Bibliometric analysis of aptamer-conjugated nanoparticles for diagnosis in the last two decades.

Objective.Aptamer-conjugated nanoparticles for diagnosis have recently gained increasing attention. Here, we performed a bibliometric analysis to provide an overview of this field over the past two decades.Methods. The terms 'aptamer, nanoparticles and diagnosis' were used to search for relevant original articles published in English from 2003 to 2022 in the Web of Science database. VOSviewer and CiteSpace software were employed to analyze the development process, knowledge structure, research hotspots, and potential trends in the field of aptamer-conjugated nanoparticles for diagnosis.Results. A total of 1076 original articles were retrieved, with a rapid increase in the annual output and citation. The journal 'Biosensors and Bioelectronics' has contributed the most in this field, and the most influential researcher, institution and country were Weihong Tan, the Chinese Academy of Sciences, China, respectively. Gold nanoparticles and quantum dots were the most used, but in the past three years, research hotspots focused on carbon dots and graphene quantum dots. Diagnostic directions primarily focused on cancer. The most used strategy was label-free electrochemical detection, but in the past two years, colorimetric analysis and fluorescence imaging emerged as hot topics.Conclusion.The bibliometric analysis reveals a rapid increase in the research on aptamer-conjugated nanoparticles for diagnosis, major contributors at the levels of journals, authors, institutions, and countries, and research preferences in diagnostic objects, nanoparticle types, and detection methods, as well as the evolution of research hotspots and future trends.

Choroidal thickness in patients with thyroid-associated ophthalmopathy, as determined by swept-source optical coherence tomography.

AIM: This study used swept-source optical coherence tomography (SS-OCT) to investigate subfoveal choroidal thickness (SFCT) in patients with thyroid-associated ophthalmopathy (TAO) who displayed different levels of disease activity and severity. METHODS: Thirty patients with TAO (60 eyes) and 38 healthy controls (67 eyes) in Shanghai, China, were recruited for this study. Disease activity and severity were graded using European Group on Graves' Orbitopathy standardised criteria. SFCT values were determined by SS-OCT. RESULTS: In total, 129 eyes were included in the final analysis. The mean SFCT was significantly thicker among patients with active disease (276.23±84.01 µm) than among patients with inactive disease (224.68±111.61 µm; p=0.049) or healthy controls (223.56±78.69 µm; p=0.01). There were no differences in SFCT among patients with moderate-to-severe disease, patients with severe disease and healthy controls (p>0.05). Changes in SFCT demonstrated strong predictive ability to distinguish active TAO from inactive TAO (area under the curve=0.659, 95% CI 0.496 to 0.822). CONCLUSIONS: SFCT was strongly associated with Clinical Activity Score in patients with TAO. Choroidal thickening was observed during active TAO. SS-OCT offers a non-invasive method for follow-up assessment.

Influence of social support on subjective well-being of patients with chronic diseases in China: chain-mediating effect of self-efficacy and perceived stress.

Introduction: The well-being of patients with chronic diseases is an issue of widespread concern in public health. While social support is thought to have a positive effect on it, the mechanisms of its influence have not been fully addressed. Thus, we explored the possible mediating effects of self-efficacy and perceived stress to determine the relationship between social support and well-being in these patients. Methods: A cross-sectional study was conducted among 4,657 patients with chronic diseases in China. The PROCESS Macro model 6 of SPSS was employed to explore the intermediary role between variables. Results: Self-efficacy and perceived stress played a partial intermediary role between social support and subjective well-being, with an effect ratio of 48.25% and 23.61%, respectively. Self-efficacy and perceived stress had a chain intermediary effect (28.14%) between social support and subjective well-being. Discussion: This study suggested that improving the self-efficacy of patients with chronic diseases to cope with the changes in social support caused by the disease could reduce stress and enhance subjective well-being.

Suppressing circIDE/miR-19b-3p/RBMS1 axis exhibits promoting-tumour activity through upregulating GPX4 to diminish ferroptosis in hepatocellular carcinoma.

