Mg alloys with antitumor and anticorrosion properties for orthopedic oncology: A review from mechanisms to application strategies.

As a primary malignant bone cancer, osteosarcoma (OS) poses a great threat to human health and is still a huge challenge for clinicians. At present, surgical resection is the main treatment strategy for OS. However, surgical intervention will result in a large bone defect, and some tumor cells remaining around the excised bone tissue often lead to the recurrence and metastasis of OS. Biomedical Mg-based materials have been widely employed as orthopedic implants in bone defect reconstruction, and, especially, they can eradicate the residual OS cells due to the antitumor activities of their degradation products. Nevertheless, the fast corrosion rate of Mg alloys has greatly limited their application scope in the biomedical field, and the improvement of the corrosion resistance will impair the antitumor effects, which mainly arise from their rapid corrosion. Hence, it is vital to balance the corrosion resistance and the antitumor activities of Mg alloys. The presented review systematically discussed the potential antitumor mechanisms of three corrosion products of Mg alloys. Moreover, several strategies to simultaneously enhance the anticorrosion properties and antitumor effects of Mg alloys were also proposed.

Functional biomacromolecules-based microneedle patch for the treatment of diabetic wound.

Diabetic wounds are a common complication of diabetes. The prolonged exposure to high glucose and oxidative stress in the wound environment increases the risk of bacterial infection and abnormal angiogenesis, leading to amputation. Microneedle patches have shown promise in promoting the healing of diabetic wounds through transdermal drug delivery. These patches target the four main aspects of diabetic wound treatment: hypoglycemia, antibacterial action, inflammatory regulation, and tissue regeneration. By overcoming the limitations of traditional administration methods, microneedle patches enable targeted therapy for deteriorated tissues. The design of these patches extends beyond the selection of needle tip material and biomacromolecule encapsulated drugs; it can also incorporate near-infrared rays to facilitate cascade reactions and treat diabetic wounds. In this review, we comprehensively summarize the advantages of microneedle patches compared to traditional treatment methods. We focus on the design and mechanism of these patches based on existing experimental articles in the field and discuss the potential for future research on microneedle patches.

Remodelers of the vascular microenvironment: The effect of biopolymeric hydrogels on vascular diseases.

Vascular disease is the leading health problem worldwide. Vascular microenvironment encompasses diverse cell types, including those within the vascular wall, blood cells, stromal cells, and immune cells. Initiation of the inflammatory state of the vascular microenvironment and changes in its mechanics can profoundly affect vascular homeostasis. Biomedical materials play a crucial role in modern medicine, hydrogels, characterized by their high-water content, have been increasingly utilized as a three-dimensional interaction network. In recent times, the remarkable progress in utilizing hydrogels and understanding vascular microenvironment have enabled the treatment of vascular diseases. In this review, we give an emphasis on the utilization of hydrogels and their advantages in the various vascular diseases including atherosclerosis, aneurysm, vascular ulcers of the lower limbs and myocardial infarction. Further, we highlight the importance and advantages of hydrogels as artificial microenvironments.

Research advances in microfluidic collection and detection of virus, bacterial, and fungal bioaerosols.

Bioaerosols are airborne suspensions of fine solid or liquid particles containing biological substances such as viruses, bacteria, cellular debris, fungal spores, mycelium, and byproducts of microbial metabolism. The global Coronavirus disease 2019 (COVID-19) pandemic and the previous emergence of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza have increased the need for reliable and effective monitoring tools for bioaerosols. Bioaerosol collection and detection have aroused considerable attention. Current bioaerosol sampling and detection techniques suffer from long response time, low sensitivity, and high costs, and these drawbacks have forced the development of novel monitoring strategies. Microfluidic technique is considered a breakthrough for high performance analysis of bioaerosols. In recent years, several emerging methods based on microfluidics have been developed and reported for collection and detection of bioaerosols. The unique advantages of microfluidic technique have enabled the integration of bioaerosol collection and detection, which has a higher efficiency over conventional methods. This review focused on the research progress of bioaerosol collection and detection methods based on microfluidic techniques, with special attention on virus aerosols and bacterial aerosols. Different from the existing reviews, this work took a unique perspective of the targets to be collected and detected in bioaerosols, which would provide a direct index of bioaerosol categories readers may be interested in. We also discussed integrated microfluidic monitoring system for bioaerosols. Additionally, the application of bioaerosol detection in biomedicine was presented. Finally, the current challenges in the field of bioaerosol monitoring are presented and an outlook given of future developments.

