
Yu [23] 2019 China Retrospective Single center 206 81.2 83.6 65 15 105 21
von Knebel Doeberitz [24] 2019 USA Retrospective Single center 103 82 94 26 6 67 4
Baumann [25] 2020 Germany Prospective Single center 57 87 95 13 2 40 2

TP: true positive value; FP: false positive value; FN: false negative value; TN: true negative value.

3.2 Meta-analysis

As shown in Figures 3–5, the pooled SEN was 0.84 (95% CI: 0.79–0.87) and SPE was 0.83 (95% CI: 0.77–0.88). The DOR was 25.15 (95% CI: 14.87–42.52) and the AUC was 0.9 (95% CI: 0.87–0.92), demonstrating high diagnostic accuracy for ML-FFRCT. Deeks’ funnel plot revealed symmetrical distribution of studies along the regression line (p = 0.15), indicating no significant publication bias. Figure 6 displays PLR of 4.95 (95% CI: 3.58–6.84) and NLR of 0.20 (95% CI: 0.15–0.26), indicating that ML-FFRCT was 4.95 times more likely to correctly identify CAD than misclassify it, while the probability of false negatives was only 0.2 times that of correct exclusions. At a pretest probability of 0.5 (50% CAD prevalence in patients with anatomical stenosis), positive ML-FFRCT results increased diagnostic certainty from 50% to 83%, while negative results reduced misdiagnosis probability to 16% (Figure 7), confirming the strong discriminative capacity of ML-FFRCT (Figure 8).

Figure 3 Pool sensitivity and specificity of ML-FFRCT for CAD.
Figure 3

Pool sensitivity and specificity of ML-FFRCT for CAD.

Figure 4 DOR of FFRCT for CAD.
Figure 4

DOR of FFRCT for CAD.

Figure 5 (a) AUC of ML-FFRCT for CAD, and (b) Deeks funnel plot.
Figure 5

(a) AUC of ML-FFRCT for CAD, and (b) Deeks funnel plot.

Figure 6 Pool estimates of PLR and NLR.
Figure 6

Pool estimates of PLR and NLR.

Figure 7 Fagan diagram of ML-FFRCT for CAD.
Figure 7

Fagan diagram of ML-FFRCT for CAD.

Figure 8 Sensitivity analysis of 13 studies included.
Figure 8

Sensitivity analysis of 13 studies included.

However, significant heterogeneity was observed across all metrics, with I 2 of 86.31% for SEN, 90.24 for SPE, 89.6% for DOR, 89.17% for PLR, and 90.88% for NLR. The effect sizes of various research reports vary greatly, with DOR ranging from 3.67 to 130. As shown in Figure 9 and Table 2, subgroup analyses and meta-regression identified several significant sources of heterogeneity. For SEN, significant heterogeneity was associated with year (p < 0.001), country (p < 0.01), study design (p < 0.01), sample source (p < 0.001), and sample size (p < 0.01). For SPE, significant heterogeneity was also observed for year (p < 0.001), country (p = 0.02), sample source (p < 0.01), and sample size (p = 0.03), but not for the study design (p = 0.11).

Figure 9 Multiple meta-regression and subgroup analysis on pooled SEN and SPE.
Figure 9

Multiple meta-regression and subgroup analysis on pooled SEN and SPE.

