Diabetic retinopathy(DR), the most common microvascular complication of diabetes, has become a leading cause of visual impairment and blindness across all age groups. The early diagnosis and severity assessment of DR rely on the precise evaluation of retinal microvascular alterations. The periarterial capillary-free zone(paCFZ), a physiological avascular region surrounding retinal arteries, has recently been recognized as an important biomarker reflecting the status of retinal microcirculation. Advances in optical coherence tomography angiography(OCTA)have enabled noninvasive, high-resolution quantification of the paCFZ, offering a novel approach for the early detection and stratification of DR. This review systematically summarizes the definition and developmental mechanism of the paCFZ, as well as its morphological characteristics across different stages of DR, with a particular focus on the advantages of OCTA in visualizing and quantifying the paCFZ. We further discuss the differential manifestations of the paCFZ in nonproliferative DR and proliferative DR, and its associations with retinal ischemia and oxygenation status. In addition, the potential clinical value of paCFZ in evaluating responses to anti-vascular endothelial growth factor(VEGF)therapy and predicting disease progression is summarized. Finally, the challenges in clinical translation and future research directions are addressed, aiming to provide theoretical support and new perspectives for early screening, risk stratification, and personalized management of DR.

ObjectiveTo investigate the effects of jatrorrhizine on endogenous metabolites and metabolic pathways in the mouse model of ulcerative colitis. MethodsThirty male C57BL/6J mice were randomly divided into the normal group， the model group， the low-dose and high-dose jatrorrhizine groups （0.04， 0.16 g·kg^-1）， and the mesalazine group （0.52 g·kg^-1）The mouse model of ulcerative colitis was established with 3% dextran sulfate sodium （DSS） and treated with different doses of jatrorrhizine by gavage. The changes in body weight， colon length， disease activity index （DAI）， and colonic histopathology were analyzed to evaluate the therapeutic effects of jatrorrhizine. UPLC-Q-TOF/MS was employed to determine the serum and fecal levels of metabolites in mice. Metabolomics methods were used to screen the differential metabolites， on the basis of which the potential therapeutic mechanism of jatrorrhizine on DSS-induced ulcerative colitis in mice was investigated. ResultsAfter intervention with jatrorrhizine， the model mice showed significantly decreased DAI（P<0.05，P<0.01）， recovered colon length，（P<0.05，P<0.01） and alleviated histopathology of the colon. The metabolomics study screened out 13 differential metabolites in the serum and 8 differential metabolites in the feces. The pathway enrichment analysis predicted three potential metabolic pathways： Biosynthesis of unsaturated fatty acids， phenylalanine， tyrosine and tryptophan biosynthesis， and phenylalanine metabolism. ConclusionJatrorrhizine may treat ulcerative colitis by regulating the biosynthesis and metabolism of amino acids and the synthesis of unsaturated fatty acids.

Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

Immune checkpoint inhibitors (ICIs) are widely used in the treatment of malignant tumors, and their related immune-related adverse events (irAEs) have attracted increasing attention. This study reports the diagnosis and treatment process of a case of immune cystitis in a patient with hepatobiliary tract malignant tumor after treatment with pembrolizumab. The patient was admitted to the hospital due to frequent urination, urgency of urination and dysuria for 1 month. Previous repeated anti-infection treatments were ineffective. Combined with medical history, laboratory tests, imaging findings, cystoscopy and pathological results, the patient was clinically diagnosed with ICIs-associated immune cystitis (Pembrolizumab) ultimately. The patient's symptoms significantly improved after treatment with glucocorticoids. This case reindicates that clinicians need to improve awareness of ICI-related urinary system irAEs. Early identification and timely intervention can significantly improve patient prognosis.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.

Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.

