Home Medicine Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
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Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study

  • Weiguo Ma , Jinfeng Li , Xiaojuan Shao , Xiaohong Yin , Chuanqing Xie , Fenfen Wang and Ya Li EMAIL logo
Published/Copyright: June 4, 2025
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Open Medicine
From the journal Open Medicine Volume 20 Issue 1

Abstract

Background

Despite the high prevalence and serious clinical implications of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM), the relationship between glycemic control and CAD is usually overlooked. This study aimed to explore the relationship between time in range (TIR), a surrogate marker for glycemic control, and CAD in patients with T2DM.

Methods

Overall, 334 patients with T2DM were included and analyzed in this cross-sectional study. The presence of CAD was determined angiographically and the Gensini score was applied to evaluate CAD severity. TIR was calculated from sensor glucose from continuous glucose monitoring. Multivariable-adjusted logistic regression analysis was used to evaluate the relationship between TIR and CAD presence.

Results

T2DM with CAD had significantly lower TIR than those without (75.68 ± 13.74 vs 66.12 ± 11.87, P < 0.01). Moreover, TIR was correlated with CAD severity as indicated by the Gensini score. Multivariable-adjusted logistic regression analysis indicated that a higher TIR was an independent protective factor for CAD in patients with T2DM (OR = 0.919, 95% CI: 0.896–0.942).

Conclusion

TIR is significantly and independently related to CAD severity in T2DM patients. Thus, TIR could be a promising biomarker for the noninvasive assessment of CAD presence and severity in T2DM.

Keywords: continuous glucose monitoring; coronary artery disease; time in range; type 2 diabetes; surrogate marker

1 Introduction

The absolute number of patients with diabetes mellitus worldwide has quadrupled in the past three decades, rendering it as the ninth major cause of mortality. It is estimated that type 2 diabetes mellitus (T2DM) accounts for approximately 90% of all diabetes mellitus cases that occurs in 1 in 11 adults [1]. By 2040, the global prevalence of diabetes is projected to exceed 640 million [2]. Alarmingly, diabetic patients have a 2–3-fold increased risk of major adverse cardiovascular events, with over two-thirds of these patients succumbing to these complications [3]. This rising cardiovascular burden has placed a significant strain on healthcare systems [4,5]. Hemoglobin A1c (HbA1c) has traditionally been used as a surrogate marker to assess glycemic control [6]. A previous study has demonstrated that maintaining HbA1c levels below 7% is associated with a reduced risk of myocardial infarction [7]. There is a strong correlation between HbA1c levels and cardiovascular mortality; a 1% increase in HbA1c is associated with a 1.15-fold higher risk of cardiovascular death [8]. Currently, the close relationship between elevated HbA1c and cardiovascular complications, as well as all-cause mortality among T2DM patients, has been firmly established [9].

While glycemic control has been suggested to be essential for the reduction of mortality in patients with T2DM, the relationship between HbA1c and glycemic control is increasingly being questioned. Some studies have observed discordance between HbA1c and parameters like fasting blood glucose (FPG), mean blood glucose or continuous glucose monitoring (CGM) [10,11]. In comparison, with the advancement of CGM technology, the metric of time in range (TIR) is increasingly regarded as a new standard for glycemic control. TIR is defined as the time or percentage of glucose in the target range (usually 3.9–10.0 or 3.9–7.8 mmol/L) within 24 h [12]. Studies have revealed that TIR could serve as a surrogate biomarker for the urgency of hypo- and hyper-glycemic events and be individually personalized to meet clinical demands [13,14]. For instance, a TIR of 70% (70–180 mg/dL [3.9–10.0 mmol/L]) corresponds to an HbA1c of approximately 7.0%, while a TIR of 50% corresponds to an HbA1c of about 8.0% [15]. Furthermore, each 10% increase in TIR is associated with an approximate 0.5% improvement in HbA1c levels [16]. A cross-sectional study has found negative associations between TIR and the prevalence of diabetic retinopathy and carotid intima-media thickness [17]. Beck et al. also identified significant correlations between TIR and the development of diabetic retinopathy and microalbuminuria [18]. Additionally, a large-scale cohort study has suggested that the TyG index could assist in risk stratification for glycemic management in diabetic patients with coronary artery disease (CAD) [19]. Although prior evidence indicates a possible link between TIR and diabetic complications [17–19], the exact association between TIR and CAD in T2DM patients remains largely unknown. Thus, the purpose of the present study is to explore such correlations to further provide a basis for the early diagnosis and evaluation of cardiovascular events.

