Does rAj-Tspin, a novel peptide from A. japonicus, exert antihepatocellular carcinoma effects via the ITGB1/ZYX/FAK/AKT signaling pathway?

rAj-Tspin, a soluble recombinant peptide from Apostichopus japonicus, can inhibit the integrin ß1 (ITGB1)/FAK/AKT signaling pathway in hepatocellular carcinoma (HCC) via cell epithelial-mesenchymal transition (EMT) and apoptosis. Zyxin (ZYX) is a focal adhesion protein that is considered a novel mediator of EMT and apoptosis. However, the inhibitory mechanisms of rAj-Tspin in HCC and whether it is related to ZYX are unclear. We examined the antitumor effect of rAj-Tspin on the Huh7 human HCC cell line and on a nude mouse model generated via subcutaneous injection or orthotopic intrahepatic transplantation of Huh7 cells. Our results revealed that rAj-Tspin strikingly reduced the viability and promoted the apoptosis of Huh7 cells and inhibited HCC tumor growth in nude mice. rAj-Tspin inhibited ITGB1 and ZYX protein expression in vivo and in vitro in a dose-dependent manner. Mechanistically, the FAK/AKT signaling pathway and the proliferation and invasion of HCC cells were suppressed upon ITGB1 and ZYX knockdown. Moreover, the effect of ITGB1 overexpression on the growth of HCC cells was inhibited by rAj-Tspin. In contrast, the promoting effect of ITGB1 overexpression could be inhibited by ZYX knockdown. ZYX knockdown had no effect on ITGB1 expression. These findings suggest that ZYX is required for the indispensable role of ITGB1 in rAj-Tspin-alleviated HCC and provide an important therapeutic target for HCC. In summary, the anti-HCC effect of rAj-Tspin potentially involves the regulation of the ITGB1/ZYX/FAK/AKT pathway, which in turn impacts EMT and apoptosis.

Congophilic fibrils in the glomeruli with polyclonal immunoglobulin gamma staining - another cause for diagnostic overlap: A case report.

BACKGROUND: Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice, with amyloidosis and fibrillary glomerulonephritis being the two most frequently encountered entities. Renal amyloid heavy and light chain (AHL) is relatively uncommon and its biopsy diagnosis is usually limited to cases that show strong equivalent staining for a single immunoglobulin (Ig) heavy chain and a single light chain, further supported by mass spectrometry (MS) and serum studies for monoclonal protein. But polyclonal light chain staining can pose a challenge. CASE SUMMARY: Herein we present a challenging case of renal AHL with polyclonal and polytypic Ig gamma (IgG) staining pattern by immunofluorescence. The patient is a 62-year-old Caucasian male who presented to an outside institution with a serum creatinine of up to 8.1 mg/dL and nephrotic range proteinuria. Despite the finding of a polyclonal and polytypic staining pattern on immunofluorescence, ultrastructural study of the renal biopsy demonstrated the presence of fibrils with a mean diameter of 10 nm. Congo red was positive while DNAJB9 was negative. MS suggested a diagnosis of amyloid AHL type with IgG and lambda, but kappa light chains were also present supporting the immunofluorescence staining results. Serum immunofixation studies demonstrated IgG lambda monoclonal spike. The patient was started on chemotherapy. The chronic renal injury however was quite advanced and he ended up needing dialysis shortly after. CONCLUSION: Tissue diagnosis of AHL amyloid can be tricky. Thorough confirmation using other available diagnostic techniques is recommended in such cases.

Long-term comparison of image-guided thermal ablation vs. lobectomy for solitary papillary thyroid microcarcinoma: a multi-center retrospective cohort study.

