Prevalence of Reproductive Tract Infections and Association with Human Papillomavirus Infection Among Reproductive-Age Women - Six Tertiary Hospitals, China, June 2021-December 2022.

What is already known about this topic?: Previous studies have indicated a possible association between reproductive tract infections (RTIs) and high-risk human papillomavirus (HPV) infection, but the evidence is still inconclusive. What is added by this report?: This multicenter study found significantly higher positive rates of HPV, including general HPV, high-risk HPV, and HPV 16/18 infections, among women who tested positive for single or multiple RTIs compared to women who tested negative for RTIs in gynecological outpatient clinics. What are the implications for public health practice?: Infection with HPV, especially high-risk types, is linked to RTIs and imbalances in the vaginal microbiota. Implementing standardized protocols for identifying and treating RTIs could support the establishment of a healthy vaginal microenvironment. This, in turn, may offer a novel approach to preventing cervical cancer.

Mesoscopic mapping of hemodynamic responses and neuronal activity during pharmacologically induced interictal spikes in awake and anesthetized mice.

Imaging hemodynamic responses to interictal spikes holds promise for presurgical epilepsy evaluations. Understanding the hemodynamic response function is crucial for accurate interpretation. Prior interictal neurovascular coupling data primarily come from anesthetized animals, impacting reliability. We simultaneously monitored calcium fluctuations in excitatory neurons, hemodynamics, and local field potentials (LFP) during bicuculline-induced interictal events in both isoflurane-anesthetized and awake mice. Isoflurane significantly affected LFP amplitude but had little impact on the amplitude and area of the calcium signal. Anesthesia also dramatically blunted the amplitude and latency of the hemodynamic response, although not its area of spread. Cerebral blood volume change provided the best spatial estimation of excitatory neuronal activity in both states. Targeted silencing of the thalamus in awake mice failed to recapitulate the impact of anesthesia on hemodynamic responses suggesting that isoflurane's interruption of the thalamocortical loop did not contribute either to the dissociation between the LFP and the calcium signal nor to the alterations in interictal neurovascular coupling. The blood volume increase associated with interictal spikes represents a promising mapping signal in both the awake and anesthetized states.

A Novel ST-YOLO Network for Steel-Surface-Defect Detection.

Recent progress has been made in defect detection using methods based on deep learning, but there are still formidable obstacles. Defect images have rich semantic levels and diverse morphological features, and the model is dynamically changing due to ongoing learning. In response to these issues, this article proposes a shunt feature fusion model (ST-YOLO) for steel-defect detection, which uses a split feature network structure and a self-correcting transmission allocation method for training. The network structure is designed to specialize the process of classification and localization tasks for different computing needs. By using the self-correction criteria of adaptive sampling and dynamic label allocation, more sufficiently high-quality samples are utilized to adjust data distribution and optimize the training process. Our model achieved better performance on the NEU-DET datasets and the GC10-DET datasets and was validated to exhibit excellent performance.

Study on mechanism of Zhenwu Decoction in treatment of heart failure based on network pharmacology: A review.

To explore the mechanism of Zhenwu Decoction (ZWD) in the treatment of heart failure (HF) by network pharmacology analysis, so as to provide a basis for the innovation and application of drugs. The effective components and targets of 5 Chinese herbal medicines in ZWD were retrieved by TCM Pharmacology Database and Analysis Platform (TCMSP).Gene card, OMIM and TTD databases were used to obtain the disease targets of HF, and the intersection with the targets of ZWD was obtained. We used Cytoscape3.9.1 software to construct a drug-active component-disease-target interaction network for ZWD treatment of HF, and performed protein-protein interaction (PPI) network and topology analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed. Fifty-nine effective components and 229 targets of ZWD were screened. Among them, ZWD for HF has 27 active components and 38 common targets, and the core targets of PPI are IL-6, ATK1 and TNF. Pathway enrichment analysis included lipid and atherosclerotic and TNF signaling pathways. This study preliminarily clarified the main active components, targets and related pathways of ZWD in the treatment of HF, and laid a foundation for further study of the pharmacological effects of ZWD.

