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Tandem mass spectrometry (MS/MS) shows great promise in the research of metabolomics, providing an abundance of information on compounds. Due to the rapid development of mass spectrometric techniques, a large number of MS/MS spectral data sets have been produced from different experimental environments. The massive data brings great challenges into the spectral analysis including compound identification and spectra clustering. The core challenge in MS/MS spectral analysis is how to describe a spectrum more quantitatively and effectively. Recently, emerging deep-learning-based technologies have brought new opportunities to handle this challenge in which high-quality descriptions of MS/MS spectra can be obtained. In this study, we propose a novel contrastive learning-based method for the representation of MS/MS spectra, called CLERMS, which is based on transformer architecture. Specifically, an optimized model architecture equipped with a sinusoidal embedder and a novel loss function composed of InfoNCE loss and MSE loss has been proposed for the attainment of good embedding from the peak information and the metadata. We evaluate our method using a GNPS data set, and the results demonstrate that the learned embedding can not only distinguish spectra from different compounds but also reveal the structural similarity between them. Additionally, the comparison between our method and other methods on the performance of compound identification and spectra clustering shows that our method can achieve significantly better results.
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In complex industrial processes such as sintering, key quality variables are difficult to measure online and it takes a long time to obtain quality variables through offline testing. Moreover, due to the limitations of testing frequency, quality variable data are too scarce. To solve this problem, this paper proposes a sintering quality prediction model based on multi-source data fusion and introduces video data collected by industrial cameras. Firstly, video information of the end of the sintering machine is obtained via the keyframe extraction method based on the feature height. Secondly, using the shallow layer feature construction method based on sinter stratification and the deep layer feature extraction method based on ResNet, the feature information of the image is extracted at multi-scale of the deep layer and the shallow layer. Then, combining industrial time series data, a sintering quality soft sensor model based on multi-source data fusion is proposed, which makes full use of multi-source data from various sources. The experimental results show that the method effectively improves the accuracy of the sinter quality prediction model.
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Ischemia reperfusion injury(IRI) is an important factor affecting the early function and long-term survival of transplanted kidney. Single cell RNA sequencing (scRNA-seq) is a powerful method for investigating cell-specific transcriptome changes in the kidney. This study aimed to identify the significant cell type and potential biomarkers in IRI. First, we downloaded the IRI related scRNA dataset GSE139506 from the GEO database. Then, classification of cell type was characterized and proximal tubule cell (PTC) was identified as a significant cell type. The functional enrichment analysis indicated that PTC were related to kidney function and is significant in the ferroptosis of IRI. Analyses of three-dimensional structure and iron binding substructure of protein was carried out basing on SWISS-MODEL database. Finally, we constructed the murine model with IRI and verify the higher expression of PHYH in IRI by PCR, Western blot (WB) and Immunohistochemistry (IHC) experiments. In conclusion, this study provided novel insights on the cell-type-specific expression gene biomarker in IRI pathogenesis.
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Biología Computacional , Daño por Reperfusión , Animales , Biomarcadores/metabolismo , Riñón/metabolismo , Ratones , Daño por Reperfusión/patología , TranscriptomaRESUMEN
Objective To assess the diagnostic value of dual energy pulmonary perfusion imaging(DEPI)for pulmonary embolism.Methods The clinical data of 87 patients with suspected pulmonary embolism who had received DEPI between August 2017 and July 2018 in Jiaxing Second Hospital were retrospectively analyzed.With the findings of CT pulmonary angiography(CTPA)as the reference standard and with patients and pulmonary lobes as evaluation units,respectively,a diagnostic test was performed to calculate the diagnostic coincidence rate,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,positive likelihood ratio,negative likelihood ratio,and Kappa coefficient value for the diagnosis of DEPI and CTPA.Results The coincidence rate,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,positive likelihood ratio,and negative likelihood ratio were 85.06%,88.41%,72.22%,92.42%,61.90%,0.61,3.18,and 0.16,respectively,when applying the patients as evaluation units.When the pulmonary lobes were invoked as evaluation units,the above-mentioned indexes were 89.57%,76.80%,96.82%,93.20%,88.02%,0.74,24.15,and 0.24,respectively.The diagnostic results of DEPI and CTPA had a good and excellent consistency,respectively(Kappa value=0.571,0.765).Conclusions DEPI has high accuracy,sensitivity,and specificity in the detection of pulmonary embolism.The combination of DEPI with CTPA can simultaneously obtain the anatomical structure and functional information images,greatly improving the diagnostic accuracy for pulmonary embolism.Thus,it can be used as the preferred examination for patients with clinically suspected pulmonary embolism.
