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Patients with ulcerative colitis are at increased risk for colorectal neoplasia compared to the general population. The risk factors include family history of colorectal cancer, wide extent of colitis, disease duration, cumulative inflammatory burden, and primary sclerosing cholangitis. Here, we report a case of colorectal neoplasia developed in a patient with ulcerative colitis.
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BACKGROUND: While some lung adenocarcinoma (LUAD) patients benefit long-term from treatment with immune checkpoint inhibitors, the sad reality is that a considerable proportion of patients do not. The classification of the LUAD tumor microenvironment (TME) can be used to conceptually comprehend primary resistance mechanisms. In addition, the most recent research demonstrates that the release of damage-associated molecular pattern (DAMP) in TME by immunogenic cell death (ICD) may contribute to the adaptive immune response. Currently, however, there is no such comprehensive research on this topic in LUAD patients. Therefore, we set out to investigate how to reverse the poor infiltration characteristics of immune cells and boost antitumor immunity by identifying DAMP model. METHODS: In this study, ICD-related DAMP genes were selected to investigate their effects on the prognosis of LUAD. To create a risk signature using the TCGA-LUAD cohort, the univariate COX regression and the least absolute shrinkage and selection operator regression were carried out, and the results were verified in a GEO dataset. Subsequently, the multivariate COX regression was applied to establish a prognostic nomogram. And the ESTIMATE and ssGSEA algorithms were utilized to analyze immune activity and the TIDE algorithm was for responsiveness to immunotherapy. Moreover, clinical tissue samples were used to verify the differential expression of 9 DAMP genes in the signature. RESULTS: We identified two distinct DAMP molecular subtypes, and there are remarkable differences in survival probability between the two subtypes, and patients with higher levels of DAMP-related genes are "hot tumors" with increased immune activity. In addition, 9 DAMP genes were selected as prognostic signature genes, and clinical outcomes and immunotherapy response were better for participants in the low-risk group. Importantly, according to the area under the curve (AUC) value in evaluating the efficacy of immunotherapy, this signature is superior to existing predictors, such as PD-L1 and TIDE. CONCLUSIONS: Our study suggests ICD plays an important part in modeling the TME of LUAD patients. And this signature could be utilized as a reliable predictor to estimate clinical outcomes and predict immunotherapy efficacy among LUAD patients.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Morte Celular Imunogênica , Imunoterapia , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/terapia , Algoritmos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Prognóstico , Microambiente Tumoral/genéticaRESUMO
BACKGROUND AND AIMS: Gastrointestinal T-cell and NK/T-cell lymphomas are relatively rare and may be difficult to diagnose. Therefore, we performed a retrospective study of the clinical, endoscopic and pathological characteristics of these lymphomas, to provide additional data on this issue. METHODS: From April 2013 to April 2021, consecutive patients diagnosed with primary gastrointestinal T-cell and NK/T-cell lymphomas were retrospectively reviewed. Their medical histories, laboratory, imaging, endoscopic, and pathology results were analyzed. RESULTS: Forty-two patients were finally chosen, among whom, 24 patients had ENKTCL, 9 patients had MEITL, 2 patients had ALCL, ALK-, 1 patient had ALCL, ALK+, and 6 patients had PTCL, NOS. The median age of all the patients was 48 years old, and 73.81% (31 patients) were male. The patients' symptoms were abdominal pain, diarrhea, gastrointestinal bleeding, weight loss, fever, and others. The endoscopic results of 26 patients could be traced, and 69.23% of the patients showed multiple lesions. Ulcerative and ulceroinfiltrative lesions were common. Among the pathologic findings, necrosis, ulceration, and crypt atrophy were commonly found while epitheliotropism was relatively less common. Twelve patients (28.57%) had a history of misdiagnosis. After a median follow-up time of 26.9 months, 26 patients (66.70%) died of the disease. The median overall survival time was 8 months. CONCLUSIONS: These lymphomas had nonspecific clinical manifestations, various endoscopic features, and were likely to be misdiagnosed as other diseases. The prognosis is still poor, and more in-depth research is needed to develop more precise treatments.
