Analysis and Comparison of the Malignant Thyroid Nodules Not Recommended for Biopsy in ACR TIRADS and AI TIRADS With a Large Sample of Surgical Series.

OBJECTIVE: To determine if the artificial intelligence-based Thyroid Imaging, Reporting and Data System (AI TIRADS) would perform better than the American College of Radiology (ACR) TIRADS in monitoring malignant thyroid nodules not recommended for biopsy using follow-up thresholds. METHODS: A total of 3499 thyroid nodules with surgical histopathology and ultrasound features were retrospectively reviewed and categorized using ACR TIRADS and AI TIRADS. The recommendations for biopsy and follow-up divided nodules into three groups 1) fine needle aspiration (FNA), 2) follow-up ultrasound, and 3) no further evaluation. RESULTS: Of the total 1608 malignant nodules in this study, 974 malignant nodules would not be biopsied in ACR TIRADS compared with 967 in AI TIRADS. While 60.0% (584/974) of these non-biopsied malignancies could be followed-up by ultrasound in ACR TIRADS and 62.8% (607/967) in AI TIRADS. For the malignancies of no further evaluation, 97.4% (380/390) were sized <10 mm in ACR TIRADS and 93.3% (336/360) in AI TIRADS. Compared with ACR TIRADS, AI TIRADS had lower unnecessary FNA rate and missing cancer rate (41.0% vs 47.8% and 22.8% vs 27.5%, P < .05, respectively) while having higher specificity and AUC as well as lower sensitivity (65.0% vs 57.9%, 0.895 vs 0.881, and 96.1% vs 97.8%, all P < .05). CONCLUSIONS: Using the follow-up thresholds, more than half of the malignancies not being biopsied were monitored by ultrasound in both ACR TIRADS and AI TIRADS, and AI TIRADS had lower missing cancer rate. More than 90% of malignancies recommended for no further evaluation were <10 mm in diameter.

Transplantation of Autologous Bone Marrow Mononuclear Cells Regulates Inflammation in a Rabbit Model of Carotid Artery Atherosclerosis.

OBJECTIVE: It is well known that inflammation plays key roles in the development of atherosclerosis and that the transplantation of bone marrow mononuclear cells (BMMNCs) can suppress inflammation in rodent models of ischemic diseases. Here, we explored whether transplantation of autologous BMMNCs could prevent the progression of atherosclerosis by the alleviation of inflammatory responses in a rabbit model of carotid artery atherosclerosis. METHODS AND RESULTS: The atherosclerotic rabbit model was established by air desiccation followed by a high-cholesterol diet for 8 weeks. Then, 1 × 107 BMMNCs labeled with BrdU or an equal volume of vehicle were injected into the rabbits via the ear vein. Using an ultrasonographic imaging method, we found that autologous BMMNC treatment significantly decreased the area of atherosclerotic plaques compared to the vehicle-treated group (p < 0.05). The results were further confirmed by hematoxylin-eosin staining. RT-PCR results demonstrated that BMMNC treatment significantly reduced the expression of interleukin (IL)-6 and CD147 but increased the expression of IL-10 and transforming growth factor-ß compared with vehicle treatment (p < 0.05), which was consistent with Western blot results. CONCLUSIONS: Transplantation of autologous BMMNCs delays the development of atherosclerosis, most probably via the attenuation of inflammatory responses, which could be a new approach for treating carotid atherosclerosis.

Comparison of ultrasound risk stratification systems for pediatric thyroid nodules.

Background: There is currently insufficient data to validate adult-based US risk stratification systems (RSSs) for the identification of malignant thyroid nodules in a pediatric population. Methods: From October 2016 and May 2023, 173 thyroid nodules of pediatric patients (age ≤ 18 years) with definitive pathology results and ultrasound (US) examination within 1 month before surgery or fine-needle aspiration (FNA) biopsy in our institution were enrolled in this study. The clinical and US characteristics of these nodules were retrospectively reviewed and categorized according to the ACR-TIRADS, C-TIRADS, and ATA guidelines. The diagnostic performance of US-based FNA criteria (original and simulating) of the three guidelines in thyroid cancer detection was estimated. Results: The three RSSs had similar AUC according to the categories(0.849-0.852, all P > 0.05). When combined with the original FNA criteria of the three RSSs to manage the nodules, the FNA rate of ACR-TIRADS and C-TIRADS were significantly less than ATA guidelines (53.18% vs. 64.63%, P < 0.05, and 52.60% vs. 64.63%, P < 0.05). The missed malignancy rate (MMR) and unnecessary FNA rate (UFR) of ATA guidelines (50.00%, 35.85%) was highest among the three RSSs, followed by the C-TIRADS (37.80%, 19.57%) and the ACR-TIRADS (37.04%, 19.57%). When nodules < 1 cm with the highest category in each RSS biopsied, that is when using the simulating FNA thresholds, the MMR was reduced overall (all P < 0.001), without a change in the UFR (all P > 0.05). All the three RSSs showed a substantial improvement in accuracy and malignant detection rate (all P < 0.05). Conclusion: The ACR-TIRADS, C-TIRADS, and ATA guidelines showed high missed malignancy rates when using their original recommended FNA criteria. When nodules < 1 cm with the highest category in each RSS biopsied, the missed malignancy rate of each RSS was decreased. Decreasing the FNA thresholds for highly suspicious malignant nodules may therefore be an effective means of managing malignant thyroid nodules in pediatric patients.

