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A 53-year-old woman presented with persistent edema and pain of the metacarpophalangeal and proximal interphalangeal joints and the wrist, knee and ankle joints, with more recent intermittent nausea and vomiting. Treatment for rheumatoid arthritis and osteoarthritis was ineffective. No clinical manifestations typical of hyperthyroidism were observed. The results of the thyroid function tests were as follows: Thyroid-stimulating hormone, 0.003 µIU/ml; triiodothyronine (T3), 4.44 ng/ml;, thyroxine (T4) >30 µg/dl; free T3, 14.03 pg/ml; and free T4, 8.84 ng/dl. The laboratory tests revealed an elevated serum calcium level (2.96 mmol/l); moderate hypophosphatemia (0.84 mmol/l); significantly reduced serum intact parathyroid hormone (4.8 pg/ml); normal 25-hydroxy vitamin D (52.13 nmol/l) and bone-specific alkaline phosphatase (22.1 ng/ml); and elevated osteocalcin (128.8 ng/ml). X-ray and quantitative ultrasound examinations revealed extensive osteoporosis of the hands, skull, knees and pelvis, with a bone mineral density of 0.254 g/cm² (T-score, -3.2). Anti-thyroid therapy (methimazole, 30 mg/day; salmon calcitonin, 50 IU/day; and alendronate, 70 mg/week) was initiated. After 2 weeks, the serum calcium and phosphate levels were normalized (2.44 and 1.19 mmol/l, respectively) and calcitonin was discontinued. After 3 months, the patient had no nausea, vomiting or joint pain, and her appetite was normal, with a weight gain of ~10 kg. Euthyroidism was achieved and the serum calcium and phosphate levels were normalized (2.31 and 1.12 mmol/l, respectively) and maintained for 6 months, by which time the osteocalcin level had diminished (80.40 ng/ml). This rare case of arthralgia, hypercalcemia and extensive osteoporosis as the first manifestations of hyperthyroidism suggests that, even without typical symptoms, hyperthyroidism should be considered in the differential diagnosis of patients with persistent arthralgia. [ABSTRACT FROM AUTHOR]

Carbon and nitrogen are essential components for plant growth. Although models of plant carbon and nitrogen metabolisms have long been established, certain gaps remain unfilled, such as how plants are able to maintain a flexible nocturnal starch turnover capacity over various light cycles, or how nitrogen remobilization is achieved during the reproductive growth stage. Recent advances in plant autophagy have shed light on such questions. Not only does autophagy contribute to starch degradation at night, but it participates in the degradation of chloroplast proteins and even chloroplasts after prolonged carbon starvation, thus help maintain the free amino acid pool and provide substrate for respiration. The induction of autophagy under these conditions may involve transcriptional regulation. Large-scale transcriptome analyses revealed that ATG8e belongs to a core carbon signaling response shared by Arabidopsis accessions, and the transcription of Arabidopsis ATG7 is tightly co-regulated with genes functioning in chlorophyll degradation and leaf senescence. In the reproductive phase, autophagy is essential for bulk degradation of leaf proteins, thus contributes to nitrogen use efficiency (NUE) both under normal and low-nitrogen conditions. [ABSTRACT FROM AUTHOR]

