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Introdução: Cicatrizes hipertróficas e queloides são tipos de cicatrizes excessivas de cicatrização anormal da pele. Galectina-3 (gal-3) é uma proteína da família das lectinas capaz de identificar carboidratos, que podem se combinar e atuar em diversas moléculas. Na literatura, a ação da gal-3 como principal agente regulador da fibrogênese já foi descrita, sendo atualmente utilizada na terapia antifibrótica de diversos órgãos como pulmão e fígado. O objetivo deste estudo piloto foi mostrar resultados preliminares encontrados na expressão de gal-3 em cicatrizes exacerbadas. Método: Foram coletadas 20 amostras de biópsias de cicatrizes excessivas (16 queloides e 4 cicatrizes hipertróficas) e 9 amostras de cicatrizes normais de 22 mulheres e 7 homens. Essas amostras foram processadas para análise histopatológica de rotina por imuno-histoquímica para detectar gal-3. As células positivas para gal-3 foram quantificadas pelo método estereológico utilizando uma grade de 36 pontos. Resultados: A imuno-histoquímica mostrou alta expressão de gal-3 em células endoteliais e epiteliais de todas as amostras de cicatrizes, bem como expressão em células distribuídas pela derme. Maior expressão de gal-3 foi encontrada em amostras de queloides (28% de células positivas) em comparação com cicatrizes normais (18%) e hipertróficas (22%) (p=0,0075). Os resultados foram obtidos de um pequeno número de pacientes, por se tratar de um estudo piloto. Conclusão: Os dados sugerem que a gal-3 participa do processo de cicatrização e, devido à sua maior presença em amostras de queloides, pode ser um potencial biomarcador para formação de queloides e um alvo terapêutico promissor a ser explorado.
Introduction: Hypertrophic scars and keloids are types of excessive scars from abnormal skin healing. Galectin-3 (gal-3) is a protein from the lectin family capable of identifying carbohydrates, which can combine and act on different molecules. In the literature, the action of gal-3 as the main regulatory agent of fibrogenesis has already been described and is currently used in anti-fibrotic therapy for various organs such as the lung and liver. The objective of this pilot study was to show preliminary results found in the expression of gal-3 in exacerbated scars. Method: Twenty biopsy samples from excessive scars (16 keloids and 4 hypertrophic scars) and 9 samples from normal scars were collected from 22 women and 7 men. These samples were processed for routine histopathological analysis by immunohistochemistry to detect gal-3. Gal-3 positive cells were quantified by the stereological method using a 36-point grid. Results: Immunohistochemistry showed high expression of gal-3 in endothelial and epithelial cells of all scar samples, as well as expression in cells distributed throughout the dermis. Higher gal-3 expression was found in keloid samples (28% positive cells) compared to normal (18%) and hypertrophic (22%) scars (p=0.0075). The results were obtained from a small number of patients, as this was a pilot study. Conclusion: The data suggest that gal-3 participates in the healing process and, due to its greater presence in keloid samples, it may be a potential biomarker for keloid formation and a promising therapeutic target to be explored.
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Resumen Introducción : Las diferentes modificaciones estructu rales que han sido descritas en el corazón del deportista de alto rendimiento dependen de factores como la edad, el género, el tipo de deporte, la intensidad y el tiempo dedicados al entrenamiento. Objetivos : Evaluación de atletas de élite por medio de la ecocardiografía para la descripción de la estructura y la función cardíacas, y la comparación entre deportistas de resistencia cardiorrespiratoria y el resto de los deportistas. Métodos : Realizamos el examen ecocardiográfico en 224 deportistas de élite, 96 mujeres y 128 varones con edades de 15 a 38 años (21.7±5.3 años) y se dividieron en 2 grupos: "Grupo de Resistencia" (resistencia cardiorres piratoria) y "Grupo de no Resistencia" el cual incluyó al resto de los deportes. Se realizó la comparación univaria da de 14 variables ecocardiográficas entre los dos grupos. Resultados : En los hombres se identificaron valores estadísticamente significativos más altos en el grupo de resistencia para septum interventricular, pared posterior, grosor parietal relativo, índice de masa del ventrículo iz quierdo y aurícula izquierda. En las mujeres, el grupo de resistencia tuvo valores de frecuencia cardíaca más bajos con diámetro diastólico e índice de masa del ventrículo izquierdo, significativamente mayores. Conclusiones : La mayoría de las variables ecocar diográficas mostró valores mayores en los atletas de resistencia. En los hombres del Grupo de Resistencia, predominó la hipertrofia excéntrica con mayor incre mento en el grosor parietal y del diámetro de la aurícula izquierda, mientras que en las mujeres las variables indi caron hipertrofia excéntrica a expensas de un aumento del diámetro del ventrículo izquierdo, sin incremento del grosor parietal.
