US of thyroid nodules: can AI-assisted diagnostic system compete with fine needle aspiration?

OBJECTIVES: Artificial intelligence (AI) systems can diagnose thyroid nodules with similar or better performance than radiologists. Little is known about how this performance compares with that achieved through fine needle aspiration (FNA). This study aims to compare the diagnostic yields of FNA cytopathology alone and combined with BRAFV600E mutation analysis and an AI diagnostic system. METHODS: The ultrasound images of 637 thyroid nodules were collected in three hospitals. The diagnostic efficacies of an AI diagnostic system, FNA-based cytopathology, and BRAFV600E mutation analysis were evaluated in terms of sensitivity, specificity, accuracy, and the κ coefficient with respect to the gold standard, defined by postsurgical pathology and consistent benign outcomes from two combined FNA and mutation analysis examinations performed with a half-year interval. RESULTS: The malignancy threshold for the AI system was selected according to the Youden index from a retrospective cohort of 346 nodules and then applied to a prospective cohort of 291 nodules. The combination of FNA cytopathology according to the Bethesda criteria and BRAFV600E mutation analysis showed no significant difference from the AI system in terms of accuracy for either cohort in our multicenter study. In addition, for 45 included indeterminate Bethesda category III and IV nodules, the accuracy, sensitivity, and specificity of the AI system were 84.44%, 95.45%, and 73.91%, respectively. CONCLUSIONS: The AI diagnostic system showed similar diagnostic performance to FNA cytopathology combined with BRAFV600E mutation analysis. Given its advantages in terms of operability, time efficiency, non-invasiveness, and the wide availability of ultrasonography, it provides a new alternative for thyroid nodule diagnosis. CLINICAL RELEVANCE STATEMENT: Thyroid ultrasonic artificial intelligence shows statistically equivalent performance for thyroid nodule diagnosis to FNA cytopathology combined with BRAFV600E mutation analysis. It can be widely applied in hospitals and clinics to assist radiologists in thyroid nodule screening and is expected to reduce the need for relatively invasive FNA biopsies. KEY POINTS: • In a retrospective cohort of 346 nodules, the evaluated artificial intelligence (AI) system did not significantly differ from fine needle aspiration (FNA) cytopathology alone and combined with gene mutation analysis in accuracy. • In a prospective multicenter cohort of 291 nodules, the accuracy of the AI diagnostic system was not significantly different from that of FNA cytopathology either alone or combined with gene mutation analysis. • For 45 indeterminate Bethesda category III and IV nodules, the AI system did not perform significantly differently from BRAFV600E mutation analysis.

Amniogenesis in Human Amniotic Sac Embryoids after Exposures to Organophosphate Flame Retardants.

BACKGROUND: Amniogenesis is a key event in biochemical pregnancy, and its failure may result in human embryonic death. However, whether and how environmental chemicals affect amniogenesis remain largely unknown. OBJECTIVES: The objective of the present study was to screen chemicals that may disrupt amniogenesis in an amniotic sac embryoid model and to investigate the potential mechanism of amniogenesis failure, with a focus on organophosphate flame retardants (OPFRs). METHODS: This study developed a high-throughput toxicity screening assay based on transcriptional activity of octamer-binding transcription factor 4 (Oct4). For the two positive OPFR hits with the strongest inhibitory activity, we used time-lapse and phase-contrast imaging to assess their effects on amniogenesis. Associated pathways were explored by RNA-sequencing and western blotting, and potential binding target protein was identified through a competitive binding experiment. RESULTS: Eight positive hits exhibiting Oct4 expression were identified, with 2-ethylhexyl-diphenyl phosphate (EHDPP) and isodecyl diphenyl phosphate (IDDPP) showing the strongest inhibitory activity. EHDPP and IDDPP were found to disrupt the rosette-like structure of the amniotic sac or inhibit its development. Functional markers of squamous amniotic ectoderm and inner cell mass were also found disrupted in the EHDPP- and IDDPP-exposed embryoids. Mechanistically, embryoids exposed to each chemical exhibited abnormal accumulation of phosphorylated nonmuscle myosin (p-MLC-II) and were able to bind to integrin ß1 (ITGß1). CONCLUSION: The amniotic sac embryoid models suggested that OPFRs disrupted amniogenesis likely by inhibiting the ITGß1 pathway, thus providing direct in vitro evidence associating OPFRs with biochemical miscarriage. https://doi.org/10.1289/EHP11958.

