RPS 111 - Glymphatic system, venous and small vessel disease: small lesions, big impact

Author Block: M. Can, A. Karaosmanoğlu, R. Göçmen, N. P. Acar Özen, M. A. Tuncer, G. F. Yavaş, I. Koç, A. I. Colpak Işıkay, E. Gümeler; Ankara/TR
Purpose: We aimed to determine whether an ocular glymphatic pathway exists on magnetic resonance imaging (MRI) and how it relates to ocular findings.
Methods or Background: Twelve healthy volunteers (age 24–52) with 23 normal fundoscopic exams were prospectively enrolled. MRI was performed with 3 T MR scanner (GE SignaTM Architect) with 48 channel head coil. Heavily T2-weighted 3D Fluid attenuated inversion recovery (FLAIR) sequence (TR/TE/TI: 9000/520/2250 ms) was used to detect subtle signal intensity (SI) changes. Three subjects were scanned at baseline and at 4, 8, 12, 18, and 24 hours following IV gadobutrol (1.0 mmol/mL) to evaluate contrast clearance from the optic nerve (ON) sheath. Based on these results, the remaining subjects were scanned at 0, 4, and 18 hours (figure 1). Subtracted images were generated (baseline vs. post-injection) using SPM25 after normalization and coregistration. SI volume in the ON sheath was semi-automatically measured. We measured enhanced volume from subtracted image of baseline from 4th hour and residual volume from subtracted image of baseline from 18th hour. We calculated clearance volume and ratio of clearance with this information (figure 2). We performed Spearman’s correlation analysis between age, intraocular pressure (IOP), retinal nerve fiber layer (RFNL) thickness and these measurements.
Results or Findings: Correlation analysis revealed a significant negative correlation between IOP and clearance volume (r=-.575, p=0.004) and clearance ratio (r=-.549, p=0.007). No correlation was found with age or RNFL thickness.
Conclusion: Our findings support the presence of a bidirectional ocular glymphatic system in humans, modulated by IOP and the intraocular–intracranial pressure gradient. While existing literature contains limited evidence for a similar pathway in humans, our preliminary findings provide the first obvious demonstration of this correlation in a human cohort.
Limitations: Intracranial pressure, concentration of contrast media not available
Funding for this study: Funded by Hacettepe University Scientific Research Projects Coordination Unit
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Hacettepe University Clinical Research Ethics Committee

Author Block: K. Yuba¹, K. Watanabe¹, N. Kuriyama², E. Ozaki¹, D. Matsui¹, Y. Marunaka¹, K. Akazawa¹, K. Hayakawa¹, K. Yamada¹; ¹Kyoto/JP, ²Shizuoka/JP
Purpose: The glymphatic system is a brain-wide clearance pathway for metabolic waste. Although dysfunction of this system has been implicated in neurodegenerative disorders, its long-term impact on brain structure remains unclear. The choroid plexus (CP) is thought to play a critical role in glymphatic function. Enlargement of CP has been reported in Alzheimer’s disease and mild cognitive impairment, suggesting a link with CP dysfunction. We hypothesized that CP dysfunction is associated with subsequent hippocampal atrophy, given the hippocampus is a key structure for memory and spatial cognition. This study aimed to investigate whether baseline CP volume predicts longitudinal hippocampal volume change.
Methods or Background: We analyzed 154 community residents (median age, 67 years; 64% male) from a brain health check-up program who underwent 1.5-T MRI at baseline (2012-2013) and follow-up (2018-2019), after excluding those scoring <27 on the Mini-Mental State Examination (MMSE) to restrict the sample to cognitively normal individuals. Three-dimensional T1-weighted images were processed using the Sequence Adaptive Multimodal SEGmentation tool implemented in FreeSurfer (v7.3.2). Linear regression models were applied to assess the association between baseline CP volume and hippocampal volume loss over six years, adjusting for age, sex, intracranial volume, and MMSE.
Results or Findings: Baseline CP volume was a significant predictor of hippocampal volume loss over the subsequent six years (β = -0.05, p < 0.01) after adjustment for covariates, with CP showing a significant increase and hippocampal a significant decrease during this period.
Conclusion: In cognitively normal older adults, larger CP volume at baseline was linked to subsequent hippocampal atrophy over six years. These findings suggest that impairment in the glymphatic system may contribute to accelerated hippocampal atrophy.
Limitations: CP volume increase may reflect other factors such as inflammation and immunity, warranting further study.
Funding for this study: No funding.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the Ethical Review Board of the Kyoto Prefectural University of Medicine (approval number: G-144), and written informed consent was obtained from all participants.

