Yin-Yang theory is one of the core components of the foundational theory of traditional Chinese medicine (TCM), yet its classification as philosophical or scientific has long been controversial. To move beyond the longstanding either-philosophy-or-science debate surrounding Yin-Yang theory in TCM, this article, for the first time, proposes a three-level framework spanning macro, meso, and micro perspectives. At the macro level, Yin and Yang are a theoretical achievement of ancient Chinese natural philosophy, used to explain universal laws governing how the cosmos operates, which constitutes Yin-Yang theory in philosophy; at the meso level, Huangdi Neijing (《黄帝内经》, Inner Canon of Huangdi) translated Yin-Yang from a cosmological framework into medical discourse, making it a core methodological basis for clinical pattern differentiation and treatment, which constitutes Yin-Yang theory in medicine; at the micro level, Yin-Yang theory in TCM has increasingly converged with modern science, showing scientific features that are testable and reproducible, which constitutes Yin-Yang theory in science. The article further demonstrates that Yin-Yang theory in TCM differs markedly from Yin-Yang as a general philosophical doctrine in core application and practical orientation: in the course of its medical transformation, elements related to life phenomena were selectively incorporated, while, within a medical context, abstract propositions such as cosmological speculation were bracketed and rendered concrete, thereby achieving a practice-oriented transition from philosophy to medicine. Based on this, the present study conducts analyses from four aspects, namely philosophical roots, clinical application, modern scientific interpretation, and implications for life sciences; it substantiates the logical basis for Yin-Yang theory in TCM as the overarching framework for clinical pattern differentiation and treatment, reviews modern research progress from perspectives such as systems science and network regulation, and explores its potential value in advancing a new paradigm of state-based medicine. The study suggests that an accurate understanding of Yin-Yang theory in TCM requires moving beyond the either-philosophy-or-science binary and analyzing specific issues on a case-by-case basis. Across different perspectives, Yin-Yang theory in TCM has philosophical, medical, and scientific attributes. Only by grounding the theory in actual clinical efficacy and engaging with modern science can the innovative development of Yin-Yang theory in TCM be promoted, thereby providing valuable Eastern insights for building a life science system with original Chinese contributions.

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.

The view of youth moral cultivation clearly defines the scope of “morality” and puts forward the requirement of “cultivating morality” for the youth. This is a systematic concept aligned with the main theme of the times and is worth deeply exploring and integrating into the practice of medical ethics education for medical students. With the requirements for innovation and development in medical education， the cultivation of medical students has also been endowed with new connotations. Guided by the connotations of the view of youth moral cultivation and aligned with the objective requirements of medical students’ cultivation， this paper leveraged the core values of traditional Chinese medicine as its entry point. It also explored the realization paths of medical ethics education for medical students that reflect advantages， highlight characteristics， and maintain clear orientation through strengthening the medical ethics education of “dedicated study of medicine，” “honesty and prudence in words and deeds，” “benevolence in heart and skills，” and “doctor-patient trust and harmony，” aiming to cultivate guardians of people’s health with noble medical ethics and superb medical skills.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P＜0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P＜0.05 or P＜0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P＞0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P＜0.05 or P＜0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P＜0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P＜0.05 or P＜0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.

Objective:To analyze the expression level of protein arginine methyltransferase 5 (PRMT5) in pancreatic cancer tissues and its correlation with prognosis using bioinformatics methods, and to explore its potential mechanisms.Methods:Expression analysis of the PRMTs family members was performed based on the gene expression profiles of 178 pancreatic cancer tissues from the Gene Expression Profiling Interactive Analysis (GEPIA) database and 171 normal pancreatic tissues from the TCGA and GTEx databases. Using the median expression level of PRMTs family members in pancreatic cancer tissues as the cutoff, patients were divided into high-expression and low-expression groups, and Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS) were plotted. The correlation between PRMT5 expression and the expression of oncogenes such as KRAS, TP53, BRCA1, BRCA2, and SLC39A4 was analyzed. Functional enrichment analysis was conducted on genes similar to PRMT5, and a protein-protein interaction (PPI) network was constructed to analyze the interaction relationships among these similar genes. Pancreatic cancer PANC1 and AsPC-1 cells cultured in standard medium served as the control group, while PANC1 and AsPC-1 cells cultured in medium supplemented with the PRMT5 inhibitor EPZ015666 served as the intervention group. Cell viability was assessed using the CCK-8 assay, and cell cycle progression was analyzed by flow cytometry.Results:The expression level of PRMT5 in pancreatic cancer tissues was significantly higher than that in normal pancreatic tissues and showed a significant negative correlation with both OS and DFS. Patients with high PRMT5 expression had a shorter median survival time compared to those with low expression (17.2 months vs 19.5 months). PRMT5 expression was significantly positively correlated with the expression of oncogenes KRAS, TP53, BRCA1, BRCA2, SLC39A4, and KLF5. Genes similar to PRMT5 were primarily enriched in cell cycle-related signaling pathways, and NOP58 identified as a hub gene in the PPI network. Compared to the control group, the proliferation activity of PANC1 and AsPC-1 cells in the intervention group was significantly reduced [(67.3±1.9)% vs (100±4.4)% for PANC1; (60.5±2.7)% vs (100.0±1.7)% for AsPC-1], and the proportion of cells in the G1 phase was significantly increased [(51.6±0.7)% vs (35.3±2.7)% for PANC1; (51.2±0.9)% vs (29.7±2.2)% for AsPC-1]. All these differences were statistically significant (all P values <0.05). Conclusions:High expression of PRMT5 was closely associated with poor prognosis in pancreatic cancer patients, and it may contribute to pancreatic cancer progression by regulating the cell cycle.

Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P＜0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P＜0.05 or P＜0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P＞0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P＜0.05 or P＜0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P＜0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P＜0.05 or P＜0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.

Objective:To analyze the expression level of protein arginine methyltransferase 5 (PRMT5) in pancreatic cancer tissues and its correlation with prognosis using bioinformatics methods, and to explore its potential mechanisms.Methods:Expression analysis of the PRMTs family members was performed based on the gene expression profiles of 178 pancreatic cancer tissues from the Gene Expression Profiling Interactive Analysis (GEPIA) database and 171 normal pancreatic tissues from the TCGA and GTEx databases. Using the median expression level of PRMTs family members in pancreatic cancer tissues as the cutoff, patients were divided into high-expression and low-expression groups, and Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS) were plotted. The correlation between PRMT5 expression and the expression of oncogenes such as KRAS, TP53, BRCA1, BRCA2, and SLC39A4 was analyzed. Functional enrichment analysis was conducted on genes similar to PRMT5, and a protein-protein interaction (PPI) network was constructed to analyze the interaction relationships among these similar genes. Pancreatic cancer PANC1 and AsPC-1 cells cultured in standard medium served as the control group, while PANC1 and AsPC-1 cells cultured in medium supplemented with the PRMT5 inhibitor EPZ015666 served as the intervention group. Cell viability was assessed using the CCK-8 assay, and cell cycle progression was analyzed by flow cytometry.Results:The expression level of PRMT5 in pancreatic cancer tissues was significantly higher than that in normal pancreatic tissues and showed a significant negative correlation with both OS and DFS. Patients with high PRMT5 expression had a shorter median survival time compared to those with low expression (17.2 months vs 19.5 months). PRMT5 expression was significantly positively correlated with the expression of oncogenes KRAS, TP53, BRCA1, BRCA2, SLC39A4, and KLF5. Genes similar to PRMT5 were primarily enriched in cell cycle-related signaling pathways, and NOP58 identified as a hub gene in the PPI network. Compared to the control group, the proliferation activity of PANC1 and AsPC-1 cells in the intervention group was significantly reduced [(67.3±1.9)% vs (100±4.4)% for PANC1; (60.5±2.7)% vs (100.0±1.7)% for AsPC-1], and the proportion of cells in the G1 phase was significantly increased [(51.6±0.7)% vs (35.3±2.7)% for PANC1; (51.2±0.9)% vs (29.7±2.2)% for AsPC-1]. All these differences were statistically significant (all P values <0.05). Conclusions:High expression of PRMT5 was closely associated with poor prognosis in pancreatic cancer patients, and it may contribute to pancreatic cancer progression by regulating the cell cycle.

Early start denver model(ESDM)is a comprehensive early intervention approach for the children with autism spectrum disorder(ASD)between 12-month-old-36-month-old.The model is built upon the theoretical foundations of applied behavior analysis,denver model(DM),and pivotal response treatment,and it is one of the naturalistic developmental behavioral interventions.Compared with the other early intervention methods,ESDM is not limited by the environment of intervention;it encompasses all the areas of development during teaching practice and has been widely adopted for the early intervention of the children with ASD,and achieves the satisfactory therapeutic effect.The ESDM typically uses an intensive one-on-one intervention approach,but variabilities have emerged in its practical application,such as group ESDM(G-ESDM),parent-implemented ESDM(P-ESDM),and peer-mediated ESDM.In particular,G-ESDM and P-ESDM have provided the learning opportunities for more families,showing a broad application prospect.This study reviews the theoretical foundations,teaching models,and the effects of various intervention modalities of the ESDM in the treatment of ASD;combined with the domestic and international research findings,this study offers a reference for further studies on the mechanism of ESDM intervention for ASD.