Diagnostic performance of C-TIRADS combined with SWE for the diagnosis of thyroid nodules.

Objective: To explore the value of the optimal parameters of shear wave elastography (SWE) to enhance the identification of benign and malignant thyroid nodules by C-TIRADS. Methods: The two-dimensional ultrasonography images and SWE images of 515 patients with a total of 586 thyroid nodules were retrospectively analyzed. The nodules were divided into the D ≤10 mm and D >10 mm groups according to size and were graded by C-TIRADS. With the pathological results as the gold standard, the receiver operating characteristic (ROC) curves were drawn, and the area under the curve (AUC) was calculated to compare the diagnostic performances of C-TIRADS, SWE, and the combination of the two on the benign and malignant thyroid nodules. Results: The ROC showed that the AUC of the maximum elastic modulus (0.875) was higher than that of the mean elastic modulus (0.798) and elasticity ratio (0.772), with an optimal cutoff point of 51 kPa, which was the optimal parameter to distinguish the malignant from the benign nodules (P < 0.001). In the D ≤10 mm group, the AUC of TIRADS combined with SWE (0.955) was elevated by 0.172 compared with the application of C-TIRADS alone (0.783), and the difference was statistically significant (P < 0.05). In the D >10 mm group, the AUC of TIRADS combined with SWE (0.904) was elevated by 0.076 compared with the application of C-TIRADS alone (0.828), and the difference was statistically significant (P < 0.05). Among all nodules, the application of C-TIRADS alone had a sensitivity of 88.14%, a specificity of 74.56%, and an accuracy of 85.50% in diagnosing benign and malignant thyroid nodules, while the sensitivity, specificity, and accuracy were 93.22%, 90.35%, and 92.66%, respectively, in combination with SWE. Conclusion: The diagnostic performance of SWE in combination with TIRADS was better than that of SWE or C-TIRADS alone. Here, SWE enhanced the diagnostic performance of C-TIRADS for the benign and malignant thyroid nodules, most significantly for nodules with D ≤10 mm.

Evaluation of the Diagnostic Value of the Ultrasound ADNEX Model for Benign and Malignant Ovarian Tumors.

OBJECTIVE: To investigate the diagnostic performance of the ADNEX model in the International Ovarian Tumor Analysis diagnostic models for ovarian tumors and further explore its application value in the staging of ovarian tumors. METHODS: A total of 224 patients who underwent ultrasound for evaluation of adnexal masses and were treated surgically owing to adnexal masses from January 2018 to June 2020 in our hospital were selected for research on the diagnostic accuracy of the ADNEX model. The clinical information and ultrasonographic findings of the patients were collected, and the pathological diagnosis was taken as the gold standard. According to the ADNEX model, the ovarian tumors were divided into five subtypes: benign and borderline, stage I, stage II-IV, and metastatic cancer. The sensitivity, specificity, positive predictive value, negative predictive value, diagnostic odds ratio, and area under the receiver operating characteristics curve (AUC) of the ADNEX model were calculated. RESULTS: Of the 224 patients, 119 (53.1%) developed benign tumors and 105 (46.9%) had malignant tumors. When the cut-off value for malignancy risk was 10%, the ADNEX model including CA 125 achieved a sensitivity of 94.3% (95% CI: 88.0-97.9%), specificity of 74.0% (95% CI: 65.1-81.6%), positive predictive value of 76.2% (95% CI: 70.2-81.3%), negative predictive value of 93.6% (95% CI: 87.0-97.0%), diagnostic odds ratio of 45.25, and an AUC of 0.94 (95% CI: 0.90-0.97) for differentiating between benign and malignant ovarian tumors. The AUC in the model excluding CA 125 was 0.93 (95% CI: 0.89-0.96), but the difference was not statistically significant (P=0.20). The accuracy of the ADNEX model for the diagnosis of ovarian tumors of all subtypes exceeds 80% when CA 125 measurements were included in the application, but the sensitivity for diagnosing borderline, stage I, and metastatic ovarian tumors was only 60.0% (95% CI:36.1-80.9%), 28.6% (95% CI:8.4-58.1%) and 45.5% (95% CI:16.7-76.6%). CONCLUSION: The ADNEX model shows good diagnostic performance in differentiating between benign and malignant ovarian tumors. The model has a certain clinical value in the diagnosis of all subtypes of ovarian tumors, but the sensitivity is unsatisfactory for the diagnosis of borderline, stage I, and metastatic ovarian tumors and needs to be verified.

