Ilexgenin A inhibits lipid accumulation in macrophages and reduces the progression of atherosclerosis through PTPN2/ERK1/2/ABCA1 signalling pathway.

Macrophage lipid accumulation indicates a pathological change in atherosclerosis. Ilexgenin A (IA), a pentacyclic triterpenoid compound, plays a role in preventing inflammation, bacterial infection, and fatty liver and induces a potential anti-atherogenic effect. However, the anti-atherosclerotic mechanism remains unclear. The present study investigated the effects of IA on lipid accumulation in macrophage-derived foam cells and atherogenesis in apoE-/- mice. Our results indicated that the expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) was up-regulated by IA, promoting cholesterol efflux and reducing lipid accumulation in macrophages, which may be regulated by the protein tyrosine phosphatase non-receptor type 2 (PTPN2)/ERK1/2 signalling pathway. IA attenuated the progression of atherosclerosis in high-fat diet-fed apoE-/- mice. PTPN2 knockdown with siRNA or treatment with an ERK1/2 agonist (Ro 67-7476) impeded the effects of IA on ABCA1 upregulation and cholesterol efflux in macrophages. These results suggest that IA inhibits macrophage lipid accumulation and alleviates atherosclerosis progression via the PTPN2/ERK1/2 signalling pathway.

The Magic and Mystery of TRIM65 in Diseases.

Tripartite-motif protein family member 65 (TRIM65) belongs to the tripartite motif (TRIM) protein family. Its typical structure consists of the RING, B-Box motif, and coiled-coil domains, which are highly conserved at the N-terminus and the variable SPRY domain at the C-terminus. TRIM65 is an E3 ubiquitin ligase that participates in physiological and pathological processes through the ubiquitination pathway, including intracellular signal transduction, protein degradation, cell proliferation, apoptosis, carcinogenesis, autophagy, and phenotypic transformation. Evidence shows that TRIM65 plays a remarkable and obscure role in diseases, including multisystem tumours, neurodegenerative diseases, immune system diseases, and inflammatory diseases. This review is devoted to elaborating on the relationship between TRIM65 and diseases and its pathogenic mechanism, providing a theoretical basis for TRIM65 as a possible pathogenic target of diseases and exploring the possible future research direction of TRIM65 and the challenges it may face.

Integrative analysis of single-cell and bulk RNA sequencing unveils a machine learning-based pan-cancer major histocompatibility complex-related signature for predicting immunotherapy efficacy.

Major histocompatibility complex (MHC) could serve as a potential biomarker for tumor immunotherapy, however, it is not yet known whether MHC could distinguish potential beneficiaries. Single-cell RNA sequencing datasets derived from patients with immunotherapy were collected to elucidate the association between MHC and immunotherapy response. A novel MHCsig was developed and validated using large-scale pan-cancer data, including The Cancer Genome Atlas and immunotherapy cohorts. The therapeutic value of MHCsig was further explored using 17 CRISPR/Cas9 datasets. MHC-related genes were associated with drug resistance and MHCsig was significantly and positively associated with immunotherapy response and total mutational burden. Remarkably, MHCsig significantly enriched 6% top-ranked genes, which were potential therapeutic targets. Moreover, we generated Hub-MHCsig, which was associated with survival and disease-special survival of pan-cancer, especially low-grade glioma. This result was also confirmed in cell lines and in our own clinical cohort. Later low-grade glioma-related Hub-MHCsig was established and the regulatory network was constructed. We provided conclusive clinical evidence regarding the association between MHCsig and immunotherapy response. We developed MHCsig, which could effectively predict the benefits of immunotherapy for multiple tumors. Further exploration of MHCsig revealed some potential therapeutic targets and regulatory networks.

The biochemical pathways of apoptotic, necroptotic, pyroptotic, and ferroptotic cell death.

Apoptosis, the first regulated form of cell death discovered in mammalian cells, is executed by caspase-3/7, which are dormant in living cells but become activated by upstream caspase-8 or caspase-9 in responding to extracellular cytokines or intracellular stress signals, respectively. The same cell death-inducing cytokines also cause necroptosis when caspase-8 is inhibited, resulting in the activation of receptor-interacting protein kinase 3 (RIPK3), which phosphorylates pseudokinase MLKL to trigger its oligomerization and membrane-disrupting activity. Caspase-1/4/5/11, known as inflammatory caspases, instead induce pyroptosis by cleaving gasdermin D, whose caspase-cleaved N terminus forms pores on the plasma membrane. The membrane protein NINJ1 amplifies the extent of membrane rupture initiated by gasdermin D. Additionally, disturbance of peroxidation of polyunsaturated fatty acid tails of membrane phospholipids triggers ferroptosis, an iron-dependent and caspases-independent necrotic death. This review will discuss how these regulated cell death pathways act individually and interconnectively in particular cell types to carry out specific physiological and pathological functions.

