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In this clinical study, we investigated the potential of melatonin (MT) supplementation in the freeze-thaw medium used for cryopreserved human oocytes. In total, 152 patients who underwent in vitro fertilization between January 2020 and December 2022 were included and categorized into different groups as follows: the donor group, comprising 108 patients who donated their oocytes, with 34 patients using a vitrification and warming medium supplemented with MT (D-MT subgroup) and 74 patients using conventional medium without MT (D-0 subgroup); and the autologous group, comprising 38 patients who used their own oocytes, with 19 patients using medium supplemented with MT (A-MT subgroup) and 19 patients using medium without MT (A-0 subgroup). After thawing, the surviving oocytes in the D-MT and A-MT subgroups and D-0 and A-0 subgroups were cultured in a fertilization media with and without 10-9 MMT for 2.5 h, respectively, followed by intracytoplasmic sperm injection insemination, embryo culture, and transfer. The survival, cleavage, high-quality embryo, clinical pregnancy, ongoing pregnancy, and implantation rates were significantly higher in the D-MT subgroup than in the D-0 subgroup (all P < 0.05). Similarly, the survival, fertilization, high-quality embryo, and high-quality blastocyst rates were significantly higher in the A-MT subgroup than in the A-0 subgroup (all P < 0.05). These findings indicate that MT addition during cryopreservation can enhance the development of vitrified-warmed human oocytes and improve clinical outcomes.
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Criopreservação , Melatonina , Oócitos , Vitrificação , Humanos , Melatonina/farmacologia , Criopreservação/métodos , Oócitos/efeitos dos fármacos , Vitrificação/efeitos dos fármacos , Feminino , Adulto , Gravidez , Taxa de Gravidez , Fertilização in vitro/métodos , Injeções de Esperma Intracitoplásmicas/métodos , Crioprotetores/farmacologia , Transferência Embrionária , Técnicas de Cultura Embrionária/métodos , Blastocisto/efeitos dos fármacosRESUMO
BACKGROUND: Increasing evidence had proved that some circular RNA (circRNA) exerted critical roles in tumors progression by functioning as "microRNAs (miRNAs) sponges" to regulate their targeted genes. METHODS: circFAM114A2 and miR-647 expression was measured in CRC tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR), and the prognostic value of circFAM114A2 evaluated by Kaplan-Meier survival curve. Subsequently, wounding healing and transwell assays were performed to assess cell proliferation, migration, and invasion. RNA pull-down and dual-luciferase reporter assays were used to confirm the interactions between circFAM114A2, miR-647, and DAB2IP. RESULTS: CircFAM114A2 was notably downregulated in CRC tissues and cells, and low circFAM114A2 expression indicated the poor prognosis of CRC patients. Next, overexpression of circFAM114A2 suppressed CRC cells proliferation, migration, and invasion in vitro and impede CRC tumor growth in vivo. Mechanically, circFAM114A2 competitively bound to miR-647 and upregulated its target gene DAB2IP expression in CRC cells. CONCLUSION: Our results indicated that circFAM114A2/miR-647/DAP2IP axis played an important role in CRC progression, suggesting that circFAM114A2 might be a novel therapeutic target in patients with CRC.
