ObjectiveTo investigate the protective effect of genistein （Gen） on etoposide-induced chondrocyte senescence and its underlying mechanism. MethodsThe C28/I2 cell line was treated with different concentrations of Gen and etoposide， and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide， with Gen intervention. Senescence-associated β-galactosidase （SA-β-gal） staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 （Prdx6）， cyclin-dependent kinaseto clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group， the C28/I2 chondrocyte viability significantly increased （P<0.01）， the expression ofsenescence-associated proteins p21 and p16 decreased （P<0.01， P<0.05）， the expression of senescence-associated genes p21 and p16 reduced （both P<0.01）， the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished （P<0.05， P<0.01）， and the proportion of SA-β-gal-positive cells decreased （P<0.01） in the Gen+etoposide group. Compared with the Control group， the expression of Prdx6 was downregulated in the etoposide group （P<0.05）. Compared with the etoposide group， the expression of Prdx6 was upregulated in the Gen+etoposide group （P<0.01）. Compared with the Control group， the GPx activity significantly decreased in the si-Prdx6 group （P<0.01）. Furthermore， compared with the si-Prdx6 group， the GPx activity increased in the si-Prdx6+Gen group （P<0.05）. Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown， the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group （both P<0.01）. ConclusionGen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.

AIM:To evaluate the accuracy of a portable non-contact tonometer(PNCT)compared with a traditional non-contact tonometer(NCT)in measuring intraocular pressure(IOP)at different levels.METHODS:Patients who presented to Ningbo Eye Hospital between January 2025 and January 2026 were retrospectively included. All patients underwent measurements using PNCT, NCT, and Goldmann applanation tonometry(GAT). Based on the GAT measurements, the patients were categorized into a low IOP group(IOP≤16 mmHg), a moderate IOP group(16 mmHg0.05). Spearman correlation analysis revealed that the IOP values measured by both PNCT and NCT were positively correlated with those measured by GAT(rs=0.86 and 0.84, respectively, P<0.05). Intraclass correlation coefficient(ICC)analysis demonstrated an ICC of 0.89 between PNCT and GAT(P<0.05), and 0.88 between NCT and GAT(P<0.05), with an overall ICC of 0.88 among the three instruments(P<0.05). Bland-Altman analysis indicated a mean bias of 0.1 mmHg [95% limits of agreement(LoA): -7.3 to 7.6 mmHg] between PNCT and GAT, and a mean bias of 0.1 mmHg(95%LoA: -8.4 to 8.6 mmHg)between NCT and GAT. Based on the GAT measurements, the eyes were categorized into a low IOP group(60 eyes, 32.6%, IOP≤16 mmHg), a moderate IOP group(63 eyes, 34.2%, 16 mmHg0.05), whereas the difference between NCT and GAT showed a positive correlation with CCT(rs=0.23, P<0.05).CONCLUSION:The IOP measurements obtained by PNCT, NCT, and GAT demonstrated strong correlation and good agreement, with PNCT being less influenced by CCT. However, as IOP levels increased, the measurement errors of both PNCT and NCT also increased. Therefore, PNCT and NCT readings should only serve as references and cannot replace GAT.

ObjectiveTo investigate the effects and mechanisms of pulchinenoside A （PSA） on tumor necrosis factor-α （TNF-α） -induced abnormal proliferation， migration， and invasion of synovial fibroblasts. MethodsA synovitis model was established by stimulating SW982 synovial cells with TNF-α. The low-density lipoprotein receptor-related protein 1 （LRP1） was knocked down using LRP1-specific siRNA or inhibited by the receptor-associated protein （RAP）. Cells were treated with various concentrations of PSA， and cell viability was assessed by CCK-8 assay. Protein levels of LRP1， matrix metalloproteinase-3 （MMP3）， and N-cadherin were measured by Western blotting. Proliferation was evaluated using an EdU incorporation assay. Migration and invasion capacities were examined by Transwell and wound-healing assays. mRNA expression of LRP1， MMP3， N-cadherin， IL-1β， IL-6， and TNF-α was detected by reverse transcription quantitative real-time PCR （RT-qPCR）. Immunofluorescence staining was used to visualize the expression of MMP3 and N-cadherin. The involvement of LRP1 was further verified with the inhibitor RAP. ResultsCompared with the TNF-α-treated model group， PSA treatment significantly reduced SW982 cell viability （P<0.05）， downregulated MMP3 and N-cadherin expression （both P<0.01）， and decreased the proportion of EdU-positive cells （P<0.05）. Moreover， TNF-α stimulation upregulated LRP1 expression compared with normal controls （P<0.01）， whereas PSA treatment reversed this increase （P<0.05）. LRP1 knockdown or inhibition markedly decreased MMP3 and N-cadherin levels compared with the model group （both P<0.01）. Similarly， the combination of PSA and RAP led to significant reductions in MMP3 and N-cadherin expression compared with the model group （both P<0.01）. ConclusionPSA inhibits TNF-α-induced abnormal proliferation， migration， and invasion of synovial， at least in part， by downregulating LRP1 expression.

