BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

Objective To investigate the effect of tritiated water on the immune system of zebrafish and its potential molecular mechanism. Methods Zebrafish embryos (2.5 to 3 hours post-fertilization [hpf]) were exposed to 3.7 × 10⁴ Bq/mL tritiated water (tritiated water group), and those exposed to E3 culture medium were used as the control group. The mortality rate, hatching rate, deformity rate, heart rate, body length, yolk sac area, neutrophil count in the tail, immune-related gene expression, and immune-related protein expression of zebrafish in the two groups were determined. Then transcriptome technology was used to further analyze the possible mechanism of tritiated water affecting the immune system of zebrafish. Results Compared with the control group, zebrafish at 72 hpf in the tritiated water group had no significant changes in the mortality rate, hatching rate, deformity rate, body length, and yolk sac area((t = 0.9045, 0.5000, 1.0000, 0.7238, 0.0337, P = 0.4169, 0.6433, 0.3739, 0.4785, 0.9735), but had significantly increased heart rate(t = 4.575，P = 0.002). At 4 days post-fertilization (dpf), the neutrophil count in the tail of zebrafish in the tritiated water group was significantly increased(t = 2.563，P = 0.0196), the mRNA expression of TNF-α was significantly decreased(t = 2.891, P = 0.045), the protein expression of nuclear factor-kappa B (NF-κB) was significantly increased(t = 3.848, P = 0.018), and the protein expression of NLRP3 was significantly decreased(t = 14.98, P = 0.001). At 7 dpf, the neutrophil count in the tail and the protein expression levels of NF-κB, NLRP3, and interleukin-1β were significantly decreased(t = 3.772, 7.048, 15.620, 4.423, P = 0.014, 0.002, 0.0001, 0.012). Transcriptome sequencing revealed that differentially expressed genes were mainly enriched in the “neutrophil activation” and “platelet activation pathways” at 4 dpf and in the “neutrophil apoptosis”, “ferroptosis”, and “necroptosis” pathways at 7 dpf. Conclusion Tritiated water exposure induces a temporally dynamic immune response in zebrafish, potentially affecting immune homeostasis by regulating neutrophil activation and apoptosis, as well as the expression of NF-κB and NLRP3.

Objective:To investigate the protective mechanism of cerium oxide nanoparticles(CeO2 NPs)against acute pancreatitis(AP),with a focus on their antioxidant and anti-inflammatory properties.Methods:CeO2 NPs were characterized by transmission elec-tron microscopy(TEM)and dynamic light scattering.In in vitro experiments,cell counting Kit-8(CCK-8)assay,flow cytometry,and Western blotting were used to validate the role of CeO2 NPs in preventing the apoptosis of pancreatic acinar cells.In in vivo experi-ments,C57BL/6 mice were divided into control group,AP group,AP+CeO2 group,SAP group,and SAP+CeO2 group to investigate the mechanism of action of CeO2 NPs in alleviating inflammation and oxidative stress in AP mice.Results:CeO2 NPs demonstrated rela-tively good stability and biocompatibility,with a particle size of(50±4)nm on TEM.In vitro experiments showed that CeO2 NPs sig-nificantly reduced the apoptosis of pancreatic acinar cells by alleviating lipid peroxidation and maintaining mitochondrial membrane potential.In vivo experiments showed that CeO2 NPs could reduce the serum levels of amylase,lipase,and inflammatory cytokines(in-terleukin-6 and tumor necrosis factor-α).This result might be related to the regulation of the IKK/P53/Bcl-2 pathway.CeO2 NPs re-duced the production of reactive oxygen species and enhanced anti-oxidant response by regulating the Nrf-2 signaling pathway.Con-clusion:CeO2 NPs exert anti-inflammatory and antioxidant effects by regulating the IκB kinase/tumor protein p53/B-cell lymphoma 2(IKK/P53/bcl-2)and nuclear factor erythroid 2-related(Nrf-2)signaling pathways,thereby showing promising potential for the treatment of AP.

