Metabolic associated fatty liver disease （MAFLD） is the main type of chronic liver disease in the world， with an increasingly higher incidence rate and a younger age of onset. At present， the treatment of MAFLD mainly depends on lifestyle intervention and comorbidity management， and there is still a lack of effective drugs for MAFLD itself. As a classic nonsteroidal anti-inflammatory drug of the salicylic acid family， aspirin can intervene in the pathological process of MAFLD by regulating lipid metabolism， relieving insulin resistance， reducing liver inflammation and oxidative stress response， exerting an anti-liver fibrosis effect， and inhibiting hepatocellular carcinoma， and therefore， it has the value of preventing disease onset， delaying disease progression， and reversing disease condition. This article systematically reviews the mechanism of action and safety of aspirin in the treatment of MAFLD， in order to provide more drug treatment options for MAFLD patients.

Icodextrin peritoneal dialysis solution may produce cytotoxic α-dicarbonyl degradation products during heat sterilization, which must be monitored and controlled. The study established an o-phenylenediamine (OPD) derivatization HPLC-MS/MS method for the detection of these degradation products, enabling qualitative and quantitative analysis of α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution. The results indicated that the main α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution are 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 4-deoxyglucosone (4-DG), and 3,4-dideoxyglucosone-3-ene (3,4-DGE), along with two monocarbonyl degradation products, furfural and 5-hydroxymethylfurfural. The quantitative method for 3-DG, 3-DGal, 3,4-DGE and their structural analog, glucosone, was validated. 3-DG, 3-DGal, and glucosone exhibited good linear relationships within the range of 5-150 ng/mL, while 3,4-DGE showed good linearity in the range of 1-150 ng/mL. The spiked recovery rates for all compounds were between 86.8% and 100.0%. The detection limits for glucosone, 3-DG, and 3-DGal were approximately 2.4 ng/mL, and approximately 0.5 ng/mL for 3,4-DGE. The method established in this study can accurately determine α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution, providing an important basis for the quality control.

BACKGROUND:In vitro construction of tissue-engineered intestinal models plays an important role in intestinal regeneration and intestinal disease research.The interaction of intestinal nervous system and intestinal epithelial barrier to maintain body homeostasis is a hot topic in the bionic construction of tissue-engineered intestinal tract.OBJECTIVE:To construct a bionic model that can mimic the enteric nervous system in vivo.METHODS:Using fibroin protein with villus structure as scaffold,human induced neural stem cells solidified with collagen were added to intestinal epithelial cells(Caco-2 and HT29-MTX-E12)for 3-day culture to construct a co-culture system of intestinal epithelial cells and nerve cells(co-culture group).Human induced neural stem cells or intestinal epithelial cells cultured alone that were inoculated with fibroin scaffolds were set as controls.Cell morphology was observed by scanning electron microscopy and hematoxylin-eosin staining.Cell activity was detected by Live/Dead cell staining.Human induced neural stem cell differentiation was detected by β-microtubulin immunofluorescence staining.Intestinal epithelial histological properties and barrier function were detected by microvillin,sucrase-isomaltase,tight junction protein 1,E-calmodulin,and mucin-2 immunofluorescence staining.The function of mucus secretion from intestinal epithelial cells was detected by Alcian blue staining.Alkaline phosphatase staining was performed to detect differentiation of intestinal epithelial cells,at the same time,sucrase-isomaltase,tight junction protein 1,and alkaline phosphatase mRNAs were detected by RT-qRCR.RESULTS AND CONCLUSION:The neuralized intestinal mucosal co-culture model with villi structure was successfully constructed,and neural stem cells and intestinal epithelial cells on the fibroin scaffold showed good cellular activities.After neuralization,the activity of alkaline phosphatase and sucrase-isomaltase in intestinal epithelial cells was enhanced,while the expression level of tight junction protein 1 was up-regulated.To conclude,the neuralized bionic intestinal epithelial model is beneficial to the maturation of intestinal mucosal epithelial cells and the formation of barrier function.

ObjectiveTo analyze the research hotspots and development trends in the field of spinal cord stimulation (SCS) for spinal cord injury (SCI). MethodsLiterature about SCS for SCI was retrieve from the Web of Science (WOS) Core Collection database, with a time range from January, 1999 to July, 2025. VOSviewer 1.6.20 and CiteSpace 6.4.R2 were used to analyze the annual publication volume, countries, authors, institutions, journals and keywords. ResultsA total of 636 literatures were included. From 1999 to 2025, the overall publication trend in this field showed an upward trajectory, with recent years fluctuating but tending to stabilize. The country with the most publications was the United States (429 papers), followed by Russia (98 papers) and China (70 papers). The institution with the highest number of publications was the University of California, Los Angeles (76 papers), the author with the most publications was V. Reggie Edgerton (70 papers), and the journal with the most publications was Journal of Clinical Medicine (31 papers). The most frequently cited study focused on exploring the combination of epidural spinal cord stimulation with task-specific training to restore motor function in patients with complete SCI. Keyword analysis showed that the research hotspots in this field were mainly focused on neuroregulation mechanisms, recovery of motor and autonomic nervous dysfunction, artificial intelligence, closed-loop stimulation and brain-computer interface technology innovations. In recent years, the research focus gradually shifted from basic mechanisms to personalized and precise multifunctional rehabilitation strategies. ConclusionThe field of SCS for SCI has undergone phases of basic mechanism exploration and clinical application expansion. Current research hotspots and future trends focus primarily on the development of new stimulation paradigms and combined innovative technologies.