BACKGROUND: Image-guided thermal ablation has been applied in patients with papillary thyroid microcarcinoma (PTMC) who refuse surgery or active surveillance. However, evidence to support ablation is limited by single-center designs and a lack of long-term data. The purpose of this study was to compare long-term outcomes between ablation and lobectomy for patients with solitary PTMC. MATERIALS AND METHODS: This multi-center retrospective study included 1021 consecutive patients with solitary PTMC who underwent ablation ( n =444) or lobectomy ( n =577) at the four university-affiliated hospitals. The primary outcomes were disease progression [lymph node metastasis (LNM), recurrent tumors, persistent tumors and distant metastasis] and disease-free survival (DFS). Secondary outcomes were complications, hospitalization, procedure time, estimated blood loss and cost. The two groups were compared using propensity score matching. RESULTS: After matching, no significant differences were observed in disease progression (4.7% vs. 3.4%, P =0.307), LNM (1.6% vs. 1.6%, P =1.000), recurrent tumors (2.9% vs. 1.8%, P =0.269), persistent tumors(0.2% vs. 0%, P =0.317) and DFS (95.5% vs. 97.1%, P =0.246) between the ablation and lobectomy groups during the median follow-up of 96.5 months. The ablation group had significantly lower complication rates (0.7% vs. 5.2%, P <0.001), shorter post-treatment hospitalization {median [interquartile range (IQR)], 0 vs. 4.0 [3.0] days, P <0.001}, shorter procedure time [8.5 (2.8) vs. 90.0 (43.8) min, P <0.001], reduced estimated blood loss [0 vs. 20.0 (10.0) ml, P <0.001], and lower cost [$1873.2 (254.0) vs. $2292.9 (797.8), P <0.001] than the lobectomy group. CONCLUSIONS: This study revealed comparable disease progression and survival outcomes between ablation and lobectomy for solitary PTMC. Imaged-guided thermal ablation could be effective and safe alternatives to lobectomy for properly selected patients with PTMC.

Development of a prediction model for predicting the prevalence of nonalcoholic fatty liver disease in Chinese nurses: the first-year follow data of a web-based ambispective cohort study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is gradually becoming a huge threat to public health. With complex working characteristics, female nurses had been found with high risk of NAFLD. To develop and validate a prediction model to predict the prevalence of NAFLD based on demographic characteristics, work situation, daily lifestyle and laboratory tests in female nurses. METHODS: This study was a part of the Chinese Nurse Cohort Study (The National Nurse Health Study, NNHS), and data were extracted from the first-year follow data collected from 1st June to 1st September 2021 by questionnaires and physical examination records in a comprehensive tertiary hospital. The questionnaires included demographic characteristics, work situation and daily lifestyle. Logistic regression and a nomogram were used to develop and validate the prediction model. RESULTS: A total of 824 female nurses were included in this study. Living situation, smoking history, monthly night shift, daily sleep time, ALT/AST, FBG, TG, HDL-C, UA, BMI, TBil and Ca were independent risk factors for NAFLD occurance. A prediction model for predicting the prevalence of NAFLD among female nurses was developed and verified in this study. CONCLUSION: Living situation, smoking history, monthly night shift, daily sleep time, ALT/AST, FBG, TG, UA, BMI and Ca were independent predictors, while HDL-C and Tbil were independent protective indicators of NAFLD occurance. The prediction model and nomogram could be applied to predict the prevalence of NAFLD among female nurses, which could be used in health improvement. TRIAL REGISTRATION: This study was a part of the Chinese Nurse Cohort Study (The National Nurse Health Study, NNHS), which was a ambispective cohort study contained past data and registered at Clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04572347 ) and the China Cohort Consortium ( http://chinacohort.bjmu.edu.cn/project/102/ ).

Ultrasound-guided microwave ablation versus surgery for solitary T1bN0M0 papillary thyroid carcinoma: a prospective multicenter study.

OBJECTIVE: Microwave ablation (MWA) has emerged as a minimally invasive technology for papillary thyroid microcarcinoma (PTMC), but it has not been widely applied to treat T1bN0M0 PTC with high-level evidence. This study was designed to compare the real-world efficacy and safety of MWA or surgery for treating T1bN0M0 PTC. METHODS: From December 2019 to April 2021, 123 continuous unifocal T1bN0M0 PTC patients without lymph node metastasis (LNM) or distant metastasis (DM) were included from 10 hospitals. Patients were allocated into the MWA or surgery group based on their willingness. The main outcomes were local tumour progression (LTP), new thyroid cancer, LNM, and DM. The secondary outcomes included changes in tumour size and volume, complications, and cosmetic results. Subgroup analyses were conducted to identify influencing factors. RESULTS: Fifty-two patients chose MWA, and 71 patients chose surgery. Patients had similar demographic information and tumour characteristics in the two groups. The follow-up durations after MWA and surgery were 10.6 ± 4.2 and 10.4 ± 3.4 months, respectively. The LNM rate was 5.8% in the MWA group and 1.4% in the surgery group (p = 0.177). No LTP, new thyroid cancer, or distant metastasis (DM) occurred in either group. Five (9.6%) of the 52 patients in the MWA group and 8 (11.3%) of the 71 patients in the surgery group had complications (p = 0.27). Better cosmetic results were found in the MWA group (p < 0.01). CONCLUSION: MWA achieved comparable short-term treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC but concerns about LNM need to be studied further. CLINICAL RELEVANCE STATEMENT: MWA achieved comparable short-time treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC. KEY POINTS: • MWA achieved comparable short-term treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC but concerns about LNM need to be studied further. • The complication rate in the surgery group was higher than that in the MWA group without a significant difference. • There was no statistically significant difference in the LNM rate between the MWA and surgery groups.