Ferroptosis is a newly characterized form of iron-dependent non-apoptotic cell death, which is closely associated with cancer progression. However, the functions and mechanisms in regulation of escaping from ferroptosis during hepatocellular carcinoma (HCC) progression remain unknown. In this study, we reported that the RNA binding motif single stranded interacting protein 1 (RBMS1) participated in HCC development，and functioned as a regulator of ferroptosis. Clinically, the downregulation of RBMS1 occurred in HCC tissues, and low RBMS1 expression was associated with worse HCC patients survival. Mechanistically, RBMS1 overexpression inhibited HCC cell growth by attenuating the expression of glutathione peroxidase 4 (GPX4)and further facilitated ferroptosis in vitro and in vivo. More importantly, a novel circIDE (hsa_circ_0000251) was identified to elevate RBMS1 expression via sponging miR-19b-3p in HCC cells. Collectively, our findings established circIDE/miR-19b-3p/RBMS1 axis as a regulator of ferroptosis, which could be a promising therapeutic target and prognostic factor.

M1-Like Macrophages Modulate Fibrosis and Inflammation of Orbital Fibroblasts in Graves' Orbitopathy: Potential Relevance to Soluble Interleukin-6 Receptor.

Background: Graves' orbitopathy (GO) is a disfiguring and sight-threatening autoimmune disease. Previous studies have shown the infiltration of macrophages in GO orbital connective tissues. However, the immunophenotypes of macrophages and their modulatory effects on orbital fibroblasts (OFs) have not been examined so far. In this study, we sought to determine the pathophysiology of macrophages in GO. Methods: In this case-control study, orbital connective tissues collected from 40 GO patients and 20 healthy controls were immunohistochemically stained for cytokines and macrophage cell surface antigens. The polarization of orbital-infiltrating macrophages was investigated by flow cytometry and immunofluorescence. Effects of interleukin (IL)-6 combined with soluble IL-6 receptor (sIL-6R) on the proliferation, differentiation, and inflammation of different OF subsets were examined by CCK-8, Western blotting, and Luminex assays, respectively. The antigen-presenting abilities of different OF subsets under IL-6/sIL-6R signaling were studied by proteomics. Finally, the differentiation of CD8+ IL-17A-producing T cells by sIL-6R was tested. Results: GO orbital connective tissues displayed increased IL-6, sIL-6R, STAT3, and IL-17A levels. CD86+ M1-like macrophages were predominant in active GO patients, while stable GO patients tended to have more CD163+ M2-like macrophages. The expression of IL-6 was higher in M1-like macrophages, and the expression of transforming growth factor-ß was higher in M2-like macrophages both in GO orbital connective tissues in situ in vivo and in cell culture system in vitro. The IL-6/sIL-6R stimulation promoted the fibrosis of both CD34+ and CD34- OFs. Monocyte chemoattractant protein-1 expression was also induced by IL-6/sIL-6R stimulation in both OF subsets. IL-6/sIL-6R stimulation enhanced the antigen processing of CD34+ OFs through upregulating the intact major histocompatibility complex I and antigen transporters. However, the protein expressions of the thyrotropin receptor and insulin-like growth factor 1 receptor could not be directly increased by IL-6/sIL-6R stimulation in CD34+ OFs. Furthermore, sIL-6R was conducive to the differentiation of CD8+ IL-17A-producing T cells. Conclusions: Our study demonstrated the immunophenotypes of orbital-infiltrating macrophages that may activate OFs depending on the IL-6/sIL-6R signaling in GO. Our preclinical findings implicate, at least in part, the molecular rationale for blocking sIL-6R as a promising therapeutic agent for GO.

Immunophenotype of Lacrimal Glands in Graves Orbitopathy: Implications for the Pathogenesis of Th1 and Th17 Immunity.