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AIM: Examine the levels of variables and explore drivers associated with shared decision-making attitudes among newly graduated nurses. DESIGN: This was a descriptive and cross-sectional study. METHODS: From August 2022 to October 2022, a cross-section of 216 newly graduated nurses from four comprehensive A-level hospitals in northern China was recruited using convenience sampling. Newly graduated nurses are generally defined as nurses with a service period of six months to one year. Data were collected using an online questionnaire support platform, including the Nursing Shared Decision-Making Attitude scale, Jefferson scale of Empathy-Health profession students and the Health Sciences Evidence-Based Practice questionnaire. All data were analysed descriptively, and correlational analysis and hierarchical regression were used to make identical connections between variables. RESULTS: Newly graduated nurses supported shared decision-making. Perceptions of shared decision-making were correlated with the experiences of empathy and evidence-based practice. Additionally, perspective-taking of empathy and beliefs, and the ability to search for and apply existing scientific findings of evidence-based practice had a significant impact on more positive attitudes. CONCLUSION: The survey showed that acceptance of shared decision-making was positive among newly graduated nurses. Clinical nursing managers and teachers should pay attention to cultivating the evidence-based practice and empathy of newly graduated nurses to adopt an optimistic attitude towards shared decision-making in the long term. IMPACT: The survey addresses attitudes of shared decision-making among newly graduated nurses and determines whether empathy and evidence-based practice has an impact on it. The main finding is that newly graduated nurses have an optimistic outlook on the implementation of shared decision-making. This survey showed that empathy and evidence-based practice competencies are associated with shared decision-making attitudes among newly graduated nurses. The results of this survey have an impact on educational institutions and hospitals in the form of recommendations. Several training programmes on empathy and evidence-based practice can help adopt the shared decision-making attitudes of newly graduated nurses. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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This study aimed to analyze the clinical effects of microdissection testicular sperm extraction (micro-TESE) surgery combined with an intracytoplasmic sperm injection (ICSI) regimen in the treatment of non-obstructive azoospermia (NOA) patients with different etiologies. In total, 128 NOA patients participated in this study, in which they received infertility treatment by micro-TESE surgery combined with an ICSI regimen, and all patients were divided into three groups [the Klinefelter syndrome (KS), the idiopathic and the secondary NOA groups]. In addition, the sperm retrieval rate (SRR), fertilization rate, embryo development status and clinical treatment effects were analyzed. Among the 128 NOA patients, the SRR of KS NOA patients was 48.65%, those of idiopathic and the secondary patients were 33.82% and 73.91%, respectively. Regardless of etiologies, there was no correlation with age, hormone value or testicular volume. Further analysis showed that the SRR of the KS group was positively related with testosterone (T) values, and the SRR of the secondary group had a positive relationship with follicle-stimulating hormone or luteinizing hormone values. In the subsequent clinical treatment, the retrieved sperm was subjected to ICSI and achieved good treatment effects, especially in the secondary group, and the implantation rate (55.56%) and clinical pregnancy rate (68.42%) were both higher than those of the idiopathic group (28.75% and 40.00%) and KS group (22.05% and 30.77%). Micro-TESE surgery combined with ICSI insemination is the most effective treatment regimen for NOA patients. The SRR of NOA patients with different etiologies are related to certain specific factors, and micro-TESE surgery seems to be the ideal and only way to have biological children.
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Azoospermia , Gravidez , Feminino , Criança , Humanos , Masculino , Azoospermia/cirurgia , Injeções de Esperma Intracitoplásmicas , Sêmen , Testículo/cirurgia , Espermatozoides , Recuperação Espermática , Estudos RetrospectivosRESUMO
