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Introduction: The glomerular filtration rate (GFR) is crucial for chronic kidney disease (CKD) diagnosis and therapy. Various studies have sought to recognize ideal endogenous markers to improve the estimated GFR (eGFR) for clinical practice. To screen out potential novel metabolites related to GFR (mGFR) measurement in CKD patients from the Chinese population, we identified more biomarkers for improving GFR estimation. Methods: Fifty-three CKD participants were recruited from the third affiliated hospital of Sun Yat-sen University in 2020. For each participant, mGFR was evaluated by utilizing the plasma clearance of iohexol and collecting serum samples for untargeted metabolomics analyses by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC–MS/MS). All participants were divided into four groups according to mGFR. The metabolite peak area data were uploaded to MetaboAnalyst5.0 for one-way ANOVA, principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) and confirmed the metabolites whose levels increased or decreased with mGFR and Variable Importance in Projection (VIP) values>1. Metabolites were ranked by correlation with the original values of mGFR, and metabolites with a correlation coefficient>0.8 and VIP >2 were identified. Results: We screened out 198 metabolites that increased or decreased with mGFR decline. After ranking by correlation with mGFR, the top 50 metabolites were confirmed. Further studies confirmed the 10 most highly correlated metabolites. Conclusion: We screened out the metabolites that increased or decreased with mGFR decline in CKD patients from the Chinese population, and 10 of them were highly correlated. They are potential novel metabolites to improve GFR estimation.

ObjectiveWhether uric acid (UA) has an effect on renal function remains controversial. We aimed to investigate the association between serum UA with the decline in estimated glomerular filtration rate (eGFR) in middle-aged and elderly populations in the China Health and Retirement Longitudinal Study (CHARLS).DesignLongitudinal cohort study.SettingThis was a second analysis of a public dataset (CHARLS).ParticipantsIn this study, 4538 middle-aged and elderly individuals were screened after removing individuals younger than 45 years old, with kidney disease, malignant tumour and missing values.Outcome measuresBlood tests were performed both in 2011 and 2015. Decline in eGFR was defined as an eGFR decrease of more than 25% or deterioration of the eGFR stage during the 4-year follow-up period. Logistic models corrected for multiple covariables were used to analyse the association of UA with the decline in eGFR.ResultsThe median (IQR) concentrations of serum UA grouped by quartiles were 3.1 (0.6), 3.9 (0.3), 4.6 (0.4) and 5.7 (1.0) mg/dL, respectively. After multivariable adjustment, the OR of the decline in eGFR was higher for quartile 2 (3.5–ConclusionsOver a 4-year follow-up period, we found that elevated UA was associated with a decline in eGFR in the middle-aged and elderly individuals with normal renal function.

Background. Chronic kidney disease (CKD) is a global public health problem. Identifying new biomarkers that can be used to calculate the glomerular filtration rate (GFR) would greatly improve the diagnosis and understanding of CKD at the molecular level. A metabolomics study of blood samples derived from patients with widely divergent glomerular filtration rates could potentially discover small molecule metabolites associated with varying kidney function. Methods. Using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), serum was analyzed from 53 participants with a spectrum of measured GFR (by iohexol plasma clearance) ranging from normal to severe renal insufficiency. An untargeted metabolomics assay (N ¼ 214) was conducted at the Calibra-Metabolon Joint Laboratory. Results. From a large number of metabolomics-derived metabolites, the top 30 metabolites correlated to increasing renal insufficiency according to mGFR were selected by the random forest method. Significant differences in metabolite profiles with increasing stages of CKD were observed. Combining candidate lists from six other unique statistical analyses, six novel, potential metabolites that were reproducibly strongly associated with mGFR were selected, including erythronate, gulonate, C-glycosyltryptophan, N-acetylserine, N6-carbamoylthreonyladenosine, and pseudouridine. In addition, hydroxyasparagine were strongly associated with mGFR and CKD, which were unique to this study. Conclusions. Global metabolite profiling of serum yielded potentially valuable biomarkers of different stages of CKD. Additionally, these potential biomarkers might provide insight into the underlying pathophysiologic processes that contribute to the progression of CKD as well as improve GFR estimation.

ObjectivesFew studies have explored correlations between metabolic syndrome (MetS) alterations and renal deterioration in longitudinal cohorts. We aim to investigate associations between MetS recovery/development and rapid estimated glomerular filtration rate (eGFR) decline in the China Health and Retirement Longitudinal Study (CHARLS).DesignLongitudinal cohort study.SettingThis study is a secondary analysis of CHARLS.ParticipantsAfter excluding individuals with age 2and clinician-reported malignant tumour, heart disease, stroke or kidney disease at baseline, 4142 participants with complete data were selected from the CHARLS during the 4-year follow-up period (2011–2015).Outcome measuresMetS were measured at 2011 and 2015 in CHARLS. A rapid eGFR decline was defined as an average annual eGFR decline of >3 mL/min/1.73 m2. The associations between rapid eGFR decline and MetS recovery/development were analysed using multivariable adjusted logistic models.ResultsAccording to MetS baseline status and follow-up, participants were divided into four groups: (1) 2460 (59.4%) in the MetS-free group, (2) 361 (8.7%) in the MetS-developed group, (3) 499 (12.0%) in the MetS recovery group and (4) 822 (19.8%) in the MetS chronic group. When compared with the MetS chronic group, the multivariable adjusted OR of rapid eGFR decline in the MetS recovery group was 0.64 (OR: 0.64; 95% CI 0.45 to 0.90, p=0.01). In contrast, when compared with the MetS-free group, the multivariable adjusted OR of rapid eGFR decline in the MetS-developed group was 1.00 (OR: 1.00; 95% CI 0.73 to 1.38, p=0.98).ConclusionsOver the 4-year follow-up period, we found that MetS recovery was associated with a reduced risk of rapid eGFR decline in middle-aged and older adults, while MetS occurrence was not related to rapid eGFR decline. Recovery from MetS appeared to protect against a rapid decline in eGFR.

Background The performance of previously published glomerular filtration rate (GFR) estimation equations degrades when directly used in Chinese population. We incorporated more independent variables and using complicated non-linear modeling technology (artificial neural network, ANN) to develop a more accurate GFR estimation model for Chinese population. Methods The enrolled participants came from the Third Affiliated Hospital of Sun Yat-sen University, China from Jan 2012 to Jun 2016. Participants with age Results Compared with the 4-variable equation, the 9-variable equation could not achieve superior performance in the internal validation data (mean of difference: 5.00 [3.82, 6.54] vs 4.67 [3.55, 5.90], P = 0.5; interquartile range (IQR) of difference: 18.91 [17.43, 20.48] vs 20.11 [18.46, 21.80], P = 0.05; P30: 76.6% [73.7%, 79.5%] vs 75.8% [72.9%, 78.6%], P = 0.4), but the 9-variable ANN model significantly improve bias and P30 accuracy (mean of difference: 2.77 [1.82, 4.10], P = 0.007; IQR: 19.33 [17.77, 21.17], P = 0.3; P30: 80.0% [77.4%, 82.7%], P Conclusions It is suggested that using complicated non-linear models like ANN could fully utilize the predictive ability of the independent variables, and then finally achieve a superior GFR estimation model.

Background: Venous thromboembolism (VTE) is an important complication in patients with malignant tumors. Its exact diagnosis and treatment are still lacking. We used a high-sensitive chemiluminescence method to detect thrombin–antithrombin III complex (TAT), plasmin-α2-plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator–inhibitor complex(t-PAIC) in combination with D-dimer and fibrin degradation product (FDP) to analyze their diagnostic and prognostic value in patients with malignant tumors. Methods: In total, 870 patients with confirmed malignant tumors were included, 82 of whom had diagnosed VTE; 200 healthy individuals were classified as the control group. The TAT, PIC, TM, and t-PAIC were detected using Sysmex HISCL5000 automated analyzers, whereas FDP and D-dimer were detected using Sysmex CS5100 coagulation analyzer. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficiency. Survival probabilities were determined using Kaplan–Meier analysis, and multivariate analyses were performed using a Cox regression model. Results: Compared with healthy controls, patients with malignant tumors showed significantly elevated TAT, PIC, TM, t-PAIC, D-dimer, and FDP. Similarly, compared with patients in the non-thrombosis group, those in the thrombosis group showed significantly elevated levels of the above mentioned markers. Logistic regression analysis showed that TAT, PIC, TM, t-PAIC, D-Dimer, and FDP were all associated with VTE. ROC analysis showed that “TAT+PIC+TM+t-PAIC+D-dimer+FDP”showed the highest sensitivity and specificity. Patients with elevated TAT, PIC, TM, and t-PAIC had a significantly shorter survival. Multivariate Cox survival analysis showed that TM and t-PAIC were significantly associated with poor prognosis. In addition, the incidence of VTE was significantly lower in patients with malignant tumors who were treated with low-molecular-weight heparin (LMWH), and their survival period was significantly longer than that of patients with malignant tumors who were not treated with LMWH. Conclusion: TAT, PIC, TM, and t-PAIC combined with D-dimer and FDP were better than the application of a single marker in the diagnosis of VTE in patients with malignant tumors. TAT and PIC can be used as sensitive markers in the diagnosis of VTE but not as prognostic markers. TM and t-PAIC might be independent prognostic indicators in patients with malignant tumors, regardless of the state of thrombus.

