PROTACs targeting androgen receptor signaling: potential therapeutic agents for castration-resistant prostate cancer.

After the initial androgen deprivation therapy (ADT), part of the prostate cancer may continuously deteriorate into castration-resistant prostate cancer (CRPC). The majority of patients suffer from the localized illness at primary diagnosis that could rapidly assault other organs. This disease stage is referred as metastatic castration-resistant prostate cancer (mCRPC). Surgery and radiation are still the treatment of CRPC, but have some adverse effects such as urinary symptoms and sexual dysfunction. Hormonal castration therapy interfering androgen receptor (AR) signaling pathway is indispensable for most advanced prostate cancer patients, and the first- and second-generation of novel AR inhibitors could effectively cure hormone sensitive prostate cancer (HSPC). However, the resistance to these chemical agents is inevitable many of patients may experience relapses. The resistance to AR inhibitor mainly involves AR mutation, splice variant formation and amplification, which indicates the important role in CRPC. Proteolysis-targeting chimera (PROTAC), a potent technique to degrade targeted protein, has recently undergone extensive development as a biological tool and therapeutic drug. This technique has the potential to become the next generation of antitumor therapeutics as it could overcome the shortcomings of conventional small molecule inhibitors. In this review, we summarize the molecular mechanisms on PROTACs targeting AR signaling for CRPC, hoping to provide insights into drug development and clinical medication.

Polymeric liposomes targeting dual transporters for highly efficient oral delivery of paclitaxel.

A novel delivery system comprising N-succinic anhydride (N-SAA) and D-fructose co-conjugated chitosan (NSCF)-modified polymeric liposomes (NSCF-PLip) were designed to enhance oral delivery of paclitaxel (PTX) by targeting monocarboxylate transporters (MCT) and glucose transporters (GLUT). The synthesized NSCF was characterised by FT-IR and 1H NMR spectra. The prepared 30.78 % (degree of substitution of N-SAA) NSCF-PTX-PLip were approximately 150 nm in size, with a regular spherical shape, the zeta potential of -25.4 ± 5.13 mv, drug loading of 2.35 % ± 0.05 %, and pH-sensitive and slow-release characteristics. Compared with PTX-Lip, 30.78 % NSCF-PTX-PLip significantly enhanced Caco-2 cellular uptake via co-mediation of MCT and GLUT, showing relatively specific binding of propionic acid and MCT. Notably, the NSCF modification of PTX-Lip had no appreciable influence on their original cellular uptake pathway. The fructose modification of 30.78 % NSC-PTX-PLip significantly increased the concentration after tmax, indicating their continuous and efficient absorption. Compared with PTX-Lip, the 30.78 % NSCF-PTX-PLip resulted in a 2.09-fold extension of MRT, and a 6.06-fold increase of oral bioavailability. It significantly increased tumour drug distribution and tumour growth inhibition rate. These findings confirm that 30.78 % NSCF-PLip offer a potential oral delivery platform for PTX and targeting the dual transporters of MCT and GLUT is an effective strategy for enhancing the intestinal absorption of drugs.

Synergistic wound repair effects of a composite hydrogel for delivering tumor-derived vesicles and S-nitrosoglutathione.

Treating chronic wounds requires transition from proinflammatory M1 to anti-inflammatory M2 dominant macrophages. Based on the role of tumor extracellular vesicles (tEVs) in regulating the phenotypic switching from M1 to M2 macrophages, we propose that tEVs may have a beneficial impact on alleviating the overactive inflammatory microenvironment associated with refractory wounds. On the other hand, as a nitric oxide donor, S-nitrosoglutathione (GSNO) can regulate inflammation, promote angiogenesis, enhance matrix deposition, and facilitate wound healing. In this study, a guar gum-based hydrogel with tEVs and GSNO was designed for the treatment of diabetic refractory wounds. This hybrid hydrogel was formed through the phenyl borate bonds, which can automatically disintegrate in response to the high reactive oxygen species (ROS) level at the site of refractory diabetic wounds, releasing tEVs and GSNO. We conducted a comprehensive evaluation of this hydrogel in vitro, which demonstrated excellent performance. Meanwhile, using a full-thickness excision model in diabetic mice, the wounds exposed to the therapeutic hydrogel healed completely within 21 days. The increased closure rate was associated with macrophage polarization and collagen deposition, accelerated fibroblast proliferation, and increased angiogenesis in the regenerating tissues. Therefore, this multifunctional hybrid hydrogel appears to be promising for clinical applications.

