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.

Diabetic Peripheral Neuropathy （DPN） is one of the most common and harmful complications of type 2 diabetes. DPN's pathogenesis include high blood sugar-induced oxidative stress， inflammation， and mitochondrial dysfunction. These factors are combined to damage nerve fibers， leading to sensory issues， pain， and numbness. Through a coordinated effect， these factors trigger nerve fiber damage and lead to sensory abnormalities， pain and numbness in limbs， and other symptoms， seriously restricting patients' activities of daily living and mobility. Recent research highlights that cellular senescence plays a critical role in DPN. Cellular senescence is manifested by the loss of cell proliferation ability， and further aggravates nerve damage via oxidative stress， mitochondrial dysfunction， autophagy impairment， inflammatory reaction， and other mechanisms， accelerating DPN occurrence and progression. In terms of medical treatment， current methods focus on blood sugar control， pain relief medicine， and microcirculation improvement， while no therapy has been developed based on cellular senescence. In contrast， traditional Chinese medicine （TCM） shows a unique advantage in DPN prevention and treatment via cellular senescence modulation. TCM emphasizes a holistic approach， as well as syndrome differentiation and treatment， effective in anti-aging and nerve damage repair. Recent studies show that TCM active ingredients， including puerarin， ginsenosides， and berberine， can reduce inflammation， oxidative stress， and apoptosis via signaling pathway regulation， thereby slowing cellular senescence to alleviate nerve damage. Furthermore， TCM compounds such as Buyang Huanwutang， Taohong Siwutang， and Huangqi Guizhi Wuwutang exert synergistic effects on cellular senescence-related pathways to improve nerve health and reduce DPN clinical symptoms. Therefore， this paper reviews the literature related to the interaction between cellular senescence and DPN from the perspective of cellular senescence， summarizing the mechanism of DPN and TCM intervention strategies.

Objective To evaluate the clinical efficacy of valve-in-valve transcatheter mitral valve replacement for the management of degenerated bioprosthetic mitral valves. Methods This study retrospectively analyzed the clinical data of patients who underwent transcatheter mitral valve replacement due to degenerated bioprosthetic mitral valves at the First Affiliated Hospital of Zhengzhou University from 2020 to 2023. The analysis included baseline characteristics, surgical details, perioperative complications, and hemodynamic changes during the early postoperative period and subsequent follow-up. Results A total of 31 patients were included in the study, comprising 7 males and 24 females, with an average age of (66.57±9.32) years. The average duration since the initial surgical placement of the bioprosthetic valves was (9.92±3.71) years. The procedures included 7 patients utilizing the transfemoral venous-atrial septal approach and 24 patients employing the transapical approach. All patients exhibited significant improvement in cardiac function postoperatively, with a reduction in the number of patients classified as New York Heart Association (NYHA) grade Ⅲ or Ⅳ and those with moderate to severe tricuspid valve regurgitation. Echocardiographic assessments revealed a decrease in peak flow velocity across the mitral valve and a reduction in the average transvalvular pressure gradient, while left ventricular ejection fraction remained unchanged. One patient experienced a recurrent stroke and died on the fifth postoperative day; however, the remaining patients were discharged uneventfully, without complications such as cardiac death, left ventricular outflow tract obstruction, or pacemaker implantation. During a median follow-up period of 12 months, no adverse events were reported, and hemodynamic stability was maintained. Conclusion Valve-in-valve transcatheter mitral valve replacement is a safe and effective option for patients with degenerated bioprosthetic mitral valves, demonstrating favorable hemodynamic outcomes and satisfactory short-term clinical results.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

