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"Clinical basic inspection technology" is one of the essential courses in the medical laboratory profession. Combining the characteristics of the discipline itself, the research and practice of the BOPPPS model based on the OBE concept in clinical basic laboratory experiment teaching are discussed, and the reform of in teaching objectives, teaching contents, and teaching design path is implemented. The "student-centered" teaching process is divided into six stages: before, during, and after class, and the teaching process is continuously improved to achieve the desired teaching effect. Results of the experiment teaching show that the model has improved students' active participation and developed their clinical thinking skills, and more than 95% of students are satisfied with this teaching model.
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Medicina , Estudantes , Humanos , Pensamento , Competência Clínica , LaboratóriosRESUMO
Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.
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Ependimoma , Adulto , Criança , Ependimoma/genética , Ependimoma/patologia , Ependimoma/cirurgia , Humanos , Mutação , RNA Mensageiro , Receptores Acoplados a Proteínas G/genética , Adulto JovemRESUMO
The simultaneous analysis of diversified biomarkers with high sensitivity and in a point-of-care (POC) manner is of great significance for facile and early cancer diagnosis. Herein, we develop a target amplification-assisted ratiometric fluorescence assay (TARFA) platform integrating the dual-amplification strategy and colorimetric readout technology for sensitive and specific detection of two malignancy-associated biomarkers. Meanwhile, the NIR-excited alkaline-earth sulfide nanodots (ASNDs) with an ultrasmall (<10 nm) diameter and tunable emission wavelength are employed to replace commonly UV/visible light-excited fluorescent labels to minimize background interference from the sample matrix. Unique advantages of the ASNDs, together with superiority of consecutive signal amplification of enzymatic target recycling (ETR) and hybridization chain reaction (HCR), realize the pg/mL-range detection limit in specifically recognizing the vascular endothelial growth factor (VEGF) and soluble interleukin-6 receptors (sIL-6R). The combination detection of the dual analyte exhibits an improved sensitivity for cancer diagnosis. The addition of the target biomarkers leads to an increasingly ratiometric RGB signal, and quantification based on the ratio-dependent signal is more reliable rather than measuring the absolute RGB signals. Moreover, perceptible color transformation makes the TARFA platform competent for visual analysis of the target analytes as convenient as reading the pH indicator strip, and hue-based image analysis also improves the method with fine precision by quantitatively identifying the visual color. This work provides a new kind of NIR-excited aptasensing platform with a low detection limit, high throughput, and great portability, which also highlights the potential of the ASNDs in biomolecular fluorescent labeling.
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Técnicas Biossensoriais , Neoplasias , Biomarcadores Tumorais , Corantes , Humanos , Limite de Detecção , Neoplasias/diagnóstico , Hibridização de Ácido Nucleico , Fator A de Crescimento do Endotélio VascularRESUMO
Seizures are a very common manifestation of autoimmune encephalitis (AE), ranging from 33% to 100% depending on the antigen, most often accompanied by other clinical features such as behavioral changes, movement disorders, memory deficits, autoimmune disturbances, and altered levels of consciousness. Unusual seizure frequency, resistance to antiepileptic treatment, and often, definitive response to immunotherapy emphasize the importance for neurologists to consider the probable etiology of immune disorders. Studies on pathogenic mechanisms of autoantibodies have improved the understanding of different pathophysiologies and clinical characteristics of different AE groups. In encephalitis with antibodies to neuronal extracellular antigens, autoantibodies play a direct role in disease pathogenesis. They have access to target antigens and can potentially alter the structure and function of antigens but induce relatively little neuronal death. Prompt immunotherapy is usually very effective, and long-term antiepileptic treatment may not be needed. In contrast, in encephalitis with antibodies against intracellular antigens, autoantibodies may not be directly pathogenic but serve as tumor markers. These autoantibodies cannot reach intracellular target antigens and are considered to result from a T-cell-mediated immune response against antigens released by apoptotic tumor cells, which contain nerve tissue or express neuronal proteins. Neuronal loss is frequently described and predominantly induced through cytotoxic T-cell mechanisms. They often exhibit an inadequate response to immunotherapy and require early tumor treatment. Long-term antiepileptic treatment is usually needed. In conclusion, each neural autoantibody can specifically precipitate seizures. Early proper management of these cases may help prevent neurological deterioration and manage the occurrence of seizures. Consequently, confirmation of the presence of neuronal autoantibodies is strongly recommended even in patients with confirmed AE, as they are not only essential in achieving a good outcome but also may provide evidence for underlying neoplasia.
