[Cerebral oxygen metabolism and brain electrical activity of healthy full-term neonates in high-altitude areas: a multicenter clinical research protocol]. / é«˜æµ·æ‹”åœ°åŒºå¥åº·è¶³æœˆæ–°ç”Ÿå„¿è„‘æ°§ä»£è°¢åŠè„‘ç”µæ´»åŠ¨å·®å¼‚çš„å¤šä¸­å¿ƒä¸´åºŠç ”ç©¶æ–¹æ¡ˆ.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates. Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity. This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes. The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes, and corresponding reference ranges will be established. The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance, with altitude gradients divided into 4 categories: 800 m, 1 900 m, 2 400 m, and 3 500 m, with an anticipated sample size of 170 neonates per altitude gradient. This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.

Modulation of plasmacytoid dendritic cell and CD4+ T cell differentiation accompanied by upregulation of the cholinergic anti-inflammatory pathway induced by enterovirus 71.

Enterovirus 71 (EV71) is a neurotropic enterovirus associated with hand, foot, and mouth disease (HFMD) fatalities. In this study, we investigated the impact of EV71 on plasmacytoid dendritic cells (pDCs) and CD4+ T cells. The results showed that pDCs were promptly activated, secreting interferon (IFN)-α and inducing CD4+ T cell proliferation and differentiation during early EV71 infection. This initiated adaptive immune responses and promoted proinflammatory cytokine production by CD4+ T cells. Over time, viral nucleic acids and proteins were synthesized in pDCs and CD4+ T cells. Concurrently, the cholinergic anti-inflammatory pathway (CAP) was activated, exhibiting an anti-inflammatory role. With constant viral stimulation, pDCs and CD4+ T cells showed reduced differentiation and cytokine secretion. Defects in pDCs were identified as a key factor in CD4+ T cell tolerance. CAP had a more significant regulatory effect on CD4+ T cells than on pDCs and was capable of inhibiting inflammation in these cells.

Underwater power compensated white light source based on synthetic white laser.

The semiconductor white laser light source is used as a light source for underwater illumination. The required standard color temperature of white light is obtained at the underwater target surface. We studied the power compensation of a synthetic white laser source and its application to underwater illumination. First, the power ratios of the red (638 nm), green (520 nm), and blue (450 nm) lasers at a color temperature of 6500 K were obtained by using chromaticity theory. Next, the three-color and synthetic white laser parameters were obtained with transmission distance, according to the exponential attenuation characteristics of different light in clear water and seawater medium. The three-color laser power at the output was compensated, and the underwater target illumination surface reached the standard 6500 K color temperature of the white laser, improving the illumination. Finally, an experimental system for underwater white laser illumination based on power compensation was established. The errors between experimental and theoretical results of color temperature and illuminance are no more than 0.43% and 22.15%. This power-compensated synthetic white laser light source has both the advantages of long-range underwater detection and the spectral advantages of LED white light sources. The white laser light source meets specific requirements by compensating for power and optimizing white light characteristics for underwater lighting applications.

Nomogram for predicting the preoperative lymph node metastasis in resectable pancreatic cancer.

BACKGROUND: Lymph node metastasis (LNM) is a critical prognostic factor in resectable pancreatic cancer (PC) patients, determining treatment strategies. This study aimed to develop a clinical model to adequately and accurately predict the risk of LNM in PC patients. METHODS: 13,200 resectable PC patients were enrolled from the SEER (Surveillance, Epidemiology, and End Results) database, and randomly divided into a training group and an internal validation group at a ratio of 7:3. An independent group (n = 62) obtained from The First Affiliated Hospital of Xinxiang Medical University was enrolled as the external validation group. The univariate and multivariate logistic regression analyses were used to screen independent risk factors for LNM. The minimum Akaike's information criterion (AIC) was performed to select the optimal model parameters and construct a nomogram for assessing the risk of LNM. The performance of the nomogram was assessed by the receiver operating characteristics (ROC) curve, calibration plot, and decision curve analysis (DCA). In addition, an online web calculator was designed to assess the risk of LNM. RESULT: A total of six risk predictors (including age at diagnosis, race, primary site, grade, histology, and T-stage) were identified and included in the nomogram. The areas under the curves (AUCs) [95% confidential interval (CI)] were 0.711 (95%CI: 0.700-0.722), 0.700 (95%CI: 0.683-0.717), and 0.845 (95%CI: 0.749-0.942) in the training, internal validation and external validation groups, respectively. The calibration curves showed satisfied consistency between nomogram-predicted LNM and actual observed LNM. The concordance indexes (C-indexes) in the training, internal, and external validation sets were 0.689, 0.686, and 0.752, respectively. The DCA curves of the nomogram demonstrated good clinical utility. CONCLUSION: We constructed a nomogram model for predicting LNM in pancreatic cancer patients, which may help oncologists and surgeons to choose more individualized clinical treatment strategies and make better clinical decisions.