Author Block: Y. Qiu, Y. Hu, Q. Fu, W. Hu, Y. Wang, Q. Xu, Y. Dai, Y. Sun, Y. Zhou; Shanghai/CN
Purpose: Glymphatic dysfunction is implicated in cognitive impairment in cerebral small vessel disease (CSVD). Iron overload within white matter hyperintensity (WMH), indicating metabolic abnormalities, may be a key mechanism underneath. This study aimed to investigate the relationships between WMH iron burden, glymphatic function, and cognition in CSVD.
Methods or Background: A total of 102 patients with CSVD and 29 matched healthy controls (HCs) were enrolled. WMH iron burden was quantified using the sub-voxel approach iterAtive magnetic suscePtibility sources sepARaTion Quantitative Susceptibility Mapping (APART-QSM), and glymphatic function was assessed with the Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS) index. Correlation and mediation analyses were performed.
Results or Findings: CSVD patients exhibited higher WMH iron burden, lower DTI-ALPS index, and poorer cognitive performance than HCs. Elevated WMH iron burden was associated with deficits in attention-executive (att-exe), memory, and visual-spatial domains, whereas reduced DTI-ALPS index correlated with impaired att-exe and memory function. More importantly, WMH iron burden fully mediated the link between DTI-ALPS index and both att-exe and memory function in CSVD patients.
Conclusion: These findings non-invasively identify WMH iron overload, a probable representative of microglial activation, as a critical mediator between glymphatic dysfunction and cognitive decline in CSVD, prompting a potential therapeutic target.
Limitations: The limitations of the study are as follows. First, the DTI-ALPS index is an indirect measure of glymphatic flow and does not quantify clearance efficiency directly; future multimodal imaging could provide a more holistic assessment. Second, in some subjects, regions of interest for DTI-ALPS were shifted to avoid WMH, which may introduce bias by excluding areas of potential glymphatic dysfunction. Third, future studies using habitat analysis and longitudinal designs are needed to clarify the spatiotemporal dynamics of iron deposition.
Funding for this study: Funding was provided by the National Natural Science Foundation of China [grant number 82171885, 82302142], Eastern Talent Plan Leading Project [grant number LJ2023127], the Shanghai Science and Technology Committee Project [Explorer Project Funding, grant number 24TS1414800], the Leading Talent Program of Shanghai Municipal Health Commission [grant number 2022LJ023], the Technology Standardized Management and Promotion Projects of Shanghai Shenkang Hospital Development Center [grant number SHDC22023022], National Natural Science Foundation Promotion Project of Ren Ji Hospital [grant number RJTJ25-MS-110], the Shanghai YRD Foundation for Innovation in Health Industry [grant number 2025-YRDFHI-086], and Medical Engineering Cross Research Foundation of Shanghai Jiao Tong University [grant number YG2022QN035, YG2022QN037].
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the Ethics Committee of Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University (reference number KY2021-179-B).

