Comparison of the effects of AgNPs on the morphological and mechanical characteristics of cancerous cells.

Currently, silver nanoparticles (AgNPs) are the most produced nanoparticles in global market and have been widely utilized in the biomedical field. Here, we investigated the morphological and mechanical effects of AgNPs on cancerous cells of A549 cells and SMMC-7721 cells with atomic force microscope (AFM). The influence of AgNPs on the morphological properties and mechanical properties of cancerous cells were characterized utilizing the force-volume (FV) mode and force spectroscopy (FS) mode of AFM measurement. We mainly focus on the comparison of the effects of AgNPs on the two types of cancerous cells based on the fitting results of calculating the Young's moduli utilizing the Sneddon model. The results showed that the morphology changed little, but the mechanical properties of height, roughness, adhesion force and Young's moduli of two cancerous cells varied significantly with the stimulation of different concentrations of AgNPs. This research has provided insights into the classification and characterization of the effects of the various concentrations of AgNPs on the cancerous cells in vitro by utilizing AFM methodologies for disease therapy.

Brazilin Inhibits the Invasion and Metastasis of Breast Cancer.

This study aimed to determine the effect of brazilin on the invasion and metastasis of breast cancer. The breast cancer MDA-MB-231 and 4T1 cells were treated with brazilin to investigate proliferation and invasion using cell proliferation assay, wound healing assay, transwell assay. BALB/C mice were randomized into normal, model, positive control, and Sappan L. extract groups (n = 6/group). The mice were injected with 4T1 cells via caudal veins to establish a lung metastasis model and via subcutaneous injection to establish a xenograft model. Metastatic nodules on the lung surface, survival rates and visceral indices were evaluated. Subcutaneous tumor volumes and weights were measured. Brazilin inhibited the proliferation of breast cancer cells and significantly inhibited the wound healing, migration, and invasion of MDA-MB-231 and 4T1 cells. Compared with the normal group, the average survival days and spleen index in the model group were significantly decreased, but the lung index and number of pulmonary metastatic nodules were significantly increased. Compared with the model group, the average survival and spleen index of dose groups were significantly increased, and the lung index, the number of pulmonary metastatic nodules, and tumor volume and weight were significantly decreased. Brazilin significantly inhibits the proliferation and metastasis of breast cancer. This study might suggest a new therapeutic agent for breast cancer.

Effects of sirtuin 1 deficiency on trophoblasts and its implications in the pathogenesis of pre-eclampsia.

BACKGROUND: Sirtuin 1 (SIRT1) is mainly localised in syncytiotrophoblasts and cytotrophoblasts, and is involved in pregnancy regulation. However, data on the association between SIRT1 and pre-eclampsia (PE) remains limited. This study aimed to investigate the role of SIRT1 in PE pathophysiology. METHODS: Placental SIRT1 expression, as well as serum SIRT1, placental growth factor (PlGF), and soluble FMS-like tyrosine kinase 1 (sFlt-1) levels, were measured using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assays in 40 healthy pregnant women (NP group) and 40 women with severe PE (PE group). Additionally, the effects of SIRT1 on the migration, invasion, PlGF, and sFlt-1 secretion of HTR-8/SVneo cells were analysed. RESULTS: SIRT1 expression was significantly reduced in the placenta of patients with severe PE compared with that in healthy pregnant women. Compared with the NP group, serum SIRT1 and PlGF expression was significantly lower in the PE group; however, the expression of serum sFlt-1 was significantly higher in the PE group. Correlation analysis showed that in the PE group, placental SIRT1 protein levels positively correlated with serum PlGF levels (r = 0.468, P = .002) and negatively correlated with serum sFlt-1 levels (r = -0.542, P < .001). Cells with downregulated SIRT1 had a significantly shorter migration distance and a prominently reduced number of invasive cells compared with the corresponding negative control group, suggesting that SIRT1 deficiency may inhibit the migration and invasive ability of HTR-8/SVneo cells. The opposite results were observed after transfection with lentivirus overexpressing SIRT1. Compared with the corresponding controls, cells with downregulated SIRT1 had significantly reduced PlGF levels and significantly increased sFlt-1 levels in the cell culture supernatants, whereas SIRT1 overexpression produced the opposite results. CONCLUSIONS: SIRT1 deficiency may contribute to the pathogenesis of pre-eclampsia by reducing trophoblastic migration, invasion, and PlGF secretion and increasing sFlt-1 secretion.