Abstract Introduction : The different structural modifications that have been described in the heart of the high-per formance athlete depend on factors such as age, gender, type of sport, and the intensity and time dedicated to training. Objectives : Evaluation of elite athletes through echo cardiography for the description of cardiac structure and function, and the comparison between athletes with cardiorespiratory endurance and the rest of the athletes. Methods : We performed the echocardiographic ex amination in 224 elite athletes, 96 women and 128 men aged 15 to 38 years (21.7±5.3 years) and they were di vided into 2 groups: "Endurance Group" (cardiorespira tory endurance) and "Non-Endurance Group" which included the rest of the sports. Univariate comparison between the two groups was performed by measuring 14 echocardiographic variables. Results : In men, statistically significant higher values were identified in the endurance group for interventricu lar septum, left ventricular posterior wall, relative wall thickness (RWT), left ventricular mass index and left atrial dimension. In women, the endurance group had signifi cantly lower heart rate values, and significantly higher left ventricular diastolic dimension with normal RWT. Conclusions : Most of the echocardiographic vari ables showed higher sample means in the endurance athletes. In the subgroup of men from the Endurance Group, eccentric hypertrophy prevailed with a greater increase in wall thickness, as well as in the diameter of the left atrium, while in women the variables indicated eccentric hypertrophy at the expense of an increase in left ventricle diameter, without increased wall thickness.
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RESUMEN Introducción. La miocardiopatía hipertrófica (MCH), es la enfermedad genética cardiovascular más común, causada por mutaciones en proteínas del sarcómero cardíaco, con una prevalencia considerable y clínica variable, desde asintomática hasta insuficiencia cardíaca y muerte súbita. Existen pacientes seguidos en centros no especializados, y es necesario conocer datos que puedan mostrar la realidad de su diagnóstico, tratamiento y pronóstico. Objetivo. Conocer las características clínicas, estrategias diagnósticas y terapéuticas al abordar la MCH en centros no especializados en la patología. Material y métodos. Estudio de corte transversal, multicéntrico, de alcance nacional, con análisis cuantitativo, de pacientes con MCH confirmada o altamente probable. Resultados. Se registraron 95 pacientes, mayormente hombres con hipertensión arterial (40 %) y dislipidemia (22 %) como principales factores de riesgo. Se observó baja proporción de comorbilidades: enfermedad pulmonar obstructiva crónica (6 %), infarto de miocardio previo (5 %), accidente cerebro vascular previo (1 %) e insuficiencia renal crónica (1 %). Los síntomas principales fueron la disnea (47 %) y el ángor (27 %), y los métodos diagnósticos más usados fueron el ecocardiograma (97 %) y la resonancia cardíaca (71 %). La localización más frecuente fue septal, con 37 % de tipo obstructivo. El test genético, realizado en un 33 %, fue positivo en más de la mitad de los pacientes. No se realizó en dos tercios de los casos principalmente por falta de cobertura. Conclusiones. Los hallazgos son concordantes con los de registros internacionales. Con base a nuestros hallazgos, se resalta la necesidad de mejorar el acceso a estudios diagnósticos más complejos y optimizar recursos en un sistema de salud fragmentado.
ABSTRACT Background . Hypertrophic cardiomyopathy (HCM) is the most common genetic disease caused by cardiac sarcomere protein mutations, with considerable prevalence and different clinical presentation, varying from asymptomatic to heart failure and sudden death. Some patients are followed-up in nonspecialized centers, and it is necessary to know data that show the reality of their diagnosis, treatment, and prognosis. Objective. The aim of this study was to know the clinical characteristics, and diagnostic and therapeutic strategies when HCM is managed in centers not specialized in this disease. Methods. This was a national, cross-sectional, multicenter study, with quantitative analysis of patients with confirmed or highly probable HCM. Results. A total of 95 patients were recruited, mostly men, with hypertension (40%) and dyslipidemia (22%) as main risk factors. A low proportion of comorbidities was observed: chronic obstructive pulmonary disease (6%), prior myocardial infarction (5%), prior stroke (1%) and chronic kidney failure (1%). The main symptoms were dyspnea (47% and angina (27%), and the most used diagnostic methods were echocardiogram (97%) and cardiac magnetic resonance imaging (71%)). The most frequent localization was septal, with 37% of hypertrophic obstructive cardiomyopathy. The genetic test, performed in 33% of patients, was positive in more than half of cases. It was not performed in the rest of the patients, mainly due to lack of health coverage. Conclusions. These findings are in agreement with international registries. Based on our findings, emphasis should be placed in improving the access to more complex diagnostic studies and optimizing the resources in a fragmented health system.
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Abstract In the presence of the left ventricle hypertrophy (LVH), the differential diagnosis with hypertrophic cardiomyopathy (HCM) or some phenocopy must be always considered, which can be easily suspected when the hypertrophy is markedly asymmetric. However, when the hypertrophy is homogeneous, especially if the patient has concomitant hypertension, it may be a challenge to distinguish between hypertensive and HCM, although some clinical features may help us to suspect it. In addition, patients with HCM may present with exertional angina due to microcirculation involvement in the setting of the hypertrophy itself or dynamic obstruction in the left ventricular outflow tract, but in some cases, the presence of concomitant coronary artery disease must be suspected as the cause of angina, especially if the patient has an intermediate or high-risk probability of having ischemic heart disease. We present the case of a 46-year-old Afro-American man with poorly controlled hypertension who was found to have severe LVH, and who presented with symptoms of exertional angina during follow-up. We will review the clinical features that can help us in the differential diagnosis in this context.
