Diagnostic value of a novel salivary gland ultrasound scoring system in IgG4-related sialadenitis.

OBJECTIVES: To develop a novel ultrasound scoring system for the major salivary glands in patients with immunoglobulin G4-related sialadenitis (IgG4-RS) and assess its diagnostic value in a multicenter cohort of Chinese patients. METHODS: Twenty clinicians (rheumatologists, stomatologists, and radiologists) participated. The study was conducted in four steps: (1) defining the ultrasonography (US) elements, (2) developing a novel ultrasound scoring system for US of the salivary glands, (3) evaluation of inter- and intra-reader reliabilities using the new ultrasound scoring system, and (4) assessing the diagnostic value of this novel ultrasound scoring system in IgG4-RS patients in a Chinese multicenter cohort. RESULTS: A novel ultrasound scoring system for the salivary glands was developed, with total scores ranging from 0 to 34. The inter- and intra-reader reliabilities of the ultrasound scoring system were excellent (0.972 and 0.940, respectively). A total of 470 people were recruited in this study; 187 patients were diagnosed with IgG4-RS, and the remaining 283 people were diagnosed with non-IgG4-RS. Patients with IgG4-RS had significantly higher US scores than the non-IgG4-RS group (mean US score=16 vs. 4, P < 0.001). The calculated area under the curve (AUC) for the total US score was 0.852 (95% CI: 0.814-0.891). The total US scores≥9 showed a sensitivity of 75.4% and a specificity of 91.9%. Association analysis showed a positive correlation between total US scores and serum IgG4 levels and hypocomplementemia (r=0.221, r=0.349; P = 0.002) and a negative correlation between total US scores and serum C3 and C4 levels (r=-0.210, r=-0.303; P = 0.005, P < 0.001). CONCLUSIONS: A novel semiquantitative ultrasound scoring system for patients with IgG4-RS was developed, with good diagnostic performance. The inter- and intra-reader reliabilities were excellent. US scores were correlated with IgG4, C3, and C4 levels and hypocomplementemia.

An updated meta-analysis on the efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitor treatment of anemia in nondialysis-dependent chronic kidney disease.

BACKGROUND: Renal anemia, a common complication and threat factor of chronic kidney disease (CKD), has long been treated with injectable erythropoietin-stimulating agents (ESAs). As concerns regarding cardiovascular safety and erythropoietin resistance to ESAs have emerged, alternative therapies are urgently needed. Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), an oral agent, has been proven to be effective in improving renal anemia. However, the effects of HIF-PHIs on nondialysis-dependent CKD (NDD-CKD) have yet to be supported by updated meta-analyses. METHODS: A meta-analysis of clinical randomized controlled trials (RCTs) on HIF-PHI treatment of NDD-CKD patients based on PubMed, EMBASE, and Cochrane databases as of July 16th, 2023, was conducted. The primary outcomes were the level of hemoglobin (Hb) postintervention and the ratio of Hb responses. Most of the analysis was conducted via RevMan 5.3 software using a random-effects model. Stata (version 15.0) was used to analyze the publication bias. RESULTS: Twenty-two studies with a total of 7178 subjects in the HIF-PHI group, 3501 subjects in the ESA group and 2533 subjects in the placebo group were enrolled. HIF-PHIs increased the level of Hb and improved iron metabolism but were not inferior to ESAs in terms of safety. CONCLUSIONS: HIF-PHIs may be a convenient and safe alternative to ESAs in patients with NDD-CKD and anemia.

The Value of Thyroid Ultrasound Computer-Aided Diagnosis System in the Evaluation of Thyroid Nodules With Concurrent Hashimoto's Thyroiditis.