Contrast Enhancement Ultrasound Improves Diagnostic Accuracy for Thyroid Nodules: A Prospective Multicenter Study.

Objective: To evaluate potential improvements in the diagnosis of thyroid nodules when conventional ultrasound (US) is combined with contrast-enhanced US (CEUS). Methods: We recruited 515 participants with 323 malignant and 192 benign nodules, who underwent both US and CEUS examinations at 8 different medical centers in China between October 2020 and October 2021. We assessed the malignancy of thyroid nodules in US using the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TIRADS). Diagnostic criteria for US and US + CEUS were developed by investigators based on evaluations of sonographic features. Using multivariate logistic regression and receiver operating characteristic (ROC) analysis, we compared diagnostic performance between the 2 methods based on criteria identified by investigators and via statistical models. Results: On the basis of diagnostic criteria identified by investigators, we measured statistically significant differences in area under the curve (AUC) values between ACR TIRADS (0.83) and CEUS TIRADS (0.87; P < .001). On the basis of diagnostic regression models, we found statistically significant differences in AUC values between US (0.76) and US + CEUS (0.84; P = .001). Models based on US + CEUS outperformed those based on US alone (Akaike information criterion of 347.7 and significant improvement in integrated discrimination). These results were confirmed by similar analyses applied to a validation cohort. Conclusion: The accuracy of conventional US for differentiating between benign and malignant thyroid nodules can be improved by combining this approach with CEUS.

Clinical outcomes of radiofrequency ablation for solitary T1aN0M0 versus T1bN0M0 papillary thyroid carcinoma: a propensity-matched cohort study.

OBJECTIVE: To conduct a cohort study comparing the treatment outcomes of radiofrequency ablation (RFA) therapy for solitary T1aN0M0 (T1a) versus T1bN0M0 (T1b) papillary thyroid carcinoma (PTC). METHODS: This retrospective analysis comprised 310 patients with low-risk PTC undergoing RFA classified into T1a (n = 272) and T1b (n = 38) groups according to the tumor size. A comparative analysis between the two groups was conducted for the volume reduction ratio (VRR), volume, local tumor progression (LTP), and recurrence-free survival (RFS) before and after 1:2 propensity score matching (PSM). Cox analysis was conducted to examine the influence of several variables, including T1b, on recurrence following RFA for PTC. RESULTS: The total VRR was 99.99 ± 0.11% throughout the median follow-up duration of 26 months, and the overall incidence of LTP was 2.58% (8/310). No irrecoverable complications occurred after RFA. The variations between the T1a and T1b groups following PSM were insignificant in terms of volume (p = 0.574), VRR (p = 0.574), complete disappearance rate (p = 0.210), LTP incidence (p = 1.000), and RFS rate (p = 0.610). The correlation between T1b and LTP continued to be insignificant (p = 0.686). No distant metastasis or delayed surgery occurred. CONCLUSIONS: The presence of T1b did not influence the patients' prognoses following RFA for T1N0M0 PTC. After appropriate patient selection and adequate preoperative assessment, RFA has the potential to serve as an effective therapy for individuals with T1a and T1b PTC.

A ultrasonic nomogram of quantitative parameters for diagnosing breast cancer.

