Diagnostic Value Of Serum Research Articles

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism; GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development. To investigate the associations of serum D-dimer (D-D) and glycosylated hemoglobin (HbA1c) levels with third-trimester fetal growth restriction (FGR) in GDM patients. The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively. Among these women, 63 whose fetuses had FGR were included in the FGR group, and 101 women whose fetuses had normal body weights were included in the normal body weight group (normal group). Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis. The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis, and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression. Serum fasting blood glucose, fasting insulin, D-D and HbA1c levels were significantly greater in the FGR group than in the normal group, while the homeostasis model assessment of insulin resistance values were lower (P < 0.05). Regarding the diagnosis of FGR based on serum D-D and HbA1c levels, the areas under the curves (AUCs) were 0.826 and 0.848, the cutoff values were 3.04 mg/L and 5.80%, the sensitivities were 81.0% and 79.4%, and the specificities were 88.1% and 87.1%, respectively. The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928, and the sensitivity and specificity were 84.1% and 91.1%, respectively. High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients (P < 0.05). D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent, and their combination can be used as an important index for the early prediction of FGR.

Diagnostic Value of Serum and Urine Endocan Levels in Nonmuscle Invasive Bladder Cancer: A Prospective Comparative Study

Objective. This prospective study aimed to explore the potential diagnostic value of endocan levels in bladder cancer by investigating a possible association of serum and urine endocan levels with the stage and grade of bladder tumors in patients with nonmuscle-invasive bladder cancer (NMIBC) in terms of risk stratification. Materials and Methods. Participants included 66 male patients with NMIBC. Patients with full pathology results, NMIBC stage T1, and healthy controls were categorized as groups 1, 2, and 3, respectively. Patients were further classified into high- and low-grade groups following their pathology results. Risk classification according to the European Association of Urology (EAU) was assigned to patients with NMIBC, and associations of risk groups with serum and urine endocan levels were analyzed. An enzyme-linked immunosorbent assay was used to identify serum and urine endocan concentrations. Results. Serum endocan levels according to pathological staging were significantly higher in groups 1 and 2 than in group 3. The urine endocan level was statistically significantly higher in group 2 than in group 3 p&lt;0.001. The predictive power of the urine endocan level was evaluated for its ability to predict T1 disease, revealing an area under the curve of 0.735 and a threshold of 903. The EAU classification was evaluated according to risk groups, and the urine endpoint was statistically significantly higher in the univariate analysis for the high and very high-risk groups p=0.034. Conclusion. Our results indicate that endocan levels hold significant promise in prognostic feature evaluation in NMIBC, particularly in the context of screening patients with hematuria.

Diagnostic value of serum miR-25-3p in hypertensive disorders in pregnancy

ABSTRACT Hypertensive disorders in pregnancy (HDIP) represent one of the leading causes of maternal and perinatal mortality. microRNA (miR)-25-3p plays roles in HDIP diagnosis. We explored miR-25-3p clinical roles in HDIP. HDIP patients [gestation hypertension (GH), mild preeclampsia (mPE), and severe preeclampsia (sPEz)], and normal pregnant women serving as the control were enrolled. Serum miR-25-3p expression patterns were detected by RT-qPCR. The diagnostic efficacy of miR-25-3p on HDIP was analyzed with a ROC curve. Patients were assigned to the high/low miR-25-3p expression groups according to the median value of miR-25-3p expression. All patients were followed up until delivery, and gestational weeks and pregnancy outcomes were recorded at delivery. The effects of miR-25-3p expression on pregnancy outcomes of GH, mPE, and sPEz patients were analyzed by Kaplan-Meier. miR-25-3p expression in GH, mPE, and sPEz patients was up-regulated. In sPEz patients, systolic and diastolic blood pressure, 24-h urine protein, AST, ALT, GGT, and SCr were increased, and PLT was decreased in the high expression group. High miR-25-3p expression was associated with an increased risk of adverse pregnancy outcomes in PE patients. Collectively, high miR-25-3p expression could aid HDIP diagnosis, and associated with an increased risk of adverse pregnancy outcomes in PE patients.