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Doenças Autoimunes do Sistema Nervoso , Encefalite , Humanos , Anticonvulsivantes , Convulsões/etiologia , Convulsões/terapia , Autoanticorpos , Doenças Autoimunes do Sistema Nervoso/complicações , Doenças Autoimunes do Sistema Nervoso/terapiaRESUMO
Introduction Most CKD patients experience cardiovascular issues before commencing renal replacement therapy. An accuracy prediction model is helpful for physicians to assess cardiovascular prognoses in each individual, and to provide insights on how to outline individualized lines of therapy. Method This study enrolled 1138 participants with non-dialysis-dependent chronic kidney disease (NDD-CKD). Following a proportion of 7:3, patients were randomly assigned to training and validation cohorts. The relevant predictors of cardiovascular events were screened using the least absolute shrinkage and selection operator (Lasso) regression. The area under the receiver operating characteristic curve (AUC) and the calibration curve with 1000 bootstraps resamples were used to assess the nomogram's performance. Tests on the discrimination of the prediction model used Kaplan-Meier (KM) curve. Results After screening all the predictors by lasso regression, the five remaining ones (albumin, estimated glomerular filtration rate, etiology of CKD, cardiovascular disease history, and age) were used to construct the prediction model. The AUC of 1-year, 2-year, and 3-year was 0.81 (95% CI = 0.75-0.87), 0.80 (95% CI = 0.75-0.86), and 0.80 (95% CI = 0.73-0.86), respectively. The calibration curve and the KM curve showed good prediction features, and the external validation also had a good prediction performance (AUC of 1-, 2-, and 3-years were 0.77, 0.84, and 0.82, respectively). Conclusion We successfully developed a novel nomogram that has decent prediction performance and can be used for assessing the probability of cardiovascular events in patients with NDD-CKD, displaying valuable potential for clinical application.
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The endoplasmic reticulum (ER) is a multifunctional organelle, which is crucial for correct folding and assembly of secretory and transmembrane proteins. Perturbations of ER function can cause ER stress. ER stress can activate the unfolded protein response (UPR) to cope with the accumulation of misfolded proteins and protein toxicity. UPR is a coordination system that regulates transcription and translation, leading to the recovery of ER homeostasis or cell death. However, cells have an integrated signaling system to cope with ER stress, which helps cells to restore and balance their ER function. The main components of this system are ER-associated degradation (ERAD), autophagy, hypoxia signaling, and mitochondrial biogenesis. If the balance cannot be restored, the imbalance will lead to cell death or apoptosis, or even to a series of diseases. In this review, a series of activities to restore the homeostasis of cells during ER stress are discussed. KEY POINTS: ⢠Endoplasmic reticulum (ER) plays a key role in the biological process of cells. ⢠Perturbations of ER function can cause ER stress, including the ER overload response (EOR), sterol-regulated cascade reaction, and the UPR. ⢠Cells have an integrated signaling system (ERAD, autophagy, hypoxia signaling, and mitochondrial biogenesis) to cope with the adverse impact caused by ER stress.
