Potential Clinical Applications Research Articles

Discovery of a molecular glue for EGFR degradation.

Aberrant expression of epidermal growth factor receptor (EGFR) plays a critical role in the pathogenesis of various tumors, potentially representing a target for therapeutic intervention. Nonetheless, EGFR remains a challenging protein to target pharmacologically in triple-negative breast cancer (TNBC). An emerging approach to address the removal of such proteins is the application of molecular glue (MG) degraders. These compounds facilitate protein-protein interactions between a target protein and an E3-ubiquitin ligase, subsequently leading to protein degradation. Herein, we identified a new MG (CDDO-Me, C-28 methyl ester of 2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oic acid), which orchestrated binding between EGFR and KEAP1 (an E3-ubiquitin ligase adapter), thereby initiating the ubiquitination and degradation of EGFR. CDDO-Me directly interacted with the tyrosine kinase (TK) domain of EGFR, resulting in its degradation via an autophagy-dependent lysosomal pathway. Knockdown of KEAP1 decreased the degradation of EGFR by reducing its K63-linked ubiquitination, leading to diminished EGFR colocalization in autophagosomes and lysosomes. Notably, CDDO-Me attenuates TNBC progression by accelerating EGFR degradation in cell-derived xenografts and patient-derived organoid models, highlighting its clinical application potential. Consequently, induction of EGFR degradation through MG degraders represents a viable therapeutic strategy for TNBC.

Degradation Pattern of a Biodegradable and Photocurable Sealants Based on Hyaluronic Acid : A Serial Magnetic Resonance Imaging Observational Study in Rat Craniectomy Model.

The aim of this study is evaluating in vivo degradation of photocrosslinkable hyaluronic acid (HA)-based dural sealant (HA photosealant) using magnetic resonance imaging (MRI) and histopathological analysis to assess its biodegradability and effectiveness in preventing cerebrospinal fluid (CSF) leakage. HA photosealants were applied to the incised dura in a rat craniectomy and durotomy. The HA photosealant quickly seal the wound upon low-energy visible light exposure (405 nm, < 5 s, < 1 J/cm2). The degradation of HA photosealants was tracked through serial MRI scans at 1, 2, and 4 weeks post-application. The remaining area of HA photosealants on the dura was measured using image processing program for volumetric analysis. Additionally, histopathological analyses were performed to evaluate the biocompatibility and effectiveness of the dural repair. The MRI and histopathological analyses showed that the HA photosealants achieved progressive degradation while successfully preventing CSF leakage without any adverse tissue reactions. The residual area of HA photosealants measured at 2 weeks ranged from 41.36% to 94.88%, with an average of 66.57%. At 4 weeks, a more distinct degradation pattern was observed compared to 2 weeks, showing a residual area of 10.28% to 56.12%. The HA photosealants maintained structural integrity until dural regeneration was complete. HA photosealant showed gradual degradation in vivo while maintaining mechanical strength until the dura was repaired for preventing CSF leakage without inflammation and toxicity. HA photosealant has great potentials for clinical application for dural repair with biodegradable properties and biocompatibility.

The immune regulatory role of exosomal miRNAs and their clinical application potential in heart failure

Heart failure (HF) is a complex and debilitating condition characterized by the heart’s inability to pump blood effectively, leading to significant morbidity and mortality. The abnormality of immune response is a key factor in the progression of HF, contributing to adverse cardiac remodeling and dysfunction. Exosomal microRNAs (miRNAs) play a pivotal role in regulating gene expression and cellular function, which are integral to the crosstalk between cardiac and immune cells, influencing immune cell functions, such as macrophage polarization, T cell activity, and cytokine production, thereby modulating various pathological processes of HF, such as inflammation, fibrosis, and cardiac dysfunction. This review emphasizes the immune-regulatory role of exosomal miRNAs in HF and highlights their clinical potential as diagnostic biomarkers and therapeutic agents.

Current Status and Future Directions of Research on Artificial Intelligence in Nasopharyngolaryngoscopy.