Diagnostic value of serum and tissue eosinophil in diagnosis of asthma among patients with chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is one of the most common chronic inflammatory diseases of sinonasal mucosa. Asthma among CRS patients is often underdiagnosed which makes the management of CRS more challenging. Therefore, using serum and tissue eosinophil as an indicator and predictor of asthma in CRS patients is vital for further preventing recurrent and increasing the effectiveness of treatment for CRS. To determine the association and diagnostic ability of serum and tissue eosinophils in the diagnosis of asthma among CRS patients. A cross-sectional study was conducted involving 24 CRS patients with asthma and without asthma, respectively, from the Otorhinolaryngology clinic of two tertiary hospitals located on the East Coast of Peninsular Malaysia. Serum and tissue eosinophils (obtained from nasal polyp) levels between both groups were compared. Association between serum and tissue eosinophils with asthma was evaluated using logistic regression analysis, adjusting for important sociodemographic characteristics. The diagnostic ability of serum and tissue eosinophil was then evaluated by assessing the receiver operating characteristic curve. A total of 48 CRS patients with a mean [SD] age of 47.50 [14.99] years were included. Patients with asthma had significantly higher serum [0.48 vs 0.35 × 109/L] and tissue eosinophil [100 vs 8.5 per HPF] levels. Tissue eosinophils were found to be an independent predictor of asthma with adjusted OR 1.05, p < 0.001, after adjusting for age and serum eosinophils. The area under the receiver operating characteristic curve for serum eosinophil was 69.0%. At optimal cut-off value (0.375 × 109/L), the sensitivity and specificity for serum eosinophil was 75.0% and 70.8%. The area under the receiver operating characteristic curve for tissue eosinophil was 93.4%. At the optimal cut-off value (58.0 per HPF), the sensitivity and specificity for tissue eosinophils were 79.2% and 91.7%, respectively. This study indicates a significantly higher level of serum and tissue eosinophils in CRS with asthma. However, there was no correlation between serum and tissue eosinophils in both group. Based on this study, the CRS patient needs to be screened for asthma if the level of serum eosinophil is > 0.375 × 109/L and tissue eosinophil > 58 per HPF.

The level distribution of serum AMH in different clinical manifestations of women of childbearing age

To investigate the distribution and diagnostic value of serum anti-Müllerian hormone (AMH) in healthy women of childbearing age, women with polycystic ovary syndrome (PCOS), ovarian dysfunction (DOR) and premature ovarian failure (POF). This study retrospectively selected female patients of childbearing age who were treated in the affiliated Obstetrics and Gynecology Hospital of Fudan University from January to December 2019. According to different clinical manifestations, they were divided into 133 cases in PCOS group, 120 cases in DOR group and 134 cases in POF group. 125 healthy women in the same period were selected as the control group. The values of serum AMH, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) were measured in the four groups. Single sample Kolmogorov-Smirnov test, one-way ANOVA, independent sample t-test, Kruskal-Wallis H test, Mann-Whitney U test, logistic regression analysis and ROC curve were used for comparative analysis. The serum AMH levels of PCOS group, DOR group, POF group and control group were 9.10 (6.67, 11.49) ng/ml, 0.11 (0.05, 0.29) ng/ml, 0.03 (0.02, 0.06) ng/ml and 2.99 (1.57, 4.98) ng/ml, respectively [M(Q1,Q3)], the differences were statistically significant (P<0.001). The basal endocrine levels including E2, FSH, LH and T also had significant differences between groups (P<0.001). The results of multiple comparisons showed that there were significant differences in AMH and LH between DOR, POF and PCOS groups and the control group. The T level of PCOS group was significantly higher than that of the control group, the E2, LH and T levels of DOR group were significantly higher than that of the control group, and the FSH level of POF group was significantly higher than that of the control group (P<0.05). The area under the curve (AUC) of AMH and AMH+LH in the diagnosis of PCOS were 0.905 and 0.922, the sensitivity was 82.7% and 85.0%, and the specificity was 88.0% and 88.8%. The AUC of DOR was 0.861 and 0.971, the sensitivity was 89.0% and 92.5%, and the specificity was 63.0% and 92.0%. The AUC of POF was 0.950 and 0.998, the sensitivity was 98.3% and 99.2%, and the specificity was 75.9% and 97.0%, respectively. The AUC of AMH and AMH+LH combined indexes in the differential diagnosis of DOR and POF were 0.768 and 0.937, the sensitivity was 70.3% and 95.5%, and the specificity was 73.9% and 80.8%.