Objective To explore the quantitative electroencephalography(qEEG)characteristics of the prefrontal cortex in patients with mild cognitive impairment(MCI)during digital screening tasks for MCI screening.Methods A total of 592 MCI patients(MCI group)and 317 normal cognitively elderly individuals(control group)were recruited from 40 communities in Nanjing,Jiangsu Province,from July to August,2024.All participants were as-sessed using Montreal Cognitive Assessment-Beijing Version(MoCA-BJ).Prefrontal EEG data were collected using a portable EEG device,and power spectral analysis was performed via Fast Fourier Transform.An XG-Boost algorithm was employed to construct an MCI identification model based on qEEG power features,and the model's performance was evaluated using receiver operating characteristic(ROC)curve.Results Compared with the control group,prefrontal δ,α,and β band power increased during screening tasks in MCI group(P<0.05);δ power was negatively correlated with MoCA-BJ total scores,and visuospatial/executive func-tion,attention and delayed recall scores(r=-0.269,-0.169,-0.133,-0.171,P<0.001);α power was negative-ly correlated with MoCA-BJ total scores,attention and delayed recall scores(r=-0.113,-0.075,-0.091,P<0.05).The XGBoost model based on δ and α power was excellent in MCI identification,with an area under the curve of 0.91,accuracy of 0.81,precision of 0.89,F1 score of 0.84,recall of 0.80,and specificity of 0.81.Conclusion MCI patients exhibit increased power in the prefrontal δ and α frequency bands during digital screening tasks,which is associated with cognitive decline.An XGBoost model based on qEEG power features can enable early prediction of MCI.

Objective To explore the quantitative electroencephalography(qEEG)characteristics of the prefrontal cortex in patients with mild cognitive impairment(MCI)during digital screening tasks for MCI screening.Methods A total of 592 MCI patients(MCI group)and 317 normal cognitively elderly individuals(control group)were recruited from 40 communities in Nanjing,Jiangsu Province,from July to August,2024.All participants were as-sessed using Montreal Cognitive Assessment-Beijing Version(MoCA-BJ).Prefrontal EEG data were collected using a portable EEG device,and power spectral analysis was performed via Fast Fourier Transform.An XG-Boost algorithm was employed to construct an MCI identification model based on qEEG power features,and the model's performance was evaluated using receiver operating characteristic(ROC)curve.Results Compared with the control group,prefrontal δ,α,and β band power increased during screening tasks in MCI group(P<0.05);δ power was negatively correlated with MoCA-BJ total scores,and visuospatial/executive func-tion,attention and delayed recall scores(r=-0.269,-0.169,-0.133,-0.171,P<0.001);α power was negative-ly correlated with MoCA-BJ total scores,attention and delayed recall scores(r=-0.113,-0.075,-0.091,P<0.05).The XGBoost model based on δ and α power was excellent in MCI identification,with an area under the curve of 0.91,accuracy of 0.81,precision of 0.89,F1 score of 0.84,recall of 0.80,and specificity of 0.81.Conclusion MCI patients exhibit increased power in the prefrontal δ and α frequency bands during digital screening tasks,which is associated with cognitive decline.An XGBoost model based on qEEG power features can enable early prediction of MCI.

