The Preventive Effect of Specific Collagen Peptides against Dexamethasone-Induced Muscle Atrophy in Mice.

Muscle atrophy, also known as muscle wasting, is the thinning of muscle mass due to muscle disuse, aging, or diseases such as cancer or neurological problems. Muscle atrophy is closely related to the quality of life and has high morbidity and mortality. However, therapeutic options for muscle atrophy are limited, so studies to develop therapeutic agents for muscle loss are always required. For this study, we investigated how orally administered specific collagen peptides (CP) affect muscle atrophy and elucidated its molecular mechanism using an in vivo model. We treated mice with dexamethasone (DEX) to induce a muscular atrophy phenotype and then administered CP (0.25 and 0.5 g/kg) for four weeks. In a microcomputed tomography analysis, CP (0.5 g/kg) intake significantly increased the volume of calf muscles in mice with DEX-induced muscle atrophy. In addition, the administration of CP (0.25 and 0.5 g/kg) restored the weight of the gluteus maximus and the fiber cross-sectional area (CSA) of the pectoralis major and calf muscles, which were reduced by DEX. CP significantly inhibited the mRNA expression of myostatin and the phosphorylation of Smad2, but it did not affect TGF-ß, BDNF, or FNDC5 gene expression. In addition, AKT/mTOR, a central pathway for muscle protein synthesis and related to myostatin signaling, was enhanced in the groups that were administered CP. Finally, CP decreased serum albumin levels and increased TNF-α gene expression. Collectively, our in vivo results demonstrate that CP can alleviate muscle wasting through a multitude of mechanisms. Therefore, we propose CP as a supplement or treatment to prevent muscle atrophy.

Comparison of HU histogram analysis and BMD for proximal femoral fragility fracture assessment: a retrospective single-center case-control study.

OBJECTIVES: To evaluate the feasibility of HU histogram analysis (HUHA) to assess proximal femoral fragility fractures with respect to BMD. METHODS: This retrospective study included 137 patients with femoral fragility fractures who underwent hip CT and 137 control patients without fractures who underwent abdominal CT between January 2018 and February 2019. HUHA was calculated with the 3D volume of interest from the femoral head to the lesser trochanter. HUHAfat (percentage of negative HU values) and HUHAbone (percentage of HU values ≥ 125 HU) were assumed to be fat and bone components, respectively. Statistical significance was assessed using the area under the receiver operating characteristic curve (AUC), Spearman correlation (ρ), and odds ratio. RESULTS: HUHAfat was strongly positively correlated (ρ = 0.56) and BMD was moderately negatively correlated with fragility fractures (ρ = - 0.37). AUC of HUHAfat (0.82, 95% CI [0.77, 0.87]) significantly differed from that of BMD (0.69, 95% CI [0.63, 0.75]) (p < .001). The cutoff value was 15.8% for HUHAfat (sensitivity: 90.4%; specificity: 67.7%) and 0.709 g/cm2 for BMD (sensitivity: 87.5%; specificity: 51.5%), with higher HUHAfat and lower BMD values indicating fragility fractures. The odds ratio of HUHAfat was 19.5 (95% CI [9.9, 38.2], p < .001), which was higher than that of BMD, 7.4 (95% CI [4.0, 13.6], p < .001). CONCLUSION: HUHAfat revealed better performance than BMD and demonstrated feasibility in assessing proximal femoral fragility fractures. KEY POINTS: • HUHAfat showed a strong positive correlation (Spearman ρ = 0.56, p < .001), and BMD showed a moderate negative correlation (Spearman ρ = - 0.37, p < .001) with proximal femoral fragility fractures. • HUHAfat (AUC = 0.82) performed significantly better than BMD in assessing proximal femoral fragility fractures (AUC = 0.69) (p < .001). • The odds ratio of HUHAfat for proximal femoral fragility fractures was higher than that of BMD (19.5 and 7.4, respectively; p < .001).

Chrysin-Induced G Protein-Coupled Estrogen Receptor Activation Suppresses Pancreatic Cancer.

