Reference Intervals of Thyroid Hormones During Pregnancy Established by Three Statistical Methods.

BACKGROUND: Monitoring the thyroid hormones during pregnancy is of great importance for fetal growth and development. Throughout the whole pregnancy, there is constant fluctuation in the thyroid hormone reference intervals (RIs). The purpose of this study is to determine method- and trimester-specific RIs for thyroid-stimulating hormone, free thyroxine, and free triiodothyronine in pregnant women in China. METHODS: In this study, 2,167 women with normal pregnancies (first trimester, n = 299; second trimester, n = 1,032; third trimester, n = 836) and 4,231 healthy nonpregnant women subjects were recruited. Serum thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) concentrations were measured using electrochemiluminescence immunoassays in Abbott Alinity i analyzer. Following the exclusion of outliers, the RIs were determined using three statistical techniques: the non-parametric method, the Hoffmann method, and the Q-Q plot method. RESULTS: Pregnant women's levels of these three thyroid hormones differ markedly from those of healthy non-pregnant women. In addition, the concentrations of these three hormones change considerably over the course of the three phases of pregnancy. The Q-Q plot method offered more comparable RIs with the non-parametric method in healthy non-pregnant women than the Hoffmann method. Three statistical techniques were used to construct the trimester-specific RIs of thyroid hormones in pregnant women, and there was little difference between them all. The RIs by the non-parametric and Q-Q plot methods indicated closer RIs, and the RIs by the Hoffmann approach were higher and wider than those by the other two methods. CONCLUSIONS: For thyroid hormones, trimester-specific RIs are required. The RIs determined by non-parametric and Q⁃Q plot indirect calculation could be used as the alternative method.

Identification and validation of a metabolism-related gene signature for the prognosis of colorectal cancer: a multicenter cohort study.

OBJECTIVE: Cell metabolism plays a vital role in the proliferation, metastasis and sensitivity to chemotherapy drugs of colorectal cancer. The purpose of this multicenter cohort study is to investigate the potential genes indicating clinical outcomes in colorectal cancer patients. METHODS: We analyzed gene expression profiles of colorectal cancer to identify differentially expressed genes then used these differentially expressed genes to construct prognostic signature based on the least absolute shrink-age and selection operator Cox regression model. In addition, the multi-gene signature was validated in independent datasets including our multicenter cohort. Finally, nomograms were set up to evaluate the prognosis of colorectal cancer patients. RESULTS: Seventeen metabolism-related genes were determined in the least absolute shrink-age and selection operator model to construct signature, with area under receiver operating characteristic curve for relapse-free survival, 0.741, 0.755 and 0.732 at 1, 3 and 5 year, respectively. External validation datasets, GSE14333, GSE37892, GSE17538 and the Cancer Genome Atlas cohorts, were analyzed and stratified, indicating that the metabolism-related signature was reliable in discriminating high- and low-risk colorectal cancer patients. Area under receiver operating characteristic curves for relapse-free survival in our multicenter validation cohort were 0.801, 0.819 and 0.857 at 1, 3 and 5 year, respectively. Nomograms incorporating the genetic biomarkers and clinical pathological features were set up, which yielded good discrimination and calibration in the prediction of prognosis for colorectal cancer patients. CONCLUSION: An original metabolism-related signature was developed as a predictive model for the prognosis of colorectal cancer patients. A nomogram based on the signature was advantageous to facilitate personalized counselling and treatment of colorectal cancer patients.

Positive Relationship of RDW with NT-proBNP and cTnI in Acute Myocardial Infarction Patients.

BACKGROUND: The goal of the study was to investigate the relationship of several parameters of complete blood count (CBC) with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in a cohort of acute myocardial infarction (AMI) patients. METHODS: One hundred and one AMI patients were analyzed in this retrospective study. CBC, serum NT-proBNP, and cTnI levels were detected at the time of admission and on the day before or the day of discharge. The correlation between CBC with NT-proBNP and cTnI was analyzed. RESULTS: In this study, we found that red cell distribution width (RDW), red cell distribution width - coefficient of variation (RDW-CV), monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), NT-proBNP, and cTnI were significantly higher in AMI patients on the day of admission than the day before or the day of discharge. RDW and RDW-CV were significantly related with serum NT-proBNP and cTnI levels both at the time of admission and the day before or the day of discharge. CONCLUSIONS: RDW and RDW-CV were changed dramatically and synchronized with serum NT-proBNP and cTnI levels after the recovery. These results suggested that RDW and RDW-CV could be used as simple and convenient indicators to assess the condition of AMI patients.

