Polydopamine-Modified Titanium Dioxide Nanotube Arrays Doped with Calcium as a Sustained Drug Delivery System.

Titanium nanotube (TNT) arrays manufactured via electrochemical anodization have been widely used as local drug carriers due to their excellent biocompatibility and customizable nanotubular structures. However, the uncontrollable and abrupt drug release at the early stage decreases the drug release duration, leading to excessive drug concentration at the implantation site. In this study, a continuous drug delivery system based on TNTs was created. Initially, a basic ultrasound-assisted approach was utilized to deposit a polydopamine (PDA) coating onto TNTs to obtain PDA-modified TNTs. Next, TNTs-PDA were submerged in a calcium chloride solution to include Ca2+ through Ca2+ coordination between the PDA layer's catechol groups. Sodium alendronate (NaAL) was used as a model drug and loaded onto TNTs-PDA-Ca2+ by immersing them in an NaAL solution. In the final step, NaAL was covalently attached to TNTs-PDA-Ca2+ through coordination bonds with Ca2+. The samples underwent characterization through the use of various techniques, including field emission scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction patterning, X-ray photoelectron spectroscopy, and inductively coupled plasma emission spectrometry. The results indicated that the bioactivity of TNTs improved, and there was an enhancement in drug loading capacity and release performance due to modification with PDA and Ca2+. Furthermore, acidic conditions can cause significant drug release due to the cleavage of coordination bonds between the drug and Ca2+ ions. Thus, the aforementioned drug delivery system represents a potentially promising approach for achieving sustained and controllable drug release.

Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial.

BACKGROUND: Many patients experience lower-extremity swelling following total knee arthroplasty (TKA), which impedes recovery. Diosmin is a semisynthetic flavonoid that is often utilized to treat swelling and pain caused by chronic venous insufficiency. We aimed to evaluate the efficacy and safety of diosmin in reducing lower-extremity swelling and pain as well as in improving functional outcomes following TKA. METHODS: This study was designed as a randomized, controlled multicenter trial and conducted in 13 university-affiliated tertiary hospitals. A total of 330 patients undergoing TKA were randomized to either receive or not receive diosmin postoperatively. The diosmin group received 0.9 g of diosmin twice per day for 14 consecutive days starting on the day after surgery, whereas the control group received neither diosmin nor a placebo postoperatively. The primary outcome was lower-extremity swelling 1, 2, 3, and 14 days postoperatively. The secondary outcomes were postoperative pain assessed with use of a visual analogue scale, Hospital for Special Surgery score, range of knee motion, levels of the inflammatory biomarkers C-reactive protein and interleukin-6, and complications. RESULTS: At all postoperative time points, diosmin was associated with significantly less swelling of the calf, thigh, and upper pole of the patella as well as with significantly lower pain scores during motion. However, no significant differences in postoperative pain scores at rest, Hospital for Special Surgery scores, range of motion, levels of inflammatory biomarkers, or complication rates were found between the diosmin and control groups. CONCLUSIONS: The use of diosmin after TKA reduced lower-extremity swelling and pain during motion and was not associated with an increased incidence of short-term complications involving the outcomes studied. However, further studies are needed to continue exploring the efficacy and safety of diosmin use in TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

A Prognostic Model Generated from an Apparent Diffusion Coefficient Ratio Reliably Predicts the Outcomes of Oral Tongue Squamous Cell Carcinoma.

This study aimed to develop an apparent diffusion coefficient (ADC) ratio-based prognostic model to predict the recurrence and disease-free survival (DFS) of oral tongue squamous cell carcinoma (OTSCC). A total of 188 patients with cT1-2 oral tongue squamous cell carcinoma were enrolled retrospectively. Clinical and laboratory data were extracted from medical records. The ADC values were measured at the regions of interest of the tumor and non-tumor tissues of the MRI images, and the ADC ratio was used for comparison between the patient with recurrence (n = 83 case, 44%) and patients without recurrence (n = 105 cases, 56%). Cox proportional hazards models were generated to analyze the risk factors of cancer recurrence. A nomogram was developed based on significant risk factors to predict 1-, 5- and 10-year DFS. The receiver operator characteristic (ROC) curves of predictors in the multivariable Cox proportional hazards prognostic model were generated to predict the recurrence and DFS. The integrated areas under the ROC curve were calculated to evaluate discrimination of the models. The ADC ratio, tumor thickness and lymph node ratio were reliable predictors in the final prognostic model. The final model had a 71.1% sensitivity and an 81.0% specificity. ADC ratio was the strongest predictor of cancer recurrence in prognostic performance. Discrimination and calibration statistics were satisfactory with C-index above 0.7 for both model development and internal validation. The calibration curve showed that the 5- and 10-year DFS predicted by the nomogram agreed with actual observations.