Pancreatic cancer (PC) has a high mortality rate due to its poor prognosis and the possibility of surgical resection in patients with the disease. Importantly, adjuvant chemotherapy is necessary to improve PC prognosis. Chrysin, a natural product with anti-inflammatory, antioxidant, and anticancer properties, has been studied for several years. Our previous study demonstrated that chrysin induced G protein-coupled estrogen receptor (GPER) expression and regulated its activity in breast cancer. Herein, we investigated whether chrysin-induced GPER activation suppresses PC progression in MIA PaCa-2 cells and a xenograft model. To determine its mechanism of action, cytotoxicity and clonogenic assays, a FACS analysis, and Western blotting were performed. Furthermore, the delay in tumor growth was evaluated in the MIA PaCa-2-derived xenograft model. Tumor tissues were investigated by Western blotting, immunohistochemistry, and a proteomic analysis. Chrysin caused cell cycle arrest and significantly decreased cell viability. Following co-treatment with chrysin and 17ß-estradiol, the inhibitory effect of chrysin on cell proliferation was enhanced. In the xenograft model, chrysin and G1 (a GPER agonist) significantly delayed tumor growth and reduced both Ki-67 (a proliferation marker) and c-Myc expressions in tumor tissues. The proteomic analysis of tumor tissues identified that rho-associated coiled-coil containing protein kinase 1 (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) levels were significantly reduced in chrysin-treated tumor tissues. High ROCK1, TAGLN2, and FCHO2 expressions were indicative of low overall PC survival as found using the Kaplan-Meier plotter. In conclusion, our results suggest that chrysin suppresses PC progression through the activation of GPER and reductions in ROCK1, TAGLN2, and FCHO2 expressions.

Comparison of the diagnostic performance of CT Hounsfield unit histogram analysis and dual-energy X-ray absorptiometry in predicting osteoporosis of the femur.

PURPOSE: To evaluate the diagnostic performance of Hounsfield unit histogram analysis (HUHA) of precontrast abdominal-pelvic CT scans for predicting osteoporosis. MATERIALS AND METHODS: The study included 271 patients who had undergone dual X-ray absorptiometry (DXA) and abdominal-pelvic CT within 1 month. HUHA was measured using commercial 3D analysis software (Aquarius iNtuition v4.4.12Ⓡ, TeraRecon) and expressed as a percentage of seven HU range categories related to the ROI: A < 0, 0 ≤ B < 25, 25 ≤ C < 50, 50 ≤ D < 75, 75 ≤ E < 100, 100 ≤ F < 130, and 130 ≤ G. A coronal reformatted precontrast CT image containing the largest Ward's triangle was selected and then the ROI was drawn over the femoral neck. Correlation (r) and ROC curve analyses were used to assess diagnostic performance in predicting osteoporosis using the femur T-score as the reference standard. RESULTS: When the femur T-score was used as the reference, the rs of HUHA-A and HUHA-G were 0.74 and -0.57, respectively. Other HUHA values had moderate to weak correlations (r = -0.33 to 0.27). The correlation of HUHA-A was significantly higher than that of HUHA-G (p = 0.03). The area under the curve (0.95) of HUHA-A differed significantly from that of HUHA-G (0.90; p < 0.01). A HUHA-A threshold ≥ 27.7% was shown to predict osteoporosis based on a sensitivity and specificity of 95.6% and 81.7%, respectively. CONCLUSION: The HUHA-A value of the femoral neck is closely related to osteoporosis and may help predict osteoporosis. KEY POINTS: • HUHA correlated strongly with the DXA femur T-score (HUHA-A, r = 0.74). • The diagnostic performance of HUHA for predicting osteoporosis (AUC = 0.95) was better than that of the average CT HU value (AUC = 0.91; p < 0.05). • HUHA may help predict osteoporosis and enable semi-quantitative measurement of changes in bone mineral density.

Factors influencing the outcome from ultrasonography-guided fine-needle aspiration of benign thyroid cysts and partially cystic thyroid nodules: A multicenter study.

PURPOSE: The effect of ultrasonography (US)-guided fine-needle aspiration (US-FNA) for the collapse of benign cystic thyroid nodules is still unclear. This study aimed to assess the positive response rate following US-FNA of the cystic component of thyroid cysts and of partially cystic thyroid nodules (PCTNs), and to evaluate the factors influencing the outcome. METHODS: From June to December 2013, seven radiologists at seven institutions prospectively performed US-FNA on 320 cystic thyroid nodules in 320 patients. Among them, 179 underwent at least one follow-up US examination following US-FNA of the cystic component at each institution by the same radiologist. A variety of factors, including US features of cystic thyroid nodules, the characteristics of the aspirates, and the follow-up US findings, were analyzed. RESULTS: Of 179 cystic thyroid nodules, there were 53 thyroid cysts and 126 PCTNs. Of 179 cystic thyroid nodules, no malignancies were detected. On follow-up US, the mean size reduction rate of the cystic component was 31.9%, and 102 out of 179 thyroid nodules (57.0%) were assigned to the response group. On univariate analysis, the degree of aspiration and time interval between US-FNA and the final follow-up US showed the significant differences between the response and no response groups. On multivariate analysis, the only factor that influenced the outcome was the nodule type. The cystic component's positive response rate after simple aspiration was higher in the thyroid cysts than in the PCTNs. CONCLUSIONS: US-FNA may be effective at collapsing the cystic components of benign thyroid cysts and PCTNs.

