RESUMEN

Whether Klotho plays any role in hypothyroidism is unknown. This study aimed to determine the relationship between serum Klotho levels and hypothyroidism in older adults. From the 2007 to 2012 National Health and Nutrition Examination Survey (NHANES), 1444 older adults aged 65-79 were included in this cross-sectional study. Hypothyroidism was diagnosed using participants' reports of current medications and TSH tests. Klotho was measured using an enzyme-linked immunosorbent assay. The relationship between serum Klotho levels and hypothyroidism in older people was analyzed by one-way analysis of variance, multiple linear regression models, subgroup analyses, interaction tests, smoothed curve fitting, and threshold effects. A total of 209 (14.47%) participants were identified as having hypothyroidism. Serum Klotho (ln transformation) is independently and significantly negatively associated with the risk of hypothyroidism after complete adjustment for confounders (OR = 0.49, 95% CI 0.31-0.80; P = 0.0039). The results remained stable based on subgroup analyses and interaction tests. However, we observed an inverted U-shaped curve between the two using a smoothed curve fitting in the subgroups of 70 < age ≤ 75 years and females, with inflection points of 6.26 and 6.17, respectively. The results of our study indicate that serum Klotho levels negatively correlate with hypothyroidism among older adults.

Asunto(s)

Glucuronidasa , Hipotiroidismo , Proteínas Klotho , Encuestas Nutricionales , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/epidemiología , Masculino , Femenino , Anciano , Estudios Transversales , Glucuronidasa/sangre

RESUMEN

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can provide tumor biological metabolism and skeletal muscle composition information. The aim of this study was to evaluate overall survival (OS) and short-term efficacy of cervical squamous cell carcinoma combining tumor biological metabolism and skeletal muscle composition parameters. Eighty two patients with cervical squamous cell carcinoma were included in the study, who received 18F-FDG PET/CT scans before treatment. Clinical characteristics, tumor biological metabolism parameters [standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis, heterogeneity of tumors, etc.] and body composition parameters were recorded. The survival analysis of cervical squamous cell carcinoma patients was performed by univariate and multivariate analysis. A combined model included clinical indicators, tumor metabolism parameters and sarcopenia was constructed to evaluate OS of patients. According to the Response Evaluation Criteria in Solid Tumours version 1.1, the relationship between sarcopenia with tumor metabolism parameters and short-term efficacy was investigated in subgroup. The results indicate that sarcopenia and high value of the sum of MTV of lesions and metastases (MTVtotal) were poor prognostic factors in patients with cervical squamous cell carcinoma. The combination of sarcopenia, MTVtotal and clinical factors provided an improved prediction of OS especially in the long term after treatment. Nutritional status of the patients and tumor metabolism may not affect the short-term efficacy of chemoradiotherapy in cervical squamous cell carcinoma patients.

Asunto(s)

Carcinoma de Células Escamosas , Sarcopenia , Neoplasias del Cuello Uterino , Femenino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Sarcopenia/diagnóstico por imagen , Sarcopenia/patología , Pronóstico , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/metabolismo , Tomografía de Emisión de Positrones , Músculo Esquelético/metabolismo , Carga Tumoral , Radiofármacos , Estudios Retrospectivos

RESUMEN

OBJECTIVE: This study aimed to evaluate the effects of three antioxidants, selenium yeast capsule, vitamin E and vitamin C, alone or in combination, on the salivary glands of patients with differentiated thyroid cancer (DTC) treated with iodine-131 ( 131 I). METHODS: A total of 69 postoperative DTC patients were randomly divided into three groups: vitamin E combined with vitamin C group (21 cases); selenium yeast group (23 cases); and selenium yeast combined with vitamin C group (25 cases). Salivary gland functional changes were assessed by salivary gland dynamic imaging functional parameters in the enrolled patients before and 1 month after 131 I treatment. RESULTS: Comparison of salivary gland function parameters before and after 131 I treatment in the three groups were evaluated. In the vitamin E combined with the vitamin C group, the left parotid gland excretion fraction (EF) value was significantly higher than that before treatment. In the selenium yeast group, the left parotid gland excretion part, bilateral parotid gland excretion ratio (ER), left submandibular gland maximum uptake ratio within 20 min (UR20), and the right submandibular gland ER values were significantly higher than that before treatment, while in the selenium yeast combined with vitamin C group, the bilateral parotid gland EF, bilateral submandibular gland UR20, EF, and left submandibular gland ER values were significantly higher than that before treatment (all P < 0.05). CONCLUSION: During high-dose 131 I treatment, vitamin E combined with vitamin C improved the excretory function of parotid glands in DTC patients; selenium supplementation had a protective effect on salivary glands; and the combination of selenium and vitamin C had a better effect.

