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Purpose: Small dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design. Methods: We identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis. Results: In univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117-1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106-1.597, P = 0.002). Conclusions: Findings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C.
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LDL-Colesterol , Estudo de Associação Genômica Ampla , AVC Isquêmico , Análise da Randomização Mendeliana , Humanos , AVC Isquêmico/genética , AVC Isquêmico/epidemiologia , AVC Isquêmico/sangue , LDL-Colesterol/sangue , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Feminino , Fatores de Risco , MasculinoRESUMO
OBJECTIVE: To examine the application of a novel pedagogical approach multidimensional supportive psychological intervention (MSPI) in the clinical practice teaching of andrological nursing care. METHODS: Using the Hamilton Depression Scale (HAMD), we assessed the psychology of 100 nursing interns about to enter clinical practice in the Department of Andrology from December 2021 to December 2022. We equally randomized the subjects into an experimental and a control group, the former receiving MSPI and the latter trained on the conventional teaching model without any psychological support intervention. RESULTS: Compared with the baseline, the HAMD scores were significantly decreased in the experimental group after intervention (12.4±2.1 vs 8.9±2.4, P<0.01), but increased in the controls (13.1±1.8 vs 14.7±1.9, P<0.01); the skill scores dramatically increased in the experimental group (82.6±4.7 vs 91.2±2.4, P<0.01), but decreased in the control group after intervention (81.0±3.5 vs 80.4±2.7, P = 0.28). CONCLUSION: MSPI can significantly enhance the learning enthusiasm of nursing students in a short period, reduce their psychological stress and improve teaching outcomes. This approach, combining psychology with teaching, can also strengthen the mental resilience of nursing students and better confront them with future professional challenges.
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Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Ensino , Intervenção Psicossocial/métodosRESUMO
The global incidence of non-tuberculous mycobacteria (NTM) infections is on the rise. This study systematically searched several databases, including PubMed, Web of Science, Google Scholar, and two Chinese libraries (Chinese National Knowledge Infrastructure and Wanfang) to identify relevant published between 2013 and 2023 related to the isolation of NTM in clinical specimens from various countries and provinces of China. Furthermore, a comprehensive literature review was conducted in PubMed and Google Scholar to identify randomized clinical trials, meta-analyses, systematic reviews, and observational studies that evaluated the diagnostic accuracy and impact of laboratory detection methods on clinical outcomes. This review presented the most recent epidemiological data and species distributions of NTM isolates in several countries and provinces of China. Moreover, it provided insights into laboratory bacteriological detection, including the identified strains, advantages and disadvantages, recent advancements, and the commercial Mycobacterium identification kits available for clinical use. This review aimed to aid healthcare workers in understanding this aspect, enhance the standards of clinical diagnosis and treatment, and enlighten them on the existing gaps and future research priorities.
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BACKGROUND: Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients. METHODS: This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients. RESULTS: RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7. CONCLUSION: Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.
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Psoríase , Proteínas Plasmáticas de Ligação ao Retinol , Humanos , Psoríase/tratamento farmacológico , Psoríase/sangue , Psoríase/imunologia , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Biomarcadores/sangue , Índice de Gravidade de Doença , Curva ROCRESUMO
Background: Challenges such as poor drug selectivity, non-target reactivity, and the development of drug resistance continue to pose significant obstacles in the clinical application of cancer therapeutic drugs. To overcome the limitations of drug resistance in chemotherapy, a viable treatment strategy involves designing multifunctional nano-platforms that exploit the unique physicochemical properties of tumor microenvironment (TME). Methods: Herein, layer-by-layer nanoparticles with polyporous CuS as delivery vehicles, loaded with a sonosensitizer (tetra-(4-aminophenyl) porphyrin, TAPP) and sequentially functionalized with pH-responsive CaCO3, targeting group hyaluronic acid (HA) were designed and synthesized for synergistic treatment involving chemodynamic therapy (CDT), sonodynamic therapy (SDT), photothermal therapy (PTT), and calcium overload. Upon cleavage in an acidic environment, CaCO3 nanoparticles released TAPP and Ca2+, with TAPP generating 1O2 under ultrasound trigger. Exposed CuS produced highly cytotoxic ·OH in response to H2O2 and also exhibited a strong PTT effect. Results: CuS@TAPP-CaCO3/HA (CTCH) delivered an enhanced ability to release more Ca2+ under acidic conditions with a pH value of 6.5, which in situ causes damage to HeLa mitochondria. In vitro and in vivo experiments both demonstrated that mitochondrial dysfunction greatly amplified the damage caused by reactive oxygen species (ROS) to tumor, which strongly confirms the synergistic effect between calcium overload and reactive oxygen therapy. Conclusion: Collectively, the development of CTCH presents a novel therapeutic strategy for tumor treatment by effectively responding to the acidic TME, thus holding significant clinical implications.