Follicular variant of papillary thyroid carcinoma: comparison of ultrasound-guided core needle biopsy and ultrasound-guided fine needle aspiration in a multicentre study.

OBJECTIVE: Pre-operative diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) by ultrasound-guided fine needle aspiration (US-FNA) remains a challenge. The goal of this study was to investigate whether ultrasound-guided core needle biopsy (US-CNB) is superior to US-FNA in refining the surgical indications for the treatment of FVPTC. DESIGN: This retrospective study enrolled 212 patients with 218 FVPTCs who were surgically confirmed at three university hospitals from January 2008 through December 2014. All patients underwent both or either US-FNA or US-CNB. FNA and CNB results were divided into identified surgical candidates or not based on the Bethesda system. Relevant clinical information and the rate of surgical candidates were compared between US-FNA and US-CNB groups. RESULTS: Among 218 thyroid nodules, US-FNA was performed for 200 nodules and US-CNB for 51 nodules. Thirty-three nodules underwent both US-FNA and US-CNB. The rates of surgical candidates identified by US-FNA and US-CNB were 61·5% and 86·3%, respectively (P = 0·001). The rates of surgical candidates identified by repeat US-FNA and initial US-FNA with subsequent US-CNB were 53·9% and 78·8%, respectively (P = 0·042). A precise diagnosis of FVPTC was made in 1% of the patients in the US-FNA group and in 29·4% of the patients in the US-CNB group. The predominant US findings of FVPTCs included solid tumours (89·4%), wider-than-tall shape (82·6%), no calcifications (51·3%), hypoechogenicity (46·3%) and indeterminate diagnosis on US (50·5%). CONCLUSIONS: In patients with FVPTC, US-CNB is a superior indicator for surgery compared to US-FNA. If a FVPTC is suspected but is initially indeterminate at FNA cytology, subsequent US-CNB should be considered instead of repeat US-FNA.

Preoperative differentiation between noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and non-NIFTP.

BACKGROUND: A recent concept was proposed that the noninvasive encapsulated follicular variant of papillary thyroid carcinoma reclassified as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)" is benign. Our aim was to identify the differences between NIFTP and non-NIFTP preoperatively. METHODS: This retrospective study included a total of 208 patients with 208 follicular variant of papillary thyroid carcinomas (FVPTC) that were surgically confirmed at three university hospitals from 2008 to 2014. Clinical factors, the biopsy techniques and ultrasonography (US) imaging characteristics were compared between the NIFTP and non-NIFTP groups. RESULTS: A total of 34 NIFTP (16·3%) and 174 non-NIFTP (83·7%) were observed. For NIFTPs, the need for surgery was indicated by ultrasonography-guided fine needle aspiration (US-FNA) in 54·3% and by ultrasonography-guided core needle biopsy (US-CNB) in 100% (P = 0·008). For non-NIFTP, no significant difference was noted in the rates of surgical indication between US-FNA and US-CNB (62·6% vs 78·9%, P = 0·054). The most common biopsy diagnosis of NIFTP was Bethesda category V (28·6%) in the US-FNA group and category IV (45·5%) in the US-CNB group. US diagnosis of NIFTP had a significantly lower rate of the high suspicion of malignancy than that of non-NIFTP (14·7% vs 37·9%, P = 0·024). Central nodal metastasis was found in only one case (2·9%) of NIFTP patients, but none had distance metastasis or recurrence. CONCLUSION: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features lacks malignant US features and is better triaged using US-CNB than using US-FNA to facilitate the surgical management. US evaluation is pivotal in determining the next step of FVPTC management.

Efficacy and safety of radiofrequency ablation for treating locoregional recurrence from papillary thyroid cancer.

