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1.
Int Urol Nephrol ; 56(1): 295-302, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37347360

RESUMEN

OBJECTIVE: To evaluate the safety and effectiveness of an individualized regional citrate anticoagulation (RCA) protocol for hemodialysis. METHODS: In this single-center, retrospective study, blood coagulation in the extracorporeal circulation, adverse reactions, in vivo ionized calcium (iCa2+) concentrations, and the infusion dose of citrate during RCA in hemodialysis were observed in 98 patients from February 2021 to March 2022. RESULTS: A total of 98 patients underwent RCA during hemodialysis 362 times, and blood coagulation occurred in the extracorporeal circulation 29 times. Among the 29 cases of coagulation, most of the patients exhibited hypercoagulability, and among approximately 80% of the treatments, the deviation between the actual infusion rate of citrate in the extracorporeal circulation and the theoretical value was ± 10%. After hemodialysis, pH values and bicarbonate ion (HCO3-) levels were clearly improved, and online conductivity monitoring (OCM) values and blood coagulation scores in the extracorporeal circulation were identical to those measured in similar studies. CONCLUSION: An individualized RCA protocol for hemodialysis is safe, effective, simple, and inexpensive and can meet the needs of individualized treatment; therefore, its application is worthy of promotion.


Asunto(s)
Anticoagulantes , Ácido Cítrico , Humanos , Ácido Cítrico/uso terapéutico , Estudios Retrospectivos , Anticoagulantes/efectos adversos , Citratos/uso terapéutico , Coagulación Sanguínea , Diálisis Renal/métodos , Calcio
2.
Semin Dial ; 37(2): 178-185, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37798864

RESUMEN

BACKGROUND: Citrate anticoagulation is an important anticoagulation method in hemodialysis (HD) but cannot completely prevent the occurrence of coagulation in the extracorporeal circulation (ECC) circuit, and the clinical coagulation status can significantly affect the effect of citrate anticoagulation. In this study, the relationships between clinical coagulation status indicators and coagulation in the ECC circuit in HD patients receiving individualized citrate anticoagulant were studied to explore indicators that may predict coagulation in the ECC circuit. METHODS: This study was a single-center, retrospective clinical study, and clinical data and laboratory tests related to the coagulation status of HD patients receiving individualized regional citrate anticoagulation (RCA) were collected. The relationships between indicators commonly used in clinical practice to evaluate clinical coagulation status and coagulation in the ECC circuit were statistically analyzed to find indicators that can predict the occurrence of coagulation in the ECC circuit. RESULTS: The individualized RCA had a good anticoagulation effect, and the actual citrate infusion rate in nearly 80% of the patients was within ±10% of the theoretical infusion rate. The combined diseases or conditions that affect the coagulation status in vivo may increase the incidence of coagulation in the ECC circuit. The clinical D-dimer level is an independent risk factor that affects and can predict coagulation in the ECC circuit, with a cutoff value of 2.03 mg/L, sensitivity of 59%, and specificity of 78%. CONCLUSION: Individualized RCA can meet the needs of most HD treatments. Abnormal coagulation status in HD patients may increase the incidence of coagulation in the ECC circuit during individualized RCA for HD, and the D-dimer level can predict the occurrence of coagulation in the ECC circuit during this treatment.


Asunto(s)
Ácido Cítrico , Diálisis Renal , Humanos , Ácido Cítrico/farmacología , Ácido Cítrico/uso terapéutico , Diálisis Renal/efectos adversos , Diálisis Renal/métodos , Estudios Retrospectivos , Anticoagulantes/uso terapéutico , Citratos/uso terapéutico , Circulación Extracorporea
3.
Int J Artif Organs ; 46(6): 329-336, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37278534