A total of 69 patients were enrolled in the study, including 23 patients with hypertrophic cardiomyopathy (HCM), 26 patients with Left Ventricle (LV) enlargement comprising 16 dilated cardiomyopathy (DCM) patients and 10 ischemic cardiomyopathy (ICM) patients, and 20 control subjects. All patients underwent 2DE, contrast-enhanced 2DE (Contrast-2DE), 3DE, Contrast-3DE, and single photon emission computed tomography (SPECT) examinations. The 2DE-AL and 3DE methods measured the left ventricular mass (LVM). The results were compared with those measured by SPECT. The measured LVM of the 69 patients was systematically overestimated by 2DE-AL (177.4 ± 56.2 g), Contrast-2DE-AL (174.5 ± 55.5 g), 3DE (167.3 ± 59.2 g), and Contrast-3DE (154.2 ± 46.7 g) when compared with SPECT (148.5 ± 52.4 g) (P < 0.05), while Contrast-3DE provided the best agreement with SPECT in LVM measurement (r = 0.898, P < 0.001) and had the smallest deviation (5.7 ± 23.1 g). 3DE overestimated LVM more compared to Contrast-3DE in LV hypertrophy group (165.5 ± 37.9 g versus 153.5 ± 27.6 g, P = 0.003) and LV enlargement group (204.5 ± 69.3 g versus 183.5 ± 53.5 g, P = 0.006). For 2DE methods, there was no significant difference between the LVM obtained with or without contrast enhancement in control group (132.3 ± 23.6 g versus 128.4 ± 23.3 g), LV hypertrophy group (177.7 ± 38.6 versus 178.3 ± 30.9 g, P = 0.889), and LV enlargement group (211.9 ± 63.2 g versus 206.5 ± 66.0 g, P = 0.386). The difference between LVM measured by 2DE-AL and SPECT was the greatest (27.9 ± 34.0 g), especially in LV hypertrophy group and LV enlargement group (LV hypertrophy group 39.7 ± 26.0 g; LV enlargement group 24.2 ± 42.8 g). To conclude, Contrast-3DE and SPECT show greater consistency in LVM measurement, especially in cardiomyopathy, when compared with 2DE. Administering contrast can effectively reduce the overestimation of LVM by non-contrast DE.
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Ecocardiografia Tridimensional , Disfunção Ventricular Esquerda , Humanos , Ecocardiografia Tridimensional/métodos , Coração , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Reprodutibilidade dos TestesRESUMO
Clear cell renal cell carcinoma (ccRCC) is the main type of malignancy in kidney related to glucose metabolism. Primary single cell culture and single cell sequencing are novel research technologies. In this study, we explored the differentiation status of ccRCC cells and its significance in prognosis and immunotherapeutic response through bioinformatics. We characterized distinct differentiation states and differentiation-related genes (DRGs) in ccRCC cells through single cell RNA sequencing (scRNA-seq) analysis. Combined with bulk RNA-seq data, we classified patients into two clusters and found that this classification was closely correlated with patient prognosis and immunotherapeutic responses. Based on machine learning, we identified a prognostic risk model composed of 14 DRGs, including BTG2, CDKN1A, COL6A1, CPM, CYB5D2, FOSB, ID2, ISG15, PLCG2, SECISBP2, SOCS3, TES, ZBTB16, and ZNF704, to predict the survival rate of patients and then constructed a nomogram model integrating clinicopathological characteristics and risk score for clinical practice. In the study of immune checkpoints, we found that patients in the high-risk group had a disposition to get worse prognosis and better effects of immune checkpoint blocking therapies. Finally, we found the expression level of model DRGs was associated with a tumor-immune microenvironment (TIME) pattern and the response of 83 compounds or inhibitors was significantly different in the two risk groups. In a word, our study highlights the potential contribution of cell differentiation in prognosis judgment and immunotherapy response and offers promising therapeutic options for ccRCC patients.
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Carcinoma de Células Renais , Proteínas Imediatamente Precoces , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Prognóstico , Diferenciação Celular/genética , Imunoterapia , Neoplasias Renais/genética , Neoplasias Renais/terapia , Microambiente Tumoral/genética , Proteínas Supressoras de Tumor , Citocromos b5RESUMO
BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a rare but serious complication of controlled ovarian stimulation. Frozen-embryo transfer (ET) is prompted to be performed in the next menstrual cycles after cancellation of fresh-ET after occurrence of OHSS. However, effects of frozen-ET in the second menstrual cycle have never been investigated. Therefore, this study aimed to assess this in the menstrual cycle after OHSS. METHODS: The OHSS group included 342 women with moderate-severe OHSS who underwent the first frozen-ET in the second menstrual cycle in the First Affiliated Hospital of Anhui Medical University from June 2018 to September 2019. A total of 342 women without OHSS who received frozen-ET in the second menstrual cycle were selected as control group matched by age, body mass index, fertility history, ovulation induction scheme. Uni- and multi-variable conditional logistic regression was used to estimate the association between moderate-severe OHSS and pregnancy outcomes. RESULTS: There were no significant differences in maternal outcomes (miscarriage, preterm birth and pregnancy complications including gestational diabetes mellitus, pregnancy-induced hypertension, placenta previa, premature rupture of membranes and postpartum hemorrhage) and in neonatal outcome (birth-weight and body length, neonatal congenital diseases and other complications) between the two groups in either uni- or multi-variable models. CONCLUSIONS: Frozen-ET in the menstrual cycle after OHSS has similar maternal and neonatal outcomes as in women without OHSS. This study indicates that frozen-ET could be performed in the second menstrual cycle in women who recovered from moderate-severe OHSS.