This study aimed to develop a nomogram through the collection of quantitative ultrasound parameters to predict breast cancer. From March 2021 to September 2022, a total of 313 breast tumors were included with pathological results. Through collecting quantitative ultrasound parameters of breast tumors and multivariate regression analysis, a nomogram was developed. The diagnostic performances, calibration and clinical usefulness of the nomogram for predicting breast cancer were assessed. A total of 182 benign and 131 malignant breast tumors were included in this study. The nomogram indicated excellent predictive properties with an AUC of 0.934, sensitivity of 0.881, specificity of 0.848, PPV of 0.795 and NPV of 0.841. The calibration curve showed the predicted values are basically consistent with the actual observed values. The optimum cut-off for the nomogram was 0.310 for predicting cancer. The decision curve analysis results corroborated good clinical usefulness. The model including BI-RADS score, SWE and VI is potentially useful for predicting breast cancer.

Multimodality US versus Thyroid Imaging Reporting and Data System Criteria in Recommending Fine-Needle Aspiration of Thyroid Nodules.

Background Current guidelines recommend the use of conventional US for risk stratification and management of thyroid nodules. However, fine-needle aspiration (FNA) is often recommended in benign nodules. Purpose To compare the diagnostic performance of multimodality US (including conventional US, strain elastography, and contrast-enhanced US [CEUS]) with the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) in the recommendation of FNA for thyroid nodules to reduce unnecessary biopsies. Materials and Methods In this prospective study, 445 consecutive participants with thyroid nodules from nine tertiary referral hospitals were recruited between October 2020 and May 2021. With univariable and multivariable logistic regression, the prediction models incorporating sonographic features, evaluated with interobserver agreement, were constructed and internally validated with bootstrap resampling technique. In addition, discrimination, calibration, and decision curve analysis were performed. Results A total of 434 thyroid nodules confirmed at pathologic analysis (259 malignant thyroid nodules) in 434 participants (mean age, 45 years ± 12 [SD]; 307 female participants) were included. Four multivariable models incorporated participant age, nodule features at US (proportion of cystic components, echogenicity, margin, shape, punctate echogenic foci), elastography features (stiffness), and CEUS features (blood volume). In recommending FNA in thyroid nodules, the highest area under the receiver operating characteristic curve (AUC) was 0.85 (95% CI: 0.81, 0.89) for the multimodality US model, and the lowest AUC was 0.63 (95% CI: 0.59, 0.68) for TI-RADS (P < .001). At the 50% risk threshold, 31% (95% CI: 26, 38) of FNA procedures could be avoided with multimodality US compared with 15% (95% CI: 12, 19) with TI-RADS (P < .001). Conclusion Multimodality US had better performance in recommending FNA to avoid unnecessary biopsies than the TI-RADS. Clinical trial registration no. NCT04574258 © RSNA, 2023 Supplemental material is available for this article.

Safety and efficacy of microwave ablation for the treatment of low-risk papillary thyroid microcarcinoma: a prospective multicenter study.

OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.

Metabolic Disease and Risk of Thyroid Disease: Evidence from the National Nurse Health Cohort in China.

BACKGROUND: Previous studies have shown that metabolic diseases are risk factors for thyroid disease; most studies are cross-sectional design. We aimed to evaluate the causal relationship between thyroid and metabolic diseases in a cohort of Chinese nurses. METHODS: We conducted an ambispective cohort study of the National Nurses' Health Study. Thyroid disease data based on ultrasonography from 2017 to 2021 were collected. We described thyroid disease incidence and the risk factors associated with a cluster of metabolic factors. We used the Mann‒Whitney U test, repeated-measures ANOVA and multivariable Cox proportional hazard regression to analyze the data. RESULTS: A total of 1529 female nurses without thyroid disease were enrolled in 2017, of which, complete data were available for 1269 nurses. In 2018-2020, thyroid nodule incidence ranged from 32.8%-46.3%, thyroiditis incidence was 13.4%-14.3%, and goiter incidence was 4.1%-29.1%, thyroid adenoma and thyroid tumors incidence were 0.1%-0.5% and 1%-1.5%. We also found that NAFLAD was an independent risk factor for thyroid adenoma (p = .003). The age at diagnosis was an independent risk factor for goiter (p <. 001) and thyroid nodules (p < .001). Fasting blood glucose was an independent risk factor for thyroid tumors (p = .004). The age at diagnosis (p = .003), Body Mass Index (p = .006) and menopause (p = .031) were risk factors for thyroiditis. CONCLUSION: Thyroid disease incidence among nurses is increasing. Age at diagnosis, BMI, fasting blood glucose, and nonalcoholic fatty liver disease are independent risk factors for different types of thyroid disease. This study provides evidence for future studies to further explore the pathogenesis and prevention of thyroid diseases.