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Carbonato de Cálcio , Cálcio , Nanopartículas , Microambiente Tumoral , Humanos , Animais , Nanopartículas/química , Cálcio/química , Carbonato de Cálcio/química , Carbonato de Cálcio/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Células HeLa , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Ácido Hialurônico/química , Porfirinas/química , Porfirinas/farmacologia , Porfirinas/farmacocinética , Porfirinas/administração & dosagem , Terapia Fototérmica/métodos , Concentração de Íons de Hidrogênio , Terapia por Ultrassom/métodos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas em MulticamadasRESUMO
Fe3O4 is barely taken into account as an electrocatalyst for oxygen reduction reaction (ORR), an important reaction for metal-air batteries and fuel cells, due to its sluggish catalytic kinetics and poor electron conductivity. Herein, how strain engineering can be employed to regulate the local electronic structure of Fe3O4 for high ORR activity is reported. Compressively strained Fe3O4 shells with 2.0% shortened FeâO bond are gained on the Fe/Fe4N cores as a result of lattice mismatch at the interface. A downshift of the d-band center occurs for compressed Fe3O4, leading to weakened chemisorption energy of oxygenated intermediates, and lower reaction overpotential. The compressed Fe3O4 exhibits greatly enhanced electrocatalytic ORR activity with a kinetic current density of 27 times higher than that of pristine one at 0.80 V (vs reversible hydrogen electrode), as well as potential application in zinc-air batteries. The findings provide a new strategy for tuning electronic structures and improving the catalytic activity of other metal catalysts.
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Purpose: Medical imaging-based machine learning (ML) for computer-aided diagnosis of in vivo lesions consists of two basic components or modules of (i) feature extraction from non-invasively acquired medical images and (ii) feature classification for prediction of malignancy of lesions detected or localized in the medical images. This study investigates their individual performances for diagnosis of low-dose computed tomography (CT) screening-detected lesions of pulmonary nodules and colorectal polyps. Approach: Three feature extraction methods were investigated. One uses the mathematical descriptor of gray-level co-occurrence image texture measure to extract the Haralick image texture features (HFs). One uses the convolutional neural network (CNN) architecture to extract deep learning (DL) image abstractive features (DFs). The third one uses the interactions between lesion tissues and X-ray energy of CT to extract tissue-energy specific characteristic features (TFs). All the above three categories of extracted features were classified by the random forest (RF) classifier with comparison to the DL-CNN method, which reads the images, extracts the DFs, and classifies the DFs in an end-to-end manner. The ML diagnosis of lesions or prediction of lesion malignancy was measured by the area under the receiver operating characteristic curve (AUC). Three lesion image datasets were used. The lesions' tissue pathological reports were used as the learning labels. Results: Experiments on the three datasets produced AUC values of 0.724 to 0.878 for the HFs, 0.652 to 0.965 for the DFs, and 0.985 to 0.996 for the TFs, compared to the DL-CNN of 0.694 to 0.964. These experimental outcomes indicate that the RF classifier performed comparably to the DL-CNN classification module and the extraction of tissue-energy specific characteristic features dramatically improved AUC value. Conclusions: The feature extraction module is more important than the feature classification module. Extraction of tissue-energy specific characteristic features is more important than extraction of image abstractive and characteristic features.