Comparison of Various Ultrasound-Based Malignant Risk Stratification Systems on an Occasion for Assessing Thyroid Nodules in Hashimoto's Thyroiditis.

Purpose: To compare the diagnostic performance and unnecessary ultrasound-guided fine-needle aspiration (US-FNA) biopsy rate of the 2015 American Thyroid Association (ATA), 2016 Korean Society of Thyroid Radiology (KSThR), and 2017 American College of Radiology (ACR) guidelines for patients with and without Hashimoto's thyroiditis (HT). Patients and Methods: This retrospective study included 716 nodules from 696 consecutive patients, which were classified using the categories defined by the three guidelines: ATA, KSThR, and ACR. The malignancy risk in each category was calculated and the diagnostic performance and unnecessary fine-needle aspiration (FNA) rates of the three guidelines were compared. Results: In total, 426 malignant and 290 benign nodules were identified. Patients with malignant nodules had lower total thyroxine levels and higher thyroid-stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody levels than those without malignant nodules (all P<0.01). The margin difference was significant in non-HT patients (P<0.01), but comparable in HT patients (P=0.55). The calculated malignancy risks of high and intermediate suspicion nodules in the ATA and KSThR guidelines and moderately suspicious nodules in the ACR guidelines were significantly lower in non-HT patients compared with HT patients (P<0.05). The ACR guidelines showed the lowest sensitivity, highest specificity, and lowest unnecessary FNA rates in patients with and without HT. Compared to non-HT patients, HT patients had significantly lower unnecessary FNA rates (P<0.01). Conclusion: HT was associated with a higher malignancy rate of thyroid nodules with intermediate suspicion according to the ATA, KSThR, and ACR guidelines. The three guidelines, especially ACR, were likely to be more effective and could allow a greater reduction in the percentage of benign nodules biopsied in patients with HT.

Benzotriazole ultraviolet stabilizer UV-234 promotes foam cell formation in RAW264.7 macrophages.

Benzotriazole ultraviolet stabilizers (BUVSs) have been reported to induce inflammatory responses which may promote cholesterol accumulation and to downregulate the expression of genes involved in cholesterol biosynthesis; hence, we speculated whether BUVSs promote foam cell formation, which plays a key role in all stages of atherosclerosis. Herein, we used high-content imaging to screen all available BUVSs; of all the 17 candidates, 6 of them could promote foam cell formation at 10 µM. Further analyses showed that one BUVS UV-234 markedly increased the foam cell staining intensity by 15.0%-55.9% in the 0.5-10 µM exposure groups in a dose-dependent manner. Cholesterol influx was markedly enhanced by 21.0%-24.5% in the 5-10 µM exposure groups and cholesterol efflux was downregulated by 21.2%-59.3% in the 0.5-10 µM exposure groups, indicating that cholesterol efflux may play a major role in foam formation considering cholesterol efflux was downregulated at a relatively low concentration. Gene expression of ABCA1 and ABCG1 which regulate the cholesterol efflux were also decreased at 0.5-10 µM. The degradation of hypoxia-inducible factor 1α (HIF1α) via the ubiquitin-proteasome system was observed at 0.5-10 µM, probably contributing to the downregulated expression of the genes encoding liver X receptors (LXR) α/ß and their targets, ABCA1 and ABCG1. Thus, our study revealed that BUVSs frequently detected in the environment can promote foam cell formation in macrophages, contributing to the risk of atherosclerosis in humans.

Single Image Dehazing Using Global Illumination Compensation.