MicroRNA-24 aggravates atherosclerosis by inhibiting selective lipid uptake from HDL cholesterol via the post-transcriptional repression of scavenger receptor class B type I.

BACKGROUND AND AIMS: Liver scavenger receptor class B type I (SR-BI) exerts atheroprotective effects through selective lipid uptake (SLU) from high-density lipoprotein cholesterol (HDL-C). Low hepatic SR-BI expression leads to high HDL-C levels in the circulation and an increased risk of atherosclerosis. Furthermore, macrophage SR-BI mediates bidirectional cholesterol flux and may protect against atherogenesis. Previous studies have revealed that miR-24 is closely related to cardiovascular disease (CVD) progression. We aimed to investigate the molecular mechanisms by which miR-24 participates in SR-BI-mediated selective HDL cholesteryl ester (HDL-CE) uptake and further atherogenesis in apoE-/- mice. METHODS: Bioinformatic predictions and luciferase reporter assays were utilized to detect the association between miR-24 and the SR-BI 3' untranslated region (3' UTR), and RT-PCR and western blotting were used to evaluate SR-BI mRNA and protein expression, respectively. The effects of miR-24 on Dil-HDL uptake were determined by flow cytometry assay. Double-radiolabeled HDL (125I-TC-/[3H] CEt-HDL) was utilized to measure the effects of miR-24 on HDL and CE binding and SLU in HepG2 and PMA-treated THP-1 cells. In addition, total cholesterol (TC) levels in HepG2 cells were analyzed using enzymatic methods, and macrophage lipid content was evaluated by high-performance liquid chromatography (HPLC) assay. Small interfering RNA (siRNA) and pcDNA3.1(-)-hSR-BI plasmid transfection procedures were utilized to confirm the role of SR-BI in the effects of miR-24 on Dil-HDL uptake, SLU and cholesterol levels in both cell types. Hepatic SR-BI level in apoE-/- mice was measured by western blotting. Liver TC, FC and CE levels and plasma triglycerides (TG), TC and HDL-C levels were evaluated enzymatically using commercial test kits. Atherosclerotic lesion sizes were measured using Oil Red O and hematoxylin-eosin staining. RESULTS: miR-24 directly repressed SR-BI expression by targeting its 3'UTR. In addition, miR-24 decreased Dil-HDL uptake and SLU in HepG2 and THP-1 macrophages. In the presence of HDL, miR-24 decreased TC levels in HepG2 cells and TC, free cholesterol (FC) and CE levels in macrophages. Overexpression and down-regulation assays showed that SR-BI mediated the effects of miR-24 on Dil-HDL uptake, SLU and cholesterol levels. Lastly, miR-24 administration decreased hepatic SR-BI expression and promoted atheromatous plaque formation in apoE-/- mice, findings in line with those of our in vitro studies. CONCLUSIONS: These findings indicate that miR-24 accelerates atherogenesis by repressing SR-BI-mediated SLU from HDL-C.

ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs.

Endothelial dysfunction plays a vital role during the initial stage of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) induces vascular endothelial injury and vessel wall inflammation. Sphingosine-1-phosphate (S1P) exerts numerous vasoprotective effects by binding to diverse S1P receptors (S1PRs; S1PR1-5). A number of studies have shown that in endothelial cells (ECs), S1PR2 acts as a pro-atherosclerotic mediator by stimulating vessel wall inflammation through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Scavenger receptor class B member I (SR-BI), a high-affinity receptor for apolipoprotein A-I (apoA-I)/high-density lipoprotein (HDL), inhibits nuclear factor-κB (NF-κB) translocation and decreases the plasma levels of inflammatory mediators via the PI3K/Akt pathway. We hypothesized that the inflammatory effects of S1P/S1PR2 on ECs may be regulated by apoA-I/SR-BI. The results showed that ox-LDL, a pro-inflammatory factor, augmented the S1PR2 level in human umbilical vein endothelial cells (HUVECs) in a dose- and time-dependent manner. In addition, S1P/S1PR2 signaling influenced the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-10, aggravating inflammation in HUVECs. Moreover, the pro-inflammatory effects induced by S1P/S1PR2 were attenuated by SR-BI overexpression and enhanced by an SR-BI inhibitor, BLT-1. Further experiments showed that the PI3K/Akt signaling pathway was involved in this process. Taken together, these results demonstrate that apoA-I/SR-BI negatively regulates S1P/S1PR2-mediated inflammation in HUVECs by activating the PI3K/Akt signaling pathway.