Background: While multiple replication origins have been observed in archaea, considerably less is known about their evolutionary processes. Here, we performed a comparative analysis of the predicted (proved in part) orc/cdc6-associated replication origins in 15 completely sequenced haloarchaeal genomes to investigate the diversity and evolution of replication origins in halophilic Archaea. Results: Multiple orc/cdc6-associated replication origins were predicted in all of the analyzed haloarchaeal genomes following the identification of putative ORBs (origin recognition boxes) that are associated with orc/cdc6 genes. Five of these predicted replication origins in Haloarcula hispanica were experimentally confirmed via autonomous replication activities. Strikingly, several predicted replication origins in H. hispanica and Haloarcula marismortui are located in the distinct regions of their highly homologous chromosomes, suggesting that these replication origins might have been introduced as parts of new genomic content. A comparison of the origin-associated Orc/Cdc6 homologs and the corresponding predicted ORB elements revealed that the replication origins in a given haloarchaeon are quite diverse, while different haloarchaea can share a few conserved origins. Phylogenetic and genomic context analyses suggested that there is an original replication origin (oriC1) that was inherited from the ancestor of archaea, and several other origins were likely evolved and/or translocated within the haloarchaeal species. Conclusion: This study provides detailed information about the diversity of multiple orc/cdc6-associated replication origins in haloarchaeal genomes, and provides novel insight into the evolution of multiple replication origins in Archaea. [ABSTRACT FROM AUTHOR]

Reverse gyrase (RG) is an ATP-dependent type I DNA topoisomerase that introduces positive supercoils into DNA in thermophiles. Four regions of RG, i.e., the N-terminal zinc-finger motif, the β-hairpin in subdomain H1, the 'latch', and the C-terminal zinc-finger motif, were predicted to be involved in DNA binding previously. In this paper, the functions of these regions in the enzymatic activity were evaluated by mutational analysis of the Thermoanaerobacter tengcongensis reverse gyrase (TtRG). We demonstrated that TtRG exhibited positive-supercoiling activity only at high temperature (>50°C) and low salt concentration (~30 mM NaCl), and three of these four regions (except for the 'latch') were involved in DNA binding. Notably, mutations in the 'latch' and β-hairpin regions of TtRG strongly impaired the ATPase activity, while mutations in the two zinc-finger motifs dramatically affected its thermal stability besides significant impairment of the DNA-binding ability. Accordingly, all of these four regions were found to be indispensable for the positive-supercoiling activity of TtRG. Taken together, we revealed that these putative DNA-contact regions affect the enzymatic activity of RG in different ways, and provided new insights into the structure and function of RG. [ABSTRACT FROM AUTHOR]

Fetal renin-angiotensin system (RAS) activity is developmentally regulated, increasing in late gestation toward term. At the same time, fetal hemodynamic parameters change, with blood pressure increasing and heart rate decreasing. During this period, fetal plasma thyroid hormone concentrations also increase significantly. In this study we utilized the technique of thyroidectomy (TX), which removes thyroid hormone from the circulation, to investigate the importance of thyroid hormone on the developmental changes in the RAS (in plasma, kidney, heart, and lung) and hemodynamic regulation in fetal sheep. TX was performed at 120 days of gestational age (dGA), and control fetuses were sham operated. Immediately before necropsy (∼137 dGA), fetuses were infused with isoproterenol and the hemodynamic responses were noted. TX significantly decreased plasma thyroid hormone concentrations and renal renin mRNA and renal active renin levels but did not change fetal plasma active renin levels. TX decreased both angiotensin II receptor subtype 1 (AT1) mRNA and protein levels in kidney and lung but not in the left ventricle. TX also was associated with increased ANG II receptor subtype 2 (AT2) mRNA and protein at the 44-kDa band in kidney, whereas AT2 protein was decreased at the 78-kDa level in kidney and lung tissue only. TX fetuses had significantly lower basal mean arterial blood pressures (MAP) and heart rates than controls. Isoproterenol infusion decreased MAP in TX fetuses. These findings support the hypothesis that thyroid hormone is important in modulating maturation of RAS and cardiovascular function in the late-gestation fetal sheep. [ABSTRACT FROM AUTHOR]

