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1.
ObjectivesThe receptor for advanced glycation end-products (RAGE) takes part in the pathogenesis of many diseases, including diabetes mellitus and cancer. AGE-precursors are detoxified by glyoxalase (GLO). sRAGE, soluble RAGE, is an inhibitor of pathological effects mediated via RAGE. The aim was to study sRAGE and polymorphisms of RAGE (AGER) and GLO genes in patients with pancreas cancer (PC).Design and MethodsThe studied group consisted of 51 patients with PC (34 with impaired glucose tolerance—IGT, 17 without IGT), 34 type 2 DM and 154 controls. For genetic analysis, the number of patients was increased to 170. Serum sRAGE was measured by ELISA and all polymorphisms (RAGE ?429T/C, ?374T/A, 2184A/G, Gly82Ser and GLO A419C) were determined by PCR-RFLP and confirmed by sequencing.ResultsSoluble RAGE is decreased in patients with PC compared to patients with DM and controls (975 ± 532 vs. 1416 ± 868 vs. 1723 ± 643 pg/mL, p < 0.001). Patients with PC and IGT have lower sRAGE levels compared to patients with PC without IGT (886 ± 470 vs. 1153 ± 616 pg/mL, p < 0.05). No relationship of sRAGE to the stage was found. We did not show any difference in allelic and genotype frequencies in all RAGE and GLO polymorphisms among the studied groups.ConclusionThis is the first study demonstrating decreased sRAGE in patients with pancreas cancer. Its levels are even lower than in diabetics and are lowest in patients with PC and IGT. Our study supports the role of glucose metabolism disorder in cancerogenesis. Further studies are clearly warranted, especially with respect to potential preventive and therapeutic implications.  相似文献   

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ObjectivesTo evaluate ultrasound elastography (USE) using strain ratio (SR), a relative quantification approach for breast lesions characterization.MethodsOne hundred forty-seven consecutive patients with a total of 156 breast lesions underwent USE. Technical accuracy was assessed automatically. For SR evaluation a rounded ROI was depicted inside fat (F), glandular tissue (G) and inside the lesion (L), preferably at the same depth. R1, mean value of the G and F ratio, stands for in background tissue composition elasticity. R2; mean value of L/F stands for in lesion elasticity, both evaluated in arbitrary unit (au). Two-years follow-up and pathology results were standard of reference. Mann–Whitney test, ROC analysis and Chi-square with Yates correction were used.ResultsWith the exception of 27 cysts, 17 malignant and 112 benign lesions were found. R1 values were 1.6 ± 0.7 au and 1.2 ± 0.9 au (p = 0.015 NS); R2 values were 6.1 ± 2.5 au and 1.9 ± 1.3 au (p < 0.001) for malignant and benign lesions, respectively. A threshold of 3.3 au showed a sensitivity and specificity of 88% and 87%, respectively with an AUC of 93%. Fifteen false positive and two false negative were detected.ConclusionRelative quantification of ultrasound elastography allows to find high levels of diagnostic accuracy in characterizing breast tumors above all in downgrading BI-RADS 3 and 4 lesions.  相似文献   

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BackgroundRecent studies have suggested that impaired nitric oxide (NO) formation in preeclampsia may result from increased concentrations of an endogenous NO synthase inhibitor, the asymmetric dimethylarginine (ADMA). However, no previous study has examined whether a negative association exists between ADMA and nitrite concentrations in preeclampsia. Moreover, no previous study has compared ADMA and nitrite levels in black and white preeclamptic pregnant women.MethodsWe measured plasma nitrite concentrations using an ozone-based chemiluminescence assay, and plasma ADMA levels using enzyme immunoassays in 94 pregnant (47 healthy pregnant: 16 blacks and 31 whites; and 47 preeclamptic: 14 blacks and 33 whites).ResultsWe found higher ADMA (2.199 ± 0.016 μmol/l vs. 2.112 ± 0.012 μmol/l; P < 0.0001) and lower plasma nitrite levels (102 ± 7.1 nmol/l vs. 214.8 ± 26.1 nmol/l; P < 0.0001) in preeclamptic compared with healthy pregnant women. Black pregnant had higher ADMA levels than white pregnant women (P < 0.05), both in preeclamptic (2.239 ± 0.020 μmol/l vs. 2.144 ± 0.019 μmol/l) and in healthy pregnant (2.172 ± 0.025 μmol/l vs. 2.077 ± 0.018 μmol/l). Conversely, we found no significant effects of ethnicity on the plasma nitrite levels, both in healthy pregnant and in preeclamptic women (P > 0.05). We found a significant negative correlation (P < 0.05) between these markers (r = ? 0.28; P < 0.05).ConclusionsOur findings show higher ADMA and lower nitrite levels in preeclamptic compared with healthy pregnant, and the concentrations of these biomarkers are inversely associated. While ethnicity affected ADMA concentrations, no such effect was found with respect to nitrite levels. These results may have important implications for studies on NO biology and therapeutic approaches of preeclampsia.  相似文献   

