Contrast-enhanced ultrasound (CEUS) characteristics of atypical-enhanced papillary thyroid carcinoma (PTC).

OBJECTIVE: To investigate the diagnostic value of CEUS in atypical-enhanced PTC. METHODS: The clinical data, qualitative and quantitative parameters of CEUS in 177 Iso/hyper-enhanced thyroid nodules with definite pathological results were retrospectively analyzed in the Lanzhou University Second Hospital from June 2019 to January 2021. And the clinical value of CEUS in the diagnosis of atypical-enhanced PTC was assessed using univariate and multivariate analysis. RESULTS: Among the 177 thyroid nodules, 59 were benign and 118 were PTC. There were significant differences in age, enhancement border, ring enhancement, speed of wash in, speed of wash out, enhancement pattern, capsule interruption, time to peak, time to wash out, RT, TPH, and TTP (P < 0.05). Multivariate analysis showed unclear enhancement border and concentric enhancement were independent risk factors for the diagnosis of atypical-enhanced PTC by CEUS. The sensitivity, specificity, PPV, NPV, and accuracy of the model in diagnosing atypical-enhanced PTC were 88.1%, 71.2%, 86.0%, 75.0%, and 82.5%, respectively. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.910. CONCLUSION: The diagnosis of atypical-enhanced PTC can be better performed by enhancement characteristics and time intensity curve (TIC) of CEUS, which have a good clinical application value.

Evaluation of the amelioration effect of Ganoderma formosanum extract on delaying PM2.5 damage to lung macrophages.

SCOPE: Particulate matter (PM) contains toxic organic matter and heavy metals that enter the entire body through blood flow and may cause mortality. Ganoderma formosanum mycelium, a valuable traditional Chinese medicine that has been used since ancient times, contains various active ingredients that can effectively impede inflammatory responses on murine alveolar macrophages induced by PM particles. METHODS AND RESULTS: An experimental study assessing the effect of G. formosanum mycelium extract's water fraction (WA) on PM-exposed murine alveolar macrophages using ROS measurement shows that WA reduces intracellular ROS by 12% and increases cell viability by 16% when induced by PM particles. According to RNA-Sequencing, western blotting, and real-time qPCR are conducted to analyze the metabolic pathway. The WA reduces the protein ratio in p-NF-κB/NF-κB by 18% and decreases the expression of inflammatory genes, including IL-1ß by 38%, IL-6 by 29%, and TNF-α by 19%. Finally, the identification of seven types of anti-inflammatory compounds in the WA fraction is achieved through UHPLC-ESI-Orbitrap-Elite-MS/MS analysis. These compounds include anti-inflammatory compounds, namely thiamine, adenosine 5'-monophosphate, pipecolic acid, L-pyroglutamic acid, acetyl-L-carnitine, D-mannitol, and L-malic acid. CONCLUSIONS: The study suggests that the WA has the potential to alleviate the PM -induced damage in alveolar macrophages, demonstrating its anti-inflammatory properties.

Pancreatic Ductal Adenocarcinoma: The Characteristics of Contrast-Enhanced Ultrasound Are Correlated with the Hypoxic Microenvironment.

A hypoxic microenvironment is associated with an increased risk of metastasis, treatment resistance and poor prognosis of pancreatic ductal adenocarcinoma (PDAC). This study aimed to identify contrast-enhanced ultrasound (CEUS) characteristics that could predict the hypoxic microenvironment of PDAC. A total of 102 patients with surgically resected PDAC who underwent CEUS were included. CEUS qualitative and quantitative characteristics were analyzed. The expression of hypoxia-inducible factor-1α (HIF-1) and glucose transporter-1 (GLUT1) were demonstrated by immunohistochemistry. The associations between CEUS characteristics and the HIF-1α and GLUT1 expression of PDACs were evaluated. We found that HIF-1α-high PDACs and GLUT1-high PDACs had a larger tumor size and were more prone to lymph node metastasis. There was a significant positive linear correlation between the expression of HIF-1α and GLUT1. CEUS qualitative characteristics including completeness of enhancement and peak enhancement degree (PED) were related to the expression of HIF-1α and GLUT1. A logistic regression analysis showed that tumor size, lymph node metastasis, incomplete enhancement and iso-enhancement of PED were independent predictors for HIF-1α-high PDACs and GLUT1-high PDACs. As for quantitative characteristics, HIF-1α-high PDACs and GLUT1-high PDACs showed higher peak enhancement (PE) and wash-in rate (WIR). CEUS can effectively reflect the hypoxia microenvironment of PDAC, which may become a noninvasive imaging biomarker for prognosis prediction and individualized treatment.