ObjectiveThe exacerbating trend of global population aging poses profound socioeconomic and public health challenges, making the comprehensive elucidation of biological aging mechanisms and the discovery of effective anti-aging interventions an urgent priority in the life sciences. Based on our previous serum metabolomics findings that dimethylglycine, an intermediate metabolite of amino acid metabolism naturally present in the human body, was significantly enriched in the serum of longevity families, this study aimed to systematically investigate the anti-aging effects of dimethylglycine both in living organisms and in controlled laboratory environments, and to preliminarily elucidate its underlying molecular mechanisms. While existing literature indicates that dimethylglycine possesses antioxidant and immunomodulatory properties, its direct anti-aging efficacy and the specific molecular pathways through which it operates remain largely unexplored. MethodsTo comprehensively evaluate the anti-aging properties of dimethylglycine, we utilized replicative senescent human embryonic lung fibroblasts, specifically the WI-38 cell line, as an experimental model in a controlled laboratory environment. Cell viability and safety were thoroughly assessed using Cell Counting Kit-8 and lactate dehydrogenase release assays across various concentrations of dimethylglycine. The impact of dimethylglycine on cellular senescence phenotypes, oxidative stress, and proliferative capacity was evaluated via senescence-associated beta-galactosidase staining, reactive oxygen species fluorescence detection, and 5-ethynyl-2'-deoxyuridine incorporation assays. Furthermore, the molecular alterations of senescence-associated secretory phenotype factors and core senescence signaling pathways were quantified using quantitative reverse transcription polymerase chain reaction for the messenger RNA levels of interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1, and enzyme-linked immunosorbent assay for the measurement of p16 and p21 protein expression levels. For the living organism model, the wild-type nematode Caenorhabditis elegans was used to evaluate systemic physiological effects. We conducted a comprehensive lifespan analysis at 20°C, heat stress resistance survival assays at 35℃, senescence-associated beta-galactosidase staining, lipofuscin accumulation tracking, intracellular reactive oxygen species measurement, and Oil Red O staining to ascertain systemic lipid accumulation. Additionally, network pharmacology bioinformatics tools, including PharmMapper and STRING databases, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were utilized to predict target pathways, alongside highly detailed molecular docking simulations utilizing SwissDock and Protein-Ligand Interaction Profiler to examine interactions with the cytochrome P450 family 2 subfamily C member 9 protein. ResultsThe experimental outcomes robustly demonstrate the potent anti-aging capabilities of dimethylglycine. At the cellular level, toxicity analyses firmly confirmed that dimethylglycine is highly safe; continuous treatment with 50 mol/L and 70 mol/L of dimethylglycine for 5 d did not induce any cellular membrane damage or cytotoxicity, but rather actively promoted cellular proliferation. Utilizing the optimal standardized concentration of 50 mol/L, dimethylglycine treatment significantly ameliorated senescent phenotypic markers in human embryonic lung fibroblasts, which was evidenced by a drastic and highly significant reduction in the senescence-associated beta-galactosidase positive cell percentage (P<0.000 1) and intracellular reactive oxygen species levels (P<0.000 1), alongside a marked increase in the 5-ethynyl-2'-deoxyuridine-positive proliferation rate (P=0.003 5). On a molecular expression scale, dimethylglycine significantly downregulated the messenger RNA expression of multiple core senescence-associated secretory phenotype inflammatory factors, including interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1. Concurrently, it effectively suppressed the protein expression of critical cell cycle arrest markers, diminishing p16 protein levels by 57.3% (P=0.000 4) and p21 protein levels by 27.2% (P=0.000 7). In the nematode Caenorhabditis elegans animal model, dimethylglycine significantly extended the mean lifespan from 20.402 d to an impressive 23.066 d (P<0.000 1) and notably enhanced overall survival rates under severe heat stress environmental conditions (P=0.017). Furthermore, systemic dimethylglycine intervention significantly mitigated age-related physiological decline by decreasing bodily lipofuscin accumulation (P<0.000 1), significantly reducing senescence-associated beta-galactosidase activity, lowering systemic reactive oxygen species fluorescence (P=0.008), and effectively alleviating overall fat accumulation (P<0.000 1). Mechanistically, extensive network pharmacology and Kyoto Encyclopedia of Genes and Genomes analyses strongly revealed that the potential targets of dimethylglycine are significantly enriched in fundamental drug metabolism and oxidative stress response pathways. Precision molecular docking simulations conclusively demonstrated that dimethylglycine forms highly stable structural interactions with the cytochrome P450 family 2 subfamily C member 9 protein, specifically highlighting the definitive formation of 5 stable hydrogen bonds involving serine 365, leucine 366, and serine 429 residues, as well as two critical salt bridge formations with arginine 97 and histidine 368 residues. It is additionally predicted to interact favorably with glutathione S-transferase family proteins. ConclusionDimethylglycine exhibits a profoundly significant and multifaceted anti-aging activity at both the cellular and entire living animal levels. By powerfully alleviating oxidative stress, heavily suppressing the core p16 and p21-dependent cellular senescence signaling pathways, and substantially mitigating the detrimental senescence-associated secretory phenotype, dimethylglycine effectively delays fundamental cellular senescence processes and drastically extends whole-organism lifespan. The biological mechanisms driving these robust protective effects are highly likely closely associated with its direct stable interactions with crucial metabolic and detoxifying enzyme systems, such as cytochrome P450 family 2 subfamily C member 9 and glutathione S-transferase family proteins, thereby systemically improving metabolic dysregulation and restoring critical redox homeostasis. This comprehensive study provides highly solid experimental evidence supporting dimethylglycine as a highly potent and safe potential anti-aging intervention agent, while simultaneously offering a clear molecular mechanistic explanation for the previously documented high abundance of dimethylglycine observed within exceptionally long-lived human populations.

