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.

Objective: To observe the distribution characteristics of sex differences in physical growth among children and adolescents aged 6-15 years in Taiwan, China from 2007 to 2024, so as to provide clues for improving growth assessment standards and promoting the health of children and adolescents. Methods: Using publicly available height and weight data for children and adolescents aged 6-15 years in Taiwan, China from 2007 to 2024 released by the statistics agency of the Taiwan education authorities, sex difference indices were analyzed. Growth curve charts and Pearson correlation were used to analyze the correlation between height/weight and year, as well as trends of change with age and year. These were compared with data from the 8th National Survey on Students Constitution and Health in 2019, covering Han and ethnic minority groups aged 6-15 years in mainland China. Results: The sex difference index for height among children and adolescents in Taiwan, China ranged from -1.20% to 6.67%, showed a trend of decreasing first and then increasing with age. The sex difference index for weight ranged from 3.76% to 19.15%, exhibited an age related trend of a slight initial increase, followed by a decrease, and then an increase. The sex difference indices for height in the 12-15 age groups and for weight in the 15-year-old group were positively correlated with the year ( r =0.74, 0.66, 0.61, 0.92 ; 0.63), while the sex difference indices for weight in the 6-8 age groups were negatively correlated with the year ( r =-0.71, -0.77, -0.53) (all P <0.05). In 2024, the height of children and adolescents in Taiwan, China increased gradually with age, but the growth rate for girls slowed down after age 12. A "two crossover" was observed in height between boys and girls, with boys being taller than girls in the 6-9 age range and after age 12. Weight for both sexes gradually increases with age, but boys have greater weight than girls at all ages. In 2019, the sexual differences in body size among children and adolescents in the Taiwan region, China (the sex difference indices for height:-0.96% to 6.49%；the sex difference indices for weight:4.69%-17.89%) fell within the variation ranges of counterparts in mainland China (the sex difference indices for height:-5.43% to 7.69%；the sex difference indices for weight:-10.12% to 21.56%). Conclusion The sex differences in physical growth among children and adolescents in Taiwan, China are dynamically changing with age and over the long term.

BACKGROUND:Long-term blood flow restriction combined with low-intensity resistance training has been shown to effectively treat obesity by alleviating chronic inflammation and endothelial dysfunction.However,the immediate effects of a single session on serum concentrations of vascular endothelial function and inflammatory biomarkers remain unclear.OBJECTIVE:To explore the short-term effects and recovery capacity of blood flow restriction during low-intensity resistance training on serum biomarkers of vascular endothelial function and inflammation in obese male college students.METHODS:Twenty obese male college students(body mass index＞30 kg/m2,body fat percentage＞25％)were randomly assigned to a control group(0％arterial occlusion pressure)or a blood flow restriction group(80％arterial occlusion pressure).Both groups performed a single session of low-intensity resistance training at an intensity corresponding to a perceived exertion of 11-13 on the Rate of Perceived Exertion Scale.The training was repeated three times,with each session lasting 30 minutes,totaling 1.5 hours.Serum biomarkers were measured before exercise,immediately post-exercise,1 hour post-exercise,and 24 hours post-exercise.The assessed biomarkers included vascular endothelial function markers,inflammatory markers,and insulin function indicators.RESULTS AND CONCLUSION:(1)Vascular endothelial function:Acute exercise increased vascular endothelial growth factor A concentrations in both groups.The blood flow restriction group significantly elevated serum platelet-derived growth factor and nitric oxide levels(P＜0.05),while the control group showed a significant increase in nitric oxide synthase levels(P＜0.05).Angiotensin Ⅱ concentrations decreased immediately after acute exercise in both groups but remained significantly higher than baseline in the blood flow restriction group after 24 hours of recovery,and there was a significant difference between the two groups(P＜0.05).(2)Regarding inflammatory markers,the blood flow restriction group induced higher levels of hypoxia and significantly upregulated tumor necrosis factor-α and hypoxia-inducible factor-1α concentrations(P＜0.05).Adiponectin and leptin levels upregulated in both groups,with a more pronounced rise in adiponectin level in the blood flow restriction group than the control group(P＜0.05).lnterleukin-6 concentrations decreased in both groups,with a greater reduction in the blood flow restriction group.(3)For insulin function,the blood flow restriction and control groups showed immediate increases and decreases in insulin levels after exercise,respectively,but these returned to below and above baseline levels after 24 hours of recovery.Both groups reduced insulin resistance index in adipose tissue,with a more significant improvement in the blood flow restriction group(P＜0.05).To conclude,compared with low-intensity resistance training,short-term blood flow restriction induces more favorable changes in inflammatory and vascular endothelial biomarkers,improving inflammation and endothelial dysfunction with longer-lasting effects.However,further studies are needed to validate these findings over long-term interventions.

