RESUMEN
Background: Free light chains κ and λ (FLC κ, FLC λ) are of great significance in diagnostic and monitoring monoclonal gammopathy. Freelite and N-Latex methods are two common monitoring methods at present. But the two meanings are not completely equivalent, especially for patients with renal insufficiency. We analyzed the changes of serum and urine FLC in renal insufficiency patients without monoclonal gammopathy and the clinical significance of these changes. Methods: This study is an observational study. Patients ≥ 18 years old, who met the diagnostic criteria of chronic kidney disease (CKD), excluding monoclonal gammopathy, were selected. Fasting serum and 24-hour urine were taken to detect serum FLC κ, serum FLC λ, SCr, serum ß 2-microglobulin, urinary FLC κ, urinary FLC λ, urinary α 1-microglobulin, and urinary ß 2-microglobulin. Results: There was a good correlation between the two methods for determining serum/urinary FLC. No matter serum or urine, FLC showed a good correlation with renal function by the N-Latex method, but not by the Freelite method. Under the N-Latex method, FLC κ/λ remained stable, which was basically within the reference range of healthy people and was not affected by renal function. There was a good correlation between FLC detected by N-Latex and microglobulin in serum and urine. Conclusion: When the concentration of FLC is low, the N-Latex method is more recommended to monitor FLC. The FLC measured by the N-Latex method is more closely related to renal function. The ratio of FLC κ/λ determined by the N-Latex method remained stable within the recommended range.
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Paraproteinemias , Insuficiencia Renal Crónica , Insuficiencia Renal , Adolescente , Humanos , Cadenas Ligeras de Inmunoglobulina , Paraproteinemias/diagnóstico , Insuficiencia Renal/diagnóstico , Insuficiencia Renal Crónica/diagnósticoRESUMEN
Our previous study indicated that microRNA 145 (miR-145) and its predicated target, erythropoietin-producing hepatoma (EPH) receptor A4 (EPHA4), was closely associated with ischemic stroke. In this study, we aimed to further explore their function in a model of oxygen-glucose deprivation (OGD). The expression of miR-145 in the blood of 44 patients with ischemic stroke and 37 normal controls was detected by qRT-PCR. After transfection with either the wild- or mutant-type pGL3-promoter EPHA4 3'UTR into the miR-145 mimic and miR-145 inhibitor, a dual-luciferase reporter assay was performed to explore the interaction between miR-145 and EPHA4. qRT-PCR and Western blot were performed to further explore the effects of miR-145 on EPHA4 expression after an miR-145 mimic, an miR-145 inhibitor or LV-sh-EPHA4 was transfected into cerebral cortical neurons. The expression of miR-145 was significantly upregulated in the blood of patients with ischemic stroke compared to that of normal controls. Dual-luciferase reporter assay, qRT-PCR and Western blot results indicated that miR-145 indeed targets EPHA4 through its 3'-UTR and regulates the expression level of EPHA4 at both the mRNA and protein levels. Moreover, the OGD model was successfully constructed, and miR-145 exerted a protective effects in cell viability in the OGD model by downregulating EPHA4. The expression of LOC105376244 could be regulated by the miR-145-EPHA4 interaction. MiR-145 exerted a protective effects in cell viability in the OGD model by downregulating EPHA4, which suggested their potential roles in ischemic stroke and requires further research.