Expression of GSK3ß, PICK1, NEFL, C4, NKCC1 and Synaptophysin in peripheral blood mononuclear cells of the first-episode schizophrenia patients.

Schizophrenia (SZ) is a severe neurodevelopmental disease with unknown pathogenic mechanisms characterized with impaired cognitive function. The disturbed synaptic plasticity and synaptic loss have been widely reported in SZ. In this study, 41 first-episode schizophrenia (FES) patients and 44 healthy controls (HC) were recruited and the expression of six genes commonly relevant to synaptic functions was examined in the peripheral blood mononuclear cells (PBMCs). These genes were glycogen synthase kinase 3ß (GSK3ß), protein interacting with C-kinase 1 (PICK1), synaptophysin (SYP), neurofilament light (NEFL), complement component 4 (C4) and Na+-K--2Cl- cotransporter 1 (NKCC1). Real-time quantitative polymerase chain reaction (qPCR) was performed to determine the quantity of individual mRNA template. Compared to HC, the expression of PICK1 and NKCC1 genes in FES patients was relatively lower whereas the expression of NEFL was higher. No difference for the mRNA expression of GSK3ß, SYP and C4 genes was detected between FES patients and HC, nor was the gender difference; Interestingly, the mRNA expression of PICK1 in female FES patients was significantly decreased compared to female HC, but not in males; and the NEFL gene was up-regulated in male FES patients but not in females. Our findings support an abnormal expression profile of synapse-related genes in the PBMCs of FES patients.

Altered Expression of Glucocorticoid Receptor and Neuron-Specific Enolase mRNA in Peripheral Blood in First-Episode Schizophrenia and Chronic Schizophrenia.

INTRODUCTION: It is well-known that altered hypothalamus-pituitary-adrenal (HPA) axis process has an important role in the neurodegenerative process in schizophrenia (SZ). However, this neurodegenerative mechanism has not been clarified in SZ. Therefore, the main purpose of this study was to determine HPA axis damage in the first-episode, unmedicated schizophrenia (FES) patients and chronic schizophrenia (CSZ) patients in comparison with healthy controls (HC) by means of quantitative analysis of the peripheral blood mRNA expression of glucocorticoid receptor (GR), GR transcripts containing exons 1B (GR-1B), and neuron specific enolase (NSE) genes and serum cortisol and NSE, a specific serum marker for neuronal damage. METHODS: In the present study, 43 FES patients, 39 CSZ, and 47 HC were included. The peripheral blood mRNA expressions for GR, GR-1B, and NSE genes were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Serum cortisol and NSE were analyzed by electrochemiluminescence immunoassay technique. RESULTS: Levels of GR mRNA were significantly lower in FES and CSZ than that in HC. The expression of GR-1B mRNA was significantly decreased in CSZ when compared with that in FES. Levels of NSE mRNA were significantly lower in CSZ than that in FES patients or HC patients. CSZ patients showed significantly lower cortisol concentrations than FES and HC patients. FES patients showed significantly higher NSE concentrations than CSZ and HC. CONCLUSION: Our findings support that there is disrupted HPA axis system in the SZ and suggest that CSZ patients suffer a greater HPA axis damage than FES patients. Our research implicated underlying GR mRNA dysregulation in SZ and the potential importance of the functional GR-1B transcription in CSZ.

Positive Relationship of Platelet Volume Indices with HbA1c in Unselected Type-2 Diabetes Mellitus Patients.

