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BACKGROUND: Minimal residual disease (MRD) is an important prognostic factor for survival in adults with acute leukemia. The role of pretransplantation MRD status in myelodysplastic syndrome with excess blasts (MDS-EB) is unknown. This study retrospectively analyzed the relationship between pretransplantation MRD status and long-term survival. MATERIALS AND METHODS: Patients with MDS-EB who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from March 5, 2005, to November 8, 2020, were included. The relationship between pretransplantation MRD status and long-term survival was analyzed using univariate and multivariate logistic regression models. RESULTS: Of 220 patients with MDS-EB who underwent allo-HSCT, 198 were eligible for inclusion in this multicenter, retrospective cohort study. Complete remission was attained in 121 (61.1%) patients, and 103 patients underwent detection of MRD pretransplantation, with 67 patients being MRD-positive and 36 patients being MRD-negative. The median follow-up time was 16 months, the median age was 41 years (6-65 years), and 58% of the patients were men. The 3-year disease-free survival (DFS) and overall survival (OS) probabilities for all patients were 70.1% and 72.9%, respectively. For patients in complete remission, the 3-year DFS and OS probabilities were 72.2% and 74.8%, respectively. Further analysis found that the 3-year DFS rates of MRD-negative and MRD-positive patients were 85.6% and 66.5% (p = .045), respectively, whereas the 3-year OS rates were 91.3% and 66.4% (p = .035), respectively. Univariate and multivariate analyses showed that poor pretransplantation MRD clearance was an independent prognostic risk factor for DFS and OS. CONCLUSION: Poor pretransplantation MRD clearance is an independent prognostic risk factor for long-term survival after allo-HSCT for patients with MDS-EB. PLAIN LANGUAGE SUMMARY: Poor minimal residual disease clearance pretransplanation is an independent prognostic risk factor for long-term survival after allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome with excess blasts.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adulto , Masculino , Humanos , Feminino , Prognóstico , Estudos Retrospectivos , Neoplasia Residual/diagnóstico , Síndromes Mielodisplásicas/terapia , Fatores de RiscoRESUMO
BACKGROUND: Nursing experts regularly visited the community to deliver safety education on the prevention of unintentional injuries in children to the parents of children aged 0-6 years and to pregnant women in a maternity school. This was undertaken to explore the effects of the measure on preventing unintentional injuries in children in Chizhou, China. METHODS: Using the convenience sampling method, the guardians(it means mother in this study)of children were investigated. The nursing experts visited communities in which the number of nursing experts is declining. Data on unintentional injuries in children in the previous year were collected retrospectively. RESULTS: After the nursing experts delivered safety education to the community, the scores of the questionnaire on unintentional injury prevention knowledge completed by children's guardians increased significantly (p < 0.01). Among the children whose guardians completed the questionnaire, there were 157 cases of unintentional injury in 2020 and 103 cases in 2021 (p < 0.05). The types of unintentional injuries included scratches, falls, sharp object injuries, swallowing of foreign bodies, burns and traffic accidents; there was no statistical difference (p > 0.05). However, there were significant differences in terms of gender ratio and location (p < 0.05). CONCLUSION: In conjunction with the maternity school for pregnant women and the vaccination programme, nursing experts delivered safety education regarding unintentional injuries in children; this may have promoted safety and protection awareness in the children's guardians and reduced unintentional injuries.