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Isquemia Encefálica/metabolismo , Corteza Cerebral/citología , MicroARNs/genética , Neuronas/citología , Receptor EphA4/metabolismo , Anciano , Apoptosis/efectos de los fármacos , Isquemia Encefálica/patología , Hipoxia de la Célula/fisiología , Supervivencia Celular/genética , Corteza Cerebral/metabolismo , Regulación hacia Abajo , Femenino , Glucosa/metabolismo , Humanos , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Neuronas/metabolismo , Oxígeno/metabolismo , Cultivo Primario de Células , ARN Mensajero/metabolismo , Accidente Cerebrovascular/metabolismoRESUMEN
BACKGROUND: Previous clinical studies found inconsistent relationship between circulating sclerostin levels and treatment outcome in patients undergoing maintenance hemodialysis (MHD). Therefore, this study aimed to assess the associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing MHD. METHODS: This retrospective study assessed 84 patients undergoing MHD at the Nephrology Department of Beijing Hospital from January to April 2012, with a median follow-up of 61.2 months (range: 11.5 to 63 months). Carotid artery intima-media thicknesses (CIMTs) and atherosclerotic plaques were measured by B-mode Doppler ultrasound at baseline. Blood samples were collected for measuring serum sclerostin and soluble klotho (s-klotho) levels. The associations of sclerostin levels with carotid artery atherosclerosis was evaluated by correlation methods. Predictive factors of mortality were assessed by multivariate COX regression. RESULTS: Baseline serum sclerostin averaged 162.01 pmol/L, with an interquartile range of 121.69 to 225.22 pmol/L, while CIMT values were 1.35 ± 0.39 mm. Carotid artery atherosclerotic plaques were detected in 68 subjects (81%). Subjects with sclerostin levels above the median value had higher CIMT (p = 0.038) and higher prevalence of atherosclerotic plaque (p = 0.025). During follow-up, 27 patients died; Kaplan-Meier curves indicated that subjects with high sclerostin levels (above the median value at baseline) had shorter survival (log rank p = 0.011). In multivariate COX regression analysis, serum sclerostin (HR, 1.095; 95% confidence interval [CI] 1.022-1.174, p = 0.010) and albumin (HR, 0.742; 95%CI 0.612-0.900, p = 0.002) levels were independent predictors of all-cause mortality. CONCLUSIONS: Sclerostin is positively associated with CIMT. In addition, patients with low baseline serum sclerostin undergoing MHD show better survival.
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Pueblo Asiatico , Proteínas Morfogenéticas Óseas/sangre , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/mortalidad , Diálisis Renal/mortalidad , Proteínas Adaptadoras Transductoras de Señales , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Arteria Carótida Común/diagnóstico por imagen , Grosor Intima-Media Carotídeo/tendencias , China/epidemiología , Estudios Transversales , Femenino , Estudios de Seguimiento , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Diálisis Renal/tendencias , Estudios RetrospectivosRESUMEN
BACKGROUND: Investigate into the medical expenditures of chronic kidney disease (CKD) patients through path analysis method of three consecutive years within a Grade-A tertiary hospital in Beijing to conduct the main influencing factors in diagnosis-related groups (DRGs) grouping of the diagnosis, and reassess the present grouping process to provide information and reference on cost control for hospitals and medical management departments. METHODS: Eight hundred and fifty-five inpatient cases whose first diagnosis were defined as CKD in the year 2014-2016 within the hospital were selected as the sample of the study, multiple linear regression and path analysis method were adopted in DRGs grouping process to investigate the main influencing factors of total medical expenditures and DRGs grouping process. RESULTS: The maximum proportion of the medical costs within CKD patients was the costs on treatment, with the highest of 35.3% on the year 2014, the second was the costs on drug, which accounted for <30% during consecutive years, and the third was the costs on examination, which accounted for about 20% on average. The main influencing factors of medical expenditures included the type of dialysis, length of hospitalization, the admission of Intensive Care Unit (ICU), and so on. The coefficients toward the effect for total costs were 0.416, 0.376, and 0.094, respectively. CONCLUSIONS: It is suggested that the type of dialysis and the admission of ICU were the major influencing factors of inpatient medical expenditures on CKD patients, and should be taken into consideration into the reassessment of DRGs grouping process to realize the localization and generalization of prospective payment system based on DRGs within the regional area and promote the implementation of medical cost control measures to reduce the economic burdens among patients and the society.
