Soluble CXCL16 is a prognostic biomarker associated with rapidly progressive interstitial lung disease complicated with dermatomyositis.

OBJECTIVES: Rapidly progressive interstitial lung disease (RPILD) in patients with dermatomyositis (DM) significantly impacts prognosis, leading to high mortality rates. Although several indicators have been demonstrated to strongly correlate with the risk of developing RPILD, their clinical utility still needs to be investigated. The objective of this study was to investigate the clinical significance of soluble CXCL16 (sCXCL16) in DM patients complicated with RPILD. METHODS: Serum sCXCL16 was measured by enzyme-linked immunosorbent assay in 96 patients with DM and 55 matching healthy donors. Correlations between sCXCL16 levels and clinical features, laboratory examinations and the predictive value of baseline sCXCL16 level for RPILD were analysed. RESULTS: The serum sCXCL16 levels were significantly higher in patients with DM (n = 96, 3.264 ± 1.516 ng/mL) compared with healthy donors (n = 55, 1.781 ± 0.318 ng/mL), especially in DM complicated with RPILD (n = 31, 4.441 ± 1.706 ng/mL). The sCXCL16 levels were positively correlated with levels of serum ferritin, C reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, hydroxybutyrate dehydrogenase, and negatively correlated with peripheral lymphocytes percentage, but showed no correlation with levels of anti-melanoma differentiation-associated gene 5 antibody, Krebs von den Lungen-6 or creatine kinase. Multivariable analysis showed that elevated sCXCL16 was an independent prognostic factor for poor prognosis of RPILD in patients with DM. The 2-year survival rate was significantly lower in patients with high sCXCL16 level than in those with low sCXCL16 level. CONCLUSION: A higher serum sCXCL16 level was identified as a predictive biomarker of RPILD in patients with DM, and closely associated with poor prognosis.

Lower serum AMH concentration is correlated with serum IgG1 decreased in the infertile woman: A real-world retrospective study.

OBJECTIVES: In this real-world approach, we examined the serum Anti-Mullerian Hormone (AMH) level and the relationship with serum IgG subclass in the infertile women. METHODS: A total of 574 female participants were recruited for this study. The serum AMH, IgG subclass(IgG1, IgG2, IgG3, IgG4) and immunoglobulin (Ig) G、IgM、IgA、IgE as well as complement C3, C4 were analyzed. The difference in serum AMH level was assessed according categorized as above or below the median of the ratio of serum IgG subclass(IgG1, IgG2, IgG3, IgG4) to total IgG (RIgG subclass/IgG). RESULTS: The serum AMH level of the low RIgG1/IgG group is significantly decreased than that high RIgG1/IgG group (p < 0.05). The Spearman correlation analysis showed that the serum AMH level was significantly negatively correlated with age and significantly positively correlated with serum IgG1 levels respectively (p < 0.05). GLMMs multivariate model showed that after adjusting the covariate and possible mixed factors including age, serum immunoglobulin, complement C3 and C4, the serum AMH level was significantly positively correlated with IgG1 level (p < 0.01). CONCLUSIONS: Decreased serum IgG1 may significantly affect the ovarian reserve function of women. Confirmation of this association and elucidation of its underlying mechanisms are needed to place these results in a clinical perspective.

The cutoff value and prognosis of anti-PLA2R antibody for idiopathic membranous nephropathy: a single-center retrospective study in China.

Serum anti-phospholipase A2 receptor (anti-PLA2R) antibody is used for the noninvasive diagnosis of idiopathic membranous nephropathy (IMN). However, the cutoff value of anti-PLA2R antibodies in IMN patients is debatable. This study aimed to investigate the cutoff value of anti-PLA2R antibodies for diagnosing IMN and the correlation of anti-PLA2R antibodies with clinical parameters and prognosis. A total of 252 IMN patients and 521 non-IMN patients with both renal biopsy and serum anti-PLA2R antibody data from April 2017 to November 2019 were enrolled. Anti-PLA2R antibody was detected by an enzyme-linked immunosorbent assay. The anti-PLA2R antibody titer was higher in the IMN group than in the non-IMN group (153.1 ± 22.4 vs. 2.0 ± 0.2 RU/mL, p < 0.001). The optimal anti-PLA2R antibody cutoff value for diagnosing IMN was 2.5 RU/mL, with a sensitivity, specificity, and Youden index of 85.7%, 88.3%, and 0.740, respectively. There was a significant positive correlation between anti-PLA2R antibody and 24-h urinary protein levels (r = 0.341, p < 0.001), and a significant negative correlation between anti-PLA2R antibody and serum albumin levels (r=-0.274, p < 0.001) in patients with IMN. The remission rates positively correlated with the immunosuppressive usage rates and increased from the low- to the high-titer subgroup. Multivariable Cox regression analysis showed that immunosuppressive therapy (adjusted HR = 4.656; 95% confidence interval [CI], 1.461-14.839; p = 0.009) was associated with a higher remission rate in patients with IMN. The optimal Anti-PLA2R antibody cutoff value for diagnosing IMN was 2.5 RU/mL, which was much lower than that indicated by the manufacturer. If IMN is actively treated, patients can have much better prognoses.Trial registration: retrospectively registered.