The emerging role of E3 ubiquitin ligase RNF213 as an antimicrobial host determinant.

Ring finger protein 213 (RNF213) is a large E3 ubiquitin ligase with a molecular weight of 591 kDa that is associated with moyamoya disease, a rare cerebrovascular disease. It is located in the cytosol and perinuclear space. Missense mutations in this gene have been found to be more prevalent in patients with moyamoya disease compared with that in healthy individuals. Understanding the molecular function of RNF213 could provide insights into moyamoya disease. RNF213 contains a C3HC4-type RING finger domain with an E3 ubiquitin ligase domain and six AAA+ adenosine triphosphatase (ATPase) domains. It is the only known protein with both AAA+ ATPase and ubiquitin ligase activities. Recent studies have highlighted the role of RNF213 in fighting against microbial infections, including viruses, parasites, bacteria, and chlamydiae. This review aims to summarize the recent research progress on the mechanisms of RNF213 in pathogenic infections, which will aid researchers in understanding the antimicrobial role of RNF213.

Exploring the regulatory mechanism of tRNA-derived fragments 36 in acute pancreatitis based on small RNA sequencing and experiments.

BACKGROUND: Acute pancreatitis (AP) is a disease featuring acute inflammation of the pancreas and histological destruction of acinar cells. Approximately 20% of AP patients progress to moderately severe or severe pancreatitis, with a case fatality rate of up to 30%. However, a single indicator that can serve as the gold standard for prognostic prediction has not been discovered. Therefore, gaining deeper insights into the underlying mechanism of AP progression and the evolution of the disease and exploring effective biomarkers are important for early diagnosis, progression evaluation, and precise treatment of AP. AIM: To determine the regulatory mechanisms of tRNA-derived fragments (tRFs) in AP based on small RNA sequencing and experiments. METHODS: Small RNA sequencing and functional enrichment analyses were performed to identify key tRFs and the potential mechanisms in AP. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to determine tRF expression. AP cell and mouse models were created to investigate the role of tRF36 in AP progression. Lipase, amylase, and cytokine levels were assayed to examine AP progression. Ferritin expression, reactive oxygen species, malondialdehyde, and ferric ion levels were assayed to evaluate cellular ferroptosis. RNA pull down assays and methylated RNA immunoprecipitation were performed to explore the molecular mechanisms. RESULTS: RT-qPCR results showed that tRF36 was significantly upregulated in the serum of AP patients, compared to healthy controls. Functional enrichment analysis indicated that target genes of tRF36 were involved in ferroptosis-related pathways, including the Hippo signaling pathway and ion transport. Moreover, the occurrence of pancreatic cell ferroptosis was detected in AP cells and mouse models. The results of interference experiments and AP cell models suggested that tRF-36 could promote AP progression through the regulation of ferroptosis. Furthermore, ferroptosis gene microarray, database prediction, and immunoprecipitation suggested that tRF-36 accelerated the progression of AP by recruiting insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) to the p53 mRNA m6A modification site by binding to IGF2BP3, which enhanced p53 mRNA stability and promoted the ferroptosis of pancreatic follicle cells. CONCLUSION: In conclusion, regulation of nuclear pre-mRNA domain-containing protein 1B promoted AP development by regulating the ferroptosis of pancreatic cells, thereby acting as a prospective therapeutic target for AP. In addition, this study provided a basis for understanding the regulatory mechanisms of tRFs in AP.

Suppression of migration and invasion by taraxerol in the triple-negative breast cancer cell line MDA-MB-231 via the ERK/Slug axis.

As one of the triterpene extracts of Taraxacum, a traditional Chinese plant, taraxerol (TRX) exhibits antitumor activity. In this study, we evaluated the effects of TRX on the migration and invasion of MDA-MB-231 cells, analyzed the molecular mechanism through network pharmacology and molecular docking, and finally verified it by in vitro experiments. The results showed that TRX could inhibit the migration and invasion of MDA-MB-231 cells in a time- and concentration-dependent manner, while MAPK3 was the most promising target and could stably combine with TRX. In addition, the relative protein expression levels were detected by Western blot, and we observed that TRX could inhibit the migration and invasion of MDA-MB-231 cells via the ERK/Slug axis. Moreover, an ERK activator (tert-butylhydroquinone, tBHQ) partially reversed the suppressive effect of TRX on MDA-MB-231 cells. In conclusion, TRX inhibited the migration and invasion of MDA-MB-231 cells via the ERK/Slug axis.

