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Biomarkers of metal toxicity in embryos in the general population

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2019; 33 (8)

Background With the development of industrialization, public exposure to toxic metals could occur everywhere, eventually affecting individuals' reproductive systems and even embryos and leading to early pregnancy loss. The aim of the study was to determine the profile of toxic metal levels in pregnant women in the general population and to identify biomarkers for metal toxicity in embryos. Methods A case-control study with pregnant women was conducted at Peking Union Medical College Hospital in 2016-2018. Women who experienced spontaneous abortion within 12 weeks of gestation comprised the case group, and women with pregnancies showing fetal cardiac activity who requested an induced abortion almost simultaneously were included in the control group. Blood and urine specimen were tested for concentrations of cadmium, chromium, selenium, arsenic, and mercury. Results A total of 195 patients were enrolled, with 95 in the case group and 100 in the control group. Significant differences in gravidity, parity, history of miscarriage, mean blood cadmium levels, and mean urine chromium levels were present between the two groups (P1 = 0.013, P2 = 0.000, P3 = 0.000, P4 = 0.002, P5 = 0.046); the odds ratios in the spontaneous abortion with blood cadmium >0.4 mu g/L, urine chromium >2 mu g/L, gravity <3, parity <2, and history of miscarriage >1 compared with the induced abortion group were 1.26 (1.09, 1.85), 1.56 (1.23, 2.53), 1.39 (1.17, 1.98), 1.72 (1.21, 4.62), and 1.18 (1.06, 1.65), with P-values of 0.003, 0.031, 0.003, 0.247, and 0.001, respectively. Conclusion Blood cadmium and urine chromium levels are two possible biomarkers of toxic metal embryotoxicity in the general population, which means that in the general population, blood cadmium >0.4 mu g/L or urine chromium >2 mu g/L might indicate an increased risk of spontaneous abortion.

IF:1.73

Role of matrix metalloproteinase-9 gene polymorphisms in glaucoma: A hospital-based study in Chinese patients

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 0; ()

Background Glaucoma is the irreversible vision loss and contributes second leading cause of blindness worldwide. Matrix metalloproteinase-9 (MMP-9) is involved with remodeling and destruction of extracellular matrix. Elevated MMP-9 levels and various functional variants of MMP-9 have been associated with glaucoma in different population. In the current investigation, we tested association of MMP-9 common variants with different clinical categories of glaucoma in Chinese population. Materials and Methods We enrolled total of 396 glaucoma patients those reported to hospital comprising of 212 primary angle closure glaucoma (PACG) cases and 184 primary open-angle glaucoma POAG patients. In addition, 329 normal individuals from similar geographical areas were enrolled as healthy controls. Five common single nucleotide polymorphisms (rs3918242, rs3918254, rs2250889, rs3918249, and rs17576) were genotyped by PCR-RFLP. Plasma levels of MMP-9 were quantified by ELISA. Results Heterozygotes (GC) and allele "G" for rs2250889 polymorphism were more frequent in PACG cases compared with healthy controls (GC: P < .0001, OR = 2.26; G: P < .0001, OR = 1.19). Similarly, heterozygous mutant and minor allele for rs3918242 polymorphism were more prevalent in POAG in comparison with healthy controls. Interestingly, distribution of rs17576 variant was statistically higher in both PACG and POAG cases than healthy controls. Furthermore, analysis of plasma MMP-9 with MMP-9 polymorphisms revealed significant association of rs2250889, rs3918242, and rs17576 with plasma levels of the protein. Conclusions MMP-9 mutants are associated with elevated plasma MMP-9 and predisposed to development of glaucoma.

