Is AI 3D-printed PSI an accurate option for patients with developmental dysplasia of the hip undergoing THA?

BACKGROUND: In traditional surgical procedures, significant discrepancies are often observed between the pre-planned templated implant sizes and the actual sizes used, particularly in patients with congenital hip dysplasia. These discrepancies arise not only in preoperative planning but also in the precision of implant placement, especially concerning the acetabular component. Our study aims to enhance the accuracy of implant placement during Total Hip Arthroplasty (THA) by integrating AI-enhanced preoperative planning with Patient-Specific Instrumentation (PSI). We also seek to assess the accuracy and clinical outcomes of the AI-PSI (AIPSI) group in comparison to a manual control group. METHODS: This study included 60 patients diagnosed with congenital hip dysplasia, randomly assigned to either the AIPSI or manual group, with 30 patients in each. No significant demographic differences between were noted the two groups. A direct anterior surgical approach was employed. Postoperative assessments included X-rays and CT scans to measure parameters such as the acetabular cup anteversion angle, acetabular cup inclination angle, femoral stem anteversion angle, femoral offset, and leg length discrepancy. Functional scores were recorded at 3 days, 1 week, 4 weeks, and 12 weeks post-surgery. Data analysis was conducted using SPSS version 22.0, with the significance level was set at α = 0.05. RESULTS AND CONCLUSION: The AIPSI group demonstrated greater prosthesis placement accuracy. With the aid of PSI, AI-planned THA surgery provides surgeons with enhanced precision in prosthesis positioning. This approach potentially offers greater insights and guidelines for managing more complex anatomical variations or cases.

Genetic and Epigenetic Landscape for Drug Development in Polycystic Ovary Syndrome.

The treatment of polycystic ovary syndrome (PCOS) faces challenges as all known treatments are merely symptomatic. The U.S. Food and Drug Administration (FDA) has not approved any drug specifically for treating PCOS. As the significance of genetics and epigenetics rises in drug development, their pivotal insights have greatly enhanced the efficacy and success of drug target discovery and validation, offering promise for guiding the advancement of PCOS treatments. In this context, we outline the genetic and epigenetic advancement in PCOS, which provide novel insights into the pathogenesis of this complex disease. We also delve into the prospective method for harnessing genetic and epigenetic strategies to identify potential drug targets and ensure target safety. Additionally, we shed light on the preliminary evidence and distinctive challenges associated with gene and epigenetic therapies in the context of PCOS.

Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway.

Fibrosis is the late stage of thyroid-associated ophthalmopathy (TAO), resulting in serious complications. Effective therapeutic drugs are still lacking. We aimed to explore the mechanism of TAO fibrosis and to find a targeted drug. High-throughput RNA sequencing was performed on orbital connective tissues from twelve patients with TAO and six healthy controls. Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and we identified the hub gene by Cytoscape software. Additionally, the RNA sequencing results were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic prediction identified the functions of differentially expressed genes (DEGs). Further orbital connective tissue and serum samples of the TAO and control groups were collected for subsequent experiments. Histologic staining, Western blotting (WB), qRT-PCR, enzyme-linked immunosorbent assays (ELISAs), gene overexpression through lentiviral infection or silencing gene by short interfering RNA (siRNA) were performed. We found that the relaxin signaling pathway is an important regulatory pathway in TAO fibrosis pathogenesis. Serelaxin exerts antifibrotic and anti-inflammatory effects in TAO. Furthermore, the downstream Notch pathway was activated by serelaxin and was essential to the antifibrotic effect of serelaxin in TAO. The antifibrotic effect of serelaxin is dependent on RXFP1.

miR-153-3p inhibits osteogenic differentiation of BMSCs by down-regulating the expression of RUNX2 in a high glucose environment.