The existing dehazing algorithms hardly consider background interference in the process of estimating the atmospheric illumination value and transmittance, resulting in an unsatisfactory dehazing effect. In order to solve the problem, this paper proposes a novel global illumination compensation-based image-dehazing algorithm (GIC). The GIC method compensates for the intensity of light scattered when light passes through atmospheric particles such as fog. Firstly, the illumination compensation was accomplished in the CIELab color space using the shading partition enhancement mechanism. Secondly, the atmospheric illumination values and transmittance parameters of these enhanced images were computed to improve the performance of atmospheric-scattering models, in order to reduce the interference of background signals. Eventually, the dehazing result maps with reduced background interference were obtained with the computed atmospheric-scattering model. The dehazing experiments were carried out on the public data set, and the dehazing results of the foggy image were compared with cutting-edge dehazing algorithms. The experimental results illustrate that the proposed GIC algorithm shows enhanced consistency with the real-imaging situation in estimating atmospheric illumination and transmittance. Compared with established image-dehazing methods, the peak signal-to-noise ratio (PSNR) and the structural similarity (SSIM) metrics of the proposed GIC method increased by 3.25 and 0.084, respectively.

High Luminous Efficacy Phosphor-Converted Mass-Produced White LEDs Achieved by AlN Prebuffer and Transitional-Refraction-Index Patterned Sapphire Substrate.

Constant advance in improving the luminous efficacy (ηL) of nitride-based light-emitting diodes (LEDs) plays a critical role for saving measurable amounts of energy. Further development is motivated to approach the efficiency limit for this material system while reducing the costs. In this work, strategies of using thin AlN prebuffer and transitional-refraction-index patterned sapphire substrate (TPSS) were proposed, which pushed up the efficiency of white LEDs (WLEDs). The AlN prebuffer was obtained through physical vapor deposition (PVD) method and TPSS was fabricated by dry-etched periodic silica arrays covered on sapphire. Devices in mass production confirmed that PVD AlN prebuffer was able to improve the light output power (φe) of blue LEDs (BLEDs) by 2.53% while increasing the productivity by ~8% through shortening the growth time. Additionally, BLEDs on TPSS exhibited an enhanced top ηext of 5.65% in contrast to BLEDs on the conventional PSS through Monte Carlo ray-tracing simulation. Consequently, φe of BLEDs was experimentally enhanced by 10% at an injected current density (Jin) of 40 A/cm2. A peak ηL of 295.2 lm/W at a Jin of 0.9 A/cm2 and the representative ηL of 282.4 lm/W at a Jin of 5.6 A/cm2 for phosphor-converted WLEDs were achieved at a correlated color temperature of 4592 K.

A new noninvasive and patient-specific hemodynamic index for the severity of renal stenosis and outcome of interventional treatment.

Renal arterial stenosis (RAS) often causes renovascular hypertension, which may result in kidney failure and life-threatening consequences. Direct assessment of the hemodynamic severity of RAS has yet to be addressed. In this work, we present a computational concept to derive a new, noninvasive, and patient-specific index to assess the hemodynamic severity of RAS and predict the potential benefit to the patient from a stenting therapy. The hemodynamic index is derived from a functional relation between the translesional pressure indicator (TPI) and lumen volume reduction (S) through a parametric deterioration of the RAS. Our in-house computational platform, InVascular, for image-based computational hemodynamics is used to compute the TPI at given S. InVascular integrates unified computational modeling for both image processing and computational hemodynamics with graphic processing unit parallel computing technology. The TPI-S curve reveals a pair of thresholds of S indicating mild or severe RAS. The TPI at S = 0 represents the pressure improvement following a successful stenting therapy. Six patient cases with a total of 6 aortic and 12 renal arteries are studied. The computed blood pressure waveforms have good agreements with the in vivo measured ones and the systolic pressure is statistical equivalence to the in-vivo measurements with p < .001. Uncertainty quantification provides the reliability of the computed pressure through the corresponding 95% confidence interval. The severity assessments of RAS in four cases are consistent with the medical practice. The preliminary results inspire a more sophisticated investigation for real medical insights of the new index. This computational concept can be applied to other arterial stenoses such as iliac stenosis. Such a noninvasive and patient-specific hemodynamic index has the potential to aid in the clinical decision-making of interventional treatment with reduced medical cost and patient risks.

Screening of Organophosphate Flame Retardants with Placentation-Disrupting Effects in Human Trophoblast Organoid Model and Characterization of Adverse Pregnancy Outcomes in Mice.

