Changes in bone turnover markers and bone mineral density after radiofrequency ablation for mild primary hyperparathyroidism: a prospective cohort study.

Background: The application of radiofrequency ablation (RFA) is becoming increasingly widespread in the treatment of primary hyperparathyroidism (PHPT). However, the effect of RFA treatment on the skeleton in mild PHPT remains unclear. Therefore, the aim of this study was to investigate the change in bone turnover markers and bone mineral density (BMD) before and 2 years after RFA in patients with mild PHPT. Methods: In this open-label, prospective study, 81 patients with mild PHPT including 36 treated with RFA and 45 observed without intervention (OBS), along with 81 age-matched healthy controls, were enrolled from November 2018 to September 2021 at Gansu Provincial Hospital. The main outcome measures were levels of serum calcium, serum intact parathyroid hormone (iPTH), and bone turnover markers, including bone-specific alkaline phosphatase (ALP), C-terminal cross-linking telopeptides of type I collagen (ß-CTx), and osteocalcin (OC). BMD (femoral neck and lumbar spine) was measured with dual-energy X-ray absorptiometry, and spine radiographs were obtained for vertebral fracture assessment. Paired and unpaired two-tailed t-tests and Spearman rank correlation coefficient were used for statistical analyses. Results: Normalized outcomes for both iPTH and calcium levels were achieved in 32 of 36 (88.9%) patients with mild PHPT treated with RFA. There was a significant treatment effect of RFA on bone turnover biomarkers compared with OBS before the treatment (P=0.04) and at the end of follow-up or (P=0.03). BMD of the lumbar spine increased by 1.8% (P=0.03) and remained stable in the femoral neck (P=0.17) after RFA. However, there was an obvious treatment effect of RFA on BMD compared with OBS (P 0.04). The only compartment with a T-score increase in the RFA group was the lumbar spine in (P<0.001). There was no difference in fracture frequency between groups during the follow-up period. Conclusions: RFA can improve serum bone turnover markers in patients with mild PHPT and can be expected to increase BMD in the L1-L4 vertebrae and preserve BMD in the femoral neck. Whether RFA can reduce fracture risk in the long-term is a clinical concern for patients with mild PHPT.

Advances in the relationship between ferroptosis and epithelial-mesenchymal transition in cancer.

Epithelial-mesenchymal transition (EMT) is a cellular reprogramming process that converts epithelial cells into mesenchymal-like cells with migratory and invasive capabilities. The initiation and regulation of EMT is closely linked to a range of transcription factors, cell adhesion molecules and signaling pathways, which play a key role in cancer metastasis and drug resistance. The regulation of ferroptosis is intricately linked to various cell death pathways, intracellular iron homeostasis, and the protein network governing iron supply and storage. The ability of ferroptosis to disrupt cancer cells and overcome drug resistance lies in its control of intracellular iron ion levels. EMT process can promote the accumulation of iron ions, providing conditions for ferroptosis. Conversely, ferroptosis may impact the regulatory network of EMT by modulating transcription factors, signaling pathways, and cell adhesion molecules. Thus, ferroptosis related genes and signaling pathways and oxidative homeostasis play important roles in the regulation of EMT. In this paper, we review the role of ferroptosis related genes and their signaling pathways in regulating cancer EMT to better understand the crosstalk mechanism between ferroptosis and EMT, aiming to provide better therapeutic strategies for eradicating cancer cells and overcoming drug resistance.

Ultrasound identification of hepatic echinococcosis using a deep convolutional neural network model in China: a retrospective, large-scale, multicentre, diagnostic accuracy study.

