Up-regulation of HSP90α in HDM-induced asthma causes pyroptosis of airway epithelial cells by activating the cGAS-STING-ER stress pathway.

Heat Shock protein 90 α (HSP90α), an main subtype of chaperone protein HSP90, involves important biological functions such as DNA damage repair, protein modification, innate immunity. However, the potential role of HSP90α in asthma occurrence and development is still unclear. This study aimed to elucidate the underlying mechanism of HSP90α in asthma by focusing on the cGAS-STING-Endoplasmic Reticulum stress pathway in inflammatory airway epithelial cell death (i.e., pyroptosis; inflammatory cell death). To accomplish that, we modeled allergen exposure in C57/6BL mice and bronchial epithelial cells with house dust mite. Protein technologies and immunofluorescence utilized to study the expression of HSP90α, activation of cGAS-STING pathway and pyroptosis. The effect of inhibitors on HDM-exposed mice detected by histological techniques and examination of bronchoalveolar lavage fluid. Results showed that HSP90α promotes asthma inflammation via pyroptosis and activation of the cGAS-STING-ER stress pathway. Treatment with the HSP90 inhibitor tanespimycin (17-AAG) significantly relieved airway inflammation and abrogated the effect of HSP90α on pyroptosis and cGAS-STING-ER stress in vitro and in vivo models of HDM. Further data indicated that up-regulation of HSP90α stabilized STING through interaction, which increased localization of STING on the ER. Activation of STING triggered ER stress and leaded to pyroptosis-related airway inflammation. The finding showed the potential role of pyroptosis caused by dysregulation of HSP90α on airway epithelial cells in allergic inflammation, suggested that targeting HSP90α in airway epithelial cells might prove to be a potential additional treatment strategy for asthma.

Tetrandrine alleviates pulmonary fibrosis by inhibiting alveolar epithelial cell senescence through PINK1/Parkin-mediated mitophagy.

Idiopathic pulmonary fibrosis (IPF) is a fatal and insidious interstitial lung disease. So far, there are no effective drugs for preventing the disease process. Cellular senescence plays a critical role in the development of IPF, with the senescence and insufficient mitophagy of alveolar epithelial cells being implicated in its pathogenesis. Tetrandrine is a natural alkaloid which is now produced synthetically. It was known that the tetrandrine has anti-fibrotic effects, but the efficacy and mechanisms are still not well evaluated. Here, we reveal the roles of tetrandrine on AECs senescence and the antifibrotic effects by using a bleomycin challenged mouse model of pulmonary fibrosis and a bleomycin-stimulated mouse alveolar epithelial cell line (MLE-12). We performed the ß-galactosidase staining, immunohistochemistry and fluorescence to assess senescence in MLE-12 cells. The mitophagy levels were detected by co-localization of LC3 and COVIX. Our findings indicate that tetrandrine suppressed bleomycin-induced fibroblast activation and ultimately blocked the increase of collagen deposition in mouse model lung tissue. It has significantly inhibited the bleomycin-induced senescence and senescence-associated secretory phenotype (SASP) in alveolar epithelial cells (AECs). Mechanistically, tetrandrine suppressed the decrease of mitochondrial autophagy-related protein expression to rescue the bleomycin-stimulated impaired mitophagy in MLE-12 cells. We revealed that knockdown the putative kinase 1 (PINK1) gene by a short interfering RNA (siRNA) could abolish the ability of tetrandrine and reverse the MLE-12 cells senescence, which indicated the mitophagy of MLE-12 cells is PINK1 dependent. Our data suggest the tetrandrine could be a novel and effective drug candidate for lung fibrosis and senescence-related fibrotic diseases.