A combination of risk stratification systems for thyroid nodules and cervical lymph nodes may improve the diagnosis and management of thyroid nodules.

Introduction: To assess the performance of the European Thyroid Association Thyroid Imaging and Reporting Data System (EU-TIRADS) and the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), which combine risk stratification systems for thyroid nodules (TN-RSS) and cervical lymph nodes (LN-RSS) in diagnosing malignant and metastatic thyroid cancer in a single referral center. Methods: We retrospectively analyzed 2,055 consecutive patients who underwent thyroidectomy or fine-needle aspiration (FNA) from January 2021 to December 2022. TNs and LNs were categorized according to the ultrasonography (US) features of EU-TIRADS and K-TIRADS, respectively. The diagnostic performance and postponed malignancy rate (PMR) were compared with those of EU-TIRADS and K-TIRADS. PMR was defined as the number of patients with malignant nodules not recommended for biopsy among patients with cervical LN metastasis. Results: According to the EU-TIRADS and K-TIRADS, for TN-RSS alone, there were no significant differences in sensitivity, specificity, accuracy, unnecessary FNA rate (UFR), missed malignancy rate (MMR), and PMR between the two TIRADSs (29.0% vs. 28.8%, 50.5% vs. 51.1%, 32.3% vs. 32.2%, 23.6% vs. 23.5%, 88.6% vs. 88.5%, and 54.2% vs. 54.5%, P > 0.05 for all). Combining the LN-RSS increased the diagnostic accuracy (42.7% vs. 32.3% in EU-TIRADS; 38.8% vs. 32.2% in K-TIRADS) and decreased the PMR (54.2% vs. 33.9% in EU-TIRADS; 54.5% vs. 39.3% in K-TIRADS). EU-TIRADS had higher sensitivity and accuracy and lower PMR than K-TIRADS (41.3% vs. 36.7%, 42.7% vs. 38.8%,33.9% vs. 39.3%, P < 0.05 for all). Conclusions: A combination of TN-RSS and LN-RSS for the management of thyroid nodules may be associated with a reduction in PMR, with enhanced sensitivity and accuracy for thyroid cancers in EU-TIRADS and K-TIRADS. These results may offer a new direction for the detection of aggressive thyroid cancers.

An economically efficient strategy for diagnosing atypia of undetermined significance or follicular lesion of undetermined significance thyroid nodules with ultrasound-based risk stratification systems and BRAFV600E testing.

Background: The management of thyroid nodules classified as atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) has been a subject of ongoing debate. Therefore, the aim of this study was to investigate a cost-effective approach for managing these nodules by combining BRAFV600E mutation analysis with the guidelines provided by the American Thyroid Association (ATA) or the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TIRADS). Methods: This study included 762 AUS/FLUS nodules in 551 patients with a postoperative pathology. A preoperative BRAFV600E gene test and an evaluation using the ATA guidelines and ACR-TIRADS were performed. Two combined diagnostic approaches were employed: In method 1, all nodules underwent BRAFV600E gene testing, and nodules testing positive for BRAFV600E or for risk stratification systems (RSSs) were diagnosed as malignant, while those with negative results in both tests were considered benign. In method 2 (modified combination method), nodules were reclassified into low-risk (category 2 and 3 in the ATA guidelines and ACR-TIRADS), medium-risk (category 4), and high-risk (category 5) groups based on the malignancy rate of the RSSs. BRAFV600E gene testing was applied only with the medium-risk group. Nodules with positive BRAFV600E mutation were upgraded to the high-risk group, while negative cases remained in the medium-risk group. Results: Both malignancy rates and positive BRAFV600E mutation rates increased with the increase in RSS category (P<0.001). The combination of ACR with BRAFV600E gene testing significantly improved the area under the curve (AUC) compared to the use of ACR or BRAFV600E alone (the AUCs for ACR combined with BRAFV600E, modified ACR combined with BRAFV600E, ACR alone, and BRAFV600E alone were 0.875, 0.878, 0.832, and 0.839, respectively; P<0.05 for both combinations vs. ACR or BRAFV600E alone). Similarly, ATA combined with BRAFV600E showed significant improvements in AUC compared to ATA alone (the AUCs for ATA combined with BRAFV600E, modified ATA combined with BRAFV600E, and ATA alone were 0.851, 0.846, 0.809, respectively; P<0.001 for both combination methods vs. ATA alone), but there was no significant difference observed compared to using BRAFV600E alone (P=0.450 and P=0.680 for both combination methods vs. BRAFV600E). Notably, the AUC of ACR combined with BRAFV600E was greater than that of ATA combined with BRAFV600E (P=0.047 and P=0.007 for both combination methods, respectively). There were no significant differences in diagnostic performance between the two combination approaches (P=0.428 for ACR combined with BRAFV600E and P=0.314 for ATA combined with BRAFV600E). Performing BRAFV600E gene testing only on the medium-risk groups (modified combination method) significantly reduced the rate of BRAFV600E gene testing (P<0.001) without increasing the false-negative rate (P=0.818 and P=0.394 for ACR and ATA, respectively). Conclusions: Incorporating the BRAFV600E gene test exclusively for nodules in the medium-risk group significantly improved diagnostic efficacy, reduced the utilization of gene tests, and maintained a consistent false-negative rate.