Expression profiling and bioinformatics analysis of circulating microRNAs in patients with acute myocardial infarction

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 0; ()

Objective Acute Myocardial Infarction (AMI) is the most severe type of coronary atherosclerotic heart diseases. MiRNA is a class of endogenous noncoding small molecule RNA, which plays an important regulatory role in the development of some diseases. Methods We examined the miRNA expression profiles in 16 patients with AMI compared with 6 non-AMI controls using RNA sequencing. Results Compared with the miRNA expression profiles of non-AMI controls, a total of 181 differentially expressed miRNAs were discriminated in AMI patients, of which 96 upregulated miRNAs and 85 downregulated miRNAs. The top ten upregulated miRNAs were as follows: miR-449a-5p, miR-126-5p, miR-93-5p, miR-199a-3p, miR-4454, miR-6880-3p, miR-3135a, miR-548ad-5p, miR-4508, and miR-556-5p; while the top ten downregulated were as follows: miR-6805-5p, miR-1228-5p, miR-939-5p, miR-615-3p, miR-6780a-5p, miR-6857-3p, miR-5088-55p, miR-7155-3p, miR-184, and miR-4525. And the qRT-PCR results of differentially expressed miRNAs showed the same result as high-throughput sequencing data. For these 181 differentially expressed miRNAs, 19 841 target genes were predicted by GO analysis. The enrichment analysis revealed 2061 involved in biological processes, 353 in molecular function and 303 in cellular components. To identify biological pathways in AMI as compared to non-AMI, the target genes of differentially expressed miRNAs were mapped to the classical signal transduction pathway in KEGG, indicating that 214 classes were enriched. ROC analysis showed that the circulating miRNAs had the important value for AMI diagnosis and supported the previous conclusions that circulating miRNAs were effective to diagnose the AMI as a novel biomarker. Conclusions Our findings require further research to confirm. It may provide a meaningful reference for the diagnosis and treatment of AMI.

Long noncoding RNA NEAT1 correlates with higher disease risk, worse disease condition, decreased miR-124 and miR-125a and predicts poor recurrence-free survival of acute ischemic stroke

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 0; ()

Objective This study aimed to investigate the predictive value of long noncoding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) for acute ischemic stroke (AIS) risk and to explore the correlation of lncRNA NEAT1 with disease severity, inflammation, recurrence and target microRNAs in patients with AIS. Methods 210 patients with AIS and 210 controls were enrolled, and their peripheral blood samples were collected within 24 hours after admission and collected on the enrollment, respectively. lncRNA NEAT1 expression was detected by quantitative polymerase chain reaction (qPCR). For patients with AIS, disease severity was evaluated by National Institute of Health Stroke Scale (NIHSS) score; plasma concentrations of inflammatory factors and lncRNA NEAT1 target microRNAs were measured by enzyme-linked immune sorbent assay and qPCR, respectively; stroke recurrence and death were recorded; and recurrence-free survival (RFS) was calculated. Results lncRNA NEAT1 expression was elevated in patients with AIS compared with controls, and it had a good predictive value for AIS risk (area under the curve [AUC]: 0.804 [95% confidence interval [CI]: 0.763-0.845]). In patients with AIS, lncRNA NEAT1 expression positively correlated with NIHSS score and inflammatory factor levels including C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and IL-22, while it negatively correlated with anti-inflammatory cytokine IL-10 level. Besides, lncRNA NEAT1 predicted increased recurrence/death risk (AUC: 0.641 [95% CI: 0.541-0.741]), and its high expression correlated with worse RFS. Additionally, lncRNA NEAT1 expression negatively correlated with microRNA-124 and microRNA-125a expressions. Conclusion LncRNA NEAT1 may serve as a novel biomarker for assisting AIS management and prognosis.