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Imagen de Perfusión , Embolia Pulmonar , Tomografía Computarizada por Rayos X , Pruebas Diagnósticas de Rutina , Humanos , Imagen de Perfusión/instrumentación , Imagen de Perfusión/normas , Embolia Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/normasRESUMEN
Following the development of synthetic aperture radar (SAR), SAR images have become increasingly common. Many researchers have conducted large studies on geolocation models, but little work has been conducted on the available models for the geometric correction of SAR images of different terrain. To address the terrain issue, four different models were compared and are described in this paper: a rigorous range-doppler (RD) model, a rational polynomial coefficients (RPC) model, a revised polynomial (PM) model and an elevation derivation (EDM) model. The results of comparisons of the geolocation capabilities of the models show that a proper model for a SAR image of a specific terrain can be determined. A solution table was obtained to recommend a suitable model for users. Three TerraSAR-X images, two ALOS-PALSAR images and one Envisat-ASAR image were used for the experiment, including flat terrain and mountain terrain SAR images as well as two large area images. Geolocation accuracies of the models for different terrain SAR images were computed and analyzed. The comparisons of the models show that the RD model was accurate but was the least efficient; therefore, it is not the ideal model for real-time implementations. The RPC model is sufficiently accurate and efficient for the geometric correction of SAR images of flat terrain, whose precision is below 0.001 pixels. The EDM model is suitable for the geolocation of SAR images of mountainous terrain, and its precision can reach 0.007 pixels. Although the PM model does not produce results as precise as the other models, its efficiency is excellent and its potential should not be underestimated. With respect to the geometric correction of SAR images over large areas, the EDM model has higher accuracy under one pixel, whereas the RPC model consumes one third of the time of the EDM model.
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Radiation resistance is a major problem preventing successful treatment. Therefore, identifying sensitizers is vitally important for radiotherapy success. Epigenetic events such as DNA methylation have been proposed to mediate the sensitivity of tumor therapy. In this study, we investigated the influence of demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on the radiosensitivity of human osteosarcoma cell lines. 5-Aza-CdR was capable of sensitizing three osteosarcoma cells to irradiation in a time-dependent manner, with the maximum effect attained by 48 h. Pretreatment with 5-Aza-CdR synchronized cells in G2/M phase of the cell cycle and enhanced irradiation-induced apoptosis compared with irradiation alone in SaOS2, HOS, and U2OS cells. Moreover, 5-Aza-CdR restored mRNA expressions of 14-3-3σ, CHK2, and DAPK-1 in the three cells, accompanied with demethylation of their promoters. These findings demonstrate that demethylation with 5-Aza-CdR increases radiosensitivity in some osteosarcoma cells through arresting cells at G2/M phase and increasing apoptosis, which is partly mediated by upregulation of 14-3-3σ, CHK2, and DAPK-1 genes, suggesting that 5-Aza-CdR may be a potential radiosensitizer to improve the therapy effect in osteosarcoma.
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Antimetabolitos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Azacitidina/análogos & derivados , Neoplasias Óseas/radioterapia , División Celular/efectos de los fármacos , Fase G2/efectos de los fármacos , Osteosarcoma/radioterapia , Tolerancia a Radiación , Proteínas 14-3-3/genética , Azacitidina/farmacología , Biomarcadores de Tumor/genética , Neoplasias Óseas/patología , Línea Celular Tumoral , Quinasa de Punto de Control 2/genética , Proteínas Quinasas Asociadas a Muerte Celular/genética , Decitabina , Exorribonucleasas/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Osteosarcoma/patologíaRESUMEN
OBJECTIVE: To assess the survival and prognostic significance of various demographic and radiographic parameters for conversion into total hip arthroplasty after treatment with a modified porous tantalum implant technology for early and intermediate stages of osteonecrosis of the femoral head (ONFH). METHODS: This study included 45 patients (59 hips) with Steinberg Stage I-IV A ONFH undergoing progressively core decompression, impaction bone grafting of 5 mm-composite bone filling material and inserting of a porous tantalum implant. Weight-bearing was forbidden within the first 3 months after implants. RESULTS: A total of 57 hips (44 patients) were available during a mean follow-up period of 44.8 (11-62) months. Their mean age was 43 (21-70) years. The mean Harris hip score significantly improved from 59.93 ± 2.80 preoperative to 77.84 ± 2.95 at the last follow-up (P < 0.001). Overall, 11 hips (19.30%) were converted into total hip arthroplasty. The overall survival rate was 72.49% at 60 months postoperatively. The Cox proportional hazard model revealed that bone marrow edema was an independent prognostic factor related with a conversion into total hip arthroplasty. CONCLUSION: Higher survival rates may be obtained from modified tantalum implant technology for early and intermediate stages of ONFH. And prognosis was poor for patients of ONFH with bone marrow edema.
