Revisiting an old relationship: the causal associations of the ApoB/ApoA1 ratio with cardiometabolic diseases and relative risk factors-a mendelian randomization analysis.

BACKGROUND: It has been confirmed that the ApoB/ApoA1 ratio is closely associated with the incidence of cardiometabolic diseases (CMD). However, due to uncontrolled confounding factors in observational studies, the causal relationship of this association remains unclear. METHODS: In this study, we extracted the ApoB/ApoA1 ratio and data on CMD and its associated risk factors from the largest European Genome-Wide Association Study. The purpose was to conduct Mendelian Randomization (MR) analysis. The causal relationship between the ApoB/ApoA1 ratio and CMD was evaluated using both univariable and multivariable MR analyses. Furthermore, bidirectional MR analysis was performed to estimate the causal relationship between the ApoB/ApoA1 ratio and risk factors for CMD. The final verification confirmed whether the ApoB/ApoA1 ratio exhibits a mediating effect in CMD and related risk factors. RESULTS: In terms of CMD, a noteworthy correlation was observed between the increase in the ApoB/ApoA1 ratio and various CMD, including ischemic heart disease, major adverse cardiovascular events, aortic aneurysm, cerebral ischemic disease and so on (all PFDR<0.05). Meanwhile, the ApoB/ApoA1 ratio was significantly associated with CMD risk factors, such as hemoglobin A1c, fasting insulin levels, waist-to-hip ratio, sedentary behavior, and various others, demonstrating a notable causal relationship (all PFDR<0.05). Additionally, the ApoB/ApoA1 ratio played a mediating role in CMD and relative risk factors. CONCLUSIONS: This MR study provides evidence supporting the significant causal relationship between the ApoB/ApoA1 ratio and CMD and its risk factors. Moreover, it demonstrates the mediating effect of the ApoB/ApoA1 ratio in CMD and its risk factors. These findings suggest that the ApoB/ApoA1 ratio may serve as a potential indicator for identifying the risk of developing CMD in participants.

CTRP13 Mitigates Endothelial Cell Ferroptosis via the AMPK/KLF4 Pathway: Implications for Atherosclerosis Protection.

BACKGROUND C1q/tumor necrosis factor-related protein 13 (CTRP13) preserves endothelial function and possesses anti-oxidation activity. However, its effects on ferroptosis of human umbilical vein endothelial cells (HUVECs) remain unclear. We investigated the effects of CTRP13 on HUVEC ferroptosis induced by oxidized low-density lipoprotein (ox-LDL) and explored the underlying mechanisms of CTRP13 against ferroptosis via the AMPK/KLF4 pathway. MATERIAL AND METHODS Cell Counting Kit-8 assay was used to evaluate cell viability. Lactate dehydrogenase activity and malondialdehyde content analysis were performed to evaluate the cell membrane integrity and lipid peroxidation. Mito-Tracker, JC-1, and 2',7'-dichlorofluorescein di-acetate were used to evaluate the biological activity of mitochondria, mitochondrial membrane potential, and reactive oxygen species (ROS) in endothelial cells. The ferroptosis indicator expressions, recombinant solute carrier family 7, member 11, glutathione peroxidase 4 (GPX4), and acyl-CoA synthetase long-chain family member 4 were examined using real-time reverse transcription-polymerase chain reaction and Western blot. Immunofluorescence staining detected GPX4 location in endothelial cells. RESULTS The results demonstrate that CTRP13 (450 ng/mL) prevented HUVEC ferroptosis by inhibiting ROS overproduction and mitochondrial dysfunction, and CTRP13 accelerated antioxidant enzyme expression levels, such as heme oxygenase 1, superoxide dismutase 1, and superoxide dismutase 2, compared with the ox-LDL (100 µg/mL) group for 48 h. Additionally, CTRP13 treatment increased p-AMPK/AMPK expression by 47.65% (P<0.05) while decreasing Krüppel-like factor 4 expression by 37.43% (P<0.05) in ox-LDL-induced HUVECs and elucidated the protective effect on endothelial dysfunction from ferroptosis. CONCLUSIONS These findings provide new insights for understanding the effects and mechanism of CTRP13 on preventing endothelial cell ferroptosis.

