Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.

Drug resistance represents a significant obstacle in cancer treatment, underscoring the need for the discovery of novel therapeutic targets. Ubiquitin-specific proteases (USPs), a subclass of deubiquitinating enzymes, play a pivotal role in protein deubiquitination. As scientific research advances, USPs have been recognized as key regulators of drug resistance across a spectrum of treatment modalities, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy. This comprehensive review examines the complex relationship between USPs and drug resistance mechanisms, focusing on specific treatment strategies and highlighting the influence of USPs on DNA damage repair, apoptosis, characteristics of cancer stem cells, immune evasion, and other crucial biological functions. Additionally, the review highlights the potential clinical significance of USP inhibitors as a means to counter drug resistance in cancer treatment. By inhibiting particular USP, cancer cells can become more susceptible to a variety of anti-cancer drugs. The integration of USP inhibitors with current anti-cancer therapies offers a promising strategy to circumvent drug resistance. Therefore, this review emphasizes the importance of USPs as viable therapeutic targets and offers insight into fruitful directions for future research and drug development. Targeting USPs presents an effective method to combat drug resistance across various cancer types, leading to enhanced treatment strategies and better patient outcomes.

Analysis of the mechanism of resistance to enzymatic hydrolysis of RS-5 resistant starch.

RS-5 refers to the resistant starch formed by complexation of starch molecules with other molecules. In this study, the molecular mechanism of RS-5 was analysed. First, it was found, when α-amylase acted on the starch-lipid complexes, the glucose residues involved in complexation cannot be hydrolyzed by α-amylase, while the glucose residues not directly involved in complexation can be hydrolyzed. Second, lipid molecules are not necessary for the formation of RS-5 and can be replaced with small peptides or decanal molecules. Considering the multiple health hazards that may result from excessive lipid intake, small peptides composed of essential amino acids may be more desirable materials for RS-5 preparation. Third, starch-lipid complexes had strong interactions with α-amylase, which provides evidence in support of the sliding continuum hydrolysis hypothesis of α-amylase. These results revealed the mechanism of RS-5 at the molecular level, which provides a reference for the production and research of RS-5.

Cellular functions, molecular signalings and therapeutic applications: Translational potential of deubiquitylating enzyme USP9X as a drug target in cancer treatment.

Protein ubiquitination, one of the most significant post-translational modifications, plays an important role in controlling the proteins activity in diverse cellular processes. The reversible process of protein ubiquitination, known as deubiquitination, has emerged as a critical mechanism for maintaining cellular homeostasis. The deubiquitinases (DUBs), which participate in deubiquitination process are increasingly recognized as potential candidates for drug discovery. Among these DUBs, ubiquitin-specific protease 9× (USP9X), a highly conserved member of the USP family, exhibits versatile functions in various cellular processes, including the regulation of cell cycle, protein endocytosis, apoptosis, cell polarity, immunological microenvironment, and stem cell characteristics. The dysregulation and abnormal activities of USP9X are influenced by intricate cellular signaling pathway crosstalk and upstream non-coding RNAs. The complex expression patterns and controversial clinical significance of USP9X in cancers suggest its potential as a prognostic biomarker. Furthermore, USP9X inhibitors has shown promising antitumor activity and holds the potential to overcome therapeutic resistance in preclinical models. However, a comprehensive summary of the role and molecular functions of USP9X in cancer progression is currently lacking. In this review, we provide a comprehensive delineation of USP9X participation in numerous critical cellular processes, complicated signaling pathways within the tumor microenvironment, and its potential translational applications to combat therapeutic resistance. By systematically summarizing the updated molecular mechanisms of USP9X in cancer biology, this review aims to contribute to the advancement of cancer therapeutics and provide essential insights for specialists and clinicians in the development of improved cancer treatment strategies.

MAGP2 promotes osteogenic differentiation during fracture healing through its crosstalk with the ß-catenin pathway.