Table 2

Pooled estimation of subgroups

Subgroup Number SEN (95% CI) SPE (95% CI) PLR (95% CI) NLR (95% CI) DOR (95% CI) AUC (95% CI)
Before 2020 8 0.83(0.8–0.86) 0.79(0.73–0.84) 4.04(3.13–5.2) 0.21(0.18–0.25) 19.16(13.66–26.89) 0.87(0.84–0.9)
After 2020 5 0.83(0.72–0.9) 0.88(0.78–0.94) 6.76(3.39–13.47) 0.2(0.11–0.35) 34.02(10.46–110.63) 0.92(0.89–0.94)
Asia 8 0.83(0.76–0.88) 0.82(0.75–0.88) 4.71(3.11–7.13) 0.21(0.14–0.31) 22.6(10.57–48.35) 0.89(0.86–0.92)
Non-Asia 5 0.86(0.81–0.89) 0.84(0.74–0.9) 5.27(3.27–8.5) 0.17(0.13–0.22) 30.91(17.57–54.37) 0.89(0.86–0.91)
Retrospective 10 0.83(0.78–0.88) 0.84(0.77–0.88) 5.1(3.58–7.27) 0.2(015–0.27) 25.6(14.06–46.61) 0.9(0.87–0.92)
Prospective 3 0.82(0.76–0.87) 0.81(0.63–0.92) 4.36(2.04–9.33) 0.22(0.15–0.31) 19.92(7.59–52.3) 0.85(0.81–0.87)
Single center 9 0.84(0.77–0.88) 0.82(0.75–0.88) 4.77(3.27–6.96) 0.2(0.14–0.29) 23.92(12.19–46.94) 0.9(0.87–0.92)
Multi-center 4 0.83(0.8–0.86) 0.84(0.73–0.91) 5.19(2.91–9.26) 0.2(0.16–0.25) 25.78(12.32–53.93) 0.84(0.81–0.87)
＜200 8 0.87(0.83–0.9) 0.84(0.77–0.89) 5.51(3.79–8.02) 0.15(0.12–0.2) 35.61(21.7–58.44) 0.9(0.87–0.92)
≥200 5 0.79(0.71–0.85) 0.81(0.7–0.89) 4.17(2.42–7.18) 0.26(0.18–0.38) 15.99(6.61–38.67) 0.86(0.83–0.89)

SEN: sensitivity; SPE: specificity; PLR: positive likelihood ratio; NLR: negative likelihood ratio; DOR: diagnostic odds ratio; AUC: area under the curve; CI: confidence interval.

Despite the observed heterogeneity in country and sample source, the diagnostic performance between Asia and non-Asia, as well as between single-center and multi-center studies, was remarkably consistent, with confidence intervals demonstrating substantial overlap. In terms of study design, retrospective studies showed higher summary estimates for both the DOR (25.6 vs 19.92) and the AUC (0.90 vs 0.85) compared to prospective studies, suggesting a potential overestimation of diagnostic accuracy in retrospective cohorts. Studies conducted after 2020 demonstrated a trend toward superior performance, with notably higher SPE (0.88 vs 0.79), PLR (6.76 vs 4.04), and DOR (34.02 vs 19.16). These findings indicate improved diagnostic accuracy and reliability in recent studies, possibly attributable to advancements in diagnostic techniques, standardized operational procedures, or accumulated investigator experience. Furthermore, studies with a sample size <200 consistently showed elevated summary estimates for SEN (0.87 vs 0.79), DOR (35.61 vs 15.99), and AUC (0.90 vs 0.86) compared to those with larger sample sizes (≥200), with minimal overlap in confidence intervals. This indicates a likely overestimation of diagnostic performance due to small-study bias. Consequently, results from larger studies (sample size ≥200) may provide more reliable and conservative estimates of the true diagnostic accuracy.

4 Discussion

This meta-analysis integrating data from 15 studies demonstrates the significant diagnostic performance of ML-FFRCT for CAD, showing a pooled SEN of 0.84, SPE of 0.83, and AUC of 0.90, indicating near-excellent discriminative ability. The DOR of 25.76, along with PLR of 4.95 and NLR of 0.20, confirms the particular advantage of ML-FFRCT in CAD exclusion, which could substantially reduce unnecessary ICA procedures while lowering medical risks and costs. Compared to conventional CCTA relying solely on anatomical assessment, ML-FFRCT overcomes these limitations by employing machine learning to simulate hemodynamics. Our findings highlight the clinical value of ML-FFRCT. Its high SEN minimizes missed diagnoses (especially valuable for atypical CAD presentations), while its strong NLR reliably excludes nonobstructive CAD, preventing overtreatment and making it suitable for both high-risk screening and intermediate/low-risk triage.