OBJECTIVE: To investigate the value of computer-aided diagnosis (CAD) system in assessing thyroid nodules concurrent with Hashimoto's thyroiditis (HT). METHODS: Totally 148 patients with 193 thyroid nodules were enrolled. A radiologist assessed the nodules using a thyroid ultrasound CAD system. Additionally, the nodules were evaluated by one experienced radiologist alone, and one training radiologist without and with CAD assistance. The diagnostic performance was compared between the CAD system and the experienced radiologist, and the training radiologist without and with CAD assistance. RESULTS: The CAD system demonstrated a similar sensitivity to that of the experienced radiologist in diagnosing thyroid cancers (89.8% versus 92.4%, P > .05). The specificity and accuracy of the CAD system were lower than that of the experienced radiologist in assessing the nodules with diffusedly altered glands (specificity, 60.0% versus 81.7%, P = .007; accuracy, 77.5% versus 88.1%, P = .011). With CAD assistance, the training radiologist had improved sensitivity and accuracy that increased to 87.9% and 86.8% in classifying nodules with sonographically evident HT (both P = .012). CONCLUSION: The CAD system has comparable sensitivity, but lower specificity compared with the experienced radiologist in diagnosing thyroid malignancies concurrent with HT. For a radiologist with less experience, the CAD system can help improve the diagnostic performance by increasing sensitivity and accuracy in assessing thyroid nodules with diffusely altered parenchyma.

Ultrasound Surveillance of Abnormal Cervical Lymph Nodes in Patients With Papillary Thyroid Carcinoma After Surgery.

OBJECTIVES: To document the changing trends of abnormal cervical lymph nodes (LNs) in patients with papillary thyroid carcinoma (PTC) who had serial follow-up ultrasound (US) scans after surgery and to determine how these node abnormalities progress in real time. METHODS: Ultrasound findings from 568 consecutive patients with PTC who were monitored postoperatively were reviewed. Abnormal LNs were classified as either suspicious or indeterminate according to the European Thyroid Association guidelines. Outcomes from US monitoring of the LNs were recorded and analyzed. RESULTS: Seventy-six (13.4%) of 568 patients were identified with abnormal LNs. Among them, 55 (72.4%) were initially found to have suspicious LNs, and the other 21 (27.6%) had indeterminate lesions. Of the 55 suspicious LNs, final scans showed that 38 (69.1%) lesions were still suspicious, whereas the remaining 17 (30.9%) nodes were shown to have resolved after a median follow-up of 36 months. Of the 21 indeterminate node abnormalities, final scans showed that 16 (76.2%) LNs remained indeterminate, whereas the other 5 (23.8%) nodes had developed into suspicious LNs after a median follow-up of 44 months. Loss of the fatty hilum and peripheral or diffusedly increased vascularity were more likely to be linked to persistent suspicious LNs (P = .02 and .04, respectively). Suspicious LNs with echogenic foci but a lack of other abnormal features were more frequently found to have resolved thereafter (P = .03). CONCLUSIONS: Abnormal LNs detected after PTC surgery can often remain indolent during US surveillance, and a small portion of the nodes would have resolved over time.

Inspection of disbonds in titanium alloy honeycomb sandwich structures with different skin thicknesses using linear frequency-modulated thermography.

This paper reports the linear frequency-modulated thermography inspection of disbonds in titanium alloy honeycomb sandwich structures with different skin thicknesses. A three-dimensional finite element model of a titanium alloy honeycomb sandwich structure is built. The maximum value of the phase difference between the disbond defect region and the nondefective region is used to optimize the heating duration and frequency bandwidth. Three titanium alloy honeycomb sandwich structure specimens, with a skin thickness of 0.6 mm, 0.85 mm, and 1.2 mm, respectively, are manufactured, in which skin-to-core disbond defects are prepared. The linear frequency-modulated thermography experiments are carried out on the specimens. The correlation algorithm is used to process the infrared image sequences. The experimental results show that linear frequency-modulated thermography can realize the fast and efficient inspection of the disbonds in titanium alloy honeycomb sandwich structures with different skin thicknesses. For skin thickness ranges from 0.6 mm to 1.2 mm, a heating duration of 22 s and a frequency range of 0.01 Hz-0.21 Hz are recommended.

Step-heating infrared thermographic inspection of steel structures by applying least-squares regression.