The performance of Carbohydrate Antigen 125-Thomsen-nouveau and anti-Müllerian hormone combined with CA125, Human epididymis protein 4 and Risk of Malignancy Algorithm in diagnosis for patients with Epithelial ovarian cancer.

OBJECTIVES: We examined the blood concentrations of Carbohydrate Antigen 125-Thomsen-nouveau (CA125-Tn) and anti-Müllerian hormone (AMH) in epithelial ovarian cancer (EOC) patients to evaluate their potential diagnostic utility together with CA125, human epididymis protein 4 (HE4) and Risk of Malignancy Algorithm (ROMA). DESIGN & METHODS: 50 healthy subjects, 45 EOC patients, 22 patients with borderline ovarian tumors (BOT), 21 patients with benign ovarian tumor (BET) and 45 patients with chocolate cyst of ovary (CCO) were studied. Blood levels of CA125, HE4, CA125-Tn and AMH were measured, and the ROMA value was calculated. We compared the differences in the levels of these biomarkers among groups. Additionally, a total of 10 testing strategies were established for comparison to maximize the diagnostic value. RESULTS: The levels of CA125, HE4, CA125-Tn and ROMA value were significantly higher in EOC group compared with either the disease control (DC) group (BOT group, BET group and CCO group) or healthy control (HC) group (p < 0.001). In addition, they had better discriminatory performance with an area under the receiver operator characteristic curve (AUC) 0.93; 0.93; 0.93; 0.85, respectively (p < 0.001) compared with the AUC value of AMH 0.67 (p < 0.001). Among all 10 testing strategies, both single-positive of ROMA and double-positive of any 2 markers showed better Youden index (0.82, 0.79, respectively) and kappa value (κ) (0.82, 0.81, respectively). CONCLUSIONS: CA125-Tn and AMH can be treated as useful biomarkers of EOC when combined with CA125, HE4 and ROMA, because when any two biomarkers of them are positive, the value of EOC diagnosis is maximized.

AMHconverter: an online tool for converting results between the different anti-Müllerian hormone assays of Roche Elecsys®, Beckman Access, and Kangrun.

Background: The anti-Müllerian hormone (AMH) is gaining attention as a key factor in determining ovarian reserve and polycystic ovarian syndrome, and its clinical applications are becoming more widespread worldwide. Objective: To identify the most accurate formula for converting AMH assay results between different platforms, so that the developed AMH converter can be used to reduce the need for multiple AMH tests at different hospitals. Methods: Assuming that the Beckman Access, Kangrun, and Roche Elecsys® AMH assays fit a linear relationship from the lowest to the highest concentration (a global relationship), we used Passing-Bablok regression to determine the conversion equation between each two assays. When the relationship between two AMH assays was a local one, spline regression was used. Bland-Altman plots were drawn to check systemic bias and heterogeneity of variance across different ranges of values. The fitting effects of the models were evaluated using the squared coefficient of determination (r2), adjusted r2, root mean square error (RMSE), Akaike information criterion (AIC), and corrected AIC. Results: The coefficient of variance for multiple controls in the Kangrun, Roche, and Beckman assays was lower than 5%, and the bias of multiple controls was lower than 7%. A global linear relationship was observed between the Kangrun and Roche assays, with the intercept being zero, for which Passing-Bablok regression was employed for data conversion between the two platforms. For the other two pairs of platforms, i.e., Roche and Kangrun or Beckman and Kangrun, spline regression was applied, with the intercepts not including zero. The six corresponding formulas were developed into an online AMH converter (http://121.43.113.123:8006/). Conclusion: This is the first time Passing-Bablok plus spline regression has been used to convert AMH concentrations from one assay to another. The formulas have been developed into an online tool, which makes them convenient to use in practical applications.

Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study.