MiR-182-5p combined with brain-derived neurotrophic factor assists the diagnosis of chronic heart failure and predicts a poor prognosis

ObjectiveChronic heart failure (CHF) is a general progressive disorder with high morbidity and poor prognosis. This study analyzed the serum expression and clinical value of miR-182-5p and brain-derived neurotrophic factor (BDNF) in CHF patients.MethodsA total of 82 CHF patients were selected as the study subjects (15 cases in NYHA stage I, 29 cases in stage II, 27 cases in stage III, and 11 cases in stage IV), with another 78 healthy people as the controls. The expression of serum miR-182-5p was detected by RT-qPCR. BDNF expression was measured by ELISA. Furthermore, the Pearson coefficient was used to analyze the correlation of miR-182-5p/BDNF with BNP and LVEF. ROC curve was employed to assess the potential of miR-182-5p or/and BDNF for the diagnosis of CHF. Kaplan–Meier survival curve was implemented to evaluate the prognostic value of miR-182-5p and BDNF.ResultsSerum miR-182-5p level was elevated and BDNF expression was lowered in CHF patients. Serum miR-182-5p in CHF patients was positively-related with BNP and inversely-correlated with LVEF, while serum BDNF was negatively-linked with BNP and positively-correlated with LVEF. ROC curve indicated the diagnostic value of serum miR-182-5p and BDNF for CHF and the diagnostic accuracy of miR-182-5p combined with BDNF was improved. Kaplan–Meier analysis unveiled that miR-182-5p low expression and BDNF high expression could predict the overall survival in CHF patients.ConclusionmiR-182-5p expression is increased and BDNF level is decreased in CHF patients. miR-182-5p combined with BDNF can assist the diagnosis of CHF and predict a poor prognosis.

Diagnostic value of serum miR-144-3p for the detection of acute cellular rejection in heart transplant patients

The development of noninvasive approaches for the early diagnosis of acute cellular rejection (ACR), an important complication of cardiac transplantation, is of great importance in clinical practice. We conducted a nontargeted transcriptomic study focused on identifying serum miRNAs to evaluate their diagnostic accuracy for detecting rejection episodes. We included consecutive serum samples from transplant recipients undergoing routine endomyocardial biopsies. In the discovery phase (n=40), an RNA sequencing analysis (Illumina HiSeq 2500 sequencer) was performed. We focused on the validation of miR-144-3p in a larger patient cohort (n=212), selected based on the criteria of higher accuracy for ACR detection. ACR was assessed according to the International Society for Heart and Lung Transplantation. In the discovery phase, 26 altered miRNAs were identified as potential markers for detecting ACR. miR-144-3p showed the best results, it was the only molecule with an AUC greater than 0.95 to detect Grade ≥2R ACR and it showed significant differences in its levels when we compared Grade 1R ACR with the nonrejection group. In the validation phase, we confirmed this finding, and it had an excellent diagnostic capacity for clinically relevant rejection (Grade ≥2R AUC=0.801, p < 0.0001), detecting mild rejection (Grade 1R AUC= 0.631, p < 0.01) and was an independent predictor for the presence of ACR (odds ratio of 14.538, p < 0.01). ACR is associated with the differential expression of specific serum miRNAs that correlate with the severity of the episode. Circulating miR-144-3p is a candidate noninvasive ACR biomarker that could contribute to improving the surveillance of cardiac transplanted patients.

MicroRNA-425-5p Is Involved in the Development of Diabetic Retinopathy and Regulates the Proliferation and Migration of Retinal Microvascular Endothelial Cells

Introduction: The objective of this article was to detect the expression pattern and clinical value of miR-425-5p in diabetic retinopathy (DR) patients and investigate its effect on the proliferation and migration of human retinal microvascular endothelial cells (HRMECs) in a high glucose (HG) state. Methods: The serum miR-425-5p level of the subjects was determined using quantitative real-time PCR. The diagnostic value of serum miR-425-5p was validated using the receiver operating characteristic curve. Pearson analysis detected the correlation between clinical indicators and microRNA. The influence of miR-425-5p on cell proliferation and migration under HG conditions was calculated by using Cell Counting Kit-8 and Transwell assay. Results: Serum miR-425-5p levels showed a gradual increasing trend in the healthy control group, the diabetic mellitus patients without DR, and DR patients. Moreover, the levels of miR-425-5p in proliferative DR (PDR) patients were elevated than that of non-PDR (NPDR) patients. Furthermore, upregulated miR-425-5p had a high diagnostic value for DR patients and can distinguish PDR patients from NPDR patients. The expression of miR-425-5p was significantly positively correlated with the fasting plasma glucose, glycosylated hemoglobin (HbA1C), homeostasis model assessment of insulin resistance, and disease course of the patients. Under HG conditions, overexpression of miR-425-5p promoted HRMEC proliferation and migration, while inhibition of miR-425-5p led to opposite results. Conclusion: Present research confirmed that serum miR-425-5p levels in DR are marked by elevation. High expression of miR-425-5p can be used as a feasible diagnostic biomarker for DR patients and can predict the development and severity of DR. Moreover, inhibiting the expression of miR-425-5p levels under the condition of hyperglycemia may be used as a valuable therapeutic strategy for preventing the pathogenesis of DR.