BACKGROUND: Diabetes mellitus with nonalcoholic fatty liver disease (DM-NAFLD) represents a complex metabolic syndrome with significant clinical challenges. This study explores the therapeutic potential and underlying mechanisms of umbilical cord-derived mesenchymal stem cells (UCMSCs)-derived extracellular vesicles (EVs) in DM-NAFLD. METHODS: UCMSCs-EVs were isolated and characterized. DM-NAFLD mouse model was developed through highenergy diet and streptozotocin injection. Additionally, primary mouse hepatocytes were exposed to high glucose to simulate cellular conditions. Hepatic tissue damage, body weight changes, lipid levels, glucose and insulin homeostasis, and hepatic lipid accumulation were evaluated. The interaction between UCMSCs-EVs and hepatocytes was assessed, focusing on the localization and function of circ-Tulp4. The study also investigated the expression of circularRNA TUBlike protein 4 (circ-Tulp4), heterogeneous nuclear ribonucleoprotein C (HNRNPC), abhydrolase domain containing 6 (ABHD6), cleaved Caspase-1, NLR family pyrin domain containing 3 (NLRP3) and cleaved N-terminal gasdermin D (GSDMD-N). The binding of circ-Tulp4 to lysine demethylase 6B (KDM6B) and the subsequent epigenetic regulation of ABHD6 by H3K27me3 were analyzed. RESULTS: Circ-Tulp4 was reduced, while HNRNPC and ABHD6 were elevated in DM-NAFLD models. UCMSCs-EVs attenuated hepatic steatosis and inhibited the NLRP3/cleaved Caspase-1/GSDMD-N pathway. EVs delivered circ-Tulp4 into hepatocytes, thereby restoring circ-Tulp4 expression. Elevated circ-Tulp4 enhanced the recruitment of H3K27me3 to the HNRNPC promoter through interaction with KDM6B, thus suppressing HNRNPC and ABHD6. Overexpression of HNRNPC or ABHD6 counteracted the protective effects of UCMSCs-EVs, exacerbating pyroptosis and hepatic steatosis in DM-NAFLD. CONCLUSION UCMSCs-EVs deliver circ-Tulp4 into hepatocytes, where circ-Tulp4 inhibits the HNRNPC/ABHD6 axis, thereby reducing pyroptosis and alleviating DM-NAFLD. These findings provide a novel therapeutic avenue for targeting DM-NAFLD through modulation of cell pyroptosis.

BACKGROUND: Diabetes mellitus with nonalcoholic fatty liver disease (DM-NAFLD) represents a complex metabolic syndrome with significant clinical challenges. This study explores the therapeutic potential and underlying mechanisms of umbilical cord-derived mesenchymal stem cells (UCMSCs)-derived extracellular vesicles (EVs) in DM-NAFLD. METHODS: UCMSCs-EVs were isolated and characterized. DM-NAFLD mouse model was developed through highenergy diet and streptozotocin injection. Additionally, primary mouse hepatocytes were exposed to high glucose to simulate cellular conditions. Hepatic tissue damage, body weight changes, lipid levels, glucose and insulin homeostasis, and hepatic lipid accumulation were evaluated. The interaction between UCMSCs-EVs and hepatocytes was assessed, focusing on the localization and function of circ-Tulp4. The study also investigated the expression of circularRNA TUBlike protein 4 (circ-Tulp4), heterogeneous nuclear ribonucleoprotein C (HNRNPC), abhydrolase domain containing 6 (ABHD6), cleaved Caspase-1, NLR family pyrin domain containing 3 (NLRP3) and cleaved N-terminal gasdermin D (GSDMD-N). The binding of circ-Tulp4 to lysine demethylase 6B (KDM6B) and the subsequent epigenetic regulation of ABHD6 by H3K27me3 were analyzed. RESULTS: Circ-Tulp4 was reduced, while HNRNPC and ABHD6 were elevated in DM-NAFLD models. UCMSCs-EVs attenuated hepatic steatosis and inhibited the NLRP3/cleaved Caspase-1/GSDMD-N pathway. EVs delivered circ-Tulp4 into hepatocytes, thereby restoring circ-Tulp4 expression. Elevated circ-Tulp4 enhanced the recruitment of H3K27me3 to the HNRNPC promoter through interaction with KDM6B, thus suppressing HNRNPC and ABHD6. Overexpression of HNRNPC or ABHD6 counteracted the protective effects of UCMSCs-EVs, exacerbating pyroptosis and hepatic steatosis in DM-NAFLD. CONCLUSION UCMSCs-EVs deliver circ-Tulp4 into hepatocytes, where circ-Tulp4 inhibits the HNRNPC/ABHD6 axis, thereby reducing pyroptosis and alleviating DM-NAFLD. These findings provide a novel therapeutic avenue for targeting DM-NAFLD through modulation of cell pyroptosis.

Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

Objective To summarize the short-term results of valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) in the treatment of bioprosthetic valve failure after aortic valve replacement. Methods We reviewed the clinical data of patients who underwent ViV-TAVI from 2021 to 2022 in the First Affiliated Hospital of Zhengzhou University. The valve function was evaluated by echocardiography before operation, immediately after operation and 3 months after operation. The all-cause death and main complications during hospitalization were analyzed. Results A total of 13 patients were enrolled, including 8 males and 5 females with a mean age of (65.9±8.5) years, and the interval time between aortic valve replacement and ViV-TAVI was (8.5±3.4) years. The Society of Thoracic Surgeons mortality risk score was 10.3%±3.2%. None of the 13 patients had abnormal valve function after operation. The mean transvalvular pressure gradient of aortic valve was decreased (P<0.001), the peak flow velocity of aortic valve was decreased (P<0.001), and the left ventricular ejection fraction was not changed significantly (P=0.480). There were slight perivalvular leakage in 2 patients and slight valve regurgitation in 3 patients. Three months after operation, the mean transvalvular pressure difference and peak flow velocity of aortic valve in 12 patients were significantly decreased compared with those before operation (P≤0.001). Conclusion This study demonstrates that ViV-TAVI for the treatment of bioprosthetic valve failure after aortic valve replacement is associated with favorable clinical and functional cardiovascular benefits, the short-term results are satisfactory.

BACKGROUND: Diabetes mellitus with nonalcoholic fatty liver disease (DM-NAFLD) represents a complex metabolic syndrome with significant clinical challenges. This study explores the therapeutic potential and underlying mechanisms of umbilical cord-derived mesenchymal stem cells (UCMSCs)-derived extracellular vesicles (EVs) in DM-NAFLD. METHODS: UCMSCs-EVs were isolated and characterized. DM-NAFLD mouse model was developed through highenergy diet and streptozotocin injection. Additionally, primary mouse hepatocytes were exposed to high glucose to simulate cellular conditions. Hepatic tissue damage, body weight changes, lipid levels, glucose and insulin homeostasis, and hepatic lipid accumulation were evaluated. The interaction between UCMSCs-EVs and hepatocytes was assessed, focusing on the localization and function of circ-Tulp4. The study also investigated the expression of circularRNA TUBlike protein 4 (circ-Tulp4), heterogeneous nuclear ribonucleoprotein C (HNRNPC), abhydrolase domain containing 6 (ABHD6), cleaved Caspase-1, NLR family pyrin domain containing 3 (NLRP3) and cleaved N-terminal gasdermin D (GSDMD-N). The binding of circ-Tulp4 to lysine demethylase 6B (KDM6B) and the subsequent epigenetic regulation of ABHD6 by H3K27me3 were analyzed. RESULTS: Circ-Tulp4 was reduced, while HNRNPC and ABHD6 were elevated in DM-NAFLD models. UCMSCs-EVs attenuated hepatic steatosis and inhibited the NLRP3/cleaved Caspase-1/GSDMD-N pathway. EVs delivered circ-Tulp4 into hepatocytes, thereby restoring circ-Tulp4 expression. Elevated circ-Tulp4 enhanced the recruitment of H3K27me3 to the HNRNPC promoter through interaction with KDM6B, thus suppressing HNRNPC and ABHD6. Overexpression of HNRNPC or ABHD6 counteracted the protective effects of UCMSCs-EVs, exacerbating pyroptosis and hepatic steatosis in DM-NAFLD. CONCLUSION UCMSCs-EVs deliver circ-Tulp4 into hepatocytes, where circ-Tulp4 inhibits the HNRNPC/ABHD6 axis, thereby reducing pyroptosis and alleviating DM-NAFLD. These findings provide a novel therapeutic avenue for targeting DM-NAFLD through modulation of cell pyroptosis.