STUDY QUESTION: What are the roles of maternal 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C combination polymorphisms on the embryological and clinical outcomes of IVF/ICSI? SUMMARY ANSWER: Our study reveals for the first time that the oocyte maturation potential gradually decreases with a reduction of maternal MTHFR activity determined by combined C677T/A1298C polymorphisms, while embryo quality was worse in women with intermediate MTHFR activity. WHAT IS KNOWN ALREADY: Although many previous studies have explored the association between MTHFR polymorphisms and IVF/ICSI outcomes, the results remain contradictory due to inadequate samples, no adjustment for potential confounders and/or the study of C677T and A1298C separately. Few studies have systematically investigated the exact role of MTHFR activity determined by combined C677T/A1298C polymorphisms on the embryological and clinical outcomes of IVF/ICSI. STUDY DESIGN SIZE DURATION: This is a retrospective cohort study investigating 1160 women who were referred for MTHFR genotyping and IVF/ICSI treatment at Peking University Third Hospital from May 2017 to May 2020. PARTICIPANTS/MATERIALS SETTING METHODS: Women who were referred for MTHFR genotyping and their first IVF/ICSI treatment at our hospital were included and those undergoing preimplantation genetic testing cycles were excluded. The included women were divided into different cohorts according to their C677T, A1298C and combined C677T/A1298C genotypes. The embryological outcomes, including oocytes retrieved, metaphase II oocytes, oocyte maturation rate, normal fertilization rate and transplantable embryo rate, were evaluated by generalized linear regression models. The clinical outcomes, including biochemical pregnancy rate, clinical pregnancy rate and live birth rate, were evaluated by log-binomial regression models. All outcomes were adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Women with the combined 677TT/1298AA genotype (hereafter abbreviated as TT/AA, as with other combined genotypes), whose enzyme activity was the lowest, had a lower oocyte maturation rate compared with those with the wild-type genotype (P = 0.007). Moreover, the oocyte maturation rate decreased linearly with the decline in MTHFR enzyme activity determined by combined C677T/A1298C genotypes (P-trend = 0.001). The combined CC/AC, CC/CC&CT/AA and CT/AC genotypes with intermediate enzyme activity were associated with a lower transplantable embryo rate (P = 0.013, 0.030 and 0.039, respectively). The differences in clinical outcomes between women with wild-type genotype and combined C677T/A1298C variant genotypes were not significant. LIMITATIONS REASONS FOR CAUTION: Our study population had comparable embryological outcomes but worse clinical outcomes than other women undergoing IVF/ICSI treatment at our hospital. Therefore, the results related to the clinical outcomes should be generalized with caution. In addition, we did not detect the folate concentration of each patient during pregnancy. However, this might not have much influence on our results because almost all of our study participants took sufficient folic acid around pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: We provide a holistic view of the effect of MTHFR C677T and A1298C polymorphisms on the IVF/ICSI outcomes, which can contribute to providing reasonable folic acid supplementation suggestions for women with different MTHFR genotypes, especially for those with a low oocyte maturation rate and/or low embryo quality. STUDY FUNDING/COMPETING INTERESTS: This work was funded by the National Natural Science Foundation of China (31871447, and 82101677), the National Key Research and Development Program (2019YFA0801400) and the Natural Science Foundation of Beijing Municipality (7202226). The authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER: N/A.

The Fluctuation Trend of Serum Anti-SARS-CoV-2 IgM/IgG Antibodies Seroprevalence in the Non-COVID-19 Infected Population and Correlation with Peripheral Blood Leukocyte Parameters in Beijing, China, 2021: A Real-World Study.

Since 2019, the coronavirus disease 2019 (COVID-19) global pandemic has caused more than 300 million cases of disease and 5 million deaths. Vaccination has been widely accepted as the most effective measure for the prevention and control of this disease. However, there is little understanding about serum anti-SARS-CoV-2 IgM/IgG levels after inactivated vaccination as well as the relationship with peripheral blood leukocytes in the non-COVID-19 infected population. A total of 16,335 male and 22,302 female participants were recruited in this study, which was conducted in the Peking University Third Hospital located in Beijing (China). The level and seroprevalence of serum anti-SARS-CoV-2 receptor-binding domain (RBD) IgM/IgG and the association with peripheral blood leukocytes classification were investigated. With an increase in the number and percentage of full immunization of COVID-19 vaccinations in Beijing, serum anti-SARS-CoV-2 IgG antibodies levels and seroprevalence were significantly elevated (p < 0.01). The serum anti-SARS-CoV-2 IgG antibodies of 60 years and older persons were significantly lower than that of individuals that are 18~60 years old (p < 0.01), and there was a positive relationship between serum anti-SARS-CoV-2 IgG antibodies levels and peripheral blood lymphocyte count. The investigation of serum anti-SARS-CoV-2 IgM/IgG antibodies and the peripheral hematological index may prompt and help understand the adaptive immune response of vaccination.

Identification of Serum Biomarkers Associated With Emergence Agitation After General Anesthesia in Adult Patients: A Metabolomics Analysis.