The efficacy and safety of apatinib in patients with recurrent or metastatic nasopharyngeal carcinoma: a systematic review and meta-analysis.

Background: Apatinib is a small-molecule tyrosine kinase inhibitor targeting VEGFR-2, which was recently used in a phase II clinical trial for the treatment of recurrent or metastatic nasopharyngeal carcinoma (rmNPC). However, there is no consistent conclusion on its efficacy and safety on rmNPC. This study conducted a meta-analysis of clinical research on the efficacy and safety of apatinib in the treatment of rmNPC. Methods: In April 2022, the PubMed, Web of Science, Scopus, Chinese National Knowledge Infrastructure (CNKI), CMB, and Wanfang databases were systematically searched, and relevant research literature were screened and analyzed. The clinical trial literatures using apatinib as the main single or combined treatment for rmNPC patients were selected and combined with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and other efficacy and safety indicators. Results: The meta-analysis included 12 studies, including 408 patients with rmNPC. The methodological index for nonrandomized studies scale was used to evaluate the bias of the included literatures and found that the bias was low. A total of 408 rmNPC patients were included in the included literature, with 11 studies being a phase II single-arm trial and one being a phase II non-randomized controlled trial. The ORR of patients with rmNPC treated with apatinib was 41.5% (95% CI: 34.8%, 48.2%), and the DCR was 80.2% (95% CI: 70.9%, 89.6%). The median PFS was 6.4 months (95% CI: 5.3, 7.4), and the median OS was 14.8 months (95% CI: 10.7, 18.9). The incidence of hypertension, hand-foot skin reaction, and proteinuria was 31% (95% CI: 19-43%), 29% (95% CI: 20-39%), and 13% (95% CI: 6-20%), respectively. Discussion: The efficacy of apatinib in the treatment of rmNPC patients is similar to that of the previous second-line chemotherapy drugs, but since most studies are phase II single-arm studies, the advantages and disadvantages of the existing second-line chemotherapy regimens cannot be determined.

MultiR-Net: A Novel Joint Learning Network for COVID-19 segmentation and classification.

The outbreak of COVID-19 has caused a severe shortage of healthcare resources. Ground Glass Opacity (GGO) and consolidation of chest CT scans have been an essential basis for imaging diagnosis since 2020. The similarity of imaging features between COVID-19 and other pneumonia makes it challenging to distinguish between them and affects radiologists' diagnosis. Recently, deep learning in COVID-19 has been mainly divided into disease classification and lesion segmentation, yet little work has focused on the feature correlation between the two tasks. To address these issues, in this study, we propose MultiR-Net, a 3D deep learning model for combined COVID-19 classification and lesion segmentation, to achieve real-time and interpretable COVID-19 chest CT diagnosis. Precisely, the proposed network consists of two subnets: a multi-scale feature fusion UNet-like subnet for lesion segmentation and a classification subnet for disease diagnosis. The features between the two subnets are fused by the reverse attention mechanism and the iterable training strategy. Meanwhile, we proposed a loss function to enhance the interaction between the two subnets. Individual metrics can not wholly reflect network effectiveness. Thus we quantify the segmentation results with various evaluation metrics such as average surface distance, volume Dice, and test on the dataset. We employ a dataset containing 275 3D CT scans for classifying COVID-19, Community-acquired Pneumonia (CAP), and healthy people and segmented lesions in pneumonia patients. We split the dataset into 70% and 30% for training and testing. Extensive experiments showed that our multi-task model framework obtained an average recall of 93.323%, an average precision of 94.005% on the classification test set, and a 69.95% Volume Dice score on the segmentation test set of our dataset.

Multiparametric CT-based assessment of pretracheal anatomical relationships for safe tracheotomy: A long-forgotten issue revisited.