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Linfoma de Células T Periférico , Linfócitos T , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Linfócitos T/patologia , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/terapia , Prognóstico , Receptores Proteína Tirosina QuinasesRESUMO
Obscure gastrointestinal bleeding (OGIB) is bleeding of unknown origin after a negative initial or primary colonoscopy and upper endoscopy result. Small bowel bleeding accounts for 5% of GI bleeding but it is the most prominent cause of OGIB. We present a case with an obscure diminutive polypoid vascular anomaly of small intestine. In this case, intraoperative enteroscopy seems to be the last trump card for OGIB, especially for large amount loss of blood. It not only helped to find the obscure cause for bleeding, but also preserved the small intestine.
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OBJECTIVE: To profile gut microbiome-associated metabolites in serum and investigate whether these metabolites could distinguish individuals with colorectal cancer (CRC) or adenoma from normal healthy individuals. DESIGN: Integrated analysis of untargeted serum metabolomics by liquid chromatography-mass spectrometry and metagenome sequencing of paired faecal samples was applied to identify gut microbiome-associated metabolites with significantly altered abundance in patients with CRC and adenoma. The ability of these metabolites to discriminate between CRC and colorectal adenoma was tested by targeted metabolomic analysis. A model based on gut microbiome-associated metabolites was established and evaluated in an independent validation cohort. RESULTS: In total, 885 serum metabolites were significantly altered in both CRC and adenoma, including eight gut microbiome-associated serum metabolites (GMSM panel) that were reproducibly detected by both targeted and untargeted metabolomics analysis and accurately discriminated CRC and adenoma from normal samples. A GMSM panel-based model to predict CRC and colorectal adenoma yielded an area under the curve (AUC) of 0.98 (95% CI 0.94 to 1.00) in the modelling cohort and an AUC of 0.92 (83.5% sensitivity, 84.9% specificity) in the validation cohort. The GMSM model was significantly superior to the clinical marker carcinoembryonic antigen among samples within the validation cohort (AUC 0.92 vs 0.72) and also showed promising diagnostic accuracy for adenomas (AUC=0.84) and early-stage CRC (AUC=0.93). CONCLUSION: Gut microbiome reprogramming in patients with CRC is associated with alterations of the serum metabolome, and GMSMs have potential applications for CRC and adenoma detection.
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Adenoma , Neoplasias Colorretais , Microbioma Gastrointestinal , Adenoma/diagnóstico , Biomarcadores Tumorais , Neoplasias Colorretais/genética , Microbioma Gastrointestinal/genética , Humanos , Metaboloma , MetagenomaRESUMO
BACKGROUND: The aim of this work is to combine radiological and pathological information of tumor to develop a signature for pretreatment prediction of discrepancies of pathological response at several centers and restage patients with locally advanced rectal cancer (LARC) for individualized treatment planning. PATIENTS AND METHODS: A total of 981 consecutive patients with evaluation of response according to tumor regression grade (TRG) who received nCRT were retrospectively recruited from four hospitals (primary cohort and external validation cohort 1-3); both pretreatment multiparametric MRI (mp-MRI) and whole slide image (WSI) of biopsy specimens were available for each patient. Quantitative image features were extracted from mp-MRI and WSI and used to construct a radiopathomics signature (RPS) powered by an artificial-intelligence model. Models based on mp-MRI or WSI alone were also constructed for comparison. RESULTS: The RPS showed overall accuracy of 79.66-87.66% in validation cohorts. The areas under the curve of RPS at specific response grades were 0.98 (TRG0), 0.93 (≤ TRG1), and 0.84 (≤ TRG2). RPS at each grade of pathological response revealed significant improvement compared with both signatures constructed without combining multiscale tumor information (P < 0.01). Moreover, RPS showed relevance to distinct probabilities of overall survival and disease-free survival in patients with LARC who underwent nCRT (P < 0.05). CONCLUSIONS: The results of this study suggest that radiopathomics, combining both radiological information of the whole tumor and pathological information of local lesions from biopsy, could potentially predict discrepancies of pathological response prior to nCRT for better treatment planning.