OBJECTIVES: To assess the efficacy and safety of ultrasound- (US) guided radiofrequency ablation (RFA) for controlling locoregional recurrent papillary thyroid cancer (PTC) in a large patient population. METHODS: We included patients who had undergone RFA for locoregional recurrent PTC between September 2008 and April 2012 who fulfilled the following criteria: no metastasis beyond the neck; not more than four tumours; confirmed recurrence by US-guided fine needle aspiration biopsy or thyroglobulin measurement of needle washouts; more than a six-month follow-up period; and surgery not feasible or was refused by the patient. RESULTS: Sixty-one recurrent tumours in 39 patients were included. The mean follow-up duration was 26.4 ± 13.7 months. Tumour volume decreased significantly from 0.20 ± 0.35 ml before ablation to 0.02 ± 0.11 ml (P < .001), with a mean volume reduction ratio of 95.1 ± 12.3%. Fifty tumours (82.0%) completely disappeared. Eleven tumours were visible at last follow-up US. The mean serum thyroglobulin level decreased from 1.21 ± 1.91 to 0.50 ± 0.80 ng/ml (P = .001). The overall complication rate was 7.7% (3/39). CONCLUSIONS: RFA can effectively control locoregional recurrent PTC without life-threatening complications; therefore, RFA may replace "berry picking surgery" in selected patients. KEY POINTS: • RFA for recurrent PTC achieved a volume reduction ratio of 95.1 ± 12.3% • Eighty-two percent (50/61) of recurrent PTC completely disappeared after RFA • The mean serum thyroglobulin level decreased significantly (P = .001) after RFA • RFA may replace "berry picking surgery" for recurrent PTC.

Radiofrequency ablation is a thyroid function-preserving treatment for patients with bilateral benign thyroid nodules.

PURPOSE: To evaluate the efficacy and safety of radiofrequency (RF) ablation for treatment of bilateral thyroid nodules as well as preservation of thyroid function. MATERIALS AND METHODS: Between January 2007 and October 2012, 18 patients (16 women and 2 men; mean age, 49.9 y; median age, 44 y; age range, 27-81 y) with bilateral thyroid nodules treated by RF ablation were included in this study. The inclusion criteria included bilateral thyroid nodules, pressure symptoms or cosmetic problems, cytologic confirmation of benignancy without atypical cells, and patient refusal of surgery. We used an RF generator (Cool-tip RF system [Covidien, Boulder, Colorado] or SSP-2000, Taewoong Medical Co, Ltd [Gyeonggi-do, Republic of Korea]) and an 18-gauge internally cooled electrode with 1-cm active tips (Cool-tip [Covidien] or Well-Point RF electrode [Taewoong Medical Co, Ltd]). RF ablation was conducted using the moving shot technique and a trans-isthmic approach. RF ablation was performed in separate sessions for nodules in each lobe. Follow-up ultrasound examinations were performed at 1-6 months, 6-12 months, and during the last month of follow-up. The diameter and volume of the nodule and clinical problems including cosmetic and symptom scores were evaluated before and after the procedure. RESULTS: The mean initial nodule size was 4.1 cm ± 1.9, although there was a significant decrease by the time of the last follow-up examination (range, 1-48 mo; mean, 18.1 mo ± 12.8; P < .001, 2.5 cm ± 1.4). The initial nodule volume was 24.4 mL ± 32.2 and was decreased at the last follow-up (6.3 mL ± 19.0, P < .001), with a mean volume reduction of 75.9% ± 19.0. The symptom (P < .001) and cosmetic (P < .001) scores were decreased. Serum hormone levels did not differ significantly before treatment and at the last follow-up (P > .05). CONCLUSIONS: RF ablation improves cosmetic problems and symptoms and preserves thyroid function in patients with bilateral thyroid nodules.

THE VALUE OF GROSS VISUAL ASSESSMENT OF SPECIMEN ADEQUACY FOR LIQUID-BASED CYTOLOGY DURING ULTRASOUND-GUIDED, FINE-NEEDLE ASPIRATION OF THYROID NODULES.

OBJECTIVE: Major problems of fine-needle aspiration (FNA) of thyroid nodules arise due to nondiagnostic results caused by inadequately obtained FNA specimens. The purpose of this study was to evaluate the value of visual assessment of liquid-based cytology specimens during FNA of thyroid nodules for predicting sampling adequacy. METHODS: For 3 months, visual assessment of FNA specimens was used for 534 consecutive nodules in 534 patients. The FNA specimens were visually graded immediately following aspiration for each nodule, and the visual grades were classified into 2 categories: inadequate (<6 cell groups) and adequate (>6 cell groups). The cytology results were classified as diagnostic or nondiagnostic based on the Bethesda system. We compared the ultrasound features and FNA characteristics between the diagnostic and nondiagnostic results. Multiple logistic regression analysis was used to determine factors independently predictive of nondiagnostic results. We also evaluated the interobserver agreement regarding the visual assessment. RESULTS: Visual assessment was feasible in all patients, and the nondiagnostic rate was 11.6% (62 of 534). Nondiagnostic results were more frequent in the inadequate visual assessment group (38.1%) than in the adequate visual assessment group (10.5%) (P = .001). Independent predictive factors for nondiagnostic results were inadequate visual assessment (odds ratio, 5.18), >50% vascularity (odds ratio, 3.98), and macrocalcification (odds ratio, 3.60). Interobserver agreement for the prediction of visual assessment was good (κ value, 0.767; P<.001). CONCLUSION: Immediate visual assessment of a specimen during FNA of a thyroid nodule is a feasible method for predicting sampling adequacy.

