Collaborative Enhancement of Consistency and Accuracy in US Diagnosis of Thyroid Nodules Using Large Language Models.

Background Large language models (LLMs) hold substantial promise for medical imaging interpretation. However, there is a lack of studies on their feasibility in handling reasoning questions associated with medical diagnosis. Purpose To investigate the viability of leveraging three publicly available LLMs to enhance consistency and diagnostic accuracy in medical imaging based on standardized reporting, with pathology as the reference standard. Materials and Methods US images of thyroid nodules with pathologic results were retrospectively collected from a tertiary referral hospital between July 2022 and December 2022 and used to evaluate malignancy diagnoses generated by three LLMs-OpenAI's ChatGPT 3.5, ChatGPT 4.0, and Google's Bard. Inter- and intra-LLM agreement of diagnosis were evaluated. Then, diagnostic performance, including accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), was evaluated and compared for the LLMs and three interactive approaches: human reader combined with LLMs, image-to-text model combined with LLMs, and an end-to-end convolutional neural network model. Results A total of 1161 US images of thyroid nodules (498 benign, 663 malignant) from 725 patients (mean age, 42.2 years ± 14.1 [SD]; 516 women) were evaluated. ChatGPT 4.0 and Bard displayed substantial to almost perfect intra-LLM agreement (κ range, 0.65-0.86 [95% CI: 0.64, 0.86]), while ChatGPT 3.5 showed fair to substantial agreement (κ range, 0.36-0.68 [95% CI: 0.36, 0.68]). ChatGPT 4.0 had an accuracy of 78%-86% (95% CI: 76%, 88%) and sensitivity of 86%-95% (95% CI: 83%, 96%), compared with 74%-86% (95% CI: 71%, 88%) and 74%-91% (95% CI: 71%, 93%), respectively, for Bard. Moreover, with ChatGPT 4.0, the image-to-text-LLM strategy exhibited an AUC (0.83 [95% CI: 0.80, 0.85]) and accuracy (84% [95% CI: 82%, 86%]) comparable to those of the human-LLM interaction strategy with two senior readers and one junior reader and exceeding those of the human-LLM interaction strategy with one junior reader. Conclusion LLMs, particularly integrated with image-to-text approaches, show potential in enhancing diagnostic medical imaging. ChatGPT 4.0 was optimal for consistency and diagnostic accuracy when compared with Bard and ChatGPT 3.5. © RSNA, 2024 Supplemental material is available for this article.

High-Density Lipoprotein Subfractions Remodeling: A Critical Process for the Treatment of Atherosclerotic Cardiovascular Diseases.

Numerous studies have shown that a low level of high-density lipoprotein cholesterol (HDL-C) is an independent biomarker of cardiovascular disease. High-density lipoprotein (HDL) is considered to be a protective factor for atherosclerosis (AS). Therefore, raising HDL-C has been widely recognized as a promising strategy to treat atherosclerotic cardiovascular diseases (ASCVD). However, several studies have found that increasing HDL-C levels does not necessarily reduce the risk of ASCVD. HDL particles are highly heterogeneous in structure, composition, and biological function. Moreover, HDL particles from atherosclerotic patients exhibit impaired anti-atherogenic functions and these dysfunctional HDL particles might even promote ASCVD. This makes it uncertain that HDL-raising therapy will prevent and treat ASCVD. It is necessary to comprehensively analyze the structure and function of HDL subfractions. We review current advances related to HDL subfractions remodeling and highlight how current lipid-modifying drugs such as niacin, statins, fibrates, and cholesteryl ester transfer protein inhibitors regulate cholesterol concentration of HDL and specific HDL subfractions.

Complementary Role of CEUS and CT/MR LI-RADS for Diagnosis of Recurrent HCC.