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Síndrome de Hiperestimulação Ovariana , Nascimento Prematuro , Recém-Nascido , Feminino , Humanos , Síndrome de Hiperestimulação Ovariana/etiologia , Estudos Retrospectivos , Transferência Embrionária/efeitos adversos , Ciclo MenstrualRESUMO
Infertility has a detrimental impact on the sexual function of involuntarily childless couples. However, the effect of male sexual function on female partner's sexual function in infertile couples remains unknown. In order to explore the association between these couples' sexual function, 324 consecutive couples with infertility and 326 female-age-matched fertile couples were enrolled in this study. The female sexual function index (FSFI) and sexual history were evaluated in female partners. In addition to the international index of erectile function-15 (IIEF-15) and sexual history, self-reported intravaginal ejaculation latency time was evaluated in male partners. The demographics and depression status of couples were also recorded. We observed a higher occurrence of female sexual dysfunction (FSD) in infertile females than in fertile females (58.6% vs. 50.3%, p = 0.033). FSD was associated with a number of risk variables, including partner's erectile dysfunction (ED), depression and sexual frequency. The overall FSFI score was positively associated with the IIEF-15 score (r = 0.347, p < 0.001). Besides, six FSFI domains were positively correlated with five IIEF-15 domains (p < 0.05). In conclusion, it is critical to assess and address FSD as well as the sexual problems in male partners in infertile couples.
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Disfunção Erétil , Infertilidade Feminina , China/epidemiologia , Ejaculação , Feminino , Humanos , Masculino , Comportamento Sexual , Inquéritos e QuestionáriosRESUMO
It is very important to assess pulmonary oedema in patients with acute heart failure. The aim of the study was to investigate the accuracy of lung ultrasound in evaluating pulmonary oedema and to explore lung ultrasound in predicting the prognosis. One hundred twenty-four acute heart failure patients were divided into 3 groups, according to the total number of lung ultrasound B-lines groups: B-lines < 15 was the mild pulmonary oedema group (33 cases), 15 ≤ B-lines < 30 was the moderate pulmonary oedema group (33 cases), and B-lines ≥ 30 was the severe pulmonary oedema group (58 cases). The PiCCO monitoring system was used in 11 patients and measured 26 times in different clinical situations. EVLWI have a higher positive correlation with B-lines (r = 0.95), compared with NT-proBNP and E/e' (r = 0.72, r = 0.62). During 1 year of follow-up, a multivariate cox regression analysis showed that age, E/e' and B-lines ≥ 30 at admission (C-index of 75%) were risk factors for prognosis. 12-month event-free survival showed a significantly worse outcome was observed in patients with ≥ 30 B-lines at admission. B-lines have a good correlation with EVLWI; age, E/e' and B-lines ≥ 30 at admission were risk factors for prognosis.
