ObjectiveThis study aimed to investigate whether Bushen Tongluo prescription inhibits macrophage polarization by regulating the Wnt3a/β-catenin signaling pathway， thereby reducing epithelial-mesenchymal transition and excessive extracellular matrix deposition， in order to elucidate the anti-pulmonary fibrosis mechanisms of Bushen Tongluo prescription and provide a new theoretical basis for the clinical treatment of pulmonary fibrosis. MethodsFifty male Sprague-Dawley （SD） rats were randomly divided into a blank group， model group， pirfenidone group， and high- and low-dose Bushen Tongluo prescription groups. Except for the blank group， the pulmonary fibrosis model was established by intratracheal instillation of bleomycin. Intervention was initiated on day 28 after modeling. The high- and low-dose Bushen Tongluo prescription groups were administered Bushen Tongluo prescription at doses of 30.88， 15.44 g·kg^-1， respectively， by intragastric gavage. The pirfenidone group was administered pirfenidone capsules at 110 mg·kg^-1 by intragastric gavage. The blank and model groups were given an equal volume of normal saline by gavage， once daily for 90 days. After treatment， the level of transforming growth factor-β₁ （TGF-β₁） in bronchoalveolar lavage fluid （BALF） was detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in lung tissue and the collagen volume fraction were compared. The protein distribution and expression of E-cadherin， cytokeratin 19， α-smooth muscle actin （α-SMA）， vimentin， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ） in lung tissue were detected by immunohistochemistry. The protein distribution and expression of CD68， arginase-1 （Arg-1）， inducible nitric oxide synthase （iNOS）， Wnt3a， and β-catenin in lung tissue were detected by immunofluorescence. The protein expression of Wnt3a and β-catenin in lung tissue was detected by Western blot， and the mRNA expression of Wnt3a and β-catenin was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， a large number of inflammatory cells infiltrated the airway walls， alveolar spaces， and interstitial tissue in the model group， with obvious fibrous tissue hyperplasia. The level of TGF-β₁ in BALF was significantly increased. The protein expression of E-cadherin and cytokeratin 19 in lung tissue was decreased， whereas the protein expression of α-SMA， Vimentin， Wnt3a， β-catenin， Col Ⅰ， and Col Ⅲ was increased. The fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue were increased. The protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue were significantly increased （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement in inflammatory cell infiltration and fibrous tissue hyperplasia in the airway walls， alveolar spaces， and interstitial tissue， decreased TGF-β₁ levels in BALF， increased protein expression of E-cadherin and cytokeratin 19 in lung tissue， decreased protein expression of α-SMA， Vimentin， Col Ⅰ， and Col Ⅲ， decreased fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue， and decreased protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue （P<0.05， P<0.01）. ConclusionBushen Tongluo prescription can improve bleomycin-induced pulmonary fibrosis in rats by inhibiting epithelial-mesenchymal transition and reducing excessive extracellular matrix deposition. The mechanism may be related to inhibition of the Wnt3a/β-catenin signaling pathway and the macrophage polarization mediated by this pathway.

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 explore the assocation of the family environment and depressive symptoms among primary and middle school students, so as to provide suggestions for further maximizing the utility of family environment in the growth of primary and secondary school students, as well as prevention and intervention of depressive symptoms among children and adolescents. Methods: From June to July 2024, through a multistage cluster random sampling method, 8 800 primary and middle school students aged 10 to 18 from 36 schools in 3 cities (Datong, Lvliang, Linfen) in Shanxi Province. A self designed questionnaire was used to conduct a family environment survey, including family socioeconomic conditions, family structure, family parenting behavior, family member health behavior, etc; and the depression symptoms of primary and secondary school students were investigated by Patient Health Questionnaire-9. The χ 2 test and binary Logistic regression to method were used to analyze the association of the family environment with depressive symptoms among primary and secondary school students, and to analyze gender and urban-rural heterogeneity in this association. Results: The detection rate of depressive symptoms among primary and middle school students was 46.7% ( n = 4 111 ). Among them, the detection rates of depressive symptoms for male and female students were 45.7% and 47.7% respectively, and the detection rates for rural and urban students were 48.0% and 44.9% respectively. The results of binary Logistic regression model showed that in the family environment, factors such as the father s education level (junior high school: OR =0.84), self assessed family socio economic status (average: OR =0.78, good: OR =0.80), parental support and understanding (yes: OR = 0.55 ), family atmosphere (harmonious: OR =0.66), living arrangement (living only with father or mother: OR =1.31, living with parents and grandparents: OR =1.19), and family rearing style (combining punishment and reward: OR =1.42, punishment only: OR =1.25) were related to depressive symptoms in primary and middle school students in Shanxi Province ( P <0.05). From the perspective of gender heterogeneity, the living arrangement (living only with father or mother: OR =1.67, others: OR =1.67) had a statistically significant association with depressive symptoms in male students ( P <0.05). From the perspective of urban rural heterogeneity, the living arrangement (living only with father or mother: OR =1.38) had a statistically significant association with depressive symptoms in rural primary and middle school students ( P <0.05). Conclusions The family environment has an important impact on depressive symptoms in primary and middle school students. Family functioning should be fully exerted to prevent depressive symptoms in primary and middle school students.