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ObjectiveThe aim of this study was to investigate the long-term in vitro stability of soluble ST2 (sST2).Design and methodsEDTA plasma samples were drawn from 15 individuals with various diseases. The PresageTM ST2 assay was used for measurement of sST2 concentrations directly after blood collection and after storing plasma samples for 18 months at ?20 °C and ?80 °C. The default criterion for analyte stability was set at 95%.ResultssST2 concentrations in the 15 individuals ranged from 12 U/mL to 140 U/mL. Directly after blood collection, the mean (± SD) sST2 concentration was 51 ± 37 U/mL, and absolute analyte recoveries were 50 ± 35 U/mL and 51 ± 34 U/mL after storage of samples for 18 months at ?20 °C and ?80 °C, respectively. Relative analyte recoveries after 18 months of storage at ?20 °C and ?80 °C were 99 ± 5% and 101 ± 7%.ConclusionsST2 is stable for at least 1.5 years in plasma samples stored at ?20 °C and ?80 °C.  相似文献   

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ObjectivesTo evaluate the urinary levels of uric acid (UA) and total antioxidant capacity (TAC) with and without UA relative contribution (TAC?UA) in children and adults with Down syndrome (DS) and to prove the clinical use of TAC.Design and methodsUrine samples were obtained from 32 individuals with DS and 29 controls. Two age groups were established (children and adults). Spectrophotometric methods were used for biochemical determinations.ResultsChildren with DS had significantly higher UA/Cr and TAC/Cr levels than controls, whereas levels of TAC?UA/Cr were lower in adults with DS than in controls (P < 0.05 for all). In DS, levels of UA/Cr, TAC/Cr and TAC?UA/Cr were higher in children than in adults (P < 0.05 for all). Positive correlations between UA/Cr and TAC/Cr were found for all groups studied. Negative correlations with age were found for UA/Cr and TAC/Cr in children of both groups.ConclusionsOur results proved that TAC is decreased in adults with DS. Besides, TAC?UA seems to provide more reliable information about the antioxidant status, at least in DS.  相似文献   

9.
Background:Patients with acute decompensated heart failure (ADHF) are frequently treated with unnecessary antibiotics since they are confused with pneumonia patients.Aim:To study the efficacy of measuring C-reactive protein (CRP) levels on admission and CRP velocity in differentiating ADHF from pneumonia.Methods:A retrospective observational study of ADHF and pneumonia patients admitted to a tertiary hospital during 2 years. Patients who were already treated with antibiotics on admission were excluded. Efficacy of CRP as a diagnostic marker was evaluated by using receiver operator curves (ROC).Results:Overall, 72 ADHF and 50 pneumonia patients were included in the study. The mean CRP levels on admission were 13.5 ± 13.5 mg/L for the ADHF patients and 127 ± 84 mg/L for the pneumonia patients (p < 0.001). CRP increases of ≥0.56 mg/L/h were diagnostic of pneumonia. CRP levels on admission together with CRP increases had a sensitivity of 0.96 and a specificity of 0.972 (p < 0.001) as markers to distinguish pneumonia from ADHF.Conclusions:This study emphasizes the dynamic nature of biomarkers. Demonstrating the efficiency of repeated CRP measurements in an acute setting will provide clinicians with a valuable tool for establishing the correct diagnosis and refraining from unnecessary use of antibiotics.  相似文献   

