Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Objective:To explore the impact of the stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)pathway on the senescence of rapid pacing HL-1 myocytes.Methods:HL-1 cells were divided into five groups: the control group(HL-1 cells without any treatment), pacing group(HL-1 cells paced for 48 hours), STING siRNA group(HL-1 cells paced for 48 hours and transfected with STING siRNA), NC siRNA group(HL-1 cells paced for 48 hours and transfected with NC siRNA), and H151 inhibitor group(HL-1 cells paced for 48 hours with the addition of 1 μmol/L STING inhibitor H151). Mitochondrial membrane potential was assessed in control and pacing group cells, and mitochondrial MitoTracker and TFAM co-localization staining was performed on these cells.Cellular senescence was evaluated using β-galactosidase staining in each group, and the positive rate of cellular senescence was observed and calculated.Western blotting was employed to detect the expression levels of STING, IRF3, P-IRF3, P16, P21, and P53 proteins in all groups.Immunofluorescence was utilized to examine the expression distribution of STING and P21 across the various groups.ELISA was performed to measure the concentrations of interleukin(IL)-1β, IL-6, and IL-8 in the cell supernatants from each group as part of the senescence-associated secretory phenotype(SASP).Results:Compared with the control group, the ratio of mitochondrial JC-1 multimer to monomer was significantly decreased in the pacing group( t=16.42, P<0.05), the co-localization of mitochondrial MitoTracker and TFAM in the cells was significantly weakened, the proportion of cells with positive cellular senescence-associated β-galactosidase staining significantly increased in the pacing group, the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 proteins were significantly elevated in the pacing group, and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants were markedly increased.Compared with the pacing group, the proportion of cells with positive cellular senescence-associated β-galactosidase staining decreased in the STING siRNA group and H151 inhibitor group ( F= 18.13, P<0.05), the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 were reduced in the STING siRNA group and H151 inhibitor group ( F=16.84, 26.56, 74.70, 31.80, 31.23, all P<0.05), and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants decreased( F=197.80、1 339.00、1 308.00, all P<0.001). Conclusions:Rapid pacing of HL-1 cells can promote mtDNA release into the cytoplasm, activate the STING-IRF3 pathway, accelerate cellular senescence, and enhance the secretion of SASP.Inhibiting the expression of STING can delay the senescence induced by the rapid pacing of HL-1 cells and reduce SASP secretion.

Objective:To analyze the conventional ultrasound（CUS）and contrast-enhanced ultrasound（CEUS）features of hepatic lymphoma，and to investigate the value of CEUS in the diagnosis of hepatic lymphoma.Methods:The images of 39 patients（39 lesions）with hepatic lymphoma pathologically confirmed by surgery and puncture from March 2012 to July 2024 at Zhongshan Hospital，Fudan University were retrospectively analyzed. Evaluations of CUS included the echogenicity，morphology，color Doppler flow imaging（CDFI）situation，evaluations of CEUS included enhancement type，enhancement degree compared to the peripheral normal liver parenchyma and time to enhancement.Results:In the 39 lesions，hypoechoic lesions were detected in 31（79.49%，31/39）patients on CUS. CDFI detected linear or branched color flow signals inside the lesions in 21（53.85%，21/39）lesions，and peripheral color flow signals around the lesions in 3 lesions，while arterial flow signals were detected in 16 of them，with a resistance index of 0.50～0.77（0.67 ± 0.02）. In addition，signs of non-compacted normal blood vessels passing through the lesions were detected in 5 lesions. After injection of contrast medium，39 lesions showed different degrees of enhancement，mainly showed entirety homogeneous enhancement，during the arterial phase of CEUS，34（87.18%，34/39）lesions showed fast enhancement，and when the enhancement reached the peak，26（66.67%，26/39）lesions revealed hyper-enhancement，showing “fast progression”. There were 38（97.44%，38/39）lesions in the portal and delayed phases showed “fast forward”.Conclusions:CUS and CEUS can provide some value in the diagnosis and differential diagnosis of hepatic lymphoma.

