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Previous studies have revealed that thyroid hormone (TH) levels are associated with the risk of diabetic peripheral neuropathy (DPN) in euthyroid patients with type 2 diabetes mellitus (T2DM). However, the relationship between TH sensitivity, a complementary method for assessing thyroid function, and DPN remains unclear. This study aimed to investigate the correlation between DPN and TH sensitivity in euthyroid patients with T2DM. Exactly 708 euthyroid adults with T2DM were retrospectively enrolled. The FT3/FT4 ratio was used to estimate peripheral TH sensitivity. Central TH sensitivity was assessed using the Thyrotroph T4 Resistance Index (TT4RI), Thyroid-Stimulating Hormone Index (TSHI), Thyroid Feedback Quantile-based Index (TFQI), and Parametric TFQI (PTFQI). DPN was assessed using neurologic symptoms, signs, and nerve conduction velocity tests. The relationship between DPN and TH sensitivity was examined using logistic regression analysis. We observed that an elevated FT3/FT4 ratio was associated with DPN (OR = 1.36, 95%CI: 1.13-1.63, p = 0.0012). For each standard deviation (SD) increase in the TT4RI, TSHI, TFQI, and PTFQI, the OR of DPN was 0.80 (95%CI: 0.68-0.94, p = 0.0078), 0.72 (95%CI: 0.60-0.86, p = 0.0002), 0.69 (95%CI: 0.58-0.83, p < 0.0001), and 0.69 (95%CI: 0.58-0.82, p < 0.0001), respectively. These results suggested that reduced central and peripheral TH sensitivity is associated with a decreased risk of developing DPN.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Hormonas Tiroideas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Masculino , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/etiología , Femenino , Persona de Mediana Edad , Hormonas Tiroideas/sangre , Anciano , Estudios Retrospectivos , Tirotropina/sangre , Adulto , Pruebas de Función de la Tiroides , Tiroxina/sangre , Triyodotironina/sangre , Glándula Tiroides/fisiopatología , Glándula Tiroides/metabolismoRESUMEN
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with diverse clinical presentations. Alterations in energy expenditure state are commonly observed in patients with PPGL. However, the reported prevalence of hypermetabolism varies significantly and the underlying mechanisms and implications of this presentation have not been well elucidated. This review discusses and analyzes the factors that contribute to energy consumption. Elevated catecholamine levels in patients can significantly affect substance and energy metabolism. Additionally, changes in the activation of brown adipose tissue (BAT), inflammation, and the inherent energy demands of the tumor can contribute to increased resting energy expenditure (REE) and other energy metabolism indicators. The PPGL biomarker, chromogranin A (CgA), and its fragments also influence energy metabolism. Chronic hypermetabolic states may be detrimental to these patients, with surgical tumor removal remaining the primary therapeutic intervention. The high energy expenditure of PPGL has not received the attention it deserves, and an accurate assessment of energy metabolism is the cornerstone for an adequate understanding and treatment of the disease.
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Neoplasias de las Glándulas Suprarrenales , Metabolismo Energético , Paraganglioma , Feocromocitoma , Humanos , Metabolismo Energético/fisiología , Feocromocitoma/metabolismo , Paraganglioma/metabolismo , Neoplasias de las Glándulas Suprarrenales/metabolismo , Catecolaminas/metabolismo , Tejido Adiposo Pardo/metabolismo , Cromogranina A/metabolismoRESUMEN
Background: Graves' disease (GD) is the most common cause of hyperthyroidism, and its pathogenesis remains incompletely elucidated. Numerous studies have implicated the gut microbiota in the development of thyroid disorders. This study employs Mendelian randomization analysis to investigate the characteristics of gut microbiota in GD patients, aiming to offer novel insights into the etiology and treatment of Graves' disease. Methods: Two-sample Mendelian randomization (MR) analysis was employed to assess the causal relationship between Graves' disease and the gut microbiota composition. Gut microbiota data were sourced from the international consortium MiBioGen, while Graves' disease data were obtained from FINNGEN. Eligible single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Multiple analysis methods, including inverse variance-weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-RAPS, were utilized. Sensitivity analyses were conducted employing MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis as quality control measures. Results: The Mendelian randomization study conducted in a European population revealed a decreased risk of Graves' disease associated with Bacteroidaceae (Odds ratio (OR) [95% confidence interval (CI)]: 0.89 [0.89 ~ 0.90], adjusted P value: <0.001), Bacteroides (OR: [95% CI]: 0.555 [0.437 ~ 0.706], adjusted P value: <0.001), and Veillonella (OR [95% CI]: 0.632 [0.492 ~ 0.811], adjusted P value: 0.016). No significant evidence of heterogeneity, or horizontal pleiotropy was detected. Furthermore, the preliminary MR analysis identified 13 bacterial species including Eubacterium brachy group and Family XIII AD3011 group, exhibiting significant associations with Graves' disease onset, suggesting potential causal effects. Conclusion: A causal relationship exists between gut microbiota and Graves' disease. Bacteroidaceae, Bacteroides, and Veillonella emerge as protective factors against Graves' disease development. Prospective probiotic supplementation may offer a novel avenue for adjunctive treatment in the management of Graves' disease in the future.