TGF-ß Down-regulates Apolipoprotein M Expression through the TAK-1-JNK-c-Jun Pathway in HepG2 Cells.

Apolipoprotein M (apoM) is a relatively novel apolipoprotein that plays pivotal roles in many dyslipidemia-associated diseases; however, its regulatory mechanisms are poorly understood. Many cytokines have been identified that down-regulate apoM expression in HepG2 cells, among which transforming growth factor-ß (TGF-ß) exerts the most potent effects. In addition, c-Jun, a member of the activated protein 1 (AP-1) family whose activity is modulated by c-Jun N-terminal kinase (JNK), decreases apoM expression at the transcriptional level by binding to the regulatory element in the proximal apoM promoter. In this study, we investigated the molecular mechanisms through which TGF-ß decreases the apoM level in HepG2 cells. The results revealed that TGF-ß inhibited apoM expression at both the mRNA and protein levels in a dose- and time-dependent manner and that it suppressed apoM secretion. These effects were attenuated by treatment of cells with either SP600125 (JNK inhibitor) or c-Jun siRNA. 5Z-7-oxozeaenol [(a TGF-ß-activated kinase 1 (TAK-1) inhibitor)] also attenuated the TGF-ß-mediated inhibition of apoM expression and suppressed the activation of JNK and c-Jun. These results have demonstrated that TGF-ß suppresses apoM expression through the TAK-1-JNK-c-Jun pathway in HepG2 cells.

ApoA-I induces S1P release from endothelial cells through ABCA1 and SR-BI in a positive feedback manner

Sphingosine-1-phosphate (S1P), which has emerged as a pivotal signaling mediator that participates in the regulation of multiple cellular processes, is derived from various cells, including vascular endothelial cells. S1P accumulates in lipoproteins, especially HDL, and the majority of free plasma S1P is bound to HDL. We hypothesized that HDL-associated S1P is released through mechanisms associated with the HDL maturation process. ApoA-I, a major HDL apolipoprotein, is a critical factor for nascent HDL formation and lipid trafficking via ABCA1. Moreover, apoA-I is capable of promoting bidirectional lipid movement through SR-BI. In the present study, we confirmed that apoA-I can facilitate the production and release of S1P by HUVECs. Furthermore, we demonstrated that ERK1/2 and SphK activation induced by apoA-I is involved in the release of S1P from HUVECs. Inhibitor and siRNA experiments showed that ABCA1 and SR-BI are required for S1P release and ERK1/2 phosphorylation induced by apoA-I. However, the effects triggered by apoA-I were not suppressed by inhibiting ABCA1/JAK2 or the SR-BI/Src pathway. S1P released due to apoA-I activation can stimulate the (ERK1/2)/SphK1 pathway through S1PR (S1P receptor) 1/3. These results indicated that apoA-I not only promotes S1P release through ABCA1 and SR-BI but also indirectly activates the (ERK1/2)/SphK1 pathway by releasing S1P to trigger their receptors. In conclusion, we suggest that release of S1P induced by apoA-I from endothelial cells through ABCA1 and SR-BI is a self-positive-feedback process: apoA-I-(ABCA1 and SR-BI)-(S1P release)-S1PR-ERK1/2-SphK1-(S1P production)-(more S1P release induced by apoA-I) (AU)

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ApoA-I induces S1P release from endothelial cells through ABCA1 and SR-BI in a positive feedback manner.

Sphingosine-1-phosphate (S1P), which has emerged as a pivotal signaling mediator that participates in the regulation of multiple cellular processes, is derived from various cells, including vascular endothelial cells. S1P accumulates in lipoproteins, especially HDL, and the majority of free plasma S1P is bound to HDL. We hypothesized that HDL-associated S1P is released through mechanisms associated with the HDL maturation process. ApoA-I, a major HDL apolipoprotein, is a critical factor for nascent HDL formation and lipid trafficking via ABCA1. Moreover, apoA-I is capable of promoting bidirectional lipid movement through SR-BI. In the present study, we confirmed that apoA-I can facilitate the production and release of S1P by HUVECs. Furthermore, we demonstrated that ERK1/2 and SphK activation induced by apoA-I is involved in the release of S1P from HUVECs. Inhibitor and siRNA experiments showed that ABCA1 and SR-BI are required for S1P release and ERK1/2 phosphorylation induced by apoA-I. However, the effects triggered by apoA-I were not suppressed by inhibiting ABCA1/JAK2 or the SR-BI/Src pathway. S1P released due to apoA-I activation can stimulate the (ERK1/2)/SphK1 pathway through S1PR (S1P receptor) 1/3. These results indicated that apoA-I not only promotes S1P release through ABCA1 and SR-BI but also indirectly activates the (ERK1/2)/SphK1 pathway by releasing S1P to trigger their receptors. In conclusion, we suggest that release of S1P induced by apoA-I from endothelial cells through ABCA1 and SR-BI is a self-positive-feedback process: apoA-I-(ABCA1 and SR-BI)-(S1P release)-S1PR-ERK1/2-SphK1-(S1P production)-(more S1P release induced by apoA-I).