RESUMEN

OBJECTIVE: To investigate non-anticoagulant factors that affect blood coagulation in the extracorporeal circulation (ECC) circuit of regional citrate anticoagulation (RCA) protocol for hemodialysis (HD). METHOD: The clinical characteristics of patients undergoing an individualized RCA protocol for HD between February 2021 and March 2022 were collected; Coagulation scores, pressures in various parts of the ECC circuit, the incidence of coagulation, and citrate concentrations in the ECC circuit during treatment were determined, and non-anticoagulant factors affecting coagulation in the ECC circuit were analyzed. RESULT: The lowest clotting rate was 2.8% in patients with arteriovenous fistula in various vascular access. Patients on Fresenius dialysis had a lower rate of clotting in the cardiopulmonary bypass line than patients on other brands of dialyzer. Low-throughput dialyzers are less likely to clot than high-throughput dialyzers. There are significant differences in the incidence of coagulation among different nurses during citrate anticoagulant hemodialysis. CONCLUSION: In the process of citrate anticoagulant hemodialysis, non-anticoagulant factors such as coagulation status, vascular access, dialyzer selection, and operator quality will affect the anticoagulant effect.


Asunto(s)
Anticoagulantes , Ácido Cítrico , Humanos , Ácido Cítrico/farmacología , Ácido Cítrico/uso terapéutico , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Estudios Retrospectivos , Diálisis Renal/efectos adversos , Diálisis Renal/métodos , Coagulación Sanguínea , Citratos/farmacología , Citratos/uso terapéutico , Circulación Extracorporea
4.
Sci Rep ; 13(1): 6037, 2023 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-37055509

RESUMEN

The cell cycle arrest markers tissue inhibitor metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as potential biomarkers of acute kidney injury (AKI) in critically ill adults in intensive care units and cardiac surgery-associated AKI (CSA-AKI). However, the clinical impact on all-cause AKI remains unclear. Here, we report a meta-analysis performed to evaluate the predictive value of this biomarker for all-cause AKI. The PubMed, Cochrane, and EMBASE databases were systematically searched up to April 1, 2022. We used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. We extracted useful information from these studies and calculated the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Twenty studies with 3625 patients were included in the meta-analysis. The estimated sensitivity of urinary [TIMP-2] × [IGFBP7] in the diagnosis of all-cause AKI was 0.79 (95% CI 0.72, 0.84), and the specificity was 0.70 (95% CI 0.62, 0.76). The value of urine [TIMP-2] × [IGFBP7] in the early diagnosis of AKI was assessed using a random effects model. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 2.6 (95% CI 2.1, 3.3), 0.31 (95% CI 0.23, 0.40), and 8 (95% CI 6, 13), respectively. The AUROC was 0.81 (95% CI 0.78-0.84). No significant publication bias was observed in eligible studies. Subgroup analysis indicated that the diagnostic value was related to the severity of AKI, time measurement, and clinical setting. This study shows that urinary [TIMP-2] × [IGFBP7] is a reliable effective predictive test for all cause-AKI. However, whether and how urinary [TIMP-2] × [IGFBP7] can be used in clinical diagnosis still requires further research and clinical trials.


Asunto(s)
Lesión Renal Aguda , Inhibidor Tisular de Metaloproteinasa-2 , Humanos , Lesión Renal Aguda/etiología , Biomarcadores/análisis , Puntos de Control del Ciclo Celular , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Curva ROC , Inhibidor Tisular de Metaloproteinasa-2/orina
5.
Medicine (Baltimore) ; 100(8): e24639, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33663073

RESUMEN

INTRODUCTION: The lack of individualized treatment protocols and complicated procedures are important factors limiting the use of regional citrate anticoagulation (RCA) technology in hemodialysis. This study aims to validate the safety and efficacy of a simplified individualized RCA protocol for hemodialysis. MATERIALS AND METHODS: From June 2019 to August 2019, 45 patients with active bleeding or bleeding tendency undergoing maintenance hemodialysis in the Nephrology Department of the First Affiliated Hospital of Nanchang University were randomly divided into a modified conventional RCA protocol group with a low-flux dialyzer, a simplified individualized RCA protocol group with a high-flux dialyzer, and a simplified individualized RCA protocol group with a low-flux dialyzer. RESULTS: A total of 45 patients were included in this study. The mean age of the patients was 57.38 ±â€Š19.05 years, and 78% were men. Forty-three patients completed 4 hours of hemodialysis, and the median total clotting scores in the 3 groups were 11, 12, and 12. Compared with the modified conventional RCA protocol group with a low-flux dialyzer, the 2 simplified individualized RCA protocol groups had better clotting scores for the dialyzer, arterial bubble trap, and single-pool urea clearance index (spKt/VBUN) and lower costs. Moreover, these parameters did not differ between the 2 simplified individualized RCA protocol groups. No electrolyte or acid-base imbalances or citrate poisoning was observed in any of the 3 groups. Adverse events did not differ significantly among the 3 groups. CONCLUSIONS: The simplified individualized RCA protocol is safe, effective, and easy to implement. Therefore, this protocol can be promoted for clinical practice. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Study Registry under registration number ChiCTR1900023801.