A comprehensive comparative assessment of eight risk stratification systems for thyroid nodules in the elderly population.

Objective: This study aims to investigate the diagnostic value of eight risk stratification systems (RSSs) for thyroid nodules in the elderly and explore the reasons in comparison with a younger group. Methods: Cases of thyroid nodules that underwent ultrasound examination with thyroidectomy or fine-needle aspiration (FNA) at our hospital between August 2013 and March 2023 were collected. The patients were categorized into two groups: an elderly group (aged ≥60) and a younger group (aged <60). Eight RSSs were applied to evaluate these nodules respectively. Results: The malignant rate in the elderly group was significantly lower than that in the younger group (28.2% vs. 49.6%, P=0.000). There were statistically significant differences in nodule diameter, multiplicity, composition, echogenicity, orientation, margin, and echogenic foci between the elderly and younger groups (P<0.05). Among the eight RSSs evaluated in elderly adults, the artificial intelligence-based Thyroid Imaging Reporting and Data System (AI TIRADS) demonstrated the highest overall diagnostic efficacy, but with relatively high unnecessary FNA rate (UFR) and missed cancer rate (MCR) of 55.0% and 51.3%, respectively. By modifying the size thresholds, the new AI TI-RADS achieved the lowest UFR and MCR while maintaining nearly the lowest FNA rate (FNAR) among all the RSSs (P=0.172, 0.162, compared to the ACR and original AI, respectively, but P<0.05 compared to the other six RSSs). Conclusion: Among the eight RSS systems, AI demonstrated higher diagnostic efficacy in the elderly population. However, the size thresholds for FNA needed to be adjusted.

The feasibility of decreasing the thresholds for biopsy in Kwak and C TIRADSs.

Objectives: To estimate the feasibility of decreasing the original thresholds for biopsy in the Kwak Thyroid Imaging Reporting and Data System (Kwak TIRADS) and Chinese Thyroid Imaging Reporting and Data System (C TIRADS). Methods: This retrospective study included 3,201 thyroid nodules from 2,146 patients with a pathological diagnosis. We lowered the original fine-needle aspiration (FNA) thresholds with the TR4a-TR5 in Kwak and C TIRADSs and calculated the ratio of additional benign-to-malignant nodules being biopsied (RABM). If the RABM is less than 1, the decreased FNA thresholds could be accepted and used to the modified TIRADSs (modified C and Kwak TIRADSs). Then, we estimated and compared the diagnostic performance between the modified TIRADS and the original TIRADS to determine if the decreased thresholds could be an effective strategy. Results: A total of 1,474 (46.0%) thyroid nodules were diagnosed as malignant after thyroidectomy. The TR4c-TR5 in Kwak TIRADS and TR4b-TR5 in C TIRADS had a rational RABM (RABM < 1). The modified Kwak TIRADS had higher sensitivity, a positive predictive value, a negative predictive value, lower specificity, an unnecessary biopsy rate, and a missed malignancy rate compared with the original Kwak TIRADS (94.1% vs. 42.6%, 59.4% vs. 44.6%, 89.9% vs. 52.8%, 45.0% vs. 54.9%, 40.6% vs. 55.4%, and 10.1% vs. 47.1%, respectively, P < 0.05 for all). Similar trends were seen in the modified C TIRADS versus the original C TIRADS (95.1% vs. 38.7%, 61.7% vs. 47.8%, 92.3% vs. 55.0%, 49.7% vs. 64.0%, 38.3% vs. 52.2%, and 7.7% vs. 44.9%, respectively, P < 0.05 for all). Conclusions: The biopsy of all nodules with TR4C-TR5 in the Kwak TIRADS and TR4B-TR5 in the C TIRADS might be an effective strategy. This paper contributes to the contradiction concerning whether to perform FNA for the nodules smaller than 10 mm.

