Central thyroid hormone sensitivity reflects the responsiveness of the hypothalamic-pituitary-thyroid feedback axis to circulating thyroid hormones. Reduced central sensitivity has been linked to age-related cardiometabolic diseases, but its association with biological age acceleration has not been well characterized. To comprehensively assess central thyroid hormone sensitivity, we developed a dual-hormone thyroid feedback quantile index (dTFQI) that integrates free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH). We investigated its associations with both body composition-related aging phenotypes and biological aging acceleration, assessed using Klemera–Doubal method biological age (KDM-BA) and Phenotypic Age (PhenoAge), in a cohort of 18,993 euthyroid adults. Multivariable linear regression, restricted cubic splines, subgroup analyses, and sensitivity analysis were performed. After full adjustment for covariates, higher dTFQI, indicating reduced central thyroid hormone sensitivity, was associated with higher visceral fat area (β = 1.35, P = 0.035) and body fat percentage (β = 0.50, P < 0.001), as well as lower skeletal muscle index (β = −0.10, P < 0.001) and bone mineral content (β = −0.03, P < 0.001). Higher dTFQI was also associated with lower KDM-BA acceleration (β = −0.42, P < 0.001) and lower PhenoAge acceleration (β = −0.14, P = 0.035). The association with PhenoAge acceleration was modest and did not reach statistical significance within individual subgroups. In this cross-sectional Chinese euthyroid population, reduced central thyroid hormone sensitivity was associated with an adverse body composition profile but lower biological age acceleration. These divergent associations suggest that thyroid feedback-axis variation may relate differently to tissue-level phenotypes and systemic biomarker-based aging metrics. The dTFQI weights require independent external validation, and longitudinal studies are needed to verify the observed associations.

Sarcopenia profoundly impacts the quality of life and longevity in elderly populations. Notably, alterations in thyroid hormone (TH) levels during ageing are intricately linked to the development of sarcopenia. In skeletal muscle, the primary action of TH is mediated through the thyroid hormone receptor alpha (TRα). Emerging evidence suggests that decreased TRα expression may precipitate mitochondrial dysfunction in ageing skeletal muscle tissues. Yet, the precise mechanisms and the potential causative role of TRα deficiency in sarcopenia are not fully understood. This study suggests that TRα may regulate mitochondrial calcium (Ca2+) transport across membranes by targeting the inositol 1,4,5-trisphosphate receptor 1 (IP3R1), as evidenced by ChIP-seq and RNA-seq analyses. Experiments using naturally aged mice, skeletal muscle-specific TRα knockout (SKT) mice, and C2C12 myoblasts were conducted to investigate this process further. Findings include increased IP3R1, mitochondria-associated endoplasmic reticulum membranes (MAM), and mitochondrial Ca2+ in aged skeletal muscle. Additionally, SKT mice exhibited smaller muscle fibres, increased IP3R1 and MAM, and mitochondrial dysfunction. ChIP-qPCR and TRα manipulation in C2C12 cells showed that TRα negatively regulates IP3R1 transcription. Moreover, TRα knockdown cells exhibited increased Ca2+ transfer in MAM and mitochondrial dysfunction, which was ameliorated by the IP3R1 inhibitor 2-aminoethoxydiphenyl borate. Reintroduction of TRα improved IP3R1-mediated mitochondrial Ca2+ overload in aged cells. Our findings uncover a novel mechanism by which TRα deficiency induces mitochondrial Ca2+ overload through IP3R1-mediated Ca2+ transfer in MAM, exacerbating skeletal muscle atrophy during ageing. The TRα/IP3R1 pathway in MAM Ca2+ transfer presents a potential therapeutic target for sarcopenia.

In mental health treatments, the recovery procedure of patients could be affected by multiple factors, such as their satisfaction toward the diagnosis, mental health conditions and willingness to receive the treatments. However, in Australia, the balance between patient-centered care and the coercive practices from the clinic has rarely been focused. Therefore, in this study, the author tries to address the gap between the ideal participation of patients in mental health treatments and real situations the author experienced. To achieve this objective, two case studies combined with literature reviews are utilized. The author concludes that playing the role of coordinators, advocating the consumer’s rights to express their true thoughts, maintaining the patient-centered practices and making efforts to refine related official documents should be considered in future mental health treatments.