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Fenômenos Biológicos , Estresse do Retículo Endoplasmático , Retículo Endoplasmático/metabolismo , Eucariotos , Resposta a Proteínas não DobradasRESUMO
BACKGROUND: To study the effects of z-guggulsterone on gastric cancer cell apoptosis and the mechanism related. MATERIALS AND METHODS: Human gastric tumor SGC-7901 cells and GES-1 normal epithelial cells were treated with z-guggulsterone (0-75 µM) for 24 h. MTT assay was applied to evaluate cell proliferation. Flow cytometry and Hoechst staining were used to assess cell apoptosis. Western blotting was applied to evaluate FXR, small heterodimer partner (SHP), Bcl-2, and Bax protein expression. ELISA was applied to gain the levels of active caspase-3 and the contents of TNF-α, TGF-ß1, and VEGF. RESULTS: The expression levels of FXR and SHP were higher in tumor cells than in normal epithelial cells. Inhibition of FXR signaling with z-guggulsterone dose-dependently inhibited SGC-7901 cell proliferation and promoted SGC-7901 cell apoptosis. Bcl-2 protein expression was significantly decreased, and active caspase-3 and Bax protein expression was increased in SGC-7901 cells incubated with z-guggulsterone. The content of TNF-α was significantly increased, and the contents of VEGF and TGF-ß1 were decreased in SGC-7901 cells incubated with z-guggulsterone. CONCLUSIONS: Inhibition of FXR signaling with z-guggulsterone induced anticancer effects in SGC-7901 cells by decreasing cell proliferation and promoting apoptosis. Z-guggulsterone induced cell apoptosis through the mitochondria-dependent pathway.
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Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Pregnenodionas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Biomarcadores , Linhagem Celular Tumoral , Citocinas/metabolismo , Citometria de Fluxo , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Neoplasias Gástricas/metabolismoRESUMO
Changes in the expression of HCN ion channels leading to changes in Ih function and neuronal excitability are considered to be possible mechanisms involved in epileptogenesis in kinds of human epilepsy. In previous animal studies of febrile seizures and temporal lobe epilepsy, changes in the expression of HCN1 and HCN2 channels at different time points and in different parts of the brain were not consistent, suggesting that transcriptional disorders involving HCNs play a crucial role in the epileptogenic process. Therefore, we aimed to assess the transcriptional regulation of HCN channels in Medial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) patients. This study included eight nonhippocampal sclerosis patients and 40 MTLE-HS patients. The mRNA expression of HCN channels was evaluated by qRT-PCR, while the protein expression was quantitatively analyzed by Western blotting. The subcellular localization of HCN channels in the hippocampus was explored by immunofluorescence. We demonstrated that the mRNA and protein expression of HCN1 and HCN2 are downregulated in controls compared to that in MTLE-HS patients. In the hippocampal CA1/CA4 subregion and GCL, in addition to a large decrease in neurons, the expression of HCN1 and HCN2 on neuronal cell membranes was also downregulated in MTLE-HS patients. These findings suggest that the expression of HCN channels are downregulated in MTLE-HS, which indicates that the decline in HCN channels in the hippocampus during chronic epilepsy in MTLE-HS patients leads to the downregulation of Ih current density and function, thereby reducing the inhibitory effect and increasing neuronal excitability and eventually causing disturbances in the electrical activity of neurons.
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Regulação para Baixo/fisiologia , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/metabolismo , Hipocampo/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Canais de Potássio/metabolismo , Adulto , Epilepsia do Lobo Temporal/patologia , Feminino , Hipocampo/patologia , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Masculino , Pessoa de Meia-Idade , Canais de Potássio/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , EscleroseRESUMO
BACKGROUND This study aimed to investigate the relationship between the expression of aspartate b-hydroxylase (ASPH) and the molecular mechanisms of ASPH-related genes in breast cancer (BC). MATERIAL AND METHODS ASPH expression was determined by immunohistochemistry and western blot analysis in samples of BC tissues and adjacent normal tissues. ASPH mRNA expression data and their clinical significance in BC were retrieved from the Oncomine and GEPIA datasets. Enrichment analysis of genes coexpressed with ASPH and annotation of potential pathways were performed with Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis. Hub genes were shown in an ASPH coexpression gene-interaction network. The expression of the hub genes associated with patient survival were analyzed to determine the role of ASPH in the progression of BC. RESULTS ASPH levels were overexpressed in BC and correlated with cancer type, lymph node involvement, and TNM stage. Conversely, ASPH levels did not correlate with patient age, invasive carcinoma types, or molecular subtypes. Enrichment analysis showed the involvement of multiple pathways, including lipid metabolism and oxidation-reduction processes. Six hub genes, PPARG, LEP, PLIN1, AGPAT2, CAV1, and PNPLA2, were related to ASPH expression and had functional roles in the occurrence and progression of BC. CONCLUSIONS ASPH may be involved in the development of BC and may have utility as a prognostic biomarker in BC. The coexpression of ASPH-associated genes may also be beneficial in improving BC prognosis.
