The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical for viral propagation and pathology. Numerous host factors have been shown to participate in the regulation of the LTR promoter. Among th...The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical for viral propagation and pathology. Numerous host factors have been shown to participate in the regulation of the LTR promoter. Among them is the thyroid hormone (T3) receptor (TR). TR has been shown to bind to the critical region of the promoter that contain the NFbB and Sp1 binding sites. Interestingly, earlier transient transfection studies in tissue culture cells have yielded contradicting conclusions on the role of TR in LTR regulation, likely due to the use of different cell types and/or lack of proper chromatin organization. Here, using the frog oocyte as a model system that allows replication-coupled chromatin assembly, mimicking that in somatic cells, we demonstrate that unliganded heterodimers of TR and RXR (9-cis retinoic acid receptor) repress LTR while the addition of T3 relieves the repression and further activates the promoter. More importantly, we show that chromatin and unliganded TR/RXR synergize to repress the promoter in a histone deacetylase-dependent manner.展开更多
Resistance to Thyroid Hormone (RTH) is a rare form of hormone resistance secondary to changes in the genes encoding thyroid hormone receptors. The two subtypes, Pituitary RTH (PRTH) and Generalized RTH (GRTH), cause c...Resistance to Thyroid Hormone (RTH) is a rare form of hormone resistance secondary to changes in the genes encoding thyroid hormone receptors. The two subtypes, Pituitary RTH (PRTH) and Generalized RTH (GRTH), cause clinically distinguishable patient presentations. In PRTH, typically only the pituitary gland is resistant to thyroid hormone (TH) while the rest of the body maintains sensitivity. Selective pituitary resistance to thyroid hormone results in dysregulation of thyroid hormone homeostasis with clinical presentation as either euthyroid or hyperthyroidism. PRTH is characterized by elevated thyroid hormone levels with an elevated or inappropriately normal TSH concentration. Herein we describe a case report of a 70-year-old woman who complained of weight loss of over 35 lbs., palpitations, jitters, hair loss, diarrhea, fatigue, muscle weakness, etc. over 6 months, thus, indicating the presence of iatrogenic hyperthyroidism while receiving levothyroxine 175 ug daily prescribed by her primary care provider because of a reported history of “Graves disease” treated by radioactive iodine ablation of the thyroid several years ago. The daily dose of levothyroxine had been increased gradually at an interval of 3 months over a year because of persistent elevation of serum TSH level. Laboratory tests revealed markedly elevated Free T4, Free T3 and TSH levels, along with low concentrations of all lipid fractions, serum creatinine and urea nitrogen levels, indicating TSH induced hyperthyroidism or PRTH. Further testing documented a mutation of thyroid hormone receptor beta gene 2 confirming presence of PRTH. We believe that the initial diagnosis of Graves Disease was erroneous and I-131 ablation further confounded and missed the diagnosis of PRTH. Thus, the purpose of this report is to report a patient with PRTH and describe potential pitfalls in diagnosis and management of this rare disorder.展开更多
This study investigated whether high-normal thyrotropin（TSH） levels are associated with metabolic syndrome in euthyroid Chinese people≥40 years old.Clinical and metabolic factors were assessed in 2,356 subjects（40...This study investigated whether high-normal thyrotropin（TSH） levels are associated with metabolic syndrome in euthyroid Chinese people≥40 years old.Clinical and metabolic factors were assessed in 2,356 subjects（40-77 years old） with TSH levels in the normal range（0.35-5.00 mU/L）.Using 2.50 mU/L as the cut-off point of TSH level within the normal range,we divided subjects into the high-TSH（2.50-5.00 mU/L;n= 1,064） and low-TSH（0.35-2.50mU/L;n= 1,292） group.The results showed that the mean levels of body mass index（BMI）,total cholesterol（TC）,low density lipoprotein cholesterol（LDL-C）,and fasting plasma glucose（FPG） were higher in the high-TSH group and TSH levels were significantly positively con-elated with BMI,LDL-C,TC,and FPG.The prevalence of central obesity,hypertriglyceridemia,low high density lipoprotein cholesterol（HDL-C）,and high FPG（〉5.60 mmol/L） was significantly higher in females and subjects with high-TSH levels.Metabolic syndrome was also more prevalent in the high-TSH group.People over the age of 40 years with high-normal TSH levels had a 1.2-fold increased risk of metabolic syndrome,compared with those with low-normal TSII levels,after adjusting for age and gender.In conclusion,high normal TSH is a risk factor for metabolic syndrome in people ≥40 years old.展开更多