Macrophage fatty acid oxidation in atherosclerosis.

Atherosclerosis significantly contributes to the development of cardiovascular diseases (CVD) and is characterized by lipid retention and inflammation within the artery wall. Multiple immune cell types are implicated in the pathogenesis of atherosclerosis, macrophages play a central role as the primary source of inflammatory effectors in this pathogenic process. The metabolic influences of lipids on macrophage function and fatty acid ß-oxidation (FAO) have similarly drawn attention due to its relevance as an immunometabolic hub. This review discusses recent findings regarding the impact of mitochondrial-dependent FAO in the phenotype and function of macrophages, as well as transcriptional regulation of FAO within macrophages. Finally, the therapeutic strategy of macrophage FAO in atherosclerosis is highlighted.

Diagnosis of Alzheimer's disease by joining dual attention CNN and MLP based on structural MRIs, clinical and genetic data.

Alzheimer's disease (AD) is an irreversible central nervous degenerative disease, while mild cognitive impairment (MCI) is a precursor state of AD. Accurate early diagnosis of AD is conducive to the prevention and early intervention treatment of AD. Although some computational methods have been developed for AD diagnosis, most employ only neuroimaging, ignoring other data (e.g., genetic, clinical) that may have potential disease information. In addition, the results of some methods lack interpretability. In this work, we proposed a novel method (called DANMLP) of joining dual attention convolutional neural network (CNN) and multilayer perceptron (MLP) for computer-aided AD diagnosis by integrating multi-modality data of the structural magnetic resonance imaging (sMRI), clinical data (i.e., demographics, neuropsychology), and APOE genetic data. Our DANMLP consists of four primary components: (1) the Patch-CNN for extracting the image characteristics from each local patch, (2) the position self-attention block for capturing the dependencies between features within a patch, (3) the channel self-attention block for capturing dependencies of inter-patch features, (4) two MLP networks for extracting the clinical features and outputting the AD classification results, respectively. Compared with other state-of-the-art methods in the 5CV test, DANMLP achieves 93% and 82.4% classification accuracy for the AD vs. MCI and MCI vs. NC tasks on the ADNI database, which is 0.2%∼15.2% and 3.4%∼26.8% higher than that of other five methods, respectively. The individualized visualization of focal areas can also help clinicians in the early diagnosis of AD. These results indicate that DANMLP can be effectively used for diagnosing AD and MCI patients.

Pax-8: Molecular biology, pathophysiology, and potential pathogenesis.

Transcription factors, as the convergence points of multiple signaling pathways in eukaryotic cells, are closely involved in disease development. Pax-8, an important transcription factor belonging to the Pax family, exerts a crucial influence on the regulation of gene expression required for both physiological conditions and pathological processes. Pax-8 contributes to the pathogenesis of many human diseases, ranging from cardiovascular disease to many cancers, and therefore, it can be imagined that Pax-8 holds great therapeutic potential. In this review, we summarize the structure, distribution, function, and regulatory mechanisms of Pax-8 to provide a new research direction for Pax-8.

A novel cross-layer dual encoding-shared decoding network framework with spatial self-attention mechanism for hippocampus segmentation.

Accurate segmentation of the hippocampus from the brain magnetic resonance images (MRIs) is a crucial task in the neuroimaging research, since its structural integrity is strongly related to several neurodegenerative disorders, such as Alzheimer's disease (AD). Automatic segmentation of the hippocampus structures is challenging due to the small volume, complex shape, low contrast and discontinuous boundaries of hippocampus. Although some methods have been developed for the hippocampus segmentation, most of them paid too much attention to the hippocampus shape and volume instead of considering the spatial information. Additionally, the extracted features are independent of each other, ignoring the correlation between the global and local information. In view of this, here we proposed a novel cross-layer dual Encoding-Shared Decoding network framework with Spatial self-Attention mechanism (called ESDSA) for hippocampus segmentation in human brains. Considering that the hippocampus is a relatively small part in MRI, we introduced the spatial self-attention mechanism in ESDSA to capture the spatial information of hippocampus for improving the segmentation accuracy. We also designed a cross-layer dual encoding-shared decoding network to effectively extract the global information of MRIs and the spatial information of hippocampus. The spatial features of hippocampus and the features extracted from the MRIs were combined to realize the hippocampus segmentation. Results on the baseline T1-weighted structural MRI data show that the performance of our ESDSA is superior to other state-of-the-art methods, and the dice similarity coefficient of ESDSA achieves 89.37%. In addition, the dice similarity coefficient of the Spatial Self-Attention mechanism (SSA) strategy and the dual Encoding-Shared Decoding (ESD) strategy is 9.47%, 5.35% higher than that of the baseline U-net, respectively, indicating that the strategies of SSA and ESD can effectively enhance the segmentation accuracy of human brain hippocampus.