The prevalence and predictors of feeding difficulties in children at self-feeding transition stage.

Aim: To understand the prevalence of feeding difficulties (FD) in young children at self-feeding transition stage (6-24 months age), and the protective and risk predictors associated with FD are to be determined through this study. Methods: A cross-sectional study was conducted within 5 representative Women's and Children's hospitals in Chengdu, Southwest China. Children age 6-24 months who underwent routine child health care examination at outpatient and their parents were enrolled, while the Montreal Children's Hospital Feeding Scale which is validated was used to determine whether these children have FD. Results: A total of 1,211 subjects were enrolled in this survey, where 380 children were reported as FD with an prevalence of 31.4%. Adjusted binary logistic regression in the multivariate analysis showed 10 independent predictors of FD. Specifically there were 6 risk predictors: (1) frequent constipation (OR = 1.603, CI = 1.006-2.555) in CHILD sub-theme; (2) anxiety (OR = 4.322, CI = 3.074-6.079) and (3) indulgent parenting style (OR = 2.108, CI = 1.306-3.405) in PARENT sub-theme; (4) luring to eat (OR = 2.806, CI = 2.000-3.937), (5) forcing to eat (OR = 2.040, CI = 1.407-2.958), and (6) allowing playing during mealtime (OR = 2.023, CI = 1.435-2.853) in FEEDING PRACTICE sub-theme. The remaining 4 factors were protective predictors including (1) food preparing (OR = 0.586, CI = 0.385-0.891) in FOOD sub-theme; (2) observing hunger and satiety signals (OR = 0.667, CI = 0.457-0.974), (3) interacting with child during mealtime (OR = 0.505, CI = 0.308-0.828), as well as (4) providing exclusive tableware (OR = 0.370, CI = 0.191-0.719) in FEEDING PRACTICE sub-theme. Conclusions: There appeared to be an increasing trend of FD prevalence. Child health care clinicians and pediatricians are expected to attach more importance to FD in their daily work, and are obliged to provide parents with practical and effective preventive strategies highlighted in this study.

Chemical Constituents from the Fruits of Amomum kravanh and Their Role in Activating Alcohol Dehydrogenase.

Alcoholism is a worldwide health problem, and diseases caused by alcoholism are killing people every year. Amomum kravanh is a traditional Chinese medicine used to relieve hangovers. However, whether its bioactive components improve alcohol metabolism is not clear. In this study, ten new (amomumols A-J, 1-10) and thirty-five known (11-45) compounds were isolated from the fruits of Amomum kravanh by an activity-guided separation. Ten novel compounds were identified as four sesquiterpenoids (1-4), three monoterpene derivatives (5-7), two neolignans (8, 9), and a novel norsesquiterpenoid (10) with a new C14 nor-bisabolane skeleton. Their structures were determined by the comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) calculation. The effects of all isolated compounds on the activity of alcohol dehydrogenase were evaluated in vitro, and it was found that eight compounds (11, 12, 15, 18, 26, and 36-38) exhibited significant activation effects on the alcohol dehydrogenase at 50 µM.

Gene Therapy Activates Retinal Pigment Epithelium Cell Proliferation for Age-related Macular Degeneration in a Mouse Model.