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Depression and Parkinson's disease share pathogenetic characteristics, meaning that they can impact each other and exacerbate their respective progression. From a pathogenetic perspective, depression can develop into Parkinson's disease and is a precursor symptom of Parkinson's disease; Parkinson's disease is also often accompanied by depression. From a pharmacological perspective, the use of antidepressants increases the risk of developing Parkinson's disease, and therapeutic medications for Parkinson's disease can exacerbate symptoms of depression. Therefore, identifying how Parkinson's disease and depression impact each other in their development is key to formulating preventive measures and targeted treatment. One commonality in the pathogenesis of depression and Parkinson's disease are alterations in the gut microbiota, with mechanisms interacting in neural, immune inflammatory, and neuroendocrine pathways. This paper reviews the role of gut microbiota in the pathogenesis of depression and Parkinson's disease; conducts a study of the relationship between both conditions and medication; and suggests that dysregulated gut microbiota may be a key factor in explaining the relationship between Parkinson's disease and depression. Finally, on the basis of these findings, this article hopes to provide suggestions that new ideas for the prevention and treatment of depression and Parkinson's disease.
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Depressão , Microbioma Gastrointestinal , Doença de Parkinson , Doença de Parkinson/microbiologia , Humanos , Microbioma Gastrointestinal/fisiologia , Depressão/microbiologia , Antidepressivos/uso terapêutico , Antidepressivos/farmacologia , Eixo Encéfalo-Intestino/fisiologia , AnimaisRESUMO
BACKGROUND: The correlation between the triglyceride-glucose index (TyG) and the prognosis of ischemic stroke has been well established. This study aims to assess the influence of the TyG index on the clinical outcomes of critically ill individuals suffering from intracerebral hemorrhage (ICH). METHODS: Patients diagnosed with ICH were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Various statistical methods, including restricted cubic spline (RCS) regression, multivariable logistic regression, subgroup analysis, and sensitivity analysis, were employed to examine the relationship between the TyG index and the primary outcomes of ICH. RESULTS: A total of 791 patients from MIMIC-IV and 1,113 ones from eICU-CRD were analyzed. In MIMIC-IV, the in-hospital and ICU mortality rates were 14% and 10%, respectively, while in eICU-CRD, they were 16% and 8%. Results of the RCS regression revealed a consistent linear relationship between the TyG index and the risk of in-hospital and ICU mortality across the entire study population of both databases. Logistic regression analysis revealed a significant positive association between the TyG index and the likelihood of in-hospital and ICU death among ICH patients in both databases. Subgroup and sensitivity analysis further revealed an interaction between patients' age and the TyG index in relation to in-hospital and ICU mortality among ICH patients. Notably, for patients over 60 years old, the association between the TyG index and the risk of in-hospital and ICU mortality was more pronounced compared to the overall study population in both MIMIC-IV and eICU-CRD databases, suggesting a synergistic effect between old age (over 60 years) and the TyG index on the in-hospital and ICU mortality of patients with ICH. CONCLUSIONS: This study established a positive correlation between the TyG index and the risk of in-hospital and ICU mortality in patients over 60 years who diagnosed with ICH, suggesting that the TyG index holds promise as an indicator for risk stratification in this patient population.