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Artroplastia de Reemplazo de Cadera , Osteonecrosis , Prótesis e Implantes , Trasplante Óseo , Descompresión Quirúrgica , Humanos , Porosidad , Periodo Posoperatorio , Pronóstico , TantalioRESUMEN
CD320, which is a transmembrane protein responsible for facilitating the absorption of vitamin B12, plays a key role in this process. However, the relationships between CD320 and immune cell infiltration levels remain unclear, with limited studies investigating the diagnostic and prognostic significance of CD320 in hepatocellular carcinoma. We used various databases, including the TIMER, GEPIA, UALCAN and TCGA databases to investigate the expression levels of CD320 in hepatocellular carcinoma. Subsequently, we analyzed the prognosis of hepatocellular carcinoma patients with different expression levels of CD320. Furthermore, we also performed Western blot, immunohistochemistry, and immunofluorescence analyses to validate the results of the database analysis. Finally, the functions of CD320 in hepatocellular carcinoma were also confirmed via relevant cell experiments and angiogenesis assays. We found that CD320 expression was significantly upregulated in tumor vascular endothelial cells. Moreover, the knockdown of CD320 led to a reduction in angiogenesis in endothelial cells. Increased expression of CD320 was also correlated with a poor prognosis in patients with hepatocellular carcinoma, which suggested that CD320 may be a potential prognostic marker. Finally, TIMER analysis demonstrated that the infiltration of six immune cell types was significantly associated with high expression levels of CD320 in hepatocellular carcinoma. Herein, we demonstrated that CD320 may play an important role in angiogenesis in hepatocellular carcinoma. These findings suggested that CD320 may be a potential clinical prognostic marker and immunotherapy target for hepatocellular carcinoma.
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Growth-regulating factors (GRFs) are transcription factors that play a pivotal role in plant growth and development. This study identifies 12 Solanum tuberosum GRF transcription factors (StGRFs) and analyzes their physicochemical properties, phylogenetic relationships, gene structures and gene expression patterns using bioinformatics. The StGRFs exhibit a length range of 266 to 599 amino acids, with a molecular weight of 26.02 to 64.52 kDa. The majority of StGRFs possess three introns. The promoter regions contain a plethora of cis-acting elements related to plant growth and development, as well as environmental stress and hormone response. All the members of the StGRF family contain conserved WRC and QLQ domains, with the sequences of these two conserved domain modules exhibiting high levels of conservation. Transcriptomic data indicates that StGRFs play a significant role in the growth and development of stamens, roots, young tubers, and other tissues or organs in potatoes. Furthermore, a few StGRFs exhibit differential expression patterns in response to Phytophthora infestans, chemical elicitors, heat, salt, and drought stresses, as well as multiple hormone treatments. The results of the expression analysis indicate that StGRF1, StGRF2, StGRF5, StGRF7, StGRF10 and StGRF12 are involved in the process of tuber sprouting, while StGRF4 and StGRF9 may play a role in tuber dormancy. These findings offer valuable insights that can be used to investigate the roles of StGRFs during potato tuber dormancy and sprouting.