To study the effect of miR-153-3p on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in a high glucose environment and its potential mechanism. The results showed that high glucose inhibited the osteogenic differentiation of BMSCs, and the expression of miR-153-3p increased during osteogenic differentiation. Further experiments found that in BMSCs induced by high glucose, overexpression of miR-153-3p inhibited the osteogenic differentiation of BMSCs, and the expressions of osteogenesis-related genes bone sialoprotein, Collagen I and alkaline phosphatase were down-regulated, while silencing of miR-153-3p alleviated the inhibition effect. The dual-luciferase reporter gene assay confirmed that the 3'-untranslated region (3'-UTR) of runt related transcription factor 2 (RUNX2) had a targeted binding site with miR-153-3p and a negative regulatory effect. Molecular studies further confirmed that miR-153-3p inhibited the osteogenic differentiation of BMSCs by targeting the 3'-UTR of RUNX2. In conclusion, our study found that as one key regulator of high glucose affecting the osteogenic differentiation of BMSCs, miR-153-3p may play a negative regulatory role by inhibiting the expression of RUNX2.

Comparison of the efficiency of anti-VEGF drugs intravitreal injections treatment with or without retinal laser photocoagulation for macular edema secondary to retinal vein occlusion: A systematic review and meta-analysis.

Objective: To compare the efficiency of anti-VEGF drugs intravitreal injections(IVI) treatment with or without retinal laser photocoagulation(LPC) for macular edema(ME) secondary to retinal vein occlusion(RVO). Methods: The randomized controlled trials and retrospective studies including anti-VEGF drug IVI combined with retinal LPC and single IVI in the treatment of macular edema secondary to RVO were collected in PubMed, Medline, Embase, Cochrane Library, and Web of Science. We extracted the main outcome indicators including the best corrected visual acuity (BCVA), central macular thickness(CMT), the number of injections and the progress of retinal non-perfusion areas(NPAs) for systematic evaluation, to observe whether IVI + LPC could be more effective on the prognosis of RVO. We use Review Manager 5.4 statistical software to analyze the data Results: 527 articles were initially retrieved. We included 20 studies, with a total of 1387 patients who were divided into the combination(IVI + LPC) treatment group and the single IVI group. All the patients completed the ocular examination including BCVA, slit-lamp test, fundus examination and Optical Coherence Tomography(OCT) test before and after each treatment. There was no statistical difference between the combination treatment group and single IVI group on BCVA(WMD = 0.12,95%CI = -3.54-3.78,p = 0.95),CMT(WMD = -4.40,95%CI = -21.33-12.53,p = 0.61) and NPAs(WMD = 0.01,95%CI = -0.28-0.30,p = 0.94).However, the number of IVI was decreased significantly in the combination treatment group in BRVO patients, compared to that in the single IVI group(WMD = -0.69,95%CI = -1.18∼-0.21,p = 0.005). Conclusion: In the treatment of RVO patients with macular edema, the combination of IVI and retinal LPC neither improves BCVA nor reduces CMT significantly compared with the single IVI treatment. However, the combination treatment can decrease the number of intravitreal injections in patients with BRVO, while it is not observed in CRVO patients.

Enamel matrix derivative expedites osteogenic differentiation of BMSCs via Wnt/ß-catenin pathway in high glucose microenvironment.

INTRODUCTION: The influence of enamel matrix derivative (EMD) on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was explored in high glucose (HG) microenvironment with interaction of Wnt/ß-catenin pathway. MATERIALS AND METHODS: Extraction of BMSCs from Sprague-Dawley rats, culture, and identification were manifested. The cells were treated with different concentration of EMD in HG to figure out the most available concentration for proliferation and osteogenic differentiation. Then, observation of cell growth curve and cell cycle changes, and detection of Osterix, runt-related transcription factor 2 (Runx2), COL-I, early osteogenic indexes, Calcium salt deposition, and ß-catenin protein in Wnt/ß-catenin pathway were assured. After adding Wnt/ß-catenin pathway inhibitor (XAV-939) in the cells with osteogenesis induction, detection of binding of ß-catenin to Osterix was clarified. RESULTS: Via identification BMSCs cultured in vitro was qualified. Different concentrations of EMD could accelerate cell proliferation in HG and osteogenesis induction, and 75 µg/mL EMD had the best effect. The HG augmented BMSCs proliferation and the propidium iodide index of flow cytometry cycle was elevated in HG, which were strengthened via the EMD. After BMSCs' osteogenesis induction, Osterix, Runx2, CoL-1, early osteogenic indexes, and calcium salt deposition were reduced, but elevated via EMD. ß-Catenin was the lowest in the HG, but elevated after EMD. After addition of XAV-939, reduction of ß-catenin and the downstream (Osterix and Runx2) were manifested. Detection of binding protein bands was in ß-catenin and Osterix of the HG after EMD treatment. CONCLUSION: EMD may facilitate the osteogenic differentiation of BMSCs via activating the Wnt/ß-catenin pathway in HG.