The nucleocapsid (N) protein of the severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is an important antigen for the early diagnosis of SARS and the development of vaccines. It was expressed in Escherichia coli as a fusion with human glutathione S-transferase (hGST) and was confirmed by Western blotting analysis. This recombinant N protein (hGST-N) was purified and used to measure the SARS-CoV N-specific antibody in the sera of eight SARS patients by enzyme-linked immunosorbent assay. Specific antibody response to this purified recombinant N protein was 100% positive in the SARS patients’ sera, while none of the control sera from 30 healthy people gave a positive reaction in the same assay. The SARS-CoV N protein was also expressed in Lactococcus lactis in the cytoplasm or secreted into the medium. The N-producing strain MG1363/pSECN and the purified hGST-N protein were respectively administered to mice, either orally or intranasally. Results indicated that orally delivered MG1363/pSECN induced significant N-specific IgG in the sera. In conclusion, our work provides a novel strategy to produce the SARS-CoV N protein for serodiagnosis and for L. lactis-based mucosal vaccines. [ABSTRACT FROM AUTHOR]

The activity of the renin-angiotensin system (RAS) increases significantly in the late-gestation fetal sheep. Fetal cortisol is also increased during this time, and it is thought that the increase in cortisol may modulate the RAS changes. Previous studies have examined the effects of cortisol infusion on RAS activity, but the effects of blocking the peripartum increase in cortisol concentrations on the developmental changes in the RAS are not known. Therefore, we utilized the technique of hypothalamic-pituitary disconnection (HPD), which prevents the cortisol surge from occurring, to investigate the importance of the late-gestation increase in cortisol on the ontogenic changes in RAS activity. HPD of fetal sheep was performed at 120 days of gestational age (dGA), and fetuses were delivered between 135 and 139 dGA. Control fetuses were sham operated. HPD blocked the late-gestation cortisol increase but did not alter renal renin mRNA, renal renin or prorenin protein content, nor plasma renin levels compared with sham operated. However, HPD fetuses had increased ANG II receptor subtype 1 (AT1) mRNA and protein expression in the kidney and lungs. ANG II receptor subtype 2 (AT2) expression was not altered in these tissues at either mRNA or protein level. HPD did not change AT1 or AT2 mRNA in the left ventricle but did result in decreased protein levels for both receptors. These studies demonstrate that blockade of the naturally occurring increase in fetal cortisol concentration in late gestation is associated with tissue-specific alterations in expression of AT1 and AT2 receptors. These changes may impact on fetal tissue maturation and hence have consequences in postnatal life. [ABSTRACT FROM AUTHOR]

A new plasmid was isolated from the haloalkaliphilic archaeon, Natronobacterium sp. strain AS7091 and named pNB101. Sequence analysis revealed that pNB101 consists of 2,538 bp, in which three major open reading frames (ORF1, ORF2, and ORF3) were identified in the same strand. The ORF1 encodes a putative replication (Rep) protein with three typical motifs (I, II, and III) found in rolling-circle (RC) replicating plasmids. The putative double-stranded origin (DSO) and single-stranded origin (SSO) were detected within ORF3 and downstream of ORF1, respectively. S1 nuclease digestion and Southern blot analysis demonstrated the existence of the single-stranded DNA (ssDNA) intermediate from pNB101, which corresponds to the leading strand in RC replication and was further confirmed by strand-specific RNA probes. A single transcript for ORF1 (rep) was detected by Northern blotting, and the 5′ end of this transcript was determined by primer extension. Both results indicate that the three motifs (I–III) are located at the very end of the N-terminal of this Rep protein. Northern blot analysis also revealed that the ORF3 was transcribed at a very high level, which may play an important role in plasmid replication because the putative DSO is located in this gene. Together, our results indicate that pNB101, the first plasmid isolated from haloalkaliphilic Archaea, represents a novel RC-replicating plasmid. [ABSTRACT FROM AUTHOR]