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Lesões Acidentais , Queimaduras , Ferimentos e Lesões , Gravidez , Criança , Humanos , Feminino , Estudos Retrospectivos , Acidentes de Trânsito , Participação da Comunidade , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/etiologia , Ferimentos e Lesões/prevenção & controleRESUMO
CONTEXT: Danggui Buxue Decoction (DBD), a traditional Chinese medicine formula, has the potential to enhance the antitumor effect of gemcitabine in non-small cell lung cancer (NSCLC) treatment by increasing gemcitabine's active metabolites. However, whether gemcitabine affects the pharmacokinetics of DBD's major components remains unclear. OBJECTIVE: This study evaluates the herb-drug interaction between DBD's major components and gemcitabine and validates the underlying pharmacokinetic mechanism. MATERIALS AND METHODS: The pharmacokinetics of 3.6 g/kg DBD with and without a single-dose administration of 50 mg/kg gemcitabine was investigated in Sprague-Dawley rats. The effects of gemcitabine on intestinal permeability, hepatic microsomal enzymes in rat tissues, and CYP3A overexpressing HepG2 cells were determined using western blot analysis. RESULTS: The combination of gemcitabine significantly altered the pharmacokinetic profiles of DBD's major components in rats. The Cmax and AUC of calycosin-7-O-ß-d-glucoside notably increased through sodium-glucose transporter 1 (SGLT-1) expression promotion. The AUC of ligustilide and ferulic acid was also significantly elevated with the elimination half-life (t1/2) prolonged by 2.4-fold and 7.8-fold, respectively, by down-regulating hepatic CYP3A, tight junction proteins zonula occludens-1 (ZO-1) and occludin expression. DISCUSSION AND CONCLUSIONS: Gemcitabine could modulate the pharmacokinetics of DBD's major components by increasing intestinal permeability, enhancing transporter expression, and down-regulating CYP3A. These findings provide critical information for clinical research on DBD as an adjuvant for NSCLC with gemcitabine and help make potential dosage adjustments more scientifically and rationally.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Ratos , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Gencitabina , Citocromo P-450 CYP3A , Regulação para Baixo , Ratos Sprague-Dawley , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Post-weaning diarrhea due to enterotoxigenic Escherichia coli (ETEC) is a common disease of piglets and causes great economic loss for the swine industry. Over the past few decades, decreasing effectiveness of conventional antibiotics has caused serious problems because of the growing emergence of multidrug-resistant (MDR) pathogens. Various studies have indicated that antimicrobial peptides (AMPs) have potential to serve as an alternative to antibiotics owing to rapid killing action and highly selective toxicity. Our previous studies have shown that AMP GW-Q4 and its derivatives possess effective antibacterial activities against the Gram-negative bacteria. Hence, in the current study, we evaluated the antibacterial efficacy of GW-Q4 and its derivatives against MDR ETEC and their minimal inhibition concentration (MIC) values were determined to be around 2~32 µg/mL. Among them, AMP Q4-15a-1 with the second lowest MIC (4 µg/mL) and the highest minimal hemolysis concentration (MHC, 256 µg/mL), thus showing the greatest selectivity (MHC/MIC = 64) was selected for further investigations. Moreover, Q4-15a-1 showed dose-dependent bactericidal activity against MDR ETEC in time-kill curve assays. According to the cellular localization and membrane integrity analyses using confocal microscopy, Q4-15a-1 can rapidly interact with the bacterial surface, disrupt the membrane and enter cytosol in less than 30 min. Minimum biofilm eradication concentration (MBEC) of Q4-15a-1 is 4× MIC (16 µg/mL), indicating that Q4-15a-1 is effective against MDR ETEC biofilm. Besides, we established an MDR ETEC infection model with intestinal porcine epithelial cell-1 (IPEC-1). In this infection model, 32 µg/mL Q4-15a-1 can completely inhibit ETEC adhesion onto IPEC-1. Overall, these results suggested that Q4-15a-1 may be a promising antibacterial candidate for treatment of weaned piglets infected by MDR ETEC.