Asunto(s)

Selenio , Neoplasias de la Tiroides , Humanos , Radioisótopos de Yodo/uso terapéutico , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Selenio/farmacología , Selenio/uso terapéutico , Saccharomyces cerevisiae , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/tratamiento farmacológico , Glándulas Salivales , Glándula Parótida , Vitamina E/farmacología , Vitamina E/uso terapéutico , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico

RESUMEN

The effects of total thyroidectomy or radioactive iodine therapy on immune activation and suppression of the tumor microenvironment remain unknown. We aimed to investigate the effects of these treatments on the immune function in patients with differentiated thyroid carcinoma (DTC). Our cohort included 45 patients with DTC treated with total thyroidectomy and radioactive iodine therapy (RAIT). Immune function tests were performed by flow cytometry at 0, 30, and 90 days post-RAIT. Both the percentage and absolute number of circulating regulatory T cells were significantly lower in the postoperative DTC compared to the healthy controls. Notably, the absolute number of multiple lymphocyte subgroups significantly decreased at 30 days post-RAIT compared to those pre-RAIT. The absolute counts of these lymphocytes were recovered at 90 days post-RAIT, but not at pre-RAIT levels. Additionally, the Th17 cell percentage before RAIT was positively correlated with thyroglobulin (Tg) levels after RAIT. The tumor burden might contribute to increased levels of circulating Tregs. In conclusion, RAIT caused transient radiation damage in patients with DTC and the percentage of Th17 cells before RAIT could be a significant predictor of poor prognosis in patients with DTC.

Asunto(s)

Adenocarcinoma , Neoplasias de la Tiroides , Adenocarcinoma/cirugía , Humanos , Inmunidad , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Microambiente Tumoral

RESUMEN

OBJECTIVE: Graves' disease (GD) is one of the most common autoimmune conditions, but the mechanisms underlying the associated induction of autoimmunity are not known. We explored the role of peripheral lymphocyte subpopulations in disease pathogenesis. METHODS: In total, 32 patients and 40 age- and sex-matched healthy controls were recruited in this study. Peripheral levels of T, B, NK, CD4+ T, CD8+ T, Th1, Th2, Th17, and Treg cells were measured using flow cytometry. For all patients, we compared all lymphocyte subpopulations between GD patients and healthy controls. Changes in patient lymphocyte subsets were compared before and after treatment. RESULTS: The absolute numbers of circulating Th17 cells (0.45 ± 1.16, p > 0.05) between GD patients and healthy controls were not significantly different. However, the percentage of Th17 cells was significantly increased (0.25 ± 0.11, p < 0.05). The absolute numbers and percentages of circulating Tregs in GD patients were significantly decreased compared with those in healthy participants (11.61 ± 2.75, p < 0.05). There was a significant difference in Treg absolute numbers between the untreated and drug-treated groups. Furthermore, we found that the Treg percentage in untreated patients (mean=4.78) was not significantly different from that in the drug-treated group (mean=4.81). In addition, circulating Treg absolute numbers in GD patients with exophthalmos were significantly lower than those in GD patients without exophthalmos (9.96 ± 4.16, p < 0.05). A similar trend was observed in GD patients with weight loss (11.97 ± 3.28, p < 0.05). CONCLUSION: GD pathogenesis was associated with a lower Treg population and an increased Th17/Treg ratio (T helper cell 17/ regulatory T cells). Th17 cells in this study were not related to the disease. Furthermore, anti-thyroid drug therapy improved immune-mediated system disorders. Finally, we found lower absolute numbers of circulating Tregs in GD patients with certain positive signs, such as exophthalmos and/or weight loss. Thus, immune changes are correlated with partial clinical manifestations.

Asunto(s)

Enfermedad de Graves , Linfocitos T Reguladores , Enfermedad de Graves/diagnóstico , Enfermedad de Graves/tratamiento farmacológico , Humanos , Recuento de Linfocitos , Células Th17 , Pérdida de Peso

RESUMEN

OBJECTIVE: This study aimed to evaluate the effect of closed-loop management on nursing disruption risk. METHODS: Using a quasi-experimental research method, convenient sampling was used to extract 20 nurses working at our hospital as the research objects. The control group members were selected from January to March 2018 via the traditional method, and the experimental group members were selected from April to June 2018 via the closed-loop management method. At three months before and after the implementation of the management model, a self-designed quantitative test form and satisfaction questionnaire were used to analyze the frequency of nursing disruption events, the accuracy rate of doctors' advice, the average drug delivery time of the static distribution center, the implementation rate of personal digital assistant (PDA) code scanning, and the report rate of risk-outcome nursing disruption events. RESULTS: After the implementation of the management model, the frequency of nursing disruptions and average drug delivery time of the static distribution center were significantly lower than before, and the differences were statistically significant (p < 0.05). Moreover, the accuracy rate of doctors' advice, the implementation rate of PDA code scanning, and the reporting rate of risk-outcome nursing disruption events were significantly higher than before, and these differences were statistically significant as well (p < 0.05). CONCLUSION: The application of a closed-loop management model could significantly reduce the occurrence and optimize the outcomes of nursing disruption events and improve the work processes of medical care.