Pre-eclampsia is a serious obstetric disorder that begins in the placenta and can occur midway through pregnancy. However, its exact disease process remains unknown. During early pregnancy, trophoblasts (cells that differentiate from fertilised eggs) evolve into new blood vessels that supply oxygen and nutrients to the placenta and maintain placental formation. In people with pre-eclampsia, problematic trophoblasts lead to abnormal placental formation and release of sFlt-1 and PlGF into the mother's blood, damaging blood vessels. Experts reported that the intracellular enzyme SIRT1 might be associated with developing pre-eclampsia. SIRT1 expression in the placenta of pregnant women with pre-eclampsia was lower than normal, and the decrease in SIRT1 levels in HTR-8/Svneo trophoblasts prevented their ability to form blood vessels and altered sFlt-1 and PlGF secretion. Hence, our findings suggest that reduced SIRT1 in trophoblasts may lead to pre-eclampsia by affecting their ability to form placental blood vessels and altering enzyme secretion.

The effects of measurement parameters on the cancerous cell nucleus characterisation by atomic force microscopy in vitro.

Cancer is now responsible for the major leading cause of death worldwide. It is noteworthy that lung cancer has been recognised as the highest incidence (11.6%) and mortality (18.4%) for combined sexes among a variety of cancer diseases. Therefore, it is of great value to investigate the mechanical properties of lung cancerous cells for early diagnosis. This paper focus on the influence of measurement parameters on the measured central Young's moduli of single live A549 cell in vitro based on the force spectroscopy mode of atomic force microscopy (AFM). The effects of the measurement parameters on the measured central Young's moduli were analysed by fitting the force-depth curves utilising the Sneddon model. The results revealed that the Young's moduli of A549 cells increased with the larger indentation force, higher indentation speed, less retraction time, deeper Z length and lower purity percentage of serum. The Young's moduli of cells increased first and then decreased with the increasing dwell time. Hence, this research may have potential significance to provide reference for the standardised detection of a single cancerous cell in vitro using AFM methodologies.

A Contrastive Investigation on the Anticorrosive Performance of Stearic Acid and Fluoroalkylsilane-Modified Superhydrophobic Surface in Salt, Alkali, and Acid Solution.

Stearic acid and fluoroalkylsilane are widely used in chemical modification to fabricate superhydrophobic surfaces in corrosion-resistant exploration. However, extensive works have just explored their anticorrosive performance in salt solution. Very rare work has focused on comparing their corrosion-resistant performance in corrosive solution (salt, alkali, and acid) systematically. In this study, two kinds of superhydrophobic surfaces were obtained on laser-processed rough IN304 surface after the stearic acid and FAS modification processes, respectively. The investigation and comparison of anticorrosion performance in salt, alkali, and acid electrolyte were carried out via potentiodynamic polarization and electrochemical impedance spectroscopy measurements. The promotion mechanism or impairing mechanism was further proposed based on the results of surface wettability, surface morphology, and X-ray photoelectron spectroscopy. Besides, the long-term anticorrosion performance and the stability of surface wettability were also investigated. It is hoped that these research findings could provide an explicit guidance of suitable anticorrosion methods selection for metals in different kinds of corrosive solution (salt, alkali, and acid), which will further raise the promising prospect of functional surfaces for practical applications in industry.

Investigation of Effects of Acid, Alkali, and Salt Solutions on Fluorinated Superhydrophobic Surfaces.