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Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias Retais , Humanos , Terapia Neoadjuvante , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Accurate failure criteria play a fundamental role in biomechanical analyses of aortic wall rupture and dissection. Experimental investigations have demonstrated a significant difference of aortic wall strengths in the circumferential and axial directions. Therefore, the isotropic von Mises stress and maximum principal stress, commonly used in computational analysis of the aortic wall, are inadequate for modeling of anisotropic failure properties. In this study, we propose a novel stress-based anisotropic failure criterion with dispersed fiber orientations. In the new failure criterion, the overall failure metric is computed by using angular integration (AI) of failure metrics in all directions. Affine rotations of fiber orientations due to finite deformation are taken into account in an anisotropic hyperelastic constitutive model. To examine fitting capability of the failure criterion, a set of off-axis uniaxial tension tests were performed on aortic tissues of four porcine individuals and 18 human ascending thoracic aortic aneurysm (ATAA) patients. The dispersed fiber failure criterion demonstrates a good fitting capability with the off-axis testing data. Under simulated biaxial stress conditions, the dispersed fiber failure criterion predicts a smaller failure envelope comparing to those predicted by the traditional anisotropic criteria without fiber dispersion, which highlights the potentially important role of fiber dispersion in the failure of the aortic wall. Our results suggest that the deformation-dependent fiber orientations need to be considered when wall strength determined from uniaxial tests are used for in vivo biomechanical analysis. More investigations are needed to determine biaxial failure properties of the aortic wall.
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Aneurisma da Aorta Torácica , Animais , Anisotropia , Fenômenos Biomecânicos , SuínosRESUMO
OBJECTIVE: Controversy exists about the optimal treatment of acute uncomplicated type B aortic dissection (auTBAD). Optimal medical therapy (OMT) provides excellent short-term outcomes, but long-term results are poor. Ideally, auTBAD patients who will fail to respond to OMT in the chronic phase could be identified and undergo thoracic endovascular aortic repair. The purpose of this study was to identify radiographic predictors of auTBAD patients who will fail to respond to OMT. METHODS: A review of the Emory aortic database from 2000 to 2017 identified 320 auTBAD patients initially treated with OMT. From this cohort, 121 patients with two or more contrast-enhanced imaging scans were available for analysis. These patients were initially divided into groups based on growth of the thoracic aorta ≥10 mm or intervention due to aneurysmal growth: growth (n = 72) and no growth (n = 49). TeraRecon (Foster City, Calif) imaging software was used to analyze characteristics of the primary intimal tear (PIT), false lumen, and overall aortic size. Finally, Cox proportional hazards models were constructed to estimate hazard ratios and to identify predictors of OMT failure. RESULTS: The mean age of all patients was 54 ± 11 years, and 67% were male. Thirty-eight patients (53%) in the growth group underwent intervention. There were no differences between groups in age, hypertension, diabetes mellitus, tobacco abuse, or chronic obstructive pulmonary disease. The distance of the PIT from the left subclavian artery in patients with auTBAD was significantly shorter in the growth group (growth, 27 mm [9-66 mm]; no growth, 77 mm [26-142 mm]; P < .01). Multivariable Cox regression analysis identified the distance of the PIT from the left subclavian artery and a thoracic aortic diameter >45 mm as independent predictors of failure of OMT. Partial false lumen thrombosis was not a predictor of aortic growth. CONCLUSIONS: The distance of the PIT from the left subclavian artery is a predictor of aortic growth in auTBAD. Patients with a primary tear located in zone 3 of the proximal descending thoracic aorta should be monitored closely and may be considered for early thoracic endovascular aortic repair in the setting of auTBAD.
