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BACKGROUND: Osteoporosis in pre-dialysis chronic kidney disease (CKD) patients has been overlooked, and the risk factors of osteoporosis in these patients have not been adequately studied. OBJECTIVE: To identify risk factors for osteoporosis in pre-dialysis CKD patients and develop predictive models to estimate the likelihood of osteoporosis. METHODS: Dual-energy X-ray absorptiometry was used to measure bone mineral density, and clinical examination results were collected from 326 pre-dialysis CKD patients. Binary logistic regression was employed to explore the risk factors associated with osteoporosis and develop predictive models. RESULTS: In this cohort, 53.4% (n = 174) were male, 46.6% (n = 152) were female, and 21.8% (n = 71) were diagnosed with osteoporosis. Among those diagnosed with osteoporosis, 67.6% (n = 48) were female and 32.4% (n = 23) were male. Older age and low 25-(OH)-Vitamin D levels were identified as risk factors for osteoporosis in males. For females, older age, being underweight, higher bone alkaline phosphatase (NBAP), and advanced CKD (G5) were significant risk factors, while higher iPTH was protective. Older age, being underweight, and higher NBAP were risk factors for osteoporosis in the G1-4 subgroup. In the G5 subgroup, older age and higher NBAP increased the risk, while high 25-(OH)-Vitamin D or iPTH had protective effects. Nomogram models were developed to assess osteoporosis risk in pre-dialysis patients based on gender and renal function stage. CONCLUSION: Risk factors for osteoporosis vary by gender and renal function stages. The nomogram clinical prediction models we constructed may aid in the rapid screening of patients at high risk of osteoporosis.
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Absorciometría de Fotón , Densidad Ósea , Osteoporosis , Insuficiencia Renal Crónica , Humanos , Femenino , Masculino , Osteoporosis/etiología , Osteoporosis/epidemiología , Osteoporosis/diagnóstico , Persona de Mediana Edad , Factores de Riesgo , Insuficiencia Renal Crónica/complicaciones , Anciano , Adulto , Vitamina D/sangre , Vitamina D/análogos & derivados , Fosfatasa Alcalina/sangre , Modelos Logísticos , Nomogramas , Diálisis RenalRESUMEN
OBJECTIVE: The relationship between serum total cholesterol (TC) and triglyceride (TG) levels and mortality in maintenance hemodialysis (MHD) patients remains inconsistent. We aimed to explore the individual and combined association of TC and TG levels with the risk of mortality in Chinese MHD patients. METHODS: 1036 MHD patients were enrolled in this multicenter, prospective cohort study. The serum levels of total cholesterol and triglycerides were measured at baseline. The primary outcome was all-cause mortality and secondary outcome was cardiovascular disease (CVD) mortality. RESULTS: During a median follow-up duration of 4.4 years (IQR= 2.0-7.9 years), 549 (53.0%) patients died, and 297 (28.7%) deaths were attributed to CVD. Compared with patients with TC levels in the first three quartiles (<182.5 mg/dL), a significantly higher risk of all-cause mortality was found in participants with TC in the fourth quartile (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.17-1.76). However, a significantly lower risk of all-cause mortality was observed in participants with TG in the fourth quartile (≥193.9 mg/dL) (HR, 0.78; 95%CI: 0.63-0.98), compared with participants with TG in the first three quartiles. Similar trends were observed in CVD mortality. When analyzed jointly, patients with lower TC (<182.5 mg/dL) and higher TG (≥193.9 mg/dL) levels had the lowest risk of all-cause mortality and CVD mortality.Conclusions: In MHD patients in southern China, higher TC levels were associated with higher risk of mortality, while higher TG levels were related to lower risk of mortality. Patients with lower TC and higher TG levels had the best survival prognosis.