Disulfiram Exerts Antiadipogenic, Anti-Inflammatory, and Antifibrotic Therapeutic Effects in an In Vitro Model of Graves' Orbitopathy.

Background: Adipogenesis, glycosaminoglycan hyaluronan (HA) production, inflammation, and fibrosis are the main pathogenic mechanisms responsible for Graves' orbitopathy (GO). We hypothesized that disulfiram (DSF), an aldehyde dehydrogenase (ALDH) inhibitor used to treat alcoholism, would have therapeutic effects on orbital fibroblasts (OFs) in GO. This study aimed at determining the therapeutic effects and underlying mechanisms of DSF on these parameters. Methods: Primary cultures of OFs from six GO patients and six control subjects were established. The OFs were allowed to differentiate into adipocytes and treated with various concentrations of DSF. Lipid accumulation within the cells was evaluated by Oil Red O staining. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to measure the expression of key adipogenic transcription factors, ALDH1A1, ALDH2, and mitogen-activated protein kinase (MAPK) signaling proteins. Apoptosis assays and reactive oxygen species levels were evaluated by flow cytometry. HA production was measured by using an enzyme-linked immunosorbent assay (ELISA) kit. The mRNA levels of proinflammatory molecules were measured by using RT-PCR after interleukin (IL)-1ß stimulation with or without DSF. The mRNA expression of markers associated with fibrosis was examined by using RT-PCR after transforming growth factor (TGF)-ß1 stimulation with or without DSF. The wound-healing assay was assessed by phase-contrast microscopy. Results: Under identical adipogenesis conditions, GO OFs effectively differentiated, while normal control (NC) OFs did not. DSF dose dependently suppressed lipid accumulation during adipogenesis in GO OFs. The expression of key adipogenic transcription factors, such as perilipin-1 (PLIN1), PPARγ (PPARG), FABP4, and c/EBPα (CEBPA), was downregulated. Further, DSF inhibited the phosphorylation of ERK by inhibiting ALDH1A1. In addition, DSF attenuated HA production and suppressed inflammatory molecule expression induced by IL-1ß in GO OFs and NC OFs. The antifibrotic effects of DSF on TGF-ß1 were also observed in GO OFs. Conclusions: In the current study, we provide evidence of the inhibitory effect of DSF on GO OFs adipogenesis, HA production, inflammation, and fibrosis in vitro. The results of this study are noteworthy and indicate the potential use of DSF as a therapeutic agent for the treatment of GO.

Tear cytokine profiles in patients with extranodal marginal zone B-cell lymphoma of the ocular adnexa.

OBJECTIVES: To comprehensively analyse the tear cytokine levels of patients with extranodal marginal zone B-cell lymphoma (EMZL) of the ocular adnexa (OA), and the association with clinical characteristics. METHODS: Tear cytokine concentrations of 21 OA-EMZL patients and 14 age- and sex-matched healthy controls were measured using a 27-multiplex bead analysis on a Luminex system. Tear break-up time, corneal fluorescent staining and other clinical and demographic data were collected as well. The diagnosis of OA-EMZL was established based on the incisional biopsy and histopathology. RESULTS: The concentrations of interleukin-1 receptor antagonist (IL-1RA) and IL-8, and the ratio of IL-1RA/IL-1ß were significantly increased in OA-EMZL tear samples (all P < 0.05), while the levels of three cytokines (FGF-2, IL-2 and IL-4), as well as IL-10/IL-6 ratio were significantly decreased (all P < 0.05). The American Joint Committee on Cancer Tumour stage was significantly associated with tear concentrations of FGF-2 (r = -0.44, P = 0.043), GM-CSF (r = -0.49, P = 0.025) and IL-2 (r = -0.45, P = 0.042), while lacrimal gland lymphoma invasion was related to levels of IL-8 (r = 0.53, P = 0.012), FGF-2 (r = -0.43, P = 0.049) and IL-10/IL-6 ratio (r = -0.48, P = 0.026). Receiver operating characteristic (ROC) curve analysis revealed moderate diagnostic accuracy of these indices in differentiating OA-EMZL from normal eyes (area under ROC: 0.69-0.74). CONCLUSIONS: Multiple tear cytokines were significantly dysregulated in OA-EMZL patients. These cytokines could potentially serve as diagnostic biomarkers and therapeutic targets in future.