BACKGROUND: Although non-thyroidal illness syndrome(NTIS) is considered a negative prognostic factor, the alterations in free triiodothyronine(f T3) levels in trauma patients requiring massive transfusion have not bee...BACKGROUND: Although non-thyroidal illness syndrome(NTIS) is considered a negative prognostic factor, the alterations in free triiodothyronine(f T3) levels in trauma patients requiring massive transfusion have not been reported.METHODS: A prospective observational study comparing 2 groups of trauma patients was conducted. Group M comprised trauma patients requiring massive transfusions(>10 units of packed red blood cells) within 24 hours of emergency admission. Group C comprised patients with an injury severity score >9 but not requiring massive transfusions. Levels of f T3, free thyroxine(f T4), and thyroidstimulating hormone(TSH) were evaluated on admission and on days 1, 2, and 7 after admission. The clinical backgrounds and variables measured including total transfusion amounts were compared and the inter-group prognosis was evaluated. Results are presented as mean±standard deviation.RESULTS: Nineteen patients were enrolled in each group. In both groups, 32 were men, and the mean age was 50±24 years. In group C one patient died from respiratory failure. The initial f T3 levels in group M(1.95±0.37 pg/m L) were signifi cantly lower than those in group C(2.49±0.72 pg/m L; P<0.01) and remained low until 1 week after admission. Initial inter-group f T4 and TSH levels were not significantly different. TSH levels at 1 week(1.99±1.64 μIU/m L) were higher than at admission(1.48±0.5 μIU/m L) in group C(P<0.05).CONCLUSION: Typical NTIS was observed in trauma patients requiring massive transfusions. When initial resuscitation achieved circulatory stabilization, prognosis was not strongly associated with NTIS.展开更多
Background Resistance to thyroid hormone （RTH） is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent h...Background Resistance to thyroid hormone （RTH） is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor β（TRβ）. We report the clinical and laboratory characteristics and the genetic analysis of a patient with this rare disorder and his family members. Methods The clinical presentations and changes of thyroid function tests （TFTs） including magnetic resonance imaging （MRI） of pituitary and other laboratory tests were analysed. TFTs of his family＇s members were detected as well. Direct DNA sequencing of the TRβ gene was done for those with abnormal TFTs. Results The RTH child had goiter, irritability, aggressiveness, and sudoresis. His TFTs showed high levels of circulating free thyroid hormones （FT4 and FT3） and normal thyroid-stimulating hormone （TSH） concentrations. He felt worse when treated as hyperthyroidism （Grave disease） with thiamazole and his clinical presentations got improved obviously when treated as RTH with bromocriptine without obvious advert effect. We identified a novel missense mutation, A317D, located in exon 9 of the gene of this boy and his mother. His mother had not any clinical presentation, but having abnormal TFTs results. Conclusions This patient reported here was concordant with the criteria of RTH. The feature is dysfunction of hypothalamus-pituitary-thyroid axis. A novel mutation was found in the TRβ, A317D, of this family. This research verified the phenomena that there is a clinical heterogeneity within the same mutation of different RTH patients.展开更多
目的系统评价姜黄素对多囊卵巢综合征大鼠模型的疗效。方法检索中国知网、万方、维普、中国生物医学数据库、Web of Science、PubMed、Embase,检索时间为各数据库建立至2023年1月1日。采用Stata16.0进行Meta分析。结局指标包括性激素、...目的系统评价姜黄素对多囊卵巢综合征大鼠模型的疗效。方法检索中国知网、万方、维普、中国生物医学数据库、Web of Science、PubMed、Embase,检索时间为各数据库建立至2023年1月1日。采用Stata16.0进行Meta分析。结局指标包括性激素、血糖、炎症因子和磷脂酰肌醇3激酶(phosphatidylinositol-3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)蛋白活性物表达水平。结果共纳入8篇随机对照动物实验,Meta分析结果表明,与对照组相比,姜黄素能够改善多囊卵巢综合征模型组的睾酮(SMD=-2.66,95%CI[-3.72,-1.61],P=0.000)、孕酮(SMD=2.82,95%CI[2.11,3.54],P=0.045)、促黄体生成素(SMD=-2.76,95%CI[-4.28,-1.23],P=0.000)、空腹血糖(SMD=-2.82,95%CI[-3.77,-1.86],P=0.000)、空腹胰岛素(SMD=-2.44,95%CI[-3.40,-1.49],P=0.000)、稳态模型胰岛素抵抗指数(SMD=-2.68,95%CI[-3.66,-1.69],P=0.000)、C反应蛋白(SMD=-1.96,95%CI[-2.71,-1.22],P=0.032)、白细胞介素6(SMD=-2.48,95%CI[-3.25,-1.72],P=0.047);而对雌二醇(SMD=-2.07,95%CI[-6.35,2.20],P=0.000)、促卵泡生成素(SMD=0.76,95%CI[-0.63,2.15],P=0.000)、肿瘤坏死因子-α(SMD=-1.64,95%CI[-6.02,2.73],P=0.000)、PI3K蛋白活性表达水平(SMD=-0.26,95%CI[-2.44,1.92],P=0.000)、AKT蛋白活性表达水平(SMD=-2.26,95%CI[-6.14,1.63],P=0.000)等指标的差异无统计学意义。结论姜黄素可作为支持性治疗手段治疗多囊卵巢综合征,通过降低血糖、缓解炎症、调节激素紊乱等多种机制发挥作用。展开更多
文摘The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical for viral propagation and pathology. Numerous host factors have been shown to participate in the regulation of the LTR promoter. Among them is the thyroid hormone (T3) receptor (TR). TR has been shown to bind to the critical region of the promoter that contain the NFbB and Sp1 binding sites. Interestingly, earlier transient transfection studies in tissue culture cells have yielded contradicting conclusions on the role of TR in LTR regulation, likely due to the use of different cell types and/or lack of proper chromatin organization. Here, using the frog oocyte as a model system that allows replication-coupled chromatin assembly, mimicking that in somatic cells, we demonstrate that unliganded heterodimers of TR and RXR (9-cis retinoic acid receptor) repress LTR while the addition of T3 relieves the repression and further activates the promoter. More importantly, we show that chromatin and unliganded TR/RXR synergize to repress the promoter in a histone deacetylase-dependent manner.
