Long-term outcomes after bentall-de bono versus modified bentall-de bono procedures: a propensity score-matched analysis

Abstract

Objective

To evaluate the impact of Bentall-de Bono (BD) versus modified Bentall-de Bono (MBD) procedures on patient survival and long-term clinical outcomes.

Methods

We reviewed 1,478 patients who underwent Bentall procedures between 2003 and 2022. Patients were initially stratified into two groups based on surgical technique: the BD group (n = 1,274), and the MBD group (n = 204). To mitigate baseline imbalances and selection bias, a 1:1 propensity score matching analysis was performed, yielding 202 matched pairs. Long-term survival was assessed using Kaplan-Meier analysis. Stroke was analyzed as an exploratory secondary cerebrovascular outcome. Predictors of mortality were identified via multivariable Cox proportional hazards regression.

Results

In the matched cohort, the median follow-up was 5.98 (interquartile range: 3.53–9.84) years. Kaplan-Meier analysis demonstrated comparable 10-year survival rates between the BD and MBD groups (90.9% vs. 88.4%, P = 0.42). Freedom from stroke was evaluated exploratorily and did not differ significantly between groups. (80.0% vs. 80.2%, P = 0.63). Multivariable Cox regression confirmed that the surgical technique (BD vs. MBD) was not an independent predictor of long-term mortality (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.40–1.74; P = 0.634). Independent predictors of late mortality included advanced age and prolonged aortic cross-clamp time.

Conclusion

There is no difference in long-term survival following BD versus MBD.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13019-026-04542-7.

Introduction

The Bentall procedure, first described by De Bono and Bentall in 1968 [1], has become a well-established surgical approach for treating aortic root pathology with consistently favorable outcomes. Initially, the in situ technique incorporating inclusion of the aortic aneurysm wall around the composite graft was the standard approach until 1987. However, following reports by Kouchoukos and colleagues in 1986 [2] documenting significant late complications associated with this technique, its use was substantially reduced.

Technical modifications of the Bentall procedure continue to evolve, with ongoing debate regarding the optimal surgical approach, particularly concerning aortic wall inclusion versus complete excision. Proponents of the inclusion technique argue that preserving the aortic wall may provide enhanced anastomotic reinforcement and reduce perioperative hemorrhagic complications [3]. Conversely, retention of dilated aortic tissue maintains a pathological substrate [4] that may predispose to multiple complications, including anastomotic distortion or obstruction, fistula formation, infection, late pseudoaneurysm development, and early reoperation for bleeding. Additional concerns include persistent aorto-right atrial fistula formation [5], increased thromboembolism risk, and potential masking of early postoperative complications that may delay critical interventions [6].

The substantial incidence of pseudoaneurysm formation associated with the inclusion technique has prompted many surgeons to adopt the modified Bentall-de Bono (MBD) technique [2, 7, 8], (widely known as the button Bentall operation), which is currently considered the standard approach in many centers. The MBD approach offers several theoretical advantages, including complete excision of diseased aortic tissue, enhanced visualization for precise suturing, and direct assessment of hemostasis. Nevertheless, the Bentall-de Bono (BD) technique remains historically and clinically relevant in selected institutional practices, particularly where the perceived benefit of perioperative hemostatic control is emphasized. In contemporary aortic root surgery, Bentall-De Bono procedures also remain an important reference standard in comparisons with valve-sparing aortic root replacement [9]. Recent institutional experience with cuff-wrapping strategies also suggests that wrapping concepts continue to be explored in selected Bentall populations [10].

Despite widespread adoption of both surgical approaches, their comparative long-term clinical efficacy remains contentious. Recent studies of aortic root replacement have increasingly focused on contemporary long-term outcomes, including prosthesis selection and comparisons between mechanical and bioprosthetic valved conduits [11]. However, direct long-term comparative evidence between BD and MBD techniques remains limited.

Therefore, this study aimed to evaluate long-term survival outcomes in patients undergoing BD versus MBD through analysis of a large retrospective cohort, providing evidence-based insights to guide surgical decision-making in clinical practice.

Methods

Study design and population

This retrospective cohort study included 1,478 patients who underwent the Bentall procedure at Beijing Anzhen Hospital between October 2003 and March 2022. The data were collected from electronic medical records and the picture archiving and communication system. Eligible participants included patients undergoing aortic root replacement with a primary diagnosis of aortic aneurysm associated with aortic stenosis and/or aortic regurgitation, including those with concomitant mitral or tricuspid valve disease. To ensure a homogeneous study population, all cases of aortic dissection and patients undergoing concomitant aortic arch procedures were excluded from the analysis.