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Objectives:To develop an isotope dilution liquid chromatography tandem mass spectrometry (LC-IDMS/MS) method for the standardization of serum creatinine.Design and methods:Supernatants obtained by protein precipitation were injected into a LC-MS/MS. Chromatography was performed on a cation exchanger pre-column in normal phase isocratic mode. Creatinine and creatinine-D3 were quantified using ion transitions of m/z 114→44 and 117→47, respectively.Results:The method was calibrated with the NIST Standard Reference Material 914a and was found to be exact in analyzing the certified reference material SRM 967 from NIST (97.1 ± 0.9% and 102.1 ± 0.9% of target value for levels 1 and 2, respectively) and by calculating recuperation of spiked creatinine in 10 different patient samples (103.6 ± 4.1%). Intra-assay imprecision was 0.9% at both 64.6 and 354 μmol/L creatinine, while inter-assay imprecisions were 1.9% and 1.8%. Absence of ion suppression was confirmed by spiking experiments. The method was shown to be free of carryover. A good correlation was obtained between the LC-MS/MS method and a Jaffe method run on an automated analyzer (r = 0.999).Conclusions:We have developed a fast and simple method for the quantification of serum creatinine by isotope dilution tandem mass spectrometry (IDMS/MS) and we propose that this method can be used as a reference method by laboratories that wish to validate their serum creatinine automated assay.  相似文献   

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BackgroundType 2 diabetic patients have a higher risk of atherosclerosis than non-diabetic subjects. This difference may be attributable to increased levels of small dense low-density lipoprotein-cholesterol (sLDL-C) in diabetic patients. As the sLDL-C concentration is elevated in hypertriglyceridemia, which is exaggerated postprandially, we examined whether the sLDL-C level increases postprandially in type 2 diabetes.MethodsWe obtained 7 blood samples (30 min before and 2 h after each meal, and at midnight) from 15 patients with diabetes and ten normal controls. Following the precipitation of very low-density lipoprotein and large buoyant LDL (bLDL) with heparin–Mg2+, the sLDL-C concentration was determined as the cholesterol concentration by a homogeneous assay.ResultsThe fasting sLDL-C concentration was 60.3% higher in the diabetic patients than in the controls (1.01 ± 0.21 vs. 0.63 ± 0.21 mmol/l, p < 0.001). The sLDL-C concentrations in both groups were highest in the fasting state, decreased after breakfast, and remained low until midnight. The maximal reduction in the absolute sLDL-C concentration was 56.5% greater in the diabetic patients than in the controls (0.36 ± 0.13 vs. 0.23 ± 0.16 mmol/l, p < 0.05). Thus, the sLDL-C/bLDL-cholesterol (bLDL-C) ratio was reduced with increases in bLDL-C.ConclusionsThe sLDL-C concentration decreases postprandially in diabetes. This absolute reduction in sLDL-C may contribute to an acceleration of atherosclerosis in diabetic patients.  相似文献   

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ObjectivesAvailable data on 24-h urinary solute excretion in healthy children are sparse. We thus documented the daily and overnight variations of urinary electrolytes (calcium, magnesium, and phosphorus), urea, and creatinine in prepubertal (Tanner stage I) boys.Design and methodsNine voluntary healthy prepubertal boys aged 10.8 ± 0.11 years participated in this study. Concentrations of variables were quantified in daytime samples (collected between 07:00 h ± 30 min and 21:00 h ± 30 min) and nighttime samples (collected between 21:00 h ± 30 min and 07:00 h ± 30 min) in spring, during a period of 24-h every 3 h.ResultsSignificant differences were found between daytime and nighttime excretion of calcium (p < 0.05), magnesium (p < 0.001), phosphorus (p < 0.01), and urea (p < 0.05), with high concentrations during the night. The 24-h solute/creatinine ratio was 0.072 ± 0.008 mg/mg for calcium, 0.069 ± 0.008 mg/mg for magnesium, 0.698 ± 0.070 mg/mg for phosphorus, and 0.017 ± 0.001 g/mg for urea. Statistically significant correlation analyses showed that urea and creatinine were positively associated with body mass index (BMI) (R = 0.790, p = 0.0113 for urea; R = 0.889, p = <0.0013 for creatinine) and weight (R = 0.717, p = 0.0297 for urea; R = 0.978, p = < 0.001 for creatinine). The other urinary variables were independent of BMI and body mass.ConclusionThese data are of interest for the diagnosis of certain renal disease in prepubertal children.  相似文献   