PURPOSE: We retrospectively compared the diagnostic performance of contrast-enhanced ultrasonography (CEUS) and contrast-enhanced computer tomography-magnetic resonance imaging (CT/MRI) for recurrent hepatocellular carcinoma (HCC) after curative treatment. MATERIALS AND METHODS: After curative treatment with 421 ultrasound (US) detected lesions, 303 HCC patients underwent both CEUS and CT/MRI. Each lesion was assigned a Liver Imaging Reporting and Data System (LI-RADS) category according to CEUS and CT/MRI LI-RADS. Receiver-operating characteristic (ROC) curves were computed to determine the optimal diagnosis algorithms for CEUS, CT and MRI. The diagnostic accuracy, sensitivity, specificity, and area under the curve (AUC) were compared between CEUS and CT/MRI. RESULTS: Among the 421 lesions, 218 were diagnosed as recurrent HCC, whereas 203 lesions were diagnosed as benign. In recurrent HCC, CEUS detected more arterial hyperenhancement (APHE) and washout than CT and more APHE than MRI. CEUS yielded better diagnostic performance than CT (AUC: 0.981 vs. 0.958) (p = 0.024) comparable diagnostic performance to MRI (AUC: 0.952 vs. 0.933) (p > 0.05) when using their optimal diagnostic criteria. CEUS missed 12 recurrent HCCs, CT missed one, and MRI missed none. The detection rate of recurrent HCC on CEUS (94.8%, 218/230) was lower than that on CT/MRI (99.6%, 259/260) (p = 0.001). Lesions located on the US blind spots and visualization score C would hinder the ability of CEUS to detect recurrent HCC. CONCLUSION: CEUS demonstrated excellent diagnostic performance but an inferior detection rate for recurrent HCC. CEUS and CT/MRI played a complementary role in the detection and characterization of recurrent HCC.

Brain cholesterol homeostasis and its association with neurodegenerative diseases.

The brain is the most cholesterol-rich organ in mammals. However, cholesterol metabolism in the brain is completely independent of other tissues due to the presence of the blood-brain barrier (BBB). Neurons, astrocytes and oligodendrocytes are the main cells responsible for cholesterol synthesis in the brain. The cholesterol content in the brain is maintained at a relatively constant level under strict regulation of synthesis, transport, and turnover, that is, brain cholesterol homeostasis. Once this balance is disrupted, neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD) ensue. This review summarizes the processes controlling cholesterol homeostasis with respect to the synthesis, transport and turnover of cholesterol in the brain. We further focus on how cholesterol imbalance contributes to neurodegenerative diseases to explore the possibilities to modulate the key steps involved, which will provide clues for the development of therapies for the treatment of central nervous system (CNS) diseases.

Integration of Artificial Intelligence Decision Aids to Reduce Workload and Enhance Efficiency in Thyroid Nodule Management.

Importance: To optimize the integration of artificial intelligence (AI) decision aids and reduce workload in thyroid nodule management, it is critical to incorporate personalized AI into the decision-making processes of radiologists with varying levels of expertise. Objective: To develop an optimized integration of AI decision aids for reducing radiologists' workload while maintaining diagnostic performance compared with traditional AI-assisted strategy. Design, Setting, and Participants: In this diagnostic study, a retrospective set of 1754 ultrasonographic images of 1048 patients with 1754 thyroid nodules from July 1, 2018, to July 31, 2019, was used to build an optimized strategy based on how 16 junior and senior radiologists incorporated AI-assisted diagnosis results with different image features. In the prospective set of this diagnostic study, 300 ultrasonographic images of 268 patients with 300 thyroid nodules from May 1 to December 31, 2021, were used to compare the optimized strategy with the traditional all-AI strategy in terms of diagnostic performance and workload reduction. Data analyses were completed in September 2022. Main Outcomes and Measures: The retrospective set of images was used to develop an optimized integration of AI decision aids for junior and senior radiologists based on the selection of AI-assisted significant or nonsignificant features. In the prospective set of images, the diagnostic performance, time-based cost, and assisted diagnosis were compared between the optimized strategy and the traditional all-AI strategy. Results: The retrospective set included 1754 ultrasonographic images from 1048 patients (mean [SD] age, 42.1 [13.2] years; 749 women [71.5%]) with 1754 thyroid nodules (mean [SD] size, 16.4 [10.6] mm); 748 nodules (42.6%) were benign, and 1006 (57.4%) were malignant. The prospective set included 300 ultrasonographic images from 268 patients (mean [SD] age, 41.7 [14.1] years; 194 women [72.4%]) with 300 thyroid nodules (mean [SD] size, 17.2 [6.8] mm); 125 nodules (41.7%) were benign, and 175 (58.3%) were malignant. For junior radiologists, the ultrasonographic features that were not improved by AI assistance included cystic or almost completely cystic nodules, anechoic nodules, spongiform nodules, and nodules smaller than 5 mm, whereas for senior radiologists the features that were not improved by AI assistance were cystic or almost completely cystic nodules, anechoic nodules, spongiform nodules, very hypoechoic nodules, nodules taller than wide, lobulated or irregular nodules, and extrathyroidal extension. Compared with the traditional all-AI strategy, the optimized strategy was associated with increased mean task completion times for junior radiologists (reader 11, from 15.2 seconds [95% CI, 13.2-17.2 seconds] to 19.4 seconds [95% CI, 15.6-23.3 seconds]; reader 12, from 12.7 seconds [95% CI, 11.4-13.9 seconds] to 15.6 seconds [95% CI, 13.6-17.7 seconds]), but shorter times for senior radiologists (reader 14, from 19.4 seconds [95% CI, 18.1-20.7 seconds] to 16.8 seconds [95% CI, 15.3-18.3 seconds]; reader 16, from 12.5 seconds [95% CI, 12.1-12.9 seconds] to 10.0 seconds [95% CI, 9.5-10.5 seconds]). There was no significant difference in sensitivity (range, 91%-100%) or specificity (range, 94%-98%) between the 2 strategies for readers 11 to 16. Conclusions and Relevance: This diagnostic study suggests that an optimized AI strategy in thyroid nodule management may reduce diagnostic time-based costs without sacrificing diagnostic accuracy for senior radiologists, while the traditional all-AI strategy may still be more beneficial for junior radiologists.

