Epidemiological characteristics and early predict model of children Mycoplasma Pneumoniae Pneumonia outbreaks after the COVID-19 in Shandong.

Since October 2023, a significant outbreak of Mycoplasma Pneumoniae Pneumonia (MPP) has been observed in children in northern China. Chinese health authorities have attributed this epidemiological to immune debt resulting from the relaxation of coronavirus disease 2019 (COVID-19) control measures. This study described the epidemiological features of Mycoplasma pneumoniae (MP) prevalence in children and developed a straightforward prediction model to differentiate between MPP and viral pneumonia in children. The infection rate of MP in children notably increased from 8.12 in 2022 to 14.94% in 2023, peaking between October and November, especially among school-age children. Logistic regression screening identified four key indicators: Age, D-Dimer levels, erythrocyte sedimentation rate, and gender. The developed nomogram exhibited a receiver operator characteristic curve-area under the curve (ROC-AUC) of 0.858, with external validation confirming an ROC-AUC of 0.794. This study examined the epidemiological characteristics of MPP prevalence in children in Shandong Province during and after the COVID-19 pandemic. An early predict model was developed and validated to differentiate between Mycoplasma Pneumoniae and viral infections.

Zinc Assisted Thermal Etching for Rich Edge-Located Fe-N4 Active Sites in Defective Carbon Nanofiber for Activity Enhancement of Oxygen Electroreduction.

Single-atom catalysts (SACs) with edge-located metal active sites exhibit superior oxygen reduction reaction (ORR) performance due to their narrower energy gap and higher electron density. However, controllably designing such active sites to fully reveal their advantages remains challenging. Herein, rich edge-located Fe-N4 active sites anchored in hierarchically porous carbon nanofibers (denoted as e1-Fe-N-C) are fabricated via an in situ zinc-assisted thermal etching strategy. The e1-Fe-N-C catalyst demonstrates superior alkaline ORR activity compared to counterparts with fewer edge-located Fe-N4 sites and commercial Pt/C. Density functional theory calculations show that the accumulation of more negative charges near the Fe-N and the formation of partially reduced Fe state in the edge-located Fe-N4 sites reduce the energy barrier for the ORR process. Additionally, the unique hierarchically porous structures with mesopores and macropores facilitate full utilization of the active sites and enhance long-range mass transfer. The zinc-air battery (ZAB) assembled with e1-Fe-N-C has a peak power density of 198.9 mW cm-2, superior to commercial Pt/C (152.3 mW cm-2). The present strategy by facile controlling the amount of the zinc acetate template systematically demonstrates the superiority of edge-located Fe-N4 sites, providing a new design avenue for rational defect engineering to achieve high-performance ORR.

Mercury isotope evidence for the importance of recycled fluids in collisional ore systems.

The sources of fluids and metals in porphyry systems of continental-collision settings are poorly constrained. Mercury isotopes display unique mass-independent fractionation (expressed as Δ199Hg) and may provide important constraints on metal and volatile sources given that Hg is a highly volatile metal. Here, we report Hg isotope data on ore-forming porphyries, barren magmatic rocks, and mantle-derived mafic magmas from southern Tibet. The fertile porphyries and coeval mafic magmas display mainly positive Δ199Hg values (up to +0.25 per mil), while Δ199Hg values in barren magmatic rocks and mafic magmas are largely negative (-0.54 to 0.00 per mil). The positive Δ199Hg values observed here are consistent with seawater and marine sediments, suggesting that the ultimate source of fluids involved in the genesis of post-subduction porphyry copper deposits was the mantle lithosphere metasomatized by previous oceanic plate subduction. Our Hg isotope data provide an alternative view to current metallogenetic models on collisional porphyry systems that focus on melting of the lower continental crust.

Prosapogenin A induces GSDME-dependent pyroptosis of anaplastic thyroid cancer through vacuolar ATPase activation-mediated lysosomal over-acidification.