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Insuficiência Cardíaca/complicações , Pulmão/diagnóstico por imagem , Edema Pulmonar/diagnóstico , Ultrassonografia/métodos , Doença Aguda , Idoso , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Monitorização Fisiológica/métodos , Prognóstico , Edema Pulmonar/etiologia , Curva ROC , Estudos Retrospectivos , Volume Sistólico/fisiologiaRESUMO
AIMS: Inhibitor for the apoptosis-stimulating protein of p53 (iASPP) has been reported to be correlated with 5-fluorouracil (5-Fu) resistance in renal cell carcinoma. Here, we uncover mechanisms of iASPP-Nrf2-ROS regulation of 5-Fu resistance which are important for the development of alternative treatment strategies for gastric adenocarcinoma treatment. METHODS: We analyzed iASPP and Nrf2 through TCGA RNA-seq data, UALCAN analysis, and cBioPortal datasets. Intracellular ROS generation was determined by 2',7'-dichloro-fluorescin diacetate staining. Transwell was used to evaluate the invasion. The expression of iASPP, Nrf2, HO-1, and GSTP1 was tested using western blot. RESULTS: We found that iASPP KD led to an apparent 5-Fu-induced ROS accumulation in MGC803 and SCG790 cells. Accompanied by iASPP KD, Nrf2 was markedly decreased. iASPP-induced ROS inhibition relies on Nrf2, and due to both knocked down iASPP and Nrf2, the level of ROS did not show an obvious difference with Nrf2 KD solely. Similarly, iASPP KD failed to enhance the Nrf2 KD-mediated ROS accumulation after 5-Fu treatment, suggesting that iASPP-induced antioxidative effects related to 5-Fu resistance are partially dependent on Nrf2. Also, the combination of iASPP KD and Nrf2 KD did not show any synergistic effect on apoptosis after 5-Fu treatment in MGC803 and SCG790 cells. Further studies revealed that iASPP KD or Nrf2 KD could decrease the expression of HO-1 and GSTP1. CONCLUSIONS: Our data highlight that iASPP plays a crucial role in the inhibition of 5-Fu-induced apoptosis resistance by removing ROS accumulation in gastric adenocarcinoma, and that the removal of ROS induced by iASPP is Nrf2 signaling dependent.
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Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fator 2 Relacionado a NF-E2/genética , Proteínas Repressoras/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
To explore whether different polyvinylpyrrolidone (PVP) concentrations affect the results of intracytoplasmic sperm injection (ICSI), a prospective study was conducted for 194 couples undergoing 210 ICSI therapy cycles. These cycles were divided into three groups (10, 7 and 5% groups) using the corresponding concentration of PVP for sperm immobilization. The main outcome measures were analyzed. Results indicated that, with a decrease in PVP concentrations, all of the main outcome measures increased. In particular, the high-quality cleavage embryo rate in the 7% group was significantly lower than in the 5% group (P < 0.01), and the cleavage, high-quality cleavage embryo, and high-quality blastocyst rates in the 5% group were significantly higher than those in the 10% group (all P < 0.001). For high-/intermediate-quality semen, all of the main outcome measures were significantly increased with 5% PVP. For the poor-quality semen, only the high-quality cleavage embryo and high-quality blastocyst rates were significantly higher in the 5% group. Therefore, lowering PVP concentrations greatly promoted the development of embryos in ICSI cycles, with an optimal concentration of 5% for ICSI.
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To investigate contamination level, origins and spatial distribution characteristics of heavy metals (Cu, Pb, Zn, Hg, Ni, Cd, As, and Cr) in agricultural soils of Gaogang Town, a typical industrial transfer-undertaking region of the Pearl River Delta (PRD), China, a total of 162 surface soil samples were collected in August 2016 and determined using inductively coupled plasma mass spectrometry, inductively coupled plasma optical emission spectrometry and atomic fluorescence spectrometry. Moreover, heavy metals contents were systematically analyzed by pollution index, enrichment factor, multivariate statistical approaches and geostatistical analysis. The results showed that the mean concentrations of Cd, Pb, Zn, Ni, Cu and Hg were higher than the soil background values of Guangdong Province, and the relatively high values of pollution index and enrichment factor indicated that these elements (Cd, Pb, Zn and Hg) had cumulative trends in soil. All results of multivariate statistical approaches and geostatistical analysis showed that pollution were heavily distributed in areas of industries, river and dense road network. The eight heavy metals in agricultural soils of Gaogang Town came from three different sources. Arsenic, Cr, Cu and Ni arose mainly from parent materials. Agricultural practices and traffic activities were the main sources of Cd, Pb and Zn. Mercury mainly came from industrial practices.