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Enfermedades Cardiovasculares , Diálisis Renal , Humanos , Triglicéridos , Estudios Prospectivos , Colesterol , HDL-Colesterol , Factores de RiesgoRESUMEN
BACKGROUND: There is no predictive tool for type 2 diabetes mellitus (T2DM) patients with acute kidney injury (AKI). Our study aimed to establish an effective nomogram model for predicting mortality in T2DM patients with AKI. METHOD: Data on T2DM patients with AKI were obtained from the Medical Information Mart for Intensive Care III. 70% and 30% of the patients were randomly selected as the training and validation cohorts, respectively. Univariate and multivariate logistic regression analyses were used to identify factors associated with death in T2DM patients with AKI. Factors significantly associated with survival outcomes were used to construct a nomogram predicting 90-day mortality. The nomogram effect was evaluated by receiver operating characteristic curve analysis, HosmerâLemeshow test, calibration curve, and decision curve analysis (DCA). RESULTS: There were 4375 patients in the training cohort and 1879 in the validation cohort. Multivariate logistic regression analysis showed that age, BMI, chronic heart failure, coronary artery disease, malignancy, stages of AKI, white blood cell count, blood urea nitrogen, arterial partial pressure of oxygen and partial thromboplastin time were independent predictors of patient survival. The results showed that the nomogram had a higher area under the curve value than the sequential organ failure assessment score and simplified acute physiology score II. The HosmerâLemeshow test and calibration curve suggested that the nomogram had a good calibration effect. The DCA curve showed that the nomogram model had good clinical application value. CONCLUSION: The nomogram model accurately predicted 90-day mortality in T2DM patients with AKI. It may provide assistance for clinical decision-making and treatment, thereby reducing the medical burden.
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Lesión Renal Aguda , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Nomogramas , Unidades de Cuidados Intensivos , Cuidados Críticos , Estudios RetrospectivosRESUMEN
PURPOSE: Oral adenoid cystic carcinoma (OACC) has high rates of both local-regional recurrence and distant metastasis. The objective of this study is to investigate the impact of Khib on OACC and its potential as a targeted therapeutic intervention. EXPERIMENTAL DESIGN: We investigated the DEPs (differentially expressed proteins) and DHMPs between OACC-T and OACC-N using LC-MS/MS-based quantitative proteomics and using several bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, subcellular localization prediction, MEA (motif enrichment analysis), and PPI (protein-protein interaction networks) to illustrate how Khib modification interfere with OACC evolution. RESULTS: Compared OACC-tumor samples (OACC-T) with the adjacent normal samples (OACC-N), there were 3243 of the DEPs and 2011 Khib sites were identified on 764 proteins (DHMPs). DEPs and DHMPs were strongly associated to glycolysis pathway. GAPDH of K254, ENO of K228, and PGK1 of K323 were modified by Khib in OACC-T. Khib may increase the catalytic efficiency to promote glycolysis pathway and favor OACC progression. CONCLUSIONS AND CLINICAL RELEVANCE: Khib may play a significant role in the mechanism of OACC progression by influencing the enzyme activity of the glycolysis pathway. These findings may provide new therapeutic options of OACC.
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Carcinoma Adenoide Quístico , Proteoma , Humanos , Proteoma/análisis , Proteoma/metabolismo , Cromatografía Liquida , Espectrometría de Masas en Tándem , Procesamiento Proteico-Postraduccional , GlucólisisRESUMEN
BACKGROUND: According to the Global Cancer Statistics in 2020, the incidence and mortality of colorectal cancer (CRC) rank third and second among all tumors. The disturbance of ubiquitination plays an important role in the initiation and development of CRC, but the ubiquitinome of CRC cells and the survival-relevant ubiquitination are poorly understood. METHODS: The ubiquitinome of CRC patients (n = 6) was characterized using our own data sets of proteomic and ubiquitin-proteomic examinations. Then, the probable survival-relevant ubiquitination was searched based on the analyses of data sets from public databases. RESULTS: For the ubiquitinomic examination, we identified 1690 quantifiable sites and 870 quantifiable proteins. We found that the highly-ubiquitinated proteins (n ≥ 10) were specifically involved in the biological processes such as G-protein coupling, glycoprotein coupling, and antigen presentation. Also, we depicted five motif sequences frequently recognized by ubiquitin. Subsequently, we revealed that the ubiquitination content of 1172 proteins were up-regulated and 1700 proteins were down-regulated in CRC cells versus normal adjacent cells. We demonstrated that the differentially ubiquitinated proteins were relevant to the pathways including metabolism, immune regulation, and telomere maintenance. Then, integrated with the proteomic datasets from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) (n = 98), we revealed that the increased ubiquitination of FOCAD at Lys583 and Lys587 was potentially associated with patient survival. Finally, we depicted the mutation map of FOCAD and elucidated its potential functions on RNA localization and translation in CRC. CONCLUSIONS: The findings of this study described the ubiquitinome of CRC cells and identified abnormal ubiquitination(s) potentially affecting the patient survival, thereby offering new probable opportunities for clinical treatment.