2 Materials and methods

2.1 Study subjects

Patients with T2DM undergoing coronary angiography between January 2018 and July 2020 at the Department of Endocrinology, The First Affiliated Hospital of Xi’an Medical University were included. Inclusion criteria were adult patients (age ≥ 18 years) with T2DM on a stable glucose-lowering regimen over the past 3 months. Diabetes mellitus was diagnosed in accordance with the 1998 WHO diagnostic criteria [20]. Exclusion criteria were presence of severe complications, such as hyperglycemic hyperosmolar state, diabetic ketoacidosis, or hypoglycemic events within the past 3 months; non-T2DM, such as T1DM; presence of malignancy or severe hepato-renal dysfunction; use of steroid within the previous 3 months; and concomitant thyroid dysfunction, infections, or previous coronary artery interventions. Overall, 334 patients with T2DM undergoing coronary angiography were included, including 64 patients without CAD (control group) and 270 patients with CAD (CAD group).

2.2 Clinical data and laboratory measurement

Hypertension was considered for those with a blood pressure ≥140/90 mmHg or currently taking any antihypertensive medications. Body mass index (BMI) was measured as weight (kg) divided by height squared (m2). Smoking history and information on current use of medications were collected by interviews during the medical examinations.

Blood samples and fresh first-void morning urine samples were collected after a 12 h overnight fast and analyzed for fasting blood glucose (FPG), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (Apo A), apolipoprotein B (Apo B), apolipoprotein E (Apo E), creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), urinary albumin/creatinine concentration, fasting insulin (FINS), and HbA1C using an automated biochemical analyzer (Hitachi 7600–110; Hitachi, Tokyo, Japan). Besides, the visit-to-visit variability of FPG was evaluated using two variability measures, calculating the following for individual participants: (1) the standard deviation (SD) and (2) the coefficient of variation (CV), calculated by SD divided by mean.

2.3 TIR measurement

All participants underwent CGM (Abbott Freestyle Libre Pro; FGM, USA) for 72 h. During the CGM period, participants adhered to a standardized diet and their initial hypoglycemic regimen. Specifically, the CGM sensor was inserted on the first day of admission (Day 0) and removed after 72 h, providing a daily record of 288 continuous sensor readings. TIR was defined as the percentage of time within a 24 h period that glucose levels were within the target range of 3.9–10.0 mmol/L. Following the 3-day monitoring period, various metrics were calculated using previously reported methods [21], including TIR, time above range (TAR), time below range (TBR), the mean amplitude of glycemic excursions (MAGE), SD, the mean of daily differences (MODD), and the glucose CV.

2.4 Coronary angiography

Severe CAD was considered in the presence of ≥50% stenosis of at least one coronary artery. The method for Gensini score is the same as previously reported [22]. Patients were divided into three groups based on the tertile of the Gensini score: Group 1, with Gensini score ≤11; Group 2, with Gensini score in the range of 12–36; Group 3, with Gensini score >36.

2.5 Statistical analysis

Statistical analysis was conducted using SPSS software. Continuous variables with normal distribution are presented as mean ± SD, while those with non-normal distribution are expressed as median (interquartile range, 25–75%). Categorical variables are presented as percentages. For continuous variables, intergroup comparisons were performed using Student’s t-test if they followed a normal distribution; otherwise, the Mann–Whitney U-test was used. For categorical variables, intergroup comparisons were conducted using the chi-square test (χ² test). A P value <0.05 was considered statistically significant.

  1. Informed consent: Written informed consent was obtained from all participants.

  2. Ethical approval: The study was approved by the Ethics Committees of The First Affiliated Hospital of Xi'an Medical University and conducted in accordance with the principles of the Declaration of Helsinki.