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Metais Pesados/análise , Poluentes do Solo/análise , Solo/química , Agricultura , China , Monitoramento Ambiental , Modelos Teóricos , Análise de Componente Principal , RiosRESUMO
Myostatin (MSTN) is a member of the TGF-ß superfamily that negatively regulates skeletal muscle growth and differentiation. However, the mechanism by which complete MSTN deletion limits excessive proliferation of muscle cells remains unclear. In this study, we knocked out MSTN in mouse myoblast lines using a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) system and sequenced the mRNA and miRNA transcriptomes. The results show that complete loss of MSTN upregulates seven miRNAs targeting an interaction network composed of 28 downregulated genes, including TGFB1, FOS and RB1. These genes are closely associated with tumorigenesis and cell proliferation. Our study suggests that complete loss of MSTN may limit excessive cell proliferation via activation of miRNAs. These data will contribute to the treatment of rhabdomyosarcoma (RMS).
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MicroRNAs/genética , Células Musculares/metabolismo , Miostatina/deficiência , Animais , Linhagem Celular , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Ordem dos Genes , Redes Reguladoras de Genes , Vetores Genéticos/genética , Camundongos , Anotação de Sequência Molecular , Interferência de RNA , RNA Mensageiro/genética , Reprodutibilidade dos TestesRESUMO
Objective To evaluate the instant effects and five-year clinical outcomes of coronary artery disease patients complicated with diabetes mellitus after StentBoost-optimized percutaneous coronary intervention (PCI). Methods From March 2009 to July 2010, 184 patients undergoing PCI at our hospital were found stent underexpansion or malapposition by StentBoost after stents implantation and were divided into the diabetic (n=73, 39.67%) and the non-diabetic group (n=111, 60.33%). All patients received StentBoost-guided post-dilatation after stent implantation. The instant procedural results were measured and clinical outcome after five-year follow-up was analyzed in each group. Between-group comparisons were performed using Chi-square test or Student's t test. Multivariate logistic regression analysis was carried out to reveal the independent predictors for long-term clinical outcomes of StentBoost-optimized PCI . Results After StentBoost-guided post-dilatation, the minimum diameter (MinLD), maximum diameter (MaxLD) and average diameter in both groups increased significantly than before (P<0.001), the (MaxLD-MinLD)/MaxLD ratio and the in-stent residual stenosis decreased accordingly (P<0.001). The five-year follow-up showed similar mortality rate (4.92% vs. 2.86%, P=0.67) and major adverse cardiac event rate (11.48% vs. 11.43%, P = 1.0) between the diabetic and the non-diabetic group, whereas the recurrence of angina pectoris was higher in the diabetic group compared to the non-diabetic group (47.54% vs. 29.52%; P=0.02). A multivariate logistic regression analysis revealed that age and left ventricular ejection fraction rather than diabetes mellitus were independent predictors for long-term clinical outcomes. Conclusions StentBoost could effectively improve instant PCI results; the long-term clinical outcomes of StentBoost-optimized PCI were similar between diabetic and non-diabetic patients. Age and left ventricular ejection fraction were the independent predictors for long-term clinical outcomes.
