A Novel Interpretable Radiomics Model to Distinguish Nodular Goiter From Malignant Thyroid Nodules.

OBJECTIVES: The purpose of this study is to inquire about the potential association between radiomics features and the pathological nature of thyroid nodules (TNs), and to propose an interpretable radiomics-based model for predicting the risk of malignant TN. METHODS: In this retrospective study, computed tomography (CT) imaging and pathological data from 141 patients with TN were collected. The data were randomly stratified into a training group (n = 112) and a validation group (n = 29) at a ratio of 4:1. A total of 1316 radiomics features were extracted by using the pyradiomics tool. The redundant features were removed through correlation testing, and the least absolute shrinkage and selection operator (LASSO) or the minimum redundancy maximum relevance standard was used to select features. Finally, 4 different machine learning models (RF Hybrid Feature, SVM Hybrid Feature, RF, and LASSO) were constructed. The performance of the 4 models was evaluated using the receiver operating characteristic curve. The calibration curve, decision curve analysis, and SHapley Additive exPlanations method were used to evaluate or explain the best radiomics machine learning model. RESULTS: The optimal radiomics model (RF Hybrid Feature model) demonstrated a relatively high degree of discrimination with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI, 0.70-0.97; P < 0.001) for the validation cohort. Compared with the commonly used LASSO model (AUC, 0.78; 95% CI, 0.60-0.91; P < 0.01), there is a significant improvement in AUC in the validation set, net reclassification improvement, 0.79 (95% CI, 0.13-1.46; P < 0.05), and integrated discrimination improvement, 0. 20 (95% CI, 0.10-0.30; P < 0.001). CONCLUSION: The interpretable radiomics model based on CT performs well in predicting benign and malignant TNs by using quantitative radiomics features of the unilateral total thyroid. In addition, the data preprocessing method incorporating different layers of features has achieved excellent experimental results. CLINICAL RELEVANCE STATEMENT: As the detection rate of TNs continues to increase, so does the diagnostic burden on radiologists. This study establishes a noninvasive, interpretable and accurate machine learning model to rapidly identify the nature of TN found in CT.

Carbon Free Radical (R⋠) Inactivates NF-κB for Radical Capping Therapy.

Inactivating hyperactivated transcription factors can overcome tumor therapy resistance, but their undruggable features limit the development of conventional inhibitors. Here, we report that carbon-centered free radicals (R⋅) can inactivate NF-κB transcription by capping the active sites in both NF-κB and DNA. We construct a type of thermosensitive R⋅ initiator loaded amphiphilic nano-micelles to facilitate intracellular delivery of R⋅. At a temperature of 43 °C, the generated R⋅ engage in electrophilic radical addition towards double bonds in nucleotide bases, and simultaneously cap the sulfhydryl residues in NF-κB through radical chain reaction. As a result, both NF-κB nuclear translocation and NF-κB-DNA binding are suppressed, leading to a remarkable NF-κB inhibition of up to 94.1 %. We have further applied R⋅ micelles in a clinical radiofrequency ablation tumor therapy model, showing remarkable NF-κB inactivation and consequently tumor metastasis inhibition. Radical capping strategy not only provides a method to solve the heat-sink effect in clinic tumor hyperthermia, but also suggests a new perspective for controllable modification of biomacromolecules in cancer therapy.

Bovine serum albumin-templated nanoplatform for magnetic resonance imaging-guided chemodynamic therapy.