3 Results

As compared to the control group, patients in the CAD group are older, have a higher BMI, longer duration of T2DM and higher systolic blood pressure (SBP), a higher prevalence of current smoking, and higher insulin use (Table 1). In terms of laboratory data, CAD group was associated with significantly elevated TC, LDL-C, ApoB, ApoE, urinary albumin/creatinine concentration, BUN, serum creatinine, UA, HbA1c, TAR% of >10.0 mmol/L, lower TIR, and lipoprotein (Lpa) (P < 0.05). No significant differences were observed between the two groups in terms of gender, diastolic blood pressure (DBP), TG, HDL-C, ApoA, FINS, SD, MODD, MAGE, TBR% of <3.9 mmol/L, and use of oral hypoglycemic agents.

Table 1

Comparison of subjects in non-CAD and CAD groups

Variables Non-CAD (n = 64) CAD (n = 270) P value for trend
Gender (%men) 51.25 52.61 0.312
Age (years) 54.63 ± 10.12 59.56 ± 11.04 <0.001
Diabetes duration (years) 5.14 ± 2.74 10.51 ± 5.21 <0.001
SBP (mmHg) 124.24 ± 24.69 130.10 ± 15.27 0.032
DBP (mmHg) 75.05 ± 17.09 76.54 ± 8.26 0.301
BMI (kg/m2) 23.71 ± 2.89 25.18 ± 3.64 0.020
Current smoker (%) 23.15 32.34 <0.001
Total cholesterol (mmol/L) 4.07 ± 1.38 4.51 ± 1.60 0.029
TG (mmol/L) 1.43 (1.01,1.34) 1.51 (1.03,2.15) 0.697
LDL-C (mmol/L) 2.47 ± 0.96 2.85 ± 0.86 0.017
HDL-C (mmol/L) 1.19 ± 0.32 1.04 ± 0.52 0.273
ApoA (mmol/L) 1.14 ± 0.21 1.15 ± 0.24 0.752
ApoB (mmol/L) 0.90 ± 0.32 1.01 ± 0.29 0.025
ApoE (mmol/L) 39.21 ± 18.01 43.97 ± 17.72 <0.001
LPa (mmol/L) 124 (47.13, 281) 106 (48.67, 241) <0.001
Urinary A/C (mg/g) 25.56 ± 5.14 66.31 ± 10.11 <0.001
BUN (mg/dl) 5.16 ± 1.07 6.74 ± 2.11 0.004
Cr (μmol/L) 70.01 ± 10.54 88.30 ± 22.01 <0.001
UA (μmol/L) 301.6 ± 88.5 483.7 ± 125.7 <0.001
FINS (mmol/L) 8.04 ± 1.25 8.71 ± 1. 26 0.071
FPG, SD (mmol/L) 2.05 ± 0.91 2.34 ± 0.87 0.237
FPG, CV (%) 27.34 ± 8.32 29.05 ± 6.01 0.034
MAGE (mmol/L) 5.01 ± 0.56 5.31 ± 1.34 0.073
MODD (mmol/L) 2.14 ± 0.78 2.15 ± 0.94 0.510
TAR% (>10.0 mmol/L) 24.12 ± 6.45 30.16 ± 1.29 0.003
TBR% (<3.9 mmol/L) 1.00 (0.00, 2.00) 1.00 (0.00, 3.00) 0.531
TIR (%) 75.68 ± 13.74 66.12 ± 11.87 <0.001
HbA1c (%) 7.16 ± 1.78 8.75 ± 1.91 <0.001
Use antidiabetes agents
Oral antidiabetes drugs (%) 55.13 57.62 0.413
Insulin therapy (%) 23.52 40.13 <0.001

Abbreviations: Non-CAD: without coronary artery disease; CAD: coronary artery disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; ApoA: apolipoprotein A; ApoB: apolipoprotein B; ApoE: apolipoprotein E; Lpa: lipoprotein a; FPG, fasting plasma glucose; FINS, fasting insulin; SD: standard deviation; CV: coefficient of variation; urinary A/C: urinary albumin/creatinine concentration; BUN: blood urea nitrogen; Cr: serum creatinine; UA: uric acid; HbA1c, hemoglobin A1c; MAGE: mean amplitude of glycemic excursions; MODD: means of daily difference; TAR, time above range; TBR, time below range; TIR, time in range.

