BACKGROUND Glycation is an important step in aging and oxidative stress,which can lead to endothelial dysfunction and cause severe damage to the eyes or kidneys of diabetics.Inhibition of the formation of advanced gly...BACKGROUND Glycation is an important step in aging and oxidative stress,which can lead to endothelial dysfunction and cause severe damage to the eyes or kidneys of diabetics.Inhibition of the formation of advanced glycation end products(AGEs)and their cell toxicity can be a useful therapeutic strategy in the prevention of diabetic retinopathy(DR).Gardenia jasminoides Ellis(GJE)fruit is a selective inhibitor of AGEs.Genipin is an active compound of GJE fruit,which can be employed to treat diabetes.AIM To confirm the effect of genipin,a vital component of GJE fruit,in preventing human retinal microvascular endothelial cells(hRMECs)from AGEs damage in DR,to investigate the effect of genipin in the down-regulation of AGEs expression,and to explore the role of the CHGA/UCP2/glucose transporter 1(GLUT1)signal pathway in this process.METHODS In vitro,cell viability was tested to determine the effects of different doses of glucose and genipin in hRMECs.Cell Counting Kit-8(CCK-8),colony formation assay,flow cytometry,immunofluorescence,wound healing assay,transwell assay,and tube-forming assay were used to detect the effect of genipin on hRMECs cultured in high glucose conditions.In vivo,streptozotocin(STZ)induced mice were used,and genipin was administered by intraocular injection(IOI).To explore the effect and mechanism of genipin in diabetic-induced retinal dysfunction,reactive oxygen species(ROS),mitochondrial membrane potential(MMP),and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose(2-NBDG)assays were performed to explore energy metabolism and oxidative stress damage in high glucose-induced hRMECs and STZ mouse retinas.Immunofluorescence and Western blot were used to investigate the expression of inflammatory cytokines[vascular endothelial growth factor(VEGF),SCG3,tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,IL-18,and nucleotide-binding domain,leucine-rich-containing family,pyrin domain-containing 3(NLRP3)].The protein expression of the receptor of AGEs(RAGE)and the mitochondria-related signal molecules CHGA,GLUT1,and UCP2 in high glucose-induced hRMECs and STZ mouse retinas were measured and compared with the genipin-treated group.RESULTS The results of CCK-8 and colony formation assay showed that genipin promoted cell viability in high glucose(30 mmol/L D-Glucose)-induced hRMECs,especially at a 0.4μmol/L dose for 7 d.Flow cytometry results showed that high glucose can increase apoptosis rate by 30%,and genipin alleviated cell apoptosis in AGEs-induced hRMECs.A high glucose environment promoted ATP,ROS,MMP,and 2-NBDG levels,while genipin inhibited these phenotypic abnormalities in AGEs-induced hRMECs.Furthermore,genipin remarkably reduced the levels of the pro-inflammatory cytokines TNF-α,IL-1β,IL-18,and NLRP3 and impeded the expression of VEGF and SCG3 in AGEs-damaged hRMECs.These results showed that genipin can reverse high glucose induced damage with regard to cell proliferation and apoptosis in vitro,while reducing energy metabolism,oxidative stress,and inflammatory injury caused by high glucose.In addition,ROS levels and glucose uptake levels were higher in the retina from the untreated eye than in the genipin-treated eye of STZ mice.The expression of inflammatory cytokines and pathway protein in the untreated eye compared with the genipin-treated eye was significantly increased,as measured by Western blot.These results showed that IOI of genipin reduced the expression of CHGA,UCP2,and GLUT1,maintained the retinal structure,and decreased ROS,glucose uptake,and inflammation levels in vivo.In addition,we found that SCG3 expression might have a higher sensitivity in DR than VEGF as a diagnostic marker at the protein level.CONCLUSION Our study suggested that genipin ameliorates AGEs-induced hRMECs proliferation,apoptosis,energy metabolism,oxidative stress,and inflammatory injury,partially via the CHGA/UCP2/GLUT1 pathway.Control of advanced glycation by IOI of genipin may represent a strategy to prevent severe retinopathy and vision loss.展开更多