Objective:To evaluate the relationship between the mechanism of preoperative sleep deprivation aggravating postoperative cognitive dysfunction and theta oscillations in the hippocampal CA1 region in aged mice.Methods:Twenty-four SPF male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 3 groups ( n=8 each) by a random number table method: normal control group (group C), operation group (group S) and preoperative sleep deprivation + operation group (group SD+ S). The sleep deprivation model was established using the sleep deprivation rod method, and the sleep deprivation time was 24 h before operation. The sleep deprivation rod was set to rotate continuously at 6 rpm/min, and the direction was randomly reversed to force the mice to exercise to achieve the purpose of sleep deprivation. Group C received no treatment. Group S underwent exploratory laparotomy under isoflurane anesthesia. After sleep deprivation for 24 h, SD+ S group underwent exploratory laparotomy under isoflurane anesthesia. Y-maze and Morris water maze tests were used to evaluate postoperative cognitive function. The theta oscillations in the hippocampal CA1 region were observed and recorded by EEG electrodes in vivo. The animals were then sacrificed and brain tissues were obtained for determination of the density of dendritic spines in the hippocampal CA1 region. Results:Compared with group C, the number of crossing the original platform was significantly decreased, and the time of staying at the original platform quadrant and time of exploring the novel arm were shortened, and the number of entries into the novel arm was reduced, the density of dendritic spines in the hippocampal CA1 region was reduced, and the percentage of theta oscillation power was decreased during the Y maze test in group S ( P<0.05). Compared with S group, the number of crossing the original platform was significantly decreased, and the time of staying at the original platform quadrant and time of exploring the novel arm were shortened, and the number of entries into the novel arm was reduced, the density of dendritic spines in the hippocampal CA1 region was reduced, and the percentage of theta oscillation power was decreased during the Y maze test in SD+ S group ( P<0.01). Conclusions:The mechanisms by which preoperative sleep deprivation exacerbates postoperative cognitive dysfunction may be related to reduction in theta oscillations in the hippocampal CA1 region of aged mice.

An elderly female melanoma patient who experienced severe liver injury after treatment with pembrolizumab and axitinib,which improved with glucocorticoid therapy.Through medication analysis and adverse reaction scale evaluated,it was considered that severe liver injury was more closely related to the immune checkpoint inhibitor,pembrolizumab.After a comprehensive analysis of the relationship between liver injury and immunotherapy,as well as the benefits and risks of immunotherapy for patients,immunotherapy was rechallenged 40 days after discontinuation of pembrolizumab.Restarting treatment with pembrolizumab after immune-mediated hepatitis poses a risk of recurrence of hepatotoxicity.After reviewing related literature,it had been found that the incidence of severe hepatotoxicity caused by rechallenging treatment was low,and the overall safety was controllable.Pembrolizumab had brought therapeutic benefits to patients,with no further immune-mediated liver injury of 5 cycles medication.This case can provide a reference for rechallenging immunotherapy after immune-mediated hepatitis.

Cancer stem cells(CSCs)are a small group of cells found in tumors that have same self-renewing properties as nor-mal stem cells.In recent years,with continuous development of science and technology in various aspects,people's research on tumor diseases has been deepened.CSCs has been defined as a key factor in promoting tumor development,especially participating in pro-moting tumor recurrence,metastasis,chemotherapy resistance,etc.Currently,CD133 has become one of popular CSCs markers,and can be highly expressed in a variety of CSCs.CD133 is closely related to diagnosis of cancer diseases,and plays an important role in dignosis and drug targeting for gastric cancer,lung cancer,brain tumor,liver cancer,ovarian cancer and colorectal cancer.This article reviews structure,function,immune mechanism escape of CD133,signal pathway of CD133 in tumorigenesis,and correlation of CD133 with various tumors as well.

Objective To explore the causal relationship between family resilience and mental health in military personnel population.Methods A total of 204 military personnel were recruited from an army unit stationed in Western China with cluster convenience sampling.Family Resilience Scale(FRS)and Symptom Checklist 90(SCL-90)were used to survey them twice,in an interval of 4 months.Amos 26.0 was applied to construct a cross-lag model and analyze the data.Results After controlling mental symptoms from the first survey,family resilience in the first measure significantly predicted mental symptoms in the second measure(β=-0.14,P＜0.05).After controlling for family resilience from the first survey,mental symptoms in the first measure significantly predicted family resilience in the second measure(β=-0.13,P＜0.05).Conclusion The relationship between family resilience and mental health is mutually causal in military personnel,and one predicts the other one.Our findings highlight the key dimensions of the relationship between the two.