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Bacteroidaceae , Enfermedad de Graves , Humanos , Bacteroides/genética , Veillonella , Estudios Prospectivos , Enfermedad de Graves/genética , Estudio de Asociación del Genoma CompletoRESUMEN
The clinical characteristics of Cushing's syndrome (CS) vary with etiology, and few studies have investigated the risk factors affecting CS recurrence after surgery. This retrospective study involved 202 patients diagnosed with CS between December 2012 and December 2022. The patients were divided into three groups according to etiology: Cushing's disease (CD), adrenocortical adenoma (ACA), and ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). Of the patients with CS, 41.9% had hypokalemia and 15.0% had hypophosphatemia. The cortisol levels were negatively correlated with blood potassium, blood chlorine, and blood phosphorus. Moreover, 22.4% of patients had an abnormal heart structure, 11.2% had centripetal remodeling, 5.6% had centripetal hypertrophy, and 5.6% had centrifugal hypertrophy. The overall recurrence rate of CS caused by pituitary tumors and adrenal adenoma was 25.7%. The recurrence times were longer in the ACA group versus the CD group, in patients < 50 years of age versus in patients ≥ 50 years old group, and in patients with CD with tumors ≥ 1 cm versus tumors < 1 cm. Age, preoperative cortisol level, postoperative cortisol level, and absolute neutrophil value were closely related to postoperative recurrence, and etiology was an independent predictor of tumor recurrence in patients with CS. The results of this study showed that CS caused by different etiologies showed different clinical manifestations, blood electrolyte characteristics, and that CS could affect patient cardiac structure and function. Etiology is an independent predictor of tumor recurrence in patients with CS.
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Adenoma Corticosuprarrenal , Síndrome de Cushing , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Humanos , Persona de Mediana Edad , Síndrome de Cushing/cirugía , Síndrome de Cushing/diagnóstico , Hidrocortisona , Estudios Retrospectivos , Recurrencia Local de Neoplasia/complicaciones , Factores de Riesgo , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/cirugía , Hipertrofia/complicacionesRESUMEN
Background: Numerous studies have demonstrated the influence of gut microbiota on the development of obesity. In this study, we utilized Mendelian randomization (MR) analysis to investigate the gut microbiota characteristics among different types of obese patients, aiming to elucidate the underlying mechanisms and provide novel insights for obesity treatment. Methods: Two-sample multivariable Mendelian randomization (MR) analysis was employed to assess causal relationships between gut microbiota and various obesity subtypes. Gut microbiota data were obtained from the international consortium MiBioGen, and data on obese individuals were sourced from the Finnish National Biobank FinnGen. Eligible single-nucleotide polymorphisms (SNPs) were selected as instrumental variables. Various analytical methods, including inverse variance weighted (IVW), MR-Egger regression, weighted median, MR-RAPS, and Lasso regression, were applied. Sensitivity analyses for quality control included MR-Egger intercept tests, Cochran's Q tests, and leave-one-out analyses and others. Results: Mendelian randomization studies revealed distinct gut microbiota profiles among European populations with different obesity subtypes. Following multivariable MR analysis, we found that Ruminococcaceae UCG010 [Odds Ratio (OR): 0.842, 95% confidence interval (CI): 0.766-0.926, Adjusted P value: 0.028] independently reduced the risk of obesity induced by excessive calorie intake, while Butyricimonas [OR: 4.252, 95% CI: 