Background: Recent studies have reported a wide spectrum of ocular surface injuries in the context of autoimmune reactions in Graves' orbitopathy (GO). Increased expression of inflammatory mediators in tears of GO patients suggests that the lacrimal glands could be a target for immune responses. However, the immunophenotype for GO lacrimal microenvironment is not known. This study aimed to elucidate the pathological changes of GO lacrimal glands. Methods: In this case-control study, lacrimal glands were surgically collected from GO patients who underwent orbital decompression surgery and control subjects who underwent other ocular-related surgery. Bulk RNA-sequencing, flow cytometry with dimensional reduction, and immunohistochemical and multiplexed stainings were conducted. Western blotting and multipathway assays were performed in CD34+ fibroblasts derived from lacrimal and orbital tissues. Results: Increased expression of cytokines and chemokines accompanied by a variety of immune cell infiltrations mainly involving T cells, B cells, and monocytes was found in GO lacrimal glands. An in-depth investigation into T cell subsets revealed interferon (IFN)-γ-producing T helper (Th)1 and interleukin (IL)-17A-producing Th17 cell-dominated autoimmunity in the active GO lacrimal microenvironment. Both fibrosis and adipogenesis were observed in GO lacrimal tissue remodeling. IL-17A, not IFN-γ, stimulated transforming growth factor-ß-initiated myofibroblast differentiation as well as 15-deoxy-Δ12,14-prostaglandin J2-initiated adipocyte differentiation in CD34+ lacrimal fibroblasts (LFs) and orbital fibroblasts (OFs), respectively. IL-17A activated many fibrotic and adipogenic-related signaling pathways in CD34+ LFs and OFs. A novel anti-IL-17A monoclonal antibody SHR-1314 could reverse the promoting effect of IL-17A on fibrosis and adipogenesis in CD34+ LFs and OFs. Conclusions: Our findings provide evidence for the infiltration of different lymphocytes into GO lacrimal microenvironment, where Th1 and Th17 cells characterize the onset of active lacrimal inflammation and contribute to tissue remodeling. These findings may have potential future therapeutic implications regarding the utility of anti-IL-17A therapy, which should be studied in future research.

Age-related difference in extraocular muscles and its relation to clinical manifestations in an ethnically homogenous group of patients with Graves' orbitopathy.

PURPOSE: To evaluate the age-related difference in EOMs and its relation to clinical manifestations by computed tomography (CT) measurement of EOMs. METHODS: The medical records and CT image review of 40 patients (80 orbits) with moderate-to-severe Graves' orbitopathy were performed. The patients were divided into two age groups, group 1 (≤ 40 years) and group 2 (> 40 years). CT scans of 30 gender- and age-matched normal controls were also obtained. The maximal cross-sectional area (MCA) and its position (pMCA) of each EOM were measured. RESULTS: Group 1 presented with more severe proptosis (p < 0.001), while group 2 had a higher risk of diplopia (p < 0.001). Motility restriction in supraduction was more likely to occur in Group 2 (p = 0.027) with even higher severity (p = 0.047). The pMCA was higher in the inferior (p = 0.001), medial (p = 0.021), and lateral rectus (p = 0.013) in group 1. Proptosis was positively correlated to pMCA while diplopia was correlated to MCA in both groups. Significant correlation was noted between restrictions levels and MCA (superior, r = 0.467, p < 0.001; inferior, r = 0.358, p = 0.007; medial, r = 0.314, p = 0.018; lateral, r = 0.308, p = 0.021) or pMCA (inferior, r = - 0.534, p < 0.001) only in group 2. CONCLUSIONS: The muscle enlargement patterns are significantly different between younger and older patients. Older patients tended to have enlarged muscle bellies more posterior in the orbit, which is responsible for more diplopia and motility restriction. Proptosis is more likely to be affected by the most enlarged position than muscle size. So younger patients tended to develop more proptosis and be less bothered by motility restriction even with enlarged muscles.

[Reversal of Drug Resistance in K562/ADM Cells Caused by RA and the Related Mechanisms].

OBJECTIVE: To investigate the effect of ursane triterpenoids 3ß,19α-dihydroxyursu-12-ene-23,28-dicarboxylic acid (Rotundioic acid, RA) on the sensitivity of adriamycin-resistant K562 cells (K562/ADM Cell) anti-tumor drug, and to explore the effect and mechanism of RA on the multidrug resistance of K562/ADM cells. METHODS: CCK-8 method was used to detect the effect of RA on the sensitivity of K562 cells and K562/ADM cells to anti-tumor drug. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression level of mRNA and the protein in K562 and K562/ADM cells, and the effect of RA on the expression of MDR1 mRNA and P-gp in K562/ADM cells was also detected; Western blot was used to detect the expression of p-JNK, p-p38 and p-ERK1/2 in K562/ADM cells. RESULTS: RA could increased the sensitivity of K562/ADM cells to adriamycin(the reversal factor was 1.61 times), the difference showed statistically significantly (P<0.05); the resistance factor of K562/ADM to ADM was 41.76 times. The expression of MDR1 mRNA in K562 cells was extremely low, and the protein product P-glycoprotein (P-gp) was almost not expressed; MDR1 mRNA and P-gp in K562/ADM cells were highly expressed; RA could down-regulate the expression levels of MDR1 and P-gp in K562/ADM cells. In addition, RA could upregulate the phosphorylation levels of p38 and ERK1/2 in K562/ADM cells, but it has no effect on the expression of p-JNK. CONCLUSION: RA may participate in the regulation of MAPK signaling pathway by upregulating the expression levels of p-p38 and p-ERK1/2 in K562/ADM cells, and thus inhibit the transcription and translation levels of MDR1, and finally reverse the multidrug resistance of leukemia cells.