A landscape of Long non-coding RNAs reveals the leading transcriptome alterations in murine aorta during aging.

Considerable studies have given convincing evidence of a forefront position for vascular aging in preventing cardiovascular disease. Various functions of Long non-coding RNAs (lncRNAs) are becoming increasingly distinct in aging-related diseases. This study aims at a better insight into the expression profile and mechanisms of lncRNAs in vascular senescence. High-throughput sequencing was used to detect the differential expression (DE) of lncRNAs and mRNAs in the aorta of 96 W and 8 W-old mice, while 1423 lncRNAs and 80 mRNAs were differentially expressed. By performing GO and KEGG enrichment analysis, we found that DE lncRNAs were mainly involved in purine metabolism and cGMP-PKG signaling pathways. In addition, a co-expression functional network of DE lncRNAs and DE mRNAs was constructed, and ENSMUST00000218874 could interact with 41 DE mRNAs, suggesting that it may play an essential role in vascular senescence. This study reveals DE lncRNAs in naturally aging vascular, which may provide new ideas and targets for aging-related cardiovascular diseases.

Vaspin alleviates the lncRNA LEF1-AS1-induced osteogenic differentiation of vascular smooth muscle cells via the Hippo/YAP signaling pathway.

Vascular calcification (VC) is closely related to higher cardiovascular mortality and morbidity, and vascular smooth muscle cell (VSMC) switching to osteogenic-like cells is crucial for VC. LncRNA LEF1-AS1 promotes atherosclerosis and dental pulp stem cells calcification, while its role in VC remains unknown. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine regulating bone metabolism. However, the relationship between vaspin and VC is still unclear. We aimed to explore the role of LEF1-AS1 on VSMC osteogenic transition, whether vaspin inhibited LEF1-AS1-mediated osteogenic differentiation of VSMCs, and the responsible mechanism. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis indicated that LEF1-AS1 overexpression significantly upregulated osteogenic marker Runt-related transcription factor-2 (RUNX2) level and downregulated VSMC contractile marker α-smooth muscle actin (α-SMA) level. Alizarin red staining, alkaline phosphatase (ALP) staining, ALP activity assay, and calcium content assay also suggested that LEF1-AS1 overexpression promoted calcium deposition in VSMCs. However, vaspin treatment abolished this phenomenon. Mechanistically, LEF1-AS1 markedly decreased phosphorylated YAP level, while vaspin reversed LEF1-AS1-induced phosphorylated YAP decline. Our results revealed that LEF1-AS1 accelerated the osteogenic differentiation of VSMCs by regulating the Hippo/YAP pathway, while vaspin eliminated the LEF1-AS1-meditated VSMCs osteogenic phenotype switch.

Combined model of radiomics, clinical, and imaging features for differentiating focal pneumonia-like lung cancer from pulmonary inflammatory lesions: an exploratory study.