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BACKGROUND AND OBJECTIVES: Treating metastatic spinal tumors poses a significant challenge because there are currently no universally applied guidelines for managing spinal metastases. This study aims to propose a new decision framework for the 12-point epidural spinal cord compression grading system to treat patients with metastatic spinal tumors and investigate its clinical effectiveness in a multicenter analysis. METHODS: This study analyzed 940 patients with metastatic spinal tumors between December 2017 and March 2023. The study provided the clinical evidence for the systemic conditions, effectiveness of systemic treatment, neurology, and oncology (SENO) decision framework among spine metastases. The SENO decision framework was launched in January 2021 in our hospitals, classifying patients into 2 groups: The non-SENO group (n = 489) consisted of patients treated between December 2017 and January 2021, while the SENO group (n = 451) comprised patients treated from January 2021 to March 2023. RESULTS: Patients in the SENO group were more likely to receive minimally invasive surgery (67.85% vs 58.69%) and less chance of receiving spinal cord circular decompression surgery (14.41% vs 24.74%) than patients in the non-SENO group ( P < .001). Furthermore, patients in the SENO group experienced fewer perioperative complications (9.09% vs 15.34%, P = .004), incurred lower hospitalization costs ( P < .001), had shorter length of hospitalization ( P < .001), and received systematic treatments for tumors earlier ( P < .001). As a result, patients in the SENO group (329.00 [95% CI: 292.06-365.94] days) demonstrated significantly improved survival outcomes compared with those in the non-SENO group (279.00 [95% CI: 256.91-301.09], days) ( P < .001). At 3 months postdischarge, patients in the SENO group reported greater improvements in their quality of life, encompassing physical, social, emotional, and functional well-being, when compared with patients in the non-SENO group. CONCLUSION: The SENO decision framework is a promising approach for treating patients with metastatic spinal tumors.
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Neurología , Compresión de la Médula Espinal , Neoplasias de la Columna Vertebral , Humanos , Neoplasias de la Columna Vertebral/secundario , Calidad de Vida , Cuidados Posteriores , Alta del Paciente , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/cirugía , Compresión de la Médula Espinal/patología , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Background: Stomach and esophageal cancer exhibit high morbidity and mortality rate in China, resulting in substantial disease burdens. It is imperative to identify the temporal trends of stomach and esophageal cancer from 1990 to 2019 and project future trends until 2030, which can provide valuable information for planning effective management and prevention strategies. Methods: We collected and analysed data from the Global Burden of Disease (GBD) between 1990 and 2019, including incidence, mortality, disability-adjusted life years (DALYs), age-standardised incidence rate (ASIR), mortality rate (ASMR) and DALYs rate. We also calculated and reported the proportion of mortality and DALYs attributable to risk factors by sex in China and different regions. The Bayesian age-period-cohort model was applied to project future trends until 2030. Results: The new cases, deaths and DALYs of stomach and esophageal cancer increased from 1990 to 2019. However, the ASIR, ASMR and age-standardised DALYs rates for stomach and esophageal cancer all decreased during the same period. These changes may be related to risks, such as smoking and diet. Furthermore, we utilised the projection model to estimate that the ASIR and ASMR of stomach and esophageal cancer among females will likely follow steady downward trends, while the ASMR of stomach cancer among males is expected to exhibit a significant decline. However, the ASIR of stomach and esophageal cancer and the ASMR of esophageal cancer among males are projected to display slight upward trends until 2030. Conclusions: The analysis of stomach and esophageal cancer trends in China from 1990 to 2030 reveals a general decline. However, it is crucial to acknowledge the persistent high burden of both cancers in the country. Adopting healthy lifestyle practices, including the reduction of tobacco and alcohol intake, avoidance of moldy foods and increased consumption of fresh fruits and vegetables can contribute to mitigating the risk of stomach and esophageal cancer. Significantly, the formulation and implementation of well-founded and efficacious public health policies are imperative for alleviating the disease burden in China.
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Neoplasias Esofágicas , Neoplasias Gástricas , Femenino , Masculino , Humanos , Carga Global de Enfermedades , Neoplasias Esofágicas/epidemiología , Neoplasias Gástricas/epidemiología , Teorema de Bayes , China/epidemiologíaRESUMEN
Myocardial fibrosis is a pathological, physiological change that results from alterations, such as inflammation and metabolic dysfunction, after myocardial infarction (MI). Excessive fibrosis can cause cardiac dysfunction, ventricular remodeling, and heart failure. Caffeic acid (CA), a natural polyphenolic acid in various foods, has cardioprotective effects. This study aimed to explore whether CA exerts a cardioprotective effect to inhibit myocardial fibrosis post-MI and elucidate the underlying mechanisms. Histological observations indicated that CA ameliorated ventricular remodeling induced by left anterior descending coronary artery ligation in MI mice and partially restored cardiac function. CA selectively targeted transforming growth factor-ß receptor 1 (TGFBR1) and inhibited TGFBR1-Smad2/3 signaling, reducing collagen deposition in the infarcted area of MI mice hearts. Furthermore, cell counting (CCK-8) assay, 5-ethynyl-2'-deoxyuridine assay, and western blotting revealed that CA dose-dependently decreased the proliferation, collagen synthesis, and activation of the TGFBR1-Smad2/3 pathway in primary cardiac fibroblasts (CFs) stimulated by TGF-ß1 in vitro. Notably, TGFBR1 overexpression in CFs partially counteracted the inhibitory effects of CA. These findings suggest that CA effectively mitigates myocardial fibrosis and enhances cardiac function following MI and that this effect may be associated with the direct targeting of TGFBR1 by CA.