This paper reports the application of the least-squares regression method in the step-heating thermographic inspection of steel structures. The surface temperature variation of a slab with finite thickness during both the step-heating phase and the cooling-down phase is presented. A mild steel slab with holes of various depths and diameters is chosen as the specimen. The step-heating thermographic inspection experiments are carried out on the specimen with different heating times. The heating as well as the cooling-down phases are recorded with an infrared camera and are analyzed separately by linear regression of the double logarithmic temperature increase versus time plots. Three statistics of the linear regression, the slope, the coefficient of determination, and the F-test value, are used to create image maps according to the processing results. The signal-to-noise ratio of each map is calculated to evaluate the performance of the three imaging methods with different durations of heating time and cooling time. The results prove that the F-test value maps present a good performance for the sequences of the step-heating phase, while the slope maps present a good performance for the sequences of the cooling-down phase. The optimal heating time and cooling time for a steel structure are also concluded. The comparison with the results of the thermographic signal reconstruction (TSR) method proves that the least-squares regression method has better detectability and a higher inspection efficiency.

Inspection of disbonds in multilayer dissimilar metal structure using lock-in thermography.

This paper reports the characterization of disbonds between a steel plate and a lead plate on the surface of the lead using lock-in thermography. Based on the photothermal model, the excitation frequency of the bonding specimen with the steel plate and the lead plate is optimized. A lock-in thermography testing system is established to inspect the specimen. The Fourier transform method is used to process the infrared image sequences. To improve the signal-to-noise ratio (SNR), a fuzzy c-means (FCM) algorithm is used to process the phase matrix. The influence of number of clusters on the processing results is researched, and the optimal value of clusters number is obtained. The shearing phase technique is used to evaluate the size of the disbonds quantitatively. The measurement results of the artificial disbonds in the specimen show good agreement with the actual values. The results prove that FCM is effective in enhancing the SNR of the phase image, which makes it feasible for the quantitative determination of defect size by the shearing phase technique.

Combing superb microvascular imaging with shear wave elastography for risk stratification of Thyroid Imaging Reporting and Data System (TI-RADS) 4 thyroid nodules.

Background: It is difficult to accurately assess the risk of Thyroid Imaging Reporting and Data System (TI-RADS) 4 thyroid nodules due to the overlap of benign and malignant conventional ultrasound (US) features of nodules. To reduce unnecessary needle biopsies and assist clinical decision-making, this study established a dynamic nomogram incorporating superb microvascular imaging (SMI) and shear wave elastography (SWE) for the risk evaluation of TI-RADS 4 thyroid nodules. Methods: A total of 248 patients who underwent US, SMI, and SWE with cytological or histopathological results were included in this retrospective study, and were randomly divided into training (174 patients) and verification (74 patients) cohorts. The clinical characteristics and US, SMI, and SWE features of patients were analyzed in the training cohort. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to screen parameters and construct dynamic nomogram. The receiver operating characteristic (ROC) curves, calibration curve, and decision curve were used to evaluate the performance of the nomogram. Results: A dynamic nomogram was constructed based on age [odds ratio (OR) =0.954; P=0.005] , shape (OR =0.345; P=0.041), SMI (OR =9.511; P<0.001), and SWE (OR =3.670; P=0.001). The nomogram showed excellent discrimination both in the training [area under the curve (AUC): 0.848; 95% confidence interval (CI): 0.784-0.911] and validation (AUC: 0.862; 95% CI: 0.780-0.944) cohorts, and better than US, SMI, and SWE alone in all cohorts (P<0.05). The Nomo-score of each patient was calculated and the cut-off value was 0.607 which can be used to distinguish high-risk and low-risk patients. Conclusions: The SMI and SWE show added predictive value on risk stratification in patients with TI-RADS 4 thyroid nodules and a dynamic nomogram was constructed to screen high-risk individuals and assist the clinical decision-making.

Nanophthalmos-Associated MYRF gene mutation facilitates intraocular inflammation in mice.