OBJECTIVE: Age-related macular degeneration (AMD) is a degenerative retinal disease. The degeneration or death of retinal pigment epithelium (RPE) cells is implicated in the pathogenesis of AMD. This study aimed to activate the proliferation of RPE cells in vivo by using an adeno-associated virus (AAV) vector encoding ß-catenin to treat AMD in a mouse model. METHODS: Mice were intravitreally injected with AAV2/8-Y733F-VMD2-ß-catenin for 2 or 4 weeks, and ß-catenin expression was measured using immunofluorescence staining, real-time quantitative reverse transcription polymerase chain reaction (PCR), and Western blotting. The function of ß-catenin was determined using retinal flat mounts and laser-induced damage models. Finally, the safety of AAV2/8-Y733F-VMD2-ß-catenin was evaluated by multiple intravitreal injections. RESULTS: AAV2/8-Y733F-VMD2-ß-catenin induced the expression of ß-catenin in RPE cells. It activated the proliferation of RPE cells and increased cyclin D1 expression. It was beneficial to the recovery of laser-induced damage by activating the proliferation of RPE cells. Furthermore, it could induce apoptosis of RPE cells by increasing the expression of Trp53, Bax and caspase3 while decreasing the expression of Bcl-2. CONCLUSION: AAV2/8-Y733F-VMD2-ß-catenin increased ß-catenin expression in RPE cells, activated RPE cell proliferation, and helped mice heal from laser-induced eye injury. Furthermore, it could induce the apoptosis of RPE cells. Therefore, it may be a safe approach for AMD treatment.

Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke.

We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357-395 of C X3 C motif chemokine ligand 1 (CX3CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3CL1 (comprising amino acids 357-395 of CX3CL1) disrupts the interaction between postsynaptic density-93 and CX3CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3CL1 (357-395aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3CL1. Furthermore, the a disintegrin and metalloprotease domain 17 (ADAM17) inhibitor GW280264x, which inhibits metalloprotease activity and prevents CX3CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3CL1 formation. Additionally, Tat-CX3CL1 (357-395aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31-34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3CL1 (357-395aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3CL1 (357-395aa) is a potential therapeutic agent for ischemic stroke.

Compensatory effects of different exercise durations on non-exercise physical activity, appetite, and energy intake in normal weight and overweight adults.

Objectives: To examine compensatory changes of different exercise durations on non-exercise physical activity (NEPA), appetite, and energy intake (EI) in normal and overweight adults, and to determine if different body mass index of individuals interact with these compensatory effects. Methods: Ten normal weight adults (nine females and one male; age: 24.0 ± 0.4 years; BMI: 20.7 ± 0.5 kg/m2) and ten overweight adults (six females and four males; age: 24.5 ± 0.9 years; BMI: 25.9 ± 0.4 kg/m2) participated in this study. The participants completed two exercise trials: short-duration continuous training (SDCT) and long-duration continuous training (LDCT), i.e., a 40 min short-duration and an 80 min long-duration continuous training in a randomized order. Total physical activity and NEPA were monitored using an accelerometer for seven consecutive days, which involved a two-day baseline observation period (C-pre-Ex), three-day exercise intervention period (Ex), and two-day follow-up period (C-post-Ex). Blood samples were collected for appetite-related hormone analysis. Appetite score was assessed using the visual analogue scale. Energy intake was evaluated by weighing the food and recording diaries. Results: The NEPA evaluation showed that it was higher for SDCT than for LDCT in the C-post-Ex period (F (1, 19) = 8.508, p = 0.009) in the total sample. Moreover, results also indicated that NEPA was lower for LDCT (F (2, 18) = 6.316, p = 0.020) and higher for SDCT (F (2, 18) = 3.889, p = 0.026) in the C-post-Ex period than in the C-pre-Ex and Ex periods in overweight group. Acyl-ghrelin revealed a main effect of time in the total sample and in normal weight and overweight groups; it was lower in the C-post-Ex period than in the C-pre-Ex and Ex periods (all p < 0.05). Total EI analysis revealed no significant changes in either the total sample or in the normal weight and overweight groups. Conclusion: These findings demonstrate that short duration exercise led to a compensatory increment in NEPA, whereas long duration exercise induced a compensatory decrease in NEPA. Moreover, there was a higher and delayed compensatory response in overweight adults than in normal weight adults. Nevertheless, energy intake was not changed across time, regardless of exercise duration.

High triiodothyronine levels induce myocardial hypertrophy via BAFF overexpression.