Resumen Ante la presencia de hipertrofia del ventrículo izquierdo (HVI), siempre se debe considerar el diagnóstico diferencial con la miocardiopatía hipertrófica (MCH) o alguna fenocopia, que puede sospecharse fácilmente cuando la hipertrofia es marcadamente asimétrica. Además, los pacientes con MCH pueden presentar angina de esfuerzo debido a la afectación de la microcirculación en el contexto de la propia hipertrofia o si ésta condiciona obstrucción dinámica al tracto de salida del ventrículo izquierdo, pero en algunos casos debe sospecharse la presencia de enfermedad coronaria concomitante como causa de la angina, especialmente si el paciente tiene una probabilidad de riesgo intermedio o alto de padecer cardiopatía isquémica. Presentamos el caso de un varón de 46 años de afroamericana con hipertensión arterial mal controlada a quien se le detectó una HVI severa, y que durante el seguimiento presentó síntomas de angina de esfuerzo. Revisaremos las características clínicas que nos pueden ayudar en el diagnóstico diferencial en este contexto.
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RESUMEN Introducción: La miectomía septal ampliada (MSA) ha demostrado ser una estrategia útil para mejorar los síntomas de los pacientes con miocardiopatía hipertrófica obstructiva (MCHO). Objetivos: El objetivo de este trabajo fue analizar el impacto de la MSA en parámetros estructurales y funcionales ecocardiográficos a corto y mediano plazo, en pacientes con MCH y obstrucción dinámica del tracto de salida del ventrículo izquierdo (VI). Material y métodos: Se analizaron los ecocardiogramas en los períodos preoperatorio, postoperatorio inmediato (1 mes post cirugía) y posoperatorio alejado (2 a 3 años) de pacientes sometidos a MSA. Resultados: Se intervinieron 94 pacientes con una edad media de 57,6 ± 13,8 años. Se observó una reducción significativa del máximo espesor septal en el postoperatorio inmediato, que se mantuvo en el posoperatorio alejado, y en el tamaño auricular izquierdo en el postoperatorio inmediato que se profundizó en el alejado (p < 0,001). El gradiente intraventricular en reposo pasó de 49,2 mmHg basal a 6,4 mmHg (p < 0,001) y de allí a 4,6 mmHg (p=0,224) en los períodos inmediato y alejado, y con la maniobra de Valsalva de 93,9 mmHg a 8,7 mmHg (p < 0,001) y de allí a 7,2 mmHg (p=0,226) respectivamente. La función diastólica fue valorada como grado II en el 58,5 % de los pacientes en el preoperatorio, 51,7 % en el postoperatorio inmediato y 29 % en el postoperatorio alejado. En la misma línea se evidenció un cambio en la relación E/e´ y la presión sistólica pulmonar, grado de insuficiencia mitral y dimensiones de la aurícula izquierda. Conclusión: En esta cohorte de pacientes con MCHO, la realización de una MSA se asoció a una mejoría significativa de la función diastólica del VI, reducción de las presiones de llenado y pulmonares y grado de insuficiencia mitral, y remodelado reverso de la aurícula izquierda. Es posible que esta combinación de efectos explique los beneficios clínicos de la intervención.
ABSTRACT Background: Extended septal myectomy (ESM) has proven to be a useful strategy to improve symptoms in patients with hypertrophic obstructive cardiomyopathy (HOCM). Objectives: The aim of this study was to analyze the impact of ESM on short and mid-term structural and functional echocardiographic parameters in patients with HCM and left ventricular (LV) outflow tract dynamic obstruction. Methods: Preoperative, immediate postoperative (1 month after surgery) and late postoperative (2 to 3 years) echocardiograms of patients undergoing ESM were analyzed. Results: A total of 94 patients with mean age of 57.6 ± 13.8 years underwent surgery. A significant reduction was observed in maximum septal thickness in the immediate postoperative period, which was sustained in the late postoperative period, and in atrial size in the immediate postoperative period, which deepened in the late postoperative period (p < 0.001). Intraventricular gradient at rest dropped from 49.2 to 6.4 mmHg (p < 0.001) and then to 4.6 mmHg (p=0.224) in the immediate and late periods and with Valsalva maneuver from 93.9 to 8.7 mmHg (p < 0.001), and then to 7.2 mmHg (p=0.226), respectively. Preoperative diastolic function was assessed as grade II in 58.5% of patients, decreasing to 51.7% in the immediate postoperative period and to 29% in the late postoperative period. In agreement with these results, a change was evidenced in the E/e´ ratio and pulmonary artery systolic pressure, degree of mitral regurgitation and left atrial dimensions. Conclusion: In this cohort of patients with HOCM, ESM was associated with a significant improvement in LV diastolic function, reduction in filling and pulmonary pressures and degree of mitral regurgitation, and left atrial reverse remodeling. It is possible that this combination of effects explains the clinical benefits of the intervention.