BACKGROUND: Only few studies have focused on differentiating focal pneumonia-like lung cancer (F-PLC) from focal pulmonary inflammatory lesion (F-PIL). This exploratory study aimed to evaluate the clinical value of a combined model incorporating computed tomography (CT)-based radiomics signatures, clinical factors, and CT morphological features for distinguishing F-PLC and F-PIL. METHODS: In total, 396 patients pathologically diagnosed with F-PLC and F-PIL from two medical institutions between January 2015 and May 2021 were retrospectively analyzed. Patients from center 1 were included in the training (n = 242) and internal validation (n = 104) cohorts. Moreover, patients from center 2 were classified under the external validation cohort (n = 50). The clinical and CT morphological characteristics of both groups were compared first. And then, a clinical model incorporating clinical and CT morphological features, a radiomics model reflecting the radiomics signature of lung lesions, and a combined model were developed and validated, respectively. RESULTS: Age, gender, smoking history, respiratory symptoms, air bronchogram, necrosis, and pleural attachment differed significantly between the F-PLC and F-PIL groups (all P < 0.05). For the clinical model, age, necrosis, and pleural attachment were the most effective factors to differentiate F-PIL from F-PLC, with the area under the curves (AUCs) of 0.838, 0.819, and 0.717 in the training and internal and external validation cohorts, respectively. For the radiomics model, five radiomics features were found to be significantly related to the identification of F-PLC and F-PIL (all P < 0.001), with the AUCs of 0.804, 0.877, and 0.734 in the training and internal and external validation cohorts, respectively. For the combined model, five radiomics features, age, necrosis, and pleural attachment were independent predictors for distinguishing between F-PLC and F-PIL, with the AUCs of 0.915, 0.899, and 0.805 in the training and internal and external validation cohorts, respectively. The combined model exhibited a better performance than had the clinical and radiomics models. CONCLUSIONS: The combined model, which incorporates CT-based radiomics signatures, clinical factors, and CT morphological characteristics, is effective in differentiating F-PLC from F-PIL.

Relationship between non-culprit lesion plaque characteristics changes and in-stent neoatherosclerosis formation: 1-year follow-up optical coherence tomography study.

The relationship between the in-stent neoatherosclerosis (ISNA) formation and the plaque's characteristic changes in the non-culprit lesion is unclear. We aim to investigate the plaque characteristics changes at non-culprit lesions between patients with ISNA and without ISNA formation at 1-year follow-up. We retrospectively enrolled patients who had DES implantation in de novo lesion and underwent immediately after stenting and 1-year follow-up optical coherence tomography (OCT) examination. OCT-defined ISNA was defined as the presence of lipid-laden neointima or calcification within the culprit stent with a longitudinal extension of ≥1 mm. Non-culprit lesions were divided into two groups: ISNA group (with ISNA) and non-ISNA group (without ISNA). Plaque characteristics of non-culprit lesions were evaluated at baseline and 1-year follow-up. In total, 89 patients with 89 non-culprit lesions (ISNA: n = 37; non-ISNA: n = 52) were included in the analyses. The lesions in the ISNA group show a smaller minimum lumen area compared to the non-ISNA group at 1-year follow-up (2.57 ± 1.08 mm2 versus 3.20 ± 1.62 mm2, p = 0.044). The lesions of the ISNA group show a significant decrease in minimum lumen area changes percent (-7.25% versus 6.46%, p = 0.039). And there are more lesions with minimum lumen area (64.9% versus 38.5%, p = 0.014) and minimum lumen diameter (64.9% versus 40.4%, p = 0.023) decrease in the ISNA group. Furthermore, the lesions in ISNA group have more plaques with lipid core length increase (25.0% versus 10.0%, p = 0.040), more plaques with FCT decrease (50.0% versus 74.0%, p = 0.027) and less TCFA change to non-TCFA (33.3% versus 87.5%, p = 0.010). The plaque characteristic changes in non-culprit lesions are closely related to ISNA formation. The ISNA formation may accompany by a tardier plaque stabilization process in non-culprit lesions.

Differentiating malignant and benign necrotic lung lesions using kVp-switching dual-energy spectral computed tomography.