LncRNA DGCR5-encoded polypeptide RIP aggravates SONFH by repressing nuclear localization of ß-catenin in BMSCs.

The differentiation fate of bone marrow mesenchymal stem cells (BMSCs) affects the progression of steroid-induced osteonecrosis of the femoral head (SONFH). We find that lncRNA DGCR5 encodes a 102-amino acid polypeptide, RIP (Rac1 inactivated peptide), which promotes the adipogenic differentiation of BMSCs and aggravates the progression of SONFH. RIP, instead of lncRNA DGCR5, binds to the N-terminal motif of RAC1, and inactivates the RAC1/PAK1 cascade, resulting in decreased Ser675 phosphorylation of ß-catenin. Ultimately, the nuclear localization of ß-catenin decreases, and the differentiation balance of BMSCs tilts toward the adipogenesis lineage. In the femoral head of rats, overexpression of RIP causes trabecular bone disorder and adipocyte accumulation, which can be rescued by overexpressing RAC1. This finding expands the regulatory role of lncRNAs in BMSCs and suggests RIP as a potential therapeutic target.

GNPNAT1 is a potential biomarker correlated with immune infiltration and immunotherapy outcome in breast cancer.

Background: Glucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a crucial enzyme involving hexosamine biosynthesis pathway and is upregulated in breast cancer (BRCA). However, its biological function and mechanism on patients in BRCA have not been investigated. Methods: In this study, the differential expression of GNPNAT1 was analyzed between BRCA tissues and normal breast tissues using the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, which was validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. Then, the potential clinical value of GNPNAT1 in BRCA was investigated based on TCGA database. Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Variation Analysis, were performed to explore the potential signaling pathways and biological functions involved in GNPNAT1 in BRCA. Tumor immune infiltration was analyzed using ESTIMATE, CIBERSORT and TISIDB database; and immune therapy response scores were assessed using TIDE. Finally, Western blot, Cell counting kit-8 and Transwell assay were used to determine the proliferation and invasion abilities of breast cancer cells with GNPNAT1 knockdown. Results: GNPNAT1 was up-regulated in BRCA tissues compared with normal tissues which was subsequently verified in different cell lines and clinical tissue samples. Based on TCGA and GEO, the overexpression of GNPNAT1 in BRCA contributed to a significant decline in overall survive and disease specific survive. Functional enrichment analyses indicated that the enriched pathways in high GNPNAT1 expression group included citrate cycle, N-glycan biosynthesis, DNA repair, and basal transcription factors. Moreover, the overexpression of GNPNAT1 was negatively correlated with immunotherapy response and the levels of immune cell infiltration of CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. Knockdown of GNPNAT1 impairs the proliferation and invasion abilities of breast cancer cells. Conclusion: GNPNAT1 is a potential diagnostic, prognostic biomarker and novel target for intervention in BRCA.

PDK1-stabilized LncRNA SPRY4-IT1 promotes breast cancer progression via activating NF-κB signaling pathway.

Pyruvate dehydrogenase kinase 1 (PDK1) is a widely known glycolytic enzyme, and some evidence showed that PDK1 promoted breast cancer by multiple approaches. However, very few lncRNAs have been identified to be associated with PDK1 in breast cancer in previous research. In this study, we found that lncRNA sprouty4-intron transcript 1 (SPRY4-IT1) was regulated by PDK1 with correlation analysis, and PDK1 upregulated SPRY4-IT1 remarkably in breast cancer cells, as PDK1 interacted with SPRY4-IT1 in the nucleus and significantly enhanced the stability of SRPY4-IT1. Furthermore, SPRY4-IT1 was highly expressed in breast cancer, significantly promoted the proliferation and inhibited apoptosis of breast cancer cells. In terms of mechanism, SPRY4-IT1 inhibited the transcription of NFKBIA and the expression of IκBα, thus promoting the formation of p50/p65 complex and activating NF-κB signaling pathway, which facilitated survival of breast cancer cells. Therefore, our finding reveals that PDK1/SPRY4-IT1/NFKBIA axis plays a crucial role that promoting tumor progression, and SPRY4-IT1 knockdown incombined with PDK1 inhibitor is promising to be a new therapeutic strategy in breast cancer.

