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BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) ranks fourth in cancer mortality, underscoring the importance of accurate prognostic predictions to improve postoperative survival rates in patients. Although micronecrosis has been shown to have high prognostic value in HCC, its application in clinical prognosis prediction requires specialized knowledge and complex calculations, which poses challenges for clinicians. It would be of interest to develop a model to help clinicians make full use of micronecrosis to assess patient survival. METHODS: To address these challenges, we propose a HCC prognosis prediction model that integrates pathological micronecrosis information through Graph Convolutional Neural Networks (GCN). This approach enables GCN to utilize micronecrosis, which has been shown to be highly correlated with prognosis, thereby significantly enhancing prognostic stratification quality. We developed our model using 3622 slides from 752 patients with primary HCC from the FAH-ZJUMS dataset and conducted internal and external validations on the FAH-ZJUMS and TCGA-LIHC datasets, respectively. RESULTS: Our method outperformed the baseline by 8.18% in internal validation and 9.02% in external validations. Overall, this paper presents a deep learning research paradigm that integrates HCC micronecrosis, enhancing both the accuracy and interpretability of prognostic predictions, with potential applicability to other pathological prognostic markers. CONCLUSIONS: This study proposes a composite GCN prognostic model that integrates information on HCC micronecrosis, collecting large dataset of HCC histopathological images. This approach could assist clinicians in analyzing HCC patient survival and precisely locating and visualizing necrotic tissues that affect prognosis. Following the research paradigm outlined in this paper, other prognostic biomarker integration models with GCN could be developed, significantly enhancing the predictive performance and interpretability of prognostic model.
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OBJECTIVES: The study aimed to investigate the correlation between medial tibial slope (MTS) and lateral tibial slope (LTS) on magnetic resonance imaging (MRI), MTS measured by different imaging, and the intra- and interobserver reliability of measurements between reviewers with gaps of experience over 10 years. PATIENTS AND METHODS: This retrospective study included 97 patients (93 males, 4 females; mean age: 30.8±8.3 years; range, 17 to 49 years) with anterior cruciate ligament (ACL) injuries who subsequently underwent double-bundle ACL reconstruction by a single surgeon between January 2005 and December 2014. The MTS was measured on lateral knee radiographs, and MTS and LTS were measured on MRIs. Three different reviewers, including a postgraduate year doctor, an orthopedic resident, and an attending orthopedic surgeon, performed the measurements. Each reviewer measured the slope of the same image three times. The correlations of MTS on radiographs and MTS/LTS on MRIs were calculated. Intra- and interobserver reliability were evaluated. RESULTS: The average MTS and LTS measured on MRI were not significantly different (6.4° and 6.9°, respectively; p=0.268) and exhibited a moderate positive correlation (r=0.544, p<0.001). The average MTS on radiographs was significantly greater than that on MRI (10.5° and 6.4°, respectively; p<0.001) with a low positive correlation (r=0.480, p<0.001). The intraobserver reliability of the postgraduate year doctor, the orthopedic resident, and the attending orthopedic surgeon were moderate to excellent. The interobserver reliability of MTS on radiographs was excellent (intraclass correlation coefficient [ICC]=0.925; p<0.001). The interobserver reliability of MTS on MRI as well as LTS on MRI was good (ICC=0.755 and 820, respectively; all p values <0.001). CONCLUSION: Average MTS and LTS measured on MRI in patients with ACL injury exhibited a moderate positive correlation. The average MTS measured on radiographs was significantly greater than that on MRI with a low positive correlation.