BACKGROUND: Necrotic pulmonary lesions manifest as relatively low-density internally on contrast-enhanced computed tomography (CT). However, using CT to differentiate malignant and benign necrotic pulmonary lesions is challenging, as these lesions have similar peripheral enhancement. With the introduction of dual-energy spectral CT (DESCT), more quantitative parameters can be obtained and the ability to differentiate material compositions has been highly promoted. This study investigated the use of kVp-switching DESCT in differentiating malignant from benign necrotic lung lesions. METHODS: From October 2016 to February 2019, 40 patients with necrotic lung cancer (NLC) and 31 with necrotic pulmonary mass-like inflammatory lesion (NPMIL) were enrolled and underwent DESCT. The clinical characteristics of patients, CT morphological features, and DESCT quantitative parameters of lesions were compared between the two groups. Binary logistic regression analysis was performed to identify the independent prognostic factors differentiating NPMIL from NLC. Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of single-parameter and multiparametric analyses. RESULTS: Significant differences in age, C-reactive protein concentration, the slope of the spectral curve from 40 to 65 keV (K40-65 keV) of necrosis in non-contrast-enhanced scanning (NCS), arterial phase (AP) and venous phase (VP), effective atomic number of necrosis in NCS, and iodine concentration (IC) of the solid component in VP were observed between groups (all p < 0.05). The aforementioned parameters had area under the ROC curve (AUC) values of 0.747, 0.691, 0.841, 0.641, 0.660, 0.828, and 0.754, respectively, for distinguishing between NLC and NPMIL. Multiparametric analysis showed that age, K40-65 keV of necrosis in NCS, and IC of the solid component in VP were the most effective factors for differentiating NLC from NPMIL, with an AUC of 0.966 and percentage of correct class of 88.7%. CONCLUSIONS: DESCT can differentiate malignant from benign necrotic lung lesions with a relatively high accuracy.

Atheroprotective effects of methotrexate via the inhibition of YAP/TAZ under disturbed flow.

BACKGROUND: Atherosclerosis preferentially develops in regions of disturbed flow (DF). Emerging evidence indicates that yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway, sense different blood flow patterns and regulate atherosclerotic lesions. We previously found that methotrexate (MTX) reduces in-stent neoatherosclerosis, decreases the plaque burden, and has an effect on local fluid shear stress. Here, we investigated the atheroprotective effect of MTX under DF and the mechanisms underlying these properties. METHODS: Human umbilical vein endothelial cells (HUVECs) were subjected to biomechanical stretch using a parallel-plate flow system and treated with or without MTX at therapeutically relevant concentrations. Additionally, an extravascular device was used to induce DF in the left common carotid artery of C57BL/6 mice, followed by treatment with MTX or 0.9% saline. The artery was then assessed histopathologically after 4 weeks on a Western diet. RESULTS: We observed that MTX significantly inhibited DF-induced endothelial YAP/TAZ activation. Furthermore, it markedly decreased pro-inflammatory factor secretion and monocyte adhesion in HUVECs but had no effect on apoptosis. Mechanistically, AMPKa1 depletion attenuated these effects of MTX. Accordingly, MTX decreased DF-induced plaque formation, which was accompanied by YAP/TAZ downregulation in vivo. CONCLUSIONS: Taken together, we conclude that MTX exerts protective effects via the AMP-dependent kinase (AMPK)-YAP/TAZ pathway. These results provide a basis for the prevention and treatment of atherosclerosis via the inhibition of YAP/TAZ.

Interleukin-35 promotes early endothelialization after stent implantation by regulating macrophage activation.

Background: Early strut coverage after sirolimus-eluting stent (SES) implantation is associated with the activation of inflammation, but the underlying mechanisms are not completely understood. The present study aimed to identify the relationship between the anti-inflammatory cytokine interleukin (IL) 35 (IL-35) and early strut coverage in vivo and in vitroMethods: We utilized a retrospective study design to measure IL-35 levels in 68 stents from 68 patients with coronary artery disease and recorded serial optical coherence tomography (OCT) images (0 and 3 months) to assess stent endothelialization. The mechanism underlying the regulatory effects of IL-35 on macrophages and human umbilical vein endothelial cells (HUVECs) was also investigated. SESs were surgically implanted into the right common carotid arteries of 200 male New Zealand White rabbits receiving intravenous injections of IL-35 or a placebo.Results: At the 3-month OCT evaluation, complete endothelium coverage was correlated with IL-35 levels. IL-35 induced the activation of an anti-inflammatory M2-like macrophage phenotype by targeting the signal transducer and activators of transcription (STAT)1/4 signalling pathway, and IL-35-treated macrophages induced endothelial proliferation and alleviated endothelial dysfunction. IL-35-treated New Zealand White rabbits with implanted SESs showed lower percentages of cross-sections with an uncovered strut, elevated mean neointimal hyperplasia (NIH) thickness, and inhibited inflammatory responses.Conclusions: We investigated the effect of IL-35 expression on early stent endothelialization in vivo and in vitro and identified a crucial role for IL-35 in inducing the activation of an anti-inflammatory M2-like macrophage phenotype. The present study highlights a new therapeutic strategy for early stent endothelialization.