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Insuficiencia Renal Crónica/economía , Beijing , Grupos Diagnósticos Relacionados , Femenino , Gastos en Salud , Costos de Hospital , Hospitalización/economía , Hospitales , Humanos , Pacientes Internos , Unidades de Cuidados Intensivos , Masculino , Sistema de Pago Prospectivo , Diálisis Renal , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapiaRESUMEN
BACKGROUND: MicroRNAs (miRNAs) are part of the brain's response to ischemia. This study aimed to screen potential miRNAs for the prediction and novel treatments of ischemic stroke. METHODS: Two mRNA and 1 miRNA microarray expression profile data were downloaded from the Gene Expression Omnibus database. Then, differentially expressed mRNAs and miRNAs were identified. Based on the miRNA-target pairs predicted, an miRNA-target interaction network was established. Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment) was applied to interpret the function of the miRNA targets. RESULTS: In total, 16 differentially expressed miRNAs and 1345 differentially expressed genes were identified in ischemic stroke, respectively. Importantly, 445 miRNA-target pairs with an inverse correlation of expression were obtained, and the miRNA functional synergistic network was generated. Two miRNAs (miR-145 and miR-122) may represent potential biomarkers in ischemic stroke by being involved in the process of postischemic neuronal damage and thrombosis, respectively. Three novel miRNAs (miR-99b, miR-542-3p, and miR-455-5p) were deregulated, suggesting their roles in the pathological processes of ischemic stroke. Functional annotation indicated that apoptotic signaling cascades play an important role in patients with ischemic stroke. CONCLUSION: miR-145 and miR-122 represent new biomarkers and underlying targets for the prevention and treatment of ischemic stroke.
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Isquemia Encefálica/genética , Biología Computacional , MicroARNs/genética , Accidente Cerebrovascular/genética , Isquemia Encefálica/diagnóstico , Estudios de Casos y Controles , Bases de Datos Genéticas , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Estudios de Asociación Genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Accidente Cerebrovascular/diagnósticoRESUMEN
BACKGROUND: To identify the relationship between predialysis pulse wave velocity (PWV), postdialysis PWV during 1 hemodialysis (HD) session, and deaths in maintenance HD patients. METHODS: 43 patients were recruited. PWV was measured before and after one HD session and dialysis- related data were recorded. Clinical data such as blood pressure, blood lipids, and blood glucose, were carefully observed and managed in a 5-year follow-up. The association between all-cause death, predialysis PWV, postdialysis PWV, change of PWV (ΔPWV), and other related variables were analyzed. RESULTS: After 5 years, 17 patients (39.5%) died. Univariate Cox regression analysis showed that all-cause death of the patients significantly correlated with age, postdialysis PWV, and ΔPWV. Multivariate Cox regression analysis revealed that postdialysis PWV was an independent predictor for all-cause death in these patients (HR: 1.377, 95% CI: 1.146 - 1.656, p = 0.001). CONCLUSION: Elevated postdialysis PWV significantly correlated with and was an independent predictor for all-cause death in maintenance HD patients.
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Causas de Muerte , Análisis de la Onda del Pulso , Diálisis Renal , Factores de Edad , Anciano , Glucemia/análisis , Presión Sanguínea/fisiología , Proteína C-Reactiva/análisis , Calcio/sangre , Arteria Carótida Común/fisiología , Femenino , Arteria Femoral/fisiología , Estudios de Seguimiento , Predicción , Hematócrito , Hemoglobinas/análisis , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Fósforo/sangre , Diálisis Renal/mortalidad , Albúmina Sérica/análisisRESUMEN
One major precursor of carbonyl stress, methylglyoxal (MG), is elevated in the plasma of chronic kidney disease (CKD) patients, and this precursor contributes to the progression of vascular injury, hypertension and renal injury in diabetic nephropathy patients. This molecule induces salt-sensitive hypertension via a reactive oxygen species-mediated pathway. We examined the role of MG in the pathogenesis of hypertension and cardio-renal injury in Dahl salt-sensitive (Dahl S) rats, which is a rat model of CKD. Nine-week-old Dahl S rats were fed a 1% NaCl diet, and 1% MG was added to their drinking water for up to 12 weeks. Blood pressure and cardio-renal injuries were compared with rats treated with tap water alone. The angiotensin II receptor blocker (ARB), candesartan (10 mg kg(-1) day(-1)), was administered to MG Dahl S rats to determine the impact of this drug on the pathogenesis of MG-induced CKD. A progressive increase in systolic blood pressure was observed (123±1-148±5 mm Hg) after 12 weeks of MG administration. MG administration significantly increased urinary albumin excretion, glomerular sclerosis, tubular injury, myocardial collagen content and cardiac perivascular fibrosis. MG also enhanced the renal expression of NÉ-carboxyethyl-lysine (an advanced glycation end product), 8-hydroxydeoxyguanosine (a marker of oxidative stress), macrophage (ED-1) positive cells (a marker of inflammation) and nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase activity. Candesartan treatment for 4 weeks significantly reduced these parameters. These results suggest that MG-induced hypertension and cardio-renal injury and increased inflammation and carbonyl and oxidative stress, which were partially preventable by an ARB.