Application of online teaching mode combining case studies and the MOOC platform in obstetrics and gynecology probation teaching.

OBJECTIVE: To explore the application effect of the clinical basic integration teaching mode constructed by case studies and the MOOC platform in obstetrics and gynecology internship teaching in the face of public health emergencies. METHODS: One hundred ten clinical medical students of grade 2020 were selected as the experimental group, and 110 clinical medical students of grade 2021 were selected as the control group. The experimental group adopted the online teaching mode combined with case studies and the MOOC platform, while the control group adopted the offline traditional probation teaching method. Comprehensive test and questionnaire were used to evaluate and compare the teaching effect of the two groups of students. RESULTS: The experimental group was found to be superior to the control group in the quality assessment of complete medical record writing and the ability assessment of diagnosis and analysis of typical obstetrics and gynecology cases (P < 0. 05). However, the score of professional knowledge was lower than that of the control group (P < 0. 05). The results of questionnaire survey showed that the satisfaction of the experimental group in stimulating learning interest, enhancing problem solving ability, enhancing communication and clinical thinking ability, enhancing team cooperation awareness and independent innovation ability was higher than that of the control group (P < 0.01). The satisfaction of teacher-student interaction was also better (P < 0.05). However, in terms of strengthening theoretical understanding, the satisfaction of the experimental group was lower than that of the control group, but with no significant difference (P > 0.05). CONCLUSION: During the epidemic period, we designed a new online teaching mode, which can be applied to the probation teaching of obstetrics and gynecology. In our study, compared with traditional offline teaching, the new online teaching mode could improve students' ability of case writing and case analysis. However, more teaching practice is needed to complete this online teaching mode.

Identification of the origin of tumor in vein: comparison between CEUS LI-RADS v2017 and v2016 for patients at high risk.

OBJECTIVES: To compare the diagnostic performance of the Contrast-Enhanced Ultrasound (CEUS) Liver Imaging Report and Data System (LI-RADS) v2016 and v2017 in identifying the origin of tumor in vein (TIV). METHODS: From April 2014 to December 2018, focal liver lesions (FLLs) accompanied by TIV formation in patients at high risk for hepatocellular carcinoma (HCC) were enrolled. Histologic evaluation or composite imaging reference standard were served as the reference standard. Each case was categorized according to the CEUS LI-RADS v2016 and v2017, respectively. Diagnostic performance of CEUS LI-RADS v2016 and v2017 in identifying the originated tumor of TIV was validated via sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value. RESULTS: A total of 273 FLLs with TIV were analyzed finally, including 266 HCCs and 7 non-HCCs. In v2016, when adopting all TIV as LR-5V, the accuracy and PPV in identifying the originated tumor were both 97.4%. In v2017, when assigning TIV according to contiguous FLLs CEUS LI-RADS category, the accuracy and PPV were 61.9% and 99.4% in subclass of LR-5 as the diagnostic criteria of HCC, and 64.1% and 99.4% in subclass of LR-4/5 as the criteria of HCC diagnosis. There were significant differences in diagnostic accuracy between CEUS LI-RADS v2016 and v2017 in identifying the originated tumor of TIV (p < 0.001). CONCLUSIONS: CEUS LI-RADS v2016 could be better than v2017 in identifying the originated tumor of TIV.