Immune exposure: how macrophages interact with the nucleus pulposus.

Intervertebral disc degeneration (IDD) is a primary contributor to low back pain. Immune cells play an extremely important role in modulating the progression of IDD by interacting with disc nucleus pulposus (NP) cells and extracellular matrix (ECM). Encased within the annulus fibrosus, healthy NP is an avascular and immune-privileged tissue that does not normally interact with macrophages. However, under pathological conditions in which neovascularization is established in the damaged disc, NP establishes extensive crosstalk with macrophages, leading to different outcomes depending on the different microenvironmental stimuli. M1 macrophages are a class of immune cells that are predominantly pro-inflammatory and promote inflammation and ECM degradation in the NP, creating a vicious cycle of matrix catabolism that drives IDD. In contrast, NP cells interacting with M2 macrophages promote disc tissue ECM remodeling and repair as M2 macrophages are primarily involved in anti-inflammatory cellular responses. Hence, depending on the crosstalk between NP and the type of immune cells (M1 vs. M2), the overall effects on IDD could be detrimental or regenerative. Drug or surgical treatment of IDD can modulate this crosstalk and hence the different treatment outcomes. This review comprehensively summarizes the interaction between macrophages and NP, aiming to highlight the important role of immunology in disc degeneration.

Copper-Single-Atom Coordinated Nanotherapeutics for Enhanced Sonothermal-Parallel Catalytic Synergistic Cancer Therapy.

Phototherapy and sonotherapy are recognized by scientific medicine as effective strategies for treating certain cancers. However, these strategies have limitations such as an inability to penetrate deeper tissues and overcome the antioxidant tumor microenvironment. In this study, a novel "BH" interfacial-confined coordination strategy to synthesize hyaluronic acid-functionalized single copper atoms dispersed over boron imidazolate framework-derived nanocubes (HA-NC_Cu) to achieve sonothermal-catalytic synergistic therapy is reported. Notably, HA-NC_Cu demonstrates exceptional sonothermal conversion performance under low-intensity ultrasound irradiation, attained through intermolecular lattice vibrations. In addition, it shows promise as an efficient biocatalyst, able to generate high-toxicity hydroxyl radicals in response to tumor-endogenous hydrogen peroxide and glutathione. Density functional theory calculations reveal that the superior parallel catalytic performance of HA-NC_Cu originates from the CuN4 C/B active sites. Both in vitro and in vivo evaluations consistently demonstrate that the sonothermal-catalytic synergistic strategy significantly improves tumor inhibition rate (86.9%) and long-term survival rate (100%). In combination with low-intensity ultrasound irradiation, HA-NC_Cu triggers a dual death pathway of apoptosis and ferroptosis in MDA-MB-231 breast cancer cells, comprehensively limiting primary triple-negative breast cancer. This study highlights the applications of single-atom-coordinated nanotherapeutics in sonothermal-catalytic synergistic therapy, which may create new opportunities in biomedical research.

Microwave Ablation for Papillary Thyroid Microcarcinoma with and without US-detected Capsule Invasion: A Multicenter Prospective Cohort Study.

Background Microwave ablation (MWA) has achieved favorable results in the treatment of papillary thyroid microcarcinoma (PTMC) confined in glandular parenchyma. However, studies on the outcome of MWA for PTMC with US-detected capsular invasion remain unclarified in the literature. Purpose To compare the feasibility, effectiveness, and safety of MWA in the treatment of PTMC with and without US-detected capsular invasion. Materials and Methods Participants from 12 hospitals with a PTMC maximal diameter of 1 cm or less without US- or CT-detected lymph node metastasis (LNM) who planned to undergo MWA were enrolled in this prospective study between December 2019 and April 2021. All tumors were evaluated with preoperative US and were divided into those with and those without capsular invasion. The participants were observed until July 1, 2022. The primary end points, including technical success and disease progression, and the secondary end points, including treatment parameters, complications, and tumor shrinkage during follow-up, were compared between the two groups, and multivariable regression was performed. Results After exclusion, 461 participants (mean age, 43 years ± 11 [SD]; 337 women) were included: 83 with and 378 without capsular invasion. After one participant with capsular invasion aborted MWA because of technical failure, 82 participants with and 378 participants without capsular invasion (mean tumor volume, 0.1 mL ± 0.1 vs 0.1 mL ± 0.1; P = .07) were analyzed with a mean follow-up period of 20 months ± 4 (range, 12-25 months) and 21 months ± 4 (range, 11-26 months), respectively. In those with and those without capsular invasion, comparable technical success rates were achieved (99% [82 of 83] vs 100% [378 of 378], P = .18), with one and 11 complications, respectively (1% [one of 82] vs 3% [11 of 378], P = .38). There was no evidence of differences in disease progression (2% [one of 82] vs 1% [four of 378]; P = .82) or tumor shrinkage (mean, 97% ± 8 [SD] vs 96% ± 13; P = .58). Conclusion Microwave ablation was feasible in the treatment of papillary thyroid microcarcinoma with US-detected capsular invasion and showed comparable short-term efficacy with or without the presence of capsular invasion. © RSNA, 2023 Clinical trial registration no. NCT04197960 Supplemental material is available for this article.