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Doença da Artéria Coronariana , Complicações do Diabetes , Intervenção Coronária Percutânea , Idoso , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/cirurgia , Complicações do Diabetes/mortalidade , Complicações do Diabetes/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females and the third in males. In this work, we aim to investigate the possible anti-cancer effects of interferon-gamma (IFN-γ) in CRC cells. We observed that IFN-γ induced mitochondria-derived reactive oxygen species (ROS) production in a time-dependent manner in SW480 and HCT116â¯cell lines. The IFN-γ-induced mitochondrial ROS generation was dependent on the activation of cytosolic phospholipase A2 (cPLA2). In addition, a mitochondria-targeted antioxidant SS31 and/or cPLA2 inhibitor AACOCF3 abolished the IFN-γ-induced ROS production and subsequent autophagy and apoptosis. Moreover, suppression of autophagy by CQ was able to reduce IFN-γ-induced cell apoptosis. Beclin-1 gene silencing resulted in caspase-3 inactivation, decreased Bax/Bcl-2 ratio and less population of apoptotic cells. Collectively, our results suggested that IFN-γ induces autophagy-associated apoptosis in CRC cells via inducing cPLA2-dependent mitochondrial ROS production.
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Apoptose , Neoplasias Colorretais/metabolismo , Interferon gama/fisiologia , Mitocôndrias/metabolismo , Fosfolipases A2 Citosólicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Autofagia , Proteína Beclina-1/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Células HCT116 , Humanos , Oligopeptídeos/farmacologiaRESUMO
OBJECTIVES: Lung ultrasound detection of B-lines has become a simple, semiquantitative, noninvasive tool for evaluating pulmonary congestion in heart failure (HF) patients. This study compared the correlation of B-lines with E/e', NT-proBNP, and ejection fraction (EF) in acute decompensated heart failure (ADHF). METHODS: Eighty-two consecutive patients who were diagnosed with acute decompensated HF were divided into two groups: preserved ejection fraction heart failure (HFpEF, EF≥50%, n=32) and reduced ejection fraction heart failure (HFrEF, EF<50%, n=50). Spearman's correlation was used to evaluate associations of B-lines with E/e', NT-proBNP, and EF in the two groups. Receiver operating characteristic (ROC) analysis was performed to compare B-lines with the E/e' ratio. RESULTS: Results revealed no significant differences were observed in the B-lines between the HFpEF and HFrEF groups. However, compared with the control group, B-lines were significantly increased in the HFpEF and HFrEF groups (P<.05). The B-lines were positively correlated with E/e' (r=0.742, r=0.52) and NT-proBNP (r=0.678, r=0.417) but were negatively correlated with EF (r=-0.365, r=-0.337), and the correlation coefficients were higher in the HFpEF group than in the HFrEF group. In ROC analyses, considering E/e' ≥14 as a reference, B-lines yielded a C-statistic value of 0.94 (sensitivity 92%, specificity 83%) in the HFpEF group and 0.84 (sensitivity 86%, specificity 78%) in the HFrEF group. CONCLUSIONS: B-lines were significantly correlated with the more established parameters of ADHF. The correlation between B-lines and E/e' was better, especially in the HFpEF group.
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Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Ultrassonografia/métodos , Doença Aguda , Idoso , Feminino , Humanos , Pulmão , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To compare three-dimensional (3D) and two-dimensional (2D) speckle tracking echocardiography (STE) techniques in the assessment of left ventricular function and myocardial infarct size (MIS). METHODS: Thirty-two patients diagnosed with ST elevation myocardial infarction and 18 healthy control patients underwent 2D echocardiography, 3D echocardiography, and single photon emission computed tomography (SPECT). 3D left ventricular global area strain (GAS), 2D and 3D global longitudinal strain (GLS), global radial strain (GRS) as well as global circumferential strain (GCS) were analyzed to correlate with myocardial infarct size detected by SPECT. 2D and 3D left ventricular ejection fraction (LVEF) as well as 2D and 3D wall motion score index (WMSI) also were measured using conventional echocardiography. RESULTS: The 2D-GLS values were significantly higher than that of 3D-GLS, while 2D-GCS and GRS were significantly lower than 3D-GCS and GRS, respectively. However, no significant differences in LVEF and WMSI could be observed between 2D and 3D echocardiography. Myocardial strain indices, LVEF, and WMSI using 2D and 3D echocardiography also had good correlations with MIS as measured by SPECT. ROC curve analysis showed that the 3D and 2D myocardial indices, LVEF, and WMSI could distinguish between small and large MIS, while 2D-GLS had the highest AUC. CONCLUSION: The 2D and 3D myocardial strain indices correlated well with MIS by SPECT. Among them, the 2D-GLS showed the highest diagnostic value, while 3D-GRS and GCS had better diagnostic value than 2D-GRS and GCS.