The course and prognostic value of tumor stiffness detected by ultrasound elastography for transarterial chemoembolization of hepatocellular carcinoma.

Background: Transarterial chemoembolization (TACE) is recommended as the first-line treatment in intermediate-stage patients with hepatocellular carcinoma (HCC) or as a palliative treatment modality in advanced patients. However, tumor control usually requires multiple TACE interventions due to the presence of residual and recurrent lesions. Elastography can provide information about tumor stiffness (TS) to predict tumor residual or recurrence. In this study, we aimed to analyze the effects of TACE on HCC stiffness using ultrasound elastography (US-E). We investigated whether quantifying TS using US-E could predict the recurrence of HCC. Methods: This retrospective cohort study included 116 patients undergoing TACE to treat HCC. US-E was performed to measure the tumor's elastic modulus within 3 days before TACE, in the 2 days after the intervention, and at the 1-month follow-up. The known prognostic factors of HCC were also analyzed. Results: The average TS before TACE was 40.1±14.36 kPa, and the average TS 1 month after TACE was 19.3±9.80 kPa. The mean progression-free survival (PFS) was 39.129 months, and the 1-, 3-, and 5-year PFS rates were 81.0%, 56.9%, and 37.9%, respectively. The mean overall survival (OS) was 48.552 months, and the 1-, 3-, and 5-year OS rates of patients with malignant hepatic tumors were 95.7%, 75.0%, and 49.1%, respectively. Tumor number, tumor location, TS before TACE, and TS 1 month after TACE were significant predictive factors for OS (P=0.02, P=0.03, P<0.001, and P<0.001, respectively). Rank correlation analysis and linear regression revealed that a higher TS before or 1 month after TACE was negatively associated with PFS. The reduction ratio in TS before and 1 month after therapy was positively associated with PFS. The optimal cutoff TS value was set at 46 and 24.5 kPa before and 1 month after TACE according to the optimal Youden index. Kaplan-Meier survival analyses demonstrated that the 2 groups had significant differences in OS and PFS and that a higher TS was positively correlated with OS and PFS. Conclusions: Our results verify that US-E provides additional information to characterize the tumoral stiffness of HCC. These findings indicate that US-E is a valuable tool for evaluating the tumor response after TACE therapy in patients. TS can also be an independent prognostic factor. Patients with a high TS had a higher risk of recurrence and a worse survival time.

Effect of the categorization method on the diagnostic performance of ultrasound risk stratification systems for thyroid nodules.

Objective: To evaluate whether the categorization methods of risk stratification systems (RSSs) is a decisive factor that influenced the diagnostic performances and unnecessary FNA rates in order to choose optimal RSS for the management of thyroid nodules. Methods: From July 2013 to January 2019, 2667 patients with 3944 thyroid nodules had undergone pathological diagnosis after thyroidectomy and/or US-guided FNA. US categories were assigned according to the six RSSs. The diagnostic performances and unnecessary FNA rates were calculated and compared according to the US-based final assessment categories and the unified size thresholds for biopsy proposed by ACR-TIRADS, respectively. Results: A total of 1781 (45.2%) thyroid nodules were diagnosed as malignant after thyroidectomy or biopsy. Significantly lowest specificity and accuracy, along with the highest unnecessary FNA rates were seen in EU-TIRADS for both US categories (47.9%, 70.2%, and 39.4%, respectively, all P < 0.05) and indications for FNA (54.2%, 50.0%, and 55.4%, respectively, all P < 0.05). Diagnostic performances for US-based final assessment categories exhibited similar accuracy for AI-TIRADS, Kwak-TIRADS, C-TIRADS, and ATA guidelines (78.0%, 77.8%, 77.9%, and 76.3%, respectively, all P > 0.05), while the lowest unnecessary FNA rate was seen in C-TIRADS (30.9%) and without significant differences to that of AI-TIRADS, Kwak-TIRADS, and ATA guideline (31.5%, 31.7%, and 33.6%, respectively, all P > 0.05). Diagnostic performance for US-FNA indications showed similar accuracy for ACR-TIRADS, Kwak-TIRADS, C-TIRADS and ATA guidelines (58.0%, 59.7%, 58.7%, and 57.1%, respectively, all P > 0.05). The highest accuracy and lowest unnecessary FNA rate were seen in AI-TIRADS (61.9%, 38.6%) and without significant differences to that of Kwak-TIRADS(59.7%, 42.9%) and C-TIRADS 58.7%, 43.9%, all P > 0.05). Conclusion: The different US categorization methods used by each RSS were not determinant influential factors in diagnostic performance and unnecessary FNA rate. For daily clinical practice, the score-based counting RSS was an optimal choice.