Extensive studies have been carried out to investigate the stability of superhydrophobic surfaces under acid, alkali, and salt solutions. It is noted that previous literature studies just demonstrated a variety of experimental phenomena. However, very few works have focused on the protection mechanism or failure mechanism of fluorinated superhydrophobic surfaces from the perspective of chemical aspects. Herein, this paper aims to investigate the effects of acid, alkali, and salt solutions on the stability of fluorinated superhydrophobic surfaces, and the anticorrosion/corrosion mechanism will be further proposed. The superhydrophobic coating was obtained on silicon substrates by laser surface texturing followed by fluoroalkyl silane modification. The resultant surfaces presented a water contact angle (WCA) of 157.6 ± 0.4° with a small water sliding angle (WSA) of 1.3 ± 0.3°. The newly fabricated superhydrophobic surfaces were then immersed in different concentrations of corrosive solutions (acid, alkali, and salt solutions). The revolution of surface wettability and surface morphology on treated silicon surfaces was evaluated through WCAs, scanning electron microscopy, and white light confocal microscopy. The results indicate that the hydrogen ions (H+) played a positive role in the retention of superhydrophobicity. However, the hydroxyl (OH-) and chloride ions (Cl-) presented the negative influence. The protection mechanism or corrosion mechanism under different solutions was proposed based on the X-ray photoelectron spectroscopy results. In addition, the potentiodynamic polarization and electrochemical impedance spectroscopy measurements provided strong support in data and were conducted to verify the rationality of the proposed mechanism.

BQ123 selectively improved tumor perfusion and enhanced nanomedicine delivery for glioblastomas treatment.

Blood perfusion was always lower in tumor tissues as compared with that in surrounding normal tissues which lead to inadequate nanomedicine delivery to tumors. Inspired by the upregulation of both endothelin-1 (ET1) and its ETA receptor in tumor tissues and the crucial contribution of ET1-ETA receptor signaling to maintain myogenic tone of tumor vessels, we supposed that inhibition of ET1-ETA receptor signaling might selectively improve tumor perfusion and help deliver nanomedicine to tumors. Using human U87 MG glioblastomas with abundant vessels as the tumor model, immunofluorescence staining demonstrated that ETA receptor was overexpressed by in glioblastomas tissues compared with normal brain tissues. A single administration of ETA receptor antagonist BQ123 at the dose of 0.5 mg/kg could effectively improve tumor perfusion which was evidenced by in vivo photoacoustic imaging. Additionally, a single treatment of BQ123 could significantly improve the accumulation of nanoparticles (NPs) around 115 nm in tumors with a more homogeneous distribution pattern by in vivo imaging, ex vivo imaging as well as in vivo distribution experiments. Furthermore, BQ123 successfully increased the therapeutic benefits of paclitaxel-loaded NPs and significantly elongated the survival time of orthotropic glioblastomas-bearing animal models. In summary, the present study provided a new strategy to selectively improve tumor perfusion and therefore benefit nanomedicine delivery for tumor therapy. As ET1-ETA receptor signaling was upregulated in a variety of tumors, this strategy might open a new avenue for tumor treatment.

A Consistency Evaluation and Calibration Method for Piezoelectric Transmitters.

Array transducer and transducer combination technologies are evolving rapidly. While adapting transmitter combination technologies, the parameter consistencies between each transmitter are extremely important because they can determine a combined effort directly. This study presents a consistency evaluation and calibration method for piezoelectric transmitters by using impedance analyzers. Firstly, electronic parameters of transmitters that can be measured by impedance analyzers are introduced. A variety of transmitter acoustic energies that are caused by these parameter differences are then analyzed and certified and, thereafter, transmitter consistency is evaluated. Lastly, based on the evaluations, consistency can be calibrated by changing the corresponding excitation voltage. Acoustic experiments show that this method accurately evaluates and calibrates transducer consistencies, and is easy to realize.

Enhancement of the binding affinity of methylene blue to site I in human serum albumin by cupric and ferric ions.

In this work, the binding characteristics of methylene blue (MB) to human serum albumin (HSA) and the influence of Cu(2+) and Fe(3+) on the binding affinity of MB to HSA were investigated using fluorescence, absorption, circular dichroism (CD) spectroscopy and molecular modelling. The results of competitive binding experiments using the site probes ketoprofen and ibuprofen as specific markers suggested that MB was located in site I within sub-domain IIA of HSA. The molecular modelling results agreed with the results of competitive site marker experiments and the results of CD spectra indicated that the interaction between MB and HSA caused the conformational changes in HSA. The binding affinity of MB to HSA was enhanced but to a different extent in the presence of Cu(2+) and Fe(3+), respectively, which indicated that the influence of different metal ions varied. Enhancement of the binding affinity of MB to HSA in the presence of Cu(2+) is due to the formation of Cu(2+)-HSA complex leading to the conformational changes in HSA, whereas in the presence of Fe(3+), enhancement of the binding affinity is due to the greater stability of the Fe(3+)-HSA-MB complex compared with the MB-HSA complex.