Anaplastic thyroid cancer (ATC) is among the most aggressive and metastatic malignancies, often resulting in fatal outcomes due to the lack of effective treatments. Prosapogenin A (PA), a bioactive compound prevalent in traditional Chinese herbs, has shown potential as an antineoplastic agent against various human tumors. However, its effects on ATC and the underlying mechanism remain unclear. Here, we demonstrate that PA exhibits significant anti-ATC activity both in vitro and in vivo by inducing GSDME-dependent pyroptosis in ATC cells. Mechanistically, PA promotes lysosomal membrane permeabilization (LMP), leading to the release of cathepsins that activate caspase 8/3 to cleave GSDME. Remarkably, PA significantly upregulates three key functional subunits of V-ATPase-ATP6V1A, ATP6V1B2, and ATP6V0C-resulting in lysosomal over-acidification. This over-acidification exacerbates LMP and subsequent lysosomal damage. Neutralization of lysosomal lumen acidification or inhibition/knockdown of these V-ATPase subunits attenuates PA-induced lysosomal damage, pyroptosis and growth inhibition of ATC cells, highlighting the critical role for lysosomal acidification and LMP in PA's anticancer effects. In summary, our findings uncover a novel link between PA and lysosomal damage-dependent pyroptosis in cancer cells. PA may act as a V-ATPase agonist targeting lysosomal acidification, presenting a new potential therapeutic option for ATC treatment.

The Circadian Rhythm of Itching among 241 Adults with Atopic Dermatitis: A Cross-sectional Study.

The pattern of itching in patients with atopic dermatitis has not been systematically studied. Therefore, this study aimed to assess the pattern of itching in adults with atopic dermatitis using questionnaires to assess for a circadian rhythm of itching in participating patients at a single institution (n = 241). A self-report questionnaire was used to assess circadian rhythm and intensity of itching in patients. In addition, the patients' disease severity (Eczema Area and Severity Index [EASI]) and quality of life (Dermatology Life Quality Index [DLQI]) were assessed. Itching occurred most frequently (74.69%) and with the greatest severity (62.66%) between 20:00 and 00:00, and the least number of patients (25.31%) experienced itching between 04:00 and 08:00. The DLQI and EASI scores both correlated with the average and maximum itch intensity (r = 0.582, r = 0.533, respectively; r = 0.539, r = 0.517, respectively; p < 0.001). The DLQI and EASI scores were associated with average itch intensity (B = 0.179, B = 0.204, respectively; 95% CI: 0.112 to 0.246, 95% CI: 0.096 to 0.313, respectively; p < 0.001), and the EASI score was associated with males and family history (B = 0.285, B = 0.287, respectively; 95% CI: 0.094 to 0.476, 95% CI: 0.096 to 0.478, respectively; p = 0.003). Adult patients with atopic dermatitis exhibited a circadian rhythm of itching; these study results could positively impact treatment approaches.

AuNPs-BP-MWCNTs-COOH-based electrochemical immunosensor for the determination of deoxynivalenol in wheat flour.

Deoxynivalenol (DON) has drawn considerable attention for its obvious pathogenicity and wide use in agro-products, which cause a potential threat to human health. In this work, an electrochemical immunosensor is developed for the highly sensitive and selective detection of DON in wheat flour using AuNPs-BP-MWCNTs-COOH and antibodies. The AuNPs-BP-MWCNTs-COOH nanocomposite was prepared via an in situ reduction reaction and ultrasonic-assisted liquid-phase exfoliation. The nanocomposite exhibits a larger surface area, decent stability, excellent electron transfer capability, good protein binding capability and prominent specificity. The plentiful carboxyl group on the nanocomposite can bind to the amino group of the antibody, and AuNPs have an affinity for the sulfhydryl group of the antibody, which makes it feasible for the nanocomposite to load the antibody. The peak currents are plotted against the logarithm of DON concentration from 0.002 to 80 ng mL-1 with a limit of detection (LOD) of 0.5 pg mL-1. This approach establishes an effective label-free immunosensor platform for the detection of DON with high sensitivity and selectivity in various food and agricultural products.

Efficacy and Safety of Acupuncture in Managing COPD: An Overview of Systematic Reviews.