Osteogenic differentiation is important for fracture healing. Microfibrial-associated glycoprotein 2 (MAGP2) is found to function as a proangiogenic regulator in bone formation; however, its role in osteogenic differentiation during bone repair is not clear. Here, a mouse model of critical-sized femur fracture was constructed, and the adenovirus expressing MAGP2 was delivered into the fracture site. Mice with MAGP2 overexpression exhibited increased bone mineral density and bone volume fraction (BV/TV) at Day 14 postfracture. Within 7 days postfracture, overexpression of MAGP2 increased collagen I and II expression at the fracture callus, with increasing chondrogenesis. MAGP2 inhibited collagen II level but elevated collagen I by 14 days following fracture, accompanied by increased endochondral bone formation. In mouse osteoblast precursor MC3T3-E1 cells, MAGP2 treatment elevated the expression of osteoblastic factors (osterix, BGLAP and collagen I) and enhanced ALP activity and mineralization through activating ß-catenin signaling after osteogenic induction. Besides, MAGP2 could interact with lipoprotein receptor-related protein 5 (LRP5) and upregulated its expression. Promotion of osteogenic differentiation and ß-catenin activation mediated by MAGP2 was partially reversed by LRP5 knockdown. Interestingly, ß-catenin/transcription factor 4 (TCF4) increased MAGP2 expression probably by binding to MAGP2 promoter. These findings suggest that MAGP2 may interact with ß-catenin/TCF4 to enhance ß-catenin/TCF4's function and activate LRP5-activated ß-catenin signaling pathway, thus promoting osteogenic differentiation for fracture repair. mRNA sequencing identified the potential targets of MAGP2, providing novel insights into MAGP2 function and the directions for future research.

Intensive vision-guided network for radiology report generation.

Objective.Automatic radiology report generation is booming due to its huge application potential for the healthcare industry. However, existing computer vision and natural language processing approaches to tackle this problem are limited in two aspects. First, when extracting image features, most of them neglect multi-view reasoning in vision and model single-view structure of medical images, such as space-view or channel-view. However, clinicians rely on multi-view imaging information for comprehensive judgment in daily clinical diagnosis. Second, when generating reports, they overlook context reasoning with multi-modal information and focus on pure textual optimization utilizing retrieval-based methods. We aim to address these two issues by proposing a model that better simulates clinicians perspectives and generates more accurate reports.Approach.Given the above limitation in feature extraction, we propose a globally-intensive attention (GIA) module in the medical image encoder to simulate and integrate multi-view vision perception. GIA aims to learn three types of vision perception: depth view, space view, and pixel view. On the other hand, to address the above problem in report generation, we explore how to involve multi-modal signals to generate precisely matched reports, i.e. how to integrate previously predicted words with region-aware visual content in next word prediction. Specifically, we design a visual knowledge-guided decoder (VKGD), which can adaptively consider how much the model needs to rely on visual information and previously predicted text to assist next word prediction. Hence, our final intensive vision-guided network framework includes a GIA-guided visual encoder and the VKGD.Main results.Experiments on two commonly-used datasets IU X-RAY and MIMIC-CXR demonstrate the superior ability of our method compared with other state-of-the-art approaches.Significance.Our model explores the potential of simulating clinicians perspectives and automatically generates more accurate reports, which promotes the exploration of medical automation and intelligence.

[Research progress of pubic symphysis diastasis].

Objective: To review the research progress of pubic symphysis diastasis and provide effective reference for orthopedic surgeons in the diagnosis and treatment of pubic symphysis diastasis. Methods: The anatomy, injury mechanism, treatment, and other aspects of pubic symphysis diastasis were summarized and analyzed by reviewing the relevant research literature at domestically and internationally in recent years. Results: The incidence of pubic symphysis diastasis is high in pelvic fractures, which is caused by the injury of the ligaments and fibrocartilage disc around the pubic symphysis by external force. The treatment plan should be individualized according to the pelvic stability and the needs of patients, aiming to restore the stability and integrity of the pelvis and improve the quality of life of patients after surgery. Conclusion: At present, the research on pubic symphysis diastasis still needs to be improved. In the future, high-quality, multi-center, and large-sample studies are of great significance for the selection of treatment methods and the evaluation of effectiveness for patients with pubic symphysis diastasis.

Disordered Convolution Region of P(VDF-TrFE) Piezoelectric Nanoparticles: The Core of Sono-Piezo Dynamic Therapy.