BACKGROUND: Abnormal placental development may result in adverse pregnancy outcomes and metabolic diseases in adulthood; however, it remains unknown whether and how xenobiotics affect human placentation. OBJECTIVES: This study aimed to screen and identify placentation-disrupting chemicals in commonly used organophosphate flame retardants (OPFRs) and, if identified, to investigate potential adverse effects on placentation in relation to adverse pregnancy outcomes and metabolic disorder in offspring in mice. METHODS: We devised a high-throughput immunofluorescence screening assay based on human trophoblast organoids and used it to screen OPFRs that inhibit the proliferation of organoids. One identified chemical was assessed for its effects on placentation by evaluating villous cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts using immunofluorescence and a mitochondrial stress test after 2 d of exposure. A 10-d exposure study was further performed to observe the dynamic effect of the OPFR on the structure of the organoids. RNA-sequencing and western blotting experiments were performed to explore the associated pathways, and a potential binding protein was identified by immunoprecipitation and in vitro kinase activity assays. Animal studies were performed to determine whether the findings in organoids could be replicated in mice and to observe adverse pregnancy outcomes. RESULTS: The proliferation of organoids exposed to three aryl-OPFRs was significantly lower than the proliferation of control organoids. Further analysis demonstrated that one such chemical, 2-ethylhexyl-diphenyl phosphate (EHDPP), disrupted placentation in organoids. Mechanistically, EHDPP interfered with insulin-like growth factor 1 receptor (IGF1R) to inhibit aerobic respiration. Mice exposed to EHDPP at a physiological human concentrations exhibited immature and mature placental disorders, which correlated with fetal growth restriction, implantation failure, stillbirth, and impaired glucose tolerance. CONCLUSIONS: The human trophoblast organoid model showed that the commonly used OPFRs disrupted placentation via IGF1R, indicating that its use may contribute to adverse pregnancy outcomes and metabolic disorders in offspring. https://doi.org/10.1289/EHP10273.

Ultrasound grayscale ratio: a reliable parameter for differentiating between papillary thyroid microcarcinoma and micronodular goiter.

BACKGROUND: The present study aimed to quantify and differentiate the echo levels of papillary thyroid microcarcinomas (PTMCs) and micronodular goiters (MNGs) using the ultrasound grayscale ratio (UGSR) and to investigate the repeatability of UGSR. METHODS: The ultrasound (US) data of 241 patients with 265 PTMCs and 141 patients with 168 MNGs confirmed by surgery and pathology were retrospectively analyzed. All patients had received outpatient ultrasonic examination and preoperative ultrasonic positioning. The RADinfo radiograph reading system was used to measure the grayscales of PTMC, MNG, and thyroid tissues at the same gain level, and the UGSR values of the PTMC, MNG, and thyroid tissue were calculated. The patients were divided into outpatient examination, preoperative positioning, and mean value groups, and the receiver operating characteristic (ROC) curves were calculated to obtain the optimal UGSR threshold to distinguish PTMC from MNG. The interclass correlation coefficient (ICC) was used to assess the consistency of UGSR measured in three groups. RESULTS: The UGSR values of the PTMC and MNG were 0.56 ± 0.14 and 0.80 ± 0.19 (t = 5.84, P < 0.001) in the outpatient examination group, 0.55 ± 0.14 and 0.80 ± 0.19 (t = 18.74, P < 0.001) in the preoperative positioning group, and 0.56 ± 0.12 and 0.80 ± 0.18 (t = 16.49, P < 0.001) in the mean value group. The areas under the ROC curves in the three groups were 0.860, 0.856, and 0.875, respectively. When the UGSR values for the outpatient examination, preoperative positioning, and mean value groups were 0.649, 0.646, and 0.657, respectively, each group obtained its largest Youden index. A reliable UGSR value was obtained between the outpatient examination and preoperative positioning groups (ICC = 0.79, P = 0.68). CONCLUSION: UGSR is a simple and repeatable method to distinguish PTMC from MNG, and hence, can be widely applicable.

Behaviors and trophodynamics of o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT) in the aquatic food web: Comparison with p,p'-DDT.