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Neoplasias Colorrectales , Proteínas Ubiquitinadas , Neoplasias Colorrectales/patología , Humanos , Proteómica , ARN/metabolismo , Ubiquitina/genética , Ubiquitina/metabolismo , Proteínas Ubiquitinadas/genética , Proteínas Ubiquitinadas/metabolismo , UbiquitinaciónRESUMEN
RATIONALE & OBJECTIVE: Although greater dietary intake of protein has been associated with beneficial health effects among patients receiving maintenance hemodialysis (MHD), the effects of plant protein intake are less certain. We studied the association of the proportion of protein intake derived from plant sources with the risk of mortality among patients receiving MHD and explored factors that may modify these associations. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 1,119 Chinese hemodialysis patients aged over 18 years receiving MHD in 2014-2015. PREDICTORS: The proportion of plant protein intake to total protein intake. OUTCOMES: All-cause mortality and cardiovascular disease (CVD) mortality. ANALYTICAL APPROACH: Segmented regression models were fit to examine the association of plant protein intake proportion with the risk of all-cause mortality and CVD mortality. Multivariable-adjusted Cox proportional and cause-specific hazards models were used to estimate the hazard ratios (HR) and 95% CI for these outcomes. RESULTS: The means of plant protein intake normalized to ideal body weight and plant protein intake proportion were 0.6±0.2 (SD) g/kg per day and 0.538±0.134, respectively. During a median follow-up period of 28.0 months, 249 deaths occurred, with 146 of these deaths resulting from CVD. Overall, there was a U-shaped association between plant protein intake proportion and the risk of all-cause mortality, with an inflection point at 45%. Among patients with a plant protein intake proportion<45%, there was a 17% lower rate of mortality with each 5% greater plant protein intake proportion (HR, 0.83 [95% CI, 0.73-0.96]). Among patients with plant protein intake proportion≥45%, there was a 9% greater rate of mortality with each 5% greater plant protein intake proportion. A similar U-shaped association was observed for CVD mortality, with an inflection point at 44%. LIMITATIONS: Observational study, potential unmeasured confounding. CONCLUSIONS: There was a U-shaped association between plant protein intake proportion and the risk of all-cause and cardiovascular mortality in MHD patients. If confirmed, these findings suggest a potential avenue to improve outcomes in this patient population.
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Enfermedades Cardiovasculares , Proteínas de Vegetales Comestibles , Adulto , Estudios de Cohortes , Humanos , Persona de Mediana Edad , Mortalidad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Diálisis Renal , Factores de RiesgoRESUMEN
High fibre intake is associated with reduced mortality risk in both general and chronic kidney disease populations. However, in dialysis patients, such data are limited. Therefore, the association between dietary fibre intake (DFI) and the risk of all-cause and CVD mortality was examined in this study. A total of 1044 maintenance haemodialysis (MHD) patients from eight outpatient dialysis centres in China were included in this study. Data on DFI were collected using 24-h dietary recalls for 3 d in a week and were normalised to actual dry weight. The study outcomes included all-cause and CVD mortality. Over a median of 46 months of follow-up, 354 deaths were recorded, of which 210 (59 %) were due to CVD. On assessing DFI as tertiles, the CVD mortality risk was significantly lower in patients in tertiles 2-3 (≥0·13 g/kg per d; hazard ratio (HR) 0·71; 95 % CI 0·51, 0·97) compared with those in tertile 1 (<0·13 g/kg per d). A similar but non-significant trend was found for the association between DFI (tertiles 2-3 v. tertile 1; HR 0·83; 95 % CI 0·64, 1·07) and all-cause mortality. In summary, higher DFI was associated with lower CVD mortality risk among Chinese MHD patients. This study emphasises the significance of DFI in MHD patients and provides information that is critical for the improvement of dietary guidelines for dialysis patients.