BACKGROUND: Ultrasonography is the most widely used technique to diagnose echinococcosis; however, challenges in using this technique and the demand on medical resources, especially in low-income or remote areas, can delay diagnosis. We aimed to develop a deep convolutional neural network (DCNN) model based on ultrasonography to identify echinococcosis and its types, especially alveolar echinococcosis. METHODS: This retrospective, large-scale, multicentre study used ultrasound images from patients assessed at 84 hospitals in China, obtained between Jan 1, 2002, and Dec 31, 2021. Patients with a diagnosis of cystic echinococcosis, alveolar echinococcosis, or seven other types of focal liver lesions were included. We tested ResNet-50, ResNext-50, and VGG-16 as the backbone network architecture for a classification DCNN model and input the perinodular information from the ultrasound images. We trained and validated the DCNN model to diagnose and classify echinococcosis using still greyscale ultrasound images of focal liver lesions in four stages: differentiating between echinococcosis and other focal liver lesions (stage one); differentiating cystic echinococcosis, alveolar echinococcosis, and other focal liver lesions (stage two); differentiating cystic echinococcosis, alveolar echinococcosis, benign other focal liver lesions, and malignant focal liver lesions (stage three); and differentiating between active and transitional cystic echinococcosis and inactive cystic echinococcosis (stage four). We then tested the algorithm on internal, external, and prospective test datasets. The performance of DCNN was also compared with that of 12 radiologists recruited between Jan 15, 2022, and Jan 28, 2022, from Qinghai, Xinjiang, Anhui, Henan, Xizang, and Beijing, China, with different levels of diagnostic experience for echinococcosis and other focal liver lesions in a subset of ultrasound data that were randomly chosen from the prospective test dataset. The study is registered at ClinicalTrials.gov (NCT03871140). FINDINGS: The study took place between Jan 1, 2002, and Dec 31, 2021. In total, to train and test the DCNN model, we used 9631 liver ultrasound images from 6784 patients (2819 [41·7%] female patients and 3943 [58·3%] male patients) from 87 Chinese hospitals. The DCNN model was trained with 6328 images, internally validated with 984 images, and tested with 2319 images. The ResNet-50 network architecture outperformed VGG-16 and ResNext-50 and was generalisable, with areas under the receiver operating characteristic curve (AUCs) of 0·982 (95% CI 0·960-0·994), 0·984 (0·972-0·992), and 0·913 (0·886-0·935) in distinguishing echinococcosis from other focal liver lesions; 0·986 (0·966-0·996), 0·962 (0·946-0·975), and 0·900 (0·872-0·924) in distinguishing alveolar echinococcosis from cystic echinococcosis and other focal liver lesions; and 0·974 (0·818-1·000), 0·956 (0·875-0·991), and 0·944 (0·844-0·988) in distinguishing active and transitional cystic echinococcosis from inactive echinococcosis in the three test datasets. Specifically, in patients with the hepatitis B or hepatitis C virus, the model could distinguish alveolar echinococcosis from hepatocellular carcinoma with an AUC of 0·892 (0·812-0·946). In identifying echinococcosis, the model showed significantly better performance compared with senior radiologists from a high-endemicity area (AUC 0·942 [0·904-0·967] vs 0·844 [0·820-0·866]; p=0·027) and improved the diagnostic ability of junior, attending, and senior radiologists before and after assistance with AI with comparison of AUCs of 0·743 (0·714-0·770) versus 0·850 (0·826-0·871); p<0·0001, 0·808 (0·782-0·832) versus 0·886 (0·864-0·905); p<0·0001, and 0·844 (0·820-0·866) versus 0·870 (0·847-0·890); p=0·092, respectively. INTERPRETATION: The DCNN model was shown to be accurate and robust, and could improve the ultrasound diagnostic ability of radiologists for echinococcosis and its types for highly endemic and remote regions. FUNDING: National Natural Science Foundation of China and National Key Research & Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Ultrasonographic and cytological characterization of ultrasound-guided fine-needle aspiration cytology of cervical lymph nodes for false-negative and false-positive diagnosis.

OBJECTIVES: The primary goal of this study was to examine the ultrasound and cytological characteristics of inconsistent cases (false negatives and false positives)of ultrasound-guided fine-needle aspiration cytology (US-FNAC) of cervical lymph nodes, to investigate factors influencing the diagnostic accuracy of fine-needle aspiration, and to improve diagnostic efficiency. METHODS: The results of US and FNAC of cervical lymph nodes in 562 cases treated at our institution from February 2019 to June 2021 were retrospectively analyzed. FNAC cytology results were compared with the final diagnostic results (242 surgical resections/core-needle biopsy, 320 cases followed up for more than 1 year), and the final diagnostic results were taken as the gold standard, and the ultrasound features and clinicopathology-related features were systematically retrospectively analyzed in cases of inconsistency. RESULTS: The overall diagnostic accuracy of US-FNAC for cervical lymph nodes was 94.9%, with a false-negative rate of 6.7% and a false-positive rate of 3.8%. Analyzing the cases, sampling error due to factors associated with ultrasound features, such as larger, more numerous nodes, non-solid, hypoechoic, inhomogeneous, and increased vascularity are the main causes of false-negative diagnosis, while smaller nodules, overlapping cytologic patterns, and overinterpretation by pathologists are associated with false-positive FNAC results. CONCLUSIONS: Proper interpretation of cytomorphologic and ultrasound features can improve diagnostic accuracy, and diagnostic misdiagnosis should be carefully observed, the identification of both features should be enhanced to reduce interpretation errors and sampling errors and to reduce the rate of misdiagnosis and missed diagnoses in fine needle aspiration of lymph nodes.