ObjectiveTo explore the clinical potential of magnetic resonance elastography （MRE） for assessing the stiffness of common intracranial tumors. MethodsA retrospective analysis was conducted on 47 patients with brain tumors who underwent surgical treatment at The First Affiliated Hospital of Sun Yat-sen University between April 2023 and September 2024. The cohort included 10 cases of glioma， 12 cases of vestibular schwannoma， and 25 cases of meningioma. All patients underwent multiparameter MRI and MRE preoperatively. After co-registering MRE images with contrast-enhanced 3D T1-weighted images， three regions of interest （ROIs） were placed in the areas of maximum and minimum tumor stiffness respectively to measure the shear stiffness values， and the mean was calculated as the average shear stiffness. Additionally， one ROI was placed in the white matter and one in the grey matter of the posterior horn of the lateral ventricle at the basal ganglia level to obtain normal reference values. A neurosurgeon， blind to the MRE results， graded the intraoperative tumor stiffness based on surgical videos using a 5-point scale （1： soft； 5： hard）. Intraclass correlation coefficient （ICC） was used to assess inter-observer consistency. Analysis of variance （ANOVA） and nonparametric tests were employed to compare the differences of shear stiffness values between groups. Spearman correlation analysis was used to examine the correlation between elasticity values and clinicopathological parameters. The discriminatory efficacy of shear stiffness values for tumor types was evaluated with receiver operating characteristic （ROC） curves. ResultsThe ICCs for elasticity values measured by two physicians in the hardest and softest tumor areas were 0.868 and 0.831， respectively （both P＜ 0.01）. The maximum， minimum， and average shear stiffness values of meningiomas［（1.91±0.28） m/s， （1.66±0.25） m/s， （1.78±0.26） m/s， respectively］ were significantly higher than those of gliomas［（1.59±0.23） m/s， （1.42±0.23） m/s， （1.50±0.22） m/s， respectively （P＜0.05）］. The shear stiffness values of vestibular schwannomas［（1.70±0.30） m/s， （1.51±0.23） m/s， （1.61±0.26） m/s， respectively） were lower than those of meningiomas and higher than those of gliomas， but these differences were not statistically significant （both P＞0.05）. The shear stiffness values of white matter were significantly higher than that of grey matter［（1.63±0.08） m/s vs. （1.39±0.12） m/s， P＜0.05）］. In the overall sample， the maximum， minimum， and average shear stiffness values were significantly positively correlated with the intraoperative hardness grade （r_s = 0.591， r_s = 0.541， r_s = 0.571， respectively； all P＜0.001）， negatively correlated with WHO grade （r_s = -0.458， r_s = -0.458， r_s = -0.480， respectively； all P＜0.01）， but showed no correlation with Ki-67 （all P＞0.05）. ConclusionMRE can be used to assess the stiffness of intracranial tumors and to some extent differentiate between tumor types， which aids in formulating more individualized preoperative surgical plans.

Abstract The cooccurrence of multi disease among children and adolescents has become increasingly prominent, necessitating a shift from "single disease separate treatment" to "multi disease co prevention". Focusing on four common health problems in children and adolescents, namely, myopia, depression, overweight/obesity, and spinal abnormalities, the paper systematically reviews the association between four categories of factors, society, environment, family, and individual behavior, and the co occurrence of the aforementioned health problems. The findings indicate that particulate matter 2.5 exposure, light at night, physical inactivity, excessive screen time, and unhealthy diet constitute the primary cross dimensional risk network. Based on these findings, the paper proposes a collaborative action framework involving family, school, and society, emphasizing systematic strategies ranging from upstream environmental governance to downstream behavioral intervention, so as to provide evidence for the practice and policy making of multi disease co-prevention in children and adolescents.