Excitatory-inhibitory mismatch shapes node recruitment in an epileptic network.

OBJECTIVE: Focal epilepsy is thought to be a network disease, in which epileptiform activity can spread noncontiguously through the brain via highly interconnected nodes, or hubs, within existing networks. Animal models confirming this hypothesis are scarce, and our understanding of how distant nodes are recruited is also lacking. Whether interictal spikes (IISs) also create and reverberate through a network is not well understood. METHODS: We injected bicuculline into the S1 barrel cortex and employed multisite local field potential and Thy-1 and parvalbumin (PV) cell mesoscopic calcium imaging during IISs to monitor excitatory and inhibitory cells in two monosynaptically connected nodes and one disynaptically connected node: ipsilateral secondary motor area (iM2), contralateral S1 (cS1), and contralateral secondary motor area (cM2). Node participation was analyzed with spike-triggered coactivity maps. Experiments were repeated with 4-aminopyridine as an epileptic agent. RESULTS: We found that each IIS reverberated throughout the network, differentially recruiting both excitatory and inhibitory cells in all connected nodes. The strongest response was found in iM2. Paradoxically, node cM2, which was connected disynaptically to the focus, was recruited more intensely than node cS1, which was connected monosynaptically. The explanation for this effect could be found in node-specific excitatory/inhibitory (E/I) balance, as cS1 demonstrated greater PV inhibitory cell activation compared with cM2, where Thy-1 excitatory cells were more heavily recruited. SIGNIFICANCE: Our data show that IISs spread noncontiguously by exploiting fiber pathways that connect nodes in a distributed network and that E/I balance plays a critical role in node recruitment. This multinodal IIS network model can be used to investigate cell-specific dynamics in the spatial propagation of epileptiform activity.

Gabrb3 is required for the functional integration of pyramidal neuron subtypes in the somatosensory cortex.

Dysfunction of gamma-aminobutyric acid (GABA)ergic circuits is strongly associated with neurodevelopmental disorders. However, it is unclear how genetic predispositions impact circuit assembly. Using in vivo two-photon and widefield calcium imaging in developing mice, we show that Gabrb3, a gene strongly associated with autism spectrum disorder (ASD) and Angelman syndrome (AS), is enriched in contralaterally projecting pyramidal neurons and is required for inhibitory function. We report that Gabrb3 ablation leads to a developmental decrease in GABAergic synapses, increased local network synchrony, and long-lasting enhancement in functional connectivity of contralateral-but not ipsilateral-pyramidal neuron subtypes. In addition, Gabrb3 deletion leads to increased cortical response to tactile stimulation at neonatal stages. Using human transcriptomics and neuroimaging datasets from ASD subjects, we show that the spatial distribution of GABRB3 expression correlates with atypical connectivity in these subjects. Our studies reveal a requirement for Gabrb3 during the emergence of interhemispheric circuits for sensory processing.

The more ambidexterity the better? The moderating effect of organizational learning between high-performance HR practices and organizational performance.