Enhanced calcite precipitation for crack healing by bacteria isolated under low-nitrogen conditions.

A nitrogen-starving isolation strategy was developed for the first time to screen bacteria with high calcium-precipitating activity (CPA) for bioremediation of damage in porous media. Meanwhile, a novel mini-tube method based on the detection of insoluble Ca2+ was established to evaluate the CPA of the isolates. A low-nitrogen-demanding strain B6, identified as Bacillus sp., was screened to exhibit the highest CPA (55 mM insoluble Ca2+). Furthermore, the effects of environmental factors and nutrient availability on B6-induced calcium precipitation were evaluated. The results show that nitrate and starch are the best nitrogen source and carbon source with optimal concentration being 4 and 2 g L-1, respectively. The suitable pH range for B6 to precipitate calcium is from 8.5 to 10.5. B6 can maintain the highest CPA at an initial spore concentration of 1.0 × 108 spores·mL-1. The optimal CaO2 dosage is 10 g L-1. Finally, the calcite precipitation is confirmed by ESEM, EDS, and XRD analysis.

Constraining Dark Matter Models with a Light Mediator at the PandaX-II Experiment.

We search for nuclear recoil signals of dark matter models with a light mediator in PandaX-II, a direct detection experiment in the China Jinping underground laboratory. Using data collected in 2016 and 2017 runs, corresponding to a total exposure of 54 ton day, we set upper limits on the zero-momentum dark matter-nucleon cross section. These limits have a strong dependence on the mediator mass when it is comparable to or below the typical momentum transfer. We apply our results to constrain self-interacting dark matter models with a light mediator mixing with standard model particles, and set strong limits on the model parameter space for the dark matter mass ranging from 5 GeV to 10 TeV.

Spin-Dependent Weakly-Interacting-Massive-Particle-Nucleon Cross Section Limits from First Data of PandaX-II Experiment.

New constraints are presented on the spin-dependent weakly-interacting-massive-particle–- (WIMP-)nucleon interaction from the PandaX-II experiment, using a data set corresponding to a total exposure of 3.3×10^{4} kg day. Assuming a standard axial-vector spin-dependent WIMP interaction with ^{129}Xe and ^{131}Xe nuclei, the most stringent upper limits on WIMP-neutron cross sections for WIMPs with masses above 10 GeV/c^{2} are set in all dark matter direct detection experiments. The minimum upper limit of 4.1×10^{-41} cm^{2} at 90% confidence level is obtained for a WIMP mass of 40 GeV/c^{2}. This represents more than a factor of 2 improvement on the best available limits at this and higher masses. These improved cross-section limits provide more stringent constraints on the effective WIMP-proton and WIMP-neutron couplings.

Limits on Axion Couplings from the First 80 Days of Data of the PandaX-II Experiment.