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Background:There is insufficient data regarding the differential diagnosis and the prognostic value of significantly elevated serum levels of C-reactive protein (CRP) in hospitalized medical patients.Design and methods:A retrospective review of medical charts of patients admitted to a tertiary hospital's Internal Medicine ward during a period of 1 year who had at least one CRP serum level measurement of 200 mg/L or more.Results:Overall, 341 patients with a mean age of 69.8 ± 1.0 years were included in the study. Acute infection was the most prevalent diagnosis (n = 293; 85.9%) with community-acquired pneumonia being the most common acute infection (n = 115; 33.7%). Non-infectious conditions accounted for 9.1% (n = 31) of the diagnoses and included mainly malignant metastatic diseases (n = 19; 5.6%). Overall, 70 (20.5%) patients died within 30 days of admission. Age and active malignancy, with metastasis or without metastasis, were independently associated with 30-day mortality.Conclusion:Significantly elevated CRP serum levels are associated with bacterial infections, malignant diseases, and very high rates of 30-day mortality in hospitalized medical patients.  相似文献   

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Intrinsic coagulation factor XII deficient (FXII?/?) mice are protected from ischemic stroke. To elucidate underlying mechanisms we investigated the early ischemic period in vivo by multimodal magnetic resonance imaging (MRI) at 17.6 Tesla.Cerebral ischemia was induced by either transient (60 min) or permanent occlusion of the middle cerebral artery (t/pMCAO). 10 FXII?/? mice underwent t- , 10 FXII?/? mice p- and 10 Wildtype (Wt) mice tMCAO. Cerebral blood flow (CBF), diffusion-weighted-imaging (DWI) and T2-relaxometry were measured at 2 h and 24 h after MCAO. Outcome measures were evaluated after motion correction and normalization to atlas space. 2 h after tMCAO CBF reduction was similar in FXII?/? and Wt mice extending over cortical (CBF (ml/100 g/min) 33.6 ± 6.9 vs. 35.3 ± 4.6, p = 0.42) and subcortical regions (25.7 ± 4.5 vs. 31.6 ± 4.0, p = 0.17). At 24 h, recovery of cortical CBF by +36% was observed only in tMCAO FXII?/? mice contrasting a further decrease of – 30% in Wt mice after tMCAO (p = 0.02, F(1,18) = 6.24). In FXII?/? mice in which patency of the MCA was not restored (pMCAO) a further decrease of ? 75% was observed. Cortical reperfusion in tMCAO FXII?/? mice was related to a lower risk of infarction of 59% vs. 93% in Wt mice (p = 0.04). Subcortical CBF was similarly decreased in both tMCAO groups (Wt and FXII?/?) relating to a similar risk of infarction of 89% (Wt) vs. 99% (FXII?/?, p = 0.17).Deficiency of FXII allows neocortical reperfusion after tMCAO and rescues brain tissue by this mechanism. This study supports the concept of FXII as a promising new target for stroke prevention and therapy.  相似文献   