Background: Emergence agitation (EA) is a conscious disturbance after general anesthesia in adult patients that can lead to severe respiratory or circulatory complications and serious physical injury to patients and caregivers. However, the pathophysiological mechanisms underlying EA remain unclear. The present study aimed to identify serum metabolites with significant alterations in EA patients after general anesthesia and enable inferences on their associations with EA. Methods: EA patients were identified by Richmond Agitation-Sedation Scale (RASS) ≥ + 2 among a cohort of adult patients who received elective surgery under general anesthesia in Peking University Third Hospital between 01 June 2020 and 30 December 2020. We further selected sex-, age-, and surgery type-matched non-EA control patients at a 1:1.5 ratio. Postoperative serum samples were collected from both groups of patients. An untargeted metabolic method was used to identify differences in serum metabolomic profiles between the EA patients and the non-EA patients. Results: A total of 19 EA patients and 32 matched non-EA patients were included in the study. After screening and mapping with a database, 12 metabolites showed significant postoperative alterations in EA patients compared with non-EA patients, and were mainly involved in lipid, fatty acid and amino acid metabolism pathways. Receiver operating characteristic curve analyses indicated that vanillic acid, candoxatril, tiglylglycine, 5-methoxysalicylic acid, decanoylcarnitine, and 24-epibrassinolide may be involved in EA pathogenesis after general anesthesia. Conclusion: In this study, we found differences in the serum levels of vanillic acid, candoxatril, tiglylglycine, 5-methoxysalicylic acid, decanoylcarnitine, and 24-epibrassinolide involved in fatty acid metabolism, lipid metabolism, and amino acid metabolism pathways in EA patients compared with non-EA patients, which may demonstrate an EA pathogenesis-associated molecular pattern and contribute toward better understanding of EA occurrence.

Matrix Metalloproteinase 3: a Novel Effective Biomarker for Predicting the Mortality and the Severity of Pneumonia.

BACKGROUND: Matrix metalloproteinase 3 (MMP3) is known as an inflammatory factor; however, the effectiveness of MMP3 for diagnosis of pneumonia and predicting outcomes is unclear. We evaluated the diagnostic and prognostic value of serum MMP3 in patients with pneumonia. METHODS: One hundred and eighty-five patients with pneumonia and 52 healthy controls were enrolled. Serum MMP3, neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) concentrations were measured at admission. The patients were followed up for 90 days. RESULTS: Compared with healthy controls, the concentrations of MMP3, NGAL, and IL-6 at admission were significantly higher in patients with pneumonia (p < 0.05). The median concentrations of MMP3, NGAL, and IL-6 were significantly higher in the patients with severe pneumonia than the group of non-severe pneumonia (p < 0.05). Compared with PCT (AUC = 0.778), CRP (AUC = 0.719), and IL-6 (AUC = 0.726), MMP3 (AUC = 0.846) and NGAL (AUC = 0.826) had significantly higher AUC values for distinguishing the severity of pneumonia. The ROC of the combination of MMP3, neutrophil to lymphocyte ratio (NLR), and D-dimer showed the best performance of predicting pneumonia severity, which gave an AUC of 0.956. The AUC of MMP3 (0.950) for predicting mortality was highest, followed by NLR (AUC = 0.945), D-dimer (AUC = 0.938), and NGAL (AUC = 0.913). Multivariable logistic regression analysis showed MMP3, D-dimer, and NLR were the independent predictors of hospital mortality in patients with pneumonia. Patients with MMP3 concentration > 124.3 ng/mL had a significantly higher risk of mortality (p < 0.05). CONCLUSIONS: MMP3 is a valuable biomarker in assessment of the severity and prediction of mortality in patients with pneumonia.

[Sensitization Spectrum of 16 362 Patients with Allergic Diseases in Peking University Third Hospital].