BACKGROUND: Nanotechnology in medicine has greatly expanded the therapeutic strategy that may be explored for cancer treatment by exploiting the specific tumor microenvironment such as mild acidity, high glutathione (GSH) concentration and overproduced hydrogen peroxide (H2O2). Among them, tumor microenvironment responsive chemodynamic therapy (CDT) utilized the Fenton or Fenton-like reaction to produce excess hydroxyl radical (·OH) for the destruction of tumor cells. However, the produced ·OH is easily depleted by the excess GSH in tumors, which would undoubtedly impair the CDT's efficiency. To overcome this obstacle and enhance the treatment efficiency, we design the nanoplatforms for magnetic resonance imaging (MRI)-guided CDT. RESULTS: In this study, we applied the bovine serum albumin (BSA)-templated CuS:Gd nanoparticles (CuS:Gd NPs) for MRI-guided CDT. The Cu2+ in the CuS:Gd NPs could be reduced to Cu+ by GSH in tumors, which further reacted with H2O2 and triggered Fenton-like reaction to simultaneously generate abundant ·OH and deplete GSH for tumor enhanced CDT. Besides, the Gd3+ in CuS:Gd NPs endowed them with excellent MRI capability, which could be used to locate the tumor site and monitor the therapy process preliminarily. CONCLUSIONS: The designed nanoplatforms offer a major step forward in CDT for effective treatment of tumors guided by MRI.

Scintillator-Based Nanohybrids with Sacrificial Electron Prodrug for Enhanced X-ray-Induced Photodynamic Therapy.

X-ray-induced photodynamic therapy (X-PDT) has high depth of penetration and has considerable potential for applications in cancer therapy. Scintillators and heavy metals have been adopted to absorb X-rays and transmit the energy to photosensitizers. However, the low efficiency of converting X-rays to reactive oxygen species (ROS) presents a challenge for the use of X-PDT to cure cancer. In this study, a new method based on LiLuF4:Ce@SiO2@Ag3PO4@Pt(IV) nanoparticles (LAPNP) is presented that could be used to enhance the curative effects of X-PDT. To make full use of the fluorescence produced by nanoscintillators (LiLuF4:Ce), a cisplatin prodrug Pt(IV) was utilized as a sacrificial electron acceptor to increase the yield of hydroxyl radicals (·OH) by increasing the separation of electrons and holes in photosensitizers (Ag3PO4). Additionally, cisplatin is produced upon the acceptance of electrons by Pt(IV) and further enhances the damage caused by ·OH. Via two-step amplification, the potential of LAPNP to enhance the effects of X-PDT has been demonstrated.

The Protective Effect of Sika Deer Antler Protein on Gentamicin-Induced Nephrotoxicity in Vitro and in Vivo.

BACKGROUND/AIMS: Sika deer (Cervus nippon Temminck) antler is traditional animal medicine of renal protection in East Asia. This study measured the effect of sika deer antler protein (SDAPR) on gentamicin (GM)-induced cytotoxicity in HEK293 cells, and investigated the effect of SDAPR against GM-induced nephrotoxicity in mice. METHODS: HEK293 cells viability and oxidative stress were measured in HEK293 cells while flow cytometry was used for apoptosis analysis. The acute kidney injury biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin c (Cys-C), were repeatedly measured by ELISA assay. ICR male mice were randomly assigned six groups: Control, GM with vehicle, single SDAPR, GM with SDAPR at three concentrations 50, 100, 200 mg/kg/d, p.o., 10 d. GM was injected for 8 consecutive days (100 mg/kg/d, i.p.). Renal function, oxidative stress and levels of inflammatory factors were measured in vivo. Renal tissues were stained with H&E to observe pathological changes. RESULTS: Pretreatment with SDAPR (0.5-4.0 mg/mL) significantly improved cell viability. Treatment with SDAPR could reduce KIM-1, NGAL and Cys-C activity. SDAPR could improve antioxidant defense and attenuated apoptosis on HEK293 cells. SDAPR also ameliorated GM-induced histopathologic changes, and decreased blood urea nitrogen (BUN) and serum creatinine (Cr). Additionally, SDAPR significantly regulated oxidative stress marker and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) inflammatory cytokines. CONCLUSION: These results show that SDAPR could be an effective dietary supplement to relieve GM-induced nephrotoxicity by improved antioxidase activity, suppressed inflammation, and inhibited apoptosis in vitro and vivo.

Construction and characterization of regulated cycle inhibiting factors induced upon Tet-On system in human colon cancer cell lines.

