Objective To explore the role of E1A binding protein p300 (EP300)-mediated crotonylation (Kcr) modification of malic enzyme 1 (ME1) in ferroptosis of renal tubular epithelial cells. Methods C57BL/6 mice were divided into Sham operation group (Sham group), DMSO vehicle control + ischemia-reperfusion (IR) injury group (Vehi + IR group), and EP300 inhibitor C646 + IR injury group (C646 + IR group), with 12 mice in each group. Pathological changes in renal tissues were evaluated in each group, and indicators of renal function, ferroptosis, and fibrosis were assessed. Another 24 mice were used to establish the IR injury model to analyze changes in Kcr modification levels and EP300 expression over the 14-day course of IR injury. The in vitro HK-2 cell experimental model was established and divided into control group, hypoxia/reoxygenation (H/R) group, and C646 + H/R group. Corresponding HK-2 cells were transfected with the ME1-K337R plasmid, in which lysine 337 (K) was mutated to arginine (R) to mimic the de-Kcr modification. Small interfering RNA was used to target EP300 and transfect the cells in order to obtain EP300 knockdown cells (siEP300). The expression of ferroptosis-related proteins and fibrosis phenotypes was detected. Results At 14 d after IR injury, the protein Kcr level and EP300 expression were increased in mice. Compared with the Sham group, the Vehi+IR group showed markedly disrupted renal tissue structure, extensive red collagen deposition in the renal interstitium, decreased expression levels of glutathione, reduced nicotinamide adenine dinucleotide phosphate (NADPH), and glutathione peroxidase 4 (GPX4, P＜0.01), increased malondialdehyde and serum creatinine levels (P＜0.01), decreased ME1 enzymatic activity (P＜0.001), and increased expression of fibronectin 1 and smooth muscle actin-α (P＜0.001). Compared with the Vehi+IR group, the C646+IR group showed alleviated renal pathological injury, improved renal function, and reduced ferroptosis and fibrosis (P＜0.05). Compared with the control group, HK-2 cells subjected to H/R treatment exhibited aggravated ferroptosis and fibrosis (P＜0.05); compared with the H/R group, the C646+H/R group showed reduced ferroptosis and fibrosis (P＜0.05). Transfection with the ME1-K337R plasmid and siEP300 showed reduced ME1 Kcr, ferroptosis, and fibrosis. Conclusions EP300 contributes to ferroptosis in renal tubular epithelial cells by mediating ME1 crotonylation, and inhibition of EP300 may help alleviate the chronic progression following IR injury.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To carry out a dynamic simulation analysis on the surgical process of the surgical robot for pedicle screw placement so as to enhance the safety of the procedure.Methods Firstly,the process of pedicle screw placement were analyzed to determine the three typical force conditions during pedicle screw track drilling including no-load condition,bone layer switching condition and spine dynamic displacement condition.Secondly,a virtual protype model of the surgical robot for pedicle screw placement was constructed with the automated dynamic analysis of mechanical systems(ADAMS).Finally,the dynamic characteristics of the surgical robot were simulated and analyzed with considerations on the three typical force conditions.Results The driving torque of the robot joints was sensitive to the load applied to the end of the opener mechanism under a wide range of operating conditions.Conclusion The surgical robot meets the requirements for pedicle screw placment,and a new idea is provided for enhancing the accuracy of pedicle screw placement.[Chinese Medical Equipment Journal,2025,46(8):32-37]

Objective To carry out a dynamic simulation analysis on the surgical process of the surgical robot for pedicle screw placement so as to enhance the safety of the procedure.Methods Firstly,the process of pedicle screw placement were analyzed to determine the three typical force conditions during pedicle screw track drilling including no-load condition,bone layer switching condition and spine dynamic displacement condition.Secondly,a virtual protype model of the surgical robot for pedicle screw placement was constructed with the automated dynamic analysis of mechanical systems(ADAMS).Finally,the dynamic characteristics of the surgical robot were simulated and analyzed with considerations on the three typical force conditions.Results The driving torque of the robot joints was sensitive to the load applied to the end of the opener mechanism under a wide range of operating conditions.Conclusion The surgical robot meets the requirements for pedicle screw placment,and a new idea is provided for enhancing the accuracy of pedicle screw placement.[Chinese Medical Equipment Journal,2025,46(8):32-37]