Objective To retrospectively analyze the sensitization spectrum of 16 362 patients with allergic diseases treated in the Peking University Third Hospital and provide reference for the prevention and treatment of allergic diseases.Methods A total of 16 362 patients with allergic diseases treated in the Peking University Third Hospital from January 2009 to September 2021 were selected.The serum levels of total IgE and antigen-specific IgE(sIgE)were determined.Furthermore,the selected patients were classified into different groups according to gender,age,and disease occurrence month.Results The mean level of total IgE in 7919 patients was 92.4(34.8, 241.0)kU/L.The sIgE levels of 34 allergens in 5495 patients were determined via the ImmunoCAP system,with a positive sIgE rate of 54.23%.The top 5 allergens with high positive rates were mountain juniper pollen(43.78%),cat dander(38.76%),egg white(33.38%),Japanese hop(32.03%),and mugwort(31.82%).The sIgE levels of 20 allergens in 10 867 patients were determined via the EURO system,with a positive sIgE rate of 35.79%.The top 5 allergens with high positive rates were mugwort(15.86%),house dust mite mix(10.17%),cat dander(8.32%),house dust(4.71%),and tree pollen mix(4.04%).The analysis based on gender showed that the allergen positive rates in males were higher than those in females.The positive rates of egg white and cow's milk gradually decreased with the increase in age,while those of the inhaled allergens gradually increased during 10-19 years and then gradually decreased.The analysis based on disease occurrence month showed that the population with allergic diseases in Beijing surged in summer and autumn due to the inhaled allergens including mugwort,tree pollen mix,common ragweed,cocklebur,goosefoots,Japanese hop,timothy grass,and weed mix.Conclusions Among the 16 362 patients with allergic diseases treated in the Peking University Third Hospital,male patients showed higher sensitivity to allergens.The positive rates of egg white and cow's milk gradually decreased with the increase in age,while those of inhaled allergens were highest in patients of 10-19 years.The population of allergic diseases in Beijing surged in summer and autumn due to the inhaled allergens.

Predictive Value of Preoperative Profiling of Serum Metabolites for Emergence Agitation After General Anesthesia in Adult Patients.

Background: Emergence agitation (EA) in adult patients under general anesthesia leads to increased postoperative complications and heavy medical burden. Unfortunately, its pathogenesis has not been clarified until now. The purpose of the present study was to explore the relationship between preoperative serum metabolites and EA. Methods: We used an untargeted metabolic analysis method to investigate the different metabolomes in the serum of EA patients and non-EA patients undergoing elective surgical procedures after the induction of general anesthesia. A Richmond Agitation-Sedation Scale score ≥ +2 was diagnosed as EA during postoperative emergence. Non-EA patients were matched with EA patients according to general characteristics. Preoperative serum samples of the two groups were collected to investigate the association between serum metabolites and EA development. Results: The serum samples of 16 EA patients with 34 matched non-EA patients were obtained for metabolic analysis. After screening and alignment with databases, 31 altered metabolites were detected between the two groups. These metabolites were mainly involved in the metabolism of lipids, purines, and amino acids. Analyses of receiver-operating characteristic curves showed that the preoperative alterations of choline, cytidine, glycerophosphocholine, L-phenylalanine, oleamide, and inosine may be associated with adult EA. Conclusion: Multiple metabolic abnormalities (including those for lipids, purines, and amino acids) and other pathological processes (e.g., neurotransmitter imbalance and oxidative stress) may contribute to EA. Several altered metabolites in serum before surgery may have predictive value for EA diagnosis. This study might afford new metabolic clues for the understanding of EA pathogenesis.

Study of risk factor of urinary calculi according to the association between stone composition with urine component.

Urolithiasis is a common urinary disease with high recurrence. The risk factor for the recurrence of calculi is not very clear. The object of the present study was to evaluate the association between calculi composition and urine component and analyse the risk factor for the recurrence of urolithiasis. In this study, a total of 223 patients with calculi and healthy control were enrolled, and the components of the calculi and urina sanguinis collected before surgery were analysed. Of the 223 patients, 157 were males and 66 were females. According to the stone composition, the case group was subdivided into three groups. 129 patients had single calcium oxalate stones, 72 had calcium oxalate stones mixed with other stones and 22 had other type of stones excluding calcium oxalate stones. Urine biochemicals were analysed and the associations were found between the chemicals in each group. Multivariate logistic analysis demonstrated that reduced urinary magnesium and uric oxalic acid were independent risk factors when comparing all cases with normal controls. Only decreased urinary magnesium was found to be a risk factor comparing the single calcium oxalate group with normal control group. Low level of urinary magnesium and uric oxalic acid were found to be risk factors comparing the mixed calcium oxalate group with normal control group. No risk factor was found comparing the other stone group with normal control group. In conclusion, there were clear relationships between stone components and urine chemicals. Urine chemicals might be risk factors to predicate the occurrence of urolithiasis.

Clinical features associated with pregnancy outcomes in women with positive antiphospholipid antibodies and previous adverse pregnancy outcomes: a real-world prospective study.