Diagnostic and therapeutic performances of three score-based Thyroid Imaging Reporting and Data Systems after application of equal size thresholds.

Background: The aim of this study was to explore the diagnostic and therapeutic performances of the artificial intelligence (AI), American College of Radiology (ACR), and Kwak Thyroid Imaging Reporting and Data Systems (TIRADSs) using the size thresholds for fine needle aspiration (FNA) and follow-up defined in the ACR TIRADS. Methods: This retrospective study included 3,833 consecutive thyroid nodules identified in 2,590 patients from January 2010 to August 2017. Ultrasound (US) features were reviewed using the 2017 white paper of the ACR TIRADS. US categories were assigned according to the ACR/AI and Kwak TIRADS. We applied the thresholds for FNA and follow-up defined in the ACR TIRADS to the Kwak TIRADS. The diagnostic and therapeutic performances were calculated and compared using the McNemar or DeLong methods. Results: The AI TIRADS had higher specificity, accuracy, and area under the curve (AUC) than did the ACR and Kwak TIRADS (specificity: 64.6% vs. 57.4% and 52.69%; accuracy: 78.5% vs. 75.4% and 73.0%; AUC: 88.2% vs. 86.6% and 86.0%; all P values <0.05). Meanwhile, the AI TIRADS had a lower FNA rate (FNAR), unnecessary FNA rate (UFR), and follow-up rate (FUR) than did the ACR and Kwak TIRADS using the size thresholds of the ACR TIRADS (specificity: 30.9% vs. 34.4% and 36.9%; accuracy: 41.1% vs. 47.8% and 48.7%; AUC: 34.2% vs. 37.7% and 41.0%; all P values <0.05). In addition, the Kwak TIRADS incorporating the size thresholds of the ACR TIRADS was almost similar to the ACR TIRADS in diagnostic and therapeutical performance. Conclusions: The ACR TIRADS can be simplified, which potentially enhances its diagnostic and therapeutic performance. The method of score-based TIRADS (counting in the Kwak TIRADS and weighting in the ACR and AI TIRADS) might not determine the diagnostic and therapeutic performances of the TIRADS. Thus, we propose choosing a straightforward and practical TIRADS in daily practice.

Metformin protects against pericyte apoptosis and promotes neurogenesis through suppressing JNK p38 MAPK signalling activation in ischemia/reperfusion injury.

Metformin (MET) has been the subject of many classic studies in possessing antiapoptotic, anti-inflammatory, antioxidation activities and antiviral. Recently investigators have examined the anti-apoptosis effects of MET in acute myocardial infarction and Intracerebral hemorrhage, but very little is currently known about how it regulates ischemic stroke-induced pericytes apoptosis and neural stem cells (NSCs) proliferation. The present research explored the potential neuroprotective mechanisms of MET using transient middle cerebral artery occlusion(tMCAO) mice. The experimental work presented that tMCAO mice treated by metformin had better neurologic outcomes on days 1, 3, and 7 after operation, and alleviated blood-brain barrier (BBB) destruction, brain water content and infarct volume on 72 h after surgery. The data showed that MET alleviated BBB disruption by reducing PDGFRß/ matrix metalloproteinase-9 (MMP9) positive cells, relieving zonula occludens-1 (ZO-1) drop away and increasing pericyte coverage through remarkably reducing the percentage of PDGFRß/caspase-3 positive cells. In addition, MET induced antiapoptotic activity followed by downregulating cleaved caspase-3 and Bax expression. Moreover, JNK signaling pathway has been proved to be pivotal in mediating apoptosis in cerebral ischemia/reperfusion (I/R) injury. The results of this research illustrated that MET treatment downregulated the levels of phosphorylated JNK and P38 in vivo, however the use of JNK activator anisomycin (ANI) could reverse the neuroprotection effect of MET, demonstrating that the JNK pathway is associated with the anti-apoptosis mechanisms of MET. Finally, metformin remarkably increased the percentage of BrdU/DCX-positive cells in subventricular zone (SVZ) and up-regulated BDNF、VEGF and NGF expression after ischemia/reperfusion(I/R) injury on day 7. Our data illustrated that metformin provides an effective therapy for I/R injury.

Efficacy on radiofrequency ablation according to the types of benign thyroid nodules.

