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Background Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals. Methods We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the nonpregnancy reference intervals included an absolute modification (per.1 mU/L TSH or 1 pmol/L free T4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 and 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity, and positive predictive value (PPV) of these methodologies with population-based trimester-specific reference intervals. Results The final study population comprised 52 496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were −5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity,.70, CI, 0.47-0.86; PPV, 0.64, CI, 0.54-0.74). For subclinical hypothyroidism, these were −20% for the upper limit of TSH and −15% for the lower limit of FT4 (sensitivity, 0.91; CI, 0.67-0.98; PPV, 0.71, CI, 0.58-0.80). Absolute and fixed modifications yielded similar results. CIs were wide, limiting generalizability. Conclusion We could not identify modifications of nonpregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned toward studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction. [ABSTRACT FROM AUTHOR]

Context: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. Methods: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. Results: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. Conclusion: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy. [ABSTRACT FROM AUTHOR]

Context: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. Objective: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. Methods: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. Results: (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. Conclusion: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria. [ABSTRACT FROM AUTHOR]

Objective: Adverse maternal outcomes and perinatal complications are associated with overt and subclinical maternal hypothyroidism. It is not clear whether these complications also occur in women with isolated hypothyroxinemia during pregnancy. The aim of this study was to evaluate the effects of isolated hypothyroxinemia on maternal and perinatal outcomes during pregnancy. Methods: This study included data from 2,864 pregnant women in the first trimester (67 women with isolated hypothyroxinemia, 784 euthyroid women) and the second trimester (70 women with isolated hypothyroxinemia, 1,943 euthyroid women) of pregnancy. Maternal serum samples were collected in the first and second trimesters to examine thyroid hormone concentration. Hypothyroxinemia was defined as a normal maternal thyroid-stimulating hormone concentration with a low maternal free thyroxine concentration and negative thyroid autoantibodies. The following maternal outcomes were recorded: gestational hypertension, gestational diabetes mellitus, placenta previa, placental abruption, prelabor rupture of membranes, and premature delivery. Perinatal outcomes, including fetal growth restriction, fetal distress, low birth weight, intrauterine fetal death, and malformation. The incidence of adverse pregnancy outcomes and perinatal complications was compared between women in the first trimester and second trimester with isolated hypothyroxinemia. Results: There were no significant differences in the incidence rates of adverse maternal outcomes and perinatal complications between patients in the first and second trimesters with isolated hypothyroxinemia. Conclusion: The results of this study indicate that isolated hypothyroidism does not increase the incidence of adverse maternal outcomes and perinatal complications. [ABSTRACT FROM AUTHOR]

Endothelial progenitor cells (EPCs) are able to trigger angiogenesis, and pro‐inflammatory cytokines have beneficial effects on angiogenesis under physiological and pathological conditions. C‐X‐C chemokine receptor type 7 (CXCR‐7), receptor for stromal cell‐derived factor‐1, plays a critical role in enhancing EPC angiogenic function. Here, we examined whether CXCR7 mediates the pro‐angiogenic effects of the inflammatory cytokine interleukin‐1β (IL‐1β) in EPCs. EPCs were isolated by density gradient centrifugation and angiogenic capability was evaluated in vitro by Matrigel capillary formation assay and fibrin gel bead assay. IL‐1β elevated CXCR7 expression at both the transcriptional and translational levels in a dose‐ and time‐dependent manner, and blockade of the nuclear translocation of NF‐κB dramatically attenuated the IL‐1β‐mediated up‐regulation of CXCR7 expression. IL‐1β stimulation significantly promoted EPCs tube formation and this effect was largely impaired by CXCR7‐siRNA transfection. IL‐1β treatment stimulated extracellular signal‐regulated kinase 1/2 (Erk1/2) phosphorylation, and inhibition of Erk1/2 phosphorylation partially impaired IL‐1β‐induced tube formation of EPCs but without significant effects on CXCR7 expression. Moreover, blocking NF‐κB had no significant effects on IL‐1β‐stimulated Erk1/2 phosphorylation. These findings indicate that CXCR7 plays an important role in the IL‐1β‐enhanced angiogenic capability of EPCs and antagonizing CXCR7 is a potential strategy for inhibiting angiogenesis under inflammatory conditions. [ABSTRACT FROM AUTHOR]