Management of cystic or predominantly cystic thyroid nodules: role of simple aspiration of internal fluid.

PURPOSE: The purpose of this study is to evaluate the efficacy of simple aspiration of cystic thyroid nodules by comparing with control groups to exclude the occurrence of spontaneous regression by the definition of current guidelines of American Thyroid Association. MATERIALS AND METHODS: 217 nodules from 210 patients with cystic thyroid nodules (cystic portion >50%) were included. Nodules were classified into three groups as follows: Group 1, observation only; Group 2, fine needle aspiration (FNA) without aspiration of internal fluid; and Group 3, FNA after aspiration of internal fluid. Significant nodule size change was defined as a difference in the largest diameter of 20%, as seen on the last follow-up ultrasound (US) compared to the initial US. RESULTS: Demographic characteristics did not show significant differences among the three groups except for the patient age (p = 0.039). Mean nodule size significantly decreased only in group 3 (p = 0.005). Significant nodule size reductions were observed in 22.0% (13/59) in group 1, 25.7% (28/109) in group 2, and 40.8% (20/49) in group 3, respectively. CONCLUSIONS: Aspiration of internal fluid should be considered as the first-line procedure for both the diagnosis and treatment of cystic or predominantly cystic thyroid nodules.

Core needle biopsy can minimise the non-diagnostic results and need for diagnostic surgery in patients with calcified thyroid nodules.

PURPOSE: To evaluate the role of core needle biopsy (CNB) for calcified thyroid nodules. METHODS: Between October 2008 and July 2011, 264 patients underwent ultrasound-guided CNB for 272 calcified thyroid nodules at our institution. We retrospectively evaluated the incidence of technical failure, non-diagnostic readings, and the diagnostic performance of CNB, and analysed the relationship between the types of calcification and the CNB results. Finally, the incidence of diagnostic surgery was calculated. RESULTS: The incidence of technical failure was 1.1 % (3/275) and that of non-diagnostic results was 0.7 % (2/272). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of CNB were 94.7 %, 89.5 %, 100 %, 100 %, and 90.2 %, respectively. There were no significant differences according to the calcification subtype for either the non-diagnostic results or the incidence of technical failure (P > 0.99 and P > 0.99). CNB could prevent diagnostic surgery for 92.9 % (13/14) of the patients who showed more than two non-diagnostic results in previous FNA. CONCLUSIONS: CNB can minimise the non-diagnostic results as well as diagnostic surgery in patients with calcified thyroid nodules. Therefore, CNB may be used as a first-line diagnostic tool for calcified thyroid nodules rather than FNA. KEY POINTS: CNB results show the low incidence of technical failure (1.1 %, 3/275). • CNB results show the low non-diagnostic rate (0.7 %, 2/272). There were no significant differences according to the calcification subtype. CNB can prevent unnecessary diagnostic surgery in 92.9 % (13/14).

Femoral osteoporosis prediction model using autosegmentation and machine learning analysis with PyRadiomics on abdomen-pelvic computed tomography (CT).