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Enfermedades Cardiovasculares , Fibras de la Dieta/administración & dosificación , Diálisis Renal , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , China , Humanos , Mortalidad , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Several studies have reported that low serum uric acid (SUA) levels are related to increased risk of mortality in maintenance hemodialysis (MHD) patients. However, the possible detrimental effects of high SUA on the mortality risk have not been well examined. Moreover, the possible effect modifiers for the SUA-mortality association have not been fully investigated. To address the aforementioned gap, we aimed to explore the nonlinear relationship between SUA levels and all-cause and cardiovascular disease (CVD) mortality risk, and to examine any possible effect modifiers in MHD patients. METHODS: We conducted a multicenter, prospective cohort study among 1,018 MHD patients from 8 hemodialysis centers. The primary outcome was all-cause mortality, and the secondary outcomes were CVD mortality and non-CVD mortality. RESULTS: The mean value for SUA in the total population was 8.5 ± 1.9 mg/dL. The lowest and highest quintiles of SUA were <7.0 and >10.1 mg/dL, respectively. Over a median follow-up of 45.6 months, 343 deaths were recorded, of which 202 (58.9%) were due to CVD. When SUA was assessed as quintiles, a significantly higher risk of all-cause mortality was found in patients in quintile 1 (<7.0 mg/dL; hazard ratio [HR], 1.33; 95% confidence interval [CI]: 1.02-1.73) or quintile 5 (≥10.1 mg/dL; HR, 1.47; 95% CI: 1.09-2.00), compared to those in quintiles 2-4 (7-10.1 mg/dL). Moreover, the U-shaped SUA-mortality association was mainly found in those with lower C-reactive protein levels (<3 compared with ≥3 mg/L; p for interaction = 0.018). Similar trends were found for CVD mortality and non-CVD mortality. CONCLUSION: There was a U-shaped relationship between SUA levels and the risk of all-cause mortality, CVD mortality, and non-CVD mortality in MHD patients.
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Enfermedades Cardiovasculares/mortalidad , Hiperuricemia/epidemiología , Fallo Renal Crónico/mortalidad , Diálisis Renal/efectos adversos , Ácido Úrico/sangre , Adulto , Anciano , Proteína C-Reactiva/análisis , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Femenino , Estudios de Seguimiento , Humanos , Hiperuricemia/sangre , Hiperuricemia/diagnóstico , Hiperuricemia/etiología , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo/estadística & datos numéricos , Factores de RiesgoRESUMEN
Maintenance haemodialysis (MHD) is the use of a machine to filter wastes, salts and fluid from blood for at least 3 months to prolong the life of patients with advanced kidney failure. Although low dietary energy intake (DEI) has been observed in MHD patients, few studies have related DEI to the risk of mortality. To explore this relationship, a study included 1039 MHD patients from eight centres was conducted. DEI was assessed by three 24-h diet recalls and was normalised to ideal body weight (IBW). All-cause mortality and CVD mortality were the primary and secondary outcomes, respectively. During a median follow-up of 28 months, a U-shaped relationship was observed between DEI and all-cause or CVD mortality. The risk of all-cause mortality decreased significantly with the increase of DEI in participants with DEI <167·4 kJ/kg IBW per d (hazard ratio (HR) 0·98; 95 % CI 0·96, 1·00) and increased significantly with the increase of DEI in those with DEI ≥167·4 kJ/kg IBW per d (HR 1·12; 95 % CI 1·04, 1·20). Similarly, the risk of CVD mortality decreased with the increase of DEI in participants with DEI <152·7 kJ/kg IBW per d (HR 0·96; 95 % CI 0·93, 0·99) and increased with the increase of DEI in participants with DEI ≥152·7 kJ/kg IBW per d (HR 1·11; 95 % CI 1·04, 1·18). In summary, there was a U-shaped association between DEI and all-cause or CVD mortality, with a turning point at about 167·4 and 152·7 kJ/kg IBW per d, respectively, in MHD patients.
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Dieta/mortalidad , Ingestión de Energía , Fallo Renal Crónico/mortalidad , Diálisis Renal/mortalidad , Adulto , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de RiesgoRESUMEN
How p53 participates in acute kidney injury (AKI) progress and what are the underlying mechanisms remain illusive. For this issue, it is important to probe into the role of p53 in cisplatin-induced AKI. We find that p53 was upregulated in cisplatin-induced AKI, yet, pifithrin-α inhibites the p53 expression to attenuated renal injury and cell apoptosis both in vivo cisplatin-induced AKI mice and in vitro HK-2 human renal tubular epithelial cells. To knock down p53 by siRNA significantly decreased the miRNA, miR-199a-3p, expression in HK-2 cells. Blockade of miR-199a-3p significantly reduced cisplatin-induced cell apoptosis and inhibited caspase-3 activity. Mechanistically, we identified that miR-199a-3p directly bound to mechanistic target of rapamycin (mTOR) 3'-untranslated region and overexpressed miR-199a-3p reduce the expression and phosphorylation of mTOR. Furthermore, we demonstrated that p53 inhibited mTOR activation through activating miR-199a-3p. In conclusion, our findings reveal that p53, upregulating the expression of miR-199a-3p affects the progress of cisplatin-induced AKI, which might provide a promising therapeutic target of AKI.