PURPOSE: Patients with nanophthalmos might be prone to developing intraocular inflammation following an acute glaucoma attack. Here, we aimed to investigate the role of MYRF in intraocular inflammation by modeling the mutation in mice. METHODS: Nanophthalmos frameshift mutation of Myrf was introduced into the mouse genome with the CRISPR-Cas9 system. Signaling pathways in eye tissues were delineated using RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Intraocular inflammation was induced by a lipopolysaccharide (LPS) intravitreal injection. Dexamethasone (DEX) was administered systemically and locally a week before the LPS injection. The anterior segment clinical scores of the mice were examined 24 h after the LPS injection. Infiltrating inflammatory cells were evaluated with histopathology and immunofluorescence. The mRNA levels of inflammatory cytokines were quantified with reverse transcription-quantitative PCR (RT-qPCR) and the corresponding protein concentrations using enzyme-linked immunosorbent assay (ELISA). RESULTS: Many inflammation-associated signaling pathways were enriched in Myrf mut/+ mice ocular tissues. Clinical scores of Myrf mut/+ mice were significantly higher than those of Myrf +/+ mice 24 h after LPS administration. Histological examination demonstrated high inflammatory cell infiltration in the anterior and vitreous chambers in Myrf mut/+ mice, with numerous CD45+ and CD11b+ inflammatory cells. Moreover, enhanced expression of inflammatory cytokines MCP-1, TGF-ß, and IL-1ß in eyes and aqueous humor of Myrf mut/+ mice was detected. Remarkably, pretreating Myrf mut/+ mice with DEX relieved the intraocular inflammation. CONCLUSION: Nanophthalmos-associated MYRF mutation renders mouse eyes more susceptible to inflammation. Dexamethasone treatment ameliorates the inflammatory response.

High glucose dialysate-induced peritoneal fibrosis: Pathophysiology, underlying mechanisms and potential therapeutic strategies.

Peritoneal dialysis is an efficient renal replacement therapy for patients with end-stage kidney disease. However, continuous exposure of the peritoneal membrane to dialysate frequently leads to peritoneal fibrosis, which alters the function of the peritoneal membrane and results in withdrawal from peritoneal dialysis in patients. Among others, high glucose dialysate is considered as a predisposing factor for peritoneal fibrosis in patients on peritoneal dialysis. Glucose-induced inflammation, metabolism disturbance, activation of the renin-angiotensin-aldosterone system, angiogenesis and noninflammation-induced reactive oxygen species are implicated in the pathogenesis of high glucose dialysate-induced peritoneal fibrosis. Specifically, high glucose causes chronic inflammation and recurrent peritonitis, which could cause migration and polarization of inflammatory cells, as well as release of cytokines and fibrosis. High glucose also interferes with lipid metabolism and glycolysis by activating the sterol-regulatory element-binding protein-2/cleavage-activating protein pathway and increasing hypoxia inducible factor-1α expression, leading to angiogenesis and peritoneal fibrosis. Activation of the renin-angiotensin-aldosterone system and Ras-mitogen activated protein kinase signaling pathway is another contributing factor in high glucose dialysate-induced fibrosis. Ultimately, activation of the transforming growth factor-ß1/Smad pathway is involved in mesothelial-mesenchymal transition or epithelial-mesenchymal transition, which leads to the development of fibrosis. Although possible intervention strategies for peritoneal dialysate-induced fibrosis by targeting the transforming growth factor-ß1/Smad pathway have occasionally been proposed, lack of laboratory evidence renders clinical decision-making difficult. We therefore aim to revisit the upstream pathways of transforming growth factor-beta1/Smad and propose potential therapeutic targets for high glucose-induced peritoneal fibrosis.

Ultrasound-Based Real-Time Imaging of Hydrogel-Based Millirobots with Volume Change Capability.

