OBJECTIVETo investigate the new biomarkers of acute kidney injury, as well as to confirm the values of response gene to complement 32 (RGC-32) for early diagnosis of acute kidney injury by comparing the values of serum creatinine (Scr) and cystatin C (CysC) in children who had undergone cardiopulmonary bypass (CPB).

METHODSixty-seven patients who had accepted CPB were recruited from the cardiac surgery intensive care unit, Children's Hospital Affiliated to Shanghai Jiao Tong University from March to June 2013 and assigned to acute kidney injury group (group AKI) or non-acute kidney injury group (group non-AKI), on the basis of the definition by the pediatric RIFLE (pRIFLE) criteria. Also 30 healthy control children were recruited. Serum samples were taken regularly from each patient after CPB at 30 min, 2 h, 4 h, 24 h, 48 h and 72 h for RGC-32. Serum samples were tested by enzyme linked immunosorbent assay (ELISA) which was employed to determine the levels of serum RGC-32. Scr and CysC were analyzed by HITACHI 7180 automatic biochemical analyzer. All the data were analyzed by receiver operator characteristic curve (ROC) and area under curve (AUC).

RESULTThe incidence of AKI was 34% (23/67), including 15 cases with risk stage AKI, 4 cases with injury stage AKI, 3 cases with failure stage AKI, 1 cases with loss stage AKI. Three out of four subjects with Failure stage AKI and the one case with Loss stage all accepted renal replacement therapy. CPB group had a higher level of serum RGC-32 than that of pre-operation after CPB 30 minute [(2.88 ± 0.68) µg/L vs. (1.39 ± 0.31) µg/L, P < 0.05]. At the same time, comparing with the non-AKI group, the levels of serum RGC-32 were higher than that of controls 30 min, 2 h, 4 h, 24 h and 48 h after CPB (t = 2.560, 2.180, 2.818, 2.226, 3.017; P < 0.05). The values for the AUC were determined for RGC-32 as 0.770, 0.707, 0.768, 0.728,0.723 and 0.770 after CPB 30 min, 2 h, 4 h, 24 h, 48 h and 72 h. The values for sensitivity of serum RGC-32 30 min, 2 h and 4 h after CPB was 0.914, 0.824, 0.824 and the values for specificity of serum RGC-32 was 0.619, 0.667, 0.810, respectively. But the values for sensitivity of CysC was 0.625, 0.813, 0.813, and specificity 0.571, 0.619, 0.571, respectively. The values for sensitivity of Scr was 0.625, 0.625, 0.813 and specificity was 0.571, 0.571, 0.524, respectively.

CONCLUSIONThe sensitivity of serum RGC-32 for detecting AKI was much higher than that of Scr and serum CysC in children who had accepted CPB, and that RGC-32 may be a new biomarker for early detection of AKI. However, the conclusion needs to be further elucidated.

Acute Kidney Injury ; blood ; diagnosis ; etiology ; Area Under Curve ; Biomarkers ; blood ; Cardiopulmonary Bypass ; adverse effects ; Case-Control Studies ; Cell Cycle Proteins ; blood ; Creatinine ; blood ; Cystatin C ; blood ; Female ; Heart Defects, Congenital ; surgery ; Humans ; Infant ; Intensive Care Units, Pediatric ; Male ; Muscle Proteins ; blood ; Nerve Tissue Proteins ; blood ; Postoperative Complications ; Predictive Value of Tests ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity

Background: and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods: We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results: Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Objective: To explore the value of magnetic resonance fat quantification technology (MR mDixon-quant) in evaluating thyroid-associated ophthalmopathy (TAO) activity. Methods: Case control study was performed.Fifty patients (100 eyes) with TAO which met Mourits criterion were enrolled from September 2016 to March 2018 in Ningxia Hui Autonomous Region People's Hospital.The TAO patients were grouped by clinical activity score (CAS). Twenty nine patients (58 eyes) with CAS≥3 served as TAO active group, twenty one patients (42 eyes) with CAS<3 served as TAO non-active group.Twenty three healthy subjects (46 eyes) were collected as normal control group at the same time.All subjects underwent orbital MR mDixon-quant and MR imaging.Orbital fat content (FF values) and exophthalmus was calculated on MR work-station.FF values and degree of exophthalmus were analyzed by analysis of variance.The correlation of FF values and CAS in TAO patients was conducted by Spearman rank correlation analysis.The cut-off values of FF in predicting TAO activity was determined by receiver operating characteristics (ROC) curve.The Kappa consistency test was chosen to assess the consistency of CAS and FF values.Intraclass correlation coefficient (ICC) were used to analyze the intra-observer and inter-observer repeatability of the FF values and the degree of exophthalmus.This study was approved by the Ethics Committee of Ningxia Hui Autonomous Region People's Hospital (No.20160718). All the candidates signed informed consent. Results: The FF values were (85.190±4.346)%, (88.715±5.686)% and (82.345±5.445)% in TAO active group, TAO inactive group and normal control group, respectively, with a significant difference among the 3 groups (F=17.072, P<0.001). The FF values of TAO active group and TAO inactive group were significantly higher than that of control group, and the FF value of TAO active group was significantly lower than that of TAO inactive group (all at P<0.01). The degrees of exophthalmos were (20.221±1.714), (20.855±2.103) and (15.363±1.667)mm in TAO active group, TAO inactive group and normal control group, respectively, with a significant difference among the three groups (F=126.298, P<0.01). The degrees of exophthalmos in TAO active group and TAO inactive group were significantly higher than that in normal control group (both at P<0.01), there was no statistical difference in degrees of exophthalmos between TAO active group and TAO inactive group (P<0.05). Spearman rank correlation revealed that FF value was negative correlated with CAS (r_s=-0.443, P<0.01). The cut-off value of FF value was 87.180%, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 74.14%(43/58), 66.67%(28/42), 75.44%(43/57), 65.12%(28/43) and 71.00%(71/100), respectively.There were consistencies of FF values with the CAS (Kappa=0.431, P<0.001). The intra-observe and inter-observer reproducibility were fairly good for FF value (ICC=0.953, 0.920) and degree of exophthalmus (ICC=0.935, 0.917). Conclusions MR mDixon-quant can quantitative measure orbital fat with good measurement repeatability.Fat quantification technology by MR is valuable in evaluating TAO activity.