BACKGROUND:Long-term blood flow restriction combined with low-intensity resistance training has been shown to effectively treat obesity by alleviating chronic inflammation and endothelial dysfunction.However,the immediate effects of a single session on serum concentrations of vascular endothelial function and inflammatory biomarkers remain unclear.OBJECTIVE:To explore the short-term effects and recovery capacity of blood flow restriction during low-intensity resistance training on serum biomarkers of vascular endothelial function and inflammation in obese male college students.METHODS:Twenty obese male college students(body mass index＞30 kg/m2,body fat percentage＞25％)were randomly assigned to a control group(0％arterial occlusion pressure)or a blood flow restriction group(80％arterial occlusion pressure).Both groups performed a single session of low-intensity resistance training at an intensity corresponding to a perceived exertion of 11-13 on the Rate of Perceived Exertion Scale.The training was repeated three times,with each session lasting 30 minutes,totaling 1.5 hours.Serum biomarkers were measured before exercise,immediately post-exercise,1 hour post-exercise,and 24 hours post-exercise.The assessed biomarkers included vascular endothelial function markers,inflammatory markers,and insulin function indicators.RESULTS AND CONCLUSION:(1)Vascular endothelial function:Acute exercise increased vascular endothelial growth factor A concentrations in both groups.The blood flow restriction group significantly elevated serum platelet-derived growth factor and nitric oxide levels(P＜0.05),while the control group showed a significant increase in nitric oxide synthase levels(P＜0.05).Angiotensin Ⅱ concentrations decreased immediately after acute exercise in both groups but remained significantly higher than baseline in the blood flow restriction group after 24 hours of recovery,and there was a significant difference between the two groups(P＜0.05).(2)Regarding inflammatory markers,the blood flow restriction group induced higher levels of hypoxia and significantly upregulated tumor necrosis factor-α and hypoxia-inducible factor-1α concentrations(P＜0.05).Adiponectin and leptin levels upregulated in both groups,with a more pronounced rise in adiponectin level in the blood flow restriction group than the control group(P＜0.05).lnterleukin-6 concentrations decreased in both groups,with a greater reduction in the blood flow restriction group.(3)For insulin function,the blood flow restriction and control groups showed immediate increases and decreases in insulin levels after exercise,respectively,but these returned to below and above baseline levels after 24 hours of recovery.Both groups reduced insulin resistance index in adipose tissue,with a more significant improvement in the blood flow restriction group(P＜0.05).To conclude,compared with low-intensity resistance training,short-term blood flow restriction induces more favorable changes in inflammatory and vascular endothelial biomarkers,improving inflammation and endothelial dysfunction with longer-lasting effects.However,further studies are needed to validate these findings over long-term interventions.