The recent focus on P(VDF-TrFE) material in biomedical engineering stems from its outstanding mechanical properties and biocompatibility. However, its application in sono-piezo dynamic therapy (SPDT) has been relatively unexplored. In this study, we developed composite piezoelectric nanoparticles (rPGd NPs@RGD) based on recrystallized P(VDF-TrFE) particles, which offer dual capabilities of MRI imaging and targeted treatment for brain gliomas. SEM observations of P(VDF-TrFE) particles in the disordered convolution region (DCR) revealed recrystallization, representing the polymer chain structure and particle polarity. In comparison to nonrecrystallized nanoparticles, rPGd NPs@RGD exhibited remarkable stability and biocompatibility. Under ultrasound excitation, they generated significantly higher levels of reactive oxygen species, effectively inhibiting tumor cell proliferation, invasion, and migration. rPGd NPs@RGD demonstrated excellent MRI imaging capabilities and antitumor activity in U87 tumor-bearing mice. This study highlights the remarkable SPDT abilities of the developed nanoparticles, attributed to the microscopic morphological changes in the DCR that increase the nanoparticle's polarity and thus boost its potential for SPDT. This research opens new possibilities for utilizing P(VDF-TrFE) materials in advanced biomedical applications.

The effects of high-pressure treatment on the structure, physicochemical properties and digestive property of starch - A review.

High hydrostatic pressure (HHP) is a novel technology used in the food-processing industry. Starch is an important renewable natural resource. The applications of starch are determined by its properties, which in turn are determined by its structure. In this study, the effects of HHP treatment on starch structure (granular structure, crystalline structure, molecular structure, and molecular conformation) and properties (pasting, retrogradation, thermal, digestive, rheological, swelling, solubility, water absorption, and oil absorption properties) are summarised. Additionally, the mechanism of HHP-induced gelatinisation is discussed. First, the strong hydration ability of starch molecules under high pressure facilitates the binding of water molecules to starch molecules via hydrogen bonding. These bound water molecules may block the channels inside the starch granules, leading to the formation of a sealed space. Finally, the granules disintegrate because of the intra/extra pressure difference. This study provides a reference for the application of HHP to starch processing and modification.

PGPointNovo: an efficient neural network-based tool for parallel de novo peptide sequencing.

Summary: De novo peptide sequencing for tandem mass spectrometry data is not only a key technology for novel peptide identification, but also a precedent task for many downstream tasks, such as vaccine and antibody studies. In recent years, neural network models for de novo peptide sequencing have manifested a remarkable ability to accommodate various data sources and outperformed conventional peptide identification tools. However, the excellent model is computationally expensive, taking up to 1 week to process about 400 000 spectrums. This article presents PGPointNovo, a novel neural network-based tool for parallel de novo peptide sequencing. PGPointNovo uses data parallelization technology to accelerate training and inference and optimizes the training obstacles caused by large batch sizes. The results of extensive experiments conducted on multiple datasets of different sizes demonstrate that compared with PointNovo the excellent neural network-based de novo peptide sequencing tool, PGPointNovo, accelerates de novo peptide sequencing by up to 7.35× without precision or recall compromises. Availability and implementation: The source code and the parameter settings are available at https://github.com/shallFun4Learning/PGPointNovo. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Direct Knockdown of PDZ and LIM Domain 1 Using an Adenoviral Delivery System Accelerates Osteogenesis and Fracture Healing in Mice.