BACKGROUND: The aim of this study is to investigate the relationship of several platelet volume indices with glycated hemoglobin (HbA1c) in a large cohort of type 2 diabetes mellitus (T2DM) patients. METHODS: This is a retrospective study conducted on 1,729 T2DM patients. The database was based on the laboratory information system of the Department of Clinical Laboratory Medicine of the First Affiliated Hospital of Shaoyang University from May 2017 to February 2018. These patients were divided into two subgroups depending on their platelet volume indices and HbA1c levels. RESULTS: Mean platelet volume (MPV), platelet distribution width (PDW) and platelet-large cell ratio (P-LCR) were positively correlated with HbA1c levels (all p < 0.01), but not the thrombocytocrit (PCT). The platelet, MPV, PDW, P-LCR, and glucose levels were significantly higher in the higher HbA1c subgroup (≥ 6.5%) than that in lower subgroup (< 6.5%) (p < 0.01). The platelet, MPV, P-LCR, PCT, HbA1c, and glucose levels were significantly higher in higher PDW subgroup (≥ 17 fL) than that in lower subgroup (< 17 fL) (p < 0.01). In the higher MPV subgroup (≥ 12 fL), the platelet, PDW, P-LCR, PCT, HbA1c, and glucose levels were significantly higher than that in lower subgroup (< 12 fL) (p < 0.01). CONCLUSIONS: These platelet volume indices were positively correlated with HbA1c in T2DM patients, which might provide potential new parameters to monitor glucose control.

Changes of Serum IL-6, IL-17, and Complements in Systemic Lupus Erythematosus Patients.

Cytokines activation and low complement levels are common in systemic lupus erythematosus (SLE) patients. This study is aimed to explore the relationship and clinical significance of cytokines and complements with SLE activity. Serum samples of 140 SLE patients and 36 age- and gender-matched healthy controls (HC) were collected. Serum interleukin (IL)-6, IL-17, high-sensitivity C-reactive proteins (hsCRP), and complements (C3, C4) were measured in all samples. These patients were divided into 3 subgroups based on clinical disease activity with SLE Disease Activity Index 2000 (SLEDAI-2K): stationary status subgroup, mild activity subgroup, and moderate/severe activity subgroup. The serum IL-6, IL-17, and hsCRP levels in SLE patients (4.72 ± 0.28 pg/mL, 23.34 ± 1.32 pg/mL, and 4.78 ± 0.34 mg/mL) were significantly higher than those in the HC group (1.51 ± 0.05 pg/mL, 18.28 ± 1.93 pg/mL, and 1.32 ± 0.29 mg/mL), whereas C3 and C4 levels in SLE patients (0.80 ± 0.28 and 0.21 ± 0.08 g/L) were significantly lower than those in the HC group (1.49 ± 0.08 and 0.36 ± 0.02 g/L). A positive correlation was noted between the SLEDAI-2K scores and serum IL-6, IL-17, and hsCRP levels. These results support the proinflammatory cytokines and complements in the pathogenesis of SLE. The serum IL-6, IL-17, and hsCRP levels were correlated with the disease activity.

Decreased Serum Oxytocin and Increased Homocysteine in First-Episode Schizophrenia Patients.

Schizophrenia (SZ) is a debilitating and heterogeneous disease. We hypothesized that the oxytocin (OXT) system, inflammation and one-carbon metabolism would have a link with SZ. In this study, serum OXT, OXT receptor (OXTR), interleukin-6 (IL-6), high sensitivity CRP (hsCRP) and homocysteine (Hcy) levels were measured in 52 first-episode schizophrenia (FES) patients and 41 healthy controls (HC) from the Second Xiangya Hospital of Central South University. Meanwhile, the mRNA expressions of OXT and OXTR genes were determined by real-time quantitative PCR. Serum OXT and OXTR levels were significantly lower in FES patients (518.96 ± 22.22 and 174.60 ± 17.11 pg/ml) than the HC group (711.58 ± 40.57 and 252.15 ± 20.62 pg/ml). Serum IL-6 and hsCRP levels showed no difference between the two groups (1.82 ± 0.30 vs. 1.69 ± 0.36 pg/ml, 0.66 (0.22, 1.07) vs. 0.31 (0.13, 0.91) mg/L), but serum Hcy levels were significantly higher in FES patients (20.18 ± 1.83 vs. 15.24 ± 0.82 µmol/ml). The FES patients (0.27 ± 0.02 and 0.20 ± 0.02) have relatively higher mRNA expressions of OXT and OXTR genes than the HC group (0.16 ± 0.01 and 0.14 ± 0.01). In summary, our results suggested the possible function of the OXT system and Hcy in the pathogenesis of SZ.

