Based on the thinking of programmatization and proceduralization， this study integrated traditional Chinese medicine （TCM） classic theories with modern knowledge expression technologies to construct a "formula-symptom" syndrome differentiation thinking model centered on "symptom clustering-main syndrome screening-formula adaptation"， and explored the standardization and intelligentization path of TCM syndrome differentiation and treatment. By establishing the mapping relationship model between formulas and syndromes including quantitative weight analysis of chief， deputy， assistant and envoy medicines， designing the logical hierarchical structure of formula-syndrome decision tree （application of three-level decision tree and fuzzy logic）， and formulating the procedural design of four diagnostic methods （structured collection， correlation model， and dynamic correction mechanism）， the standardization and visualization of the syndrome differentiation process are realized. This model can be transformed into the core data set for artificial intelligence training. Through ternary knowledge graph and machine learning algorithms， it can improve the repeatability of syndrome differentiation and the efficiency of diagnosis and treatment， and implement the strategy of "group model + individual modification" to balance the conflict between quantification and individualization. The core value of this model lies in promoting the objectification and precision development of TCM syndrome differentiation and treatment through the integration of traditional syndrome differentiation thinking and modern system science.

AIM: To analyze the reasons and clinical outcomes of intraocular lens(IOL)exchange.METHODS:This retrospective case series study included 47 patients(53 eyes)who underwent IOL exchange surgery at the Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, between April 2020 and May 2024, aged from 5 to 87(44.8±3.6)years old. Patients' demographics, surgical indications, surgical techniques, preoperative and postoperative uncorrected visual acuity(UCVA)and best-corrected visual acuity(BCVA), as well as postoperative complications were recorded.RESULTS:The reasons for IOL exchange included refractive error(18 cases, 23 eyes, 43%), IOL dislocation(12 cases, 13 eyes, 25%), IOL opacification(12 cases, 12 eyes, 23%), neuroadaptation failure(3 cases, 3 eyes, 6%), and patient dissatisfaction with visual quality(2 cases, 2 eyes, 4%). The surgical techniques for IOL exchange included in-the-bag IOL fixation(16 eyes, 30%), ciliary sulcus fixation(27 eyes, 51%), and scleral suture fixation(10 eyes, 19%). There was statistical significant difference between preoperative UCVA(LogMAR)and UCVA(LogMAR)at 1 d postoperatively(1.03±0.64 vs 0.50±0.46, P<0.05), and there was statistical significant difference between preoperative BCVA(LogMAR)and BCVA(LogMAR)at 1 mo postoperatively(0.41±0.37 vs 0.17±0.21, P<0.05). Postoperative complications included posterior capsule opacification in 2 eyes and IOL dislocation in 1 eye.CONCLUSION:Refractive error, IOL dislocation, and IOL opacification were the three most common reasons for IOL exchange. Although less frequent, factors such as neuroadaptation issues associated with multifocal IOLs and patient-reported visual quality dissatisfaction reflect growing expectations for improved visual outcomes. IOL exchange surgery, though technically challenging, demonstrates favorable clinical efficacy and a low complication rate, representing an effective intervention for managing postoperative IOL-related issues following cataract surgery.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective To investigate how vismodegib(Vis)influences the pathogenesis of basal cell carcinoma(BCC)via a chromatin remodeling factor,bromodomain containing protein 9(BRD9),and to analyze the expression profile of BRD9 in BCC and its relationship with the immune checkpoint,programmed cell death-1 ligand 1(PD-L1)and the Hedgehog(Hh)signaling pathway.Methods ① A UVB-induced BCC model was established in SKH-1 hairless background Ptch1+/-;LacZ reporter mice.Then the mice were treated with Vis,and those without treatment served as control.X-gal staining,immunohistochemistry(IHC)staining,immunofluorescence(IF)assay,and Western blotting were used to assess the expression and localization of BRD9 and PD-L1 in tumor tissues and to evaluate immune-cell infiltration.② In vitro,mouse BCC cell line ASZ001(ASZ cells)were treated with Vis or a BRD9 degrader(dBRD9),and BRD9-overexpressing cells were generated.Cell viability and the protein and mRNA levels of BRD9,PD-L1,Gli1,and cyclin D1(Ccnd1)were measured.ChIP-qPCR was performed to examine BRD9 and H3K27ac enrichment at the PD-L1 promoter,including the promoter-proximal site(P1)and an upstream active segment(P2).Results ① At the tissue level,BRD9 was highly expressed in BCC,and co-localization of BRD9 and PD-L1 was observed within tumor regions,with evident immune-cell infiltration.Vis markedly suppressed UVB-induced BCC formation,reduced the probability of large-volume tumors(by probability-density analysis),decreased the X-gal-positive lesion area(P<0.000 1),down-regulated BRD9(P=0.024 9),and attenuated immune-cell infiltration.② At the cellular level,Vis treatment reduced cell viability and down-regulated BRD9,Gli1,and Ccnd1 in ASZ cells(P<0.000 1).dBRD9 inhibited ASZ cell viability in a dose-dependent manner and decreased PD-L1,Gli1,and Ccnd1(P<0.000 1),whereas its overexpression increased the expression of these molecules(P<0.000 1).In ASZ cells,BRD9 and H3K27ac were enriched at the PD-L1 promoter P1/P2 regions.Treatment with dBRD9 or Vis reduced BRD9 and H3K27ac enrichment at P1/P2 regions(P<0.000 1).Conclusion In BCC,BRD9 maintains chromatin activation at the proximal PD-L1 promoter and modulates Hh/Gli1 signaling,thereby promoting immune evasion.Vis remodels the tumor immune microenvironment by inhibiting the Hh-BRD9-PD-L1 axis.