OBJECTIVES: To assess the anatomical relationships and variations in the pretracheal space and to guide tracheotomy procedures in a safe manner with image-based evidence. MATERIALS AND METHODS: A retrospective study was conducted on unirradiated patients requiring elective tracheotomies. Preoperative contrast-enhanced CT (CECT)/CT venography (CTV) was applied for an anatomical evaluation of the pretracheal region. Vascular morphologies were compared for three vessels: the anterior jugular vein (AJV), the innominate artery (IA) and the inferior thyroid vascular plexus (ITVP). The relationships between the thyroid isthmus and the 2nd-4th tracheal rings were also analyzed. RESULTS: A total of 120 patients were identified, most of whom (n = 110, 91.7%) had head and neck squamous cell carcinomas. Patients with recognizable AJVs (n = 118) were divided into 3 groups: single-branch (n = 11, 9.2%), double-branch (n = 105, 87.5%), and multibranch (n = 2, 1.7%). In addition, IAs were categorized as low-bifurcation (n = 51, 42.5%), high-bifurcation (n = 40, 33.3%), platform (n = 27, 22.5%) and variant types (n = 2, 1.7%). Within the platform types, high-lying IAs (n = 15, 8.3%) might have interfered with the standard tracheal incisions due to possible IA-tracheal overlay. This interference was also related to the height of intraoperative tracheal incisions (rn = 0.364, P = 0.001). Within ITVPs, independent-trunk types were found in 71 cases (59.2%), while common-trunk types were found in 45 (37.5%). In addition, a low thyroid isthmus (suprasternal-isthmus distance <3 cm) was found in 83 cases (69.2%). CONCLUSIONS: CT image-based evidence can prepare junior practitioners with important pretracheal anatomical information, thereby facilitating safer tracheotomy procedures. Our results shed light on vascular relationships for emergent tracheotomy.

Efficient Magnetic Nanocatalyst-Induced Chemo- and Ferroptosis Synergistic Cancer Therapy in Combination with T1-T2 Dual-Mode Magnetic Resonance Imaging Through Doxorubicin Delivery.

Excessive iron ions in cancer cells can catalyze H2O2 into highly toxic •OH and then promote the generation of reactive oxygen species (ROS), inducing cancer ferroptosis. However, the efficacy of the ferroptosis catalyst is still insufficient because of low Fe(II) release, which severely limited its application in clinic. Herein, we developed a novel magnetic nanocatalyst for MRI-guided chemo- and ferroptosis synergistic cancer therapies through iRGD-PEG-ss-PEG-modified gadolinium engineering magnetic iron oxide-loaded Dox (ipGdIO-Dox). The introduction of the gadolinium compound disturbed the structure of ipGdIO-Dox, making the magnetic nanocatalyst be more sensitive to weak acid. When ipGdIO-Dox entered into cancer cells, abundant Fe(II) ions were released and then catalyzed H2O2 into highly toxic OH•, which would elevate cellular oxidative stress to damage mitochondria and cell membranes and induce cancer ferroptosis. In addition, the iRGD-PEG-ss-PEG chain coated onto the nanoplatform was also broken by high expression of GSH, and then, the Dox was released. This process not only effectively inhibited DNA replication but also further activated cellular ROS, making the nanoplatform achieve stronger anticancer ability. Besides, the systemic delivery of ipGdIO-Dox significantly enhanced the T1- and T2-weighted MRI signal of the tumor, endowing accurate diagnostic capability for tumor recognition. Therefore, ipGdIO-Dox might be a promising candidate for developing an MRI-guided chemo- and ferroptosis synergistic theranostic system.

Application of Multi-Slice Computed Tomography for the Preoperative Diagnosis and Classification of Pulmonary Cystic Echinococcosis.

Pulmonary cystic echinococcosis remains a serious threat to public health. A standardized, imaging-based classification method for pulmonary echinococcosis has not yet been developed despite the existence of a standardized ultrasound classification method and treatment plan for hepatic cystic echinococcosis. Chest computed tomography (CT) images from 34 cases of pulmonary cystic echinococcosis with 46 lesions were used for classification based on the World Health Organization (WHO) standardized ultrasound classification of hepatic cystic echinococcosis. CT findings were compared with intraoperative observations and postoperative pathological results to assess accuracy. Pulmonary cystic echinococcosis was common in women (14/34, 41.2%) and children (14/34, 41.2%) with a single cyst (28/46, 60.9%). Most lesions were classified as cystic echinococcosis 1(CE1, 19/46) or cystic echinococcosis 3(CE3, 21/46). Blood leukocytosis was mostly observed in CE3 lesions (100%, 9/9) (p < 0.05). The preoperative CT diagnosis of pulmonary cystic echinococcosis had an accuracy rate of 100%. The preoperative CT typing, and postoperative pathological typing had a coincidence rate of 97.8% (45/46). Our study provided a classification method based on CT imaging for pulmonary cystic echinococcosis that can be used during pre-surgical planning to reduce patient's postoperative complications and mortality.