Background: The tight junction protein claudin18.2 (CLDN18.2) has been implicated in poor prognosis and suboptimal immunotherapy response in gastric cancer (GC). This study investigates the clinicopathological relevance of CLDN18.2 expression and its association with molecular subtypes in GC patients from a high-incidence region, combining transcriptomic and proteomic approaches to explore how CLDN18.2 contributes to progression and metastasis. Methods: A retrospective cohort of 494 GC patients (2019–2024) underwent immunohistochemical analysis for CLDN18.2, Epstein-Barr virus (Epstein–Barr virus–encoded RNA), p53, human epidermal growth factor receptor 2 (HER2), and mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6). CLDN18.2 positivity was defined as moderate to strong (2+/3+) membranous staining in ≥75% of tumor cells. Clinicopathological correlations, biomarker associations, and survival outcomes were evaluated. Transcriptomic and proteomic sequencing was performed to explore molecular mechanisms. Results: CLDN18.2 positivity was observed in 26.9% (133/494) of gastric adenocarcinomas. CLDN18.2-positive tumors correlated with TNM stage (p = .003) and shorter overall survival (p = .018). No associations were identified with age, sex, HER2 status, microsatellite instability, or Epstein-Barr virus infection. Transcriptomic profiling revealed CLDN18.2-high tumors enriched in pathways involving cell junction disruption, signaling regulation, and immune modulation. Proteomic profiling showed that tumors with high CLDN18.2 were enriched in multiple mechanism-related pathways such as integrated metabolic reprogramming, cytoskeletal recombination, immune microenvironment dysregulation, and pro-survival signaling. These mechanisms may collectively contribute to tumor progression and metastasis. Conclusions CLDN18.2 overexpression is associated with poor prognosis in GC patients. Transcriptomic and proteomic analyses demonstrate that CLDN18.2 promotes tumor progression and metastasis, underscoring its potential as an independent prognostic factor in regions with a high incidence of GC.

Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

Acute kidney injury (AKI) is a prevalent and life-threatening clinical syndrome characterised by a rapid decline in renal function and diverse pathological etiologies. The condition has been demonstrated to be associated with elevated mortality rates and an increased risk of progression to chronic kidney disease. At present, clinicians depend heavily on conventional functional markers, such as serum creatinine and urine output, for the diagnosis and staging of the disease. It is evident that these conventional indicators characteristically manifest a considerable temporal delay and only undergo modification subsequent to considerable tissue damage. This severely restricts the timeframe for early detection and timely therapeutic intervention. Furthermore, standard markers fail to provide specific biological information regarding the underlying cellular injury mechanisms. The utilisation of advanced probe technologies in molecular imaging offers a robust alternative to overcome these inherent diagnostic limitations.This comprehensive review systematically evaluates recent progress in the design and application of two primary categories of molecular imaging tools for acute kidney disease, specifically reactive probes and enzyme-activated probes. Reactive probes are engineered to specifically interact with redox-active chemical species, including hydrogen peroxide, peroxynitrite, hypochlorous acid, and sulfur dioxide. Because oxidative stress constitutes a primary early event in acute renal tubular damage, these probes enable researchers and clinicians to visualize early cellular injury and radical accumulation well before global renal functional decline becomes evident. We discuss the application of these reactive probes across multiple imaging modalities including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic techniques. Photoacoustic imaging combines high spatial resolution with deep tissue penetration and has successfully demonstrated the ability to provide diagnostic alerts up to 12 h before any detectable rise in serum creatinine levels. Additionally, specific reactive probes have shown promising translational potential when tested by high-throughput screening in clinical human urine samples. Enzyme-activated probes target the specific catalytic activity of disease-relevant enzymes. These include well-documented renal tubular structural biomarkers such as NAG, GGT, and ALP, along with apoptosis-related caspases and specific nitroreductases. By responding only to enzymatic cleavage, these tools provide highly specific and pathology-directed imaging readouts. Recent structural design strategies in this field have advanced significantly beyond single-enzyme detection. Researchers are now focusing on sophisticated dual-target recognition to minimize background noise, multimodal integration to cross-validate imaging signals, and theranostic applications where probes simultaneously deliver diagnostic feedback and therapeutic agents to injured tissues. Nanotechnology serves as a fundamental enabler for realizing these advanced probe functions. By precisely optimizing nanoparticle parameters such as hydrodynamic size, surface charge, and targeting ligands, researchers can achieve amplified signal output, highly precise kidney delivery, and protection against premature degradation in the systemic circulation. For example, modifying surface charges can significantly enhance the active uptake of nanoprobes by damaged renal tubular epithelial cells.While preclinical probe development has progressed rapidly, moving these technologies into routine clinical practice remains a major challenge. We analyze the translational feasibility and current obstacles from biological, technological, and regulatory perspectives. Although biological targets such as KIM-1, FAP, and ALP have been validated in extensive patient cohorts, practical barriers severely limit their immediate clinical application. These obstacles involve complex changes in in vivo pharmacokinetics. During an acute injury episode, the extreme drop in the glomerular filtration rate alters probe clearance and can cause unwanted systemic accumulation or confusing background imaging signals. Other major hurdles include a lack of comprehensive long-term toxicity data and the absence of standardized manufacturing protocols to ensure batch-to-batch consistency. Future successful translation will require rigorous multi-center clinical studies to confirm the true diagnostic value of these probes over traditional markers. Researchers must also establish strict standardization of imaging procedures and comprehensive safety evaluations. Ultimately, this review provides a thorough reference framework for designing clinically translatable molecular probes and building a precision diagnostic imaging system for acute kidney injury.