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Glicemia , Hemorragia Cerebral , Estado Terminal , Mortalidade Hospitalar , Triglicerídeos , Humanos , Masculino , Feminino , Idoso , Estado Terminal/mortalidade , Mortalidade Hospitalar/tendências , Hemorragia Cerebral/sangue , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/diagnóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Triglicerídeos/sangue , Glicemia/análise , Glicemia/metabolismo , Unidades de Terapia Intensiva/tendências , Idoso de 80 Anos ou mais , Prognóstico , Valor Preditivo dos TestesRESUMO
OBJECTIVES: To investigate the clinicopathological characteristics and prognosis of patients with primary sarcoma of the uterine cervix. METHODS: We identified all patients with primary cervical sarcomas treated at our institution from 2002 to 2020 and analyzed the clinicopathological characteristics and prognosis. RESULTS: 34 patients were identified, 7 (20.6%) patients had leiomyosarcoma, 6 (17.6%) had carcinosarcoma, 5 (14.7%) had Ewing sarcoma, 4 (11.8%) had rhabdomyosarcoma, 4 (11.8%) had undifferentiated sarcoma, 2 (5.9%) had adenosarcoma, 2 (5.9%) had endometrial stromal sarcoma, 1 (2.9%) had dermatofibrosarcoma protuberans, 1 (2.9%) had alveolar soft tissue sarcoma and 2 (5.9%) had sarcoma not otherwise specified. The median age of the whole patients was 43.5 years (range, 13-63). The median age of patients with Ewing sarcoma or rhabdomyosarcoma was 22 years (range, 13-39) and 17 years (range, 13-36 years), respectively. The distribution by stage was: stage I in 21 (61.8%) patients, stage II in 4 (11.8%), stage III in 6 (17.6%) and stage IV in 3 (8.8%). Overall, 30 patients (88.2%) received surgical treatment. The median follow-up was 33.3 months (range 3.6-187.3 months). 11 patients died within 2 years after diagnosis, most of them were patients with carcinosarcoma or undifferentiated sarcoma (45.5%, 5/11). In the entire cohort, 2- and 5-year OS were 67.2% and 56.9%, respectively. 5-year OS was 25.0% for undifferentiated sarcoma, 50.0% for rhabdomyosarcoma, 50.0% for carcinosarcoma, 53.3% for Ewing sarcoma, 57.1% for leiomyosarcoma. CONCLUSION: Cervical sarcomas are rare neoplasms with multiple histological subtypes and follow an aggressive course. Prognosis may be associated with tumor histology and stage.
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Carcinossarcoma , Leiomiossarcoma , Rabdomiossarcoma , Sarcoma de Ewing , Sarcoma , Neoplasias do Colo do Útero , Neoplasias Uterinas , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Leiomiossarcoma/patologia , Sarcoma de Ewing/cirurgia , Neoplasias do Colo do Útero/cirurgia , Neoplasias Uterinas/diagnóstico , Sarcoma/cirurgia , Sarcoma/diagnóstico , Carcinossarcoma/patologia , Rabdomiossarcoma/cirurgia , PrognósticoRESUMO
Mural paintings, as the main components of painted cultural relics, have essential research value and historical significance. Due to their age, murals are easily damaged. Obtaining intact sketches is the first step in the conservation and restoration of murals. However, sketch extraction often suffers from problems such as loss of details, too thick lines, or noise interference. To overcome these problems, a mural sketch extraction method based on image enhancement and edge detection is proposed. The experiments utilize Contrast Limited Adaptive Histogram Equalization (CLAHE) and bilateral filtering to enhance the mural images. This can enhance the edge features while suppressing the noise generated by over-enhancement. Finally, we extract the refined sketch of the mural using the Laplacian Edge with fine noise remover (FNR). The experimental results show that this method is superior to other methods in terms of visual effect and related indexes, and it can extract the complex line regions of the mural.
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BACKGROUND: Idiopathic granulomatous mastitis (IGM) results in notable clinical symptoms and breast deformity. This study aimed to evaluate the clinical feasibility of microwave ablation (MWA) for the treatment of IGM through comparison with surgical excision. METHODS: From June 2016 to December 2020, a total of 234 consecutive patients admitted to the hospital were retrospectively included in this study. IGM was pathologically confirmed via breast biopsy in all included patients. These patients were divided into the MWA group (n = 91) and surgical group (n = 143) based on the type of treatment. Patients in both groups received oral prednisone prior to intervention. The clinical remission rate, recurrence rate, operative pain, complications, and BREAST Q score were compared between the two groups. RESULTS: There were 340 lesions in the MWA group, and 201 lesions in the surgical group were ultimately included. Significant differences in the complete remission rate (96.7% vs. 86.7%, p = 0.020), recurrence rate (3.3% vs. 13.3%, p = 0.020), operation time (48.7±14.6 min vs. 68.1±36.4 min, p < 0.001), postoperative pain (p < 0.001) and postoperative BREAST Q score (p < 0.001) were observed between the MWA and surgical groups. CONCLUSIONS: Microwave ablation is feasible for the treatment of IGM, due to its high curative rate and low recurrence rate. Because of the minimal invasiveness of MWA and sufficient preservation of the gland and contour of the breast, patients are more satisfied with the appearance of the breast. Therefore, for patients with complex conditions requiring surgery, MWA is a good alternative treatment.