Saliva Analysis Based on Microfluidics: Focusing the Wide Spectrum of Target Analyte.

Saliva is one of the most critical human body fluids that can reflect the state of the human body. The detection of saliva is of great significance for disease diagnosis and health monitoring. Microfluidics, characterized by microscale size and high integration, is an ideal platform for the development of rapid and low-cost disease diagnostic techniques and devices. Microfluidic-based saliva testing methods have aroused considerable interest due to the increasing need for noninvasive testing and frequent or long-term testing. This review briefly described the significance of saliva analysis and generally classified the targets in saliva detection into pathogenic microorganisms, inorganic substances, and organic substances. By using this classification as a benchmark, the state-of-the-art research results on microfluidic detection of various substances in saliva were summarized. This work also put forward the challenges and future development directions of microfluidic detection methods for saliva.

Advances in NIR-Responsive Natural Macromolecular Hydrogel Assembly Drugs for Cancer Treatment.

Cancer is a serious disease with an abnormal proliferation of organ tissues; it is characterized by malignant infiltration and growth that affects human life. Traditional cancer therapies such as resection, radiotherapy and chemotherapy have a low cure rate and often cause irreversible damage to the body. In recent years, since the traditional treatment of cancer is still very far from perfect, researchers have begun to focus on non-invasive near-infrared (NIR)-responsive natural macromolecular hydrogel assembly drugs (NIR-NMHADs). Due to their unique biocompatibility and extremely high drug encapsulation, coupling with the spatiotemporal controllability of NIR, synergistic photothermal therapy (PTT), photothermal therapy (PDT), chemotherapy (CT) and immunotherapy (IT) has created excellent effects and good prospects for cancer treatment. In addition, some emerging bioengineering technologies can also improve the effectiveness of drug delivery systems. This review will discuss the properties of NIR light, the NIR-functional hydrogels commonly used in current research, the cancer therapy corresponding to the materials encapsulated in them and the bioengineering technology that can assist drug delivery systems. The review provides a constructive reference for the optimization of NIR-NMHAD experimental ideas and its application to human body.

Nanoparticles exhibiting virus-mimic surface topology for enhanced oral delivery.

The oral delivery of nano-drug delivery systems (Nano-DDS) remains a challenge. Taking inspirations from viruses, here we construct core-shell mesoporous silica nanoparticles (NPs, ~80 nm) with virus-like nanospikes (VSN) to simulate viral morphology, and further modified VSN with L-alanine (CVSN) to enable chiral recognition for functional bionics. By comparing with the solid silica NPs, mesoporous silica NPs and VSN, we demonstrate the delivery advantages of CVSN on overcoming intestinal sequential barriers in both animals and human via multiple biological processes. Subsequently, we encapsulate indomethacin (IMC) into the nanopores of NPs to mimic gene package, wherein the payloads are isolated from bio-environments and exist in an amorphous form to increase their stability and solubility, while the chiral nanospikes multi-sited anchor and chiral recognize on the intestinal mucosa to enhance the penetrability and ultimately improve the oral adsorption of IMC. Encouragingly, we also prove the versatility of CVSN as oral Nano-DDS.

Brain-Tumor Interface-Based MRI Radiomics Models to Determine EGFR Mutation, Response to EGFR-TKI and T790M Resistance Mutation in Non-Small Cell Lung Carcinoma Brain Metastasis.