Epidemiological investigation and antimicrobial susceptibility analysis of mycoplasma in patients with genital manifestations

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 0; ()

Background The aim of this study was to investigate the infection and antimicrobial resistance of Ureaplasma urealyticum and Mycoplasma hominis in patients with genitourinary symptoms among Hakka population in Meizhou, China. Methods A total of 12 633 females and 3315 males who presented urogenital symptoms and were subjected to mycoplasma tests from 2014 to 2018 were enrolled in this study. The mycoplasma detection and antimicrobial susceptibility were tested using the Mycoplasma ID/AST kit. Results The total incidence of mycoplasma infection, as well as the incidence of U urealyticum in Hakka population was annually increasing from 2014 to 2018. The total incidences and U urealyticum infection were more prevalent in females than males. Higher positive rate of mycoplasmas infection was observed in women aged 16-20 (50.9%) and men aged 26-30 (25.4%). The occurrence of antimicrobial resistance of mycoplasma to antibacterial agents remained relatively similar in the past five years. Ureaplasma urealyticum infection, M hominis infection, and co-infection of resistance to levofloxacin, erythromycin, ciprofloxacin, ofloxacin, roxithromycin, azithromycin, clarithromycin, and sparfloxacin were dramatically higher in females than in males. Conclusion Our findings indicate a high burden of mycoplasmas infection and antimicrobial resistance of mycoplasmas infection among females, and josamycin and minocycline may be recommended as the primary choice in clinical treatment of anti-mycoplasmas.

Identification of long non-coding RNA MVIH as a prognostic marker and therapeutic target in acute myeloid leukemia

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 0; ()

Background This study aimed to investigate the correlation of long non-coding RNA microvascular invasion in hepatocellular carcinoma (lncRNA MVIH) with disease risk, disease conditions, and prognosis of acute myeloid leukemia (AML), and also to investigate the influence of lncRNA MVIH on AML cell activities in vitro. Methods A total of 212 AML patients and 70 controls were consecutively recruited. Their bone marrow mononuclear cells (BMMCs) were isolated, and lncRNA MVIH was detected by reverse transcription quantitative-polymerase chain reaction. In AML patients, complete remission (CR), event-free survival (EFS), and overall survival (OS) were assessed. In vitro, lncRNA MVIH expression in AML cell lines was determined, and the effect of lncRNA MVIH on AML cell proliferation and apoptosis was assessed. Results LncRNA MVIH expression was increased in AML patients compared to controls, and receiver operating characteristic curve showed that lncRNA MVIH predicted elevated AML risk (area under curve: 0.742 [95% CI: 0.674-0.810]). In AML patients, no correlation of lncRNA MVIH expression with French-American-British classification was observed, while lncRNA MVIH high expression correlated with worse risk stratification. Moreover, lncRNA MVIH expression negatively correlated with CR achievement, EFS and OS. In vitro, lncRNA MVIH was overexpressed in AML cell lines (KG-1, ME-1, and HT-93) compared to normal BMMCs. Furthermore, lncRNA MVIH downregulation reduced KG-1 cell proliferation but increased apoptosis, whereas lncRNA MVIH upregulation raised HL-60 cell proliferation but decreased apoptosis. Conclusion LncRNA MVIH may not only serve as a prognostic marker but also act as a therapeutic target in AML.

Evaluation of an optimized method to directly identify bacteria from positive blood cultures using MALDI-TOF mass spectrometry

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 0; ()

Background Although various methods have been developed to directly identify bacteria from positive blood cultures by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), the necessity of using commercial kits still leads to a high cost and long assay time. Moreover, few evaluations of these methods have been conducted. This study aimed to evaluate the feasibility of an optimized MALDI-TOF MS method for direct identification of bacteria in positive blood cultures. Methods A total of 829 non-repeated positive cultures were collected from July 2018 to August 2019, and direct identification was performed by an optimized MALDI-TOF MS method. The same positive blood cultures were sub-cultivated to obtain a single bacterial colony and identified by classical biochemical BD testing, which is the gold standard to compare the accuracy of direct identification of positive blood cultures by MALDI-TOF MS. Results After excluding 7 false-positive samples from the 829 positive blood cultures, the most accurate rate of direct identification by this optimized MALDI-TOF MS method was for gram-negative bacteria (91.5%), followed by gram-positive bacteria (88.3%), fungi (84.8%), anaerobic bacteria (80%), and other rare bacteria (66.67%). Conclusion Common bacteria in positive blood cultures can be identified directly within 1 hour by MALDI-TOF MS, and thus, this optimized method can be used as a primary identification method by clinicians. Routine implementation of this method may significantly increase the optimal utilization rate of antibiotics and decrease mortality in bacteremia patients.