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Mastite Granulomatosa , Feminino , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Mastite Granulomatosa/cirurgia , Micro-Ondas/uso terapêutico , Ultrassonografia de Intervenção , Imunoglobulina M/uso terapêuticoRESUMO
Endometrioid endometrial carcinoma (EEC) stands as a prevalent gynecologic malignancy in developed regions. However, predicting relapse cases remains challenging, necessitating the identification of a novel biomarker for EEC relapse. The assessment of tumor mutational burden (TMB) is pivotal for immunotherapy in EEC patients. However, both whole-exome sequencing (WES) and targeted sequencing encountered application-related difficulties. In light of this, standardized and simplified techniques for TMB measurement are imperative. In this study, we employed WES on 25 EEC patients (12 relapsed cases and 13 non-relapsed cases) who accepted hysterectomy surgery (CHCAMS cohort). We additionally obtained a total of 391 tumor samples with clinicopathological features from TCGA website to broaden the study cohort. In the CHCAMS cohort, the TTN mutant group showed shorter progression-free survival (p < 0.001) and overall survival (p < 0.001) than TTN wild-type group. Additionally, we discovered that the number of TTN mutations per sample was significantly linked with TMB-WES in CHCAMS cohort and TCGA cohort (p < 0.05). And the number of TTN mutations per sample in POLE mutant group was greater than in the POLE wild-type group (p < 0.0001). In conclusion, TTN mutation may serve as a biomarker for EEC prognosis. TTN mutation is also associated with WES-TMB, and could be a simplified TMB measurement technique.
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Carcinoma Endometrioide , Conectina , Neoplasias do Endométrio , Mutação , Humanos , Feminino , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/mortalidade , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/mortalidade , Pessoa de Meia-Idade , Conectina/genética , Biomarcadores Tumorais/genética , Idoso , Prognóstico , Sequenciamento do Exoma/métodos , AdultoRESUMO
INTRODUCTION: Breast cancer-related bone metastasis can lead to skeletal-related events (SREs), which decrease patient quality of life. Inhibition of osteoclastogenesis is a key treatment for SREs; however, the availability of clinical drugs remains limited, and all existing ones disrupt physiological bone formation, while exhibiting no effect on patient survival time. OBJECTIVES: This study aimed to identify a novel osteoclast inhibitor for the treatment of breast cancer-induced SREs. METHODS: The MDA-MB-231 breast cancer cell-induced bone loss model was used to investigate the therapeutic effects of erianin in vivo. Then, we evaluated the inhibitory effects of erianin on osteoclastogenesis and signalling in bone marrow-derived macrophages (BMMs) induced by conditioned medium from MDA-MB-231 breast cancer cells (231 CM) and receptor activator of nuclear factor-κB ligand (RANKL) in vitro. Next, a Cellular Thermal Shift Assay and siRNA-mediate knockdown were performed, to investigate the target of erianin during osteoclast formation. The effects of erianin on human osteoclastogenesis were evaluated using CD14+ monocytes obtained from patients with breast cancer. RESULTS: Erianin effectively improved breast cancer cells-induced bone destruction at doses of 2 and 20 mg/kg/day in vivo, while suppressing osteoclastogenesis and the upregulation of SRC-NFATc1, INTEGRIN ß3-MMP9 signals induced by 231 CM and RANKL in vitro. Furthermore, erianin interacted with NFATc1 but not SRC, and Nfatc1 knockdown eliminated the inhibitory effects of erianin on osteoclastogenesis. Notably, lower expression of NFATc1 positively correlated with longer survival in patients with cancer and a high risk of bone metastasis. We further revealed that 62.5-250 nM erianin suppresses NFATc1 and excessive osteoclastogenesis in CD14+ monocytes from patients with breast cancer. CONCLUSION: Erianin acts as an NFATc1 inhibitor that attenuates breast cancer-induced osteoclastogenesis and bone destruction.