BACKGROUND: Preoperative assessment of epidermal growth factor receptor (EGFR) status, response to EGFR-tyrosine kinase inhibitors (TKI) and development of T790M mutation in non-small cell lung carcinoma (NSCLC) patients with brain metastases (BM) is important for clinical decision-making, while previous studies were only based on the whole BM. PURPOSE: To investigate values of brain-to-tumor interface (BTI) for determining the EGFR mutation, response to EGFR-TKI and T790M mutation. STUDY TYPE: Retrospective. POPULATION: Two hundred thirty patients from Hospital 1 (primary cohort) and 80 patients from Hospital 2 (external validation cohort) with BM and histological diagnosis of primary NSCLC, and with known EGFR status (biopsy) and T790M mutation status (gene sequencing). FIELD STRENGTH/SEQUENCE: Contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) fast spin echo sequences at 3.0T MRI. ASSESSMENT: Treatment response to EGFR-TKI therapy was determined by the Response Evaluation Criteria in Solid Tumors. Radiomics features were extracted from the 4 mm thickness BTI and selected by least shrinkage and selection operator regression. The selected BTI features and volume of peritumoral edema (VPE) were combined to construct models using logistic regression. STATISTICAL TESTS: The performance of each radiomics model was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 7, 3, and 3 features were strongly associated with the EGFR mutation status, response to EGFR-TKI and T790M mutation status, respectively. The developed models combining BTI features and VPE can improve the performance than those based on BTI features alone, generating AUCs of 0.814, 0.730, and 0.774 for determining the EGFR mutation, response to EGFR-TKI and T790M mutation, respectively, in the external validation cohort. DATA CONCLUSION: BTI features and VPE were associated with the EGFR mutation status, response to EGFR-TKI and T790M mutation status in NSCLC patients with BM. EVIDENCE LEVEL: 3 Technical Efficacy: Stage 2.

The effect of GelMA/alginate interpenetrating polymeric network hydrogel on the performance of porous zirconia matrix for bone regeneration applications.

Bone tissue is a natural composite, exhibiting complicated structures and unique mechanical/biological properties. With an attempt of mimicking the bone tissue, a novel inorganic-organic composite scaffolds (ZrO2-GM/SA) was designed and prepared via the vacuum infiltration method and the single/double cross-linking strategy by blending GelMA/alginate (GelMA/SA) interpenetrating polymeric network (IPN) into the porous zirconia (ZrO2) scaffold. The structure, morphology, compressive strength, surface/interface properties, and biocompatibility of the ZrO2-GM/SA composite scaffolds were characterized to evaluate the performance of the composite scaffolds. Results showed that compared to ZrO2 bare scaffolds with well-defined open pores, the composite scaffolds prepared by double cross-linking of GelMA hydrogel and sodium alginate (SA) presented a continuous, tunable and honeycomb-like microstructure. Meanwhile, GelMA/SA showed favorable and controllable water-uptake capacity, swelling property and degradability. After the introduction of IPN components, the mechanical strength of composite scaffolds was further improved. The compressive modulus of composite scaffolds was significantly higher than the bare ZrO2 scaffolds. In addition, ZrO2-GM/SA composite scaffolds had highly biocompatibility and displayed a potent proliferation and osteogenesis of MC3T3-E1 pre-osteoblasts compared to bare ZrO2 scaffolds and ZrO2-GelMA composite scaffolds. At the same time, ZrO2-10GM/1SA composite scaffold regenerated significantly greater bone than other groups in vivo. This study demonstrated that the proposed ZrO2-GM/SA composite scaffolds had great research and application potential in bone tissue engineering.

Insight into the effect of biomaterials on osteogenic differentiation of mesenchymal stem cells: A review from a mitochondrial perspective.