Surgical procedure

Patients were divided into two groups based on surgical approach: the BD group (n = 1,274) and the MBD group (n = 204). Following median sternotomy and the initiation of cardiopulmonary bypass under systemic hypothermia, aortic root replacement was performed using either technique. In the MBD group, the aneurysmal aortic wall was completely excised after the implantation of the composite graft, leaving the prosthesis exposed and the coronary ostia reimplanted using the button technique. In the BD group, the native aneurysmal wall was preserved. Following the implantation of the composite graft, the residual aortic wall was wrapped around the prosthesis, and a shunt was constructed between the perigraft space and the right atrium. Meticulous surgical hemostasis was performed in both groups before chest closure, and the decision to re-explore for bleeding was based on the surgeon’s assessment of ongoing drainage, hemodynamic status, coagulation profile, and response to correction of coagulopathy. The composite grafts used for root replacement consisted of two types: pre-assembled valved conduits or surgeon-assembled composite grafts. The choice of prosthesis (mechanical vs. biological) and the assembly method were determined by the surgeon’s preference, patient age, and the specific anatomical requirements of the aortic root. Postoperative drainage volume was defined as the cumulative chest tube drainage during the entire period of postoperative chest tube retention, rather than drainage within the first 24 h only. Mediastinal drainage tubes were generally retained for approximately 3 to 4 days after surgery and were removed when drainage had decreased and there was no clinical concern for ongoing bleeding. Re-exploration for bleeding was generally considered when chest tube drainage exceeded 500 mL within the first 2 postoperative hours, particularly when bleeding persisted despite correction of coagulopathy or was accompanied by hemodynamic instability. The final decision to re-explore was made by the operating surgeon based on drainage volume and trend, hemodynamic status, coagulation profile, and response to correction of coagulopathy. In procedures, hemostatic Copeland sutures and surgical glue were used when considered necessary according to intraoperative bleeding, tissue quality, and surgeon judgment. Bentall procedures are performed independently only by surgeons who have completed specialist training and institutional credentialing for high-complexity aortic surgery. The choice between BD and MBD techniques was not randomized but was based on surgeon experience, aortic root anatomy, tissue quality, perceived bleeding risk, hemostatic requirements, and intraoperative judgment.

Ethics statement

This study was approved by the Institutional Review Board of Beijing Anzhen Hospital (Protocol No 2025293x; November 21, 2025). The requirement for informed consent was waived due to the retrospective nature of the study and de-identification of patient data.

Data collection

Comprehensive patient variables were systematically collected, including: (1) demographic characteristics and comorbidities; (2) preoperative echocardiographic parameters including aortic root diameter, left ventricular end-systolic and end-diastolic diameters, and aortic annular dimensions (both anteroposterior and transverse); and (3) perioperative variables encompassing operative time, cardiopulmonary bypass duration, aortic cross-clamp time, intraoperative fluid administration, binary indicators of blood product transfusion, cumulative postoperative drainage volume, and reoperation for bleeding. Complete preoperative echocardiographic assessment was available for all study participants.

Outcome measures and follow-up

The primary endpoint was all-cause mortality. Stroke was evaluated as an exploratory cerebrovascular outcome rather than a technique-specific structural endpoint, given its clinical relevance after aortic root replacement and its potential association with prosthesis type, anticoagulation status, aortic manipulation, and perioperative or long-term thromboembolic risk. Additionally, to comprehensively evaluate clinical events, reoperations were recorded and further categorized into early reoperations (during the index admission, primarily for bleeding) and late cardiac reoperations (during the follow-up period). Clinical follow-up was conducted through a multi-channel approach, including a systematic review of institutional electronic medical records and structured telephone interviews conducted by trained specialists from our hospital’s Follow-up Center. The follow-up period concluded in March 2024. Vital status was confirmed for all 1,478 patients through the last available clinical contact, structured telephone follow-up, official medical documentation, or national death registry query. Therefore, follow-up for the primary endpoint of all-cause mortality was 100% complete through March 2024.