Diagnostic Value of Nucleocapsid Protein in Blood for SARS-CoV-2 Infection.

BackgroundBiomarkers have been widely explored for coronavirus disease 2019 diagnosis. Both viral RNA or antigens (Ag) in the respiratory system and antibodies (Ab) in blood are used to identify active infection, transmission risk, and immune response but have limitations. This study investigated the diagnostic utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (N-Ag) in serum.MethodsWe retrospectively studied 208 randomly selected cases with SARS-CoV-2 infection confirmed by viral RNA test in swabs. N-Ag concentrations were measured in remnant serum samples, compared to viral RNA or Ab results, and correlated to electronic health records for clinical value evaluation.ResultsSerum N-Ag was detected during active infection as early as day 2 from symptom onset with a diagnostic sensitivity of 81.5%. Within 1 week of symptom onset, the diagnostic sensitivity and specificity reached 90.9% (95% CI, 85.1%–94.6%) and 98.3% (95% CI, 91.1%–99.9%), respectively. Moreover, serum N-Ag concentration closely correlated to disease severity, reflected by highest level of care, medical interventions, chest imaging, and the length of hospital stays. Longitudinal analysis revealed the simultaneous increase of Abs and decline of N-Ag.ConclusionsSerum N-Ag is a biomarker for SARS-CoV-2 acute infection with high diagnostic sensitivity and specificity compared to viral RNA in the respiratory system. There is a correlation between serum N-Ag concentrations and disease severity and an inverse relationship of N-Ag and Abs. The diagnostic value of serum N-Ag, as well as technical and practical advantages it could offer, may meet unsatisfied diagnostic and prognostic needs during the pandemic.

MicroRNA‑1323 serves as a biomarker in gestational diabetes mellitus and aggravates high glucose‑induced inhibition of trophoblast cell viability by suppressing TP53INP1

Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes, and microRNAs (miRNAs/miRs) have been suggested to be associated with GDM, but the pathological mechanisms remain unclear. The present study aimed to investigate the diagnostic value of miR-1323 in GDM patients and its effects on trophoblast cell viability. Additionally, the present study investigated the correlation between miR-1323 and TP53INP1 to understand the pathological mechanism of GDM progression. Reverse transcription-quantitative polymerase chain reaction was used to detect the miR-1323 expression and TP53INP1 mRNA expression. The diagnostic value of serum miR-1323 was evaluated by receiver operating characteristic analysis. HTR-8/SVneo and BeWo cells were treated with high glucose (HG) to construct cell models of GDM, and trophoblast cell viability was assessed using an MTT assay. The protein expression of TP53INP1 was detected by western blot analysis. The correlation between miR-1323 and TP53INP1 was investigated by luciferase reporter assay. The miR-1323 expression was increased in patients with GDM, which had relatively high diagnostic accuracy for GDM screening and was positively correlated with fasting blood glucose in patients GDM. HG upregulated the miR-1323 expression and inhibited trophoblast cell viability. Overexpression of miR-1323 significantly inhibited the viability of HG-induced trophoblast cells. TP53INP1, a target gene of miR-1323, was negatively correlated with miR-1323. TP53INP1 overexpression reversed the inhibitory effect of miR-1323 overexpression on the viability of HG-treated trophoblast cells. Increased levels of serum miR-1323 may be a diagnostic biomarker for GDM. Additionally, miR-1323 may inhibit trophoblast cell viability by inhibiting TP53INP1, suggesting that it may be a potential therapeutic target for GDM.