Substantial advances have been made in understanding the role of partial PDZ and LIM domain family's proteins in skeletal-related diseases. Yet, little is known about the effect of PDZ and LIM Domain 1 (Pdlim1) on osteogenesis and fracture repair. This study aimed to investigate whether direct gene delivery using an adenovirus vector carrying Pdlim1 (Ad-oePdlim1) or encoding shRNA-Pdlim1 (Ad-shPdlim1) could affect the osteogenic activity of preosteoblastic MC3T3-E1 cells in vitro, and influence the fracture healing of mice in vivo. We found that Ad-shPdlim1 transfection contributed to the calcified nodule formation in MC3T3-E1 cells. Downregulation of Pdlim1 enhanced the alkaline phosphatase activity and increased the expression of osteogenic markers (Runt-related transcription factor 2 [Runx2], collagen type I alpha 1 chain [Col1A1], osteocalcin [OCN], and osteopontin [OPN]). Further analysis indicated that Pdlim1 knockdown could activate ß-catenin signaling, as evidenced by the accumulation of ß-catenin in the nucleus and the increase levels of downstream regulators such as Lef1/Tcf7, axis inhibition protein 2, cyclin D1, and SRY-box transcription factor 9. By contrast, Pdlim1 overexpression resulted in inhibition of the osteogenic activity of MC3T3-E1 cells. In vivo, at day 3 after fracture,Ad-shPdlim1 adenovirus particles were injected into the fracture site of the femur of mice, and the process of fracture healing was evaluated by X-ray, micro-computed tomography and histological examination. Local injection of Ad-shPdlim1 promoted the early cartilage callus formation, restored bone mineral density, and accelerated cartilaginous ossification, with the upregulation of osteogenic gene (Runx2, Col1A1, OCN, and OPN) expression and activation of ß-catenin signaling. Thus, we concluded that inhibition of Pdlim1 contributed to osteogenesis and fracture healing by activating the ß-catenin signaling pathway.

Daytime warming strengthened delaying effect of precipitation on end of the vegetation growing season on the Tibetan Plateau.

Many studies have reported that daytime warming advances the end of the vegetation growing season (EOS) in arid and semi-arid ecosystems in the northern middle latitudes. This finding, however, seems to contradict the fact that low temperature constrains alpine vegetation activity. Using EOS from 1982 to 2015 retrieved from satellite observations, we show that daytime warming could facilitate a delay in EOS on the Tibetan Plateau, the world's largest and highest alpine region, with a dry and cold climate. Our analysis revealed a positive partial correlation (REOS-Tmax) between EOS and preseason mean daily maximum temperature (Tmax) on 57 % of the Plateau in wetter years, but on only 41 % of it in drier years. At a regional level, REOS-Tmax was 0.69 (P < 0.05, t-test) during wetter years and -0.56 (P = 0.11) during drier years, indicating that daytime warming could directly delay EOS on the Plateau. On the other hand, we found a positive partial correlation (REOS-Prec) between EOS and preseason cumulative precipitation on 62 % of the Plateau during warmer years, but on only 47 % during colder years. At a regional level, REOS-Prec was 0.68 (P < 0.05) during warmer years and - 0.28 (P = 0.46) during colder years. Moreover, REOS-Prec increased on 60 % of the Plateau under increasing Tmax during 1982-2015, suggesting that daytime warming facilitates a delay in EOS on the Tibetan Plateau by regulating the effect of precipitation on EOS. Thus, to improve autumn phenology models in this region, researchers should consider the interactive effects of temperature and precipitation on EOS.

Microfibril-Associated Glycoprotein-2 Promoted Fracture Healing via Integrin αvß3/PTK2/AKT Signaling.

Fracture healing is a complex physiological process in which angiogenesis plays an essential role. Microfibril-associated glycoprotein-2 (MAGP2) has been reported to possess a proangiogenic activity via integrin αvß3, yet its role in bone repair is unexplored. In this study, a critical-sized femoral defect (2 mm) was created in mice, followed by the delivery of an adenovirus-based MAGP2 overexpression vector or its negative control at the fracture site. At days 7, 14, 21, and 28 postfracture, bone fracture healing was evaluated by radiography, micro-computed tomography, and histopathologic analysis. Adenovirus-based MAGP2 overexpression vector-treated mice exhibited increased bone mineral density and bone volume fraction. MAGP2 overexpression contributed to an advanced stage of endochondral ossification and induced cartilage callus into the bony callus. Further analysis indicated that MAGP2 was associated with enhanced angiogenesis, as evidenced by marked MAGP2 and integrin αvß3 costaining and increased endothelial cell markers such as endomucin and CD31 levls, as well as elevated phosphorylation of protein tyrosine kinase 2 (PTK2) and AKT serine/threonine kinase 1 (AKT) in the callus. In vitro, recombinant human MAGP2 treatment enhanced the viability, migration, and tube formation ability of human microvascular endothelial cells, which was partially reversed by integrin αvß3 inhibition or MK-2206, a specific AKT inhibitor. Inhibition of integrin αvß3 abolished MAGP2-induced PTK2 and AKT activation. Taken together, our data provide the first evidence that MAGP2 promotes angiogenesis and bone formation by activating the integrin αvß3/PTK2/AKT signaling pathway.