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Aneurisma da Aorta Torácica/diagnóstico por imagem , Dissecção Aórtica/diagnóstico por imagem , Aortografia/métodos , Angiografia por Tomografia Computadorizada , Artéria Subclávia/diagnóstico por imagem , Adulto , Idoso , Pontos de Referência Anatômicos , Dissecção Aórtica/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Aneurisma da Aorta Torácica/tratamento farmacológico , Bases de Dados Factuais , Progressão da Doença , Feminino , Georgia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Falha de TratamentoRESUMO
Hyperhomocysteinemia (HHcy) has been shown to promote vascular inflammation and atherosclerosis, but the underlying mechanisms remain largely unknown. The NLRP3 inflammasome has been identified as the cellular machinery responsible for activation of inflammatory processes. In this study, we hypothesized that the activation of NLRP3 inflammasomes contributes to HHcy-induced inflammation and atherosclerosis. ApoE-/- mice were fed regular chow, high-fat (HF) diet, or HF plus high methionine diet to induce HHcy. To assess the role of NLRP3 inflammasomes in HHcy-aggravated atherosclerosis, NLRP3 shRNA viral suspension was injected via tail vein to knock down the NLRP3 gene. Increased plasma levels of IL-1ß and IL-18, aggravated macrophage infiltration into atherosclerotic lesions, and accelerated development of atherosclerosis were detected in HHcy mice as compared with control mice, and were associated with the activation of NLRP3 inflammasomes. Silencing the NLRP3 gene significantly suppressed NLRP3 inflammasome activation, reduced plasma levels of proinflammatory cytokines, attenuated macrophage infiltration and improved HHcy-induced atherosclerosis. We also examined the effect of homocysteine (Hcy) on NLRP3 inflammasome activation in THP-1-differentiated macrophages in the presence or absence of NLRP3 siRNA or the caspase-1 inhibitor Z-WEHD-FMK. We found that Hcy activated NLRP3 inflammasomes and promoted subsequent production of IL-1ß and IL-18 in macrophages, which were blocked by NLRP3 gene silencing or Z-WEHD-FMK. As reactive oxygen species (ROS) may have a central role in NLRP3 inflammasome activation, we next investigated whether antioxidant N-acetyl-l-cysteine (NAC) prevented Hcy-induced NLRP3 inflammasome activation in macrophages. We found Hcy-induced NLRP3 inflammasome activation was abolished by NAC. Treatment with NAC in HHcy mice also suppressed NLRP3 inflammasome activation and improved HHcy-induced atherosclerosis. These data suggest that the activation of NLRP3 inflammasomes contributes to HHcy-aggravated inflammation and atherosclerosis in apoE-/- mice. Hcy activates NLRP3 inflammasomes in ROS-dependent pathway in macrophages. These results may have implication for the treatment of HHcy-associated cardiovascular diseases.
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Apolipoproteínas E/genética , Aterosclerose/metabolismo , Hiper-Homocisteinemia/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genéticaRESUMO
Background and aims: Cap polyposis (CP) is a rare kind of benign disease, and the majority of previously published relevant articles involve a small number of patients. Hence, we summarized our experience to contribute additional data, hoping to raise awareness of this disease. Methods: From 1 January 2017 to 1 November 2021, consecutive patients diagnosed with CP were retrospectively reviewed. Their medical histories, and laboratory, imaging, endoscopic, and pathology results were analyzed. We made telephone calls to the patients and searched for the information in our electronic medical records to obtain the follow-up results. Results: Forty-one patients were chosen for analysis. The median age of the patients was 20 years old, and 90.24% (37 patients) of the patients were male. The majority of the patients presented with hematochezia. The rectum was the most commonly affected site, and the Helicobacter pylori infection rate was high. There were multiple and combined treatments for these patients. These treatments can be divided into 3 main categories: medical therapy, endotherapy and surgery. Medical therapy helped to diminish the size of but the polyps were difficult to resolve; however, the patients' symptoms could be diminished. Twenty-three patients underwent surgical resection, and 12 patients received endotherapy. We further compared the two methods of polyp resection. Both endotherapy and surgery were safe, and the recurrence risk was not significantly different between the two kinds of therapy (p = 0.321). Conclusion: The clinical improvement of medical treatments was not satisfactory, and endotherapy or surgical resection could remove the polyposis and provide temporary relief, but the recurrence rates were high.
