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.

ObjectiveTo enhance teaching in postoperative cancer rehabilitation, this study developed an integrative Chinese-Western medicine postoperative oncology rehabilitation system, termed the medical oncology generative pre-trained transformer (MedOncoGPT). By introducing MedOncoGPT as an intelligent assistant, an integrated teaching model combining Chinese and Western medicine was established. The study evaluated its impact on students’ integrative clinical reasoning and practical abilities, providing support for instructional reform in related courses. MethodsUsing teaching resources as the knowledge base, MedOncoGPT was built upon the open-source ChatGLM model and incorporated Low-Rank Adaptation (LoRA) fine-tuning and retrieval-augmented generation (RAG) techniques to address postoperative integrative oncology scenarios. The system was applied in courses and clinical clerkships related to integrative oncology. In alignment with course objectives, a five-stage instructional process—pre-class preparation, in-class inquiry, simulated multidisciplinary consultation, clinical reinforcement, and teaching reflection—was designed to guide students in completing syndrome differentiation, comprehensive assessment, and follow-up planning within real or simulated case contexts. Comparative analyses of student engagement, syndrome differentiation thinking, evidence-based awareness, and interdisciplinary integration skills before and after the teaching reform were conducted using questionnaires, course assessments, classroom observations, and semi-structured interviews. ResultsFollowing the implementation of MedOncoGPT, students demonstrated improved performance in case analysis, prescription formulation, and integrative Chinese-Western medical evaluation compared with those receiving traditional instruction. Classroom participation and the relevance of student inquiries also increased. Self-assessment results indicated high levels of satisfaction with respect to clarity of integrative clinical reasoning, ability to retrieve and apply guideline-based evidence, and awareness of appropriate use of intelligent tools in clinical decision-making. More than 92% of students reported that the system facilitated understanding of abstract theoretical concepts presented in textbooks. Instructors noted that the system helped reduce lesson preparation time, enriched typical case materials and discussion scenarios, and promoted the translation of research findings into classroom teaching. Pilot data showed that, with MedOncoGPT assistance, the mean time for initial syndrome differentiation decreased from 18.4 min to 12.1 min, and the agreement rate increased from 68.3% to 82.5%. In the teaching pilot, the experimental group achieved a higher mean score on the final case analysis assessment than the control group (82.6 vs. 74.3). ConclusionThe integration of MedOncoGPT into teaching on postoperative integrative cancer rehabilitation enabled the establishment of a stable instructional process within existing curricula and enhanced students’ integrative clinical reasoning and evidence-based practice capabilities. The approach demonstrates positive potential for advancing the integration of research, clinical practice, and education and represents a valuable exploratory strategy for instructional reform in courses on integrative Chinese-Western medicine.

ObjectiveTo enhance teaching in postoperative cancer rehabilitation, this study developed an integrative Chinese-Western medicine postoperative oncology rehabilitation system, termed the medical oncology generative pre-trained transformer (MedOncoGPT). By introducing MedOncoGPT as an intelligent assistant, an integrated teaching model combining Chinese and Western medicine was established. The study evaluated its impact on students’ integrative clinical reasoning and practical abilities, providing support for instructional reform in related courses. MethodsUsing teaching resources as the knowledge base, MedOncoGPT was built upon the open-source ChatGLM model and incorporated Low-Rank Adaptation (LoRA) fine-tuning and retrieval-augmented generation (RAG) techniques to address postoperative integrative oncology scenarios. The system was applied in courses and clinical clerkships related to integrative oncology. In alignment with course objectives, a five-stage instructional process—pre-class preparation, in-class inquiry, simulated multidisciplinary consultation, clinical reinforcement, and teaching reflection—was designed to guide students in completing syndrome differentiation, comprehensive assessment, and follow-up planning within real or simulated case contexts. Comparative analyses of student engagement, syndrome differentiation thinking, evidence-based awareness, and interdisciplinary integration skills before and after the teaching reform were conducted using questionnaires, course assessments, classroom observations, and semi-structured interviews. ResultsFollowing the implementation of MedOncoGPT, students demonstrated improved performance in case analysis, prescription formulation, and integrative Chinese-Western medical evaluation compared with those receiving traditional instruction. Classroom participation and the relevance of student inquiries also increased. Self-assessment results indicated high levels of satisfaction with respect to clarity of integrative clinical reasoning, ability to retrieve and apply guideline-based evidence, and awareness of appropriate use of intelligent tools in clinical decision-making. More than 92% of students reported that the system facilitated understanding of abstract theoretical concepts presented in textbooks. Instructors noted that the system helped reduce lesson preparation time, enriched typical case materials and discussion scenarios, and promoted the translation of research findings into classroom teaching. Pilot data showed that, with MedOncoGPT assistance, the mean time for initial syndrome differentiation decreased from 18.4 min to 12.1 min, and the agreement rate increased from 68.3% to 82.5%. In the teaching pilot, the experimental group achieved a higher mean score on the final case analysis assessment than the control group (82.6 vs. 74.3). ConclusionThe integration of MedOncoGPT into teaching on postoperative integrative cancer rehabilitation enabled the establishment of a stable instructional process within existing curricula and enhanced students’ integrative clinical reasoning and evidence-based practice capabilities. The approach demonstrates positive potential for advancing the integration of research, clinical practice, and education and represents a valuable exploratory strategy for instructional reform in courses on integrative Chinese-Western medicine.

