Hormone and Metabolic Research最新文献

This study explored the association between serum Hcy level and the all-cause mortality among osteoarthritis (OA) patients. This cohort study included patients diagnosed as OA from the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Abbott Homocysteine assay, a fully automated fluorescence polarization immunoassay (FPIA) method, was used to measure the level of serum Hcy. Covariates included sociodemographic information, lifestyles, history of diseases and medications were extracted from the database. The weighted univariate, multivariate Cox proportional hazard models and restricted cubic splines (RCS) were utilized to explore the association between Hcy level and all-cause mortality in OA patients, with hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses based on different age, gender, duration of OA, complications and C-reactive protein (CRP) were further assessed by this association. Totally 1384 OA patients were included in this study, of which 817 (59.03%) died by 31 December 2019. After adjusting all covariates, high Hcy level was associated with the high all-cause mortality among OA patients (HR=1.31, 95%CI: 1.02-1.67), especially in females (HR=1.43, 95%CI: 1.07-1.91), aged >60 years (HR=1.49, 95%CI: 1.14-1.94), duration of OA >10 years (HR=1.40, 95%CI: 1.01-1.95), with the history of hypertension (HR=1.37, 95%CI: 1.03-1.80), without the history of diabetes (HR=1.36, 95%CI: 1.01-1.82) or CRP >0.29 mg/l (HR=1.51, 95%CI: 1.04-2.19). High serum Hcy level was associated with high risk of all-cause mortality in OA patients. Our results suggest that serum Hcy is a promising biomarker for the prognosis of OA patients.

Thyrotropin receptor antibodies (TRAb) are specific for Graves' disease (GD) and play a crucial role in the pathogenesis of GD. TRAb assays have recently been greatly improved. This review discusses the clinical application of TRAb in the differential diagnosis of hyperthyroidism, the prognosis of GD, GD in gestation and pediatrics, and GD related ophthalmopathy (GO). In addition to the classical competition and bioassays, a new bridging assay has emerged for TRAb assays. TRAb is the main pathogenic mechanism of hyperthyroidism in GD. Treated GD still has a high rate of recurrence and even a short-term surge of TRAb, leading to rapid deterioration of GO. Fetal goiter may be associated with elevated maternal TRAb during pregnancy, overtreatment may lead to fetal hypothyroidism. Pediatric patients with GD have high TRAb, poor remission from treatment, and insignificant manifestations of GO. TRAb is significantly correlated with GO activity and severity. Currently, TRAb assay has high specificity and sensitivity and can be used directly to identify the cause of hyperthyroidism. TRAb can be used to predict recurrence of drug treated GD or progression of GO after RAI therapy. TRAb should be measured regularly for GD in gestation to guide anti-thyroid medication to avoid thyrotoxicosis or hypothyroidism in the fetus. Monitoring TRAb in pediatric GD may help control the progression of GO. TRAb assay is an important guide for the treatment of GO.

After the COVID-19 pandemic, many patients have reported chronic fatigue and severe post-exertional malaise, with symptoms similar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The accumulation of agonistic receptor autoantibodies targeting beta-adrenergic (β1 and β2) and muscarinic (M3 and M4) neurotransmitter receptors may play a crucial role in the pathomechanism of both ME/CFS and post-COVID conditions. Therapeutic apheresis has been suggested as an effective treatment option for alleviating and mitigating symptoms in this desperate group of patients. In this single-center pilot study, we analyzed autoantibodies in a cohort of 20 post-COVID patients before and after therapeutic apheresis. Apheresis resulted in a decline of β1 or β2 adrenergic receptor antibodies in all patients. Additionally, the majority of patients experienced a concurrent reduction in symptoms such as fatigue, physical activity restrictions, myalgia, post-exertional malaise, and concentration disorders. This study clearly demonstrates an association between autoantibodies and the clinical improvement of post-COVID patients. Even if future sham-controlled trials do not show a positive outcome, extracorporeal apheresis may still be valuable for this patient group by temporarily improving microperfusion and symptoms. Success in restoring patients to work and normal life, as observed in many individuals after therapeutic apheresis, should be recognized. Therefore, we believe that extracorporeal therapeutic apheresis, as part of a multimodal treatment, should be considered an early intervention for postinfectious syndromes in selected patients.

Denosumab is a completely human monoclonal high-affinity antibody that binds to the nuclear factor kappa-B ligand (RANKL) and is widely used to treat osteoporosis. Furthermore, it can potentially lower serum calcium levels by inhibiting osteoclast activation and preventing bone calcium from being released into the blood. This review aimed to provide evidence of the efficacy and safety of denosumab in treating hypercalcemia in primary hyperparathyroidism (PHPT). PubMed and the Cochrane Library were searched for published studies that described denosumab for hypercalcemia management in PHPT. Data were extracted by two independent investigators and analyzed using SPSS 23. The risk of bias was assessed by NIH Quality Assessment Tool. In total, 161 patients with PHPT from 18 studies were included in this review. The average age was 61 (47-72) years and the highest serum calcium was 3.76 (3.11-4.20) mmol/l. We found that denosumab can effectively reduce the serum calcium level by a median reduction of 0.5 mmol/l within 3 days. Significant reduction was maintained for 14 days. The serum calcium-lowering effect weakened after one month. In conclusion, denosumab has a potential clinical value in treating hypercalcemia in patients with PHPT.

Glucagon-like peptide-1 (GLP-1) receptor agonists are effective hypoglycemic agents for type 2 diabetes mellitus (T2DM). It was reported that T2DM was implicated in pancreatic β-cell senescence. Whether loxenatide regulates cellular senescence of pancreatic β-cells is to be investigated. Our results revealed that high glucose (HG)-induced cellular senescence and elevated expression of SASP factors inhibited cell proliferation and stimulated DNA damage, which were reversed by loxenatide treatment. In addition, HG induction resulted in promoted insulin secretion and insulin synthesis of pancreatic β-cells and loxenatide treatment further strengthened these influences. In addition, loxenatide could inactivate the PERK/eIF2α signaling pathway via decreasing the levels of p-PERK and p-eIF2α in HG-induced pancreatic β-cells. Furthermore, CCT020312, an activator of the PERK/eIF2α signaling pathway, abolished loxenatide-mediated inhibiting cellular senescence, elevating cell proliferation and improving DNA damage and enhancing insulin secretion of HG-induced pancreatic β-cells. In conclusion, our results indicated that loxenatide impeded cellular senescence, promoted cell proliferation, improved DNA damage, enhanced insulin secretion and insulin synthesis of HG-induced pancreatic β-cells through modulating the PERK/eIF2α signaling pathway.

Insulin and thyroid hormones play important roles in our body. Insulin helps regulate the glucose level while the thyroid hormones affect various cells and tissues, metabolizing protein, lipids, and glucose. Hyperthyroidism and thyrotoxicosis are potential hazards for type 2 diabetes mellitus. There is a high prevalence of hypothyroidism being more common compared to hyperthyroidism coexisting with diabetes mellitus. Thyroid hormones affect glucose metabolism through its action on peripheral tissues (gastrointestinal tract, liver, skeletal muscles, adipose tissue, and pancreas). High-level thyroid hormone causes hyperglycemia, upregulation of glucose transport, and reduction in glycogen storage. The reverse is observed during low levels of thyroid hormone along with insulin clearance. The net result of thyroid disorder is insulin resistance. Type 2 diabetes mellitus can downsize the regulation of thyroid stimulating hormones and impair the conversion of thyroxine to triiodothyronine in peripheral tissues. Furthermore, poorly managed type 2 diabetes mellitus may result in insulin resistance and hyperinsulinemia, contributing to the proliferation of thyroid tissue and an increase in nodule formation and goiter size. Although metformin proves advantageous for both type 2 diabetes mellitus and thyroid disorder patients, other antidiabetics like sulfonylureas, pioglitazone, and thiazolidinediones may have adverse effects on thyroid disorders. Moreover, antithyroid drugs such as methimazole can weaken glycemic control in individuals with diabetes. Thus, an interplay between both endocrinopathies is observed and individualized care and management of the disorder needs to be facilitated.

There has been an increase in the diagnosis of thyroid nodules in recent years. In addition to the well-known criteria, features that are likely to increase the risk of malignancy are in the research process. In this study, we aimed to evaluate the malignant potential of nodules that expand the thyroid capsule ultrasonographically. A total of 109 patients with thyroid capsule-expanding nodules and 288 patients with non-expanding nodules were included in the study. Demographical data, ultrasonography features, and cytology results were noted, and histopathological findings were determined in operated patients. While malignant cytology was detected in 5.5% of capsule-expanding nodules in FNAB results, this rate was 0.7% in the non-capsule expanding group (p<0.001). According to the histopathological results, the incidence of malignancy was 15.6% in the capsule-expanding nodule group, while it was 3.1% in the other group (p=0.001). As a result of logistic regression analysis, it was determined that the risk of malignancy increased by 4.44-fold (95% CI 1.4-13.8, p=0.01) in patients with capsule-expanding nodules. Other features that increased the risk of malignancy were hypoechogenicity, microcalcification, and irregular margin presence. In this study, we found that the risk of malignancy increased in nodules expanding the thyroid capsule. Based on the increasing study data on this subject, monitoring thyroid capsule expansion in nodules may take its place among the criteria for malignancy in future evaluations.

The study aimed to develop a risk prognostic model using platelet-related genes (PRGs) to predict sepsis patient outcomes. Sepsis patient data from the Gene Expression Omnibus (GEO) database and PRGs from the Molecular Signatures Database (MSigDB) were analyzed. Differential analysis identified 1139 differentially expressed genes (DEGs) between sepsis and control groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed enrichment in functions related to immune cell regulation and pathways associated with immune response and infectious diseases. A risk prognostic model was established using LASSO and Cox regression analyses, incorporating 10 PRGs selected based on their association with sepsis prognosis. The model demonstrated good stratification and prognostic effects, confirmed by survival and receiver operating characteristic (ROC) curve analyses. It served as an independent prognostic factor in sepsis patients. Further analysis using the CIBERSORT algorithm showed higher infiltration of activated natural killer (NK) cells and lower infiltration of CD8 T cells and CD4 T cells naïve in the high-risk group compared to the low-risk group. Additionally, expression levels of human leukocyte antigen (HLA) genes were significantly lower in the high-risk group. In conclusion, the 10-gene risk model based on PRGs accurately predicted sepsis patient prognosis and immune infiltration levels. This study provides valuable insights into the role of platelets in sepsis prognosis and diagnosis, offering potential implications for personalized treatment strategies.

The relationship between serum homocysteine (Hcy) levels and atrial fibrillation (AF) recurrence following catheter ablation remains unclear. This meta-analysis aims to investigate this association. Comprehensive searches in PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) databases identified relevant studies published up to May 25, 2024. Cohort studies that measured pre-ablation serum Hcy levels and reported AF recurrence post-ablation were included. Data were analyzed using random-effects models by incorporating the potential influence of heterogeneity, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated for the association between serum Hcy levels and AF recurrence. Eleven retrospective cohort studies involving 2147 patients with AF who underwent catheter ablation were analyzed. Higher pre-ablation serum Hcy levels were associated with an increased risk of AF recurrence (OR for per 1 μmol/l increment of Hcy: 1.22, 95% CI: 1.17 to 1.28, p<0.001; I²=0%). Additionally, studies that categorized Hcy levels also found a higher risk of AF recurrence in patients with elevated Hcy (OR for patients with a high versus a low serum Hcy: 2.75, 95% CI: 2.02 to 3.75, p <0.001; I²=0%). Funnel plots and Egger's regression test indicated low risks of publication bias. In conclusions, elevated pre-ablation serum Hcy levels are significantly associated with an increased risk of AF recurrence post-catheter ablation. These findings suggest that Hcy could be a valuable biomarker for predicting AF recurrence and may inform pre-ablation risk stratification. Further prospective studies are warranted to confirm these results.