1.Role of inflammation in diabetic retinopathy:pathogenesis and treatment strategies
Recent Advances in Ophthalmology 2024;44(1):1-12
Diabetic retinopathy(DR)is considered to be a chronic medium-and low-grade inflammatory disease(mi-croinflammation).Inflammation runs through the entire process of DR,manifesting as an increase in ocular and systemic inflammation biomarkers.In the eyes of DR patients,there is an increase in pro-inflammatory mediators,such as interleu-kin(IL)-1 β,IL-6 and tumor necrosis factor-α,as well as activated and increased number of inflammatory cells,such as ac-tivated microglia,Müller cells in the retina,and infiltration of mononuclear macrophage.In addition,immunocytes are also involved in the pathogenesis of DR,such as the involvement of circulating T cells in leukostasis.These indicate that chronic inflammation is an inducing factor of DR,with multiple inflammation-related factors participating and influencing each other,leading to the destruction of the blood-retinal barrier and neuronal injury and exacerbating the development of DR.There-fore,personalized anti-inflammatory therapy is of great significance in the treatment of DR.
2.Interpretation of the International Myopia Institute's management and re-search focus of myopia in different ages
Ruihua WEI ; Haoru LI ; Jinyuan SUI ; Xinrui SHI ; Bei DU
Recent Advances in Ophthalmology 2024;44(1):13-17,23
The increasing incidence of myopia has become a significant public health issue worldwide.Since its estab-lishment in 2015,the International Myopia Institute(IMI)has published a series of white papers on myopia prevention and control in 2019 and 2021,advancing the scientific management and clinical research of myopia prevention and control worldwide.In 2023,IMI released new white papers on myopia prevention and control.In this paper,the highlights of the third series of IMI white papers on children,young adults,and emerging research areas in myopia are interpreted,intend-ing to help related professionals understand the management and research focus of myopia patients of different ages.
3.Effects of blue light on the development of the dioptric system in guinea pigs
Xiao WANG ; Changlin LUAN ; Yifan SUN ; Shiqiao YANG ; Kailei WANG ; Rui HAO ; Wei ZHANG
Recent Advances in Ophthalmology 2024;44(1):18-23
Objective To investigate the effect of blue light on the dioptric development of the eyes of lens-induced myopia(LIM)guinea pigs.Methods Three-week-old trichromatic guinea pigs were randomly divided into three groups:control group,white light LIM(WL)group,and blue light LIM(BL)group(420 nm LED light,with an illuminance of 700 lx);guinea pigs in the latter two groups wore-10.00 D lenses in their right eyes to induce myopia.All guinea pigs under-went a 12 h light/12 h dark treatment cycle.Before and 2,4 weeks after the intervention,the diopter,axial length,retinal thickness and choroidal thickness were measured in all groups.After 4 weeks of intervention,the corneal fluorescent stai-ning and retinal Hematoxylin and Eosin(HE)staining were conducted.Results Compared with the control group,from week 0 to week 2 of the intervention(changes in weeks 0-2),the eyes in the WL group drifted(-2.22±1.28)D towards myopia,the axial length lengthened by(0.40±0.05)mm,and the retinal and choroidal thicknesses reduced by(-7.42± 7.04)μm and(-6.29±4.66)μm,respectively;compared with the WL group,in the BL group,the eyes drifted toward hyperopia by(0.48±1.16)D,the axial length increased by(0.20±0.10)mm,and retinal and choroidal thicknesses in-creased by(1.36±7.46)μm and(8.05±8.08)μm,respectively(all P<0.05).From week 2 to week 4(changes in weeks 2-4),compared with the control group,the diopter in the WL and BL groups progressed towards myopia,with changes of(-4.64±0.50)D and(-2.11±2.02)D,respectively(both P<0.05);the axial length lengthened,and reti-nal and choroidal thicknesses reduced in the WL group,with changes of(0.44±0.06)mm,(-7.35±5.87)μm and(-4.84±2.61)μm,while the choroidal thickness and the retinal thickness decreased in the BL group,with changes of(-0.33±5.95)μm and(-4.78±4.96)μm,respectively.Observations of corneal fluorescence staining and retinal HE staining indicated that prolonged blue light exposure could lead to damage to corneal and retinal cells.Conclusion Blue light may influence the development of myopia through choroid-related mechanisms,but its inhibitory effect is not positive-ly correlated with time.Prolonged exposure to blue light can damage the cornea and retina,thereby reducing the inhibitory effect.