Objective: The objective of this study is to test the directly impact of high-performance HR practices on organizational performance, and the mediating effect of organizational ambidexterity empirically. Moreover, the moderating role of organizational learning in the relationship between ambidexterity and specialization in exploitation or exploration on firm performance has also been examined. Ultimately, we construct a moderated mediation model. Methods: Questionnaires were distributed to the target enterprises mainly through the contacts of the research group members, the local management consulting association and the training opportunities for leaders. Finally, a total of 347 CEO questionnaire data were collected from Chinese SMEs. The sample cover Shanghai, Beijing, Chongqing, Jiangsu, Zhejiang, Guangdong, Henan, Sichuan and other eastern and central regions. SPSS 23.0 and AMOS 24.0 were used to analyze the data. Results: The results revealed that high-performance HR practices had a positive effect on organizational performance and that organizational ambidexterity played a partially mediating role between high-performance HR practices and organizational performance. Further, organizational learning moderated the effects of organizational ambidexterity and organizational specificity on firm performance. Discussion: This study provided valuable practical insights. On one hand, this study provides a concrete operational scheme for SMEs in China to realize organizational ambidexterity by integrating a series of HR practices such as employees' ability, motivation and opportunity. On the other hand, through organizational ambidexterity, firms can not only obtain organizational long-term performance by enhancing their new product R & D capabilities, that is, exploratory innovation, but also utilize their existing resources to improve and expand their existing products and services, that is, to achieve short-term performance by exploitative innovation.

Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model.

Seizures are thought to arise from an imbalance of excitatory and inhibitory neuronal activity. While most classical studies suggest excessive excitatory neural activity plays a generative role, some recent findings challenge this view and instead argue that excessive activity in inhibitory neurons initiates seizures. We investigated this question of imbalance in a zebrafish seizure model with two-photon imaging of excitatory and inhibitory neuronal activity throughout the brain using a nuclear-localized calcium sensor. We found that seizures consistently initiated in circumscribed zones of the midbrain before propagating to other brain regions. Excitatory neurons were both more prevalent and more likely to be recruited than inhibitory neurons in initiation as compared with propagation zones. These findings support a mechanistic picture whereby seizures initiate in a region of hyperexcitation, then propagate more broadly once inhibitory restraint in the surround is overcome.

The diagnostic value of soluble TIM-3 in oral squamous cell carcinoma.

Objective: To evaluate the soluble TIM-3 (sTIM-3) expression level in oral squamous cell carcinoma (OSCC) and determine its clinical diagnostic potential. Methods: The sTIM-3 and squamous cell carcinoma antigen (SCCAg) levels of 199 OSCC patients and 107 healthy individuals were assessed using an enzyme-linked immunosorbent assay and their individual and combined efficiency rates were compared. Results: The results showed higher sTIM-3 and SCCAg levels in the OSCC patients and better diagnostic potential for a combination of these markers than for their individual assessments, as well as positive correlation of sTIM-3 levels with clinicopathological factors. Conclusion: sTIM-3 is a potential novel and readily accessible OSCC biomarker, which in combination with SCCAg expression level might better diagnose OSCC patients.

Lay abstract Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer. It affects the patients' swallowing, speech, appearance, social interactions and other aspects. Soluble TIM-3 (sTIM-3) is a negative regulatory molecule. Serum levels of squamous cell carcinoma antigen are closely related to the growth of OSCC tumors. Herein, the serum levels of sTIM-3 in OSCC patients were examined. This study demonstrated that the combined assessment of sTIM-3 and squamous cell carcinoma antigen expression levels might better distinguish OSCC patients from healthy individuals.

Residual refinement for interactive skin lesion segmentation.

BACKGROUND: Image segmentation is a difficult and classic problem. It has a wide range of applications, one of which is skin lesion segmentation. Numerous researchers have made great efforts to tackle the problem, yet there is still no universal method in various application domains. RESULTS: We propose a novel approach that combines a deep convolutional neural network with a grabcut-like user interaction to tackle the interactive skin lesion segmentation problem. Slightly deviating from grabcut user interaction, our method uses boxes and clicks. In addition, contrary to existing interactive segmentation algorithms that combine the initial segmentation task with the following refinement task, we explicitly separate these tasks by designing individual sub-networks. One network is SBox-Net, and the other is Click-Net. SBox-Net is a full-fledged segmentation network that is built upon a pre-trained, state-of-the-art segmentation model, while Click-Net is a simple yet powerful network that combines feature maps extracted from SBox-Net and user clicks to residually refine the mistakes made by SBox-Net. Extensive experiments on two public datasets, PH2 and ISIC, confirm the effectiveness of our approach. CONCLUSIONS: We present an interactive two-stage pipeline method for skin lesion segmentation, which was demonstrated to be effective in comprehensive experiments.