OBJECTIVE: This study aims to analyze factors related to pregnancy outcomes in women with positive antiphospholipid antibodies and previous adverse pregnancy outcomes (APOs) prospectively. METHODS: Patients' characteristics were described. Factors associated with obstetric complications were analyzed using logistic regression analysis. RESULTS: A total of 128 females with 73.4% non-criteria obstetric antiphospholipid syndrome (NC-OAPS) were included. APOs accounted for 38.3%, of which 65.3% were fetal losses. Live birth rates in criteria OAPS and NC-OAPS were similar (76.5% and 74.5%). For the whole patients, antinuclear antibody (ANA) titer ≥ 1:160 (OR 5.064, 95% CI (1.509, 16.995), P = 0.009) was a risk factor for APOs and low molecular weight heparin (LMWH) use (OR 0.149, 95% CI (0.029, 0.775), P = 0.024)) was a protective factor. Age (OR 1.159, 95% CI (1.011, 1.329), P = 0.034) and previous APOs ≥ 3 times (OR 3.772, 95% CI (1.14, 12.435), P = 0.029) were risk factors for fetal loss, and LMWH use (OR 0.068, 95% CI (0.009, 0.486), P = 0.007) was a protective factor. Regular rheumatology visits was a protective factor for APOs and fetal loss (OR 0.085, 95% CI (0.024, 0.306), P < 0.001; OR 0.019, 95% CI (0.004, 0.104), P < 0.001). The proportion of it decreased in APOs and fetal loss groups (53.1% and 28.1%). Glucocorticoid use was a risk factor for APOs in NC-OAPS and higher serum C3 levels in the first gestational trimester was a protective factor for fetal loss (OR 3.703, 95% CI (1.402, 9.777), P = 0.008; OR 0.041, 95% CI (0.002, 0.947), P = 0.046). CONCLUSION: Age, APO history, ANA titer, LWMH and glucocorticoid use, serum C3 levels, and regular rheumatology visits were related to obstetric complications. Key Points • This was one of the few prospective studies focused on patients with positive antiphospholipid antibodies and previous adverse pregnancy outcomes. The majority were NC-OAPS patients. • The study first evaluated the impact of rheumatologists' monitoring based on individual disease assessments on pregnancy outcomes. The live birth proportion was similar in patients with criteria OAPS and NC-OAPS when treated. • Age, APO history (≥ 3 times), ANA titer (≥ 1:160), LMWH use, glucocorticoid use, and serum C3 were factors related to obstetric complications.

The performance of the chemiluminescent immunoassay for measuring serum myeloperoxidase and proteinase 3 antibodies.

BACKGROUND: Enzyme-linked immunosorbent assay (ELISA) has traditionally been used to detect myeloperoxidase (MPO) and proteinase 3 (PR3) antibodies, although it is time-consuming and physically demanding. As a novel and highly effective immunoassay, we compared chemiluminescent immunoassay (CIA) with ELISA to verify the application value of CIA in MPO and PR3 antibodies detection. METHODS: By ELISA and CIA, serum levels of anti-MPO and anti-PR3 antibodies were measured in 63 anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients (AAV group), including 47 microscopic polyangiitis (MPA) patients and 16 granulomatosis with polyangiitis (GPA) patients, in addition, 68 patients in interference control group (IC group), 19 healthy subjects in healthy control group (HC group). We compared MPO and PR3 antibodies levels and positive rates measured by these two methods among groups. Relationship and coincidence rate between ELISA and CIA were investigated. Diagnostic values for clinical outcomes for MPO and PR3 antibodies were assessed by receiver operator characteristic (ROC) curve. RESULTS: In AAV patients, when detecting anti-MPO (r = .90) and anti-PR3 (r = .81), CIA was highly correlated with ELISA, companying with highly total (88.89%, 92.06%, respectively) and positive coincidence rates (84.78%, 77.27%, respectively). In HC group, anti-PR3 positive rate detected by both immunoassay were 0, anti-MPO almost were 0, which without statistically significant difference (P = .32). In IC group, the total (76.47%, 58.82, respectively) and positive coincidence rates (48.38%, 30.00%, respectively) of anti-MPO and anti-PR3 were the lowest, but the negative coincidence rates reached 100%. By CIA, similar to ELISA, the levels of anti-MPO were significantly higher both in AAV patients (56.00; [4.40-235.30]) and MPA patients (98.00; [27.90-324.70]) compared with either IC group (3.20; [3.20-18.55) (P < .0001) or HC group (3.20; [3.20-3.20]) (P < .0001), yielded an area under curve (AUC) of 0.76 for AAV and 0.89 for MPA, the concentration of anti-PR3 in GPA group (66.65; [24.43-150.00]) was significantly higher than that in IC group (2.3; [2.3-10.95]) (P < .0001) and HC group (2.3; [2.3-2.3]) (P < .0001), with an AUC of 0.92. CONCLUSION: Similar to ELISA, CIA was competent to detect MPO and PR3 antibodies in AAV patients and healthy population, thus distinguish AAV patients from IC group and HC group and effectively diagnose MPA and GPA.

Comparison and evaluation of Abbott chemiluminescent microparticle immunoassay and ChIVD light-initiated chemiluminescent assay in the detection of Treponema pallidum antibody.