Activated B cells contribute to heart diseases, and inhibition of B-cell activating factor (BAFF) expression is an effective therapeutic target for heart diseases. Whether activated B cells participate in the development and progression of hyperthyroid heart disease, and what induces B cells activation in hyperthyroidism are unknown. The present study aimed to determine the roles of BAFF overexpression induced by high concentrations of triiodothyronine (T3) in the pathogenesis of hyperthyroid heart disease. Female C57BL/6J mice were subcutaneously injected with T3 for 6 weeks, and BAFF expression was inhibited using shRNA. Protein and mRNA expression of BAFF in mouse heart tissues evaluated via immunohistochemistry, western blotting and polymerase chain reaction (PCR). Proportions of B cells in mouse cardiac tissue lymphocytes were quantified via flow cytometry. Morphology and left ventricle function were assessed using pathological sections and echocardiography, respectively. Here, we demonstrate that compared with the control group, the proportion of myocardial B cells was larger in the T3 group; immunohistochemistry, western blotting and PCR analyses revealed increased protein and mRNA expression levels of TNF-α and BAFF in heart tissues of the T3 group. Compared with the normal controls group, in the T3 group, the diameter of myocardial cells and some echocardiographic values significantly increased and hypertrophy and structural disorder were noticeable. Our results revealed that elevated levels of circulating T3 can promote the expression of BAFF in myocardial cells and can lead to B-cell activation, an elevated inflammatory response and ventricular remodelling.

A Hypoxia-Regulated Retinal Pigment Epithelium-Specific Gene Therapy Vector Reduces Choroidal Neovascularization in a Mouse Model.

BACKGROUND: Wet age-related macular degeneration (wAMD) is characterized by the presence of choroidal neovascularization (CNV). Although there are some clinical drugs targeting vascular endothelial growth factor (VEGF) and inhibiting CNV, two major side effects limit their application, including the excessive activity of anti-VEGF and frequent intraocular injections. To explore better treatment strategies, researchers developed a hypoxic modulator retinal pigment epithelium (RPE)- specific adeno-associated virus (AAV) vector expressing endostatin to inhibit CNV. However, the mechanism of endostatin is complex. Instead, soluble fms-like tyrosine kinase-1 (sFlt-1) can inhibit VEGF-induced angiogenesis through two simple and clear mechanisms, giving rise to sequestration of VEGF and forming an inactive heterodimer with the membrane-spanning isoforms of the VEGF receptor Flt-1 and kinase insert domain-containing receptor. OBJECTIVE: In this study, we chose sFlt-1 as a safer substitute to treat wAMD by inhibiting VEGFinduced angiogenesis. METHODS: The AAV2/8-Y733F-REG-RPE-sFlt-1 vector was delivered by intravitreal injection to the eyes of mice. AAV2/8-Y733F vector is a mutant of the AAV2/8 vector, and the REG-RPE promoter is a hypoxia-regulated RPE-specific promoter. Two animal models were used to evaluate the function of the vector. RESULTS: In the cobalt chloride-induced hypoxia model, the results demonstrated that the AAV2/8- Y733F-REG-RPE-sFlt-1 vector induced the expression of the sFlt-1 gene in RPE cells through hypoxia. In the laser-induced CNV model, the results demonstrated that the AAV2/8-Y733F-REG-RPE-sFlt- 1 vector reduced laser-induced CNV. CONCLUSION: Hypoxia regulated, RPE-specific AAV vector-mediated sFlt-1 gene is a hypoxiaregulated antiangiogenic vector for wAMD.

Two POM-based compounds containing Zn-capped Keggin anions as decent heterogeneous catalysts for sulfur oxidation and CO2 cycloaddition reactions.