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Lesões do Ligamento Cruzado Anterior , Imageamento por Ressonância Magnética , Tíbia , Humanos , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Adolescente , Estudos Retrospectivos , Adulto , Tíbia/diagnóstico por imagem , Adulto Jovem , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Reconstrução do Ligamento Cruzado Anterior , Variações Dependentes do Observador , Radiografia/métodos , Articulação do Joelho/diagnóstico por imagem , Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior/cirurgiaRESUMO
PURPOSE: Multifaceted factors contribute to inferior outcomes following anterior cruciate ligament (ACL) reconstruction surgery. A particular focus is placed on the posterior tibial slope (PTS). This study introduces the integration of machine learning and artificial intelligence (AI) for efficient measurements of tibial slopes on magnetic resonance imaging images as a promising solution. This advancement aims to enhance risk stratification, diagnostic insights, intervention prognosis and surgical planning for ACL injuries. METHODS: Images and demographic information from 120 patients who underwent ACL reconstruction surgery were used for this study. An AI-driven model was developed to measure the posterior lateral tibial slope using the YOLOv8 algorithm. The accuracy of the lateral tibial slope, medial tibial slope and tibial longitudinal axis measurements was assessed, and the results reached high levels of reliability. This study employed machine learning and AI techniques to provide objective, consistent and efficient measurements of tibial slopes on MR images. RESULTS: Three distinct models were developed to derive AI-based measurements. The study results revealed a substantial correlation between the measurements obtained from the AI models and those obtained by the orthopaedic surgeon across three parameters: lateral tibial slope, medial tibial slope and tibial longitudinal axis. Specifically, the Pearson correlation coefficients were 0.673, 0.850 and 0.839, respectively. The Spearman rank correlation coefficients were 0.736, 0.861 and 0.738, respectively. Additionally, the interclass correlation coefficients were 0.63, 0.84 and 0.84, respectively. CONCLUSION: This study establishes that the deep learning-based method for measuring posterior tibial slopes strongly correlates with the evaluations of expert orthopaedic surgeons. The time efficiency and consistency of this technique suggest its utility in clinical practice, promising to enhance workflow, risk assessment and the customization of patient treatment plans. LEVEL OF EVIDENCE: Level III, cross-sectional diagnostic study.
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BACKGROUND: The impact of anatomical factors, such as the lateral tibial slope (LTS), on outcomes following anterior cruciate ligament (ACL) reconstruction is an area of growing interest. This study was led by the observation that patients with a higher LTS may have different recovery trajectories. HYPOTHESIS/PURPOSE: The purpose of this study was to investigate the correlation between a higher LTS and long term subjective outcomes following single-bundle ACL reconstruction. STUDY DESIGN: This study was designed as a retrospective cohort study. METHODS: The study comprised 138 patients who underwent single-bundle ACL reconstruction. The LTS was measured on preoperative radiographs. Patient-reported outcome measures (PROMs) were collected, which included the Lysholm Knee Score, UCLA Activity Score, IKDC Score, and Tegner Activity Score, over a mean follow-up duration of 137 months. RESULTS: A significant negative correlation was found between LTS and all measured PROMs (p < 0.001). The established cut-off value of LTS distinguishing between "Good" and "Fair" Lysholm scores was 8.35 degrees. Female patients have statistically significant higher LTS and lower PROMs scores than male. Patients with LTS greater than or equal to 8.35 had significantly lower PROMs, indicative of poorer functional and subjective outcomes. CONCLUSION: Our findings suggest that a higher LTS is associated with inferior subjective outcomes following single-bundle ACL reconstruction in long term. The LTS cut-off value of 8.35 degrees could potentially be used as a reference in preoperative planning and patient counseling. CLINICAL RELEVANCE: Understanding the relationship between LTS and ACL reconstruction outcomes could inform surgical planning and postoperative management. These findings highlight the need to consider anatomical variances, such as LTS, when assessing patient-specific risks and recovery expectations, contributing to the advancement of personalized care in sports medicine.