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth.Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth.Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded.Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models.Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age).Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]).Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Here, the relationship of pioglitazone efficacy to single nucleotide polymorphisms (SNP) of the adiponectin gene, a critical gene directly regulated by the drug, was examined in a cohort of Chinese Han type 2 diabetic patients. Methods: Eighty type 2 diabetic patients were treated with pioglitazone (15 mg/day) for 12 weeks without interruption of their current therapeutic regimen. Fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and glycated hemoglobin (HbA1c%) were collected both prior to and following pioglitazone treatment. Response to pioglitazone was defined as a decrease of at least 15% in HbA1c% levels. Three regions of the adiponectin gene containing SNPs (promoter, intron 2 and exon 2, and exon 3) were amplified and sequenced to determine genotype. Results: Serum adiponectin levels were significantly increased (p<0.001) whereas fasting plasma glucose, fasting insulin, HOMA-IR, and HbA1c% values were significantly decreased relative to baseline measurements (p<0.001). Response of patients with TG and TT genotypes at rs2241766 (exon2; 52.9% vs. 12.7%, respectively p = 0.001) was statistically significant relative to all other patients. Amongst rs2241766 TG and TT patients, the mean decrease in HbA1c% levels was greater where the genotype was TG (1.15±0.80 vs. 0.52±0.64, p = 0.001). Conclusions: The adiponectin gene polymorphism rs2241766 T/G is associated with pioglitazone efficacy in type 2 diabetic patients, and status of the polymorphism may be an important clinical factor to consider prior to pioglitazone treatment. [ABSTRACT FROM AUTHOR]

Background: Thyroid dysfunction during pregnancy is associated with multiple adverse outcomes, but whether all women should be screened for thyroid disorders during pregnancy remains controversial. Objective: To evaluate the effectiveness of the targeted high risk case-finding approach for identifying women with thyroid dysfunction during the first and second trimesters of pregnancy. Methods: Levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOAb) were measured in 3882 Chinese women during the first and second trimester of pregnancy. All tested women were divided into the high risk or non-high risk groups, based on their history, findings from physical examination, or other clinical features suggestive of a thyroid disorder. Diagnosis of thyroid disorders was made according to the standard trimester-specific reference intervals. The prevalence of thyroid disorders in each group was determined, and the feasibility of a screening approach focusing exclusively on high risk women was evaluated to estimate the ability of finding women with thyroid dysfunction. Results: The prevalence of overt hypothyroidism or hyperthyroidism in the high risk group was higher than in the non-high risk group during the first trimester (0.8% vs 0, χ2 = 7.10, p = 0.008; 1.6% vs 0.2%, χ2 = 7.02, p = 0.008, respectively). The prevalence of hypothyroxinemia or TPOAb positivity was significantly higher in the high risk group than in the non-high risk group during the second trimester (1.3% vs 0.5%, χ2 = 4.49, p = 0.034; 11.6% vs 8.4%, χ2 = 6.396, p = 0.011, respectively). The total prevalence of hypothyroidism or hyperthyroidism and the prevalence of subclinical hypothyroidism or hyperthyroidism were not statistically different between the high risk and non-high risk groups, for either the first or second trimester. Conclusion: The high risk screening strategy failed to detect the majority of pregnant women with thyroid disorders. Therefore, we recommend universal screening of sTSH, FT4, and TPOAb during the first trimester and second trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Background: Lipotoxicity is a key feature of the pathogenesis of diabetic kidney disease, and is attributed to excessive lipid accumulation (hyperlipidemia). Increasing evidence suggests that fibroblast growth factor (FGF)21 has a crucial role in lipid metabolism under diabetic conditions. Objective: The present study investigated whether FGF21 can prevent hyperlipidemia- or diabetes-induced renal damage, and if so, the possible mechanism. Methods: Mice were injected with free fatty acids (FFAs, 10 mg/10 g body weight) or streptozotocin (150 mg/kg) to establish a lipotoxic model or type 1 diabetic model, respectively. Simultaneously the mice were treated with FGF21 (100 µg/kg) for 10 or 80 days. The kidney weight-to-tibia length ratio and renal function were assessed. Systematic and renal lipid levels were detected by ELISA and Oil Red O staining. Renal apoptosis was examined by TUNEL assay. Inflammation, oxidative stress, and fibrosis were assessed by Western blot. Results: Acute FFA administration and chronic diabetes were associated with lower kidney-to-tibia length ratio, higher lipid levels, severe renal apoptosis and renal dysfunction. Obvious inflammation, oxidative stress and fibrosis also observed in the kidney of both mice models. Deletion of the fgf21 gene further enhanced the above pathological changes, which were significantly prevented by administration of exogenous FGF21. Conclusion: These results suggest that FFA administration and diabetes induced renal damage, which was further enhanced in FGF21 knock-out mice. Administration of FGF21 significantly prevented both FFA- and diabetes-induced renal damage partially by decreasing renal lipid accumulation and suppressing inflammation, oxidative stress, and fibrosis. [ABSTRACT FROM AUTHOR]

