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.

To summarize the clinical characteristics, antibody spectrum and neuroelectrophysiological features of autoimmune nodopathy(AN), and to explore the phenotypic differences among different antibody-positive subgroups.

Neural oscillatory changes play a critical role in pain and analgesia research. Previous studies on pain-related neural oscillations have primarily utilized electroencephalogram (EEG) power spectral analysis, revealing a strong correlation between alpha ( α) power and subjective pain perception. However, alpha power may be influenced by the baseline of the power spectrum, making it difficult to accurately capture the true changes in alpha oscillations. This study employed power spectral analysis and further applied a power spectral parameterization method, which decomposed the power spectrum into periodic and aperiodic components, to compare EEG α power in 50 primiparous women who underwent severe pain during the first stage of labor before and after epidural analgesia. The results indicated no significant differences in α power between pre- and post-analgesia conditions. However, following power spectral parameterization, the aperiodic component of the EEG significantly decreased after analgesia, whereas the periodic component of α power showed a significant increase. This study not only validates the effectiveness and validity of the power spectral parameterization method in analgesia research but also uncovers the differential regulatory mechanism by which analgesia modulates the periodic and aperiodic components of α oscillations.
Humans ; Electroencephalography/methods* ; Female ; Adult ; Alpha Rhythm ; Pregnancy ; Young Adult ; Analgesia, Epidural

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 investigate the correlation of combined detection of p16 and Rb with high-risk human papilloma virus (HR-HPV) infection in non-oropharyngeal squamous cell carcinoma (NOPSCC) of the head and neck.Methods:A total of 68 NOPSCC cases of the head and neck (23 cases of the nasal cavity and paranasal sinuses and 45 cases of larynx) with complete clinical and pathological data, diagnosed at the Beijing Tongren Hospital, Capital Medical University, Beijing, China from November 2013 to December 2023, were collected. The expression of p16 and Rb was detected using immunohistochemistry of the EnVision two-step method, while the HR-HPV mRNA expression was detected using in situ hybridization. The concordance, sensitivity, and specificity of p16 alone and the combined detection of p16 and Rb for detecting HR-HPV infection were analyzed.Results:Among the 68 patients with NOPSCC, 53 were male and 15 were female, with a median age of 63.5 (range, 57.3 to 66.8) years. 41 patients had a smoking history and 27 did not. 33 patients had an early T stage (T1/T2) and 35 had advanced T stage (T3/T4). 14 patients had lymph node metastasis and 2 had distant metastasis. Histological types included 62 cases of keratinized squamous cell carcinoma, 5 cases of non-keratinized squamous cell carcinoma, and 1 case of basal-like squamous cell carcinoma. 25 cases were positive for p16. Among the 25 cases, 16 cases were positive for Rb, and 6 cases were positive for HR-HPV mRNA. 43 cases were negative for p16, including 38 cases positive for Rb and no cases positive for HR-HPV mRNA. The concordance between p16 and HR-HPV mRNA expression was poor ( Kappa=0.285, P=0.001), with a sensitivity of 100.0% and specificity of 69.4%. In contrast, the combined detection of p16+/Rb- showed high concordance with HR-HPV mRNA expression ( Kappa=0.719, P<0.001), with a sensitivity of 100.0% and specificity of 95.2%. Conclusions:In NOPSCC of the head and neck, the combined detection of p16 and Rb may be used as a marker for assessing HR-HPV infection. Recognizing the p16+/Rb- expression pattern in NOPSCC can improve the specificity of HR-HPV detection.