Noninvasive assessment of carotid plaque with subharmonic aided pressure estimation from a US contrast agent: A preliminary study.

Stroke is closely associated with carotid plaques. The assessment of carotid plaque is still the key issue of stroke prevention in clinical practice. This prospective cross-sectional study included patients with carotid plaque evaluated by ultrasonography (US). The intima-media thickness (IMT), lumen stenosis severity, thickness, and length of carotid plaque were measured by the routine US, and the amplitudes of subharmonics in the upstream shoulder, top, and downstream shoulder of all plaques and corresponding lumens were observed by Subharmonic Aided Pressure Estimation (SHAPE) US examination from the US contrast agent perflubutane microbubbles (Sonazoid), which analyzed the clinical parameters of patients, the subharmonic amplitude characteristics of all plaques and lumens, and the parameter differences between the ischemic stroke (IS) group and control group. From May 2021 to February 2022, 46 carotid plaques of 23 patients were included. For plaques, the subharmonic amplitude in the plaque (-60.52 ± 4.46) was lower than that in the opposing level lumen (-56.82 ± 5.68 dB), the subharmonic gradient across the plaque cap was negatively correlated with plaque thickness (r = -0.51, p < 0.001), and with the lumen stenosis severity (r = -0.42, p = 0.003). The median IMT of the IS group was thicker than the control group. The subharmonic gradient of the intraplaque of the IS group was larger than the control group (p = 0.004). In this analysis, we use the receiver operating characteristic (ROC) curve to establish the cutoff value of the difference to predict a new monitoring method for plaque without invasion to predict IS. It still needs a large-scale study with long-term follow-up to validate these findings.

Multimodal ultrasound-based carotid plaque risk biomarkers predict poor functional outcome in patients with ischemic stroke or TIA.

BACKGROUND: Carotid vulnerable plaque is an important risk factor for stroke occurrence and recurrence. However, the relationship between risk parameters related to carotid vulnerable plaque (plaque size, echogenicity, intraplaque neovascularization, and plaque stiffness) and neurological outcome after ischemic stroke or TIA is unclear. This study investigates the value of multimodal ultrasound-based carotid plaque risk biomarkers to predict poor short-term functional outcome after ischemic stroke or TIA. METHODS: This study was a single-center, prospective, continuous, cohort study to observe the occurrence of adverse functional outcomes (mRS 2-6/3-6) 90 days after ischemic stroke or TIA in patients, where the exposure factors in this study were carotid plaque ultrasound risk biomarkers and the risk factors were sex, age, disease history, and medication history. Patients with ischemic stroke or TIA (mRS ≤3) whose ipsilateral internal carotid artery stenosis was ≥50% within 30 days were included. All patients underwent multimodal ultrasound at baseline, including conventional ultrasound, superb microvascular imaging (SMI), and shear wave elastography (SWE). Continuous variables were divided into four groups at interquartile spacing for inclusion in univariate and multifactorial analyses. After completion of a baseline ultrasound, all patients were followed up at 90 days after ultrasound, and patient modified neurological function scores (mRSs) were recorded. Multivariate Cox regression and ROC curves were used to assess the risk factors and predictive power for predicting poor neurological function. RESULTS: SMI revealed that 20 (30.8%) patients showed extensive neovascularization in the carotid plaque, and 45 (69.2%) patients showed limited neovascularization in the carotid plaque. SWE imaging showed that the mean carotid plaque stiffness was 51.49 ± 18.34 kPa (23.19-111.39 kPa). After a mean follow-up of 90 ± 14 days, a total of 21 (32.3%) patients had a mRS of 2-6, and a total of 10 (15.4%) patients had a mRS of 3-6. Cox regression analysis showed that the level of intraplaque neovascularization and plaque stiffness were independent risk factors for a mRS of 2-6, and the level of intraplaque neovascularization was an independent risk factor for a mRS of 3-6. After correcting for confounders, the HR of intraplaque neovascularization level and plaque stiffness predicting a mRS 2-6 was 3.06 (95% CI 1.05-12.59, P = 0.041) and 0.51 (95% CI 0.31-0.83, P = 0.007), respectively; the HR of intraplaque neovascularization level predicting a mRS 3-6 was 6.11 (95% CI 1.19-31.45, P = 0.031). For ROC curve analysis, the mRSs for intraplaque neovascularization level, plaque stiffness, and combined application to predict 90-day neurological outcome ranged from 2 to 6, with AUCs of 0.73 (95% CI 0.59-0.87), 0.76 (95% CI 0.64-0.89) and 0.85 (95% CI 0.76-0.95), respectively. The mRSs for the intraplaque neovascularization level to predict 90-day neurological outcome ranged from 3 to 6, with AUCs of 0.79 (95% CI 0.63-0.95). CONCLUSION: Intraplaque neovascularization level and plaque stiffness may be associated with an increased risk of poor short-term functional outcome after stroke in patients with recent anterior circulation ischemic stroke due to carotid atherosclerosis. The combined application of multiple parameters has efficacy in predicting poor short-term functional outcome after stroke.

