RESUMO
The development of thermostable vaccines can relieve the bottleneck of existing vaccines caused by thermal instability and subsequent poor efficacy, which is one of the predominant reasons for the millions of deaths caused by vaccine-preventable diseases. Research into the mechanism of viral thermostability may provide strategies for developing thermostable vaccines. Using Newcastle disease virus (NDV) as model, we identified the negative surface charge of attachment glycoprotein as a novel determinant of viral thermostability. It prevented the temperature-induced aggregation of glycoprotein and subsequent detachment from virion surface. Then structural stability of virion surface was improved and virus could bind to and infect cells efficiently after heat-treatment. Employing the approach of surface charge engineering, thermal stability of NDV and influenza A virus (IAV) vaccines was successfully improved. The increase in the level of vaccine thermal stability was determined by the value-added in the negative surface charge of the attachment glycoprotein. The engineered live and inactivated vaccines could be used efficiently after storage at 37°C for at least 10 and 60 days, respectively. Thus, our results revealed a novel surface-charge-mediated link between HN protein and NDV thermostability, which could be used to design thermal stable NDV and IAV vaccines rationally.
Assuntos
Doença de Newcastle , Vacinas Virais , Animais , Galinhas/metabolismo , Glicoproteínas , Proteína HN/metabolismo , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/metabolismoRESUMO
Pseudorabies virus (PRV) belongs to the alpha herpesvirus family and is responsible for Aujeszky's disease in pigs. Similar to other alpha herpesviruses, PRV establishes a lifelong latent infection in trigeminal ganglion. These latently infected pigs serve as a reservoir for recurrent infections when reactivation is triggered, making the eradication of PRV a challenging task. However, the molecular mechanism underlying PRV latency and reactivation in neurons is still poorly understood due to limitations in the in vitro model. To establish a pseudorabies virus latency and reactivation model in primary neuron cultures, we isolated dorsal root ganglion (DRG) from newborn Kunming mice using a method named epineurium-pulling for DRG collection (EPDC) and cultured primary neurons in vitro. A dual-colour recombinant PRV BAC mRuby-VP16 was constructed and 0.5 multiplicity of infection (MOI) was found as an appropriate dose in the presence of aciclovir to establish latency. Reactivation was induced using UV-inactivated herpesviruses or a series of chemical inhibitors. Interestingly, we found that not only UV-PRV, but also UV-HSV-1 and UV-BHoV-5 were able to induce rapid PRV reactivation. The efficiency of reactivation for LY294002, forskolin, etoposide, dexamethasone, and acetylcholine was found to be dependent on their concentration. In conclusion, we developed a valuable model of PRV latency and reactivation, which provides a basis for future mechanism research.
Assuntos
Herpesvirus Suídeo 1 , Pseudorraiva , Camundongos , Animais , Suínos , Herpesvirus Suídeo 1/fisiologia , Gânglios Espinais , Latência Viral , Ativação ViralRESUMO
PURPOSE: To reduce the potential risk during radiotherapy treatment of patients with head and neck tumors, we improved upon the design of an existing immobilization device by adding a feature to improve patient safety during emergency releases, and we verified its clinical application. METHOD: We designed an improved automatic unlocking baseplate (AUB), and conducted a dosimetry comparison with Solo Align Full Body System (SAFBS, Klarity, China). The dosimetry comparison included dose-attenuation measurements and results from human simulation. We selected four points for measurement to allow comparison between the SAFBS and our AUB. A simulated human body model was used for CT scanning, whereby the target area and structure and simulated radiotherapy plan were conducted according to the American Academy of Pain Medicine Task Group-119 report (TG-119), whereby the dose differences were compared. The purpose of the clinical test was to verify the reliability of the AUB system in practical clinical applications. The application tests were conducted in CT simulation (CT-sim) and treatment rooms. The test included assessments of the stability of the system and the reliability of our device. RESULTS: The dose-attenuation measurements of the two baseplates were as follows: The transmission values with our unlocking system were 0.10% higher at the first point and 0.67% lower at the third. The same dose was obtained at points 2 and 4. In the simulation study, the PTV of the AUB was lower than that of the SAFBS, including 0.39% lower D99 and 0.18% lower D90 . Among the organ-at-risk doses, the average dose of the AUB in the spinal cord was 0.6% higher than that of the SAFBS, and the average dose in the left and right parotid glands was more than 1.4% lower than that of SAFBS. The clinical test results were applied in treatment room and a CT-sim room, which show a 100% success rate after being unlocked more than 5000 times. CONCLUSION: The AUB designed for head and neck patients had good functional versatility, the dose distribution met the requirements, and the automatic unlocking function was demonstrated to be stable and reliable.