Long-term Outcomes of Ultrasound-guided Thermal Ablation for the Treatment of Solitary Low-risk Papillary Thyroid Microcarcinoma: A Multicenter Retrospective Study.

OBJECTIVE: To report more than 5-year outcomes of ultrasound-guided thermal ablation (TA) for patients with solitary low-risk papillary thyroid microcarcinoma (PTMC) in a large multicenter cohort. BACKGROUND: TA, including radiofrequency ablation (RFA) and microwave ablation (MWA) have been used in patients with low-risk PTMC who refuse surgery or active surveillance. However, its clinical value remains controversial. MATERIALS AND METHODS: This retrospective multicenter study included 474 patients with solitary low-risk PTMC treated with TA (357 for RFA; 117 for MWA) from 4 centers and followed up for at least 5 years. Disease progression including lymph node metastasis and recurrent tumors, volume reduction rate (VRR), tumor disappearance rate, complications, and delayed surgery were assessed. RFA and MWA outcomes were compared using propensity score matching. RESULTS: During the median follow-up period of 77.2 months, disease progression incidence, lymph node metastasis, and recurrent tumors rates were 3.6%, 1.1%, and 2.5%, respectively. Age below 40 years old, male sex, Hashimoto thyroiditis, and tumor size were not independent factors associated with disease progression by Cox analysis. The median VRR was 100% and 471 tumors disappeared radiographically. Eight patients experienced transient voice change (1.7%) which recovered within 3 months. None of the patients underwent delayed surgery because of anxiety. After 1:1 matching, no significant differences were found in the disease progression, VRR, tumor disappearance rate, or complications between RFA and MWA subgroups. CONCLUSION: This multicenter study revealed that TA was an effective and safe treatment for patients with solitary low-risk PTMC, which could be offered as a treatment option for the management for low-risk PTMC.

Microwave ablation vs. surgery for papillary thyroid carcinoma with minimal sonographic extrathyroid extension: a multicentre prospective study.

OBJECTIVES: Minimal extrathyroid extension (mETE) was removed from the TNM staging system. This study was designed prospectively to compare the safety and efficacy of microwave ablation (MWA) versus surgery for treating T1N0M0 papillary thyroid carcinomas (PTC) with sonographically detected mETE. METHODS: From December 2019 to April 2021, 198 patients with T1N0M0 mETE-PTCs evaluated by preoperative ultrasound from 10 hospitals were included. Ninety-two patients elected MWA, and 106 patients elected surgery for treatment. MWA was performed using extensive ablation with hydrodissection. Surgery consisted of lobectomy with ipsilateral central lymph node dissection (CLD), lobe and isthmus excision with ipsilateral CLD and total thyroidectomy with ipsilateral CLD. The rates of technical success, cost, oncologic outcomes, complications and quality of life of the two groups were assessed. RESULTS: The follow-up times for the MWA and surgery groups were 12.7 ± 4.1 and 12.6 ± 5.0 months, respectively. The technical success rate was 100% for both groups. Oncological outcomes of the two groups were similar during the follow-up (all p > 0.05). The MWA group had a shorter operation time, less blood loss and lower costs (all p < 0.001). Three complications (3.3%) were reported in the MWA group and 4 (3.8%) in the surgery group (p = 0.846). The surgery group had higher scores for scar problems and anxiety (p < 0.001 and p = 0.003, respectively). CONCLUSIONS: Microwave ablation was comparable in the short term to surgery in terms of treatment safety and efficacy in selected patients with T1N0M0 mETE-PTC detected by ultrasound. KEY POINTS: • Microwave ablation is comparable to surgery in the safety and short-term efficacy for PTCs with sonographically detected mETE. • Thermal ablation is technically feasible for mETE-PTC treatment. • Patients with mETE-PTC have similar quality of life in the two groups, except for worse scar problems and anxiety in the surgery group.

