The Value of Circulating microRNAs for Diagnosis and Prediction of Preeclampsia: a Meta-analysis and Systematic Review.

Preeclampsia (PE) is one of the main causes of maternal death worldwide, but our understanding of the molecular characteristics of disease progression is limited. In this meta-analysis, we aimed to assess the value of peripheral blood microRNAs (miRNAs) as diagnostic and predictive markers of PE. We screened PubMed, Web of Science, and Embase databases; searched articles about "miRNAs and PE" up to November 30, 2020; and conducted biological information and subgroup analysis. We used QUADAS-2 (quality assessment of diagnostic accuracy studies-2) to evaluate the included articles by two independent reviewers, calculated the combined diagnostic and predictive indicators using the random effects model, explored the sources of potential heterogeneity through subgroup analysis, and evaluated publication bias using Deeks' funnel plot asymmetry test using Stata 14.0 and Review Manager 5.3 software. Forty-three miRNAs from 15 studies, including 2042 healthy controls and 2685 PE patients, had a pooled sensitivity of 0.86 (95% CI: 0.81-0.90), specificity of 0.89 (95% CI: 0.85-0.92), and an AUC of 0.94 (95% CI: 0.91-0.96). Moreover, before 20 weeks of gestation, the combined sensitivity was 0.86 (95% CI: 0.75-0.92), and the specificity was 0.90 (95% CI: 0.83-0.95), which indicated that some of the circulating miRNAs had changed significantly before the clinical symptoms appeared in PE patients. Circulating miRNAs have high diagnostic and predictive accuracy and may be used as non-invasive biomarkers for the diagnosis and prediction of PE. However, a large sample prospective study is still needed.

Application of Capillary Electrophoresis in Monoclonal Gammopathies and the Cutoff Value of Monoclonal Protein in Differential Diagnosis of Multiple Myeloma and Other Monoclonal Gammopathies.

OBJECTIVE: Monoclonal protein (MP) exists in various diseases, and capillary electrophoresis (CE) has been widely used to detect MP. However, there is not much research on the application value of MP in the differential diagnosis of monoclonal gammopathies. This study aimed to explore MP's cutoff value for the differential diagnosis of multiple myeloma (MM) and other monoclonal gammopathies (MGs). METHODS: A retrospective analysis of 8167 cases was conducted. Serum MP was detected by CE, and the patients' clinical information was collected from the clinical database of our hospital. RESULTS: 985 cases had MP with high peaks, and 91.1% were diagnosed with malignant diseases. The MP showed small peaks in 471 cases, and only 24.4% were diagnosed with malignant diseases. Among the MPs, the IgG-κ type was the most common type, followed by the IgG-λ, IgA-κ, IgA-λ, free λ light chain, IgM-κ, free κ light chain, double clone, and IgM-λ types. Differences in the MP of the IgG, IgA, IgM, and FLC types between the MM group and MGUS group were statistically different (P<0.01). The MP of the IgG, IgA, and FLC types showed clear specificity and sensitivity in discriminating MM from other monoclonal gammopathies in ROC curve analysis. Serum IgM had statistical significance in the differential diagnosis between WM and other MGs (P<0.01). However, there was no statistical significance in the differential diagnosis between MM and other MGs (P=0.140). The cutoff values of the MP of the IgG, IgA, and FLC types were >18.67g/L, >13.86g/L, and >10.15g/L, respectively, for the differential diagnosis of MM and other MGs. The cutoff value of the MP of IgM for the WM diagnosis was >37.75 g/L. CONCLUSION: CE has good clinical application value in the diagnosis of monoclonal gammopathies, and MP can be used in the differential diagnosis of MM and other monoclonal gammopathies.

The NLRP3 rs10754558 polymorphism is a risk factor for preeclampsia in a Chinese Han population.

OBJECTIVE: Previous studies have indicated that the nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3) inflammasome is activated by monosodium urate in the trophoblast of preeclampsia (PE) patients, leading to augmented placental IL-1ß levels. Thus, the purpose of our study was to investigate the association between NLRP3 polymorphisms, rs10754558 and rs2027432, and PE in Chinese Han population. METHODS: The NLRP3 polymorphisms, rs10754558 and rs2027432, were genotyped by real-time PCR in 1024 PE patients and 1194 control subjects. A χ2 test was used to compare the genetic distribution between the two groups, and an analysis of variance was used to conduct the genotype-phenotype analysis. RESULTS: We demonstrated a significant difference in genotypic frequency of the rs10754558 (χ2 = 9.97, p = .007) in NLRP3 between PE patients and controls. Additionally, there was a significant difference between cases and controls in the dominant model of G allele (χ2 = 7.70, p = .006, odds ratio =0.77, 95%confidence interval 0.64-0.93). What's more, the genotypes distributions of rs10754558 were found to be associated with both the severe and late onset PE. (χ2 = 8.53 p = .01, χ2 = 9.24, p = .01.) However, no significant statistic differences were found in the genotypic distributions and allelic frequencies for rs2027432 between two groups (for genotypic distribution, χ2 = 0.17, p = .92; for allelic frequency, χ2 = 2.26, p = .13, odds ratio =0.90, 95% confidence interval 0.79-1.03). CONCLUSIONS: Our results reveal that NLRP3 may be involved in the development of PE in a Chinese Han population. However, further validation of the associations of other NLRP3 SNPs with PE in other populations is required.