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Ácidos Cafeicos , Fibrosis , Ratones Endogámicos C57BL , Infarto del Miocardio , Miocardio , Receptor Tipo I de Factor de Crecimiento Transformador beta , Transducción de Señal , Animales , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Infarto del Miocardio/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Transducción de Señal/efectos de los fármacos , Masculino , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/uso terapéutico , Miocardio/patología , Miocardio/metabolismo , Ratones , Remodelación Ventricular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Colágeno/metabolismo , Proteína Smad2/metabolismo , Células CultivadasRESUMEN
BACKGROUND: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. PURPOSE: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. METHODS: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. RESULTS: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. CONCLUSION: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.
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BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.
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Medicamentos Herbarios Chinos , Ferroptosis , Factor 2 Relacionado con NF-E2 , Sepsis , Animales , Masculino , Ratones , Ratas , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Ferroptosis/efectos de los fármacos , Cardiopatías/tratamiento farmacológico , Cardiopatías/etiología , Ratones Endogámicos C57BL , Miocardio/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Farmacología en Red , Factor 2 Relacionado con NF-E2/metabolismo , Ratas Sprague-Dawley , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Transducción de Señal/efectos de los fármacosRESUMEN
The objective of this study was to explore the O(6)-methylguanine-DNA methyltransferase (MGMT) gene methylation status and its protein expression, as well as the effects of demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on MGMT gene expression and its resistance to alkylating agents, and to elucidate MGMT expression mechanism and significance in osteosarcoma. The human osteosarcoma cell lines Saos-2 and MG-63 were collected and treated with 5-Aza-CdR for 6 days. The cells not treated with 5-Aza-CdR were set as a negative control. The genomic DNA was extracted from the Saos-2 and MG-63 cells using methylation-specific PCR to detect the promoter CpG island methylation status of the MGMT gene. Cell sensitivity to alkylating agents before and after drug administration was detected by the MTT method. The variation in MGMT gene mRNA and protein was detected by reverse transcription PCR (RT-PCR) and Western blotting. The MGMT promoter gene of normal Saos-2 cells was methylated, with reduced MGMT mRNA and protein expression; the MGMT mRNA and protein expression of Saos-2 cells treated with 5-Aza-CdR was obviously enhanced, and its sensitivity to alkylating agents was reversed. Meanwhile, with promoter CpG island unmethylation of the MGMT gene, MGMT protein was expressed in the normal MG-63 cells and the MG-63 cells treated with 5-Aza-CdR, and both showed resistance to alkylating agents. The methylation status of the MGMT gene promoter in human osteosarcoma cells reflected the cells' ability to induce MGMT protein expression and can be used as a molecular marker to project the sensitivity of cancer tissues to alkylating agent drugs.