Transcranial sonography with clinical and demographic characteristics to predict cognitive impairment in PD: a longitudinal study.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease and is clinically characterized by a series of motor symptoms (MS) and nonmotor symptoms (NMS). NMS often appear before MS, while cognitive impairment mostly occurs within a few years after the diagnosis of PD. Therefore, we aimed to predict the risk factors for cognitive impairment (CI) in PD patients based on transcranial sonography, clinical symptoms, and demographic characteristics. METHODS: Based on the occurrence time of CI, a total of 172 PD patients were divided into non-CI (N-CI, n = 48), CI at the first treatment (F-CI, n = 58), and CI at the last treatment (L-CI, n = 66) groups. Clinical data (including MS and NMS) and ultrasonic data of all patients at the first treatment and the last treatment were collected retrospectively. Independent samples t tests were used to compare continuous data, and chi-square tests were used to compare categorical data. The risk factors for CI and Parkinson's disease dementia were identified by logistic regression analysis, and an ROC curve was established to explore the diagnostic efficacy. RESULTS: 1) The age of onset, first treatment and smoking history of CI patients were significantly different from those of N-CI patients. When age of first treatment ≥61 years was considered the boundary value to diagnose CI, the sensitivity and specificity were 77.40 and 66.70%, respectively. 2) The severity of depression was significantly different between F-CI and N-CI patients at the first treatment, while the cumulative and new or aggravated memory deficit was significantly different between the L-CI and N-CI patients at the last treatment. 3) There was a significant difference in TCS grading between the first and last treatment in L-CI patients. 4) Depression, sexual dysfunction, and olfactory dysfunction in NMS were independent risk factors for CI during the last treatment. 5) The sensitivity and specificity of predicting CI in PD patients were 81.80 and 64.60%, respectively. CONCLUSIONS: PD patients with CI were older, and most of them had a history of smoking. Furthermore, there was good diagnostic efficiency for predicting CI in PD via TCS combined with clinical characteristics (especially NMS).

Ultrasound-guided thermal ablation for papillary thyroid microcarcinoma: A systematic review.

OBJECTIVE: Thyroidectomy is the first-line treatment for papillary thyroid microcarcinoma (PTMC), but often involves aggressive overtreatment. Thermal ablation (TA) has been gradually used for the treatment of recurrent PTMC. However, it is not recommended for the treatment of primary PTMC according to the Korean and Italian guidelines. Therefore, this systematic review aimed to analyse the indications, efficacy, and safety of TA in the treatment of PTMC. DESIGN: Systematic review. PATIENTS AND MEASUREMENTS: A search strategy was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A total of 27 articles were included in this study until January 2022. RESULTS: According to current guidelines and studies, we divided the indications of TA for PTMC into six primary and three secondary indications. Laser ablation (LA) has the advantages of a small needle, accurate output energy and precision ablation, and it is safe to important organs around the lesion. The patients recover quickly after radiofrequency ablation (RFA), with no major complications, recurrence, or lymph node metastasis. The volume reduction rate after RFA was the highest, followed by microwave ablation and LA, and the improvement in patient quality of life after TA was significantly better than after thyroidectomy. CONCLUSIONS: TA is an effective alternative method for surgery in the treatment of low-risk PTMC and has the advantages of being minimally invasive, economical, having less bleeding and having a high postoperative quality of life.