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Neoplasias da Mama/genética , Proteínas de Ligação ao Cálcio/genética , Carcinoma Ductal de Mama/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Proteínas de Membrana/genética , Oxigenases de Função Mista/genética , Proteínas Musculares/genética , Aciltransferases/genética , Aciltransferases/metabolismo , Adulto , Idoso , Atlas como Assunto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Caveolina 1/genética , Caveolina 1/metabolismo , Conjuntos de Dados como Assunto , Progressão da Doença , Feminino , Ontologia Genética , Humanos , Leptina/genética , Leptina/metabolismo , Lipase/genética , Lipase/metabolismo , Proteínas de Membrana/metabolismo , Redes e Vias Metabólicas/genética , Pessoa de Meia-Idade , Oxigenases de Função Mista/metabolismo , Anotação de Sequência Molecular , Proteínas Musculares/metabolismo , Estadiamento de Neoplasias , PPAR gama/genética , PPAR gama/metabolismo , Perilipina-1/genética , Perilipina-1/metabolismo , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de SobrevidaRESUMO
OBJECTIVE: To analyze the clinical effect of nasal continuous positive airway pressure (CPAP) combined with pulmonary surfactant in the treatment of neonatal respiratory distress syndrome (NRDS). METHODS: Eighty-two NRDS patients who received treatment from August 2017 to June 2019 in our hospital were selected and divided into a control group and an observation group using random number table, 41 in each group. The control group was treated with CPAP, and the observation group was treated with pulmonary surfactant injection besides CPAP. The therapeutic effect, blood gas index, mechanical ventilation parameters and occurrence of complications were compared between the two groups. RESULTS: The total response rate of the observation group was 90.24%, which was significantly higher than 70.73% of the control group, and the difference had statistical significance (P<0.05). After treatment, the improvement of blood gas indexes of the observation group was better than that of the control group. The hospitalization time and duration of oxygen treatment of the observation group were shorter than those of the control group, and the hospitalization cost was higher than the control group (P<0.05). The difference of incidence of complications between the two groups was statistically significant (P<0.05). CONCLUSION: Endotracheal injection of pulmonary surfactant combined with CPAP in the treatment of NRDS can enhance the efficacy, promote the recovery of blood gas index, and reduce the parameters of mechanical ventilation and the incidence of complications, which is conducive to improving the respiratory function of the newborn. The therapy is worth application in the treatment of NRDS patients.
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Nasopharyngeal carcinoma (NPC) has a high metastatic clinicopathological feature. As a carcinogen factor, N,N'-dinitrosopiperazine (DNP) is involved in NPC metastasis, but its precise mechanism has not been fully elucidated. Herein, we showed that DNP promotes NPC metastasis through upregulating miR-149. DNP was found to decrease Plakophilin3 (PKP3) expression, further DNP-decreased PKP3 was verified to be through upregulating miR-149. We also found that DNP induced proliferation, adhesion, migration and invasion of NPC cell, which was inhibited by miR-149-inhibitor. DNP may promote NPC metastasis through miR-149-decreased PKP3 expression. Therefore, DNP-increased miR-149 expression may be an important factor of NPC high metastasis, and miR-149 may serve as a molecular target for anti-metastasis therapy of NPC.