Imaging Findings From Different Pathological Types of Oral and Maxillofacial Intramuscular Hemangiomas for Selecting Optimum Management.

OBJECTIVES: To assess computed tomography (CT) and magnetic resonance imaging (MRI) findings of intramuscular hemangiomas (IMHs) in oral and maxillofacial region and correlate them with the histopathological classifications for selecting optimum management. METHODS: The clinical data and pretreatment findings of 32 patients with pathologically proven IMHs on CT (n = 10), MRI (n = 27), or both (n = 5) were analyzed retrospectively. Correspondence of clinical and imaging characters with 3 different pathological classifications (cavernous, capillary, and mixed) of IMHs was studied. A number of pitfalls and overlap of imaging features can result in misdiagnosis of different IMHs lesions. RESULTS: Four patients had multi-muscular lesions, and 28 had single-muscular lesions. The predilection site were the tongue (11 cases, 34.4%) and the masseter muscle (10 cases, 31.2%). Cavernous type (17 cases, 53.1%) was the most common IMHs type. All patients showed slightly hypointense or isointense on T1-weighted imaging, 3 patients showed hyperintense on T2-weighted imaging and the others showed slightly hyperintense. The most common enhancement pattern was progressive (29 cases, 90.6%). The capillary type (9 cases, 28.1%) and mixed type (6 cases, 28.1%) of IMHs on imaging indicated characteristics of lesions with rich blood supply status, the cavernous type (17cases, 53.1%) of IMHs belonged to relatively poor blood supply lesions. A total of 5 patients (15.6%) were initially misdiagnosed, there were recurrences in 4 IMHs patients. Extra functional MRI (fMRI) was performed on these 5 misdiagnosed patients, the average ADC of the 5 patients was 1.50 × 10-3 mm2/s. The presence of vermicular vessels was different among these three types of IMHs. CONCLUSIONS: The reason for the misdiagnosis in localized IMHs may be the obvious border of mass-like lesions and the lack of enlarged vessels. Combined evaluation of presence of vermicular vessels and fMRI might be more accurately for determining the IMHs and create a preoperative plan.

Assessment of a biofluid mechanics-based model for calculating portal pressure in canines.

BACKGROUND: Portal hypertension is a severe complication caused by various chronic liver diseases. The standard methods for detecting portal hypertension (hepatic venous pressure gradient and free portal pressure) are available in only a few hospitals due to their technical difficulty and invasiveness; thus, non-invasive measuring methods are needed. This study aimed to establish and assess a novel model to calculate free portal pressure based on biofluid mechanics. RESULT: Comparison of each dog's virtual and actual free portal pressure showed that a biofluid mechanics-based model could accurately predict free portal pressure (mean difference: -0.220, 95% CI: - 0.738 to 0.298; upper limit of agreement: 2.24, 95% CI: 1.34 to 3.14; lower limit of agreement: -2.68, 95% CI: - 3.58 to - 1.78; intraclass correlation coefficient: 0.98, 95% CI: 0.96 to 0.99; concordance correlation coefficient: 0.97, 95% CI: 0.93 to 0.99) and had a high AUC (0.984, 95% CI: 0.834 to 1.000), sensitivity (92.3, 95% CI: 64.0 to 99.8), specificity (91.7, 95% CI: 61.5 to 99.8), positive likelihood ratio (11.1, 95% CI: 1.7 to 72.8), and low negative likelihood ratio (0.08, 95% CI: 0.01 to 0.6) for detecting portal hypertension. CONCLUSIONS: Our study suggests that the biofluid mechanics-based model was able to accurately predict free portal pressure and detect portal hypertension in canines. With further research and validation, this model might be applicable for calculating human portal pressure, detecting portal hypertensive patients, and evaluating disease progression and treatment efficacy.

ATM Expression Is Elevated in Established Radiation-Resistant Breast Cancer Cells and Improves DNA Repair Efficiency.