PCB118, a 2,3',4,4',5-pentachlorobiphenyl, has been shown to destroy thyroidal ultrastructure and induce thyrocyte autophagy. Previously, we reported that PCB118 promoted autophagosome formation in vivo and in vitro, but more details remain to be revealed. To explore the underlying mechanism by which PCB118 regulates thyrocyte autophagy, Fischer rat thyroid cell line-5 (FRTL-5) cells were exposed to different doses of PCB118 at 0, 0.25, 2.5, and 25 nM for 0-48 h. Western blot analysis of autophagy-related proteins P62, BECLIN1, and LC3 demonstrated that PCB118 induced autophagy formation in dose- and time-dependent manner. Moreover, laser scanning confocal microscopy and flow cytometry showed PCB118 treatment led to time- and dose-dependent increase in intracellular calcium concentration ([Ca2+]i). Additionally, PCB118 promoted store-operated Ca2+ entry (SOCE) channel followed by significant increase of ORAI1 and STIM1 protein levels. On the other hand, PCB118 induced thyroidal autophagy via class III β-tubulin (TUBB3)/death-associated protein kinase 2 (DAPK2)/myosin regulatory light chain (MRLC)/autophagy-related 9A (ATG9A) pathway in FRTL-5 cells. Pretreatment with SOCE inhibitor SKF96365 reduced cytosolic Ca2+, ORAI1, STIM1, and BECLIN1 levels as well as LC3 II/LC3 I ratio, while increased P62 expression. SKF96365 also inhibited TUBB3/DAPK2/MRLC/ATG9A pathway in FRTL-5 cells treated by PCB118. Our results provide evidence that PCB118 may induce thyroidal autophagy through TUBB3-related signaling pathway, and these effects are likely to be regulated by calcium influx via SOCE channel.

BACKGROUND AND AIM:Skeletal muscle (SM) has been shown as a target of thyroid hormones (THs). However, the status of TH signaling in aged SM remains unclear. This study aimed to explore the mechanism of TH signaling in SM of aging mice.METHODS:Thirty C57BL/6J male mice were divided into 6-, 15- and 22-month (6, 15 and 22M) groups according to different age. Physical parameters were evaluated by analytical balance, grip strength test and histological analysis. Thyroid function was detected by enzyme-linked immunosorbent assay. TH signaling was compared among the three groups by real-time PCR and western blotting analysis.RESULTS:p16, p21, and p53 mRNA levels in SM increased in age-dependent manner. The muscle weight and strength decreased in 22M group compared to 6 and 15M groups. Concentrations of thyroid hormones, including free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 22 M mice were not shown significant difference compared to 6M or 15M mice, although FT3 showed slightly decrease and TSH appeared a mild increase accompanying with age. mRNA levels of TH transporters, including MCT8 and MCT10, as well as iodothyronine deiodinase type 2 (DIO2) and type 3 (DIO3), were higher in 22M, while TH receptor α (TRα) mRNA and protein expression was lower in 22M, compared to the other groups. Type-I myosin heavy chain (MyHC I), MyHC IIx, and MyHC IIa were upregulated and Type-IIb MyHC (MyHC IIb) was downregulated in SM with advancing age.CONCLUSIONS:TH signaling in SM changes with aging.

目的 评估 Graves甲状腺功能亢进症(甲亢)患者甲亢缓解早期健康相关生活质量.方法 采用SF-36健康调查量表和临床症状调查问卷,对 33例初发未治的 Graves甲亢患者进行调查,评估抗甲状腺药物(ATD)治疗前和治疗 6周和 12周患者的健康相关生活质量.结果 ATD治疗后,患者的常见的临床症状均逐步改善;但焦躁易怒和记忆力在ATD治疗 6周反而呈现恶化趋势,至12周时仍未见明显改善.与治疗前比较,ATD治疗 12周后,生理功能和生命活力评分增加(P＜0.05),总体健康评分增加(P＜0.01).治疗 12周后的健康变化评分也高于治疗前(P＜0.01).总体健康评分从治疗前的(48.56± 18.79)分增加至(60.61± 13.61)分,精神健康评分从治疗前的(64.22±15.97)分增加至(68.67± 18.11)分.结论 Graves甲亢患者在甲亢急性期及缓解早期心理健康状况有明显波动.临床实践中,除了关注甲亢患者的生理健康外,心理健康状况亦不容忽视.