The role and molecular mechanism of metabolic reprogramming of colorectal cancer by UBR5 through PYK2 regulation of OXPHOS expression study.

Colorectal carcinoma (CRC) is the third most malignant tumor in the world, but the key mechanisms of CRC progression have not been confirmed. UBR5 and PYK2 expression levels were detected by RT-qPCR. The levels of UBR5, PYK2, and mitochondrial oxidative phosphorylation (OXPHOS) complexes were detected by western blot analysis. Flow cytometry was used to detect ROS activity. The CCK-8 assay was used to assess cell proliferation and viability. The interaction between UBR5 and PYK2 was detected by immunoprecipitation. A clone formation assay was used to determine the cell clone formation rate. The ATP level and lactate production of each group of cells were detected by the kit. EdU staining was performed for cell proliferation.Transwell assay was performed for cell migration ability. For the CRC nude mouse model, we also observed and recorded the volume and mass of tumor-forming tumors. The expression of UBR5 and PYK2 was elevated in both CRC and human colonic mucosal epithelial cell lines, and knockdown of UBR5 had inhibitory effects on cancer cell proliferation and cloning and other behaviors in the CRC process by knockdown of UBR5 to downregulate the expression of PYK2, thus inhibiting the OXPHOS process in CRC; rotenone (OXPHOS inhibitor) treatment enhanced all these inhibitory effects. Knockdown of UBR5 can reduce the expression level of PYK2, thus downregulating the OXPHOS process in CRC cell lines and inhibiting the CRC metabolic reprogramming process.

Brain targeted borneol-baicalin liposome improves blood-brain barrier integrity after cerebral ischemia-reperfusion injury via inhibiting HIF-1α/VEGF/eNOS/NO signal pathway.

Baicalin (BA) is widely used in the treatment of cerebral ischemia-reperfusion injury (CIRI). The key to treating encephalopathy is to increase the amounts of drugs entering the brain. Borneol-baicalin liposome (BO-BA-LP) was prepared in previous research based on the characteristics of borneol (BO) in promoting drug brain entry. In this study, the effect of BO-BA-LP on improving blood-brain barrier (BBB) integrity was researched. Results showed BO-BA-LP may increase ability of BA to penetrate the cell membrane in vitro. Pharmacokinetic results showed the BO-BA-LP could increase concentrations of BA in plasma and brain tissues of normal and CIRI mice. Pharmacological results revealed BO-BA-LP could improve the neurological function, brain edema, and histopathology of CIRI mice. Besides, BO-BA-LP could protect BBB by regulating hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway. The research showed that BO in BO-BA-LP could increase the absorption of BA by increasing BBB permeability, leading to a better therapeutic effect of BO-BA-LP on CIRI mice.

Macrophage membrane biomimetic drug delivery system: for inflammation targeted therapy.

In recent years, there have been many exciting developments in the biomedical applications of the macrophage membrane bionic drug delivery system (MM-Bio-DDS). Macrophages, as an important immune cell, are involved in initiating and regulating the specific immune response of the body. Therefore, the inflammatory process related to macrophages is an important goal in the diagnosis and treatment of many diseases. In this review, we first summarise the different methods of preparation, characterisation, release profiles and natural advantages of using macrophages as a drug delivery system (DDS). Second, we introduce the processes of various chronic inflammatory diseases and the role of macrophages in them, specifically clarifying how the MM-Bio-DDS provides a wide and effective treatment for the targeted inflammatory site. Finally, based on the existing research, we propose the application prospect and existing challenges of the MM-Bio-DDS, especially the problems in clinical transformation, to provide new ideas for the development and utilisation of the MM-Bio-DDS in targeted drug delivery for inflammation and the treatment of diseases.

Cell-Penetrating Peptide Conjugated Au Nanoclusters Selectively Suppress Refractory Lymphoma Cells via Targeting Both Canonical and Noncanonical NF-κB Signaling Pathways.

Activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is the most aggressive form of DLBCL, with a significantly inferior prognosis due to resistance to the standard R-CHOP immunochemotherapy. Survival of ABC-DLBCL cells addicted to the constitutive activations of both canonical and noncanonical NF-κB signaling makes them attractive therapeutic targets. However, a pharmaceutical approach simultaneously targeting the canonical and noncanonical NF-κB pathway in the ABC-DLBCL cell is still lacking. Peptide-conjugated gold nanoclusters (AuNCs) have emerged unique intrinsic biomedical activities and possess a great potential in cancer theranostics. Here, we demonstrated a Au25 nanocluster conjugated by cell-penetrating peptides that can selectively repress the growth of ABC-DLBCL cells by inducing efficient apoptosis, more efficiently than glutathione (GSH)-conjugated AuNCs. The mechanism study showed that the cell-penetrating peptides enhanced the cellular internalization efficiency of AuNCs, and the selective repression in ABC-DLBCL cells is due to the inhibition of inherent constitutive canonical and noncanonical NF-κB activities by AuNCs. Several NF-κB target genes involved in chemotherapy resistance in ABC-DLBCL cells, including anti-apoptotic Bcl-2 family members and DNA damage repair proteins, were effectively down-regulated by the AuNC. The emerged novel activity of AuNCs in targeting both arms of NF-κB signaling in ABC-DLBCL cells may provide a promising candidate and a new insight into the rational design of peptide-conjugated Au nanomedicine for molecular targeting treatment of refractory lymphomas.

Corrigendum: Identification of differentially expressed hub genes associated with immune cell recruitment in claudin-low breast cancer.

[This corrects the article DOI: 10.3389/fonc.2022.848206.].

Identification of Differentially Expressed Hub Genes Associated With Immune Cell Recruitment in Claudin-Low Breast Cancer.

Breast cancer (BCa) is the most common malignancy in women and claudin-low breast cancer (CL-BCa) is a newly identified BCa subtype characterized by low expression of claudin 3&4&7. However, the hub genes associated with the recruitment of immune cells into CL-BCa were rarely described. This study aimed at exploring the differentially expressed hub genes associated with tumor-infiltrating immune cells in CL-BCa by a multi-approach bioinformatics analysis. The top 200 genes associated with CL-BCa were screened in the METABRIC dataset; the PPI network was constructed using STRING and Cytoscape; tumor-infiltrating immune cells were analyzed by TIMER 2.0; and the correlation of feature cytokines and claudins on survival was examined in METABRIC and TCGA datasets. Consequently, we found that the fraction of tumor-infiltrating immune cells, especially CD8+T cells and macrophages, increased in the CL-BCa. Differentially expressed cytokines (CCL5, CCL19, CXCL9 and CXCL10) and claudins (CLDN8, CLDN11 and CLDN19) were related to the overall survival, and their expression levels were also examined both in tumor tissues of CL-BCa patients by IHC and in typical CL-BCa cell lines by qPCR. Finally, the BCa patients with high expression of these DEGs (CCL5, CCL19, CXCL9, CLDN8 and CLDN11) showed a better overall survival. This study sheds light on molecular features of CL-BCa on immune microenvironments and contributes to identification of prognosis biomarkers for the CL-BCa patients.

Macrophage membrane modified baicalin liposomes improve brain targeting for alleviating cerebral ischemia reperfusion injury.

Baicalin (BA) has a good intervention effect on encephalopathy. In this study, macrophage membrane was modified on the surface of baicalin liposomes (BA-LP) by extrusion method. Macrophage membrane modified BA-LP (MM-BA-LP) was characterized by various analytical techniques, and evaluated for brain targeting. The results presented MM-BA-LP had better brain targeting compared with BA-LP. Pharmacokinetic experiments showed that MM-BA-LP improved pharmacokinetic parameters and increased the residence time of BA. Pharmacodynamic of middle cerebral artery occlusion (MCAO) rat model was studied to verify the therapeutic effect of MM-BA-LP on cerebral ischemia reperfusion injury (CIRI). The results showed that MM-BA-LP could significantly improve the neurological deficit, cerebral infarction volume and brain pathological state of MCAO rats compared with BA-LP. These results suggested that MM-BA-LP could significantly enhance the brain targeting and improve the circulation of BA in blood, and had a significantly better neuroprotective effect on MCAO rats than BA-LP.