TLR‑4, TLR‑5 and IRF4 are diagnostic markers of knee osteoarthritis in the middle-aged and elderly patients and related to disease activity and inflammatory factors

Expression and diagnostic value of serum toll-like receptor-4 (TLR-4), Toll-like receptor-5 (TLR-5) and interferon regulatory factor 4 (IRF4) in middle-aged and elderly patients with knee osteoarthritis (KOA) and their correlation with Interleukin 1β (IL-1β), interleukin-6 (IL-6), matrix metalloproteinase-1 and tumor necrosis factor-α (TNF-α) were investigated. Sixty-eight middle-aged and elderly patients with KOA in Puyang Hospital of Traditional Chinese Medicine were selected as the study group and 49 healthy people receiving physical examination were the control group. Levels of serum TLR-4, TLR-5, IRF4, IL-1β, IL-6, MMP-1 and TNF-α were measured by enzyme linked immunosorbent assay (ELISA). Correlation between the expression levels of serum TLR-4, TLR-5, IRF4 and K-L grades was determined by Spearman correlation analysis. The diagnostic efficacy of serum TLR-4, TLR-5 and IRF4 for KOA was analyzed by the receiver operator characteristics analysis (ROC). Expression of serum TLR-4, TLR-5 and IRF4 in the study group was significantly higher than those in the control group. The sensitivity and specificity of TLR-4 in the diagnosis of KOA were, respectively, 76.47 and 93.88%, those of TLR-5 were 73.29 and 87.76%, those of IRF4 were 72.06 and 95.92%, and those of TLR-4, TLR-5 and IRF4 were 94.12 and 97.96%. Expression of serum TLR-4, TLR-5 and IRF4 was significantly higher in the severe group than in the moderate group, and significantly higher in the moderate group than those the in mild group, and significantly higher in the mild group than those in the suspected mild group. Expression of TLR-4, TLR-5 and IRF4 in serum was positively correlated with the concentration of IL-1β, IL-6, MMP-1 and TNF-α, respectively (P<0.001). The combined detection of TLR-4, TLR-5 and IRF4 can be used for early diagnosis of KOA, and they are positively correlated with IL-1β and IL-6, MMP-1 and TNF-α.

Diagnostic value of serum D-dimer, CA125, and neutrophil-to-lymphocyte ratio in differentiating ovarian cancer and endometriosis.

To assess the utility of hematologic, inflammatory, and immunologic biomarkers for differentiating between ovarian cancer and endometriosis. Data were retrospectively reviewed from women diagnosed with ovarian cancer and endometriosis after ovarian cyst surgery in Zhejiang, China, 2014-2016. Serologic and hematologic biomarkers, including white blood cell count, lymphocyte count, neutrophil count, red blood cell count, hemoglobin, platelets, and D-dimer, albumin, globulin, cancer antigen 125 (CA125) and CA199 serum levels recorded pre-operatively were assessed by ROC curve and logistic regression analysis. Overall, 49 women were diagnosed with ovarian cancer and 192 with endometriosis. For predicting ovarian cancer, the area under the curve (AUC) was 0.96 (95% confidence interval [CI], 0.94-0.99); sensitivity, 93.2%; specificity, 87.5%) for log(D-dimer), 0.95 (95% CI, 0.91-0.98; sensitivity, 81.3%; specificity, 96.3%) for log(CA125), and 0.92 (95% CI, 0.86-0.98; sensitivity, 92.6%; specificity, 79.2%) for neutrophil-to-lymphocyte ratio (NLR). The AUC for the combination of D-dimer, NLR, and CA125 was 0.96 (95% CI, 0.94-0.99; sensitivity, 91.6%; specificity, 89.6%). Serum D-dimer, NLR, and CA125 were found to be potential diagnostic factors for ovarian cancer. Combined measurement of D-dimer, NLR, and CA125 might offer a convenient screening method.