As shown in Table 2, TIR was 71.32 ± 18.74, 56.87 ± 15.31, and 41.57 ± 13.69 in group 1, group 2, and group 3, respectively. The severity of CAD in patients with T2DM decreases as TIR increases (Table 2, P < 0.01). Logistic regression analysis revealed that TIR, TAR, or CV were independently correlated with the occurrence of CAD after adjusting for confounding factors including age, sex, and BMI (Model 1) (TIR: OR = 0.924 (0.905, 0.943), p = 0.002; TAR: OR = 1.143 (1.102, 1.184), p = 0.039; CV: OR = 1.030 (1.001, 1.059), p = 0.025). Then, after adding diabetes duration, SBP, TG, HDL-C, and LDL-C (Model 2) or diabetes duration, SBP, TG, HDL-C, LDL-C, smoking status, use of insulin therapy, and HbA1c (Model 3) as a confounding factor, the TIR was still an independent risk factor for CAD (Table 3).

Table 2

Value of TIR in different GS groups

Variables Group 1 (Gensini score ≤ 11), N = 112 Group 2 (Gensini score 12–36), N = 98 Group 3 (Gensini score > 36), N = 60 P value for trend
TIR (%) 71.32 ± 18.74 56.87 ± 15.31 41.57 ± 13.69 <0.001
HbA1c 7.37 ± 1. 56 7.91 ± 2.01 8.34 ± 1.93 0.024
CV 28.05 ± 7.11 28.21 ± 5.93 29.34 ± 7.52 0.051
SD 2.34 ± 0.73 2.33 ± 0.56 2.76 ± 1.01 0.231
MAGE 5.09 ± 1.52 5.28 ± 1.93 5.44 ± 1.07 0.054

Abbreviations: TIR, time in range; GS, Gensini score; HbA1c, hemoglobin A1c; CV: coefficient of variation; MAGE: mean amplitude of glycemic excursions.

Table 3

Association of TIR, TAR, and CV metrics with presence of coronary artery disease by logistic regression analyses

Variable OR (95% CI) P value
TIR Crude 0.927 (0.912, 0.942) <0.001
Model 1 0.924 (0.905, 0.943) 0.002
Model 2 0.920 (0.903, 0.937) 0.013
Model 3 0.919 (0.896, 0.942) 0.011
TAR Crude 1.151 (1.114, 1.188) 0.022
Model 1 1.143 (1.102, 1.184) 0.039
Model 2 1.056 (0.998, 1.114) 0.054
Model 3 1.061 (0.996, 1.126) 0.055
CV Crude 1.128 (1.017, 1.239) 0.044
Model 1 1.030 (1.001, 1.059) 0.025
Model 2 1.079 (1.024, 1.134) 0.046
Model 3 1.048 (0.882, 1.380) 0.057

Abbreviations: TIR, time in range; TAR, time above range; CV: coefficient of variation; OR, odd ratio; CI, confidence interval.

Model 1 is adjusted for age, sex, and (BMI.

Model 2 includes all variables in Model 1 plus diabetes duration, SBP, TG, HDL-C, and LDL-C.

Model 3 includes all variables in Model 2 plus smoking status, use of insulin therapy, and HbA1c.

To further analyze the correlation between TIR and CAD, we conducted a binary logistic regression analysis with the severity of CAD. The results demonstrated that TIR were independently correlated with the severity of CAD after adjusting for confounding factors including age, gender, BMI, duration of diabetes, blood pressure, blood lipid, and HbA1c (Model 1) (P < 0.05, Table 4). This association remained significant in group 2 and group 3 after further adjustment for TAR (group 2: p = 0.024; group 3: p = 0.002) and CV (group 2: p = 0.037; group 3: p = 0.019) (Table 4).