Diagnostic performance of simplified TI-RADS for malignant thyroid nodules: comparison with 2017 ACR-TI-RADS and 2020 C-TI-RADS.

BACKGROUND: The aim of this study is to propose a new TI-RADS and compare it with the American College of Radiology (2017 ACR)-TI-RADS and the 2020 Chinese (2020 C)-TI-RADS. METHODS: A retrospective analysis of 749 thyroid nodules was performed. Based on the calculated odds ratio of ultrasonic signs between benign and malignant nodules, a new thyroid nodule score and malignancy rate were calculated. A receiver operating characteristic curve was drawn to analyze the new system's effectiveness in the differential diagnosis of benign and malignant thyroid nodules and was compared with the 2020 C-TI-RADS and 2017 ACR-TI-RADS. Five ultrasound physicians with different qualifications graded another 123 thyroid nodules according to the 2017ACR-TI-RADS, 2020 C-TI-RADS, and the newly proposed TI-RADS. Intergroup and intragroup consistency was evaluated using the Kappa test and intraclass correlation coefficient (ICC) test. RESULTS: 1) The new thyroid nodule score was divided into 0, 1, 2, 3, 4, and 5 points, with malignancy rates of 1.52%, 7.69%, 38.24%, 76.00%, 90.75%, and 93.75%, respectively. Using 3 points as the cutoff value to diagnose benign and malignant thyroid nodules, the sensitivity and specificity were 94.03% and 67.39%, respectively, which were higher than those of the 2017 ACR-TI-RADS and 2020 C-TI-RADS. The simplified TI-RADS, namely, sTI-RADS, was established as follows: sTI-RADS 3 (0 points), malignancy rate < 2%; sTI-RADS 4a (1 point), malignancy rate 2-10%; sTI-RADS 4b (2 points), malignancy rate 10-50%; sTI-RADS 4 (3 points), malignancy rate 50-90%; and sTI-RADS 5 (4 and 5 points), malignancy rate > 90%. 2) Five ultrasound doctors graded thyroid nodules by the 2017 ACR-TI-RADS, 2020C-TI-RADS and sTI-RADS. Intragroup consistency was good among all tests; ICC were 0.86 (0.82-0.90), 0.84 (0.78-0.88), and 0.88 (0.84-0.91), respectively, while only sTI-RADS had good intergroup consistency. CONCLUSION: In summary, we proposed a new TI-RADS, namely, sTI-RADS, which was obtained using a simple assignment method with higher specificity, accuracy, positive predictive value, and Youden index than the 2017 ACR-TI-RADS and 2020 C-TI-RADS.

Noninvasive assessment of intracranial pressure using subharmonic-aided pressure estimation: An experimental study in canines.