Application of Magnetic Resonance Imaging in the Evaluation of Disease Activity in Graves' Ophthalmopathy.

OBJECTIVE: To evaluate magnetic resonance imaging parameters, T2 signal intensity ratios (SIRs), and normalized apparent diffusion coefficients (n-ADC) of the extraocular muscles (EOMs) in the identification of different stages of Graves' ophthalmopathy (GO) and to find out the correlation of T2-SIRs and n-ADC values with disease changes after anti-inflammatory treatment. METHODS: Altogether, 43 patients (86 orbits) were enrolled and classified into "active" or "inactive" stages by clinical activity score (CAS). Twenty-three (53.5%) patients received anti-inflammatory treatment and underwent a follow-up evaluation. Fifteen age- and gender-matched control participants (30 orbits) were included. T2-SIRs and n-ADC values of EOMs were calculated among GO and healthy controls and were correlated with CAS. Changes in these parameters were also evaluated before and after anti-inflammatory treatment. RESULTS: Mean T2-SIRs and n-ADC values were both significantly higher in GO patients than in controls and higher in active GO than in inactive GO. In the inactive stage, n-ADC values of inferior rectus muscles were still higher than those in healthy controls. Both T2-SIRs and n-ADC values decreased after intravenous steroid pulse therapy. The cutoff value of pretreatment n-ADC was 1.780 to detect stages with specificity of 93.7% and sensitivity of 48.3% (P = .035). CONCLUSION: T2-SIRs and n-ADC values are valuable magnetic resonance imaging indicators of the inflammatory activity in GO by detecting involvement of EOMs. They are also ideal tools to monitor the efficacy of anti-inflammatory treatment in patients with active stage GO. n-ADC values, when combined with CAS, can be promising predictive factors in the detection of stages of diseases.

Evidence for Associations Between Th1/Th17 "Hybrid" Phenotype and Altered Lipometabolism in Very Severe Graves Orbitopathy.

PURPOSE: The purpose of this article is to investigate the characteristics of Th1-cell and Th17-cell lineages for very severe Graves orbitopathy (GO) development. METHODS: Flow cytometry was performed with blood samples from GO and Graves disease (GD) patients and healthy controls, to explore effector T-cell phenotypes. Lipidomics was conducted with serum from very severe GO patients before and after glucocorticoid (GC) therapy. Immunohistochemistry and Western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization. RESULTS: In GD, Th1 cells predominated in peripheral effector T-cell subsets, whereas in GO, Th17-cell lineage predominated. In moderate-to-severe GO, Th17.1 cells expressed retinoic acid receptor-related orphan receptor-γt (RORγt) independently and produced interleukin-17A (IL-17A), whereas in very severe GO, Th17.1 cells co-expressed RORγt and Tbet and produced interferon-γ (IFN-γ). Increased IFN-γ-producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GC therapy inhibited both Th1-cell and Th17-cell lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GC-resistant, very severe GO, IFN-γ-producing Th17.1 cells remained at a high level, correlating with increased serum triglycerides. Further, retro-orbital tissues from GC-resistant, very severe GO were shown to be infiltrated by CXCR3+ Th17 cells expressing Tbet and STAT4 and rich in triglycerides that promoted Th1 phenotype in Th17 cells in vitro. CONCLUSIONS: Our findings address the importance of Th17.1 cells in GO pathogenesis, possibly promoting our understanding of the association between Th17-cell plasticity and disease severity of GO.