Identification of potential LncRNAs as papillary thyroid carcinoma biomarkers based on integrated bioinformatics analysis using TCGA and RNA sequencing data.

The roles and mechanisms of long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remain elusive. We obtained RNA sequencing (RNA-seq) data of surgical PTC specimens from patients with thyroid cancer (THCA; n = 20) and identified differentially expressed genes (DEGs) between cancer and cancer-adjacent tissue samples. We identified 2309 DEGs (1372 significantly upregulated and 937 significantly downregulated). We performed Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment, and protein-protein interaction network analyses and screened for hub lncRNAs. Using the same methods, we analyzed the RNA-seq data from THCA dataset in The Cancer Genome Atlas (TCGA) database to identify differentially expressed lncRNAs. We identified 15 key differentially expressed lncRNAs and pathways that were closely related to PTC. Subsequently, by intersecting the differentially expressed lncRNAs with hub lncRNAs, we identified LINC02407 as the key lncRNA. Assessment of the associated clinical characteristics and prognostic correlations revealed a close correlation between LINC02407 expression and N stage of patients. Furthermore, receiver operating characteristic curve analysis showed that LINC02407 could better distinguish between cancerous and cancer-adjacent tissues in THCA patients. In conclusion, our findings suggest that LINC02407 is a potential biomarker for PTC diagnosis and the prediction of lymph node metastasis.

Detection of BRAF V600E in Fine-Needle Aspiration Samples of Thyroid Nodules by Droplet Digital PCR.

Background: BRAF exon 15 p.V600E (BRAF V600E) mutation has been established as an important molecular marker for papillary thyroid carcinoma diagnosis by ultrasound-guided fine-needle aspiration biopsy (FNAB). Sanger sequencing is the gold standard for detecting BRAF V600E mutations but fails to identify low-frequency mutations. However, droplet digital PCR (ddPCR) is a popular new method for detecting low-frequency mutations. Here, we compare the efficiency of droplet digital PCR (ddPCR) and Sanger sequencing for detection of the BRAF V600E mutation in thyroid fine-needle aspiration (FNA) samples. Methods: Thyroid fine-needle aspiration samples from 278 patients with 310 thyroid nodules were collected. Sanger sequencing and ddPCR were conducted to detect the BRAF V600E mutation. Results: The BRAF V600E mutation was found in 94 nodules (30.32%) by ddPCR and 40 nodules (12.90%) by Sanger sequencing in 310 FNA samples. A total of 119 nodules were confirmed PTC by postsurgical pathology. Among which the BRAF mutation was found in 80 (67.23%) nodules by ddPCR and 31 (26.05%) by Sanger sequencing. All nodules carrying the mutation detected by Sanger sequencing (SS+) were verified by ddPCR (ddPCR+). Also, all nodules with no mutation detected by ddPCR were interpreted as wild-type by Sanger sequencing (SS-). In addition. Almost all SS+/ddPCR + nodules (95.00%; 38/40) and SS-/ddPCR + nodules (100.00%; 54/54) displayed a BRAF mutation rate of >5% and <15%, respectively, indicating easy misdetection by Sanger sequencing when the mutation rate is between 5 and 15%. Conclusion: ddPCR has higher sensitivity than Sanger sequencing and we propose ddPCR as a supplement to Sanger sequencing in molecular testing of BRAF using FNAB samples.

Mammalian Target of Rapamycin as the Therapeutic Target of Vascular Proliferative Diseases: Past, Present, and Future.