Melatonin Attenuates Vascular Smooth Muscle Contraction Through the γ-Secretase/Notch Intracellular Domain/Myocardin Pathway.

ABSTRACT: Inositol 1, 4, 5-trisphosphate (IP3) signaling-mediated calcium release drives the contraction of vascular smooth muscles and hence regulates blood vessel volume and blood pressure. Melatonin supplementation has been suggested to be beneficial for hypertension. To determine whether the blood pressure-lowering effect of melatonin was accounted for by IP3 signaling, we evaluated the vasoconstriction response and IP3 signaling in isolated mouse thoracic aortic rings during melatonin incubation. C57BL/6 mice were given intraperitoneal injections daily with melatonin, and the systolic blood pressure and contractility of aortic rings from melatonin-treated mice were decreased, and the contraction suppression effect of melatonin was attributed to the impaired expression of contractile proteins in vascular smooth muscle cells rather than IP3 signaling. Our results further showed that melatonin increased the expression of γ-secretase, which could cleave and release the notch intracellular domain, and the notch intracellular domain prevented the transcription of contractile genes by interfering with the interaction between serum response factor and myocardin, the master regulator of contractile protein. In this article, we report a novel mechanism by which melatonin regulates smooth muscle contractility that does not depend on IP3 signaling.

The Mechanism of Downregulation of Twist1 Inhibiting Trophoblast Invasion and Aggravating the Development of Preeclampsia.

To study the expression of under expressed transcription factor Twist1 in preeclampsia (PE) and its effect on the invasion of placental trophoblast cells and to explore its related mechanism on the development of PE by establishing a pregnant rat model. Methods: the villi were collected from the induced abortion in the first trimester (6-8 weeks), the normal placenta (18-20 weeks) induced by the second trimester, the term placenta tissue of normal pregnancy (37-40 weeks), and the placental tissue of patients with PE, to detect the expression of Twist1. Trophoblast cells were subjected to primary culture in placental tissues of normal pregnant women and placental tissues of PE patients. The invasion ability of the two groups of trophoblasts was detected, and the primary cultured trophoblasts were divided into two groups: an experimental group and a control group. Specific Twist1 siRNA was added to the experimental group, and no reagents were added to the control group. The above-mentioned cells were given different interventions. To explore the effect of Twist1 on trophoblast cell invasion, cells were cultivated for 72 h. The SD rats were conceived. After the pregnancy was stable, the SD rats in different groups were treated with different treatments (interference with Twist1), and the average systolic blood pressure and urine protein of the gestational mothers in the different treatment groups were measured at 1 week, 2 weeks, and full-term pregnancy. The expression of Twist1 in the placenta tissue of SD rats with different interventions at full-term pregnancy was detected. The results showed that Twist1 expression is down-regulated in PE, and the invasion ability of placental trophoblast cells in PE patients is weak. After inhibiting Twist1, the mean tail artery pressure and urine protein level of SD pregnant rats increase, showing a trend of PE. The mechanism may be related to the inhibition of the placenta by Twist1 Trophoblast cell invasion.

Using new criteria to improve the differentiation between HCC and non-HCC malignancies: clinical practice and discussion in CEUS LI-RADS 2017.

PURPOSE: Using contrast-enhanced ultrasound (CEUS) to evaluate the diagnostic performance of liver imaging reporting and data system (LI-RADS) version 2017 and to explore potential ways to improve the efficacy. METHODS: A total of 315 nodules were classified as LR-1 to LR-5, LR-M, and LR-TIV. New criteria were applied by adjusting the early washout onset (< 45 s) and the time of marked washout (within 3 min). Two subgroups of the LR-M nodules were recategorized as LR-5, respectively. The diagnostic performance was evaluated by calculating the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: By adjusting early washout onset to < 45 s, the LR-5 as a standard for diagnosing HCC had an improved sensitivity (74.1% vs. 56.1%, P < 0.001) without significant change in PPV (93.3% vs. 96.1%, P = 0.267), but the specificity was decreased (48.3% vs. 78.5%, P = 0.018). The LR-M as a standard for the diagnosis of non-HCC malignancies had an increase in specificity (89.2% vs. 66.2%, P < 0.001) but a decrease in sensitivity (31.5% vs. 68.4%, P = 0.023). After reclassification according to the time of marked washout, the sensitivity of the LR-5 increased (80% vs. 56.1%, P < 0.001) without a change in PPV (94.9% vs. 96.1%, P = 0.626) and specificity (80% vs. 78.5%, P = 0.879). For reclassified LR-M nodules, the specificity increased (87.5% versus 66.2%, P < 0.001) with a non-significant decrease in sensitivity (47.3% vs. 68.4%, P = 0.189). CONCLUSIONS: The CEUS LI-RADS showed good confidence in diagnosing HCC while tended to misdiagnose HCC as non-HCC malignancies. Adjusting the marked washout time within 3 min would reduce the possibility of this misdiagnosis.