Arnicolide D Inhibits Oxidative Stress-Induced Breast Cancer Cell Growth And Invasion Through Apoptosis, Ferroptosis, And Parthanatos.

BACKGROUND: Breast cancer is the most common malignant tumor in women, and its pathogenesis is very complicated. More and more studies have found that Traditional Chinese Medicine plays an important role in tumor prevention. OBJECTIVE: To investigate the mechanism of arnicolide D isolated from Centipeda minima in breast cancer. METHODS: Cell Counting Kit-8 (CCK-8), western blot, RT-qPCR, ELISA, flow cytometry, and Transwell were used to detect the effect of arnicolide D on the biological function of breast cancer cells. RESULTS: Arnicolide D promoted reactive oxygen species (ROS) production and induced a decrease in mitochondrial membrane potential in breast cancer cells, thereby inhibiting cell viability and increasing lactate dehydrogenase (LDH) release. Arnicolide D activated the classical apoptosis pathway to induce cell apoptosis; it significantly promoted PARP-1 expression, enhanced the nuclear translocation of apoptosis-inducing factor (AIF), and reduced the expression of AIF in mitochondria, indicating that it can induce the occurrence of parthanatos in a ROS dependent manner. In addition, arnicolide D down-regulated glutathione peroxidase 4 (GPX4) expression and increased the accumulation of Fe2+ and malondialdehyde (MDA), thereby activating ferroptosis. Apoptosis inhibitor, ferroptosis inhibitor, PARP inhibitor, PARP-1 siRNA, AIF siRNA and GPX4 overexpression vector significantly attenuated the inhibitory effect of arnicolide D on cell viability and reduced LDH release, which indicates that arnicolide D inhibits breast cancer cell growth by inducing apoptosis, parthanatos and ferroptosis. Arnicolide D also reduced breast cancer cell invasion and inhibited the expression of matrix metallopeptidase (MMP)-2 and MMP-9. CONCLUSION: Arnicolide D can activate a variety of cell death modes by inducing oxidative stress, thereby inhibiting the growth and invasion of breast cancer cells, indicating that arnicolide D has a good anti-tumor effect.

Different effects of intravenous and local anesthesia in patients undergoing ultrasound-guided radiofrequency ablation of thyroid nodules: a prospective cohort study.

PURPOSE: To compare the efficacy and safety of intravenous anesthesia (IV) with local anesthesia (LA) in patients undergoing ultrasound (US)-guided radiofrequency ablation (RFA) of thyroid nodules. METHODS: 50 patients with American Society of Anesthesiologists classification grades I-II undergoing US-guided thyroid RFA were enrolled and randomly (1:1) divided into IV (conscious sedation with Ramsay Sedation Scale [RSS] scores of 2-3 with an anesthesiologist) and LA (subcutaneous anesthesia with lidocaine without an anesthesiologist) groups. Pre-, intra- and post-procedural blood pressure (BP) (SBP0/DBP0, SBP1/DBP1, and SBP2/DBP2), intra- and post-procedural pain (NRS1 and NRS2), ablated area volume, treatment time and adverse events were analyzed and compared. RESULTS: Age, sex, weight, number, nature, volume of nodules, and SBP0/DBP0 showed no difference between both groups. 11 and 0 patients' SBP1/DBP1 were elevated in the LA and IV groups. NRS1 differed between both groups. 6 patients in the LA group had moderate or severe pain, but none in the IV group. No between-group difference in SBP2/DBP2, NRS2, ablation completion rate and ablated volume was noted. The median procedure duration differed from 1109 (176) s in IV group and 723 (227) s in LA groups. There was no increased incidence of adverse events in IV group. CONCLUSIONS: IV with RSS scores of 2-3 maintained intra-procedural BP and relieved intra-procedural pain better, without affecting the ablation efficacy and increasing complications. Despite increased treatment time, IV is a potential option for patients undergoing US-guided RFA of thyroid nodules.