AIM:To evaluate the safety,effectiveness,and predictability of small incision lenticule extraction(SMILE)for the treatment of anisometropia,and to explore the personalized design scheme of SMILE in correcting adult my...AIM:To evaluate the safety,effectiveness,and predictability of small incision lenticule extraction(SMILE)for the treatment of anisometropia,and to explore the personalized design scheme of SMILE in correcting adult myopia anisometropia based on the nomogram.METHODS:It’s a prospective cohort study.Patients with anisometropic myopia of refractive difference≥2.0 diopters(D)who underwent SMILE between September 2020 and March 2021 were enrolled.Clinical features and visual function were assessed preoperatively and at 1wk,1,3,and 6mo after the operation.The examination included tests for uncorrected distance visual acuity(UDVA),corrected distance visual acuity(CDVA),refractive errors,effectiveness index(preoperative CDVA/postoperative UDVA),safety index(postoperative CDVA/preoperative CDVA),nomogram and stereoscopic function.Paired t-test,Wilcoxon signed-rank test and repeated-measures analyses of variance were used for continuous variables,and Pearson Chi-squared test was used for categorical variables.RESULTS:The study involved 45 consecutive patients(average age:25.0±6.9y;82 out of 90 eyes underwent SMILE,while 8 eyes were not operated).The average preoperative spherical equivalent(SE)was-4.74±0.22 D.Six months after surgery,the effectiveness index was 1.05±0.12,and the safety index was 1.09±0.11.Seventy eyes(85.4%)exhibited SE correction error within±0.5 D.The percentage of eyes with Titmus stereoscopic function equal to or less than 200”significantly increased from 55.6%preoperatively to 88.9%postoperatively(P<0.05).There was statistically significant difference between higher myopia eyes and contralateral eyes in average nomogram value/spherical refraction ratio.CONCLUSION:SMILE is safe,effective and predictable in correcting myopic anisometropia,and it improves stereoscopic visual function of anisometropia patients.The precise and individualized design of the nomogram is a vital element to ensure the balance of both eyes after SMILE.展开更多
BACKGROUND Optical coherence tomography angiography(OCTA)is a new and reliable machine used to evaluate retinal structure and macular perfusion in children.The use of OCTA under bad condition such as high altitude,low...BACKGROUND Optical coherence tomography angiography(OCTA)is a new and reliable machine used to evaluate retinal structure and macular perfusion in children.The use of OCTA under bad condition such as high altitude,low atmospheric oxygen,and low humidity,in children is rarely.AIM To quantify the macular micro-vasculature in healthy children of various ages using OCTA in Qamdo.METHODS Design:Prospective cross-sectional,school-based study.Three hundred and fortyseven normal students from 9 schools in 4 different areas in Qamdo were included.OCTA was performed on a 3 mm×3 mm area centered on the macular region and macular cube 512×128 showed details in macular.Early treatment of diabetic retinopathy study Vessel Flow Density(VD)of the macular central vascular plexus density(CVD),inner vascular plexus density(IVD),full vascular plexus density(FVD),and the size of the foveal avascular zone(FAZ)were measured.All these results corrected by t/s=3.382×0.01306×(axial length-1.82).The differences were compared among various ages,sexes and living environments.RESULTS The mean FAZ area in all eyes was 0.27 mm^(2)±0.12 mm^(2).The mean foveal thickness(MFT)in the macular cube was 227.64μm±23.51μm.Compared with girls,boys had a lager FAZ(P=0.0029).Among the different age groups,MFT(P<0.001)and FVD(P<0.0001),IVD(P<0.0001),and CVD(P=0.0050)increased with age.FAZ areas were not correlated with age(P=0.8853)or others(MFT,area).CONCLUSION OCTA can use to evaluate macular perfusion in children.Our data bridge the gap between structural OCT and perfusion density in children in high altitude.Even though these were not a longitudinal study,it may provide us with hints about retina development during puberty and clinical implications of OCTA in children.展开更多
AIM: To investigate the distribution of bone morphogenetic protein receptors (BMPRs) in human scleral fibroblsasts (HSFs) and in human sclera. METHODS: Primary HSFs were cultured in vitro . The mRNA levels of BMP-2 an...AIM: To investigate the distribution of bone morphogenetic protein receptors (BMPRs) in human scleral fibroblsasts (HSFs) and in human sclera. METHODS: Primary HSFs were cultured in vitro . The mRNA levels of BMP-2 and BMPRs in HSFs were assayed by reverse transcription-polymerase chain reaction (RT-PCR). The protein distributions of BMP-2 and BMPRs in HSFs were further detected by immunocytofluorescence and western blot. Their protein expression was also detected in frozen human posterior scleral sections by immunohistofluorescence. RESULTS: BMP-2 and BMPRs were expressed in both HSFs and human sclera not only at mRNA level but also at protein level. The expressions of BMPRIA and BMPRII were higher than that of BMPRIB in the cytoplasm and cell membrane of HSFs in vitro. Western blot further verified the results of immunocytofluorescence. In human sclera, BMP2, BMPR IB and BMPR II were found to be expressed in the cytomatrix of HSF, and weak signal was detected about BMPRIA. CONCLUSION: BMP-2 and all three subtypes of BMPRs were found in HSFs and may play a role in scleral remodeling.展开更多