Percutaneous radiofrequency ablation (RFA) has been recommended as minimally invasive treatment for patients with symptomatic benign thyroid nodules (BTNs) because of the large number of clinical applications. This retrospective observational study sought to evaluate the clinical outcomes of RFA for BTNs. From 2014 to 2019, a sample size of 1289 patients treated by RFA were 262 ones with solid nodules and 1027 ones with cystic-solid nodule, respectively. The efficacy including the nodule maximal diameter reduction ratio (MDRR), the volume reduction ratio (VRR) and the cosmetic scores reduction ratio (CSRR). The results of the nodule MDRR and VRR in the cystic-solid nodule group were significantly better than those in the solid nodule group at the 3rd and 6th month, and the CSRR in the two groups showed statistically significant difference at the 3rd month. In a word, RFA is an effective method for symptomatic benign solid or cystic-solid nodules. The achieved MDRR and VRR in the cystic-solid nodule group were significantly better than those in the solid nodule group at the 3rd and 6th month.

Protective effects of Dimethyl malonate on neuroinflammation and blood-brain barrier after ischemic stroke.

OBJECTIVES: After ischemic stroke, microglia will be activated and play a key role in neuroinflammation and the destruction of the blood-brain barrier (BBB), and activated microglia could polarize into pro-inflammation M1 phenotype and anti-inflammation M2 phenotype. Dimethyl malonate (DMM) could reduce reactive oxygen species and we speculate DMM could regulate microglia to protect ischemic brain. METHODS: We used transient middle cerebral artery occlusion (tMCAO) mouse model to simulate ischemic stroke and adult male C57BL/6 mice were used in our study. 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct volume. Evans Blue and Brain water content were used to evaluate the destruction of BBB. We used a five-point scale to assess the neurologic function of mice. Western blot and Immunofluorescence were used to measure microglia, pericytes and the expression of related proteins. RESULTS: DMM reduced cerebral infarct volume, Evans blue leakage, brain water content and improved neurologic deficits after tMCAO. The number of activated microglia and M1 microglia were decreased and the number of M2 microglia and pericytes were increased after DMM treatment. The expression of tumor necrosis factor-α was reduced while protein levels of IL-10 and ZO-1 were increased through DMM treatment. CONCLUSIONS: DMM could regulate activation and polarization of microglia to inhibit neuroinflammation and protect BBB.

DNA Hypomethylation of DOCK1 Leading to High Expression Correlates with Neurologic Deterioration and Poor Function Outcomes after Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) is a blood clot arising in the brain parenchyma in the absence of trauma or surgery and accounts for 10% to 15% of all strokes, leading to higher rates of mortality and morbidity than either ischemic stroke or subarachnoid hemorrhage. We sought to investigate the potential association of DOCK1 with neurological deficits and outcomes in patients with spontaneous ICH. METHODS: Identification of methylation-regulated differentially expressed genes (MeDEGs) between ICH patients and matched controls was performed by analyzing the raw data from the GSE179759 and GSE125512 datasets deposited in the Gene Expression Omnibus. A total of 114 patients who were admitted to our hospital for spontaneous ICH were retrospectively analyzed, with 108 healthy volunteers who had received physical examinations at the same period as controls. The mRNA expression of DOCK1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The hematoma volume was calculated according to the Coniglobus formula. The severity of neurological deficits was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores and function outcomes were evaluated by modified Rankin Scale (mRS) scores. RESULTS: A total of 15 MeDEGs between ICH patients and matched controls were identified. The mRNA expression of DOCK1 was remarkably higher in the serum samples of patients with spontaneous ICH than in the healthy controls. According to hematoma volume after ICH attack, small (<10 mL), medium (10 to 30 mL), and large (>30 mL) groups were arranged. The proportions of male patients and patients aged ≥60 years were significantly higher in the large group than in the small and medium groups (P < 0.05). The mRNA expression of DOCK1 was significantly higher in the large group than in the small and medium groups (P < 0.05). According to NIHSS scores, mild (NIHSS scores ≤15), moderate (NIHSS scores from 16 to 30), and severe (NIHSS scores from 31 to 45) groups were classified. It was observed that the severe group had higher proportions of male patients and patients aged ≥60 years than the mild and moderate groups (P < 0.05). The severe group exhibited a higher mRNA expression of DOCK1 than the mild and moderate groups (P < 0.05). According to mRS scores, higher proportions of male patients and patients aged ≥60 years were observed in the unfavorable group than the favorable group (P < 0.05). The patients in the unfavorable group showed an elevated DOCK1 mRNA expression compared to those in the favorable group (P < 0.05). CONCLUSION: The study provided evidence that male gender, older age, and higher DOCK1 mRNA expression were related to higher admission hematoma volume, neurologic deterioration, and poor function outcomes in patients with spontaneous ICH.

Donepezil promotes neurogenesis via Src signaling pathway in a rat model of chronic cerebral hypoperfusion.