Background: Acupuncture has been used as an adjuvant therapy for Chronic obstructive pulmonary disease (COPD). However, systematic reviews (SRs) and meta-analyses (MAs) have reported inconsistent results and unknown quality. This overview aimed to summarize the current SRs/MAs to provide evidence for the effectiveness and safety of acupuncture in the treatment of COPD. Methods: SRs/MAs were searched via eight databases from their establishment to December 31, 2023. The methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The risk of bias was assessed using the Risk of Bias in Systematic Review (ROBIS) tool. The Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A) to evaluate the reporting quality. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to determine the strength of evidence. In addition, we also conducted an analysis of the acupuncture points used in the primary RCTs. Results: Twenty-two SRs/MAs were included in this overview. Based on the assessment using AMSTAR 2, nineteen SRs/MAs were "critically low". Eight SRs/MAs had a low risk of bias. Based on PRISMA-A, the reporting completeness of eighteen SRs/MAs were more than 70%. As for GRADE assessment, only three outcome measures were of high quality. COPD patients can benefit from moxibustion, acupoint application, acupoint catgut embedding, manual acupuncture, and electroacupuncture, as indicated by effectiveness in measures including lung function, 6MWD, mMRC, CAT, and acute exacerbation. In addition, the efficacy of TENS needed to be further demonstrated. The commonly used acupuncture points in the RCTs include BL13, BL23, and EX-B1. Conclusion: Evidence from SRs showed that acupuncture is beneficial to lung function, acute exacerbation, 6MWD, mMRC and CAT. For SGRQ and brog scale, acupuncture should be used selectively, but this finding should still be taken with caution.

PGC1-Alpha/Sirt3 Signaling Pathway Mediates the Anti-Pulmonary Fibrosis Effect of Hirudin by Inhibiting Fibroblast Senescence.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease for which there is a lack of effective pharmacological treatments. Hirudin, a natural peptide extracted from leeches, has been used for broad pharmacological purposes. In this study, we investigated the therapeutic effects of hirudin on IPF and its related mechanism of action. By constructing a mouse model of pulmonary fibrosis and treating it with hirudin in vivo, we found that hirudin exerted anti-fibrotic, anti-oxidative, and anti-fibroblast senescence effects. Moreover, using an in vitro model of stress-induced premature senescence in primary mouse lung fibroblasts and treating with hirudin, we observed inhibition of fibroblast senescence and upregulation of PGC1-alpha and Sirt3 expression. However, specific silencing of PGC1-alpha or Sirt3 suppressed the anti-fibroblast senescence effect of hirudin. Thus, the PGC1-alpha/Sirt3 pathway mediates the anti-fibroblast senescence effect of hirudin, potentially serving as a molecular mechanism underlying its anti-fibrosis and anti-oxidative stress effects exerted on the lungs.

Non-Equilibrium Enhancement of Classical Information Transmission.

Information transmission plays a crucial role across various fields, including physics, engineering, biology, and society. The efficiency of this transmission is quantified by mutual information and its associated information capacity. While studies in closed systems have yielded significant progress, understanding the impact of non-equilibrium effects on open systems remains a challenge. These effects, characterized by the exchange of energy, information, and materials with the external environment, can influence both mutual information and information capacity. Here, we delve into this challenge by exploring non-equilibrium effects using the memoryless channel model, a cornerstone of information channel coding theories and methodology development. Our findings reveal that mutual information exhibits a convex relationship with non-equilibriumness, quantified by the non-equilibrium strength in transmission probabilities. Notably, channel information capacity is enhanced by non-equilibrium effects. Furthermore, we demonstrate that non-equilibrium thermodynamic cost, characterized by the entropy production rate, can actually improve both mutual information and information channel capacity, leading to a boost in overall information transmission efficiency. Our numerical results support our conclusions.

Enhancing clinical decision-making: Sysmex UF-5000 as a screening tool for bacterial urinary tract infection in children.