Assuntos
Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Radioterapia de Intensidade Modulada/métodos , Radioterapia Conformacional/métodosRESUMO
BACKGROUND: Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) induce osteogenesis in adipose-derived stem cells (ADSCs). This study aimed to explore the role of lncRNAs AC092155 in promoting osteogenic differentiation of ADSCs. METHODS: MicroRNA (miRNA) and lncRNA sequencing were performed in ADSCs that underwent normal or osteogenic induction. Differentially expressed miRNAs and lncRNAs were identified using R software. The relative expression levels of lncRNA AC092155, miR-143-3p, and STMN1 during the process of osteogenic induction were determined by real-time polymerase chain reaction (RT-PCR). ADSCs were then transfected with agomiR-143-3p and pcDNA3.1-sh-lncRNA AC092155. Alkaline phosphatase (ALP) and alizarin red staining (ARS) were used to confirm the regulatory function of the lncRNA AC092155/miR-143-3p/STMN1 axis in osteogenic differentiation of ADSCs. RESULTS: lncRNA AC092155 was significantly upregulated in ADSCs following induction in the osteogenic medium. lncRNA AC092155 and STMN1 mimics increase the markers of osteogenic differentiation in the early and late phases, which was reflected in increased ALP activity as well as the higher deposition of calcium nodules. An miR-143-3p mimic showed the opposite effect. Luciferase reporter gene analysis demonstrated that lncRNA AC092155 directly targets miR-143-3p. Moreover, the lncRNA AC092155/miR-143-3p/STMN1 regulatory axis was found to activate the Wnt/ß-catenin signaling pathway. CONCLUSIONS: lncRNA AC092155 contributes to the osteogenic differentiation of ADSCs. The lncRNA AC092155/miR-143-3p/STMN1 axis may be a new therapeutic target for bone-related diseases.
Assuntos
Tecido Adiposo/citologia , Osteogênese/genética , RNA Longo não Codificante/genética , Estatmina/genética , Células-Tronco/citologia , Diferenciação Celular/genética , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Células-Tronco/fisiologia , Regulação para CimaRESUMO
Pseudorabies virus (PRV) establishes a lifelong latent infection in swine trigeminal ganglion (TG) following acute infection. Increased corticosteroid levels, due to stress, increases the incidence of reactivation from latency. Muscle injection combined with intravenous deliver of the synthetic corticosteroid dexamethasone (DEX) consistently induces reactivation from latency in pigs. In this study, PRV-free piglets were infected with PRV. Viral shedding in nasal and ocular swabs demonstrated that PRV infection entered the latent period. The anti-PRV antibody was detected by enzyme-linked immunosorbent assay and the serum neutralization test, which suggested that the PRV could establish latent infection in the presence of humoral immunity. Immunohistochemistry and viral genome detection of TG neurons suggested that PRV was reactivated from latency. Viral gene expressions of IE180, EP0, VP16, and LLT-intron were readily detected at 3-h post-DEX treatment, but gB, a γ1 gene, was not detectable. The differentially expressed phosphorylated proteins of TG neurons were analyzed by ITRAQ coupled with LC-MS/MS, and p-EIF2S2 differentially expression was confirmed by western blot assay. Taken together, our study provides the evidence that typical gene expression in PRV reactivation from latency in TG is disordered compared with known lytic infection in epithelial cells.