Pan-mediastinal neoplasm diagnosis via nationwide federated learning: a multicentre cohort study.

BACKGROUND: Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. METHODS: In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human-AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. FINDINGS: In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969-0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738-0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497-0·554) and 0·799 (0·778-0·822), respectively. In the human-AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383-0·633) and 0·800 (0·700-0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345-0·411) and top-3 accuracy by 13·0% (0·545-0·616). INTERPRETATION: For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Clinical Results, Risk Factors, and Future Directions of Ultrasound-Guided Percutaneous Microwave Ablation for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a relatively poor prognosis, especially for advanced HCC. With the availability of a variety of treatment options, the treatment strategies for HCC have become more and more diversified. Microwave ablation (MWA) has gradually been considered as a viable alternative to surgical resection (SR) owing to its comparable long-term survival, reduced complications, and greater preservation of hepatic parenchyma. However, clinical outcomes, tumor progression, and recurrence of HCC after MWA remain major concerns. Here, after reviewing the current therapeutic options for HCC, we focus on MWA, describing the advantages and challenges of MWA and the clinical results after treatment. We then focused on prognostic factors that influence post-ablation clinical outcomes and briefly presented the strategy of MWA for future clinical treatment.

Role of contrast-enhanced ultrasound with time-intensity curve analysis for differentiating hypovascular solid pancreatic lesions.

OBJECTIVES: To evaluate the clinical value of contrast-enhanced ultrasound (CEUS) with time-intensity curve (TIC) in distinguishing different types of hypovascular solid pancreatic lesions. METHODS: A total of 89 patients with 90 pancreatic lesions (all confirmed by surgery or biopsy pathology) that manifested hypoenhancement on contrast-enhanced ultrasound (CEUS) were included in this study. Six peak enhancement patterns were proposed for differentiating hypovascular pancreatic lesions. CEUS qualitative and TIC-based quantitative parameters were analyzed, and each lesion was scored based on the statistically significant qualitative parameters to evaluate the diagnostic ability of CEUS for hypovascular solid pancreatic lesions. RESULTS: Qualitative parameters such as peak enhancement pattern II/III/IV, penetrating vessels, centripetal enhancement, and early washout were reliable indicators of malignant lesions, and lesions scored based on these qualitative parameters, with a score ≥ 2, were highly suspected to be malignant lesions. Pattern I had an accuracy of 83.33% for predicting mass-forming pancreatitis (MFP), pattern V had an accuracy of 96.67% for predicting solid pseudopapillary tumors of the pancreas (SPTP), and pattern VI had an accuracy of 81.11% for predicting neuroendocrine tumors/carcinomas (NETs/NECs). For quantitative analysis, nodule/pancreatic parenchyma echo intensity reduction ratio was significantly greater in malignant lesions. CONCLUSIONS: CEUS qualitative and TIC-based quantitative parameters have clinical value in distinguishing malignant from benign hypovascular pancreatic lesions. KEY POINTS: • Contrast-enhanced ultrasound helps clinicians assess patients with pancreatic lesions. • Six peak enhancement patterns are proposed for differentiating pancreatic hypovascular lesions. • Qualitative parameters such as peak enhancement pattern II/III/IV, penetrating vessels, centripetal enhancement, early washout, and quantitative parameter nodule/pancreatic parenchyma echo intensity reduction ratio were important characteristics to discriminate malignant from hypovascular benign lesions.