Overexpression of long non-coding RNA WT1-AS or silencing of PIK3AP1 are inhibitory to cervical cancer progression.

Accumulating evidence demonstrate that long non-coding RNAs (lncRNAs) play an important role in regulating the biological function of cervical cancer cells. However, the regulatory role of lncRNA Wilms tumor 1 homolog antisense RNA (WT1-AS) in cervical cancer cells remains uncertain. In this study, we explored the participation of WT1-AS in cervical cancer by first using the reverse transcription quantitative polymerase-chain reaction (RT-qPCR) was to analyze the expression of WT1-AS and phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1) in cervical cancer tissues and cells. Dual-luciferase reporter gene assay, RNA pull-down/RNA immunoprecipitation (RIP) assays and Chromatin Immunoprecipitation (ChIP) assay were conducted to explore the interactions among WT1-AS, PIK3AP1, and SPI1. Gain- and loss-of-function approaches were carried out to determine the effects of lncRNA WT1-AS, PIK3AP1 on cell biological characteristics, followed by assays of cell proliferation, autophagy, and apoptosis abilities using, respectively, EdU, monodansylcadaverine (MDC) staining, and flow cytometry. Finally, we measured growth of xenograft tumors in nude mice. We found decreased expression of lncRNA WT1-AS and increased expression of PIK3AP1 in cervical cancer samples. Moreover, PIK3AP1 was negatively regulated by WT1-AS, which promoted apoptosis, but inhibited cell proliferation and autophagy of cervical cancer cells. Furthermore, WT1-AS inhibited PIK3AP1 expression by recruiting SPI1, and inhibited the progression of cervical cancer through the SPI1/PIK3AP1 axis in vivo and in vitro. In summary, lncRNA WT1-AS repressed the development of cervical cancer by reducing PIK3AP1 expression through an interaction with SPI1, which may suggest new therapeutic approaches for treating cervical cancer.Abbreviations: HPV, human papillomavirus; lncRNAs, Long non-coding RNAs; WT1-AS, wilms tumor 1 antisense RNA; HCC, hepatocellular carcinoma; SFFV, Spleen focus forming virus; SPI1, Spleen focus forming virus proviral integration oncogene 1; TF, transcription factor; PIK3AP1, Phosphoinositide-3-kinase adaptor protein 1; NCBI, National Center for Biotechnology Information; oe, overexpressed; sh-PIK3AP1, short hairpin RNA against PIK3AP1; RIPA, radioimmunoprecipitation; PMSF, phenylmethylsulfonyl fluoride; HRP, horseradish peroxidase; IgG, immunoglobulin G; GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; PCR, polymerase chain reaction; EP, Eppendorf; RIP, RNA-binding protein immunoprecipitation; CHIP, Chromatin immunoprecipitation; EdU, 5-ethynyl-2'-deoxyuridine; PI, propidium iodide; MDC, Monodansylcadaverine; PFA, paraformaldehyde; SPF, specific pathogen free; TV, tumor volume; DLG1-AS1, discs large MAGUK scaffold protein 1 antisense RNA 1; TOB1-AS1, transducer of epidermal growth factor receptor-2.1 antisense RNA 1; LC3II, light chain 3 type II; LC3I, light chain 3 type I; IRF4, interferon regulatory factor 4.

AHNAK suppresses ovarian cancer progression through the Wnt/ß-catenin signaling pathway.