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Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Escherichia coli Enterotoxigênica/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Doenças dos Suínos/tratamento farmacológico , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli Enterotoxigênica/patogenicidade , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Testes de Sensibilidade Microbiana , Suínos/microbiologia , Doenças dos Suínos/microbiologia , Doenças dos Suínos/patologiaRESUMO
Three-dimensional (3D) organic-inorganic lead halide hybrids have become a hot academic topic because of their various functional properties. However, 3D lead halide hybrid ferroelectrics are still very rare until now. Here, we report a new 3D lead halide perovskite-related ferroelectric, (EATMP)Pb2Br6 [EATMP = (2-aminoethyl)trimethylphosphanium]. Based on nonferroelectric CH3NH3PbBr3, by replacing PbBr6 octahedra with a Pb2Br10 dimer of edge-sharing octahedra as the basic building unit, the expanded 3D lead bromide perovskite analog was formed with the large [EATMP]2+ cations occupying the voids of framework. Notably, (EATMP)Pb2Br6 displays a direct bandgap of 2.81 eV, four polarization directions, and a high Curie temperature (Tc) of 518 K (much beyond that of BaTiO3, 393 K), which is the highest among all reported 3D organic-inorganic hybrid ferroelectrics. Such a high Tc may result from the high rotational energy barrier of cations induced by a larger molecular volume and relatively low crystal symmetry. Our work provides an efficient avenue to construct new 3D organic-inorganic lead halide hybrids and would inspire the further exploration of 3D lead halide ferroelectrics.
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Chiral organic-inorganic perovskites (COIPs) have recently attracted increasing interest due to their unique inherent chirality and potential applications in next-generation optoelectronic and spintronic devices. However, COIP ferroelectrics are very sparse. In this work, for the first time, we present the nickel-nitrite ABX3 COIP ferroelectrics, [(R and S)-N-fluoromethyl-3-quinuclidinol]Ni(NO2)3 ([(R and S)-FMQ]Ni(NO2)3), where the X-site is the rarely seen NO2- bridging ligand. [(R and S)-FMQ]Ni(NO2)3 display mirror-relationship in the crystal structure and vibrational circular dichroism signal. It is emphasized that [(R and S)-FMQ]Ni(NO2)3 show splendid ferroelectricity with both an extremely high phase-transition point of 405 K and a spontaneous polarization of 12 µC/cm2. To our knowledge, [(R and S)-FMQ]Ni(NO2)3 are the first examples of nickel-nitrite based COIP ferroelectrics. This finding expands the COIP family and throws light on exploration of high-performance COIP ferroelectrics.
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RESEARCH QUESTION: Granulosa cells (GCs) dysfunction plays a crucial role in the pathogenesis of polycystic ovary syndrome (PCOS). It is reported that YTH domain-containing family protein 2 (YTHDF2) is upregulated in mural GCs of PCOS patients. What effect does the differential expression of YTHDF2 have in PCOS patients? DESIGN: Mural GCs and cumulus GCs from 15 patients with PCOS and 15 ovulatory controls and 4 cases of pathological sections in each group were collected. Real-time PCR, Western Blot, immunohistochemistry, and immunofluorescence experiments were conducted to detect gene and protein expression. RNA immunoprecipitation assay was performed to evaluate the binding relationship between YTHDF2 and MSS51. Mitochondrial morphology, cellular ATP and ROS levels and glycolysis-related gene expression were detected after YTHDF2 overexpression or MSS51 inhibition. RESULTS: In the present study, we found that YTHDF2 was upregulated in GCs of PCOS patients while MSS51 was downregulated. YTHDF2 protein can bind to MSS51 mRNA and affect MSS51 expression. The reduction of MSS51 expression or the increase in YTHDF2 expression can lead to mitochondrial damage, reduced ATP levels, increased ROS levels and reduced expression of LDHA, PFKP and PKM. CONCLUSIONS: YTHDF2 may regulate the expression of MSS51, affecting the structure and function of mitochondria in GCs and interfering with cellular glycolysis, which may disturb the normal biological processes of GCs and follicle development in PCOS patients.