Statistical analysis

All statistical analyses were performed using SPSS version 24.0 (IBM Corporation, Armonk, NY, USA) and R software version 4.0.0 (R Foundation for Statistical Computing, Vienna, Austria) via RStudio. Continuous variables are presented as medians with interquartile ranges (IQR), and categorical variables are expressed as frequencies and percentages. Comparisons of continuous variables between the BD and MBD groups were conducted using the Mann-Whitney U test, while categorical variables were compared using Pearson’s chi-square test or Fisher’s exact test. Multiple imputation by chained equations (MICE) was employed to manage potential missing data in the original cohort.

To minimize selection bias and account for the inherent imbalance in group sizes, propensity score matching (PSM) was performed. Propensity scores were estimated using a multivariable logistic regression model incorporating 15 preoperative baseline variables: age, sex, body mass index, hypertension, diabetes, hyperlipidemia, coronary artery disease, aortic stenosis, aortic regurgitation, mechanical valve use, left ventricular ejection fraction, left ventricular end-diastolic diameter, aortic annulus diameter, aortic sinus diameter, and ascending aortic diameter. These variables were selected because they were available before surgery and were considered clinically relevant to treatment selection and long-term outcomes. Patients were matched in a 1:1 ratio using the nearest-neighbor method with a caliper of 0.05. Covariate balance after matching was primarily assessed using absolute standardized mean differences (SMDs), with an absolute SMD < 0.10 considered indicative of acceptable balance. A Love plot was generated to visually display covariate balance before and after matching.(Figure S2).

Long-term survival was estimated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. Freedom from stroke was analyzed exploratorily using the Kaplan-Meier method and was interpreted descriptively because death represents a competing event for late stroke. The primary multivariable Cox proportional hazards model for all-cause mortality included clinically relevant preoperative and intraoperative variables selected a priori: surgical technique, age, sex, left ventricular ejection fraction, coronary artery disease, hypertension, diabetes, aortic sinus diameter, and aortic cross-clamp time. Postoperative events, including stroke and reoperation, were excluded from the primary model to avoid reverse causality and immortal time bias. The proportional hazards assumption was assessed using Schoenfeld residuals, and multicollinearity among covariates was evaluated using variance inflation factors. Results are reported as hazard ratios with corresponding 95% confidence intervals. All statistical tests were two-sided, and P values < 0.05 were considered statistically significant.

Results

Baseline characteristics of the study population

A total of 1,478 patients who underwent the Bentall procedure were screened. Given the substantial asymmetry in sample size (BD: n = 1,274, 86.2% vs. MBD: n = 204, 13.8%) and baseline characteristics between the two groups, a 1:1 propensity score matching (PSM) was performed. This yielded a well-balanced matched cohort of 404 patients (202 in each group) for the primary comparative analysis. The baseline and perioperative characteristics of the original unmatched cohort are detailed in Supplementary Tables S1 and S2. The annual distribution of surgical techniques over the study period is presented in Supplementary Figure S1.

Demographic and clinical baseline data for the matched cohort are summarized in Table 1. Following PSM, the significant baseline disparities observed in the unmatched cohort were effectively eliminated. All post-matching absolute SMD values were below 0.10, with a maximum SMD of 0.086, indicating acceptable covariate balance after matching. The mean age of the matched cohort was 49.7 ± 12.6 years, with a male predominance (86.1%). The median aortic sinus diameter was approximately 50 mm in both groups, consistent with indications for aortic root replacement.

Table 1.

Baseline demographic and clinical characteristics of the propensity score-matched cohort

Variables	Overall	MBD	BD	SMD
n	404	202	202
Age	49.70 (12.64)	50.00 (12.80)	49.40 (12.51)	0.047
Male (%)	348 (86.1)	171 (84.7)	177 (87.6)	0.086
BMI	24.71 (3.69)	24.64 (3.48)	24.77 (3.90)	0.036
Hypertension (%)	133 (32.9)	63 (31.2)	70 (34.7)	0.074
Diabetes (%)	17 (4.2)	9 (4.5)	8 (4.0)	0.025
Hyperlipidemia (%)	19 (4.7)	10 (5.0)	9 (4.5)	0.023
CoronaryArteryDisease (%)	30 (7.4)	14 (6.9)	16 (7.9)	0.038
AorticStenosis (%)	35 (8.7)	19 (9.4)	16 (7.9)	0.053
AorticRegurgitation (%)	400 (99.0)	200 (99.0)	200 (99.0)	< 0.001
MechanicalValve (%)	334 (82.7)	168 (83.2)	166 (82.2)	0.026
LeftVentricularEjectionFraction	58.75 (8.15)	59.02 (7.80)	58.47 (8.49)	0.068
LeftVentricularEndDiastolicDiameter	63.71 (10.31)	63.67 (10.23)	63.76 (10.41)	0.009
AorticAnnulusDiameter	25.93 (3.63)	26.06 (3.72)	25.80 (3.54)	0.072
AorticSinusDiameter	50.17 (12.54)	49.82 (12.30)	50.53 (12.78)	0.057
AscendingAortaDiameter	45.90 (10.01)	46.02 (9.62)	45.78 (10.41)	0.024