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Lesión Renal Aguda/genética , MicroARNs/genética , Neoplasias/genética , Proteína p53 Supresora de Tumor/genética , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Animales , Apoptosis/efectos de los fármacos , Benzotiazoles/farmacología , Proliferación Celular/efectos de los fármacos , Cisplatino/efectos adversos , Cisplatino/farmacología , Resistencia a Antineoplásicos/genética , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Ratones , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Serina-Treonina Quinasas TOR/genética , Tolueno/análogos & derivados , Tolueno/farmacología , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Free vitamin D is the biologically active form of vitamin D. Vitamin D deficiency is associated with cardiovascular disease, the most common cause of mortality in hemodialysis patients. The goal of our current study was to investigate the relation between blood concentrations of free 25-hydroxyvitamin D with cardiovascular events in end-stage chronic kidney disease patients on hemodialysis, because this is unknown so far. We measured free vitamin D levels in 117 stable consecutive prevalent patients in September as a surrogate of vitamin D exposure during the past 6 months, and recorded the number of cardiovascular events during the previous 6 months defined as hospitalization due to heart failure, episodes of acute coronary syndrome, and stroke. Fourteen events occurred during the observation period. In patients without any cardiovascular events the free vitamin D levels were significantly higher as compared to those with cardiovascular events (patients without events: 5.68 [4.37-9.27] pg/mL; patients with events: 4.74 [3.46-5.37] pg/mL, p = 0.015). This finding remained stable after multiple regression analysis considering confounding factors such as age, time on dialysis, preexisting diabetes, hypertension, and coronary heart disease. In conclusion, our study shows that free vitamin D serum concentrations are independently associated with major cardiovascular events in chronic kidney disease patients on dialysis.
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Enfermedades Cardiovasculares/sangre , Insuficiencia Renal Crónica/complicaciones , Vitamina D/análogos & derivados , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Vitamina D/sangre , Deficiencia de Vitamina D/complicacionesRESUMEN
BACKGROUND: The serum immunoglobulin A (IgA)/C3 ratio is considered to be an effective predictor of IgA nephropathy (IgAN). This study sought to explore the diagnostic value of the IgA/C3 ratio in IgAN among primary glomerular nephropathy patients in China. METHODS: We recruited 1095 biopsy-diagnosed primary glomerular nephropathy patients, including 757 IgAN patients and 338 non-IgAN patients. Patient demographics, serum immunological indices, and other clinical examinations were measured. IgAN cases were propensity score matched (PSM) to non-IgAN cases on the logit of the propensity score using nearest neighbor matching in a 1:1 fashion, with a caliper of 0.02 with no replacements, according to age, gender, BMI, proteinuria level, and estimated glomerular filtration rate (eGFR). RESULTS: We found that in both the full cohort and PSM cohort, the IgA/C3 ratio in the IgAN group was significantly higher than that of the non-IgAN group. The same results were also obtained with stratification by different levels of proteinuria and renal function. In the PSM cohort, there was no difference in IgA/C3 ratio in patients with IgAN between different proteinuria groups and different chronic kidney disease (CKD) groups. The area under the ROC curve (AUROC) of the IgA/C3 ratio in distinguishing IgAN among primary glomerular disease was 0.767 in the full cohort, and 0.734 in the PSM cohort. The highest AUROC of the IgA/C3 ratio was in the ≤1 g/d proteinuria group (0.801 in the full cohort, and 0.803 in the PSM cohort); however, there was no difference between all CKD groups. Meanwhile, the diagnostic accordance rate for the diagnosis of IgAN among all patients with an IgA/C3 ratio > 3.5304 was as high as 92.02% in the full cohort. IgAN was independently correlated with IgA/C3 ratio in the full cohort by multivariate logistic regression analysis. CONCLUSIONS: The present study provides clear evidence that the IgA/C3 ratio is an effective predictor of IgA diagnosis, especially in patients with proteinuria ≤1 g/d. In order to study the effectiveness of this biomarker, and to determine a standardized cut-off value, additional multicenter large-scale studies are needed.