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Reconstrução do Ligamento Cruzado Anterior , Medidas de Resultados Relatados pelo Paciente , Tíbia , Humanos , Reconstrução do Ligamento Cruzado Anterior/métodos , Masculino , Feminino , Estudos Retrospectivos , Adulto , Tíbia/cirurgia , Tíbia/diagnóstico por imagem , Adulto Jovem , Resultado do Tratamento , Adolescente , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos de Coortes , Seguimentos , Fatores de TempoRESUMO
PURPOSE: To determine if there is a correlation between lateral tibial slope and long-term clinical results in patients who underwent double-bundle ACL reconstruction. METHODS: We retrospectively reviewed patients that received double-bundle ACL reconstruction at a single institution by a single surgeon from January 2011 to December 2014. All the magnetic resonance imaging were reviewed and lateral tibial slopes (LTS) were recorded by an experienced surgeon and rechecked by the other two authors of this study that specialized in orthopedic knee surgery. The relationship between PROMs measurement and lateral tibial slope were analyzed. The patients were then separated into two groups (LTS > 7.4° and < 7.4°) according to the previous study. RESULTS: A total of 119 patients were enrolled in this study. All enrolled patients were followed for at least 8 years. The PROMS result were negatively correlated with the lateral tibial slope (p values all < 0.001). The patients with high lateral tibial slope had significantly lower PROMS values (Lysholm 94.26 ± 5.61 vs 80.15 ± 8.28, p = 0.013; IKDC 82.99 ± 4.55 vs 70.09 ± 7.15, p = 0.003; Tegner 9.32 ± 0.95 vs 6.85 ± 1.99, p < 0.001). Finally, the LTS cutoff value between patients with "Good" and "Fair" Lysholm score in our study was 7.55 degrees. CONCLUSIONS: Patients with high lateral tibial slope may result in inferior long-term subjective outcomes. The using of double-bundle ACL reconstruction along cannot overcome the negative impact caused by steep lateral tibial slope. A lateral tibial slope of 7.55° may be used as a cut-off for a good clinical outcome. LEVEL OF EVIDENCE: III retrospective comparative prognostic trial.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Humanos , Estudos Retrospectivos , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Articulação do Joelho/cirurgia , Tíbia/cirurgiaRESUMO
This study assesses the efficacy and safety of dapagliflozin in Chinese patients with heart failure through a systematic review of randomized controlled trials from PubMed and the China National Knowledge Infrastructure databases. Focusing on 977 patients across eight trials, the meta-analysis used Review Manager 5.4.1 for data analysis. Key findings include a significant reduction in N-terminal pro-B-type natriuretic peptide levels (standardized mean difference: -2.88, 95% CI: -4.31 to -1.44, p<0.001) and an increase in left ventricular ejection fraction (weighted mean difference: 5.10, 95% CI: 2.32 to 10.32, p<0.001). However, changes in left ventricular end-diastolic diameter were not significant (weighted mean difference: -1.33, 95% CI: -2.80 to 0.15, p=0.08) and the relative risk of adverse reactions was comparable between the control and observation groups (RR: 1.17, 95% CI: 0.82 to 1.68, p=0.38). Overall, dapagliflozin demonstrates good efficacy and safety in treating heart failure in this population.
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Insuficiência Cardíaca , Função Ventricular Esquerda , Humanos , Volume Sistólico , Insuficiência Cardíaca/tratamento farmacológico , Compostos Benzidrílicos/efeitos adversosRESUMO
BACKGROUND: Abnormal myocardial Nav1.5 expression and function cause lethal ventricular arrhythmias during myocardial ischemia-reperfusion (I/R). Protein inhibitor of activated STAT Y (PIASy)-mediated caveolin-3 (Cav-3) SUMO modification affects Cav-3 binding to the voltage-gated sodium channel 1.5 (Nav1.5). PIASy activity is increased after myocardial I/R, but it is unclear whether this is attributable to plasma membrane Nav1.5 downregulation and ventricular arrhythmias. METHODS: Using recombinant adeno-associated virus subtype 9 (AAV9), rat cardiac PIASy was silenced using intraventricular injection of PIASy short hairpin RNA (shRNA). After two weeks, rat hearts were subjected to I/R and electrocardiography was performed to assess malignant arrhythmias. Tissues from peri-infarct areas of the left ventricle were collected for molecular biological measurements. RESULTS: PIASy was upregulated by I/R (P < 0.01), with increased SUMO2/3 modification of Cav-3 and reduced membrane Nav1.5 density (P < 0.01). AAV9-PIASy shRNA intraventricular injection into the rat heart downregulated PIASy after I/R, at both mRNA and protein levels (P < 0.05 vs. Scramble-shRNA + I/R group), decreased SUMO-modified Cav-3 levels, enhanced Cav-3 binding to Nav1.5, and prevented I/R-induced decrease of Nav1.5 and Cav-3 co-localization in the intercalated disc and lateral membrane. PIASy silencing in rat hearts reduced I/R-induced fatal arrhythmias, which was reflected by a modest decrease in the duration of ventricular fibrillation (VF; P < 0.05 vs. Scramble-shRNA + I/R group) and a significantly reduced arrhythmia score (P < 0.01 vs. Scramble-shRNA + I/R group). The anti-arrhythmic effects of PIASy silencing were also evidenced by decreased episodes of ventricular tachycardia (VT), sustained VT and VF, especially at the time 5-10 min after ischemia (P < 0.05 vs. Scramble-shRNA + IR group). Using in vitro human embryonic kidney 293 T (HEK293T) cells and isolated adult rat cardiomyocyte models exposed to hypoxia/reoxygenation (H/R), we confirmed that increased PIASy promoted Cav-3 modification by SUMO2/3 and Nav1.5/Cav-3 dissociation after H/R. Mutation of SUMO consensus lysine sites in Cav-3 (K38R or K144R) altered the membrane expression levels of Nav1.5 and Cav-3 before and after H/R in HEK293T cells. CONCLUSIONS: I/R-induced cardiac PIASy activation increased Cav-3 SUMOylation by SUMO2/3 and dysregulated Nav1.5-related ventricular arrhythmias. Cardiac-targeted PIASy silencing mediated Cav-3 deSUMOylation and partially prevented I/R-induced Nav1.5 downregulation in the plasma membrane of cardiomyocytes, and subsequent ventricular arrhythmias in rats. PIASy was identified as a potential therapeutic target for life-threatening arrhythmias in patients with ischemic heart diseases.
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Antiarrítmicos , Caveolina 3 , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas Inibidoras de STAT Ativados/genética , Animais , Arritmias Cardíacas/genética , Caveolina 3/genética , Caveolina 3/metabolismo , Regulação para Baixo , Inativação Gênica , Células HEK293 , Humanos , Isquemia/complicações , Lisina/genética , Lisina/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , RNA Mensageiro , RNA Interferente Pequeno , Ratos , Reperfusão/efeitos adversosRESUMO
OBJECTIVE: To evaluate the analgesic effect of ultrasound-guided subcostal anterior quadratus lumborum block (QLB) for laparoscopic radical gastrectomy surgery. METHODS: Patients (aged 20-65 years, ASA I - II, and weighing 40-75 kg) scheduled for elective laparoscopic radical gastrectomy were enrolled in the current study. Sixty patients were randomly assigned to two groups by computer-generated randomization codes: an ultrasound-guided oblique subcostal transversus abdominis plane block (TAPB) group (group T, n=30) or an ultrasound-guided subcostal anterior QLB group (group Q, n=30). In both groups, bilateral ultrasound-guided oblique subcostal TAPB and subcostal anterior QLB were performed before general anesthesia with 0.25% ropivacaine 0.5 mL/kg. For postoperative management, all patients received patient-controlled intravenous analgesia (PCIA) with nalbuphine and sufentanil after surgery, maintaining visual analogue scale (VAS) scores ≤4 within 48 h. The intraoperative consumption of remifentanil, the requirement for sufentanil as a rescue analgesic, and the VAS scores at rest and coughing were recorded at 1, 6, 12, 24 and 48 h after surgery. The recovery (extubation time after surgery, first ambulation time, first flatus time and length of postoperative hospital stay) and the adverse events (nausea and vomiting, skin pruritus, respiratory depression and nerve-block related complications) were observed and recorded. The primary outcome was the perioperative consumption of opioids. RESULTS: Compared with group T, the intraoperative consumption of remifentanil, requirement for sufentanil and the frequency of PCIA were reduced in group Q. Meanwhile, VAS scores at all points of observation were significantly lower in group Q than in group T. Patients in group Q were also associated with shorter time to first out-of-bed activity and flatus, and shorter length of postoperative hospital stay than group T (P<0.05). There were no skin pruritus, respiratory depression or nerve-block related complications in both groups. CONCLUSION: Compared with ultrasound-guided oblique subcostal TAPB, ultrasound-guided subcostal anterior QLB provided greater opioid-sparing effect, lower visual analogue scores, and shorter postoperative hospital stay for laparoscopic radical gastrectomy.