Globally, ovarian cancer is the 2nd most frequent cause of gynecologic-associated cancer fatalities among women. It has an unfavorable prognosis. There is a need to elucidate on the mechanisms involved in ovarian cancer progression and to identify novel cancer targets. We investigated and verified AHNAK contents in ovarian cancer tissues and corresponding healthy tissues. Then, we overexpressed AHNAK in vitro and in vivo to establish the roles of AHNAK in ovarian cancer cell proliferation and metastasis. Finally, we evaluated the possible molecular mechanisms underlying. We established that AHNAK was downregulated in ovarian cancer. Elevated AHNAK contents in ovarian cancer cell lines remarkably repressed ovarian cancer cell growth, along with metastasis in vitro, as well as in vivo. Moreover, AHNAK suppressed the progress of ovarian cancer partly via dampening the Canonical Wnt cascade. Therefore, AHNAK may be a biomarker and treatment target for ovarian cancer.

Pyroptotic cell-derived microparticle: An atherogenic factor in infectious diseases.

Chronic infection is considered a risk factor for atherosclerosis. The link between infectious agents and atherosclerosis is manifested by the presence of infection-induced pyroptotic cells in atherosclerotic lesions. Pyroptosis is an inflammatory form of programmed cell death that occurs most frequently upon infection. However, inflammation is not the only cause by which pyroptosis involved in atherosclerosis. During pyroptosis, a large amount of microparticles are released from pyroptotic cells, which not only transfer inflammatory mediators to arterial vessel, but also mediate the interaction between a variety of cells, leading to endothelial injury, macrophage infiltration, vascular smooth muscle cell migration and proliferation, thereby accelerating atherosclerosis. Thus, we proposed hypothesis that pyroptotic cell-derived microparticle is an atherogenic factor in infectious diseases.

Diagnostic Performance of Quantitative and Qualitative Elastography for Axillary Lymph Node Metastasis in Breast Cancer: A Systematic Review and Meta-Analysis.

Background: Studies have shown inconsistent results regarding the diagnostic performance of ultrasound elastography for axillary lymph node metastasis (ALNM) in breast cancer. This meta-analysis aimed to estimate the diagnostic performance of ultrasound elastography (divided into quantitative and qualitative elastography) for ALNM in patients with breast cancer. Methods: The PubMed and Embase databases were searched for eligible studies exploring the diagnostic performance of ultrasound elastography for ALNM in patients with breast cancer. The included studies were divided into quantitative and qualitative elastography groups to perform separate meta-analyses. The diagnostic performance was investigated with pooled sensitivity and specificity and diagnostic odds ratio (DOR) using a bivariate mixed-effects regression model. A summary receiver operating characteristic curve was constructed, and the area under the curve (AUC) was calculated. Results: Seven and 11 studies were included in the quantitative and qualitative elastography meta-analyses, respectively. The pooled sensitivity and specificity, DOR, and AUC with their corresponding 95% confidence intervals were 0.82 (0.75, 0.87), 0.88 (0.78, 0.93), 33 (13, 83), and 0.89 (0.86, 0.91), respectively, for quantitative elastography and 0.81 (0.69, 0.89), 0.92 (0.79, 0.97), 46 (12, 181), and 0.92 (0.89, 0.94), respectively, for qualitative elastography. No significant publication bias existed. Fagan plots demonstrated good clinical utility. However, substantial heterogeneity existed among studies. Study design, measurement, and reference standard served as potential sources of heterogeneity for quantitative studies, which were measurement and reference standard for qualitative studies. Conclusions: Both quantitative and qualitative elastography seem to be feasible, non-invasive diagnostic tools for ALNM in breast cancer. Nevertheless, the results must be interpreted carefully, paying attention to heterogeneity issues, especially for quantitative elastography studies.

circKIF4A sponges miR-127 to promote ovarian cancer progression.

Ovarian cancer is a major gynecologic cancer and common cause of gynecologic cancer death worldwide. However, the molecular mechanisms of ovarian cancer progression are still unclear. circular RNAs (circRNAs) are recently reported to be involved in cancer progression regulation but the potential functions of circRNAs in ovarian cancer remains unknown. In this study, we explored the expression of circKIF4A in ovarian cancer tissues. Then, a series of experiments were conducted to investigate how circKIF4A functioned in ovarian cancer in vitro and in vivo. The results revealed that circKIF4A was highly expressed in ovarian cancer tissues. Knockdown of circKIF4A suppressed cell proliferation and migration in ovarian cancer. Subsequent mechanism study revealed that circKIF4A acted as a competitive endogenous RNA (ceRNA) to promoted ovarian cancer progression by sponging miR-127 and upregulated the expression of Junctional adhesion molecule 3 (JAM3). Therefore, circKIF4A could be a novel biomarker and therapeutic target for ovarian cancer.