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Complemento C3/análisis , Glomerulonefritis por IGA/diagnóstico , Inmunoglobulina A/sangre , Proteinuria/sangre , Adulto , Factores de Edad , Análisis de Varianza , Biomarcadores/sangre , Estudios de Cohortes , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Puntaje de Propensión , Curva ROC , Análisis de Regresión , Factores SexualesRESUMEN
Assisted PD (assPD) is an option of home dialysis treatment for dependent end-stage renal patients and worldwide applied in different countries since more than 40 years. China and Germany shares similar trends in demographic development with a growing proportion of elderly referred to dialysis treatment. So far number of patients treated by assPD is low in both countries. We analyze experiences in the implementation process, barriers, and benefits of ass PD in the aging population to provide a model for sustainable home dialysis treatment with PD in both countries. Differences and similarities of different factors (industrial, patient and facility based) which affect utilization of assPD are discussed. AssPD should be promoted in China and Germany to realize the benefits of home dialysis for the aging population by providing a structured model of implementation and quality assurance.
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Hemodiálisis en el Domicilio/métodos , Fallo Renal Crónico/tratamiento farmacológico , Diálisis Peritoneal/métodos , China , Alemania , Humanos , Diálisis Peritoneal Ambulatoria ContinuaRESUMEN
BACKGROUND: Uremic encephalopathy (UE), a toxic metabolic encephalopathy, is an uncommon complication resulting from endogenous uremic toxins in patients with severe renal failure. UE syndrome can range from mild inattention to coma. The imaging findings of UE include cortical or subcortical involvement, basal ganglia involvement and white matter involvement. The basal ganglia type is uncommon, although previous cases have reported that Asian patients with diabetes mellitus (DM) are usually affected. CASE PRESENTATION: A 32 year-old woman with a history of non-diabetic hemodialysis for 3 years suffered from severe involuntary movement, and brain magnetic resonance imaging showed symmetrical T2-weighted imaging (T2WI) and T2/fluid-attenuated inversion recovery (T2FLAIR) hyperintense nonhemorrhagic lesions in the bilateral basal ganglia. She was diagnosed with UE as syndrome of bilateral basal ganglia lesions, due to a combined effect of uremic toxins and hyperthyroidism. After treatment with high frequency and high flux dialysis, hyperbaric oxygen therapy and declining parathyroid hormone, the patient achieved complete remission with normal body movement and was discharged. CONCLUSION: UE with basal ganglia involvement is uncommon, although generally seen in Asian patients with DM. Our case reported a hemodialysis patient that had non-diabetic UE with typical bilateral basal ganglia lesions, presenting with involuntary movement.
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Ganglios Basales/diagnóstico por imagen , Encefalopatías/diagnóstico por imagen , Discinesias/diagnóstico por imagen , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Uremia/etiología , Adulto , Encefalopatías/etiología , Discinesias/etiología , Femenino , Humanos , Hipertiroidismo/complicaciones , Imagen por Resonancia Magnética , Diálisis Renal , SíndromeRESUMEN
Polylysine has broad biomedical applications, though little is known about its hemocompatibility. Here, we studied the influence of polylysine on human red blood cells (RBCs) and blood clotting. We observed the morphology and aggregation and determined the hemolysis of RBCs incubated with polylysine. Plasma coagulation in the presence of polylysine was evaluated by measuring the activated partial thromboplastin time (APTT) and prothrombin time (PT). Human whole blood coagulation in the presence of polylysine was evaluated with the thromboelastograph (TEG). We found that polylysine at 0.01 mg/mL did not result in RBC aggregation or morphological change, while polylysine at ≥ 0.1 mg/mL caused RBC aggregation. The RBCs did not lyze in the presence of 0.010.5 mg/mL of polylysine. Polylysine at 0.001 mg/mL did not cause a significantly different APTT from the control, while polylysine at ≥ 0.01 mg/mL caused a significantly higher APTT than the control. Polylysine at ≤ 0.1 mg/mL did not cause a significantly different PT from the control, while polylysine at 1 mg/mL caused a significantly higher PT than the control. TEG parameters for whole blood coagulation in the presence of 0.01 mg/mL polylysine were within the normal range; while polylysine ≥ 0.1 mg/mL caused one or more abnormal TEG parameters. From these results, the effect of polylysine on RBC aggregation and blood coagulation was concentration-dependent. The results provide important information for the biomedical applications of polylysine.