Background: With the advancement of artificial intelligence technology and radiomics analysis, opportunistic prediction of osteoporosis with computed tomography (CT) is a new paradigm in osteoporosis screening. This study aimed to assess the diagnostic performance of osteoporosis prediction by the combination of autosegmentation of the proximal femur and machine learning analysis with a reference standard of dual-energy X-ray absorptiometry (DXA). Methods: Abdomen-pelvic CT scans were retrospectively analyzed from 1,122 patients who received both DXA and abdomen-pelvic computed tomography (APCT) scan from January 2018 to December 2020. The study cohort consisted of a training cohort and a temporal validation cohort. The left proximal femur was automatically segmented, and a prediction model was built by machine-learning analysis using a random forest (RF) analysis and 854 PyRadiomics features. The technical success rate of autosegmentation, diagnostic test, area under the receiver operator characteristics curve (AUC), and precision recall curve (AUC-PR) analysis were used to analyze the training and validation cohorts. Results: The osteoporosis prevalence of the training and validation cohorts was 24.5%, and 10.3%, respectively. The technical success rate of autosegmentation of the proximal femur was 99.7%. In the diagnostic test, the training and validation cohorts showed 78.4% vs. 63.3% sensitivity, 89.4% vs. 98.1% specificity. The prediction performance to identify osteoporosis within the groups used for training and validation cohort was high and the AUC and AUC-PR to forecast the occurrence of osteoporosis within the training and validation cohorts were 90.8% [95% confidence interval (CI), 88.4-93.2%] vs. 78.0% (95% CI, 76.0-79.9%) and 94.6% (95% CI, 89.3-99.8%) vs. 88.8% (95% CI, 86.2-91.5%), respectively. Conclusions: The osteoporosis prediction model using autosegmentation of proximal femur and machine-learning analysis with PyRadiomics features on APCT showed excellent diagnostic feasibility and technical success.

Millingtonia hortensis L.f. ethanol extract exerts in vivo and in vitro anti-inflammatory activities through inhibition of Syk kinase in NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Millingtonia hortensis L.f., commonly known as tree jasmine or Indian cork tree, is native to South Asia and Southeast Asia. Traditionally, its stem bark, leaves, and roots are employed for pulmonary, gastrointestinal, and antimicrobial purposes, while the flowers are used in treating asthma and sinusitis. AIM OF THE STUDY: The underlying anti-inflammatory mechanisms of M. hortensis remain relatively unexplored. Therefore, we studied the anti-inflammatory effects of M. hortensis and the molecular mechanisms of its ethanol extracts (Mh-EE) both in vitro and in vivo. MATERIALS AND METHODS: Nitric oxide (NO) production was assessed using Griess reagent, while cell viability of RAW264.7 cell and HEK293T cells were determined via the MTT assay. Constituent analysis of Mh-EE using GC/MS-MS and HPLC, and mRNA expression of inflammatory cytokines was measured through PCR and RT-PCR. Protein levels were analyzed using western blotting. The thermal stability of Mh-EE was evaluated by CESTA. Lastly, a gastritis in vivo model was induced by HCl/EtOH, and protein expression levels were measured using western blotting. RESULTS: Mh-EE significantly reduced NO production in LPS-induced RAW264.7 cells without substantially affecting cell viability. Additionally, Mh-EE decreased the expression of proinflammatory factors, such as iNOS, IL-1ß and COX2. Furthermore, Mh-EE downregulated TLR4 expression, altered MyD88 recruitment, and suppressed phosphorylation of Syk, IKKα, IκBα and AKT. Simultaneously, Mh-EE also attenuated NF-κB signaling in HCl/EtOH-induced mice. CONCLUSIONS: Mh-EE exerts anti-inflammatory effects by suppressing p-Syk in the NF-κB pathway, and it has potential as a novel treatment agent for inflammatory diseases.

ANXA2 (annexin A2) is crucial to ATG7-mediated autophagy, leading to tumor aggressiveness in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is associated with a poor prognosis and metastatic growth. TNBC cells frequently undergo macroautophagy/autophagy, contributing to tumor progression and chemotherapeutic resistance. ANXA2 (annexin A2), a potential therapeutic target for TNBC, has been reported to stimulate autophagy. In this study, we investigated the role of ANXA2 in autophagic processes in TNBC cells. TNBC patients exhibited high levels of ANXA2, which correlated with poor outcomes. ANXA2 increased LC3B-II levels following bafilomycin A1 treatment and enhanced autophagic flux in TNBC cells. Notably, ANXA2 upregulated the phosphorylation of HSF1 (heat shock transcription factor 1), resulting in the transcriptional activation of ATG7 (autophagy related 7). The mechanistic target of rapamycin kinase complex 2 (MTORC2) played an important role in ANXA2-mediated ATG7 transcription by HSF1. MTORC2 did not affect the mRNA level of ANXA2, but it was involved in the protein stability of ANXA2. HSPA (heat shock protein family A (Hsp70)) was a potential interacting protein with ANXA2, which may protect ANXA2 from lysosomal proteolysis. ANXA2 knockdown significantly increased sensitivity to doxorubicin, the first-line chemotherapeutic regimen for TNBC treatment, suggesting that the inhibition of autophagy by ANXA2 knockdown may overcome doxorubicin resistance. In a TNBC xenograft mouse model, we demonstrated that ANXA2 knockdown combined with doxorubicin administration significantly inhibited tumor growth compared to doxorubicin treatment alone, offering a promising avenue to enhance the effectiveness of chemotherapy. In summary, our study elucidated the molecular mechanism by which ANXA2 modulates autophagy, suggesting a potential therapeutic approach for TNBC treatment.Abbreviation: ATG: autophagy related; ChIP: chromatin-immunoprecipitation; HBSS: Hanks' balanced salt solution; HSF1: heat shock transcription factor 1; MTOR: mechanistic target of rapamycin kinase; TNBC: triple-negative breast cancer; TFEB: transcription factor EB; TFE3: transcription factor binding to IGHM enhancer 3.