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Músculos Abdominais/diagnóstico por imagem , Gastrectomia/métodos , Nalbufina/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Remifentanil/administração & dosagem , Ropivacaina/administração & dosagem , Sufentanil/administração & dosagem , Adulto , Anestesia Geral , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Bloqueio Nervoso/métodos , Medição da Dor , Distribuição Aleatória , Ultrassonografia de Intervenção , Adulto JovemRESUMO
BACKGROUND: Acute lung injury (ALI), manifested by progressive hypoxemia and respiratory distress, is associated with high morbidity and mortality, which lacks the effective therapies in clinics. Our previous studies demonstrated that maresin1 (MaR1), a specialized proresolving mediator, could effectively mitigate the inflammation of lipopolysaccharide (LPS)-induced ALI. However, whether MaR1 impacts the macrophage polarization to alleviate ALI remains unclear. Our study explored the effects and underlying mechanisms of MaR1 on the macrophage phenotypes in ALI. MATERIAL AND METHODS: Male BALB/c mice were subjected to endotracheal instillation of LPS to induce ALI and then intravenously injected with MaR1 or normal saline. Intraperitoneal administration of peroxisome proliferator-activated receptor-γ (PPAR-γ) inhibitor GW9662 was given 30 mins before MaR1. We measured the pathohistologic changes, pulmonary edema, inflammatory cytokines, and the flow cytometry of macrophage phenotypes. RESULTS: Our results illustrated that MaR1 ameliorated lung injury and increased monocyte or macrophage recruitment and the release of anti-inflammatory cytokines. The flow cytometry showed that MaR1 promoted polarization of CD11c-CD206+ (M2) macrophages and inhibited polarization of CD11c+CD206- (M1) macrophages. Besides, the western blotting revealed that MaR1 increased the expression of PPAR-γ. The pretreatment with PPAR-γ antagonist GW9662 could significantly suppress the polarization of M2 macrophages and antagonize the protective effects of MaR1 on LPS-stimulated ALI. CONCLUSIONS: MaR1 was able to promote M2 macrophage polarization by reversing LPS-mediated PPAR-γ inhibition, thereby expediting the recovery of LPS-stimulated ALI.
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Lesão Pulmonar Aguda/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/farmacologia , Macrófagos/efeitos dos fármacos , PPAR gama/agonistas , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Anilidas/administração & dosagem , Animais , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/uso terapêutico , Humanos , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , PPAR gama/antagonistas & inibidores , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologiaRESUMO
Renal cancer is a common genitourinary malignance, of which clear cell renal cell carcinoma (ccRCC) has high aggressiveness and leads to most cancer-related deaths. Identification of sensitive and reliable biomarkers for predicting tumorigenesis and progression has great significance in guiding the diagnosis and treatment of ccRCC. Here, we identified 2397 common differentially expressed genes (DEGs) using paired normal and tumor ccRCC tissues from GSE53757 and The Cancer Genome Atlas (TCGA). Then, we performed weighted gene co-expression network analysis and protein-protein interaction network analysis, 17 candidate hub genes were identified. These candidate hub genes were further validated in GSE36895 and Oncomine database and 14 real hub genes were identified. All the hub genes were up-regulated and significantly positively correlated with pathological stage and histologic grade of ccRCC. Survival analysis showed that the higher expression level of each hub gene tended to predict a worse clinical outcome. ROC analysis showed that all the hub genes can accurately distinguish between tumor and normal samples, and between early stage and advanced stage ccRCC. Moreover, all the hub genes were positively associated with distant metastasis, lymph node infiltration, tumor recurrence and the expression of MKi67, suggesting these genes might promote tumor proliferation, invasion and metastasis. Furthermore, the functional annotation demonstrated that most genes were enriched in cell-cycle related biological function. In summary, our study identified 14 potential biomarkers for predicting tumorigenesis and progression, which might contribute to early diagnosis, prognosis prediction and therapeutic intervention.