Objective:To evaluate long-term outcomes of endoscopic papillectomy (EP) for duodenal papillary adenomas and to identify risk factors for incomplete resection.Methods:Clinical data of 180 patients diagnosed as having duodenal papillary adenoma via postoperative pathology after EP in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2010 to December 2022 were retrospectively analyzed. Patients were divided into two groups based on their postoperative margin status: the complete resection group (negative resection margins) and the incomplete resection group (positive/uncertain resection margins). Recurrence rates were compared between the two groups, and logistic regression analysis was performed to identify risk factors for incomplete resection.Results:Among the 180 patients included in the study, 137 underwent complete resection, and 43 had incomplete resections. Recurrence rate was significantly higher in the incomplete resection group than that in the complete resection group (30.2% VS 15.3%, χ2=4.75, P=0.029). logistic regression analysis indicated that high-grade intraepithelial neoplasia was an independent risk factor for incomplete resection ( OR=2.43, 95% CI:1.12-5.26, P=0.024). Conclusion:Patients with incomplete resection after EP have a higher recurrence rate in the long-term follow-up. High-grade intraepithelial neoplasia is an independent risk factor for incomplete resection. Close surveillance and aggressive management are warranted for patients with positive or uncertain resection margins to mitigate the recurrence risk.

Objective To analyze the research hotspots and development trends regarding the effect of proprioceptive training in the rehabilitation of anterior cruciate ligament(ACL)injury.Methods Relevant literatures on the effect of proprioceptive training on ACL injury rehabilitation were retrieved in the Web of Science Core Collection database from 2015 to 2024,and were analyzed with CiteSpace 6.2 R4.Results A total of 108 articles were included,with a fluctuating trend in publication volume,and the number of publica-tions peaked in 2021.The United States and China published the most articles.High-frequency keywords includ-ed posture balance,neuromuscular control,joint position sense,muscle strength and gait analysis.The most cen-tral keyword was posture stability.The research focused on improving the postoperative rehabilitation outcomes and efficiency of ACL injury,with particular emphasis on returning to play,posture stability,strength training and knee joint function.Conclusion Proprioceptive training can enhance proprioception and motor control of patients with ACL injury and im-prove rehabilitation outcomes by strengthening rehabilitation techniques and optimizing treatment approaches.Future research should continue to focus on the diversification of proprioceptive training,the individulization of rehabilitation plans and the application of new technologies.

Objective:To construct a model of mitochondria-related genes (Mito-RGs) in hepatocellular carcinoma (HCC), and predict the immune, prognostic and therapeutic characteristics of HCC based on the model, so as to provide a new idea for the diagnosis and treatment of HCC.Methods:The expression profiles of HCC and corresponding clinical information were obtained from the Cancer Genome Atlas (TCGA) database. Univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate Cox regression were used to construct a prognostic model of HCC based on Mito-RGs, and the International Cancer Genome Consortium-Liver Cancer-RIKEN-Japan ICGC-LIRI-JP dataset were used for validation. GO and KEGG analyses were performed to investigate the signaling pathways enriched for differentially expressed genes in the high- and low-risk groups. Immune infiltration was assessed using CIBERSORT. Single-cell data were used to study the proportion of immune cells in high- and low-risk groups of HCC samples and the relationship with cell proliferation. Cellminer was used to assess the relationship between risk score models and drug sensitivity.Results:A risk-prognostic model of HCC containing seven Mito-RGs ( DTYMK, ACADS, HMGCS2, CYP27A1, TOMM40L, STOM, and AKR1B10) was constructed. High-risk HCC patients had a worse prognosis. Genes upregulated in the high- and low-risk groups of differentially expressed genes were enriched in cell cycle and metabolism-related pathways. Single-cell data showed higher proportions of CD8 + T cells, macrophages and monocytes, and proliferating cells in the high-risk group. CIBERSORT analysis suggested that Treg cells and M0 macrophages were more abundant in the high-risk group, whereas CD8 + T cells and CD4 + memory T cells were less abundant. Patients in the high-risk group were more sensitive to myeloid cell leukemia sequence 1 inhibitor, vincristine, phosphatidylinositol kinase beta subunit inhibitor, and aurora kinase A, while trametinib, selumetinib, extracellular regulated protein kinase, and mitogen-activated extracellular signal-regulated kinase were more effective in the low-risk group. Conclusion:The constructed Mito-RGs model is capable of providing a more accurate assessment of the prognosis and the degree of immune cell infiltration in HCC patients.