Author Block: B. Atalay, O. Cetin, M. Gezgin, M. B. Doğan, H. Yıldız, F. B. Ozdilek; Istanbul/TR
Purpose: The choroid plexus, which regulates cerebrospinal fluid dynamics and contributes to the glymphatic clearance system, has been implicated in neurodegenerative processes. This study aimed to investigate the association between the choroid plexus volume (CPV), and clinical status of Parkinson’s disease (PD).
Methods or Background: We retrospectively analyzed 57 patients with PD, and 45 controls who underwent brain MRI. CPV was manually segmented using ITK-SNAP on T1-weighted FSPGR images and normalized to intracranial volüme (ICV), which was calculated using volBrain software. Clinical parameters included Mini Mental State Examination (MMSE), Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr (HY) scale, disease duration, and levodopa equivalent daily dose (LEDD). Group comparisons were conducted using Mann–Whitney U, and chi-square tests where appropriate. Correlation analyses were performed using Spearman’s test.
Results or Findings: Mean CPV was 27.6±4.2 cm3 in patients and 28.5±7.2 cm3 in controls (p = 0.68). Within the Parkinson’s cohort, CPV and CPV/ICV showed significant negative correlations with MMSE (r = –0.38, p = 0.01; r = –0.45, p = 0.01, respectively). Conversely, positive correlations were observed with UPDRS-III (r = 0.30, p = 0.03; r = 0.27, p = 0.04, respectively) and HY stage (r = 0.32, p = 0.02; r = 0.33, p = 0.02, respectively). CPV was also negatively correlated with LEDD (r = –0.31, p = 0.03). Furthermore, CPV was significantly higher in patients with dementia (2.18 ± 0.65) compared to those without dementia (1.53 ± 0.70; p = 0.01).
Conclusion: CPV correlates with cognitive and motor symptoms severity in PD, highlighting its potential as an imaging biomarker of disease progression.
Limitations: The retrospective design, use of manual segmentation, and absence of longitudinal data limit causal interpretation.
Funding for this study: Not applicable
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information:

Author Block: J. Lu¹, X. Zhang¹, Y. Wang², R. Tang², B. Zhang¹; ¹Nanjing/CN, ²Shanghai/CN
Purpose: To compare PVS visualization and quantification between 3T and 5T ultra–high in-plane resolution 2D T2-weighted imaging, and to examine associations with glymphatic-related diffusion and volumetric metrics, as well as behavioral measures.
Methods or Background: From September 2025 to May 2025, 36 healthy adults (mean age ± SD, 26.6 ± 3.3 years; 12 men) underwent same-day 3T and 5T brain MRI, including 2D T2-weighted imaging, 3D T1-weighted imaging, and multi-shell diffusion prospectively. PVS were segmented from Enhanced PVS Contrast images, and five morphological metrics (volume, volume fraction [VF], diameter, solidity, length) were extracted for whole brain, basal ganglia, and hemispheric regions. Associations with free water fraction (FWF), ALPS index, choroid plexus volume (CPV), and clinical scales (HAMA, BMI, PSQI) were evaluated. Paired t-tests and interaction models were applied.
Results or Findings: Median qualitative PVS visualization scores were higher at 5T versus 3T (5.0 vs 3.0, P<.001). Quantitatively, 5T imaging yielded increases of 49.5% in PVS volume, 37.2% in VF, 5.6% in diameter, 14.5% in solidity, and 14.5% in length (all P<.001). 5T-derived PVS metrics showed stronger associations with FWF, ALPS index, and CPV (R² up to 0.41) than 3T (R² < .01), with significant field strength interactions (P = .032). Only 5T detected significant correlations between PVS morphology and behavioral measures, including HAMA, BMI, and PSQI.
Conclusion: 5T MRI substantially improves PVS visualization and quantification compared with 3T, enabling stronger detection of structural–functional coupling and behavioral associations relevant to glymphatic function.
Limitations: This study is limited by its focus on healthy young adults, the limited availability of 5T MRI systems, and its cross-sectional design, which precludes causal inference. These factors may restrict generalizability and immediate clinical translation.
Funding for this study: None
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: the institutional review board of Nanjing Drum Tower Hospital