15-epi-lipoxin A4 inhibits TNF-α-induced tissue factor expression via the PI3K/AKT/ NF-κB axis in human umbilical vein endothelial cells.

Inflammation and coagulation are two important processes implicated in venous thromboembolism (VTE). 15-epi-lipoxin A4 (15-epi-LXA4) is the epimer of LXA4, a small lipid molecule, is known to play a key role in the resolution of inflammation. This study aimed to demonstrate whether 15-epi-LXA4 could suppress the inflammatory factor tumor necrosis factor-alpha (TNF-α)-induced upregulation of tissue factor (TF), an important regulator of the blood coagulation cascade, and evaluated the possible underlying mechanisms. We found that 15-epi-LXA4 not only reduced the up-regulation of mRNA and antigens, but also lowered the activity of TF (elevated by TNF-α) in primary culture of human umbilical vein endothelial cells (pc-HUVECs). In addition, 15-epi-LXA4 suppressed the activation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, induced by TNF-α, in pc-HUVECs. 15-epi-LXA4 also inhibited the binding of NF-κB on the TF promoter, which is otherwise enhanced by TNF-α. The role of 15-epi-LXA4 in regulating TNF-α-induced effects was enhanced by the PI3K inhibitor and prevented by the PI3K activator. In conclusion, 15-epi-LXA4 lowered the TNF-α-induced high TF expression and activity by suppressing PI3K/AKT signaling activation, thereby reducing the binding capacity of NF-κB on the TF promoter in pc-HUVECs.

Prolonged lumbosacral pain as the initial presentation in acute lymphoblastic leukemia in an adult: A case report.

RATIONALE: The differential diagnosis of conditions manifesting as bone and joint pain is complex. Although many individuals with acute leukemia experience bone pain, lumbosacral pain as an early feature of acute lymphoblastic leukemia (ALL) is rare. PATIENT CONCERNS: Here we report a case of an adult who presented with a 7-month history of persistent lumbosacral pain which had become more severe during the previous month. DIAGNOSES: Prior to referral, his full blood count revealed no abnormalities, and a computerized tomography scan revealed mild bone hyperplasia of his lumbar vertebrae, with disc herniations of L3-S1. His blood biochemistry and urinary test results had been normal. After referral to our clinic, tests of the morphology, immunology, cytogenetics, and molecular biology of his bone marrow led to a diagnosis of MLL-AF4 fusion positive B-cell ALL. INTERVENTIONS: Prior to his referral, he had been treated with painkillers by local doctors. The painkillers initially provided pain relief, but their effect wore off over time. After diagnosis, he was started on an adult ALL chemotherapy protocol. OUTCOMES: His symptoms resolved within a week of starting chemotherapy. At his most recent assessment, 10 months after diagnosis, he was on maintenance chemotherapy and in remission. LESSONS: This case illustrates that prolonged lumbosacral pain may be a symptom of a life-threatening condition, rather than only attributable to chronic inflammation or disk herniations. Therefore, clinicians need to pay attention to subtle differences in the clinical presentation of patients with lumbosacral pain.

Insights Into Local Orbital Immunity: Evidence for the Involvement of the Th17 Cell Pathway in Thyroid-Associated Ophthalmopathy.