Nonhypovascular pancreatic ductal adenocarcinomas: CEUS imaging findings and differentiation from other types of solid pancreatic lesions.

OBJECTIVES: To observe and assess the diagnostic value of contrast-enhanced ultrasound (CEUS) in patients with iso-/hypervascular solid pancreatic lesions. METHODS: 70 pancreatic lesions (all confirmed by surgery or biopsy pathology) that manifested iso-/hyperenhancement on CEUS were retrospectively studied from January 2018 to January 2022, including 24 pancreatic ductal adenocarcinomas (PDAC), 15 mass-forming pancreatitis (MFP), 24 pancreatic neuroendocrine tumors (PNET) (14 hyper-PNETs, 10 iso-PNETs), and 7 solid pseudopapillary tumors of pancreas (SPTP). 65 pancreatic ductal adenocarcinomas (PDAC) that manifested hypoenhancement on CEUS were retrospectively studied from January 2020 to January 2022. CEUS patterns and the clinical and pathologic features were analyzed, and the diagnostic ability of CEUS for iso/hyperenhanced solid pancreatic lesions was assessed. RESULTS: Centripetal enhancement, heterogeneous enhancement, early washout, and hypoenhancement in the late phase mostly appeared in iso-/hyper-PDACs (p < 0.05). Heterogeneous enhancement in small lesions (< 3 cm) as the diagnostic criterion for iso-/hyper-PDACs had an accuracy of 74.3% and a specificity of 91.3%. Iso-PNETs more commonly had larger tumor sizes and more often showed heterogeneous enhancement than hyper-PNETs (p = 0.007, p = 0.035, respectively). The characteristics of the combination of isoenhancement, homogeneous enhancement, and synchronous wash-in/out for MFP had a high accuracy of 90%. Capsular enhancement with heterogeneous enhancement inside for SPTP had an accuracy of 97.1%. CONCLUSION: CEUS enhancement patterns have potentially great value in the differentiation of iso-/hyperenhanced pancreatic lesions.

Oxaliplatin and Gedatolisib (PKI-587) Co-Loaded Hollow Polydopamine Nano-Shells with Simultaneous Upstream and Downstream Action to Re-Sensitize Drugs-Resistant Hepatocellular Carcinoma to Chemotherapy.

Multidrug resistance (MDR) is a key to the ineffectiveness of hepatocellular carcinoma (HCC) chemotherapy. Oxaliplatin (OXA), as one of the first-line chemotherapeutic drugs for HCC, abnormally activates the PI3K/AKT/mTOR signaling pathway and DNA damage repair pathway (NHEJ and HR), causing drug resistance and consequnet compromised efficacy. Herein, we developed a hollow polydopamine nanoparticle (H-PDA)-based nano-delivery system (O/P-HP) that contained OXA and a dual PI3K/mTOR inhibitor PKI-587 with complementary effects for combating drug resistance in cancer chemotherapy. The hollow structure of H-PDA endowed O/P-HP with high loading efficiencies of OXA and PKI-587-up to 49.6% and 7.0%, respectively. In addition, benefiting from the intracellular delivery of H-PDA as well as the highly concentrated drugs therein, O/P-HP inhibited the proliferation of OXA-resistant HR cells, resulting in a cell viability of only 17.63%. These values were significantly superior to those with OXA single-agent treatment and treatment with free OXA in combination with PKI-587. We examined the intrinsic mechanisms of the combination therapy: O/PHP had excellent anti-cancer effects via the simultaneous upstream and downstream action to re-sensitize HR cells to chemotherapy; OXA induced strong apoptosis via the direct platinum lesions on DNA molecules, while PKI-587 normalized the abnormally activated PI3K/AKT/mTOR signaling pathway and DNA damage repair pathway (NHEJ and HR) that could attenuate the effectiveness of OXA, thus resulting in inhibition of cell proliferation, migration and DNA repair enzyme activity and the augment of apoptotic effects. Such combination therapy, with simultaneous upstream and downstream action, may be a strategy for minimizing resistance for anti-cancer treatments.