Distribution of serum amyloid A and establishment of reference intervals in healthy adults

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 0; ()

BackgroundSerum amyloid A (SAA) plays a critical role in acute or chronic and is used in clinical laboratories as an indicator of inflammation. The elevated SAA is closely related to inflammation-mediated diseases, such as liver diseases, autoimmune diseases, metabolism-related diseases, amyloidosis, and tumors. However, there is no unified population reference interval for SAA. This study aimed to investigate the distribution of SAA in healthy Chinese adults 20-79 years of age and to establish its population reference interval. MethodsA total of 2365 healthy subjects met the requirements of this study. The levels of SAA were detected using an AU5821 automatic biochemical analyzer and its original reagents. According to the recommended methods of CLSI C28-A3 and WS/T 402-2012, the population reference interval of SAA was established using the unilateral 95th percentile (P-95), and the 90% confidence interval of upper limits was calculated. ResultsThe distributions of SAA levels were not significantly different between sexes (P> .05) and also did not differ by age (P> .05). Therefore, the population reference interval for SAA was established as an upper limit of 11.0 mg/L (90% confidence interval: 9.3-12.3 mg/L) by using the method of latex immunoturbidimetry. ConclusionsSerum amyloid A is closely related to the occurrence and progression of various diseases. The preliminary establishment of a population reference interval for SAA can fully exert its potential clinical value.

Correlation of pre-operative circulating inflammatory cytokines with restenosis and rapid angiographic stenotic progression risk in coronary artery disease patients underwent percutaneous coronary intervention with drug-eluting stents

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 0; ()

Background This study aimed to explore the associations of common inflammatory cytokine levels with restenosis and rapid angiographic stenotic progression (RASP) risk in coronary artery disease (CAD) patients underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods Two hundred and ten CAD patients underwent PCI with DES were consecutively recruited, then pre-operative serum levels of TNF-alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-21, and IL-23 were determined by ELISA. The 12-month in-stent restenosis and RASP of non-intervened lesion were assessed by quantitative coronary angiography analysis. Results The pre-operative TNF-alpha, IL-6, IL-17A, and IL-23 expressions were increased while IL-4 expression was decreased in restenosis patients compared with non-restenosis patients. Further analysis revealed that IL-6, IL-8, hypercholesteremia, diabetes mellitus, and HsCRP could independently predict restenosis risk, and subsequent ROC curve revealed that their combination was able to differentiate restenosis patients from non-restenosis patients with an AUC of 0.951 (95%CI: 0.925-0.978). Meanwhile, the pre-operative TNF-alpha, IL-6, IL-17A, IL-21, and IL-23 expressions were increased whereas IL-4 level was decreased in RASP patients compared with non-RASP patients. Further analysis revealed that TNF-alpha, IL-6, IL-23, hypercholesteremia, SUA, HsCRP, and multivessel artery lesions could independently predict RASP risk, and subsequent ROC curve disclosed that their combination could discriminate RASP patients from non-RASP patients with an AUC of 0.886 (95%CI: 0.841-0.931). Conclusions This study unveils the potentiality of pre-operative circulating inflammatory cytokines as markers for predicting restenosis and RASP risk in CAD patients underwent PCI with DES.