BACKGROUND:In vitro construction of tissue-engineered intestinal models plays an important role in intestinal regeneration and intestinal disease research.The interaction of intestinal nervous system and intestinal epithelial barrier to maintain body homeostasis is a hot topic in the bionic construction of tissue-engineered intestinal tract.OBJECTIVE:To construct a bionic model that can mimic the enteric nervous system in vivo.METHODS:Using fibroin protein with villus structure as scaffold,human induced neural stem cells solidified with collagen were added to intestinal epithelial cells(Caco-2 and HT29-MTX-E12)for 3-day culture to construct a co-culture system of intestinal epithelial cells and nerve cells(co-culture group).Human induced neural stem cells or intestinal epithelial cells cultured alone that were inoculated with fibroin scaffolds were set as controls.Cell morphology was observed by scanning electron microscopy and hematoxylin-eosin staining.Cell activity was detected by Live/Dead cell staining.Human induced neural stem cell differentiation was detected by β-microtubulin immunofluorescence staining.Intestinal epithelial histological properties and barrier function were detected by microvillin,sucrase-isomaltase,tight junction protein 1,E-calmodulin,and mucin-2 immunofluorescence staining.The function of mucus secretion from intestinal epithelial cells was detected by Alcian blue staining.Alkaline phosphatase staining was performed to detect differentiation of intestinal epithelial cells,at the same time,sucrase-isomaltase,tight junction protein 1,and alkaline phosphatase mRNAs were detected by RT-qRCR.RESULTS AND CONCLUSION:The neuralized intestinal mucosal co-culture model with villi structure was successfully constructed,and neural stem cells and intestinal epithelial cells on the fibroin scaffold showed good cellular activities.After neuralization,the activity of alkaline phosphatase and sucrase-isomaltase in intestinal epithelial cells was enhanced,while the expression level of tight junction protein 1 was up-regulated.To conclude,the neuralized bionic intestinal epithelial model is beneficial to the maturation of intestinal mucosal epithelial cells and the formation of barrier function.

With the rapid aging of the global population, the demand for prosthodontic rehabilitation of partial edentulism continues to increase. Among the available treatment options, removable partial dentures remain an essential clinical modality for restoring partially edentulous arches and masticatory function because of their broad indications, minimal invasiveness, and cost-effectiveness. However, unlike fixed prosthodontics, which have undergone substantial digitalization, removable partial denture therapy is characterized by dual tooth-tissue support, complex biomechanics, and highly variable anatomical morphology. As a result, the digital design and fabrication of removable partial dentures have long faced major bottlenecks, including limited standardization, steep learning curves, and heavy dependence on expert experience. In recent years, artificial intelligence (AI) has undergone a paradigm shift from early expert systems to machine learning and deep learning, creating new opportunities to address the complexity and precision demands of removable partial denture design. Based on a comprehensive literature review and our team's clinical experience, this article systematically elaborates on the specific applications and normative standards of AI throughout the entire removable partial denture fabrication workflow. In the data acquisition phase, we emphasize multimodal data fusion and digital pressure impression strategies. In the intelligent diagnosis and planning phase, deep learning is utilized to achieve the automatic identification of edentulous areas and undercuts, while machine learning and expert systems assist in abutment selection and treatment plan generation. Regarding automated design logic, the article analyzes the process from the intelligent planning of the common path of insertion to parametric design based on biomechanical optimization. At the clinical operation level, a standardized human-machine collaborative workflow of “AI generation-clinician review-local fine-tuning” is proposed. In terms of ethics and accountability, the principles of algorithmic transparency and “the clinician as the ultimate responsible subject” are emphasized. Furthermore, integrating clinical practice, this article innovatively proposes a “capability grading system for AI-assisted removable partial denture design (comprising the auxiliary analysis level, the rule-based design level, and the intelligent adaptive level)”. The aim is to offer practical recommendations for dental clinicians, dental technicians, and researchers, thereby facilitating the transition of removable partial denture prosthodontics toward greater precision, intelligence, and standardization.