Mesoscopic Mapping of Ictal Neurovascular Coupling in Awake Behaving Mice Using Optical Spectroscopy and Genetically Encoded Calcium Indicators.

Unambiguously identifying an epileptic focus with high spatial resolution is a challenge, especially when no anatomic abnormality can be detected. Neurovascular coupling (NVC)-based brain mapping techniques are often applied in the clinic despite a poor understanding of ictal NVC mechanisms, derived primarily from recordings in anesthetized animals with limited spatial sampling of the ictal core. In this study, we used simultaneous wide-field mesoscopic imaging of GCamp6f and intrinsic optical signals (IOS) to record the neuronal and hemodynamic changes during acute ictal events in awake, behaving mice. Similar signals in isoflurane-anesthetized mice were compared to highlight the unique characteristics of the awake condition. In awake animals, seizures were more focal at the onset but more likely to propagate to the contralateral hemisphere. The HbT signal, derived from an increase in cerebral blood volume (CBV), was more intense in awake mice. As a result, the "epileptic dip" in hemoglobin oxygenation became inconsistent and unreliable as a mapping signal. Our data indicate that CBV-based imaging techniques should be more accurate than blood oxygen level dependent (BOLD)-based imaging techniques for seizure mapping in awake behaving animals.

The Effects of a 10-Week Neuromuscular Training on Postural Control in Elite Youth Competitive Ballroom Dancers: A Randomized Controlled Trial.

The purpose of this randomized controlled trial was to evaluate the efficacy of a 10-week neuromuscular training (NMT) program on the postural control of elite youth competitive ballroom dancers. Forty-two dancers (21 couples) were randomly assigned to either the NMT group (n = 22) or the control group (CG; n = 20). Participants in NMT underwent a three-sessions-per-week NMT program for 10 weeks. Testing at baseline and after the 10 weeks intervention included the Y-balance test (YBT) and Modified-Balance Error Scoring System (M-BESS). Results of YBT indicated that NMT participants demonstrated increased reach in the posterolateral and posteromedial directions for the right and left lower limb, whereas no significant change was found in the anterior direction for both limbs. Results of Modified-Balance Error Scoring System (M-BESS) showed that NMT participants displayed significantly decreased errors of the double-leg floor (p = 0.026), single-leg foam (p = 0.010), double-leg foam (p = 0.003), tandem floor (p = 0.031), and tandem foam (p = 0.038), while no significant change was found in single-leg floor performance (p = 0.476). CG participants did not exhibit any significant change during the 10-week period. In summary, the study affirmed that the 10-week NMT program enhanced the postural control performance of youth ballroom dancers and showed effects on ballroom dance-specific performance and lower-limb injury prevention. The results suggest that NMT may be a valuable addition to ballroom dance training regimens.

Regional differences in socioeconomic trends: The spatiotemporal evolution from individual cities to a megacity region over a long time series.

Regional differences in socioeconomic factors are important for assessing the regional development of an area. While much research has focused on the overall patterns of regional differences within independent cities and areas, the hierarchical spatiotemporal structures of megacity regions have seldom been discussed. To fill this gap, this paper investigates the multilevel regional differences within megacity regions. Employing GDP, population and total retail sales as socioeconomic indicators, the spatiotemporal patterns of socioeconomic trends are identified. A hierarchical clustering approach that utilizes socioeconomic similarities is proposed for the identification of the spatiotemporal patterns of individual cities. At the megacity regional level, gravity centers and pathways are constructed to evaluate spatial imbalances and temporal change intensities. Taking the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) as its study area, this research produces results that show diverse spatiotemporal patterns among the individual cities, revealing high/low starting point and high/low growth rate modes in terms of city interactions. From the perspective of the entire GBA, the spatial imbalance of GDP is the highest of the factors, followed by the spatial imbalance of the total retail sales of the region and, finally, by that of its population. Total retail sales exhibit the highest level of temporal change intensity, followed by GDP and population. In terms of the contribution of the various cities to the overall regional changes, Guangzhou, Shenzhen and Hong Kong dominate the spatiotemporal changes in the gravity centers, while Foshan and Dongguan show significant potential to contribute to these socioeconomic patterns. These results provide effective guidance for the sustainable development of megacity regions.