Donepezil, a selective acetylcholinesterase (AchE) inhibitor, enhances stroke-induced neurogenesis within subventricular zone (SVZ). Src/Pyk-2 is one of the downstream pathways of acetylcholine receptors (AchRs), and has been shown to participate in the activation of fibroblast growth factor receptor (FGFR)/epidermal growth factor receptor (EGFR) signaling in cancer cells. In this study, we investigated whether donepezil could promote SVZ neurogenesis in chronic cerebral hypoperfusion (CCH) injury via Src signaling pathway. In the bilateral carotid artery occlusion (2VO) rat model, we observed more nestin/5-bromo-2'-deoxyuridine (BrdU)-positive cells and doublecortin (DCX)/BrdU-positive cells in the SVZ than that in the sham group. Further, donepezil obviously improved neurologic function after 2VO, induced the greater number of SVZ proliferative NSCs and neuroblasts, and elevated levels of Src, p-FGFR1, p-EGFR, p-Akt and p-Raf in ipsilateral SVZ. Lastly, Src inhibitor KX-01 abolished the beneficial effects of donepezil in 2VO rats. These results suggest that donepezil could upregulate Src signaling pathway to enhance CCH-induced SVZ neurogenesis.

Neuroprotective Action of Teriflunomide in a Mouse Model of Transient Middle Cerebral Artery Occlusion.

Teriflunomide has been reported to inhibit microglial activation in experimental models of traumatic brain injury. However, its roles in ischemic stroke and underlying mechanisms of action are still undiscovered. In this study, we investigated the effects of teriflunomide on brain edema, neurologic deficits, infarct volume, neuroinflammation, blood-brain barrier (BBB) permeability, and neurogenesis in a mouse model of transient middle cerebral artery occlusion (tMCAO). tMCAO mice treated with teriflunomide showed lower brain water content on day 3, milder neurologic deficits and smaller infarct volume on day 7 than those treated with vehicle. Additionally, mice received teriflunomide had fewer activated Iba-1-positive microglia and lower protein levels of interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), and 3-Nitrotyrosine (3-NT) compared with those received vehicle on day 3. Further, teriflunomide alleviated Evans blue dye leakage, increased pericyte coverage and protein levels of platelet-derived growth factor B (PDGFB), platelet-derived growth factor receptor ß (PDGFRß) and Bcl2, and decreased the number of PDGFRß/matrix metalloproteinase 9 (MMP9)-positive cells. Moreover, teriflunomide reduced the loss of zonula occludens-1 (ZO-1) and occludin. Finally, teriflunomide significantly upregulated the number of 5-bromo-20-deoxyuridine (BrdU)/doublecortin (DCX)-positive cells and expression of mammalian achaete-scute homolog 1 (Mash1), DCX and Pbx1 in subventricular zone (SVZ) on day 7 after stroke. Our results indicate that teriflunomide exhibits protective roles in ischemic stroke by inhibiting neuroinflammation, alleviating BBB disruption and enhancing neurogenesis.

Papillary thyroid carcinoma with tracheal invasion: A case report.

RATIONALE: Compared with most malignant tumors, papillary thyroid carcinoma (PTC) is usually associated with favorable survival and low recurrence rate. The prognostic factors of PTC include age, sex, tumor size, enlarged lymph nodes, and extrathyroidal extension. Among the extrathyroidal extension, upper aerodigestive tract (ADT) invasion by PTC is a marker of more aggressive tumor behavior, defining a subpopulation of patients at a greater risk of recurrence and death. PATIENT CONCERNS: A 61-year-old woman had a cervical mass that was slowly growing for three years. Additionally, she had haemoptysis of 1-year duration. During the month prior to her visit, she had difficulty breathing. DIAGNOSIS: Neck ultrasonography (US) and thyroid computed tomography (CT) images both showed a well-defined calcified mass on the left lobe of the thyroid gland. Additionally, the thyroid CT revealed that part of the mass protruded into the lumen which resulted in the thickening on the left side of the trachea. Accordingly, her diagnoses were as follows: firstly, a solid mass on the left lobe of the thyroid gland with tracheal compression; and finally, the space-occupying airway lesion. INTERVENTIONS: She underwent a bronchoscopic examination, which revealed a mass blocking most of the upper endoluminal trachea. Thus, the mass was resected at the upper tracheal segment, followed by electrotome and argon plasma coagulation treatment. She was then transferred to the Thyroid Surgery Department. Thyroid surgeons took the surgical type of bilateral subtotal thyroidectomy + exploration of bilateral recurrent laryngeal nerve + dissection of the lymph node in neck central area + circumferential sleeve resection + end-to-end anastomosis + tracheotomy in the patient. OUTCOMES: After surgery, she recovered well without any local recurrence or distant metastasis. LESSONS: When patients with PTC have haemoptysis, hoarseness, dyspnea, or any other symptoms, and the imaging examinations reveal a space-occupying lesion in the thyroid and airway, clinicians should focus on PTC with tracheal invasion, a bronchoscopic examination must be immediately performed because the subsequent surgical management depends on the degree of tracheal invasion.

