ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

Mitochondrial biogenesis represents a promising therapeutic target in triple-negative breast cancer (TNBC) due to its essential role in cancer cell metabolism and survival. The natural compound γ-Elemene exhibits potent anti-tumor activity, but its effects on mitochondrial regulation in TNBC remain unclear. In this study, we demonstrate that γ-Elemene induces dose-dependent cytotoxicity in MDA-MB-468 and HCC1806 TNBC cells while significantly impairing mitochondrial function, as shown by reduced membrane potential, oxidative phosphorylation capacity, and ATP production. γ-Elemene treatment markedly suppressed mitochondrial biogenesis, decreasing mitochondrial DNA content and downregulating key mitochondrial genes and proteins. These effects were associated with reduced expression of the master regulators NRF1 and TFAM, but independent of PGC-1α expression levels.Mechanistically, γ-Elemene upregulated the acetyltransferase GCN5, leading to enhanced PGC-1α acetylation. This upregulation occurs primarily through increased GCN5 transcription. Genetic ablation of GCN5 completely reversed γ-Elemene-induced PGC-1α acetylation and restored mitochondrial biogenesis and cell viability, establishing a critical role for GCN5 in mediating these effects. Our findings reveal a novel mechanism whereby γ-Elemene disrupts mitochondrial function in TNBC through GCN5-mediated PGC-1α acetylation, providing new insights into its anti-cancer properties and potential therapeutic applications against TNBC.

Natural products (NPs) are an important source of new drugs for the treatment of stroke. Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke. Small-molecule probes play a unique role in target discovery. However, drawbacks to these probes include non-specificity, unstable activity, and difficulty in synthesis. Small-molecule probes based on NPs at least partially compensate for these shortcomings. NPs feature rich chemical and structural diversity, biocompatibility, and unique biological activities. These features could be exploited to provide new ideas and tools for target discovery. Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules. This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases. We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.

Idiopathic pulmonary fibrosis （IPF） is a chronic interstitial lung disease characterized by dyspnea and progressive deterioration of lung function， which significantly impacts patients' quality of life and imposes a major burden on society. Although modern medicine has increasingly enriched the treatment options for pulmonary fibrosis， unfavorable factors such as high costs and significant side effects contribute to the persistently low survival rate of patients. Studies have shown that the occurrence and development of pulmonary fibrosis are closely related to abnormalities in multiple pathways. Among these， Rho/Rho-associated coiled-coil protein kinase （ROCK） plays a key role in the disease progression of IPF by regulating the cytoskeleton. This pathway not only transmits biochemical molecular signals that promote the progress of fibrosis but also responds to the biomechanical environment， such as the increased lung tissue stiffness caused by the deposition of extracellular matrix （ECM） during the process of pulmonary fibrosis. Therefore， research on this pathway is of great significance for the prevention and treatment of IPF. In recent years， traditional Chinese medicine （TCM） has shown remarkable effects in preventing and treating IPF. Many TCM compounds and active components can reduce the production of α-smooth muscle actin （α-SMA）， CollagenⅠ （ColⅠ）， ColⅢ， and inflammatory factors in lung tissue by regulating the Rho/ROCK signaling pathway. These compounds inhibit the transformation of fibroblasts （FBs） into myofibroblasts （MyoFBs）， intervening in the process of pulmonary fibrosis. Based on this， the article briefly reviews relevant research from recent years， discusses the key role of the Rho/ROCK pathway in pulmonary fibrosis from an interdisciplinary perspective， and summarizes the mechanisms through which TCM regulates Rho/ROCK to prevent and treat IPF， based on resources from PubMed， CNKI， and other databases， in order to provide important references for the broader clinical application of TCM in the prevention and treatment of IPF.

Experimental teaching of Medical Immunology is an important way to achieve the teaching goal of cultivating"prac-tical,applied,and innovative high-quality medical talents".Applying the ATR teaching mode to Medical Immunology experimental teaching,fully utilizing the advantages of artificial intelligence teaching assistants,can not only stimulate students'learning enthusi-asm,achieve simultaneous progress of"knowledge learning"and"thinking exercise",promote deep learning,and improve teaching quality,but also enhance students'teamwork ability,achieve a dual approach of"value thinking"and"practical exercise",integrate ideological and political education into the curriculum,and achieve moral education.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of ileocecal valve lipoma.Methods:A retrospective cohort study was performed on data of ileocecal lipoma patients who underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2013 to June 2023. According to the lesion location, the patients were divided into ileocecal valve group and cecum group. The operation time, operation speed, en bloc resection rate, complications, and follow-up outcomes between the two groups were compared.Results:A total of 59 patients with ileocecal lipoma were enrolled, including 31 patients in the ileocecal valve group and 28 patients in the cecum group.There were no significant differences in gender, age, specimen size, or lesion size between the two groups ( P>0.05). Lipomas in both the ileocecal valve group and the cecum group were successfully resected by ESD. The en bloc resection rates were 100.0% (31/31) and 92.9% (26/28) respectively, and the difference was not statistically significant ( χ2=0.033, P=0.133). Median operative duration significantly differed between the two groups ( ileocecal valve group 26 min VS cecum group 20 min, Z=-0.136, P=0.027), as did resection speed (ileocecal valve group 0.14 cm2/min VS cecum group 0.24 cm2/min, Z=-0.223, P=0.022). Adverse events included one postoperative fever in the ileocecal valve group and one delayed bleeding in the cecum group. During the median follow-up of 38 months (7-106 months), there was no case of residual tumor or recurrence. Conclusion:Despite technical challenges in ESD of ileocecal valve lipoma, it is still a safe, feasible and effective treatment method.