Chronic Physical Activity for Attention Deficit Hyperactivity Disorder and/or Autism Spectrum Disorder in Children: A Meta-Analysis of Randomized Controlled Trials.

Purpose: To explore the effects of physical activity (PA) intervention on executive function (EF) and motor skills (MS) among children with attention deficit hyperactivity disorder and/or autism spectrum disorder (ASD). Methods: Relevant studies were sourced from PubMed, Web of Science, EMBASE, Cochrane Library, CNKI and Wanfang Data. Only randomized controlled trials (RCT) were included based upon the following criteria: (1) participants were children and clinically diagnosed with ADHD/ASD, (2) intervention strategies were identified as chronic physical activity, and (3) EF (e.g., cognitive flexibility) and/or MS (e.g., gross motor skills) were measured at baseline and post-intervention and compared with an eligible control group. Results: Eleven studies involving 346 participants were finally identified. PA elicited significant improvements in EF and MS in children with ADHD/ASD. Regarding changes in the EF of participants, PA showed a great improvement in overall EF [standardized mean difference (SMD): 0.90, 95% confidence interval (CI) 0.49-1.30, p < 0.00001], inhibitory control (SMD: 1.30, 95% CI 0.58-2.02, p = 0.0004) and cognitive flexibility (SMD: 0.85, 95% CI 0.42-1.29, p = 0.0001), but no significant improvement in working memory (SMD: 0.28, 95% CI -0.15-0.71, p = 0.20). Significant improvements were also found with respect to gross motor skills (SMD: 0.80, 95% CI 0.30-1.30, p = 0.002), but no significant changes were found in fine motor skills (SMD: 0.30, 95% CI -0.91-1.52, p = 0.62). Conclusion: Chronic PA interventions may promote EF and MS in children with ADHD/ASD, especially in inhibitory control, cognitive flexibility, and gross motor skills. However, PA interventions seemed to have insignificant effects on working memory and fine motor skills to children with ADHD/ASD. PROSPERO registration number: CRD42019118622.

Multimodal Detection for Cryptogenic Epileptic Seizures Based on Combined Micro Sensors.

The cryptogenic epilepsy of the neocortex is a disease in which the seizure is accompanied by intense cerebral nerve electrical activities but the lesions are not observed. It is difficult to locate disease foci. Electrocorticography (ECoG) is one of the gold standards in seizure focus localization. This method detects electrical signals, and its limitations are inadequate resolution which is only 10 mm and lack of depth information. In order to solve these problems, our new method with implantable micro ultrasound transducer (MUT) and photoplethysmogram (PPG) device detects blood changes to achieve higher resolution and provide depth information. The basis of this method is the neurovascular coupling mechanism, which shows that intense neural activity leads to sufficient cerebral blood volume (CBV). The neurovascular coupling mechanism established the relationship between epileptic electrical signals and CBV. The existence of mechanism enables us to apply our new methods on the basis of ECoG. Phantom experiments and in vivo experiments were designed to verify the proposed method. The first phantom experiments designed a phantom with two channels at different depths, and the MUT was used to detect the depth where the blood concentration changed. The results showed that the MUT detected the blood concentration change at the depth of 12 mm, which is the position of the second channel. In the second phantom experiments where a PPG device and MUT were used to monitor the change of blood concentration in a thick tube, the results showed that the trend of superficial blood concentration change provided by the PPG device is the same as that provided by the MUT within the depth of 2.5 mm. Finally, in the verification of in vivo experiments, the blood concentration changes on the surface recorded by the PPG device and the changes at a certain depth recorded by the MUT all matched the seizure status shown by ECoG. These results confirmed the effectiveness of the combined micro sensors.