Halocins are bacteriocin-like proteins or peptides produced by many species of the family Halobacteriaceae. Halocin C8, excreted by the Halobacterium strain AS7092, is a single 6.3-kDa polypeptide with an isoelectric point of 4.4, which is sensitive to proteinase K but not to trypsin. Halocin C8 is quite stable, as it can be desalted, boiled, frozen, subjected to organic solvents, and stored in culture supernatant at 4°C or in dH2O at -20°C for more than 1 year without losing activity. The purification of this halocin was achieved by combination of tangential flow filtration (TFF), Sephadex G50 and DEAE-sepharose chromatography. The N-terminal amino acid sequence was also determined by Edman degradation. Halocin C8 appeared to have a very wide activity spectrum, including most haloarchaea and even some haloalkaliphilic rods. When a sensitive strain of Halorubrum saccharovorum was exposed to halocin C8, the treated cells swelled at the initial stage, the cell wall appeared to be nicked and the cytoplasm was then extruded out, and the whole cell was eventually completely lysed. These results indicate that halocin C8 is a novel microhalocin and its primary target might be located in the cell wall of the sensitive cells. [ABSTRACT FROM AUTHOR]

The importance of prostaglandins in the regulation of the renin-angiotensin system during development is not known. These experiments were conducted to examine the effects of prostaglandin synthesis inhibitors on basal and isoproterenolinduced plasma renin concentration and renin gene expression in the late-gestation fetal lamb. Eighteen lamb fetuses ranging in gestational age from 129 to 138 days underwent surgical insertion of femoral arterial and venous catheters under general endotracheal anesthesia. After a period of recovery, animals underwent an infusion of isoproterenol after administration of a saline bolus (control experiments); 24-48 h later a second study was performed after administration of NS-398, a cyclooxygenase (COX)-2 inhibitor, or saline for a second control study. Administration of COX-2 inhibitor significantly reduced baseline plasma renin levels and attenuated responses in fetal renin secretion to isoproterenol infusions. Renal cortical cells from animals receiving COX-2 inhibitor had significantly lower levels of renin mRNA compared with animals receiving only saline. Renal cortical cells in culture from animals receiving only saline exhibited increased levels of renin mRNA when treated with isoproterenol, forskolin, or IBMX. Only forskolin increased renin mRNA levels in renal cortical cells in culture from animals receiving COX-2 inhibitor. We conclude that prostaglandins play a stimulatory role in the regulation of the renin-angiotensin system and are necessary for β-adrenergic stimulation of renin secretion and gene expression in the late-gestation fetal lamb. [ABSTRACT FROM AUTHOR]

Flexibility, waterproof and breathability of substrates are the key issues restricting the application of electronic skin. Composite nanofibrous membranes (CNFMs) as substrates of electronic skin are prepared from polyvinylidene fluoride and silver nitrate blended solution by electrospinning technique. The microstructure and performances of the CNFMs are characterized by scanning electron microscopy, x-ray diffraction, capillary pore size analyzer, gravimetric method, water vapor permeability tester, optical contact angle tester, water permeability tester, intelligent electronic strength tester, hand-held electronic thickness meter and seveneasy conductivity meter. The results indicate that with the introduction of silver nitrate, the waterproof and breathability of CNFMs are balanced and optimized. The moisture permeability increases by 22%–69% from 2915.9 g · m−2 · 24 h−1 of pristine nanofibrous membrane (PNFM) to 3801.2–4151.5 g · m−2 · 24 h−1 of CNFMs and the hydraulic pressure decreases from 23.4 kPa to 21.6–16.5 kPa. However, the change of contact angle is irregular, which depends on the presence of like lotus-leaf-papillae morphology on fiber surface. The tensile strength of CNFMs decreases greatly and the elongation increases by 3–8 times from 7.7% of PNFM to 25.1%–63.2% of the CNFMs. The improvement of CNFMs flexibility is attributed to the hierarchical roughness of nanofiber surface, the unlock bonding between fibers and various combination forms of silver particles in CNFMs. Thus it was suitable to be applied as the substrate of electronic skin. [ABSTRACT FROM AUTHOR]