A previous study has proven that cycle inhibiting factors (Cifs) inhibit Cullin E3 ubiquitin ligases, resulting in cell cycle arrest. More importantly, Cifs are also involved in cancer progression by deamidating Nedd8. Here we aimed to explore a novel insight into the treatment implications of Cifs in colon cancers by Tet-on system. The anticancer activity of Cif by doxycycline induction was investigated in the colon cell lines based upon Tet-On system. The expression of Cif in the colon cancer cells was determined by western blot. Furthermore, the cell viability and flow cytometry analysis were respectively performed to evaluate the cell proliferation and survival of colon cells. More importantly, the p21 and p27 levels were also evaluated after the induction of Cif with Tet-On system. Multiple clones of colon cancer cells for doxycycline-regulated Cif expression were constructed for maintenance purposes including HCT116 and SW480 cell lines. The result of western blot displayed good inducibility of expressing Cif in the cell lines. The clones with Cif preserved their transformed phenotype compared with the control group (clones with GFP or with Cif), in terms of the inhibition of cancer cell proliferation and survival. Furthermore, western blot analysis showed that p27 and p21 were accumulated in the clones with Cif, compared with the colon cancer cell lines with GFP or with Cif. Using the Tet-On system, we developed an efficient approach toward generation of colon cancer cells induced with Cif. These engineered colons tightly controlled Cif expression in vitro, which is a good inducible model system for cancer treatment.

Local Tumor Progression Predictive Model Based on MRI for Colorectal Cancer Liver Metastases after Radiofrequency Ablation.

PURPOSE: To investigate the post-radiofrequency ablation (RFA) magnetic resonance imaging (MRI) characteristics in patients with liver metastases from colorectal cancer and to build a predictive model for local tumor progression based on these imaging markers. MATERIALS AND METHODS: A cohort of 73 patients with 110 colorectal cancer liver metastases (CRCLM) who underwent RFA and MRI one month post-ablation was included in image signs analysis and predictive model training. Using a newly developed MRI appearance scoring criteria, MR Image Appearance Scoring at One Month after RFA (MRIAS 1MO), the semi-quantitative analysis of MRI findings within the ablation zone were conducted independently by two radiologists. The intraclass correlation coefficient (ICC) was calculated to evaluate measurement reliability. Differences in MRIAS 1MO scores were compared using Mann-Whitney U test, focusing on local tumor response outcomes. Using local tumor progression (LTP) as the primary end point, MRIAS 1MO scores and other lesion morphological and clinical characteristics were included to establish predictive model. Predication accuracy was subsequently evaluated using calibration curve, time-dependent concordance index (C index) curve, and LTP-free survival (LTPFS) curve. Another cohort comprising 60 patients with 76 CRCLMs provided additional MRIAS 1MO scores and clinical data associated with LTP. We evaluated the performance of the established predictive model using calibration curve, time-dependent C index curve, and LTPFS curve. RESULTS: The MRIAS 1MO criteria exhibited strong measurement reliability. The ICC values of T1S (scores from T1WI), T2S (scores form T2WI) and NCES (scores by adding T1S to T2S) MRIS (the overall scores) were 0.825, 0.779, 0.826 and 0.873, respectively. Lesions with LTP showed significantly higher median values for the overall MRIAS 1MO score (MRIS) compared to lesions without LTP (16 vs. 12, p < 0.001). MRIS and lesion diameter were independent prognostic factors of LTP and were included in predictive model (hazard ratio: MRIS over 13.5:4.275, lesion diameter larger than 30 mm: 2.056). The predictive model demonstrated an overall C index of 0.721 and risk stratification using the predictive model resulted in significantly different LPTFS times. In the validation cohort, the C index were 0.825, 0.794 and 0.764 at six, twelve and twenty-four months, respectively. Patients classified as high-risk in the validation cohort had a median LTPFS time of 10.0 months, while the median LTPFS time was not reached in the low-risk group. CONCLUSIONS: The semi-quantitative MRIAS 1MO criteria, used for post-RFA MRI appearance analysis, exhibited strong measurement reliability. Prediction models established based on overall MRIAS 1MO score (MRIS) and lesion diameter had good predictive performance for LTP in patients undergoing RFA for CRCLM treatment.