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BACKGROUND: The role of stress hyperglycemia ratio (SHR) on the prognosis of spontaneous intracerebral hemorrhage (ICH) in patients with different diabetic status has not been elucidated. This study aimed to evaluate the prognostic value of SHR and admission blood glucose (ABG) for the short- and long-term mortality in diabetic and nondiabetic populations with ICH. METHOD: Participants with ICH were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC-IV). The primary outcome was all-cause 30-day and 1-year mortality. The association of SHR and ABG with the primary outcomes in diabetic and nondiabetic cohorts were assessed by Cox proportional hazard regression. RESULTS: Overall, 1029 patients with a median age of 71.09 (IQR: 60.05-81.97) were included. Among them, 548 (53%) individuals were male, and 95 (19%) as well as 323 (31%) ones experienced the 30-day and 1-year mortality, respectively. After adjusting for confounding variables, individuals in quintile 5 of SHR had significantly higher risk of the 30-day and 1-year mortality than those in quintile 1 in the whole cohort (30-day mortality: HR 3.33, 95%CI 2.01-5.51; 1-year mortality: HR 2.09, 95% CI 1.46-3.00) and in nondiabetic patients (30-day mortality: HR 4.55, 95%CI 2.33-8.88; 1-year mortality: HR 3.06, 95%CI 1.93-4.86), but no significant difference was observed in diabetic patients. Similar results were observed for ABG as a categorical variable. As continuous variable, SHR was independently correlated with the 30-day and 1-year mortality in both of the diabetic and nondiabetic cohorts (30-day mortality: HR 2.63, 95%CI 1.50-4.60. 1-year mortality: HR 2.12, 95%CI 1.33-3.39), but this correlation was only observed in nondiabetic cohort for ABG (HR 1.00, 95%CI 0.99-1.01 for both of the 30-day and 1-year mortality). Moreover, compared with ABG, SHR can better improve the C-statistics of the original models regarding the 30-day and 1-year outcomes, especially in patients with diabetes (p < 0.001 in all models). CONCLUSION: SHR might be a more useful and reliable marker than ABG for prognostic prediction and risk stratification in critically ill patients with ICH, especially in those with diabetes.
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OBJECTIVE: To describe the features of ETV6::ABL1 AML as well as the clinical treatment and outcomes. METHODS: Clinical data were collected from three patients diagnosed with ETV6::ABL1 AML at Hebei Yanda Lu Daopei Hospital and Beijing Lu Daopei Hospital. Their clinical and laboratory features were analyzed, and the treatment process and outcomes were described. Ten reported cases of ETV6::ABL1 AML from the literature were also included for analysis. RESULTS: The median age of the patients was 34 years, and 2 patients were male. No patient had a history of blood disorders before diagnosis. After relapse, they were referred to our hospital, where the ETV6::ABL1 gene was detected. Unfortunately, Patient 1 died rapidly after leukemia relapse due to severe infection. Patients 2 and 3 received salvage therapy with a dasatinib-containing regimen, followed by allo-HSCT, and are currently alive and disease-free. CONCLUSION: ETV6::ABL1 is a rare but recurrent genetic aberration in AML, and the combined use of fluorescence in situ hybridization and PCR can better identify this fusion gene. Patients carrying ETV6::ABL1 have a high relapse rate and a poor prognosis. TKIs are a reasonable treatment option for this group, and allo-HSCT may be curative.
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Variante 6 da Proteína do Fator de Translocação ETS , Leucemia Mieloide Aguda , Proteínas de Fusão Oncogênica , Proteínas Proto-Oncogênicas c-ets , Proteínas Repressoras , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-abl/genética , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Repressoras/genética , Resultado do TratamentoRESUMO
L-threo-p-nitrophenylserine (component 2) is an important intermediate during synthesis of chloramphenicol. However, its biosynthesis is limited by enzyme activity and stereoselectivity. In this study, we achieved a breakthrough in the high-efficiency production of 2 by employing engineered Chitiniphilus shinanonensis L-threonine transaldolase (ChLTTA) in conjunction with a by-product elimination system within a one-pot reaction. Notably, a novel visual stepwise high-throughput screening method was developed for the directed evolution of ChLTTA, leveraging its characteristic color. The engineered mutant F70D/F59A (Mu6 variant) emerged as a star performer, exhibiting a remarkable 2.6-fold increase in catalytic efficiency over the wild-type ChLTTA, coupled with an outstanding 91.5 % diastereoisomer excess (de). Molecular dynamics (MD) simulations unraveled the mechanism responsible for the enhanced catalytic performance observed in the Mu6 variant. Meanwhile, the Mu6 variant was coupled with Saccharomyces cerevisiae ethanol dehydrogenase (ScADH) and Candida boidinii formate dehydrogenase (CbFDH) to create a high-efficiency cascade system (E.coli/pRSF-Mu6-ScADH-CbFDH). Under optimized conditions, this cascade system demonstrated unparalleled performance, yielding 201.5 mM of 2 with an impressive conversion of 95.9 % and a de value of 94.5 %. This achievement represents the highest reported yield to date. This study offers a novel insight into the sustainable and efficient production of chloramphenicol intermediate.