4.Mechanism of electroacupuncture on improving corneal inflammation in dia-betic dry eye rats by regulating Toll-like receptor 4-mediated inflammatory signaling pathway
Zhangyitian FU ; Mimi WAN ; Sihua LAI ; Xinyi SUN ; Xiaoying LI ; Weiping GAO
Recent Advances in Ophthalmology 2024;44(1):24-29
Objective To observe the effect of electroacupuncture on corneal Toll-like receptor 4(TLR4)-mediated inflammatory signaling pathway in diabetic dry eye rats and to explore the mechanism of electroacupuncture in the treat-ment of diabetic dry eye.Methods A type 2 diabetic rat model was established in 32 healthy male Sprague-Dawley(SD)rats by intraperitoneal injection of streptozotocin(30 mg·kg-1)for 12 weeks after feeding with high-sugar and high-fat di-et for 4 weeks.Twenty-five successfully modeled diabetic dry eye rats were randomly divided into the model group(non-in-tervention),electroacupuncture group(the"Jingming","Cuanzhu","Sizhukong","Taiyang"and"Tongziliao"acupoints were treated with acupuncture,and then"Cuanzhu"and"Tongzilao"acupoints were treated with electroacupuncture,15 min for each time,once a day),sham acupuncture group(blunt-tip needle pricking was performed at the same acupoints as the electroacupuncture group),and fluorometholone group(1 g·L-1fluorometholone eye drops were used in both eyes at 8 o'clock,13 o'clock,and 18 o'clock,1 drop each time),with 6 rats in each group,lasting for 2 weeks.Another 6 healthy male SD rats were selected as a blank group.Random blood glucose,tear film breakup time(BUT),tear secre-tion,corneal fluorescein staining(FL)score,and corneal touch threshold(CTT)of rats in each group were detected be-fore modeling,after modeling,and after the intervention.Hematoxylin and Eosin(HE)staining was performed to observe the corneal morphologic changes in each group.Immunofluorescence histochemical staining was adopted to detect the cor-neal TLR4-positive expression in each group.The TLR4,phosphorylated nuclear factor-kappa P65(P-NF-KB P65),inter-leukin(IL)-1β,and IL-18 expression levels in the cornea were detected by Western blot.Results After modeling,com-pared with the blank group,BUT,tear secretion and CTT decreased and FL increased in all experimental groups,and the differences were statistically significant(all P<0.01).After the intervention,compared with the model group,FL de-creased,and BUT,tear secretion and CTT increased in the electroacupuncture group,and the differences were statistically significant(all P<0.05).Corneal HE staining showed that after the intervention,the corneal surface of rats in the model group and sham acupuncture group was not smooth,and the corneal epithelial cells were thickened and disorganized;the corneal surface of rats in the electroacupuncture group and fluorometholone group was smooth,and the corneal epithelial cells were arranged neatly.After the intervention,compared with the blank group,the corneal TLR4 expression of rats in all other groups was elevated,and the differences were statistically significant(all P<0.05);compared with the model group,the corneal TLR4 expression of rats in the electroacupuncture group and fluorometholone group was reduced(both P<0.01).Compared with the blank group,corneal TLR4,P-NF-κBP65,IL-1β and IL-18 protein expressions increased in the model group and sham acupuncture group(all P<0.05);compared with the model group,these expressions decreased in the electroacupuncture group and the fluorometholone group(all P<0.05).Conclusion Electroacupuncture can im-prove the ocular surface signs and inhibit the expressions of TLR4,P-NF-κB P65,IL-1 β,and IL-18 in the cornea of type 2 diabetic dry eye rats,and its mechanism of action may be related to the regulation of TLR4-mediated inflammatory signaling pathway,which inhibits ocular surface inflammation in diabetic dry eye rats.