The broad-spectrum insecticide p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) has been banned in most countries since the 1970s on account of its environmental persistence as well as the high biomagnification of its major metabolite 1,1-dichloro-2,2-bis(4-chorophenyl)ethylene (p,p'-DDE). However, the information on the bioaccumulation and behavior of p,p'-DDTs in aquatic organisms is lacking. In this study, all 6 DDT isomers were detected in biota from the food web of the Liaodong Bay, China, and the total concentrations of DDT isomers in Chinese anchovy (Thrissa kammalensis) and Japanese Spanish mackerel (Scomberomrus niphonius) were 223 ± 42 ng/g ww and 242 ± 70 ng/g ww, respectively. In biota, o,p'-DDD dominated among the o,p'-isomers (80.5 ± 17.3%), while p,p'-DDE dominated among the p,p'-isomers (61.8 ± 15.2%). Contrastingly, sediment from the Liaodong Bay contained similar proportions of o,p'-DDT and p,p'-DDTs, suggesting an isomer-specific metabolism of the compounds in biota. A well-controlled laboratory exposure experiment with Japanese medaka (Oryzias latipes) demonstrated that o,p'-DDT was more difficult to metabolize to o,p'-DDE compared with that of p,p'-DDT. Significantly positive regressions were found between trophic levels and lipid equivalent concentrations for both o,p'-DDT and o,p'-DDD, and the trophic magnification factors (TMFs) were estimated as 12.3 and 9.12 (p < 0.05), respectively. The TMFs of o,p'-DDT and o,p'-DDD in the aquatic food web were higher than p,p'-DDT (7.76), p,p'-DDD (4.17), and p,p'-DDE (3.39), which may be explained by the isomer-specific metabolism differences in biota.

Ultrasound-guided transperineal laser ablation for percutaneous treatment of benign prostatic hyperplasia: a new minimally invasive interventional therapy.

BACKGROUND: Although there are different treatments for benign prostate hyperplasia, their efficacy and safety differ. We are currently exploring a new minimally invasive interventional therapy for benign prostatic hyperplasia (BPH). PURPOSE: To determine the feasibility, effectiveness, and safety of ultrasound-guided transperineal laser ablation (US-TPLA) for the treatment of BPH. MATERIAL AND METHODS: Twenty patients with BPH (mean age = 73.9 ± 9.2 years) who underwent US-TPLA from June 2018 to January 2020 with a subsequent six-month follow-up were retrospectively reviewed. After local anesthesia, a 21-G trocar was inserted into the prostate tissue under ultrasound monitoring, followed by 1064 nm diode laser irradiation. Changes in international prostate symptom score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), postvoid residual (PVR), prostate volume, and complications were evaluated six months after surgery. RESULTS: All patients underwent the operation successfully without serious complications. After six months, the average IPSS improved from 22.7 ± 5.3 to 9.1 ± 3.2 (P < 0.001), the QoL improved from 4.9 ± 1.7 to 2.3 ± 1.3 (P < 0.001), the Qmax improved from 8.5 ± 3.0 to 15.2 ± 4.8 mL/s (P < 0.001), the PVR increased from 78.7 ± 58.8 to 30.3 ± 34.2 (P < 0.05), and the mean prostate volume ranged from 70.8 ± 23.8 to 54.7 ± 20.9 mL (P < 0.05). CONCLUSION: US-TPLA is safe and feasible for the treatment of BPH. An evaluation at the six-month follow-up is effective.

Prospective Evaluation of Ultrasound in a Novel Position with MRI Virtual Navigation for MRI-Detected Only Breast Lesions: A Pilot Study of a More Efficient and Economical Method.

The aim of this study was to evaluate the clinical utility of ultrasound (US) with magnetic resonance imaging (MRI) virtual navigation in a novel prone position for MRI-detected incidental breast lesions. Between June 2016 and June 2020, 30 consecutive patients with 33 additional Breast Imaging Reporting and Data System (BI-RADS) category 4 or 5 lesions that were detected on MRI but occult on second-look US were enrolled in the study. All suspicious lesions were located in real-time US using MRI virtual navigation in the prone position and then followed by US-guided biopsy or surgical excision. Pathological results were taken as the standard of reference. The detection rate of US with MRI virtual navigation was calculated. The MRI features and pathological types of these lesions were analyzed. A total of 31 lesions were successfully located with real-time US with MRI virtual navigation and then US-guided biopsy or localization, and the detection rate was 93.9% (31/33). Twenty-seven (87.1%, 27/31) proved to be benign lesions and four (12.9%, 4/31) were malignant lesions at pathology. Of the 33 MRI-detected lesions, 31 (93.9%, 31/33) were non-mass enhancements and two (6.1%, 2/33) were masses. This study showed that real-time US with prone MRI virtual navigation is a novel efficient and economical method to improve the detection and US-guided biopsy rate of breast lesions that are detected solely on MRI.