BACKGROUND: A rapid screening test for urinary tract infections (UTIs) in children is needed to avoid unnecessary cultures and provide prompt reports to make appropriate clinical decisions. We have evaluated for the first time the performance of the Sysmex UF-5000 flow cytometer as a screening tool for UTIs in children. METHODS: This study included 4445 pediatric patients, with urinary sediment and urine culture data collected from January 2020 to September 2023. The Sysmex UF-5000 analyzer was utilized to measure urine white blood cell (WBC) and bacteria (BACT), with the findings being compared to the culture results. RESULTS: At ≥ 104 colony-forming unit (CFU)/mL, 513 samples were culture-positive (400 samples presented 104-105 CFU/mL, and 113 demonstrated ≥ 105 CFU/mL bacterial growth). Optimal indicators for positive cultures were BACT counts of 92.2/µL (AUC: 0.944) and WBC counts of 40.8/µL (AUC:0.863). False negative rate were 0.9% when using a 7.8 bacteria/µL cut-off and avoiding unnecessary cultures in 28.1%. The UF-5000 has a higher consistency rate for Gram-negative (GN) bacteria (90.3%) than Gram-positive (GP) bacteria (86.8%). For samples with 105 CFU/mL, UF-5000's Bacteria -Information flags showed superior concordance for samples with 104-105 CFU/mL bacteria. CONCLUSIONS: Screening pediatric urine cultures with the UF-5000 showed potential application value in identifying negative cultures and significant bacterial growth, although performance may vary depending on the study population. Furthermore, detecting Gram typing aids in guiding early clinical empirical medication, particularly for UTIs caused by GN bacteria.

Senegenin Attenuates Pulmonary Fibrosis by Inhibiting Oxidative-Stress-Induced Epithelial Cell Senescence through Activation of the Sirt1/Pgc-1α Signaling Pathway.

Idiopathic pulmonary fibrosis is a fatal interstitial lung disease for which effective drug therapies are lacking. Senegenin, an effective active compound from the traditional Chinese herb Polygala tenuifolia Willd, has been shown to have a wide range of pharmacological effects. In this study, we investigated the therapeutic effects of senegenin on pulmonary fibrosis and their associated mechanisms of action. We found that senegenin inhibited the senescence of epithelial cells and thus exerted anti-pulmonary-fibrosis effects by inhibiting oxidative stress. In addition, we found that senegenin promoted the expression of Sirt1 and Pgc-1α and that the antioxidative and antisenescent effects of senegenin were suppressed by specific silencing of the Sirt1 and Pgc-1α genes, respectively. Moreover, the senegenin-induced effects of antioxidation, antisenescence of epithelial cells, and antifibrosis were inhibited by treatment with Sirt1 inhibitors in vivo. Thus, the Sirt1/Pgc-1α pathway exerts its antifibrotic effect on lung fibrosis by mediating the antioxidative and antisenescent effects of senegenin.

Diagnostic Value of Single LH and LH/FSH Ratio at 60-minute after GnRHa Stimulation Test for Central Precocious Puberty.

OBJECTIVES: To evaluate the diagnostic value of luteinizing hormone (LH) and LH/follicle stimulating hormone (FSH) ratio at 60 min after gonadotropin-releasing hormone analogs (GnRHa) stimulation test for central precocious puberty (CPP) in girls. METHODS: Two hundred and fifty-seven girls, aged 3 to 7.5 y, suspected of precocious puberty at authors' hospital from April 2020 through November 2023 were enrolled in the study. The blood was taken at 0, 30, 60 min after GnRHa stimulation test, and LH and LH/FSH were detected by chemiluminescence assay. The diagnostic efficacy was analysed by Mann-Whitney U test, spearman's correlation analysis and receiver operating characteristic (ROC) analysis. The proportion of obesity was analysed by Chi-square test. RESULTS: LH and LH/FSH at different times were statistically significantly different (P <0.05) between the CPP and non-CPP groups. Spearman's correlation analysis showed that the level of LH and LH/FSH at 60 min had the strongest consistency with the peak of LH (r = 0.9988, P <0.001) and LH/FSH (r = 0.9981, P <0.001). ROC curve analysis showed that the area under the ROC curves at 60 min of LH and LH/FSH were 0.975 and 0.997 with a cut-off value of 5.70 IU/L and 0.609, respectively. CONCLUSIONS: The peak of LH and LH/FSH in the diagnosis of CPP can be determined by LH and LH/FSH at 60 min after the triptorelin acetate is injected. This will reduce the number of blood draws required compared with the traditional stimulation test, which is more effective and acceptable for children.

Transcriptomic Insights into Different Stimulation Intensity of Electroacupuncture in Treating COPD in Rat Models.

Background: Electroacupuncture (EA), with varying stimulation intensities, has demonstrated therapeutic potentials in both animal and clinical studies for the treatment of chronic obstructive pulmonary disease (COPD). However, a comprehensive investigation of the intensity-related effects, particularly 1mA and 3mA of EA, and the underlying mechanisms remains lacking. Methods: A COPD rat model was established by prolonged exposure to cigarette smoke and intermittent intratracheal instillation of lipopolysaccharide. EA treatment was administered at acupoints BL13 (Feishu) and ST36 (Zusanli), 20 minutes daily for 2 weeks, with intensities of 1mA and 3mA. EA effectiveness was evaluated by pulmonary function, histopathological change, serum level of inflammatory cytokines, and level of oxidative stress markers in serum and lung tissues. Transcriptome profiling and weighted gene co-expression network analysis (WGCNA) were performed to reveal gene expression patterns and identify hub genes. Real-time quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect the mRNA and protein expression levels, respectively. Results: EA at both 1mA and 3mA exerted differing therapeutic effects by improving lung function and reducing inflammation and oxidative stress in COPD rats. Transcriptome analysis revealed distinct expression patterns between the two groups, functionally corresponding to shared and intensity-specific (1mA and 3mA) enriched pathways. Eight candidate genes were identified, including Aqp9, Trem1, Mrc1, and Gpnmb that were downregulated by EA and upregulated in COPD. Notably, Msr1 and Slc26a4 exclusively downregulated in EA-1mA, while Pde3a and Bmp6 upregulated solely in EA-3mA. WGCNA constructed 5 key modules and elucidated the module-trait relationship, with the aforementioned 8 genes being highlighted. Additionally, their mRNA and protein levels were validated by RT-qPCR and WB. Conclusion: Our results demonstrated that 1mA and 3mA intensities induce distinct gene expression patterns at the transcriptional level, associated with shared and 1mA vs 3mA-specific enriched pathways. Genes Mrc1, Gpnmb, Trem1, and Aqp9 emerge as promising targets, and further studies are needed to elucidate their functional consequences in COPD.

PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α.

Pyruvate dehydrogenase kinase 1 (PDK1) phosphorylates the pyruvate dehydrogenase complex, which inhibits its activity. Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis, which plays an important role in tumor progression. This study aims to elucidate how PDK1 promotes breast cancer progression. We found that PDK1 was highly expressed in breast cancer tissues, and PDK1 knockdown reduced the proliferation, migration, and tumorigenicity of breast cancer cells and inhibited the HIF-1α (hypoxia-inducible factor 1α) pathway. Further investigation showed that PDK1 promoted the protein stability of HIF-1α by reducing the level of ubiquitination of HIF-1α. The HIF-1α protein levels were dependent on PDK1 kinase activity. Furthermore, HIF-1α phosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer cells. The phosphorylation of HIF-1α at Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1α with von Hippel-Lindau and prolyl hydroxylase domain. We also found that PDK1 enhanced HIF-1α transcriptional activity. In summary, PDK1 enhances HIF-1α protein stability by phosphorylating HIF-1α at Ser451 and promotes HIF-1α transcriptional activity by enhancing the binding of HIF-1α to P300. PDK1 and HIF-1α form a positive feedback loop to promote breast cancer progression.

TROP2 is highly expressed in triple-negative breast cancer CTCs and is a potential marker for epithelial mesenchymal CTCs.