LINK‑A lncRNA participates in the pathogenesis of glioma by interacting with survivin

Long intergenic non-coding RNA for kinase activation (LINK-A) long non-coding RNA (lncRNA) has been characterized in triple negative breast cancer, but its potential involvement in glioma has not been investigated. In the present study, serum levels of LINK-A lncRNA and survivin in patients with glioma and healthy controls were determined by RT-qPCR and ELISA, respectively. The diagnostic value of serum LINK-A lncRNA for glioma was evaluated by receiver operating characteristic (ROC) curve analysis. Potential correlations between serum levels of LINK-A lncRNA and survivin were analyzed by Pearson correlation coefficient. LINK-A lncRNA siRNA, LINK-A lncRNA-carrying expression vector and survivin-carrying expression vector were transfected into glioma cells, and the effects on LINK-A lncRNA expression, survivin expression and cell apoptosis were explored by RT-qPCR, western blot analysis and annexin V/propidium iodide staining. It was observed that the serum levels of LINK-A lncRNA and survivin were significantly higher in patients with glioma compared with healthy controls. Increased levels of LINK-A lncRNA distinguished glioma patients from healthy controls, based on ROC curve analysis. Serum levels of LINK-A lncRNA and survivin were positively correlated in glioma patients, but not in healthy controls. Overexpression of LINK-A lncRNA led to increased survivin protein expression, while survivin overexpression had no effect on LINK-A lncRNA expression. LINK-A lncRNA and survivin overexpression each reduced glioma cell apoptosis, but LINK-A lncRNA siRNA-mediated knockdown increased apoptosis. Survivin overexpression attenuated the inducing effects of LINK-A lncRNA knockdown on apoptosis. In conclusion, LINK-A lncRNA inhibited glioma cell apoptosis potentially by the upregulation of survivin. The present study revealed that LINK-A may serve as possible diagnostic marker for glioma.

Potential diagnostic and prognostic value of serum and cerebrospinal fluid biomarkers in traumatic spinal cord injury: A systematic review.

It remains unclear whether biomarkers in the serum or CSF can be used for diagnosis or prognosis of spinal cord injuries (SCI). Therefore, a systematic review was undertaken to evaluate the prognostic or diagnostic value of serum and CSF biomarkers in assessing the severity of SCI and the outcome of patients. Two independent reviewers summarized the human studies retrieved from the electronic databases of Medline, Embase, Scopus and ISI Web of Science until April 2018. Seventeen studies were included (1065 patients aged 16-94years old). Although the findings of the included studies suggest that inflammatory and structural proteins may be useful in assessing the severity of SCI and prediction of neurological outcome, the level of evidence is generally low. Given limitations to the available evidence, further investigation in this field is required using large prospective data sets with rigorous analysis of sensitivity, specificity and prediction.

MiRNA-373 promotes urinary bladder cancer cell proliferation, migration and invasion through upregulating epidermal growth factor receptor.

MicroRNA (miRNA)-373 has been demonstrated to be involved in several types of cancer, whereas its involvement in urinary bladder cancer and the mechanism of its function remains poorly understood. The present study aimed to investigate the functionality of miRNA-373 in urinary bladder cancer. Tumor tissues and adjacent healthy tissues were collected from patients with urinary bladder cancer (n=55), and blood samples were collected from patients with urinary bladder cancer and healthy controls (n=45). The expression of miRNA-373 in these tissues was detected by reverse transcription quantitative polymerase chain reaction. The diagnostic value of serum miRNA-373 for urinary bladder cancer was investigated by receiver operating characteristic curve analysis and survival curve analysis, respectively. miRNA-373 mimics were transfected into urinary bladder cancer cells, and the effects on cancer cell proliferation, migration and invasion, and on epidermal growth factor receptor (EGFR) expression was assessed by Cell Counting kit-8 assay, Transwell migration and invasion assays, and western blot analysis. It was identified that the miRNA-373 expression level was increased in tumor tissues compared with adjacent healthy tissues. The serum level of miRNA-373 was increased in patients with cancer compared with the healthy controls. Serum miRNA-373 may be used to accurately predict urinary bladder cancer. miRNA-373 overexpression promoted tumor cell proliferation, migration and invasion, and resulted in upregulated EGFR expression in urinary bladder cancer cells. It was concluded that miRNA-373 overexpression may promote urinary bladder cancer cell proliferation, migration and invasion by upregulating EGFR.