Asunto(s)
Anticoagulantes/uso terapéutico , Ácido Cítrico/uso terapéutico , Protocolos Clínicos/normas , Diálisis Renal/métodos , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Coagulación Sanguínea/efectos de los fármacos , Análisis de los Gases de la Sangre , Ácido Cítrico/administración & dosificación , Ácido Cítrico/efectos adversos , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad
6.
Ren Fail ; 42(1): 600-606, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32602387

RESUMEN

Background: Serum C-reactive protein to albumin ratio (CAR) was recently identified as a poor marker of prognosis among various populations. The current study aimed to examine the association between CAR and all-cause mortality among patients undergoing peritoneal dialysis (PD).Methods: A total of 758 patients with PD were included in this study during the period from 1 November 2005 to 28 February 2017 and followed up until 31 May 2017. The primary outcome was all-cause mortality. We used multivariate Cox proportional hazard models and Kaplan-Meier survival curves to assess the relationship between CAR and all-cause mortality in these patients.Results: Among 758 participants, mean age was 49.1 ± 14.2 years, with 56% males and 18.6% prevalence of diabetes. Median CAR was 0.13 (interquartile range [IQR], 0.07-0.34). After 27 months (IQR, 14-40 months) of follow-up, 157 deaths had been reported. After adjusting for confounding factors, we found a significant association between serum CAR and all-cause mortality among those in the highest CAR group (hazard ratio 1.91, 95% confidence interval 1.05- 3.47, p = 0.034).Conclusions: In patients undergoing PD, an increase in serum CAR is independently associated with increased risk for all-cause mortality.


Asunto(s)
Proteína C-Reactiva/análisis , Diálisis Peritoneal/mortalidad , Insuficiencia Renal Crónica/terapia , Albúmina Sérica/análisis , Adulto , Anciano , Biomarcadores/sangre , Causas de Muerte , China/epidemiología , Diabetes Mellitus/sangre , Diabetes Mellitus/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Peritoneal/efectos adversos , Pronóstico , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo
8.
N Engl J Med ; 381(11): 1001-1010, 2019 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-31340089

RESUMEN

BACKGROUND: Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis. METHODS: In this phase 3 trial conducted at 29 sites in China, we randomly assigned 154 patients with chronic kidney disease in a 2:1 ratio to receive roxadustat or placebo three times a week for 8 weeks in a double-blind manner. All the patients had a hemoglobin level of 7.0 to 10.0 g per deciliter at baseline. The randomized phase of the trial was followed by an 18-week open-label period in which all the patients received roxadustat; parenteral iron was withheld. The primary end point was the mean change from baseline in the hemoglobin level, averaged over weeks 7 through 9. RESULTS: During the primary-analysis period, the mean (±SD) change from baseline in the hemoglobin level was an increase of 1.9±1.2 g per deciliter in the roxadustat group and a decrease of 0.4±0.8 g per deciliter in the placebo group (P<0.001). The mean reduction from baseline in the hepcidin level (associated with greater iron availability) was 56.14±63.40 ng per milliliter in the roxadustat group and 15.10±48.06 ng per milliliter in the placebo group. The reduction from baseline in the total cholesterol level was 40.6 mg per deciliter in the roxadustat group and 7.7 mg per deciliter in the placebo group. Hyperkalemia and metabolic acidosis occurred more frequently in the roxadustat group than in the placebo group. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the 18-week open-label period. CONCLUSIONS: In Chinese patients with chronic kidney disease who were not undergoing dialysis, those in the roxadustat group had a higher mean hemoglobin level than those in the placebo group after 8 weeks. During the 18-week open-label phase of the trial, roxadustat was associated with continued efficacy. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652819.).