Role of Sonazoid-based contrast-enhanced ultrasonography in the microwave ablation of primary hyperparathyroidism.

OBJECTIVES: This study aimed to determine the performance of Sonazoid-based contrast-enhanced ultrasound (CEUS) in the microwave ablation (MWA) of primary hyperparathyroidism (pHPT). METHODS: Forty patients with pHPT were enrolled and treated with percutaneous ultrasound (US)-guided MWA assisted by CEUS. All patients underwent immediate CEUS examinations following MWA. On post-ablation day 1, patients who did not display a decrease in intact parathyroid hormone (iPTH) levels to the norm were examined by CEUS to evaluate an incomplete ablation. We compared the serum iPTH and calcium levels and the nodule volumes before and after MWA. The complications were evaluated during and after treatment. RESULTS: Immediately following MWA, CEUS demonstrated complete ablation with all 44 parathyroid nodules. On post-ablation day 1, five nodules in five patients displayed annular enhancement around the ablation zone on CEUS. The average maximum diameters of the nodules and the ablation zone were 1.09 ± 0.28 cm and 1.36 ± 0.23 cm, respectively. An ablation zone larger than the primary lesion (p < 0.05) generated a higher rate of complete ablation. Compared with pre-MWA, serum iPTH and calcium levels were significantly improved. Treatment success was achieved in 38 patients (95%). Hoarseness was a major complication in six patients (15%); however, it improved spontaneously within 1-4 months. We observed two recurrences (2/40, 5%) at 9 months and 11 months following MWA, respectively. CONCLUSION: US-guided percutaneous MWA assisted by CEUS for pHPT is an effective and safe therapy. CEUS can avoid operative failure and improve the cure rate.

Practice of the new supervised machine learning predictive analytics for glioma patient survival after tumor resection: Experiences in a high-volume Chinese center.

Objective: This study aims to assess the effectiveness of the Gradient Boosting (GB) algorithm on glioma prognosis prediction and to explore new predictive models for glioma patient survival after tumor resection. Methods: A cohort of 776 glioma cases (WHO grades II-IV) between 2010 and 2017 was obtained. Clinical characteristics and biomarker information were reviewed. Subsequently, we constructed the conventional Cox survival model and three different supervised machine learning models, including support vector machine (SVM), random survival forest (RSF), Tree GB, and Component GB. Then, the model performance was compared with each other. At last, we also assessed the feature importance of models. Results: The concordance indexes of the conventional survival model, SVM, RSF, Tree GB, and Component GB were 0.755, 0.787, 0.830, 0.837, and 0.840, respectively. All areas under the cumulative receiver operating characteristic curve of both GB models were above 0.800 at different survival times. Their calibration curves showed good calibration of survival prediction. Meanwhile, the analysis of feature importance revealed Karnofsky performance status, age, tumor subtype, extent of resection, and so on as crucial predictive factors. Conclusion: Gradient Boosting models performed better in predicting glioma patient survival after tumor resection than other models.

Smart-Polypeptide-Coated Mesoporous Fe3O4 Nanoparticles: Non-Interventional Target-Embolization/Thermal Ablation and Multimodal Imaging Combination Theranostics for Solid Tumors.

Tumor theranostics hold great potential for personalized medicine in the future, and transcatheter arterial embolization (TAE) is an important clinical treatment for unresectable or hypervascular tumors. In order to break the limitation, simplify the procedure of TAE, and achieve ideal combinatorial theranostic capability, here, a kind of triblock-polypeptide-coated perfluoropentane-loaded mesoporous Fe3O4 nanocomposites (PFP-m-Fe3O4@PGTTCs) were prepared for non-interventional target-embolization, magnetic hyperthermia, and multimodal imaging combination theranostics of solid tumors. The results of systematic animal experiments by H22-tumor-bearing mice and VX2-tumor-bearing rabbits in vivo indicated that PFP-m-Fe3O4@PGTTC-6.3 has specific tumor accumulation and embolization effects. The tumors' growth has been inhibited and the tumors disappeared 4 weeks and ≤15 days post-injection with embolization and magnetic hyperthermia combination therapy, respectively. The results also showed an excellent effect of magnetic resonance/ultrasound/SPECT multimodal imaging. This pH-responsive non-interventional embolization combinatorial theranostics system provides a novel embolization and multifunctional theranostic candidate for solid tumors.