CCTA, as a noninvasive anatomical imaging modality, demonstrates unique clinical advantages by ruling out significant stenosis in low-risk patients, making it an ideal screening tool [26]. However, its reliance solely on luminal stenosis assessment may overestimate ischemic risk while potentially leading to unnecessary ICA, revealing inherent functional limitations of anatomical evaluation [27,28]. In functional assessment, ICA-FFR remains the gold standard, particularly valuable for clinically ambiguous borderline lesions [29,30,31], yet carries intrinsic constraints. Its invasive nature risks vascular injury and arrhythmias, while high costs and restricted applicability to revascularization candidates limit screening utility [32]. CFD-FFRCT emerged to address these limitations by solving Navier–Stokes equations to enable completely noninvasive functional assessment, demonstrating superior hemodynamic simulation accuracy in complex anatomies (bifurcation lesions, diffuse stenosis) [33,34]. It can also simulate post-stenting hemodynamic improvements, enabling precise revascularization planning [35]. This technology shows particular specificity for detecting ischemia-causing stenoses, potentially preventing unnecessary interventions and optimizing treatment strategies. However, CFD modeling depends critically on cardiac cycle-dependent coronary flow variations requiring integrated heart-artery modeling, with computational complexity resulting in prolonged processing times (typically hours) [36].

The computational time required for CFD remains a major barrier to its widespread clinical adoption, whereas ML-FFRCT effectively addresses this limitation. Wang et al. [37] demonstrated that AI could automate both geometric quantification of coronary arteries and ML-FFRCT prediction from CCTA images, achieving remarkable sensitivity (97.14%) and specificity (75%) in assessing ischemia risk from stenotic lesions, with a processing time of just 120 ± 13 s. Further studies [38] revealed that machine learning algorithms can automatically extract and analyze key vascular parameters (lumen diameter and cross-sectional area) from both the lesion site and adjacent normal segments for comprehensive evaluation. Compared to CFD, the diagnostic performance of ML-FFRCT is less affected by the “halo effect” of calcified plaques. As machine learning applications in CAD diagnosis continue to mature, these algorithms not only enable sophisticated analysis of CCTA data for noninvasive FFR computation but also, through convolutional neural networks trained on low-dose CT features, can produce coronary image quality comparable to standard-dose acquisitions from reduced radiation scans [39].

However, our analysis revealed substantial heterogeneity with I² values exceeding 85%. Such significant heterogeneity may lead to inconsistencies across studies, potentially affecting the robustness of our pooled analysis. Subgroup analyses suggested that year, country, study design, sample source, and sample size might influence the diagnostic performance of ML-FFRCT. Post-2020 studies showed improved specificity and overall reliability, likely reflecting algorithmic and procedural standardization. Most notably, studies with sample sizes ≥200 yielded consistently lower and more conservative estimates of SEN (0.79 vs 0.87), SPE (0.81 vs 0.84), PLR (4.17 vs 5.51), NLR (0.26 vs 0.15), DOR (15.99 vs 35.61), and AUC (0.86 vs 0.90) compared to smaller studies. Smaller studies tend to overestimate effect sizes due to publication bias or methodological variability. Therefore, the subgroup comprising studies with sample sizes ≥200 most likely represents the true diagnostic performance of ML-FFRCT. These larger studies are methodologically more robust, less susceptible to sampling variability and publication bias, and provide more precise and generalizable estimates.

5 Limitation

This study provides robust evidence supporting the diagnostic value of ML-FFRCT for CAD. However, several limitations must be acknowledged. Most notably, we observed substantial heterogeneity (I 2 > 85%). Besides year, country, study design, sample source, and sample size, potential sources of heterogeneity may include differences in specific machine learning algorithms employed, variations in CCTA acquisition protocol, inconsistencies in the application of reference standards, and unmeasured population differences not captured in baseline characteristics. Additionally, over 25% of the included studies were rated as having a potential risk of bias (unclear) in the patient selection domain according to QUADAS-2 assessment, which may represent another source of heterogeneity and potentially impact the validity of the pooled estimates. Although insufficient data were available to perform meta-regression on analyses for these factors, they represent plausible contributors to the variability observed. Furthermore, detailed descriptions of the machine learning algorithms used across included studies were often lacking, limiting further subgroup assessment. The high degree of heterogeneity underscores that our pooled estimates should be interpreted with caution. Clinicians should be aware that the diagnostic performance of ML-FFRCT may vary meaningfully across specific clinical settings and technical implementations.