Mitochondria play a crucial role as organelles, managing several physiological processes such as redox balance, cell metabolism, and energy synthesis. Initially, the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria. Recent scholarly works, however, suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer. This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms. Specifically, we review the role of mitochondria transfer in regulating cellular metabolism restoration, excess reactive oxygen species (ROS) generation, proliferation, invasion, metastasis, mitophagy activation, mitochondrial DNA (mtDNA) inheritance, immune system modulation and therapeutic resistance in cancer. Additionally, we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.

The Solomon four-group design， a critical method for improving internal validity in clinical research， can reduce bias and control the interference of Hawthorne effects and pretest sensitization on research results， which offers unique advantages in evaluating complex intervention outcomes. This paper systematically outlined the core framework and key points of statistical analysis of the Solomon four-group design， summarized its applications in clinical research at home and abroad， explored its advantages and limitations， and discussed the potential value in traditional Chinese medicine （TCM） clinical trials. It is believed that the Solomon four-group design can help distinguish between testing effects and intervention effects in TCM clinical studies， and reduce the bias in the evaluation of subjective indicators. Meanwhile， given the complexity of the Solomon four-group design and the particularity of TCM clinical research， it is proposed that future TCM clinical studies should focus on using psychological scales， know-ledge， attitude， and behavior measurements， and other similat evaluations as endpoints. It also advocates strengthening interdisciplinary collaboration to provide new methodological paths for TCM clinical research.

ObjectiveTo explore the potential mechanisms by which spleen deficiency affects lipid metabolism in hyperlipidemia， from the perspective of gut microbiota and fecal endogenous metabolites. MethodsEighteen Sprague-Dawley （SD） rats were randomly divided into control group， hyperlipidemia group， and spleen-deficiency with hyperlipidemia group， with 6 rats in each group. The control group was fed with standard diet； the hyperlipi-demia group was given high-fat diet to induce hyperlipidemia model； and the spleen-deficiency with hyperlipidemia group received combination of high-fat diet， irregular feeding， and exercise restriction to induce the model. After 12 weeks of modeling， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured. 16S rRNA gene sequencing was used to analyze gut microbiota composition in fecal samples， and fecal metabolites were analyzed using high-performance liquid chromatography-mass spectrometry （HPLC-MS）. Differential metabolites and microbial taxa were screened for pathway enrichment and functional prediction analysis， followed by correlation analysis. ResultsCompared with the control group， rats in the hyperlipidemia and spleen-deficiency with hyperlipidemia groups showed significantly increased serum TG， TC， and LDL-C levels， and decreased HDL-C levels （P＜0.01）. Compared with the hyperlipidemia group， the spleen-deficiency with hyperlipidemia group showed further increases in TG， TC， and LDL-C and further decrease in HDL-C （P＜0.05 or P＜0.01）. Gut microbiota analysis revealed 3,066 unique species in the control group， 2,637 in the hyperlipidemia group， and 1,581 in the spleen-deficiency group. Chao1， Simpson， and Shannon indices were significantly reduced in the spleen-deficiency group compared with the hyperli-pidemia group， with an increased Firmicutes/Bacteroidetes ratio. Differentially abundant genera such as Romboutsia， Lactobacillus， Clostridium， Allobaculum， and Xylanibacter were significantly upregulated （P＜0.05 or P＜0.01）. Metabolomics identified 25 differential metabolites in feces of spleen-deficient rats， with 18 downregulated and 7 upregulated. Key enriched pathways included serotonergic synapse， nucleotide metabolism， vascular smooth muscle contraction， and arachidonic acid metabolism. Spearman correlation analysis showed significant positive correlations between Romboutsia and Desulfovibrio and metabolites such as digalactosyldiacylglycerol （48∶5）， dehydrated artemetin， lysophosphatidylcholine （26∶4）， and glucuronosyldiacylglycerol （46∶5）； Clostridium was positively correlated with cyclopassifloric acid E1， digalactosyldiacylglycerol （48∶5）， and lysophosphatidylcholine （26∶4）； Xylanibacter was positively correlated with digalactosyldiacylglycerol （48∶5）， dehydrated artemetin， and lysophosphatidylcholine （26∶4）. ConclusionSpleen deficiency can further alter gut microbiota composition in hyperlipi-demia model rats， leading to microbial dysbiosis and metabolic disturbances that aggravate lipid metabolism disorders. This mechanism may be associated with changes in pathways such as serotonergic synapse， nucleotide metabolism， vascular smooth muscle contraction， and arachidonic acid metabolism.