Triphenyl phosphate delayed pubertal timing and induced decline of ovarian reserve in mice as an estrogen receptor antagonist.

Although concerns have been raised about the adverse effects of triphenyl phosphate (TPhP) on female fertility, its risk to ovarian functioning remains unknown. In this study, female C57BL/6 mice at postnatal day 21 were exposed on a daily basis to TPhP dose of 2, 10, and 50 mg/kg for 40 days. A significant delay in pubertal timing was observed in the mice exposed to 50 mg/kg of TPhP. An estrogen-responsive reporter transgenic mice assay demonstrated that TPhP significantly downregulated the estrogen receptor (ER) signaling by 45.1% in the whole body in the 50 mg/kg group, and by 14.7-43.7% in the uterus for all exposure groups compared with the control. This strong antagonistic activity of TPhP toward ER explained the delay in pubertal timing. A significant reduction in the number of follicles in all stages was observed in mice after being exposed to TPhP for 40 days at concentrations of 10 and 50 mg/kg, resulting in a decline of the ovarian reserve. The elevation of the follicle-stimulating hormone concentration may have contributed to this phenomenon, as controlled by the antagonistic activity of TPhP toward ER in the brain. The toxic effects of TPhP on ovarian functioning highlight this chemical as a potential risk factor for female fertility.

Imaging manifestations of Caroli disease with autosomal recessive polycystic kidney disease: a case report and literature review.

BACKGROUND: Both Caroli disease (CD) and autosomal recessive polycystic kidney disease (ARPKD) are autosomal recessive disorders, which are more commonly found in infants and children, for whom surviving to adulthood is rare. Early diagnosis and intervention can improve the survival rate to some extent. This study adopted the case of a 26-year-old pregnant woman to explore the clinical and imaging manifestations and progress of CD concomitant with ARPKD to enable a better understanding of the disease. CASE PRESENTATION: A 26-year-old pregnant woman was admitted to our hospital for more than 2 months following the discovery of pancytopenia and increased creatinine. Ultrasonography detected an enlarged left liver lobe, widened hepatic portal vein, splenomegaly, and dilated splenic vein. In addition, both kidneys were obviously enlarged and sonolucent areas of varying sizes were visible, but color Doppler flow imaging revealed no abnormal blood flow signals. The gestational age was approximately 25 weeks, which was consistent with the actual fetal age. Polyhydramnios was detected but no other abnormalities were identified. Magnetic resonance imaging revealed that the liver was plump, and polycystic liver disease was observed near the top of the diaphragm. The T1 and T2 weighted images were the low and high signals, respectively. The bile duct was slightly dilated; the portal vein was widened; and the spleen volume was enlarged. Moreover, the volume of both kidneys had increased to an abnormal shape, with multiple, long, roundish T1 and T2 abnormal signals being observed. Magnetic resonance cholangiopancreatography revealed that intrahepatic cystic lesions were connected with intrahepatic bile ducts. The patient underwent a genetic testing, the result showed she carried two heterozygous mutations in PKHD1. The patient was finally diagnosed with CD with concomitant ARPKD. The baby underwent a genetic test three months after birth, the result showed that the patient carried one heterozygous mutations in PKHD1, which indicated the baby was a PKHD1 carrier. CONCLUSIONS: This case demonstrates that imaging examinations are of great significance for the diagnosis and evaluation of CD with concomitant ARPKD.

Bedside cardiopulmonary ultrasonography evaluates lung water content in very low-weight preterm neonates with patent ductus arteriosus.