Assuntos
Ecocardiografia/métodos , Infarto do Miocárdio/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ecocardiografia Tridimensional , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
PURPOSE: Inflammation participates centrally in all stages of atherosclerosis (AS), which begins with pro-inflammatory processes and inflammatory changes in the endothelium, related to lipid metabolism. MicroRNA (miRNA) inhibition of inflammation related to SIRT1 has been shown to be a promising therapeutic approach for AS. However, the mechanism of action is unknown. METHODS: We investigated whether miRNAs regulate the SIRT1 and its downstream SREBP-lipogenesis-cholesterogenesis metabolic pathway in human umbilical vein endothelial cells (HUVECs). HUVECs were transfected with miR-132 mimics and inhibitors, and then treated with or without tumor necrosis factor α (TNFα). The effects of miR-132 on pro-inflammatory processes, proliferation and apoptosis were assessed. RESULTS: We identified that the relative 3' UTR luciferase activities of SIRT1 were significantly decreased in miR-132 transfected HUVECs (0.338 ± 0.036) compared to control (P = 0.000). miR-132 inhibited SIRT1 expression of mRNA level in HUVECs (0.53 ± 0.06) (P < 0.01) as well as proteins of SIRT1. mRNA expression and protein levels of SREBP (0.45 ± 0.07), fatty acid synthase (FASN) (0.55 ± 0.09) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) (0.62 ± 0.08) (P < 0.01), which are downstream regulated genes, were reduced in HUVECs by miR-132. MiR-132 promoted pro-inflammatory processes and apoptosis of HUVECs induced by TNF-α, and inhibited its proliferation, viability and migration. CONCLUSIONS: SIRT1 mRNAs are direct targets of miR-132. miR-132 controls lipogenesis and cholesterogenesis in HUVECs by inhibiting SIRT1 and SREBP-1c expression and their downstream regulated genes, including FASN and HMGCR. Inhibition of SIRT1 by miR-132 was associated with lipid metabolism-dependent pro-inflammatory processes in HUVECs. The newly identified miRNA, miR-132 represents a novel targeting mechanism for AS therapy.
Assuntos
Células Endoteliais da Veia Umbilical Humana/metabolismo , MicroRNAs/genética , Sirtuína 1/antagonistas & inibidores , Proteína de Ligação a Elemento Regulador de Esterol 1/antagonistas & inibidores , Apoptose , Células Cultivadas , Endotélio Vascular/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Lipogênese/genética , Metaloproteinase 9 da Matriz/metabolismo , Transdução de Sinais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Transfecção , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: The seeds of Pulsatilla cernua were used as tested materials for screening and establishing the main factors with different levels to control fast development of seed embryonic and seedlings of Pulsatilla cernua. METHODS: The main factors with different levels for development of seed embryonic and seedlings of Pulsatilla cernua were investigated through repeated experiments with multifactorial and cross. RESULTS: The method for development of seedlings and seeds germination of Pulsatilla cernua were to soak the seeds in the mixed solutions with 2.40 mg/L KT, 2.80 mg/L GA3 and 0.30 -0.70 mg/L 2,4-D for 24 h. The seeds and sand (1:2) were mixed, treated with temperature change in 63 - 70 d. The extent of temperature change and time were (23 ± 2) degrees C and 14 h in day, while (10 ± 2) degrees C and 10 h in night. The incidence rate of the embryo with cotyledons was 95.1%, and the germination rate of seed was 92.3%. CONCLUSION: The plant regeneration control technology for development of seed embryonic and seedling of Pulsatilla cernua have been solved, which is suitable for industrial seedlings of Pulsatilla cernua.