Innovations in the Neurosurgical Management of Epilepsy.

Technical limitations and clinical challenges have historically limited the diagnostic tools and treatment methods available for surgical approaches to the management of epilepsy. By contrast, recent technological innovations in several areas hold significant promise in improving outcomes and decreasing morbidity. We review innovations in the neurosurgical management of epilepsy in several areas, including wireless recording and stimulation systems (particularly responsive neurostimulation [NeuroPace]), conformal electrodes for high-resolution electrocorticography, robot-assisted stereotactic surgery, optogenetics and optical imaging methods, novel positron emission tomography ligands, and new applications of focused ultrasonography. Investigation into genetic causes of and susceptibilities to epilepsy has introduced a new era of precision medicine, enabling the understanding of cell signaling mechanisms underlying epileptic activity as well as patient-specific molecularly targeted treatment options. We discuss the emerging path to individualized treatment plans, predicted outcomes, and improved selection of effective interventions, on the basis of these developments.

Development, Validation and Comparison of Artificial Neural Network Models and Logistic Regression Models Predicting Survival of Unresectable Pancreatic Cancer.

Background: Prediction models for the overall survival of pancreatic cancer remain unsatisfactory. We aimed to explore artificial neural networks (ANNs) modeling to predict the survival of unresectable pancreatic cancer patients. Methods: Thirty-two clinical parameters were collected from 221 unresectable pancreatic cancer patients, and their prognostic ability was evaluated using univariate and multivariate logistic regression. ANN and logistic regression (LR) models were developed on a training group (168 patients), and the area under the ROC curve (AUC) was used for comparison of the ANN and LR models. The models were further tested on the testing group (53 patients), and k-statistics were used for accuracy comparison. Results: We built three ANN models, based on 3, 7, and 32 basic features, to predict 8 month survival. All 3 ANN models showed better performance, with AUCs significantly higher than those from the respective LR models (0.811 vs. 0.680, 0.844 vs. 0.722, 0.921 vs. 0.849, all p < 0.05). The ability of the ANN models to discriminate 8 month survival with higher accuracy than the respective LR models was further confirmed in 53 consecutive patients. Conclusion: We developed ANN models predicting the 8 month survival of unresectable pancreatic cancer patients. These models may help to optimize personalized patient management.

Changes in autonomic nervous function and influencing factors in a rat insular cortex electrical kindling model.

In mammals, the insular cortex plays an important role in autonomic regulation. In patients with insular epilepsy, seizures are always accompanied by autonomic changes. Accordingly, we aimed to establish an electrical kindling model in autonomic-mediating areas of the insular cortex, and to conduct a long-term observation of epileptic genesis in these animals until sudden unexpected death. To establish this model in adult rats, we implanted stimulation electrodes in the granular cell layer of the insular cortex, which controls the heart rate (HR) and respiratory rate (RR). Subsequently, seizure was induced successfully in 92.3 % of the rats, and typical autonomic changes were observed during these seizures. Interestingly, the model was established more easily in older rats, and the rats in which electrical stimulation led to a greater reduction in the HR. Moreover, death occurred in 25 % of the kindled rats. In conclusion, our kindling model demonstrates the ability of insular cortex stimulation to generate epilepsy. Our model thus offers a practical tool for studies of the role of the insular cortex in sudden unexpected death in epilepsy.

Isoflurane-Induced Burst Suppression Is a Thalamus-Modulated, Focal-Onset Rhythm With Persistent Local Asynchrony and Variable Propagation Patterns in Rats.