EPO promotes axonal sprouting via upregulating GDF10.

Erythropoietin (EPO) has an exact neuroprotective effect on stroke. However, it remains unknown whether it participates in axonal sprouting after neuron damage. Growth and differentiation factor 10 (GDF10) has been shown to be a trigger of axonal sprouting after stroke. Hence, it was hypothesized that EPO promotes axonal sprouting mainly through GDF10. In the present in vitro experiment, it was found that EPO could promote axonal sprouting and GDF10 expression in a dose-dependent manner. The knockdown of GDF10 using siRNA abolished the effect of EPO-mediated axonal sprouting, indicating that GDF10 is the executor of EPO-mediated axonal sprouting. The treatment of neurons with nuclear factor-kappaB (NF-κB) inhibitor JSH-23 could inhibit the accumulation of NF-κB phospho-p65 (p-p65) in the nucleus, the upregualtion of GDF10 and extending of axonal length. Furthermore, the addition of Janus kinase 2 (JAK2) inhibitor CEP-33779 or phosphoinositide 3-kinase (PI3K) inhibitor LY294002 to the culture medium also blocked the nuclear translocation of p-p65, the expression of GDF10, and axonal sprouting, suggesting that EPO induces axonal sprouting via activating cellular JAK2 and PI3K signaling. Impeding JAK2 signaling with CEP-33779 can suppress the phosphorylation of PI3K, and this confirms that the upstream of PI3K signaling is JAK2. These present results provide a novel insight into the role of EPO and the molecular mechanism of axonal sprouting, which is beneficial for the development of novel approaches for neurological recovery after brain injury, including stroke.

Wnt-3a alleviates neuroinflammation after ischemic stroke by modulating the responses of microglia/macrophages and astrocytes.

Neuroinflammation crucially influences functional recovery after ischemic stroke. Wnt-3a, a novel Wnt protein that specifically promotes Wnt/ß-catenin signaling pathway, has been shown to regulate apoptosis and cell proliferation, but how it affects ischemic stroke-induced toxic brain inflammation remains unknown. Using a transient middle cerebral artery occlusion (tMCAO) mouse model in this study, we found that intranasal Wnt-3a-treated tMCAO mice had apparently reduced infarct volume and decreased brain water content after being allowed to recover for 72 h, as well as better neurologic outcomes on days 3, 7, and 14. Mice received Wnt-3a had significantly fewer tMCAO-induced peri-infarct TUNEL-positive cells compared with those received vehicle. Further, Wnt-3a-delivered tMCAO mice had notably fewer peri-infarct CD68-positive cells and lower ionized calcium-binding adapter molecule (Iba)-1 protein level. Wnt-3a significantly downregulated the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α, and upregulated the expression of arginase 1 (Arg1) and CD206. Finally, Wnt-3a obviously decreased the number of tMCAO-induced peri-infarct glial fibrillary acidic protein (GFAP)/C3-positive cells, increased the number of GFAP/S100A10-positive cells, attenuated the protein levels of GFAP and interleukin 15 (IL15), and elevated IL33 protein level. Our findings suggest that intranasal Wnt-3a could ameliorate toxic responses of microglia/macrophages and astrocytes in ischemic brain injury, supporting that Wnt-3a might be potentially appropriate for ischemic stroke treatment functioning as an immunomodulatory agent.

Chinese association of ultrasound in medicine and engineering, superficial organs and peripheral vessels committee expert consensus on clinical frequently asked questions in breast ultrasonography, June 2018.

Ultrasonography, the preferred imaging modality for breast diseases, has merits such as absence of radiation, high diagnostic accuracy, and convenience for follow-up, thus playing an important role in clinical diagnosis and management. The American College of Radiology (ACR) proposed Breast Imaging-Reporting and Data System (BI-RADS ) and has updated for several times. Gradually, the BI-RADS has been accepted and adopted by ultrasound physicians at all levels of hospitals in China, and it has played a certain role in improving the diagnostic level of breast ultrasound in China. In order to standardize breast ultrasound application and raise the status of ultrasound in clinical decision-making of breast diseases, based on the latest edition of ACR BI-RADS Atlas 2013, the committee has reached the "Expert Consensus on Clinical Frequently Asked Questions in Breast Ultrasonography"on a number of controversial Frequently Asked Questions (FAQs) in clinical practice (hereafter referred to as "Consensus"), and will be dedicated to updating the contents of the "Consensus", through further experience in clinical practice and the advent of new information from further studies. This consensus is only for reference purposes for medical personnel, and the processes outlined are not mandatory by law.