Lung cancer, the malignancy with the highest global mortality rate, is currently undergoing a paradigm shift from precision medicine to intelligent medicine in its diagnostic and therapeutic models. Artificial intelligence (AI), leveraging its core advantages in multimodal data fusion and high-dimensional featureextraction, has deeply permeated the entire disease continuum of lung cancer screening, diagnosis, and individualized treatment. AI demonstrates significant value in improving patient outcomes and enhancing clinical efficiency, thereby reshaping the fundamental logic and clinical practice pathways of lung cancer management. This article reviews the latest advances of AI in real-world clinical diagnosis and treatment scenarios for lung cancer, with a focus on multimodal data fusion architectures, breakthrough applications of AI-assisted lung cancer diagnosis and treatment, and the practical barriers to clinical translation. It critically analyzes core challenges including data standardization, privacy protection, and ethical compliance. Finally, it envisions the future landscape of a nationwide intelligent ecosystem for lung cancer diagnosis and treatment—driven by federated learning and empowered by data elements—providing a reference for the standardized application and innovative development of AI in precision lung cancer care.

Objective To analyze the infection status and epidemic trends of soil-borne nematode infections in Yubei, Chongqing City, in 2010,2021, and 2022. Methods The local populations from four survey sites of four towns in 2010 and five sites of five towns in 2021 and 2022 were surveyed regarding their basic information using a unified form. Fecal samples of the participants were collected and tested for soil-borne nematode infections using the modified Kato-Katz thick smear method. Results In 2010, 2 049 participants were surveyed, followed by 1 000 participants in 2021 and 2022. The overall prevalence of parasitic infections declined significantly from 3.86% to 0.20%. In 2010, soil-transmitted nematode included hookworms(3.81%) and roundworms(0.29%). In 2021, the infection rates of roundworms and hookworms were 1.70% and 0.10% respectively. Notably, only Ascaris was identified in 2022(0.20%). The≥60 age group consistently exhibited the highest infection rates across all surveys, followed by the 40-59 age group. The infection rates of males in the three surveys were 3.31%,1.92%, and 0.20% respectively, and those of females were 4.37%, 1.46%, and 0.20% respectively. There was no statistically significant difference in the infection rates between males and females. Educational attainment was inversely associated with infection; in 2010, the highest prevalence was observed among those with primary education or below, whereas in 2021, illiterate or semi-literate individuals showed the highest susceptibility. The occupational distribution of infections in 2010 indicated that retirees (8.33%), farmers(4.86%), and homemakers or unemployed individuals(3.45%)were the most affected. However, in 2021 and 2022, farmers emerged as the predominant occupational group with soil-transmitted nematode infections. Conclusions The infection rate of soil-borne nematodes showed a decreasing trend in Yubei, and the infection species changed from hookworms in 2010 to Ascaris in 2022. Farmers, the elderly, and people with low education levels should continue to be the focus of preventive and control efforts.