Infection microenvironment-activated core-shell nanoassemblies for photothermal/chemodynamic synergistic wound therapy and multimodal imaging.

The development of intelligent designs of new antibacterial modalities for diagnosing and treating chronic multidrug-resistant bacterial infections is an urgent need, but achieving the precisive theranostic in response to specific inflammatory microenvironments remains a great challenge. This paper describes our work designing and demonstrating infection microenvironment-activated core-shell Gd-doped Bi2S3@Cu(II) boron imidazolate framework (Bi2S3:Gd@Cu-BIF) nanoassemblies. Upon exposure to a single beam of 808 nm laser, Bi2S3:Gd@Cu-BIF nanoassemblies showed exceptional photothermal conversion (η = 52.6%) and produced several cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, by depleting the intracellular glutathione and in-situ catalyzing the decomposition of endogenous hydrogen peroxide in the inflammatory microenvironment. The broad-spectrum antibacterial properties of nanoassemblies were confirmed to be effective against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) with an inhibition rate of 99.99% in vitro. Additionally, in vivo wound-healing studies revealed that Bi2S3:Gd@Cu-BIF nanoassemblies could serve as an effective wound spray to accelerate healing following MRSA infections via photothermal/chemodynamic (PTT/CDT) synergistic therapy. The effective wound healing rate in the synergistic treatment group was 99.8%, which is higher than the 69.5% wound healing rate in the control group. Furthermore, magnetic resonance and computed tomography dual-modal imaging mediated by Bi2S3:Gd@Cu-BIF nanoassemblies also exhibits promising potential as an integrated diagnostic nanoplatform. Overall, this work provides useful insights for developing all-in-one theranostic nanoplatforms for clinical treatment of drug-resistant bacterial infections. STATEMENT OF SIGNIFICANCE: New treatments and effective diagnostic strategies are critical for fighting drug-resistant bacterial infections. Infection microenvironment-activated Bi2S3@Cu-BIF nanoassemblies can simultaneously increase eigen temperature and generate cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, under near-infrared laser irradiation, achieving the synergistic effect of photothermal and chemodynamic therapy, which has been proven to be highly effective for inhibiting bacterial activity and speeding wound healing from methicillin-resistant Staphylococcus aureus infection. More importantly, the nanoassemblies could enable early precise visualized detection of bacterial abscess using magnetic resonance/computed tomography dual-modal bio-imaging techniques.

Giant Cell Tumors of Bone in Patients Aged 18 Years Old or Younger: Imaging Features and Tumor Characteristics.

OBJECTIVE: The majority of giant cell tumors of bone (GCTB) occur in adult patients, especially between the ages of 20 and 40. This study aims to investigate the imaging features of GCTBs in pediatric patients and compare their characteristics with adult cases. METHODS: Fifty-seven cases of patients aged 18 years old or younger were retrospectively analyzed, accounting for 12.8% of GCTBs in the First Affiliated Hospital of Zhengzhou University from 2001 to 2019. One hundred twenty-six adult patients (19 years of age and older) with GCTB occurring in long tubular bones were also included in this study. The following clinical information was identified from the medical records: age, sex, and follow-up data. Imaging features were reviewed by two musculoskeletal radiologists. Patient characteristics and imaging features between the two groups were compared. RESULTS: A total of 57 patients (32 females, 25 males) were included in the study. The patients' ages ranged from 9 to 18 (median = 17 y). The majority of tumors occurred in tubular bones (n = 38, 66.7%) and the pelvis (n = 8, 14.0%). Imaging features were identified in GCTB cases occurring in the long tubular bones. Compared with adult GCTB patients, pediatric GCTB patients had a larger superior-inferior (SI) diameter (P = 0.005) and smaller left-to-right diameter/SI diameter ratio (P = 0.001). Epiphyseal involvement was relatively less common in pediatric patients with GCTBs than in adult patients (P = 0.009). The median age of patients without epiphyseal involvement was lower than the median age of patients with epiphyseal involvement (11 vs 17 y). CONCLUSION: GCTB in the pediatric age group is rare. This study has found that, in pediatric patients with GCTBs, the epiphysis is relatively less involved, and the tumor is more likely to grow longitudinally. These findings are helpful in the diagnosis of GCTBs in the pediatric population.