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Objective:To investigate the relationship between triglyceride glucos (TyG), C-reaction protein/albumin (CRP/Alb), 25-hydroxy vitamin D[25(OH)D] and the prognosis of patients with continous ambulatory peritoneal dialysis (CAPD).Methods:A total of 220 CAPD patients in the Affiliated Hospital of Jining Medical University from January 2017 to March 2020 were prospectively selected and divided into death group and survival group according to the 6-month prognosis. The peritoneal urea clearance index (Kt/V urea), TyG, CRP/Alb, 25(OH)D were compared between the two groups. Logistic regression was used to analyze the prognostic factors of CAPD patients. The predictive value of TyG, CRP/Alb and 25(OH)D on the prognosis of CAPD patients was analyzed by receiver operating characteristic (ROC) curve. Results:After 3 months and 6 months of dialysis, the peritoneal Kt/V urea in the death group [(1.21±0.18)ml/(s·1.73 m 2), (1.02±0.14)ml/(s·1.73 m 2)] was significantly lower than that in the survival group [(1.57±0.40)ml/(s·1.73 m 2), (1.49±0.42)ml/(s·1.73 m 2)] (all P<0.05). After 3 months and 6 months of dialysis, the TyG [(8.79±0.86), (9.24±1.03)] and CRP/Alb [(4.98±0.94)×10 -4, (5.14±1.39)×10 -4] in the death group were higher than those in the survival group [(8.03±0.60), (7.26±0.93), (3.57±1.19)×10 -4, (3.07±0.88)×10 -4], while the 25(OH)D [(19.14±2.29)ng/ml, (17.79±3.17)ng/ml] was lower than that of survival group [(22.67±3.03)ng/ml, (24.31±2.51)ng/ml] (all P<0.05). TyG and CRP/Alb at 3 months and 6 months of dialysis were negatively correlated with Kt/V urea, while the 25(OH)D was positively correlated with Kt/V urea (all P<0.05). Logistic regression analysis showed that Kt/Vurea, TyG, CRP/Alb and 25(OH)D were associated with prognosis in the two groups after 3 and 6 months of dialysis (all P<0.05). The AUC of TyG, CRP/Alb and 25(OH)D at 6 months of dialysis combined to predict the prognosis of CAPD patients was the highest, which was 0.911. Conclusions:TyG, CRP/Alb and 25(OH)D are associated with all-cause mortality in CAPD patients. High TyG and CRP/Alb and low 25(OH)D suggest a higher risk of all-cause mortality. Combined detection of all indicators can effectively predict the prognosis of CAPD, which is convenient for early clinical intervention.
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Maternal adverse endocrine environment severely affects the growth and development of offspring. This article reviews relevant cohort studies and animal experiments on the influence of intrauterine hyper androgen on offspring health and the mechanisms, aiming to provide a new perspective for further research, mechanism exploration, and early interventions in this field.
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Resumen: La enfermedad de Gaucher (GD) es el trastorno de almacenamiento lisosomal que se caracteriza por la deficiencia en la actividad enzimática de la β-glucosidasa (BGLU), lo que produce la acumulación de glucosilceramida en las células. Su diagnóstico se orienta a la valoración de la enzima en los leucocitos afectados. Se han realizado estudios en DBS para la actividad de BGLU en el seguimiento de poblaciones de alto riesgo; sin embargo, presentan interferencias relacionadas a leucopenias severas o expresión aumentada de la isoforma neutra de la enzima BGLU, molécula no relacionada con GD. El objetivo de este estudio fue la estandarización de un método de tamizaje en DBS (punch: 5 mm) con el uso de 4-metilumbeliferil-β-D-glucósido y conduritol-β-epóxido. Se analizaron muestras de DBS de 395 individuos con sospecha clínica (población de alto riesgo o AR), 151 controles y 16 pacientes afectados, usando la elución de un corte de 5 mm (≈10 μl de sangre) en 300 μl de Tritón X-100/(0,5 %). Como resultados, se obtuvieron los rangos, AR: 0,84-26,92 nmol/ml/h, controles: 3,56- 8,92 nmol/ml/h (M = 5,56, DS = 1,15) y pacientes confirmados con GD: 0,82- 2,88 nmol/ml/h (M = 1,64, DS = 0,57). El punto de corte entre deficientes y controles fue 3,22 nmol/ml/h, obtenido a partir de análisis ROC (99 % confianza, 100 % sensibilidad y 100 % especificidad). El protocolo permitió evidenciar la deficiencia en todos los casos de GD, confirmados mediante el análisis en paralelo de la enzima en aislamiento leucocitario. Se recomienda el uso del CBE y realizar la elución del corte a 5 mm, a fin de llevar a cabo la valoración enzimática con un volumen mayor aproximado de sangre y en ausencia de la actividad generada por la isoforma neutra.
Abstract: Gaucher disease (GD) is a lysosomal storage disorder characterized by a deficiency in the enzymatic activity of β-glucosidase (BGLU), resulting in the accumulation of glucosylceramide in cells. Its diagnosis is aimed at checking the enzyme in the affected leukocytes. Studies have been conducted on dried blood spots (DBS) for bglu activity to monitor high-risk populations; however, they exhibit interferences related to severe leukopenias or increased expression of the neutral bglu isoform, a molecule not related to gd. This study intends to standardize a screening method on dbs (punch: 5 mm) using 4-methylumbelliferyl-β-D-glucoside and conduritol-β-epoxide (CβE). dbs samples from 395 individuals clinically suspected of gd (high-risk or hr population), 151 controls, and 16 affected patients were analyzed using the elution of 5 mm punches (≈10 μl of blood) in 300 μl of Triton X-100/ (0.5 %). As a result, the following ranges were obtained; HR: 0.84-26.92 nmol/ml/h, controls: 3.56-8.92 nmol/ml/h (M = 5.56, SD = 1.15), and patients with confirmed GD: 0.82-2.88 nmol/ml/h (M = 1.64, SD = 0.57). The cut-off point between patients with gd and controls was 3.22 nmol/ml/h, obtained from roc analysis (99 % ci, 100 % sensitivity, and 100 % specificity). The protocol revealed a deficiency in all gd cases, confirmed by parallel bglu analysis in isolated leukocytes. The use of cbe and the elution of 5 mm punches are recommended for enzymatic evaluation with a higher approximate volume of blood and in the absence of neutral isoform activity.
Resumo: A doença de Gaucher (GD) é o trastorno de armazenamento lisosomal caracterizado pela deficiência na atividade enzimática da β-glucosidase (BGLU), o que produz a acumulação de glucossilceramida nas células. Seu diagnóstico está orientado à avaliação da enzima nos leucócitos afetados. Foram realizados estudos em dbs para a atividade de BGLU no seguimento de populações de alto risco; contudo, são apresentadas interferências relacionadas a leucopenias graves ou a expressão aumentada da isoforma neutra da enzima BGLU, molécula não relacionada com GD. O objetivo deste estudo foi a padronização de um método de tamisação emdbs (punch: 5 mm) com o uso de 4-metilumbeliferil-β-D- glicosídeo e conduritol-β-epóxido. Foram analisadas amostras de dbs de 395 indivíduos com suspeita clínica (população de alto risco ou ar), 151 controles e 16 pacientes afetados, usando a eluição de um corte de 5 mm (≈10 μl de sangue) em 300 μl de Tritão X-100/(0,5 %). Como resultados, foram obtidos os intervalos: AR: 0,84-26,92 nmol/ml/h, controles: 3,56-8,92 nmol/ml/h (M = 5,56, DS = 1,15) e pacientes confirmados com GD: 0,82- 2,88 nmol/ml/h (M = 1,64, DS = 0,57). O ponto de corte entre deficientes e controles foi 3,22 nmol/ml/h, obtido a partir de análise ROC (99 % confiança, 100 % sensibilidade e 100 % especificidade). O protocolo permitiu evidenciar a deficiência em todos os casos de GD, confirmados mediante a análise em paralelo da enzima em isolamento leucocitário. É recomendado o uso do cbe e a realização da eluição do corte a 5 mm, a fim de implementar a avaliação enzimática com um volume maior aproximado de sangue e em ausência da atividade gerada pela isoforma neutra.
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We prepared gold nanostar (GNS) through seed growth method firstly,then formation of COX-2 siRNA(siCOX-2) and GNS composite modified with polyethylene glyco (PEG),2-amino-2-deoxy-D-glucos (DG) and 9-D-arginin (9R) was prepared.Mterwords,paclitaxel temperature sensitive liposome (PTX-TSL) was prepared by film dispersion method.Finally,siCOX-2 delivery systerm (PTX-TSL-(siCOX-2(9R/DG-GNS)))was obtained by hydrosulfuryl ligand reaction between siCOX-2 (9R/DG-GNS) and PTX-TSL The successful build of siCOX-2 (9R/DG-GNS) was vetified by nuclear magnetic resonance (NMR),sodium dodecyl sulfate polyacryl amide gel electrophoresis (SDS-PAGE),and ultraviolet spectrophotometry and agarose gel electrophoresis method.Particle size of PTX-TSL-(siCOX-2(9R/DG-GNS)) was (292 ± 14) nm and Zeta potential was about -(2.59 ± 0.12) mV,which were measured by Zetasizer Nano ZS90.The morphology of PTX-TSL-(siCOX-2 (9R/DG-GNS)) measured by transmissionelectronmicroscopy showed homogeneous star structure with phospholipid bilayer on the surface,and it showed good thermal conversion efficiency under radiation of 808 nm laser.Differential scanning calorimetry test showed that PTX-TSL phase transition temperature is about 42.6 ℃.The drug loading content(using dialysis method) and encapsulation efficiency of PTX-TSL were about 7.5％ and 95.4％,at the same time,the release process experiment of PTX-TSL showed that it had a good temperature sensitive release performance.It is hopeful that this siCOX-2 system can be used for reducing drug resistance of PTX and improving the treatment effect of PTX through the synergistic antitumor drug resistance effect of siCOX-2.