Association of HLA-DQA1 gene polymorphisms with the risk of children primary nephrotic syndrome in Chinese population

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2019; 33 (1)

Background The association between gene polymorphisms and the risk of primary nephrotic syndrome (PNS) is uncovering recently. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on HLA-DQA1 gene and the risk of PNS. Methods In this study, we genotyped eight single nucleotide polymorphisms (SNPs) in the HLA-DQA1 gene in 501 PNS patients and 532 healthy people in Chinese population. Then we analyzed associations of these SNPs with the clinical features in primary nephrotic syndrome of children in Chinese population. Results Significant associations with PNS were found on missense SNP rs1129740 (GG vs AA, odds ratio (OR) = 1.987, 95% confidence interval (CI) = 1.468-2.652, P = 0.00177049) and rs1047992 (AA vs GG, OR = 1.857, 95% CI = 1.325-2.391, P = 1.1073E-10) of the HLA-DQA1 gene. Conclusions This work suggests SNPs of HLA-DQA1 are risk factors for PNS in Chinese population, which implies roles of immune response in the pathogenesis of PNS.

IF:1.73

Influenza A virus inhibits influenza virus replication by inducing IL-37

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2019; 33 (1)

Backgrounds The influenza virus is one of the major pathogens that seriously affect human health. It can cause a strong immune response and trigger a series of complications. Interleukin 37 (IL-37) is a newly discovered cytokine that plays an important regulatory role in infection and immunity. To date, there have been few studies on the correlation between influenza virus infection and IL-37. Methods Serum levels of IL-37 in 115 patients with influenza A virus (IAV) infection and 102 healthy subjects were measured by an enzyme-linked immunosorbent assay (ELISA). Real-time quantitative PCR (RT-qPCR) was used to detect differences in IL-37 expression in peripheral blood mononuclear cells (PBMCs) between IAV patients and healthy subjects. IL-37 expression was measured in A549 cells and PBMCs infected with IAV H3N2 using ELISA and RT-qPCR. After the H3N2-infected A549 cells were treated with human IL-37, the concentration of viral RNA was determined using RT-qPCR, and the titer of influenza virus was determined by a hemagglutination test. Results The IL-37 levels in the sera and PBMCs of patients infected with IAV were higher than those of healthy subjects. The expression of IL-37 mRNA and protein in IAV-infected A549 cells and PBMCs was upregulated, and IL-37 protein was able to inhibit the replication of IAV RNA. Conclusion IAV-induced IL-37 expression inhibits IAV replication.

IF:1.73

D-dimer level in liver transplant recipients on the first day after surgery is correlated with postoperative thrombosis recurrence

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2019; 33 (1)

Objective This study aimed to investigate the relationship between plasma D-dimer level, preoperative complications, and thrombosis in liver transplant recipients. Methods The clinical data of 525 liver transplant recipients with end-stage liver disease (ESLD) in the First Affiliated Hospital of Zhejiang University from October 2012 to December 2015 were retrospectively analyzed. The patients were grouped based on thrombosis before and after surgery to determine the risk factors for postoperative thrombosis recurrence. Results Of the preoperative complications assessed, esophageal varices and thrombosis were significantly correlated (P = 0.000); ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy were significantly correlated with preoperative D-dimer level (P < 0.001, P < 0.001, and P = 0.002, respectively); during the first week after surgery, the D-dimer level was significantly and consecutively higher than that before surgery and was significantly higher in the group with both preoperative and postoperative thrombosis than in the other groups on the first day after surgery (P < 0.001); the area under the curve (AUC) for diagnosis of postoperative thrombosis recurrence in the preoperative thrombosis group using plasma D-dimer level on the first day after surgery was 0.698 (P = 0.001); Cox regression analysis showed that D-dimer was an independent risk factor for postoperative thrombosis recurrence (HR = 3.062, P = 0.029). Conclusion D-dimer level on the first day after liver transplant is related to thrombosis recurrence and is an independent risk factor for postoperative thrombosis recurrence.