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BackgroundCirculating β2-glycoprotein-I-oxidized low-density lipoprotein (β2-GPI–ox-LDL) complexes have been found in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases as a contributor to the development of autoimmune-mediated atherosclerosis. In vitro study showed that β2-GPI also bound with high affinity to atherogenic lipoprotein (a) [Lp(a)] which shares structural similarity to LDL. We examined the existence and clinical significance of serum complexes of β2-GPI with Lp(a) in SLE patients.MethodsA “sandwich” ELISA was developed for measuring serum concentrations of β2-GPI–Lp(a) complexes, using rabbit anti-human β2-GPI antibody as capturing antibody, and quantitating with antibody against apo(a). Forty-seven SLE patients and 42 healthy controls were studied.ResultsBoth Lp(a) (400 ± 213 mg/l vs. 181 ± 70 mg/l) and ox-Lp(a) (27.07 ± 22.30 mg/l vs. 8.20 ± 4.55 mg/l) concentrations were higher in SLE patients than in controls (P < 0.0001). β2-GPI–Lp(a) complexes were detectable in both controls and SLE. The complexes levels in SLE were higher than in controls (0.96 ± 0.41 U/ml vs. 0.59 ± 0.20 U/ml, P < 0.0001) and was positively correlated with ox-Lp(a) (P < 0.001).ConclusionsWe report the existence of β2-GPI–Lp(a) complexes in both controls and SLE patients. The complexes levels increase in SLE.  相似文献   

16.
BackgroundPatients undergoing continuous ambulatory peritoneal dialysis (CAPD) often have inflammation and dyslipidemia that accelerate to atherosclerosis. This study aimed to evaluate chronic inflammation and dyslipidemia in CAPD patients.MethodsWe measured inflammatory markers and lipoprotein subclasses in 20 CAPD patients (12 men and 8 women, aged 59.5 ± 9.9 y) and 20 gender-matched controls. Lipoproteins were separated by high-performance liquid chromatography (HPLC) using an anion-exchange column.ResultsHigh-sensitivity C-reactive protein and serum amyloid A protein (SAA) were higher among CAPD patients vs. controls (1.6 ± 2.2 vs. 0.8 ± 1.2 mg/l, p < 0.05; 11.9 ± 12.8 vs. 4.5 ± 2.4 mg/l). HPLC analysis revealed that chylomicron, VLDL, and IDL cholesterol levels were higher among CAPD vs. controls. In contrast, HDL cholesterol was lower among CAPD patients vs. controls. In the subgroup analysis, SAA levels were significantly lower among patients receiving CAPD for > 3 y than among controls. However, IDL cholesterol was consistently higher among CAPD patients vs. controls.ConclusionsCAPD patients have chronic inflammation and dyslipidemia. IDL cholesterol is the only lipoprotein subclass that is consistently elevated regardless of CAPD duration. More attention should be paid to dyslipidemia in the management of the CAPD patients.  相似文献   

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Objectives:Amyloid fibrils and amyloid-like structures are implicated in atherosclerosis via macrophage activation and inflammation. A common property of amyloid-like structures is their ability to induce thioflavin T (ThT) fluorescence. We measured ThT fluorescence in serum and related these levels to traditional cardiovascular risk factors and non-invasive measures of vascular dysfunction (elasticity). In addition, chemically modified serum components that contribute to serum ThT fluorescence were explored and identified.Design, Methods, and Results:Sera from 105 people, including 35 healthy subjects, and 70 high cardiovascular risk patients (36 with rheumatoid arthritis and 34 with systemic lupus erythrematosus) showed an 8.75-fold variation in induced ThT fluorescence. Although mean (± SD) ThT fluorescence did not differ significantly between groups (controls 0.97 ± 0.26, RA 1.12 ± 0.45, and SLE 0.74 ± 0.23), the combined data set showed significant inverse correlation (p = 0.046) between ThT fluorescence tertiles and small artery elasticity. Correlation was also found between ThT fluorescence tertiles and LDL-cholesterol, total-cholesterol, and C-reactive protein. Floatation fractionation of apoB containing lipoproteins showed that ThT reactivity in this fraction correlated with both serum oxidised-LDL and LDL-cholesterol levels. However, approximately 94% of ThT reactivity in serum was associated with the non-apoB containing serum fraction, with the majority of ThT fluorescence associated with albumin. Incubation of purified albumin with glucose or with methylglyoxal induced ThT fluorescence, suggesting that glycated or chemical adducts of albumin contribute to the variation in ThT fluorescence of human serum.Conclusions:We propose that the detection of these adducts in serum using ThT fluorescence measurements may provide a marker for chemically modified protein structures that could assist the assessment of cardiovascular disease risk.  相似文献   