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Biomarcadores Tumorais/genética , Carcinoma de Células Renais/diagnóstico , Perfilação da Expressão Gênica/métodos , Neoplasias Renais/diagnóstico , Regulação para Cima , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Progressão da Doença , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Mapas de Interação de Proteínas , Análise de SobrevidaRESUMO
CXCL14 is a relatively novel chemokine with a wide spectrum of biological activities. The present study was designed to investigate whether CXCL14 overexpression attenuates sepsis-associated acute kidney injury (AKI) in mice. Sepsis model has been established by cecal ligation and puncture (CLP). CLP induced AKI in mice as assessed by increased renal neutrophil gelatinase-associated lipocalin (NGAL) expression and serum creatinine levels. We found that renal CXCL14 expression in the kidney was significantly decreased at 12 hours after CLP. Correlation analysis demonstrated a negative association between renal CXCL14 expression and AKI markers including serum creatinine and renal NGAL. Moreover, CXCL14 overexpression reduced cytokine (TNF-α, IL-6, and IL-1ß) production and NGAL expression in the kidney and decreased serum creatinine levels. In vivo and in vitro experiments found that CXCL14 overexpression inhibited M1 macrophage polarization but increased M2 polarization. Together, these results suggest that CXCL14 overexpression attenuates sepsis-associated AKI probably through the downregulation of macrophages-derived cytokine production. However, further studies are required to elucidate the underlying mechanism.
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Quimiocinas CXC/metabolismo , Sepse/metabolismo , Animais , Western Blotting , Quimiocinas CXC/genética , Creatinina/metabolismo , Ensaio de Imunoadsorção Enzimática , Rim/metabolismo , Rim/patologia , Lentivirus/genética , Ligadura/efeitos adversos , Lipocalina-2/genética , Lipocalina-2/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Punções/efeitos adversos , Células RAW 264.7 , Reação em Cadeia da Polimerase em Tempo Real , Sepse/genéticaRESUMO
Breast cancer is the most common type of female cancer. Reactive oxygen species (ROS) are vital in regulating signaling pathways that control cell survival and cell proliferation. Chemotherapeutic drugs such as anthracyclines induce cell death via ROS induction. Chemoresistance development is associated with adaptive response to oxidative stress. NRF2 is the main regulator of cytoprotective response to oxidative stress. NRF2 can enhance cell growth, antioxidant expression, and chemoresistance by providing growth advantage for malignant cells. Previously, we identified BQ323636.1 (BQ), a novel splice variant of nuclear co-repressor NCOR2, which can robustly predict tamoxifen resistance in primary breast cancer. In this study, we found that BQ was overexpressed in epirubicin-resistant cells and demonstrated that BQ overexpression could reduce the levels of epirubicin-induced ROS and confer epirubicin resistance. In vivo analysis using tissue microarray of primary breast cancer showed direct correlation between BQ expression and chemoresistance. In vitro experiments showed BQ could modulate NRF2 transcriptional activity and upregulate antioxidants. Luciferase reporter assays showed that although NCOR2 repressed the transcriptional activity of NRF2, the presence of BQ reduced this repressive activity. Co-immunoprecipitation confirmed that NCOR2 could bind to NRF2 and that this interaction was compromised by BQ overexpression, leading to increased transcriptional activity in NRF2. Our findings suggest BQ can regulate the NRF2 signaling pathway via interference with NCOR2 suppressive activity and reveals a novel role for BQ as a modulator of chemoresistance in breast cancer.
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The activation of NLRP3 inflammasome and NF-κB pathway, associating with oxidativestress, have been implicated in the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). NecroX-5 has been reported to exhibit theeffectsofanti-oxidation and anti-stress in various diseases. However, the role of NecroX-5 in ALI has not been explicitly demonstrated. The aim of this study was to explore the therapeutic effects and potential mechanism action of NecroX-5 on ALI. Here, we found that NecroX-5 pretreatment dramatically diminished the levels of IL-1ß, IL-18 and ROS in in RAW264.7 cells challenged with LPS and ATP. Furthermore, NecroX-5 suppressed the activation of NLRP3 inflammasome and NF-κB signalpathway. In addition, NecroX-5 also inhibited the thioredoxin-interacting protein (TXNIP) expression. In vivo, NecroX-5 reduced the LPS-induced lung histopathological injury, the number of TUNEL-positive cells, lung wet/dry (W/D) ratio, levels of total protein and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) in mice. Additionally, LPS-induced upregulation of myeloperoxidase (MPO), ROS production and malondialdehyde (MDA) were inhibited by NecroX-5 administration. Thus, our results demonstrate that NecroX-5 protects against LPS-induced ALI by inhibiting TXNIP/NLRP3 and NF-κB.