MiRNA-134 suppresses esophageal squamous cell carcinoma progression by targeting FOXM1.

Previous studies showed that the dysregulation of miRNAs was closely associated with cancer progression. The aim of this study was to verify whether miR-134, miR-10a, miR-29c, miR-942, miR-93, and miR-218 could inhibit esophageal squamous cell carcinoma (ESCC) cell invasion and migration. ESCC tissue and normal esophageal tissue adjacent to carcinoma from patients (54 cases) undergoing surgery were collected. RT-PCR was used to test the expression of miR-134, miR-10a, miR-29c, miR-942, miR-93, and miR-218 in these tissues. In addition, western blot was applied to test the expression of MMP-2, MMP-9, COL1A1, COL1A5 and FOXM1. In the vitro experiment, EC9706 cells were transfected with miR-134 mimics, then wound healing was employed to test the migratory ability of EC9706 cells. Transwell chambers was used to test the invasion ability of cells. The expression of MMP-2, MMP-9, COL1A1, COL1A5, and FOXM1 waas detected by western blot. In order to confirm whether FOXM1-3'-UTR was the target gene of miR-134, we performed a luciferase assay. FOXM1 over-expression plasmid was transfected to further confirm miR-134 played its role by targeting FOXM1. Our results showed that the expression of miR-134 was decreased in the ESCC tissue compared with normal esophageal tissue, (P<0.01), but the expression of MMP-2, MMP-9, COL1A1, COL1A5 and FOXM1 were significantly increased (P<0.01). In an in vitro experiment, compared with the mimic control, the expression of MMP-2, MMP-9, COL1A1, COL1A5 and FOXM1 were decreased in the miR-134 mimic-transfected EC9706 cells (P<0.01). The migration and invasion activity of EC9706 cells was also decreased after transfection with miR-134 mimics (P<0.01). The luciferase activity of the FOXM1-3'-UTR plasmid was significantly suppressed by miR-134 (P<0.01). Overexpression of FOXM1 abrogated miR-134-mediated inhibition of EC9706 cell migration and invasion. In conclusion, miR-134 inhibited EC9706 cell migration and invasion by targeting FOXM1. miR-134 may be a novel treatment target for ESCC.

Dimethylarginine Dimethylaminohydrolase 2 (DDAH 2) Gene Polymorphism, Asymmetric Dimethylarginine (ADMA) Concentrations, and Risk of Coronary Artery Disease: A Case-Control Study.

Asymmetric dimethylarginine (ADMA) has been shown to be an independent predictor of cardiovascular diseases. Dimethylarginine dimethylaminohydrolase 2 (DDAH 2) promotes the metabolism of ADMA and plays a key role in the regulation of acute inflammatory response. With the present study, we investigated the relationship between DDAH 2 polymorphisms and risk of coronary artery disease (CAD) and its association to plasma ADMA concentrations. We used the haplotype-tagging SNP approach to identify tag SNPs in DDAH 2. The SNPs were genotyped by PCR and sequenced in 385 CAD patients and 353 healthy controls. Plasma concentrations of ADMA were determined using enzyme-linked immunosorbent assay (ELISA). A promoter polymorphism -449C/G (rs805305) in DDAH 2 was identified. Compared with the ADMA concentrations in CC genotype (0.328 ± 0.077 µmol/l), ADMA concentrations in CG + GG genotype were significantly increased (0.517 ± 0.090 µmol/l, P < 0.001). No significant associations between the -449C/G and risk of CAD were detected in the genetic models. The results of this study suggest that Genetic -499C/G polymorphism in DDAH 2 gene may affect the plasma ADMA concentrations in patients with CAD. However, it does not indicate a novel genetic risk marker for CAD.

Investigation of a Possible Role for the Histidine Decarboxylase Gene in Tourette Syndrome in the Chinese Han Population: A Family-Based Study.