6 Conclusion

Preliminary findings suggest that ML-FFRCT has the potential to serve as a noninvasive adjunct tool with promising diagnostic performance compared to conventional methods. However, its clinical utility must be validated in larger, prospective trials.

  1. Funding information: No funds, grants, or other support were received during the preparation of this manuscript.

  2. Author contributions: Z.X. contributed to the conception of the study; L.R. and Z.X. contributed significantly to literature search, data extraction, quality assessment, data analyses, and manuscript preparation; L.R. and Z.X. revised the manuscript and approved the final version.

  3. Conflict of interest: The authors declare that they have no competing interests.

  4. Data availability statement: All the data generated during the study are within the manuscript.

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Received: 2025-05-12
Revised: 2025-09-07
Accepted: 2025-10-06
Published Online: 2025-11-04

© 2025 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/med-2025-1320
Keywords for this article
machine learning; FFRCT; CAD; meta
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
  5. Risk factors for severe adverse drug reactions in hospitalized patients
  6. Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
  7. Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
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  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
  11. Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
  15. Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
  17. Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  19. Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
  20. Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
  21. Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
  22. The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
  23. Health literacy and health-related quality of life: The mediating role of irrational happiness
  24. Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
  25. Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
  26. Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
  27. Clinical analysis of ten cases of HIV infection combined with acute leukemia
  28. Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
  29. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
  30. Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
  31. Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
  32. Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
  33. The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
  34. The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
  35. Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
  36. Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
  40. A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
  42. Identifying early screening factors for depression in middle-aged and older adults: A cohort study
  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
  47. Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
  48. Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
  49. The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
  50. Expression and clinical significance of ITGA3 in breast cancer
  51. Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
  52. rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
  53. Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
  54. Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
  55. Gender beliefs and legitimization of dating violence in adolescents
  56. Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
  57. Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
  58. Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
  59. Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
  60. Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
  61. Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
  62. GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
  63. Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
  64. MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
  65. Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
  66. Trends in research on preterm birth in twin pregnancy based on bibliometrics
  67. Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
  68. Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
  69. Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
  70. Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
  71. Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
  72. CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
  73. Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
  74. Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
  75. Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
  76. Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
  78. Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
  79. Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
  80. The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
  81. The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
  82. Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
  83. Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
  84. The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
  85. Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
  87. Correlation of serum calprotectin with outcome of acute cerebral infarction
  88. Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
  89. Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
  90. The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
  91. Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
  92. Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
  93. Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
  94. Analysis of serum metabolomics in patients with different types of chronic heart failure
  95. Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
  96. Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
  97. Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
  98. METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
  99. The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
  100. Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
  101. Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
  102. Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
  103. Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
  104. Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
  105. Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
  106. Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
  107. Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
  108. Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
  111. HALP score in Demodex blepharitis: A case–control study
  112. Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. 10.1515/med-2025-1198
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Review Articles
  152. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  153. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  154. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  155. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  156. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  157. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  158. The application of augmented reality in robotic general surgery: A mini-review
  159. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  160. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  161. Plant polyphenols, terpenes, and terpenoids in oral health
  162. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  163. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  164. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  165. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  166. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  167. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  168. Giant borderline ovarian tumours – review of the literature
  169. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  170. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  171. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  172. Supplement strategies for infertility in overweight women: Evidence and legal insights
  173. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  174. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  175. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  176. Strategies for hyperkalemia management in dialysis patients: A systematic review
  177. Case Reports
  178. Delayed graft function after renal transplantation
  179. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  180. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  181. Giant right atrial hemangioma presenting with ascites: A case report
  182. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  183. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  184. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  185. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  186. Rapid Communication
  187. Biological properties of valve materials using RGD and EC
  188. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  189. Letter to the Editor
  190. Role of enhanced external counterpulsation in long COVID
  191. Expression of Concern
  192. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  193. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  194. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  195. Corrigendum
  196. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  197. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  198. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  199. Retraction
  200. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  201. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  202. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  203. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  204. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  205. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  206. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  207. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  208. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  209. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  210. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  211. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  212. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  213. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  214. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  215. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  216. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  217. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  218. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  219. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  220. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  221. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  222. A review of brain research on T2DM-related cognitive dysfunction
  223. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  224. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  225. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
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