Author Block: M. Xu, H. Mao, J. Yang, M. Li, Q. Gao, Y. Shi, L. Ma, F. Wang, X. Fang; Wuxi/CN
Purpose: To investigate alterations in cortical individualized structural networks and their molecular basis in patients with cerebral small vessel disease and mild cognitive impairment (CSVD-MCI), using a multi-modal imaging–transcriptomic approach, and to compare the identified molecular signatures with peripheral blood transcriptomic profiles.
Methods or Background: T1-weighted images were processed with FreeSurfer to extract five cortical morphological features and construct individualized structural networks. Regional group differences were assessed, followed by spatial transcriptomic analysis using Allen Human Brain Atlas data and partial least squares (PLS) regression. Significant genes were identified by bootstrap and FDR correction. Functional enrichment and cross-system comparisons were performed with peripheral blood RNA-seq.
Results or Findings: In this prospective study, 245 CSVD patients (152 NCI, 93 MCI) underwent neuropsychological testing and MRI. Compared with the NCI group, MCI patients showed significantly lower whole-brain mean MIND values (p = 0.002) and regional reductions across 90 cortical regions, mainly in the frontal, parietal, temporal, insular, and cingulate cortices. Network analyses showed pronounced decreases in default mode and dorsal attention networks (p < 0.005). PLS1 explained the strongest spatial covariance (ρ = 0.397, p_spin < 0.001), identifying 860 positively and 594 negatively weighted genes. Enrichment analyses indicated positive weights for ion transport and synaptic signaling, and negative weights for protein translation and MAPK regulation. Overlapping pathways were observed with peripheral blood profiles.
Conclusion: CSVD-MCI involves widespread cortical network reorganization with distinct transcriptional signatures, partially mirrored in peripheral blood, supporting their potential as molecular markers of cognitive impairment. These findings highlight a novel cross-system molecular link, offering opportunities for early risk stratification and targeted interventions.
Limitations: Cross-sectional design and reliance on postmortem transcriptomic data may limit causal inference.
Funding for this study: Medical Expert Team Program of Wuxi Taihu Talent Plan (THRC-TD-YXYXK-2021),Wuxi Medical Innovation Team Program (CXTD2021002)
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The Affliated Wuxi People's Hospital of Nanjing Medical University

Author Block: Y. Hao¹, X. Fan¹, E. Li², H. You¹, Y. Zhu¹, F. Feng¹; ¹Beijing/CN, ²Shanghai/CN
Purpose: Cerebral small vessel disease (CSVD) is associated with microstructural changes in subcortical gray matter that relate to cognitive performance, with potential regional heterogeneity across subregions. This study investigates the predictive value of baseline quantitative susceptibility mapping (QSM) metrics for cognitive function in patients with CSVD
Methods or Background: From September 2022 to June 2025, a prospective cohort of 248 participants [90 with mild CSVD vs 108 with severe CSVD vs 50 healthy control (HC)] were recruited. All participants had cognitive examination including Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) and MRI including multiecho gradient echo (mGRE) sequence. QSM images were segmented into 32 subcortical gray matter regions, with baseline QSM metrics (mean, median, interquartile range [IQR], and maximum susceptibility) analyzed. Propensity score matching adjusted for baseline confounders. Cognitive function were evaluated using Cox regression models, and risk stratification was performed based on thresholds identified through receiver operating characteristic (ROC) analysis
Results or Findings: After adjusting for potential confounders, the susceptibility values in right posterior caudate (β = 4.675, P = 0.003) and the right posterior hippocampus (β = 1.516, P = 0.025) were positively associated with CSVD severity, and those in the globus pallidus, putamen and caudate nucleus were negatively associated with cognitive function. Baseline QSM metrics, particularly the mean susceptibility (QSMmean) (AUC=0.833) and the median susceptibility (QSMmedian) (AUC=0.750) demonstrated moderatetosubstantial predictive performance for cognitive decline. Patients with severe CSVD showed a 5.2-fold increased risk of cognitive impairment compared to those with mild CSVD
Conclusion: QSM metrics, serving as a complementary imaging biomarker, demonstrated significant predictive value for cognitive function. Validation in larger, independent cohorts is warranted
Limitations: Susceptibility values are affected by noniron-related molecules, especially myelin, which are consistently found in structures like the thalamus
Funding for this study: This study was supported by the National Natural Science Foundation of China (grants 82371946 and 82401557), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (grant 2021-I2M-1-025), and the National Postdoctoral Researcher Funding Program (No. GZC20240138)
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the Ethics Committee of Peking Union Medical College Hospital (approval number: 1-23PJ2044)