Table 4

Associations between TIR and various stages of Gensini score group after controlling for confounding factor

Non-CAD Group 1 (Gensini score ≤ 11) Group 2 (Gensini score 12–36) Group 3 (Gensini score > 36)
OR (95% CI) OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value
Model 1
TIR 1.00 (Ref) 0.94 (0.91, 0.97) 0.003 0.96 (0.91, 1.01) 0.005 0.95 (0.92, 0.98) <0.001
Model 2
TIR 1.00 (Ref) 0.95 (0.89, 1.01) 0.17 0.96 (0.89, 1.03) 0.024 0.96 (0.93, 0.99) 0.002
TAR 1.00 (Ref) 1.03 (1.01, 1.05) 0.008 1.02 (0.96, 1.08) 0.145 1.13 (1.09, 1.17) 0.016
Model 3
TIR 1.00 (Ref) 0.93 (0.83, 1.03) 0.163 0.94 (0.89, 0.99) 0.037 0.95 (0.92, 0.98) 0.019
CV 1.00 (Ref) 0.88 (0.64, 1.12) 0.41 1.28 (0.98, 1.58) 0.062 1.52 (0.97, 2.07) 0.06

Abbreviations: TAR, time above range; TIR, time in range; OR, odd ratio; CI, confidence interval; CV: coefficient of variation.

Model 1 was adjusted for age, gender, body mass index, duration of diabetes, blood pressure, blood lipid, and HbA1c.

Model 2 includes all variables in model 1 plus TAR.

Model 3 includes all variables in model 1 plus CV.

4 Discussion

In this study, we explored the cross-sectional relationship between TIR and CAD in patients with T2DM who underwent 72 h CGM. Our findings revealed that TIR levels were inversely correlated with the severity of CAD. Furthermore, TIR emerged as an independent determinant for the occurrence of CAD in patients with T2DM.

Diabetes is a chronic disease characterized primarily by elevated blood glucose levels [23]. The global prevalence of diabetes is expected to be as high as 10.2% in 2030, which is a significant increase from 9.3% in 2019 [24]. Notably, 90% of the diabetes cases were diagnosed as T2DM [25,26]. T2DM significantly impacts survival and quality of life, particularly in patients diagnosed at a younger age [27,28]. Although all complications of T2DM are important, cardiovascular diseases and CAD remain the leading causes of morbidity and mortality in this population [29]. Therefore, early detection and management of CAD are essential to reduce the burden of disease complications.

An increasing number of studies have shown that HbA1c alone is not sufficient to provide an optimal picture of one’s glycemic control [30,31]. With the growing use of CGM, we can now track patients’ dynamic glucose fluctuations throughout the day and obtain new glycemic management metrics. TIR has emerged as a critical metric of CGM for the assessment of short-term glucose control that has been the subject of much research interest. Previous research has established an intimate relationship between TIR and diabetic complications, such as diabetic retinopathy and microalbuminuria progression [18,32]. Recently, Lu et al. demonstrated that TIR was inversely correlated with intima-media thickness in the carotid arteries in T2DM, highlighting a potentially plausible link between TIR and diabetic macrovascular complications [33]. Our previous work that showed TIR was an independent protective factor for diabetic peripheral artery disease also lends support to this relationship. Therefore, we believed that TIR may potentially serve as a research endpoint in T2DM-related clinical trials [34]. To the best of our knowledge, the correlation between TIR and CAD has not been investigated previously. In the current study, we found that patients with T2DM and CAD had significantly lower TIR compared to those without CAD (66.12 ± 11.87 vs 75.68 ± 13.74). Moreover, CAD severity as indicated by the Gensini score tends to decrease with total internal reflection. T2DM patients with different CAD severities were found to have dramatically disparate TIR values and the multivariable-adjusted logistic regression analysis supported that TIR was an independent determinant for CAD occurrence in patients with T2DM.