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Metilación de ADN , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , O(6)-Metilguanina-ADN Metiltransferasa/genética , Osteosarcoma/metabolismo , Alquilantes/farmacología , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Islas de CpG , Ensayos de Selección de Medicamentos Antitumorales/métodos , Humanos , Regiones Promotoras Genéticas , Factores de TiempoRESUMEN
OBJECTIVE: To evaluate the efficacies of core decompression and implantation of concentrated autologous bone marrow containing mononuclear cells (BMMCs) with porous hydroxylapatite composite in the treatment of osteonecrosis of the femoral head. METHODS: A total of 35 patients with 57 osteonecrosis hips with ARCO stage I, stage II and stage IIIA disease were treated by BMMCs with a porous hydroxylapatite composite. The mean age at surgery was 39.4 (26-58) years and the mean period of follow-up 28 (12-40) months. In the control group, cell-free porous hydroxylapatite composite was implanted into 17 patients (27 hips) with osteonecrosis of the femoral head and the outcomes were compared. RESULTS: At the last follow-up, postoperative Harris hip scores significantly increased in both groups (P < 0.0001). The magnitude of increase was significantly greater in the BMMCs group compared with the control group (28.3% ± 0.9% vs 18.4% ± 1.7%, P < 0.01). Postoperative visual analog scale (VAS) scores significantly decreased in both groups (P < 0.01). The magnitude of decrease was significantly greater in the BMMCs group compared with the control group (-70.2% ± 2.1% vs -51.7% ± 2.9%, P < 0.001). The clinical success rate was significantly higher in the BMMCs group compared with the control group (75.4% vs 37.0%, P < 0.01). The radiological success rates were similar between the BMMCs and control groups (59.6% vs 40.7%, P = 0.1046). CONCLUSION: The combined regimen of core decompression and implantation of concentrated autologous BMMCs with porous hydroxylapatite composite appears to confer benefits in the treatment of in stages I-IIIA osteonecrosis of the femoral head.
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Trasplante de Médula Ósea , Descompresión Quirúrgica , Durapatita/uso terapéutico , Necrosis de la Cabeza Femoral/cirugía , Leucocitos Mononucleares/trasplante , Adulto , Artroplastia de Reemplazo de Cadera , Femenino , Prótesis de Cadera , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND CONTEXT: The assessment of epidural spinal cord compression (ESCC) plays a crucial role in clinical decision-making, yet the current grading system lacks reliability and requires improvements. PURPOSE: The study aims to develop a reliable grading system for evaluating ESCC and to investigate its association with the neurological status of patients. STUDY DESIGN/SETTING: A prospective cohort study. PATIENT SAMPLE: A total of 330 patients with metastatic spinal disease were included in the study. OUTCOME MEASURES: The main outcome was the neurological status evaluated using the American Spinal Injury Association (ASIA) scale. METHODS: We proposed a novel grading system, called the 12-point ESCC grading system, to evaluate ESCC based on findings from spinal magnetic resonance imaging (MRI). This new grading system consists of 12 grades, ranging from Grade 0 to 3, with higher grades indicating more severe ESCC. The detailed information about the sagittal image of the spine and the severity of spinal cord swelling was considered in this new grading system. The Spearman correlation analysis and logistic regression analysis were employed to investigate the correlation between the previous 6-point grading system and ASIA, as well as between the new 12-point ESCC grading system and ASIA. The prediction effectiveness was evaluated using the area under curve (AUC) analysis. RESULTS: Patients with higher grades in the 12-point ESCC grading system exhibited a higher likelihood of experiencing a worse neurological condition. Specifically, patients with grades 2a to 2d and 3a to 3d according to the new 12-point ESCC grading system were significantly associated with more complete paralysis (p<.001) compared with patients with grade 0. The Spearman correlation coefficient was 0.729 between the previous 6-point ESCC grading system and ASIS and 0.750 between the new 12-point ESCC grading system and ASIS. When categorizing ASIS into complete paralysis and other neurological statuses, the 6-point ESCC score yielded an AUC of 0.820, which increased to 0.860 with the new 12-point ESCC grading system. Furthermore, when ASIS was divided into normal and abnormal neurological statuses, the AUC increased from 0.889 to 0.906. Additionally, spinal cord swelling was significantly associated with more complete paralysis (p<.001) and abnormal neurological status (p<.001) based on the new 12-point ESCC grading system. CONCLUSIONS: The new 12-point ESCC grading system provides more detailed information and further improves the prediction effectiveness for evaluating neurological status compared with the previous 6-point ESCC grading system. In the new 12-point ESCC grading system, higher grades or the presence of spinal cord swelling are indicative of a worse neurological condition.
