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.

Premature ovarian insufficiency(POI),also known as premature ovarian failure(POF),is one of the major causes of female infertility.Its incidence has been increasing year by year,seriously af-fecting women's reproductive health and becoming an increasingly serious public health problem world-wide.The pathogenesis of POI is complex and may be related to genetic,immune and environmental fac-tors,but in recent years,oxidative stress(OS)has received widespread attention as a key factor that can affect the function of ovarian granulosa cells(GCs),which can lead to the occurrence of POI.Reactive oxygen species(ROS)regulate the proliferation,survival and apoptosis of GCs through multiple signaling pathways,such as PI3K-Akt,MAPK,TGF-β/Smad,Notch,etc.AMPK and mitochondrial autophagy play important roles in attenuating the ROS damage and protecting the ovarian function.Excessive ROS disrupts the autophagy and lysosomal functions,leading to the accumulation of intracellular waste prod-ucts,thus affecting the physiological function and endocrine stability of GCs.In addition,OS can in-crease the risk of POI by affecting hormone synthesis and disrupting the function of GCs,leading to an imbalance in estrogen and progesterone levels.Herein we review the mechanism of OS in POI,explore how OS affects ovarian decline through the regulation of signaling pathways and cellular functions,and provide a theoretical basis for the clinical treatment of POI,which in turn provides new research ideas for its early diagnosis and prevention.

BACKGROUND:Knee osteoarthritis is a common degenerative disease that significantly impacts patients'quality of life and increases the societal healthcare burden.Early and accurate diagnosis of knee osteoarthritis is crucial for the treatment and prognosis of patients.Traditional diagnostic methods are not only subjective and time-consuming but also do not guarantee consistently high accuracy.OBJECTIVE:To develop an automatic diagnostic method for knee osteoarthritis based on deep learning,utilizing deep learning networks to improve diagnostic accuracy and efficiency.METHODS:A new network model,YOLOV8-ViT,was proposed by replacing the backbone network of YOLOv8n with the Efficient-ViT network and incorporating attention mechanisms for the automatic identification and classification of X-ray images of knee osteoarthritis.The experimental dataset included 5 078 X-ray images of patients with knee osteoarthritis obtained from the Third Affiliated Hospital of Guangzhou University of Chinese Medicine.Three imaging physicians annotated the sites of knee osteoarthritis and classified them according to the Kellgren-Lawrence grading standard using Labelme software,and the results were combined.The evaluation indicators used in this study included Precision,F1 score,mean average precision(mAP),Recall,val/box_loss,val/cls_loss,and val/dfl_loss.RESULTS AND CONCLUSION:The experimental results showed that the YOLOV8-ViT model outperformed the YOLOv5n,YOLOv8n,and YOLOv9n models in terms of precision,mAP50,mAP50-95,F1 score,and Recall,while lowering val/box_loss,val/cls_loss,and val/dfl_loss by 0.496,0.45,and 0.523;1.037,0.305,and 0.728;and 0.267,0.654,and 0.854,respectively.These experimental data validate that this model has high detection accuracy.

Objective To investigate the correlation between cognitive function and medication compliance in patients with type 2 diabetes mellitus(T2DM).Methods Patients with T2DM who were admitted to the Department of Endocrinology,Drum Tower Hospital,Nanjing University School of Medicine from July 2023 to December 2023 were selected.The clinical data and laboratory results of the patients were collected.The medication compliance of the patients was evaluated by Adherence to Refills and Medications Scales(ARMS).And the overall cognitive function and independent cognitive domain tests were performed.According to the diagnostic criteria of mild cognitive impairment(MCI),patients were divided into normal cognitive group and MCI group.Linear regression analysis was used to evaluate the correlation between cognitive function and medication compliance in T2DM patients.Multivariate logistic regression analysis was used to explore the relationship between cognitive dysfunction and poor medication compliance in T2DM patients.Results A total of 216 patients with T2DM were enrolled,including 113 patients with normal cognitive function and 103 patients with MCI.The ARMS score(16.4±4.1 vs.15.1±2.8)and the rate of poor medication compliance(54.4%vs.31.0%)in the MCI group were higher than those in the normal cognitive group(all P<0.05).After adjusting for gender,age,years of education and glycosylated hemoglobin,ARMS scores were significantly negatively correlated with immediate memory,attention and delayed memory scores(all P<0.05).Multivariate logistic regression analysis showed that patients with MCI had a higher risk of poor medication adherence[OR=2.645,95%CI=(1.414,4.946),P<0.001].Conclusions Poor cognitive function,especially memory and concentration,is associated with reduced medication compliance in patients with T2DM.Patients with memory and attention problems should be given appropriate medication advice to improve their compliance in clinical practice.

Objective To design a dynamic monitoring platform for mastering the changes of outpatient service in public tertiary grade A hospitals.Methods An outpatient dynamic monitoring platform was designed with B/S architecture and developed with Java platform,which used Oracle 11g database for data storage and hypertext transfer protocol encapsulated as WebAPI to realize data transmission with systems.There were five functional modules involved in the platform for patient flow monitoring,doctor attendance monitoring,public service monitoring,outpatient medical staff communication and data storage and analysis for decision making.Results The platform developed realized comprehensive monitoring and closed-loop management of the outpatient department,and enhanced the quality and efficiency of patient service.Conclusion The platform developed solves the problems of outpatient management in terms of monitoring and early warning,personnel communication and assisted decision making,and improves outpatient management in intellectualization and automation.[Chinese Medical Equipment Journal,2025,46(5):39-47]

Objective:The aim of this study was to present an institution's experience with cochlear reimplantation（CRI）, to assess surgical challenges and post-operative outcomes and to increase the success rate of CRI. Methods:We retrospectively evaluated data from 76 reimplantation cases treated in a tertiary center between 2001 and 2022. Clinical features include caused of CRI, type of failure, surgical issues, and auditory speech performance were analyzed. Categorical Auditory Performance （CAP） and Speech Intelligibility Rating （SIR） scores were used to evaluate pre-and post-CRI outcomes. Our center's consecutive cohort of 1 126 patients had seven patients, while 69 patients were from other cochlear implant centers. Device failure was the most common cause of CRI（68/76）, with the remaining cases including flap complications（3/76）, magnet displacement（3/76）, secondary meningitis（1/76）, and foreign bodies around the implant（1/76）. Postoperative auditory and speech outcome improved in 31.6%（24/76） of patients, remained unchanged in 63.2%（48/76）, and decreased in CAP and SIR scores in 5.2%（4/76） of patients. Postoperatively, the seven patients with cochlear ossification and fibrosis scored lower on the overall CAP and SIR scale than non-ossification individuals, which is a significant factor in surgical success rates and auditory-speech outcomes. Conclusion:CRI surgery is a challenging but relatively safe procedure, and most reimplanted patients experience favorable postoperative outcomes. Medical complications and intracochlear damage are the main causes of poor postoperative results. Therefore, minimally invasive CI has a positive significance for reducing the difficulty of CRI surgery and improving the CI performance.
Humans ; Cochlear Implantation/methods* ; Retrospective Studies ; Cochlear Implants ; Male ; Female ; Postoperative Period ; Treatment Outcome ; Adult ; Speech ; Middle Aged ; Postoperative Complications ; Replantation ; Cochlea/surgery*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.