2.177-8.307, Adjusted P value: 0.002] independently increased the risk of medication-induced obesity. For localized adiposity, Pasteurellaceae [OR: 0.213, 95% CI: 0.115-0.395, Adjusted P value: <0.001] acted as a protective factor. In the case of extreme obesity with alveolar hypoventilation, lactobacillus [OR: 0.724, 95% CI: 0.609-0.860, Adjusted P value: 0.035] reduced the risk of its occurrence. Additionally, six gut microbiota may have potential roles in the onset of different types of obesity. Specifically, the Ruminococcus torques group may increase the risk of its occurrence. Desulfovibrio and Catenabacterium may serve as protective factors in the onset of Drug-induced obesity. Oxalobacteraceae, Actinomycetaceae, and Ruminiclostridium 9, on the other hand, could potentially increase the risk of Drug-induced obesity. No evidence of heterogeneity or horizontal pleiotropy among SNPs was found in the above studies (all P values for Q test and MR-Egger intercept > 0.05). Conclusion: Gut microbiota abundance is causally related to obesity, with distinct gut microbiota profiles observed among different obesity subtypes. Four bacterial species, including Ruminococcaceae UCG010, Butyricimonas, Pasteurellaceae and lactobacillus independently influence the development of various types of obesity. Probiotic and prebiotic supplementation may represent a novel approach in future obesity management.
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Actinomycetaceae , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Obesidad/genética , Bacteroidetes , Clostridiales , Lactobacillus , Nonoxinol , Estudio de Asociación del Genoma CompletoRESUMEN
Impaired macroautophagy/autophagy flux has been implicated in the treatment of prostate cancer (PCa). However, the mechanism underlying autophagy dysregulation in PCa remains unknown. In the current study, we investigated the role of diacylglycerol acyltransferases 1 (DGAT1) and its potential effects on cellular energy homeostasis and autophagy flux in PCa. The results of immunohistochemical staining suggested that DGAT1 expression was positively corrected with tumor stage and node metastasis, indicating DGAT1 is an important factor involved in the development and progression of PCa. Furthermore, targeting DGAT1 remarkably inhibited cell proliferation in vitro and suppressed PCa growth in xenograft models by triggering severe oxidative stress and subsequently autophagy flux blockage. Mechanically, DGAT1 promoted PCa progression by maintaining cellular energy homeostasis, preserving mitochondrial function, protecting against reactive oxygen species, and subsequently promoting autophagy flux via regulating lipid droplet formation. Moreover, we found that fenofibrate exhibits as an upstream regulator of DGAT1. Fenofibrate performed its anti-PCa effect involved the aforementioned mechanisms, and partially dependent on the regulation of DGAT1. Collectively. These findings indicate that DGAT1 regulates PCa lipid droplets formation and is essential for PCa progression. Targeting DGAT1 might be a promising method to control the development and progression of PCa. Schematic representation of DGAT1 affects autophagy flux by regulating lipid homeostasis and maintaining mitochondrial function in prostate cancer (PCa). PCa is characterized up-regulation of DGAT1, leading to the translocation of free fatty acids into lipid droplets, thereby preventing PCa cell from lipotoxicity. Inhibition of DGAT1 suppresses growth of PCa by inducing oxidative stress and subsequently autophagy flux blockage. Further, the current results revealed that fenofibrate exhibits as an upstream regulator of DGAT1, and fenofibrate plays an anti-PCa role partially dependent on the regulation of DGAT1, suggesting a potential therapeutic approach to ameliorate this refractory tumor.