Data are presented as n (%), median (IQR), or mean ± SD. BD, Bentall-de Bono; MBD, modified Bentall-de Bono.SMD, standardized mean difference

Perioperative outcomes in the matched cohort

Perioperative data for the matched cohort are detailed in Table 2. Although operative complexity—reflected by cardiopulmonary bypass (CPB) time (BD: 121.1 ± 37.8 min vs. MBD: 130.6 ± 68.4 min, P = 0.084) and aortic cross-clamp time (BD: 83.0 ± 24.0 min vs. MBD: 88.0 ± 30.7 min, P = 0.069)—showed a trend toward longer durations in the MBD group, these differences did not reach statistical significance.

Table 2.

Intraoperative data and perioperative outcomes of the propensity score-matched cohort

Variables	Overall	MBD	BD	P value
n	404	202	202
CardiopulmonaryBypassTime	125.88 (55.42)	130.64 (68.44)	121.12 (37.79)	0.084
AorticCrossClampTime	85.45 (27.63)	87.95 (30.69)	82.95 (24.02)	0.069
SurgicalTime	4.69 (1.13)	4.73 (1.19)	4.64 (1.08)	0.454
FluidInput	2063.23 (837.63)	1978.32 (865.51)	2148.14 (801.97)	0.041
PlasmaTransfusion (%)	117 (29.0)	75 (37.1)	42 (20.8)	< 0.001
PackedRedBloodCellsTransfusion (%)	75 (18.6)	51 (25.2)	24 (11.9)	0.001
PlateletTransfusion (%)	26 (6.4)	15 (7.4)	11 (5.4)	0.543
CumulativePostoperativeDrainage	2042.19 (1123.30)	2178.95 (1249.85)	1905.44 (964.45)	0.014
Reoperation (%)	16 (4.0)	8 (4.0)	8 (4.0)	1.000
LongTermReoperation (%)	17 (4.2)	9 (4.5)	8 (4.0)	1.000

Data are presented as n (%), median (IQR), or mean ± SD. BD, Bentall-de Bono; MBD, modified Bentall-de Bono

Notably, significant differences were observed in transfusion requirements and postoperative bleeding. Patients in the MBD group were more likely to require plasma (37.1% vs. 20.8%, P < 0.001) and packed red blood cell transfusions (25.2% vs. 11.9%, P = 0.001). Consequently, the cumulative postoperative drainage volume over the entire period of chest tube retention was significantly higher in the MBD group (2,179 ± 1,250 mL vs. 1,905 ± 964 mL, P = 0.014). The incidence of early reoperation for bleeding was similar between the groups (4.0% in both, P = 1.000). There was no in-hospital mortality recorded in either the BD or the MBD group within the matched cohort.

Long-term outcomes

The median follow-up time for the matched cohort was 5.98 years (IQR: 3.53–9.84 years), with a maximum follow-up of 20.02 years. During this period, 34 deaths occurred. During the long-term follow-up, the annualized incidence rate of stroke in the matched cohort was 1.41 per 100 person-years in the BD group and 2.00 per 100 person-years in the MBD group.

Kaplan-Meier analysis showed similar observed long-term survival estimates between the two surgical techniques (Fig. 1). The estimated 10-year survival rate was 88.4% (95% CI: 82.9%–94.3%) in the MBD group and 90.9% (95% CI: 86.1%–96.0%) in the BD group (Log-rank P = 0.42).

Fig. 1.

Kaplan-Meier survival curves for all-cause mortality in the matched cohort.BD, Bentall-de Bono; MBD, modified Bentall-de Bono

As an exploratory cerebrovascular outcome, freedom from stroke during the follow-up period was also evaluated using Kaplan-Meier analysis. As shown in Fig. 2, the 10-year freedom from stroke was 80.0% (95% CI: 68.5%–93.3%) in the BD group and 80.2% (95% CI: 70.6%–91.0%) in the MBD group (Log-rank P = 0.63).