Author Block: R. Mu¹, P. Yang¹, W. Zheng¹, X. Qin¹, J. Lv¹, B. Huang¹, X. Liu², L. Cheng¹, X. Zhu¹; ¹Guilin/CN, ²Guangzhou/CN
Purpose: Structural covariance networks (SCNs) provide an important framework for understanding large-scale brain network damage across the continuum of cerebral small vessel disease (CSVD). However, it remains unclear how progressive cross-regional structural injury drives SCN disruption.
Methods or Background: From May 2020 to November 2021, 500 community participants were enrolled, including patients with vascular dementia, vascular mild cognitive impairment, CSVD with preserved cognition, and cognitively normal elderly controls. A multimodal CSVD cognitive impairment database was established, integrating neuroimaging (3D T1-weighted MRI), neuropsychological assessments, and clinical data. T1-weighted images were automatically preprocessed using a standardized SPM12 pipeline. Morphology-based independent component analysis was applied to extract gray matter SCNs, enabling network-level characterization of CSVD-related structural alterations and whole-brain atrophy patterns. Causal structural covariance networks (CaSCNs) were further constructed with a sliding time-window approach to identify the temporal causal relationships between key driving nodes and progressive atrophy. Finally, functional decoding was used to map structural alterations to behavioral domains and to explore their associations with cognitive impairment.
Results or Findings: Compared with normal aging, SCNs exhibited progressive disruption in CSVD with preserved cognition, vascular mild cognitive impairment, and vascular dementia. Dynamic CaSCN analysis based on composite cognitive scores identified hippocampus and frontal lobes as key causal hubs, with their atrophy significantly predicting subsequent atrophy in other regions. Functional decoding confirmed specific associations between network-level damage originating from these regions and impairments in executive function, attention, and memory.
Conclusion: This study systematically delineated the spatial distribution and interregional associations of brain atrophy across the CSVD continuum. Hippocampus and frontal lobes emerged as central origins of atrophy, whose degeneration predicted widespread secondary atrophy. These findings highlight the causal and temporal dynamics of whole-brain atrophy and provide novel network-level insights into CSVD progression.
Limitations: None
Funding for this study: None
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: None

Author Block: J. Zhang, J. MIAO; Shanghai/CN
Purpose: The aim of this study was to investigate the predictive value of intracranial plaques and cerebral small vessel diseases (CSVDs) imaging characteristics for ischemic stroke, further elucidated the impact of coexisted large and small intracranial vessel diseases on stroke events.
Methods or Background: Patients who underwent contrast-enhanced higher–resolution vessel wall MRI (HRVW-MRI) with intracranial atherosclerotic disease were recruited from January 2021 to April 2024. Plaque features like intraplaque hemorrhage (IPH), enhancement grade, maximum wall thickness (Max WT), lumen area (LA) were assessed in HRVW-MRI. We used total CSVDs score based on 4 CSVDs imaging markers, including lacunes, white matter hyperintensities (WMLs), cerebral microbleeds (CBMs), and enlarged perivascular spaces (EPVSs), and the overall CSVDs burden score was 0–4. Binary logistic regression analysis and receiver operating characteristic (ROC) curve were used for data analysis.
Results or Findings: Of the total 237 patients (the median age was 63, 154 males), 163 patients occurred stroke. Binary logistic regression revealed that patients with greater Max WT, larger LA, more CBMs and EPVSs, higher enhancement grade, total CSVDs and WMLs score were more likely occurred stroke (all p < 0.05). The combination of these variables achieved a higher area under the curve (0.85, 95% CI 0.80-0.96, p＜0.000) than that of the plaques (0.77, 95% CI 0.71-0.89, p＜0.000) and CSVDs (0.79, 95% CI 0.72-0.87, p＜0.000) imaging characteristics alone.
Conclusion: Plaque features combined with CSVDs imaging makers provides incremental value for stroke prediction, which is helpful for the clinical management of high-risk patients.
Limitations: Firstly, the sample size was small. Secondly, the present study was restricted to patients with anterior circulation infarct. Thirdly, this was a retrospective study with bias.
Funding for this study: Shanghai Explorer Program (Grant no. 24TS1410900)
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information:

Author Block: T. Torgan, W. Norhøy, C. M. Page, F. Fridtjof Heyerdahl, A. Bjørnerud, L. Tjelta Westlye, P. W. Sowa; Oslo/NO
Purpose: To investigate longitudinal changes in gray matter (GM) cerebral blood flow (CBF) following accidental carbon monoxide (CO) poisoning, using arterial spin labeling (ASL).
Methods or Background: Survivors of CO intoxication may experience persistent or recurrent neurological symptoms, even when conventional MRI findings are minimal. ASL perfusion imaging may detect subtle changes.
Twenty-six young adults (average 24.6 years old) with varying degrees of CO poisoning were admitted to the hospital and recruited in this longitudinal study. MRI was done at four timepoints (TP), after average of 5.1 days (TP1), 2.1 months (TP2), 7.6 months (TP3), and 18.2 months (TP4). ASL data were processed using ExploreASL and compared with HbCO levels. CBF was assessed globally, in subcortical regions, and across vascular-territorial cortical areas. Linear and mixed effects regression were used to evaluate the association between HbCO levels and CBF at each TP, and across all TPs.
Results or Findings: There was decrease of CBF in TP1 in Putamen, and negative correlation between CBF and HbCO levels at TP2 in all but one evaluated brain regions (CBF falling 0.34 ml/100g/min per 1 % increase HbCO for global grey matter, p=0.031).
The mixed-effects analysis showed association between HbCO levels and CBF across all TPs in most areas, with the strongest effect in Putamen (CBF falling 0.63ml/100g/min per 1 % increase in HbCO, p=0.001), as well as effect of TP4 for CBF reduction in thalamus (p=0.049).
Conclusion: GM ASL perfusion is reduced in CO poisoning after 2.1 months (earliest and most strongly in putamen), indicating usefulness of ASL for evaluating neurotoxicity. There is a dose-dependent association between HbCO levels and reduced perfusion. Perfusion in thalamus appears to be affected also at a later timepoint.
Limitations: Small study, variations in CO exposure, new technique
Funding for this study: Funded by Oslo University Hospital
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: REK sør-øst C

Author Block: Q. Yu, R. Wang, C. Sun, D. Geng, J. Lin, S. Piao, Y. Li; Shanghai/CN
Purpose: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare maternally inherited disease. As a recurrent paroxysmal clinical event, the heterogeneity underlying the progression of stroke-like episode (SLE) remains unclear.
Methods or Background: In this retrospective, multicenter, observational cohort study, we sought to confirm the clinical, genetics, radiological and temporal evolution characteristics of SLEs. Brain atrophy was assessed using Global Cortical Atrophy (GCA) and quantitative brain volumetric measures(QBVM). Both methods were employed to explore brain atrophy changes over time among these patients.
Results or Findings: Between August 2012 and December 2024, we identified 171 MELAS patients who developed SLEs. Based on the age of first SLE, these patients were divided into two groups, juvenile group and adult group. Hearing loss and diabetes mellitus were significantly more frequent in the adult group (p<0.05). Nausea/vomiting was significantly more frequent in the juvenile group (p=0.017). SLEs were significantly more prone to involve the frontal lobe in the juvenile group (p=0.002). Stroke-like lesion (SLL) areas were significantly larger in the juvenile group (p=0.005). Furthermore, a total of 67 patients with available follow-up imaging data were assessed for GCA and QBVM. MELAS patients showed rapidly annual increasing scores according to the GCA (median, IQR; 2.55, [1.48,5.14]), and significant ventricular enlargement based on QBVM (median annual change rate, IQR; 0.05, [-0.01, 0.14]). In the longitudinal assessment of GCA , an exponential-like change was observed. By approximately two years of follow-up, the progression appeared to stabilize, entering a phase where changes were markedly less pronounced.
Conclusion: Our findings highlight the clinical, radiological and temporal evolution characteristics of SLEs between both groups. We demonstrated that MELAS shows a rapid brain atrophy progression within a 2-year interval and follows different natural courses.
Limitations: Not applicable.
Funding for this study: This work was supported by Science and Technology Commission of Shanghai Municipality (22TS1400900, 22ZR1409500, 23S31904100, 24SF1904200, 24SF1904201); and Huashan Hospital Foundation (Basic Research Youth Cultivation Program) (2024JC018).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The studies involving humans were approved by the Institutional Review Board of Huashan hospital.