The global impact of the International Federation of Clinical Chemistry and Laboratory Medicine, Education and Management Division: engaging stakeholders and assessing HbA1c quality in a multicentre study across China

Background: Diabetes mellitus is a major global issue and high quality testing is essential for the diagnosis and treatment of the disease. The IFCC Committee for the Education in the Utility of Biomarkers in Diabetes (C-EUBD) plays a global role in improving knowledge and understanding around diabetes testing. This paper describes a multi-stakeholder approach, to improving diagnostic and therapeutic testing for diabetes, using a multicentre study in China as an example of the global impact of the group. Methods: Educational workshops were developed to support the scientific aims of the study in which 30 centres around China received identical, fresh frozen whole blood samples with values assigned using IFCC secondary reference methods and undertook precision (EP-5) and trueness studies. Performance was assessed using sigma metrics. Results: A successful multi-stakeholder group was developed and sustained throughout the study through several educational workshops, which enabled the formation of a long-term collaboration with key opinion leaders and policy makers in China. All 30 centres showed good performance with within and between laboratory coefficient of variations (CVs) below 3% in SI units at both low and high haemoglobin A1c (HbA1c) levels. All individual laboratories met the criteria of a sigma of two or more at a total allowable error (TAE) of 5 mmol/mol (0.46% NGSP). Conclusions: The study led to a successful multi-partner approach to improving diabetes testing in China. All centres involved in the study meeting the published IFCC quality criteria, paving the way for future clinical trials and an expanded role for HbA1c testing across the country

Iodine-induced thyroid dysfunction: a scientometric study and visualization analysis

ObjectiveIodine is essential in thyroid hormone production. Iodine deficiency is associated with serious complications (i.e miscarriage and stillbirth), whereas excess can cause thyroid dysfunction (i.e hyperthyroidism, hypothyroidism, thyroid autoimmunity). We conducted this scientometric study to visualize hot spots and trends in iodine-induced thyroid dysfunction over past two decades. The aim of this paper was to help scholars quickly understand the development and potential trend in this field, and guide future research directions.MethodsArticles on iodine-induced thyroid dysfunction from 2000 to 2022 were retrieved from the Web of Science Core Collection (WoSCC) using the following search terms: (((((TS=(hypothyroid*)) OR TS=(hyperthyroid*)) OR TS= (“TSH deficiency”)) OR TS= (“thyroid stimulating hormone deficiency”)) AND TS=(Iodine)) NOT TS=(radioiodine). Only publications in English were selected. CiteSpace, VOSviewer, Tableau, Carrot2, and R software were used to analyze the contribution and co-occurrence relationships of different countries, institutes, keywords, references, and journals.ResultsA total of 2986 publications from 115 countries and 3412 research institutions were included. From 2000 to 2022, research on iodine-induced thyroid dysfunction progressed over a three-stage development period: initial development (2000-2009), stable development (2010-2016), and rapid development (2016-2022) period. The Journal of Clinical Endocrinology and Metabolism had the most co-citations followed and China Medical University (n=76) had the most publications. The top three clusters of co-citation references were isolated maternal hypothyroxinemia, subclinical hyperthyroidism, and brain development. Various scientific methods were applied to reveal acknowledge structure, development trend and research hotspots in iodine-induced thyroid dysfunction.ConclusionOur scientometric analysis shows that investigations related to pregnant women, epidemiology surveys, and iodine deficiency are promising topics for future iodine-induced thyroid dysfunction research and highlights the important role of iodine on thyroid function

Lymphocyte Homing to Bronchus-associated Lymphoid Tissue (BALT) Is Mediated by L-selectin/PNAd, α4β1 Integrin/VCAM-1, and LFA-1 Adhesion Pathways

Bronchus-associated lymphoid tissue (BALT) participates in airway immune responses. However, little is known about the lymphocyte–endothelial adhesion cascades that recruit lymphocytes from blood into BALT. We show that high endothelial venules (HEVs) in BALT express substantial levels of VCAM-1, in marked contrast to HEVs in other secondary lymphoid tissues. BALT HEVs also express the L-selectin ligand PNAd. Anti–L-selectin, anti-PNAd, and anti–LFA-1 mAbs almost completely block the homing of B and T lymphocytes into BALT, whereas anti–α4 integrin and anti–VCAM-1 mAbs inhibit homing by nearly 40%. α4β7 integrin and MAdCAM-1 are not involved. Importantly, we found that mAbs against α4 integrin and VCAM-1 significantly block the migration of total T cells (80% memory phenotype) but not naive T and B cells to BALT. These results suggest that an adhesion cascade, which includes L-selectin/PNAd, α4β1 integrin/VCAM-1, and LFA-1, targets specific lymphocyte subsets to BALT. This high level of involvement of α4β1 integrin/VCAM-1 is unique among secondary lymphoid tissues, and may help unify lymphocyte migration pathways and immune responses in BALT and other bronchopulmonary tissues

Gestational TSH and FT4 Reference Intervals in Chinese Women: A Systematic Review and Meta-Analysis

Background: Serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) change dynamically during pregnancy. Differences in geographic regions, populations, and manufacturer's methodologies can affect the reference intervals for thyroid function tests. The 2017 guidelines of the American Thyroid Association (ATA) recommended 4.0 mU/L as the cut-off point for the upper limit of serum TSH in early pregnancy. A systematic review is called for to establish practical, gestational-specific TSH and FT4 reference intervals for pregnant Chinese women and to explore whether the criteria are suitable for China.Methods: English and Chinese articles published from inception to Aug 2017 were searched in the PubMed, EMBASE, and SCIE English-language databases and the CNKI, WanFang, and CQVIP Chinese databases. The relative descent or ascent rates of serum TSH and FT4 were calculated, after which Comprehensive Meta-Analysis V2.0 software was used to analyze the data.Results: Eleven studies (6 in English and 5 in Chinese), five kits and 11,629 Chinese women from nine cities were considered in this meta-analysis. Compared with the reference ranges provided by manufacturers, serum TSH decreased in the first trimester, with the upper limit declining by 21.7% (5.0–36.6%), to a value close to 4.0 mU/L, and the lower limit declining by 85.7% (73.5–97.1%). It continued decreasing in the second trimester, with the upper limit declining by 24.0% (6.4–40.9%) and the lower limit declining by 40.7% (9.0–85.7%). For FT4, the upper limit fluctuated slightly, and the lower limit increased by 6.8% (1.0–14.6%) in the first trimester. Serum FT4 dropped gradually, with the upper limit declining by 21.8% (2.5–31.8%) and the lower limit declining by 12.7% (2.6–19.6%) in the second trimester. During the third trimester, the upper limit decreased by 25.1% (12.7–35.0%), while the lower limit decreased by 20.9% (14.8–27.3%).Conclusions: Various regions, kits and test methods affect the gestational TSH and FT4 levels. The non-pregnant serum TSH upper limit minus 22% is very close to 4.0 mU/L, which can be used as a sub-optimal approach to represent the cut-off value for pregnant Chinese women in the first trimester

IL-34 Expression Is Reduced in Hashimoto's Thyroiditis and Associated With Thyrocyte Apoptosis

Hashimoto's thyroiditis (HT) is a common autoimmune disease accompanied by lymphocyte infiltration and thyroid tissue destruction. IL-34 was first described in 2008, and its involvement in the development of many autoimmune diseases has been recently identified. However, whether IL-34 is a regulatory factor in HT is unclear. Here, we demonstrate that IL-34 is expressed on thyroid follicular epithelial cells and that IL-34 expression is significantly reduced in thyroid tissue in patients with HT and spontaneous autoimmune thyroiditis (SAT) models. Serum IL-34 levels in patients with HT are also significantly reduced. In addition, IL-34 is associated with thyroid autoantibodies in both thyroid tissue and serum. Furthermore, our data show that IL-34 participates in the apoptosis resistance of thyrocytes in HT induced by CSF-1R and may be a potential indicator for evaluating thyrocyte damage

The Association Between an Addictive Tendency Toward Food and Metabolic Characteristics in the General Newfoundland Population

Background: Our previous study of 29 obese food addiction (FA) patients found that FA is associated with lipid profiles and hormones which may be a factor in cardiovascular disease (CVD) and insulin resistance (IR). However, there is currently no data available regarding the relationship between FA symptoms and metabolic characteristics of CVD and IR in the general population. We designed this study to investigate the correlation between FA symptoms with lipid profiles and IR in men and women of the general Newfoundland population. Methods: 710 individuals (435 women and 275 men) recruited from the general Newfoundland population were used in analysis. FA symptoms were evaluated using the Yale Food Addiction Scale (YFAS). Glucose, insulin, HDL, LDL, total cholesterol and triglycerides levels were measured. IR was evaluated using the homeostatic model of assessment (HOMA). Participants were grouped by sex and menopausal status. Age, physical activity, calories and total % body fat were controlled. Results: Partial correlation analysis revealed that in men, YFAS symptom counts were significantly correlated with HOMA-b (r = 0.196, p = 0.021), triglycerides (r = 0.140, p = 0.025) and inversely correlated with HDL (r = −0.133, p = 0.033). After separating by menopausal status, pre-menopausal women exhibited no correlations and post-menopausal women had a significantcorrelation with triglycerides (r = 0.198, p = 0.016). Conclusion: FA is significantly correlated with several markers of metabolic disturbance in men and to a lesser extent, post-menopausal women, in the general population. Further research is required to explain sex specific associations and elucidate any potentially causal mechanisms behind this correlation

Estrogen Induces Metastatic Potential of Papillary Thyroid Cancer Cells through Estrogen Receptor α

Estradiol (E2) promotes metastatic propensity. However, the detailed mechanism remains largely unknown. E-cadherin, vimentin, and MMP-9 play a dominant role in the metastatic process. We aimed to investigate the effects of E2 on metastatic potential of PTC cell line BCPAP and on E-cadherin, vimentin, and MMP-9 protein expression. PTC cell line BCPAP was evaluated for the presence of estrogen receptor (ER) by western blot analysis. The effects of E2, PPT (a potent ERα-selective agonist), and DPN (a potent ERβ-selective agonist) on modulation of metastatic phenotype were determined by using in vitro scratch wound assay and invasion assay. In addition, the effects on E-cadherin, vimentin, and matrix metalloproteinase-9 (MMP-9) protein expression were evaluated by Western blot analysis. We found that BCPAP cells expressed ERα and ERβ. E2 and PPT enhanced, but DPN inhibited, the migration and invasion of BCPAP cells in an in vitro experimental model system that is modulated by E-cadherin, vimentin, and MMP-9. These findings indicate that E2 induces the metastatic potential of BCPAP cells through ERα and ERβ. The two ER subtypes play differential roles in modulation of BCPAP cell metastasis and the related molecule expressions including E-cadherin, vimentin, and MMP-9

The Correlation between Thyrotropin and Dyslipidemia in a Population-based Study

This study investigated the relationship between serum thyrotrophin levels and dyslipidemia in subclinical hypothyroid and euthyroid subjects. A total of 110 subjects with subclinical hypothyroidism and 1,240 euthyroid subjects enrolled in this study. Patients with subclinical hypothyroidism had significantly lower high density lipoprotein cholesterol (HDL-C) levels than those who were euthyroid. The lipid profiles were each categorized and mean thyrotrophin levels were higher in subjects in the dyslipidemia subclasses than subjects in the normal subclasses. Thyrotrophin was positively associated with serum triglyceride and negatively associated with serum HDL-C in women. Thyrotrophin was also positively associated with total cholesterol (TC) in the overweight population along with TC and LDL-C in overweight women. In the euthyroid population, thyrotrophin was positively associated with TC in the overweight population. In conclusion, serum thyrotrophin was correlated with dyslipidemia in subclinical hypothyroid and euthyroid subjects; the correlation was independent of insulin sensitivity

Glutamic acid decarboxylase autoantibodies are dominant but insufficient to identify most Chinese with adult-onset non-insulin requiring autoimmune diabetes: LADA China study 5.

AIMS: Adult-onset autoimmune diabetes is prevalent in China, in contrast to childhood-onset type 1 diabetes mellitus. Islet autoantibodies are the most important immune biomarkers to diagnose autoimmune diabetes. We assayed four different islet autoantibodies in recently diagnosed adult non-insulin-requiring diabetes Chinese subjects to investigate the best antibody assay strategy for the correct diagnosis of these subjects. METHODS: LADA China study is a nation-wide multicenter study conducted in diabetes patients from 46 university-affiliated hospitals in China. Non-insulin-treated newly diagnosed adult diabetes patients (n = 2388) were centrally assayed for glutamic acid decarboxylase autoantibody (GADA), protein tyrosine phosphatase-2 autoantibody (IA-2A), and zinc transporter 8 autoantibody (ZnT8A) by radioligand assay and insulin autoantibody (IAA) by microtiter plate radioimmunoassay. Clinical data were determined locally. RESULTS: Two hundred and six (8.63 %) subjects were autoantibody positive, of which GADA identified 5.78 % (138/2388) of the total, but only 67 % (138/206) of the autoimmune cases. IA-2A, ZnT8A, and IAA were found in 1.51, 1.84, and 1.26 % of the total study subjects, respectively. When assaying three islet autoantibodies, the most effective strategy was the combination of GADA, ZnT8A, and IAA, which could identify 92.2 % (190/206) autoimmune diabetes patients. The clinical data showed that those subjects with positive GADA had lower random C-peptide than autoantibody negative subjects (P < 0.05). CONCLUSIONS: As with Europeans, GADA is the dominant autoantibody in this form of autoimmune diabetes in China, but in contrast to Europeans, screening should include other diabetes-associated autoantibodies