OBJECTIVES:With the increase in aging population worldwide, the incidence of sarcopenia is also increasing. Thyroid hormones are important regulators that can affect body composition and physical function. The association between thyroid hormone levels and sarcopenia in susceptible elderly euthyroid subjects remains unclear. In this study, we investigated the effect of thyroid hormone concentrations on body muscle mass, muscle strength and physical function related to sarcopenia in elderly Chinese euthyroid subjects.METHODS:A total of 94 elderly Chinese euthyroid subjects (73 men, 21 women) without medications or diseases which obviously affected muscle metabolism or thyroid function were included in our study. Concentrations of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were determined by immunoassays. Appendicular skeletal muscle mass (ASM) was assessed by dual-energy X-ray absorptiometry. Handgrip strength was measured using a Jamar hand dynamometer, and physical function was assessed by the Short Physical Performance Battery (SPPB).RESULTS:Muscle function, both handgrip strength and SPPB, was negatively associated with age, and FT3 demonstrated age-dependent decline. Pearson's correlation analysis showed positive associations of FT3 with ASM, handgrip strength and SPPB. Neither FT4 nor TSH was associated with these parameters of sarcopenia in euthyroid subjects. Significantly positive correlations between FT3 and ASM, handgrip strength and SPPB were also observed in multiple linear regression analysis adjusted for age, gender and BMI, while no significant correlations were found between FT4 or TSH and aforementioned four parameters of sarcopenia. Subjects with sarcopenia had lower level of FT3.CONCLUSIONS:Higher FT3 concentration within normal range was correlated to muscle mass and muscle function in elderly subjects.

Objective:This study is aimed to explore the relationship between thyroid hormone and body composition in the elderly with euthyroid gland.Methods:Seventy-four euthyroid subjects with an average age 74.6±7.7 years old have been involved.Body weight,thyroid function and body composition have been measured.Results:Appendicular muscle mass (ASM) was positively associated with FT3 (P=0.003).There is still a positive correlation between the two indexes after adjusting for age,sex and body mass index (BMI) (P0.011).FT3 was positively correlated with lean subtotal(P=0.024).We found the same correlation between ASW and FT3 in female (P=0.043),but not male,after adjusting for age,sex and BMI.TSH was negatively correlated with appendicular fat mass and fat subtotal(P=0.039;P=0.038).None correlation between the two has been found after adjusting for confounding factors.Conclusion:Thyroid hormone is related with body composition in the elderly with euthyroid gland.

Polychlorinated biphenyls (PCBs) can severely interfere with multiple animals and human systems. To explore the molecular mechanisms underlying 2, 3', 4, 4', 5- pentachlorobiphenyl (PCB118)-induced thyroid dysfunction, Fischer rat thyroid cell line-5(FRTL-5) cells were treated with either different concentrations of PCB118 or dimethyl sulfoxide (DMSO). The effects of PCB118 on FRTL-5 cells viability and apoptosis were assessed by using a Cell Counting Kit-8 assay and apoptosis assays, respectively. Quantitative real-time polymerase chain reaction was used to quantify protein kinase B (Akt), Forkhead box protein O3a (FoxO3a), and sodium/iodide symporter (NIS) mRNA expression levels. Western blotting was used to detect Akt, phospho-Akt (p-Akt), FoxO3a, phospho-FoxO3a (p-FoxO3a), and NIS protein levels. Luciferase reporter gene technology was used to detect the transcriptional activities of FoxO3a and NIS promoters. The effects of the constitutively active Akt (CA-Akt) and dominant-negative Akt (DN-Akt) plasmids on p-Akt, p-FoxO3a, and NIS levels were examined in PCB118-treated FRTL-5 cells. The effects of FoxO3a siRNA on FoxO3a, p-FoxO3a, and NIS protein levels were examined in the PCB118-treated FRTL-5 cells. The effects of pcDNA3 (plsmid vectors designed for high-level stable and transient expression in mammalian host)-FoxO3a on NIS promoter activity were examined in the PCB118-treated FRTL-5 cells. Our results indicated that relatively higher PCB118 concentrations can inhibit cell viability in a concentration- and time-dependent manner. Akt, p-Akt, and p-FoxO3a protein or mRNA levels increased significantly in PCB118-treated groups and NIS protein and mRNA levels decreased considerably compared with the control groups. FoxO3a promoter activity increased significantly, whereas NIS promoter activity decreased. These effects on p-FoxO3a and NIS could be decreased by the DN-Akt plasmid, enhanced by the CA-Akt plasmid, and blocked by FoxO3a siRNA. The overexpressed FoxO3a could reduce NIS promoter activity. Our results suggested that PCB118 induces thyroid cell dysfunction through the Akt/FoxO3a/NIS signaling pathway.