BACKGROUND: Patent ductus arteriosus (PDA) is a common congenital heart abnormality in preterm neonates with a high incidence in neonates with very low birth weights. When PDA persists, interstitial lung water content increases, which could lead to abnormal circulation hemodynamics and pulmonary edema. It is important to perform early and reliable assessment of lung water content in very low-weight preterm neonates with persistent PDA. AIM: To evaluate the role of bedside cardiopulmonary ultrasonography in the lung water content assessment in very low-weight preterm neonates with persistent PDA. METHODS: From January 2018 to March 2020, 69 very low-weight preterm neonates with echocardiography-confirmed PDA were selected as the PDA group. At the same time, 89 very low-weight preterm neonates without PDA were randomly selected as the control group. All neonates underwent echocardiography and 6-segment lung ultrasonography on the fourth day after birth. The clinical characteristics and main ultrasonography results were compared between the two groups. Pearson's analysis was used to analyze the correlation between lung ultrasonography score (LUS) and other related clinical and ultrasonography results in all neonates. In the PDA group, PDA diameters were recorded, and the correlation with LUS and left atrium to aortic (LA/AO) dimension ratio were also analyzed. LA/AO ratio is one of the ultrasonic diagnostic criteria for hemodynamically significant PDA. When the ratio is ≥ 1.5, it suggests the possibility of hemodynamic changes in persistent PDA. A receiver operating characteristic curve was established using the sensitivity of LUS to predict the hemodynamic changes in neonates with PDA as the ordinate and 1-specificity as the abscissa. RESULTS: A total of 158 neonates were enrolled in this study, including 69 in the PDA group and 89 in the control group. There were no statistical differences in sex, gestational age, birth weight, ventilator dependence, hospitalization length and left ventricular ejection fraction between the two groups (P > 0.05). The LUS and LA/AO ratio in the PDA group were higher than those in the control group (P < 0.05), but there was no difference of LUS in neonates with or without use of the ventilator (t = 0.58, P = 0.16). In all cases, LUS was negatively correlated with gestational age (r = -0.28, P < 0.01) and birth weight (r = -0.36, P < 0.01), while positively correlated with the LA/AO ratio (r = 0.27, P < 0.01). In the PDA group, PDA diameter was positively correlated with the LA/AO ratio (r = 0.39, P < 0.01) and LUS (r = 0.31, P < 0.01). Receiver operating characteristic results showed that LUS had the moderate accuracy for predicting hemodynamic changes in PDA (area under the curve = 0.741; sensitivity = 93.75%; specificity = 50.94%). CONCLUSION: Bedside cardiopulmonary ultrasonography can evaluate lung content in neonates with PDA and predict the possibility of hemodynamic changes in persistent PDA.

Hounsfield Unit Values in ACR TI-RADS 4-5 Thyroid Nodules with Coarse Calcifications: An Important Imaging Feature Helpful for Diagnosis.

PURPOSE: The purpose of this study is to investigate the diagnostic role of Hounsfield unit (HU) values on noncontrast computed tomography (CT) for differentiating benignity from malignancy in the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) 4-5 nodules with coarse calcifications. PATIENTS AND METHODS: CT images of 216 ACR TI-RADS 4-5 nodules with coarse calcifications from 207 patients who underwent surgery in our hospital between 2017 and 2019 were retrospectively reviewed. The average HU values (AHUVs) and maximum HU values (MHUVs) of the nodules were measured on noncontrast CT. The distribution of AHUVs and MHUVs in benign and malignant nodules with coarse calcifications was analyzed using the Mann-Whitney test. Receiver operating characteristic (ROC) curves were used to identify the best cut-off values. Diagnostic performances were assessed according to the area under the ROC curve (AUC), sensitivity and specificity. RESULTS: Of the 216 ACR TI-RADS 4-5 nodules with coarse calcifications, 170 were benign and 46 were malignant. The AHUVs of benign and malignant nodules were 791 HU [interquartile range (IQR), 543-1025 HU] and 486 HU (IQR, 406-670 HU), respectively (P < 0.001). The MHUVs of benign and malignant nodules were 1084 HU (IQR, 717-1477 HU) and 677 HU (IQR, 441-986 HU), respectively (P < 0.001). The AUCs for AHUVs and MHUVs for predicting benign nodules with coarse calcifications were 0.759 and 0.732, and the cut-off values were 627.5 HU and 806.0 HU, with sensitivities of 67.6% and 68.8% and specificities of 73.9% and 67.4%, respectively. The sensitivity and specificity of the combination were 68.8% and 76.1%. CONCLUSION: AHUVs and MHUVs were helpful in differentiating benignity from malignancy in ACR TI-RADS 4-5 nodules with coarse calcifications. This may provide an important basis for reducing misdiagnosis and unnecessary aspiration or surgical trauma.