Asunto(s)
Anemia/tratamiento farmacológico , Glicina/análogos & derivados , Hemoglobinas/análisis , Prolina Dioxigenasas del Factor Inducible por Hipoxia/antagonistas & inhibidores , Isoquinolinas/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Acidosis/inducido químicamente , Adulto , Anciano , Anemia/etiología , Colesterol/sangre , Método Doble Ciego , Femenino , Glicina/efectos adversos , Glicina/uso terapéutico , Hematínicos/efectos adversos , Hematínicos/uso terapéutico , Humanos , Hiperpotasemia/inducido químicamente , Isoquinolinas/efectos adversos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/sangre
9.
N Engl J Med ; 381(11): 1011-1022, 2019 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-31340116

RESUMEN

BACKGROUND: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis. METHODS: In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values. RESULTS: A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 µg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group. CONCLUSIONS: Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).


Asunto(s)
Anemia/tratamiento farmacológico , Epoetina alfa/uso terapéutico , Glicina/análogos & derivados , Hematínicos/uso terapéutico , Hemoglobinas/análisis , Prolina Dioxigenasas del Factor Inducible por Hipoxia/antagonistas & inhibidores , Isoquinolinas/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Adulto , Anciano , Análisis de Varianza , Anemia/etiología , Colesterol/sangre , Método Doble Ciego , Epoetina alfa/efectos adversos , Femenino , Glicina/efectos adversos , Glicina/uso terapéutico , Hematínicos/efectos adversos , Humanos , Hiperpotasemia/inducido químicamente , Hipertensión/inducido químicamente , Isoquinolinas/efectos adversos , Masculino , Persona de Mediana Edad , Diálisis Renal , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/terapia
10.
Am J Physiol Renal Physiol ; 314(6): F1087-F1095, 2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-29357421

RESUMEN

Although epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells was recognized as the key process of peritoneal fibrosis, which is a major cause of peritoneal failure related to peritoneal dialysis (PD), mechanisms underlying these processes remain largely unknown. In this study, we found that miR-200a was significantly downregulated in peritoneal tissues with fibrosis in a rat model of PD. In vitro, transforming growth factor (TGF)-ß1-induced EMT, identified by de novo expression of α-smooth muscle actin and a loss of E-cadherin in human peritoneal mesothelial cells (HPMCs), was associated with downregulation of miR-200a but upregulation of zinc finger E-box-binding homeobox 1/2 (ZEB1/2), suggesting a close link between miR-200a and ZEB1/2 in TGF-ß1-induced EMT. It was further demonstrated that miR-200a was able to bind to the 3'UTR of ZEB1/2, and overexpression of miR-200a blocked TGF-ß1-induced upregulation of ZEB1/2 and, therefore, inhibited EMT and collagen expression. In contrast, overexpression ZEB1/2 blocked miR-200a inhibition of EMT and collagen expression in HMPCs. In conclusion, miR-200a could negatively regulate TGF-ß1-induced EMT by targeting ZEB1/2 in peritoneal mesothelial cells. Blockade of EMT in HPMCS indicates the therapeutic potential of miR-200a as a treatment for peritoneal fibrosis associated with PD.