Tourette syndrome (TS) is a polygenic neuropsychiatric disease. Previous studies have indicated that dysregulation in the histaminergic system may play a crucial role in disease onset. In this study, we investigated the role of the histidine decarboxylase gene (HDC) in TS susceptibility in the Chinese Han population. After genotyping 241 TS nuclear families trios, we analyzed three tag HDC single nucleotide polymorphisms (rs854150, rs854151, and rs854157) in a family-based study using the transmission disequilibrium test (TDT) and haplotype relative risk (HRR). TDT showed no over-transmission in these SNPs across the HDC region (for rs854150: χ2 = 0.472, P = 0.537, OR = 1.097, 95%CI = 0.738-1.630; for rs854151: χ2 = 0.043, P = 0.889, OR = 1.145, 95%CI = 0.767-1.709; for rs854157:χ2 = 0.984, P = 0.367, OR = 1.020, 95%CI = 0.508-2.049). HRR also showed the same tendency (for rs854150: χ2 = 0.211, P = 0.646, OR = 1.088, 95%CI = 0.759-1.559; for rs854151: χ2 = 0.134, P = 0.714, OR = 0.935, 95%CI = 0.653-1.339; for rs854157:χ2 = 0.841, P = 0.359, OR = 1.206, 95%CI = 0.808-1.799). Additionally, the haplotype-based haplotype relative risk showed a negative association. Although these findings indicate an unlikely association between HDC and TS in the Chinese Han population, a potential role for HDC cannot be ruled out in TS etiology. Future research should investigate this more thoroughly using different populations and larger samples.

Lack of genetic association of 5-HTR2A 102 T/C and -1438A/G polymorphisms with Tourette syndrome in a family-based association study in a Chinese Han population.

INTRODUCTION: Our purpose is to investigate whether polymorphisms of 102 T/C and -1438A/G in 5HTR2A are associated with Tourette syndrome (TS) in Chinese Han population. METHODS: A total of 178 TS trios were recruited in this study. After the allelic and genotypic distributions of two polymorphisms were genotyped using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), we compared their genetic distributions with what is expected with Hardy-Weinberg to explore whether there might be an association of these polymorphisms with TS by haplotype relative risk (HRR) and transmission disequilibrium test (TDT) statistics. RESULTS: Our results showed that no significant associations were found between the HTR2A 102 T/C and -1438A/G polymorphisms and TS (for HTR2A 102 T/C: TDT = 2.041, df = 1, P = 0.175; HRR = 1.468, χ(2) = 1.905, P = 0.168, 95% confidence interval: 0.850-2.535; for HTR2A: -1438A/G, TDT = 0.093, df = 1, P = 0.819; HRR = 0.965, χ(2) = 0.018, P = 0.894, 95% confidence interval: 0.574-1.624). DISCUSSION: Our study suggested that the HTR2A 102T/C and -1438A/G polymorphisms may not be associated with susceptibility to TS, and thus do not play a major role in the development of TS in the Chinese Han population. However, these results need to be confirmed in a larger sample collected from different populations.

Prognostic significance of CD44V6 expression in osteosarcoma: a meta-analysis.

Numerous individual studies evaluating the relationship between CD44V6 over-expression and prognostic impact in patients with osteosarcoma (OS) have yielded in conclusive results. This meta-analysis aimed to determine the value of cell adhesion molecule CD44V6 in prognosis of OS by conducting a systematic review and meta-analysis. A comprehensive search was conducted using PubMed (medline), Embase, ISI Web of Knowledge, Springer, the Cochrane Library, Scopus, BioMed Central, ScienceDirect, Wanfang, Weipu, and China National Knowledge Internet (CNKI) databases from inception through May 26, 2015. All available articles written in English or Chinese that investigated the expression of CD44V6 and the prognosis of OS were included. The quantity of the studies was evaluated according to the critical review checklist of the Dutch Cochrane Centre proposed by MOOSE. Finally, a total of eight studies with 486 OS patients were involved and the results indicated that the positive expression of CD44V6 predicts neoplasm metastasis (RR = 1.76, 95 % CI 1.38-2.25, p < 0.00001), and poor survival in OS with the pooled HR of 1.53 (95 % CI 1.25-1.88, p < 0.0001). No significant heterogeneity was observed among all studies. In conclusion, the present meta-analysis and systematic review strongly suggest that CD44V6 over-expression is associated with overall survival rate and metastasis in OS, and may be used as a prognostic biomarker to guide the clinical therapy for OS.

Family-based association study between monoamine oxidase A (MAOA) gene promoter VNTR polymorphism and Tourette's syndrome in Chinese Han population.

To clarify the association of monoamine oxidase A- variable number of tandem repeat (MAOA-pVNTR) with susceptibility to Tourette's syndrome (TS) in Chinese Han population we discuss the genetic contribution of MAOA-VNTR in 141 TS patients including all their parents in Chinese Han population using transmission disequilibrium test (TDT) design. Our results revealed that no significant association was found in the MAOA gene promoter VNTR polymorphism and TS in Chinese Han population (TDT = 1.515, df = 1, p > 0.05). The negative result may be mainly due to the small sample size, but we don't deny the role of gene coding serotonergic or monoaminergic structures in the etiology of TS.