Correlation between US-FNAC with BRAF V600E Mutation Analysis and Central Neck Lymph Node Metastasis in cN0 Papillary Thyroid Cancer.

The aim of this study was to explore the correlation between ultrasound-guided fine-needle aspiration cytology(US-FNAC) combined with BRAF V600E mutation analysis and central neck lymph node metastasis in cN0 papillary thyroid cancer, so as to provide reliable molecular evidence to use it for preoperative evaluation, operation procedure design, and postoperative follow-up planning in clinic. Specimens were obtained from 250 patients with cN0 thyroid cancer (TI-RADS≥4a, highly suspected of PTC by US-FNAC) after bilateral thyroidectomy and central neck lymph node dissection with accessible postoperative pathologic results of PTC and central neck lymph nodes and used for cytological diagnosis by H&E stain and BRAF V600E mutation detection. Single-factor analysis showed that differences between the central neck lymph node metastasis and nonmetastasis groups were statistically significant in gender, BRAF V600E mutation, and extracapsular extension. Logistic multivariate regression analysis showed significant differences in gender, BRAF V600E mutation, and extracapsular extension. Positive BRAF V600E mutations by US-FNAC, extracapsular extension, and male gender are risk factors of central neck lymph node metastasis in cN0 PTC metastatic PTC to central neck lymph node. Patients with those factors should undergo prophylactic central neck lymph node dissection.

Nomogram for the diagnosis of suspected papillary thyroid carcinomas based on sonographic patterns: a retrospective study.

BACKGROUND: High resolution ultrasonography (US) is the first choice for diagnosis of thyroid cancer and is based on many sonographic features: composition, echogenicity, margins, calcifications, shape and vascularity. Here, we tried to develop a nomogram to evaluate papillary thyroid carcinoma (PTC) based on sonographic features. METHODS: From Aug 2016 to Dec 2017, a primary cohort of 382 patients with suspicious thyroid nodules and accepted US examinations were included in Gansu Provincial Hospital. Sonographic features were used to develop a nomogram with Cox regression analysis. The nomogram was validated using prospective data from 162 patients as the validation group. RESULTS: The primary and validation cohort showed comparable clinical and US features in all aspects. Univariate and multivariate analyses showed solid composition [odds ratio (OR): 3.785; 95% confidence interval (CI): 1.504-9.528, P=0.005], hypoechoic (OR: 15.840; 95% CI: 5.754-43.602, P<0.001) and irregular margins (OR: 15.953; 95% CI: 5.897-43.160, P<0.001), microcalcifications (OR: 21.730; 95% CI: 7.119-66.329, P<0.001), taller than wide shape (OR: 5.153; 95% CI: 1.997-13.311, P=0.001), internal high vascularization (OR: 6.288; 95% CI: 2.175-18.181, P=0.001), and obscure borders (OR: 5.648; 95% CI: 2.118-15.065, P=0.001) as risk factors for PTC. Based on the seven risk factors, nomogram was developed and validated by a prospective group, and discrimination and calibration were measured using the concordance index (C-index). CONCLUSIONS: Our novel nomogram risk score model based on the US features accurately predicted PTC nodule diagnosis.