The nasopharyngolaryngoscopy (NPL) has emerged as a valuable tool for detecting early cases of head and neck cancers (HNCs). However, misdiagnoses and missed diagnoses are still common phenomena. The expertise of examining physicians often serves as the primary limiting factor, leading to issues such as incomplete visualization, imprecise identification, and unclear vision. Over recent years, the application of artificial intelligence (AI) in medical imaging, particularly in the realm of gastrointestinal endoscopy, has instigated revolutionary changes in site quality control, lesion identification, and report generation. However, there remains a lack of standardized guidelines for the proper application of NPL across various countries. While AI-related research in NPL is still in its nascent stages, it shows substantial potential for clinical application and endoscopic training. In this paper, we set our sights on reviewing the current clinical applications and summarizing the primary shortcomings of NPL. In addition, we encapsulate the progress of AI application within gastrointestinal endoscopy and NPL. Drawing from real-world clinical practice, we propose future directions and prospects for AI research in NPL. We firmly believe that the pace of clinical application of AI in NPL will accelerate significantly in the near future.

Construction and application of an electrochemical sensor based on MIL-101-NH2(Fe)-derived Fe-C porous materials doped with reduced graphene oxide for baicalin detection

Baicalin (Bn), a natural flavonoid compound, possesses high pharmacological effects. Here, an electrochemical sensor has been proposed based on an MIL-101-NH2(Fe)-derived Fe porous carbon composite (Fe-C) doped with reduced graphene oxide (rGO) for detecting Bn, designated as Fe-C/rGO. Fabricated through a straightforward physical doping process, Fe-C/rGO exhibits remarkable electrochemical activity. This superiority stems primarily from two key factors. Firstly, the porous structure of Fe-C efficiently concentrates Bn, facilitating its capture and recognition. Secondly, graphene oxide, serving as a substrate for anchoring metal–organic frameworks (MOFs), boosts the electrochemical performance of the composite due to its distinctive two-dimensional structure, abundant active sites, and unparalleled stability. The synergistic interaction between Fe-C and rGO maximizes their respective advantages, leading to a significant enhancement in the sensitivity and selectivity of the electrochemical sensor. Boasting a low detection limit of 7.5 nM and a broad detection range spanning from 30 to 180 nM, this sensor holds immense potential in clinical applications and drug monitoring, offering a reliable and efficient method for Bn detection.

Construction of acidic microenvironment by Cu-TCPP nanozyme composited deprotonatable polymeric nanofibers for efficient antibacterial activity

The issue of bacterial resistance caused by conventional antibiotics has emerged as a major challenge in clinical treatment. Nanozymes, based on catalysis and devoid of bacterial resistance, provide a novel approach to eradicating bacteria. However, the practical potential of these nanozymes is limited by their low and readily pH-affected catalytic activity. Herein, the enzyme activity was optimized starting from the synthesis of nanozyme and the selection of carboxylate-containing polymers for the matrix. Specifically, various copper-tetrakis (4-carboxyphenyl) porphyrin (Cu-TCPP) were initially synthesized employing three copper sources, and among them, Cu-TCPP derived from Cu2O with higher catalytic activity was preferred. Subsequently, Cu-TCPP composite fibrous membranes were further obtained by electrospinning from their blend solutions with different polymers with distinct deprotonation capabilities. Thus, an acidic microenvironment conducive to the exertion of enzyme activity was constructed. The fabricated composite nanofibrous membrane could dissociate hydrogen ions to construct a localized acidic microenvironment even under weakly alkaline conditions, thereby enhancing the enzyme activity and improving the antibacterial effect. Further in vivo experiments demonstrated its favorable antibacterial ability and accelerated wound healing effect. The enhancement strategy of enzyme activity in this study brings inspiration for the design of nanozyme composited wound dressings and holds significant potential for clinical antibacterial applications

Automated Visceral Adipose Tissue Segmentation and Quantification from Abdominal MRI using an Enhanced U-Net and Region-growing

The study focuses on enhancing the accuracy and reliability of visceral adipose tissue (VAT) segmentation and quantification from abdominal MRI images. Accurate segmentation of VAT is crucial for assessing obesity-related health risks, as traditional methods struggle with irregular shapes and varying intensities. The research utilizes a methodology consisting of three key modules: homomorphic filtering for intensity inhomogeneity correction, a U-Net architecture with attention mechanisms for primary segmentation, and a region-growing algorithm for refining segmentation. Homomorphic filtering effectively separates bias fields, enhancing image quality by transforming multiplicative artifacts into additive ones and removing them with high-pass filtering. This process ensures precise segmentation by maintaining high-frequency anatomical details. The U-Net model incorporates attention mechanisms and skip connections to focus on VAT regions, utilizing both local and global image contexts.The Combined Healthy Abdominal Organ Segmentation (CHAOS) challenge dataset and the Cancer Imaging Archive (TCIA) dataset are used to train and evaluate the model. It achieves a Dice Similarity Coefficient (DSC) of up to 0.985 on the CHAOS dataset and 0.972 on the TCIA dataset, outperforming existing methods in terms of segmentation accuracy. The region-growing algorithm further refines the segmentation by expanding VAT regions from high-confidence seed points, ensuring accurate boundary delineation and reducing noise. The study's results, evaluated using k-fold cross-validation, show that the proposed methodology significantly improves VAT segmentation efficiency, achieving a median DSC of 0.96 for the CHAOS dataset and 0.95 for the TCIA dataset in the most comprehensive experimental scenario. Comparative analysis indicates that the proposed approach outperforms other models, with higher sensitivity and specificity values, highlighting its potential for clinical applications in obesity management..