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Nuclei classification provides valuable information for histopathology image analysis. However, the large variations in the appearance of different nuclei types cause difficulties in identifying nuclei. Most neural network based methods are affected by the local receptive field of convolutions, and pay less attention to the spatial distribution of nuclei or the irregular contour shape of a nucleus. In this paper, we first propose a novel polygon-structure feature learning mechanism that transforms a nucleus contour into a sequence of points sampled in order, and employ a recurrent neural network that aggregates the sequential change in distance between key points to obtain learnable shape features. Next, we convert a histopathology image into a graph structure with nuclei as nodes, and build a graph neural network to embed the spatial distribution of nuclei into their representations. To capture the correlations between the categories of nuclei and their surrounding tissue patterns, we further introduce edge features that are defined as the background textures between adjacent nuclei. Lastly, we integrate both polygon and graph structure learning mechanisms into a whole framework that can extract intra and inter-nucleus structural characteristics for nuclei classification. Experimental results show that the proposed framework achieves significant improvements compared to the previous methods. Code and data are made available via https://github.com/lhaof/SENC.
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Fatty acid binding protein 5 (FABP5) is an intracellular chaperone of fatty acid molecules that regulates lipid metabolism and cell growth. However, its role in intestinal inflammation remains enigmatic. Through examination of human tissue samples and single-cell data, we observed a significant upregulation of FABP5 within the mucosa of patients afflicted with ulcerative colitis (UC) and Crohn's disease (CD), predominantly localized in intestinal macrophages. Herein, we investigate the regulation of FABP5-IN-1, a FABP5 inhibitor, on various cells of the gut in an inflammatory environment. Our investigations confirmed that FABP5 ameliorates DSS-induced colitis in mice by impeding the differentiation of macrophages into M1 macrophages in vitro and in vivo. Furthermore, following FABP5-IN-1 intervention, we observed a notable restoration of intestinal goblet cells and tuft cells, even under inflammatory conditions. Additionally, FABP5-IN-1 exhibits a protective effect against DSS-induced colitis by promoting the polarization of macrophages towards the M2 phenotype in vivo. In summary, FABP5-IN-1 confers protection against DSS-induced acute colitis through a multifaceted approach, encompassing the reduction of inflammatory macrophage infiltration, macrophage polarization, regulating Th17/Treg cells to play an anti-inflammatory role in IBD. The implications for IBD are underscored by the comprehensive in vivo and in vitro experiments presented in this article, thereby positioning FABP5 as a promising and novel therapeutic target for the treatment of IBD.