Assuntos
Dexametasona/farmacologia , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Herpesvirus Suídeo 1/efeitos dos fármacos , Pseudorraiva/virologia , Doenças dos Suínos/virologia , Gânglio Trigeminal/efeitos dos fármacos , Ativação Viral/efeitos dos fármacos , Animais , Anticorpos Antivirais/sangue , Olho/virologia , Glucocorticoides/farmacologia , Proteína Vmw65 do Vírus do Herpes Simples/genética , Proteína Vmw65 do Vírus do Herpes Simples/imunologia , Herpesvirus Suídeo 1/genética , Herpesvirus Suídeo 1/imunologia , Herpesvirus Suídeo 1/patogenicidade , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/imunologia , Imunidade Humoral/efeitos dos fármacos , Cavidade Nasal/virologia , Neurônios/efeitos dos fármacos , Neurônios/imunologia , Neurônios/virologia , Pseudorraiva/imunologia , Pseudorraiva/patologia , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/patologia , Gânglio Trigeminal/imunologia , Gânglio Trigeminal/virologia , Latência Viral/efeitos dos fármacos , Eliminação de Partículas Virais/efeitos dos fármacosRESUMO
BACKGROUND: The development of tumor cells inside the lymphatics or blood vessels is known as lymphovascular invasion (LVI). The correlation between LVI, lymph node metastasis (LNM), and the diagnosis of superficial esophageal carcinoma (SEC) remains unclear. METHODS: We searched Embase, PubMed, Web of Science, and Cochrane Library databases for prospective articles to better understand the relationship between LVI, LNM, and SEC diagnosis. RESULTS: We included 23 articles containing data for 4749 patients (range: 54-598) in our meta-analysis. The hazard ratio between LVI and overall survival (OS) was 1.85 with 95% confidence interval (CI) (1.10-3.11, P = 0.02). LNM rate was higher in SEC patients with LVI than SEC patients without LVI (univariate: OR = 4.94, 95% CI: 3.74-6.53, P < 0.0001; multivariate: OR = 5.72, 95%CI: 4.38-7.4, P < 0.0001). No obvious publication was found. CONCLUSIONS: The results indicate that LVI plays a dominant role in the prognosis of LNM in SEC and in the prognostic prediction for SEC.
Assuntos
Neoplasias Esofágicas/patologia , Metástase Linfática/patologia , Feminino , Humanos , Masculino , Invasividade Neoplásica , Prognóstico , Estudos Prospectivos , Análise de SobrevidaRESUMO
Comprehensive knowledge of strain rate-dependent viscoelastic properties of bony materials is necessary to understand the mechanisms of bone fracture under impact loading conditions (e.g., falls, traffic accidents, and military environments). Although the mechanical properties of bones have been studied for several decades, the high strain rate data and corresponding material parameters of the rate-dependent constitutive models are still limited. In this study, split Hopkinson pressure bar technique was used to test bovine cortical bones, to obtain the rate-dependent stress-strain curves in two directions (along and perpendicular to the bone fibers). A constitutive relationship comprising two terms was then applied to identify the material constants with strain rate effect and viscoelastic properties. In this model, the linear elasticity was combined with nonlinear viscoelasticity components to describe the overall nonlinear strain rate dependence. The presented data give strong experimental evidence and basis for further development of numerical biomechanical models to simulate human cortical bone fracture.
Assuntos
Força Compressiva , Animais , Bovinos , Elasticidade , Modelos Biológicos , Estresse Mecânico , ViscosidadeRESUMO
BACKGROUND: Dislocation is the second most common complication after total hip arthroplasty (THA). The effectiveness of soft tissue repair to reduce dislocation rate is still debated and thus a meta-analysis was conducted. METHODS: A systematic search in PubMed, Embase, and Cochrane databases was conducted for this meta-analysis. INCLUSION CRITERIA: clinical comparative trials on the use of soft tissue repair including rotators and capsule repair in primary THA. The main data outcome were the incidences of early hip dislocation after primary THA. HSS score, incidence of other complications was also included in the outcomes. RESULTS: A total of 4816 cases were included for the analysis from ten studies (3 RCTs/7 Retrospective trials). Overall, the soft tissue repair group showed a significant lower early dislocation rate and higher HSS score compared to the no repair group; but no significant difference was observed between the two groups in regards to the early dislocation rate in RCT studies only. The capsule repair group showed a significant lower early dislocation rate than no capsule repair group while no significant difference was observed between the rotators repair group and no rotators repair group. In all included studies, 4 greater trochanter fractures, 2 sciatic nerve palsies and 1 infection were reported in soft tissue repair group while no cases were observed in the no repair group. CONCLUSIONS: The efficacy of soft tissue repair is positive but still not conclusive to reduce the early dislocation rate after primary THA while soft tissue repair may bring more other complications. Capsule repair seems more effective than rotators repair only.
Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Tecido Conjuntivo/cirurgia , Luxação do Quadril/prevenção & controle , Articulação do Quadril/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Luxação do Quadril/etiologia , Humanos , Incidência , Estudos RetrospectivosRESUMO
BACKGROUND: The incidence of breast cancer ranks highest among cancers and is exceedingly heterogeneous. Immunohistochemical staining is commonly used clinically to identify the molecular subtype for subsequent treatment and prognosis. PURPOSE: Raman spectroscopy and support vector machine (SVM) learning algorithm were utilized to identify blood samples from breast cancer patients in order to investigate a novel molecular typing approach. METHOD: Tumor tissue coarse needle aspiration biopsy samples, and peripheral venous blood samples were gathered from 459 invasive breast cancer patients admitted to the breast department of Sichuan Cancer Hospital between June 2021 and September 2022. Immunohistochemical staining and in situ hybridization were performed on the coarse needle aspiration biopsy tissues to obtain their molecular typing pathological labels, including: 70 cases of Luminal A, 167 cases of Luminal B (HER2-positive), 57 cases of Luminal B (HER2-negative), 84 cases of HER2-positive, and 81 cases of triple-negative. Blood samples were processed to obtained Raman spectra taken for SVM classification models establishment with machine algorithms (using 80% of the sample data as the training set), and then the performance of the SVM classification models was evaluated by the independent validation set (20% of the sample data). RESULTS: The AUC values of SVM classification models remained above 0.85, demonstrating outstanding model performance and excellent subtype discrimination of breast cancer molecular subtypes. CONCLUSION: Raman spectroscopy of serum samples can promptly and precisely detect the molecular subtype of invasive breast cancer, which has the potential for clinical value.
Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Análise Espectral Raman , Máquina de Vetores de Suporte , Humanos , Feminino , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Análise Espectral Raman/métodos , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptor ErbB-2/análise , Receptor ErbB-2/sangue , Adulto , Biomarcadores Tumorais/sangue , Tipagem Molecular/métodos , Idoso , Prognóstico , Invasividade NeoplásicaRESUMO
Human epidermal growth factor receptor 2 (HER2) is a transmembrane receptor-like protein with tyrosine kinase activity that plays a vital role in processes such as cell proliferation, differentiation, and angiogenesis. The degree of malignancy of different cancers, notably breast cancer, is strongly associated with HER2 amplification, overexpression, and mutation. Currently, widely used clinical HER2 tyrosine kinase inhibitors (TKIs), such as lapatinib and neratinib, have several drawbacks, including susceptibility to drug resistance caused by HER2 mutations and adverse effects from insufficient HER2 selectivity. To address these issues, it is essential to create innovative HER2 TKIs with enhanced safety, effectiveness against mutations, and high selectivity. Typically, SPH5030 has advanced to phase I clinical trials for its strong suppression of four HER2 mutations. This review discusses the latest research progress in HER2 TKIs, with a focus on the structural optimization process and structure-activity relationship analysis. In particular, this study highlights promising design strategies to address these challenges, providing insightful information and inspiration for future development in this field.
Assuntos
Antineoplásicos , Desenho de Fármacos , Inibidores de Proteínas Quinases , Receptor ErbB-2 , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Relação Estrutura-Atividade , Estrutura Molecular , Neoplasias/tratamento farmacológicoRESUMO
Given the significant therapeutic efficacy of anti-HER-2 treatment, the HER-2 status is a crucial piece of information that must be obtained in breast cancer patients. Currently, as per guidelines, HER-2 status is typically acquired from breast tissue of patients. However, there is growing interest in obtaining HER-2 status from serum and other samples due to the convenience and potential for dynamic monitoring. In this study, we have developed a serum Raman spectroscopy technique that allows for the rapid acquisition of HER-2 status in a convenient manner. The established HER-2 negative and positive classification model achieved an area under the curve of 0.8334. To further validate the reliability of our method, we replicated the process using immunohistochemistry and in situ hybridization. The results demonstrate that serum Raman spectroscopy, coupled with artificial intelligence algorithms, is an effective technical approach for obtaining HER-2 status.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Inteligência Artificial , Reprodutibilidade dos Testes , Análise Espectral Raman , Receptor ErbB-2/genética , Receptor ErbB-2/uso terapêutico , Hibridização In SituRESUMO
Leucine-rich repeat containing 15 (LRRC15) has been identified as a contributing factor for cartilage damage in osteoarthritis; however, its involvement in rheumatoid arthritis (RA) and the underlying mechanisms have not been well characterized. The purpose of this study was to explore the function of LRRC15 in RA-associated fibroblast-like synoviocytes (RA-FLS) and in mice with collagen-induced arthritis (CIA) and to dissect the epigenetic mechanisms involved. LRRC15 was overexpressed in the synovial tissues of patients with RA, and LRRC15 overexpression was associated with increased proliferative, migratory, invasive, and angiogenic capacities of RA-FLS and accelerated release of pro-inflammatory cytokines. LRRC15 knockdown significantly inhibited synovial proliferation and reduced bone invasion and destruction in CIA mice. Runt-related transcription factor 1 (RUNX1) transcriptionally represses LRRC15 by binding to core-binding factor subunit beta (CBF-ß). Overexpression of RUNX1 significantly inhibited the invasive phenotype of RA-FLS and suppressed the expression of proinflammatory cytokines. Conversely, the effects of RUNX1 were significantly reversed after overexpression of LRRC15 or inhibition of RUNX1-CBF-ß interactions. Therefore, we demonstrated that RUNX1-mediated transcriptional repression of LRRC15 inhibited the development of RA, which may have therapeutic effects for RA patients.
Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Camundongos , Artrite Experimental/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Movimento Celular , Proliferação de Células , Células Cultivadas , Subunidade alfa 2 de Fator de Ligação ao Core/farmacologia , Citocinas/metabolismo , Epigênese Genética , Fibroblastos/metabolismo , Membrana Sinovial/metabolismo , HumanosRESUMO
Amorphous solid dispersion (ASD) is a promising strategy to enhance solubility and bioavailability of poorly water-soluble drugs. Due to higher free energy of ASD, supersaturated drug solution could be generated during dissolution. When amorphous solubility of a drug is exceeded, drug-rich nanodroplets could form and act as a reservoir to maintain the maximum free drug concentration in solution, facilitating the absorption of the drug in vivo. Dissolution behavior of ASD has received increasing interests. This review will focus on the recent advances in ASD dissolution, including the generation and maintenance of supersaturated drug solution in absence or presence of liquid-liquid phase separation. Mechanism of drug release from ASD including polymer-controlled dissolution and drug-controlled dissolution will be introduced. Formation of amorphous drug-rich nanodroplets during dissolution and the underlying mechanism will be discussed. Phase separation morphology of hydrated ASD plays a critical role in dissolution behavior of ASD, which will be highlighted. Supersaturated drug solution shows poor physical stability and tends to crystallize. The effect of polymer and surfactant on supersaturated drug solution will be demonstrated and some unexpected results will be shown. Physicochemical properties of drug and polymer could impact ASD dissolution and some of them even show opposite effect on dissolution and physical stability of ASD in solid state, respectively. This review will contribute to a better understanding of ASD dissolution and facilitate a rational design of ASD formulation.
Assuntos
Polímeros , Tensoativos , Solubilidade , Liberação Controlada de Fármacos , Polímeros/químicaRESUMO
Supersaturating drug delivery system (SDDS) is a promising approach to enhance the solubility of hydrophobic functional components. However, SDDS is thermodynamically unstable and crystallization tends to occur. In this work, curcumin was used as a model compound, and the crystallization inhibitory effect of konjac glucomannan (KGM), sodium alginate (SA) and xanthan gum (XTG) on curcumin in supersaturated solution was investigated. Amorphous solubility of curcumin was determined using ultraviolet extinction, fluorescence spectroscopy and dynamic light scattering methods. Nucleation induction time (NIT) and crystal growth rate of curcumin were evaluated using ultraviolet probe in the absence and presence of various natural polysaccharides (NPs). Results showed that amorphous solubility of curcumin was approximately 30 µg/mL in pH 6.8 phosphate buffer. NPs used in this work restrained nucleation or crystal growth of curcumin effectively. The NITs of curcumin in the absence of NPs and in the presence of XTG, KGM and SA (1 µg/mL) were 3.7, 60.7, 20.0 and 8.0 min, respectively. The crystal growth rate of curcumin in the absence of NPs and in the presence of XTG, SA and KGM (1 µg/mL) were 0.0103, 0.00752, 0.00286 and 0.000306 min-1, respectively. The nucleation inhibitory effect of NPs on curcumin was ranked as XTG > KGM > SA. The order of crystal growth inhibition capacity of NPs was KGM > SA > XTG. In conclusion, NPs could be incorporated into SDDS to maintain supersaturation of hydrophobic components for enhanced bioavailability.