BACKGROUND: Laboratory tests play an important role in the diagnosis of syphilis. This study aimed to compare and assess the performance of the Abbott chemiluminescent microparticle immunoassay (CMIA) and the ChIVD light-initiated chemiluminescent assay (LICA) in the detection of Treponema pallidum (TP) antibody. METHODS: A total of 10 498 serum samples were detected with two assays, and the Treponema pallidum particle agglutination assay (TPPA) and recombinant immunoblot assay (RIBA) methods were used for confirmation. The sensitivity, specificity, positive predictive value, and negative predictive value of the Abbott CMIA and ChIVD LICA were calculated. The coincidence rate between two assays was also evaluated. The causes of false positive and false negative of two assays were studied. RESULTS: For the Abbott CMIA and ChIVD LICA, the sensitivity was 94.44% and 98.15%, the specificity was 99.89% and 99.81%, the positive predictive value was 93.29% and 88.83%, and the negative predictive value was 99.91% and 99.97%, respectively. The coincidence rate between Abbott CMIA and ChIVD LICA was 99.26%, and κ value was .790. The disease of infertility, hypertensive disease, liver disease, and cancer were the common causes of false positive in both assays, while infertility was also the main reason lead to false negative. CONCLUSION: Our results demonstrated that the Abbott CMIA and ChIVD LICA generally had high sensitivity and specificity and therefore may be suitable for the detection of TP antibody and screening for syphilis.

SET7/9 promotes multiple malignant processes in breast cancer development via RUNX2 activation and is negatively regulated by TRIM21.

Although the deregulation of lysine methyltransferase (su(var)-3-9, enhancer-of-zeste, trithorax) domain-containing protein 7/9 (SET7/9) has been identified in a variety of cancers, the potential role of SET7/9 and the molecular events in which it is involved in breast cancer remain obscure. Using the online Human Protein Atlas and GEO databases, the expression of SET7/9 was analyzed. Furthermore, we investigated the underlying mechanisms using chromatin immunoprecipitation-based deep sequencing (ChIP-seq) and quantitative ChIP assays. To explore the physiological role of SET7/9, functional analyses such as CCK-8, colony formation, and transwell assays were performed and a xenograft tumor model was generated with the human breast cancer cell lines MCF-7 and MDA-MB-231. Mass spectrometry, co-immunoprecipitation, GST pull-down, and ubiquitination assays were used to explore the mechanisms of SET7/9 function in breast cancer. We evaluated the expression of SET7/9 in different breast cancer cohorts and found that higher expression indicated worse survival times in these public databases. We demonstrated positive effects of SET7/9 on cell proliferation, migration, and invasion via the activation of Runt-related transcription factor 2 (RUNX2). We demonstrate that tripartite motif-containing protein 21 (TRIM21) physically associates with SET7/9 and functions as a major negative regulator upstream of SET7/9 through a proteasome-dependent mechanism and increased ubiquitination. Taken together, our data suggest that SET7/9 has a promoting role via the regulation of RUNX2, whereas TRIM21-mediated SET7/9 degradation acts as an anti-braking system in the progression of breast cancer.

Diagnostic value of serum neutrophil gelatinase-associated lipocalin, interleukin-6 and anti-citrullinated alpha-enolase peptide 1 for lower respiratory tract infections.

OBJECTIVES: The aim of this study was to explore the auxiliary diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) and anti-citrullinated alpha-enolase peptide 1 (CEP-1) in lower respiratory tract infections (LRTIs). METHODS: Blood samples were collected from 99 in-patients with LRTIs [62 community-acquired pneumonia (CAP), 14 acute exacerbated chronic obstructive pulmonary diseases (AECOPD), 23 other diseases] and 50 healthy subjects. NGAL, CEP-1 and IL-6 were measured and compared. IL-6 was tested by electrochemiluminescence assay kit on Roche E601 immunology analyzer, CEP-1 was assessed with enzyme-linked immunosorbent assay kit, and NGAL was detected by latex immunoturbidimetric assay kit on Beckman Coulter AU2700. RESULTS: Compared with healthy controls, NGAL and IL-6 levels were significantly increased in the patients with LRTIs, the area under the curves (AUC) was 0.97 and 0.88 respectively (P < 0.01). The sensitivity and specificity of NGAL at a cut-off of 86 ng/ml were 93.0% and 96.0%, respectively, in which the sensitivity was consistent with IL-6 (P = 0.21) and the specificity was better than IL-6 (P < 0.01). CEP-1 slightly increases in the patient group, however the difference was not significant (P = 0.41). The levels of NGAL and IL-6 was no differences in different diseases, the P-value was 0.50 and 0.29, respectively. LRTIs with and without underlying diseases have similar NGAL and IL-6 values. CONCLUSIONS: NGAL, rather than CEP-1, may be appealing adjuncts for diagnosis of LRTIs. NGAL proved to be a better biomarker than IL-6.