[Mass spectrometry imaging technology and its application in breast cancer research].

The incidence of breast cancer, one of the most common malignancies affecting women, is increasing significantly worldwide. Given the rapid development of medical technology, early and effective diagnostic methods should be able to improve the survival rate and quality of life of patients suffering from disease. However, although existing treatment options, including chemotherapy and endocrine therapies, have greatly improved the survival of patients, disease recurrence in the long term remains a challenge. Because breast cancer is a heterogeneous and complex disease, which includes several subtypes with different responses to treatment, the continual acquisition of spatial information on related biomolecules is important for accurate tracking of the tumor heterogeneity and microenvironment. At present, prognostic and predictive biomarkers, such as human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), Ki-67, progesterone receptor (PR), and programmed death-ligand 1 (PD-L1), are validated for use in the decision-making over breast cancer therapies. Mass spectrometry imaging (MSI) is a useful technique for acquiring molecular information about biological tissues, including qualitative, quantitative, and spatial distribution information, because it is based on the ion mass-to-charge ratio of the biomolecules and avoids the need for their labeling and staining. MSI can also acquire molecular information on drugs and their metabolites, as well as that on molecules related to endogenous metabolism, such as lipids, peptides, and proteins. Of the various ion sources available for MSI, the most popular are matrix-assisted laser desorption ionization, secondary ion mass spectrometry, and desorption electrospray ionization, and modifications or derivatives of these sources are still emerging. MSI-based techniques provide new ideas and directions for the molecular typing of tumors, as well as knowledge on the metabolism of related antitumor drugs. The process of MSI analysis generally involves tissue acquisition, section preparation, mass spectrometry ionization, map acquisition, and data analysis, with the most crucial step being sample handling to preserve the original chemical and location information of the analytes. The sample preparation steps are sample collection, storage, and slicing, tissue pretreatment, and matrix spraying. This review focuses mainly on the preparation of biological specimens for MSI analysis and the recent progress made in breast cancer research with this technology. With regard to sample preparation, four aspects are discussed: small-molecule samples, macromolecular samples, paraffin-embedded samples, and matrix spraying methods. To solve the difficulties associated with small-molecule sample processing, including the low extraction efficiency for certain lipids and matrix interference in the low-molecular-weight region, the addition of a cationic reagent to the extractant, the use of a new matrix, and tissue derivatization have been used. In the review of macromolecular sample processing, several different washing protocols are summarized. With regard to paraffin-embedded samples, the solutions to several common problems are reviewed. Additionally, the application of MSI to three models associated with breast cancer research is discussed, viz. cell models, animal models, and clinical tumor samples. For these models, MSI technology is used to evaluate the penetration and metabolism of antitumor agents in breast cancer, which can better reflect the malignant transformation of cells and changes in the microenvironment. With regard to lipid molecules, the use of MSI to study differences in their spatial distribution may provide a better understanding of the relationship between lipid metabolism and cancer. This review also provides important information for accurate molecular typing and drug screening in cancer research. Analytically, the tissue preparation method, tissue storage conditions, instrumentation choice, and experimental parameters have all been associated with variability in the imaging and mass-spectral qualities of MSI, thereby affecting the performance of the method. Large-scale studies using diverse sample cohorts are therefore needed to properly evaluate the robustness of MSI molecular markers and workflows for the clinical diagnosis and characterization of breast cancer variants. Our review provides strong evidence that MSI is a reliable, highly reproducible, and rapid technique for the diagnosis of breast cancer biopsies and may be useful in clinical application.

[Detection method of nonlinear magnetized harmonic signal of medical magnetic nanoparticles].