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MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Metástase Neoplásica/genética , Nitrosaminas/toxicidade , Placofilinas/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/genética , Nitrosaminas/química , Piperazina/química , Placofilinas/metabolismo , Regulação para Cima , Adulto JovemRESUMO
The aim of this study is to explore the effect of timing of initiation of pulsed electromagnetic field (PEMF) therapy on bone mass, microarchitecture, and biomechanical properties, and to investigate receptor activator of NF-kB (RANK) expression in ovariectomized (OVX) rats. Sixty female Sprague-Dawley rats were randomly divided into two equal batches of three groups each (10 rats in each group). The first batch comprised of sham-operated (Sham-0 group), ovariectomized (OVX-0 group), and ovariectomized plus treated with PEMF starting from the day of OVX (Early PEMF group). The second batch comprised of sham-operated (Sham-12 group), ovariectomized (OVX-12 group), and ovariectomized plus treated with PEMF starting 12 weeks after OVX (Late PEMF group). Rats (whole body) in the early and late PEMF groups were exposed to PEMF (3.8 mT peak, 8 Hz pulse burst repetition rate). After 12 weeks of PEMF therapy, Early PEMF prevented OVX-induced deterioration in bone mineral density (BMD) and mechanical properties in lumbar vertebral body and femur, and deterioration in bone microarchitecture in lumbar vertebral body and proximal tibia. Late PEMF intervention only inhibited deterioration of BMD, bone microarchitecture, and mechanical properties in lumbar vertebral body. Both early and late PEMF therapy suppressed RANK protein expression in OVX rats without a concomitant effect on RANK mRNA expression. These results demonstrate that timing of initiation of PEMF therapy plays an important role in achieving optimal beneficial effects. The specific PEMF parameters may exert these favorable biological responses, at least partially, via inhibition of protein expression of RANK. Bioelectromagnetics. 38:456-465, 2017. © 2017 Wiley Periodicals, Inc.
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Magnetoterapia/métodos , Osteoporose/etiologia , Osteoporose/terapia , Ovariectomia/efeitos adversos , Animais , Fenômenos Biomecânicos/efeitos da radiação , Densidade Óssea/efeitos da radiação , Feminino , Fêmur/metabolismo , Fêmur/fisiopatologia , Fêmur/efeitos da radiação , Osteoporose/genética , Osteoporose/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Ativador de Fator Nuclear kappa-B/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Coluna Vertebral/metabolismo , Coluna Vertebral/fisiopatologia , Coluna Vertebral/efeitos da radiação , Fatores de Tempo , Microtomografia por Raio-XRESUMO
Ibandronate (IBN) and pulsed electromagnetic field (PEMF) have each shown positive effects for treating osteoporosis, but no study has evaluated the relative effects of these treatments combined. This study investigated the effects of IBN + PEMF on bone turnover, mineral density, microarchitecture, and biomechanical properties in an ovariectomized (OVX) rat model of osteoporosis. Fifty 3-month-old rats were randomly apportioned to receive a sham-operation (n = 10), or ovariectomy (n = 40). The latter group was equally divided as the model (OVX control) or to receive IBN, PEMF, or IBN + PEMF. Beginning the day after surgery, the IBN and IBN + PEMF groups received weekly subcutaneous IBN; the PEMF and IBN + PEMF groups were given daily PEMF during the same 12 weeks. After 12 weeks of treatments, biochemical parameters, bone mineral density (BMD), microarchitecture parameters, biomechanical properties, and some metabolic modulators that are involved in bone resorption were compared. The L5 lumbar vertebral body BMDs of the IBN, PEMF, and IBN + PEMF groups were 121.6%, 119.5%, and 139.6%; maximum loads were 111.4%, 112.7%, and 121.9%; and energy to failure was 130.8%, 129.2%, and 154.9% of the OVX model, respectively. The IBN + PEMF group had significantly lower levels of serum tartrate-resistant acid phosphatase 5b, and greater improvement in BMD, bone microarchitecture, and strength of the lumbar spine compared with monotherapy groups. Results showed that IBN + PEMF had a more favorable effect on the lumbar spine in this osteoporosis model than did either monotherapy. Bioelectromagnetics. 38:31-40, 2017. © 2016 Wiley Periodicals, Inc.