Efficient contact-based registration for minimally invasive anterior hip arthroplasty

This paper introduces an efficient contact-based registration method for minimally invasive anterior hip arthroplasty. Unlike existing methods that involve radiation exposure, implanted screws, or tedious point collection, our method requires only one contact within the acetabulum and two contacts on the landmarks. Inspired by the probe’s ball tip, we define a unique position, named stable point, to decouple translation from the overall transformation. The stable point in patient space is easily acquired by our tool, simplifying translation estimation to compute the stable point in image space. We present a fast computation method based on dichotomic search. After aligning the stable points, we introduce two bone landmarks for rotation estimation in a center-aware manner. Additionally, a deltille grid position-sensing (DGPS) marker is used to improve instrument tracking robustness. Experiments were conducted to evaluate the performance of our methods, demonstrating an average accuracy of 0.16±0.03mm for instrument tracking and 1.41±0.16mm for registration. Moreover, the entire process takes less than 1 minute. Results suggest that our method has significant potential for clinical application.

Gastro retentive floating drug delivery system of levofloxacin based on Aloe vera hydrogel: In vitro and in vivo assays

Gastro retentive drug delivery systems (GRDDS) have gained immense popularity as they reduce dosing frequency, improve bioavailability, and enhance patient compliance. Herein, a plant-based, controlled swelling, and pH-sensitive GRDDS based on Aloe vera hydrogel and cellulose was developed for the sustained release of levofloxacin (LEVO). The properties of five various floating tablet formulations including dynamic swelling, pH-responsiveness, hardness, friability, drug release, and buoyant time were evaluated. The optimized formulation (FF) was characterized using FTIR and SEM, and the surface morphology exhibited a porous texture with microchannels that facilitated tablet swelling and prolonged release of LEVO. The formulation FF remained buoyant (> 12 h) in the simulated gastric fluid with a buoyancy time of 303 s. A pH-dependent swelling behavior of the formulation FF was revealed with the highest swelling (7.1 g/g) in water, followed by buffers of pH 6.8 (5.4 g/g), 4.5 (3.8 g/g), and 1.2 (2 g/g). The controlled release of LEVO was demonstrated for >12 h following the Hixson-Crowell model and non-Fickian diffusion. Pharmacokinetic parameters of LEVO were determined using in vivo studies. The non-toxic nature of the formulation under study was demonstrated. The results render this approach promising in reducing the dosing frequency, suggesting its potential for clinical applications.

New insights into FGF21 alleviates diabetic cardiomyopathy by suppressing ferroptosis: a commentary.

Diabetic cardiomyopathy (DCM) is a severe cardiovascular complication of diabetes characterized by myocardial hypertrophy, fibrosis, and impaired cardiac function. Fibroblast growth factor 21 (FGF21) has emerged as a promising therapeutic target due to its antifibrotic, antioxidant, and anti-inflammatory properties. Our commentary summarizes and affirms the recent study by Wang et al., which demonstrates the significant role of ferroptosis in DCM pathogenesis. FGF21 has shown promise as a therapeutic target for DCM, potentially inhibiting ferroptosis, mitigating oxidative damage, and protecting cardiomyocyte function. Mechanistically, the study identified ATF4 as an upstream regulator of FGF21 in DCM, revealing that FGF21 directly interacts with ferritin and extends its half-life, thus inhibiting ferroptosis in DCM. These findings provide a theoretical basis for understanding the pathogenesis and treatment of DCM. Our commentary suggests that future studies should explore the role of non-cardiomyocyte cell types in DCM, verify findings with clinical samples, and address comprehensive methods for ferroptosis detection. Additionally, we discuss the clinical application and future potential of FGF21-based therapies for DCM. Such efforts may contribute to advancing DCM diagnosis and treatment, fostering the development of innovative therapeutic strategies.