Increased Dysfunctional and Plastic Regulatory T Cells in Idiopathic Orbital Inflammation.

Background: Idiopathic orbital inflammation (IOI) is a disfiguring and vision-threatening fibroinflammatory disorder. The pathogenesis of IOI has not been elucidated. We sought to clarify the regulatory T cell (Treg) distribution and function in patients with IOI. Methods: The frequency, phenotype and function of Tregs were identified by multicolor flow cytometry and in vitro cell functional assays. Plasma and tissue samples were obtained to investigate cytokines, chemokines and their receptors of interest by relative real-time polymerase chain reaction (PCR) and Luminex assays. Results: Compared with healthy subjects, patients with IOI exhibited obvious increases of Tregs in peripheral blood and affected orbital tissues. Circulating Tregs from patients with IOI were significantly more polarized to a Th17-like phenotype with defective regulatory function, whereas orbit-derived Tregs were polarized to a Th2-like phenotype. Furthermore, ST2 expression levels in circulating Tregs and interleukin (IL)-33 mRNA levels in orbital tissues were decreased in IOI. IL-33 restored the suppressive function of Tregs, reduced interferon (IFN)-γ production by Tregs and decreased the activation of orbital fibroblasts (OFs) cocultured with Tregs in IOI. Conclusion: Increased Tregs with proinflammatory and profibrotic polarization were first identified in IOI, suggesting that Treg plasticity and heterogeneity plays an essential role in IOI pathogenesis. Additionally, our study identified a regulatory effect of IL-33 on inflammation and fibrosis in IOI. Reversing the plastic Tregs via IL-33 might be a potential option for IOI patients.

IL-38 Exerts Anti-Inflammatory and Antifibrotic Effects in Thyroid-Associated Ophthalmopathy.

CONTEXT: Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease closely associated with Graves' disease. IL-38, a novel cytokine in the IL-1 superfamily, has been reported to be involved in the pathogenesis of various autoimmune diseases. OBJECTIVE: We aimed to evaluate the relationship between IL-38 and TAO disease activity and its role in inflammation and fibrosis in TAO. METHODS: Blood samples and orbital connective tissues were collected from TAO patients and controls. Orbital fibroblasts were isolated from patients with TAO. Enzyme-linked immunosorbent assay, immunohistochemistry, flow cytometry, immunofluorescence, quantitative real-time PCR and Western blot analysis were performed. RESULTS: Here, we demonstrated that IL-38 levels decreased in the circulation and orbital connective tissues of patients with TAO compared with the controls, and levels were negatively correlated with the clinical activity score. In vitro, potent anti-inflammatory and antifibrotic effects of IL-38 were observed. Furthermore, we revealed that IL-38 can counteract the phosphorylation of star molecules in multiple classical pathways. CONCLUSION: IL-38 plays a protective role in TAO and is associated with its pathogenesis. Our data suggest that IL-38 may be a promising marker of TAO disease activity and a potential target for TAO therapy.

Clinical features and outcomes of IgG4-related idiopathic orbital inflammatory disease: from a large southern China-based cohort.