Background and Objectives: To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in postmenopausal elderly women with type 2 diabetes mellitus (T2DM). Methods and Study Design: A total of 141 postmenopausal elderly women with T2DM was divided into OP and normal bone mineral density (BMD) groups, the differences in GRNI levels between the two groups were compared. According to the tertile levels of GRNI, T2DM were divided into three groups (T1, T2, T3 groups), and the differences in OP prevalence and levels of BMD among the three groups were compared. Results: Among postmenopausal elderly women with T2DM, GNRI levels were lower in the OP group compared to the normal BMD group [(103±5.46) vs. (105±5.46), p<0.05)]. With elevated GNRI levels, the BMD levels of femoral, total hip, total body, and lumbar vertebrae (L) were gradually increased, which were higher in the T3 group than in the T1 group (all p< 0.05). GNRI levels were positively correlated with the BMD levels of femoral, spine, total hip, total body, L1, L2, L3, L4, and L1-L4. GNRI was an independent influencing factor for the occurrence of OP (OR=0.887, 95%CI [0.795,0.988]). The ROC curve showed that the GNRI combined with serum ALP and P levels had a high predictive value for OP, with an area under the curve of 0.725 (p<0.01). Conclusions: In postmenopausal elderly women with T2DM, GNRI was independently and positively correlated with BMD levels. GNRI may be a predictor development of OP. [ABSTRACT FROM AUTHOR]

Background: Web-based physician reviews are invaluable gold mines that merit further investigation. Although many studies have explored the text information of physician reviews, very few have focused on developing a systematic topic taxonomy embedded in physician reviews. The first step toward mining physician reviews is to determine how the natural structure or dimensions is embedded in reviews. Therefore, it is relevant to develop the topic taxonomy rigorously and systematically.Objective: This study aims to develop a hierarchical topic taxonomy to uncover the latent structure of physician reviews and illustrate its application for mining patients' interests based on the proposed taxonomy and algorithm.Methods: Data comprised 122,716 physician reviews, including reviews of 8501 doctors from a leading physician review website in China (haodf.com), collected between 2007 and 2015. Mixed methods, including a literature review, data-driven-based topic discovery, and human annotation were used to develop the physician review topic taxonomy.Results: The identified taxonomy included 3 domains or high-level categories and 9 subtopics or low-level categories. The physician-related domain included the categories of medical ethics, medical competence, communication skills, medical advice, and prescriptions. The patient-related domain included the categories of the patient profile, symptoms, diagnosis, and pathogenesis. The system-related domain included the categories of financing and operation process. The F-measure of the proposed classification algorithm reached 0.816 on average. Symptoms (Cohen d=1.58, Δu=0.216, t=229.75, and P<.001) are more often mentioned by patients with acute diseases, whereas communication skills (Cohen d=-0.29, Δu=-0.038, t=-42.01, and P<.001), financing (Cohen d=-0.68, Δu=-0.098, t=-99.26, and P<.001), and diagnosis and pathogenesis (Cohen d=-0.55, Δu=-0.078, t=-80.09, and P<.001) are more often mentioned by patients with chronic diseases. Patients with mild diseases were more interested in medical ethics (Cohen d=0.25, Δu 0.039, t=8.33, and P<.001), operation process (Cohen d=0.57, Δu 0.060, t=18.75, and P<.001), patient profile (Cohen d=1.19, Δu 0.132, t=39.33, and P<.001), and symptoms (Cohen d=1.91, Δu=0.274, t=62.82, and P<.001). Meanwhile, patients with serious diseases were more interested in medical competence (Cohen d=-0.99, Δu=-0.165, t=-32.58, and P<.001), medical advice and prescription (Cohen d=-0.65, Δu=-0.082, t=-21.45, and P<.001), financing (Cohen d=-0.26, Δu=-0.018, t=-8.45, and P<.001), and diagnosis and pathogenesis (Cohen d=-1.55, Δu=-0.229, t=-50.93, and P<.001).Conclusions: This mixed-methods approach, integrating literature reviews, data-driven topic discovery, and human annotation, is an effective and rigorous way to develop a physician review topic taxonomy. The proposed algorithm based on Labeled-Latent Dirichlet Allocation can achieve impressive classification results for mining patients' interests. Furthermore, the mining results reveal marked differences in patients' interests across different disease types, socioeconomic development levels, and hospital levels. [ABSTRACT FROM AUTHOR]

