The role of circulating miRNAs in mechanism of action and prediction of therapeutic responses of metformin in polycystic ovarian syndrome.

OBJECTIVE: To study the involvement of microribonucleic acids (miRNAs) in the pathogenesis of chronic anovulation and mechanism of metformin treatment in polycystic ovary syndrome (PCOS). DESIGN: Case-control and prospective validation cohort study. SETTING: Tertiary university hospital. PATIENT(S): A total of 146 patients with PCOS and chronic anovulation and 20 non-PCOS controls were enrolled. Patients who resumed ovulation after metformin treatment (MET-OV) and remained anovulatory after metformin treatment (MET-AO) were assigned to MET-OV and MET-AO groups, respectively. INTERVENTION(S): All patients with PCOS received metformin treatment for 6 months. MAIN OUTCOME MEASURE(S): Baseline and chronological changes in the plasma levels of 14 miRNAs (miR-21, 93, 132, 193b, 221, 222, 223, 27a, 125b, 200b, 212, 320a, 429, and 483) selected by literature review, anthropometric data, and hormonal as well as metabolic profiles were measured. Predictive modeling based on baseline circulatory miRNA levels and clinical parameters was performed to predict ovulation recovery after metformin treatment. RESULT(S): No significant differences were observed in the baseline hormonal and metabolic profiles between the MET-OV and MET-AO groups. However, the expression of miR-27a, miR-93, and miR-222 was significantly higher in the MET-OV group than that for the MET-AO and control groups. After 6 months of metformin treatment, the levels of insulin, luteinizing hormone, and 6 circulating miRNAs (miR-21, 27a, 93, 221, 222, and 223) and homeostatic model assessment for insulin resistance decreased significantly in the MET-OV group, but remained unchanged in the MET-AO group. The area under curve, sensitivity, and specificity of the adjusted prediction model, based on miRNA levels and clinical parameters using logistic regression analysis for predicting ovulatory response after metformin treatment, were 0.807, 0.892, and 0.632, respectively. CONCLUSION(S): The present study demonstrated a distinct pattern of baseline expression and chronological changes in the levels of several circulatory miRNAs between the MET-OV and MET-AO groups, suggesting that aberrantly overexpressed diabetogenic miRNAs are involved in the pathophysiology of chronic anovulation in PCOS, and their down-regulation might contribute toward the therapeutic effects of metformin. This could provide new insights into the mechanism of action and applicability of individualized metformin therapy in women with PCOS.

Complement 3 and the Prognostic Nutritional Index Distinguish Kawasaki Disease from Other Fever Illness with a Nomogram.

OBJECTIVE: This study aimed to establish a model to distinguish Kawasaki disease (KD) from other fever illness using the prognostic nutritional index (PNI) and immunological factors. METHOD: We enrolled a total of 692 patients (including 198 with KD and 494 children with febrile diseases). Of those, 415 patients were selected to be the training group and 277 patients to be the validation group. Laboratory data, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the prognostic nutritional index (PNI), and immunological factors, were retrospectively collected for an analysis after admission. We used univariate and multivariate logistic regressions and nomograms for the analysis. RESULT: Patients with KD showed significantly higher C3 and a lower PNI. After a multivariate logistic regression, the total leukocyte count, PNI, C3, and NLR showed a significance (p < 0.05) and then performed well with the nomogram model. The areas under the ROC in the training group and the validation group were 0.858 and 0.825, respectively. The calibration curves of the two groups for the probability of KD showed a near agreement to the actual probability. CONCLUSIONS:  Compared with children with febrile diseases, patients with KD showed increased C3 and a decreased nutritional index of the PNI. The nomogram established with these factors could effectively identify KD from febrile illness in children.

A Nomogram Model Identifies Eosinophilic Frequencies to Powerfully Discriminate Kawasaki Disease From Febrile Infections.