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Resumo Fundamento A cardiomiopatia hipertrófica (CMH) e a doença de Fabry (DF) são doenças herdadas geneticamente com características fenotípicas de hipertrofia ventricular esquerda (HVE) que causam resultados cardíacos adversos. Objetivos Investigar as diferenças demográficas, clínicas, bioquímicas, eletrocardiográficas (ECG) e ecocardiográficas (ECO) entre CMH e DF. Métodos 60 pacientes com CMH e 40 pacientes com DF foram analisados retrospectivamente como uma subanálise do "estudo LVH-TR" após exclusão de pacientes com fibrilação atrial, ritmo de estimulação, bloqueios de ramo e bloqueios atrioventriculares (AV) de segundo e terceiro graus. O nível de significância foi aceito como <0,05. Resultados O sexo masculino (p=0,048) e a creatinina (p=0,010) são significativamente maiores a favor da DF; entretanto, infradesnivelamento do segmento ST (p=0,028), duração do QT (p=0,041), espessura do septo interventricular (SIVd) (p=0,003), espessura da parede posterior (PWd) (p=0,009), insuficiência mitral moderada a grave (IM) (p=0,013) e o índice de massa ventricular esquerda (IMVE) (p=0,041) são significativamente maiores a favor da CMH nas análises univariadas. Na análise multivariada, a significância estatística apenas permanece na creatinina (p=0,018) e na duração do intervalo QT (0,045). A DF foi positivamente correlacionada com a creatinina (rho=0,287, p=0,004) e a CMH foi positivamente correlacionada com o PWd (rho=0,306, p=0,002), IVSd (rho=0,395, p<0,001), IM moderada-grave (rho= 0,276, p<0,005), IMVE (rho=0,300, p=0,002), espessura relativa da parede (ERP) (rho=0,271, p=0,006), duração do QT (rho=0,213, p=0,034) e depressão do segmento ST (rho =0,222, p=0,026). Conclusão Características bioquímicas, ECG e ECO específicas podem auxiliar na diferenciação e no diagnóstico precoce da CMH e da DF.
Abstract Background Hypertrophic cardiomyopathy (HCM) and Fabry disease (FD) are genetically inherited diseases with left ventricular hypertrophy (LVH) phenotype characteristics that cause adverse cardiac outcomes. Objectives To investigate the demographic, clinical, biochemical, electrocardiographic (ECG), and echocardiographic (ECHO) differences between HCM and FD. Methods 60 HCM and 40 FD patients were analyzed retrospectively as a subanalysis of the 'LVH-TR study' after excluding patients with atrial fibrillation, pace rhythm, bundle branch blocks, and second and third-degree atrioventricular (AV) blocks. The significance level was accepted as <0.05. Results Male gender (p=0.048) and creatinine (p=0.010) are significantly higher in favor of FD; however, ST depression (p=0.028), QT duration (p=0.041), interventricular septum thickness (IVSd) (p=0.003), posterior wall thickness (PWd) (p=0.009), moderate-severe mitral regurgitation (MR) (p=0.013), and LV mass index (LVMI) (p=0.041) are significantly higher in favor of HCM in the univariate analyses. In multivariate analysis, statistical significance only continues in creatinine (p=0.018) and QT duration (0.045). FD was positively correlated with creatinine (rho=0.287, p=0.004) and HCM was positively correlated with PWd (rho=0.306, p=0.002), IVSd (rho=0.395, p<0.001), moderate-severe MR (rho=0.276, p<0.005), LVMI (rho=0.300, p=0.002), relative wall thickness (RWT) (rho=0.271, p=0.006), QT duration (rho=0.213, p=0.034) and ST depression (rho=0.222, p=0.026). Conclusion Specific biochemical, ECG, and ECHO characteristics can aid in the differentiation and early diagnosis of HCM and FD.
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RESUMEN La enfermedad de Menetrier representa una entidad clínica de baja prevalencia, caracterizada por la complejidad en su diagnóstico, especialmente debido a la necesidad de excluir su posible asociación con cáncer gástrico. En este contexto, se presenta el caso clínico de un varón de 54 años con síntomas gastrointestinales inespecíficos e hipoalbuminemia. Durante el procedimiento de endoscopía alta se observó un notorio engrosamiento de los pliegues gástricos asociado a lesiones polipoideas múltiples en estómago, a predominio de fondo y cuerpo. Dado que el paciente no mostró mejoría de sus síntomas y a la imposibilidad de descartar cáncer gástrico, se decidió como tratamiento la gastrectomía total. La pieza quirúrgica e histología permitió la confirmación de enfermedad de Menetrier.
ABSTRACT Menetrier's disease represents a low prevalence clinical entity, characterized by complexity in its diagnosis, particularly due to the need to exclude its potential association with gastric cancer. In this context, we present the clinical case of a 54-year-old male with nonspecific gastrointestinal symptoms and hypoalbuminemia. During the upper endoscopy procedure, a noticeable thickening of gastric folds was observed, associated with multiple polypoid lesions in the stomach, predominantly in the fundus and body. Since the patient did not show improvement in symptoms and given the inability to rule out gastric cancer, total gastrectomy was chosen as the treatment. Surgical specimen and histology confirmed the presence of Menetrier's disease.