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IntroductionCerebral perfusion is compromised during cardiopulmonary resuscitation (CPR). We hypothesized that beneficial effects of gravity on the venous circulation during CPR performed in the head-up tilt (HUT) position would improve cerebral perfusion compared with supine or head-down tilt (HDT).MethodsTwenty-two pigs were sedated, intubated, anesthetized, paralyzed and placed on a tilt table. After 6 min of untreated ventricular fibrillation (VF) CPR was performed on 14 pigs for 3 min with an automated CPR device called LUCAS (L) plus an impedance threshold device (ITD), followed by 5 min of L-CPR + ITD at 0° supine, 5 min at 30° HUT, and then 5 min at 30° HDT. Microspheres were used to measure organ blood flow in 8 pigs. L-CPR + ITD was performed on 8 additional pigs at 0°, 20°, 30°, 40°, and 50° HUT.ResultsCoronary perfusion pressure was 19 ± 2 mmHg at 0° vs. 30 ± 3 at 30° HUT (p < 0.001) and 10 ± 3 at 30° HDT (p < 0.001). Cerebral perfusion pressure was 19 ± 3 at 0° vs. 35 ± 3 at 30° HUT (p < 0.001) and 4 ± 4 at 30° HDT (p < 0.001). Brain–blood flow was 0.19 ± 0.04 ml min−1 g−1 at 0° vs. 0.27 ± 0.04 at 30° HUT (p = 0.01) and 0.14 ± 0.06 at 30° HDT (p = 0.16). Heart blood flow was not significantly different between interventions. With 0, 10, 20, 30, 40 and 50° HUT, ICP values were 21 ± 2, 16 ± 2, 10 ± 2, 5 ± 2, 0 ± 2, −5 ± 2 respectively, (p < 0.001), CerPP increased linearly (p = 0.001), and CPP remained constant.ConclusionDuring CPR, HDT decreased brain flow whereas HUT significantly lowered ICP and improved cerebral perfusion. Further studies are warranted to explore this new resuscitation concept.  相似文献   

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ObjectivesTo evaluate oxidative stress and the extent of oxidation of plasma proteins in type 2 diabetic patients.Design and methodsStudy was carried out on blood from 31 diabetic patients of both sexes (mean age = 58 ± 7; duration of diabetes 12 ± 5 years) and healthy age and sex matched normal subjects. Biomarkers of protein oxidation; plasma protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and –SH group and free radical scavenging capacity of plasma was measured.ResultsPCO and AOPPS levels were significantly (P < 0.005) higher in diabetic patients in comparison to healthy volunteers. Reduced free radical scavenging capacity (P < 0.001) and –SH group (P < 0.05) was observed in plasma of type 2 diabetic patients.ConclusionsOur data suggest that diabetics are susceptible to protein oxidation. Oxidative modulation of proteins due to reduced radical scavenging activity of plasma patients may be one of the reasons of altered physiological processes in type 2 diabetic patients.  相似文献   

20.
BackgroundRecently, soluble corin was detected in human plasma. In patients with heart failure, plasma corin levels were lower than that of normal controls. In this study, we analyzed experimental conditions for measuring plasma or serum corin by an immunoassay.MethodsSerum and plasma corin levels were measured by ELISA. Effects of different anticoagulants (EDTA, heparin and sodium citrate) on plasma corin levels were examined.ResultsCorin levels in serum were similar to that in plasma with heparin (950 ± 305 vs. 929 ± 301 pg/ml, n = 40, p = 0.73), but were significantly higher than those in plasma with sodium citrate (735 ± 237 pg/ml, p < 0.01) or EDTA (716 ± 261 pg/ml, p < 0.001). Native and recombinant human corin proteins were stable in human plasma with EDTA at 4 °C or underwent freezing-and-thawing. In 348 healthy Chinese individuals, plasma corin levels ranged from 216 to 1663 pg/ml. The levels were higher in males than that in females (842 ± 283 vs. 569 ± 192 pg/ml, p < 0.001).ConclusionSoluble corin was stable in plasma samples. Plasma soluble corin levels vary depending on anticoagulants used. Samples containing heparin had significantly higher levels of corin than that in samples with EDTA or sodium citrate.  相似文献   

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