Aptamer-Gadolinium Conjugates for Targeted Magnetic Resonance Imaging of Early-Stage Bladder Cancer.

Bladder cancer (BCa) poses a significant threat to human health, with early-stage diagnosis being particularly valuable yet challenging due to the limited availability of highly efficient targeted contrast agents. In this study, we have developed a novel aptamer-gadolinium conjugate (Apt-Gd) designed as a targeted contrast agent for the magnetic resonance imaging (MRI) of early-stage BCa. The synthesis of Apt-Gd involved the direct conjugation of aptamers with chelating agents through a bioorthogonal reaction, followed by gadolinium chelation. Notably, Apt-Gd exhibited high longitudinal relaxivity, exceptional BCa specificity, and good biocompatibility. Furthermore, our research revealed that intravesical instillation of Apt-Gd effectively enhanced the stability of aptamers and boosted the local contrast enhancement in BCa-bearing mice. The utilization of Apt-Gd yielded a satisfactory signal-to-noise ratio during BCa imaging and significantly prolonged the imaging time window. On the whole, the accurate detection of early-stage BCa using Apt-Gd was achieved for the first time, making a breakthrough in BCa diagnosis with promising potential for practical clinical applications.

Enhanced dual-mode imaging: Superior photoacoustic and ultrasound endoscopy in live pigs using a transparent ultrasound transducer.

Dual-mode photoacoustic/ultrasound endoscopy (ePAUS) is a promising tool for preclinical and clinical interventions. To be clinically useful, ePAUS must deliver high-performance ultrasound imaging comparable to commercial systems and maintain high photoacoustic imaging performance at long working distances. This requires a transducer with an intact physical aperture and coaxial alignment of acoustic and optical beams within the probe, a challenging integration task. We present a high-performance ePAUS probe with a miniaturized, optically transparent ultrasonic transducer (TUT) called ePAUS-TUT. The 1.8-mm-diameter probe, fitting into standard endoscopic channels, aligns acoustic and optical beams efficiently, achieving commercial-level ultrasound and high-resolution photoacoustic imaging over long distances. These imaging capabilities were validated through in vivo imaging of a rat's rectum and a pig's esophagus. The ePAUS-TUT system substantially enhances feasibility and potential for clinical applications.

Modular Reconfigurable Approach Toward Noninvasive Wearable Body Net for Monitoring Sweat and Physiological Signals.

In the realm of wearable technology, strategically placing sensors at various body locations enhances the detection of diverse physiological indicators crucial for remote medical care. However, current devices often focus on a single body part for specific physical parameters, which hinders the seamless integration of sensors across multiple body parts and necessitates redesign for new detection capabilities. Here, we propose a modular, reconfigurable circuit assembly method that can be adaptable for multiple body locations to construct the body net. By simply reassembling different child modules with the base module using flexible printed circuit board connectors, we can efficiently detect various parameters including sweat ion indicators, electrocardiogram signals, electromyography signals, motion data, heart rate, blood oxygen saturation, and skin temperature. These data can be transmitted to a mobile phone app via a Bluetooth Low Energy protocol for further evaluation. Comparative evaluations against established commercial devices substantiate the viability of our sensor technology. In addition, results from wearable body network detections using reconfigurable sensors across multiple body parts of volunteers also indicate promising application prospects, demonstrating the extensive potential for regular health monitoring and clinical applications.

Nucleus accumbens shell electrical lesion attenuates seizures and gliosis in chronic temporal lobe epilepsy rats.

Temporal lobe epilepsy (TLE) is the most prevalent form of epilepsy. Prior research has indicated the involvement of the nucleus accumbens shell (NAcSh) in the process of epileptogenesis, thereby implying its potential as a therapeutic target for TLE. In the present study, we investigated the antiepileptic effect of the NAcSh electrical lesion. Chronic TLE was induced by stereotactic injection of kainic acid (KA) into the hippocampus 3 weeks after KA administration, and NAcSh electrical lesions were performed. Seizures in rats were monitored by video electroencephalogram (EEG) 1 week following the NAcSh electrical lesion. Besides, the spatial memory function assessment in rats was conducted using the Morris water maze (MWM) test in the final week of the experiment. Later, hippocampal glial cell activation and neuron loss in rats were evaluated through immunohistochemistry. TLE rats subjected to NAcSh electrical lesion exhibited a significant reduction in the frequency of seizures compared to untreated TLE rats. Furthermore, NAcSh electrical lesion led to less activation of hippocampal glial cells and fewer neuronal loss in TLE rats. It is worth noting that the NAcSh electrical lesion did not cause additional memory impairment. In the present study, the NAcSh electrical lesion exhibited a definitive therapeutic effect on the chronic TLE rat model, potentially due to decreased hippocampal TLE-induced activation of glial cells and neuron loss. In conclusion, our results indicated that the NAcSh is a promising therapeutic target for TLE and possesses high potential for clinical application.