DUS4L Silencing Suppresses Cell Proliferation and Promotes Apoptosis in Human Lung Adenocarcinoma Cell Line A549.

PURPOSE: This study aims to investigate the potential role of DUS4L (dihydrouridine synthase 4 like) in lung adenocarcinoma (LUAD) and explore its associated pathways in human LUAD. METHODS: Firstly, we evaluated the relationships between clinicopathological characteristics and DUS4L expression via analysis of TCGA RNA sequencing data and other publicly available databases. Then, DUS4L was effectively silenced in LUAD cell line A549 using the lentiviral shRNA (short-hairpin RNA) transfection to assess its effects on cell proliferation, cycle and apoptosis in LUAD cells. RNA-seq technology was applied to shDUS4L and shCtrl-transfected cells to generate the corresponding gene expression profiles. Differentially expressed genes (DEGs) were identified using the DESeq2 program package. Also, DEGs were subjected to Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis to explore the associated molecular signaling pathways and relevant biological functions. RESULTS: Analysis of TCGA data revealed that DUS4L was highly upregulated in LUAD tissues which was related to clinical T and TNM stages of LUAD. The knockdown of DUS4L effectively inhibited cell proliferation and promoted apoptosis in A549 cells. Furthermore, the DEGs between the shDUS4L and shCtrl A549 cells were mainly enriched in biological processes associated with spliceosome, ribosome, RNA catabolic process, ncRNA (non-coding RNA) processing, and p53 signaling pathway. CONCLUSION: Altogether, our results suggest that DUS4L is significantly associated with tumorigenesis and could be utilized as a novel biomarker and therapeutic target for LUAD.

Prevalence and risk factors of postoperative delirium after spinal surgery: a meta-analysis.

OBJECTIVE: Postoperative delirium (POD) was common after spinal surgery, but the main findings in previous studies remained conflicting. This current meta-analysis was aimed at exploring the prevalence and risk factors of POD after spinal surgery. METHODS: PubMed and Embase were searched from inception to June 2019. Studies which reported the prevalence and risk factors of POD after spinal surgery were included. STATA version 12.0 was employed to analyze the pooled data. Statistical heterogeneity across included studies was identified using the I2 statistics. RESULTS: A total of 28 studies with 588,732 patients were included in the meta-analysis. The pooled prevalence of POD after spinal surgery was 0.85% (95%CI, 0.83-0.88%) with substantial heterogeneity (I2 = 97.3%). The central nervous system disorder (OR 4.73; 95%CI, 4.30-5.19) was a strong predictor for POD, whereas age (OR 1.16; 95%CI, 1.05-2.47; I2 = 99.2%) and blood loss (OR 1.10; 95%CI, 1.01-1.20; I2 = 93.3%) were weaker predictors. The funnel plot and statistical tests suggested that there existed potential publication bias, but the trim and fill method indicated that the pooled prevalence basically kept stable after adding two "missing" studies. CONCLUSIONS: The pooled POD after spinal surgery ranges from 0.83 to 0.88%. The central nervous system disorder, age, and blood loss were potential risk factors for POD.

Immune Infiltration Landscape in Clear Cell Renal Cell Carcinoma Implications.

The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor infiltrating immune cells (TIICs) recruited to the cancer microenvironment. Clear cell renal cell carcinoma (ccRCC) immune microenvironment plays an important role in the tumorigenesis. This research investigated the characteristics of immune cell invasion of renal cell carcinoma and provided clues for future clinical implementation. Retrospectively, ccRCC gene expression was analyzed with appropriate clinicopathological data from the Cancer Genome Atlas (TCGA) and GEO database up to December 2019. The CIBERSORT algorithm, meta-analysis, principal component analysis (PCA), Single-Sample Gene Set Enrichment Analysis (ssGSEA) and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. We also focused on evaluating the association with TIICs subpopulations and clinical features and molecular subtypes. TIICs subpopulation, especially Macrophages subgroup, T follicular helper (Tfh) cells and CD8 T cells, all contribute to tumorigenesis. Unsupervised clustering analysis revealed that there existed two distinct TIICs subgroups with different survival patterns. TIICs are extensively involved in the pathogenesis and development of the ccRCC. Characterizing the composition of TIICs influences the metabolism of tumors, activity, level, stage, and survival of patients. Collectively, the TIIC analysis has the potential to assist in the assessment and selection of ccRCC prognosis and treatment.