Fig. 2.

Kaplan-Meier Analysis for Freedom from Stroke (Matched Cohort) BD.Bentall-de Bono; MBD, modified Bentall-de Bono

Reoperation rates

During the index hospitalization, 48 patients in the original cohort required early reoperation, predominantly for re-exploration due to postoperative bleeding. Following propensity score matching, documented late cardiac or aortic-related reinterventions were infrequent. A total of 17 patients in the matched cohort underwent late secondary procedures, including 9 in the MBD group and 8 in the BD group (P = 1.000). Detailed procedural descriptions were available for 12 of these 17 patients. In the MBD group, recorded late events included distal or non-root aortic interventions, such as thoracoabdominal aortic replacement, intervention for type B dissection, and stent-grafting, as well as coronary interventions. In the BD group, recorded late procedures included valve-related repair, radiofrequency ablation, and abdominal aortic stent-grafting. No clearly documented redo Bentall procedure or reoperation specifically attributed to an anastomotic pseudoaneurysm was identified in the matched cohort records.

Predictors of long-term mortality

To further evaluate the impact of surgical technique on survival while controlling for confounders, a multivariable Cox proportional hazards regression analysis was performed on the matched cohort (Fig. 3). After adjusting for clinically relevant covariates—including age, sex, left ventricular ejection fraction, coronary artery disease, hypertension, diabetes, aortic sinus diameter, and aortic cross-clamp time—the surgical technique (BD vs. MBD) was not identified as an independent predictor of long-term all-cause mortality (BD HR: 0.84, 95% CI: 0.40–1.74, P = 0.634). The full multivariable Cox regression model is provided in Supplementary Table S3. No substantial multicollinearity was detected among the variables included in the model. (Table S4).

Fig. 3.

Forest plot of multivariable Cox regression analysis for all-cause mortality in the matched cohort. BD, Bentall-de Bono; MBD, modified Bentall-de Bono.HR, hazard ratio; CI, confidence interval; BD, Bentall-de Bono; LVEF, left ventricular ejection fraction

Instead, the analysis confirmed that patient-specific and intraoperative factors were the primary drivers of long-term mortality. Specifically, advanced age was significantly associated with higher mortality (HR: 1.07, 95% CI: 1.03–1.11, P < 0.001), and prolonged aortic cross-clamp time was an independent predictor of poorer survival (HR: 1.02, 95% CI: 1.01–1.03, P < 0.001). Aortic sinus diameter also demonstrated a moderate but statistically significant association with mortality (HR: 0.97, 95% CI: 0.94–1.00, P = 0.035).

To address potential confounding effects related to the extensive study period (2003–2022), an additional analysis was conducted by incorporating “surgical era” as a covariate into the Cox model. The inclusion of the operative era did not alter the primary findings: the BD technique remained non-significant regarding mortality (Era-adjusted HR: 0.78, 95% CI: 0.47–1.30).

Discussion

The Bentall procedure, introduced nearly six decades ago, has evolved through multiple technical refinements to become the standard approach for complete aortic root replacement. Despite its widespread clinical adoption, comprehensive long-term comparative data remain limited. This large retrospective cohort study, encompassing 1,478 patients with a median follow-up of 6.3 years and extending beyond 18 years, represents one of the most extensive comparative analyses of BD versus MBD techniques to date. Crucially, to mitigate the inherent selection bias and baseline asymmetries associated with retrospective observational studies, we employed a rigorous propensity score matching (PSM) analysis, ensuring a highly balanced comparison between the two surgical cohorts.

Our primary findings showed similar observed long-term survival estimates between groups in the propensity score-matched cohort. In the matched cohort, the estimated 10-year survival rates were 90.9% and 88.4%, respectively. Multivariable Cox regression analysis further confirmed that the choice of surgical technique was not an independent predictor of long-term mortality (HR: 0.84; 95% CI, 0.40–1.74; P = 0.634). Instead, our analysis confirmed that patient-specific and intraoperative factors—specifically advanced age and prolonged aortic cross-clamp time—were the primary drivers of late mortality. These survival outcomes align favorably with previously published series. The observed in-hospital mortality rates were consistent with contemporary reports [10], demonstrating no significant difference between surgical approaches. Furthermore, our 10-year survival rates compare favorably to the 7-year survival rate of 93% ± 2% reported in earlier studies [12]. Collectively, these findings corroborate the excellent long-term outcomes achievable with both surgical techniques when performed at experienced centers.