Soft-bodied robots driven by external fields have better environmental adaptability, extending their applications. Nature also provides lots of inspiration for shape-morphing robot development, for example, larvae and jellyfish. This paper presents magnetically propelled hydrogel-based millirobots with volume changeability. The millirobot can be imaged in real time in a completely enclosed space with an ultrasound imaging system. Firstly, a custom-designed magnetic generating system with six square coils was introduced to generate a uniform field to propel the robot. The robot was fabricated using hydrogel with a thickness of around 300 µm. After programmable magnetization, the robot could change its shape and move using the rotating magnetic field. With the near-infrared illumination, the robot could shrink and could recover when the illumination stopped. Even when the robot shrank, it could be propelled by the external field, showing its potential usage in complex environments. Moreover, the posture information of the robot including the position and shape could be obtained in real time using ultrasound image technology.

Retraction notice to "The role of laryngeal ultrasound in diagnosis of infant laryngomalacia" [Int. J. Pediatr. Otorhinolaryngol. 124 (2019) 111-115].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Authors and the Editor-in-Chief. After a thorough investigation, the Editor-in-Chief has concluded that details in the origin of data and permissions integral to the article's acceptance in the journal necessitate a retraction. A single hospital was mentioned in the article but this was not where the data was collected. Reviewers would have assumed that informed consent was received and properly reviewed by this institution, as it was not otherwise specified. Several oversights within the article that were brought forward by the Authors make it clear that the article that was accepted had misrepresentation of key data. While the Authors presented some differences of opinion about how these concerns about the key data originated, it is clear that when the manuscript was accepted that Reviewers and Editors would not have had knowledge of these difficulties, and this may have created a different review process and outcome for this manuscript. One of the Authors has requested an ability to provide additional information to address the concerns. However, the Editor-in-Chief has decided that this would not follow the process for accepted manuscripts or address some of the concerns presented and, therefore, has settled on the retraction of the manuscript as the final decision regarding this paper.

Recent Progress on Graphene-Based Nanocomposites for Electrochemical Sodium-Ion Storage.

In advancing battery technologies, primary attention is paid to developing and optimizing low-cost electrode materials capable of fast reversible ion insertion and extraction with good cycling ability. Sodium-ion batteries stand out due to their inexpensive price and comparable operating principle to lithium-ion batteries. To achieve this target, various graphene-based nanocomposites fabricate strategies have been proposed to help realize the nanostructured electrode for high electrochemical performance sodium-ion batteries. In this review, the graphene-based nanocomposites were introduced according to the following main categories: graphene surface modification and doping, three-dimensional structured graphene, graphene coated on the surface of active materials, and the intercalation layer stacked graphene. Through one or more of the above strategies, graphene is compounded with active substances to prepare the nanocomposite electrode, which is applied as the anode or cathode to sodium-ion batteries. The recent research progress of graphene-based nanocomposites for SIBs is also summarized in this study based on the above categories, especially for nanocomposite fabricate methods, the structural characteristics of electrodes as well as the influence of graphene on the performance of the SIBs. In addition, the relevant mechanism is also within the scope of this discussion, such as synergistic effect of graphene with active substances, the insertion/deintercalation process of sodium ions in different kinds of nanocomposites, and electrochemical reaction mechanism in the energy storage. At the end of this study, a series of strategies are summarized to address the challenges of graphene-based nanocomposites and several critical research prospects of SIBs that provide insights for future investigations.

Construction of α-MnO2 on Carbon Fibers Modified with Carbon Nanotubes for Ultrafast Flexible Supercapacitors in Ionic Liquid Electrolytes with Wide Voltage Windows.