RESUMEN

OBJECTIVE: To investigate the value of (99)Tc(m)N-NOET dual-phase SPECT in differential diagnosis of benign and malignant lung tumors. METHODS: CT scan, early (20 to 30 min) and delayed (2 h) imaging of NOET SPECT were performed on 61 patients suspected of lung lesions before operation. The results were compared with the pathological findings. All cases were not treated with radiotherapy, chemotherapy or surgery before checks. Moreover, all patients had pathological diagnosis. To determine the value in differential diagnosis of tumors by analyzing the tumor uptake and excretion of (99)Tc(m)N-NOET, and the results were compared with that of CT. RESULTS: The value of early T/N ratio (ER) in the malignant (G1) and benign (G2) groups was 1.25 ± 0.15 and 1.09 ± 0.11 (P < 0.001), respectively, and delayed T/N ratio (DR) was 1.40 ± 0.17 and 1.18 ± 0.21 (P < 0.001). The retention index (RI) of groups G1 was (12.22 ± 6.38)% and group G2 was (8.3 ± 10.91)%, with a non-significant difference between them (P > 0.05). The ER, DR and RI of NOET SPECT in the malignant patients were not significantly correlated with TNM staging, pathological types, tumor diameter, cavity in the lung tumor mass, history of smoking, tumor size and patient gender (P > 0.05). The sensitivity of NOET dual-phase SPECT and CT in the differential diagnosis of benign and malignant lung tumors was 94.1% vs. 90.2%, specificity was 70.0% vs. 80.0% , positive predictive value (PPV) was 94.1% vs. 95.8%, negative predictive value (NPV) was 70.0% vs. 61.5 %, and accuracy was 90.2%. vs. 88.5% (P > 0.05 for all). CONCLUSIONS: (99)Tc(m)N- NOET dual-phase SPECT could be used in differential diagnosis of benign and malignant lung tumors, with no significant differences compared with the efficacy of CT imaging. The semiquantitative indexes (ER, DR and RI) of NOET SPECT can also be used in differential diagnosis of benign and malignant lung tumors, and are not significantly correlated with TNM staging, pathological types, tumor diameter, cavity of the lung tumor mass, history of smoking, tumor size and patient gender.

Asunto(s)

Neoplasias Pulmonares/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Diagnóstico Diferencial , Humanos , Estadificación de Neoplasias , Tomografía Computarizada de Emisión de Fotón Único/métodos

RESUMEN

Structural changes in hepatocellular mitochondria are characteristic of Wilson disease (WD). Features include variability in size and shape, increased density of matrix, discreet inclusions, and cystic dilatation of the cristae. We examined the functional basis for these mitochondrial changes in the toxic milk (tx-j) mouse model for WD. Its normal syngeic strain, C3H, served as control. Hepatic histology was near-normal in tx-j mice at 3-4-months-old and showed mild inflammation and steatosis at 6-months-old. Transmission electron microscopy showed typical mitochondrial abnormalities, specifically cystic dilatation of tips of cristae, in 3, 4, and 6-month-old tx-j mice and none in normal 3-month-old C3H mice. Citrate synthase (CS) activity was initially lower in tx-j mice than age-matched controls but increased over the first 6 months such that it was significantly greater at 5 and 6-months-old (p<0.003). No evidence for hepatic mtDNA depletion was found by long-PCR analysis. NB-PAGE showed preservation of all complexes in the oxidative-phosphorylation chain except complex IV which declined markedly from 5-months-old onwards. Hepatic complex IV activity was significantly decreased in 5-month-old tx-j mice (p<0.04). Expression of mitochondrial transfer factor A (TFAM) mRNA declined progressively in 6-8-month-old tx-j mice; immunodetectable protein levels declined in parallel. Expression of mtSSB mRNA was uniformly low in tx-j mice from 1-8-months-old. Levels of two mitochondrial antioxidant proteins capable of binding copper, thioredoxin-2 and peroxiredoxin-3, rose over the first 6 months of life. Mitochondrial changes occur early in WD and reflect complex, probably oxidative, injury.