Habitat-based radiomics analysis for evaluating immediate response in colorectal cancer lung metastases treated by radiofrequency ablation.

PURPOSE: To create radiomics signatures based on habitat to assess the instant response in lung metastases of colorectal cancer (CRC) after radiofrequency ablation (RFA). METHODS: Between August 2016 and June 2019, we retrospectively included 515 lung metastases in 233 CRC patients who received RFA (412 in the training group and 103 in the test group). Multivariable analysis was performed to identify independent risk factors for developing the clinical model. Tumor and ablation regions of interest (ROI) were split into three spatial habitats through K-means clustering and dilated with 5 mm and 10 mm thicknesses. Radiomics signatures of intratumor, peritumor, and habitat were developed using the features extracted from intraoperative CT data. The performance of these signatures was primarily evaluated using the area under the receiver operating characteristics curve (AUC) via the DeLong test, calibration curves through the Hosmer-Lemeshow test, and decision curve analysis. RESULTS: A total of 412 out of 515 metastases (80%) achieved complete response. Four clinical variables (cancer antigen 19-9, simultaneous systemic treatment, site of lung metastases, and electrode type) were utilized to construct the clinical model. The Habitat signature was combined with the Peri-5 signature, which achieved a higher AUC than the Peri-10 signature in the test set (0.825 vs. 0.816). The Habitat+Peri-5 signature notably surpassed the clinical and intratumor radiomics signatures (AUC: 0.870 in the test set; both, p < 0.05), displaying improved calibration and clinical practicality. CONCLUSIONS: The habitat-based radiomics signature can offer precise predictions and valuable assistance to physicians in developing personalized treatment strategies.

Percutaneous computed tomography-guided core needle biopsy can be used to histologically confirm the clinical features and long-term prognosis of pulmonary neuroendocrine neoplasms.

PURPOSE: We investigated the clinical features and prognosis outcomes of pulmonary neuroendocrine neoplasms (PNENs) which were histologically confirmed after percutaneous computed tomography-guided core needle biopsy (PCT-CNB). MATERIALS AND METHODS: We retrospectively investigated 173 patients who had PNENs which were histologically confirmed after PCT-CNB; patients were split into low and intermediate-grade neuroendocrine tumor (LIGNET) (typical carcinoid (TC) and atypical carcinoid (AC)) and high-grade neuroendocrine carcinoma-tumor (HGNEC) groups. In this latter group, patients were further subdivided into large-cell neuroendocrine carcinoma (LCNEC), small-cell lung cancer (SCLC), and high-grade neuroendocrine carcinoma-not otherwise specified (HGNEC-NOS) groups. Complications after biopsy were recorded. We also assessed overall survival (OS) rates using Kaplan-Meier curves, with prognostic factors determined using univariate and multivariate analyses. RESULTS: Complications were mainly pneumothorax (22.5; 39/173 patients), chest tube placement (4.0; 7/173 patients), and pulmonary bleeding (33.5%; 58/173 procedures)-no patient mortality was recorded. Definitive diagnoses were ascribed to 102 SCLC, 10 LCNEC, 43 HGNEC-NOS, 7 TC, and 11 AC patients. The 1- and 3-year OS rates in the LIGNET group were 87.5% and 68.1%, respectively, and 59.2 and 20.9% in the HGNEC group, respectively these data were statistically significant (P = 0.010). For SCLC, 1- and 3-year OS rates were 63.3 and 22.3%, 30.0 and 10.0% for LCNEC, and 53.3% and 20.1% for HGNEC-NOS, respectively (P = 0.031). Independent prognostic factors for OS included disease type and distant metastasis. CONCLUSION: PNENs may be pathologically diagnosed using PCT-CNB. While differential diagnoses between LCNEC and SCLC are problematic in some patients, a HGNEC-NOS diagnosis was ascribed and PCT-CNB samples were shown to predict NEN OS rates.