Objectives: Lonely death is defined as “a person living in a state of social isolation, disconnected from family, relatives, and others, who dies from suicide, illness, or other causes”. This study investigated the characteristics of individuals who die alone in Korea. Methods: We constructed a database of lonely death cases by linking data from the Korea Crime Scene Investigation Unit of the Korea National Police Agency with National Health Insurance Service (NHIS) records. A descriptive analysis was performed to evaluate the demographics, underlying diseases, and healthcare utilization patterns among lonely death cases. Results: Among the 3122 individuals identified as lonely death cases, 2621 (84.0%) were male and 501 (16.0%) were female. The most common age group was 50-59 years (n=930, 29.8%). The NHIS covered 2161 individuals (69.2%), whereas 961 individuals (30.8%) were enrolled in Medical Aid (MA). The highest number of lonely deaths occurred in Seoul areas, with 1468 cases (47.0%). Mood disorders were diagnosed in 1020 individuals (32.7%), and various alcohol-related diseases, including alcoholic liver disease, were also observed. Outpatient visits increased leading up to death but declined in the final 3 months, while hospitalizations decreased and emergency room visits slightly increased. Conclusions Most lonely death cases involved male in their 50s, with a disproportionately high number of MA beneficiaries compared to the general population. Many of these individuals also experienced mental health issues or alcohol-related disorders. Preventing social isolation and strengthening social safety nets are critical to reducing the occurrence of lonely deaths.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Persistent inflammation plays a pivotal role in the initiation and progression of renal fibrosis. Activation of the pattern recognition receptor retinoic acid-inducible gene-I (RIG-I) is implicated in the initiation of inflammation. This study aimed to investigate the upstream mechanisms that regulates the activation of RIG-I and its downstream signaling pathway. Eight-week-old male C57BL/6 mice were used to establish unilateral ureteral obstruction (UUO)-induced renal fibrosis model, and the renal tissue samples were collected 14 days later for analysis. Transforming growth factor-β (TGF-β)-treated mouse renal tubular epithelial cells were used in in vitro studies. The results demonstrated that, compared to the control group, UUO kidney exhibited significant fibrosis, which was accompanied by the increases of RIG-I, p-NF-κB p65 and inflammatory cytokines, such as TNF-α and IL-1β. Additionally, the protein level of the E3 ubiquitin ligase RNF125 was significantly downregulated and predominantly localized in the renal tubular epithelial cells. Similarly, the treatment of tubular cells with TGF-β induced the increases in RIG-I, p-NF-κB p65 and inflammatory cytokines while decreasing RNF125. Co-immunoprecipitation (Co-IP) assays confirmed that RNF125 was able to interact with RIG-I. Overexpression of RNF125 promoted the ubiquitination of RIG-I, and accelerated its degradation via the ubiquitin-proteasome pathway. Overexpression of RNF125 in UUO kidneys and in vitro tubular cells effectively mitigated the inflammatory response and renal fibrosis. In summary, our results demonstrated that the decrease in RNF125 under pathological conditions led to reduction in RIG-I ubiquitination and degradation, activation of the downstream NF-κB signaling pathway and increase in inflammatory cytokine production, which promoted the progression of renal fibrosis.
Animals ; Fibrosis ; Male ; Ubiquitination ; Mice ; Mice, Inbred C57BL ; DEAD Box Protein 58 ; Ubiquitin-Protein Ligases/physiology* ; Inflammation/metabolism* ; Ureteral Obstruction/complications* ; Kidney/pathology* ; Signal Transduction ; Transforming Growth Factor beta/pharmacology*

As an innovative dosage form, traditional Chinese medicine(TCM) dry powder inhalers have emerged as a focal point in the research and development of new preparations due to its high efficiency, safety, and bioavailability. This paper systematically reviewed the relevant literature and patents associated with TCM dry powder inhalers to analyze the origins and the current research and development status. Furthermore, this paper probed into the research and development ideas of TCM dry powder inhalers regarding clinical positioning, prescription screening, and druggability. Additionally, the paper thoroughly analyzed the technical barriers in druggability studies and elaborated on corresponding research techniques and coping measures. Furthermore, it emphasized the need for improved regulations and policies governing TCM dry powder inhalers, advocated for strengthened oversight, and called for the establishment of a scientific quality evaluation system. Measures such as promoting production-education-research collaboration, enhancing personnel training, and fostering international exchanges were proposed to provide a scientific and systematic reference for the future research, development, and application of TCM dry powder inhalers, thereby facilitating the rapid modernization of TCM.
Humans ; Dry Powder Inhalers/trends* ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/instrumentation* ; Administration, Inhalation