Asunto(s)
Células Epiteliales/efectos de los fármacos , Transición Epitelial-Mesenquimal , MicroARNs/metabolismo , Fibrosis Peritoneal/metabolismo , Peritoneo/efectos de los fármacos , Factor de Crecimiento Transformador beta1/farmacología , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Regiones no Traducidas 3' , Animales , Sitios de Unión , Línea Celular , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , MicroARNs/genética , Fibrosis Peritoneal/genética , Fibrosis Peritoneal/patología , Peritoneo/metabolismo , Peritoneo/patología , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética
11.
BMC Neurol ; 15: 38, 2015 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-25885757

RESUMEN

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a life-threatening channelopathy manifesting as recurrent episodes of hypokalemia and muscle weakness in the presence of hyperthyroidism. Recent findings indicate defects of inward rectifying K+ (Kir) channels are associated with some TPP patients. The associations are not only found in Caucasian population (mainly Brazilian), but also in Singaporean population. However, potential genetic risk factors for mainland Chinese patients, the largest group of TPP cases in the world, have been largely unexplored. METHODS: Samples of DNA from 127 individuals with TPP and 102 hyperthyroidism male controls self-reported as mainland Chinese were collected from 5 clinical centers from Jan 2011 to Jan 2014. The KCNJ2 gene, KCNJ18 gene, as well as loci polymorphisms (rs623011and rs312691) at 17q24.3 were directly sequenced in TPP patients and controls. Clinical data were summarized from TPP participants for genotype/phenotype correlations. RESULTS: 3.1% of TPP cases harbored KCNJ18 gene mutations in mainland Chinese patients. Patients with KCNJ18 mutation had shorter attack duration, higher prevalence of muscle soreness and weakness recurrence than patients without KCNJ18 mutation. The alleles at 17q24.3 (rs623011and rs312691) were more common in patients with TPP than in controls, and therefore were significant risk factors for TPP (odds ratio, 11.94 and 10.57; 95% CI, 5.93-24.05 and 5.48-20.40; P = 1.81 × 10(-14) and 1.07 × 10(-14) respectively). CONCLUSIONS: This study demonstrates that the KCNJ18 variants are only responsible for a small proportion of TPP patients in mainland China. There are significant clinical differences between patients with KCNJ18 mutations and patients without KCNJ18 mutations. In addition, the rs623011and rs312691 loci are significantly associated with TPP patients in mainland China, and highlight the Kir2.1 channel as a causative target in TPP.


Asunto(s)
Pueblo Asiatico/genética , Parálisis Periódica Hipopotasémica/genética , Debilidad Muscular/genética , Mialgia/genética , Canales de Potasio de Rectificación Interna/genética , Tirotoxicosis/genética , Adulto , Estudios de Casos y Controles , China , Cromosomas Humanos Par 17/genética , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Hipertiroidismo/genética , Masculino , Mutación , Polimorfismo Genético , Síndrome , Adulto Joven
12.
J Obstet Gynaecol Res ; 39(1): 317-25, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22889453

RESUMEN

AIM: Endometrial carcinoma (EC) is a common gynecologic malignancy. EC has a favorable prognosis because it is usually diagnosed at an early stage. However, the recurrence rate is high and the prognosis is poor for high-risk EC. Identification of new biomarkers for the prediction of high-risk features will help to guide the treatment and improve the prognosis of patients with EC. MATERIAL AND METHODS: Differentially expressed proteins among high-risk EC, low-risk EC, and normal endometrial tissues were determined by two-dimensional gel electrophoresis (2-DE) and a liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) proteomics approach. Then, the candidate proteins were examined by immunohistochemical analysis. RESULTS: Thirteen protein spots were differentially expressed between the high- and low-risk groups, and 25 protein spots were differentially expressed between the high-risk and normal endometrium groups. Twenty-two proteins were identified by MS analysis. PKM2 and HSPA5 were elevated in the high-risk EC tissues compared with both the low-risk EC and normal endometrial tissues. The elevated expression of PKM2 and HSPA5 in high-risk EC tissue was confirmed by immunohistochemical analysis. DISCUSSION: PKM2 and HSPA5 may play an important role in the progression of EC. These two proteins are potential biomarkers to better predict high-risk EC and thereby guide clinical therapy.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Endometrioide/diagnóstico , Proteínas Portadoras/metabolismo , Neoplasias Endometriales/diagnóstico , Proteínas de Choque Térmico/metabolismo , Proteínas de la Membrana/metabolismo , Hormonas Tiroideas/metabolismo , Anciano , Carcinoma Endometrioide/metabolismo , Electroforesis en Gel Bidimensional , Neoplasias Endometriales/metabolismo , Chaperón BiP del Retículo Endoplásmico , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Proteómica/métodos , Espectrometría de Masas en Tándem , Proteínas de Unión a Hormona Tiroide
13.
Oncol Lett ; 4(6): 1219-1224, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23226798