Clinicopathological and prognostic significance of epithelial cell transforming sequence 2 expression in cancers: a systematic review and meta-analysis.

Numerous studies have investigated the prognostic significance of ECT2 (epithelial cell transforming sequence 2) expression in patients with cancer. Nevertheless, conflicting results have been obtained. We thus performed a meta-analysis to systematically assess the prognostic significance of ECT2 in cancer. Electronic databases (PubMed and EMBASE) were searched for eligible studies. Hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (CIs) were used to estimate effect sizes. A total of 5,305 patients from 19 articles and 21 studies were included. The pooled results revealed that high ECT2 expression was correlated with advanced TNM stage (OR = 2.17; 95% CI: 1.42-3.32), positive lymph node metastasis (OR = 2.98; 95% CI: 2.28-3.89), distant metastasis (OR = 2.25; 95% CI: 1.03-4.92), and poor tumour differentiation (OR = 2.25; 95% CI: 1.03-4.92). More importantly, high ECT2 expression was significantly associated with poor overall survival (HR = 2.26; 95% CI, 1.84-2.78) and recurrence-free survival (HR = 1.52; 95% CI, 1.24-1.86). Our results suggested that ECT2 is a promising prognostic indicator and therapeutic target for cancer.

MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma.

The long-term prognosis of patients with lung cancer remains poor and thus it is imminent to further elucidate the molecular mechanism for the oncogenesis of lung cancer. In this study, we observed that surfactant protein C (SFTPC) expression was downregulated in human lung adenocarcinoma tissues and cell lines, and low SFTPC expression correlated with poor overall survival of lung adenocarcinoma patients. Moreover, we found that overexpression of SFTPC could inhibit lung cancer cell proliferation in vitro and in vivo, but downregulation of SFTPC showed the opposite results. Besides, it was observed that miR-629-3p expression was upregulated in human lung adenocarcinoma tissues and cell lines. More importantly, we found that miR-629-3p could downregulate SFTPC expression by directly binding to the SFTPC 3'-UTR and inhibit the regulatory effect of SFTPC on lung adenocarcinoma cell proliferation. In conclusion, these data suggested that miR-629-3p-meditated downregulation of SFTPC may promote lung adenocarcinoma progression.

Tumor-derived exosomal HMGB1 promotes esophageal squamous cell carcinoma progression through inducing PD1+ TAM expansion.

Macrophages constitute one of the most common components of immune cells, which penetrate tumors and they have a key role in tumor prognosis. Here, we identified an unrecognized macrophage subpopulation, which favors tumorigenesis. These macrophages express programmed cell death protein 1 (PD1) in a constitutive manner and accumulates in esophageal squamous cell carcinoma (ESCC) in advanced stage of the disease and is negatively associated with the survival of ESCC patients. The PD1+ tumor-associated macrophages (PD1+ TAMs) displayed surface pattern and function akin to M2: a substantial enhancement in CD206 and IL-10 expression; a specific reduction in HLA-DR, CD64, and IL-12 expression; and a significant increase in the ability to inhibit CD8+ T-cell proliferation. Triggering of PD1 signal is effective in increasing PD1+ TAM function. Moreover, exosomal HMGB1 obtained from tumors are efficient in triggering differentiation of monocytes into PD1+ TAMs, which display phenotypic and functional properties of M2. Overall, our work is the first finding to confirm that exosomal HMGB1 obtained from ESCC can successfully trigger clonal expansion of PD1+ TAM. Further, as the macrophages exhibit an M2-like surface profile and function, thereby creating conditions for development of ESCC. Thus, effective methods of treatment include combining immunotherapy with targeting PD1+ TAMs and tumor-derived exosomal HMGB1 to resuscitate immune function in individuals suffering from ESCC.