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 analyze the medication law and compatibility characteristics of TCM compounds for the treatment of myocardial infarction in the national patent database.Methods TCM compounds for treating myocardial infarction were retrieved from CNIPA patent publication website.A prescription database was built using Excel 2019 software to statistically analyze the frequency of medicinal use and their properties,taste and meridian tropism;SPSS Modeler 18.0 software was used to analyze the association rules of drugs;a network of Chinese materia medica co-occurrence was constructed using Cytoscape 3.10.0,and systematic clustering analysis was performed on the Chinese materia medica in the core network.Results A total of 146 patents of TCM compounds were included,involved 440 kinds of Chinese materia medica.High frequency drugs included Salviea Miltiorrhizae Radix et Rhizoma,Chuanxiong Rhizoma,Angelicae Sinensis Radix,Glycyrrhizae Radix et Rhizoma,etc.The main property was warm,the main tastes were bitter,sweet and pungent,and the medicines mostly belongs to the liver meridian,heart meridian and spleen meridians.Commonly used medicinal pairs included Angelicae Sinensis Radix-Chuanxiong Rhizoma,Astragali Radix-Salviea Miltiorrhizae Radix et Rhizoma,Paeoniae Radix Rubra-Angelicae Sinensis Radix,etc.Commonly used tripartite combinations included Paeoniae Radix Rubra-Chuanxiong Rhizoma-Angelicae Sinensis Radix,Carthami Flos-Angelicae Sinensis Radix-Chuanxiong Rhizoma,Carthami Flos-Chuanxiong Rhizoma-Angelicae Sinensis Radix,etc.Clustering analysis showed four types of combinations.Conclusion TCM compound patents for the treatment of myocardial infarction is based on promoting blood circulation,removing blood stasis,and relieving pain,while also using methods such as eliminating phlegm,tonifying qi,warming yang,and nourishing yin.It can provide references for clinical medication.

Objective: To explore the association between school climate and suicide behavior among primary and secondary school students, so as to provide recommendations for preventing student suicide in schools. Methods: From June to July 2024, a stratified cluster random sampling method was employed to conduct a questionnaire survey on suicidal behavior and school climate among 8 722 students from 36 schools in Lüliang, Linfen, and Datong cities, Shanxi Province. The relationship between school climate and suicidal behavior was analyzed using Chi square test and binary Logistic regression, supplemented by gender heterogeneity and interaction analyses. Results: The prevalence of suicidal behavior among students in Shanxi Province was 11.1%. After adjusting for age, gender, educational stage, parents educational level, residential status, family economic condition, parents marital status and depressive symptoms, binary Logistic regression analysis revealed that peer relationships ( OR=0.72, 95%CI =0.57- 0.91 ), peer trust ( OR=0.73, 95%CI =0.58-0.92), teacher support ( OR=0.66, 95%CI =0.53-0.82), school safety ( OR=0.61, 95%CI =0.48-0.78), having more than six friends ( OR=0.64, 95%CI =0.43-0.98), and school belongingness ( OR=0.70, 95%CI =0.56-0.88) among primary and secondary school students were associated with a lower risk of suicidal behavior (all P <0.05). Students who experienced school bullying showed a higher risk of suicidal behavior ( OR=2.95, 95%CI =1.80-4.82, P <0.05). Gender specific analysis revealed that peer relationships ( OR=0.67, 95%CI =0.48-0.92), peer trust ( OR=0.66, 95%CI =0.49-0.90), and school belongingness ( OR=0.62, 95%CI =0.45-0.84) were associated with a lower risk of suicidal behavior suicide behavior in girls; teacher support ( OR=0.50, 95%CI =0.36-0.70) and having more than six friends ( OR=0.51, 95%CI =0.27- 0.96 ) were associated with a lower risk of suicidal behavior in boys, who experienced school bullying showed a higher risk of suicidal behavior ( OR=4.19, 95%CI =2.18-8.03) (all P <0.05). Interactive analysis revealed that the dual interaction between peer support and school safety could reduced the risk of suicide behavior among primary and secondary school students safety ( OR= 0.83 , 95%CI=0.70-0.99, P <0.05). Conclusions School climate is closely associated with suicidal behavior among primary and secondary school students in Shanxi Province, with gender differences present. Schools should foster a positive school environment to prevent student suicide behaviors.