Meta-analysis study of small extracellular vesicle nursing application therapies for healing of wounds and skin regeneration.

We designed and performed this meta-analysis to investigate the impact of the application of extracellular small vesicle therapies on regeneration of skin and wound healing. The findings of this study were computed using fixed or random effect models. The mean differences (MDs), and odds ratio (ORs) with their 95% confidence intervals (CIs) were calculated. In this study, 43 publications were included, encompassing 530 animals with artificial wounds. Small extracellular vesicle therapy had a significant greater rate of wound closure (MD, 24.0; 95% CI, 19.98-28.02, P < 0.001), lower scar width (MD, -191.33; 95%CI, -292.26--90.4, P < 0.001), and higher blood vessel density (MD,36.11; 95%CI, 19.02-53.20, P < 0.001) compared to placebo. Our data revealed that small extracellular vesicle therapy had a significantly higher regeneration of skin and healing of wounds based on the results of wound closure rate, lower scar width, and higher blood vessel density compared to placebo. Future studies with larger sample size are needed.

Design and Preparation Technology of Green Multiple Solid Waste Cementitious Materials.

For solid waste-based cementitious materials, most scholars focus their research on the hydration reaction of cementitious materials, but there is still a lack of solid waste design that comprehensively considers mechanical properties and durability. Therefore, this article focuses on exploring the mix of design and the microscopic and macroscopic properties of multi solid waste cementitious materials (MSWCMs), namely steel slag (SS), slag powder (SP), desulfurization gypsum (DG), fly ash (FA), and ordinary Portland cement (OPC). According to the orthogonal experimental results, the compressive strength of MSWCMs is optimal when the OPC content is 50% and the SS, SP, DG, and FA contents are 10%, 20%, 5%, and 15%, respectively. The MSWCMs group with an OPC content of 50% and SS, SP, DG, and FA contents of 5%, 15%, 5%, and 25% was selected as the control group. The pure OPC group was used as the blank group, and the optimal MSWCMs ratio group had a 28-day compressive strength of 50.7 megapascals, which was 14% and 7.6% higher than the control group and blank group, respectively. The drying shrinkage rate and resistance to chloride ions were also significantly improved, with maximum increases of 22.9%, 22.6%, and 8.9%, 9.8%, respectively. According to XRD, TG-DTG, and NMR testing, the improvement in macroscopic performance can be attributed to the synergistic effect between various solid wastes. This synergistic effect produces more ettringite (AFt) and C-(A)-S-H gel. This study provides a good theoretical basis for improving the comprehensive performance of MSWCMs and is conducive to reducing the use of cement, with significant economic and environmental benefits.

Multi-scale characterization and analysis of cellular viscoelastic mechanical phenotypes by atomic force microscopy.

The viscoelasticity of cells serves as a biomarker that reveals changes induced by malignant transformation, which aids the cytological examinations. However, differences in the measurement methods and parameters have prevented the consistent and effective characterization of the viscoelastic phenotype of cells. To address this issue, nanomechanical indentation experiments were conducted using an atomic force microscope (AFM). Multiple indentation methods were applied, and the indentation parameters were gradually varied to measure the viscoelasticity of normal liver cells and cancerous liver cells to create a database. This database was employed to train machine-learning algorithms in order to analyze the differences in the viscoelasticity of different types of cells and as well as to identify the optimal measurement methods and parameters. These findings indicated that the measurement speed significantly influenced viscoelasticity and that the classification difference between the two cell types was most evident at 5 µm/s. In addition, the precision and the area under the receiver operating characteristic curve were comparatively analyzed for various widely employed machine-learning algorithms. Unlike previous studies, this research validated the effectiveness of measurement parameters and methods with the assistance of machine-learning algorithms. Furthermore, the results confirmed that the viscoelasticity obtained from the multiparameter indentation measurement could be effectively used for cell classification. RESEARCH HIGHLIGHTS: This study aimed to analyze the viscoelasticity of liver cancer cells and liver cells. Different nano-indentation methods and parameters were used to measure the viscoelasticity of the two kinds of cells. The neural network algorithm was used to reverse analyze the dataset, and the methods and parameters for accurate classification and identification of cells are successfully found.