IF:1.73

Influence of lag length on repetition priming in emotional stimuli: ERP evidence

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2019; 33 (1)

Background Previous studies have demonstrated both behavioral and neural evidence for the potential mediations of lag length and pre-existing memory representation on repetition priming. However, such mediations on emotional stimuli have not been described. Methods The current experiment intended to disentangle lag length from pre-existing memory representation. A lexical decision task was performed, in which different emotional characters (either normal or transposed) were re-presented either immediately or delayed. Results In immediate repetition, one early and two late (ie, N400 and late positive complex) repetition-related event-related potential (ERP) effects were elicited, but these were not sensitive to pre-existing memory representation. The delayed repetition case merely observed the N400. Conclusion These results suggest that the repetition-related priming effect is neutrally sensitive to lag length. Emotional information potentially exerts early and later influences in the processing underlying stimuli memory.

IF:1.73

Neutrophil-to-C3 ratio and neutrophil-to-lymphocyte ratio were associated with disease activity in patients with systemic lupus erythematosus

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2019; 33 (1)

Background Systemic lupus erythematosus is prone to recurrent attacks, and its treatment is related to disease activities. It is important to accurately assess the patient's disease activity. So, the purpose of this study was to investigate the relation between neutrophil-to-C-3 ratio (NC3R), neutrophil-to-lymphocyte ratio (NLR), and disease activity in patients with Systemic lupus erythematosus (SLE). Methods This was a retrospective study. One hundred and ninety-four patients with SLE and 71 healthy controls were included in this study. We divided the patients into two groups according to the SLE disease activity (SLEDAI). Group 1 included patients with a score of >9 (patients with severe disease activity), and Group 2 included patients with a score of 9 and lower (patients with mild disease activity). Correlations between NC3R, NLR, and disease activity were analyzed. Results NC3R and NLR in patients with SLE were obviously higher compared to healthy controls (P < 0.05). There was an obviously significant difference in NC3R and NLR between Group 1 and Group 2 (P < 0.05). SLEDAI scores were positively correlated with NC3R (r = 0.353, P < 0.01) and NLR (r = 0.237, P = 0.01). Receiver operating characteristic (ROC) curve analysis showed that the cutoff value of NC3R to identify SLE with high disease activity was 5.935, with sensitivity and specificity being 75.9% and 67.0%, while that of NLR was 2.293, with sensitivity being 68.9% and specificity being 82.8%. Conclusion NC3R and NLR are two useful inflammatory markers for evaluating disease activity in patients with SLE.

IF:1.73

Tumor suppression effect of targeting periostin with siRNA in a nude mouse model of human laryngeal squamous cell carcinoma

期刊: JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2019; 33 (1)

Background The incidence of laryngeal carcinoma is increasing, however, the mechanism is not fully understood. We aimed to investigate the efficacy of periostin gene silencing by siRNA on tumor inhibition, in a novel nude mouse model of human laryngeal squamous cell carcinoma, and to explore possible inhibitory mechanisms. Methods Tumors were established in nude mice by transplantation of LSCC AMC-HN-8 cell line. Forty-eight nude mice were randomly divided into groups of eight each, and treated with high (1.0 OD) or low (0.5 OD) doses of periostin-siRNA or appropriate control solutions. Tumor growth was observed and used to calculate an inhibition rate (%). Routine pathological and electron microscopic examination were used to determine tumor apoptosis and proliferation. Changes in periostin mRNA and protein levels were analyzed. Results Tumor growth was significantly inhibited in mice treated by high dose periostin-siRNA compared to untreated and those treated with low dose periostin-siRNA (P < 0.05). Pathological examination showed increased tumor necrosis and apoptotic changes in treated mice, which was confirmed by electron microscopy. Periostin mRNA and protein expression were significantly reduced in tumors from mice treated with high dose periostin-siRNA, compared to controls and low-dose periostin-siRNA treatment groups (P < 0.05). Conclusion Periostin silencing was associated with growth inhibition of tumor cells in a nude mouse model of LSCC. The underlying mechanism may be due to receptor-mediated induction of relevant signal transduction pathways that modulate the microenvironment needed for cancer cell survival. Periostin is expected to become a new target for cancer therapy.

IF:1.73

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