Bone damage may be triggered by a variety of factors, and the damaged area often requires a bone graft. Bone tissue engineering can serve as an alternative strategy for repairing large bone defects. Mesenchymal stem cells (MSCs), the progenitor cells of connective tissue, have become an important tool for tissue engineering due to their ability to differentiate into a variety of cell types. The precise regulation of the growth and differentiation of the stem cells used for bone regeneration significantly affects the efficiency of this type of tissue engineering. During the process of osteogenic induction, the dynamics and function of localized mitochondria are altered. These changes may also alter the microenvironment of the therapeutic stem cells and result in mitochondria transfer. Mitochondrial regulation not only affects the induction/rate of differentiation, but also influences its direction, determining the final identity of the differentiated cell. To date, bone tissue engineering research has mainly focused on the influence of biomaterials on phenotype and nuclear genotype, with few studies investigating the role of mitochondria. In this review, we provide a comprehensive summary of researches into the role of mitochondria in MSCs differentiation and critical analysis regarding smart biomaterials that are able to "programme" mitochondria modulation was proposed. STATEMENT OF SIGNIFICANCE: This review proposed the precise regulation of the growth and differentiation of the stem cells used to seed bone regeneration. • This review addressed the dynamics and function of localized mitochondria during the process of osteogenic induction and the effect of mitochondria on the microenvironment of stem cells. • This review summarized biomaterials which affect the induction/rate of differentiation, but also influences its direction, determining the final identity of the differentiated cell through the regulation of mitochondria.

The Role of Microsphere Structures in Bottom-Up Bone Tissue Engineering.

Bone defects have caused immense healthcare concerns and economic burdens throughout the world. Traditional autologous allogeneic bone grafts have many drawbacks, so the emergence of bone tissue engineering brings new hope. Bone tissue engineering is an interdisciplinary biomedical engineering method that involves scaffold materials, seed cells, and "growth factors". However, the traditional construction approach is not flexible and is unable to adapt to the specific shape of the defect, causing the cells inside the bone to be unable to receive adequate nourishment. Therefore, a simple but effective solution using the "bottom-up" method is proposed. Microspheres are structures with diameters ranging from 1 to 1000 µm that can be used as supports for cell growth, either in the form of a scaffold or in the form of a drug delivery system. Herein, we address a variety of strategies for the production of microspheres, the classification of raw materials, and drug loading, as well as analyze new strategies for the use of microspheres in bone tissue engineering. We also consider new perspectives and possible directions for future development.

Multiparametric MRI-based radiomics for the prediction of microvascular invasion in hepatocellular carcinoma.

BACKGROUND: Preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is essential in obtaining a successful surgical treatment, in decreasing recurrence, and in improving survival. PURPOSE: To investigate the value of multiparametric magnetic resonance imaging (MRI)-based radiomics in the prediction of peritumoral MVI in HCC. MATERIAL AND METHODS: A total of 102 patient with pathologically proven HCC after surgical resection from June 2014 to March 2018 were enrolled in this retrospective study. Histological analysis of resected specimens confirmed positive MVI in 48 patients and negative MVI in 54 patients. Radiomics features were extracted from four MRI sequences and selected with the least absolute shrinkage and selection operator (LASSO) regression and used to analyze the tumoral and peritumoral regions for MVI. Univariate logistic regression was employed to identify the most important clinical factors, which were integrated with the radiomics signature to develop a nomogram. RESULTS: In total, 11 radiomics features were selected and used to build the radiomics signature. The serum level of alpha-fetoprotein was identified as the clinical factor with the highest predictive value. The developed nomogram achieved the highest AUC in predicting MVI status. The decision curve analysis confirmed the potential clinical utility of the proposed nomogram. CONCLUSION: The multiparametric MRI-based radiomics nomogram is a promising tool for the preoperative diagnosis of peritumoral MVI in HCCs and helps determine the appropriate medical or surgical therapy.

Preoperative MRI-Based Radiomics of Brain Metastasis to Assess T790M Resistance Mutation After EGFR-TKI Treatment in NSCLC.