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Difosfonatos/farmacologia , Campos Eletromagnéticos , Magnetoterapia , Osteoporose/etiologia , Osteoporose/terapia , Ovariectomia/efeitos adversos , Animais , Fenômenos Biomecânicos , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/efeitos da radiação , Terapia Combinada , Difosfonatos/uso terapêutico , Feminino , Fêmur/efeitos dos fármacos , Fêmur/fisiopatologia , Fêmur/efeitos da radiação , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Ácido Ibandrônico , Osteoporose/metabolismo , Osteoporose/fisiopatologia , Osteoprotegerina/genética , Ligante RANK/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Coluna Vertebral/efeitos dos fármacos , Coluna Vertebral/fisiopatologia , Coluna Vertebral/efeitos da radiação , Fosfatase Ácida Resistente a Tartarato/sangue , Microtomografia por Raio-XRESUMO
BACKGROUND AND OBJECTIVE: Fatigue failure of the humeral stem is a severe long-term failure after shoulder arthroplasty, causing harm to patients and resulting in complex revision surgeries. However, there are few studies on humeral stem fatigue testing, and corresponding testing standards have not been established. Therefore, this study aims to investigate the fatigue performance of the humeral stem by establishing an efficient numerical simulation method. METHODS: Material properties are obtained by uniaxial tensile and fatigue tests. A parameterized static analysis program was written, and an automated fatigue numerical simulation platform was established using Abaqus, Fe-safe, and Isight in combination, enabling the establishment of a numerical simulation method for the fatigue performance of the humeral stem. RESULT: Standard testing conditions include an 8 mm diameter humeral stem, a 40-21B humeral head, an 8° tilt angle, and a 2 mm fillet radius. Further research found that the fatigue life of the humeral stem decreases with increasing patient weight, and patients should control their weight after surgery. CONCLUSIONS: The established automated fatigue numerical simulation platform avoids repetitive operations and efficiently completes large-scale calculations, guiding preoperative humeral stem selection and testing.
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The development of enzyme activity analysis methods is critical for precise and rapid assessments of enzyme activity levels within biological systems, facilitating a more profound comprehension of physiological functions and disease mechanisms. Alkaline phosphatase (ALP) participates in various physiological processes involving phosphate ester hydrolysis. Altered ALP activity levels are often indicative of different diseases, underscoring the necessity for accurate ALP activity determination in medical diagnostics. This study innovatively applies turbidity as a physical variable, proposing a turbidimetric sensor based on an enhanced ammonium molybdate reagent for phosphate analysis. By integrating this with the ALP substrate p-nitrophenyl phosphate, a turbidimetric sensor was devised and employed for ALP activity analysis. The proposed turbidimetric sensor demonstrated high sensitivity both for phosphate (0.18 µmol/L) and ALP activity (0.03 mU/mL) assay. In practical applications, this turbidimetric sensor has been effectively employed to detect ALP activity in mouse feces, showcasing its potential for auxiliary diagnosis of inflammatory bowel disease. Significantly, this novel turbidity-based approach offers not only swift and straightforward procedures but also remarkable portability and cost-efficiency. Requiring solely a handheld turbidimeter and eliminating the need for bulky instruments, this approach holds significant potential for point-of-care testing applications.
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Chorea-acanthocytosis (ChAc) is a rare, neurodegenerative disorder caused by mutations in the VPS13A gene. In this article, we report on a 32-year-old man diagnosed with ChAc, with involuntary movements of the mouth and trunk, drooling of the mouth, slurred speech, and abnormal vocalizations as the main clinical manifestations. Three weeks after implantation of globus pallidus internal (GPi)-deep brain stimulation (DBS), the patient's symptoms improved significantly. For example, articulation is clear, involuntary trunk movements and salivation have largely disappeared, and abnormal vocalizations have been significantly reduced. After 1 year of follow-up, the improvement in involuntary movement symptoms is essentially the same as before. As far as we know, we are the first to report the relief of involuntary vocalizations in a patient with GPi-DBS treatment, and that salivation and involuntary trunk movements have almost disappeared, and all other symptoms are significantly relieved, which is rare in previous cases. All of the above proves that the treatment of our case with DBS was very successful and that longer term follow-up is critical. We also hope that our case will provide new references and therapeutic ideas for the future treatment of patients with ChAc.