Increased Serum C3 and Decreased UA in Patients of Bipolar Disorder in Chinese Han Population.

The aim of this study is to explore the changes and clinical significance of serum C3, C4, hypersensitive C-reactive protein (hsCRP) and uric acid (UA) in patients of bipolar disorder (BD). In this case-control study, we recruited 141 BD patients from The Second Xiangya Hospital, Central South University, and 151 age and gender matched healthy controls (HC) from the health management central of The Second Xiangya Hospital. These patients were divided into two subgroups based on medicines use: 91 patients were treated with psychiatric drugs and 50 patients were drugs free, or four subgroups based on mood states: 54 patients in manic/hypomanic phase, 30 patients in depressive phase, 52 patients in euthymic phase and 5 patients in mixed phase. Serum levels of C3, C4, hsCRP and UA were measured in all subjects. The serum C3 levels in BD patients (0.9981 ± 0.1849 g/L) were significantly lower than that in HC group (1.0637 ± 0.2186 g/L), especially the drugs free subgroup and the euthymic subgroup (0.975 ± 0.153 and 0.983 ± 0.182 g/L), while the serum UA levels were significantly higher (354.6 ± 90.4 vs. 332.9 ± 88.7 µmol/L), especially the drug-treated subgroup and manic/hypomanic subgroup (361.56 ± 93.20 and 376.70 ± 88.89 µmol/L), and rates of hyperuricaemia (31.91 vs. 17.88%) were significantly higher in BD patients than in HC group. The serum C4 and hsCRP levels in HC group showed no significant difference with BD patients in whole or those subgroups. These findings suggested that the complement and purinergic systems of BD patients might be disrupted, the UA levels could be a potential marker in manic phase and the C3 might be the marker of therapeutic evaluation of BD patients.

Assessment of a combination of Serum Proteins as potential biomarkers to clinically predict Schizophrenia.

Schizophrenia (SZ) is a devastating psychiatric disorder. Validation of potential serum biomarkers during first-episode psychosis (FEP) is especially helpful to understand the onset and prognosis of this disorder. To address this question, we examined multiple blood biomarkers and assessed the efficacy to diagnose SZ. The expression levels of Neuregulin1 (NRG1), ErbB4, brain-derived neurotrophic factor (BDNF), DNA methyltransferases 1 (DNMT1) and ten-eleven translocation 1 (TET1) proteins in peripheral blood of 53 FEP patients and 57 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression including biomarker concentration as covariates was used to predict SZ. Differentiating performance of these five serum protein levels was analyzed by Receiver Operating Characteristic (ROC) curve analysis. We found that patients with SZ present a higher concentration of DNMT1, and TET1 in peripheral blood, but a lower concentration of NRG1, ErbB4 and BDNF than controls. Multivariable logistic regression showed that ErbB4, BDNF and TET1 were independent predictors of SZ, and when combined, provided high diagnostic accuracy for SZ. Together, our findings highlight that altered expression of NRG1, ErbB4, BDNF, DNMT1 and TET1 are involved in schizophrenia development and they may serve as potential biomarkers for the diagnosis of the schizophrenia. Therefore, our study provides evidence that combination of ErbB4, BDNF and TET1 biomarkers could greatly improve the diagnostic performance.

Up-regulated expression of oxytocin mRNA in peripheral blood lymphocytes from first-episode schizophrenia patients.

Schizophrenia (SZ) is a severe neuropsychiatric disorder with significant social cognition impairment. Increasing evidence has suggested that neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are important mediators of complex social cognition and behavior associates with SZ. In the present study, forty-three first-episode schizophrenia (FES) patients and forty-seven healthy controls (HC) were included. The peripheral mRNA expression of OXT, OXT receptor (OXTR), AVP, AVP 1a receptor (AVPR1a) and CD38 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The FES patients have a relatively higher mRNA level of OXT and OXTR genes and lower expression of AVP and CD38 genes than HC. No difference was found for AVPR1a between FES patients and HC. As for the sex difference, the mRNA expression of OXT and OXTR showed no difference in both male and female FES patients compared to HC group. The AVP and CD38 genes in female FES patients showed decreased mRNA expression than female HC. Our findings support disrupted OXT and AVP systems in the FES patients.