BACKGROUND: Preoperative assessment of the acquired resistance T790M mutation in patients with metastatic non-small cell lung cancer (NSCLC) based on brain metastasis (BM) is important for early treatment decisions. PURPOSE: To investigate preoperative magnetic resonance imaging (MRI)-based radiomics for assessing T790M resistance mutation after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment in NSCLC patients with BM. STUDY TYPE: Retrospective. POPULATION: One hundred and ten primary NSCLC patients with pathologically confirmed BM and T790M mutation status assessment from two centers divided into primary training (N = 53), internal validation (N = 27), and external validation (N = 30) sets. FIELD STRENGTH/SEQUENCE: Contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) fast spin echo sequences at 3.0 T. ASSESSMENT: Forty-five (40.9%) patients were T790M-positive and 65 (59.1%) patients were T790M-negative. The tumor active area (TAA) and peritumoral edema area (POA) of BM were delineated on pre-treatment T1CE and T2W images. Radiomics signatures were built based on features selected from TAA (RS-TAA), POA (RS-POA), and their combination (RS-Com) to assess the T790M resistance mutation after EGFR-TKI treatment. STATISTICAL TESTS: Receiver operating characteristic (ROC) curves were used to assess the capabilities of the developed RSs. The area under the ROC curves (AUC), sensitivity, and specificity were generated as comparison metrics. RESULTS: We identified two features (from TAA) and three features (from POA) that are highly associated with the T790M mutation status. The developed RS-TAA, RS-POA, and RS-Com showed good performance, with AUCs of 0.807, 0.807, and 0.864 in the internal validation, and 0.783, 0.814, and 0.860 in the external validation sets, respectively. DATA CONCLUSION: Pretreatment brain MRI of NSCLC patients with BM might effectively detect the T790M resistance mutation, with both TAA and POA having important values. The multi-region combined radiomics signature may have potential to be a new biomarker for assessing T790M mutation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Preparation and Properties of Partial-Degradable ZrO2-Chitosan Particles-GelMA Composite Scaffolds.

In the field of bone repair, the inorganic-organic composite scaffold is a promising strategy for mimicking the compositions of the natural bone. In addition, as implants for repairing load-bearing sites, an inert permanent bone substitute composites with bioactive degradable ingredients may make full use of the composite scaffold. Herein, the porous zirconia (ZrO2) matrix was prepared via the template replication method, and the partial degradable ZrO2-chitosan particles-GelMA composite scaffolds with different chitosan/GelMA volume ratios were prepared through the vacuum infiltration method. Dynamic light scattering (DLS) and the scanning electron microscope (SEM) were adopted to observe the size of the chitosan particles and the morphologies of the composites scaffold. The mechanical properties, swelling properties, and degradation properties of the composite scaffolds were also characterized by the mechanical properties testing machine and immersion tests. The CCK-8 assay was adopted to test the biocompatibility of the composite scaffold preliminarily. The results show that chitosan particles as small as 60 nm were obtained. In addition, the ratio of chitosan/GelMA can influence the mechanical properties and the swelling and degradation behaviors of the composites scaffold. Furthermore, improved cell proliferation performance was obtained for the composite scaffolds.

Multi-parametric MRI-based radiomics for the diagnosis of malignant soft-tissue tumor.

PURPOSE: To develop and validate a multiparametric magnetic resonance imaging-based radiomics nomogram for differentiating malignant and benign soft-tissue tumors. METHODS: A total of 91 patients with pathologically confirmed soft-tissue tumors were enrolled between January 2017 and October 2020. Forty-eight patients were consecutively enrolled between November 2020 and March 2022, as a time-independent cohort. All patients underwent contrast-enhanced T1-weighted and T2-weighted fat-suppression magnetic resonance scans at 3.0 T. Radiomics features were extracted and selected from the two modalities to develop the radiomics signature. Significant clinical/morphological characteristics were identified using a multivariate logistic regression analysis. The least absolute shrinkage and selection operator regression were applied to identify discriminative features. A clinical-radiomics nomogram was constructed based on clinical/morphological characteristics and radiomics features. Finally, the performance of the nomogram was validated using the receiver operating characteristic and decision curve analysis (DCA). RESULTS: Six features were selected to establish the combined RS. Size, margin, and peritumoral edema were identified as the most important clinical and morphological factors, respectively. The radiomics signature outperformed the clinical model in terms of AUC and sensitivity. The nomogram integrating the combined RS, size, margin, and peritumoral edema achieved favorable predictive efficacy, generating AUCs of 0.954 (95% confidence interval [CI]: 0.907-1.000, Sen = 0.861, Spe = 0.917), 0.962 (95% CI: 0.901-1.000, Sen = 0.944, Spe = 0.923), and 0.935 (95% CI: 0.871-0.998, Sen = 0.815, Spe = 0.952) in the training (n = 60), validation (n = 31) and time-independent (n = 48) cohorts, respectively. The DCA curve indicated good clinical usefulness of the nomogram. CONCLUSIONS: Our study demonstrated the clinical potential of multiparametric MRI-based radiomics in distinguishing malignant from benign soft-tissue tumors, which can be considered as a noninvasive tool for individual treatment management.