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Purpose: Lung cancer is a devastating disease, with brain metastasis being one of the most common distant metastases of lung adenocarcinoma. This study aimed to investigate the prognostic characteristics of individuals with brain metastases originating from invasive lung adenocarcinoma of distinct pathological subtypes, providing a reference for the management of these patients. Methods: Clinical data from 156 patients with lung adenocarcinoma-derived brain metastases were collected, including age, sex, smoking status, Karnofsky Performance Status scores, pathological subtype, lymph node metastasis, tumor site, treatment mode, T stage, and N stage. Patients were classified into two groups (highly differentiated and poorly differentiated) based on their pathological subtypes. Propensity score matching was used to control for confounding factors. The prognostic value of pathological subtypes was assessed using Kaplan-Meier analysis and Cox proportional hazards regression modeling. Results: Kaplan-Meier analysis indicated that patients in the moderately to highly differentiated group had better prognoses. Multivariate analysis revealed that being in the poorly differentiated group was a risk factor for poorer prognosis. Thoracic tumor radiation therapy, chemotherapy, and surgery positively influenced the time interval between lung cancer diagnosis and brain metastasis. Conclusions: The pathological subtypes of lung adenocarcinoma-derived brain metastases are associated with patient prognosis. Patients in the poorly differentiated group have worse prognoses compared to those in the moderately to highly differentiated group. Therefore, patients in the poorly differentiated group may require more frequent follow-ups and aggressive treatment.
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The ankle joint, which connects the lower limbs and the sole of the foot, is prone to sprain during walking and sports, which leads to ankle arthritis. Supratroleolar osteotomy is an ankle preserving operation for the treatment of ankle arthritis, in which the osteotomy is an important fixing and supporting part. In order to avoid stress shielding effect as much as possible, the osteotomy block is designed as a porous structure. In this study, the osteotomy block was designed based on three-period minimal surface, and the designed structure was manufactured by 3D printing. The mechanical properties of different structures were studied by mechanical test and finite element simulation. In mechanical tests, the Gyroid structure showed a progressive failure mechanism from bottom to bottom, while the Diamond structure showed a shear failure zone at 45° Angle, which was not conducive to energy absorption and was more prone to brittle fracture than the Gyroid structure. Therefore, the Gyroid structure is valuable for further research in the development of porous osteotomy.
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Análise de Elementos Finitos , Osteotomia , Impressão Tridimensional , Osteotomia/métodos , Humanos , Pé/cirurgia , Articulação do Tornozelo/cirurgiaRESUMO
Charge trap materials that can store carriers efficiently and controllably are desired for memory applications. 2D materials are promising for highly compacted and reliable memory mainly due to their ease of constructing atomically uniform interfaces, however, remain unexplored as being charge trap media. Here it is discovered that 2D semiconducting PbI2 is an excellent charge trap material for nonvolatile memory and artificial synapses. It is simple to construct PbI2 -based charge trap devices since no complicated synthesis or additional defect manufacturing are required. As a demonstration, MoS2 /PbI2 device exhibits a large memory window of 120 V, fast write speed of 5 µs, high on-off ratio around 106 , multilevel memory of over 8 distinct states, high reliability with endurance up to 104 cycles and retention over 1.2 × 104 s. It is envisioned that PbI2 with ionic activity caused by the natively formed iodine vacancies is unique to combine with unlimited 2D materials for versatile van der Waals devices with high-integration and multifunctionality.
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The oldest known highly conserved modification of RNA, N4-acetylcytidine, is widely distributed from archaea to eukaryotes and acts as a posttranscriptional chemical modification of RNA, contributing to the correct reading of specific nucleotide sequences during translation, stabilising mRNA and improving transcription efficiency. Yeast Kre33 and human NAT10, the only known authors of ac4C, modify tRNA with the help of the Tan1/THUMPD1 adapter to stabilise its structure. Currently, the mRNA for N4-acetylcytidine (ac4C), catalysed by NAT10 (N-acetyltransferase 10), has been implicated in a variety of human diseases, particularly cancer. This article reviews advances in the study of ac4C modification of RNA and the ac4C-related gene NAT10 in normal physiological cell development, cancer, premature disease and viral infection and discusses its therapeutic promise and future research challenges.