Evaluation of the Value of Anti-Citrullinated α-enolase Peptide 1 Antibody in the Diagnosis of Rheumatoid Arthritis.

GOALS: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. The α enolase is a nuclear glycolytic enzyme. Antibodies to citrullinated-enolase peptide1(anti-CEP-1) are found in approximately 40% of patients with RA, but the diagnostic value of anti-CEP-1 for RA is not clear. METHODS: We enrolled 282 patients with RA according to the 2010 ACR Classification criteria, referred to the department of Rheumatology in Peking University Third Hospital, 120 sex- and age-matched healthy donors (HD), and 30 patients with osteoarthritis (OA). Anti-CEP-1 IgG antibodies were assessed with a commercially available ELISA kit (Euroimmun, Germany) according to the manufacturers' instructions. Anti-CCP antibodies were assessed with ECLIA (Roche, Germany). Data was processed with SPSS 19. The scatter diagram was drawn in GraphPad Prism. RESULTS: The specificity and sensitivity was 83.3% and 65.2%, respectively. The positive predictive value was 88% and the negative predictive value was 56%. The AUC of anti-CEP1 for diagnosis of RA is 0.80, while that of Anti-CCP is 0.919; the value of anti-CCP combined with anti-CEP1 is 0.914. Ten anti-CEP1 positive results are found in 48 patients of RA with anti-CCP negative result. CONCLUSION: The anti-CEP-1 is suitable for diagnosing of RA, but not superior to anti-CCP.

Clinical diagnostic performance of light-initiated chemiluminescent assay compared with the Architect chemiluminescence immunoassay for detection of HCV antibody.

BACKGROUND: Hepatitis C virus antibody (anti-HCV) test had been approved as a preliminary screening test for HCV infection. Light-initiated chemiluminescent assay (LiCA) was a homogenous method. We aimed to assess the clinical diagnostic performance of LiCA and compare it with that of chemiluminescence immunoassay (CLIA) which was widely used in clinical laboratories. METHODS: A total of 10 772 patients from the Peking University Third Hospital were enrolled. The serum samples were detected on the ChIVD LiCA500 and Abbott Architect i2000SR platforms. Recombinant immunoblot assay (RIBA) and HCV RNA assay were used for confirmation. RESULTS: The negative agreement rate between ChIVD LiCA anti-HCV assay and Abbott Architect anti-HCV assay was 99.91%, the positive agreement rate was 37.31%, the total agreement rate was 98.74%, and the kappa coefficient (κ) was 0.519. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ChIVD LiCA anti-HCV assay were 96.39%, 99.95%, 89.58%, and 99.97%, respectively, which were superior to those of Abbott Architect anti-HCV assay (93.98%, 99.25%, 51.90%, and 99.95%, respectively). CONCLUSION: ChIVD LiCA anti-HCV assay was a highly sensitive, specific homogenous method with good diagnostic performance, and was applicable for the routine screening of HCV infection in clinical laboratories.

An efficient method to simultaneously analyze multi-class organic pollutants in human serum.

The degree of population exposure to various organic pollutants (OPs), including polycyclic aromatic hydrocarbons, organochlorinated pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers, can be determined by measuring their concentrations in human serum. However, performing large-scale measurements with such a variety of compounds in serum is challenging in terms of efficiency and cost. We describe herein the development of a high-efficiency extraction and sample cleanup protocol for simultaneous and quantitative analyses of OPs using gas chromatography-mass spectrometry. OPs, together with crude lipid impurities, were extracted from human serum with a mixture of n-hexane and methyl tert-butyl ether. A disperse sorbent composed of primary secondary amine and C18 (PSA/C18) was used to roughly remove co-extracted impurities. A combined column of neutral silica gel and neutral alumina oxide (AlO/SiG) was then used for deep cleanup. For the removal of impurities, the overall performance of our protocol for the analysis of OPs in serum was comparable to that of traditional gel permeation chromatography (GPC) and dramatically better than that of PSA/C18, which is a frequently used QuEChERS (quick, easy, cheap, effective, rugged, safe) based method. While both the proposed protocol and GPC yielded recoveries of 80%-110% for four classes of OPs, our protocol consumed about 10 times less solvent, resulting in lower experimental expenses and a lower risk of contamination from residual OPs in the solvent and other supplies. In contrast to GPC, our protocol also permits efficient batch processing of serum samples, allowing for large sample sizes such as those encountered in epidemiological studies.