Ultrasound combined with biochemical parameters can be used to differentiate parathyroid carcinoma from benign tumors in patients with primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) results from excessive secretion of parathyroid hormone from parathyroid tumors. Differentiating parathyroid tumors can be challenging before operation. OBJECTIVES: To differentiate parathyroid carcinoma from benign tumors in patients with PHPT by the application of ultrasound and biochemical parameters. METHODS: This study is a retrospective study. The study enrolled 17 patients with parathyroid carcinoma (PC) and 57 patients with parathyroid adenoma (PA), confirmed by postoperative pathology, between September 2010 and July 2017. This study retrospectively compared the ultrasonic features of the tumors included echotexture, maximum lesion diameter, shape, margin, blood flow inside the mass, intralesional calcifications, cysts in the mass, and biochemical parameters included serum calcium, phosphorus, parathyroid hormone (PTH), alkaline phosphatase (ALP) levels, gender distribution and age of patients between patients with PC and those with PA. RESULTS: In the US images, the two groups showed significant differences in heterogeneity, the appearance of a taller-than-wide shape, irregular or lobulated margins, and intralesional calcifications (p < #x003C;< #x200A;0.05). However, no significant difference was found in echogenicity, maximum lesion diameter, blood flow, and cystic components of the mass (p > #x003E;> #x200A;0.05). The mean PTH levels were significantly different between the two groups (p < #x003C;< #x200A;0.05). The PC and PA patients did not differ significantly in terms of mean serum calcium, mean serum phosphorus, and mean ALP levels (p > #x003E;> #x200A;0.05). There were significant differences to distinguish PC from PA in calcifications in mass or/and taller-than-wide shape combine with PTH > #x003E;> #x200A;1000 pg/mL (p < #x003C;< #x200A;0.05). Significant difference existed in the age between the two groups (p < #x003C;< #x200A;0.001). No significant difference existed in the gender distribution between the two groups (p > #x003E;> #x200A;0.05). CONCLUSION: Ultrasound features especially intralesional calcifications and taller-than-wide shape combine with an extremely high serum PTH (>1000 pg/mL) are helpful in differentiating between benign and parathyroid tumors in patients with PHPT.

Propofol­induced miR­125a­5p inhibits the proliferation and metastasis of ovarian cancer by suppressing LIN28B.

Propofol, a commonly used intravenous anesthetic agent during surgery, has relatively widespread pharmacological actions. Previous studies have reported that propofol may act as an antitumor drug in several cancer types, such as pancreatic cancer, lung cancer and gastric cancer. However, the underlying mechanism in ovarian cancer remain unknown. Therefore, the present study investigated the pharmacological effect of propofol on microRNAs (miRNAs) in ovarian cancer treatment. Propofol (1, 5 or 10 µg/ml) was used to treat A2780 and SKOV3 ovarian cancer cells for 1, 2, 3, 4 or 5 days. The MTT assay was used to detect cell viability, while wound healing and Transwell assays were utilized to assess the invasive and migratory abilities. The bioinformatics prediction approach identified differentially expressed miRNAs (miRs) that were used in Gene Ontology, Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes analyses. The expression levels of miR­125a­5p and lin­28 homolog B (LIN28B) were evaluated by reverse transcription­quantitative PCR (RT­qPCR). A luciferase assay was performed to identify the relationship between miR­125a­5p and LIN28B. Western blotting was conducted to measure the protein expression of LIN28B. It was demonstrated that propofol significantly upregulated miR­125a­5p to exert its antitumor activity. RT­qPCR results suggested that propofol could upregulate miR­125a­5p and LIN28B expression levels in ovarian cancer cell lines. Western blot analysis also indicated that propofol could enhance the expression of LIN28B in ovarian cancer cell lines. The luciferase assay identified that miR­125a­5p could directly inhibit the expression of LIN28B to suppress proliferation and metastasis in ovarian cancer. In conclusion, these results suggested that propofol inhibited ovarian cancer proliferation and metastasis by enhancing miR­125a­5p, which targets LIN28B.

Value of multimodality imaging in the diagnosis of breast lesions with calcification: A retrospective study.