CAD is influenced by multiple factors. Dyslipidemia is a well-recognized risk factor for CAD across various populations [35]. Tseng identified that age, hypertension, HDL-C, and percent body fat are independently associated with CAD [36]. Similarly, Bittencourt et al. demonstrated that glucose and HbA1c levels correlate with the extent and severity of coronary artery lesions [37]. Therefore, when assessing the relationship between TIR and CAD, we adjusted for potential confounding factors. After these adjustments, the independent association between TIR and CAD remained significant, indicating that the relationship between TIR and CAD is not influenced by other risk factors such as age, gender, BMI, duration of diabetes, blood pressure, blood lipid levels, and HbA1c.

This study suffers from several limitations. First, the study was a cross-sectional design and could not establish a causal relationship between TIR and CAD. Second, despite adjusting the models for numerous factors, residual confounding may still exist. Additionally, the study population consisted solely of hospitalized T2DM patients, excluding non-hospitalized individuals, which may limit the generalizability of the findings. Therefore, the results should be interpreted with caution. Third, this study did not compare the predictive value of TIR and HbA1c for the severity of CAD. Fourth, we did not explore whether TIR can be practically implemented in routine clinical practice or whether specific TIR thresholds can guide treatment decisions for CAD in patients with T2DM. To address these limitations, future research with greater precision is necessary.

In conclusion, our findings provide evidence that TIR is associated with the severity of CAD in patients with T2DM and serves as an independent prognostic factor for CAD. We suggest that TIR should be more widely accepted as a research endpoint or clinical measure. However, further studies, ideally prospective in nature, are needed to confirm our findings and to better characterize the role of TIR in relation to CAD severity in T2DM patients.

# Co-first authors.

tel: +86-29-84277526

  1. Funding information: This study was supported by Science and Technology Development Fund of Shanghai Pudong New Area (No. PKJ2022-Y34).

  2. Author contributions: Conception and design of the research: W.G.M. and J.F.L.; acquisition of data: X.J.S. and X.H.Y.; data analysis and interpretation: W.G.M. and C.Q.X.; validation and visualization: J.F.L. and F.F.W.; statistical analysis: X.J.S. and Y.L.; drafting the manuscript: W.G.M. and J.F.L.; revision of manuscript for important intellectual content: Y.L. All authors reviewed the manuscript.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Data availability statement: The data used to support the findings of this study are available from the corresponding author upon request.

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Received: 2024-05-19
Revised: 2024-12-23
Accepted: 2025-02-06
Published Online: 2025-06-04

© 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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  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
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https://doi.org/10.1515/med-2025-1158
Keywords for this article
continuous glucose monitoring; coronary artery disease; time in range; type 2 diabetes; surrogate marker
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
  8. CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
  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. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  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. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Review Articles
  158. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  159. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  160. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  161. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  162. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  163. 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
  164. The application of augmented reality in robotic general surgery: A mini-review
  165. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  166. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  167. Plant polyphenols, terpenes, and terpenoids in oral health
  168. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  169. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  170. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  171. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  172. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  173. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  174. Giant borderline ovarian tumours – review of the literature
  175. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  176. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  177. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  178. Supplement strategies for infertility in overweight women: Evidence and legal insights
  179. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  180. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  181. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  182. Strategies for hyperkalemia management in dialysis patients: A systematic review
  183. C-reactive protein-to-albumin ratio in peripheral artery disease
  184. Case Reports
  185. Delayed graft function after renal transplantation
  186. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  187. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  188. Giant right atrial hemangioma presenting with ascites: A case report
  189. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  190. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  191. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  192. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  193. Rapid Communication
  194. Biological properties of valve materials using RGD and EC
  195. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  196. Letter to the Editor
  197. Role of enhanced external counterpulsation in long COVID
  198. Expression of Concern
  199. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  200. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  201. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  202. Corrigendum
  203. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  204. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  205. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  206. Retraction
  207. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  208. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  209. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  210. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  211. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  212. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  213. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  214. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  215. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  216. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  217. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  218. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  219. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  220. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  221. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  222. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  223. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  224. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  225. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  226. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  227. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  228. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  229. A review of brain research on T2DM-related cognitive dysfunction
  230. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  231. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  232. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
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