CONTEXT: Unique features of local immunity in thyroid-associated ophthalmopathy (TAO) may affect disease progression. OBJECTIVE: To investigate the association between the orbital immune microenvironment and TAO development. DESIGN/SETTING/PARTICIPANTS: TAO and control orbital connective tissues were collected. MAIN OUTCOME MEASURES: Single-cell sequencing examined orbital lymphocytic infiltrates. Multicolor flow cytometry explored the phenotypes of different cell subsets and in vitro models for cell functional studies. Coculture experiment and western blotting assay were used to determine underlying mechanism of the enhanced T helper 17 (Th17) cell pathway. RESULTS: The TAO orbital microenvironment was composed of natural killer cells, dendritic cells, macrophages, T cells, plasma cells, and CD34+ orbital fibroblasts, but few B cells. Increases in CD3+CD8- IL-17A-producing and RAR-related orphan receptor (ROR)γt-expressing T cells and in CD3+CD8- IL-13-producing and GATA3-expressing T cells suggested Th17 and Th2 cell responses in TAO orbits. Increased interferon-γ (IFN-γ)-producing and RORγt+Tbet+ T cells indicated a Th1-like phenotype of orbital-infiltrating Th17 cells. Higher IL-23R and IL-1R expression and lower IL-21R expression were also observed on Th17 cells in TAO orbits. Multivariate analyses revealed that the Th17 pathway [IL-17A (P = 0.001), IFN-γ (P = 0.009), RORγt (P = 0.003), IL-23R (P = 0.033), IL-21R (P = 0.019)], and Th2 pathway [IL-13 (P = 0.015), GATA3 (P = 0.012)] were associated with TAO. IL-17A, IL-23R, and IL-1R correlated with clinical activity score and visual acuity. CD34+ orbital fibroblasts exhibited distinct cell surface marker expression and promoted IL-23R and IL-1R expression on T cells to facilitate the Th17-cell phenotype through prostaglandin E2-EP2/EP4-cAMP signaling. CONCLUSION: Our study addresses the importance of retroorbital immunity and suggests possible means of disrupting TAO pathogenesis.

Interaction Between CCR6+ Th17 Cells and CD34+ Fibrocytes Promotes Inflammation: Implications in Graves' Orbitopathy in Chinese Population.

Purpose: Recent reports suggest that Th17 immunity and bone marrow-derived CD34+ fibrocytes contribute to the pathogenesis of Graves' orbitopathy (GO). This study investigated interactions between Th17 cells and fibrocytes in GO inflammation in Chinese subjects. Methods: Th17 cells and fibrocytes were derived from blood samples from Chinese GO patients and healthy controls. Proportions and phenotypes of Th17 cells, regulatory T cells (Tregs), and fibrocytes were examined by flow cytometry. Exogenous IL-17A was used to study inflammatory activity of fibrocytes from GO patients and control subjects. Coculture, quantitative RT-PCR, Luminex, and transwell assays were performed to investigate the relationship between Th17 cells and fibrocytes. Results: CC-chemokine receptor 6 (CCR6+) Th17 cells were increased in both active (P < 0.001) and inactive (P < 0.05) GO patients, compared with healthy controls. There was a positive correlation between number of CCR6+ Th17 cells and GO clinical activity score (P < 0.0001, r = 0.8176). Further, CD34+ fibrocytes were increased in GO patients, with increased expression of IL-17RA (P < 0.05), CD80 (P < 0.05), and CD86 (P < 0.05). A decreased population of effector Treg cells (P < 0.01) and increased CTLA-4 expression on naïve Treg cells (P < 0.05) were observed in GO patients. IL-17A stimulated cytokine production in fibrocytes; GO fibrocytes exhibited more robust production than normal fibrocytes. Autologous Th17 cells promoted inflammatory and antigen-presenting functions of GO fibrocytes; conversely, fibrocytes enhanced Th17 cell-function and recruited Th17 cells in a macrophage inflammatory protein 3 (MIP-3)/CCR6-dependent manner. Conclusions: The crosstalk between CCR6+ Th17 cells and fibrocytes plays a role in the pathogenesis of GO. Suppressing these interactions may be a candidate molecular target for therapeutic approaches of GO.

Bovine Acellular Dermal Matrix for Levator Lengthening in Thyroid-Related Upper-Eyelid Retraction.

BACKGROUND Eyelid retraction is the most common and often the first sign of thyroid eye disease (TED). Upper-eyelid retraction causes both functional and cosmetic problems. In order to correct the position of the upper eyelid, surgery is required. Many procedures have demonstrated good outcomes in mild and moderate cases; however, unpredictable results have been obtained in severe cases. Dryden introduced an upper-eyelid-lengthening procedure, which used scleral grafts, but outcomes were unsatisfactory. A new technique is introduced in this study as a reasonable alternative for TED-related severe upper-eyelid retraction correction. MATERIAL AND METHODS An innovative technique for levator lengthening using bovine acellular dermal matrix as a spacer graft is introduced for severe upper-eyelid retraction secondary to TED. Additionally, 2 modifications were introduced: the fibrous cords scattered on the surface of the levator aponeurosis were excised and the orbital fat pad anterior to the aponeurosis was dissected and sutured into the skin closure in a "skin-tarsus-fat-skin" fashion. RESULTS The modified levator-lengthening surgery was performed on 32 eyelids in 26 patients consisting of 21 women and 5 men (mean age, 37.8 years; age range, 19-67 years). After corrective surgery, the average upper margin reflex distance was lowered from 7.7±0.85 mm to 3.3±0.43 mm. Eighteen cases (69%) had perfect results, while 6 cases (23%) had acceptable results. CONCLUSIONS A modified levator-lengthening procedure using bovine acellular dermal matrix as a spacer graft ameliorated both the symptoms and signs of severe upper-eyelid retraction secondary to TED. This procedure is a reasonable alternative for correction of TED-related severe upper-eyelid retraction.