Carbon dioxide (CO2) and the combustion of sulfide in gasoline are the main causes of air pollution. A great deal of attention has been paid to solving the problem and the catalytic reaction seems to be a decent choice. Due to the high-density of Lewis acidic active sites, polyoxometalates are undoubtedly an ideal choice for the sulfur oxidation reaction. With the reasons foregoing, two novel Zn-capped polyoxometalate-based organic-inorganic hybrids, {[α-PMoV2MoVI10O39(OH)Zn2][bbbm]3}·0.5C2H5OH (1) and TBA2{[ε-PMoV8MoVI4O37(OH)3Zn4][phim]3} (2) ((where bbbm = 1-(4-imidazol-1-ylbutyl) imidazole) and phim = 2-phenylimidazole) were successfully obtained by hydrothermal synthesis. In the two compounds, the N-donor ligands in a monodentate or bidentate coordination mode are directly connected to the Keggin anions by Zn-capped atoms, forming an extended one-dimensional chain. It is noteworthy that compound 2 ends up with an interesting spiral infinite chain possibly thanks to the TBA+ cations residing in gaps as structure-directing agents. Simultaneously, the catalytic properties indicate that compounds 1 and2 as efficient heterogeneous catalysts display a decent catalytic activity in the sulfur removal process. Especially, 2 enabled satisfying catalytic oxidation of dibenzothiophene (DBT) to produce more valuable dibenzothiophene sulfone (DBTO2) at 55 °C, and the conversion almost reached 99%. Besides, compound 2 also shows satisfactory catalytic effectiveness in the oxidation of various epoxides in the CO2 cycloaddition reaction, which suggests that compound 2 has the potential to function as a dual functional material with tremendous prospects in sulfur oxidation and carbon dioxide cycloaddition for the first time.

A new family of boat-shaped Ln8 clusters exhibiting the magnetocaloric effect and slow magnetic relaxation.

Designing and synthesizing lanthanide clusters have always been a research hotspot. Herein, three lanthanide clusters with the formula [Ln8(IN)14(µ3-OH)8(µ2-OH)2(H2O)8]·xH2O (Ln = 1-Gd and x = 11; Ln = 2-Dy and x = 8; Ln = 3-Eu and x = 8) have been isolated in the presence of isonicotinic acid under solvothermal conditions. Structural analysis indicates that those three compounds are isostructural, featuring boat-shaped {Ln8} metal frameworks. Magnetic measurements reveal that 1-Gd exhibits a larger MCE with the maximum -ΔSm value of 31.77 J kg-1 K-1 at 2 K for ΔH = 7 T, while 2-Dy displays slow magnetization relaxation. Besides, the photoluminescence properties of 3-Eu were investigated.

Two Ni-Substituted Trilacunary Keggin-Type Polyoxometalates: Syntheses, Crystal Structures, NLO Studies, and Magnetic Properties.

Two Ni-substituted polyoxometalates (NiSPs), [Ni6(Py)6(H2O)5(µ3-OH)3(PW9O34)]2·10H2O (1), [Ni7(Py)6(Im)(H2O)5O(WO4)(µ3-OH)3(H2PW9O34)]·3H2O (2) (Py = pyridine, Im = imidazole), were successfully hydrothermally synthesized. Compounds 1 and 2 have significantly different configurations by introducing different amounts of imidazole ligands. For compound 1, two malposed {Ni6(Py)6PW9} units that are face to face are bridged by two Ni-O-W bonds to constitute an isolated dimeric structure. Differently, the {Ni7(Py)6(Im)PW9}2 dimer in compound 2 connects with four adjacent dimers by four {WO4} groups in an interesting two-dimensional (2-D) arrangement. The magnetism of compounds 1 and 2 was studied, and magnetic test results demonstrated that both compounds have ferromagnetic interactions between the nickel centers. Meanwhile, the third-order nonlinear optical (NLO) measurements indicated that compound 1 can serve as potential nonlinear optical materials.

A Purely Inorganic Quasi-Keggin Polyoxometalate for Photocatalytic Conversion of Carbon Dioxide to Carbon Monoxide.

A pure inorganic cluster, H47 Na2 Co4 Mo24 (PO4 )11 O72 ⋅ 15H2 O (denoted as {Co4 Mo24 }), has been successfully synthesized by hydrothermal method. Notably, the assembly of a central {Co2 PO4 } tetrahedron and four peripheral {Co[P4 Mo6 ]} fragments gives rise to a rare "quasi-Keggin" structure of {Co4 Mo24 }, in which Co linkers continue to bridge adjacent substructures, resulting in the generation of 3D framework with large cavities. Benefitting from the combination of strong reductive {P4 Mo6 } units and Co active centers, the photocatalytic system with {Co4 Mo24 } as heterogeneous catalyst exhibits excellent activity for CO2 conversion to CO, offering the CO formation rate of 1848.3 µmol g-1 h-1 with high selectivity of 97.0 %. Besides, thermogravimetric and X-ray diffraction analysis confirm that {Co4 Mo24 } can maintain stable during the photocatalytic reaction process.