ObjectiveGastric hemorrhage is one of the most common and life-threatening emergencies of the upper digestive tract. Early identification and continuous monitoring are essential for reducing rebleeding rates and mortality, particularly within the critical early hours after onset. Although endoscopy and radiological imaging can accurately localize bleeding sites, these approaches are invasive, resource-intensive, and unsuitable for continuous bedside monitoring. Electrical impedance tomography (EIT), as a noninvasive and radiation-free functional imaging technique, offers real-time visualization of conductivity distribution and has the potential for detecting intragastric bleeding based on the electrical contrast between blood and surrounding gastric tissues. In this study, a three-dimensional gastric EIT (3D-gEIT) framework is proposed to achieve noninvasive, real-time, and dynamic monitoring of gastric hemorrhage, with emphasis on spatial localization and quantitative volume assessment. MethodsA three-dimensional upper-abdominal simulation model incorporating the stomach, gastric wall, gastric contents, and surrounding tissues was established. Three electrode configurations, namely the dual layer ring, the four layer staggered ring, and the opposed dual plane array, were designed and systematically compared to evaluate their influence on depth sensitivity and spatial resolution. Based on the Tikhonov-Noser hybrid regularization scheme, a region-clustering constraint was introduced to develop the TK-Noser-RCC algorithm. This approach aggregates spatially adjacent elements with similar conductivity variations, thereby enhancing structural continuity and suppressing isolated noise artifacts. To validate the proposed framework, an upper-abdominal physical phantom was constructed using agar to simulate background tissue conductivity. Hemispherical high-conductivity inclusions with volumes ranging from 10 ml to 50 ml were attached to the inner gastric wall to mimic localized bleeding under different gastric filling states. Boundary voltages were acquired under a 120 kHz excitation current and reconstructed using the TK-Noser-RCC algorithm. Furthermore, an in vivo animal experiment was performed using a porcine model with adult-scale abdominal dimensions. A total of 100 ml of autologous blood was injected incrementally into the stomach to simulate progressive gastric hemorrhage, and time-difference EIT reconstruction was conducted at each injection stage to assess the dynamic system response under physiological conditions. ResultsSimulation results demonstrated that the opposed dual-plane electrode array achieved superior depth sensitivity distribution and spatial resolution. For a 40 ml hemorrhage model, the average ICC and SSIM improved by 55.9% and 38.8% compared with the dual-layer ring configuration, and by 64.0% and 39.5% compared with the four-layer staggered configuration. The proposed region-clustering constraint significantly enhanced reconstruction stability. Under added Gaussian noise of 40 dB and 30 dB, ICC values remained approximately 0.85, indicating effective artifact suppression and preservation of boundary integrity. In physical phantom experiments, reconstructed hemorrhage volumes increased approximately linearly with the preset hemispherical volumes, and the reconstructed high-conductivity regions closely matched the actual bleeding locations. Both empty-stomach and full-stomach conditions were evaluated, demonstrating that the opposed dual-plane configuration maintained stable imaging performance across varying gastric contents. In the animal experiment, reconstructed low-impedance regions expanded progressively with increasing injected blood volume. The spatial localization of the hemorrhage remained stable throughout the procedure, and no significant artifacts were observed. Quantitative analysis showed that reconstructed volume and average conductivity variation exhibited an approximately linear growth trend with injected blood volume, confirming the sensitivity of the system to dynamic intragastric conductivity changes. ConclusionThe proposed 3D-gEIT framework enables quantitative reconstruction of gastric hemorrhage volume and spatial distribution with improved depth sensitivity, structural continuity, and noise robustness compared with conventional EIT approaches. By integrating optimized electrode configuration and a region-clustering-constrained reconstruction algorithm, the system provides stable dynamic monitoring under both controlled phantom conditions and in vivo physiological environments. This method offers a noninvasive, real-time, and low-cost imaging strategy for early diagnosis, postoperative monitoring, and bedside surveillance of gastric bleeding.