Detection and classification of hepatocytes and hepatoma cells using atomic force microscopy and machine learning algorithms.

Hepatocellular carcinoma is a high-risk malignant tumor. Hepatoma cells are transformed from normal cells and have unique surface nanofeatures in addition to the characteristics of the original cells. In this paper, atomic force microscopy was used to extract the three-dimensional morphology and mechanical information of HL-7702 human hepatocytes and SMMC-7721 and HepG2 hepatoma cells in culture, such as the elastic modulus and viscoelasticity. The characteristics of different cells were compared and analyzed. Finally, the cell morphology and mechanics information were used for training machine learning algorithms. With the trained model, the detection of cells was realized. The classification accuracy was as high as 94.54%, and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.99. Thus, hepatocytes and hepatoma cells were accurately identified and assessed. We also compared the classification effects of other machine learning algorithms, such as support vector machine and logistic regression. Our method extracts cellular nanofeatures directly from the surface of cells of unknown type for cell classification. Compared with microscope image-based analysis and other methods, this approach can avoid the misjudgment that may occur when different doctors have different levels of experience. Thus, the proposed method provides an objective basis for the early diagnosis of hepatocellular carcinoma. RESEARCH HIGHLIGHTS: The 3D appearance and mechanical characteristics of hepatocellular carcinoma cells are very similar to those of hepatocytes. Application of atomic force microscopy with machine learning algorithm. Collect the data set of nano-characteristic parameters of the cell. The machine learning algorithms is trained by data set, and its classification effect is better than that of a single nano-parameter.

Prevalence of psychological symptoms and associated risk factors among nurses in 30 provinces during the COVID-19 pandemic in China.

Background: With the outbreak of the coronavirus disease 2019 (COVID-19), nurses have won well-deserved recognition for their indispensable roles in providing humane and professional healthcare for patients. However, by the nature of their role working at the forefront of patient care, nurses are prone to experiencing mental health consequences. Therefore, we pay attention to measuring the magnitude of psychological symptoms and identifying associated factors among nurses in China. Methods: We launched a nationwide, cross-sectional survey of nurses who worked in secondary or tertiary hospitals and public or private hospitals from 30 provinces in China. The prevalence and severity of symptoms of burnout, depression, and anxiety were investigated, respectively. Multivariable logistic regression analyses were performed to identify factors associated with each psychological symptom. Findings: A total of 138 279 respondents who worked in 243 hospitals completed this survey. A substantial proportion of nurses reported symptoms of burnout (34%), depression (55·5%), and anxiety (41·8%). In line with the disproportionality of economic development, we noted that the middle or western region was an independent risk factor for depression and anxiety. Compared with those working in the secondary hospital, nurses who worked in tertiary hospitals were associated with a higher likelihood of burnout and depression. Interpretation: Nurses are experiencing emotional, physical, and mental exhaustion during the COVID-19 epidemic. Governments and health policymakers need to draw attention to reinforcing prevention and ameliorating countermeasures to safeguard nurses' health. Funding: The strategic consulting project of the Chinese Academy of Engineering [2021-32-5]. Advanced Institute of Infomation Technology, Peking University, Zhejiang Province [2020-Z-17].

Catalyst- and Additive-free, Regioselective 1,6-Hydroarylation of para-Quinone Methides with Anilines in HFIP.