Background: Kawasaki disease (KD) is a form of systemic vasculitis that occurs primarily in children under the age of 5 years old. No single laboratory data can currently distinguish KD from other febrile infection diseases. The purpose of this study was to establish a laboratory data model that can differentiate between KD and other febrile diseases caused by an infection in order to prevent coronary artery complications in KD. Methods: This study consisted of a total of 800 children (249 KD and 551 age- and gender-matched non-KD febrile infection illness) as a case-control study. Laboratory findings were analyzed using univariable, multivariable logistic regression, and nomogram models. Results: We selected 562 children at random as the model group and 238 as the validation group. The predictive nomogram included high eosinophil percentage (100 points), high C-reactive protein (93 points), high alanine transaminase (84 points), low albumin (79 points), and high white blood cell (64 points), which generated an area under the curve of 0.873 for the model group and 0.905 for the validation group. Eosinophilia showed the highest OR: 5.015 (95% CI:-3.068-8.197) during multiple logistic regression. The sensitivity and specificity in the validation group were 84.1 and 86%, respectively. The calibration curves of the validation group for the probability of KD showed near an agreement to the actual probability. Conclusion: Eosinophilia is a major factor in this nomogram model and had high precision for predicting KD. This report is the first among the existing literature to demonstrate the important role of eosinophil in KD by nomogram.

A novel nomogram model for differentiating Kawasaki disease from sepsis.

Kawasaki disease (KD) is a form of systemic vasculitis that occurs in children under the age of 5 years old. Due to prolonged fever and elevated inflammatory markers that are found in both KD and sepsis, the treatment approach differs for each. We enrolled a total of 420 children (227 KD and 193 sepsis) in this study. Logistic regression and a nomogram model were used to analyze the laboratory markers. We randomly selected 247 children as the training modeling group and 173 as the validation group. After completing a logistic regression analysis, white blood cell (WBC), anemia, procalcitonin (PCT), C-reactive protein (CRP), albumin, and alanine transaminase (ALT) demonstrated a significant difference in differentiating KD from sepsis. The patients were scored according to the nomogram, and patients with scores greater than 175 were placed in the high-risk KD group. The area under the curve of the receiver operating characteristic curve (ROC curve) of the modeling group was 0.873, sensitivity was 0.893, and specificity was 0.746, and the ROC curve in the validation group was 0.831, sensitivity was 0.709, and specificity was 0.795. A novel nomogram prediction model may help clinicians differentiate KD from sepsis with high accuracy.

[CD11b expression in neutrophils and lymphocytes of children with systemic inflammatory response syndrome].

OBJECTIVE: To investigate the significance of CD11b expression in neutrophils and lymphocytes in children with systemic inflammatory response syndrome (SIRS). METHODS: CD11b expression in neutrophils and lymphocytes was measured using flow cytometry in 36 children with SIRS (SIRS group) and 28 children with infectious disease but without SIRS (control group). The sensitivity and specificity of neutrophil CD11b for diagnosis of SIRS were evaluated. RESULTS: During the acute phase, an increased CD11b expression in neutrophils (96.7+/-8.1%) was observed in the SIRS group compared with the control group (85.1+/-5.1%) (p<0.05). Using neutrophil CD11b expression >92.2% as a cut-off value for diagnosis of SIRS, the sensitivity and the specificity were 97.2 % and 92.9% respectively. Lymphocytic CD11b expression in the SIRS group (13.4+/-8.6%) was lower than that in the control group (19.2+/-6.4%) in the acute phase (p<0.05). In the SIRS group, lymphocytic CD11b expression was remarkably suppressed in the severe sepsis subgroup (7.27+/-3.04%), showing significantly decreased expression compared with the non-infectious subgroup (19.3+/-2.9%) and the sepsis subgroup (15.9+/-12.5%) (p<0.01). In the convalescence stage lymphocytic CD11b expression in the SIRS group was similar to that in the control group. CONCLUSIONS: CD11b expression in neutrophils may serve as a reliable indicator for diagnosis of SIRS. The down-regulation of lymphocytic CD11b expression might be a signal of the condition aggravation in children with SIRS.