Thyroid nodules with initially nondiagnostic cytologic results: the role of core-needle biopsy.

PURPOSE: To evaluate the role of core-needle biopsy (CNB) in thyroid nodules with nondiagnostic results at previous fine-needle aspiration (FNA). MATERIALS AND METHODS: From October 2008 to July 2011, 155 nodules from 155 patients (37 men, 118 women) with a mean age of 51.8 years (age range, 22-76 years) with nondiagnostic results at previous FNA were reviewed retrospectively. The Bethesda system for reporting thyroid cytopathologic results was used to assign FNA and CNB findings. Malignant nodules (n = 37) were diagnosed after surgery. Benign nodules (n = 79) were diagnosed either after surgery, with benign findings after FNA and/or CNB that had been repeated at least twice, or after benign cytology findings at FNA or CNB with a stable size at follow-up. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ultrasonographically guided CNB were evaluated. RESULTS: At CNB, two nodules (1.3%) showed nondiagnostic results, and 135 nodules (87.1%) had conclusive diagnoses. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of core biopsies for the detection of malignancy were 94.6% (35 of 37), 100% (79 of 79), 100% (35 of 35), 97.5% (79 of 81), and 98.3% (114 of 116), respectively. For 28 nodules, nondiagnostic results were found after two or more FNA procedures; however, diagnostic surgery was performed in only one patient. CONCLUSION: CNB of the thyroid nodule demonstrates high rates of conclusive and accurate diagnoses in patients for whom previous FNA results were nondiagnostic, thereby reducing the need for unnecessary diagnostic surgery.

Radiofrequency ablation of benign non-functioning thyroid nodules: 4-year follow-up results for 111 patients.

OBJECTIVES: To evaluate the clinical outcomes and safety of radiofrequency (RF) ablation for benign non-functioning thyroid nodules over a 4-year follow-up. METHODS: We evaluated 126 benign non-functioning thyroid nodules of 111 patients treated with RF ablation and followed-up more than 3 years. RF ablation was performed using the Cool-Tip RF system and an internally cooled electrode. Nodule volume and cosmetic and symptom scores were evaluated before treatment and during follow-up. Complications and factors related to efficacy were evaluated. RESULTS: The mean follow-up duration was 49.4 ± 13.6 months. Thyroid nodule volume decreased significantly, from 9.8 ± 8.5 ml before ablation to 0.9 ± 3.3 ml (P < 0.001) at final evaluation: a mean volume reduction of 93.4 ± 11.7 %. The mean cosmetic (P < 0.001) and symptom scores (P < 0.001) improved significantly. Factors related to efficacy were initial solidity and volume. The overall recurrence rate was 5.6 % (7/126). The overall complication rate was 3.6 % (4/111). CONCLUSIONS: RF ablation was effective in shrinking benign thyroid nodules and in controlling nodule-related problems over a 4-year follow-up. There were no life-threatening complications or sequelae. Therefore, RF ablation can be used as a non-surgical treatment for patients with benign non-functioning thyroid nodules.

Reducing contrast-agent volume and radiation dose in CT with 90-kVp tube voltage, high tube current modulation, and advanced iteration algorithm.