A simple and efficient method for the synthesis of diarylmethyl-functionalized anilines through the hexafluoroisopropanol (HFIP)-mediated regioselective 1,6-hydroarylation reaction of para-quinone methides (p-QMs) with anilines under catalyst- and additive-free conditions is reported. Various kinds of p-QMs and amines (e. g. primary, secondary and tertiary amines) are well tolerated in this transformation without the pre-protection of amino group, and the corresponding products could be generated with good to excellent yields and satisfactory regioselectivity under the optimized reaction conditions. In addition to adaptable amine compounds, indoles and their derivatives are also compatible with this reaction system. This transformation can be easily extended to a gram scale-synthesis level to synthesize the target product. Furthermore, it is worth noting that some complex small aniline molecules with biological activity can be selectively modified using this method. The possible reaction mechanism is proposed through the step-by-step control experiments and DFT calculations, showing that the key process for achieving the regioselective 1,6-hydroarylation of p-QMs is the hydrogen bonding effect of HFIP to substrates.

[Pattern of Recurrence and Metastasis after Radical Resection of 
Non-small Cell Lung Cancer].

The rate of recurrence and metastasis of non-small cell lung cancer after radical resection is still very high. The risk factors for recurrence and metastasis have been extensively studied, but the dynamic pattern of postoperative recurrence hazard over time is relatively lacking. The dynamic recurrence hazard rate curve is applied to describe the rate of recurrence at any point time among the "at-risk" patients. In this article, by reviewing the previous literature, the characteristics of the dynamic recurrence and metastasis pattern after radical resection of non-small cell lung cancer and the clinical factors affecting the recurrence and metastasis pattern are summarized, in order to screen out specific populations with high recurrence risk and give them personalized follow-up strategy and diagnosis and treatment.
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EGFR mutation is not a prognostic factor for CNS metastasis in curatively resected lung adenocarcinoma patients.

INTRODUCTION: For NSCLC patients with complete resection, the prognostic role of EGFR mutation for recurrence, especially for CNS metastasis, is still controversial. In this study, we aimed to identify the characteristics of the recurrence pattern of lung adenocarcinoma based on EGFR mutation status. METHODS: Overall, 888 patients with completely surgically resected LUAD who underwent EGFR mutation status analysis from two Chinese institutions were included. Sites and data of initial recurrence were recorded. The recurrence patterns according to EGFR mutation status were estimated by Kaplan-Meier analysis, and hazard rate curves were generated. RESULTS: 245 (27.6%) of 888 patients suffered from recurrence. Before and after PSM, there were no statistically significant differences between the EGFR mutation and EGFR WT groups for all types of recurrence, including CNS metastasis. Multivariable Cox analysis revealed that EGFR status was not a risk factor for all types of recurrence, including CNS metastasis (HR 0.88, 95% CI 0.54-1.46, p = 0.632). The CNS metastasis hazard curve in the EGFR mutation group showed that the first peak occurred at approximately 24-26 months after surgery, which was 10 months later than that in the EGFR WT group. In addition, the second peak time in the EGFR mutation group was approximately 2 years later than that in the EGFR WT group. CONCLUSIONS: EGFR mutation was not an independent prognostic factor for postoperative recurrence. EGFR-mutated LUADs did not have a clinical course with a higher incidence of CNS metastasis. However, the peak hazards for recurrence of CNS metastasis occur at a later time point in the EGFR mutant group compared with the EGFR wild type group.

Aptamer-Modified Erythrocyte Membrane-Coated pH-Sensitive Nanoparticles for c-Met-Targeted Therapy of Glioblastoma Multiforme.

Biomimetic drug delivery systems, especially red blood cell (RBC) membrane-based nanoparticle drug delivery systems (RNP), have been extensively utilized in tumor drug delivery because of their excellent biocompatibility and prolonged circulation. In this study, we developed an active targeting pH-sensitive RNP loaded with DOX by decorating an aptamer SL1 on RBC membranes (SL1-RNP-DOX) for c-Met-targeted therapy of glioblastoma multiforme (GBM). SL1 could specifically bind to c-Met, which is highly expressed in GBM U87MG cells and facilitate DOX delivery to GBM cells. In vitro studies demonstrated that U87MG cells had a higher uptake of SL1-RNP-DOX (3.25 folds) and a stronger pro-apoptosis effect than unmodified RNP-DOX. In vivo fluorescence imaging and tissue distribution further demonstrated the higher tumor distribution of SL1-RNP-DOX (2.17 folds) compared with RNP-DOX. As a result, SL1-RNP-DOX presented the best anti-GBM effect with a prolonged median survival time (23 days vs. 15.5 days) and the strongest tumor cell apoptosis in vivo among all groups. In conclusion, SL1-RNP-DOX exhibited a promising targeting delivery strategy for GBM therapy.