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Objective·To analyze the differences and classify hypertrophic cardiomyopathy(HCM)patients and healthy controls(HC)using short-axis cine cardiac magnetic resonance(CMR)images-derived radiomics features.Methods·One hundred HCM subjects were included,and fifty HC were randomly selected at 2∶1 ratio during January 2018 to December 2021 in the Department of Cardiology,Renji Hospital,Shanghai Jiao Tong University School of Medicine.The CMR examinations were performed by experienced radiologists on these subjects.CVI 42 post-processing software was used to obtain left ventricular morphology and function measurements,including left ventricular ejection fraction(LVEF),left ventricular end-diastolic volume(LVEDV)and left ventricular end-diastolic mass(LVEDM).The 3D radiomic features of the end-diastolic myocardial region were extracted from short-axis images CMR cine.The distribution of the radiomic features in the two groups was analysed and machine learning models were constructed to classify the two groups.Results·One hundred and seven 3D radiomic features were selected and extracted.After exclusion of highly correlated features,least absolute shrinkage and selection operator(LASSO)was used,and a 5-fold cross-validation was performed.There were still 11 characteristics with non-zero coefficients.The K-best method was used to decide the top 8 features for subsequent analysis.Among them,four features were significantly different between the two groups(all P<0.05).Support vector machine(SVM)and random forest(RF)models were constructed to discriminate the two groups.The results showed that the maximum area under the curve(AUC)for the single-feature model(first order grayscale:entropy)was 0.833(95%CI 0.685?0.968)and the maximum accuracy for the multi-feature model was 83.3%with an AUC of 0.882(95%CI 0.705?0.980).Conclusion·There are significant differences in both left ventricular function and left ventricular morphology between HCM and HC.The 3D myocardial radiomic features of the two groups are also significantly different.Although single feature is able to distinguish the two groups,the combination of multi-features show better classification performance.
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Objective To evaluate the change of cardiac structure and function in patients with hypertrophic obstructive cardiomyopathy(HOCM)after ultrasound-guided percutaneous intramyocardial septal radiofrequency ablation(PIMSRA)via cardiac magnetic resonance(CMR).Methods Patients with HOCM who underwent PIMSRA,echocardiography and CMR preoperative scanning and one year after surgery were analyzed retrospectively.Myocardial structural and functional parameters were measured by Circle cardiovascular imaging post-processing software.The changes of myocardial parameters before and after surgery were compared by using paired sample t-test and Chi-square test.Results Compared with the preoperative assessment,patients'clinical symptoms and the cardiac function were significantly improved one year after surgery.The left ventricular outflow tract pressure gradient(LVOT-PG)was significantly decreased and length of mitral regurgitation was shortened one year after surgery compared with before surgery via ultrasound(P<0.05).Compared with the preoperative assessment,CMR showed that patients with end-systolic volume of left atrium,minimum volume of left atrium,transverse diameter of left atrium,thickness of ventricular septum and free wall of left ventricular at end-systolic section were significantly reduced,and left ventricular mass(LVM)was significantly decreased one year after surgery,with statistical significance between before and after surgery(P<0.001).One year after surgery,the left atrium ejection fraction(LAEF)was significantly increased(P<0.05),the maximum slope and the maximum signal intensity of the ventricular septum and the left ventricular free wall of the papillary muscle were significantly increased(P<0.001),and the peak time was significantly decreased(P<0.001)compared with before surgery.Conclusion After PIMSRA treatment,the systolic function of left atrium in HOCM patients is improved,and the microcirculation perfusion of left ventricular is significantly improved.
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BACKGROUND:At present,effective preventive and therapeutic measures for hypertrophic scar are still limited.In contrast,most of botanical herbs have few side effects and abundant sources,offering new ideas and approaches for the prevention and treatment for hypertrophic scar. OBJECTIVE:To explore the potential molecular mechanism of plant-derived β-sitosterol on hypertrophic scar fibroblasts by network pharmacology and molecular docking techniques and to initially verify it by cytological experiments. METHODS:Through the network pharmacology,the relevant database and software were used to screen the drug targets of β-sitosterol and obtain the hypertrophic scar-related disease targets.The potential(intersection)targets of β-sitosterol on hypertrophic scar were obtained.Cytoscape software and STRING database were used to construct the"drug-target-disease"network and protein-protein interaction network,and screen out the core targets in the protein-protein interaction network.Gene ontology(GO)biological function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses of intersection targets were conducted through the DAVID database,and the signaling pathways and core target genes closely related to the intersection targets were further identified through literature analysis.AutoDock software was used to perform the molecular docking of β-sitosterol and core target proteins.In vitro cellular assays were used to verify the effects of β-sitosterol on proliferation,apoptosis,cell cycle distribution and mRNA expression of core target genes in human hypertrophic scar fibroblasts. RESULTS AND CONCLUSION:There were 56 intersection targets of β-sitosterol and hypertrophic scar and 10 core targets were identified in the protein-protein interaction network,including tyrosine kinase,mitogen-activated protein kinase 3(MAPK3),cysteine protease 3(CASP3),apolipoprotein E,estrogen receptor 1,sterol regulatory element-binding transcription factor 1,peroxisome proliferator-activated receptor alpha,C-reactive protein,intercellular adhesion molecule 1,and catalase.Combined with the literatures and the functional analysis of the KEGG and GO,the MAPK signaling pathway was further identified to be closely related to the intersection targets,and MAPK3(ERK1-MAPK),CASP3,P53 and tumor necrosis factor were identified as the core targets.The molecular docking results indicated that β-sitosterol was well bound to the core target proteins.Cellular assays showed that 100 μmol/L β-sitosterol inhibited hypertrophic scar fibroblast proliferation,decreased mitochondrial membrane potential and induced apoptosis(P<0.01),increased the proportion of G1-phase cells and decreased the proportion of S-phase cells(P<0.05),upregulated the mRNA expression of CASP3,P53 and tumor necrosis factor(P<0.05),and downregulated the mRNA expression of MAPK3(P<0.001).To conclude,β-sitosterol may induce cell apoptosis in hypertrophic scar fibroblasts by activating the tumor necrosis factor pathway and upregulating the expression of CASP3 and P53,while inhibiting the ERK-MAPK pathway to arrest cell cycle and thus reduce the proliferation of hypertrophic scar fibroblasts.