Objective : To explore the effects and mechanisms of Kobophenol A ( KPA) on lipopolysaccharide ( LPS) -induced M1 macrophage polarization，and to provide a theoretical basis for the treatment of inflammatory immune diseases and the development of new drugs． Methods: The M1 macrophage polarization model of RAW264. 7 was established by LPS induction，and the peroxiredoxin 6 ( Prdx6) knockdown model was constructed using the Prdx6 inhibitor MJ33 and Prdx6-siRNA．RAW264. 7 cells，a mouse macrophage cell line，were treated with various concentrations of KPA． Cell viability was assessed using the CCK-8 assay．The expression levels of Prdx6 and M1 macrophage polarization-related proteins，including inducible nitric oxide synthase ( iNOS) and cyclooxygenase-2 ( COX-2) ，were detected by Western blot and immunofluorescence staining．The expression levels of Prdx6 and M1 macrophage polarization-related genes iNOS，interleukin-6 ( IL-6) ，and tumor necrosis factor α ( TNF-α) ，were measured by RT-qPCR. Flow cytometry was employed to detect the expression of cluster of differentiation 86 ( CD86) ，a marker of M1 macrophages． Results: Compared with the LPS-induced M1 macrophage polarization model ， KPA significantly reversed the morphological changes of M1 macrophage polarization in RAW264. 7 macrophages and decreased the expression of M1 macrophage polarization-related proteins iNOS，COX- 2，CD86 and related genes iNOS，IL-6，TNF-α ( all P＜0. 05) ．In addition，LPS significantly downregulated the expression of Prdx6 in RAW264. 7 macrophages，while KPA upregulated the expression of Prdx6．Moreover，treatment with the Prdx6 inhibitor MJ33 significantly upregulated the expression of iNOS，a marker of M1 macrophage polarization，in RAW264. 7 macrophages，whereas treatment with KPA significantly downregulated the expression of iNOS ( all P＜0. 05) ． Conclusion KPA inhibits LPS-induced M1 polarization of RAW264. 7 macrophages by upregulating the expression of Prdx6．

This research investigates the regulatory role of the transcription factor PU.1 in type 1 conventional dendritic cells(cDC1)and its therapeutic potential of modulating the nuclear factor kappaB(NF-κB)cells signaling pathway in non-small cell lung cancer(NSCLC).Utilizing single-cell transcriptome sequencing and comprehensive bioinformatics tools,including the CIBERSORT algorithm,we analyzed the immune cell landscape within NSCLC tissues.Our analysis revealed distinct NSCLC subtypes and delineated the developmental trajectories and functional distinctions of cDC1 cells.Key differentially expressed genes(DEGs)and pivotal functional modules within these cells were identified,highlighting PU.1 as a critical mediator underexpressed in NSCLC samples.Functionally,PU.1 demonstrated the induction of the NF-κB pathway,which led to inhibited tumor proliferation and enhanced activation of cDC1,thereby suggesting its role in tumor immune surveillance.In vivo models confirmed the suppressive effect of PU.1 on NSCLC progression,mediated through its influence on cDC1 functionality via the NF-κB pathway.These findings propose PU.1 as a promising target for NSCLC therapeutic strategies,emphasizing the importance of transcriptional regulators in the tumor microenvironment.

This research investigates the regulatory role of the transcription factor PU.1 in type 1 conventional dendritic cells (cDC1) and its therapeutic potential of modulating the nuclear factor kappaB (NF-κB) cells signaling pathway in non-small cell lung cancer (NSCLC). Utilizing single-cell transcriptome sequencing and comprehensive bioinformatics tools, including the CIBERSORT algorithm, we analyzed the immune cell landscape within NSCLC tissues. Our analysis revealed distinct NSCLC subtypes and delineated the developmental trajectories and functional distinctions of cDC1 cells. Key differentially expressed genes (DEGs) and pivotal functional modules within these cells were identified, highlighting PU.1 as a critical mediator underexpressed in NSCLC samples. Functionally, PU.1 demonstrated the induction of the NF-κB pathway, which led to inhibited tumor proliferation and enhanced activation of cDC1, thereby suggesting its role in tumor immune surveillance. In vivo models confirmed the suppressive effect of PU.1 on NSCLC progression, mediated through its influence on cDC1 functionality via the NF-κB pathway. These findings propose PU.1 as a promising target for NSCLC therapeutic strategies, emphasizing the importance of transcriptional regulators in the tumor microenvironment.