5.Anti-inflammatory effect of Celastrol in the ocular tissues of mice with exper-imental autoimmune uveitis and its impact on microglia polarization
Binbin PANG ; Qinyun XIA ; Zhen CHEN ; Yiqiao XING
Recent Advances in Ophthalmology 2024;44(1):30-34,38
Objective To investigate the anti-inflammatory action of Celastrol in the ocular tissues of mice with ex-perimental autoimmune uveitis(EAU)and its effect on microglia polarization.Methods A total of 36 healthy B10.RⅢmice at 6-8 weeks of age were selected and randomly divided into the normal control group,EAU solvent control group and Celastrol intervention group,with 12 mice in each group.The interphotoreceptor retinoid-binding protein(IRBP)161-180 and Freund's complete adjuvant were mixed by thorough emulsification and injected subcutaneously into the bilateral thighs and tails of mice in the EAU solvent control group and the Celastrol intervention group with a total volume of 200 μL and 50 μg IRBP 161-180 in each mouse.On 7-14 days after immunization,mice in the Celastrol intervention group received a daily intraperitoneal injection of 0.5 mg·kg-1 Celastrol,and mice in the EAU solvent control group were injected with an equivalent dose of sterile Phosphate Buffered Saline solution.On the 14th day after immunization,the anterior segment of mice in each group was observed by slit-lamp microscope and Hematoxylin and Eosin(HE)staining of tissue sections was performed;the clinical and histopathological scores of mice in each group were obtained by reference to the Caspi grading standards;immunofluorescence staining was used to observe the activation of microglia in the eyes of mice;Western blot was used to detect the protein expression levels of inducible nitric oxide synthase(iNOS)and arginase-1(Argl)in the reti-na;quantitative real-time PCR was used to detect the relative mRNA expression of inflammatory factors in the retina,such as tumor necrosis factor(TNF)-α,interleukin(IL)-1β and IL-6.GraphPad Prism 9.0 was used for data analysis.Results On the 14th day after immunization,it was observed by the slit-lamp microscope that the anterior segment of mice in the EAU solvent control group was markedly congested with dilated iris blood vessels,corneal edema,and anterior chamber exudation;the inflammation in the anterior segment of mice in the Celastrol intervention group was markedly at-tenuated,and the iris blood vessels were seen to be mildly congested.Compared with the normal control group,the clini-cal scores of mice in the EAU solvent control group and the Celastrol intervention group were significantly elevated(both P<0.05);the clinical scores of mice in the Celastrol intervention group were lower than those in the EAU solvent control group(P<0.05).HE staining results showed that on the 14th day after immunization,mice in the EAU solvent control group showed severe retinal folds and detachment with diffuse infiltration of inflammatory cells,while mice in the Celastrol intervention group showed slight structural damage to the retina and a small amount of inflammatory cell infiltration.Com-pared with the normal control group,the histopathological scores of mice in the EAU solvent control group and the Celas-trol intervention group were significantly elevated(both P<0.05);the histopathological scores of mice in the Celastrol in-tervention group were lower than those in the EAU solvent control group(P<0.05).The intraocular Iba1+cell densities of mice in the normal control,EAU solvent control and Celastrol intervention groups were(1.00±0.12)%,(36.07± 4.57)%,and(1.83±0.36)%,respectively.Compared with the normal control group,the number of Iba1+cells in the eyes of mice in the EAU solvent control group and the Celastrol intervention group significantly increased(both P<0.05);compared with the EAU solvent control group,the number of Iba1+cells in the eyes of mice in the Celastrol intervention group was significantly reduced(P<0.05).Compared with the normal control group,the expression levels of iNOS and Arg1 proteins in the retinas of mice in the EAU solvent control group were significantly elevated(both P<0.01);compared with the EAU solvent control group,the expression of iNOS protein in the retinas of mice in the Celastrol intervention group was significantly reduced(P<0.01).Compared with the normal control group,the relative mRNA expressions of TNF-α.IL-1β,and IL-6 in the retinas of mice in the EAU solvent control group was significantly elevated(all P<0.05);compared with the EAU solvent control group,the relative mRNA expressions of TNF-α,IL-1 β,and IL-6 in the retinas of mice in the Celastrol intervention group significantly decreased(all P<0.05).Conclusion Celastrol inhibits Ml microglia activation and reduces the production of retinal inflammatory factors TNF-α,IL-1 β and IL-6 in EAU mice,thereby attenuating the in-flammatory reaction.