Assuntos
Curcumina , Cristalização , Curcumina/farmacologia , Alginatos , Mananas/química , SolubilidadeRESUMO
Whether long non-coding RNA Mir-99a-Let-7c Cluster Host Gene (LncRNA MIR99AHG) is involved in osteoporosis (OP) remains vague, so we hereby center on its implication. Old C57BL/6J mice were injected with the silencing lentivirus of MIR99AHG and subjected to microCT analysis and immunohistochemistry on osteogenic cells. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) with or without transfection was determined by alkaline phosphatase (ALP) and Alizarin Red S staining. Total N(6)-methyladenosine (m6A) on the bone marrow mesenchymal stem cells (BMSCs) was quantified. The potential methylation site and the complementary binding sites with candidate microRNA (miR) were predicted via bioinformatic analyses, with the latter being confirmed via dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Quantitative real-time PCR and Western blot were used for quantification assays. MIR99AHG was decreased during the osteogenic differentiation of BMSCs, where increased Osterix (OSX), Collagen, Type I, Alpha 1 (Col1A1), Osteocalcin (OCN) and RUNX Family Transcription Factor 2 (RUNX2) as well as more color-stained areas were found. Also, silencing MIR99AHG relieved the OP in mice and reduced the loss of osteogenic cells. M6A methylation in undifferentiated BMSCs was low and MIR99AHG overexpression abolished the effects of overexpressed METTL3 on promoting osteogenic differentiation. MiR-4660, which was downregulated in BMSCs without differentiation but increased during osteogenic differentiation, could bind with MIR99AHG. Furthermore, miR-4660 promoted osteogenic differentiation and reversed the effects of overexpressed MIR99AHG. The present study demonstrated that METTL3-mediated LncRNA MIR99AHG methylation enhanced the osteogenic differentiation of BMSCs via targeting miR-4660.
Assuntos
Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Camundongos , Animais , RNA Longo não Codificante/genética , Osteogênese/genética , Metilação , Células Cultivadas , Camundongos Endogâmicos C57BL , Diferenciação Celular/genética , MicroRNAs/genética , Células-Tronco Mesenquimais/metabolismo , Células da Medula Óssea/metabolismo , Metiltransferases/metabolismoRESUMO
Introduction: This study aimed to evaluate the feasibility of using general Raman spectroscopy as a method to screen for breast cancer. The objective was to develop a machine learning model that utilizes Raman spectroscopy to detect serum samples from breast cancer patients, benign cases, and healthy subjects, with puncture biopsy as the gold standard for comparison. The goal was to explore the value of Raman spectroscopy in the differential diagnosis of breast cancer, benign lesions, and healthy individuals. Methods: In this study, blood serum samples were collected from a total of 333 participants. Among them, there were 129 cases of tumors (pathologically diagnosed as breast cancer and labeled as cancer), 91 cases of benign lesions (pathologically diagnosed as benign and labeled as benign), and 113 cases of healthy controls (labeled as normal). Raman spectra of the serum samples from each group were collected. To classify the normal, benign, and cancer sample groups, principal component analysis (PCA) combined with support vector machine (SVM) was used. The SVM model was evaluated using a cross-validation method. Results: The results of the study revealed significant differences in the mean Raman spectra of the serum samples between the normal and tumor/benign groups. Although the mean Raman spectra showed slight variations between the cancer and benign groups, the SVM model achieved a remarkable prediction accuracy of up to 98% for classifying cancer, benign, and normal groups. Discussion: In conclusion, this exploratory study has demonstrated the tremendous potential of general Raman spectroscopy as a clinical adjunctive diagnostic and rapid screening tool for breast cancer.
RESUMO
It has been proved that Raman spectral intensities could be used to diagnose lung cancer patients. However, the application of Raman spectroscopy in identifying the patients with pulmonary nodules was barely studied. In this study, we revealed that Raman spectra of serum samples from healthy participants and patients with benign and malignant pulmonary nodules were significantly different. A support vector machine (SVM) model was developed for the classification of Raman spectra with wave points, according to ANOVA test results. It got a good performance with a median area under the curve (AUC) of 0.89, when the SVM model was applied in discriminating benign from malignant individuals. Compared with three common clinical models, the SVM model showed a better discriminative ability and added more net benefits to participants, which were also excellent in the small-size nodules. Thus, the Raman spectroscopy could be a less-invasive and low-costly liquid biopsy.