文摘Resistance to Thyroid Hormone (RTH) is a rare form of hormone resistance secondary to changes in the genes encoding thyroid hormone receptors. The two subtypes, Pituitary RTH (PRTH) and Generalized RTH (GRTH), cause clinically distinguishable patient presentations. In PRTH, typically only the pituitary gland is resistant to thyroid hormone (TH) while the rest of the body maintains sensitivity. Selective pituitary resistance to thyroid hormone results in dysregulation of thyroid hormone homeostasis with clinical presentation as either euthyroid or hyperthyroidism. PRTH is characterized by elevated thyroid hormone levels with an elevated or inappropriately normal TSH concentration. Herein we describe a case report of a 70-year-old woman who complained of weight loss of over 35 lbs., palpitations, jitters, hair loss, diarrhea, fatigue, muscle weakness, etc. over 6 months, thus, indicating the presence of iatrogenic hyperthyroidism while receiving levothyroxine 175 ug daily prescribed by her primary care provider because of a reported history of “Graves disease” treated by radioactive iodine ablation of the thyroid several years ago. The daily dose of levothyroxine had been increased gradually at an interval of 3 months over a year because of persistent elevation of serum TSH level. Laboratory tests revealed markedly elevated Free T4, Free T3 and TSH levels, along with low concentrations of all lipid fractions, serum creatinine and urea nitrogen levels, indicating TSH induced hyperthyroidism or PRTH. Further testing documented a mutation of thyroid hormone receptor beta gene 2 confirming presence of PRTH. We believe that the initial diagnosis of Graves Disease was erroneous and I-131 ablation further confounded and missed the diagnosis of PRTH. Thus, the purpose of this report is to report a patient with PRTH and describe potential pitfalls in diagnosis and management of this rare disorder.
基金supported by the grants from the Chinese Society of Endocrinology and National Clinical Research Center for Metabolic Diseases(81170726)
文摘This study investigated whether high-normal thyrotropin（TSH） levels are associated with metabolic syndrome in euthyroid Chinese people≥40 years old.Clinical and metabolic factors were assessed in 2,356 subjects（40-77 years old） with TSH levels in the normal range（0.35-5.00 mU/L）.Using 2.50 mU/L as the cut-off point of TSH level within the normal range,we divided subjects into the high-TSH（2.50-5.00 mU/L;n= 1,064） and low-TSH（0.35-2.50mU/L;n= 1,292） group.The results showed that the mean levels of body mass index（BMI）,total cholesterol（TC）,low density lipoprotein cholesterol（LDL-C）,and fasting plasma glucose（FPG） were higher in the high-TSH group and TSH levels were significantly positively con-elated with BMI,LDL-C,TC,and FPG.The prevalence of central obesity,hypertriglyceridemia,low high density lipoprotein cholesterol（HDL-C）,and high FPG（〉5.60 mmol/L） was significantly higher in females and subjects with high-TSH levels.Metabolic syndrome was also more prevalent in the high-TSH group.People over the age of 40 years with high-normal TSH levels had a 1.2-fold increased risk of metabolic syndrome,compared with those with low-normal TSII levels,after adjusting for age and gender.In conclusion,high normal TSH is a risk factor for metabolic syndrome in people ≥40 years old.