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BACKGROUND:Hypertrophic scar is a skin fibrosis disease characterized by excessive proliferation of fibroblasts,epidermal thickening,and stratum corneum dysfunction.At present,the pathogenesis of Hypertrophic scar is still unclear. OBJECTIVE:To screen the core(Hub)genes and important signaling pathways in hypertrophic scar-related datasets based on bioinformatics,and then verify them by cell experiments to predict small molecule drugs that may have therapeutic effects on hypertrophic scar. METHODS:Datasets related to hypertrophic scar were searched from Gene Expression Omnibus(GEO)database,and differentially expressed genes were identified by R software analysis.Gene ontology and KEGG enrichment analyses were performed for differentially expressed genes.Protein-protein interaction network of differentially expressed genes was constructed using String online platform.Then,the key genes and core modules in the protein-protein interaction network were screened by Cytohubba and MCODE plugin-in Cytoscape software respectively,and the Hub genes were obtained by the intersection of the above key genes and the genes that formed the core module.Real-time fluorescent quantitative PCR was used to verify the difference in Hub gene mRNA expression between human hypertrophic scar and normal skin epidermal stem cells.The histological data from the Human Protein Atlas were used to verify the differences in the expression and distribution of Hub gene-encoded proteins in the two kinds of human tissues.Finally,the potential drugs for hypertrophic scar were predicted by the connectivity map database. RESULTS AND CONCLUSION:Among the identified differentially expressed genes,102 genes were up-regulated and 702 genes were down-regulated.Gene ontology and KEGG analysis showed that the enriched signaling pathways and biological processes were mainly involved in tight junction,arachidonic acid metabolism,extracellular matrix receptor interaction,epidermal development and keratinization.Eight Hub genes were found to be closely related to the mevalonate pathway that regulates cholesterol metabolism,including HMGCS1,DHCR7,MSMO1,FDPS,MVK,HMGCR,MVD and ACAT2.Compared with the normal skin group,the mRNA expression of HMGCS1,DHCR7,MSMO1,FDPS,HMGCR,MVD and ACAT2 in the hypertrophic scar group decreased significantly(P＜0.05),while MVK mRNA expression had no significant change(P＞0.05).Except for MVK,the expression levels of other Hub gene-encoded proteins in normal skin tissue were higher than those in hypertrophic scar tissue(P＜0.05).The top 10 candidate drugs included protein kinase A inhibitor(H-89),serine protease inhibitor(Dabigatran-Etexilate),FLT3 inhibitor(sunitinib),among which resveratrol and β-sitosterol are plant extracts.To conclude,Hub genes closely related to mevalonate metabolism may affect the structure and function of the epidermis by regulating lipid metabolism,which may an important pathogenesis of hypertrophic scar.The small-molecule compounds identified in this study can be used as candidate drugs for the treatment of hypertrophic scar.
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Objective:To apply cardiovascular magnetic resonance (CMR) to quantitatively evaluate the morphology and tissue characteristics of thoracic skeletal muscle (TSM) in patients with Danon disease and hypertrophic cardiomyopathy (HCM), in order to provide auxiliary differential diagnostic information.Methods:A retrospective study was conducted on 15 Danon disease patients (Danon disease group) who completed CMR examination, and 15 HCM patients (HCM group) and 15 healthy volunteers (control group) who were matched by gender and age were compared. TSM (pectoralis major, pectoralis minor, erector spinae, and subscapularis) area index (TSMAi), T1 relaxation time of four groups, and extracellular volume (ECV) of skeletal muscles of two groups (pectoralis major and subscapularis) were measured for all subjects. Single factor analysis of variance and KruskalWallis test were used to compare three sets of values.Results:The total TSMAi of the Danon disease group was lower than that of the HCM group and the control group [(15.37±3.28)cm 2/m 2 vs (23.02±3.88)cm 2/m 2 vs (22.33±4.67)cm 2/m 2, P<0.001], and the TSMAi of each TSM was also lower than that of the HCM group and the control group (all P<0.05). There was no statistically significant difference in TSMAi between the HCM group and the control group (all P>0.05). The native T1 values of the pectoralis major muscle in the Danon disease group and HCM group were higher than those in the control group (all P<0.05). The ECV of the pectoralis major muscle and subscapularis muscle in the Danon disease group were higher than those in the HCM group and control group, and the enhanced T1 values were lower than those in the HCM group and control group (all P<0.05); There was no statistically significant difference in ECV and the enhanced T1 values between the HCM group and the control group ( P>0.05). Conclusions:The application of CMR can effectively evaluate the changes in TSM morphology and tissue characteristics in Danon disease patients. Compared with HCM patients, Danon disease patients showed significant atrophy of TSM with increased extracellular volume. CMR provides a quantitative reference for TSM in the differential diagnosis of the two.