Chromatin landscape dynamics during reprogramming towards human naïve and primed pluripotency reveals the divergent function of PRDM1 isoforms

Induced pluripotent stem cells (iPSCs) technology holds great potential in both scientific research and clinical applications. It enables the generation of naïve and primed iPSCs from various cell types through different strategies. Despite extensive characterizations of transcriptional and epigenetic factors, the intricacies of chromatin landscape dynamics during naïve and primed reprogramming, particularly in humans, remain poorly understood. In this study, we employed ATAC-seq and RNA-seq analyses to delineate and compare the chromatin landscape of naïve and primed pluripotency through the human secondary reprogramming system. Our investigations revealed several key transcriptional and epigenetic factors pivotal for reprogramming-associated chromatin remodeling. Notably, we found two isoforms of PRDM1, PRDM1α, and PRDM1β, bind to distinct genomic loci and play different roles in the naïve reprogramming process. We proposed an auto-regulatory model explaining the distinct functions of PRDM1α and PRDM1β. Overall, our findings highlight the complexity and diversity of transcription factors in shaping chromatin landscape dynamics and directing the fates of pluripotent cells.

A Modified Transformer Network for Seizure Detection Using EEG Signals.

Seizures have a serious impact on the physical function and daily life of epileptic patients. The automated detection of seizures can assist clinicians in taking preventive measures for patients during the diagnosis process. The combination of deep learning (DL) model with convolutional neural network (CNN) and transformer network can effectively extract both local and global features, resulting in improved seizure detection performance. In this study, an enhanced transformer network named Inresformer is proposed for seizure detection, which is combined with Inception and Residual network extracting different scale features of electroencephalography (EEG) signals to enrich the feature representation. In addition, the improved transformer network replaces the existing Feedforward layers with two half-step Feedforward layers to enhance the nonlinear representation of the model. The proposed architecture utilizes discrete wavelet transform (DWT) to decompose the original EEG signals, and the three sub-bands are selected for signal reconstruction. Then, the Co-MixUp method is adopted to solve the problem of data imbalance, and the processed signals are sent to the Inresformer network for seizure information capture and recognition. Finally, discriminant fusion is performed on the results of three-scale EEG sub-signals to achieve final seizure recognition. The proposed network achieves the best accuracy of 100% on Bonn dataset and the average accuracy of 98.03%, sensitivity of 95.65%, and specificity of 98.57% on the long-term CHB-MIT dataset. Compared to the existing DL networks, the proposed method holds significant potential for clinical research and diagnosis applications with competitive performance.

Targeting autophagy: polydatin's role in inducing cell death in AML.

Acute myeloid leukemia (AML), a malignant disorder of the hematopoietic system, arises from leukemic stem cells (LSCs) and is the most prevalent form of blood cancer in adults. This study aimed to evaluate the therapeutic potential of polydatin (PD) in AML through ex vivo and in vivo studies, respectively. This study was prompted by PD's novel role in enhancing tumor apoptosis and modulating autophagy. In vitro studies were conducted using the PD-responsive AML cell line KASUMI-1 and found that PD was able to suppress cell proliferation and induce apoptosis by regulating the autophagy pathway. Subsequently, molecular docking was employed to predict the interaction between PD and Autophagy-related protein 5 (ATG5), a key regulator in the autophagy pathway. It was observed that PD inhibited the ubiquitination of ATG5 and enhanced its protein stability, leading to an increase in ATG5 protein levels and subsequent activation of the autophagy pathway (see in Abstract Graphed). The effectiveness and safety of PD in treating AML were confirmed through in vivo experiments using a mouse transplant tumor model, yielding definitive results. Collectively, these results suggest that PD is a promising candidate for the early therapeutic intervention of AML, with a strong potential for clinical application.