ObjectiveTo investigate the molecular mechanisms related to angiogenesis during the development and progression of diabetic retinopathy （DR）. MethodsAngiogenesis-related genes were obtained from the Gencard website and intersected with differentially expressed genes from DR datasets （GSE60436 and GSE94019）. Functional enrichment and protein-protein interaction （PPI） networks were then used to screen candidate genes and evaluate their diagnostic value. Gene set enrichment analysis （GSEA） was used to explore potential pathways underlying candidate genes， and immune infiltration analysis revealed associations between candidate genes and immune cells. Cellular experiments were conducted to validate the role of fibronectin 1 （FN1） in human retinal microvascular endothelial cells （HRMECs） under high glucose （HG） conditions. ResultsA total of 237 differentially expressed genes related to angiogenesis were identified， enriched in pathways such as phosphoinositide 3-kinase/protein kinase B signaling pathway （PI3K-Akt）， tumor suppressor protein 53 （P53）， tumor necrosis factor （TNF）， and Janus kinase （JAK）/signal transducer and activator of transcription signaling pathway （STAT）. Among them， collagen type I alpha 1 chain （COL1A1）， COL1A2， FN1， TNF， and tumor protein p53 （TP53） were key genes with high diagnostic value. GSEA indicated that these genes were involved in multiple signaling pathways， including P53. CIBERSORTx analysis revealed significant associations with the infiltration of multiple immune cells. HG treatment led to the upregulation of FN1. In HG-induced HRMECs， compared with the si-NC control group， si-FN1 significantly reduced cell proliferation， migration， and tube formation， while P53 protein expression was increased. ConclusionThis study reveals the important role of FN1 in angiogenesis in DR and suggests that it may be a potential diagnostic and therapeutic target.

Objective:This study aims to investigate the differences in hemostatic efficacy and patient comfort between an innovative domestically produced biodegradable nasal packing sponge and a traditional absorbent sponge following endoscopic nasal surgery. Methods:A prospective, randomized controlled trial design was utilized, including 30 patients who were divided into two groups according to random allocation, each receiving one of the two types of nasal packing. The study assessed the hemostatic efficacy, comfort, and safety of the materials by comparing the rates of no bleeding within 24 hours after packing, re-bleeding rates after 48 hours, pain ratings in the head and nasal areas, scores on a visual analog scale for nasal ocular symptoms, and safety indicators between the two groups. Results:The rates of no bleeding within 24 hours post-packing were 73.33% for both the experimental and control groups, with a no-bleeding rate of 100% after 48 hours in both groups. The pain rating in the head and nasal areas at various times post-packing was Grade Ⅰ（100%） in both groups, with no statistically significant difference（P=1.000）. The experimental groups sneezing score on the day of packing was（0.73±1.03）, lower than the control groups（2.27±1.67）, （P=0.007）; after 48 hours, the experimental groups sneezing score was（0.67±0.98）, also lower than the control groups（1.67±1.18）, （P=0.019）. There was no significant difference between the two groups in the Lund-Kennedy scoring during endoscopic examinations at the screening period, 7 days, 1 month, and 3 months post-packing（P>0.05）. Laboratory tests for other examination indicators were normal in both groups. Conclusion:The innovative domestically produced biodegradable nasal packing sponge not only provides hemostatic efficacy comparable to imported materials but also significantly improves patient comfort after surgery. It represents an economical and effective choice for nasal packing materials.
Humans ; Prospective Studies ; Surgical Sponges ; Endoscopy/methods* ; Male ; Female ; Epistaxis/prevention & control* ; Middle Aged ; Nasal Surgical Procedures/methods* ; Adult