RESUMO
BACKGROUND: This study aimed to compare the clinical and radiographic outcomes of the proximal femoral nail antirotation (PFNA) and external fixation in the management of unstable intertrochanteric fractures in elderly patients. METHODS: Eighty-seven of 114 patients with unstable intertrochanteric fractures were included in this study between January 2015 and June 2019, 46 were fixed with PFNA implant and 41 with external fixator. Patient baseline characteristics, functional and radiographic results, and postoperative complication were documented and compared between the 2 groups. RESULTS: Prolonged operation duration, increased fluoroscopy time, and excess blood loss occurred in PFNA group. The functional results scores seemed higher in the PFNA than external fixation group in the first semester, and thereafter, there was no significant difference between groups. On early postoperative radiographs, better femur neck-shaft angle was acquired in the external fixators device, but the difference did not continue at final visit. The incidence rate of overall complications was 43.5% for the group PFNA and 100% for the group external fixation. CONCLUSIONS: Fewer postoperative complications occurred in PFNA than external fixator group when unstable intertrochanteric fractures were treated. Nevertheless, there was no significant difference detected in final functional and radiographic outcome between the 2 groups.
Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas do Quadril , Idoso , Pinos Ortopédicos , Fixadores Externos , Fraturas do Fêmur/cirurgia , Fixação de Fratura , Fixação Intramedular de Fraturas/métodos , Fraturas do Quadril/cirurgia , Humanos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Based on the modified Hopkinson torsion bar, a high-temperature dynamic shear test method was proposed for the Ti-1023 alloy, and the microstructural evolution of the tested material at different temperatures was studied. By using the modified high-temperature Hopkinson torsion bar, high-temperature testing within 1000 °C can be achieved. As the specimen-heating rate was fast, and the temperature gradient of the experimental environment was small, valid experimental data can be ensured during the experiment. The experimental results show that stress-induced martensite can significantly enhance the strength of the Ti-1023 alloy. Dynamically recrystallized grains similar to those in adiabatic shear bands appear in the microstructure of the Ti-1023 alloy after severe plastic deformation. Therefore, it is possible to regulate the content of stress-induced martensite in the microstructure to improve the mechanical properties of other alloys that are similar to ß titanium alloys.
RESUMO
The printing quality and strength of specialty papers such as money, maps, newspapers and bank notes have been a significance challenge in recent years. The adhesive effect between ink and paper is depend on both the secondary binding force between the molecules and the mechanical anchoring effect of the ink on the paper. Also, the porous and fibrous structures of base paper restrain its application in printed products because of the strong capillary effect leading to the diffusion of ink particles. To address the problems involved in ink diffusion and mechanical reinforcement, surface sizing is an attractive choice from the perspective of paper handling. Herein, the surface sizing system of specialty paper with an interpenetrating polyvinyl alcohol-blocked polyurethane polymer network was applied to fabricate paper of high ink adhesive properties. In the case of the same external factors (gluing temperature, drying time, etc.), the surface sizing effect of paper samples (sizing with TBPU, polyvinyl alcohol and TBPU/PVA system) were evaluated by infrared spectroscopy, X-ray photoelectron spectroscopy, water contact angle measurements and scanning electron microscopy. Some of the pure cotton pulp paper with surface sizing treatment was treated via adhering inks to paper by spraying, smearing and soaking. The bonding strength was tested by peel-off tape tests, soaking tests, and simulated washing tests. The results showed that the water contact angle of the sized-paper increased from 67.6° to 89.7°. The mechanical properties had been greatly improved after treatment and SEM, AFM and XPS analyses indicated an increase in surface roughness and the oxygen-containing polar groups (C[double bond, length as m-dash]O, C-OH, -NH-COO- and COOH) enhanced the fixation of ink particles on the fiber surface. These tests indicated that the novel composite system of TBPU/PVA could endow specialty paper with superb mechanical properties and more than 90% ink retention rate. All these advantages of this composite system may contribute to its wide application in the fields of papermaking and printing.