Objective:This study aimed to explore the effects of tea polyphenols(TP)on inflammation of orbital fibroblasts in Graves’ophthalmopathy(GO)and to provide new ideas for GO treatment.Methods:Primary orbital fibroblasts...Objective:This study aimed to explore the effects of tea polyphenols(TP)on inflammation of orbital fibroblasts in Graves’ophthalmopathy(GO)and to provide new ideas for GO treatment.Methods:Primary orbital fibroblasts were extracted from orbital adipose/connective tissues of patients with and without GO.Real-time quantitative PCR(RT-qPCR)was used to detect the expression of interleukin(IL)-6,IL-1β,and monocyte chemotactic protein(MCP)-1 in non-GO and GO orbital fibroblasts.The CCK-8 assay was used to determine the appropriate concentration of TP for subsequent experiments.RT-qPCR and enzyme-linked immunosorbent assay(ELISA)were performed to investigate the effects of TP on lipopolysaccharide(LPS)-induced production of inflammatory cytokines.Nuclear factor-κB(NF-κB)expression was measured using Western blotting analysis.NOD-like receptor 3(NLRP3)expression was detected using both Western blotting analysis and immunofluorescence staining.Results:The mRNA levels of IL-6,IL-1β,and MCP-1 in GO orbital fibroblasts were significantly higher than those in non-GO cells.TP treatment significantly inhibited LPS-induced production of inflammatory factors,including IL-6,IL-1β,and MCP-1.TP also inhibited the expression levels of NF-κB and NLRP3.Inflammation in the GO orbital fibroblasts was higher than that in non-GO cells.TP inhibited the production of inflammatory cytokines in GO orbital fibroblasts in vitro through the NF-κB/NLRP3 pathway.Conclusion:These findings suggest that TP may have a potential role in GO treatment.展开更多
AIM： To evaluate the long-term results of different orbital decompression techniques performed in patients with Graves＇ ophthalmopathy（GO）.METHODS： Totally 170 cases with GO underwent orbital decompression betwee...AIM： To evaluate the long-term results of different orbital decompression techniques performed in patients with Graves＇ ophthalmopathy（GO）.METHODS： Totally 170 cases with GO underwent orbital decompression between 1994 and 2014. Patients were divided into 4 groups as medial-inferior, mediallateral（balanced）, medial-lateral-inferior, and lateral only according to the applied surgical technique. Surgical indications, regression degrees on Hertel exophthalmometer, new-onset diplopia in the primary gaze and new-onset gaze-evoked diplopia after surgery and visual acuity in cases with dysthyroid optic neuropathy（DON） were compared between different surgical techniques.RESULTS： The study included 248 eyes of 149 patients. The mean age for surgery was 42.3±13.2 y. DON was the surgical indication in 36.6% of cases, and three-wall decompression was the most preferred technique in these cases. All types of surgery significantly decrease the Hertel values（P〈0.005）. Balanced medial-lateral, and only lateral wall decompression caused the lowest rate of postoperative new-onset diplopia in primary gaze. The improvement of visual acuity in patients with DON did not significantly differ between the groups（P=0.181）. CONCLUSION： The study show that orbital decompression surgery has safe and effective long term results for functional and cosmetic rehabilitation of GO. It significantly reduces Hertel measurements in disfiguring proptosis and improves visual functions especially in DON cases.展开更多
Objective: To investigate the association of Graves’ disease and Graves’ ophthalmopathy with the C/T transition polymorphism at position –318 of promoter and the A/G transition polymorphism at position 49 of exon 1...Objective: To investigate the association of Graves’ disease and Graves’ ophthalmopathy with the C/T transition polymorphism at position –318 of promoter and the A/G transition polymorphism at position 49 of exon 1 within cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene. Methods: Thirty-three patients with ophthalmopathy of Graves’ disease, fifty-six Graves’ patients without ophthalmopathy and sixty normal subjects as control were involved in the present case-control study. The polymorphisms were evaluated by polymerase chain reaction fragment length polymorphism (PCR-RFLP). Com-parisons were made of gene frequencies and allele frequencies between the groups. Results: The gene frequencies of CT and allele frequencies of T were much higher in Graves’ patients with ophthalmopathy than that in the group without ophthalmopathy (P=0.020, P=0.019). The gene frequencies of GG and allele frequencies of G in patients with Graves’ disease were significantly increased as compared with control group (P=0.008, P=0.007). The data suggest that smokers with Graves’ disease seemed to be more predisposed to ophthalmopathy than non-smokers (P=0.018). Conclusion: Our results suggest that an allele of T at position –318 of promoter is associated with genetic susceptibility to Graves’ ophthalmopathy while an allele of G at position 49 of exon 1 is associated with genetic susceptibility to Graves’ disease instead. Smoking is believed to be a major risk factor for ophthalmo-pathy.展开更多
