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.

In order to investigate the mechanical response of lumbar vertebrae during gait cycle in adolescents with idiopathic scoliosis (AIS), the present study was based on computed tomography (CT) data of AIS patients to construct model of the left support phase (ML) and model of the right support phase (MR), respectively. Firstly, material properties, boundary conditions and load loading were set to simulate the lumbar vertebra-pelvis model. Then, the difference of stress and displacement in the lumbar spine between ML and MR was compared based on the stress and displacement cloud map. The results showed that in ML, the lumbar stress was mostly distributed on the convex side, while in MR, it was mostly distributed on the concave side. The stress of the two types of stress mainly gathered near the vertebral arch plate, and the stress of the vertebral arch plate was transmitted to the vertebral body through the pedicle with the progress of gait. The average stress of the intervertebral tissue in MR was greater than that in ML, and the difference of stress on the convex and convex side was greater. The displacement of lumbar vertebrae in ML decreased gradually from L1 to L5. The opposite is true in MR. In conclusion, this study can accurately quantify the stress on the lumbar spine during gait, and may provide guidance for brace design and clinical decision making.
Humans ; Lumbar Vertebrae/diagnostic imaging* ; Scoliosis/diagnostic imaging* ; Adolescent ; Gait/physiology* ; Biomechanical Phenomena ; Tomography, X-Ray Computed ; Stress, Mechanical ; Female ; Male

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

Objective To observe the effect of preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer on lung function and mRNA expression of GATA-binding protein 3(GATA3)and forkhead protein P3(Foxp3)in peripheral blood.Methods Sixty esophageal cancer patients who underwent modified Ivor-Lewis surgery in our hospital from January 2022 to October 2023 were selected and divided into two groups by simple random method.The control group was given conventional diet before operation,and the observation group was given enteral nutrition support before operation.The two groups were compared in terms of nutritional support.Results Both groups showed significantly decreases in one-second exertion expiratory volume/exertion lung volume(FEV1/FVC)(P<0.05),FVC(P<0.05),FEV1(P<0.05)and the levels of peripheral blood GATA3(P<0.05),Foxp3 mRNA(P<0.05)expression compared with those at admission(P<0.05),but no significant differences in pulmonary function(P>0.05),peripheral blood GATA3(P>0.05),and Foxp3 mRNA(P>0.05)expression between them at 1 week postoperatively.Both groups exhibited significantly lower levels of albumin,prealbumin,haemoglobin,transferrin,PNI and body mass and body mass index at admis-sion as compared to those at one week after surgery(P<0.05).The observation group showed significantly higher levels of albumin,prealbumin,haemoglobin,transferrin,and PNI at 1 week postoperatively(P<0.05),but no significant differences in ventilation time,defecation time,drain retention time,hospitalisation time,and compli-cation rate as compared to the control group(P>0.05).Conclusion Preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer improves postoperative nutritional status,and ren-ders less effect on postoperative lung function and peripheral blood GATA3 and Foxp3 mRNA expression.

The finite element method(FEM)is a widely employed mathematical technique in mechanical research that divides an object into discrete and interacting finite elements. Medically, finite element analysis(FEA)enables the simulation of biomechanical experiments that are challenging to conduct. Orbital surgery poses significant challenges to ophthalmologists due to its inherent difficulty and steep learning curve. FEM enables the simulation and analysis of the mechanical properties of orbital tissue, offering a novel approach for diagnosing and treating orbital-related diseases. With technological advancements, FEM has significantly matured in the diagnosis and treatment of orbital diseases, becoming a popular area of research in orbital biomechanics. This paper reviewed the latest advancements in orbital FEM, encompassing the development of orbital FEA models, simulation of orbital structure, and its application in orbital-related diseases. Additionally, the limitations of FEM and future research directions are also discussed. As a digital tool for auxiliary diagnosis and treatment, orbital FEA will progressively unlock its potential for diagnosing and treating orbital diseases alongside technological advancements.