Crossmodal transfer is the ability to apply the knowledge acquired in one sensory modality to another. Researches on crossmodal transfer investigate how the brain represents information from different sensory modalities, and provide new insights to improve cognitive processing efficiency and reduce repeated learning. To clarify the characteristics and mechanism of crossmodal transfer, this article first introduced the crossmodal transfer effect in different field of research, such as object recognition, category learning, and time perception. After that, the theoretical researches on the representation type of crossmodal transfer were reviewed, mainly including multisensory theory and multisensory mental imagery theory as well as the supportive and opposite findings. The research progresses on the neural mechanism of crossmodal transfer using ERP and fMRI techniques were introduced, mainly including metamodal theory, and multisensory reverse hierarchy theory as well as the supportive and opposite findings. The objective and subjective factors which influenced crossmodal transfer effect were sorted out, in which we suggested that the modality dominance phenomenon supports the metamodal theory, while other factors such as sensory experience, age, setting of learning tasks and stimulus features support theories such as the multisensory hypothesis. Finally, we described the potential applications of the current research findings on crossmodal transfer and pointed out future research questions in this field.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Aim To investigate whether diallyl disul-fide (DADS) augments the sensitivity of DJ-1 (protein/ nucleic acid deglycase) overexpressed human gastric SGC7901 cells to 5-FU (5-fluorouracil). Methods The experimental groups include control group, DADS group, VCR (vincristine) group, VCR + DADS group, DJ-1 group, DJ-1 + DADS group. MTT was used to analyze the effect of DADS on 5 -FU (5 -fluorou- racil) induced proliferation inhibition. Flow cytometry was performed to examine the effect of DADS on cell apoptosis. RT-PCR, Western blot, and immunofluo-rescence were used for determine the effect of DADS on the drug resistance associated gene expression. Results DADS enhanced the proliferation inhibitory effect of 5-FU on DJ-1 overexpressed cells and VCR resistant cells. DADS could induce apoptosis in VCR-resistant cells. DADS downregulated the expression of DJ-1 while inducing apoptosis in DJ-1 overexpressed cells. DJ-1 overexpression upregulated the expression of P-gp (P-glycoprotein), Bcl-2, and XIAP (X-linked inhibitor of apoptosis protein), downregulated the expression of caspase-3. DADS decreased the expression of P-gp, Bcl-2, and XIAP, while increased the expression of caspase-3 in DJ-1 overexpressed cells and VCR-resistant cells. Conclusions DADS can augment the sensitivity of DJ-1 overexpressed cells to 5-FU, which is related to its antagonism against DJ-1 mediated upregula- tion of P-gp, Bcl-2, XIAP, and downregulation of caspase-3.

OBJECTIVE: To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects. METHODS: Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles. RESULTS: A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness. CONCLUSION The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.
Humans ; Male ; Middle Aged ; Female ; Ankle Brachial Index ; Cohort Studies ; Gene-Environment Interaction ; Vascular Stiffness/genetics* ; Pedigree ; Pulse Wave Analysis/methods* ; Genotype

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

OBJECTIVE: The study aimed to analyze the applicability of the World Health Organization's exclusionary guidelines for Urinary creatinine (Ucr) in the general Chinese population, and to identify Ucr related factors. METHODS: We conduct a cross-sectional study using baseline data from 21,167 participants in the China National Human Biomonitoring Program. Mixed linear models and restricted cubic splines (RCS) were used to analyze the associations between explanatory variables and Ucr concentration. RESULTS: The geometric mean and median concentrations of Ucr in the general Chinese population were 0.90 g/L and 1.01 g/L, respectively. And 9.36% samples were outside 0.3-3.0 g/L, including 7.83% below the lower limit and 1.53% above the upper limit. Middle age, male, obesity, smoking, higher frequency of red meat consumption and chronic kidney disease were associated significantly with higher concentrations of Ucr. Results of the RCS showed Ucr was positively and linearly associated with body mass index, inversely and linearly associated with systolic blood pressure, diastolic blood pressure, triglycerides level, and glomerular filtration rate, and were non-linearly associated with triiodothyronine. CONCLUSION The age- and gender-specific cut-off values of Ucr that determine the validity of urine samples in the general Chinese population were recommended. To avoid introducing bias into epidemiologic associations, the potential predictors of Ucr observed in the current study should be considered when using Ucr to adjust for variations in urine dilution.
Middle Aged ; Male ; Humans ; Creatinine ; Cross-Sectional Studies ; Asian People ; Glomerular Filtration Rate ; China