Circulating tumor cells (CTCs) are the seeds of distant metastases of malignant tumors and are associated with malignancy and risk of metastasis. However, tumor cells undergo epithelial-mesenchymal transition (EMT) during metastasis, leading to the emergence of different types of CTCs. Real-time dynamic molecular and functional typing of CTCs is necessary to precisely guide personalized treatment. Most CTC detection systems are based on epithelial markers that may fail to detect EMT CTCs. Therefore, it is clinically important to identify new markers of different CTC types. In this study, bioinformatics analysis and experimental assays showed that trophoblast cell surface antigen 2 (TROP2), a target molecule for advanced palliative treatment of triple-negative breast cancer (TNBC), was highly expressed in TNBC tissues and tumor cells. Furthermore, TROP2 can promote the migration and invasion of TNBC cells by upregulating EMT markers. The specificity and potential of TROP2 as an EMT-associated marker of TNBC CTCs were evaluated by flow cytometry, immunofluorescence, spiking experiments, and a well-established CTC assay. The results indicated that TROP2 is a potential novel CTC marker associated with EMT, providing a basis for more efficacious markers that encompass CTC heterogeneity in patients with TNBC.

Evaluating the causal association between bronchiectasis and different types of inflammatory bowel disease: a two-sample Mendelian randomization study.

Background and objectives: Previous observational studies have established a connection between bronchiectasis and inflammatory bowel disease (IBD), but none of these studies have provided a clear explanation for the underlying cause of this relationship. The present study thus implemented Mendelian randomization (MR) design to explore possible bidirectional relationships between IBD and bronchiectasis risk, with an additional focus on Crohn's disease (CD) and ulcerative colitis (UC) as IBD subtypes. Materials and methods: A large genome-wide association study (GWAS)-derived data pool was leveraged to examine the relationships between bronchiectasis and IBD, CD, and UC. Two-sample MR analyses were performed with an inverse variance weighted (IVW) approach supplemented with the MR-Egger and weighted median methods. Sensitivity analyses were used to further assess the reliability of the main MR study findings. The possibility of reverse causation was also evaluated using a reverse MR approach. Results: The IVW MR analytical approach revealed that IBD (p = 0.074), UC (p = 0.094), and CD (p = 0.644) had no significant impact on the incidence of bronchiectasis, with the converse also being true (p = 0.471, p = 0.700, and p = 0.099, respectively). Conclusion: This MR analysis demonstrated that the higher occurrence of bronchiectasis in patients with IBD is not caused by genetic predisposition.

Early gastric cancer detection and lesion segmentation based on deep learning and gastroscopic images.

Gastric cancer is a highly prevalent disease that poses a serious threat to public health. In clinical practice, gastroscopy is frequently used by medical practitioners to screen for gastric cancer. However, the symptoms of gastric cancer at different stages of advancement vary significantly, particularly in the case of early gastric cancer (EGC). The manifestations of EGC are often indistinct, leading to a detection rate of less than 10%. In recent years, researchers have focused on leveraging deep learning algorithms to assist medical professionals in detecting EGC and thereby improve detection rates. To enhance the ability of deep learning to detect EGC and segment lesions in gastroscopic images, an Improved Mask R-CNN (IMR-CNN) model was proposed. This model incorporates a "Bi-directional feature extraction and fusion module" and a "Purification module for feature channel and space" based on the Mask R-CNN (MR-CNN). Our study includes a dataset of 1120 images of EGC for training and validation of the models. The experimental results indicate that the IMR-CNN model outperforms the original MR-CNN model, with Precision, Recall, Accuracy, Specificity and F1-Score values of 92.9%, 95.3%, 93.9%, 92.5% and 94.1%, respectively. Therefore, our proposed IMR-CNN model has superior detection and lesion segmentation capabilities and can effectively aid doctors in diagnosing EGC from gastroscopic images.

NBR1-p62-Nrf2 mediates the anti-pulmonary fibrosis effects of protodioscin.

BACKGROUND: Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress. METHODS: A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-ß to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-ß with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected. RESULTS: In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding. CONCLUSION: The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.