We report new searches for solar axions and galactic axionlike dark matter particles, using the first low-background data from the PandaX-II experiment at China Jinping Underground Laboratory, corresponding to a total exposure of about 2.7×10^{4} kg day. No solar axion or galactic axionlike dark matter particle candidate has been identified. The upper limit on the axion-electron coupling (g_{Ae}) from the solar flux is found to be about 4.35×10^{-12} in the mass range from 10^{-5} to 1 keV/c^{2} with 90% confidence level, similar to the recent LUX result. We also report a new best limit from the ^{57}Fe deexcitation. On the other hand, the upper limit from the galactic axions is on the order of 10^{-13} in the mass range from 1 to 10 keV/c^{2} with 90% confidence level, slightly improved compared with the LUX.

Dark Matter Results from 54-Ton-Day Exposure of PandaX-II Experiment.

We report a new search for weakly interacting massive particles (WIMPs) using the combined low background data sets acquired in 2016 and 2017 from the PandaX-II experiment in China. The latest data set contains a new exposure of 77.1 live days, with the background reduced to a level of 0.8×10^{-3} evt/kg/day, improved by a factor of 2.5 in comparison to the previous run in 2016. No excess events are found above the expected background. With a total exposure of 5.4×10^{4} kg day, the most stringent upper limit on the spin-independent WIMP-nucleon cross section is set for a WIMP with mass larger than 100 GeV/c^{2}, with the lowest 90% C.L. exclusion at 8.6×10^{-47} cm^{2} at 40 GeV/c^{2}.

Association of Platelet to lymphocyte ratio with non-culprit atherosclerotic plaque vulnerability in patients with acute coronary syndrome: an optical coherence tomography study.

BACKGROUND: The platelet to lymphocyte ratio (PLR), an indirect inflammatory biomarker, has been recently demonstrated to be associated with severity of coronary artery disease. In the present study, we sought to investigate whether PLR is associated with vulnerable plaque characteristics of non-culprit lesions in patients with acute coronary syndrome (ACS). METHODS: The patients in our study were divided into two groups (high PLR group and low PLR group). A total of 119 non-culprit plaques from 71 patients with ACS were assessed by optical coherence tomography (OCT). RESULTS: The non-culprit plaques in high PLR group exhibited thinner fibrous cap thickness (FCT) (88.60 ± 44.70 vs. 119.28 ± 50.22 µm, P = 0.001), greater maximum lipid arc (271.73 ± 71.66 vs. 240.60 ± 76.69°, P = 0.027) and increased incidence of thin-cap fibroatheroma (TCFA) (34.0% vs. 15.9%, P = 0.022) compared with those in low PLR group. Meanwhile, PLR was negatively associated with FCT (r = -0.329, P < 0.001). Furthermore, multivariate regression analysis showed that PLR [OR: 1.023 (95% CI: 1.005-1.041), P = 0.012] and LDL-C [OR: 1.892 (95% CI: 1.106-3.239), P = 0.020] were significant predictors of TCFA. CONCLUSIONS: High level of PLR may be associated with vulnerable plaque features of non-culprit lesions in patients with ACS. PLR, a cheap and easily available index, may surve as a useful inflammatory marker in reflecting plaque vulnerability.

Dark Matter Results from First 98.7 Days of Data from the PandaX-II Experiment.

We report the weakly interacting massive particle (WIMP) dark matter search results using the first physics-run data of the PandaX-II 500 kg liquid xenon dual-phase time-projection chamber, operating at the China JinPing underground laboratory. No dark matter candidate is identified above background. In combination with the data set during the commissioning run, with a total exposure of 3.3×10^{4} kg day, the most stringent limit to the spin-independent interaction between the ordinary and WIMP dark matter is set for a range of dark matter mass between 5 and 1000 GeV/c^{2}. The best upper limit on the scattering cross section is found 2.5×10^{-46} cm^{2} for the WIMP mass 40 GeV/c^{2} at 90% confidence level.

Relationship between Serum fibroblast growth factor 21 levels and morphological atherosclerotic plaque characteristics in patients with coronary heart disease.