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Células da Granulosa , Mitocôndrias , Síndrome do Ovário Policístico , Proteínas de Ligação a RNA , Humanos , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Feminino , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Mitocôndrias/metabolismo , Mitocôndrias/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Adulto , Espécies Reativas de Oxigênio/metabolismo , Regulação da Expressão Gênica , Trifosfato de Adenosina/metabolismo , Glicólise/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
In the present study, a new strategy for heparin detection and quantification in biological media, such as fetal bovine serum (FBS), is developed by monitoring the emission change of a functional ruthenium polypyridyl complex ([Ru(phen)(2)dppz-idzo](2+), complex 1) in buffer solution. Polyanionic heparin is found to interact with a positively charged Ru-complex through electrostatic effects and/or hydrogen bonding interactions, which leads to a significant fluorescence enhancement of the Ru-complex. To get insight into this fluorescence "switch on" behavior, the binding model of the Ru-complex to heparin is established by employing molecular docking simulations based on the fluorescence and UV absorption results. The selectivity results of the fluorescence assay reveal that our complex displayed good fluorescence selectivity towards heparin over its analogues, such as chondroitin 4-sulfate (Chs) or hyaluronic acid (Hya), which have lower charge density and/or structural compatibility as compared to that of heparin. Quantification of heparin is also performed and a linear calibration curve is observed in the range of 0.01-4.87 U mL(-1) (the limit of detection is 0.01 U mL(-1)) for heparin detection in diluted FBS solution. This "one-step" fluorescence "switch on" assay for heparin detection is label-free, convenient, sensitive and selective, and has a long emission wavelength and large Stokes shift.
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Heparina/análise , Compostos Organometálicos/química , Rutênio/química , Espectrometria de Fluorescência/métodos , Absorção , Animais , Configuração de Carboidratos , Bovinos , Heparina/sangue , Heparina/química , Simulação de Acoplamento MolecularRESUMO
OBJECTIVE: To discuss the suitable water and nitrogen management mode in artificial cultivation of Chuzhou Chrysanthemum morifolium. METHODS: According to two factors quadratic regression rotation design experience, pot experiment was conducted. RESULTS: There were remarkable effects of water and nitrogen coupling on inflorescence number, yield and overground part biomass of Chuzhou Chrysanthemum morifolium, and there were significant positive interaction between water and nitrogen. Effects of water on early-term inflorescence yield and overground part biomass of Chuzhou Chrysanthemum morifolium were higher than that of nitrogen fertilizer, but the effect on total inflorescence yield was opposite. CONCLUSION: Considering for the fresh inflorescence yield, the suitable water and nitrogen management mode is to keep 93% of the water holding capacity and nitrogen fertilizer (N) 0.34 g/kg of Chuzhou Chrysanthemum morifolium in pot experiment, and as for the dry inflorescence yield, the suitable water and nitrogen management mode is to keep 75% of the water holding capacity and nitrogen fertilizer (N) 0.2 g/kg.
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Biomassa , Chrysanthemum/crescimento & desenvolvimento , Fertilizantes , Nitrogênio/metabolismo , Água , Absorção , Agricultura/métodos , Chrysanthemum/metabolismo , Flores/crescimento & desenvolvimento , Flores/metabolismo , Fósforo/metabolismo , Componentes Aéreos da Planta/crescimento & desenvolvimento , Componentes Aéreos da Planta/metabolismo , Potássio/metabolismo , Estações do Ano , SoloRESUMO
This article proposes two adaptive asymptotic tracking control schemes for a class of interconnected systems with unmodeled dynamics and prescribed performance. By applying an inherent property of radial basis function (RBF) neural networks (NNs), the design difficulties aroused from the unknown interactions among subsystems and unmodeled dynamics are overcome. Then, in order to ensure that the tracking errors can be suppressed in the specified range, the constrained control problem is transformed into the stabilization problem by using an auxiliary function. Based on the adaptive backstepping method, a time-triggered controller is constructed. It is proven that under the framework of Barbalat's lemma, all the variables in the closed-loop system are bounded and the tracking errors are further ensured to converge to zero asymptotically. Furthermore, the event-triggered strategy with a variable threshold is adopted to make more precise control such that the better system performance can be obtained, which reduces the system communication burden under the condition of limited communication resources. Finally, an illustrative example is provided to demonstrate the effectiveness of the proposed control scheme.
