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The wide ranging System involving Biological Variation towards the Low-Se Diet regime and Its Health risks in the Standard Native to the island Areas of Keshan Illnesses.
01), spent more time in the center zone (p less then 0.05), and showed lower thigmotaxis (p less then 0.01) when compared to OVX group. None of the hormonal manipulations affected anxiety-like behavior in the elevated plus maze test significantly, but a mild effect of interaction between ovarian condition and treatment was shown (p = 0.05). In conclusion, ovariectomy had slight negative effect on open-field ambulation and short-term recognition memory in middle-aged rats. In addition, a test-specific anxiolytic effect of estradiol supplementation was found. In contrast, letrozole treatment neither affected anxiety-like behavior nor memory.The estrogen receptor alpha (ERα) is a ligand-activated transcription factor whose activity is modulated by its interaction with multiple protein complexes. In this work, we have identified the protein interferon alpha inducible protein 27 (IFI27/ISG12) as a novel ERα-associated protein. IFI27/ISG12 transcription is regulated by interferon and estradiol and its overexpression is associated to reduced overall survival in ER+ breast cancer patients but its function in mammary gland tissue remains elusive. In this study we showed that overexpression of IFI27/ISG12 in breast cancer cells attenuates ERα transactivation activity and the expression of ERα-dependent genes. Our results demonstrated that IFI27/ISG12 overexpression in MCF-7 cells reduced their proliferation rate in 2-D and 3-D cell culture assays and impaired their ability to migrate in a wound-healing assay. We show that IFI27/ISG12 downregulation of ERα transactivation activity is mediated by its ability to facilitate the interaction between ERα and CRM1/XPO1 that mediates the nuclear export of large macromolecules to the cytoplasm. IFI27/ISG12 overexpression was shown to impair the estradiol-dependent proliferation and tamoxifen-induced apoptosis in breast cancer cells. Our results suggest that IFI27/ISG12 may be an important factor in regulating ERα activity in breast cancer cells by modifying its nuclear versus cytoplasmic protein levels. We propose that IFI27/ISG12 may be a potential target of future strategies to control the growth and proliferation of ERα-positive breast cancer tumors.Fetuin-A is a multifunctional glycoprotein that has been implicated in insulin resistance and bone metabolism. We assessed whether fetuin-A is associated with poor or excessive fetal growth. In the Shanghai Birth Cohort, we conducted a nested case-control study of 60 trios of small-for-gestational-age (SGA, birth weight 0.2). Higher fetuin-A concentrations were associated with increased risks of SGA [OR = 1.67 (1.08-2.58) per SD increment, P = 0.024] and LGA [OR = 2.36 (1.53-3.66), P less then 0.001]. Adjusting for maternal and neonatal characteristics and fetal growth factors, the elevated risk changed little for LGA [adjusted OR = 2.28 (1.29-4.01), P = 0.005], but became non-significant for SGA (P = 0.202). Our study is the first to demonstrate that fetuin-A may be involved in excessive fetal growth. This association is independent of fetal growth factors.
Coronavirus disease 2019 (COVID-19) has been shown to affect almost every organ throughout the body. However, it is not clear whether the thyroid gland is impaired in COVID-19 patients. Euthyroid sick syndrome (ESS) is usually associated with the disease severity and deterioration prognosis in critical illness. In this study, the thyroid function of COVID-19 patients was assessed and factors associated with outcomes were analyzed to determine the potential predictive value of ESS.

Clinical and laboratory data of COVID-19 patients with or without ESS in Changsha, China, were collected and analyzed on admission. Kaplan-Meier curve and cox regression model were utilized to determine the correlation between ESS and the endpoints. Subsequently, a receiver operating characteristic (ROC) curve was plotted to evaluate the predictive performances of FT3 and C-reactive protein (CRP) in the disease severity.

Forty-one (27.52%) cases of COVID-19 patients diagnosed with ESS. Polyinosinic acid-polycytidylic acid solubility dmso ESS patients had higher proportions of fever, shortness of breath, hypertension, diabetes, and severe events than those of non-ESS patients. The levels of erythrocyte sedimentation rate and C-reactive protein, and the positive rate of procalcitonin were significantly higher, whereas the lymphocyte count was apparently lower in ESS patients than in non-ESS patients. The regression analysis showed that ESS was significantly associated with the disease severity of COVID-19 (HR = 2.515, 95% CI 1.050-6.026,
= 0.039). The areas under the curve (AUCs) for predicting the severe disease were [0.809 (95% CI 0.727-0.892),
< 0.001] and [0.792 (95% CI 0.689-0.895),
< 0.001] for FT3 and CRP, respectively.

ESS was significantly associated with the disease severity and inflammatory parameters in COVID-19 patients.
ESS was significantly associated with the disease severity and inflammatory parameters in COVID-19 patients.Thyroid hormones control both metabolic pathways and body composition, whereas little knowledge is available about the possible influence of skeletal muscle mass (MM) on thyroid hormone metabolism and circulating levels. This was a cross-sectional study conducted at the Population Health Unit of the National Institute of Gastroenterology IRCCS "S. de Bellis" (Italy) and investigating the extent to which skeletal MM affects thyroid function in obesity. Two hundred twenty-seven consecutive healthy volunteers (155 women and 72 men) with overweight and obesity (BMI ≥ 25 kg/m2) and taking no medication or supplement were assessed for hormone, metabolic and routine laboratory parameters. Body composition parameters were collected by using bioelectrical impedance analysis (BIA). MM was directly related to the body mass index (BMI), waist circumference (WC), insulin, triglycerides, uric acid and free-triiodothyronine (FT3) serum levels, FT3 to the free-thyroxine (FT4) ratio, and insulin-resistance (HOMA-IR), and inversely related to age, total, and HDL-cholesterol serum levels. Multiple regression models confirmed the relationship between MM and the FT3 to FT4 ratio, independently of age, BMI, TSH, triglycerides, and insulin serum levels. The same analyses run by gender showed that this relationship maintained significance only in men. Increased skeletal MM in obesity results in improved thyroid activity mediated by increased T4 conversion to T3, and higher FT3 circulating levels, particularly in men. In conclusion, preserving a greater skeletal MM in obesity helps to enhance thyroid activity.
ClinicalTrials.gov, identifier NCT04327375.
ClinicalTrials.gov, identifier NCT04327375.GPER-1 is a novel membrane sited G protein-coupled estrogen receptor. Clinical studies have shown that patients suffering an estrogen receptor α (ERα)/GPER-1 positive, breast cancer have a lower survival rate than those who have developed ERα-positive/GPER-1 negative tumors. Moreover, absence of GPER-1 improves the prognosis of patients treated with tamoxifen, the most used selective estrogen receptor modulator to treat ERα-positive breast cancer. MCF-7 breast cancer cells were continuously treated with 1,000 nM tamoxifen for 7 days to investigate its effect on GPER-1 protein expression, cell proliferation and intracellular [Ca2+]i mobilization, a key signaling pathway. Breast cancer cells continuously treated with tamoxifen, exhibited a robust [Ca2+]i mobilization after stimulation with 1,000 nM tamoxifen, a response that was blunted by preincubation of cells with G15, a commercial GPER-1 antagonist. Continuously treated cells also displayed a high [Ca2+]i mobilization in response to a commercial GPER-1 agon.Background Ultrasound-guided radiofrequency ablation (RFA) of thyroid nodules (TNs) is a minimally invasive procedure that has been widely used to induce volume reduction in symptomatic solid benign TNs. The goal of this study was to investigate a novel therapeutic approach for single-session ablation of large thyroid nodules (LTNs, vol > 20 ml). Methods We performed a pilot cohort study of 21 patients with symptomatic solid benign LTNs (vol > 20 ml), who accepted ultrasound-guided RFA treatment between September 2018 and November 2019. RFA was performed using an 18-gauge internally cooled electrode with ultrasonographic guidance in a single session combined with intraoperative hydrodissection and immediate contrast-enhanced ultrasound (CEUS) to optimize safety and efficacy. Nodule volume was evaluated before ablation and at 1, 3, and 6 months after initial ablation, and all patients were asked to assess the cosmetic score (from 1 to 4) and symptom score (from 0 to 10) before ablation and at every follow-up after ablation. Results At the 6 month follow-up, there was significant nodule volume reduction, from 27.49 ml ± 7.9 (standard deviation) to 3.82 ml ± 5.02 (p = 0.001). Cosmetic signs (p = 0.001) and pressure symptoms (p = 0.001) were significantly improved. All patients underwent RFA without any major complications, and very few patients developed a change in voice (2/21). However, the changes subsided within 1 month. Almost half of the patients received an additional RFA (11/21) treatment to achieve complete ablation on the intraoperative immediate CEUS evaluation. Conclusion RFA is effective for treating LTNs (vol > 20 ml) and controlling clinical symptoms with a low complication rate. Patients were satisfied with cosmetic sign and pressure symptom improvement. The intraoperative hydrodissection and immediate CEUS represent a novel therapeutic approach for single-session ablation of LTNs.
To evaluate whether metformin use assuredly alters overall all-cause death in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).

Pubmed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to Feb. 29, 2020 with no language restriction. All related articles comparing all-cause death of T2DM and CKD patients after metformin use (monotherapy or combination) versus non-metformin treatment were identified. Pooled risk ratios (RR) and 95% confidence intervals (CI)were computed using random-effects models regardless of the heterogeneity quantified by Cochrane χ
and I
statistics.

Totally 13 studies (9 cohort studies [CSs], 3 subanalyses or post-hoc analyses of randomized controlled trials [RCTs], and 1 nested case-control article) involving 303,540 patients were included. Metformin-based treatments relative to any other measure displayed significantly lower risks of all-cause mortality (Pooled RRs 0.71, 95%CI 0.61 to 0.84; I
79.0%) and cardiovascular events (Pooled RRs 0.76, 95%CI 0.60 to 0.97; I
87.0%) in CKD patients at stage G1-3, with substantial heterogeneity. Metformin use was not significantly related with these end points in advanced CKD patients.

Metformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess whether these key benefits extend to later stages of CKD by dose adjustment.
Metformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess whether these key benefits extend to later stages of CKD by dose adjustment.
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