A CT-based radiomics approach to predict immediate response of radiofrequency ablation in colorectal cancer lung metastases.

Objectives: To objectively and accurately assess the immediate efficacy of radiofrequency ablation (RFA) on colorectal cancer (CRC) lung metastases, the novel multimodal data fusion model based on radiomics features and clinical variables was developed. Methods: This case-control single-center retrospective study included 479 lung metastases treated with RFA in 198 CRC patients. Clinical and radiological data before and intraoperative computed tomography (CT) scans were retrieved. The relative radiomics features were extracted from pre- and immediate post-RFA CT scans by maximum relevance and minimum redundancy algorithm (MRMRA). The Gaussian mixture model (GMM) was used to divide the data of the training dataset and testing dataset. In the process of modeling in the training set, radiomics model, clinical model and fusion model were built based on a random forest classifier. Finally, verification was carried out on an independent test dataset. The receiver operating characteristic curves (ROC) were drawn based on the obtained predicted scores, and the corresponding area under ROC curve (AUC), accuracy, sensitivity, and specificity were calculated and compared. Results: Among the 479 pulmonary metastases, 379 had complete response (CR) ablation and 100 had incomplete response ablation. Three hundred eighty-six lesions were selected to construct a training dataset and 93 lesions to construct a testing dataset. The multivariate logistic regression analysis revealed cancer antigen 19-9 (CA19-9, p<0.001) and the location of the metastases (p< 0.05) as independent risk factors. Significant correlations were observed between complete ablation and 9 radiomics features. The best prediction performance was achieved with the proposed multimodal data fusion model integrating radiomic features and clinical variables with the highest accuracy (82.6%), AUC value (0.921), sensitivity (80.3%), and specificity (81.4%). Conclusion: This novel multimodal data fusion model was demonstrated efficient for immediate efficacy evaluation after RFA for CRC lung metastases, which could benefit necessary complementary treatment.

Exploration of the impact of multimode thermal therapy versus radiofrequency ablation on CD8+ T effector cells of liver malignancies based on single cell transcriptomics.

Introduction: Multimode thermal therapy (MTT) is an innovative interventional therapy developed for the treatment of liver malignancies. When compared to the conventional radiofrequency ablation (RFA), MTT typically offers improved prognosis for patients. However, the effect of MTT on the peripheral immune environment and the mechanisms underlying the enhanced prognosis have yet to be explored. The aim of this study was to further investigate the mechanisms responsible for the difference in prognosis between the two therapies. Methods: In this study, peripheral blood samples were collected from four patients treated with MTT and two patients treated with RFA for liver malignancies at different time points before and after the treatment. Single cell sequencing was performed on the blood samples to compare and analyze the activation pathways of peripheral immune cells following the MTT and RFA treatment. Results: There was no significant effect of either therapy on the composition of immune cells in peripheral blood. However, the differential gene expression and pathway enrichment analysis demonstrated enhanced activation of T cells in the MTT group compared to the RFA group. In particular, there was a remarkable increase in TNF-α signaling via NF-κB, as well as the expression of IFN-α and IFN-γ in the CD8+ effector T (CD8+ Teff) cells subpopulation, when compared to the RFA group. This may be related to the upregulation of PI3KR1 expression after MTT, which promotes the activation of PI3K-AKT-mTOR pathway. Conclusion: This study confirmed that MTT could more effectively activate peripheral CD8+ Teff cells in patients compared with RFA and promote the effector function, thus resulting in a better prognosis. These results provide a theoretical basis for the clinical application of MTT therapy.

E3 Ubiquitin Ligase MARCH8 Promotes Pancreatic Cancer Growth and Metastasis by Activating STAT3 via Degradation of PTPN4.