RESUMEN

The aim of this study was to investigate the antitumor effect of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib on endometrial adenocarcinoma in mice. Various amounts of celecoxib were added to HEC-1B cells in vitro for different durations. Cell cycle and apoptosis were analyzed using flow cytometry. HEC-1B cytostasis, invasiveness and COX-2 expression were examined by MTT, transwell cabin and western blot assays, respectively. An in vivo human endometrial adenocarcinoma model was established in BALB/c nude mice using HEC-1B cells. For two weeks, the celecoxib groups were treated with celecoxib 2 or 4 mg/day via oral administration and the control group was treated with saline. Tumor volume, growth curves and the inhibition rate (IR) were recorded. COX-2 expression levels and microvessel density (MVD) were investigated using an immunohistochemical technique. In the celecoxib groups, cell proliferation was significantly inhibited in a concentration- and time-dependent manner. The proportion of cells in the G0/G1 phase increased within 24 h after the addition of celecoxib whereas those in the S and G2/M phases decreased with an increasing apoptosis peak (sub-G1) and apoptosis rate. The microporous Matrigel-coated polycarbonate membrane of the Transwell cabin was traversable for the HEC-1B cells. The invasiveness was attenuated when the celecoxib concentration was increased. The tumor growth was also greatly inhibited when the celecoxib concentration was increased. The tumor IRs were 32.4 and 48.6% following treatment with 2 and 4 mg/day celecoxib, respectively. COX-2 was mainly expressed in the cytoplasm of the tumor cells. In the celecoxib groups, the COX-2 expression levels were concentration-dependent. The COX-2 expression level and MVD decreased when the celecoxib concentration was increased. The results of dependability analysis revealed that the COX-2 expression level was positively correlated with MVD (r=0.921; P<0.01). The antitumor effect of celecoxib on endometrial adenocarcinoma in nude mice may be related to the inhibition of COX-2 expression and microangiogenesis.

14.
Zhonghua Fu Chan Ke Za Zhi ; 45(5): 326-30, 2010 May.
Artículo en Chino | MEDLINE | ID: mdl-20646439

RESUMEN

OBJECTIVE: To identify the morphological characteristics of pelvic diaphragm hiatus in pregnant women with stress urinary incontinence (SUI) by transperineal three-dimensional (3-D) ultrasound. METHODS: From Oct. 2008 to Mar. 2009, 145 pregnant women (third trimester group) at 37-41 weeks of gestation underwent transperineal 3-D ultrasound investigation at Department of Obstetrics and Gynecology, the Sixth People's Hospital, Shanghai Jiaotong University, including 38 pregnant women with stress urinary incontinence (SUI) and the other 107 non SUI pregnant women. In the mean time, 50 normal nulliparous healthy women were chosen as control group. The morphological characteristics of pelvic diaphragm hiatus, the diameter of pelvic diaphragm hiatus, pubovisceral muscle thickness and genitohiatal and levator ani angle were measured at rest, on maximum Valsalva and maximum pelvic floor contraction by 3-D ultrasound, respectively. RESULTS: Loosen connective tissue and pubococcygeus avulsion were observed in some pregnant women at third trimester. The area of pelvic diaphragm hiatus were (15.2+/-1.9), (16.4+/-2.0) and (13.6+/-1.9) cm2, pubovisceral muscle thickness were (0.72+/-0.11), (0.68+/-0.14) and (0.77+/-0.11) cm, levator ani angle were (60+/-8) degrees, (57+/-10) degrees and (64+/-14) degrees at rest, on maximum Valsalva and maximum pelvic floor contraction respectively. These parameters were significantly increased than those in control group [(11.2+/-2.6), (14.5+/-4.5) and (9.2+/-2.6) cm2; (0.66+/-0.10), (0.67+/-0.14) and (0.71+/-0.14) cm; (50+/-4) degrees, (51+/-5) degrees and (46+/-5) degrees] at three maneuvers, respectively (P<0.05). And those parameters of the anteroposterior hiatal diameter, lateral hiatal diameter, perimeter of pelvic diaphragm hiatus and area of pelvic diaphragm hiatus in SUI pregnant women were increased than those in non SUI pregnant women at three maneuvers, respectively (P<0.05). Pubovisceral muscle thickness in SUI pregnant women was significantly lower than that in non SUI pregnant women at maximum pelvic floor contraction (P<0.05), but there were not significant difference between SUI and non SUI pregnant women at rest and on maximum Valsalva in pubovisceral muscle thickness and genitohiatal and levator ani angle (P>0.05). CONCLUSIONS: Pelvic floor anatomic remodeling is identified in late pregnant women. When compared with non pregnant women, the loosen pelvic floor connective tissue and the bigger diameters of pelvic diaphragm are observed in late pregnant women. It is observed that the increased diameters of pelvic diaphragm and decreased thickness of pubovisceral muscle in later pregnant SUI women than those in non SUI pregnant women.