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

Objective:To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.Methods:Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale(NIHSS)score≤3 and a platelet count<100×109/L were obtained from a multicenter register.Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded.Short-term safety outcomes were in-hospital bleeding events,while the long-term safety outcome was a 1-year all-cause death.The short-term neurological outcomes were evaluated by modified Rankin scale(mRS)score at discharge.Results:A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled.Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge(OR=1.657,95%CI:1.253-2.192,P<0.01)and did not increase the risk of intracranial hemorrhage(OR=2.359,95%CI:0.301-18.503,P>0.05),compared with those without antiplatelet therapy.However,dual-antiplatelet therapy did not bring more neurological benefits(OR=0.923,95%CI:0.690-1.234,P>0.05),but increased the risk of gastrointestinal bleeding(OR= 2.837,95%CI:1.311-6.136,P<0.01)compared with those with mono-antiplatelet therapy.For patients with platelet counts≤75×109/L and>90×109/L,antiplatelet therapy significantly improved neurological functional outcomes(both P<0.05).For those with platelet counts(>75-90)×109/L,antiplatelet therapy resulted in a significant improvement of 1-year survival(P<0.05).For patients even with concurrent coagulation abnormalities,mono-antiplatelet therapy did not increase the risk of various types of bleeding(all P>0.05)but improved neurological functional outcomes(all P<0.01).There was no significant difference in the occurrence of bleeding events,1-year all-cause mortality risk,and neurological functional outcomes between aspirin and clopidogrel(all P>0.05).Conclusions:For non-cardioembolic mild stroke patients with thrombocytopenia,antiplatelet therapy remains a reasonable choice.Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.

Objective:To analyze the effect of perineural invasion(PNI)on immune cell infiltration in pancreatic ductal adenocarcinoma(PDAC)by the CIBERSORT deconvolution algorithm.Methods:The pancreatic cancer patients from the dataset GSE102238 were re-evaluated for the severity of PNI.And then the high and low PNI subgroups were subjected to immune scoring and immune cell infiltration analysis using the ESTIMATE and CIBERSORT algorithms to find immune cell subgroups associated with PNI.Finally,the results were validated by tissue microarrays.Results:Twenty-five cases were selected from 50 pancreatic cancer specimens for PNI reassessment and then divided into two high and low groups.Compared to the low PNI group,specimens from patients in the high group showed significantly less CD8+T-cell infiltration(P<0.05)and significantly more resting memory CD4+T-cells and M0 macrophages(P<0.05).Significantly reduced CD8+T cells(P<0.01)and slightly increased CD4+T cells(P<0.05)were confirmed in the patients with the high PNI using tissue microarrays.Meanwhile,macrophages significantly increased in the high PNI group(P<0.001).Conclusion:High PNI in PDAC inhibits infiltration of CD8+T cells which promote the infiltration of macrophages.

Objective:To analyze the effect of perineural invasion(PNI)on immune cell infiltration in pancreatic ductal adenocarcinoma(PDAC)by the CIBERSORT deconvolution algorithm.Methods:The pancreatic cancer patients from the dataset GSE102238 were re-evaluated for the severity of PNI.And then the high and low PNI subgroups were subjected to immune scoring and immune cell infiltration analysis using the ESTIMATE and CIBERSORT algorithms to find immune cell subgroups associated with PNI.Finally,the results were validated by tissue microarrays.Results:Twenty-five cases were selected from 50 pancreatic cancer specimens for PNI reassessment and then divided into two high and low groups.Compared to the low PNI group,specimens from patients in the high group showed significantly less CD8+T-cell infiltration(P<0.05)and significantly more resting memory CD4+T-cells and M0 macrophages(P<0.05).Significantly reduced CD8+T cells(P<0.01)and slightly increased CD4+T cells(P<0.05)were confirmed in the patients with the high PNI using tissue microarrays.Meanwhile,macrophages significantly increased in the high PNI group(P<0.001).Conclusion:High PNI in PDAC inhibits infiltration of CD8+T cells which promote the infiltration of macrophages.