The Association Between Endocan Levels and Subclinical Atherosclerosis in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Proinflammatory conditions induced by circulating factors in diabetes play a pivotal role in endothelial dysfunction and related vascular complications. Endothelial cell-specific molecule-1 or endocan is a dermatan sulfate proteoglycan secreted primarily by the vascular endothelium. Although endocan has been shown to be a potential biomarker in coronary heart disease, its role in the pathogenesis of atherosclerosis (AS) in diabetes remains unclear. In this study, we investigated the correlation between serum endocan levels and subclinical AS in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Patients (n = 69) with T2DM were included. All the patients were stratified based on the absence (n = 42) or presence (n = 27) of subclinical AS. Healthy subjects (n = 28) served as controls. Serum levels of endocan, fasting blood glucose, glycosylated hemoglobin A1, high-sensitivity C-reactive protein and carotid intima-media thickness (cIMT) were measured. RESULTS: Endocan levels were significantly elevated in both the T2DM (0.89 ± 0.28ng/mL) and T2DM with subclinical AS (1.20 ± 0.33ng/mL) groups relative to the control group (0.68 ± 0.24ng/mL) (P < 0.05 for all). Endocan levels were also positively correlated with glycosylated hemoglobin A1, fasting blood glucose and cIMT (r = 0.292, P = 0.004; r = 0.224, P = 0.027 and r = 0.496, P < 0.001, respectively). In addition, endocan levels were independently associated with cIMT (ß = 0.220, t = 5.816, P = 0.000) and were a significant risk factor for T2DM with subclinical AS (odds ratio = 1.98, 95% CI: 1.43-2.73, P < 0.001). CONCLUSIONS: These findings suggest that serum endocan levels may be a useful biomarker for the early diagnosis of subclinical AS in patients with T2DM.

Reduced serum milk fat globule-epidermal growth factor 8 (MFG-E8) concentrations are associated with an increased risk of microvascular complications in patients with type 2 diabetes.

BACKGROUND: The association between serum milk fat globule-epidermal growth factor 8 (MFG-E8) concentrations and vascular complications in T2DM remains unclear. METHODS: A total of 149 patients with T2DM were included. The serum concentrations of MFG-E8, glycosylated hemoglobin (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were measured. RESULTS: There was no significant difference in serum MFG-E8 concentrations between the T2DM group and the T2DM with subclinical atherosclerosis (AS) group (615.49±143.54 vs. 596.22±79.46ng/ml, P=0.365), while the serum concentrations of MFG-E8 in the T2DM with microvascular complications group (446.70±61.53ng/ml) and the T2DM with subclinical AS and microvascular complications group (200.87±38.86ng/ml) were significantly lower than those in the T2DM group (P=0.000 for both). In addition, hs-CRP and HbAlc concentrations were independently associated with serum MFG-E8 concentrations (P=0.024 and P=0.01, respectively), and low serum MFG-E8 concentrations were significantly associated with an increased risk of microvascular complications in T2DM patients. CONCLUSIONS: Serum concentrations of MFG-E8 were negatively associated with the risk of microvascular complications in patients with T2DM. Thus, it might be a potential candidate biomarker for diabetic microvascular complications.

Role of mimic of manganese superoxide dismutase in proliferation and apoptosis of gastric carcinoma BGC-823 cells in vitro and in vivo.

The aim of this study was to investigate the anti-cancer effect and mechanism of mimic of manganese superoxide dismutase (MnSODm) in gastric carcinoma cells in vitro and in vivo. The MTT was used to measure cytotoxicity of the MnSODm. The appearance of apoptotic BGC-823 cells was detected by flow cytometry analysis. Apoptosis proteins, caspase family and Bcl-2 family were viewed by Western blotting. The phosphoinositide 3 kinase (PI3K)/Akt signaling pathway and the NF-κB pathway were also examined. PI3K inhibitor LY294002 was used to examine the involvement of the PI3K/Akt signaling pathway in this apoptosis-inducing effect. BGC-823 cell xenograft serious combined immunodeficiency disease mice were used for the in vivo study. The result showed that MnSODm could induce growth arrest and apoptosis of BGC-823 cells in vitro and in vivo. Further analysis demonstrated the involvement of activation of caspase cascade in MnSODm induced apoptosis. The expression of anti-apoptotic Bcl-2 was decreased, whereas the expression of pro-apoptotic Bax protein was increased. The main mechanisms on MnSODm-induced apoptosis were related to the inhibition of PI3K expression, which inactivated the phosphorylation of Akt involving the prevention of NF-κB phosphorylation and nuclear translocation. This phenomenon could be inhibited by the PI3K inhibitor LY294002. We demonstrated that the mechanisms of MnSODm inhibited the BGC-823 cell proliferation in vitro primarily are related to the induced apoptosis, which appears to be regulated by the PI3K/Akt pathway involving the prevention of NF-κB nuclear translocation, and then triggering the activation of the caspase cascades. Moreover, the anticancer effect in vivo on BGC-823 cells xenografted mice was also due to MnSODm-mediated apoptosis.