Intratumoral analysis of digital breast tomosynthesis for predicting the Ki-67 level in breast cancer: A multi-center radiomics study.

PURPOSE: To non-invasively evaluate the Ki-67 level in digital breast tomosynthesis (DBT) images of breast cancer (BC) patients based on subregional radiomics. METHODS: A total of 266 patients who underwent DBT scans were consecutively enrolled at two centers, between September 2017 and September 2021. The whole tumor region was partitioned into various intratumoral subregions, based on individual- and population-level clustering. Handcrafted radiomics and deep learning-based features were extracted from the subregions and from the whole tumor region, and were selected by least absolute shrinkage and selection operator (LASSO) regression, yielding radiomics signatures (RSs). The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to assess the developed RSs. RESULTS: Each breast tumor region was partitioned into an inner subregion (S1) and a marginal subregion (S2). The RSs derived from S1 always generated higher AUCs compared with those from S2 or from the whole tumor region (W), for the external validation cohort (AUCs, S1 vs. W, handcrafted RSs: 0.583 [95% CI, 0.429-0.727] vs. 0.559 [95% CI, 0.405-0.705], p-value: 0.920; deep RSs: 0.670 [95% CI, 0.516-0.802] vs. 0.551 [95% CI, 0.397-0.698], p-value: 0.776). The fusion RSs, combining handcrafted and deep learning-based features derived from S1, yielded the highest AUCs of 0.820 (95% CI, 0.714-0.900) and 0.792 (95% CI, 0.647-0.897) for the internal and external validation cohorts, respectively. CONCLUSIONS: The subregional radiomics approach can accurately predict the Ki-67 level based on DBT data; thus, it may be used as a potential non-invasive tool for preoperative treatment planning in BC.

Subregional radiomics analysis for the detection of the EGFR mutation on thoracic spinal metastases from lung cancer.

The present study intended to use radiomic analysis of spinal metastasis subregions to detect epidermal growth factor receptor (EGFR) mutation. In total, 94 patients with thoracic spinal metastasis originated from primary lung adenocarcinoma (2017-2020) were studied. All patients underwent T1-weighted (T1W) and T2 fat-suppressed (T2FS) MRI scans. The spinal metastases (tumor region) were subdivided into phenotypically consistent subregions based on patient- and population-level clustering: Three subregions, S1, S2 and S3, and the total tumor region. Radiomics features were extracted from each subregion and from the whole tumor region as well. Least shrinkage and selection operator (LASSO) regression were used for feature selection and radiomics signature definition. Detection performance of S3 was better than all other regions using T1W (AUCs, S1 versus S2 versus S3 versus whole tumor, 0.720 versus 0.764 versus 0.786 versus 0.758) and T2FS (AUCs, S1 versus S2 versus S3 versus whole tumor, 0.791 versus 0.708 versus 0.838 versus 0.797) MRI. The multi-regional radiomics signature derived from the joint of inner subregion S3 from T1W and T2FS MRI achieved the best detection capabilities with AUCs of 0.879 (ACC = 0.774, SEN = 0.838, SPE = 0.840) and 0.777 (ACC = 0.688, SEN = 0.947, SPE = 0.615) in the training and test sets, respectively. Our study revealed that MRI-based radiomic analysis of spinal metastasis subregions has the potential to detect the EGFR mutation in patients with primary lung adenocarcinoma.

Roles of melatonin in the field of reproductive medicine.