ABSTRACT: The abnormal proliferation of vascular smooth muscle cells (VSMCs) is a key pathological characteristic of vascular proliferative diseases. Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that plays an important role in regulating cell growth, motility, proliferation, and survival, as well as gene expression in response to hypoxia, growth factors, and nutrients. Increasing evidence shows that mTOR also regulates VSMC proliferation in vascular proliferative diseases and that mTOR inhibitors, such as rapamycin, effectively restrain VSMC proliferation. However, the molecular mechanisms linking mTOR to vascular proliferative diseases remain elusive. In our review, we summarize the key roles of the mTOR and the recent discoveries in vascular proliferative diseases, focusing on the therapeutic potential of mTOR inhibitors to target the mTOR signaling pathway for the treatment of vascular proliferative diseases. In this study, we discuss mTOR inhibitors as promising candidates to prevent VSMC-associated vascular proliferative diseases.

Upregulation of GBP1 in thyroid primordium is required for developmental thyroid morphogenesis.

PURPOSE: Congenital hypothyroidism (CH) is a common congenital endocrine disorder in humans. CH-related diseases such as athyreosis, thyroid ectopy, and hypoplasia are primarily caused by dysgenic thyroid development. However, the underlying molecular mechanisms remain unknown. METHODS: To identify novel CH candidate genes, 192 CH patients were enrolled, and target sequencing of 21 known CH-related genes was performed. The remaining 98 CH patients carrying no known genes were subjected to exome sequencing (ES). The functions of the identified variants were confirmed using thyroid epithelial cells in vitro and in zebrafish model organisms in vivo. RESULTS: Four pathogenic GBP1 variations from three patients were identified. In zebrafish embryos, gbp1 knockdown caused defective thyroid primordium morphogenesis and hypothyroidism. The thyroid cells were stuck together and failed to dissociate from each other to form individual follicles in gbp1-deficient embryos. Furthermore, defects were restored with wild-type human GBP1 (hGBP1) messenger RNA (mRNA) except for mutated hGBP1 (p.H150Y, p.L187P) overexpression. GBP1 promoted ß-catenin translocation into the cytosol and suppressed the formation of cellular adhesion complexes. Suppression of cell-cell adhesion restored the thyroid primordium growth defect observed in gbp1-deficient zebrafish embryos. CONCLUSION: This study provides further understanding regarding thyroid development and shows that defective cellular remodeling could cause congenital hypothyroidism.

A five-gene panel refines differential diagnosis of thyroid nodules.

BACKGROUND: Molecular testing for oncogenic mutations in fine-needle aspiration has showed high predictive value in identifying malignant lesions from thyroid nodules with indeterminate cytology. METHODS: To figure out an efficient and economical gene panel for most medical institutions in China, we designed a five-gene panel including BRAF/NRAS/KRAS/HRAS/TERT genes and conducted a retrospective study to evaluate the role of this five-gene diagnostic panel in differential diagnosis of thyroid nodules. RESULTS: A total of 665 patients with 695 thyroid nodules were investigated in the current study. The fine-needle aspiration biopsy and surgically separated thyroid tissue specimens were harvested to test BRAF, TERT, NRAS, KRAS, and HRAS mutations. We identified 261 mutations in 665 patients, including 177 V600E mutations in BRAF. Three hundred and sixty-nine patients who underwent thyroid surgery after completion of the initial clinical and cytological evaluation were enrolled in the final analysis. The diagnostic sensitivity, specificity, and accuracy of the combination of FNAB cytology and five-gene detection were 74.7%, 93.8%, and 84.8%, respectively. BRAF V600E and five-gene panel could recognize 46.4% and 53.6% of papillary thyroid carcinoma in the patients with cytologically indeterminate nodules. CONCLUSION: The five-gene panel can effectively improve the sensitivity, negative predictive value, and accuracy of fine-needle aspiration biopsy cytology, especially in the patients with cytologically indeterminate nodules.

Similar Antimicrobial Resistance of Escherichia coli Strains Isolated from Retail Chickens and Poultry Farms.

Antimicrobial resistance (AMR) is a major public health challenge and spreads through humans, animals, and the environment. Many reports show that AMR genes (ARGs) or phenotypes can be transferred from food animals to humans. However, the level and correlation of AMR in different nodes of the poultry meat supply chain are still poorly understood. Herein, 225 Escherichia coli isolates were recovered from chilled chicken samples from markets (123) and chicken fecal samples from farms (102) in Zhejiang Province, China. The dominant sequence types (STs) were ST155 (8.89%), ST48 (7.56%), and ST10 (7.11%), which are common in chicken and fecal samples. Antimicrobial susceptibility testing (AST) analysis showed that the E. coli isolates from fecal samples and retail chickens were resistant to ampicillin (61.77% and 63.42%, respectively) and trimethoprim (56.87% and 52.85%). Moreover, 36.59% of the E. coli isolates from chilled chickens and 39.22% of the isolates from fecal samples were resistant to three or more antimicrobial agents. A total of 59 ARGs were identified in sequenced E. coli genomes, including the mcr-1 gene involved in colistin resistance. The E. coli from farms and markets could be clustered in the same branch according to core single nucleotide polymorphisms. In addition, toxin genes astA and hlyE were also predicted in 86.5% (32/37) and 13.5% (5/37) of the above genomes, respectively. Taken together, these findings demonstrated that E. coli isolates from markets and farms showed similar AMR patterns, suggesting that E. coli strains in markets may originate from farms.