Triphenyl phosphate modulated saturation of phospholipids: Induction of endoplasmic reticulum stress and inflammation.

Although triphenyl phosphate (TPHP) has been reported to disrupt lipid metabolism, the effect of TPHP on lipid saturation remains unexplored. In this study, a lipidomic analysis demonstrated decreases in the levels of poly-unsaturated phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) in RAW264.7 murine macrophage cells exposed to 10 µM TPHP. The expression of the gene encoding lysophosphatidylcholine acyltransferase 3 (Lpcat3) was significantly downregulated by 0.76 ± 0.03 and 0.70 ± 0.08-fold in 10 and 20 µM TPHP exposure groups, relative to the control group. This finding explains the observed decrease in lipid saturation. Correspondingly, exposure to 10 and 20 µM TPHP induced endoplasmic reticulum (ER) stress and inflammatory responses, which have been linked to metabolic dysfunction such as insulin resistance and hypertriglyceridemia. Therefore, TPHP may pose a risk to human health by promoting metabolic diseases.

Canagliflozin inhibits p-gp function and early autophagy and improves the sensitivity to the antitumor effect of doxorubicin.

Cancer easily induces resistance to most chemotherapy drugs. In this study, we investigated the combination cytotoxic and antitumor effects of canagliflozin (CAN) and doxorubicin (DOX) in vitro and in vivo. CAN significantly increased the cytotoxicity of DOX in HepG2, HepG2-ADR (adriamycin or doxorubicin-resistant) and MCF7 cells. CAN significantly promoted the intracellular uptake of DOX in HepG2 cells. CAN also reduced the P-glycoprotein (P-gp) level in HepG2 cells. The function of P-gp required ATP, but CAN significantly reduced the intracellular ATP level. CAN might inhibit the function of p-gp, increase the intracellular DOX concentration and contribute to an enhanced cytotoxic activity. Autophagy plays a protective role in chemotherapy-induced cell survival. However, CAN significantly inhibited DOX-induced autophagy in HepG2 cells, and the mechanism appeared to be mediated by promoting ULK1 ser 757 phosphorylation. The downregulation of P-gp may be associated with protein degradation but is independent of the autophagy pathway. Furthermore, in HepG2-xenograft BALB/c nude mice, CAN significantly increased the antitumor effect of DOX. This study is the first to report that a classical antidiabetic drug, CAN improved the sensitivity to the antitumor effect of DOX, and the potential molecular mechanisms of CAN may involve the inhibition of P-gp function and the autophagy pathway.

Integrated bioinformatics analysis to screen hub genes in the lymph node metastasis of thyroid cancer.

Thyroid cancer (TC) is one of the most common types of malignancy of the endocrine-system. At present, there is a lack of effective methods to predict neck lymph node metastasis (LNM) in TC. The present study compared the expression profiles from The Cancer Genome Atlas between N1M0 and N0M0 subgroups in each T1-4 stages TC in order to identify the four groups of TC LNM-associated differentially expressed genes (DEGs). Subsequently, DEGs were combined to obtain a total of 493 integrated DEGs by using the method of Robust Rank Aggregation. Furthermore, the underlying mechanisms of LNM were investigated. The results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses demonstrated that the identified DEGs may promote LNM via numerous pathways, including extracellular matrix-receptor interaction, PI3K-AKT signaling pathway and focal adhesion. Following construction of a protein-protein interaction network, the significance score for each gene was calculated and seven hub genes were screened, including interleukin 6, actinin α2, collagen type I α 1 chain, actin α1, calbindin 2, thrombospondin 1 and parathyroid hormone. These genes were predicted to serve crucial roles in TC with LNM. The results from the present study could therefore improve the understanding of LNM in TC. In addition, the seven DEGs identified may be considered as potential novel targets for the development of biomarkers that could be used in the diagnosis and therapy of TC.