6.Relationship between the continuity of ellipsoid zone and best corrected visu-al acuity in patients with idiopathic epiretinal membrane
Xiaobo ZHU ; Yanni YAN ; Qian WANG ; Jingyan YANG ; Jinqiong ZHOU ; Wenbin WEI
Recent Advances in Ophthalmology 2024;44(1):35-38
Objective To investigate the relationship between the central foveal thickness(CFT),ellipsoid zone(EZ)interruption ratio and best corrected visual acuity(BCVA)in patients with idiopathic epiretinal membranes(iERM).Methods A retrospective case-control study was conducted.The cluster sampling method was used to select 336 iERM patients(500 eyes)who underwent physical examinations in 9 community hospitals of the Kailuan Group from 2014 to 2018.Among them,215 were male(64.0%)and 121 were female(36.0%),with an average age of 31-89(66.4±8.8)years.According to the gass classification,these patients were divided into three groups:gass 0 group(201 patients,305 eyes),gass 1 group(75 patients,101 eyes),and gass 2 group(60 patients,94 eyes).Pearson correlation analysis was used to evaluate the correlation between BCVA(converted to logMAR visual acuity)and gass classification,EZ interruption ratio,CFT.Results The average BCVA(logMAR)and CFT of 500 eyes were 0.45±0.28 and(337.6±101.8)μm,re-spectively,with EZ interruption in 86 eyes(17.2%).There were statistically significant differences in BCVA(logMAR)(0.62±0.29,0.48±0.23,0.26±0.32),CFT[(283.20±79.30)μm,(335.50±84.50)μm,(394.00±135.60)μm],and EZ interruption ratio(2.6%,20.8%,60.6%)among gass 0,gass 1 and gass 2 groups(all P<0.05).Pearson correlation analysis showed that there was no correlation between age and BCVA among different groups(r2=0.021,P=0.314);BCVA was positively correlated with CFT(r2=0.531,P=0.000),EZ interruption ratio(r2=0.304,P=0.000),and gass classification(r2=0.587,P=0.000).Conclusion The EZ interruption may occur in the early stage of iERM.BCVA is correlated with CFT,EZ interruption ratio and gass classification;the incidence of EZ interruption in gass 2 iERM signifi-cantly increases.
7.Correlation between baseline aqueous humor cytokine levels and anti-vascu-lar endothelial growth factor treatment in patients with macular edema sec-ondary to retinal vein obstruction
Ying HUANG ; Jiaqin CHEN ; Qin JIANG ; Jin YAO
Recent Advances in Ophthalmology 2024;44(1):39-43
Objective To analyze the effect of baseline cytokines in aqueous humor in predicting the improvement of the central macular thickness(CMT)and best corrected visual acuity(BCVA)of patients with macular edema secondary to retinal vein obstruction(RVO-ME)after anti-vascular endothelial growth factor(VEGF)treatment for 3 months.Meth-ods Totally 30 eyes of 30 patients initially diagnosed with RVO-ME in the Affiliated Eye Hospital of Nanjing Medical Uni-versity from October 2021 to January 2023 were enrolled.Aqueous humor was collected by anterior chamber puncture be-fore the anti-VEGF drug injection.The levels of 11 cytokines in aqueous humor,including VEGF,intercellular adhesion molecule(ICAM)-1,interleukins(ILs)and interferon-γ(IFN-γ),were measured by Luminex xMAP technology.The cor-relation between baseline aqueous humor cytokine levels and CMT,BCVA(logMAR)as well as their changes(difference between baseline and anti-VEGF treatment for 3 months)in RVO-ME patients was analyzed;the correlation between CMT and BCVA(logMAR)was analyzed at baseline and 3 months after anti-VEGF treatment.CMT and BCVA responders were defined as patients with 50%or more reduction in CMT and BCVA(logMAR)from baseline to the third month.A Logistic regression model was used to analyze the relationship between baseline aqueous humor cytokines and RVO-ME patients be-coming CMT or BCVA responders after 3 months of anti-VEGF treatment.Results Compared with baseline,the CMT sig-nificantly decreased and BCVA significantly improved in RVO-ME patients after anti-VEGF treatment for 3 months(both P<0.001).The CMT was positively correlated with BCVA(logMAR)of RVO-ME patients at baseline and after anti-VEGF treatment for 3 months(P=0.026,0.002).At baseline,the levels of VEGF and IL-8 of RVO-ME patients were positively correlated with CMT(P=0.032,0.035);the levels of IL-6 and IL-8 were positively correlated with BCVA(logMAR)(P=0.018,0.002).The baseline IL-8 level in RVO-ME patients was negatively associated with the change in CMT(P=0.024).Logistic regression analysis showed that elevated baseline ICAM-1 level could increase the risk of RVO-ME patients becom-ing BCVA non-responders after 3 months of anti-VEGF treatment(P=0.023).Conclusion Baseline IL-8 and ICAM-1 may be predictors of CMT and BCVA improvement after anti-VEGF treatment of RVO-ME.