Objective To analyze the correlation of cholecystectomy and changes in intestinal microbiota composition and function by observing functional characteristics of differential microbial communities.Methods A cross-sectional study was conducted on the patients(PC group,n=73)undergoing cholecystectomy in our hospital from 2020 to 2021.Another 56 healthy age-and gender-matched individuals(HC group)without a history of cholecystectomy were subjected and served as the control group.Fecal specimens were collected from the 2 groups.16S rRNA sequencing analysis was performed to examine the changes in composition and function of intestinal microbiota.Results There were no statistical differences between the 2 groups in baseline indicators,such as gender,age,BMI,smoking and drinking history,blood pressure,heart rate,and comorbidities,but significant difference was observed in total bilirubin(TBIL)between them(P<0.01).Alpha diversity analysis showed no significant difference in Chao1,Shannon,and Simpson indices between the 2 groups.Beta diversity analysis using the Bray-Curtis distance algorithm revealed a significant difference between the 2 groups at the class and genus levels(P<0.05).The analysis of microbiota relative abundance using LEFSE showed that Enterobacteriaceae,Lactobacillales,Citrobacter,Megasphaera,Lactobacillus,Enterococcus,Akkermansia,Streptococcus,Klebsiella,and Ruminococcus_gnavus were up-regulated in the PC group,and Lachnospiraceae,Sutterellaceae,Lachnospirales,Lachnospira,and Sutterella were down-regulated.Kyoto Encyclopedia of Genes and Genomes(KEGG)functional prediction analysis indicated that significant differences were seen between the 2 groups in metabolic pathways,including ascorbic acid(vitamin C)metabolism and aldonic acid metabolism(P<0.05),tricarboxylic acid cycle(TCA cycle)(P<0.05),glutathione metabolism(P<0.05),glutamic acid metabolism(P<0.05),secondary bile acid metabolism(P<0.05),and pentose phosphate pathway(P<0.01).Conclusion Cholecystectomy is closely associated with the structural alterations in the composition of intestinal microbiota.Variations in microbiota composition and function may induce perturbations in TCA cycle and glutathione metabolism,glutamate metabolism,secondary bile acid metabolism,and pentose phosphate pathways.

Objective To investigate the diversity and composition of gut fungi microbiota in patients with polycystic kidney disease(PKD)and its correlation with clinical indicators.Methods A total of 44 PKD patients,44 patients with non-polycystic chronic kidney disease(NPCKD)and 22 healthy controls(HC)admitted to our hospital from February 2023 to February 2024 were recruited.ITS1 DNA sequencing was applied to analyze the gut fungal composition.Bioinformatics analysis was used to compare the diversity and structural differences of fungi among the 3 groups.Pearson correlation analysis was performed to analyze the relationship between gut fungi and clinical indicators.Results There were no significant differences in baseline characteristics(gender,age,body mass index,etc.)among the 3 groups,but statistical differences were seen in terms of serum indicators(such as serum creatinine,blood urea nitrogen,uric acid,estimated glomerular filtration rate,etc.)(P<0.01).Alpha diversity analysis showed no significant difference was seen between the PKD and HC groups,but the PKD group had significant differences to the NPCKD group(P<0.01).Beta diversity analysis revealed significant differences among the 3 groups and in pairwise comparisons(P=0.001).Fungi composition analysis found that the abundance of Candida was significantly higher in the PKD group than the other 2 groups(P<0.01),while the abundances of Aspergillus and Cladosporium were significantly lower in the PKD group than the HC group(P<0.05).Linear discriminant analysis(LEFSe)indicated that Candida was significantly enriched,while Aspergillus and Cladosporium were significantly reduced in the PKD group.Correlation analysis revealed that the abundance of Cladosporium was negatively correlated with cyst diameter and immunoglobulin light chain Kappa/Lambda ratio in the PKD group(P<0.05),while the abundance of Candida was positively correlated with liver/kidney cyst diameter(P<0.01).Conclusion PKD patients exhibit characteristic changes in gut fungi diversity and composition.The abundances of Cladosporium and Candida are closely associated with clinical indicators of PKD patients.