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BACKGROUND: Reflectance confocal microscopy (RCM) images skin at cellular resolution and has shown utility for the diagnosis of nonmelanoma skin cancer in vivo. It has the potential to define lesion margins before surgical therapy. OBJECTIVES: To investigate the feasibility of RCM in defining the margins of basal cell carcinoma before surgery. METHODS: The margins of 10 lesions were evaluated using RCM. Biopsies of the margins were used to confirm the results. A protocol was constructed to define margins. RCM was used to delineate preoperative surgical margins in 13 patients. Intraoperative frozen biopsy was used to confirm the margins. RESULTS: In seven of 10 (70.0%) cases, the margins of the cancer were identified suing RCM. The tumor island was the critical feature in identifying the margins. In 12 of 13 (92.3%) cases, frozen biopsy corroborated that the surgical margins delineated by RCM were clear. CONCLUSION: RCM imaging of the margins is feasible and demonstrates the possibility of preoperative mapping of cancer margins.
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Carcinoma Basocelular/patologia , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/cirurgia , Estudos de Viabilidade , Humanos , Microscopia Confocal , Neoplasias Cutâneas/cirurgiaRESUMO
OBJECTIVE: To explore the different expression of proteins between human clear-cell renal cell carcinoma (ccRCC) cell line RLC-310 and normal renal proximal tubule epithelial cell line HK-2, and to search new differentially expressed proteins of RCC. METHODS: RLC-310 and HK-2 cells were cultured in vitro. The total proteins were separated by ProteomeLab PF 2D protein fractionation system and the differential expression protein fractions of the two cell lines were analyzed and identified by capillary liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS). RT-PCR and Western blot were used to confirm the representative differential expression at mRNA and protein levels. RESULTS: One hundred and ninty-six differentially expressed proteins were identified. These differentially expressed proteins involved in many aspects, including cell proliferation and anti-apoptosis, energy metabolism, mitochondria reduction and oxidation, oxidative stress and resistance, cell signaling, invasion and adhesion, cytoskeleton and motion, neovascularization, etc. Except for previously reported RCC associated proteins: annexin A2, fatty acid-binding protein, vimentin, fibronectin, and so on, Septin-9 was firstly found highly expressed in RLC-310 cells when compared with that in the HK-2 cells. Moreover, the overexpression of Septin-9 was confirmed by RT-PCR and Western blot analysis at both mRNA and protein levels (P < 0.05). CONCLUSIONS: The human ccRCC cell line RLC-310 cells display differential protein profiles compared with those of the normal renal cell line HK-2 cells. The identified differential expression proteins are involved in many aspects of RCC development. It is worth further study and elucidate the molecular mechanisms of RCC. The representative differential protein Septin-9 deserves further study its role in the angiogenesis of ccRCC.
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Carcinoma de Células Renais/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/metabolismo , Proteômica/métodos , Septinas/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular , Linhagem Celular Tumoral , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , Neoplasias Renais/patologia , Túbulos Renais Proximais/citologia , RNA Mensageiro/metabolismo , Septinas/genéticaRESUMO
Fluoroscopy-induced chronic radiation dermatitis (FICRD) is an uncommon but increasing complication that is challenging to diagnose due to its varied symptoms and delayed onset, usually from months to years after radiation exposure. For patients undergoing cardiac catheterization, high-risk factors for radiodermatitis include obesity, the presence of complex or chronic total occlusion lesions, the use of a fixed large beam angulation, and a procedure time of more than 2 hours. We present an individual with FICRD that had an indurated plaque on his back for 7 years to familiarize physicians with high-risk groups and early recognition of the disease.