8.Effect of residual corneal astigmatism on visual acuity of patients undergoing regional refractive intraocular lens implantation
Xiaoting MA ; Kejun LI ; Zhihua ZHAO ; Yin ZHANG ; Yinghua DU ; Fuzhen LIANG
Recent Advances in Ophthalmology 2024;44(1):43-47
Objective To investigate the effect of residual corneal astigmatism on visual acuity after regional refrac-tive intraocular lens(IOL)implantation.Methods A retrospective cohort study was conducted.The medical records and follow-up data of 73 eyes of 57 cataract patients who underwent ultrasound emulsification cataract extraction combined with LENTIS Comfort LS-313 MF15 IOL implantation in the Ophthalmology Department of the Hebei General Hospital from June 2020 to March 2022 were collected.These patients were grouped according to postoperative residual corneal astigmatism:32 patients(40 eyes)with a residual corneal astigmatism of 0.75(exclusive)-1.50 D were taken as the experimental group,and 25 patients(33 eyes)with a residual corneal astigmatism ≤0.75 D were taken as the control group.The uncor-rected distance visual acuity(5 m),uncorrected intermediate visual acuity(80 cm),uncorrected near visual acuity(40 cm),out-of-focus curve,objective visual quality,subjective visual quality,satisfaction degree and lens removal rate of pa-tients in the two groups were recorded 6 months postoperatively.Results The postoperative uncorrected distance visual acuity(logMAR)was 0.10(0.00,0.22),the uncorrected intermediate visual acuity(logMAR)was 0.00(0.00,0.10),and the uncorrected near visual acuity(logMAR)was 0.20(0.10,0.30)and 0.20(0.10,0.20)in the experimental and control groups,with no statistically significant differences(all P>0.05).The postoperative out-of-focus curves showed that the distance visual acuity of patients with additional spherical equivalent refraction ranged from+2.00 D to-4.00 D in the two groups had no statistically significant difference(all P>0.05).There were statistically significant differences in to-tal aberration,coma aberration,modulation transfer function and Strehl ratio in the objective visual quality of patients after surgery(all P<0.05),and there was no statistically significant difference in the total higher-order aberration,spherical ab-erration and cloverleaf aberration(all P>0.05).There was no statistically significant difference in the subjective visual quality,satisfaction degree and lens removal rate in the two groups(all P>0.05).Conclusion Residual corneal astig-matism of 0.75 D to 1.50 D after LENTIS Comfort LS-313 MF15 IOL implantation has no effect on higher-order aberration,spherical aberration,and cloverleaf aberration in subjective and objective visual quality,and has an impact on total aberra-tion,coma aberration,modulation transfer function and Strehl ratio in objective visual quality.