Repair of damaged DNA induced by radiation plays an important role in the development of radioresistance, which greatly restricts patients' benefit from radiotherapy. However, the relation between radioresistance development and DNA double-strand break repair pathways (mainly non-homologous end joining and homologous recombination) and how these pathways contribute to radioresistance are unclear. Here, we established a radioresistant breast cancer cell line by repeated ionizing radiation and studied the alteration in DNA repair capacity. Compared with parental sham-treated cells, radioresistant breast cancer cells present elevated radioresistance, enhanced malignancy, increased expression of Ataxia-telangiectasia mutated (ATM), and increased DNA damage repair efficiency, as reflected by accelerated γ-H2AX kinetic. These defects can be reversed by ATM inhibition or ATM knockdown, indicating a potential link between ATM, DNA repair pathway and radiosensitivity. We propose that cancer cells develop elevated radioresistance through enhanced DNA damage repair efficiency mediated by increased ATM expression. Our work might provide a new evidence supporting the potential of ATM as a potential target of cancer therapy.

Differential diagnostic value of diffusion-weighted and dynamic contrast-enhanced MR imaging in non-cystic lesions in floor of the mouth.

METHODS:: A total of 82 patients were included in this study. The apparent diffusion coefficient (ADC) values and time-signal intensity curves (TICs) were measured. Clinical characteristics, ADC value, and TIC pattern were compared between benign and malignant FOM lesions. Receiver operating characteristic curve and logistic regression analyses were performed to evaluate respective and combined value of ADC value and TIC pattern for differential diagnosis. The retrospective study was approved by our institutional review board, and the need for informed consent was waived. RESULTS:: The area under the curve ADC value and TIC pattern were 0.71 and 0.73, respectively. The combined use of ADC value and TIC pattern increased the area under the curve value to 0.81 [95% confidence interval (CI), (0.66-0.97)]. ADC < 1.23 × 10-3 mm2 s-1 (odds ratio, 45.8; 95% CI, 2.8-737.9) and both the plateau and washout TIC patterns (OR, 6.8; 95% CI, 1.8-24.8) were significantly associated with malignancy of FOM lesions. CONCLUSIONS:: Our results suggest that both diffusion-weighted imaging and DCE-MRI could contribute to the differential diagnosis of non-cystic FOM lesions, especially when used in combination.

Aptamer-conjugated Mn3O4@SiO2 core-shell nanoprobes for targeted magnetic resonance imaging.

The objective of this study was to evaluate the targeted T1-magnetic resonance imaging (MRI), quantitative biodistribution and toxicity of aptamer (AS411) conjugated Mn3O4@SiO2 core-shell nanoprobes (NPs) in human cervical carcinoma tumor-bearing mice. The NPs were firstly prepared by encapsulating a hydrophobic Mn3O4 core within an amino functionalized silica shell. The fluorophore rhodamine (RB) was doped into the silica shell and the amphiphilic polymer poly(ethylene glycol) (PEG) was modified on the surface of the shell to improve its biocompatibility, then the aptamer AS411 was conjugated onto the end of the PEG chains as targeting ligands. The final NPs were abbreviated as Mn3O4@SiO2(RB)-PEG-Apt. By means of in vitro fluorescence confocal imaging and in vivo MRI, the NPs have been demonstrated to target cancer cells and prominent tumor aggregation effectively. The imaging results were further confirmed by a quantitative biodistribution study. In addition, histological, hematological and biochemistry analysis also proved the low toxicity of NPs in vivo. Our results showed the great potential of the Mn3O4@SiO2(RB)-PEG-Apt NPs could be used as a multifunctional nanoplatform for long-term targeted imaging and therapy of cancer.

From members to teams to committee-a robust approach to gestural and multimodal recognition.

When building a complex pattern recognizer with high-dimensional input features, a number of selection uncertainties arise. Traditional approaches to resolving these uncertainties typically rely either on the researcher's intuition or performance evaluation on validation data, both of which result in poor generalization and robustness on test data. This paper describes a novel recognition technique called members to teams to committee (MTC), which is designed to reduce modeling uncertainty. In particular, the MTC posterior estimator is based on a coordinated set of divide-and-conquer estimators that derive from a three-tiered architectural structure corresponding to individual members, teams, and the overall committee. Basically, the MTC recognition decision is determined by the whole empirical posterior distribution, rather than a single estimate. This paper describes the application of the MTC technique to handwritten gesture recognition and multimodal system integration and presents a comprehensive analysis of the characteristics and advantages of the MTC approach.