Melatonin, mostly released by the pineal gland, is a circadian rhythm-regulated and multifunctional hormone. Great advances in melatonin research have been made, including its role in rhythms of the sleep-wake cycle, retardation of ageing processes, as well as antioxidant or anti-inflammatory functions. Melatonin can scavenge free radicals such as reactive oxygen species (ROS), a key factor in reproductive functions. Melatonin plays an important role in oocyte maturation, fertilization and embryonic development as well. The concurrent use of melatonin increases the number of mature oocytes, the fertilization rate, and number of high-quality embryos, which improves the clinical outcome of assisted reproductive technology (ART). This review discusses the relationship between melatonin and human reproductive function, and potential clinical applications of melatonin in the field of reproductive medicine.

Microfluidic Preparation of Janus Microparticles With Temperature and pH Triggered Degradation Properties.

Based on the phase separation phenomenon in micro-droplets, polymer-lipid Janus particles were prepared on a microfluidic flow focusing chip. Phase separation of droplets was caused by solvent volatilization and Janus morphology was formed under the action of interfacial tension. Because phase change from solid to liquid of the lipid hemisphere could be triggered by physiological temperature, the lipid hemisphere could be used for rapid release of drugs. While the polymer we selected was pH sensitive that the polymer hemisphere could degrade under acidic conditions, making it possible to release drugs in a specific pH environment, such as tumor tissues. Janus particles with different structures were obtained by changing the experimental conditions. To widen the application range of the particles, fatty alcohol and fatty acid-based phase change materials were also employed to prepare the particles, such as 1-tetradecanol, 1-hexadecanol and lauric acid. The melting points of these substances are higher than the physiological temperature, which can be applied in fever triggered drug release or in thermotherapy. The introduction of poly (lactic-co-glycolic acid) enabled the formation of multicompartment particles with three distinct materials. With different degradation properties of each compartment, the particles generated in this work may find applications in programmed and sequential drug release triggered by multiple stimuli.

MRI-based radiomics analysis for predicting the EGFR mutation based on thoracic spinal metastases in lung adenocarcinoma patients.

PURPOSE: This study aims to develop and evaluate multi-parametric MRI-based radiomics for preoperative identification of epidermal growth factor receptor (EGFR) mutation, which is important in treatment planning for patients with thoracic spinal metastases from primary lung adenocarcinoma. METHODS: A total of 110 patients were enrolled between January 2016 and March 2019 as a primary cohort. A time-independent validation cohort was conducted containing 52 patients consecutively enrolled from July 2019 to April 2021. The patients were pathologically diagnosed with thoracic spinal metastases from primary lung adenocarcinoma; all underwent T1-weighted (T1W), T2-weighted (T2W), and T2-weighted fat-suppressed (T2FS) MRI scans of the thoracic spinal. Handcrafted and deep learning-based features were extracted and selected from each MRI modality, and used to build the radiomics signature. Various machine learning classifiers were developed and compared. A clinical-radiomics nomogram integrating the combined rad signature and the most important clinical factor was constructed with receiver operating characteristic (ROC), calibration, and decision curves analysis (DCA) to evaluate the prediction performance. RESULTS: The combined radiomics signature derived from the joint of three modalities can effectively classify EGFR mutation and EGFR wild-type patients, with an area under the ROC curve (AUC) of 0.886 (95% confidence interval [CI]: 0.826-0.947, SEN =0.935, SPE =0.688) in the training group and 0.803 (95% CI: 0.682-0.924, SEN = 0.700, SPE = 0.818) in the time-independent validation group. The nomogram incorporating the combined radiomics signature and smoking status achieved the best prediction performance in the training (AUC = 0.888, 95% CI: 0.849-0.958, SEN = 0.839, SPE = 0.792) and time-independent validation (AUC = 0.821, 95% CI: 0.692-0.929, SEN = 0.667, SPE = 0.909) cohorts. The DCA confirmed potential clinical usefulness of our nomogram. CONCLUSION: Our study demonstrated the potential of multi-parametric MRI-based radiomics on preoperatively predicting the EGFR mutation. The proposed nomogram model can be considered as a new biomarker to guide the selection of individual treatment strategies for patients with thoracic spinal metastases from primary lung adenocarcinoma.