Objective To investigate the relationship between the expression levels of mir-155/Th17 and mir-23b-3p/Tfh in peripheral blood and the prognostic value of secondary atopic dermatitis(AD)in AIDS patients.Methods In this study,80 AIDS patients were treated in our hospital from February 2021 to December 2023.The subjects were divided into AD group and non-AD group according to whether they had secondary AD.The levels of mir-155,Th17,mir-23b-3p and Tfh in peripheral blood of AD group and non-AD group were compared.Spearman method was used to analyze the relationship between levels of mir-155,Th17,mir-23b-3p and Tfh in peripheral blood and secondary AD in AIDS patients.At the same time,according to the prognosis of patients,the subjects were divided into good prognosis group and poor prognosis group,and the risk factors affecting the prognosis of patients were screened by Logistic regression analysis.Receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of peripheral blood mir-155,Th17,mir-23b-3p and Tfh levels on the prognosis of AIDS patients.Results Compared with non-AD group,the levels of miR-155,Th17 and Tfh in peripheral blood of AD group were higher(P＜0.05),and the levels of miR-23b-3p were lower(P＜0.05).The level of miR-155,Th17 and Tfh in peripheral blood were positively correlated with secondary AD of AIDS(r=0.487,0.492,0.495,P＜0.05),and the level of miR-23b-3p in peripheral blood was negatively correlated with secondary AD of AIDS(r=-0.503,P＜0.05).The levels of HIV load(high dose),lymphoma,PLT,NLR,CRP,miR-155,Th17 and Tfh in the poor prognosis group were higher than those in the good prognosis group(P＜0.05),while the levels of albumin and miR-23b-3p in the poor prognosis group were lower than those in the good prognosis group(P＜0.05).Logistic regression analysis showed that lymphoma,PLT,NLR,low albumin,CRP,miR-155,Th17,Tfh and low miR-23b-3p were all risk factors for poor prognosis of AIDS patients(P＜0.05).ROC curve results showed that the AUC(95％CI)and sensitivity of combined detection of peripheral blood miR-155,Th17,Tfh and miR-23b-3p in predicting poor prognosis of AIDS patients were 0.883(0.805～0.992)and 96.70％,respectively.All of them were higher than the above peripheral blood indexes alone(P＜0.05).Conclusion The abnormal expression of miR-155,Th17,Tfh,and miR-23b-3p in peripheral blood is closely related to secondary AD in AIDS patients,and is a risk factor affecting the poor prognosis of AIDS patients.The combined detection of these indicators has a high predictive value for the poor prognosis of AIDS patients.