OBJECTIVE: The role E3 ubiquitin ligase membrane-associated RING-CH 8 (MARCH8) has not been studied in pancreatic cancer. METHOD: Pancreatic cancer cell lines and the normal pancreatic cells were tested in vitro studies and male athymic nude mice were tested in vivo studies. Measuring cell viability by Cell Counting Kit-8 assay (CCK8), 5-ethynyl-2'- deoxyuridine (Edu) staining, and colony formation assay. Wound healing assay was implemented for cell migration and Transwell assay was performed for cell invasion to evaluate the histological status by hematoxylin and eosin staining and to detect the protein ubiquitination by ubiquitination assay. The protein expression was determined by immunohistochemistry staining and western blotting, and mRNA expression was measured by quantitative reverse transcription polymerase chain reaction. RESULT: The expression of MARCH8 was increased whereas PTPN4 was decreased in pancreatic cancer cells. Overexpression of MARCH8 promoted the growth, migration, and invasion of cells, and knockdown of PTPN4 had the similar effects both in vitro and in vivo. MARCH8 promoted PTPN4 protein degradation through ubiquitination. Moreover, PTPN4 suppressed the transcription activities of STAT3 by impairing the level of pSTAT3 (705), while inhibition of PTPN4 activated phosphorylation of STAT3. CONCLUSIONS: MARCH8 promoted pancreatic cancer growth and invasion through mediating the degradation of PTPN4 and activated the phosphorylation of STAT3.

Safety and efficacy of splenic artery coil embolization for hypersplenism in liver cirrhosis.

BACKGROUND: Partial splenic artery embolization is an effective treatment for hypersplenism but often lacks long-term benefits. PURPOSE: To evaluate the long-term effects of coil embolization of the splenic artery in patients with liver cirrhosis and hypersplenism. MATERIAL AND METHODS: Forty-nine patients with liver cirrhosis and hypersplenism underwent coil embolization of the main splenic artery. The coils were deployed in the mid- or distal segment of the splenic artery to allow collateral blood flow to the spleen. The following data were collected from 2 weeks to 4 years after the embolization: technical success, length of hospital stay, white blood cell count, platelet count, splenic volume, and complication. RESULTS: The technical success rate of splenic artery coil embolization was 100%. The post embolization syndrome rate was 75% (36/49) with no incidence of major complications. The mean length of hospital stay was 9 days. After embolization, the patient's white blood and platelet counts increased significantly, peaked at 2 weeks, and gradually decreased during the 4-year follow-up period, but remained at significantly higher levels than pre-embolization levels. Follow-up CT scans demonstrated a gradual increase in the volume of the enhanced portions of the spleens with a decrease in the volume of unenhanced portion. No significant changes occurred in the red blood cell count and liver function after the embolization. CONCLUSION: Embolization of the mid-and distal main splenic artery with coils is a safe and effective treatment of hypersplenism in cirrhosis with long-term hematologic benefits.

Effect of sub-acute exposure to acrylamide on GABAergic neurons and astrocytes in weaning rat cerebellum.

Occupational exposure and experimental intoxication of acrylamide (ACR) can produce skeletal muscle weakness and ataxia. In this study, we tested whether ACR would affect cerebellar function through the regulation of gamma-aminobutyric acid (GABA) and glial fibrillary acidic protein (GFAP) expression in cerebellum. Weaning male Sprague-Dawley rats were gavaged with ACR (5, 15, 30 mg/kg, 5 days per week) or saline for 4 weeks. Effects of ACR on the cerebellum were observed. For the 5 mg/kg group, no obvious change was observed, whereas moderate and severe ataxia were observed in the 15 mg/kg and 30 mg/kg groups, respectively. For the 15 mg/kg and 30 mg/kg groups, cerebellum concentrations of glutamate and GABA were dose-dependently decreased and increased, respectively. Moreover, the expression of GABA, the GABAergic presynaptic marker glutamate acid decarboxylase-65 (GAD65) and GFAP were significantly increased in those 2 groups. The results suggested that weaning rats were sensitive to ACR and that the toxic effects of ACR on the cerebellum may be associated with the increased expression of GABA and reactive astrocytes hypertrophy.

Electron Transfer Strategies to Regulate Carriers' Separation for Intensive Pyroelectric Dynamic Therapy With Simultaneous Photothermal Therapy.