Recurrent pregnancy loss (RPL) is often associated with dysregulated Annexin A5 (ANXA5) expression. Moreover, the variants of Anxa5, a protein that is enriched in the placenta to prevent coagulation, have been reported to affect RPL risks. The haplotypes M1 [including single nucleotide polymorphisms (SNPs) 1A/C and 27T/C] and M2 (including SNPs 19G/A, 1A/C, 27T/C and 76G/A) of ANXA5 were also reported to affect RPL risks. The present study aimed to investigate the association between the haplotype located in the promoter region of ANXA5 and the risk of RPL. Patients with RPL (n=235) or intrauterine fetus death (IUFD; n=154), as well as healthy control subjects (n=375) were enrolled in the current research. Their haplotypes of ANXA5 were determined using genotyping, and the association between ANXA5 haplotypes and the risk of RPL was accordingly analyzed. A luciferase assay was conducted to investigate the haplotype responsible for ANXA5 activity. Reverse transcription-quantitative PCR, western blot analysis, immunohistochemistry and ELISA were performed to assess the expression level and activity of ANXA5 in patients with RPL. Consequently, the majority (n=214) of patients with RPL had a history of early RPL, whereas 31 patients with RPL had a history of both early and late RPL episodes. A significant difference was found between cases and controls in terms of gravidity and parity, whereas no significant differences were found in terms of age. The percentage of patients with RPL carrying the M2 haplotype of ANXA5 was significantly higher compared with that in control subjects, indicating that the M2 haplotype of ANXA5 was an independent risk of RPL as it influenced the transcription efficiency of ANXA5 promoter. In patients with RPL, ANXA5 activity was suppressed and the mRNA and protein expression levels of Anxa5 were decreased. Thus, the ANXA5 M2 haplotype may be an independent risk factor of RPL by affecting Anxa5 activity. [ABSTRACT FROM AUTHOR]

Context: Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes., Objective: To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes., Methods: We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders., Results: The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA., Conclusion: This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Autoimmune thyroid disease is a prevalent condition affecting women of reproductive age, leading to thyroid dysfunction and impacting pregnancy outcomes. While the critical role of thyroid hormone in pregnancy outcomes is well-established, the potential association between positive anti-thyroid peroxidase antibodies (TPOAb) and adverse pregnancy outcomes in pregnant women with normal thyroid function remains unclear., Objective: This study aims to investigate the relationship between maternal TPOAb positivity and adverse pregnancy outcomes with normal thyroid function., Methods: We collected baseline information from pregnant women who visited our hospital between February 2009 and June 2012. Blood samples were taken to measure thyroid stimulating hormone (TSH), free thyroxine (FT4), TPOAb, and anti-thyroglobulin antibodies (TGAb). The incidence of adverse pregnancy outcomes was compared between TPOAb-positive and TPOAb-negative groups among participants with normal thyroid function., Results: A total of 7,046 pregnant women with normal thyroid function were included, comprising 6,700 with negative TPOAb and 346 with positive TPOAb. The TPOAb-positive group exhibited a higher age (26.0 vs. 27.0 years, p = 0.02) and greater serum TSH levels (1.72 vs. 1.94 mIU/L, p = 0.029), while the gestational week of blood collection was lower (31.9 vs. 26.5 weeks, p = 0.001). Univariate analysis revealed a higher incidence of low birth weight (LBW) in offspring of TPOAb-positive women compared to the TPOAb-negative group (3.5% vs. 1.9%, p = 0.035). After adjusting for confounding factors such as age, gestational week of blood collection, menstrual history, education level, gestational diabetes, gestational hypertension, TGAb, TSH, and FT4, TPOAb positivity emerged as an independent risk factor for LBW infants (OR: 2.317, 95% CI: 1.057-5.076, p = 0.036), while other adverse pregnancy outcomes did not show a significant correlation with TPOAb positivity., Conclusion: Our findings suggest that TPOAb-positive pregnant women with normal thyroid function are more likely to deliver LBW infants. Regular monitoring of TPOAb-positive pregnancies and timely interventions throughout all stages of pregnancy are crucial., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Lin, Lin, Ye, Sun and Lu.)