ObjectiveTo explore the function and related molecular mechanisms of magnoflorine against colon cancer via network pharmacology， molecular docking， and in vitro cell experiments. MethodsIn this study， the canonical SMILES of magnoflorine was obtained from the PubChem database， and the potential targets of magnoflorine were predicted by the Swiss Target Prediction database， while the disease targets of colon cancer were obtained from the DisGeNET， GeneCards and OMIM databases. The intersecting targets between magnoflorine's predicted targets and colon cancer disease targets were taken， and a protein-protein interaction （PPI） network was constructed and analyzed. The DAVID online database was employed to conduct Gene Ontology （GO） and KEGG pathway enrichment analyses on core targets. The top five key targets screened were docked with magnoflorine using AutoDock software. Finally， cellular experiments including CCK-8 assays， EdU experiments， cell scratch assays， and Transwell assays were conducted to validate the results from network pharmacology and molecular docking. Results44 key targets of magnoflorine in resisting colon cancer were acquired. The molecular docking results showed that magnoflorine had a strong binding activity with the core target signal transducer and activator of transcription 3 （STAT3） in the top five of the PPI network. Cellular experiments confirmed that magnoflorine could inhibit the proliferation and migration of colon cancer cells by suppressing the JAK/STAT3 signaling pathway. ConclusionMagnoflorine may inhibit the proliferation and migration of colon cancer cells by regulating the JAK/STAT3 signaling pathway.

ObjectiveTo explore the application effects of environmentally friendly reagents versus traditional reagents in tissue processing， paraffin sectioning， hematoxylin-eosin （HE） staining， special staining， and immunohistochemistry. MethodsPancreatic， renal， splenic， hepatic， pulmonary， skeletal muscle， and cardiac tissues were collected from mice and New Zealand rabbits， and randomly divided into a traditional group （Group A）， an environmentally friendly reagent I group （Group B）， and an environmentally friendly reagent Ⅱ group （Group C）. The processed tissue sections from all three groups were subjected to paraffin sections， HE staining， phosphotungstic acid-hematoxylin staining， and Mallory trichrome staining. The pancreatic tissue sections were subjected to immunohistochemical detection of insulin protein. Evaluation criteria included tissue morphological integrity， embedding operability， section quality， and staining effects. ResultsNo significant differences were observed among the three groups of samples in terms of fixation efficacy， embedding operations， and section quality. After HE staining， all groups exhibited bright nuclear and cytoplasmic staining with clear contrast， with excellent-and-good rates of 98%， 99%， and 97% for Groups A， B， and C， respectively， showing no statistically significant differences （A vs. B， P=0.561； A vs. C， P=0.651）. In phosphotungstic acid-hematoxylin staining， Groups A and C showed clear structural contrast and bright staining for striated muscle and collagen fibers， whereas Group B exhibited uneven staining. The excellent-and-good rates were 100%， 10%， and 95% for Groups A， B， and C， respectively， with significant differences between Group A and Group B （P＜0.01） but no statistical difference between Group A and Group C （P=0.311）. In Mallory trichrome staining， Groups A and B outperformed Group C. The excellent-and-good rates were 95%， 90%， and 15% for Groups A， B， and C， respectively， with significant differences between Group A and Group C （P＜0.01）， but no statistical difference between Group A and Group B （P=0.548）. Immunohistochemical results showed that Group A had a clean background with no non-specific staining， while Groups B and C exhibited significant non-specific staining， with statistically significant differences in non-specific staining rates between the groups （A vs. B， 5% vs. 100%， P＜0.01； A vs. C， 5% vs.100%， P＜0.01）. ConclusionIn HE staining， environmentally friendly reagents demonstrated effective tissue fixation and staining results comparable to traditional reagents， meeting the teaching requirements. For special staining， Group B and Group C performed better in Mallory trichrome staining and phosphotungstic acid-hematoxylin staining， respectively. However， environmentally friendly reagents exhibited non-specific staining issues in immunohistochemistry， where further optimization is required.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism* ; Arthritis, Rheumatoid/immunology* ; Animals ; Dendritic Cells/metabolism* ; Paroxetine/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Lymphocyte Activation/drug effects* ; Female ; T-Lymphocytes/metabolism* ; Middle Aged

Hepatocellular carcinoma （HCC） is a malignant tumor with high incidence and mortality rates in China， and advanced HCC is a difficult issue in current treatment. Immune checkpoint inhibitor （ICI）， as an emerging treatment regimen， has shown a certain effect in clinical practice， but there are still problems such as low overall response rate and a high incidence rate of immune-related adverse events （irAEs）. Traditional Chinese medicine exhibits unique advantages in the treatment of advanced HCC. Through a retrospective analysis of related studies in recent years， this article shows that traditional Chinese medicine combined with ICI can control disease progression， prolong survival time， and reduce irAEs in the treatment of advanced HCC through the synergistic effect between multiple components， targets， and pathways. The potential mechanism of this treatment modality may involve various aspects such as the direct inhibition of tumor cells and the regulation of immune system and intestinal flora.