AIM:To assess the effects of hypoxia on human orbital fibroblasts(OF)on adipogenesis and adipocytokine production.METHODS:Human OF were derived from tissues obtained from patients with Graves’ophthalmopathy(GO)and fr...AIM:To assess the effects of hypoxia on human orbital fibroblasts(OF)on adipogenesis and adipocytokine production.METHODS:Human OF were derived from tissues obtained from patients with Graves’ophthalmopathy(GO)and from patients without known thyroid diseases undergoing blepharoplasty.The OF were cultured separately under normoxic and hypoxic conditions.Comparisons of adipocytokine concentrations using multiplex ELISA and lipid accumulation in the cells using Oil Red O staining were subsequently performed.RESULTS:There was increased adipogenesis in OF from GO subject when exposed to hypoxic culture conditions.This was not observed in OF from normal controls.Hypoxia led to an increase in leptin and a decrease in MCP-1 secretion in OF cultures.CONCLUSION:Hypoxia induces adipogenesis in OF and may represent a mechanism by which smoking contributes to deterioration of GO.We also found novel changes to leptin and MCP-1 production in OF cultures exposed to hypoxia suggesting important roles of these cytokines in the disease process.展开更多
The clinical application of orbital magnetic resonance（MR） T2-mapping imaging in detecting the disease activity of Graves＇ ophthalmopathy（GO）, and the predictive values of therapy response to intravenous glucocor...The clinical application of orbital magnetic resonance（MR） T2-mapping imaging in detecting the disease activity of Graves＇ ophthalmopathy（GO）, and the predictive values of therapy response to intravenous glucocorticoid（iv GC） were investigated. Approved by the local institutional review board（IRB）, 106 consecutive patients with GO were included in this prospective study. All subjects were divided into two groups according to the patients＇ clinical activity score（CAS）： the CAS positive group（CAS ≥3） or the CAS negative group（CAS 〈3）. T2 relaxation time of extraocular muscles（T2RT; ms） and the areas of four extra-ocular muscles（AEOMs; mm2） were measured by 3D T2-mapping MR sequence before and after methylprednisolone treatment, so as the CAS and some ophthalmic examinations including visual acuity, intra-ocular pressure, eyeball movement, diplopia and proptosis. In addition, 24 healthy volunteers were recruited as the control group. The mean T2RT and AEOMs in CAS positive group were higher than those in CAS negative group. Both CAS positive and negative groups had significantly higher mean T2RT and AEOMs than the control group（P〈0.01）. There was a positive correlation between T2RT and AEOMs values in GO patients, both of them had a positive correlation with CAS and the ophthalmic examinations. It was concluded that to evaluate the activity of GO, CAS was mostly related to inflammation symptoms of ocular surface, more than that, T2RT and AEOMs were also related to abnormal findings of the ophthalmic examinations including high ocular pressure, impaired eyeball movement, diplopia and proptosis. T2RT and AEOMs can reflex the inflammation state of ocular muscles better. CAS combined with 3D T2-mapping MR imaging could improve the sensitivity of detection of active GO so as the prediction and evaluation of the response to methylprednisolone treatment.展开更多