A single-center retrospective study of factors related to the effects of intravenous glucocorticoid therapy in moderate-to-severe and active thyroid-associated ophthalmopathy.

BACKGROUND: Intravenous glucocorticoids (ivGC) have been recommended as a first-line treatment of moderate-to-severe and active thyroid-associated ophthalmopathy (TAO). However, not all patients are responsive to ivGC. The identification of potential factors used to predict their efficacy and the selection of suitable patients have both been lacking. METHODS: It was a single center retrospective study. Potential factors related to the effects of ivGC were analyzed using logistic regression in 90 consecutive patients with moderate-to-severe and active TAO, who received 4.5 g ivGC therapy. Response was defined as the achievement of at least three points of the overall response. RESULTS: Fifty-two (57.8%) patients showed a positive response to ivGC therapy. Significant correlations were observed between the effects of ivGC and pretreatment clinical activity score (CAS), duration of eye symptoms, and restoration of euthyroidism. The two latter factors were both independent. The duration of eye symptoms was negatively correlated with the effects of ivGC, with an odds ratio (OR) of 0.984 (p = 0.012). Restoration of euthyroidism (OR = 3.282, p = 0.039) and pretreatment CAS (OR = 1.653, p < 0.01) were both positively correlated with the effects of ivGC. The diagnostic accuracy of the duration of eye symptoms was ≤13 months (p = 0.000), with a specificity of 76.9%, and sensitivity of 65.8%. The diagnostic accuracy of the pretreatment CAS was more than 2.5 (p = 0.000), with a specificity of 61.5% and sensitivity of 80.5%. Besides, a multi-variables prediction model were established as well, which was better in the forecasting aspect with an area under curve of 0.784 (p = 0.000). CONCLUSIONS: The duration of eye symptoms and restoration of euthyroidism are independent factors that are associated with the effects of ivGC. The following practical implications were inferred: firstly, the shorter the duration of eye symptoms, the more favorable the effects of ivGC therapy. Thus, prompt diagnosis and treatment (within 13 months) is important. Secondly, the restoration of euthyroidism improves the efficacy of ivGC. Thirdly, hope the multi-variables prediction model can be applied to clinical therapy in the future.

Orbital radiotherapy plus three-wall orbital decompression in a patient with rare ocular manifestations of thyroid eye disease: case report.

BACKGROUND: Thyroid eye disease (TED) is a debilitating autoimmune orbital disease that is often a result of Graves' disease. Dysthyroid optic neuropathy (DON) is a rare but sight-threatening manifestation of TED with therapeutic challenges that can potentially lead to visual loss. CASE PRESENTATION: A 74-year-old man experienced active TED with extremely severe redness and swelling of the conjunctiva, loss of visual acuity and exacerbation of disfiguring proptosis. Computed tomography revealed the involvement of extraocular muscles resulting in optic nerve compression. He was in poor general condition and was intolerant to steroids. To achieve the optimal operating conditions for orbital decompression surgery, the patient was initially treated with orbital radiotherapy. The patient responded well, with improvements in clinical activity score and visual acuity. CONCLUSION: This case demonstrates a rare and severe case of DON with therapeutic challenges. To date, no cases has been reported of a patient with such severe and unusual ocular manifestations. Early awareness of the occurrence of optic nerve compression and prompt treatment are important to prevent irreversible outcomes. Orbital radiotherapy should be considered as a useful surgery-delaying alternative for DON, especially in patients who have contraindications to steroids.

Regulation of Orbital Fibrosis and Adipogenesis by Pathogenic Th17 Cells in Graves Orbitopathy.