PURPOSE: To investigate the clinical features and treatment outcomes of IgG4-related ophthalmic disease (IgG4-ROD) among idiopathic orbital inflammatory disease (IOID) patients. METHODS: The medical records of 165 biopsy-proven IOID patients were retrospectively reviewed. Biopsy specimens were immunostained to detect IgG4 and IgG, and data regarding the clinicopathologic features, treatment outcomes, and recurrence were analyzed. RESULTS: Among the 165 IOID patients enrolled, 100 (60.6%) were histopathologically IgG4-positive. The IgG4-positive patients had a lower rate of painful swelling or mass (17.0% versus 33.8%, p = 0.013), a longer symptom duration (p = 0.070), and a lower proportion of eyelid hyperemia (39.0% versus 58.5%, p = 0.014) than the IgG4-negative patients. Increased Ki-67 expression (15.02 ± 6.86%, p < 0.001) was observed in the IgG4-positive patients with characteristic pathological manifestations (more lymphocyte infiltration, nodular plasma cell infiltration, and follicular hyperplasia). IgG4-positive group had a higher recurrence rate in the subgroup of patients treated with surgery plus oral glucocorticoids (p = 0.046), and combined radiotherapy group has a higher cumulative proportion with recurrence (p = 0.011). CONCLUSION: Over 60% of biopsy-proven IOID were classified as IgG4-ROD with a stronger proliferation potential. Additional radiotherapy after surgical debulking with oral corticosteroids still has a higher relapse rate, and more effective treatments are needed to prevent recurrence.

Elevated Immunoglobulin G4 Levels in Patients with Thyroid Eye Disease and Their Clinical Implications.

Purpose: The purpose of this study was to assess the relationship between thyroid eye disease (TED) in patients undergoing orbital decompression and immunoglobulin G4 (IgG4) levels. Methods: A prospective observational cohort study was conducted among 185 consecutive patients who were diagnosed with TED and underwent orbital decompression. Serum levels of IgG4 were measured, and immunohistochemical staining for IgG and IgG4 was performed in orbital adipose tissue. Data related to clinicopathologic features were analyzed. Results: Among the 185 enrolled patients with TED, 64 (34.6%) were IgG4-positive. The IgG4-positive patients were older, had higher clinical activity scores (CAS), and had worse best-corrected visual acuity (BCVA) than the IgG4-negative patients. Higher thyrotropin receptor antibody (TRAb) levels, histopathological IgG4 counts, IgG4/IgG ratios, and dense lymphocyte infiltration were more frequently observed in IgG4-positive than in IgG4-negative patients. Definitive and probable IgG4 subtypes were independently associated with the active stage in patients with TED. Conclusions: Our data suggest that the IgG4 subtype in TED is common. IgG4-positive patients with TED may be older, have more severe disease, and have higher clinical activity scores. IgG4 may play an important role in the pathogenesis of TED.

The Therapeutic Effect of Combination of Orbital Decompression Surgery and Methylprednisolone Pulse Therapy on Patients with Bilateral Dysthyroid Optic Neuropathy.

PURPOSE: To investigate the synergic effect of combination of orbital decompression surgery and methylprednisolone pulse therapy (MPT) and MPT alone on the visual function in patients with bilateral dysthyroid optic neuropathy (DON). METHODS: For each involved patient with bilateral DON, only one eye was treated with orbital decompression surgery which was conducted by the same doctor, and each of them received MPT after surgery. If the visual function deteriorated despite treatment, patients would switch to the other treatment. All the patients were followed up for 3 months after surgery. Clinical features of patients including best corrected visual acuity (BCVA), intraocular pressure (IOP), proptosis, upper eyelid retraction, and clinical activity score (CAS) before and after surgery were analyzed, respectively. Visual field and visual evoked potential (VEP) tests were also performed. Paired t-test and Wilcoxon matched-pairs signed ranks sum test were used to analyze the data. RESULT: A prospective cohort of 23 patients with bilateral DON was enrolled in this cohort study. No patients failed to the therapy or switched to another treatment. The quantitative variables were shown as means and standard deviations (SD). After 3 months of combined treatment of orbital decompression surgery and MPT, BCVA (logMAR) improved, proptosis was reduced and the upper eyelid retraction was relieved in both eyes of patients; however, these improvements were more significant in the operated eyes than in the fellow (nonoperated) eyes. IOP decreased significantly in the operated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (P=0.002), while having no significant change in the nonoperated eyes (. CONCLUSION: A combination of orbital decompression and MPT can significantly improve visual function in patients with DON, reduce intraocular pressure, and relieve clinical symptoms such as upper eyelid retraction and proptosis, while MPT alone has a limited effect. For DON patients, orbital decompression should be performed promptly to improve the visual function.