Triglyceride(TG)is transported in the blood as specific triglyceride-rich lipoprotein(TRL).When TRL is overproduced or the catabolism is not timely,cholesterol ester-rich residues is formed.Both TRL and its residues contribute to the development of atherosclerosis(As)through various direct and indirect mechanisms.Currently,the combination of lifestyle interventions and Western medicines is considered the preferred treatment strategy for As.Howev-er,lipid-lowering therapy alone cannot fully eliminate the residual risk of As.In contrast,traditional Chinese medicine emphasizes the holistic regulation of bodily functions to prevent and treat As.This paper will begin by examining the met-abolic mechanisms of TRL,elucidate the role of TRL and its residues in the risk of As occurrence,and summarize current strategies targeting the TRL metabolic pathway to reduce the incidence of As.

Triglyceride(TG)is transported in the blood as specific triglyceride-rich lipoprotein(TRL).When TRL is overproduced or the catabolism is not timely,cholesterol ester-rich residues is formed.Both TRL and its residues contribute to the development of atherosclerosis(As)through various direct and indirect mechanisms.Currently,the combination of lifestyle interventions and Western medicines is considered the preferred treatment strategy for As.Howev-er,lipid-lowering therapy alone cannot fully eliminate the residual risk of As.In contrast,traditional Chinese medicine emphasizes the holistic regulation of bodily functions to prevent and treat As.This paper will begin by examining the met-abolic mechanisms of TRL,elucidate the role of TRL and its residues in the risk of As occurrence,and summarize current strategies targeting the TRL metabolic pathway to reduce the incidence of As.

Objective:To analyze the application effects of case-based learning (CBL) + Seminar teaching method based on Toulmin model in the education and teaching of clinical medicine innovation class.Methods:A total of 60 students from the clinical medicine innovation class at The Second Affiliated Hospital of Guangzhou Medical University from September 2021 to September 2023 were selected as research objects. These students were divided into control group ( n=30) and research group ( n=30) according to different teaching programs. The traditional teaching method was adopted in the control group, and the CBL + Seminar teaching method based on Toulmin model was adopted in the research group. The two groups were compared in terms of clinical knowledge, clinical skill, and clinical case analysis scores; changes in clinical thinking ability after teaching; and satisfaction with the teaching process. SPSS 22.0 was used for t-test and chi-square test. Results:The research group significantly outperformed the control group in clinical knowledge [(89.59±3.46) points vs. (83.23±3.02) points], clinical skill [(88.87±3.23) points vs. (83.62±3.13) points], and clinical case analysis [(89.73±3.51) points vs. (82.62±3.19) points] ( t=7.58, 6.39, 8.21, P<0.001). The clinical thinking ability after teaching was significantly higher in the research group compared to the control group [(258.49±13.36) points vs. (242.56±13.02) points] ( t=4.67, P<0.001). The overall satisfaction rate of teaching was significantly higher in the research group compared to the control group (100.00% vs. 80.00%, χ2=4.63, P=0.031). Conclusions:The CBL + Seminar teaching method based on Toulmin model can effectively improve student learning performance and clinical thinking ability, demonstrating a promising application value in the education and teaching of clinical medicine innovation class.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of ileocecal valve lipoma.Methods:A retrospective cohort study was performed on data of ileocecal lipoma patients who underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2013 to June 2023. According to the lesion location, the patients were divided into ileocecal valve group and cecum group. The operation time, operation speed, en bloc resection rate, complications, and follow-up outcomes between the two groups were compared.Results:A total of 59 patients with ileocecal lipoma were enrolled, including 31 patients in the ileocecal valve group and 28 patients in the cecum group.There were no significant differences in gender, age, specimen size, or lesion size between the two groups ( P>0.05). Lipomas in both the ileocecal valve group and the cecum group were successfully resected by ESD. The en bloc resection rates were 100.0% (31/31) and 92.9% (26/28) respectively, and the difference was not statistically significant ( χ2=0.033, P=0.133). Median operative duration significantly differed between the two groups ( ileocecal valve group 26 min VS cecum group 20 min, Z=-0.136, P=0.027), as did resection speed (ileocecal valve group 0.14 cm2/min VS cecum group 0.24 cm2/min, Z=-0.223, P=0.022). Adverse events included one postoperative fever in the ileocecal valve group and one delayed bleeding in the cecum group. During the median follow-up of 38 months (7-106 months), there was no case of residual tumor or recurrence. Conclusion:Despite technical challenges in ESD of ileocecal valve lipoma, it is still a safe, feasible and effective treatment method.