PURPOSE: To assess the value of conventional ultrasound (US), contrast-enhanced ultrasound (CEUS) and mammography in the diagnosis of breast lesions with calcifications. METHODS: A total of 87 breast lesions with calcification were subjected to US, CEUS and mammography and divided into 3 groups: Group A (all cases), Group A1 (31 cases who underwent US and CEUS first followed by mammography), and Group A2 (56 cases who underwent mammography first followed by US and CEUS). A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of different methods in different groups. RESULTS: In Group A, the area under the ROC curve (AUROC) of CEUS were 0.937, which were significantly higher than that of mammography (p < 0.05). In Group A1, the AUROC of CEUS were 0.842, which were not significantly different from that of US and mammography (p > 0.05). In Group A2, the AUROC of CEUS were 0.987, which were significantly higher than that of mammography and US (p < 0.05). CONCLUSION: Based on the mammography results, the combination of US and CEUS might improve the diagnostic efficacy in breast lesions with calcification.

Does contrast-enhanced ultrasound (CEUS) play a better role in diagnosis of breast lesions with calcification? A comparison with MRI.

OBJECTIVE: To compare the efficacy of contrast-enhanced ultrasound enabled reclassification of Breast Imaging Reporting and Data System (CEUS-BI-RADS) with MRI in the diagnosis of breast lesions with calcification. METHODS: A total of 52 breast lesions with calcification from 51 patients were detected by ultrasound as hyperechoic foci and categorized as BI-RADS 3-5. The 51 patients further underwent CEUS scan and MRI. The ultrasound-BI-RADS combined with CEUS 5-point score system redefined the classification of BI-RADS which was called CEUS-BI-RADS. The diagnostic efficacy of three methods was assessed by receiver operating characteristic (ROC) curve analysis. Histopathological assessment used as the gold-standard. RESULTS: The sensitivities of Ultrasound-BI-RADS, MRI classification of BI-RADS (MRI-BI-RADS) and CEUS-BI-RADS were 85%, 90% and 95% without significant difference among the three modalities (p > 0.05). The diagnostic specificities of ultrasound-BI-RADS, MRI-BI-RADS and CEUS-BI-RADS were 78.1%, 78.1% and 96.8%, respectively (p < 0.05); and the accuracy were 80.7%, 82.6% and 96.1% for ultrasound-BI-RADS, MRI-BI-RADS and CEUS-BI-RADS, respectively (p < 0.05). The area under ROC (AUROC) in differentiation of breast lesions with calcification was 0.945 for CEUS-BI-RADS, 0.907 for MRI-BI-RADS and 0.853 for ultrasound-BI-RADS, with no significant difference among the three modalities (p > 0.05). CONCLUSION: The CEUS-BI-RADS has a better diagnostic efficiency than MRI-BI-RADS in the differentiation of the breast lesions with calcification. ADVANCES IN KNOWLEDGE: •CEUS is a better method in differentiation of breast lesions with calcification.•CEUS-BI-RADS increases the efficiency of diagnosis compared to MRI.

Tanshinone II A enhances pyroptosis and represses cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway.

Cervical cancer is the fourth most common cancer in women globally. Lack of effective pharmacotherapies for cervical cancer mainly attributed to an elusive understanding of the mechanism underlying its pathogenesis. Pyroptosis plays a key role in inflammation and cancer. Our study identified microRNA (miR) 145 (miR-145)/gasdermin D (GSDMD) signaling pathway as critical mediators in the effect of tanshinone II A on HeLa cells. In the present study, we found that treatment of tanshinone II A led to an obvious repression of cell proliferation and an increase in apoptosis on HeLa cells, especially in high concentration. Compared with the controlled group, tanshinone II A enhanced the activity of caspase3 and caspase9. Notably, the results demonstrated that tanshinone II A regulated cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway. Treatment of tanshinone II A significantly up-regulated the expression of GSDMD and miR-145. After transfection of si-miR-145 plasmids, the effects of tanshinone II A on HeLa cells were converted, including cell proliferation, apoptosis and pyroptosis. In addition, the results showed that tanshinone II A treatment altered the expression level of PI3K, p-Akt, NF-kB p65 and Lc3-I. Collectively, our findings demonstrate that tanshinone II A exerts anticancer activity on HeLa cells by regulating miR-145/GSDMD signaling. The present study is the first time to identify miR-145 as a candidate target in cervical cancer and show an association between miR-145 and pyroptosis, which provides a novel therapy for the treatment of cervical cancer.