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Radiodermite , Humanos , Radiodermite/diagnóstico , Radiodermite/etiologia , Radiodermite/patologia , Fluoroscopia/efeitos adversos , Fatores de Risco , Alopecia/complicações , Cateterismo Cardíaco/efeitos adversosRESUMO
A salicylaldehyde Schiff base hybrid lead iodide perovskite [SAPD]PbI3 (SAPD = 1-((2-hydroxybenzylidene)amino)pyridin-1-ium) was found to show a robust nonlinear optical response and large spontaneous polarization. We expect this work to inspire researchers to investigate the optical control of ferroelectricity in hybrid perovskites.
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The outcomes of 80 patients with hematologic malignancies who received haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) combined with unrelated cord blood (UCB) from March 2017 to June 2020 were analyzed in this retrospective study. Anti-thymocyte globulin(ATG) was administered at a dose of 7.5 mg/kg. The median time for neutrophil and platelet engraftment was 13(range: 8-22) days and 14(range: 8-103) days, respectively. The 30-day cumulative incidence of neutrophil engraftment was 100%, and the 100-day cumulative incidence of platelet engraftment was 95%. All patients achieved complete haploidentical peripheral blood stem cell engraftment, and no cord blood chimerism was observed. The cumulative incidence of grades II-IV and grades III-IV acute graft-versus-host disease (aGVHD) on 100-day was 26.3%(95%CI: 17.2%-36.3%) and 5.0%(95%CI: 1.6%-11.4%), respectively. The estimated cumulative incidence of chronic GVHD (cGVHD) and moderate-severe cGVHD at 3-year was 43.3%(95%CI: 31.6%-54.4%) and 16.0%(95%CI: 8.7%-25.2%), respectively. The estimated 3-year cumulative incidence of relapse and non-relapse mortality was 18.8%(95%CI: 10.0%-29.7%) and 17.8%(95%CI: 9.9%-27.5%), respectively. The estimated 3-year probabilities of overall survival, disease-free survival, GVHD/relapse-free survival were 77.6%(95%CI: 68.3%-88.1%), 63.4%(95%CI: 52.6%-76.5%), and 55.5%(95%CI: 44.8%-68.7%), respectively. These satisfying results suggested that haplo-PBSCT combined with UCB is an alternative transplantation protocol for hematologic malignancies.
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Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Soro Antilinfocitário , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Recidiva Local de Neoplasia/complicações , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: Acute graft-versus-host disease (aGVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Accumulating evidence suggests that imbalanced Treg/Th17 ratio accelerates the progression of aGVHD. The aryl hydrocarbon receptor (AhR) is a basic helix-loop-helix transcription factor activated through cognate ligand binding. Current evidence supports that AhR plays a critical regulatory role in the differentiation of Treg and Th17 cells. However, the relationship between AhR and aGVHD remains unclear. RESULTS: Our results showed that AhR expression was downregulated significantly in CD4+ T cells from patients with aGVHD compared with the non-aGVHD group. We also discovered that after activating AhR deficient CD4+ T cells, the expression levels of the activation markers-CD40L, CD134 and CD137 and cell proliferation activity were significantly higher than those of AhR-expressing CD4+ T cells. Restoring the expression of AhR in aGVHD CD4+ T cells resulted in significantly increased percentage of Tregs and associated gene transcripts, including Foxp3, IL-10 and CD39. In contrast, Th17 cell amounts and the transcription of related genes, including RORγt, IL-17A and IL-17F, were significantly reduced. We confirmed that CTCF recruited EP300 and TET2 to bind to the AhR promoter region and promoted AhR expression by mediating histone H3K9/K14 hyperacetylation and DNA demethylation in this region. The low expression of CTCF caused histone hypoacetylation and DNA hypermethylation of the AhR promoter, resulting in insufficient expression in aGVHD CD4+ T cells. CONCLUSIONS: CTCF is an important inducer of AhR transcription. Insufficient expression of CTCF leads to excessive AhR downregulation, resulting in substantial CD4+ T cell activation and Th17/Treg ratio increase, thereby mediating the occurrence of aGVHD.