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Fenofibrato , Neoplasias de la Próstata , Humanos , Masculino , Autofagia , Diacilglicerol O-Acetiltransferasa/antagonistas & inhibidores , Diacilglicerol O-Acetiltransferasa/genética , Diacilglicerol O-Acetiltransferasa/metabolismo , Fenofibrato/metabolismo , Fenofibrato/farmacología , Fenofibrato/uso terapéutico , Estrés Oxidativo , Próstata/patología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismoRESUMEN
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis. The disease originates from the cortex of adrenal gland and lacks effective treatment. Efforts have been made to elucidate the pathogenesis of ACC, but the molecular mechanisms remain elusive. To identify key genes and pathways in ACC, the expression profiles of GSE12368, GSE90713 and GSE143383 were downloaded from the Gene Expression Omnibus (GEO) database. After screening differentially expressed genes (DEGs) in each microarray dataset on the basis of cut-off, we identified 206 DEGs, consisting of 72 up-regulated and 134 down-regulated genes in three datasets. Function enrichment analyses of DEGs were performed by DAVID online database and the results revealed that the DEGs were mainly enriched in cell cycle, cell cycle process, mitotic cell cycle, response to oxygen-containing compound, progesterone-mediated oocyte maturation, p53 signaling pathway. The STRING database was used to construct the protein-protein interaction (PPI) network, and modules analysis was performed using Cytoscape. Finally, we filtered out eight hub genes, including CDK1, CCNA2, CCNB1, TOP2A, MAD2L1, BIRC5, BUB1 and AURKA. Biological process analysis showed that these hub genes were significantly enriched in nuclear division, mitosis, M phase of mitotic cell cycle and cell cycle process. Violin plot, Kaplan-Meier curve and stage plot of these hub genes confirmed the reliability of the results. In conclusion, the results in this study provided reliable key genes and pathways for ACC, which will be useful for ACC mechanisms, diagnosis and candidate targeted treatment.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Humanos , Perfilación de la Expresión Génica/métodos , Carcinoma Corticosuprarrenal/genética , Redes Reguladoras de Genes , Reproducibilidad de los Resultados , Neoplasias de la Corteza Suprarrenal/genética , Biología Computacional/métodosRESUMEN
Obesity and type 2 diabetes(T2D) lead to defects in intestinal hormones secretion, abnormalities in the composition of bile acids (BAs), increased systemic and adipose tissue inflammation, defects of branched-chain amino acids (BCAAs) catabolism, and dysbiosis of gut microbiota. Bariatric surgery (BS) has been shown to be highly effective in the treatment of obesity and T2D, which allows us to view BS not simply as weight-loss surgery but as a means of alleviating obesity and its comorbidities, especially T2D. In recent years, accumulating studies have focused on the mechanisms of BS to find out which metabolic parameters are affected by BS through which pathways, such as which hormones and inflammatory processes are altered. The literatures are saturated with the role of intestinal hormones and the gut-brain axis formed by their interaction with neural networks in the remission of obesity and T2D following BS. In addition, BAs, gut microbiota and other factors are also involved in these benefits after BS. The interaction of these factors makes the mechanisms of metabolic improvement induced by BS more complicated. To date, we do not fully understand the exact mechanisms of the metabolic alterations induced by BS and its impact on the disease process of T2D itself. This review summarizes the changes of intestinal hormones, BAs, BCAAs, gut microbiota, signaling proteins, growth differentiation factor 15, exosomes, adipose tissue, brain function, and food preferences after BS, so as to fully understand the actual working mechanisms of BS and provide nonsurgical therapeutic strategies for obesity and T2D.
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Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Hormonas Gastrointestinales , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Obesidad/complicaciones , Obesidad/cirugía , Obesidad/metabolismo , Pérdida de PesoRESUMEN
Background and purpose: Observational studies have shown that sarcopenia and diabetic nephropathy (DN), are closely related; however, the causal relationship is unclear. This study aims to address this issue using a bidirectional Mendelian randomization (MR) study. Methodology: We data from genome-wide association studies including appendicular lean mass (n = 244,730), grip strength (right: n = 461,089, left: n = 461026), walking speed (n = 459,915), and DN (3283 cases and 181,704 controls) to conduct a bidirectional MR study. First, we conducted a Forward MR analysis to evaluate the causality of sarcopenia on the risk of DN from the genetic perspective with appendicular lean mass, grip strength, and walking speed as exposure and DN as the outcome. Then, DN as the exposure, we performed a Reverse MR analysis to determine whether DN impacted the appendicular lean mass, grip strength, and walking speed of the appendices. Finally, a series of sensitivity studies, such as heterogeneity tests, pleiotropy evaluations, and Leave-one-out analyses, were conducted to assess the MR analysis's accuracy further. Results: According to a forward MR analysis, a genetically predicted decrease in appendicular lean mass is associated with an increased risk of developing DN risk (inverse variance weighting[IVW]: odd ratio [OR] = 0.863, 95% confidence interval [CI] 0.767-0.971; P = 0.014). According to reverse MR results, grip strength decreased as DN progressed (IVW: right ß = 0.003, 95% CI: - 0.021 to - 0.009, P = 5.116e-06; left ß = 0.003, 95% CI: - 0.024 to - 0.012, P = 7.035e-09). However, the results of the other MR analyses were not statistically different. Conclusion: Notably, our findings suggest that the causal relationship between sarcopenia and DN cannot be generalized. According to analysis of the individual characteristic factors of sarcopenia, reducing in appendicular lean mass increases the risk of developing DN and DN is linked to reduced grip strength. But overall, there is no causal relationship between sarcopenia and DN, because the diagnosis of sarcopenia cannot be determined by one of these factors alone.
