Based on the theory of "shaoyang（少阳） resembling the pivot" and collateral diseases， this article proposes that pulmonary fibrosis （PF） can be divided into three stages including wind bi （痹）， constraint bi， and atrophy bi. The core pathogenesis of PF is the obstruction of the pivot and pulmonary collateral obstruction. In terms of treatment， the basic principles are to harmonize and regulate the pivot， and to promote the circulation of the lung collaterals. Depending on the different characteristics of the "essence-attribute-function"， treatment methods such as harmonizing and regulating the pivot， resolving phlegm and removing stasis， supplementing deficiency and harmonizing collaterals are suggested. This approach ensures the regulation of the pivot， smooth circulation of qi and blood， unblocking of the lung collaterals and nourishing the lung body， achieving the goals of balancing the ascending and descending of qi， removing phlegm and stasis， and relieving cough and wheezing.

Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

BACKGROUND: Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment. METHODS: The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process. RESULTS: The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC. CONCLUSIONS This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Combined Modality Therapy ; Perioperative Care

Based on the pharmacokinetics theory, this study investigated the pharmacokinetic characteristics of albiflorin, paeoniflorin, wogonoside, and wogonin in normal and febrile rats and summarized absorption and elimination rules of Dayuanyin in them to provide reference for further development and clinical application of Dayuanyin. Blood samples were taken from the fundus venous plexus of normal and model rats after intragastric administration of Dayuanyin at different time points. The concentration of each substance in blood was determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS) technique at different time points. DAS 2.0, a piece of pharmacokinetics software, was used to calculate the pharmacokinetic parameters of each component. The results show that the 4 components had good linear relationship in their respective ranges, and the results of methodological investigation met the requirements. The pharmacokinetic parameters of C_(max), T_(max), t_(1/2), AUC_(0-t), AUC_(0-∞), and MRT_(0-t) were calculated by the DAS 2.0 non-compartmental model. Compared with those in the normal group, C_(max) and AUC_(0-t) of the 4 components in the model group were significantly increased. There were significant differences in the pharmacokinetic characteristics between the normal and model groups, suggesting that the absorption and elimination of Dayuanyin may be affected by the changes of internal environment of the body in different physiological states.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Fever/metabolism* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Glucosides/pharmacokinetics* ; Monoterpenes

Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Molecular Docking Simulation ; Male ; Antipyretics/metabolism* ; Rats, Sprague-Dawley ; Tissue Distribution ; Mass Spectrometry ; Chromatography, High Pressure Liquid ; Hypothalamus/metabolism*

AIM To investigate the variations in mercury dissolution from HgS-containing traditional medicines in three kinds of simulated gastrointestinal dissolution media.METHODS 39 batches of 15 types of HgS-containing traditional medicines were collected,total mercury content and dissolved mercury concentrations in simulated gastric fluid,simulated intestinal fluid,and L-cysteine-containing simulated intestinal fluid were measured.The maximum daily intake of total mercury and soluble mercury was calculated based on the maximum daily clinical dosage.RESULTS Among the 15 types of medicines,the maximum daily intake of total mercury varied by 156 times,the daily intake of soluble mercury varied by 3 502 times in simulated gastric fluid,313 times in simulated intestinal fluid,and 10 663 times in L-cysteine-containing simulated intestinal fluid,approximately.CONCLUSION For the 15 types of HgS-containing traditional medicines,the daily maximum intake of soluble mercury showed greater variations than that of total mercury.Soluble mercury concentration is more closely correlated with intestinal absorption of mercury and thus represents a more rational quality control indicator for HgS-containing traditional medicines.