To study the effects of third trimester maternal isolated hypothyroxinemia (serum low free thyroxine and normal thyroid stimulating hormone level) on pregnancy outcomes, we performed a retrospective cohort study in women with singleton pregnancy between February 2009 and June 2012. Pregnant women were assigned to two groups, a hypothyroxinemia group (with maternal isolated hypothyroxinemia in the third trimester and normal thyroid function in the first and second trimesters) and a control group (with normal serum thyroid functions). The pregnancy outcomes, including preterm birth, fetal distress, birth weight, premature rupture of membranes, and Apgar score at one minute after the birth, were recorded and compared between the two groups. A total of 3,945 pregnant women (median age 26 year old) were included in the study, with 195 women in the hypothyroxinemia group and 3,750 women in the control group. Compared with the women in the control group, women in the hypothyroxinemia group had higher incidences of premature rupture of membranes and low Apgar score at one minute after the birth. The multivariate logistic regression analysis showed that the low third trimester serum thyroxine level was the independent risk factor for the premature rupture of membranes and low Apgar score. There were no statistically significant differences in preterm birth, macrosomia, and intrauterine fetal distress between two groups. Third trimester maternal isolated hypothyroxinemia was associated with adverse pregnancy outcomes. The maternal serum thyroxine level should be monitored during late pregnancy and necessary management should be applied to improve the pregnancy outcomes.

Background: Identifying accurate prognostic molecular markers for papillary thyroid carcinoma (PTC) is important because many patients with PTC may be erroneously considered to have low-risk tumors. Evidence is also accumulating to support the existence of cancer stem cells in PTC., Methods: Thirty controls and 167 patients with PTC were selected to establish a tissue microarray to investigate cancer stem cell marker expression in samples from an established pathological database. The protein expressions of CD44, CD133, epithelial cell adhesion molecule (EpCAM), CD45, and CD90 were evaluated by immunohistochemical assay in the tissue microarray., Results: The protein levels of CD44, CD133, and EpCAM were significantly increased in PTC tissue compared with tissue from the controls. A positive correlation was found between cancer stem cell markers and tumor, node, and metastasis staging., Conclusions: Among a subset of patients with PTC, cancer stem cells detected by immunohistochemistry can be used as prognostic markers to screen for potential tumor dissemination. Whether these cancer stem cell markers are potentially therapeutic targets - and, thus, could be used for effective adjuvant treatment strategies - remains to be seen, and more data are needed.

The present study was to investigate whether a magnolia extract, named BL153, can prevent obesity-induced liver damage and identify the possible protective mechanism. To this end, obese mice were induced by feeding with high fat diet (HFD, 60% kcal as fat) and the age-matched control mice were fed with control diet (10% kcal as fat) for 6 months. Simultaneously these mice were treated with or without BL153 daily at 3 dose levels (2.5, 5, and 10 mg/kg) by gavage. HFD feeding significantly increased the body weight and the liver weight. Administration of BL153 significantly reduced the liver weight but without effects on body weight. As a critical step of the development of NAFLD, hepatic fibrosis was induced in the mice fed with HFD, shown by upregulating the expression of connective tissue growth factor and transforming growth factor beta 1, which were significantly attenuated by BL153 in a dose-dependent manner. Mechanism study revealed that BL153 significantly suppressed HFD induced hepatic lipid accumulation and oxidative stress and slightly prevented liver inflammation. These results suggest that HFD induced fibrosis in the liver can be prevented partially by BL153, probably due to reduction of hepatic lipid accumulation, inflammation and oxidative stress.