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Diabetes Mellitus , Nefropatías Diabéticas , Sarcopenia , Humanos , Sarcopenia/complicaciones , Sarcopenia/genética , Sarcopenia/diagnóstico , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo , Nefropatías Diabéticas/genética , Fuerza de la ManoRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) and diabetic complications threaten human health seriously. Healthy lifestyles can lower the risk of cardiovascular disease (CVD) and long-term complications. However, the relationship between alcohol consumption and CVD mortality is still controversial, and there is a lack of evidence from large-scale longitudinal studies in the Chinese population. Based on the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study), this paper explores the association between alcohol consumption and all-cause mortality, stroke, and coronary heart disease (CHD) in patients with abnormal glucose metabolism during a 10-year follow-up period to provide evidence for lifestyle counselling for these patients. METHODS: First, baseline data were collected from the REACTION study cohort in Changchun, Jilin Province, China, in 2011-2012. A questionnaire survey was performed among patients with abnormal glucose metabolism aged over 40 years. The frequency of their alcohol intake, the type of alcohol, and the amount of alcohol consumed daily were surveyed. Physical and biochemical examinations were also performed. Then, through the Primary Public Health Service System of Jilin Province, we collected outcomes during the 10-year follow-up up to October 1, 2021, including all-cause mortality, stroke, and CHD. Next, we conducted logistic regression to analyze the relationship between baseline alcohol consumption and 10-year outcomes, and risk ratio (RR) and 95% CI were calculated by adjusting for different clinical indicators. A p value < 0.05 was considered statistically significant. RESULTS: A total of 4855 patients with T2DM and prediabetes (35.2% men and 64.8% women) were included in the baseline analysis. Outcomes of 3521 patients during the 10-year follow-up were obtained, including 227 deaths, 296 new-onset strokes and 445 new-onset CHD. Occasional drinking (less than once a week) was associated with a reduced 10-year all-cause mortality, with an RR of 0.511 (95% CI [0.266, 0.982]) after adjustment for age, gender, medical history, and lifestyles and an RR of 0.50 (95% CI [0.252, 0.993]) in a fully adjusted model including additional biochemical indicators. In addition, heavy alcohol consumption (≥30 g/day for men and ≥15 g/day for women) was significantly associated with an increased incidence of stroke, with an RR of 2.503 (95% CI [1.138, 5.506]) after the adjustment for age, gender, medical history, lifestyles, and biochemical indicators. No significant association was found between alcohol consumption and new-onset CHD. CONCLUSIONS: For patients with abnormal glucose metabolism, occasional drinking (less than once a week) reduces the risk of all-cause mortality, while heavy alcohol consumption (≥30 g/day for men and ≥15 g/day for women) significantly increases the risk of new-onset stroke. They should avoid heavy alcohol intake, but light alcohol consumption or occasional drinking is acceptable. Additionally, it is crucial to control blood glucose and blood pressure and keep performing physical activities.
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Enfermedades Cardiovasculares , Enfermedad Coronaria , Diabetes Mellitus Tipo 2 , Accidente Cerebrovascular , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Estudios Longitudinales , Estudios de Seguimiento , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Estudios Prospectivos , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/etiología , Enfermedades Cardiovasculares/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/complicaciones , Factores de RiesgoRESUMEN
Lipotoxicity is the dysregulation of the lipid environment and/or intracellular composition that leads to accumulation of harmful lipids and ultimately to organelle dysfunction, abnormal activation of intracellular signaling pathways, chronic inflammation and cell death. It plays an important role in the development of acute kidney injury and chronic kidney disease, including diabetic nephropathy, obesity-related glomerulopathy, age-related kidney disease, polycystic kidney disease, and the like. However, the mechanisms of lipid overload and kidney injury remain poorly understood. Herein, we discuss two pivotal aspects of lipotoxic kidney injury. First, we analyzed the mechanism of lipid accumulation in the kidney. Accumulating data indicate that the mechanisms of lipid overload in different kidney diseases are inconsistent. Second, we summarize the multiple mechanisms by which lipotoxic species affect the kidney cell behavior, including oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, dysregulated autophagy, and inflammation, highlighting the central role of oxidative stress. Blocking the molecular pathways of lipid accumulation in the kidney and the damage of the kidney by lipid overload may be potential therapeutic targets for kidney disease, and antioxidant drugs may play a pivotal role in the treatment of kidney disease in the future.