Polychlorinated biphenyls (PCBs) are durable and widely distributed environmental contaminants that can compromise the normal functions of multiple organs and systems; one important mechanism is the induction of inflammatory disorders. In this study, we explored the influences of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on inflammatory responses and its underlying mechanisms in the thyroid. Wistar rats were administered PCB118 intraperitoneally at 0, 10, 100, and 1000 μg/kg/d, 5 days a week for 13 weeks; rat thyroid FRTL-5 cells were treated with PCB118 (0, 0.25, 2.5, and 25 nM) for indicated time. Results revealed that PCB118 promoted the generation of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in a time- and dose-related manner and decreased sodium/iodide symporter (NIS) protein expression. Moreover, stimulation with PCB118 resulted in the upregulation of the aryl hydrocarbon receptor (AhR)-responsive gene cytochrome P450 1A1 in FRTL-5 cells; whereas pretreatment with the AhR inhibitor α-naphthoflavone or AhR small interfering RNA (siRNA) suppressed AhR, CYP1A1, IL-6, and ICAM-1 and restored NIS expression. In vivo and in vitro studies also suggested that the c-Jun N-terminal kinase (JNK) pathway was activated on PCB118 exposure, and the experiments using siRNA for JNK partially blocked PCB118-induced upregulation of IL-6 and ICAM-1 and downregulation of NIS. Altogether, PCB118 stimulates production of IL-6, TNF-α, and ICAM-1 in the thyroid through AhR and JNK activations and subsequently interferes with NIS expression, resulting in the disruption of thyroid structure and function.

Subclinical hypothyroidism is a common disease among the elderly people.The diagnostic criteria is the abnormally high thyroid stimulating hormone (TSH) level accompanied by normal free T4 (FT4) level.It has been proved that the upper limit of normal TSH rises with age,therefore age-adjusted normal range of TSH values are needed which so far are not set up yet.The symptom of subclinical hypothyroidism is extremely similar to that of the aging and easly to be neglected.Persistentsubclinical hypothyroidism could affect multiple systems such as cardiovascular system,cognitive function,bone and muscle mass in elder individuals,but mildly elevated TSH (＜ 10 mIU/L) is associated with longevity for whose age were above 75 years old.Individualized treatment should be stressed for aged patients.Thyroxine replacement therapy is generally recommended when TSH is more than 10 mIU/L or there exists other risk factors.The recommended initial dose is 25-75μg/d and should be modified every 4 to 6 weeks according to TSH level and clinical manifestations.Thyroid function should be monitored every 6-12 months after maintenance dose is reached.

目的：了解我国现行医疗保险制度对糖尿病患者治疗费用的影响以及患者支出与赔付机制之间的关系，为完善医疗保险制度、全面施惠患者提供依据。方法对74例2012年—2013年间在江苏省人民医院糖友俱乐部注册成员进行问卷调查，采用SPSS11.5软件进行描述性分析。结果患者中门诊月均医疗费用743元，医疗总费用的70%由医保账户支出。病程超过10年的患者家庭收入的22%用于糖尿病治疗，病程10年以上的患者医疗开支较病程1~2年的患者高460%。结论中国的基本医疗保险制度值得肯定，但仍存在不完善之处。