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Colite Ulcerativa , Colite , Doenças Inflamatórias Intestinais , Humanos , Animais , Camundongos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Colite/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Macrófagos , Anti-Inflamatórios/farmacologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Colo , Ativação de Macrófagos , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismoRESUMO
Although methods in diagnosis and therapy of hepatocellular carcinoma (HCC) have made significant progress in the past decades, the overall survival (OS) of liver cancer is still disappointing. Machine learning models have several advantages over traditional cox models in prognostic prediction. This study aimed at designing an optimal panel and constructing an optimal machine learning model in predicting prognosis for HCC. A total of 941 HCC patients with completed survival data and preoperative clinical chemistry and immunology indicators from two medical centers were included. The OCC panel was designed by univariate and multivariate cox regression analysis. Subsequently, cox model and machine-learning models were established and assessed for predicting OS and PFS in discovery cohort and internal validation cohort. The best OCC model was validated in the external validation cohort and analyzed in different subgroups. In discovery, internal and external validation cohort, C-indexes of our optimal OCC model were 0.871 (95% CI, 0.863-0.878), 0.692 (95% CI, 0.667-0.717) and 0.648 (95% CI, 0.630-0.667), respectively; the 2-year AUCs of OCC model were 0.939 (95% CI, 0.920-0.959), 0.738 (95% CI, 0.667-0.809) and 0.725 (95% CI, 0.643-0.808), respectively. For subgroup analysis of HCC patients with HBV, aged less than 65, cirrhosis or resection as first therapy, C-indexes of our optimal OCC model were 0.772 (95% CI, 0.752-0.792), 0.769 (95% CI, 0.750-0.789), 0.855 (95% CI, 0.846-0.864) and 0.760 (95% CI, 0.741-0.778), respectively. In general, the optimal OCC model based on RSF algorithm shows prognostic guidance value in HCC patients undergoing individualized treatment.
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BACKGROUND: Tertiary lymphoid structures (TLSs) exert a crucial role in the tumor microenvironment (TME), impacting tumor development, immune escape, and drug resistance. Nonetheless, the heterogeneity of TLSs in colorectal cancer (CRC) and their impact on prognosis and treatment response remain unclear. METHODS: We collected genome, transcriptome, clinicopathological information, and digital pathology images from multiple sources. An unsupervised clustering algorithm was implemented to determine diverse TLS patterns in CRC based on the expression levels of 39 TLS signature genes (TSGs). Comprehensive explorations of heterogeneity encompassing mutation landscape, TME, biological characteristics, response to immunotherapy, and drug resistance were conducted using multi-omics data. TLSscore was then developed to quantitatively assess TLS patterns of individuals for further clinical applicability. RESULTS: Three distinct TLS patterns were identified in CRC. Cluster 1 exhibited upregulation of proliferation-related pathways, high metabolic activity, and intermediate prognosis, while Cluster 2 displayed activation of stromal and carcinogenic pathways and a worse prognosis. Both Cluster 1 and Cluster 2 may potentially benefit from adjuvant chemotherapy. Cluster 3, characterized by the activation of immune regulation and activation pathways, demonstrated a favorable prognosis and enhanced responsiveness to immunotherapy. We subsequently employed a regularization algorithm to construct the TLSscore based on 9 core genes. Patients with lower TLSscore trended to prolonged prognosis and a more prominent presence of TLSs, which may benefit from immunotherapy. Conversely, those with higher TLSscore exhibited increased benefits from adjuvant chemotherapy. CONCLUSIONS: We identified distinct TLS patterns in CRC and characterized their heterogeneity through multi-omics analyses. The TLSscore held promise for guiding clinical decision-making and further advancing the field of personalized medicine in CRC.
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The present study investigated whether lowering plasma homocysteine (Hcy) with folic acid (FA) could attenuate hyperhomocysteinemia (HHcy)-associated glomerular damage and possible mechanisms. The HHcy animal model was established by intragastric administration with l-methionine in rats. FA was also given intragastrically. Plasma Hcy and creatinine and urinary albumin were measured. Histological and ultrastructural changes were observed by light and electron microscopes. The expression of alpha-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA) and transforming growth factor-beta1 (TGF-ß1) in the kidney was examined by immunohistochemical staining and western blot analysis. The administration of l-methionine induced HHcy in rats. The HHcy rats developed glomerulosclerosis and fibrosis. Plasma creatinine concentration and urinary albumin excretion were also significantly increased in HHcy rats. Effacement and extensively fusion of podocyte foot process was observed in HHcy rats, which was associated with decreased expression of nephrin protein in renal cortex of HHcy rats. Supplementation with FA lowered plasma Hcy significantly. Plasma creatinine concentration and urinary albumin excretion were also significantly attenuated by FA. Morphologically, HHcy-associated glomerulosclerosis, fibrosis, podocyte foot process effacement and loss of podocyte nephrin, were significantly improved by FA. The expressions of α-SMA, PCNA and TGF-ß1 were increased in renal cortex of HHcy rats, and which were also partially reversed by FA. These data suggest that elevated plasma Hcy is an important pathogenic factor for glomerular damage. Lowering plasma Hcy by FA can inhibit TGF-ß1 expression and attenuate HHcy-induced glomerular damage.