BACKGROUND: Intracranial hypertension is a common clinicopathological syndrome in neurosurgery, and a timely understanding of the intracranial pressure (ICP) may help guide clinical treatment. We aimed to investigate the correlation between subharmonic contrast-enhanced ultrasound (SHCEUS) parameters and ICP in experimental canines. METHODS: A dynamic model of ICP change from 11 mm Hg to 50 mm Hg was established in experimental canines by placing a latex balloon into the epidural space and injecting saline into the balloon. In addition, a pressure sensor was placed in the brain parenchyma to record the changes in ICP. When the ICP stabilized after each increase, subharmonic-aided pressure estimation (SHAPE) technology was performed to obtain the SHCEUS parameters, including the basal venous and adjacent intracranial arterial subharmonic amplitude and SHAPE gradient (subharmonic amplitude in the intracranial artery minus that in the basal vein). The correlation between these parameters and ICP was analyzed. RESULTS: The subharmonic amplitude of the basal vein was negatively correlated with the ICP (r = -0.798), and the SHAPE gradient was positively correlated with the ICP (r = 0.628). According to the guidelines for ICP monitoring in patients with traumatic brain injury, we defined 20 mm Hg, 25 mm Hg, and 30 mm Hg as the cutoff ICP levels. The area under the receiver operating characteristic curve of the basal venous subharmonic amplitude for diagnosing intracranial hypertension ≥20 mm Hg, ≥25 mm Hg, and ≥30 mm Hg was 0.867 (95% confidence interval [CI], 0.750-0.943), 0.884 (95% CI, 0.770-0.954), and 0.875 (95% CI, 0.759-0.948), respectively. The area under the receiver operating characteristic curve of the SHAPE gradient for diagnosing intracranial hypertension ≥20 mm Hg, ≥25 mm Hg, and ≥30 mm Hg was 0.839 (95% CI, 0.716-0.924), 0.842 (95% CI, 0.720-0.926), and 0.794 (95% CI, 0.665-0.890), respectively. CONCLUSION: SHCEUS parameters are correlated with ICP. The SHAPE technique can assist in evaluating ICP changes in canines, which provides a new idea and method for evaluating ICP.

Efficacy and Safety of Thermal Ablation for Treating Lymph Node Metastasis From Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy and safety of thermal ablation, including radiofrequency ablation (RFA), microwave ablation (MVA), and laser ablation (LA), for treating lymph node metastasis (LNM) from papillary thyroid carcinoma (PTC). Design and Methods: PubMed and EMBASE were searched for studies reporting the efficacy and safety of thermal ablation for treating LNM in PTC. After selecting the relevant literature (including 11 papers, 208 patients, 412 lymph nodes), the QUADAS-2 tool was used to evaluate its quality. Then, both the fixed-effects and random-effects models combined with subgroup analysis were used to calculate data on volume changes in metastatic lymph nodes and changes in serum thyroglobulin (Tg) levels. We pooled the proportion of major and overall complication rates and complete disappearance rates and used subgroup forest plots and funnel plots for visual representation. Because of publication bias, we also performed a trim-and-filled model for correction. The rate of recurrence and distant metastasis with ablated details were pooled. Results: In the 11 articles (208 patients and 412 diseased lymph nodes), all thermal ablation methods showed effectiveness in reducing lymph node volume (P = 0.02) and serum Tg levels (P < 0.01) which showed no between-group difference. The pooled proportion of major complications was 0%(95% CI: -0.14; 0.15, P = 1) and the overall complication rate was 5% (95% CI: -0.09; 0.20, P = 1), which revealed no significant difference among modalities. The pooled proportion of the complete disappearance rate was 82% (95% CI: 0.43; 0.96, P < 0.01) and the data with statistical significance which contains RFA and LA showed complete disappearance rate was 59% and 81% respectively. Conclusion: All thermal ablation methods, including RFA, MWA, and LA, were effective and safe for treating LNM in PTC and were especially suitable for nonsurgical patients. Besides, subgroup analysis showed no significant difference, except for LA is better than RFA in complete disappearance rate.

Ultrasound-guided thermal ablation for hyperparathyroidism: current status and prospects.

BACKGROUND: Hyperparathyroidism (HPT) is classified into primary HPT (PHPT), secondary HPT (SHPT), tertiary HPT (THPT), and pseudohyperparathyroidism. Parathyroid surgery is generally reserved for patients with symptomatic PHPT and asymptomatic patients who meet the surgical guideline criteria. However, the risk of complications and mortality after parathyroid gland surgery increases with increasing patient age. AIM: This study aimed to review existing research on laser ablation, radiofrequency ablation, microwave ablation, and high-intensity focused ultrasound in the treatment of HPT and analyze its application prospects. CONCLUSIONS: Thermal ablation is a good alternative treatment for patients with parathyroid hyperplasia who do not meet the criteria or decline surgery. Being a type of minimally invasive treatment, ultrasound-guided thermal ablation has the advantages of easy operation, rapid recovery, and reusability and is used widely.