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Objective:To investigate the hemodynamic changes in the ascending aorta (AAo) before and after interventricular septal myocardial resection in obstructive hypertrophic cardiomyopathy (HOCM) using cardiac magnetic resonance four-dimensional blood flow (CMR 4D Flow) technology.Methods:HOCM patients who underwent interventricular septal myocardial resection at Guangdong Provincial People′s Hospital from May 2021 to September 2022 were prospectively included. Age and gender matched healthy volunteers (control group) were included during the same period. Both the control group and HOCM patients underwent CMR examination (including cine sequence and 4D Flow sequence) before and 6 months after surgery. CMR 4D flow technology was used to evaluate changes in AAo preoperative and postoperative blood flow patterns (eddy currents, spiral flow), maximum energy loss (EL max), and average energy loss (EL avg). HOCM patients underwent laboratory tests, including N-terminal pro-brain natriuretic peptide (N-pro BNP) and high-sensitivity troponin T (hsTnT). At the same time, the correlation between postoperative energy loss in HOCM patients and the degree of improvement in laboratory biomarkers was explored. Results:A total of 15 HOCM patients and 15 healthy volunteers were included. (1) In terms of blood flow patterns, the preoperative spiral flow degree of HOCM patients was significantly higher than that of the control group ( P=0.001), but the postoperative difference was not statistically significant ( P=0.059). The degree of eddy currents in HOCM patients before and after surgery was higher than that in the control group (all P<0.05). (2) In terms of energy loss, the preoperative EL max [21.17(14.30-28.10)mW vs 10.17(7.66-13.07)mW, P<0.001] and EL avg [4.87(3.46-5.77)mW vs 2.27(2.19-2.27)mW, P=0.023] of HOCM patients were higher than those of the control group, but there was no statistically significant difference between the postoperative and control groups (all P>0.05). Compared with preoperative, the postoperative EL max [12.33(8.70-17.41)mW] and EL avg [3.10(2.25-4.40)mW] of AAo in HOCM patients were significantly reduced (mean P=0.001). (3) Correlation analysis showed that there was a positive correlation ( r=0.587, P=0.021) between the EL max of AAo and the degree of improvement in hsTNT after interventricular septum myocardial resection, but no significant correlation ( r=0.229, P=0.413) with the degree of improvement in NT-pro BNP. Conclusions:The degree of postoperative AAo blood flow disorder in HOCM patients is reduced, and EL max and EL avg are significantly reduced. The EL max of postoperative AAo is positively correlated with the degree of improvement in hsTNT, suggesting that EL max may be applicable for prognostic evaluation of patients.
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Objective To propose a distribution feature extraction algorithm based on wavelet packet coefficients to reconstruct the signal energy sequence for effectively identifying the pathological features of heart sounds,thereby realizing the early screening of heart diseases.Methods The original heart sound signal was decomposed into 10 layers using wavelet packet decomposition algorithm.After obtaining the wavelet packet coefficients of each layer,each coefficient was reconstructed,and the energy of the reconstructed signal was calculated and arranged in the original order to form the energy sequence.The distribution characteristics of the energy sequence of the reconstructed signals at each layer were analyzed,and distribution features were taken as classification features.Support vector machine,K-nearest neighbor,and decision tree were used to classify and recognize normal heart sounds and the heart sound signals of various diseases.Results The combination of the distribution features of the reconstructed signal energy sequence and decision tree classifier had an accuracy of 93.6%for classifying 5 types of heart sounds on the public dataset,and the accuracy was 95.6%for identifying normal heart sounds and hypertrophic cardiomyopathy heart sounds.Conclusion The proposed algorithm can extract the effective pathological information of abnormal heart sounds,providing a reference for clinical cardiac auscultation.
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Objective To observe the feasibility of T1 mapping technique for evaluating myocardial gadolinium deposition in patients with apical hypertrophic cardiomyopathy(AHCM).Methods Data of 60 AHCM patients were retrospectively analyzed.The patients were divided into enhanced group and control group according to underwent gadolinium-based contrast agent(GBCA)enhanced examination or not(each n=30).Myocardial T1 value at the basal,middle and apical myocardium of the left ventricle as well as spleen T1 at the same layers were measured.T1 relative-value(T1R)was calculated and then compared between groups and among different parts of left ventricle in enhanced group.T1R in enhanced group were further analyzed based on gender,age,body mass index,cardiac function,hypertension,hyperlipidemia,diabetes,apical thickness,ejection fraction,delayed enhancement and interval time from the first enhanced examination to the last review and total dose of GBCA.Results No significant difference of T1Rbasal,T1Rmiddle nor T1Rapical was found between groups(t=0.329,1.484,0.720,all P＞0.05),nor of T1R in different parts of left ventricle within enhanced group(F=0.765,P＞0.05).In enhanced group,significant differences of myocardial T1R was found between different genders as well as patients with or without hypertension(both P＜0.05).Conclusion T1 mapping technology could be used for evaluating myocardial gadolinium deposition in patients with AHCM.
