Association of maternal thyroid dysfunction and autoimmunity with adverse birth outcomes.

This study aimed to explore the relationship between thyroid function and autoimmunity and adverse birth outcomes. Serum levels of thyroid function were detected by electrochemiluminescence assay. Urine iodine concentration was detected using the acid digestion method. We used multiple linear regression to assess the correlation between thyroid function indicators and birth weight according to trimester stratification and binary logistic regression to evaluate the correlation between thyroid dysfunction and adverse birth outcomes. Reference ranges for trimester-specific thyroid hormones were established in our 2564 pregnant women cohort with mild iodine deficiency. The higher the maternal thyroid-stimulating hormone in the first trimester (B = 0.09, P = 0.048) and total triiodothyronine (TT3) in the third trimester (B = 0.16, P < 0.001) of TPOAbnegative women, the higher the birth weight Z-score, whereas in the second trimester, free-thyroxine of mothers with TPOAb negative was lower (B = -0.10, P = 0.026) and the birth weight Z-score was higher. Pregnant women with overt and subclinical hyperthyroidism had a higher risk of preterm births than euthyroid women (11.9% vs 4.5%; odds ratio (OR): 2.84; P = 0.009). Women with higher TT3 had a higher risk of preterm (17.0% vs 4.5%; OR: 4.19; P < 0.001) and LGA (34.0% vs 11.1%; OR: 3.70; P < 0.001) births than euthyroid women. In conclusion, thyroid function during pregnancy could affect birth weight and birth outcome.

Dynamics of leukocyte telomere length in adults aged 50 and older: a longitudinal population-based cohort study.

It is well established from previous cross-sectional studies that telomeres shorten with age. However, due to a considerable inter-individual variation in telomere length (TL), its relationship with biological aging is difficult to unpick. Longitudinal repeated assessments of TL changes within individuals should augment our understanding of TL dynamics in aging. This study disentangles within- and inter-individual effects of age on leukocyte telomere length (LTL) dynamics in a large population-based cohort of older adults. A total of 4053 subjects aged 50 and older from the WHO Study on global AGEing and adult health (SAGE) in Shanghai were studied. Relative LTL (T/S ratio) was measured at baseline (2009-2010) and follow-up (2017-2018) by quantitative real-time polymerase chain reaction. We used linear random slope models to analyze LTL dynamics in relation to age and sex and within-subject centering method to distinguish within- versus between-subject effects. We observed LTL shortening in 66.32%, maintenance in 11.23%, and elongation in 22.45% of the study participants. LTL declined significantly with age both cross-sectionally and longitudinally. More importantly, the longitudinal decline in LTL was much greater than the cross-sectional decline (- 0.017 (p < 0.001) versus - 0.002 (p < 0.001) per year). Furthermore, women had a lower within-subject LTL shortening rate than men (- 0.014 versus - 0.020 per year, p < 0.001). The within-individual longitudinal decline in LTL was much greater than the inter-individual cross-sectional decline, indicating that chronological age might impose a greater impact on LTL shortening than other influencing factors combined. Moreover, women showed a lower within-individual LTL shortening rate than men.

Association between anemia and frailty in 13,175 community-dwelling adults aged 50 years and older in China.

BACKGROUND: Anemia and frailty contribute to poor health outcomes in older adults; however, most current research in lower income countries has concentrated on anemia or frailty alone rather than in combination. The aim of the present study was to investigate the association between anemia and frailty in community-dwelling adults aged 50 years and older in China. METHODS: The study population was sourced from the 2007/10 SAGE China Wave 1. Anemia was defined as hemoglobin less than 13 g/dL for men and less than 12 g/dL for women. A Frailty Index (FI) was compiled to assess frailty. The association between anemia and frailty was evaluated using a 2-level hierarchical logistic model. RESULTS: The prevalence of anemia was 31.0% (95%CI: 28.4, 33.8%) and frailty 14.7% (95%CI: 13.5, 16.0%). In the univariate regression model, presence of anemia was significantly associated with frailty (OR = 1.62, 95% CI: 1.39, 1.90) and the effect remained consistent after adjusting for various potential confounding factors including age, gender, residence, education, household wealth, fruit and vegetable intake, tobacco use, alcohol comsumption and physical activity (adjusted OR = 1.31, 95% CI:1.09, 1.57). Each 1 g/dL increase in hemoglobin concentration was associated with 4% decrease in the odds of frailty after adjusting for several confounding variables (adjusted OR = 0.96, 95% CI: 0.93, 0.99). CONCLUSION: Anemia and low hemoglobin concentrations were significantly associated with frailty. Therefore, health care professionals caring for older adults should increase screening, assessment of causes and treatment of anemia as one method of avoiding, delaying or even reversing frailty.

Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis.

The detection of nonsmall cell lung cancer (NSCLC) at an early stage presents a daunting challenge due to the lack of a specific noninvasive marker. The discovery of microRNAs (miRNAs), particularly those found in serum, has opened a new avenue for tumor diagnosis. To determine whether the expression profile of serum miRNAs can serve as a NSCLC fingerprint, we performed Taqman probe-based quantitative RT-PCR assay to selected differentially expressed serum miRNAs from a sample set including 400 NSCLC cases and 220 controls, and risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. After a two-phase selection and validation process, 10 miRNAs were found to have significantly different expression levels in NSCLC serum samples compared with the control serum samples. Risk score analysis showed that this panel of miRNAs was able to distinguish NSCLC cases from controls with high sensitivity and specificity. Under ROC curves, the AUC for tumor identification in training set and validation set were 0.966 and 0.972, respectively. Furthermore, the expression profile of the 10-serum miRNAs was correlated with the stage of NSCLC patients, especially in younger patients and patients with current smoking habits. More importantly, the serum miRNA-based biomarker for early NSCLC detection was supported by a retrospective analysis in which the 10-serum miRNA profile could accurately classify serum samples collected up to 33 months ahead of the clinical NSCLC diagnosis. Taken together, we demonstrate that the profiling of 10-serum miRNAs provides a novel noninvasive biomarker for NSCLC diagnosis.

Identification of Serum Biomarkers for Biliary Tract Cancers by a Proteomic Approach Based on Time-of-Flight Mass Spectrometry.

Biliary tract cancers (BTCs) are lethal malignancies currently lacking satisfactory methods for early detection and accurate diagnosis. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a promising diagnostic tool for this disease. In this pilot study, sera samples from 50 BTCs and 30 cholelithiasis patients as well as 30 healthy subjects from a population-based case-control study were randomly grouped into training set (30 BTCs, 20 cholelithiasis and 20 controls), duplicate of training set, and blind set (20 BTCs, 10 cholelithiasis and 10 controls); all sets were analyzed on Immobilized Metal Affinity Capture ProteinChips via SELDI-TOF-MS. A decision tree classifier was built using the training set and applied to all test sets. The classification tree constructed with the 3,400, 4,502, 5,680, 7,598, and 11,242 mass-to-charge ratio (m/z) protein peaks had a sensitivity of 96.7% and a specificity of 85.0% when comparing BTCs with non-cancers. When applied to the duplicate set, sensitivity was 66.7% and specificity was 70.0%, while in the blind set, sensitivity was 95.0% and specificity was 75.0%. Positive predictive values of the training, duplicate, and blind sets were 82.9%, 62.5% and 79.2%, respectively. The agreement of the training and duplicate sets was 71.4% (Kappa = 0.43, u = 3.98, P < 0.01). The coefficient of variations based on 10 replicates of one sample for the five differential peaks were 15.8-68.8% for intensity and 0-0.05% for m/z. These pilot results suggest that serum protein profiling by SELDI-TOF-MS may be a promising approach for identifying BTCs but low assay reproducibility may limit its application in clinical practice.

[Serum proteomic spectra of esophageal squamous cell carcinoma patients analyzed with IMAC3 protein chip].

BACKGROUND & OBJECTIVE: Serum protein fingerprinting technology can help to identify the molecular changes related to esophageal carcinogenesis. This study was to screen serum markers and establish the predictive models that may be of help to serologic diagnosis of esophageal squamous cell carcinoma (ESCC). METHODS: Serum samples were collected from 68 ESCC patients and 44 age-and sex-matched healthy subjects, and randomized into a training set (55 ESCC patients and 35 healthy subjects) and a blind testing set (13 ESCC patients and 9 healthy subjects). Serum samples were applied to immobilized metal affinity capture (IMAC3) proteinchip surfaces and tested by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). The data were analyzed by Biomarker Wizard software to screen serum proteomic biomarkers. Decision classification tree models were established by bioinformatics. Double-blind test was used to determine the sensitivity and specificity of the classification tree models. RESULTS: A total of 78 effective protein peaks were detected at the molecular range of 1.5 to 20 ku, among which 25 were significantly different between ESCC patients and healthy subjects (P<0.001). All the peptide pattern data were sampled randomly for 1,000 times using 3-cross validation approach, and 1,000 decision tree models were obtained. Twenty decision trees with the highest cross validation rate were chosen to construct the classification models which can differentiate ESCC patients from healthy subjects. With these decision trees, 18 samples were correctly forecasted from 22 blind testing samples, with a sensitivity of 92.31% and a specificity of 66.67%. CONCLUSION: SELDI-TOF-MS technique combined with decision tree model can help to identify serum proteomic biomarkers related to ESCC and the predictive models can discriminate ESCC patients from healthy people effectively.

Detection of mutant p53 protein in workers occupationally exposed to benzidine.

To investigate the expression of mutant p53 protein in workers occupationally exposed to benzidine, we detected mutant p53 protein by immuno-PCR assay in the serum of 331 benzidine-exposed healthy workers, while we classified exfoliated urothelial cells in urine samples with Papanicoloau's grading (PG). The Papanicoloau's grading classified exfoliated urothelial cells of the subjects from grade I (normal cells) to grade III (suspicious malignant cells). The subjects were also divided into high, medium and low exposure groups according to the exposure intensity index. The results revealed that mutant p53 protein in the medium and high exposure groups were significantly higher than the in low exposure group (p<0.05), and in PG II and III were significantly higher than in the PG I (p<0.05). There was no significant differences among Papanicoloau's gradings strata in the low exposure group on the incidence and quantity of mutant p53 protein. In the medium and high exposure groups, the incidence and/or quantity of mutant p53 protein in the stratum of PG II and/or III were significantly higher than that of PG I (p<0.05). Detection of mutant p53 protein in conjunction with benzidine exposure level and Papanicoloau's gradings of exfoliated urothelial cells could provide more information to help us elevate surveillance efficiency and diagnose bladder cancer in the early period.

[Genetic polymorphism of UDP-glucuronosyltransferase 1F and susceptibility to hepatocellular carcinoma].

OBJECTIVE: To study the genetic polymorphisms of UDP-glucuronosyltransferase 1F(UGT1F) and the relationship between polymorphisms and susceptibility to hepatocellular carcinoma (HCC). METHODS: The polymorphisms of UGT1F of 84 patients with HCC and 144 healthy controls were detected by PCR-denaturation gradient gel electrophoresis-sequencing or PCR-single strain conformation polymorphsim-sequencing. RESULTS: Three new single nucleotide polymorphisms(SNP) were found: the first one was a transversion of TrarrG at nucleotide 232; the second one was the transition of ArarrG at nucleotide 528 in exon 1; the last one was the transition of ArarrG at nucleotide 376 in intron 2. Additionally, the polymorphism at nucleotide 754 was proved in this study. The frequencies of genotype and allele of 4 loci in cases and controls were analyzed. Both frequencies of genotype G/G(13.10%) and allele G (29.17%) of position 754 of UGT1F in cases were sig nificantly greater than those in controls (2.78% and 19.44% ) respectively. For other loci, the difference between the two groups were not significant. CONCLUSION: Exons 2-5 of UGT1F are highly conservative, but exon 1 emerges highly polymorphic. And the polymorphism at locus 754 may be related with HCC.

[Studies of genetic polymorphisms of ADH2 and ALDH2 among the Han population in Luoyang China].

In order to investigate genetic polymorphisms of ADH2 and ALDH2 among the Han population in Luoyang City,portions of exon 3 of ADH2 and exon 12 of ALDH gene were amplified by using polymerase chain reaction. The amplified products were electrophoresed on 10% undenatured vertical polyacrylamide gels and stained with argentine. Frequencies of ADH2*1 and ADH2*2 alleles are 42.86% and 57.14%. Frequencies of three genotypes of ADH2 are 22.86%,40.00% and 37.14%,respectively. Frequencies of ALDH2*1 and ALDH2*2 alleles are 85.24% and 14.76%. Genotype frequencies of ALDH2 loci are 71.43%,27.62% and 0.95%,respectively. Genetic polymorphisms of ADH2 and ALDH2 among the Han population in Luoyang City are different from those among Taiwanese and Shanghainese. Frequency of ALDH2*1/*1 in Luoyang people is higher than those in Shanghai and Taiwan. Therefore,there is a higher resistance to alcohol drinking in the Han population in Luoyang.