BACKGROUND:Cross-sectional area and fat infiltration are the standard parameters for quantifying paravertebral muscle,but it is too cumbersome and time-consuming to introduce new quantifying indicators. OBJECTIVE:To investigate the relationship between paravertebral muscle and spinopelvic sagittal parameters and the predictive value of lumbar indentation value for sagittal balance in patients with isthmic spondylolisthesis.METHODS:The study included 87 patients diagnosed with spondylolisthesis,all of whom had grade Ⅱ spondylolisthesis according to Meyerding classification,including 40 males and 47 females,with a mean age of (51.4±9.1) years. The sagittal vertical axis,pelvic incidence angle,pelvic inclination angle,sacral inclination angle,lumbar lordosis,thoracic kyphosis,and the difference between pelvic incidence and lumbar lordosis were measured. The total cross-sectional area,functional cross-sectional area,and fat infiltration of lumbar paracolateral muscles were measured. Pearson correlation analysis was used to investigate the correlation between sagittal parameters and paravertebral muscle measurements. Multiple linear regression was used to analyze the effects of lumbar indentation value,age,sex,and body mass index on spinopelvic sagittal balance. The receiver operating characteristic curve was used to find the best cut-off point of the indentation value of the lumbar spine,and the relationship of sagittal vertical axis and pelvic incidence with lumbar lordosis was evaluated.RESULTS AND CONCLUSION:(1) According to Pearson correlation analysis,the total cross-sectional area of the multifidus muscle was significantly correlated with lumbar lordosis (r=0.464,P<0.01) and the difference between pelvic incidence and lumbar lordosis (r=-0.306,P<0.01). The functional cross-sectional area of multifidus muscle was significantly correlated with lumbar lordosis (r=0.367,P<0.01) and the difference between pelvic incidence and lumbar lordosis (r=-0.228,P<0.05). The indentation value of lumbar spine was significantly correlated with the sagittal vertical axis (r=-0.300,P<0.01),lumbar lordosis(P=0.417,P<0.01),thoracic kyphosis (r=0.351,P<0.01),and the difference between pelvic incidence and lumbar lordosis (r=-0.319,P<0.01). (2) According to multiple linear regression analysis,the indentation value of lumbar spine was independently correlated with the difference between pelvic incidence and lumbar lordosis and the sagittal vertical axis. 55％ (11/20) of patients with lumbar indentation value ≤11.5 mm had sagittal vertical axis ≤ 50 mm,while 96％(64/67) of patients with lumbar indentation value>11.5 mm had sagittal vertical axis ≤ 50 mm. 30％ (6/20) of patients with the difference between pelvic incidence and lumbar lordosis ≤ 11.5 mm had the difference between pelvic incidence and lumbar lordosis ≤ 10°,while 66％ (44/67) of patients with lumbar indentation value>11.5 mm had the difference between pelvic incidence and lumbar lordosis ≤ 10°. (3) It is concluded that both total cross-sectional area and functional cross-sectional area were significantly correlated with lumbar lordosis and the difference between pelvic incidence and lumbar lordosis. Lumbar indentation value,as a new indicator for the evaluation of paravertebral degeneration,was independently correlated with the sagittal vertical axis and the difference between pelvic incidence and lumbar lordosis,and had certain predictive value for postoperative sagittal plane correction. It was a simple and practical method for the evaluation of spinopelvic sagittal plane and paravertebral muscle degeneration. The degeneration of the paravertebral muscle is related to spinopelvic sagittal balance.

Objective To analyze the effects of postoperative radiotherapy and other factors on the prognosis of metastatic sarcomatoid renal cell carcinoma(sRCC)so as to provide reference for the clinical decision-making.Methods Data of all sRCC patients during 2004-2018 were extracted from the American Surveillance,Epidemiology,and End Results(SEER)database,and 337 patients were ultimately enrolled.Patients were divided into the postoperative non-radiotheropy group(n=255)and postoperative radiotherapy group(n=82)based on different treatment modalities.Baseline data were compared between the two groups.The 1-year overall survival(OS)and cancer-specific survival(CSS)rates were calculated.Kaplan-Meier(K-M)survival curves were plotted.The prognostic factors were identified with univariate and multivariate Cox regression analyses.Results No significant differences were observed in baseline data between the two groups(P＞0.05).The 1-year OS(25.6％vs.30.1％)and CSS(26.2％vs.30.8％)in the postoperative radiotherapy group were lower than those in the postoperative no-radiotheropy group,but the differences were not statistically significant(P＞0.05).Multivariate Cox regression analysis showed that year of diagnosis,patients' age,tumor size,T stage,N stage and chemotherapy were independent prognostic factors of sRCC(P＜0.05).Patients diagnosed in 2015-2018 and treated with chemotherapy had a good prognosis,while patients＞61 years,with tumor size＞147 mm,tumor stage T3-T4,and stage N1 had a poor prognosis.Conclusion The year of diagnosis,patients'age,tumor size,tumor stage and chemotherapy were independent prognostic factors,and postoperative radiotherapy did not significantly improve the prognosis of metastatic sRCC patients.