Objective To investigate the relationship between the expression levels of mir-155/Th17 and mir-23b-3p/Tfh in peripheral blood and the prognostic value of secondary atopic dermatitis(AD)in AIDS patients.Methods In this study,80 AIDS patients were treated in our hospital from February 2021 to December 2023.The subjects were divided into AD group and non-AD group according to whether they had secondary AD.The levels of mir-155,Th17,mir-23b-3p and Tfh in peripheral blood of AD group and non-AD group were compared.Spearman method was used to analyze the relationship between levels of mir-155,Th17,mir-23b-3p and Tfh in peripheral blood and secondary AD in AIDS patients.At the same time,according to the prognosis of patients,the subjects were divided into good prognosis group and poor prognosis group,and the risk factors affecting the prognosis of patients were screened by Logistic regression analysis.Receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of peripheral blood mir-155,Th17,mir-23b-3p and Tfh levels on the prognosis of AIDS patients.Results Compared with non-AD group,the levels of miR-155,Th17 and Tfh in peripheral blood of AD group were higher(P＜0.05),and the levels of miR-23b-3p were lower(P＜0.05).The level of miR-155,Th17 and Tfh in peripheral blood were positively correlated with secondary AD of AIDS(r=0.487,0.492,0.495,P＜0.05),and the level of miR-23b-3p in peripheral blood was negatively correlated with secondary AD of AIDS(r=-0.503,P＜0.05).The levels of HIV load(high dose),lymphoma,PLT,NLR,CRP,miR-155,Th17 and Tfh in the poor prognosis group were higher than those in the good prognosis group(P＜0.05),while the levels of albumin and miR-23b-3p in the poor prognosis group were lower than those in the good prognosis group(P＜0.05).Logistic regression analysis showed that lymphoma,PLT,NLR,low albumin,CRP,miR-155,Th17,Tfh and low miR-23b-3p were all risk factors for poor prognosis of AIDS patients(P＜0.05).ROC curve results showed that the AUC(95％CI)and sensitivity of combined detection of peripheral blood miR-155,Th17,Tfh and miR-23b-3p in predicting poor prognosis of AIDS patients were 0.883(0.805～0.992)and 96.70％,respectively.All of them were higher than the above peripheral blood indexes alone(P＜0.05).Conclusion The abnormal expression of miR-155,Th17,Tfh,and miR-23b-3p in peripheral blood is closely related to secondary AD in AIDS patients,and is a risk factor affecting the poor prognosis of AIDS patients.The combined detection of these indicators has a high predictive value for the poor prognosis of AIDS patients.

Objective:To explore the impact of the stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)pathway on the senescence of rapid pacing HL-1 myocytes.Methods:HL-1 cells were divided into five groups: the control group(HL-1 cells without any treatment), pacing group(HL-1 cells paced for 48 hours), STING siRNA group(HL-1 cells paced for 48 hours and transfected with STING siRNA), NC siRNA group(HL-1 cells paced for 48 hours and transfected with NC siRNA), and H151 inhibitor group(HL-1 cells paced for 48 hours with the addition of 1 μmol/L STING inhibitor H151). Mitochondrial membrane potential was assessed in control and pacing group cells, and mitochondrial MitoTracker and TFAM co-localization staining was performed on these cells.Cellular senescence was evaluated using β-galactosidase staining in each group, and the positive rate of cellular senescence was observed and calculated.Western blotting was employed to detect the expression levels of STING, IRF3, P-IRF3, P16, P21, and P53 proteins in all groups.Immunofluorescence was utilized to examine the expression distribution of STING and P21 across the various groups.ELISA was performed to measure the concentrations of interleukin(IL)-1β, IL-6, and IL-8 in the cell supernatants from each group as part of the senescence-associated secretory phenotype(SASP).Results:Compared with the control group, the ratio of mitochondrial JC-1 multimer to monomer was significantly decreased in the pacing group( t=16.42, P<0.05), the co-localization of mitochondrial MitoTracker and TFAM in the cells was significantly weakened, the proportion of cells with positive cellular senescence-associated β-galactosidase staining significantly increased in the pacing group, the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 proteins were significantly elevated in the pacing group, and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants were markedly increased.Compared with the pacing group, the proportion of cells with positive cellular senescence-associated β-galactosidase staining decreased in the STING siRNA group and H151 inhibitor group ( F= 18.13, P<0.05), the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 were reduced in the STING siRNA group and H151 inhibitor group ( F=16.84, 26.56, 74.70, 31.80, 31.23, all P<0.05), and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants decreased( F=197.80、1 339.00、1 308.00, all P<0.001). Conclusions:Rapid pacing of HL-1 cells can promote mtDNA release into the cytoplasm, activate the STING-IRF3 pathway, accelerate cellular senescence, and enhance the secretion of SASP.Inhibiting the expression of STING can delay the senescence induced by the rapid pacing of HL-1 cells and reduce SASP secretion.