Diagnostic value of serum chitinase-3-like protein 1 in chronic liver disease of significant fibrosis and cirrhosis

Objective: To study the correlation between the level of serum Chitinase-3-like protein 1 (CHI3L1) and the significant liver fibrosis and liver cirrhosis in patients with chronic liver disease, and to evaluate its diagnostic value. Methods: 165 patients with chronic liver disease were selected, liver histopathological examination was performed to detect serum CHI3L1 concentration. Four indexes of hepatic fibrosis (type III procollagen, collagen IV, laminin, hyaluronic acid), aspartate aminotransferase/platelet ratio index (APRI) and FIB-4 (fibrosis- 4) scores were based on the pathological findings of liver biopsy and compared the advantages and disadvantages of serum CHI3L1 with other methods for the diagnosis of hepatic fibrosis and liver cirrhosis. A multivariate regression analysis model was created, and receiver operating characteristic curve was analyzed. Results: The level of serum CHI3L1 increased with increase of fibrosis stage and was highest in liver cirrhosis stage. In the period of S0 to 1, the levels of S2 to 3 and S4 were 62.82 (41.40 ~ 87.20), 70.94 (48.47 to 122.60) and 141.06 (78.18 ~ 197.40), and there were statistically significant differences between the groups (P < 0.001). The area under the curve for the diagnosis of significant liver fibrosis was 0.68 (0.60 to 0.77), and 0.74 (0.65 to 0.83) for cirrhosis in CHI3L1. Multivariate regression analysis showed that CHI3L1 was an independent predictor of significant fibrosis and cirrhosis. The combined diagnostic model based on CHI3L1, collagen IV and FIB-4 scores further improved the diagnostic value. The area under the curve for the diagnosis of significant fibrosis and cirrhosis was 0.79 (0.72 to 0.86) and 0.80 (0.73 to 0.87), respectively. Conclusion: CHI3L1 has a good diagnostic value in patients with chronic liver disease with significant fibrosis and liver cirrhosis. The diagnostic model in combination with other markers like Collagen IV and FIB-4 scores could further improve the diagnostic value and is worthy of further study.

The Diagnostic Value of Serum miRNA-221-3p, miRNA-382-5p, and miRNA-4271 in Ischemic Stroke

Circulating miRNAs have been demonstrated as biomarkers for a number of diseases. In the present study, we aimed to compare the serum levels of the miRNA-221-3p, miRNA-382-5p, and miRNA-4271 between ischemic stroke and healthy control subjects and explore the potential roles as noninvasive biomarkers in the diagnosis of ischemic stroke. Seventy-eight patients with ischemic stroke (60 ± 10.47 years old) and 39 healthy control subjects (61 ± 5.14 years old), age and sex matched, were recruited into the present study. The circulating miRNA levels were determined by quantitative real-time polymerase chain reaction using miRNA qPCR Assay Kit (CW Biotech, Beijing, China). Receiver operating characteristic (ROC) curves were analyzed using the SPSS software package (version 17) (SPSS Inc., Chicago, IL). Circulating serum miRNA-221-3p and miRNA-382-5p levels were significantly lower in patients with ischemic stroke compared to healthy control subjects, whereas there was no significant difference in the serum levels of miRNA-4271 between the stroke patients and healthy controls (P > .05). ROC curves revealed the areas under the curve for circulating miRNA-221-3p, miRNA-382-5p, and miRNA-4271 to be .8106, .7483, and .6317 in ischemic stroke patients compared with healthy volunteers, respectively. There were no correlations between circulating miRNAs and laboratory determinations except that the levels of circulating miRNA-4271 were positively correlated with glucose (r = .274, P = .031). Our findings suggest that serum circulating miRNA-221-3p and miRNA-382-5p might be used as potential noninvasive biomarkers for the diagnosis of ischemic stroke.

The Importance of Liver-Fatty Acid Binding Protein in Diagnosis of Liver Damage in Patients with Acute Hepatitis.

Acute hepatitis is acute inflammation of liver elicited by a large number of causes. It sometimes spontaneously recovers, sometimes may progress to chronic hepatitis. Liver- Fatty Acid Binding Protein (L-FABP) is a small protein that is abundant in hepatocytes, and which binds most of the long-chain fatty acids present in the cytosol. The present study was aimed to investigate the levels of serum and urine L-FABP in acute hepatitis and diagnostic value of serum and urine L-FABP levels in patients with acute hepatitis. The present study included a total of 85 patients. Total number of patients with acute hepatitis were 17 (five of acute hepatitis B, one of acute hepatitis A, two of acute hepatitis C, five of autoimmune hepatitis and four of toxic hepatitis), 19 of hepatic encephalopathy, 29 of liver cirrhosis, and 20 controls were included. Serum and urinary L-FABP levels were analyzed by the Enzyme-Linked Immunosorbent Assay (ELISA). Serum L-FABP levels were 9110±3352.5, 9410±1355, 9715±2462 and 3672±982.5 ng/l in patients with acute hepatitis, hepatic encephalopathy and cirrhosis and control subjects, respectively. There were statistically significant positive correlations between serum levels of L-FABP and Aspartate Aminotransferases (AST), Alanine Aminotransferases (ALT), Creatinine (Cre) and Gamma Glutamyl Transferases (GGT) (p<0.001, p<0.001, p<0.001 and p<0.001, respectively). While the cut-off value of serum L-FABP for all of the patients was 5183 ng/l {p<0.001 and Area Under Curve (AUC) 0.985}, the sensitivity and specificity were 95.4% and 100%, respectively. Positive and negative predictive values for serum L-FABP were 100% and 87%, respectively. Serum and urine L-FABP may be a new diagnostic marker for liver damage in patients with acute hepatitis. However, our study showed that except of aminotransferases, L-FABP should be used for diagnosis of liver damage in patients with acute hepatitis, chronic hepatitis and also cirrhosis.