In this study, α-MnO2 and Fe2O3 nanomaterials are prepared on a carbon fiber modified with carbon nanotubes to produce the nonbinder core-shell positive (α-MnO2@CNTs/CC) and negative (Fe2O3@CNTs/CC) electrodes that can be operated in a wide voltage window in ultrafast asymmetrical flexible supercapacitors. MnO2 and Fe2O3 have attracted wide research interests as electrode materials in energy storage applications because of the abundant natural resources, high theoretical specific capacities, environmental friendliness, and low cost. The electrochemical performance of each electrode is assessed in 1 M Na2SO4 and the energy storage properties of the supercapacitors consisting of the two composite electrodes are determined in Na2SO4 and EMImBF4 electrolytes in the 2 V and 4 V windows. The 2 V supercapacitor can withstand a large scanning rate of 5000 mV S-1 without obvious changes in the cyclic voltammetry (CV) curves, besides showing a maximum energy density of 57.29 Wh kg-1 at a power density of 833.35 W kg-1. Furthermore, the supercapacitor retains 87.06% of the capacity after 20,000 galvanostatic charging and discharging (GCD) cycles. The 4 V flexible supercapacitor shows a discharging time of 1260 s and specific capacitance of 124.8 F g-1 at a current of 0.5 mA and retains 87.77% of the initial specific capacitance after 5000 GCD cycles. The mechanical robustness and practicality are demonstrated by physical bending and the powering of LED arrays. In addition, the contributions of the active materials to the capacitive properties and the underlying mechanisms are explored and discussed.

Caffeine intake improves the cognitive performance of patients with chronic kidney disease.

Objective: Cognitive impairment is a common complication of chronic kidney disease (CKD). Caffeine intake has been reported to improve cognitive performance in several studies. However, whether the benefits of caffeine intake on cognitive function apply to patients with CKD remains unknown. Methods: We performed a retrospective cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). The data of CKD subjects and non-CKD subjects from NHANES 2011-2014 were analyzed. Propensity score matching (PSM) was performed based on age, sex, diabetes, cancer, educational level, energy intake and protein intake to select subjects. The Consortium to Establish a Registry for Alzheimer's Disease Word Learning Test (CERAD-WL), the CERAD Word List Recall Test (CERAD-DR), the Animal Fluency Test (AF) and the Digit Symbol Substitution Test (DSST) were used, whereby the occurrence of cognitive impairment was identified. Logistic regression models were performed to evaluate the association between caffeine intake and cognitive performance in CKD and non-CKD participants. Stratified analyses according to the stage of CKD and the urinary albumin/creatinine ratio levels were performed. Plot curves were then generalized to present a non-linear relationship, and the inflection point for each non-linear model was obtained by using a recursive algorithm. Results: Cognitive impairment was more prevalent in CKD patients than in non-CKD subjects. For CKD patients, caffeine intake was associated with higher CERAD-WL, CERAD-DR, AF and DSST scores. For non-CKD subjects, caffeine intake was associated with higher DSST scores only. Subgroup analysis revealed that caffeine only benefited the cognitive function of patients with CKD stages 2 and 3. The analysis showed non-linear relationships of caffeine intake and cognitive function for both CKD and non-CKD subjects. The inflection point of caffeine intake for CKD patients was 279 mg/day. Conclusion: The recommended dose of caffeine intake to improve the cognitive function of CKD patients is ≤279 mg/day.

The role of laryngeal ultrasound in diagnosis of infant laryngomalacia.

OBJECTIVE: The purpose of this study was to evaluate the role of laryngeal ultrasound in diagnosis of infant laryngomalacia. METHODS: Forty consecutive infant patients with inspiratory stridor or other laryngeal symptoms underwent flexible fiberoptic nasopharyngolaryngoscopy and laryngeal ultrasound examination from January 2014 to May 2014. The curling angle of the epiglottis and/or arytenoid tissue collapses on laryngeal ultrasound during inspiration were used to diagnose infant laryngomalacia. The value of laryngeal ultrasound in diagnosis of infant laryngomalacia was evaluated and further compared to that of flexible fiberoptic nasopharyngolaryngoscopy. RESULTS: The mean angle of the curling epiglottis in 26 patients with laryngomalacia was 69.1 ±â€¯8.1 degrees, while the mean angle of the slightly curling epiglottis in 12 patients without laryngomalacia was 89.6 ±â€¯9.7 degrees (p < 0.0001). Arytenoid tissue collapses were found in 24 patients with laryngomalacia and only one patient without laryngomalacia had a local collapse of arytenoid tissue (p < 0.0001). Twenty six of the 28 patients with laryngomalacia diagnosed by flexible fiberoptic nasopharyngolaryngoscopy were detected by laryngeal ultrasound. There was an excellent consistency between laryngeal ultrasound and flexible fiberoptic nasopharyngolaryngoscopy in the detection of infant laryngomalacia (κ = 0.826). Laryngeal ultrasound had a sensitivity of 96.3%, a specificity of 84.6%, a positive predictive value of 92.9%, and a negative predictive value of 91.7% in diagnosing infant laryngomalacia. CONCLUSIONS: Laryngeal ultrasound can help diagnose infant laryngomalacia through visualizing omega-shaped epiglottis and/or arytenoid tissue collapse during inspiration. The modality has an excellent consistency with flexible fiberoptic nasopharyngolaryngoscopy in diagnosis of the disease.