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Purpose To evaluate the feasibility of cardiac magnetic resonance fractal analysis in evaluating left ventricular trabecular complexity in hypertrophic cardiomyopathy(HCM),and to study the degree of left ventricular trabecular complexity in HCM and the relationship between excessive trabecular complexity and cardiac function.Materials and Methods From August 2020 to December 2022,a total of 80 patients with HCM from the Second Affiliated Hospital of Nanchang University were retrospectively analyzed.Additionally,80 healthy volunteers were recruited as the control group.Left ventricular functional parameters and fractal dimension(FD)of left ventricular trabecular myocardium were measured.The differences of mean global FD,max basal FD and max apical FD were compared between the HCM group and the control group,the correlation between FDs and cardiac function parameters was evaluated.The diagnostic efficiency of mean global FD,max apical FD and max basal FD was analyzed via receiver operating characteristic curve.Results The mean global FD of HCM group was significantly higher than that of normal group,and the difference was statistically significant(1.303±0.047 vs.1.229±0.026;t=-12.387,P<0.001).Mean global FD showed the best performance in differentiating HCM from normal control group.The optimal cut-off value for the diagnosis of HCM was 1.251,with the area under curve of 0.933(95%CI 0.896-0.969).Mean global FD was positively correlated with maximum wall thickness and left ventricular mass index(r=0.686,0.687,P<0.001),and max apical FD was positively correlated with left ventricular ejection fraction(r=0.520,P<0.001).Conclusion The FD obtained by cardiac magnetic resonance fractal analysis technique is reproducible and has definite value in the diagnosis of HCM,with association with the structure and function of left heart.
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Objective:To evaluate the value of the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) in evaluating right ventricular function of patients with hypertrophic cardiomyopathy (HCM) and heart failure with preserved ejection fraction (HFpEF).Methods:A total of 74 patients with HCM and HFpEF and 22 healthy individuals who visited the First Affiliated Hospital of Zhengzhou University from January 2021 to January 2023 were included in this study. The HCM patients with HFpEF were divided into three groups based on the tertiles of the TAPSE/PASP (low group: <0.280 0 mm/mmHg; middle group: 0.280 0-0.476 2 mm/mmHg; high group: >0.476 2 mm/mmHg). Conventional echocardiographic parameters were collected, and two-dimensional speckle tracking technology was used to obtain right ventricular strain parameters. The differences in parameters among the groups were compared, and the correlations between TAPSE/PASP and clinical parameters and right ventricular function parameters were analyzed.Results:The results of difference analysis showed that there were significant differences in 6-minute walking test, New York Heart Association grade (NYHA grade), incidence of atrial fibrillation, left atrial area (LAA), left ventricular global longitudinal strain (LVGLS), TAPSE, PASP, right ventricular fractional area change (RVFAC), right ventricular global longitudinal strain (RVGLS), right ventricular free wall strain (RVFWST) and cardiac magnetic resonance right ventricular ejection fraction (CMR-RVEF) among the three groups. The results of correlation analysis and multiple linear regression analysis showed that the TAPSE/PASP was positively correlated with 6-minute walking distance, RVFAC, tricuspid annulus peak systolic velocity (RV s′), and CMR-RVEF ( r=0.449, 0.284, 0.358, 0.577; all P<0.05). It was negatively correlated with N-terminal pro-brain natriuretic peptide (NT-proBNP), NYHA grade, LAA, mitral early diastolic peak velocity / mitral annulus early diastolic peak velocity (LV E/e′), LVGLS, RVGLS, RVFWST and tricuspid early diastolic peak velocity / tricuspid annulus early diastolic peak velocity (RV E/e′) (r/ rs=-0.336, -0.349, -0.468, -0.452, -0.444, -0.339, -0.405, -0.320; all P<0.05). The LAA and CMR-RVEF correlated independently with TAPSE/PASP(all P<0.05). Conclusions:The TAPSE/PASP can provide an early, simple, rapid, and convenient evaluation of right ventricular function in patients with HCM and HFpEF, so as to guide clinical treatment and monitoring disease progression.
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This study reports a case of pachydermoperiostosis combined with posterior cruciate ligament femoral insertion avulsion fracture. The avulsion fracture was treated by arthroscopic surgery of suspension fixation. The symptom of the pachydermoperiostosis was relieved by non-steroidal anti-inflammatory drugs. Literature search and review were carried out by searching the key words of ("pachydermoperiostosis" OR "primary hypertrophic osteoarthropathy" OR "Touraine-solente-gole syndrome") OR ("posterior cruciate ligament" AND "avulsion fracture"). This patient was confirmed to be the first case reported suffering both diseases mentioned above. For the search results, there were 14 articles on posterior cruciate ligament femoral insertion avulsion fracture and 7 articles on pachydermoperiostosis. This study focused on the impact of pachydermoperiostosis on bone quality, possible factors for the avulsion fracture, and the advantages of arthroscopic surgery. Pachydermoperiostosis is a rare autosomal recessive disease. The incidence of posterior cruciate ligament femoral insertion avulsion fracture is extremely low. It is a seriously sports injury affecting the stability of the knee joint. Standardized surgical treatment can help patients obtain a satisfactory clinical outcome.