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Coagulación Sanguínea/efectos de los fármacos , Agregación Eritrocitaria/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Polilisina/farmacología , Humanos , Ensayo de MaterialesRESUMEN
Translumbar tunneled dialysis catheter (TLDC) is a temporary dialysis access for patients exhausted traditional access for dialysis. While few small studies reported successes with TLDC, additional studies are warranted to understand the short- and long-term patency and safety of TLDC. We conducted a retrospective analysis of adult patients who received TLDC for hemodialysis access from June 2006 to June 2013. Patient demographics, comorbid conditions, dialysis details, catheter insertion procedures and associated complications, catheter patency, and patient survival data were collected. Catheter patency was studied using Kaplan-Meier curve; catheter functionality was assessed with catheter intervals and catheter-related complications were used to estimate catheter safety. There were 84 TLDCs inserted in 28 patients with 28 primary insertions and 56 exchanges. All TLDC insertions were technically successful with good blood flow during dialysis (>300 ml/minute) and no immediate complications (major bleeding or clotting) were noted. The median number of days in place for initial catheter, secondary catheter, and total catheter were 65, 84, and 244 respectively. The catheter patency rate at 3, 6, and 12 months were 43%, 25%, and 7% respectively. The main complications were poor blood flow (40%) and catheter-related infection (36%), which led to 30.8% and 35.9% catheter removal, respectively. After translumbar catheter, 42.8% of the patients were successfully converted to another vascular access or peritoneal dialysis. This study data suggest that TLDC might serve as a safe, alternate access for dialysis patients in short-term who have exhausted conventional vascular access.
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Catéteres/efectos adversos , Diálisis Renal/instrumentación , Falla de Equipo , Femenino , Humanos , Región Lumbosacra , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Estrogen-related receptor alpha (ERRα) plays an important role in the development of hormone-dependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects of ERRα on the proliferation and metastasis of lung cancer A549 cells. The mRNA and protein levels of ERRα were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by qRT-PCR and Western blotting, respectively. ERRα plasmid transfection and XCT-790 (an inverse agonist of ERRα) were used to up-regulate or down-regulate ERRα expression in A549 cells, respectively. The viability of A549 cells was measured by cell counting kit-8 (CCK-8) and the motility of A549 cells by wound healing assay and Transwell migration/invasion assay. The epithelial markers E-cadherin (E-Cad) and zona occludin-1 (ZO-1), the mesenchymal markers fibronectin (FN) and vimentin (Vim) and the transcription factors (Snail, Zeb1 Twist and Slug) were further detected at mRNA and protein levels by qRT-PCR and Western blotting, respectively. The results showed that ERRα promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly inhibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithelial-to-mesenchymal transition (EMT) of A549 cells, down-regulated the epithelial makers E-Cad and ZO-1, and up-regulated the mesenchymal makers FN and Vim. Silencing of Slug, but not other transcription factors, significantly abolished the ERRα-induced EMT of A549 cells. It was suggested that ERRα promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRα might be an efficient approach for lung cancer treatment.
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Proliferación Celular , Transición Epitelial-Mesenquimal , Regulación de la Expresión Génica , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/biosíntesis , Receptores de Estrógenos/biosíntesis , Línea Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/prevención & control , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Receptores de Estrógenos/genética , Receptor Relacionado con Estrógeno ERRalfaRESUMEN
Chronic kidney disease (CKD) is often a common comorbidity in critically ill patients with type 2 diabetes mellitus (T2DM). This study explored the relationship between blood urea nitrogen to serum albumin ratio (BAR) and mortality in T2DM patients with CKD in intensive care unit (ICU). Patients were recruited from the Medical Information Mart database, retrospectively. The primary and secondary outcomes were 90-day mortality, the length of ICU stay, hospital mortality and 30-day mortality, respectively. Cox regression model and Kaplan-Meier survival curve were performed to explore the association between BAR and 90-day mortality. Subgroup analyses were performed to determine the consistency of this association. A total of 1920 patients were enrolled and divided into the three groups (BAR < 9.2, 9.2 ≤ BAR ≤ 21.3 and BAR > 21.3). The length of ICU stay, 30-day mortality, and 90-day mortality in the BAR > 21.3 group were significantly higher than other groups. In Cox regression analysis showed that high BAR level was significantly associated with increased greater risk of 90-day mortality. The adjusted HR (95%CIs) for the model 1, model 2, and model 3 were 1.768 (1.409-2.218), 1.934, (1.489-2.511), and 1.864, (1.399-2.487), respectively. Subgroup analysis also showed the consistency of results. The Kaplan-Meier survival curve analysis revealed similar results as well that BAR > 21.3 had lower 90-day survival rate. High BAR was significantly associated with increased risk of 90-day mortality. BAR could be a simple and useful prognostic tool in T2DM patients with CKD in ICU.
Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Humanos , Nitrógeno de la Urea Sanguínea , Diabetes Mellitus Tipo 2/complicaciones , Pronóstico , Estudios Retrospectivos , Insuficiencia Renal Crónica/complicaciones , Albúmina SéricaRESUMEN
Diabetic nephropathy (DN) remains the primary cause of end-stage renal disease (ESRD), warranting equal attention and separate analysis of glomerular, tubular, and interstitial lesions in its diagnosis and intervention. This study aims to identify the specific proteomics characteristics of DN, and assess changes in the biological processes associated with DN. 5 patients with DN and 5 healthy kidney transplant donor control individuals were selected for analysis. The proteomic characteristics of glomeruli, renal tubules, and renal interstitial tissue obtained through laser capture microscopy (LCM) were studied using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Significantly, the expression of multiple heat shock proteins (HSPs), tubulins, and heterogeneous nuclear ribonucleoproteins (hnRNPs) in glomeruli and tubules was significantly reduced. Differentially expressed proteins (DEPs) in the glomerulus showed significant enrichment in pathways related to cell junctions and cell movement, including the regulation of actin cytoskeleton and tight junction. DEPs in renal tubules were significantly enriched in glucose metabolism-related pathways, such as glucose metabolism, glycolysis/gluconeogenesis, and the citric acid cycle. Moreover, the glycolysis/gluconeogenesis pathway was a co-enrichment pathway in both DN glomeruli and tubules. Notably, ACTB emerged as the most crucial protein in the protein-protein interaction (PPI) analysis of DEPs in both glomeruli and renal tubules. In this study, we delve into the unique proteomic characteristics of each sub-region of renal tissue. This enhances our understanding of the potential pathophysiological changes in DN, particularly the potential involvement of glycolysis metabolic disorder, glomerular cytoskeleton and cell junctions. These insights are crucial for further research into the identification of disease biomarkers and the pathogenesis of DN.
Asunto(s)
Nefropatías Diabéticas , Riñón , Captura por Microdisección con Láser , Proteoma , Proteómica , Espectrometría de Masas en Tándem , Humanos , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Proteómica/métodos , Captura por Microdisección con Láser/métodos , Masculino , Persona de Mediana Edad , Femenino , Espectrometría de Masas en Tándem/métodos , Riñón/química , Riñón/metabolismo , Riñón/patología , Proteoma/análisis , Proteoma/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Adulto , AncianoRESUMEN
Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) that has a detrimental effect on patients' survival and prognosis. The aim of this study was to develop and validate a practical and reliable prediction model for VC in CKD5 patients. The medical records of 544 CKD5 patients were reviewed retrospectively. Multivariate logistic regression analysis was used to identify the independent risk factors for vascular calcification in patients with CKD5 and then created a nomogram prediction model. The area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow test, and decision curve analysis (DCA) were used to assess model performance. The patients were split into groups with normal and high serum uric acid levels, and the factors influencing these levels were investigated. Age, BUN, SUA, P and TG were independent risk factors for vascular calcification in CKD5 patients in the modeling group (P < 0.05). In the internal validation, the results of model showed that the AUC was 0.917. No significant divergence between the predicted probability of the nomogram and the actual incidence rate (x2 = 5.406, P = 0.753) was revealed by the calibration plot and HL test, thus confirming that the calibration was satisfactory. The external validation also showed good discrimination (AUC = 0.973). The calibration chart and HL test also demonstrated good consistency. Besides, the correlation analysis of serum uric acid levels in all CKD5 patients revealed that elevated uric acid levels may be related to gender, BUN, P, and TG.