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.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Background Polycyclic aromatic hydrocarbons (PAHs) are significant organic components of PM_2.5 and exhibit carcinogenic and mutagenic properties. Long-term exposure to high level of atmospheric particulate matter and particle-bound PAHs may contribute to the burden of environmentally related diseases in China. Objective To characterize PM_2.5 concentrations and PM_2.5-bound PAHs in three districts of Guangzhou from 2016 to 2024, and to assess the incremental lifetime cancer risk (ILCR) associated with inhalation exposure to PAHs among different population groups. Methods PM_2.5 samples were collected monthly from the 10th to the 16th day of each month at rooftop monitoring sites on office buildings in Yuexiu, Conghua, and Panyu districts between 2016 and 2024. PM_2.5 concentrations were measured, and 16 priority PAHs were quantified using high-performance liquid chromatography (HPLC). Seasonal and regional variations in PM_2.5 and PAH concentrations were analyzed using the Kruskal-Wallis test. Potential PAH sources were identified using diagnostic ratio analysis and principal component analysis (PCA). The ILCR model was employed to estimate inhalation-related cancer risks for different population groups. Results From 2016 to 2024, the annual median PM_2.5 concentrations in Guangzhou were 51.0, 46.0, 45.0, 41.5, 31.0, 32.0, 30.0, 26.0, and 37.5 μg·m⁻³, respectively, showing an overall declining trend. PM_2.5 concentrations varied significantly by season, following the order of winter > spring/autumn > summer (H=475.341, P < 0.001). Spatially, PM_2.5 concentrations were highest in Yuexiu, followed by Panyu and Conghua (H=36.226, P < 0.001). The annual median PAH concentrations were 3.95, 4.22, 3.73, 3.13, 2.54, 2.16, 2.78, 2.36, and 1.75 ng·m⁻³, respectively. PAH concentrations showed a similar seasonal pattern (winter > spring/autumn > summer; H=320.392, P < 0.001). However, their spatial distribution differed from that of PM_2.5: Conghua > Panyu > Yuexiu (H=55.938, P < 0.001). Diagnostic ratios and PCA indicated that the major sources of PAHs were traffic-related emissions (gasoline and diesel combustion) and coal combustion, with additional contributions from petroleum volatilization and biomass burning. Benzo[a]pyrene (BaP) toxic equivalent concentrations declined over time and remained below the Chinese standard limit of 1 ng·m⁻³ after 2018. The median inhalation-related ILCRs were 0.094×10⁻⁶ for children, 0.035×10⁻⁶ for adolescents, and 0.293×10⁻⁶ for adults. Conclusion From 2016 to 2024, PM_2.5 and PM_2.5-bound PAH pollution levels in Guangzhou generally declined. Suburban areas had the lowest PM_2.5 concentrations but the highest PAHs concentrations. Both PM_2.5 and PM_2.5-bound PAHs exhibited significant seasonal variations, with the highest levels in winter and the lowest levels in summer. The primary sources of PAHs were vehicular emissions and coal combustion, and PAHs posed no significant carcinogenic risk to the study population.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To investigate influence of different phantoms on the results of quality control for the images of cone beam computed tomography(CBCT)for breast on the basis of quality control for breast CBCT.Methods:Five different manufacturers'phantoms were selected,and they were placed at the position of testing breast in clinical examination to conduct position for phantom according to the method of the national health industry standard WS 818-2023.The analysis focused on the differences of evaluation results of using different phantoms for image quality on the basis of a series of parameters included uniformity,resolution of high contrast,resolution of low contrast,and CT value of water in scanning images of different phantoms.Data collection and image reconstruction were performed respectively by using commonly clinical procedures.Corresponding module images were selected from the reconstructed images of standard breast phantom.The common layer thickness and projection method of the system were set to record and analyze data.Results:The image uniformity of measured results of the five phantoms were respectively 42.37±2.01,-5.83±0.15,3.76±0.15,2.16±0.06,3.60±0.10.The differences of the image uniformities among the five phantoms were statistically significant(F=1310.02,P<0.001),and the differences of the CT values of the measured water among the five phantoms were statistically significant(F=9 846.46,P<0.001).The differences in the resolution of low contrast among them were also statistically significant(F=27.50,P<0.001).However,the results of the resolution of high contrast were stability,and there was no significant difference in that among the five phantoms.Conclusion:The measured results of quality control of different phantoms are different.

AIM To establish the near-infrared spectroscopy quantitative models for moisture,23-acetylalismol B and 23-acetylalismol C in Alismatis Rhizoma decoction pieces.METHODS The near-infrared spectroscopy(NIRS)data were collected in 95 batches of decoction pieces,after which drying method was adopted in the content determination of moisture,HPLC was applied to determining the contents of 23-acetylalismol B and 23-acetylalismol C,the quantitative models were established by partial least squares method combined with feature extraction algorithms.RESULTS The model training determination coefficients were 0.952 6,0.958 1 and 0.920 8,along with the prediction determination coefficients of 0.930 0,0.905 2 and 0.906 4,the residual prediction deviations(PRD)of 4.00,3.58 and 3.46,and the root mean square error ratios of prediction values to calibration values(RMSEP/RMSEC)of 1.15,1.11 and 1.06,respectively.CONCLUSION The quantitative models based on NIRS exhibit good prediction effects,which can be used for the rapid quality detection of Alismatis Rhizoma decoction pieces.

Objective:To investigate the value of coronary CTA (CCTA)-based traditional features and radiomics of plaque in the identification of culprit lesions that caused acute myocardial infarction (AMI).Methods:This was a retrospective multicenter study. From July 2016 to November 2023, a total of 344 patients from the Affiliated Hospital of Qingdao University (training cohort, n=184), Shandong Provincial Hospital Affiliated to Shandong First Medical University (validation cohort, n=88) and Qilu Hospital of Shandong University (test cohort, n=72) who received percutaneous coronary intervention (PCI) due to AMI and underwent CCTA within 48 hours of AMI were enrolled. The culprit plaques and non-culprit plaques were identified using a combination of electrocardiogram, CCTA, and angiographic findings. The vessel, plaque location, plaque type, Coronary Artery Disease-Reporting and Data System (CAD-RADS) score, high-risk plaque characteristics, plaque length, plaque volume, and burden were analyzed, and 1 904 radiomics features were extracted for each plaque. The traditional imaging model, the radiomics model, and the combined model were established by using multivariate Logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each model in identifying culprit lesions. The DeLong test was used for the comparison of AUC between every two models. The net reclassification index (NRI) was used to evaluate the incremental value of the combined model to the traditional imaging model and the radiomics model. The decision curve analysis (DCA) was used to assess the clinical net benefit of these models. A correlation heatmap was used to evaluate the correlation between the radiomics score and traditional CCTA factors. The interpretable analysis of the decision process of the combined model was performed by the Shapley Additive exPlanations (SHAP). Results:In the validation cohort and the test cohort, the AUC of the traditional imaging model developed by the vessel, plaque type, positive remodeling and CAD-RADS score was 0.898 (95% CI 0.869-0.922) and 0.881 (95% CI 0.848-0.910), respectively. The radiomics model developed by six radiomics features was 0.863 (95% CI 0.831-0.891) and 0.863 (95% CI 0.827-0.864), respectively. The AUC of the combined model was 0.930 (95% CI 0.905-0.950)and 0.919 (95% CI 0.889-0.942), respectively. In the validation cohort and the test cohort, the AUC of the combined model was higher than that of the traditional imaging model ( Z=4.013, 4.272, P<0.001) and that of the radiomics model ( Z=4.819, 3.784, P<0.001), respectively. In the validation cohort, the combined model yielded an NRI of 20.43% (95% CI 10.43%-30.44%, P<0.001) and 20.21% (95% CI 9.62%-30.80%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. In the test cohort, the combined model yielded an NRI of 28.05% (95% CI 16.72%-39.38%, P<0.001) and 23.57% (95% CI 13.58%-33.56%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. DCA showed the combined model had the highest clinical net benefit. The correlation heatmap showed the radiomics score was not correlated or only weakly correlated with traditional CCTA factors. SHAP indicated the radiomics and CAD-RADS score contributed significantly to the model. Conclusion:The CCTA-based traditional features and radiomics of plaque have favorable performance for the identification of culprit plaques in patients with AMI.