Total nodule number as an independent prognostic factor in resected stage III non-small cell lung cancer: a deep learning-powered study.

Background: Almost every patient with lung cancer has multiple pulmonary nodules; however, the significance of nodule multiplicity in locally advanced non-small cell lung cancer (NSCLC) remains unclear. Methods: We identified patients who had undergone surgical resection for stage I-III NSCLC at the Peking University People's Hospital from 2005 to 2018 for whom preoperative chest computed tomography (CT) scans were available. Deep learning-based artificial intelligence (AI) algorithms using convolutional neural networks (CNN) were applied to detect and classify pulmonary nodules (PNs). Maximally selected log-rank statistics were used to determine the optimal cutoff value of the total nodule number (TNN) for predicting survival. Results: A total of 33,410 PNs were detected by AI among the 2,126 participants. The median TNN detected per person was 12 [interquartile range (IQR) 7-20]. It was revealed that AI-detected TNN (analyzed as a continuous variable) was an independent prognostic factor for both recurrence-free survival (RFS) [hazard ratio (HR) 1.012, 95% confidence interval (CI): 1.002 to 1.022, P=0.021] and overall survival (OS) (HR 1.013, 95% CI: 1.002 to 1.025, P=0.021) in multivariate analyses of the stage III cohort. In contrast, AI-detected TNN was not significantly associated with survival in the stage I and II cohorts. In a survival tree analysis, rather than using traditional IIIA and IIIB classifications, the model grouped cases according to AI-detected TNN (lower vs. higher: log-rank P<0.001), which led to a more effective determination of survival rates in the stage III cohort. Conclusions: The AI-detected TNN is significantly associated with survival rates in patients with surgically resected stage III NSCLC. A lower TNN detected on preoperative CT scans indicates a better prognosis for patients who have undergone complete surgical resection.

Different pathologic types of early stage lung adenocarcinoma have different post-operative recurrence patterns.

OBJECTIVES: To accurately describe the pattern, timing and predictors of disease recurrence after curative resection for different types of early-stage lung adenocarcinoma (LUAD). METHODS: A total of 1962 patients with early-stage LUAD were included. The presence of micropapillary, solid components or poorly differentiated cancer as a clinical variable was named "high-grade" adenocarcinoma (HGADC), while others were classified as "low-grade" adenocarcinoma (LGADC). Predictive factors for specific recurrence patterns were assessed by univariate and multivariate analyses using Cox-proportional hazard regression models. Event dynamics, based on the hazard rate, were evaluated. RESULTS: At a median follow-up of 36.0 months, 137 (6.98%) of 1962 patients suffered from recurrence. Multivariable Cox analysis revealed that HGADC was an independent predictor for overall recurrence (hazard ratio [HR] 3.08, 95% confidence interval [CI] 2.09-4.52, p < 0.001), local recurrence (HR 2.77, 95% CI 1.38-5.55, p < 0.001), distant metastasis (HR 3.22, 95% CI 2.03-5.11, p < 0.001), chest recurrence (HR 2.80, 95% CI 1.65-4.75, p < 0.001) and brain recurrence (HR 4.11, 95% CI 1.83-9.22, p < 0.001). However, HGADC (HR 1.56, 95% CI 0.63-3.86, p = 0.335 in univariate analysis) was not a risk factor for bone recurrence. The hazard curve of the whole group presented a double-peaked pattern. Different types of LUAD had different hazard curves. HGADC patients exhibited higher hazard rates than LGADC patients during the whole follow-up. In addition, the recurrence hazard curve in HGADC patients showed a typical "double-peaked" pattern, while the curve in LGADC patients displayed a smooth curve after surgery. CONCLUSIONS: Different postoperative recurrence patterns were seen in HGADC and LGADC. Site-specific recurrence patterns were also different in HGADC and LGADC types.