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Ácido Fólico/farmacologia , Hiper-Homocisteinemia/tratamento farmacológico , Hiper-Homocisteinemia/metabolismo , Glomérulos Renais/metabolismo , Rim/efeitos dos fármacos , Albuminúria/metabolismo , Animais , Proliferação de Células , Colágeno/química , Creatinina/metabolismo , Regulação da Expressão Gênica , Homocisteína/metabolismo , Imuno-Histoquímica , Córtex Renal/metabolismo , Nefropatias/metabolismo , Nefropatias/patologia , Podócitos/citologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismo , Regulação para CimaRESUMO
INTRODUCTION: The study aimed to improve the qualified rate of hand hygiene and reduce the incidence of peritonitis in peritoneal dialysis (PD) patients. METHODS: A hand hygiene questionnaire was distributed to patients during home visits and outpatient visits in 2015 and 2020. Hand-washing practices were evaluated by collecting cultures from the hands of patients after hand washing, evaluating their household environment, and recording the antimicrobial resistance of pathogenic bacteria. RESULTS: Compared to patients in 2015, patients in 2020 had fewer errors in hand washing (p < 0.05), but the rate of qualification after hand washing was lower (p < 0.01). Furthermore, patients who used hand disinfectants after washing had a higher qualified rate. Coagulase-negative staphylococcus (CNS) was the most common isolated bacteria. From 2015 to 2020, the annual incidence of CNS PD peritonitis did not decrease, while the proportion of methicillin-resistant CNS decreased. CONCLUSION: The use of hand disinfectants after standard hand washing may help reduce the incidence of peritonitis in PD patients.
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Higienizadores de Mão , Diálise Peritoneal , Peritonite , Humanos , Diálise Renal/efeitos adversos , Diálise Peritoneal/efeitos adversos , Staphylococcus , Peritonite/etiologiaRESUMO
Historically, optimal medical therapy (OMT) has been the primary therapy for acute uncomplicated type B aortic dissection (auTBAD). However, recent data suggest that OMT provides poor long-term results, and aortic remodeling induced by thoracic endovascular aortic repair (TEVAR) may improve survival. This study compares adverse events and survival among auTBAD patients receiving either TEVAR or OMT. A retrospective analysis identified 146 consecutive auTBAD patients presenting to a single institution between 1/2012 and 10/2020. Patients were divided into 2 groups based upon whether they received TEVAR (n = 50) or OMT (n = 96) at index hospitalization. Major morbidity and survival were compared between groups. 67.1% of patients presented with a Debakey IIIB dissection with maximum thoracic aortic diameter of 4.3 ± 1.0 cm. Over follow-up, 35% of OMT patients failed medical therapy and underwent intervention (n = 23 TEVAR, n = 11 open). An additional 13 died for an all-cause failure rate of 49%. The composite incidence of renal failure, stroke, spinal cord ischemia, and retrograde type A dissections was similar between groups (TEVAR:6.0% vs OMT:4.2%). In-hospital mortality was 0%. Kaplan-Meier analysis demonstrated a trend towards improved survival among the TEVAR group at 1 and 3 years but no difference in overall survival (HR:0.30, 95% CI:0.08-1.08, P = 0.066). Five-year survival was 91% with TEVAR and 82% with OMT. Complete false lumen thrombosis was achieved in 72.1% with TEVAR and 20.0% with OMT (P < 0.001). In experienced centers, there is equivalent early mortality in the treatment of auTBAD with TEVAR compared to OMT. TEVAR provides superior aortic remodeling to OMT in auTBAD, which may translate into improved long-term survival.