Two three-dimensional polyanionic clusters [M(P4Mo6)2] (M = Co, Zn) exhibiting excellent photocatalytic CO2 reduction performance.

Two captivating {P4Mo6}-based compounds, formulated as (H2bbi)2{[Co2(bbi)][Co2.33(H2O)4][H9.33CoP8Mo12O62]}·4H2O (1) and (H2bbi){[Zn(Hbbi)]2[Zn0.75(bbi)][K2Zn(H2O)4][H8.5ZnP8Mo12O62]} (2) [bbi = 1,1'-(1,4-butanediyl)bis(imidazole)], were successfully synthesized under hydrothermal conditions. Structural analysis demonstrates that compounds 1 and 2 are constructed from hourglass-shaped structures [M(P4Mo6O31)2]n- (M = Co, Zn), which are all made up of molybdophosphates and one transition metal ion as the central connecting node. Compounds 1 and 2 feature three-dimensional (3D) frameworks, which are all connected to form a 3D structure by metal ions and bbi ligands. More interestingly, compound 1 exhibits higher catalytic activity than 2 in CO2 photoreduction due to the suitable energy band structure of Co species in {P4Mo6} clusters. The CO yield was 3261 µmol g-1 with high selectivity in 8 h for compound 1 in photocatalytic CO2 reduction, which is highly promising in the photocatalytic field. Additionally, the photoluminescence properties of 2 were investigated.

A Review of Three Chinese Cases of Acromicric/Geleophysic Dysplasia with FBN1 Mutations.

OBJECTIVE: This study aims to explore the clinical features and molecular diagnosis of FBN1-related acromelic dysplasia in Chinese patients. METHODS: The clinical and genetic features of three FBN1-related acromicric dysplasia (AD)/geleophysic dysplasia (GD) Chinese patients from two families were reviewed, and comprehensive medical evaluations were performed. Targeted next-generation sequencing was used to detect genetic mutations associated with short statures, including FBN1. Sanger sequencing was used to determine the de novo mutation origin. RESULTS: Patient 1 presented with short stature, short and stubby hands and feet, mild facial dysmorphism, hepatomegaly, delayed bone age and beak-like femoral heads. Patient 2 and this patient's father merely presented with short stature, wide and short hands, and beak-like femoral heads. One novel mutation, c.5272G>T(p.D1758Y), and one known mutation, c.5183C>T(p.A1728V), were identified in these patients. CONCLUSION: The clinical features varied among these patients. The variant c.5272G>T(p.D1758Y) is a novel mutation.

High Levels of Thyroid Hormone Impair Regulatory T Cell Function Via Reduced PD-1 Expression.

CONTEXT: Regulatory T cell (Treg) dysfunction plays an important role in the development and progression of Graves' disease (GD). Programmed cell death 1 (PD-1) prompts FoxP3 in Treg expression and enhances the suppressive activity of Tregs. Whether abnormal expression of PD-1 contributes to the breakdown of Tregs and the role of thyroid hormone in the PD-1 expression of Tregs in GD remain substantially undefined. OBJECTIVE: To evaluate the role of PD-1 in Treg function and triiodothyronine (T3) in PD-1 expression in patients with GD and mice treated with T3. METHODS: We recruited 30 patients with GD and 30 healthy donors. PD-1 expression in Tregs and Treg function were determined. To evaluate the effects of thyroid hormone on PD-1 expression in Tregs, we used T3 for the treatment of human peripheral blood mononuclear cells (PBMCs). We then treated mice with T3 to confirm the effect of thyroid hormone on PD-1 expression in Tregs and Tregs function in vivo. RESULTS: PD-1 expression in Tregs and the suppressive function of Tregs significantly decreased in patients with GD. T3 reduced PD-1 expression in human Tregs in a concentration- and time-dependent manner in vitro. High levels of circulating T3 reduced PD-1 expression in Tregs, impaired Treg function, and disrupted T-helper cell (Th1 and Th2) balance in mice treated with T3. CONCLUSION: Treg dysfunction in GD patients might be due to downregulation of PD-1 expression in Tregs induced by high levels of serum T3.