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Anti-Inflamatórios/uso terapêutico , Proteínas de Transporte/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Pulmão/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Sulfonas/uso terapêutico , Tiorredoxinas/metabolismo , Animais , Proteínas de Transporte/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Lipopolissacarídeos/imunologia , Pulmão/patologia , Masculino , Camundongos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peroxidase/metabolismo , Células RAW 264.7 , Síndrome do Desconforto Respiratório/imunologia , Transdução de Sinais , Tiorredoxinas/genéticaRESUMO
Enhanced recovery after cesarean (ERAC) delivery is an evidence-based, multi-disciplinary approach throughout pre-, intra-, post-operative period. The ultimate goal of ERAC is to enhance recovery and improve the maternal and neonatal outcomes. This review highlights the role of anesthesiologist in ERAC protocols. This review provided a general introduction of ERAC including the purposes and the essential elements of ERAC protocols. The tool used for evaluating the quality of ERAC (ObsQoR-11) was discussed. The role of anesthesiologist in ERAC should cover the areas including management of peri-operative hypotension, prevention and treatment of intra- and post-operative nausea and vomiting, prevention of hypothermia and multi-modal peri-operative pain management, and active pre-operative management of unplanned conversion of labor analgesia to cesarean delivery anesthesia. Although some concerns still remain, ERAC implementation should not be delayed. Regular assessment and process improvement should be imbedded into the protocol. Further high-quality studies are warranted to demonstrate the effectiveness and efficacy of the ERAC protocol.
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Cesárea/métodos , Recuperação Pós-Cirúrgica Melhorada , Anestesiologistas , Feminino , Humanos , Náusea e Vômito Pós-Operatórios , GravidezRESUMO
BACKGROUND: Obstetric hemorrhage is a major cause of maternal death during cesarean delivery. The objective of this retrospective observational study was to evaluate the efficacy and safety of intra-operative cell salvage (IOCS) in cesarean section. METHODS: We included a total of 361 patients diagnosed with central placenta previa who underwent cesarean section from May 2016 to December 2018. In this study, 196 patients received autologous transfusion using IOCS (IOCS group) and 165 patients accepted allogeneic blood transfusion (ABT group). Propensity score matched analysis was performed to balance differences in the baseline variables between the IOCS group and ABT group. Patients in the IOCS group were matched 1:1 to patients in the ABT group. RESULTS: After propensity score matching, 137 pairs of cases between the two groups were successfully matched and no significant differences in baseline characteristics were found between the IOCS group and ABT group. Patients in the IOCS group were associated with significantly shorter length of hospital stay, compared with ABT group (8.9â±â4.1 days vs. 10.3â±â5.2 days, tâ=â-2.506, Pâ=â0.013). The postoperative length of hospital stay was 5.3â±â1.4 days for patients in the IOCS group and 6.6â±â3.6 days for those in the ABT group (tâ=â-4.056, Pâ<â0.001). The post-operative hemoglobin level in the IOCS group and ABT group was 101.3â±â15.4 and 96.3â±â16.6âg/L, respectively, which were significantly different (tâ=â2.615, Pâ=â0.009). Allogeneic red blood cell transfusion was significantly lower at 0 unit (range: 0-11.5 units) in the IOCS group when compared with 2 units (range: 1-20 units) in the ABT group (Pâ<â0.001). CONCLUSIONS: This retrospective observational study using propensity score matched analysis suggested that IOCS was associated with shorter length of postoperative hospital stay and higher post-operative hemoglobin levels during cesarean delivery.