Primase, encoded by dnaG in bacteria, is a specialized DNA-dependent RNA polymerase that synthesizes RNA primers de novo for elongation by DNA polymerase. Genome sequence analysis has revealed two distantly related dnaG genes, TtdnaG and TtdnaG2, in the thermophilic bacterium Thermoanaerobacter tengcongensis. Both TtDnaG (600 amino acids) and TtDnaG2 (358 amino acids) exhibit primase activities in vitro at a wide range of temperatures. Interestingly, the template recognition specificities of these two primases are quite distinctive. When trinucleotide-specific templates were tested, TtDnaG initiated RNA primer synthesis efficiently only on templates containing the trinucleotide 5′-CCC-3′, not on the other 63 possible trinucleotides. When the 5′-CCC-3′ sequence was flanked by additional cytosines or guanines, the initiation efficiency of TtDnaG increased remarkably. Significantly, TtDnaG could specifically and efficiently initiate RNA primer synthesis on a limited set of tetranucleotides composed entirely of cytosines and guanines, indicating that TtDnaG initiated RNA primer synthesis more preferably on GC-containing tetranucleotides. In contrast, it seemed that TtDnaG2 had no specific initiation nucleotides, as it could efficiently initiate RNA primer synthesis on all templates tested. The DNA binding affinity of TtDnaG2 was usually 10-fold higher than that of TtDnaG, which might correlate with its high activity but low template specificity. These distinct priming activities and specificities of TtDnaG and TtDnaG2 might shed new light on the diversity in the structure and function of the primases. [ABSTRACT FROM AUTHOR]

The adaptive immune system comprising CRISPR (dustered regularly interspaced short palindromic repeats) arrays and cas (CRISPR-associated) genes has been discovered in a wide range of bacteria and archaea and has recently attracted comprehesive investigations. However, the subtype I-B CRISPR-Cas system in haloarchaea has been less characterized. Here, we invest gated Cas6-mediated RNA processing in Haloferax mediterranei. The Cas6 cleavage site, as well as the CRISPR transcription start site, was experimentally determined, and processing of CRISPR transcripts was detected with a progressively increasing pattern from early log to stationary phase. With genetic approaches, we discovered that the lack of Cas 1, Cas3, or Cas4 unexpectedly resulted in a decrease of CRISPR transcripts, while Cas5, Cas6, and Cas7 were found to be essential in stabilizing mature CRISPR RNA (crRNA). Intriguingly, we observed a CRISPR- and Cas3-independent inhibition of a defective provirus, in which the putative Cascade (CRISPR-associated complex for antiviral defense) proteins (Cas5, Cas6, Cas7, and Cas8b) were indispensably required. A sequence carried by a proviral transcript was found to be homologous to the CRISPR repeat RNA and vulnerable to Cas6-mediated cleavage, implying a distinct interference mechanism that may account for this unusual inhibition. The results provide fundamental information for the subtype I-B CRISPR-Cas system in halophilic archaea and suggest diversified mechanisms and multiple physiological functions for the CRISPR-Cas system. [ABSTRACT FROM AUTHOR]

Haloarcula hispanica is an extremely halopbilic archaeon that has an unusually low restriction barrier and is therefore significant for studying archaeal genetics, metabolism, and virus-host interactions. Here we report the complete genome sequence (3,890,005 bp) of H. hispanica strain CGMCC 1.2049, consisting of two chromosomes and one megaplasmid. [ABSTRACT FROM AUTHOR]