Objective To investigate the distribution of serum specific IgG antibodies against food in children with autism spectrum disorders(ASD),and provide experimental evidence for improving gastrointestinal symptoms of ASD children.Methods A retrospec-tive study was conducted on 411 children with ASD visited the Department of Psychology and Behavior of Hebei Children's Hospital from January 2021 to December 2022.Additionally,631 healthy children who underwent physical examination during the same period were collected as the healthy control group.Their venous blood samples were collected,and ELISA was used to detect the levels of 14 kinds of serum specific IgG antibodies against food.The distribution characteristics of food intolerance in children with different genders and ages were investigated.Results The total positive rate of specific IgG antibodies against food in children with ASD reached 91.84%(405/441).The top 3 positive rates of specific IgG antibodies were against egg(71.89%),milk(56.70%),and wheat(56.02%),respectively,which were significantly higher than those in the healthy control group(χ2=42.81,27.48,and 26.88,re-spectively,P＜0.05).The comparative results of gender composition showed that the positive rate of specific IgG antibody against rice in female ASD children(15.96%)was significantly higher than that in male ASD children(4.90%,χ2=11.84,P＜0.05).The posi-tive rates of specific IgG antibodies against egg and wheat in male and female ASD children were significantly higher than those in the healthy control group(χ2=19.44 and 4.42 for males,χ2=4.66 and 10.93 for females,P＜0.05).The positive rate of specific IgG anti-body against milk in male ASD children was significantly higher than that in the healthy control group(χ2=12.62,P＜0.05),while those against soybean and rice in female ASD children were also significantly higher than that in the healthy control group(χ2=7.00 and 5.42,P＜0.05).There were significant differences in the positive rates of food intolerance to milk and soybean in ASD children with different ages(χ2=13.74 and 9.70,P＜0.05)and they decreased with age.The positive rates of specific IgG antibody against wheat in ASD children aged 2-3 and 4-6 years were significantly higher than those in the healthy control group(χ2=5.78 and 4.55,P＜0.05).The positive rate of specific IgG antibody against milk in ASD children aged 4-6 years was significantly higher than that in the healthy control group(χ2=7.57,P＜0.05).Conclusion The highest positive rate of specific IgG antibodies against food in ASD chil-dren is against egg,which is not related to the patient's gender.Next are milk and wheat.The gastrointestinal issues and related food intolerance should be taken into account in the management of patients with ASD.

Bronchial asthma is a heterogeneous chronic inflammatory airway disease.Its pathogenesis is closely associated with abnormal immune responses within T-helper(Th)cell subsets,characterized by excessive effector Th cell activation and impaired immunosuppression by regulatory T cells.The concept of natural harmony of yin-yang epitomizes the understanding of traditional Chinese medicine(TCM)of the body's inherent capacity for autonomous regulation and homeostasis maintenance.Building upon the description in the Inner Canon of Yellow Emperor regarding asthma as"internal yin qi contention,external yang qi interference,"this study aims to bridge the TCM macro-level etiology and pathogenesis of"yin-yang disharmony"with the Western micro-level mechanism of loss of immune homeostasis control.The core pathogenesis of bronchial asthma involves yin-yang disorder in the body,leading to internal-external imbalance.Yang deficiency with a hidden yin pathogen and intermingled phlegm with blood stasis in the lungs is the root of pathogenesis.Pathogenic invading qi and yang hyperactivity induce bronchial asthma.These align with the Western medical concepts of imbalanced immunometabolic self-stabilization and defective immunotolerance.Based on the above content,corresponding therapeutic principles are proposed according to the disease stage.In the acute phase,dispelling wind pathogens and relieving cough are recommended.In chronic persistent asthma,calming yang disturbance and resolving the yin conflict are emphasized.In the clinical remission phase,kidney yang should be warmed and invigorated,thereby consolidating body resistance.The corresponding treatment methods are implemented based on the above content.In the acute phase,self-made Mahuang Qingyang Decoction is administered to dispel wind pathogens and ventilate lung qi.In chronic persistent asthma,self-made Qingfei Xiegan Decoction is administered to clear liver-fire and purge the lungs,self-made Xuanfu Qingwei Decoction is employed to harmonize the stomach for descending adverse yang qi,modified Suzi Jiangqi Decoction is applied to conduct deficient yang back to its source,and modified Erchen Decoction and Taohong Siwu Decoction are utilized to expel phlegm and blood stasis.In the clinical remission phase,modified Sijunzi Decoction,modified Mahuang Fuzi Xixin Decoction,and Erxian Decoction are administered to invigorate the spleen and kidney.These approaches ward off yang disturbance and resolve yin contention to restore the body's normal immune homeostasis.The ultimate therapeutic aim is to achieve a state of natural harmony of yin-yang,thereby ceasing wheezing and coughing spontaneously,and to provide new ideas for clinical treatment of bronchial asthma.

In the context of the new medical reform,the formation mechanism of drug prices is one of the important is-sues of this round of medical reform.Drug prices involve the interests of drug companies,hospitals,patients,and other parties,so it is particularly important to establish a reasonable mechanism for the formation of drug prices to safeguard the interests of all parties.This paper first analyzes the characteristics of drugs and the drug market,and then discusses the actual situation and challenges faced by the formation mechanism of drug prices.On this basis,it proposes basic principles for drug pricing and opti-mization recommendations for the formation mechanism of drug prices in the context of the new medical reform.This can provide a reference for the country to formulate relevant drug price policies and promote the rational development of drug prices.