Kaempferol alleviates acute alcoholic liver injury in mice by regulating intestinal tight junction proteins and butyrate receptors and transporters.

An impaired gut-liver axis is a potential factor that contributes to alcoholic liver disease. Specifically, ethanol decreases intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is negatively altered following acute ethanol exposure. This study aimed to determine whether kaempferol could protect against alcoholic liver injury (AALI) in mice by regulating tight junction (TJ) proteins and butyrate receptors and transporters in intestines. Male Institute of Cancer Research (ICR) mice were randomly divided into five treatment groups: control, ethanol administered (5 g/kg), and the low-, medium- and high-dosage kaempferol (25, 50, 100 mg/kg) treatments. Intestinal expression was evaluated for the TJ proteins ZO-1 and occludin and the butyrate receptor GPR109A and butyrate transporter SLC58A proteins, in addition to plasma ALT and AST levels and pathomorphological changes in liver and intestinal tissues. The expression of the TJ proteins ZO-1 and occludin, butyrate receptors, and butyrate transporters in the ileum and proximal colon decreased in AALI mice, while plasma ALT and AST levels markedly increased. Kaempferol supplementation reversed these effects. These results suggest that kaempferol could serve as a prophylactic treatment against AALI in mice by increasing the expression of butyrate receptors, transporters, and TJ proteins in the intestinal mucosa.

Head and Eye Trauma Before Retinoblastoma Diagnosis.

PURPOSE: To improve public and medical awareness of the possibility of retinoblastoma (RB) in children who experienced inadvertent trauma with or without trauma-related symptoms and signs. PATIENTS AND METHODS: Retrospective study of the clinical characteristics of children with a trauma history preceding a diagnosis of RB at the Zhongshan Ophthalmic Center, Sun Yat-sen University, between January 2013 and August 2018, and the number of children hospitalized with eye trauma during the same period. RESULTS: Among 793 consecutive patients with RB, 10 (1.3%) had a history of trauma. Two of these 10 patients (20%, accounting for nearly 0.2% of the 1103 eye trauma patients who were treated at our center) had undergone vitrectomy in an eye with unsuspected tumors. Of the 10 cases (12 eyes), only 5 (7 eyes) were initially diagnosed with RB or an intraocular space-occupying mass before referral to the oncology clinic, and 8 patients (80%) with 8 eyes that were ultimately staged as cT2b or higher underwent enucleation on referral to the oncology clinic. Although additional treatment was performed, two of these patients experienced intracranial metastasis and death during a mean follow-up time of 25.9 months from treatment. CONCLUSION: More attention should be paid to the possibility of underlying RB in children of preschool age who have experienced trauma with or without eye signs.

Defective Regulatory B Cells Are Associated With Thyroid-Associated Ophthalmopathy.

PURPOSE: To investigate the change in IL-10-producing regulatory B cells (Breg), which suppress peripheral immune responses, in patients with thyroid-associated ophthalmopathy (TAO). METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls (n = 54), patients with Graves disease (n = 26), and patients with TAO (N=125), and stimulated with CpG/CD40L. The frequency of IL-10-producing Bregs and the expression of IL-10 in response to TSH stimulation were measured by flow cytometry. CD4+ T cells were cultured with Breg-depleted PBMCs to elucidate the function of Bregs in patients with TAO. The potential immunoregulatory mechanism was also investigated by Western blot and chromatin immunoprecipitation assays. RESULTS: Patients with active TAO had higher baseline levels of Bregs in their peripheral blood than both healthy controls and inactive patients. TSH promoted Bregs. Bregs from patients with TAO were defective in suppressing the activation of interferon (IFN)-γ+ and IL-17+ T cells in vitro. CONCLUSIONS: Regulatory B cells in patients with TAO are functionally defective, suggesting that the defective Bregs might be responsible for the pathogenesis of TAO.