Cosmetics may be an important source of human exposure to per-and polyfluoroalkyl substances(PFASs),posing risks to human health.In this study,a nontarget screening method for PFASs in cosmetics was developed using ultra-high performance liquid chromatography-high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS)based on the Kendrick mass defect(KMD).The sample was extracted by ultrasonic assisted extraction prior to being analyzed by UHPLC-Q-Orbitrap HRMS.Acquisition of HRMS data was achieved in both full scan and data-dependent(Full MS/dd MS2)mode.The data collected by HRMS were imported into an in-lab built R script for processing.Samples retained the mass spectra peaks with KMD values in the range of 0.85-1 or 0-0.15 for in-and out-of-library matching;when KMD deviation(δKMD)<0.001 and CF 2 mass error(δMS)<15 ppm,it was considered as a potential PFASs homologues.According to matches of parent ions(MS),fragment ions(MS2)and retention time(RT)with the in-house built PFASs database,the screened and identified potential PFASs were categorized to 5 confidence levels(CL1-CL5).A total of 15 kinds of PFASs homologues with confidence level of CL3 and above were screened from 13 cosmetics products and 8 cosmetic raw materials,including perfluoroalkyl alcohol,hydroperfluoroalkyl sulfonic acid,chloroperfluoroalkyl sulfonic acid,etc.with concentrations ranging from 1.9 ng/g to 98.1 ng/g.The nontarget screening method could be used to screen and identify PFASs homologues feasibly and therefore provided data basis for management and control of PFASs addition in cosmetics.

Adenosine triphosphate(ATP),as the core energy metabolism molecule in living systems,has dynamic changes closely related to fundamental physiological processes.To meet the urgent demand for spatiotemporal ATP detection in vivo and in situ,the development of highly sensitive multifunctional synchronous sensing fluorescent probes has become a recent research focus.These dual-function probes achieve fluorescence detection of dual targets by designing recognition sites for ATP alongside biological factors or microenvironment parameters such as reactive oxygen/nitrogen/sulfur species,metal ions,and enzymes,enabling physiological/pathological state correlation analysis through bioimaging.This paper systematically reviews recent advances in fluorescent probes for the collaborative detection of ATP and key biomolecules.It specifically examines probe construction strategies based on specific molecular recognition mechanisms(e.g.,metal coordination competition,electrostatic interactions,and host-guest recognition),multi-modal optical signal transduction mechanisms(ratiometric fluorescence,fluorescence lifetime,and photodynamic therapy),and their applications in pathological models such as oxidative stress monitoring,metal homeostasis imbalance,and enzyme activity co-detection.Finally,from the perspective of molecular probe engineering,current challenges and future research directions are proposed to provide methodological support for precise analysis of ATP-related life process regulation networks.

Objective To verify the efficacy of a domestic human DNA quantification kit based on real-time fluorescence quantitative PCR in detecting the total human DNA concentration,male DNA concen-tration in mixed male/female DNA samples,the degree of DNA degradation and inhibitor tolerance.Methods Samples with different concentrations,different male/female ratios,different concentrations of inhibitors,and different degradation degrees were tested using the domestic human DNA quantification kit based on real-time fluorescence quantitative PCR.This kit was compared with a similar product on the market and was applied to the detection of DNA from real cases.Results This human DNA quan-tification kit can effectively detect human DNA as low as 0.001 65 ng/μL,and 6.25 pg/μL of male DNA in mixed samples with a male-to-female ratio of 1∶15 000.Even when the sample contains as high as 400 ng/μL of humic acid or 1 000 μmol/L of hemin alone,the DNA concentration can still be accurately detected.The degradation index can effectively characterize the degradation degree of the sample.This kit has been successfully applied in forensic practice.Conclusion This human DNA quan-tification kit is accurate and reliable in detection.It can accurately reflect the degradation of DNA and inhibitor tolerance.It has good performance in quantitative accuracy,determination of the male/female ratio in mixed samples,and inhibitor tolerance.It has application potential in forensic case examination.