文摘BACKGROUND: Although non-thyroidal illness syndrome(NTIS) is considered a negative prognostic factor, the alterations in free triiodothyronine(f T3) levels in trauma patients requiring massive transfusion have not been reported.METHODS: A prospective observational study comparing 2 groups of trauma patients was conducted. Group M comprised trauma patients requiring massive transfusions(>10 units of packed red blood cells) within 24 hours of emergency admission. Group C comprised patients with an injury severity score >9 but not requiring massive transfusions. Levels of f T3, free thyroxine(f T4), and thyroidstimulating hormone(TSH) were evaluated on admission and on days 1, 2, and 7 after admission. The clinical backgrounds and variables measured including total transfusion amounts were compared and the inter-group prognosis was evaluated. Results are presented as mean±standard deviation.RESULTS: Nineteen patients were enrolled in each group. In both groups, 32 were men, and the mean age was 50±24 years. In group C one patient died from respiratory failure. The initial f T3 levels in group M(1.95±0.37 pg/m L) were signifi cantly lower than those in group C(2.49±0.72 pg/m L; P<0.01) and remained low until 1 week after admission. Initial inter-group f T4 and TSH levels were not significantly different. TSH levels at 1 week(1.99±1.64 μIU/m L) were higher than at admission(1.48±0.5 μIU/m L) in group C(P<0.05).CONCLUSION: Typical NTIS was observed in trauma patients requiring massive transfusions. When initial resuscitation achieved circulatory stabilization, prognosis was not strongly associated with NTIS.
文摘Background Resistance to thyroid hormone （RTH） is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor β（TRβ）. We report the clinical and laboratory characteristics and the genetic analysis of a patient with this rare disorder and his family members. Methods The clinical presentations and changes of thyroid function tests （TFTs） including magnetic resonance imaging （MRI） of pituitary and other laboratory tests were analysed. TFTs of his family＇s members were detected as well. Direct DNA sequencing of the TRβ gene was done for those with abnormal TFTs. Results The RTH child had goiter, irritability, aggressiveness, and sudoresis. His TFTs showed high levels of circulating free thyroid hormones （FT4 and FT3） and normal thyroid-stimulating hormone （TSH） concentrations. He felt worse when treated as hyperthyroidism （Grave disease） with thiamazole and his clinical presentations got improved obviously when treated as RTH with bromocriptine without obvious advert effect. We identified a novel missense mutation, A317D, located in exon 9 of the gene of this boy and his mother. His mother had not any clinical presentation, but having abnormal TFTs results. Conclusions This patient reported here was concordant with the criteria of RTH. The feature is dysfunction of hypothalamus-pituitary-thyroid axis. A novel mutation was found in the TRβ, A317D, of this family. This research verified the phenomena that there is a clinical heterogeneity within the same mutation of different RTH patients.
文摘目的系统评价姜黄素对多囊卵巢综合征大鼠模型的疗效。方法检索中国知网、万方、维普、中国生物医学数据库、Web of Science、PubMed、Embase,检索时间为各数据库建立至2023年1月1日。采用Stata16.0进行Meta分析。结局指标包括性激素、血糖、炎症因子和磷脂酰肌醇3激酶(phosphatidylinositol-3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)蛋白活性物表达水平。结果共纳入8篇随机对照动物实验,Meta分析结果表明,与对照组相比,姜黄素能够改善多囊卵巢综合征模型组的睾酮(SMD=-2.66,95%CI[-3.72,-1.61],P=0.000)、孕酮(SMD=2.82,95%CI[2.11,3.54],P=0.045)、促黄体生成素(SMD=-2.76,95%CI[-4.28,-1.23],P=0.000)、空腹血糖(SMD=-2.82,95%CI[-3.77,-1.86],P=0.000)、空腹胰岛素(SMD=-2.44,95%CI[-3.40,-1.49],P=0.000)、稳态模型胰岛素抵抗指数(SMD=-2.68,95%CI[-3.66,-1.69],P=0.000)、C反应蛋白(SMD=-1.96,95%CI[-2.71,-1.22],P=0.032)、白细胞介素6(SMD=-2.48,95%CI[-3.25,-1.72],P=0.047);而对雌二醇(SMD=-2.07,95%CI[-6.35,2.20],P=0.000)、促卵泡生成素(SMD=0.76,95%CI[-0.63,2.15],P=0.000)、肿瘤坏死因子-α(SMD=-1.64,95%CI[-6.02,2.73],P=0.000)、PI3K蛋白活性表达水平(SMD=-0.26,95%CI[-2.44,1.92],P=0.000)、AKT蛋白活性表达水平(SMD=-2.26,95%CI[-6.14,1.63],P=0.000)等指标的差异无统计学意义。结论姜黄素可作为支持性治疗手段治疗多囊卵巢综合征,通过降低血糖、缓解炎症、调节激素紊乱等多种机制发挥作用。