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Metabolismo de los Lípidos , Insuficiencia Renal Crónica , Humanos , Riñón/metabolismo , Insuficiencia Renal Crónica/metabolismo , Inflamación/metabolismo , LípidosRESUMEN
The prevalence of obesity has increased dramatically during the past decades, which has been a major health problem. Since 1975, the number of people with obesity worldwide has nearly tripled. An increasing number of studies find obesity as a driver of chronic kidney disease (CKD) progression, and the mechanisms are complex and include hemodynamic changes, inflammation, oxidative stress, and activation of the renin-angiotensin-aldosterone system (RAAS). Obesity-related kidney disease is characterized by glomerulomegaly, which is often accompanied by localized and segmental glomerulosclerosis lesions. In these patients, the early symptoms are atypical, with microproteinuria being the main clinical manifestation and nephrotic syndrome being rare. Weight loss and RAAS blockers have a protective effect on obesity-related CKD, but even so, a significant proportion of patients eventually progress to end-stage renal disease despite treatment. Thus, it is critical to comprehend the mechanisms underlying obesity-related CKD to create new tactics for slowing or stopping disease progression. In this review, we summarize current knowledge on the mechanisms of obesity-related kidney disease, its pathological changes, and future perspectives on its treatment.
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Glomeruloesclerosis Focal y Segmentaria , Enfermedades Renales , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/complicaciones , Obesidad/complicaciones , Sistema Renina-Angiotensina/fisiología , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Enfermedad Crónica , Riñón , Progresión de la EnfermedadRESUMEN
Plurihormonal pituitary adenoma (PPA) is a type of pituitary tumor capable of producing two or more hormones and usually presents as an aggressive, large adenoma. As yet, its pathogenesis remains unclear. This is the first study to systematically summarize the underlying pathogenesis of PPA. The pathogenesis is related to plurihormonal primordial stem cells, co-transcription factors, hormone co-expression, differential gene expression, and cell transdifferentiation. We conducted a literature review of PPA and analyzed its clinical characteristics. We found that the average age of patients with PPA was approximately 40 years, and most showed only one clinical symptom. The most common manifestation was acromegaly. Currently, PPA is treated with surgical resection. However, recent studies suggest that immunotherapy may be a potentially effective treatment.
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Background: The correlation between benign thyroid disease (BTD) and breast cancer (BC) has long been discussed. However, the definite relationship and potential mechanism between them are still disputed. The current meta-analysis aimed at performing a comprehensive assessment of the relationship between different types of benign thyroid disease and the risk of breast cancer, furthermore, assessing whether benign thyroid disease exerts an influence on the aggressiveness of breast cancer. Method: A systematic literature search (PubMed, Web of Science, MEDLINE, and Embase databases) identified studies to evaluate the correlation between BTD and BC risk. Data were analyzed using version 16.0 STATA software, including the odds ratio (OR) and its corresponding 95% confidence intervals (CIs). Publication bias and quality assessment were conducted for the included studies. Result: Overall, 18 studies involving 422,384 patients with BTD were incorporated. The outcome showed that autoimmune thyroiditis (OR: 2.56, 95%CI: 1.95-3.37, I2 = 0.0%, p=0.460), goiter (OR: 2.13, 95%CI: 1.19-3.79, I2 = 80.6%, p=0.000), and Graves' disease (OR: 5.01, 95%CI: 1.49-16.82, I2 = 0.0%, p=0.358) was connected with a higher risk of BC. Both hypothyroidism (OR: 0.82, 95%CI: 0.64-1.04, I2 = 85.0%, p=0.000) and hyperthyroidism (OR: 1.07, 95%CI: 0.93-1.24, I2 = 24.9%, p=0.206) had no significant association with the risk of BC. Additionally, the pooled analysis showed no apparent correlation between BTD and aggressiveness of BC. However, subgroup analysis indicated a positive relationship between BTD and aggressiveness of BC in the Europe subgroup (HR: 2.05, 95%CI: 1.32-3.17, I2 = 86.4%, p=0.000). Conclusion: Autoimmune thyroiditis, goiter, and Graves' disease are connected with an increased risk of BC. Furthermore, subgroup analysis suggested that BTD increases the aggressiveness of BC in the European population geographically. Nevertheless, further research is needed to prove these discoveries.