[Influence of stress from work and negative life events during pregnancy on different types of low birth weight].

OBJECTIVE: To explore the influence of occupational stress and negative life events that occur during pregnancy on different types of low birth weight (LBW). METHODS: 438 singleton LBW infants (birth weight of less than 2500 g and their pregnancy term from 28 to 42 weeks) were selected as case group, and they were further divided into symmetric LBW infants (337 cases) and asymmetric LBW infants (101 cases). According to situation of each LBW infant, a singleton with full term and normal birth weight was selected as control group matched by sex, pregnancy term, time during delivery and types of hospital. All of their mothers were inquired by well trained investigators on their socio-demographic characteristics, occupational stress, and negative life events that occurred in different pregnancy term. After controlling for mother's age, occupation, education level and family income, multinomial logistic regression was employed to asses the influence of occupational stress and negative life events on symmetric LBW and asymmetric LBW. RESULTS: Compared with those using low technical skills, mothers with high technical skill utilization significantly decreased the risk of laboring both symmetric LBW (OR = 0.69, 95% CI: 0.49-0.98) and asymmetric LBW (OR = 0.53, 95% CI: 0.31-0.89). Compared with those without exposure to negative life events, mothers with negative life event score > or = 3 in the whole duration of pregnancy had significantly increased the risk of delivering symmetric LBW (OR = 2.30, 95% CI: 1.08-4.88), mothers with negative life event score > or = 3 in the middle three months of pregnancy, > or = 3 in the last three months of pregnancy, = 2 and > or = 3 in the whole duration of pregnancy had significantly increased the risk of delivering asymmetric LBW, and their OR (95% CI) was 8.85 (1.97-39.68), 3.80 (1.40-10.29), 3.58 (1.33-9.66) and 3.48 (1.32-9.13), respectively. CONCLUSION: Occupational stress and negative life events might produce different influence on symmetric LBW and negative life events that occur in the different terms of pregnancy had different impact on symmetric LBW and asymmetric LBW.

[Relationship of occupational stress and negative life events with low birth weight].

OBJECTIVE: To explore the influence of occupational stress and negative life events on low birth weight (LBW). METHODS: 1:1 matched case-control study was employed, in which 438 singleton LBW infants with birth weight less than 2500 g (their pregnancy term being 28 to 42 weeks) served as case group while 438 with singleton term normal birth weight served as control group matched by sex, delivery time and hospital. All of their mothers were inquired by well trained investigators about their socio-demographic characteristics, occupational stress, and negative life events occurring in different pregnancy term. After controlling for mother's age, occupation, education level and family income, conditional logistic regression was employed to asses the influence of occupational stress and negative life events on LBW. RESULTS: Compared with those with low technical skill utilization and low job decision, mothers with high technical skill utilization (OR=0.62; 95% CI=0.43 approximately 0.91) and high job decision (OR=0.67; 95% CI=0.46 approximately 0.97) significantly decreased the risk of laboring LBW. Compared with those not exposed to negative life events, mothers with negative life event score being=3 in the middle three months of pregnancy (OR=18.85; 95% CI=1.58 approximately 225.02), with negative life event score being 1 in the later three months of pregnancy (OR=2.67; 95% CI=1.14 approximately 6.28), with negative life event score being 2 (OR=2.80; 95% CI=1.04 approximately 7.52) and=3 in the whole time of pregnancy (OR=2.94; 95% CI=1.22 approximately 7.09) were the risk factors of LBW. CONCLUSION: Negative life events might affect LBW and negative life events occurring in the different term of pregnancy impact LBW differently.