Precise Detection of Gene Mutations in Fine-Needle Aspiration Specimens of the Papillary Thyroid Microcarcinoma Using Next-Generation Sequencing.

PURPOSE: To assess the feasibility of next-generation sequencing (NGS) to detect mutations in BRAF, RAS, TERT promoter, and TP53 genes in ultrasound-guided fine-needle aspiration (FNA) biopsy samples of the papillary thyroid microcarcinoma (PTMC). METHODS: A total of 135 FNA samples out of 135 patients with suspected PTMC were submitted for mutation testing using NGS. NGS was successfully performed in 114 specimens, while the remaining 21 samples were excluded due to insufficient amount/poor quality of DNA and sequencing failure. Of those 114 samples, 72 who were confirmed as having PTMC by postoperative histopathology were enrolled in our study, and the other 42 who had a follow-up with ultrasound were excluded. Mutations of genes including BRAF, NRAS, HRAS, KRAS, TERT promoter, and TP53 were evaluated using NGS. The associations of gene mutations and clinicopathological characteristics of PTMC were analyzed. RESULTS: BRAF mutation was observed in 59 (81.94%) of 72 specimens. This mutation detected in BRAF was p.V600E (c.1799T>A) in exon 15 of all 59 specimens. NRAS mutation was identified in 1 (1.39%) specimen classified as Bethesda III and pathologically confirmed as a follicular variant PTMC. There were no mutations found in TERT promoter or TP53. The tumor with a maximum diameter (D max) larger than 5 mm was shown to be significantly correlated with the BRAF mutation in a multivariate analysis (OR 5.52, 95% CI 1.51-26.42, P = 0.033). But the BRAF mutation was not found to be significantly associated with the gender or age of patients with PTMC (P > 0.05). CONCLUSIONS: This study demonstrated that gene mutations in FNA specimens of PTMC could be successfully analyzed with a higher sensitivity using NGS compared to conventional methods for mutation detection. BRAF mutation of p.V600E was statistically associated with PTMC with a D max larger than 5 mm.

Dual pH/reduction-responsive hybrid polymeric micelles for targeted chemo-photothermal combination therapy.

The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation. In vitro cellular uptake study indicated FA Co-PMs achieved significant targeting to BEL-7404 cells via folate receptor-mediated endocytosis, and laser-induced hyperthermia further enhanced drug accumulation into cancer cells. In vivo biodistribution study indicated that FA Co-PMs prolonged drug circulation and enhanced drug accumulation into the tumor via EPR effect and FA targeting. Furthermore, the ICG-based photo-triggered hyperthermia combined with DOX-based chemotherapy synergistically induced the BEL-7404 cell death and apoptosis, and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs were promising theranostic nanocarriers for versatile antitumor drug delivery and imaging-guided cancer chemo-photothermal combination therapy. STATEMENT OF SIGNIFICANCE: The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed novel pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs triggered DOX release in response to acid pH and reduction environment and exhibited excellent temperature conversion with laser irradiation. The results indicated FA Co-PMs achieved significant targeting to BEL-7404 cells in vitro and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs displayed great potential in imaging-guided cancer chemo-photothermal combination therapy as theranostic nanocarriers.