AIMS: Fibroblast growth factor (FGF) 21, as an important regulator for systemic glucose and lipid metabolism, has recently been demonstrated to be associated with atherosclerosis, but the relationship between serum FGF21 and characteristics of atherosclerotic plaques remains unclear. The aims of the current study were to evaluate the association between serum FGF21 and morphological characteristics of atherosclerotic plaques in vivo. METHODS AND RESULTS: Overall, 68 patients with coronary heart disease were evaluated by virtual histology-intravascular ultrasound, and circulating FGF21 concentration were measured by enzyme-linked immunosorbent assay. Serum FGF21 levels showed a significant and positive correlation with plaque burden (plaque+media divided by external elastic membrane) (r = 0.28, P = 0.01). Conversely, serum FGF21 levels in patients with VH thin-cap fibroatheroma were lower than those with VH thick-cap fibroatheroma (P < 0.01). CONCLUSION: Serum FGF21 is positively correlated with atherosclerotic plaque burden, and interestingly, the high level of serum FGF21 may represent a positive response to atherosclerosis.

The differential computed tomography features between small benign and malignant solid solitary pulmonary nodules with different sizes.

Background: Computed tomography (CT) has been widely known to be the first choice for the diagnosis of solid solitary pulmonary nodules (SSPNs). However, the smaller the SSPN is, the less the differential CT signs between benign and malignant SSPNs there are, which brings great challenges to their diagnosis. Therefore, this study aimed to investigate the differential CT features between small (≤15 mm) benign and malignant SSPNs with different sizes. Methods: From May 2018 to November 2021, CT data of 794 patients with small SSPNs (≤15 mm) were retrospectively analyzed. SSPNs were divided into benign and malignant groups, and each group was further classified into three cohorts: cohort I (diameter ≤6 mm), cohort II (6 mm < diameter ≤8 mm), and cohort III (8 mm < diameter ≤15 mm). The differential CT features of benign and malignant SSPNs in three cohorts were identified. Multivariable logistic regression analyses were conducted to identify independent factors of benign SSPNs. Results: In cohort I, polygonal shape and upper-lobe distribution differed significantly between groups (all P<0.05) and multiparametric analysis showed polygonal shape [adjusted odds ratio (OR): 12.165; 95% confidence interval (CI): 1.512-97.872; P=0.019] was the most effective variation for predicting benign SSPNs, with an area under the receiver operating characteristic curve (AUC) of 0.747 (95% CI: 0.640-0.855; P=0.001). In cohort II, polygonal shape, lobulation, pleural retraction, and air bronchogram differed significantly between groups (all P<0.05), and polygonal shape (OR: 8.870; 95% CI: 1.096-71.772; P=0.041) and the absence of pleural retraction (OR: 0.306; 95% CI: 0.106-0.883; P=0.028) were independent predictors of benign SSPNs, with an AUC of 0.778 (95% CI: 0.694-0.863; P<0.001). In cohort III, 12 CT features showed significant differences between groups (all P<0.05) and polygonal shape (OR: 3.953; 95% CI: 1.508-10.361; P=0.005); calcification (OR: 3.710; 95% CI: 1.305-10.551; P=0.014); halo sign (OR: 6.237; 95% CI: 2.838-13.710; P<0.001); satellite lesions (OR: 6.554; 95% CI: 3.225-13.318; P<0.001); and the absence of lobulation (OR: 0.066; 95% CI: 0.026-0.167; P<0.001), air space (OR: 0.405; 95% CI: 0.215-0.764; P=0.005), pleural retraction (OR: 0.297; 95% CI: 0.179-0.493; P<0.001), bronchial truncation (OR: 0.165; 95% CI: 0.090-0.303; P<0.001), and air bronchogram (OR: 0.363; 95% CI: 0.208-0.633; P<0.001) were independent predictors of benign SSPNs, with an AUC of 0.869 (95% CI: 0.840-0.897; P<0.001). Conclusions: CT features vary between SSPNs with different sizes. Clarifying the differential CT features based on different diameter ranges may help to minimize ambiguities and discriminate the benign SSPNs from malignant ones.