LncRNA FAM230B promotes the metastasis of papillary thyroid cancer by sponging the miR-378a-3p/WNT5A axis.

Emerging evidence indicates that the dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in the progression of papillary thyroid cancer (PTC). In this study, we found consistently elevated expression levels of the lncRNA FAM230B in PTC tissues, both in newly generated RNA-seq data and in datasets from the GEO and TCGA databases. We demonstrated that the expression of FAM230B can be used for the diagnosis of PTC and is also strongly associated with lymph node metastasis. The potential biological functions of FAM230B and molecular mechanisms by which it regulates PTC progression were investigated. Functionally, FAM230B promoted the migration and invasion of PTC cells in vitro and in vivo. Mechanistically, FAM230B sponged miR-378a-3p and showed competitive binding to the 3'-UTR of WNT5A. FAM230B overexpression resulted in elevated WNT5A expression and thereby regulated the epithelial-mesenchymal transition in PTC cells. Finally, we verified that both miR-378a-3p overexpression and WNT5A silencing effectively offset the impacts of FAM230B on PTC cell migration and invasion. In conclusion, our study demonstrated the oncogenic function of the lncRNA FAM230B in PTC cells, providing a novel target for PTC diagnosis and therapy.

Microglia-associated neuroinflammation is a potential therapeutic target for ischemic stroke.

Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke. Microglial activation and polarization, and the inflammatory response mediated by these cells play important roles in the development, progression and outcome of brain injury after ischemic stroke. Currently, there is no effective strategy for treating ischemic stroke in clinical practice. Therefore, it is clinically important to study the role and regulation of microglia in stroke. In this review, we discuss the involvement of microglia in the neuroinflammatory process in ischemic stroke, with the aim of providing a better understanding of the relationship between ischemic stroke and microglia.

Intraoperative 99mTc-MIBI-Guided Parathyroidectomy Improves Curative Effect of Parathyroidectomy, Bone Metabolism, and Bone Mineral Density.

This study aimed to compare the postoperative effects of total parathyroidectomy plus forearm transplantation and radioguided parathyroidectomy on bone metabolism and bone mineral density (BMD). From June 2013 to October 2017, 67 patients with renal secondary hyperparathyroidism (SHPT) received surgical treatment. The control group included 30 cases of classical total parathyroidectomy plus forearm transplantation for SHPT. In the experimental group, 37 patients underwent 99mTc-MIBI-guided parathyroidectomy. Demographics, parathyroid hormone (PTH) level, blood calcium level, and pathological results were compared between the 2 groups. The curative effect of parathyroidectomy and its effect on BMD were also compared. The BMDs in the L1-L4 segments and femoral neck in both groups were significantly improved after operation (all P < .05). The T scores of the L1-L4 segments and femoral neck in both groups were significantly improved after operation (all P < .05). The improvement in the T score of the L4 in the experimental group was significantly higher than that in the control group (P < .05). No significant differences in the improvement in the L1-L3 segments and femoral neck were found between the 2 groups. Both traditional total parathyroidectomy plus forearm transplantation and 99mTc-MIBI-guided parathyroidectomy can improve PTH level, blood calcium level, phosphorus level, bone metabolism, and BMD to varying degrees in patients with SHPT. Compared with the traditional surgery, 99mTc-MIBI-guided parathyroidectomy can improve blood calcium and phosphorus metabolisms, reduce PTH level, and improve the T scores of L4 to a greater extent.

Effect of CXCR5-Positive Cell Infiltration on the Immune Contexture and Patient Prognosis in Head and Neck Squamous Cell Carcinoma.