Objective:To analyze the conventional ultrasound（CUS）and contrast-enhanced ultrasound（CEUS）features of hepatic lymphoma，and to investigate the value of CEUS in the diagnosis of hepatic lymphoma.Methods:The images of 39 patients（39 lesions）with hepatic lymphoma pathologically confirmed by surgery and puncture from March 2012 to July 2024 at Zhongshan Hospital，Fudan University were retrospectively analyzed. Evaluations of CUS included the echogenicity，morphology，color Doppler flow imaging（CDFI）situation，evaluations of CEUS included enhancement type，enhancement degree compared to the peripheral normal liver parenchyma and time to enhancement.Results:In the 39 lesions，hypoechoic lesions were detected in 31（79.49%，31/39）patients on CUS. CDFI detected linear or branched color flow signals inside the lesions in 21（53.85%，21/39）lesions，and peripheral color flow signals around the lesions in 3 lesions，while arterial flow signals were detected in 16 of them，with a resistance index of 0.50～0.77（0.67 ± 0.02）. In addition，signs of non-compacted normal blood vessels passing through the lesions were detected in 5 lesions. After injection of contrast medium，39 lesions showed different degrees of enhancement，mainly showed entirety homogeneous enhancement，during the arterial phase of CEUS，34（87.18%，34/39）lesions showed fast enhancement，and when the enhancement reached the peak，26（66.67%，26/39）lesions revealed hyper-enhancement，showing “fast progression”. There were 38（97.44%，38/39）lesions in the portal and delayed phases showed “fast forward”.Conclusions:CUS and CEUS can provide some value in the diagnosis and differential diagnosis of hepatic lymphoma.

Objective To analyze the effects of down-regulation+hormone replacement therapy(HRT)endometrial preparation regimen on the pregnancy outcomes of advanced age women(≥35 years old)undergoing frozen-thawed embryo transfer.Methods The clinical data of 329 patients with frozen-thawed em-bryo transfer in this hospital from June 2020 to June 2022 were analyzed retrospectively.Among them,149 pa-tients receiving gonadotropin-releasing hormone analogue(GnRHa)down-regulation+HRT endometrial preparation were included in the group A,and the other 180 patients with HRT endometrial preparation were included in the group B.The basic situation,endometrial transformation day situation and clinical outcome were compared between the two groups.The group A and group B were further divided into the two sub-groups according to age:group A1(35-＜40 years old,n=101),group A2(≥40 years old,n=48),group B1(35-＜40 years old,n=99)and group B2(≥40 years old,n=81).The effects of two endometrial prepara-tion regimens were compared among the different age groups.Results There were no significant differences in the age,infertility years,BMI,anti-Mullerian hormone level,as well as basal hormones levels such as estra-diol,progesterone,follicle-stimulating hormone,luteinizing hormone(LH),prolactin and testosterone between the two groups(P＞0.05).The levels of estradiol and LH on the endometrial transformation day in the group A were significantly lower than those in the group B(P＜0.05),the endometrial thickness,proportion of the patients with endometrial thickness ≥8 mm and proportion of the patients with type Ⅲ blood intima in the group A were significantly higher than those in the group B(P＜0.05).There was no significant difference in the number of transplanted embryos and the number of transplanted excellent embryos between the two groups(P＞0.05).The clinical pregnancy rate and embryo implantation rate in the group A were significantly higher than those in the group B(46.31％vs.35.56％;33.33％vs.25.18％,P＜0.05),and there was no significant difference in the early miscarriage rate between the two groups(P＞0.05).The further subgroup analysis showed that the clinical pregnancy rate and embryoimplantation rate in the group A2 were significant-ly higher than those in the group B2(35.42％vs.18.52％;21.43％vs.12.40％,P＜0.05),while there was no significant difference between the group A1 and group B1(P＞0.05).Conclusion The advanced age pa-tients undergoing frozen-thawed embryo transfer could select GnRHa down-regulation+HRT regimen to a-chieve better pregnancy outcomes,especially for those age ≥40 years old.