Value of CT-Based Deep Learning Model in Differentiating Benign and Malignant Solid Pulmonary Nodules ≤ 8 mm.

RATIONALE AND OBJECTIVES: We examined the effectiveness of computed tomography (CT)-based deep learning (DL) models in differentiating benign and malignant solid pulmonary nodules (SPNs) ≤ 8 mm. MATERIALS AND METHODS: The study patients (n = 719) were divided into internal training, internal validation, and external validation cohorts; all had small SPNs and had undergone preoperative chest CTs and surgical resection. We developed five DL models incorporating features of the nodule and five different peri-nodular regions with the Multiscale Dual Attention Network (MDANet) to differentiate benign and malignant SPNs. We selected the best-performing model, which was then compared to four conventional algorithms (VGG19, ResNet50, ResNeXt50, and DenseNet121). Furthermore, another five DL models were constructed using MDANet to distinguish benign tumors from inflammatory nodules and the one performed best was selected out. RESULTS: Model 4, which incorporated the nodule and 15 mm peri-nodular region, best differentiated benign and malignant SPNs. The model had an area under the curve (AUC), accuracy, recall, precision, and F1-score of 0.730, 0.724, 0.711, 0.705, and 0.707 in the external validation cohort. Model 4 also performed better than the other four conventional algorithms. Model 8, which incorporated the nodule and 10 mm peri-nodular region, was the best model for distinguishing benign tumors from inflammatory nodules. The model had an AUC, accuracy, recall, precision, and F1-score of 0.871, 0.938, 0.863, 0.904, and 0.882 in the external validation cohort. CONCLUSION: The study concludes that CT-based DL models built with MDANet can accurately discriminate among small benign and malignant SPNs, benign tumors and inflammatory nodules.

Solitary lung adenocarcinoma: follow-up CT, pathological-molecular characteristics, and surgical prognosis for different morphological classifications.

OBJECTIVE: To investigate the dynamic changes during follow-up computed tomography (CT), histological subtypes, gene mutation status, and surgical prognosis for different morphological presentations of solitary lung adenocarcinomas (SLADC). MATERIALS AND METHODS: This retrospective study compared dynamic tumor changes and volume doubling time (VDT) in 228 patients with SLADC (morphological types I-IV) who had intermittent growth during follow-ups. The correlation between the morphological classification and histological subtypes, gene mutation status, and surgical prognosis was evaluated. RESULTS: Among the 228 patients, 66 (28.9%) were classified as type I, 123 (53.9%) as type II, 16 (7%) as type III, and 23 (10.1%) as type IV. Type I had the shortest VDT (254 days), followed by types IV (381 days) and III (501 days), and then type II (993 days) (p < 0.05 each). Type I had a greater proportion of solid/micropapillary-predominant pattern than type II, and the lepidic-predominant pattern was more common in type II and III than in type I (p < 0.05 each). Furthermore, type II and IV SLADCs were correlated with positive epidermal growth factor receptor mutation (p < 0.05 each). Lastly, the Kaplan-Meier curves showed that the disease-free survival was longest for patients with type II tumors, followed by those with type III and IV tumors, and then those with type I tumors (p < 0.001 each). CONCLUSION: A good understanding of the natural progression and pathological-molecular characteristics of different morphological SLADC types can help make accurate diagnoses, develop individual treatment strategies, and predict patient outcomes. CRITICAL RELEVANCE STATEMENT: A good understanding of the natural progression and pathological-molecular characteristics of different morphological solitary lung adenocarcinoma types can help make accurate diagnoses, develop individual treatment strategies, and predict patient outcomes. KEY POINTS: • Type I-IV solitary lung adenocarcinomas exhibit varying natural progression on serial CT scans. • Morphological classification of solitary lung adenocarcinomas predicts histological subtype, gene status, and surgical prognosis. • This classification of solitary lung adenocarcinomas may help improve diagnostic, therapeutic, and prognosticating abilities.