Endogenic heat shock proteins and uneven local heat distribution are two main problems in traditional tumor hyperthermia therapy strategies. Aiming at solving these problems, we designed Au-SnSe-PVP nanomaterials (ASNPs) by modifying Au nanoparticles (Au-NPs) and biocompatible PVP on SnSe nanorods via a new reactive oxygen species production strategy. The ASNPs with excellent photothermal conversion performance can produce thermoelectric effects in response to temperature differences during photothermal conversion. The modification of Au-NPs can attract free electron (e-) to accumulate and promote the separation of e- and holes (h+) in the thermoelectric process, thereby further promoting e--rich Au-NPs-induced H2O2 homolysis and h+-H2O half-reaction to generate hydroxyl radicals, realizing the synergistic application of photothermal therapy and pyroelectric dynamic therapy in tumor treatment.

Fusion of CT images and clinical variables based on deep learning for predicting invasiveness risk of stage I lung adenocarcinoma.

PURPOSE: To develop a novel multimodal data fusion model by incorporating computed tomography (CT) images and clinical variables based on deep learning for predicting the invasiveness risk of stage I lung adenocarcinoma that manifests as ground-glass nodules (GGNs) and compare the diagnostic performance of it with that of radiologists. METHODS: A total of 1946 patients with solitary and histopathologically confirmed GGNs with maximum diameter less than 3 cm were retrospectively enrolled. The training dataset containing 1704 GGNs was augmented by resampling, scaling, random cropping, and so forth, to generate new training data. A multimodal data fusion model based on residual learning architecture and two multilayer perceptron with attention mechanism combining CT images with patient general data and serum tumor markers was built. The distance-based confidence scores (DCS) were calculated and compared among multimodal data models with different combinations. An observer study was conducted and the prediction performance of the fusion algorithms was compared with that of the two radiologists by an independent testing dataset with 242 GGNs. RESULTS: Among the whole GGNs, 606 GGNs are confirmed as invasive adenocarcinoma (IA) and 1340 are non-IA. The proposed novel multimodal data fusion model combining CT images, patient general data, and serum tumor markers achieved the highest accuracy (88.5%), area under a ROC curve (0.957), F1 (81.5%), F1weighted (81.9%), and Matthews correlation coefficient (73.2%) for classifying between IA and non-IA GGNs, which was even better than the senior radiologist's performance (accuracy, 86.1%). In addition, the DCSs for multimodal data suggested that CT image had a stronger influence (0.9540) quantitatively than general data (0.6726) or tumor marker (0.6971). CONCLUSION: This study demonstrated that the feasibility of integrating different types of data including CT images and clinical variables, and the multimodal data fusion model yielded higher performance for distinguishing IA from non-IA GGNs.

Anticoagulation with warfarin for Budd-Chiari syndrome with chronic inferior vena cava thrombosis: an initial clinical experience.

BACKGROUND: To evaluate the initial clinical safety and feasibility of anticoagulation using warfarin for Budd-Chiari syndrome (BCS) with chronic inferior vena cava (IVC) thrombosis. METHODS: Between October 2005 and June 2009, a total of 16 consecutive BCS patients with chronic IVC thrombosis were treated with warfarin. Warfarin was administered orally at 2.5 mg/d for approximately 3-12 months. Transluminal balloon dilatation of the IVC with a 30-mm balloon catheter was applied for the patients with complete resolution of the thrombus. Data relating to the technical success, angiographic results, complications, and final clinical outcome were collected retrospectively and follow-ups were performed at 1, 3, 6, and 12 months after the stent placement, and annually thereafter. RESULTS: Warfarin was successfully used for anticoagulation in all patients without any complications. Patients were followed up as outpatients for 6.43 ± 2.19 months, and in 14 cases, complete disappearance of the thrombosis was achieved with successful treatment by balloon dilation. In two patients with partial resolution of the thrombosis, Z-stent placement was initiated to compress the thrombus to prevent migration of the thrombosis, followed by dilation of the IVC. During the follow-up for 20.94 ± 10.31 months after the procedure, all the IVC remained patent without complications or pulmonary embolus, and all patients were alive with resolution of symptoms at the time of this study. CONCLUSIONS: The use of warfarin for anticoagulation proved to be simple, safe, and feasible for BCS with chronic IVC thrombosis.