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Compresión de la Médula Espinal , Neoplasias de la Columna Vertebral , Humanos , Compresión de la Médula Espinal/diagnóstico por imagen , Compresión de la Médula Espinal/etiología , Estudios Prospectivos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Parálisis , Neoplasias de la Columna Vertebral/secundarioRESUMEN
Neurofibromatosis type 1 (NF1) is a dominant hereditary disease characterized by the mutation of the NF1 gene, affecting 1/3000 individuals worldwide. Most NF1 patients are predisposed to benign peripheral nerve sheath tumors (PNSTs), including cutaneous neurofibromas (CNFs) and plexiform neurofibromas (PNFs). However, 5%-10% of PNFs will ultimately develop into malignant peripheral nerve sheath tumors (MPNSTs), which have a poor prognosis. Early and reliable differentiation of benign and malignant tumors in NF1 patients is of great necessity. Pathological evaluation is the "gold standard" for a definite diagnosis, but the invasive nature of the biopsy procedure restricts it from applying as a screening tool during the decades-long follow-up of these patients. Non-invasive image-based diagnostic methods such as CT and MRI are often considered essential screening tools for multiple types of tumors. For NF1 patients' lifelong regular follow-ups, these radiological methods are currently used for tumor evaluation. However, no consensus was established on screening the malignant transformation of benign PNSTs. Moreover, novel technologies like radiogenomics and PET-MRI have not been well evaluated and fully adopted for NF1 patients. This review summarizes current studies of different imaging methods for differentiating benign and malignant tumors in NF1. Meanwhile, we discussed the prospects of the usage of new tools such as radiogenomics and PET-MRI to distinguish MPNST from benign PNSTs more precisely. Summarizing these findings will help clarify the directions of future studies in this area and ultimately contribute to the radiology images-based clinical screening of MPNST in NF1 patients and finally improve the overall survival rates of these patients.
RESUMEN
Background: Renal transplantation is a very effective treatment for renal failure patients following kidney transplant. However, the clinical benefit is restricted by the high incidence of organ rejection. Therefore, there exists a wealth of literature regarding the mechanism of renal transplant rejection, including a large library of expression data. In recent years, research has shown the immune microenvironment to play an important role in renal transplant rejection. Nephrology web analysis tools currently exist to address chronic nephropathy, renal tumors and children's kidneys, but no such tool exists that analyses the impact of immune microenvironment in renal transplantation rejection. Methods: To fill this gap, we have developed a web page analysis tool called Comprehensive Analysis of Renal Allograft Rerejction in Immune Microenvironment (CARARIME). Results: CARARIME analyzes the gene expression and immune microenvironment of published renal transplant rejection cohorts, including differential analysis (gene expression and immune cells), prognosis analysis (logistics regression, Univariable Cox Regression and Kaplan Meier), correlation analysis, enrichment analysis (GSEA and ssGSEA), and ROC analysis. Conclusions: Using this tool, researchers can easily analyze the immune microenvironment in the context of renal transplant rejection by clicking on the available options, helping to further the development of approaches to renal transplant rejection in the immune microenvironment field. CARARIME can be found in http://www.cararime.com.
Asunto(s)
Trasplante de Riñón , Insuficiencia Renal Crónica , Niño , Humanos , Trasplante de Riñón/efectos adversos , Riñón , Trasplante Homólogo , Complicaciones Posoperatorias , AloinjertosRESUMEN
To study the inhibitory effect of Hepatocyte growth factor (HGF) on the responsive hyperplasia of damaged astrocytes in vitro. We prepared damaged model of astrocytes to simulate the responsive hyperplasia of damaged astrocytes in vivo by culturing astrocytes in vitro; After the first day of Ad-HGF transfection, astrocytes were scratched, then after the first, the third, and the fifth day of scratch, we detect the expression amount of astrocytes specific glial fibrillary acidic protein (GFAP) and the ratio of S-phase cells with flow cytometry, both of which can reflect the proliferation status of damaged astrocytes; After HGF was added in scratched astrocytes, the activity of SPK and MAPK (P42/44) were detected by autoradiography and immunoblotting test; After adding different concentrations of HGF protein in astrocytes cultured in different serum concentrations and adding diverse concentrations of HGF protein, SPK and SPK inhibitor DMS in scratched astrocytes, we detect cell proliferation with 3H-TDR incorporation. The first day after Ad-HGF transfected astrocytes were scratched, the amount of GFAP secreted by astrocytes were decreased significantly (P < 0.05), and the cells in S phase were declined obviously. HGF has bidirectional regulation on SPK of scratched astrocytes: increases the SPK activity when HGF in low dose, while inhibits when in high dose. In addition, DMS can block the signal passage; HGF had no effects on MAPK (P42/44) of damaged astrocytes cells. In conclusion, after the transfection of Ad-HGF, it can inhibit the responsive hyperplasia of damaged astrocytes by the means of blocking SPK passage.