A novel chitosan-peptide system for cartilage tissue engineering with adipose-derived stromal cells

The natural healing process of cartilage injuries often fails to fully restore the tissue’s biological and mechanical functions. Cartilage grafts are costly and require surgical intervention, often associated with complications such as intraoperative infection and rejection by the recipient due to ischemia. Novel tissue engineering technologies aim to ideally fill the cartilage defect to prevent disease progression or regenerate damaged tissue. Despite many studies on designing biocompatible composites to stimulate chondrogenesis, only few focus on peptides and carriers that promote stem cell proliferation or differentiation to promote healing. Our research aimed to design a carbohydrate chitosan-based biomaterial to stimulate stem cells into the chondrogenesis pathway. Our strategy was to combine chitosan with a novel peptide (UG28) that sequence was based on the copin protein. The construct stimulated human adipose-derived stem cells (AD-SCs) cells to undergo chondrogenic differentiation. Chitosan 75/500 allows AD-SCs to grow and has no harmful effects on the cells. The combination of UG28 peptide with the chitosan composite offers promising properties for cell differentiation, indicating its potential for clinical applications in cartilage regeneration.

Investigating the Imperative Role of microRNAs Expression in Human Embryo Implantation: A Narrative Review Based on Recent Evidence.

Embryo implantation is a highly complex process that requires the precise regulation of numerous molecules to be orchestrated successfully. Micro RNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a crucial role in the regulation of embryo implantation. This article aims to summarize the key findings of the literature regarding the role of miRNAs in human embryo implantation, emphasizing their involvement in critical stages such as decidualization, endometrial receptivity and trophoblast adhesion. This review includes primary research articles from the past decade. The studies utilize a range of experimental methodologies, including gene expression analysis and in vitro studies. MicroRNAs, like miR-320a, miR-149, and miR30d secreted by preimplantation embryos and blastocysts significantly influence endometrial receptivity by promoting essential cellular processes, such as cell migration and trophoblast cell attachment, while others-miR17-5p, miR-193-3p, miR-372, and miR-542-3p-secreted from the endometrium regulate the decidualization phase. During the apposition and adhesion phases, miRNAs play a complex role by promoting, for example, miR-23b-3p, and inhibiting-as do miR-29c and miR-519d-3p-important biological pathways of these stages. During invasion, miR-26a-5p and miR-125-5p modulate important genes. This review underscores the critical impact of miRNAs in the regulation of embryo implantation and early pregnancy. The ability of miRNAs to modulate gene expression at various stages of reproduction presents promising therapeutic avenues for improving assisted reproductive technologies outcomes and addressing infertility. Further research into miRNA-based diagnostic tools and therapeutic strategies is essential to enhance our understanding of their role in reproductive health and to exploit their potential for clinical applications.

Graft-derived cell free DNA: used for assessment of early graft status and its implications for long-term kidney function.

The long-term graft survival is closely related to its early status, yet the indices for assessing the early graft status are complex and lack quantitative values. The aim of this study is to investigate the potential of GcfDNA as a comprehensive, non-invasive, convenient, and quantifiable indicator for evaluating early graft status. In this study, 138 recipients who underwent primary kidney transplantation were enrolled. Peripheral blood samples, each 10 mL, were collected on days 1 and 7 post-transplantation. The quantification of both the graft cell-free DNA (GcfDNA) fraction (%) and GcfDNA concentration (copies per milliliter, cp/mL) was performed using droplet digital PCR (ddPCR). For most recipients, both the GcfDNA fraction and concentration had a rapid decline at 7 days post-transplantation, reaching median values of approximately 0.7% and 53.5 cp/mL, respectively. No significant associations were found between GcfDNA values and other clinical parameters. On the seventh postoperative day, we observed a significant elevation in GcfDNA concentration among recipients with eGFR values < 60 mL/min/1.73 m2. Additionally, notable increases were identified in both GcfDNA fraction and concentration variations within this specific subgroup. The findings of our study indicate a negative correlation between the concentration and fractional changes of GcfDNA on postoperative days 1 and 7, as well as the GcfDNA concentration on postoperative day 7, with eGFR within the 1-2 years post-transplantation period. The ROC curve of GcfDNA_Copies_Variation. day1-day 7 showed the highest AUC value AUC = 0.8006, with high sensitivity (90.14%) and specificity (77.61%), and PPV and NPV were 81.01% and 88.14%, respectively. Using four classical algorithm models, we found that the xgboost regression model achieved the best predictive performance (area under the curve (AUC) values = 0.862) for eGFR within 1-2 years post-transplantation, with high sensitivity (85.7%) and specificity (85%). The changes of GcfDNA levels in the early stage are closely related to kidney function within 1-2 years post-transplantation. As a comprehensive indicator of graft function, GcfDNA has great potential for clinical application.