9.Correlation of corneal biomechanical changes with corneal volume changes and high-order aberration changes in the early stage after small incision lent-icule extraction
Recent Advances in Ophthalmology 2024;44(1):48-51,57
Objective To observe the corneal biomechanical changes of patients in the early stage after small inci-sion lenticule extraction(SMILE),and to analyze the correlation between the corneal biomechanical changes and changes in corneal volumes and higher-order aberrations.Methods A total of 72 patients(72 eyes)with myopia or myopic astig-matism who were scheduled for SMILE in the Optometric Center of Second People's Hospital of Foshan from January to August 2021 were included.The right eye was selected for observation.Before and 3 months after the SMILE,novel corne-al biomechanical parameters,such as biomechanical intraocular pressure(bIOP),DA ratiomax(2 mm)(DA2 ratio),inte-grated radius(IR),Ambrósio's relational thickness(for evaluation of the morphology and quality of the cornea,ARTh),stiffness parameter applanation 1(SP-A1),Corvis biomechanical index(CBI)and stress-strain index(SSI),were meas-ured by the new generation of Corvis? ST.The Pentacam anterior segment analysis system was used to measure corneal bi-omechanical parameters,including corneal volume(CV3 mm,CV5 mm,CV7 mm and CV10 mm);total root mean square of whole cornea,anterior and posterior corneal surface[RMS(Cornea,CF,CB)];root mean square of high-order aberrations of total cornea,anterior and posterior corneal surface[RMS HOA(Cornea,CF,CB)].Paired t-test or Wilcoxon singed-rank test was used to compare the changes in parameters before and after SMILE.Spearman correlation analysis and partial least squares regression were used to study the correlation between changes in novel corneal biomechanical parameters with cor-neal volume changes and high-order corneal aberration changes after the SMILE.Results Three months after SMILE,the bIOP,ARTh,SP-A1 and SSI decreased significantly,while the DA2 ratio,IR and CBI increased significantly(all P<0.05).Three months after SMILE,CV3 mm,CV5 mm,CV7 mm and CV10 mm decreased significantly(all P<0.05).The corneal volume changes from small to large were CV3 mm,CV5 mm,CV7 mm and CV10 mm,with a maximum decrease in the outmost periphery.The RMS(Cornea,CF,CB)and RMS HOA(Cornea,CF,CB)increased significantly(all P<0.05);compared with the changes in high-order aberration on the anterior corneal surface,the changes in higher-order aberration on the posterior corneal surface were relatively stable.Correlation analysis shows that △ARTh was positively correlated with △CV3mm and△CV5mm,and negatively correlated with △CV10mm(all P<0.05);△bIOP was negatively correlated with △CV3mm,△CV5mm,△RMS HOA(CF)and △RMS HOA(Cornea)and positively correlated with △CV10mm(all P<0.05);△IR was negatively correlated with △CV10 mm(P<0.05);△SP-A1 was positively correlated with △CV10 mm(P<0.05);△ CBI was negatively correlated with △CV3 mm and △CV5 mm,and positively correlated with △CV10mmand △RMS(CF)(all P<0.05).Conclusion The changes in corneal biomechanical parameters occur in the early stage after SMILE,with a certain corre-lation with the corneal volume changes in different regions and high-order corneal aberration changes.
10.Logistic regression analysis and risk model construction of choroidopathy sec-ondary to high myopia
Recent Advances in Ophthalmology 2024;44(1):52-57
Objective To analyze the influencing factors of choroidopathy(choroidal atrophy and choroidal neovas-cularization)secondary to high myopia based on Logistic regression analysis and to construct a Nomogram risk prediction model based on the related factors,so as to provide guidance for clinical treatment.Methods A total of 340 patients(680 eyes)with high myopia admitted to Beijing Jishuitan Hospital from January 2021 to January 2023 were selected and di-vided into group A(170 patients,340 eyes)and group B(170 patients,340 eyes).The incidence of choroidopathy in the two groups was compared.The groups A and B were divided into two subgroups,subgroup a and subgroup b,according to whether choroidopathy occurred or not.Multivariate Logistic regression analysis was carried out to explore the influencing factors of choroidopathy secondary to high myopia.A Nomogram risk prediction model for choroidopathy secondary to high myopia was constructed based on the influencing factors and externally validated.Results In groups A and B,the age,proportion of diabetes mellitus,axial length,and level of seruim transforming growth factor β1(TGF-β1)of patients in subgroup a were higher than those in the subgroup b,and the diopter was lower than that in the subgroup b(all P<0.05).The Logistic regression analysis showed that age,diabetes mellitus,axial length and serum TGF-β1 level were independent risk factors for choroidopathy secondary to high myopia,and diopter was a protective factor(all P<0.05).Age,diabetes mellitus,axial length and serum TGF-β1 level were positively correlated risk factors for choroidopathy secondary to high myopia,and diopter was a negatively correlated risk factor(all P<0.05).The area under the curve of the Nomogram risk prediction model for predicting choroidopathy secondary to high myopia was 0.818,and the calibration was good.Con-clusion Age,diabetes mellitus,axial length,diopter and serum TGF-β1 level are the influential factors for choroidopa-thy secondary to high myopia.The Nomogram risk prediction model established based on these factors has a certain value for predicting choroidopathy secondary to high myopia.The clinical therapeutic schedules should be made based on this model to reduce the risk of secondary choroidopathy.

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