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Treonina , Transaldolase , Cloranfenicol , Escherichia coli/genéticaRESUMO
A serious game titled "Crossing the Jungle" was developed in this study to train children's inhibition skills using the Stroop task. The effects of inhibitory control on children were tested by a pre-test, post-test, and one-month follow-up test. In the control groups, children were asked to play a commercial game instead. In experiment 1, 48 participants chose either the training or control game voluntarily, whereas, in experiment 2, 44 participants were randomly assigned to either group. In both experiments, children exposed to the serious game demonstrated training effects from the Stroop spatial task and near-transfer effects from the Flanker task. However, transferring effects were not produced by the Go/No-go task. As a result, although the serious game "Crossing the Jungle" does not improve response inhibition, children aged 9 to 12 who play it may benefit from improved interference inhibition abilities. This provides evidence for the mutual independence of interference inhibition and response inhibition in children at this stage.
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Sonodynamic therapy (SDT), a tumor treatment modality with high tissue penetration and low side effects, is able to selectively kill tumor cells by producing cytotoxic reactive oxygen species (ROS) with ultrasound-triggered sonosensitizers. N-type inorganic semiconductor TiO2 has low ROS quantum yields under ultrasound irradiation and inadequate anti-tumor activity. Herein, by using atomic layer deposition (ALD) to create a heterojunction between porous TiO2 and CoOx, the sonodynamic therapy efficiency of TiO2 can be improved. Compared to conventional techniques, the high controllability of ALD allows for the delicate loading of CoOx nanoparticles into TiO2 pores, resulting in the precise tuning of the interfaces and energy band structures and ultimately optimal SDT properties. In addition, CoOx exhibits a cascade of H2O2âO2â·O2 - in response to the tumor microenvironment, which not only mitigates hypoxia during the SDT process, but also contributes to the effect of chemodynamic therapy (CDT). Correspondingly, the synergistic CDT/SDT treatment is successful in inhibiting tumor growth. Thus, ALD provides new avenues for catalytic tumor therapy and other pharmaceutical applications.
Assuntos
Peróxido de Hidrogênio , Nanopartículas , Humanos , Espécies Reativas de Oxigênio , Catálise , HipóxiaRESUMO
PURPOSE: To explore the association between preoperative WBC count and the long-term survival outcomes and clinical outcomes in different stage patients who underwent surgical resection for colorectal cancer (CRC). PATIENTS AND METHODS: A cohort of 8121 Chinese patients who underwent surgical resection for CRC from January 1, 2008 to December 31, 2014 were enrolled as part of the retrospective cohort were retrospectively analyzed. Based on that the preoperative WBC optimal cut-off value was 7*109/L (7,000/µL), the high preoperative WBC group and the low preoperative WBC group was defined. Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce confounding. The impact of preoperative WBC count on overall survival (OS) and disease-free survival (DFS) was investigated using the Kaplan-Meier method and Univariate Cox proportional hazards models in different stage subgroup respectively. RESULTS: After IPTW, the clinical characters in the high preoperative WBC count group and the low preoperative WBC count group were balanced. Kaplan-Meier analysis showed that the 5-year OS rate were significantly lower in the high preoperative WBC count group overall, in stage II and IV. The 5-year DFS rate was significantly lower overall, in stage II and III in the high preoperative WBC count group. High preoperative WBC count was associated with poorer OS overall in stage II and stage IV. CONCLUSIONS: This study suggests that preoperative WBC count is an independent risk factor for survival in patients undergoing colorectal surgery and may need to consider the stage of cancer when applied to predict long-term adverse outcome prognosis.