Context: T helper (Th)17 cells are correlated with many human autoimmune disorders, including Graves disease, and may play key roles in the pathogenesis of Graves orbitopathy (GO). Objective: To study the phenotype of Th17 cells in patients with GO and healthy subjects, investigate the fibrosis and adipogenesis in orbital fibroblasts (OFs) modulated by interleukin (IL)-17A, and determine the interaction between Th17 cells and OFs. Design/Setting/Participants: Blood samples and orbital tissues from GO patients and healthy controls were collected. Main Outcome Measures: We conducted multicolor flow cytometry, immunohistochemical and immunofluorescent stainings, Western blotting, a PathScan intracellular signaling assay, Luminex and enzyme-linked immunosorbent assays, and protein mass spectrum. Results: Interferon-γ- and IL-22-expressing Th17 cells are increased in GO patients, which are positively related to clinical activity score. Costimulatory molecules are highly expressed in GO orbits and most GO OFs are CD90+. IL-17A promotes TGF-ß-induced fibrosis in CD90+ OFs but impedes 15-deoxy-Δ12,14-prostaglandin J2-induced adipogenesis in CD90- OFs. Th17 cells promote proinflammatory cytokine secretion in both CD90+ and CD90- OFs. Meanwhile, both CD90+ and CD90- OFs contribute to Th17 cell differentiation through prostaglandin E2 production, which can be attenuated by indomethacin. Furthermore, Th17 cells upregulate costimulatory molecule expression on OFs. Conclusion: Our findings unravel the pathogenicity of IL-17A in the initiation and progression of GO. In-depth interpretation of the molecular basis of OFs delineated by CD90 and Th17-OF interaction will help to afford a novel approach to better therapeutic strategies for GO.

Adiponectin Inhibits TNF-α-Activated PAI-1 Expression Via the cAMP-PKA-AMPK-NF-κB Axis in Human Umbilical Vein Endothelial Cells.

BACKGROUND: Tumor necrosis factor (TNF)-α can upregulate the expression of plasminogen activator inhibitor (PAI)-1, an inhibitor of fibrinolysis. Adiponectin (Adp) antagonizes TNF-α by negatively regulating its expression in various tissues. In the present study, the ability of Adp to suppress TNF-α-induced PAI-1 upregulation and the underlying mechanisms were evaluated. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with TNF-α in the presence or absence of Adp, and PAI-1 mRNA and antigen expression, activated signaling pathways, and molecular mechanisms were analyzed by qRT-PCR and ELISA. RESULTS: Adp decreased the TNF-α-induced upregulation of PAI-1 mRNA and protein expression and suppressed TNF-α-induced cAMP-PKA-AMPK inactivation. Adp also suppressed the TNF-α-induced NF-kB binding capability on the PAI-1 promoter. Moreover, these Adp-induced effects were further enhanced or prevented by treatment with the cAMP inhibitor Rp-cAMPs or activator forskolin, respectively. CONCLUSIONS: Our data suggest that Adp abrogates TNF-α-activated PAI-1 expression by activating cAMP-PKA-AMPK signaling to suppress NF-kB binding to the PAI-1 promoter in HUVECs. Given the antifibrotic effect of PAI-1 abrogation, Adp may be utilized as a novel agent in the treatment of fibrotic diseases.

Hierarchical layered Ni(3)S(2)-graphene hybrid composites for efficient photocatalytic reduction of Cr(VI).

Exploring visible light responsive media remains a challenge for solar energy photocatalysis applications. We report the Ni3S2-reduced graphene oxide (NG) hybrid composites with sheet-on-sheet structures synthesized by a facile microwave-assisted method. Their morphology, structure and photocatalytic activity in the reduction of Cr(VI) were characterized by scanning electron microscopy, X-ray diffraction, UV-Vis absorption spectroscopy, and electrochemical impedance spectra, respectively. The results show that NG hybrid composites show excellent visible light photocatalytic activity in the reduction of Cr(VI) compared to pure Ni3S2. The Cr(VI) reduction rate of higher than 90% has been achieved with 1wt.% reduced graphene oxide under visible light irradiation at 180min. Improvement is attributed to its efficient charge separation and more active sites due to the integrative effect and good interfacial contact between Ni3S2 and reduced graphene oxide.