Asunto(s)

Modelos Animales de Enfermedad , Degeneración Hepatolenticular/patología , Mitocondrias Hepáticas/fisiología , Mitocondrias Hepáticas/ultraestructura , Animales , Citrato (si)-Sintasa/metabolismo , ADN Mitocondrial/análisis , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Progresión de la Enfermedad , Proteínas del Complejo de Cadena de Transporte de Electrón/metabolismo , Proteínas del Complejo de Cadena de Transporte de Electrón/fisiología , Femenino , Hepatocitos/ultraestructura , Degeneración Hepatolenticular/genética , Degeneración Hepatolenticular/metabolismo , Degeneración Hepatolenticular/fisiopatología , Proteínas del Grupo de Alta Movilidad/genética , Proteínas del Grupo de Alta Movilidad/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Mutantes , Leche , Mitocondrias Hepáticas/metabolismo , Fosforilación Oxidativa , Peroxiredoxina III , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo , Tiorredoxinas/genética , Tiorredoxinas/metabolismo , Factores de Tiempo

RESUMEN

Wilson disease (WD) is due to mutations in ATP7B, which encodes an intracellular metal-transporting P-type ATPase. In WD holoceruloplasmin production and biliary excretion of copper are decreased, leading to copper overload, oxidative stress and apoptotic cell death. Other copper-binding proteins include COMMD1, which is inactive in the Bedlington terrier hereditary copper toxicosis, and XIAP, which regulates apoptosis. We examined developmental expression of Commd1 and Xiap in the Jackson toxic milk mouse (Atp7b(tx-J), G712D missense mutation in Atp7b). Expression of Commd1 mRNA appeared unchanged by PCR but real-time PCR demonstrated 3- to 4-fold increase over the first 6 months of life. Immunodetectable Xiap dropped over the first 8 months of life and was nearly undetectable from 6 months onward. Cytosolic NF-kappaB rose then dropped precipitously at 5-6 months. In tx-j mice hepatic copper accumulation leads to decreased Xiap, increased Commd1; these responses ultimately fail to prevent progressive apoptotic cell damage.

Asunto(s)

Regulación del Desarrollo de la Expresión Génica , Hígado/crecimiento & desarrollo , Hígado/metabolismo , Proteínas/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Animales , Citosol/metabolismo , Femenino , Masculino , Ratones , FN-kappa B/metabolismo , Proteínas/genética , ARN Mensajero/genética , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo

RESUMEN

The metalloproteome is defined as the set of proteins that have metal-binding capacity by being metalloproteins or having metal-binding sites. A different metalloproteome may exist for each metal. Mass spectrometric characterization of metalloproteomes provides valuable information relating to cellular disposition of metals physiologically and in metal-associated diseases. We examined the Cu and Zn metalloproteomes in three human hepatoma lines: Hep G2 and Mz-Hep-1, which retain many functional characteristics of normal human hepatocytes, and SK-Hep-1, which is poorly differentiated. Additionally we studied a single specimen of normal human liver and Hep G2 cells depleted in vitro of cellular copper. We used matrix-assisted laser desorption ionization and electrospray ionization quadrupole time-of-flight mass spectrometry to analyze peptide sequences of tryptic digests obtained by either in-gel digestion of metal-binding proteins or peptides on an immobilized metal affinity chromatography column loaded with either Cu or Zn. Mainly high abundance proteins were identified. Cu-binding proteins identified included enolase, albumin, transferrin, and alcohol dehydrogenase as well as certain intracellular chaperone proteins. The Cu metalloproteome was not identical to the Zn metalloproteome. Peptide binding experiments demonstrated that Cu coordination prefers the order of residues histidine > methionine > cysteine. Although the Cu metalloproteome was similar from line to line, subtle differences were apparent. Gel profiling showed more extensive variation in expression of annexin II in SK-Hep-1 and Mz-Hep-1 than in Hep G2 and normal liver tissue. Glycerylphosphorylethanolamine was identified as a post-translational modification at residue Glu-301 of elongation factor 1-alpha in Hep G2. Intracellular copper depletion was associated with loss of the glycerylphosphoryl side group. These findings suggest that post-translational modification could be affected by intracellular actions of copper. Comparison of the Cu and Zn metalloproteomes in Hep G2 with a published general proteome of Hep G2 disclosed little overlap (Seow, T. K., et al. (2001) Proteomics 1, 1249-1263). Proteins in the metalloproteomes of human hepatocytes can be identified by these methods. Variations in these metalloproteomes may have important physiological relevance.

Asunto(s)

Cobre/metabolismo , Metaloproteínas/metabolismo , Proteoma/metabolismo , Zinc/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Carcinoma Hepatocelular , Línea Celular Tumoral , Electroforesis en Gel Bidimensional , Humanos , Hígado/metabolismo , Datos de Secuencia Molecular , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción