Abstract Background Six Sigma methodology with a zero‐defect goal has long been applied in commercial settings and was utilized in this study to assure/improve the quality of various analytes. Methods Daily internal quality control (QC) and external quality assessment data were collected and analyzed by calculating the sigma (σ) values for 19 analytes based on the coefficient of variation, bias, and total error allowable. Standardized QC sigma charts were established with these parameters. Quality goal index (QGI) analysis and root cause analysis (RCA) were used to discover potential problems for the analytes. Results Five analytes with σ ≥ 6 achieved world‐class performance, and only the Westgard rule (1 3s ) with one control measurement at two QC material levels (N2) per QC event and a run size of 1000 patient samples between QC events (R1000) was needed for QC. In contrast, more control rules (2 2s /R 4s /4 1s ) along with high N values and low R values were needed for quality assurance for five analytes with 4 ≤ σ < 6. However, the sigma levels of nine analytes were σ < 4 at one or more QC levels, and a more rigorous QC procedure (1 3s /2 2s /R 4s /4 1s /8 x with N4 and R45) was implemented. The combination of QGI analysis and RCA further revealed inaccuracy or imprecision problems for these analytes with σ < 4 and discovered five aspects of potential causes considered for quality improvement. Conclusions Six Sigma methodology is an effective tool for evaluating the performance of biochemical analytes and is conducive to quality assurance and improvement.
Cytokines activation and low complement levels are common in systemic lupus erythematosus (SLE) patients. This study is aimed to explore the relationship and clinical significance of cytokines and complements with SLE activity. Serum samples of 140 SLE patients and 36 age- and gender-matched healthy controls (HC) were collected. Serum interleukin (IL)-6, IL-17, high-sensitivity C-reactive proteins (hsCRP), and complements (C3, C4) were measured in all samples. These patients were divided into 3 subgroups based on clinical disease activity with SLE Disease Activity Index 2000 (SLEDAI-2K): stationary status subgroup, mild activity subgroup, and moderate/severe activity subgroup. The serum IL-6, IL-17, and hsCRP levels in SLE patients (4.72 ± 0.28 pg/mL, 23.34 ± 1.32 pg/mL, and 4.78 ± 0.34 mg/mL) were significantly higher than those in the HC group (1.51 ± 0.05 pg/mL, 18.28 ± 1.93 pg/mL, and 1.32 ± 0.29 mg/mL), whereas C3 and C4 levels in SLE patients (0.80 ± 0.28 and 0.21 ± 0.08 g/L) were significantly lower than those in the HC group (1.49 ± 0.08 and 0.36 ± 0.02 g/L). A positive correlation was noted between the SLEDAI-2K scores and serum IL-6, IL-17, and hsCRP levels. These results support the proinflammatory cytokines and complements in the pathogenesis of SLE. The serum IL-6, IL-17, and hsCRP levels were correlated with the disease activity.
Objective
This study aimed to assess the diagnostic value of anti-mutated citrullinated vimentin (MCV) antibodies in rheumatoid arthritis (RA) and its correlation with disease progression, extra-articular manifestations and overlap syndrome.
Methods
Retrospective Studies. Clinical data of 837 patients in PekingUnionMedicalCollegeHospitalfrom June to August 2017 were collected, including the result of anti-MCV, anti-cyclic citrullinated peptide (anti-CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and High-sensitivity-C-reactive protein (CRP). According to the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis, there were 323 patients diagnosed with RA, including 59 males and 264 females with the average age of 51 years. According to whether the RA patients have overlap syndrome with other autoimmune disease (AID) or have extra-articular manifestations, 258 cases were categorized into RA group, including 47 males and 211 females with the average age of 50 years; 14 cases were categorized into the group of overlap syndrome, including 1 male and 13 females with the average age of 36 years; 51 cases were categorized into the group of extra-articular manifestations, including 11 males and 40 females with the average age of 59 years.According to 2010 rheumatoid arthritis classification criteria for destruction in joints, the radiographic changes were divided into 4 stages.There were 203 casesenrolled in our study, 88 caseswere fitted into early stage group (stage I)including 21 males and 67 females with the average age of 48 years; 115 caseswere fitted into progressive stage group, which compromisedstageⅡ (interim stage), stage Ⅲ (severe stage) and stage Ⅳ (final stage) cases, including 19 males and 96 females with the average age of 53 years. Mann-Whitney U test, χ2 test,Receiver operating characteristic (ROC) curves and Spearmancorrelation coefficientwere used in Statistical analysis.