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Doença Enxerto-Hospedeiro , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Metilação de DNA , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/metabolismo , Histonas/metabolismo , Humanos , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Linfócitos T Reguladores , Células Th17RESUMO
Despite advantages of arsenic trioxide (ATO) in oncological practice, its clinical applications have been hampered by severe cardiotoxicity. The general mechanism of ATO-induced cardiotoxicity has been attributed to its damage to mitochondria, resulting in cardiac remodeling. Honokiol (HKL) is a naturally occurring compound derived from Magnolia bark. Previous studies have demonstrated that HKL exerts cardio-protective effects on ischemia/reperfusion (I/R) or chemical-induced cardiotoxicity by counteracting the toxic effects on mitochondria. The present study was conducted to investigate whether HKL pretreatment protects against ATO-induced cardiac oxidative damage and cell death. For the in vitro study, we evaluated the effects of ATO and/or Honokiol on reactive oxygen species (ROS) production and apoptosis induction in primary cultured cardiomyocytes; for the in vivo study, BALB/c mice were administrated with ATO and/or HKL for a period of 4 weeks, myocardial apoptosis, cardiac function, and cardiac remodeling (cardiac hypertrophy and cardiac fibrosis) were assessed at the end of administration. Our results demonstrated Honokiol pretreatment alleviated the ATO-induced boost in ROS concentration and the following apoptosis induction in primary cultured cardiomyocytes. In the mouse model, Honokiol pretreatment ameliorated ATO-induced myocardial apoptosis, cardiac dysfunction, and cardiac remodeling. Collectively, these results indicated that Honokiol provide a protection against ATO-induced cardiotoxicity by reducing mitochondrial damage. In addition, given that Honokiol has shown considerable suppressive effects on leukemia cells, our data also imply that ATO and Honokiol combination may possibly be a superior avenue in leukemia therapy.
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Apoptose/efeitos dos fármacos , Trióxido de Arsênio/toxicidade , Compostos de Bifenilo/farmacologia , Cardiotoxicidade/prevenção & controle , Lignanas/farmacologia , Animais , Compostos de Bifenilo/isolamento & purificação , Cardiotoxicidade/etiologia , Lignanas/isolamento & purificação , Magnolia/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Ferroelectrics usually exhibit temperature-triggered structural changes, which play crucial roles in controlling their physical properties. However, although light is very striking as a non-contact, non-destructive, and remotely controlled external stimuli, ferroelectric crystals with light-triggered structural changes are very rare, which holds promise for optical control of ferroelectric properties. Here, an organic molecular ferroelectric, N-salicylidene-2,3,4,5,6-pentafluoroaniline (SA-PFA), which shows light-triggered structural change of reversible photoisomerization between cis-enol and trans-keto configuration is reported. SA-PFA presents clear ferroelectricity with the saturate polarization of 0.84 µC cm-2 , larger than those of some typical organic ferroelectrics with thermodynamically structural changes. Benefit from the reversible photoisomerization, the dielectric real part of SA-PFA can be reversibly switched by light. More strikingly, the photoisomerization enables SA-PFA to show reversible optically induced ferroelectric polarization switching. Such intriguing behaviors make SPFA a potential candidate for application in next-generation photo-controlled ferroelectric devices. This work sheds light on further exploration of more excellent molecular ferroelectrics with light-triggered structural changes for optical control of ferroelectric properties.