Bubble-generating polymersomes loaded with both indocyanine green and doxorubicin for effective chemotherapy combined with photothermal therapy.

The combination of chemotherapy and photothermaltherapy (PTT) via stimuli-responsive nanovesicles has great potential in tumor treatment. In the present study, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug and photosensitizing agent for the synergistic chemo-photothermal tumor therapy. Photosensitizer indocyanine green (ICG) was encapsulated into the bilayer of polymersomes formed by amphiphilic triblock copolymer PCL8000-PEG8000-PCL8000 through thin film re-hydration method, while chemotherapeutic doxorubicin (DOX) was loaded into the hydrophilic lumen using a transmembrane ammonium bicarbonate gradient loading procedure. Under acidic condition or laser irradiation, the ammonium bicarbonate (NH4HCO3) encapsulated in the bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would decompose to produce CO2 bubbles, resulting in destruction of vesicle structure and rapid drug release. In vitro drug release study confirmed that acidic environment and NIR laser irradiation could accelerate DOX release from the BG-DIPS. Cellular uptake study indicated that laser-induced hyperthermia highly enhanced endocytosis of BG-DIPS into 4T1-Luc cancer cells. In vitro cytotoxicity study demonstrated that BG-DIPS exhibited much higher cytotoxicity than free drugs under laser irradiation. In vivo biodistribution study indicated that BG-DIPS could accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. Furthermore, in vivo antitumor study showed that BG-DIPS with laser irradiation efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy. STATEMENT OF SIGNIFICANCE: The combination of chemotherapy and photothermaltherapy via stimuli-responsive nanovesicles has great potential in tumor treatment. Herein, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug (DOX) and photosensitizing agent (ICG) for the synergistic chemo-photothermal tumor therapy. The results in vitro and in vivo demonstrated that bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would accelerate DOX release from the BG-DIPS and accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. BG-DIPS with laser irradiation could efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy.

The value and limitations of contrast-enhanced transrectal ultrasonography for the detection of prostate cancer.

OBJECTIVES: To evaluate the role of contrast-enhanced transrectal ultrasonography (CE-TRUS) for detecting prostate carcinoma. METHODS: Sixty-five patients with elevated serum prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE) were assessed using transrectal ultrasound (TRUS) and CE-TRUS. In all the patients, CE-TRUS was performed with intravenous injection of contrast agent (SonoVue, 2.4 ml) before biopsy. The cancer detection rates of the two techniques were compared. False-positive and false-negative findings related to CE-TRUS were analyzed in comparison to the pathological results of biopsy or radical prostatectomy. The targeted biopsy to abnormal CE-TRUS areas was also compared to systematic biopsy. RESULTS: Prostate cancer was detected in 29 of the 65 patients. CE-TRUS showed rapid focal enhancement or asymmetric vessels of peripheral zones in 28 patients; 23 of them had prostate cancer. CE-TRUS had 79.3% sensitivity, compared to 65.5% of TRUS (P<0.05). There were five false-positive and six false-negative findings from CE-TRUS. Benign prostate hyperplasia, and acute and chronic prostatitis were important causes related to the false-positive results of CE-TRUS. Prostate cancer originating from the transition zone or peripheral zone with lower PSA levels, small-size foci, and moderately or well-differentiated tumor was missed by CE-TRUS. The cancer detection rate of targeted biopsy (75%, 33/44 cores) was significantly higher than one of systematic biopsy (48.2%, 162/336) in those 28 cases (P<0.05). In addition, no significant correlation was found between the cancer detection rate with CE-TRUS and serum PSA levels. CONCLUSION: CE-TRUS may improve the detection rate of prostate cancer through targeted biopsy of contrast-enhanced abnormalities. Our findings indicate that systematic biopsies should not be eliminated on the basis of false-positive and false-negative findings related to CE-TRUS.