AIM: To evaluate the benefit and harms of high-dose intravenous glucocorticoids(IVGC) as first-line treatment for Graves’ ophthalmopathy(GO).METHODS: A systematic review and Meta-analysis of randomized clinical trial...AIM: To evaluate the benefit and harms of high-dose intravenous glucocorticoids(IVGC) as first-line treatment for Graves’ ophthalmopathy(GO).METHODS: A systematic review and Meta-analysis of randomized clinical trials(RCTs) comparing IVGC for the treatment of GO, with placebo or other treatments, were conducted. Electronic databases were searched, and standard methodological guidance of Cochrane Handbook for Systematic Reviews of Interventions was used. The primary outcome was overall response, and secondary outcomes included the improvement and change in clinical activity score(CAS), and adverse events.RESULTS: Ten RCTs were included in the Meta-analysis. Low quality evidence(one trial) showed that participants receiving IVGC achieved significantly higher response compared to participants receiving placebo [risk ratio(RR) 7.50, 95% confidence interval(CI) 1.14 to 49.26]. Moderate quality evidence(four trials) support appreciable benefit of IVGC in response compared with oral glucocorticoids(OGC), with of RR being 1.51(95%CI 1.25 to 1.83). There was low quality evidence(one trial) compatible with appreciable benefit for IVGC plus orbital radiotherapy in response(RR 1.38, 95%CI 1.07 to 1.79), compared with OGC plus orbital radiotherapy. One IVGC versus rituximab trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lowerresponse compared to participants using rituximab(RR 0.70, 95%CI 0.50 to 0.98). One IVGC versus mycophenolate mofetil(MMF) trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lower response compared to participants using MMF(RR 0.74, 95%CI 0.63 to 0.88). Very low quality evidence(one trial) showed that participants with dysthyroid optic neuropathy(DON) receiving IVGC were more likely to achieve response compared to participants receiving orbital decompression(RR 3.33, 95%CI 0.51 to 21.89).CONCLUSION: The current evidence is moderate quality, which is sufficient to support IVGC to be as the first-line treatment for moderate-to-severe GO, and the use of rituximab or MMF to be the second-line treatment instead of IVGC. However, the evidence is very low quality, which is insufficient to support the use of IVGC or orbital decompression as the first-line treatment of DON.展开更多
Many patients with Graves’ophthalmopathy(GO)suffer from dry eye syndrome(DES),and this is one of the most common reasons of eye discomfort in patients with GO.The prevalence of DES in patients with GO is significantl...Many patients with Graves’ophthalmopathy(GO)suffer from dry eye syndrome(DES),and this is one of the most common reasons of eye discomfort in patients with GO.The prevalence of DES in patients with GO is significantly higher than normal subjects.The ocular surface changes involving changes in tears,cornea,conjunctiva and glands occur in GO patients.However,the mechanism of how DES occurs in GO still remains unclear.In this review,the ocular surface changes were illustrated and analyzed the reasons for high prevalence of DES in GO patients.展开更多
基金supported by the National Natural Science Foundation of China(No.82160206 and No.81360152),the Natural Science Foundation of Guangxi Province(No.2018GXNSFAA281234),2019 Guangxi One Thousand Young and Middle-Aged College and University Backbone Teachers Cultivation Program and“Medical Excellence Award”Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University.
文摘Objective:This study aimed to explore the effects of tea polyphenols(TP)on inflammation of orbital fibroblasts in Graves’ophthalmopathy(GO)and to provide new ideas for GO treatment.Methods:Primary orbital fibroblasts were extracted from orbital adipose/connective tissues of patients with and without GO.Real-time quantitative PCR(RT-qPCR)was used to detect the expression of interleukin(IL)-6,IL-1β,and monocyte chemotactic protein(MCP)-1 in non-GO and GO orbital fibroblasts.The CCK-8 assay was used to determine the appropriate concentration of TP for subsequent experiments.RT-qPCR and enzyme-linked immunosorbent assay(ELISA)were performed to investigate the effects of TP on lipopolysaccharide(LPS)-induced production of inflammatory cytokines.Nuclear factor-κB(NF-κB)expression was measured using Western blotting analysis.NOD-like receptor 3(NLRP3)expression was detected using both Western blotting analysis and immunofluorescence staining.Results:The mRNA levels of IL-6,IL-1β,and MCP-1 in GO orbital fibroblasts were significantly higher than those in non-GO cells.TP treatment significantly inhibited LPS-induced production of inflammatory factors,including IL-6,IL-1β,and MCP-1.TP also inhibited the expression levels of NF-κB and NLRP3.Inflammation in the GO orbital fibroblasts was higher than that in non-GO cells.TP inhibited the production of inflammatory cytokines in GO orbital fibroblasts in vitro through the NF-κB/NLRP3 pathway.Conclusion:These findings suggest that TP may have a potential role in GO treatment.