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OBJECTIVE: To explore the perioperative features of surgical treatment in valvular patients with severe dilated left ventricle and investigate the structural changes of left ventricle and its correlation with cardiac functions. METHODS: A total of 126 patients with severe dilated left ventricle underwent mitral valve and/or aortic valve operation from January 2003 to December 2008, including mitral valve replacement (MVR) (n = 27), mitral valvuloplasty (MVP) (n = 13), aortic valve replacement (AVR) (n = 51), AVR+MVR (n = 25) and AVR + MVP (n = 10). There were 79 males and 47 females with a mean age of (52 ± 13) years old. The mean pathological course was (18 ± 12) years. The pathological changes were mainly of aortic and/or mitral incompetence. The concomitant procedures included Bentall procedure (n = 6), coronary artery bypass grafting (n = 3), tricuspid valvuloplasty (n = 58) and left atrial folding (n = 62). RESULTS: The perioperative mortality was 3.17% (4/126). Two died of multiple organ failure (MOF) secondarily to severe low-output syndrome while another 2 died of sudden ventricular fibrillation. Forty-six (36.5%) patients suffered from ventricular arrhythmia during the earlier postoperative period and they required a venous injection of lidocaine and/or amiodarone. Fourteen (11.1%) patients suffered from severe low-output syndrome. Among them, 4 patients were resuscitated with an intra-aortic balloon pump for another 4 - 6 days. And 26 (20.6%) cases were complicated with multiple organ failure. The echocardiographic examinations showed that left ventricular dimensions decreased significantly at Days 7 - 14 postoperatively and progressively at Months 6 - 12 postoperatively. Left ventricular end-diastolic diameter (LVEDD) was (77 ± 6) mm preoperatively and (63 ± 12) mm (Days 7 - 14), (58 ± 10) mm (Months 6 - 12) postoperatively (P < 0.01). The contractile function of left ventricle temporarily decreased during the early postoperative stage and improved gradually afterwards. But it was not restored to normal range even until 6 - 12 m post-operation. Ejection fraction was 49% ± 12% preoperatively and 42% ± 9% (Days 7 - 14), 51% ± 7% (Months 6 - 12) postoperatively (P < 0.01). Left ventricular fraction shortness was 28% ± 7% preoperatively and 25% ± 4% (Days 7 - 14), 29% ± 5% (Months 6 - 12) postoperatively (P < 0.05). CONCLUSION: For the patients with severe dilated left ventricle, cardiovascular operation can achieve an excellent outcome through a rigorous perioperative regiment. The prevention and treatment of postoperative ventricular arrhythmia should be emphasized. The dimension of left ventricle decreases progressively during the early postoperative period. There is a postoperative decline of cardiac functions.
Assuntos
Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/cirurgia , Ventrículos do Coração/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Because the study population with gliosarcoma (GSM) is limited, the understanding of this disease is insufficient. In this study, the authors aimed to determine the clinical characteristics and independent prognostic factors influencing the prognosis of GSM patients and to develop a nomogram to predict the prognosis of GSM patients after craniotomy. A total of 498 patients diagnosed with primary GSM between 2004 and 2015 were extracted from the 18 Registries Research Data of the Surveillance, Epidemiology, and End Results (SEER) database. The median disease-specific survival (DSS) was 12.0 months, and the postoperative 0.5-, 1-, and 3-year DSS rates were 71.4%, 46.4% and 9.8%, respectively. We applied both the Cox proportional hazards model and the decision tree model to determine the prognostic factors of primary GSM. The Cox proportional hazards model demonstrated that age at presentation, tumour size, metastasis state and adjuvant chemotherapy (CT) were independent prognostic factors for DSS. The decision tree model suggested that age <71 years and adjuvant CT were associated with a better prognosis for GSM patients. The nomogram generated via the Cox proportional hazards model was developed by applying the rms package in R version 3.5.0. The C-index of internal validation for DSS prediction was 0.67 (95% confidence interval (CI), 0.63 to 0.70). The calibration curve at one year suggested that there was good consistency between the predicted DSS and the actual DSS probability. This study was the first to develop a disease-specific nomogram for predicting the prognosis of primary GSM patients after craniotomy, which can help clinicians immediately and accurately predict patient prognosis and conduct further treatment.