Toxicological effects of acrylamide on the reproductive system of weaning male rats.

It has been reported that acrylamide can be detected in starchy food treated by high temperature (120 °C). People could be exposed to acrylamide in factory, laboratory, or even in daily life via diet and drinking water. Recently, the toxicity of acrylamide receives more attention. In addition to the neurotoxicity in humans, other toxic effects of acrylamide are worth further investigation. In this study, we investigated whether acrylamide affected the male reproductive system using high-performance liquid chromatography. In this study, the reproductive toxicity of acrylamide was observed in 3-week-old weaning male Sprague-Dawley rats treated with acrylamide at various doses (0, 5, 15 or 30 mg/kg/day). The results showed that food availability and reproductive organ indexes of the weaning male rats decreased. Levels of follicle-stimulating hormone and testosterone in serum increased while luteinizing hormone in serum decreased. The histopathological lesions and abnormal sperms presented in weaning rats after acrylamide treatment. The results suggested that there is a toxicological effect of acrylamide on the reproductive system of weaning male rats. Based on the findings above, we suggested that more attention should be paid to the toxicological study of acrylamide on weaning male rats or human beings, rather than just on adult male animals.

CPNE1 Enhances Colorectal Cancer Cell Growth, Glycolysis, and Drug Resistance Through Regulating the AKT-GLUT1/HK2 Pathway.

INTRODUCTION: Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Copines-1 (CPNE1) has been shown to be overexpressed in various cancers; however, the role of CPNE1 in CRC remains unknown. Therefore, it is of great importance to elucidate the role of CPNE1 in CRC and its underlying mechanism of action. METHODS: CPNE1 expression in CRC tissues was measured by quantitative real-time PCR and immunohistochemical (IHC) staining. CPNE1 was knocked down (KD) or overexpressed using small inferring RNAs or lentiviral transduction in CRC cells. The proliferation, apoptosis, glycolysis, and mitochondrial respiration of CRC cells were assessed by cell counting kit-8, flow cytometry, and Xfe24 extracellular flux analyzer assays, respectively. The role of CPNE1 in tumor growth and chemoresistance was further confirmed in xenograft and patient-derived tumor xenograft models, respectively. RESULTS: CPNE1 mRNA and protein were upregulated in CRC tissues. CPNE1 promoted proliferation, inhibited apoptosis, increased mitochondrial respiration, enhanced aerobic glycolysis by activating AKT signaling, upregulated glucose transporter 1 (GLUT1) and hexokinase 2 (HK2), and downregulated the production of cleaved Caspase-3 (c-Caspase 3). CPNE1 also contributed to chemoresistance in CRC cells. CPNE1 KD inhibited tumor growth and increased the sensitivity of tumors to oxaliplatin in vivo. CONCLUSION: CPNE1 promotes CRC progression by activating the AKT-GLUT1/HK2 cascade and enhances chemoresistance.

68Ga-FAPI and 18F-FDG PET/CT Images in a Patient With Extrapulmonary Tuberculosis Mimicking Malignant Tumor.

Extrapulmonary tuberculosis (TB) is difficult to diagnose. Here, we report a case of extrapulmonary TB in a 68-year-old woman presented with mental fatigue, poor appetite, and weight loss. F-FDG PET/CT revealed elevated F-FDG uptake in the left inferior cervical, left supraclavicular, mediastinal, and splenic hilum lymph nodes and spleen, which were suspected of malignant tumor. To further differentiate benign and malignant diseases, Ga-FAPI PET/CT was performed. Ga-FAPI PET/CT also showed intense Ga-FAPI uptake in the previously mentioned FDG-avid lesions. However, biopsy of the left supraclavicular lymph node demonstrated the presence of TB.