文摘AIM： To evaluate the long-term results of different orbital decompression techniques performed in patients with Graves＇ ophthalmopathy（GO）.METHODS： Totally 170 cases with GO underwent orbital decompression between 1994 and 2014. Patients were divided into 4 groups as medial-inferior, mediallateral（balanced）, medial-lateral-inferior, and lateral only according to the applied surgical technique. Surgical indications, regression degrees on Hertel exophthalmometer, new-onset diplopia in the primary gaze and new-onset gaze-evoked diplopia after surgery and visual acuity in cases with dysthyroid optic neuropathy（DON） were compared between different surgical techniques.RESULTS： The study included 248 eyes of 149 patients. The mean age for surgery was 42.3±13.2 y. DON was the surgical indication in 36.6% of cases, and three-wall decompression was the most preferred technique in these cases. All types of surgery significantly decrease the Hertel values（P〈0.005）. Balanced medial-lateral, and only lateral wall decompression caused the lowest rate of postoperative new-onset diplopia in primary gaze. The improvement of visual acuity in patients with DON did not significantly differ between the groups（P=0.181）. CONCLUSION： The study show that orbital decompression surgery has safe and effective long term results for functional and cosmetic rehabilitation of GO. It significantly reduces Hertel measurements in disfiguring proptosis and improves visual functions especially in DON cases.
文摘Objective: To investigate the association of Graves’ disease and Graves’ ophthalmopathy with the C/T transition polymorphism at position –318 of promoter and the A/G transition polymorphism at position 49 of exon 1 within cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene. Methods: Thirty-three patients with ophthalmopathy of Graves’ disease, fifty-six Graves’ patients without ophthalmopathy and sixty normal subjects as control were involved in the present case-control study. The polymorphisms were evaluated by polymerase chain reaction fragment length polymorphism (PCR-RFLP). Com-parisons were made of gene frequencies and allele frequencies between the groups. Results: The gene frequencies of CT and allele frequencies of T were much higher in Graves’ patients with ophthalmopathy than that in the group without ophthalmopathy (P=0.020, P=0.019). The gene frequencies of GG and allele frequencies of G in patients with Graves’ disease were significantly increased as compared with control group (P=0.008, P=0.007). The data suggest that smokers with Graves’ disease seemed to be more predisposed to ophthalmopathy than non-smokers (P=0.018). Conclusion: Our results suggest that an allele of T at position –318 of promoter is associated with genetic susceptibility to Graves’ ophthalmopathy while an allele of G at position 49 of exon 1 is associated with genetic susceptibility to Graves’ disease instead. Smoking is believed to be a major risk factor for ophthalmo-pathy.
基金Supported by Endocrinology and Metabolic Society of Singapore
文摘AIM:To assess the effects of hypoxia on human orbital fibroblasts(OF)on adipogenesis and adipocytokine production.METHODS:Human OF were derived from tissues obtained from patients with Graves’ophthalmopathy(GO)and from patients without known thyroid diseases undergoing blepharoplasty.The OF were cultured separately under normoxic and hypoxic conditions.Comparisons of adipocytokine concentrations using multiplex ELISA and lipid accumulation in the cells using Oil Red O staining were subsequently performed.RESULTS:There was increased adipogenesis in OF from GO subject when exposed to hypoxic culture conditions.This was not observed in OF from normal controls.Hypoxia led to an increase in leptin and a decrease in MCP-1 secretion in OF cultures.CONCLUSION:Hypoxia induces adipogenesis in OF and may represent a mechanism by which smoking contributes to deterioration of GO.We also found novel changes to leptin and MCP-1 production in OF cultures exposed to hypoxia suggesting important roles of these cytokines in the disease process.