Objective:To construct a medical equipment management system based on improved evidence theory,and to analyze its application effect in the equipment management of geriatric gastroenterology department in hospitals.Methods:With the help of improved evidence theory,the risk of medical equipment management in geriatric gastroenterology department was identified,dynamic weights and static weights were introduced,and a medical equipment management system based on improved evidence theory was constructed by combining the game idea with the portfolio empowerment approach.A total of 60 medical devices in clinical use in the department of geriatric gastroentero1ogy of Xi'an No.1 Hospital from 2021 to 2023 were selected,and the medical devices used from 2021 to 2022 were managed by conventional methods,and the medical devices used from 2022 to 2023 were managed by using the improved evidence theory(improved evidence theory management).The equipment management quality,equipment data integrity score and comprehensive assessment score of equipment management team were compared between the two management methods.Results:The average failure rate and scrap rate of equipment managed by the improved evidence theory method were(12.36±3.65)％and(2.65±0.54)％,respectively,which were lower than those of the conventional management method(t=9.897,15.877,P＜0.05),the average self-maintenance rate and upgrade rate of faults were(90.69±6.25)％and(91.25±5.25)％,respectively,which were higher than those of the conventional management method,the difference was statistically significant(t=13.191,14.828,P＜0.05).The average scores of equipment data management,diagnosis and treatment data analysis and clinical application data integrity using the improved evidence theory method were(92.36±2.36)points,(93.69±2.36)points and(94.39±3.26)points,respectively,which were higher than those of the conventional management method,the difference was statistically significant(t=13.044,13.893,15.036,P＜0.05).The average comprehensive assessment scores of technical support team,technical development team,technical practice team and auxiliary management team members adopting the improved evidence theory method were(91.36±3.26)points,(94.26±3.59)points,(95.36±4.36)points and(96.36±3.26)points,respectively,which were higher than those of the conventional management method,the difference was statistically significant(t=8.224,14.796,14.129,19.005,P＜0.05).Conclusion:The medical equipment management system based on the improved evidence theory can evaluate the risks in the application of equipment,improve the quality of equipment management,enhance the level of equipment management team,and provide decision-making assistance for the equipment management in geriatric gastroenterology department.

To investigate the formation of polystyrene nanoplastic-plant protein corona and its potential impact on plants, three differently modified polystyrene nanoplastics with an average particle size of 200 nm were taken to interact with the leaf proteins of Impatiens hawkeri for 2 h, 4 h, 8 h, 16 h, 24 h, and 36 h, respectively. The morphological changes were observed by scanning electron microscopy (SEM), the surface roughness was determined by atomic force microscopy (AFM), the hydrated particle size and zeta potential were determined by nanoparticle size and zeta potential analyzer, and the protein composition of the protein corona was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteins were classified in terms of biological processes, cellular components, and molecular functions to study the adsorption selection of nanoplastics to proteins, investigate the formation and characteristics of polystyrene nanoplastic-plant protein corona and predict the potential impact of protein corona on plants. The results showed that the morphological changes of the nanoplastics became clearer as the reaction time extends, as evidenced by the increase in size and roughness and the enhancement of stability, thus demonstrating the formation of protein corona. In addition, the transformation rate from soft to hard protein corona was basically the same for the three polystyrene nanoplastics in the formation of protein corona with leaf proteins under the same protein concentration conditions. Moreover, in the reaction with leaf proteins, the selective adsorption of the three nanoplastics to proteins with different isoelectric points and molecular weights differed, and the particle size and stability of the final formed protein corona also differed. Since a large portion of the protein fraction in protein corona is involved in photosynthesis, it is hypothesized that the formation of the protein corona may affect photosynthesis in I. hawkeri.
Polystyrenes/chemistry* ; Protein Corona/chemistry* ; Microplastics ; Plant Proteins ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Nanoparticles/chemistry*