Carboxypeptidase E (CPE) is one of the most important carboxypeptidases involved in biosynthesis of numerous peptide hormones and neurotransmitters and has an important role in endocrine regulation. A splice variant of CPE (CPE-ΔN) has been detected and the mechanism of CPE-ΔN action in tumorigenesis has been studied in many different cancers. The aim of this study was to examine CPE-ΔN expression in human colorectal cancer (CRC) and to evaluate its possible use as a potential prognostic marker. Two hundred nineteen primary colorectal tumors and corresponding normal tissues were included in the study. We have analyzed CPE-ΔN isoform expression by qRT-PCR and Western blot in 219 CRC patients. Correlations between CPE-ΔN mRNA expression and clinicopathological variables were determined with chi-square tests. Survival probabilities were determined using Kaplan–Meier analysis, and univariate and multivariate analyses of the prognostic factors were performed with a Cox regression model. Our results show that CPE-ΔN is overexpressed in colorectal tumor tissue and that high CPE-ΔN mRNA expression is closely correlated with tumor differentiation, pT classification, pN classification, tumor recurrence, and lymph node metastasis (P = 0.042, 0.036, 0.031, 0.006, and 0.008, respectively). However, no correlation was observed between CPE-ΔN expression and age, gender, tumor localization, gross features, and the tumor size. In addition, patients with high CPE-ΔN expression had a significantly shorter survival (P

Despite the improved ability to detect mutations in recent years, tissue specimens cannot always be procured in a clinical setting, particularly from patients with recurrence of tumors or metastasis. Therefore, the aim of this study was to investigate whether plasma is able to be used for mutation analysis instead of tissue specimens. We collected plasma from 62 patients with colorectal cancer (CRC) prior to treatment. DNA extracted from plasma and matched tumor tissues were obtained. Mutations in KRAS were amplified from the tissue specimens and sequenced by regular polymerase chain reaction (PCR) and co-amplification at lower denaturation temperature (COLD)-PCR. Plasma KRAS gene mutation on codon 12 (GGT>GAT) was detected using a nested COLD-PCR/TaqMan® -MGB probe. Mutations in plasma and matched tumors were compared. KRAS mutation on codon 12 (GGT>GAT) was found in 13 (21.0%) plasma specimens and 12 (19.4%) matched tumor tissues. The consistency of KRAS mutations between plasma and tumors was 75% (9/12), which indicated a high correlation between the mutations detected in plasma DNA and the mutations detected in the corresponding tumor DNA (P

Introduction: This study examines the effectiveness of double-marker analysis for α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) combined with measurement of nuchal fold thickness (NT) in the detection of Down’s syndrome (DS) in Mainland Chinese subjects during second trimester prenatal screening. Materials and Methods: We examined pregnant women with a singleton pregnancy between 15 and 21 weeks of gestation who underwent second trimester screening for DS using double-marker analysis for AFP and β-hCG combined with ultrasound measurement of NT. The combined risk of DS was calculated. A cut-off of 1/270 was used to defi ne a pregnancy at high-risk of DS. Amniocentesis was offered to all patients with high-risk pregnancies. Results: Using double-marker analysis for AFP and β-hCG in combination with measurement of NT, the detection rate of DS increased from 66.7% to 77.8% when compared with double-marker analysis alone with similar false-positive rates (4.35%, 4.83% respectively). Using receiver operating characteristic curve (ROC) analysis, we determined that the double-marker analysis combined with measurement of NT exhibited an increased area under the curve (AUC) of 0.835 (95% CI: 0.743 to 0.927) when compared to double-marker analysis alone, which had an AUC of 0.748 (95% CI: 0.635 to 0.860). In addition, both methods were more effective than any other single test such as AFP, free β-hCG or NT measurement. Conclusion: Second trimester prenatal screening using double-marker analysis for AFP and β-hCG combined with measurement of NT is effective for the detection of DS in Mainland Chinese pregnancies. Key words: Down’s syndrome, Prenatal screening, Second trimester