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Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Correção Endovascular de Aneurisma , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Fatores de RiscoRESUMO
MicroRNA-92a (miR-92a) may serve as a novel promising biomarker in multiple cancers, including colorectal cancer (CRC); however, the diagnostic accuracy and the underlying molecular mechanism of miR-92a in CRC is poorly understood. We first carried out meta-analysis and found that serum/plasma miR-92a yield better diagnostic efficacy when compared to stool samples and CRC tissues, and this finding was validated by our independent study through stool sample. Multiple bioinformatics assay indicated that miR-92a expression was positively correlated with heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) expression and closely related with the clinical characteristics of CRC. Experimental evidence showed that knockdown of HNRNPA2B1 could significantly decrease miR-92a expression and secretion in RKO cells. HNRNPA2B1 mediated miR-92a via m6A RNA modification. These findings indicate that HNRNPA2B1-m6A RNA modification-derived MicroRNA-92a upregulation and section from the local CRC acts a candidate noninvasive serum biomarker in colorectal cancer. Our study provides a novel insight into miR-92a mechanisms in relation to both expression and secretion for CRC diagnosis.
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Following the publication of the above article, a concerned reader drew to the authors' attention that the data shown for the 'CAOV3/NC mimics' experiment in Fig. 2D on p. 443 appeared to be the same as that shown for the 'TUG1sh+miR1299 inhibitors' experiment in Fig. 4H on p. 444. The authors have examined their original data, and realize that the same data was inadvertently included in the two figures. Consequently, the corrected version of Fig. 2, featuring the correct data for the 'CAOV3/NC mimics' experiment in Fig. 2D, is shown opposite. The overall conclusions of this study were not affected by this error. All the authors agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this; furthermore, they apologize to the readership for any inconvenience caused. [Oncology Reports 44: 438-448, 2020; DOI: 10.3892/or.2020.7623].
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Objective: To investigate the prognostic factors in and role of postoperative radiotherapy (PORT) for surgically resected thymomas. Methods: A total of 1540 patients with pathologically confirmed thymomas undergoing resection between 2000 and 2018 were identified retrospectively from the SEER (Surveillance, Epidemiology, and End Results) database. Tumors were restaged as local (limited to thymus), regional (invasion to mediastinal fat and other neighboring structures), or distant stage. Disease-specific survival (DSS) and overall survival (OS) were estimated by the Kaplan-Meier method and the log-rank test. Adjusted hazard ratios (HRs) with 95% CIs were calculated by Cox proportional hazards modeling. Results: Tumor stage and histology were independent predictors of both DSS (regional: HR, 3.711; 95% CI, 2.006-6.864; distant: HR, 7.920; 95% CI, 4.061-15.446; type B2/B3: HR, 1.435; 95% CI, 1.008-2.044) and OS (regional: HR, 1.461; 95% CI, 1.139-1.875; distant: HR, 2.551; 95% CI, 1.855-3.509; type B2/B3: HR, 1.409; 95% CI, 1.153-1.723). For patients with regional stage and type B2/B3 thymomas, PORT was associated with better DSS after thymectomy/thymomectomy (HR, 0.268; 95% CI, 0.099-0.727), but the association was not significant after extended thymectomy (HR, 1.514; 95% CI, 0.516-4.44). Among patients with lymph node metastases, those who received PORT (HR, 0.372; 95% CI, 0.146-0.949), chemotherapy (HR, 0.843; 95% CI, 0.303-2.346), or both (HR, 0.296, 95% CI, 0.071-1.236) had a better OS. Conclusions: The extent of invasion and tumor histology were independent predictors of worse survival following surgical resection of thymoma. Patients with regional invasion and type B2/B3 thymoma who undergo thymectomy/thymomectomy may benefit from PORT, while patients with nodal metastases may benefit from multimodal therapy, including PORT and chemotherapy.