The eukaryote-like DNA replication system of the model haloarchaeon Halobacterium NRC-1 is encoded within a circular chromosome and two large megaplasmids or minichromosomes, pNRC100 and pNRC200. We previously showed by genetic analysis that 2 (orc2 and orc10) of the 10 genes coding for Orc-Cdc6 replication initiator proteins were essential, while a third (orc7), located near a highly conserved autonomously replicating sequence, oriC1, was nonessential for cell viability. Here we used whole-genome marker frequency analysis (MFA) and found multiple peaks, indicative of multiple replication origins. The largest chromosomal peaks were located proximal to orc7 (oriC1) and orc10 (oriC2), and the largest peaks on the extrachromosomal elements were near orc9 (oriP1) in both pNRC100 and -200 and near orc4 (oriP2) in pNRC200. MFA of deletion strains containing different combinations of chromosomal orc genes showed that replication initiation at oriC1 requires orc7 but not orc6 and orc8. The initiation sites at oriC1 were determined by replication initiation point analysis and found to map divergently within and near an AT-rich element flanked by likely Orc binding sites. The oriC1 region, Orc binding sites, and orc7 gene orthologs were conserved in all sequenced haloarchaea. Serial deletion of orc genes resulted in the construction of a minimal strain containing not only orc2 and orc10 but also orc9. Our results suggest that replication in this model system is intriguing and more complex than previously thought. We discuss these results from the perspective of the replication strategy and evolution of haloarchaeal genomes. [ABSTRACT FROM AUTHOR]

Most cases associated with Hereditary Severe Insulin Resistance Syndrome (H-SIRS) are linked to mutations in the insulin receptor ( INSR ) gene. Patients with H-SIRS typically manifest symptoms of hyperinsulinemia, insulin resistance, and diabetes mellitus. Other symptoms include impaired glucose regulation, hyperandrogenism, and the presence of acanthosis nigricans (AN). In this report, we present two cases of H-SIRS in female children exhibiting various symptoms, such as hyperinsulinemia, fasting hypoglycemia, postprandial hyperglycemia, overweight, fatty liver, hyperandrogenism, and varying degrees of AN. One patient also presented with mental retardation. Gene sequencing identified specific mutations in the INSR gene for both patients: c.2663A > G (p.Tyr888Cys) and c.38&#95;61del (p.Pro13&#95;Ala20del). These mutations have the potential to disrupt the interaction between INSR and insulin, leading to abnormal insulin signaling, insulin resistance, and various clinical manifestations.

The aim of the work was to investigate the correlation between serum TSH (thyrotropin) levels within normal range and serum lipids. A total of 1962 subjects with normal thyroid function were enrolled. The subjects were divided into four groups according to the quartiles of serum normal TSH levels, [Q 1 (0.27-1.68) mIU/l, Q 2 (1.69-2.35) mIU/l, Q 3 (2.36-3.07) mIU/l, and Q 4 (3.08-4.20) mIU/l]. The effect of serum normal TSH levels on serum lipid profiles of different age or gender was analyzed. The total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels of the Q 3 group and TG levels of the Q 4 group were higher than those of the Q 1 group in youth (p <0.05). The TC levels of the Q 3 group were higher than those of the Q 2 group in middle age (p <0.05). The LDL-C levels of middle age or elderly were higher than those of youth at the same TSH levels (p <0.05), while the TC levels of middle age were higher than those of youth in Q 1 , Q 3 , or Q 4 group (p <0.05), and the TC and HDL-C levels of elderly were higher than those of youth in the Q 2 group (p <0.05). The TG levels of the Q 3 group were higher than those of Q 1 group in males (p <0.05). The LDL-C levels of the Q 3 group were higher than those of the Q 1 group in females (p <0.05). In conclusion, the normal serum TSH levels were found to be closely related to serum lipid profiles, and with increasing TSH levels, serum lipids levels increased gradually., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)