The chapter Zhouyu in Guoyu says "Qi of the heaven and the earth moves without losing its order." With lucidity ascending and turbidity descending， Qi moves in a normal state， and Yin and Yang consolidate the foundation of the body. The mutual interference between lucidity and turbidity leads to the disorder of Qi movement， thus causing diseases. It is a pathological state of disorder between ascending and descending， as well as between entering and exiting， gradually evolving into a state of turbidity affecting lucidity and transforming into pathogen， which can be used to interpret and analyze the core of disease pathogenesis. The theory of lucidity and turbidity is connected with the harmony of nutrient and defensive aspects， Qi circulation， and sweat pore associating with Qi movement， and it has common implications with immune responses and nutrient metabolism system， intestinal mucosal barrier function， and mitochondrial energy synthesis. Modern studies have shown that intestinal flora imbalance， bile acid receptor inactivation， macrophage polarization imbalance， epithelial-mesenchymal transition， ferroptosis and other related microscopic pathological mechanisms are involved in the development and progression of ulcerative colitis. By delving into the common meaning of the classic theory of mutual interference between lucidity and turbidity in traditional Chinese medicine and modern medical pathological mechanisms， this paper summarizes the correspondence between the micropathological mechanism and the theory of mutual interference between lucidity and turbidity in the regulation and mamagement of ulcerative colitis. The combined use of sweet and warm medicinal materials consolidates the middle Qi and activates Qi circulation， thus ascending lucidity and descending turbidity. The combined use of pungent medicinal materials for dispersing and bitter medicinal materials for descending simultaneously raises warm and clear Qi. Wind-extinguishing medicinal materials facilitate the ascending of Qi and the opening of sweat pores. Accordingly， turbidity descends and lucidity ascends. The prescriptions incorporating these medication principles are in agreement with the therapeutic approach of following the normal flow of lucidity and turbidity. This paper clarifies the scientific connotation and micropathologic mechanism of ulcerative colitis from the perspective of mutual interference between lucidity and turbidity， providing new theories and prescriptions for the clinical diagnosis， treatment， and prevention of ulcerative colitis.

The historical development of endogenous wind （内风） is traced with time as the thread， based on the progression of factors such as syndromes， causes of disease， and pathogenesis. It is believed that the concept of wind syndrome originated in The Inner Canon of Yellow Emperor （《黄帝内经》）， encompassing both exogenous wind （外风） and endogenous wind syndrome. Over time， exogenous wind syndrome gradually evolved into mild syndromes and severe syndromes， while endogenous wind syndrome emerged from severe syndromes of exogenous wind. Endogenous wind syndrome has both syndrome and pathogenic attributes， and its theoretical system has gradually become more refined. Based on the theories of ancient and modern medical practitioners， and combining the holistic perspectives with Xiang （象） thinking， it is proposed that endogenous wind has both physiological and pathological distinctions. The physiological endogenous wind refers to the liver's moderate dispersing and regulating function， which helps to distribute qi （气）， blood， and body fluids， while pathological endogenous wind arises from abnormal liver dispersal. Therefore， in clinical practice， different treatment methods， such as tonifying， unblocking， and warming， can be applied according to the differentiation of deficiency and excess in the pathogenesis.

The theory of "Yang transforming Qi while Yin constituting form" in the Huangdi's Internal Classic is derived from the application， transformation， movement， and balance of Tao. It is highly condensed， revealing the true meaning of Tao and guiding the changes and progress of all natural things， including diseases. Therefore， the appearance of various physical diseases is the manifestation of Yin-Yang Qi transformation. Sweat pore， formed by the Qi transformation of Yin and Yang， is the nourishing and regulating system. It serves as the hub and channel， assisting in the flow and transformation of Qi， facilitating the exchange of material， energy， and information with the outside world. With sweat pore as the hub and based on the macro-control and holistic thinking of "Yang transforming Qi while Yin constituting form"， this paper explores the microscopic mechanisms underlying chronic liver disease. In combination with the roles of mitochondria， exosomes， and the ultraliver sieve structure in the formation and progression of chronic liver disease， this paper elucidates the close internal relationship between the disease's initial quality， symptom signs， and its physiological and pathological functions under the guidance of this theory. Modern studies have shown that autophagy， intestinal flora disorders， glucose and lipid metabolism disturbances， activation of inflammatory factors， ferroptosis， and other microscopic pathological mechanisms are involved in the occurrence and development of chronic liver disease. The common connotation of the Yin-Yang concept in traditional Chinese medicine （TCM） and the pathological mechanisms in modern medicine is deeply analyzed. The corresponding relevant microscopic mechanisms and the guiding role of the theory of "Yang transforming Qi while Yin constituting form-sweat pore" in the management of chronic liver disease are summarized. Wind medicine promotes growth and transformation through sweat pore. The combination of pungent and sweet medicines facilitates Yang and disperse Yin. The formulas， combining the characteristics of wind medicine and pungent and sweet medicines， fit the principle of "Yang transforming Qi while Yin constituting form-sweat pore". This paper combines both macro and micro perspectives to explain the scientific connotation and microscopic mechanisms of chronic liver disease based on the theory of "Yang transforming Qi while Yin constituting form-sweat pore"， and explore the prevention and treatment of chronic liver disease through the principles， methods， prescriptions， and medicines featured by combination of pungent and sweet medicines， facilitating Yang， activating sweat pore， and dispersing Yin， providing new ideas and reference for the clinical treatment of chronic liver disease.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

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.

Drug repurposing offers a promising alternative to traditional drug development and significantly reduces costs and timelines by identifying new therapeutic uses for existing drugs. However, the current approaches often rely on limited data sources and simplistic hypotheses, which restrict their ability to capture the multi-faceted nature of biological systems. This study introduces adaptive multi-view learning (AMVL), a novel methodology that integrates chemical-induced transcriptional profiles (CTPs), knowledge graph (KG) embeddings, and large language model (LLM) representations, to enhance drug repurposing predictions. AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning (MVL), matrix factorization, and ensemble optimization techniques to integrate heterogeneous multi-source data. Comprehensive evaluations on benchmark datasets (Fdataset, Cdataset, and Ydataset) and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art (SOTA) methods, achieving superior accuracy in predicting drug-disease associations across multiple metrics. Literature-based validation further confirmed the model's predictive capabilities, with seven out of the top ten predictions corroborated by post-2011 evidence. To promote transparency and reproducibility, all data and codes used in this study were open-sourced, providing resources for processing CTPs, KG, and LLM-based similarity calculations, along with the complete AMVL algorithm and benchmarking procedures. By unifying diverse data modalities, AMVL offers a robust and scalable solution for accelerating drug discovery, fostering advancements in translational medicine and integrating multi-omics data. We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.