基金supported by National Natural Sciences Foundation of China(No.81501552,and No.81401388)
文摘The clinical application of orbital magnetic resonance（MR） T2-mapping imaging in detecting the disease activity of Graves＇ ophthalmopathy（GO）, and the predictive values of therapy response to intravenous glucocorticoid（iv GC） were investigated. Approved by the local institutional review board（IRB）, 106 consecutive patients with GO were included in this prospective study. All subjects were divided into two groups according to the patients＇ clinical activity score（CAS）： the CAS positive group（CAS ≥3） or the CAS negative group（CAS 〈3）. T2 relaxation time of extraocular muscles（T2RT; ms） and the areas of four extra-ocular muscles（AEOMs; mm2） were measured by 3D T2-mapping MR sequence before and after methylprednisolone treatment, so as the CAS and some ophthalmic examinations including visual acuity, intra-ocular pressure, eyeball movement, diplopia and proptosis. In addition, 24 healthy volunteers were recruited as the control group. The mean T2RT and AEOMs in CAS positive group were higher than those in CAS negative group. Both CAS positive and negative groups had significantly higher mean T2RT and AEOMs than the control group（P〈0.01）. There was a positive correlation between T2RT and AEOMs values in GO patients, both of them had a positive correlation with CAS and the ophthalmic examinations. It was concluded that to evaluate the activity of GO, CAS was mostly related to inflammation symptoms of ocular surface, more than that, T2RT and AEOMs were also related to abnormal findings of the ophthalmic examinations including high ocular pressure, impaired eyeball movement, diplopia and proptosis. T2RT and AEOMs can reflex the inflammation state of ocular muscles better. CAS combined with 3D T2-mapping MR imaging could improve the sensitivity of detection of active GO so as the prediction and evaluation of the response to methylprednisolone treatment.
基金Supported by National Natural Science Foundation of China(No.81170874)
文摘AIM: To evaluate the benefit and harms of high-dose intravenous glucocorticoids(IVGC) as first-line treatment for Graves’ ophthalmopathy(GO).METHODS: A systematic review and Meta-analysis of randomized clinical trials(RCTs) comparing IVGC for the treatment of GO, with placebo or other treatments, were conducted. Electronic databases were searched, and standard methodological guidance of Cochrane Handbook for Systematic Reviews of Interventions was used. The primary outcome was overall response, and secondary outcomes included the improvement and change in clinical activity score(CAS), and adverse events.RESULTS: Ten RCTs were included in the Meta-analysis. Low quality evidence(one trial) showed that participants receiving IVGC achieved significantly higher response compared to participants receiving placebo [risk ratio(RR) 7.50, 95% confidence interval(CI) 1.14 to 49.26]. Moderate quality evidence(four trials) support appreciable benefit of IVGC in response compared with oral glucocorticoids(OGC), with of RR being 1.51(95%CI 1.25 to 1.83). There was low quality evidence(one trial) compatible with appreciable benefit for IVGC plus orbital radiotherapy in response(RR 1.38, 95%CI 1.07 to 1.79), compared with OGC plus orbital radiotherapy. One IVGC versus rituximab trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lowerresponse compared to participants using rituximab(RR 0.70, 95%CI 0.50 to 0.98). One IVGC versus mycophenolate mofetil(MMF) trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lower response compared to participants using MMF(RR 0.74, 95%CI 0.63 to 0.88). Very low quality evidence(one trial) showed that participants with dysthyroid optic neuropathy(DON) receiving IVGC were more likely to achieve response compared to participants receiving orbital decompression(RR 3.33, 95%CI 0.51 to 21.89).CONCLUSION: The current evidence is moderate quality, which is sufficient to support IVGC to be as the first-line treatment for moderate-to-severe GO, and the use of rituximab or MMF to be the second-line treatment instead of IVGC. However, the evidence is very low quality, which is insufficient to support the use of IVGC or orbital decompression as the first-line treatment of DON.
基金Supported by the National Key R&D Program of China(No.2018YFC1106100,No.2018YFC1106101)the Science and Technology Commission of Shanghai(No.17DZ2260100,No.19410761100,No.19DZ2331400)Interdisciplinary Program of Shanghai Jiao Tong University(No.ZH2018QNA07,No.ZH2018ZDA12)。
文摘Many patients with Graves’ophthalmopathy(GO)suffer from dry eye syndrome(DES),and this is one of the most common reasons of eye discomfort in patients with GO.The prevalence of DES in patients with GO is significantly higher than normal subjects.The ocular surface changes involving changes in tears,cornea,conjunctiva and glands occur in GO patients.However,the mechanism of how DES occurs in GO still remains unclear.In this review,the ocular surface changes were illustrated and analyzed the reasons for high prevalence of DES in GO patients.