The independent predictors of mortality identified in our analysis are largely consistent with prior investigations. Prifti and colleagues [13] identified age ≥ 65 years, aortic dissection, aneurysm rupture, emergency status, prior cardiac interventions, concomitant coronary artery disease, poor functional class, and reduced ejection fraction as predictors of early mortality. Similarly, Tsunekawa and colleagues [14] confirmed age as an independent predictor of late mortality in their 27-year follow-up study. Our findings significantly expand this evidence base in terms of both follow-up duration and cohort size.

Notable differences in perioperative management and hemostasis were observed between the groups. Following PSM, patients in the MBD group demonstrated significantly increased transfusion requirements for both plasma and packed red blood cells, culminating in higher mean postoperative drainage volumes (2,179 mL vs. 1,905 mL). Despite these variations in early hemostatic challenges, the incidence of early reoperation for bleeding was identical (4.0%) between the groups, and operative complexity—reflected by cardiopulmonary bypass and cross-clamp times—was comparable. These findings suggest lower observed transfusion requirements and cumulative postoperative drainage in the BD group. However, they do not establish comparable technique-specific late structural safety, particularly because systematic imaging surveillance for subclinical graft-related complications was not available.

These findings suggest that similar observed long-term survival can be achieved in selected patients treated with either technique at an experienced center. However, the study was not designed or powered as an equivalence or non-inferiority analysis. Surgical approach should therefore remain individualized according to patient anatomy, tissue quality, bleeding risk, and surgeon judgment.

Several limitations should be acknowledged. First, this retrospective, single-center study remains subject to selection bias and residual confounding despite propensity score matching. Surgical technique selection was influenced by patient anatomy, tissue quality, bleeding risk, operative era, institutional experience, and surgeon preference, while surgeon-level experience and learning-curve effects could not be formally adjusted for. Second, the single-center design may limit the generalizability of our findings. Finally, systematic imaging surveillance was not available for all asymptomatic patients; therefore, non-reintervened late aortic-related complications, including asymptomatic or conservatively managed anastomotic pseudoaneurysms, could not be reliably assessed. Consequently, our findings do not establish comparable technique-specific structural safety. Further multicenter prospective studies with standardized imaging surveillance are warranted.

Conclusions

Our study confirms that both BD and MBD techniques achieve excellent and comparable long-term survival, with late mortality primarily driven by patient-specific and intraoperative factors rather than the surgical technique itself. However, while long-term survival and freedom from stroke were equivalent, these findings do not establish definitive equivalence in technique-specific graft-related safety or late subclinical structural complications due to database limitations. Future prospective studies with rigorous, standardized imaging protocols are warranted to fully delineate the long-term complication profiles of each approach.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

IQR

Interquartile ranges

CI

Confidence interval

HR

Hazard Ratio

LVEF

Left ventricular ejection fraction

LVEDD

Left ventricular end diastolic diameter

CPB

Cardiopulmonary Bypass

BAV

Bicuspid aortic valve

BD

Bentall-de Bono

BMI

Body Mass Index

MBD

Modified Bentall-de Bono

Author contributions

S.W. wrote the original manuscript and contributed to data curation, formal analysis, investigation, methodology, and visualization. M.H. contributed to formal analysis, methodology, validation, interpretation of the results, and writing – review and editing. J.Z. (Jinwei Zhang) and P.S. contributed to data curation, investigation, and validation. Y.L. contributed to funding acquisition and resources. J.Z. (Junming Zhu) contributed to resources. H.C. and C.R. contributed to conceptualization, investigation, project administration, supervision, and writing – review and editing. H.C. also contributed to funding acquisition and resources. All authors reviewed and approved the final manuscript.

Funding

This study was supported by the National Natural Science Foundation of China (82170374); Beijing Natural Science Foundation (L251020); the Excellent Youth Fund of the National Natural Science Foundation of China and the Excellent Youth Fund of Capital Medical University (KCA-2305).

Data availability

No datasets were generated or analysed during the current study.

Declarations

IRB approval

This study was approved by Institutional Review Board of Beijing Anzhen Hospital (Protocol No 2025293x; November 21, 2025). Patient written consent for the publication of the study data was waived by the IRB because the research involves no more than minimal risk to participants, as the study utilizes existing data without additional interventions or harm.

Competing interests

The authors declare no competing interests.