PURPOSE: CXCR5-positive (CXCR5+) tumor cell infiltration has different prognostic values in different types of cancer. The objective was to evaluate the effect of CXCR5+ cell infiltration in head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: The study included two patient cohorts: The Cancer Genome Atlas cohort (TCGA, n = 472) and the Renji Hospital cohort (RJHC, n = 201). The TCGA and RJHC cohorts were analyzed for CXCR5-related mRNAs and CXCR5+ cell infiltration, respectively. We then evaluated the correlation between CXCR5 mRNA and CXCR5+ cell infiltration in terms of overall survival and the immune contexture. RESULTS: The 5-year overall survival rate was significantly correlated with high CXCR5 mRNA expression and CXCR5+ cell infiltration in the TCGA and RJHC cohorts, respectively (p < 0.01), even after adjusting for confounders. Moreover, high CXCR5 mRNA expression was associated with more CD4+ T cells, CD8+ T cells, plasma cells, and less dendritic cells. A high CXCR5 mRNA expression was also correlated with increased expression of cytotoxic IFNG, TNFSF11 (RANKL), GZMA, GZMB, GZMK, GZMM, and PRF1 and increased expression of the immunosuppressive gene PDCD1 (PD-1), CD274 (PD-L1), CTLA4, LAG3, HAVCR2 (TIM-3), BTLA, and TIGIT. CONCLUSION: HNSCC patients with a high intratumoral CXCR5 expression had a better prognosis than those with low intratumoral CXCR5 expression. Moreover, CXCR5+ cell infiltration could be used as an independent prognostic biomarker or as a potential therapeutic target. The presence of CXCR5+ cells affects the infiltration of immunocytes in head and neck cancer, differently from what was reported in other cancer types. Further randomized controlled trials or studies with more patients are needed to validate our results.

Activation of AMPK promotes thyroid cancer cell migration through its interaction with PKM2 and ß-catenin.

AMP-activated protein kinase (AMPK) is induced by the exhaustion of cellular energy and activates adaptive alterations in cellular metabolism, which is the basis for cell survival during different environmental stresses. We aimed to investigate the biological functions of AMPK and its molecular mechanism in regulating thyroid cancer (TC) progression. In current study, we found that activation of AMPK by multiple agonists suppresses TC cell proliferation. However, AMPK activation also led to TC cell migration at the same time. Depletion of AMPK abolished the effect of its agonist on cell multiplication and migration. Mechanistic investigations revealed that the impact of AMPK in terms of cell migration is dependent on its nuclear translocation, since site mutation of AMPK in its nuclear translocation domain (K244A) abolished TC cell migration but did not affect the inhibition of cell proliferation by AMPK agonist. Moreover, the nuclear AMPK recruits PKM2 and ß-catenin by their interaction, which promotes the transcription of cell migration related genes, including MMP7 and c-Myc. Furthermore, depletion of PKM2/ß-catenin abolished the migration effect of AMPK agonists, but did not affect their effects on suppression of cell proliferation. Our results provided a novel function of AMPK in cancer migration, and suggested that a combination of AMPK activation and PKM2 depletion or inhibition can be a new strategy to achieve better therapeutic effects for TC patients.

Comparisons and Combined Application of Two-Dimensional and Three-Dimensional Real-time Shear Wave Elastography in Diagnosis of Thyroid Nodules.

Purpose Two-dimensional and three-dimensional real-time shear wave elastography (2D+3D SWE) represents a new technology for the quantification of tissue elasticity. This study investigated whether they could be performed to differentiate between benign and malignant thyroid nodules. Methods Conventional B-mode ultrasound, 2D and 3D SWE were performed in 96 patients with 97 thyroid nodules with pathology results. Results All the elastography values of 2D&3D SWE in malignant thyroid nodules were higher than those in benign nodules. These two elastography methods alone could not improve diagnostic value comparing to B-mode ultrasound significantly. However, B-mode US + 2D SWE (TI-RADS ≥ 4c or S-Emean ≥ 23.75 kPa, suspicious), B-mode US + 3D SWE (TI-RADS ≥ 4c or 3D-T-Emean ≥ 20.75 kPa, suspicious), B-mode US + 2D + 3D SWE (TI-RADS ≥ 4c or S-Emean ≥ 23.75 kPa or 3D-T-Emean ≥ 20.75 kPa, suspicious) had higher sensitivity and accuracy values than those of 3 methods alone but lower specificity values. Among them, B-mode ultrasound + 2D SWE had the highest sensitivity, NPV, accuracy and Youden's index (0.881, 0.788, 0.804 and 0.57). Conclusions 2D SWE or 3D SWE alone could not improve the diagnostic value of differentiating malignant from benign thyroid nodules comparing to conventional B-mode ultrasound. But combination methods could improve the diagnostic value, especially B-mode US + 2D SWE.