Abstract 1952: Diagnostic potential of serum and exosomal microRNAs for patients with pre-malignant lesions of colorectal cancer: Detection of adenoma

Abstract Background: MicroRNAs (miRNAs) are dysregulated during colorectal cancer (CRC) development and progression. Profiling of CRC tissue has elicited interest in the potential use of miRNAs as non-invasive biomarkers for early detection of CRC. Exosomes have capacity to envelop specific miRNAs, and maintain the integrity of contents in circulation. Therefore, circulating miRNAs in exosomes are more stable than other forms. Thus miRNAs extracted from exosome in serum may have significant potential as disease specific biomarker; however there is no report to assess whether whole serum or exosome-derived miRNAs from serum is a more accurate diagnostic marker and indicator of tumor progression in CRC. This study aimed to evaluate the diagnostic value of serum and exosomal miRNAs for adenoma patients, respectively. Methods: Following a literature review, we investigated the expression of candidate miRNAs in 20 normal colonic mucosa, 27 adenoma, and 19 CRC tissue samples. Then, we quantified their expression in serum and in exosome from 26 adenoma patients and 47 healthy controls to evaluate their clinical significance. Additionally, we compared the expression levels of serum miRNAs with of exosomal miRNAs to investigate their potential as biomarker. Results: We selected four miRNAs, miR-21, miR-29a, miR-92a, and miR-135b, for further investigation. MiR-21, miR-29a, miR-92a, and miR-135b expression in adenoma were significantly higher than in normal colonic mucosa. Regarding the miRNAs expression in serum, miR-21, miR-29a, miR-92a levels in adenoma patients were significantly higher than in healthy controls, and significantly correlated with adenoma size and total adenoma counts in the colorectum. MiR-21, miR-29a and miR-92a levels in serum could significantly discriminate patients with adenoma, and in the patients with advanced adenoma (&amp;gt;1.0 cm), the capacity to discriminate advanced adenoma improved. On the other hand, exosomal miR-21 and miR-29a levels in serum from adenoma patients were significantly higher than that from healthy volunteer. Only exosomal miR-21 significantly correlated with adenoma size and total adenoma counts in the colorectum, and could differentiate patients with adenomas significantly. In the patients with advanced adenoma, the capacity of exosomal miR-21 for biomarker did not improve, and significance disappeared. Conclusion: Our results revealed that although both serum and exosomal miRNAs could be non-invasive biomarkers for the early detection of CRC, but exosomal miRNAs were unfavorable for the identification of high-risk adenomatous polyps. Serum miR-21, miR-29a and miR-92a are potential diagnostic biomarkers in high-risk adenomatous polyp patients. Citation Format: Ryo Uratani, Yuji Toiyama, Takahito Kitajima, Hiroyuki Fujikawa, Jyunichiro Hiro, Minako Kobayashi, Koji Tanaka, Yasuhiro Inoue, Yasuhiko Mohri, Takao Mori, Toshio Kato, Ajay Goel, Masato Kusunoki. Diagnostic potential of serum and exosomal microRNAs for patients with pre-malignant lesions of colorectal cancer: Detection of adenoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1952.

An Investigation of the Diagnostic Value of Serum D- Lactate Levels Measurement in Patient Suspected of Having Acute Appendicitis

An Investigation of the Diagnostic Value of Serum D- Lactate Levels Measurement in Patient Suspected of Having Acute Appendicitis