Asunto(s)
Diafragma Pélvico/diagnóstico por imagen , Complicaciones del Embarazo/diagnóstico por imagen , Ultrasonografía/métodos , Incontinencia Urinaria de Esfuerzo/diagnóstico por imagen , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Imagenología Tridimensional/métodos , Contracción Muscular , Diafragma Pélvico/anatomía & histología , Perineo/anatomía & histología , Perineo/diagnóstico por imagen , Embarazo , Complicaciones del Embarazo/fisiopatología , Tercer Trimestre del Embarazo , Estudios Retrospectivos , Incontinencia Urinaria de Esfuerzo/fisiopatología , Adulto Joven
15.
Zhonghua Fu Chan Ke Za Zhi ; 42(12): 812-4, 2007 Dec.
Artículo en Chino | MEDLINE | ID: mdl-18476512

RESUMEN

OBJECTIVE: To investigate static closure functional characteristics of lower urinary tract in continence in late pregnancy of primigravida through perineal ultrasound and urodynamical measurement. METHODS: From January of 2003 to December of 2005, 83 primigravida undergoing antenatal health care in Shanghai Jiaotong University Affiliated Shanghai Sixth People's Hospital were randomly enrolled in the study, while 28 nulliparous women were recruited as control. The perineal ultrasound and urodynamical measurement were performed at the gestation age of 36-40 weeks, in both groups. We analysed the parameters of lower urinary tract function in late pregnancy compared with nullipara, such as maximal urethral closure pressure (MUCP), functional urethral length (FUL), maximal urethral pressure (MUP), valsalva leak point pressure (VLPP), postvoid residual bladder volume (PVRBV) and volume of first desire to voiding (VFDV). RESULTS: The average weight of 83 neonates was (3504 +/- 404) g. In all of 83 primigravida PVRBV was less than 10 ml. MUP (110 +/- 22) cm H2O (1 cm H2O = 0.098 kPa), MUCP (96 +/- 22)cm H2O and FUL (44 +/- 9) mm were significantly increased in the third trimester compared with nullipara (P < 0.01), but VFDV showed nonsignificant difference (141 +/- 44 vs. 149 +/- 41 ml, P > 0.05). There were 33 pregnant women suffering from urinary leakage throughout the terms. The data showed that MUCP was significantly lower in the pregnant women with symptoms of leaking than without leaking. CONCLUSION: the static closure function increased significantly compared with nulliparous women. The VLPP was decreased and had relationship with symptoms of leakage. The results suggest that the function of lower urinary tract in continence in late pregnancy of primigravida is complex.


Asunto(s)
Número de Embarazos , Presión , Vejiga Urinaria/fisiología , Incontinencia Urinaria de Esfuerzo/fisiopatología , Micción/fisiología , China , Femenino , Humanos , Recién Nacido , Paridad , Embarazo , Tercer Trimestre del Embarazo , Embarazo Prolongado
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