Background: Inhalational anesthetic-induced burst suppression (BS) is classically considered a bilaterally synchronous rhythm. However, local asynchrony has been predicted in theoretical studies and reported in patients with pre-existing focal pathology. Method: We used high-speed widefield calcium imaging to study the spatiotemporal dynamics of isoflurane-induced BS in rats. Results: We found that isoflurane-induced BS is not a globally synchronous rhythm. In the neocortex, neural activity first emerged in a spatially shifting, variably localized focus. Subsequent propagation across the whole cortex was rapid, typically within <100 milliseconds, giving the superficial resemblance to global synchrony. Neural activity remained locally asynchronous during the bursts, forming complex recurrent propagating waves. Despite propagation variability, spatial sequences of burst propagation were largely preserved between the hemispheres, and neural activity was highly correlated between the homotopic areas. The critical role of the thalamus in cortical burst initiation was demonstrated by using unilateral thalamic tetrodotoxin injection. Conclusion: The classical impression that anesthetics-induced BS is a state of global brain synchrony is inaccurate. Bursts are a series of shifting local cortical events facilitated by thalamic projection that unfold as rapid, bilaterally asynchronous propagating waves.

Identification of prognostic gene signature associated with microenvironment of lung adenocarcinoma.

BACKGROUND: Lung cancer has the highest morbidity and mortality worldwide, and lung adenocarcinoma (LADC) is the most common pathological subtype. Accumulating evidence suggests the tumor microenvironment (TME) is correlated with the tumor progress and the patient's outcome. As the major components of TME, the tumor-infiltrated immune cells and stromal cells have attracted more and more attention. In this study, differentially expressed immune and stromal signature genes were used to construct a TME-related prognostic model for predicting the outcomes of LADC patients. METHODS: The expression profiles of LADC samples with clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) related to the TME of LADC were identified using TCGA dataset by Wilcoxon rank sum test. The prognostic effects of TME-related DEGs were analyzed using univariate Cox regression. Then, the least absolute shrinkage and selection operator (LASSO) regression was performed to reduce the overfit and the number of genes for further analysis. Next, the prognostic model was constructed by step multivariate Cox regression and risk score of each sample was calculated. Then, survival and Receiver Operating Characteristic (ROC) analyses were conducted to validate the model using TCGA and GEO datasets, respectively. The Kyoto Encyclopedia of Genes and Genomes analysis of gene signature was performed using Gene Set Enrichment Analysis (GSEA). Finally, the overall immune status, tumor purity and the expression profiles of HLA genes of high- and low-risk samples was further analyzed to reveal the potential mechanisms of prognostic effects of the model. RESULTS: A total of 93 TME-related DEGs were identified, of which 23 DEGs were up-regulated and 70 DEGs were down-regulated. The univariate cox analysis indicated that 23 DEGs has the prognostic effects, the hazard ratio ranged from 0.65 to 1.25 (p < 0.05). Then, seven genes were screened out from the 23 DEGs by LASSO regression method and were further analyzed by step multivariate Cox regression. Finally, a three-gene (ADAM12, Bruton Tyrosine Kinase (BTK), ERG) signature was constructed, and ADAM12, BTK can be used as independent prognostic factors. The three-gene signature well stratified the LADC patients in both training (TCGA) and testing (GEO) datasets as high-risk and low-risk groups, the 3-year area under curve (AUC) of ROC curves of three GEO sets were 0.718 (GSE3141), 0.646 (GSE30219) and 0.643 (GSE50081). The GSEA analysis indicated that highly expressed ADAM12, BTK, ERG mainly correlated with the activation of pathways involving in focal adhesion, immune regulation. The immune analysis indicated that the low-risk group has more immune activities and higher expression of HLA genes than that of the high-risk group. In sum, we identified and constructed a three TME-related DEGs signature, which could be used to predict the prognosis of LADC patients.