RNF130 protects against pulmonary fibrosis through suppressing aerobic glycolysis by mediating c-myc ubiquitination.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease,characterized by an excessive accumulation of extracellular matrix (ECM) proteins in response to chronic lung injury. Current evidence suggests that metabolic reprogramming is always accompanied by myofibroblast activation in IPFof whichthe underlying mechanisms remain unclear. Ring finger protein 130 (RNF130), was demonstrated involved in multiple diseases. However, whether RNF130 plays a critical role in the pathogenesis of IPF needs to be clarified. METHODS: We first investigated the expression of RNF130 in pulmonary fibrosis in vivo and in vitro. We then observed the effect and explored the molecular mechanism of RNF130 on the transition of fibroblast to myofibroblast and aerobic glycolysis. Further, we assessed the effects of adeno-associated virus (AAV)-induced RNF130 overexpression in the pulmonary fibrosis model, conducting pulmonary function, assessment of collagen depositionusing the hydroxyproline assay, and biochemical and histopathological analyses. RESULTS: We found that RNF130 was down-regulated in lung tissues of mice with bleomycin-induced pulmonary fibrosis and lung fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). Then we demonstrated that RNF130 inhibitedthe transition of fibroblast to myofibroblast by suppressing aerobic glycolysis. Mechanistically, we revealed that RNF130 promotedc-myc ubiquitination and degradation, while c-myc overexpression reverses the inhibitory effects of RNF130. Importantly, pulmonary function, collagen deposition and fibroblast differentiation were significantly alleviated in adeno-associated virus serotype (AAV)6-RNF130 treated mice, which further validated the contribution of RNF130/c-myc signaling axis in pulmonary fibrosis pathological process. CONCLUSIONS: In summary, RNF130 participates in the pathogenesis of pulmonary fibrosis by inhibiting the transition of fibroblast to myofibroblast and aerobic glycolysis through promoting c-myc ubiquitination and degradation. Targeting RNF130-c-myc axismightrepresent a promising strategy to alleviate the progression of IPF.

Effects of running on sports injuries during rehabilitation / Efeitos da corrida sobre as lesões esportivas durante a reabilitação / Efectos de la carrera en las lesiones deportivas durante la rehabilitación

ABSTRACT Introduction: Running is a simple, comfortable, low-cost aerobic exercise that promotes health and prevents obesity and heart and brain diseases. Its practice has grown considerably as therapy, and recent studies indicate that there may also be benefits during physical rehabilitation. Objective: Study the effects of running on sports injuries during rehabilitation. Methods: A search was made in the current medical literature to develop a therapeutic management plan. The experimental test method consisted of a study with 38 healthy runners. They were divided into healthy and injured groups according to their sports injuries. Within one year after the experiment, the physical function of the two groups of runners was evaluated again. The result was compared through mathematical statistics among other research methods. results: The total score of the injured group in the FMS test of screening general body movement function was ≤14 points; the comparison found that the athletes in the injured group generally showed weaker bilateral function than the healthy group. Conclusion: Running exercise is feasible in patients with sports injuries, medium intensity running can improve the speed of recovery in these patients. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A corrida é um exercício aeróbico simples, confortável e de baixo custo que pode promover a saúde e prevenir a obesidade, doenças cardíacas e cerebrais. Sua prática tem crescido bastante como uma terapia e estudos recentes indicam que possam haver benefícios também durante o processo de reabilitação física. Objetivo: Estudar os efeitos da corrida sobre lesões esportivas durante a reabilitação. Métodos: Efetuou-se uma pesquisa na literatura médica atual para elaborar um plano de conduta terapêutica. O método de teste experimental consistiu num estudo com 38 corredores saudáveis. Eles foram divididos em grupo saudável e grupo lesionado, de acordo com suas lesões esportivas. Dentro de um ano após o experimento, avaliou-se novamente a função física dos dois grupos de atletas. O resultado foi comparado através do método de estatística matemática entre outros métodos de pesquisa. Resultados: A pontuação total do grupo lesionado no teste FMS de triagem da função de movimento corporal geral foi de ≤14 pontos, a comparação constatou que os atletas do grupo lesionado geralmente mostraram uma função bilateral mais fraca do que o grupo saudável. Conclusão: O exercício de corrida mostrou-se viável em pacientes com lesões esportivas, uma corrida de média intensidade pode melhorar a velocidade de recuperação desses pacientes. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La carrera es un ejercicio aeróbico sencillo, cómodo y de bajo coste que puede promover la salud y prevenir la obesidad y las enfermedades cardíacas y cerebrales. Su práctica ha crecido mucho como terapia y estudios recientes indican que puede haber beneficios también durante el proceso de rehabilitación física. Objetivo: Estudiar los efectos de la carrera en las lesiones deportivas durante la rehabilitación. Métodos: Se realizó una búsqueda en la literatura médica actual para elaborar un plan de manejo terapéutico. El método de prueba experimental consistió en un estudio con 38 corredores sanos. Se dividieron en un grupo sano y otro lesionado según sus lesiones deportivas. Un año después del experimento, se volvió a evaluar la función física de los dos grupos de corredores. El resultado se comparó mediante el método de la estadística matemática, entre otros métodos de investigación. Resultados: La puntuación total del grupo lesionado en la prueba FMS de detección de la función de movimiento corporal general fue de ≤14 puntos, la comparación encontró que los atletas del grupo lesionado mostraron generalmente una función bilateral más débil que el grupo sano. Conclusión: Se demostró que el ejercicio de correr es factible en pacientes con lesiones deportivas, la carrera de intensidad media puede mejorar la velocidad de recuperación en estos pacientes. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

A new rapid and sensitive method for detecting chicken infectious anemia virus.

Since the chicken infectious anemia virus (CIAV) was discovered in 1979, which has been reported as an economically significant and immunosuppressive poultry disease in the world. A novel clinical detection method for the prevention and control of CIAV in the poultry sector is urgently needed. Here, we established a real-time recombinase-aided amplification assay (RAA) for CIAV on-site with a rapid, highly sensitive, strongly specific, low-cost, and simple operational molecular diagnosis detection method. The primers and probe were developed using the CIAV VP2 gene sequence, which has a 117-bp specific band. This assay, which could be carried out at 41°C and completed in 30 min without cross-reactivity with other viruses, had the lowest detection limit of 10 copies of CIAV DNA molecules per reaction. Furthermore, the kappa value of this assay was 0.947, the sensitivity was 93.33%, and the specificity was 100% when compared to the real-time quantitative polymerase chain reaction assay (real-time qPCR). These results indicate that using a real-time RAA assay to detect CIAV on-site could be beneficial. In the future, the real-time RAA test may be a regular assay for the prevention and control of CIAV, as well as help the reduction of economic losses in the poultry business.

Activation of ß2-adrenergic Receptor Ameliorates Amyloid-ß-induced Mitophagy Defects and Tau Pathology in Mice.

Defective mitophagy and mitochondrial dysfunction have been linked to aging and Alzheimer's disease (AD). ß2-Adrenergic receptor (ADRB2) is critical for mitochondrial and cognitive function. However, researchers have not clearly determined whether ADRB2 activation ameliorates defective mitophagy and cognitive deficits in individuals with AD. Here, we observed that the activation of ADRB2 by clenbuterol (Clen, ADRB2 agonist, 2 mg/kg/day) ameliorated amyloid-ß-induced (Aß1-42 bilateral intracerebral infusion, 2 µl, 5 µg/µl) memory deficits. Activation of ADRB2 also attenuated Aß-induced mitochondrial dysfunction, as revealed by increased ATP levels, mitochondrial membrane potential (MMP/Δψm) and complex I activity. Further studies revealed that ADRB2 activation restored mitophagy deficits, as revealed by the increased light chain 3 (LC3)-II/LC3-I ratio, Atg5 levels, and Atg7 levels and decreased p62 levels, along with the upregulation of PTEN-induced putative kinase 1 (PINK1), Parkin and NAD+ levels. Activation of ADRB2 rescued Aß-induced oxidative stress and neuronal death. ADRB2 activation also attenuated Aß-induced tau hyperphosphorylation by regulating glycogen synthase kinase-3ß expression in the hippocampus. Finally, we established that Clen improved mitophagy and attenuated mitochondrial dysfunction, and tau pathology in mice by activating the ADRB2/Akt/PINK1 signaling pathway. Conversely, the inhibition of ADRB2 by propranolol (ßAR antagonist, 10 µM) blocked the Clen-mediated improvements in pathological changes in N2a cells. The results from the present study indicate that ADRB2 activation may be a therapeutic strategy for AD.

New rapid detection by using a constant temperature method for avian leukosis viruses.

The avian leukemia virus causes avian leukemia (AL), a severe immunosuppressive disease in chickens (ALV). Since the 1990s, the diversity of ALV subpopulations caused by ALV genome variation and recombination, and the complexity of the infection and transmission, with currently no effective commercial vaccine and therapeutic for ALV, has resulted in severe economic losses to the chicken business in various parts of the world. Therefore, as a key means of prevention and control, an effective, rapid, and accurate detection method is imperative. A new real-time reverse transcription recombinase-aided amplification (RT-RAA) assay for ALV with rapid, highly specific, low-cost, and simple operational characteristics have been developed in this study. Based on the amplification of 114 base pairs from the ALV P12 gene, real-time RT-RAA primers and a probe were designed for this study. The lowest detection line was 10 copies of ALV RNA molecules per response, which could be carried out at 39°C in as fastest as 5 min and completed in 30 min, with no cross-reactivity with Marek's disease virus, avian reticuloendothelial virus, Newcastle disease virus, infectious bronchitis virus, infectious bursal disease virus, infectious laryngotracheitis virus, and avian influenza virus. Furthermore, the kappa value of 0.91 (>0.81) was compared with reverse transcription-polymerase chain reaction (RT-PCR) for 44 clinical samples, and the coefficients of variation were within 5.18% of the repeated assays with three low-level concentration gradients. These results indicate that using a real-time RT-RAA assay to detect ALV could be a valuable method.

Extracellular HSP90α promotes cellular senescence by modulating TGF-ß signaling in pulmonary fibrosis.

Recent findings suggest that extracellular heat shock protein 90α (eHSP90α) promotes pulmonary fibrosis, but the underlying mechanisms are not well understood. Aging, especially cellular senescence, is a critical risk factor for idiopathic pulmonary fibrosis (IPF). Here, we aim to investigate the role of eHSP90α on cellular senescence in IPF. Our results found that eHSP90α was upregulated in bleomycin (BLM)-induced mice, which correlated with the expression of senescence markers. This increase in eHSP90α mediated fibroblast senescence and facilitated mitochondrial dysfunction. eHSP90α activated TGF-ß signaling through the phosphorylation of the SMAD complex. The SMAD complex binding to p53 and p21 promoters triggered their transcription. In vivo, the blockade of eHSP90α with 1G6-D7, a specific eHSP90α antibody, in old mice attenuated the BLM-induced lung fibrosis. Our findings elucidate a crucial mechanism underlying eHSP90α-induced cellular senescence, providing a framework for aging-related fibrosis interventions.

HDM induce airway epithelial cell ferroptosis and promote inflammation by activating ferritinophagy in asthma.

Asthma is a disease characterized by airway epithelial barrier destruction, chronic airway inflammation, and airway remodeling. Repeated damage to airway epithelial cells by allergens in the environment plays an important role in the pathophysiology of asthma. Ferroptosis is a novel form of regulated cell death mediated by lipid peroxidation in association with free iron-mediated Fenton reactions. In this study, we explored the contribution of ferroptosis to house dust mite (HDM)-induced asthma models. Our in vivo and in vitro models showed labile iron accumulation and enhanced lipid peroxidation with concomitant nonapoptotic cell death upon HDM exposure. Treatment with ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (Fer-1) illuminated the role of ferroptosis and related damage-associated molecular patterns in HDM-treated airway epithelial cells. Furthermore, DFO and Fer-1 reduced HDM-induced airway inflammation in model mice. Mechanistically, NCOA4-mediated ferritin-selective autophagy (ferritinophagy) was initiated during ferritin degradation in response to HDM exposure. Together, these data suggest that ferroptosis plays an important role in HDM-induced asthma and that ferroptosis may be a potential treatment target for HDM-induced asthma.

Anti-PD-L1 antibody alleviates pulmonary fibrosis by inducing autophagy via inhibition of the PI3K/Akt/mTOR pathway.

Pulmonary fibrosis is a fatal lung disease for which no effective treatment is available. Previous studies have shown that the expression of programmed cell death-Ligand (PD-L1) is significantly increased in pulmonary fibrosis, and that this is related to the occurrence of this disease. However, the underlying mechanism is not clear. To clarify the efficacy and mechanism of an anti-PD-L1 monoclonal antibody (anti-PD-L1 mAb) as a treatment for pulmonary fibrosis, we conducted histopathological, molecular, and functional analyses in a mouse model of bleomycin-induced pulmonary fibrosis and a cell model of fibrosis induced by transforming growth factor-beta 1 (TGF-ß1). Our results indicate that PD-L1 is highly expressed in the lung fibrosis model. The anti-PD-L1 mAb significantly alleviated bleomycin-induced lung structural disorders and collagen deposition in mice and inhibited the proliferation, migration, activation and extracellular matrix deposition of TGF-ß1-induced lung fibroblasts. Interestingly, the anti-PD-L1 mAb could also alleviate the autophagy impairment observed in pulmonary fibrosis. The potential mechanism is through the downregulation of the PI3K/Akt/mTOR signaling pathway. Our study provides evidence of the crucial ability of anti-PD-L1 mAbs to activate autophagy in the context of pulmonary fibrosis, providing a new strategy for the treatment of this disease.

Tetrandrine Modulates Rheb-mTOR Signaling-Mediated Selective Autophagy and Protects Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a progressive fatal disease characterized by interstitial remodeling, with high lethality and a lack of effective medical therapies. Tetrandrine has been proposed to present anti-fibrotic effects, but the efficacy and mechanisms have not been systematically evaluated. We sought to study the potential therapeutic effects and mechanisms of tetrandrine against lung fibrosis. The anti-fibrotic effects of tetrandrine were evaluated in bleomycin-induced mouse models and TGF-ß1-stimulated murine lung fibroblasts. We performed Chromatin Immunoprecipitation (ChIP), Immunoprecipitation (IP), and mRFP-GFP-MAP1LC3B adenovirus construct to investigate the novel mechanisms of tetrandrine-induced autophagy. Tetrandrine decreased TGF-ß1-induced expression of α-smooth muscle actin, fibronectin, vimentin, and type 1 collagen and proliferation in fibroblasts. Tetrandrine restored TGF-ß1-induced impaired autophagy flux, accompanied by enhanced interaction of SQSTM1 and MAP1LC3-Ⅱ. ChIP studies revealed that tetrandrine induced autophagy via increasing binding of NRF2 and SQSTM1 promoter. Furthermore, tetrandrine inhibited TGF-ß1-induced phosphorylation of mTOR by reducing activation of Rheb. In vivo tetrandrine suppressed the bleomycin-induced expression of fibrotic markers and improved pulmonary function. Our data suggest that protective effect of tetrandrine against lung fibrosis might be through promoting Rheb-mTOR and NRF2-SQSTM1 mediated autophagy. Tetrandrine may thus be potentially employed as a novel therapeutic medicine against IPF.

Anlotinib Inhibits PFKFB3-Driven Glycolysis in Myofibroblasts to Reverse Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease in which the normal alveolar network is gradually replaced by fibrotic scars. Current evidence suggests that metabolic alterations correlate with myofibroblast activation in IPF. Anlotinib has been proposed to have antifibrotic effects, but the efficacy and mechanisms of anlotinib against lung fibrosis have not been systematically evaluated. The antifibrotic effects of anlotinib were evaluated in bleomycin-induced mouse models and transforming growth factor-beta 1 (TGF-ß1)-stimulated lung fibroblasts. We measured lactate levels, 2-NBDG glucose uptake and the extracellular acidification rate (ECAR) to assess glycolysis in fibroblasts. RNA-protein coimmunoprecipitation (RIP) and polysome analyses were performed to investigate novel mechanisms of glycolytic reprogramming in pulmonary fibrosis. We found that anlotinib diminished myofibroblast activation and inhibited the augmentation of glycolysis. Moreover, we show that PCBP3 posttranscriptionally increases PFKFB3 expression by promoting its translation during myofibroblast activation, thus promoting glycolysis in myofibroblasts. Regarding mechanism, anlotinib exerts potent antifibrotic effects by downregulating PCBP3, reducing PFKFB3 translation and inhibiting glycolysis in myofibroblasts. Furthermore, we observed that anlotinib had preventative and therapeutic antifibrotic effects on bleomycin-induced pulmonary fibrosis. Therefore, we identify PCBP3 as a protein involved in the regulation of glycolysis reprogramming and lung fibrogenesis and propose it as a therapeutic target for pulmonary fibrosis. Our data suggest that anlotinib has antifibrotic effects on the lungs, and we provide a novel mechanism for this effect. Anlotinib may constitute a novel and potent candidate for the treatment of pulmonary fibrosis.

Extracellular HSP90α Interacts With ER Stress to Promote Fibroblasts Activation Through PI3K/AKT Pathway in Pulmonary Fibrosis.

Pulmonary fibrosis is characterized by alveolar epithelial cell injury, lung fibroblast proliferation, differentiation, and extracellular matrix (ECM) deposition. Our previous study indicated that extracellular HSP90α (eHSP90α) promotes pulmonary fibrosis by activating the MAPK signaling pathway. Thus, treatment with 1G6-D7 (a selective HSP90α monoclonal antibody) to antagonize eHSP90α could effectively ameliorate fibrosis. This study aimed to elucidate the mechanism underlying the effects of eHSP90α in pulmonary fibrosis by focusing on its link with endoplasmic reticulum (ER) stress. Our results showed that eHSP90α promoted lung fibroblast differentiation by activating ER stress. Treatment with the ER stress inhibitor tauroursodeoxycholate (TUDCA) or glucose-regulated protein 78 kDa (GRP78) depletion significantly abrogated the effect of eHSP90α on ER stress and fibroblast activation. In addition, eHSP90α induced ER stress in fibroblasts via the phosphoinositide-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, which could be blocked by the PI3K/AKT inhibitor LY294002, and blockade of eHSP90α by 1G6-D7 markedly inhibited ER stress in the model, indicating preventive and therapeutic applications. Intriguingly, we observed that TUDCA effectively reduced the secretion of eHSP90α in vitro and in vivo. In conclusion, this study shows that the interaction between eHSP90α and ER stress plays a crucial role in pulmonary fibrosis, indicating a positive feedback in lung fibroblasts. Targeting eHSP90α and alleviating fibroblast ER stress may be promising therapeutic approaches for pulmonary fibrosis.

A Lightweight Attention-Based CNN Model for Efficient Gait Recognition with Wearable IMU Sensors.

Wearable sensors-based gait recognition is an effective method to recognize people's identity by recognizing the unique way they walk. Recently, the adoption of deep learning networks for gait recognition has achieved significant performance improvement and become a new promising trend. However, most of the existing studies mainly focused on improving the gait recognition accuracy while ignored model complexity, which make them unsuitable for wearable devices. In this study, we proposed a lightweight attention-based Convolutional Neural Networks (CNN) model for wearable gait recognition. Specifically, a four-layer lightweight CNN was first employed to extract gait features. Then, a novel attention module based on contextual encoding information and depthwise separable convolution was designed and integrated into the lightweight CNN to enhance the extracted gait features and simplify the complexity of the model. Finally, the Softmax classifier was used for classification to realize gait recognition. We conducted comprehensive experiments to evaluate the performance of the proposed model on whuGait and OU-ISIR datasets. The effect of the proposed attention mechanisms, different data segmentation methods, and different attention mechanisms on gait recognition performance were studied and analyzed. The comparison results with the existing similar researches in terms of recognition accuracy and number of model parameters shown that our proposed model not only achieved a higher recognition performance but also reduced the model complexity by 86.5% on average.

Development and Validation of a 18F-FDG PET/CT-Based Clinical Prediction Model for Estimating Malignancy in Solid Pulmonary Nodules Based on a Population With High Prevalence of Malignancy.

PURPOSE: To develop a prediction model based on 18F-fludeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for solid pulmonary nodules (SPNs) with high malignant probability. PATIENTS AND METHODS: We retrospectively reviewed the records of CT-undetermined SPNs, which were further evaluated by PET/CT between January 2008 and December 2015. A total of 312 cases were included as a training set and 159 as a validation set. Logistic regression was applied to determine independent predictors, and a mathematical model was deduced. The area under the receiver operating characteristic curve (AUC) was compared to other models. Model fitness was assessed based on the American College of Chest Physicians guidelines. RESULTS: There were 215 (68.9%) and 127 (79.9%) malignant lesions in the training and validation sets, respectively. Eight independent predictors were identified: age [odds ratio (OR) = 1.030], male gender (OR = 0.268), smoking history (OR = 2.719), lesion diameter (OR = 1.067), spiculation (OR = 2.530), lobulation (OR = 2.614), cavity (OR = 2.847), and standardized maximum uptake value of SPNs (OR = 1.229). Our AUCs (training set, 0.858; validation set, 0.809) was better than those of previous models (Mayo: 0.685, P = .0061; Peking University People's Hospital: 0.646, P = .0180; Herder: 0.708, P = .0203; Zhejiang University: 0.757, P = .0699). The C index of the nomogram was 0.858. Our model reduced the diagnosis of indeterminate nodules (26.4% vs. 79.2%, 53.5%, 39.6%, and 34.0%, respectively) while improved sensitivity (81.3% vs. 16.4%, 49.2%, 62.5%, and 68.0%, respectively) and accuracy (65.4% vs. 16.4%, 39.6%, 52.8%, and 58.5%, respectively). CONCLUSION: Our model could permit accurate diagnoses and may be recommended to identify malignant SPNs with high malignant probability, as our data pertain to a very high-prevalence cohort only.