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Neoplasias de la Mama , Bocio , Enfermedad de Graves , Enfermedades de la Tiroides , Tiroiditis Autoinmune , Humanos , Femenino , Tiroiditis Autoinmune/complicaciones , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Enfermedades de la Tiroides/complicaciones , Enfermedades de la Tiroides/epidemiología , Bocio/complicaciones , Enfermedad de Graves/complicacionesRESUMEN
Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS), which mainly occurs in children and young adults. Treatment options with proven clinical efficacy for PPNAD include adrenalectomy (bilateral or unilateral adrenalectomy) and drug treatment to control hypercortisolemia. Previously, the main treatment of PPNAD is bilateral adrenal resection and long-term hormone replacement after surgery. In recent years, cases reports suggest that unilateral or subtotal adrenal resection can also lead to long-term remission in some patients without the need for long-term hormone replacement therapy. Medications for hypercortisolemia, such as Ketoconazole, Metyrapone and Mitotane et.al, have been reported as a preoperative transition for in some patients with severe hypercortisolism. In addition, tryptophan hydroxylase inhibitor, COX2 inhibitor Celecoxib, somatostatin and other drugs targeting the possible pathogenic mechanisms of the disease are under study, which are expected to be applied to the clinical treatment of PPNAD in the future. In this review, we summarize the recent progress on treatment of PPNAD, in which options of surgical methods, research results of drugs acting on possible pathogenic mechanisms, and the management during gestation are described in order to provide new ideas for clinical treatment.
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Enfermedades de la Corteza Suprarrenal , Síndrome de Cushing , Niño , Adulto Joven , Humanos , Síndrome de Cushing/tratamiento farmacológico , Síndrome de Cushing/complicaciones , Adrenalectomía , Hormona Adrenocorticotrópica , Mitotano , Resultado del Tratamiento , Enfermedades de la Corteza Suprarrenal/terapia , Enfermedades de la Corteza Suprarrenal/etiologíaRESUMEN
Shapiro's syndrome (SS) is characterized by spontaneous periodic hypothermia. It occurs to patients regardless of age or sex. To date, <60 cases have been reported worldwide. Current knowledge of the disease is limited to clinical feature since the pathogenesis and etiology are still controversial. In this review, the clinical characteristics, pathological mechanism, and possible etiology of the syndrome were reviewed to improve the clinical understanding of the disease.
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RATIONALE: Thyroid storm (TS) is a rare life-threatening hypermetabolic thyrotoxicosis with an incidence of 0.57-0.76/100,000. The coexistence of TS and acute cerebral infarction is rare. Previous studies have shown that hyperthyroidism complicated by cerebral infarction mainly occurs in the intracranial basal ganglia; however, there are no reports of corpus callosum infarction. We report a case of TS complicated by cerebral infarction of the corpus callosum at our hospital. PATIENT CONCERNS: A 31-year-old male patient with a history of hyperthyroidism was admitted to the hospital because of fatigue, palpitations, fever, and profuse sweating accompanied by a mild decrease in the muscle strength of the left limb. Diagnosis of a TS was confirmed by the laboratory test results. The patient's clinical symptoms gradually improved after treatment. However, his left limb muscle strength progressively decreased, and the bilateral pathological signs were positive at the same time. Magnetic resonance imaging (MRI) of the head revealed acute cerebral infarction of the corpus callosum and pons. DIAGNOSIS: The diagnosis was thyroid strom with acute cerebral infarction of the corpus callosum and pons and severe stenosis or occlusion of the basilar artery. INTERVENTIONS: The patient was given 300 mg hydrocortisone intravenously per day, propylthiouracil tablets of 200 mg 3 times a day by nasal feeding, and 20 mg propranolol three times a day by nasal feeding. Aspirin and clopidogrel were administered to prevent platelet aggregation, and atorvastatin calcium was administered to lower lipid levels to stabilize plaques. OUTCOMES: The patient's left limb muscle strength recovered to grade 4+, and he could walk beside the bed with support. Simultaneously, thyroid function was better than before. LESSONS: Careful physical examination should be performed in patients with thyroid storm, and head imaging examination should be improved for the early detection of cerebral infarction.