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Enfermedades Cardiovasculares/etiología , Hipertensión/etiología , Enfermedades Renales/etiología , Carbonilación Proteica/fisiología , Circulación Renal/fisiología , Estrés Fisiológico/fisiología , Albuminuria/metabolismo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Animales , Bencimidazoles/uso terapéutico , Compuestos de Bifenilo , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/fisiopatología , Fibrosis/patología , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Inmunohistoquímica , Inflamación/patología , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/fisiopatología , Masculino , NADPH Oxidasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Carbonilación Proteica/efectos de los fármacos , Piruvaldehído/sangre , Ratas , Ratas Endogámicas Dahl , Circulación Renal/efectos de los fármacos , Sistema Renina-Angiotensina/efectos de los fármacos , Cloruro de Sodio Dietético/efectos adversos , Estrés Fisiológico/efectos de los fármacos , Tetrazoles/uso terapéuticoRESUMEN
Luminescent dendritic cyclometalated iridium(III) polypyridine complexes [{Ir(N--C)(2)}(n)(bpy-n)](PF(6))(n) (HN--C = 2-phenylpyridine, Hppy, n = 8 (ppy-8), 4 (ppy-4), 3 (ppy-3); HN--C = 2-phenylquinoline, Hpq, n = 8 (pq-8), 4 (pq-4), 3 (pq-3)) have been designed and synthesized. The properties of these dendrimers have been compared to those of their monomeric counterparts [Ir(N--C)(2)(bpy-1)](PF(6)) (HN--C = Hppy (ppy-1), Hpq (pq-1)). Cyclic voltammetric studies revealed that the iridium(IV/III) oxidation and bpy-based reduction occurred at about +1.24 to +1.29 V and -1.21 to -1.27 V versus SCE, respectively, for all the complexes. The molar absorptivity of the dendritic iridium(III) complexes is approximately proportional to the number of [Ir(N--C)(2)(N--N)] moieties in one complex molecule. However, the emission lifetimes and quantum yields are relatively independent of the number of [Ir(N--C)(2)(N--N)] units, suggesting negligible electronic communications between these units. Upon photoexcitation, the complexes displayed triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir) --> pi*(bpy-n)) emission. The interaction of these complexes with plasmid DNA has been investigated by agarose gel retardation assays. The results showed that the dendritic iridium(III) complexes, unlike their monomeric counterparts, bound to the plasmid, and the interaction was electrostatic in nature. The lipophilicity of all the complexes has been determined by reversed-phase high-performance liquid chromatography (HPLC). Additionally, the cellular uptake of the complexes by the human cervix epithelioid carcinoma (HeLa) cell line has been examined by inductively coupled plasma mass spectrometry (ICP-MS), laser-scanning confocal microscopy, and flow cytometry. Upon internalization, all the complexes were localized in the perinuclear region, forming very sharp luminescent rings surrounding the nuclei. Interestingly, in addition to these rings, HeLa cells treated with the dendritic iridium(III) complexes showed specific labeled compartments, which have been identified to be the Golgi apparatus. Furthermore, the cytotoxicity of these iridium(III) complexes has been evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay.