Further learning of clinical characteristics and imaging manifestations of nonketotic hyperglycemic hemichorea.

OBJECTIVE: To summarize the clinical characteristics and imaging manifestations of patients with nonketotic hyperglycemic hemichorea (NH-HC) and to explore the possible pathogenesis, diagnosis. and treatment of the disease in order to improve the understanding of this disease and avoid misdiagnosis. METHODS: Retrospective analysis was performed on the case data of five patients with NH-HC admitted to our hospital in recent years. The patients were treated in the department of endocrinology, department of neurology, and department of neurosurgery in our hospital, respectively. Meanwhile, relevant literatures were consulted for further learning. RESULTS: NH-HC is usually presented as a triad of nonketotic hyperglycemia, lateral chorea, and typical imaging manifestations of head magnetic resonance imaging or computed tomography, but the clinical manifestations are not the same, and imaging features may also be different, presenting a diversified trend in clinical practice. All five patients were given glucose-lowering drugs and improved with or without combination of drugs to control symptoms of chorea. CONCLUSION: NH-HC is a rare complication of diabetes, characterized by hyperglycemia and hemichorea. How to identify the extreme situation and make fast judgment is a top priority. Timely and correct control of blood glucose is the key to the treatment, and when necessary, application of dopamine receptor antagonists in patients with combination therapy can accelerate improvement of the clinical symptoms. The prognosis of NH-HC is good, the clinician should strengthen comprehensive understanding of this disease to avoid missed diagnosis or misdiagnosis and enable patients to get more timely and effective treatment.

Thyroid-stimulating hormone may participate in insulin resistance by activating toll-like receptor 4 in liver tissues of subclinical hypothyroid rats.

BACKGROUND: Thyroid-stimulating hormone (TSH) is an independent risk factor of and closely associated with metabolic disorders. In the present study, we explored the potential mechanism and adverse effects of TSH on insulin resistance in the liver of subclinical hypothyroidism models in vivo. METHODS: The mean glucose infusion rate (GIR), free fatty acids (FFAs), the homeostatic model assessment for insulin resistance (HOMA-IR), fasting plasma insulin (FINS), the TLR4 signal pathway and its intracellular negative regulator-toll-interacting protein (Tollip), and the modulators of insulin signaling were evaluated. RESULTS: Compared to the normal control group (NC group), the subclinical hypothyroidism rat group (SCH group) showed decreases in GIR and increases in FFAs, FINS, and HOMA-IR. The levels of TLR4 and of its downstream molecules like p-NF-κB, p-IRAK-1, IL-6 and TNF-α were evidently higher in the SCH group than in the NC group. Conversely, the level of Tollip was significantly lower in the SCH group than in the NC group. Compared to the NC group, the levels of phosphorylated IRS-1-Tyr and GLUT2 were decreased in the SCH group. Macrophage infiltration was higher in the SCH group than in the NC group. CONCLUSION: TSH may participate in aggravating inflammation by increasing macrophage infiltration; furthermore, it may activate the TLR4-associated inflammatory signaling pathway, thus interfering with insulin signals in liver tissues. Targeting TSH may have therapeutic benefits against metabolic disorders.

Metabolic Syndrome Is Associated with Poor Omicron Infection Prognosis While Inactivated Vaccine Improves the Outcome of Coronavirus Disease 2019 among Chinese Inhabitants: A Retrospective Observational Study from a Chinese Municipality.

Coronavirus disease 2019 (COVID-19) and metabolic syndrome (MetS) are currently highly prevalent diseases worldwide. Studies on clinical outcomes of patients with Omicron and MetS, especially after vaccination with an inactivated vaccine are limited. Herein, we explored the relationship between MetS and the outcome of Omicron infection. STUDY DESIGN: This was a retrospective observational study. METHODS: This study recruited 316 individuals with Omicron infection. The inpatient data from between 8 January and 7 February 2022 were obtained from designated isolation hospitals in Tianjin, China. Hierarchical and multivariable analysis was conducted on age, gender, number of complications, and vaccination status. RESULTS: Among the 316 study participants, 35.1% were diagnosed with MetS. The results showed that MetS was strongly associated with Intensive Unit Care (ICU) admission, Polymerase Chain Reaction (PCR) re-positivity, and severe COVID-19. The ICU admission rates of the unvaccinated individuals, those who received two-dose and full vaccination (3 doses), were 66.7%, 19.2%, and 0, respectively (p < 0.01). Two-dose and three-dose vaccinations significantly reduced PCR re-positivity. CONCLUSIONS: In summary, MetS increases the risk of ICU admission, PCR re-positivity, and severe COVID-19. MetS is a composite predictor of poor outcomes of Omicron infection. Two shots of inactivated vaccine, specifically three doses, effectively protect against Omicron even in the high-risk group.

Anti­PD­1 immune checkpoint inhibitor inducing endocrine toxicity in a patient with advanced lung cancer: A case report and literature review.

The anti-programmed cell death protein 1 (anti-PD-1) antibody is a breakthrough immune checkpoint inhibitor that modulates T-cell function. However, it may result in multiple immune-related adverse events (irAEs), such as endocrine toxicity. The present case report describes a 59-year-old female patient with advanced non-small cell lung cancer with a tumor proportion score of 50% for programmed death ligand 1. The patient developed dry skin, dizziness and fatigue after receiving the third infusion of the anti-PD-1 antibody pembrolizumab. Based on several clinical indicators, including low serum free T3 and free T4 titers, an elevated thyroid-stimulating hormone level and a high titer of thyroid peroxidase autoantibody, the patient was diagnosed with immune-induced autoimmune thyroiditis. The patient received continuous thyroxine replacement therapy until her thyroid function returned to normal. After the fifth infusion of pembrolizumab, the patient exhibited hyperglycemia, high serum ketone levels and low arterial blood pH, thus meeting the criteria for immune-induced autoimmune diabetes and diabetic ketoacidosis. As a result, the immunotherapy was discontinued and the patient was diagnosed with insulin-dependent diabetes mellitus. Following anti-PD-1 medication, the patient experienced autoimmune thyroid damage and autoimmune diabetes. Therefore, clinicians should regularly monitor patients undergoing immunotherapy and pay close attention to the characteristics irAEs. Patients with underlying thyroiditis should be carefully monitored due to this being a risk factor, and for patients with thyroiditis care should be taken when deciding on whether they should be treated with immunotherapy. The article also discusses the features and general mechanisms of immune-related endocrine toxicity.

The Factors Influencing the Renal Glucose Threshold in Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

OBJECTIVE: This study aims to explore the factors influencing the renal glucose threshold (RTG) in patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted on 1009 hospitalized patients with T2DM using stratified random sampling. Blood glucose was monitored using a dynamic blood glucose monitor to obtain the mean blood glucose (MBG), which is used to calculate the RTG. The factors influencing the RTG were then analyzed. RESULTS: The mean RTG in patients with newly diagnosed T2DM was 203.58 ± 55.22 mg/dl. The correlation between the RTG and the various variables was analyzed, and the results demonstrated that the RTG was correlated with the patient's age (r = -0.14539, P = 0.0001); MBG (r = -0.35009, P = 0.0001); renal long neck (r = 0.16762, P = 0.0001); homeostatic model assessment for insulin resistance (r = -0.38322, P = 0.0001); homeostatic model assessment for beta-cell function (r = -0.22770, P = 0.0001); and the levels of glycated hemoglobin (HbA1c; r = 0.98994, P = 0.0001), blood urea nitrogen (r = -0.11093, P = 0.0004), creatinine (r = -0.26414, P = 0.0001), uric acid (r = -0.20149, P = 0.0001), total cholesterol (r = 0.13192, P = 0.0001), low-density lipoprotein (r = 0.12466, P = 0.0001), thyroid-stimulating hormone (r = -0.06346, P = 0.0460), beta-2 microglobulin (r = -0.08884, P = 0.0056), and 24-hour urine glucose (r = 0.32115, P = 0.0001). Multiple linear stepwise regression analysis revealed that the HbA1c, 24-hour urine glucose, estimated glomerular filtration rate (eGFR), D-dimer, and body mass index (BMI) should be included in the final model, and HbA1c had the greatest impact on the RTG followed in descending order by the 24-hour urine glucose, eGFR, D-dimer, and BMI (P < 0.05). CONCLUSION: The RTG increases in most patients with newly diagnosed diabetes. The risk factors for the RTG are HbA1c, 24-hour urine glucose, eGFR, D-dimer, and BMI.

Epigallocatechin Gallate Suppresses Inflammatory Responses by Inhibiting Toll-like Receptor 4 Signaling and Alleviates Insulin Resistance in the Livers of High-fat-diet Rats.

EGCG is a major pharmacological compound in green tea. Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Inflammation and insulin resistance are involved in the development of the disease. In this study, we investigated the beneficial effect of EGCG on the liver tissue of NAFLD rats induced by a high-fat diet and its underlying mechanism. Thirty Sprague-Dawley rats received a normal diet, a HFD and a HFD+EGCG. The expression levels of inflammatory signaling pathway genes (e.g., TLR4, TRAF6, IKKß, NF-κB, TNF-α) and insulin signaling transduction pathway genes (e.g., PI3K, AKT, IRS-1, IRS-2) were detected in the liver. We observed that EGCG decreased the triglyceride (TG) concentration in rat livers and suppressed TLR4, TRAF6, IKKß, p-IKKß, p-NF-κB, and TNF-α levels compared with those in the HFD group, whereas PI3K, AKT, IRS-1, and IRS-2 indicators were improved. EGCG improves obesity-associated subacute hepatic inflammation states, probably through the TLR4 signaling pathway. Furthermore, EGCG also alleviated hepatic insulin resistance. These data indicate that EGCG improves NAFLD from two ways: inhibition of inflammation and improvement of insulin resistance in liver tissues.

Thyrotropin Regulates eNOS Expression in the Endothelium by PGRN Through Akt Pathway.

To investigate the expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) in the aorta of subclinical hypothyroidism (SCH) rat model. The mechanisms underlying thyrotropin (TSH) affecting eNOS and PGRN expression in human umbilical vein endothelial cells (HUVECs) cultured in vitro were investigated. In the current study, SCH rat models were established by the administration of L-T4 injection after thyroidectomy in Wistar rats, as opposed to that in the normal and clinical hypothyroidism (CH) groups. The concentrations of NO (pmol/µL) in the SCH and CH groups were significantly lower than that in the normal group (40.8 ± 7.6 and 32.9 ± 10.8 vs. 51.2 ± 12.1, P < 0.05). However, the expression level of eNOS is increased significantly (P < 0.05) in both SCH and CH groups; a similar result was observed for the PGRN protein. In cultured HUVECs, TSH can also up-regulate the expression of eNOS; however, it is accompanied by a reduced concentration of NO and increased level of superoxide anion, thereby indicating uncoupled eNOS. As eNOS is increased, we found that Akt in HUVECs were upregulated by TSH, as well as PGRN expression. While inhibiting the expression of PGRN in HUVECs using siRNA, the expression of eNOS, as well as Akt were also inhibited. In conclusion, SCH can induce vascular endothelial dysfunction in rats, and PGRN participated in the process of TSH-induced expression of Akt/eNOS in the endothelium.

Expression of Iodotyrosine Deiodinase in Thyroid and Other Organs in Iodine-Deficient and Iodine-Excess Rats.

In mammals, iodothyronine deiodinase and iodotyrosine deiodinase (IYD) are known to catalyze the reductive dehalogenation. IYD is a critical enzyme in maintaining iodine homeostasis. Advances in the study of iodothyronine deiodinase have been published steadily; research on IYD has been slow on its function and regulation. We studied the expression of IYD in thyroid, liver, and kidney in conditions such as iodine deficiency and excess to determine its regulation and role in iodine recycling. Sixty 4-week-old female Wistar rats were randomly divided into two groups, with each group containing three subgroups. The rats were fed with different iodine intake for 3 months. After 3 months, all the rats were sacrificed, and the expression of IYD in thyroid, liver, and kidney of the rats were determined. We found that the expression of thyroidal IYD in 0.3-fold-iodine intake group was significantly higher as compared with the low-iodine feed control group (p < 0.01), whereas the expression in 6-fold-iodine intake group was significantly decreased as compared with normal-iodine feed control group (p < 0.01). However, the variation of IYD expression in thyroid was not similar to liver and kidney. In conclusion, iodine deficiency results in an increased expression of IYD in thyroid, whereas excess iodine decreases the expression of thyroidal IYD. In humans, daily iodine intake of <75 or >500 µg can affect the expression of thyroidal IYD. The safety range of iodine intake is narrow. In addition, further investigations are required to study the expression and regulation of IYD in various organs.

Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced Toll-like receptor 4 (TLR4) activity via 67 kDa laminin receptor (67LR) in 3T3-L1 adipocytes.

Obesity-related insulin resistance is associated with chronic systemic low-grade inflammation, and toll-like receptor 4 (TLR4) regulates inflammation. We investigated the pathways involved in epigallocatechin gallate (EGCG) modulation of insulin and TLR4 signaling in adipocytes. Inflammation was induced in adipocytes by lipopolysaccharide (LPS). An antibody against the 67 kDa laminin receptor (67LR, to which EGCG exclusively binds) was used to examine the effect of EGCG on TLR4 signaling, and a TLR4/MD-2 antibody was used to inhibit TLR4 activity and to determine the insulin sensitivity of differentiated 3T3-L1 adipocytes. We found that EGCG dose-dependently inhibited LPS stimulation of adipocyte inflammation by reducing inflammatory mediator and cytokine levels (IKKß, p-NF-κB, TNF-α, and IL-6). Pretreatment with the 67LR antibody prevented EGCG inhibition of inflammatory cytokines, decreased glucose transporter isoform 4 (GLUT4) expression, and inhibited insulin-stimulated glucose uptake. TLR4 inhibition attenuated inflammatory cytokine levels and increased glucose uptake by reversing GLUT4 levels. These data suggest that EGCG suppresses TLR4 signaling in LPS-stimulated adipocytes via 67LR and attenuates insulin-stimulated glucose uptake associated with decreased GLUT4 expression.

Maternal Subclinical Hypothyroidism Impairs Neurodevelopment in Rat Offspring by Inhibiting the CREB Signaling Pathway.

Thyroid hormone is indispensable for fetal brain development, and maternal thyroid hormone deficiency is thought to result in severe and irreversible brain impairments in learning and memory. Epidemiological and animal studies by our group had shown that maternal subclinical hypothyroidism had significant negative impact on neurodevelopment. But, the underlying mechanisms responsible for these neurological alterations remain unclear. In the present study, we performed thyroidectomy and injected L-T4 daily in Wistar rats to induce maternal subclinical hypothyroidism. Our data indicated that the pups from subclinical group showed prolonged latencies during the learning process in the Morris water maze as compared to the control group. Transcription factor cAMP response element-binding protein (CREB) signaling pathway is closely associated with synaptic plasticity, learning, and memory. Consistent with behavioral results, Western blotting also showed decreased activation of three important upstream modulators of CREB signaling pathway: phospho-mitogen-activated protein kinases (P-ERK1/2), phospho-calcium-dependent-calmodulin kinase IV (P-CaMKIV), phospho-serine/threonine protein kinase AKT(P-AKT), as well as total CREB and phospho-CREB as compared to the control at postnatal day 7 (PND 7) in hippocampus. Our findings suggested that decreased activation of the CREB signaling pathway in pups was related to impairments of cognitive function caused by maternal subclinical hypothyroidism.

Continuous effect with long-term safety in zoledronic acid therapy for polyostotic fibrous dysplasia with severe bone destruction.

Polyostotic fibrous dysplasia (PFD) is a rare non-inherited genetic disorder characterized by osteolytic lesions in multiple bones causing bone pain, deformity, and pathological fracture. As an anti-osteolytic agent, the new generation bisphosphonate zoledronic acid (ZOL) restricts lesion progression by inhibiting osteoclastic activity. Although ZOL is more effective than pamidronate, its efficacy and safety in long-term therapy in PFD is unknown. We report a case of PFD advanced to extensive bone destruction in the skull and ribs and evaluate the efficacy and long-term safety of early first-line ZOL in PFD with severe bone disease, recommending possible future treatments. The annual infusion of 5 mg ZOL was intravenously administered, cumulatively 20 mg over four courses, with oral supplementation of calcium, vitamin D, and potassium. No long-term use side effect was observed, and mild transient symptoms were easily resolved. Significant radiological improvement was seen in filling of destroyed bone and cortical thickening. ZOL decreased both serum collagen type 1 cross-linked C-telopeptide and type 1 procollagen N-terminal (P1NP) from extremely high baseline levels. An unexpected direct increase in P1NP after long-term therapy could indicate discontinuation of ZOL to observe its prolonged effect. Early first-line ZOL therapy is effective in PFD with severe bone destruction and is safe for long-term therapy. The use of bisphosphonates in FD remains off-label, and regular monitoring is highly advised.

Epigallocatechin gallate prevents inflammation by reducing macrophage infiltration and inhibiting tumor necrosis factor-α signaling in the pancreas of rats on a high-fat diet.

In this study, we hypothesized that epigallocatechin gallate (EGCG) would suppress inflammation in the pancreas, and thus, we investigated the effects that EGCG administration had in the pancreas of rats fed a high-fat diet (HFD). To test our hypothesis, 30 male Sprague-Dawley rats were divided into 2 groups: normal diet (control) group and HFD group. When there was a significant difference in body weight between the 2 groups (P < .05), the HFD group was further divided into 2 subgroups: the HFD group (HFD, n = 10, 16 weeks) and the EGCG group (HFD + 3.2 g/kg EGCG, n = 10, 16 weeks). Metabolite levels and the expression of inflammatory markers (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], and toll-like receptor 4) were measured using standard biochemical techniques. Insulin secretion and pancreatic histology were also evaluated. Epigallocatechin gallate significantly decreased fasting insulin levels as well as the homeostasis model assessment-insulin resistance index. In the HFD group, the average glucose infusion rate and the TNF-α and IL-6 levels increased, whereas toll-like receptor 4 and TNF receptor-associated factor-6 did not. A pathologic analysis of pancreatic tissue revealed an increase in inflammatory TNF-α and infiltrating CD68+ macrophages in the islets of the HFD rats, but rarely is this observed in the in the HFD + EGCG rats. Overall, these data suggest that EGCG suppresses inflammation, partially reverses metabolic abnormalities, and ultimately increases insulin sensitivity in the pancreas of HFD rats.

Maternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study.

BACKGROUND: Increasing data suggest that subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes, but there are limited data on the association of these conditions in early pregnancy with subsequent miscarriage. METHODS: In this prospective cohort study, we screened 3315 women at low risk for thyroid dysfunction at four to eight weeks' gestation from iodine-sufficient areas of China between January 2012 and September 2012. Thyrotropin (TSH), free thyroxine (fT4), and the autoantibodies thyroid-peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were measured. Based on these results, women were divided into four groups for comparison: euthyroidism (ET), isolated SCH, isolated TAI (positive TPOAb or/and TgAb), and SCH with TAI (SCH+TAI). The SCH group was stratified into two subgroups (SCH 1 and SCH 2) on the basis of the level of TSH (2.5 ≤ TSH < 5.22 or 5.22 ≤ TSH < 10 respectively). Accordingly, the SCH+TAI group was also stratified into two subgroups (SCH+TAI 1 and SCH+TAI 2). The outcome of interest was miscarriage, defined as spontaneous pregnancy loss prior to 20 weeks. RESULTS: Compared to women with ET, the risk of miscarriage was significantly higher among women with SCH 2 (7.1% vs. 2.2%, aOR 3.40 [CI 1.62-7.15]; p = 0.002), isolated TAI (5.7% vs. 2.2%, aOR 2.71 [CI 1.43-5.12]; p = 0.003), SCH+TAI 1 (10.0% vs. 2.2%, aOR 4.96 [CI 2.76-8.90]; p = 0.000), and SCH+TAI 2 (15.2% vs. 2.2%, aOR 9.56 [CI 3.76-24.28]; p = 0.000). The gestational ages of 110 women at miscarriage were lower among women with subclinical thyroid abnormalities compared to ET (11.13 ± 3.21 weeks with subclinical thyroid abnormalities vs. 9.33 ± 1.71 weeks with ET; p = 0.024). In parallel with the higher TSH levels, there were earlier gestation ages at miscarriage between subgroups of SCH and SCH+TAI (SCH 1 vs. SCH 2: 10.79 ± 1.77 vs. 9.70 ± 1.47 weeks, p = 0.039; SCH+TAI 1 vs. SCH+TAI 2: 9.59 ± 1.97 vs. 8.88 ± 1.24 weeks, p = 0.031). CONCLUSIONS: Women with SCH and TAI are at an increased risk of miscarriage between four and eight gestational weeks. Women with a combination of SCH and TAI were found to have the highest risk and earlier gestational ages of miscarriage.

Epigallocatechin gallate improves insulin signaling by decreasing toll-like receptor 4 (TLR4) activity in adipose tissues of high-fat diet rats.

SCOPE: In this study, we investigated the beneficial effects and the underlying mechanism of epigallocatechin gallate (EGCG) in adipose tissues of rats fed with a high-fat diet (HFD). METHODS AND RESULTS: Fasting plasma insulin, epididymal fat coefficient and free fatty acids, homeostasis model assessment-insulin resistance index, and the average glucose infusion rate were determined. EGCG significantly decreased free fatty acids, fasting insulin, homeostasis model assessment-insulin resistance index, and epididymal fat coefficient, and increased glucose infusion rate in HFD group. The levels of toll-like receptor 4, TNF receptor associated factor 6, inhibitor-kappa-B kinase ß, p-nuclear factor κB, tumor necrosis factor α, and IL-6 in the EGCG group were all significantly lower than the HFD control group. EGCG also decreased the level of phosphorylated insulin receptor substrate 1 and increased phosphoinositide-3-kinase and glucose transporter isoform 4 in the HFD group. Decreased macrophage infiltration was in EGCG group versus HFD group, and the protein level of CD68 in EGCG group was also significantly lower than that of HFD group. CONCLUSION: EGCG attenuated inflammation by decreasing the content of macrophages, interfered the toll-like receptor 4 mediated inflammatory response pathway, thus, improving insulin signaling in adipose tissues.