Medical magnetic nanoparticles are nano-medical materials with superparamagnetism, which can be collected in the tumor tissue through blood circulation, and magnetic particle imaging technology can be used to visualize the concentration of magnetic nanoparticles in the living body to achieve the purpose of tumor imaging. Based on the nonlinear magnetization characteristics of magnetic particles and the frequency characteristics of their magnetization, a differential detection method for the third harmonic of magnetic particle detection signals is proposed. It was modeled and analyzed, to study the nonlinear magnetization response characteristics of magnetic particles under alternating field, and the spectral characteristics of magnetic particle signals. At the same time, the relationship between each harmonic and the amount of medical magnetic nanoparticle samples was studied. On this basis, a signal detection experimental system was built to analyze the spectral characteristics and power spectral density of the detected signal, and to study the relationship between the signal and the excitation frequency. The signal detection experiment was carried out by the above method. The experimental results showed that under the alternating excitation field, the medical magnetic nanoparticles would generate a spike signal higher than the background sensing signal, and the magnetic particle signal existed in the odd harmonics of the detected signal spectrum. And the spectral energy was concentrated at the third harmonic, that is, the third harmonic magnetic particle signal detection that meets the medical detection requirement could be realized. In addition, the relationship between each harmonic and the particle sample volume had a positive growth relationship, and the detected medical magnetic nanoparticle sample volume could be determined according to the relationship. At the same time, the selection of the excitation frequency was limited by the sensitivity of the system, and the detection peak of the third harmonic of the detection signal was reached at the excitation frequency of 1 kHz. It provides theoretical and technical support for the detection of medical magnetic nanoparticle imaging signals in magnetic particle imaging research.

Feasibility and efficacy of microwave ablation for treating breast fibroadenoma.

BACKGROUND: To investigate the safety, efficacy, and follow-up outcomes of microwave ablation (MWA) in patients with breast fibroadenoma. METHODS: An institutional review board-approved this study of patients treated with MWA for breast fibroadenoma from October 2017 to March 2019. Clinical features of patients and breast fibroadenoma were analyzed. At follow-up all patients received physical examination and ultrasound imaging. RESULTS: In total, 171 patients with 271 lesions were enrolled. The mean lesion diameter was 1.35 ± 0.47 cm. The results revealed differential lesion states, including stability, enlargement, reduction, and complete regression, at 1-6, 6-12, and >12 months of follow-up. The size was reduced in 22.14% (31/140), 26.36% (29/110), and 36.36% (16/44) of the lesions at 1-6, 6-12, and >12 months of follow-up, respectively. The proportion of lesions with complete regression was 24.29% (34/140) at 1-6 months, 45.45% (50/110) at 6-12 months, and 40.91% (18/44) at >12 months of follow up. There was no significant relationship between the curative effect and age, lesion location, and blood flow in patients with breast fibroadenoma after MWA (p > .05), but there was statistically significant relationship with lesion diameter (categorized as <1.5 cm and ≥1.5 cm) (p < .05). CONCLUSIONS: The current evidence indicates that MWA is a safe and effective method for treating breast fibroadenoma. Nevertheless, further large-scale prospective trials and well-designed future studies are warranted to validate our findings.

A novel technology to reduce astringency of tea polyphenols extract and its mechanism.

Objective: Tea polyphenols are natural extracts used widely throughout the world. However, the severe astringency of tea polyphenols has reduced patient compliance. Based on the analysis of the formation mechanism of astringency, this paper hopes to propose a new method to control the astringency of tea polyphenols and improve patient compliance without changing its effect. Methods: Artificial saliva was used to prepare the tea polyphenols solution with different pH, using ß-casein to imitate salivary protein, and preparing 1.2 mg/mL ß-casein solution. A fluorescence quenching test was used to study the interaction between tea polyphenols and ß-casein, combined with the stability test results of the compound, we can choose the pH with weak binding but good stability as the best pH for masking astringency. The taste-masking tablets were prepared under the best pH conditions, and the Xinnaojian Original Tablets were prepared according to the conventional preparation method. The disintegration time limit and solubility were tested respectively. The astringency of Xinnaojian original tablets and taste-masking tablets was evaluated by visual analogue scale (VAS). Results: The result of the fluorescence quenching test prompted that the combination force was the weakest when the pH was 4.9. Further synchronous fluorescence analysis showed that an increase in pH resulted in a decrease of the binding sites between tea polyphenols and ß-casein, and this decrease was closely related to changes in tryptophan residues in ß-casein. Both original and taste-masking Xinnaojian Tablets were prepared. Volunteers' VAS scores illustrated that the astringency improved significantly with the masking tablets (P < 0.05). Conclusion: This pH-adjusting masking treatment had little effect on the recovery of polyphenols from the tablets or the dissolution of the tablets. This study provides a novel and feasible astringency masking technology for tea polyphenols and its preparation.