Results
Ⅰ Amongdiagnosed RA patients, 199 (61.6%) cases were positive for anti-MCV, anti-CCP and RFsimultaneously, 42 (13%) cases were positive for anti-MCV, which was higher than anti-CCP positive (1 cases, 0.3%) or RF positive (7cases, 2.2%). The difference was statistically significant(P<0.001, P<0.001). Ⅱ ROC was calculated and MCV=35.95 U/ml was used as best-fit cut-off value. The AUC for anti-MCV was 0.867, while the sensitivity was 80.5% and specificity was 80.9%. Ⅲ The detection levels of anti-MCV (682.8 (106.4-1000.0)), anti-CCP (407 (4.0-1536.0)) and RF (82.8 (21.1-244.9)) in the group of progressive stage were higher than those in the group of early stage (114.5 (28.5-1000.0), 62.5 (5.0-1020.7), 50.1 (6.7-127.1)), which showed a significant difference (P<0.05, P<0.05, P<0.05). The anti-MCV, anti-CCP and RF were positively related to the degree of joint destruction (r=0.229, P<0.05; r=0.187, P<0.05; r=0.167, P<0.05); anti-MCV and anti-CCP were positively related to extra-articular manifestation (r=0.152, P<0.05; r=0.136, P<0.05).
Conclusion
Anti-MCV antibodies are more sensitive in patients with RA, and have complementary diagnostic value for anti-CCP and RF-negative patients; high levels of anti-MCV and anti-CCP in RA patients are associated with RA progression and extra-articular involvement.
Key words:
Arthritis, rheumatoid; Autoantibodies; Peptides, cyclic; Vimentin
Background Primary biliary cholangitis (PBC) is a chronic intrahepatic cholestatic autoimmune liver disease characterized by inflammatory injury of small and medium-sized bile ducts in the liver. The pathogenesis of PBC has yet to be entirely understood. CD47/signal-regulatory protein alpha (SIRPα) is closely related to developing autoimmune diseases by promoting inflammatory response. However, the effect of CD47/SIRPα on inflammatory response in PBC patients is still unclear. Objective We investigated the expression of CD47/SIRPα and the effect of inflammatory cytokines on the CD47 expression, analyzed potential autoantibodies against CD47 and the effect of anti-CD47 antibody on the inflammatory response in PBC, provided laboratory basis for the study of the pathogenesis and targets for non-invasive diagnosis and treatment on PBC. Methods The expression levels of CD47 and SIRPα on peripheral blood mononuclear cells (PBMC) were measured in 14 patients with PBC (the PBC group) and 13 healthy subjects (the Control group) by flow cytometry (FCM). The PBMC derived from healthy subjects were stimulated with healthy subjects’ serum, PBC patients’ serum, IFN-α or TNF-α, and the CD47 expression level on CD14 + monocytes was detected by FCM. The level of serum anti-CD47 antibody or IFN-α in PBC patients and healthy subjects was analyzed by ELISA. FCM was used to examine the TNF-α expression level in CD14 + monocytes of healthy subjects stimulated with isotype control antibody, anti-CD47 antibody, LPS or LPS combined with CD47 antibody. Results The CD47 expression level on the CD14 + monocytes in PBC patients was statistically higher than that in the Control group ( P <0.01). Compared with the Control group (PBMC+healthy serum), the CD47 expression on CD14 + monocyte stimulated with the PBC patients’ serum (PBMC+PBC patients’ serum) was increased ( P <0.001); the CD47 expression on CD14 + monocyte stimulated with IFN-α (PBMC + IFN-α) increased gradually with the increased concentration of IFN-α ( P <0.05). However, there was no similar trend on CD14 + monocyte stimulated with the TNF-α (PBMC+TNF-α) ( P >0.05). The levels of serum anti-CD47 antibody and IFN-α in the PBC patients were higher than those in healthy subjects ( P <0.05). The TNF-α expression level in CD14 + monocyte stimulated with the LPS (PBMC+LPS) or anti-CD47 antibody+LPS group (PBMC+LPS+anti-CD47 antibody) was significantly increased than that in the Control group (PBMC+isotype control antibody) ( P <0.01 and P <0.001, respectively). The TNF-α expression level in CD14 + monocyte stimulated with the anti-CD47 antibody + LPS was higher than that with the LPS ( P < 0.05). Conclusion The CD47 may be related to the pathogenesis of PBC by inflammatory response. The CD47/SIRPα signal were imbalanced in PBC patients. The presence of serum anti-CD47 antibodies in PBC patients provides a laboratory basis for clinical diagnosis and treatment.
Schizophrenia (SZ) is a devastating psychiatric disorder. Validation of potential serum biomarkers during first-episode psychosis (FEP) is especially helpful to understand the onset and prognosis of this disorder. To address this question, we examined multiple blood biomarkers and assessed the efficacy to diagnose SZ. The expression levels of Neuregulin1 (NRG1), ErbB4, brain-derived neurotrophic factor (BDNF), DNA methyltransferases 1 (DNMT1) and ten-eleven translocation 1 (TET1) proteins in peripheral blood of 53 FEP patients and 57 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression including biomarker concentration as covariates was used to predict SZ. Differentiating performance of these five serum protein levels was analyzed by Receiver Operating Characteristic (ROC) curve analysis. We found that patients with SZ present a higher concentration of DNMT1, and TET1 in peripheral blood, but a lower concentration of NRG1, ErbB4 and BDNF than controls. Multivariable logistic regression showed that ErbB4, BDNF and TET1 were independent predictors of SZ, and when combined, provided high diagnostic accuracy for SZ. Together, our findings highlight that altered expression of NRG1, ErbB4, BDNF, DNMT1 and TET1 are involved in schizophrenia development and they may serve as potential biomarkers for the diagnosis of the schizophrenia. Therefore, our study provides evidence that combination of ErbB4, BDNF and TET1 biomarkers could greatly improve the diagnostic performance.
Aldo‐keto reductase family 1 member B10 (AKR1B10) is a secretory protein overexpressed in hepatocellular carcinoma (HCC). We aimed to evaluate AKR1B10 as a serum marker for detection of HCC. Herein, we conducted a cohort study that consecutively enrolled 1,244 participants from three independent hospitals, including HCC, healthy controls (HCs), benign liver tumors (BLTs), chronic hepatitis B (CHB), and liver cirrhosis (LC). Serum AKR1B10 was tested by time‐resolved fluorescent assays. Data were plotted for receiver operating characteristic (ROC) curve analyses. Alpha‐fetoprotein (AFP) was analyzed for comparison. An exploratory discovery cohort demonstrated that serum AKR1B10 increased in patients with HCC (1,567.3 ± 292.6 pg/mL; n = 69) compared with HCs (85.7 ± 10.9 pg/mL; n = 66; P < 0.0001). A training cohort of 519 participants yielded an optimal diagnostic cutoff of serum AKR1B10 at 267.9 pg/mL. When ROC curve was plotted for HCC versus all controls (HC + BLT + CHB + LC), serum AKR1B10 had diagnostic parameters of the area under the curve (AUC) 0.896, sensitivity 72.7%, and specificity 95.7%, which were better than AFP with AUC 0.816, sensitivity 65.1%, and specificity 88.9%. Impressively, AKR1B10 showed promising diagnostic potential in early‐stage HCC and AFP‐negative HCC. Combination of AKR1B10 with AFP increased diagnostic accuracy for HCC compared with AKR1B10 or AFP alone. A validation cohort of 522 participants confirmed these findings. An independent cohort of 68 patients with HCC who were followed up showed that serum AKR1B10 dramatically decreased 1 day after operation and was nearly back to normal 3 days after operation. Conclusion : AKR1B10 is a potent serum marker for detection of HCC and early‐stage HCC, with better diagnostic performance than AFP.
Schizophrenia (SZ) is a debilitating and heterogeneous disease. We hypothesized that oxytocin (OXT) system, inflammation and one-carbon metabolism would have a link with SZ. In this study, serum OXT, OXT receptor (OXTR), interleukin-6 (IL-6), high sensitivity CRP (hsCRP) and homocysteine (Hcy) levels were measured in fifty-two first-episode schizophrenia (FES) patients and forty-one healthy controls (HC) from the Second Xiangya Hospital of Central South University. Meanwhile, the mRNA expressions of OXT and OXTR genes were determined by real-time quantitative PCR. Serum OXT and OXTR levels were significantly lower in FES patients (518.96 ± 22.22 and 174.60±17.11 pg/ml) than HC group (711.58 ± 40.57 and 252.15 ± 20.62 pg/ml). Serum IL-6 and hsCRP levels showed no difference between two groups (1.82 ± 0.30 vs 1.69 ± 0.36 pg/ml, 0.66 (0.22, 1.07) vs 0.31 (0.13, 0.91) mg/L), but serum Hcy levels were significantly higher in FES patients (20.18 ± 1.83 vs 15.24 ± 0.82 μmol/ml). The FES patients (0.27 ± 0.02 and 0.20 ± 0.02) have relatively higher mRNA expressions of OXT and OXTR genes than HC group (0.16 ± 0.01 and 0.14 ± 0.01). In summary, our results suggested the possible function of OXT system and Hcy in the pathogenesis of SZ.
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