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Accidente Cerebrovascular , Crisis Tiroidea , Adulto , Aspirina , Infarto Cerebral/complicaciones , Infarto Cerebral/patología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Humanos , Imagen por Resonancia Magnética/efectos adversos , Masculino , Accidente Cerebrovascular/complicaciones , Crisis Tiroidea/complicaciones , Crisis Tiroidea/diagnósticoRESUMEN
Cushing's syndrome (CS) is caused by hypercortisolemia, leading to the occurrence of characteristic clinical symptoms. A small number of patients with CS have periodic and intermittent increases in cortisol levels, resulting in recurrent episodes of clinical symptoms. Such patients are known as having cyclic CS (CCS). The cortisol secretion cycle of patients with CCS is unpredictable, and laboratory tests often show negative results during the normal cortisol secretion period; therefore, the diagnosis and treatment of the disease are currently difficult. Although the pathogenesis of CCS remains uncertain, recent studies have suggested that it may be closely related to hypothalamic factors, feedback mechanisms, and tumor infarction. Our review summarizes the current state of research on the potential mechanisms, diagnosis, and treatment of CS and provides an outlook for future studies.
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Síndrome de Cushing , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiología , Síndrome de Cushing/terapia , Humanos , HidrocortisonaRESUMEN
BACKGROUND: Antidiabetic medications (ADMs) may modify prostate cancer (PCa) risk in patients with diabetes mellitus (DM). Accordingly, the current study assessed the possible associations between ADMs and the risk of PCa in diabetics. METHODS: A systematic literature search (PubMed, Embase and Cochrane Library) identified studies evaluating the associations between ADMs and incidence of PCa. A meta-analysis followed PRISMA was performed using odds ratio (OR) with 95% confidence interval (CI) as effect measures. RESULTS: In total of 47 studies involving 3094,152 patients with diabetes were included. Results of meta-analysis of the observational studies suggested no significant association between metformin, thiazolidinediones, sulfonylureas, insulin or dipeptidyl peptidase-4 inhibitors administration and the risk of PCa (All p-values > 0.05). Separate analysis of randomized controlled trials (RCTs) revealed a significant reduction in PCa risk with thiazolidinediones (OR = 0.55, p = 0.04) or glucagon-like peptide-1 receptor agonists (GLP-1RA) administration (OR = 0.53, p = 0.006), whereas no significant association was found in SGLT2 inhibitors (p = 0.3). CONCLUSION: Thiazolidinediones or GLP-1RA administration may have benefits in PCa based on RCTs, however, further research is needed to confirm these findings.
Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Neoplasias de la Próstata , Tiazolidinedionas , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/epidemiologíaRESUMEN
PURPOSE: Liquid biopsy refers to the detection and analysis of the components from biological fluids non-invasively, including circulating tumor cells, nucleic acids, and extracellular vesicles (EVs). It is necessary to review the clinical value of liquid biopsy assays in PC and explore its potential application. MATERIALS AND METHODS: We systematically reviewed of PubMed was performed to identify relevant literature on potential clinical applications of circulating tumor cells, circulating nucleic acids, and EVs in prostate cancer (PC). RESULTS: Liquid biopsy has emerged as a powerful tool to elucidate dynamic genomic, transcriptomic, and epigenomic tumor profiling in real-time. Here, the potential clinical applications of liquid biopsy include early detection, prognosis of survival, assessment of treatment response, and mechanisms of drug resistance in PC. CONCLUSIONS: Liquid biopsy provides great value in diagnosis, prognosis, and treatment response in PC. Characterization of liquid biopsy components provides benefits both to unravel underlying resistance mechanisms and to exploit novel clinically actionable targets in PC. In addition, we suggest that analysis of multiparametric liquid biopsies should be analyzed comprehensively, assisting in monitoring tumor characteristics in real-time, guiding therapeutic selection, and early therapeutic switching during disease progression.