Increasing utilization of computed tomography (CT) has raised concerns regarding CT radiation dose and technology has been developed to achieve an appropriate balance between image quality, radiation dose, and the amount of contrast material. This study was planned to evaluate the image quality and radiation dose in pancreatic dynamic computed tomography (PDCT) with 90-kVp tube voltage and reduction of the standard amount of contrast agent, compared with 100-kVp PDCT of the research hospital's convention. Total of 51 patients with both CT protocols were included. The average Hounsfield units (HU) values of the abdominal organs and image noise were measured for objective image quality analysis. Two radiologists evaluated five categories of image qualities such as subjective image noise, visibility of small structure, beam hardening or streak artifact, lesion conspicuity and overall diagnostic performance for subjective image quality analysis. The total amount of contrast agent, radiation dose, and image noise decreased in the low-kVp group, by 24.4%, 31.7%, and 20.6%, respectively (p < 0.001). The intraobserver and interobserver agreements were moderate to substantial (k = 0.4-0.8). The contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and figure of merit of the almost organs except psoas muscle in the low-kVp group were significantly higher (p < 0.001). Except for lesion conspicuity, both reviewers judged that subjective image quality of the 90-kVp group was better (p < 0.001). With 90-kVp tube voltage, 25% reduced contrast agent volume with advanced iteration algorithm and high tube current modulation achieved radiation dose reduction of 31.7%, as well as better image quality and diagnostic confidence.

Cystic versus predominantly cystic thyroid nodules: efficacy of ethanol ablation and analysis of related factors.

OBJECTIVES: To compare the efficacy of ethanol ablation (EA) of cystic and predominantly cystic thyroid nodules, and to evaluate factors affecting efficacy. METHODS: From October 2008 to December 2010, a total of 217 thyroid nodules were treated with EA. Nodule volumes, symptoms and cosmetic scores were evaluated before and after EA. EA efficacy in treating cystic and predominantly cystic nodules was compared; and factors related to EA efficacy in each type, including initial volume, solid component, vascularity, fluid nature, ethanol retention time and number of EA sessions, were evaluated. RESULTS: Mean nodule volume decreased from 15.7 ± 18.1 ml to 3.0 ± 7.9 ml (mean volume reduction, 85.2 ± 16.1%) and the therapeutic success rate was 90.3% at last follow-up. EA was significantly more effective in cystic than predominantly cystic nodules. Independent predictors of EA efficacy for all nodules included initial volume, solid component and vascularity. Initial volume and vascularity were independent predictors of EA efficacy in predominantly cystic nodules, but no factor was independently related to efficacy in cystic nodules. CONCLUSIONS: EA is effective in both cystic and predominantly cystic nodules, especially the former. EA is less effective in large or vascular predominantly cystic nodules, but is effective in cystic nodules regardless of related factors. KEY POINTS: • Ethanol ablation under ultrasound guidance is increasingly used for cystic thyroid nodules. • EA seems effective for cystic and predominantly cystic nodules, especially cystic nodules. • The effectiveness of EA was reduced in large or vascular predominantly cystic nodules.

Comparison of diagnostic accuracy of 2D and 3D measurements to determine opportunistic screening of osteoporosis using the proximal femur on abdomen-pelvic CT.

OBJECTIVES: To compare the osteoporosis-predicting ability of computed tomography (CT) indexes in abdomen-pelvic CT using the proximal femur and the reliability of measurements in two- and three-dimensional analyses. METHODS: Four hundred thirty female patients (age range, 50-96 years) who underwent dual-energy X-ray absorptiometry and abdominal-pelvic CT within 1 month were retrospectively selected. The volumes of interest (VOIs) from the femoral head to the lesser trochanter and the femoral neck were expressed as 3DFemur. Round regions of interest (ROIs) of image plane drawn over the femoral neck touching the outer cortex were determined as 2Dcoronal. In HU histogram analysis (HUHA), the percentages of HU histogram ranges related to the ROI or VOI were classified as HUHAFat (<0 HU) and HUHABone (126 HU≤). Diagnostic performance, correlation analysis and measurement reliability were analyzed by receiver operating characteristic curves, correlation coefficient and interobserver correlation coefficient (ICC), respectively. RESULTS: AUCs of each HUHA and mean-HU measurement on 2D-ROI and 3D-VOI were 0.94 or higher (P < 0.001). Both 3DFemur-Mean-HU and 3DFemur-HUHABone showed the highest AUC (0.96). The cut-off value of 3DFemur-Mean-HU was 231HU or less, (sensitivity: 94.8%; specificity: 85.0%; correlation coefficient: -0.65; P <0.001) for diagnosis of osteoporosis. There was no superiority between AUCs in 2D-ROI and 3D-VOI measurements (P > 0.05). Reliability of the 3D-VOI measurement showed perfect agreement (ICC ≥ 0.94), and 2D-ROI showed moderate to good agreement (ICC range: 0.63~0.84). CONCLUSIONS: CT indexes on 3D-VOI for predicting femoral osteoporosis showed similar diagnostic accuracy with better reproducibility of measurement, compared with 2D-ROI.