Two TiAl alloys,Ti-47.5Al-3.7(Cr,V,Zr)and Ti-47.5Al-3.7(Cr,V,Zr)-0.1C(at.%),were prepared by cold crucible levitation melting to couple the hard-oriented directional lamellar microstructure with carbon microalloying s...Two TiAl alloys,Ti-47.5Al-3.7(Cr,V,Zr)and Ti-47.5Al-3.7(Cr,V,Zr)-0.1C(at.%),were prepared by cold crucible levitation melting to couple the hard-oriented directional lamellar microstructure with carbon microalloying strengthening.The creep behavior and mechanism for the improvement in creep properties by carbon addition were investigated by mechanical tests and electron microscopy characterizations.The results show that obvious improvements on the creep properties at 760°C and 276 MPa are achieved by 0.1 at.%C addition into TiAl alloy with directional lamellar microstructure,which promotes the creep strain and minimum creep rate decreasing with a large content.The minimum creep rate is reduced from 4.37×10^(-8) to 3.97×10^(-9) s^(-1),and the duration entering into creep acceleration is prolonged for more than 10 times.The mechanism for creep property improvement by 0.1%C addition is attributed to two aspects.The first one is that Ti_(2) AlC is found to be strong obstacles of 1/2[110]dislocations when moving across the lamellar interface in the carbon containing alloy.The other one is that the in terfacial dislocatio ns are effectively impeded and the release process is hindered by dynamic precipitation of Ti_(3) AlC,which is proposed to be the special mechanism for creep resistance improvement of this hard-oriented directional lamellar microstructure.展开更多
基金the National Natural Science Foundation of China,No.81870650,No.81570832,and No.81900885Science and Technology Program Chongqing,No.2018GDRC008 and No.XKTS049。
文摘BACKGROUND Glycation is an important step in aging and oxidative stress,which can lead to endothelial dysfunction and cause severe damage to the eyes or kidneys of diabetics.Inhibition of the formation of advanced glycation end products(AGEs)and their cell toxicity can be a useful therapeutic strategy in the prevention of diabetic retinopathy(DR).Gardenia jasminoides Ellis(GJE)fruit is a selective inhibitor of AGEs.Genipin is an active compound of GJE fruit,which can be employed to treat diabetes.AIM To confirm the effect of genipin,a vital component of GJE fruit,in preventing human retinal microvascular endothelial cells(hRMECs)from AGEs damage in DR,to investigate the effect of genipin in the down-regulation of AGEs expression,and to explore the role of the CHGA/UCP2/glucose transporter 1(GLUT1)signal pathway in this process.METHODS In vitro,cell viability was tested to determine the effects of different doses of glucose and genipin in hRMECs.Cell Counting Kit-8(CCK-8),colony formation assay,flow cytometry,immunofluorescence,wound healing assay,transwell assay,and tube-forming assay were used to detect the effect of genipin on hRMECs cultured in high glucose conditions.In vivo,streptozotocin(STZ)induced mice were used,and genipin was administered by intraocular injection(IOI).To explore the effect and mechanism of genipin in diabetic-induced retinal dysfunction,reactive oxygen species(ROS),mitochondrial membrane potential(MMP),and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose(2-NBDG)assays were performed to explore energy metabolism and oxidative stress damage in high glucose-induced hRMECs and STZ mouse retinas.Immunofluorescence and Western blot were used to investigate the expression of inflammatory cytokines[vascular endothelial growth factor(VEGF),SCG3,tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,IL-18,and nucleotide-binding domain,leucine-rich-containing family,pyrin domain-containing 3(NLRP3)].The protein expression of the receptor of AGEs(RAGE)and the mitochondria-related signal molecules CHGA,GLUT1,and UCP2 in high glucose-induced hRMECs and STZ mouse retinas were measured and compared with the genipin-treated group.RESULTS The results of CCK-8 and colony formation assay showed that genipin promoted cell viability in high glucose(30 mmol/L D-Glucose)-induced hRMECs,especially at a 0.4μmol/L dose for 7 d.Flow cytometry results showed that high glucose can increase apoptosis rate by 30%,and genipin alleviated cell apoptosis in AGEs-induced hRMECs.A high glucose environment promoted ATP,ROS,MMP,and 2-NBDG levels,while genipin inhibited these phenotypic abnormalities in AGEs-induced hRMECs.Furthermore,genipin remarkably reduced the levels of the pro-inflammatory cytokines TNF-α,IL-1β,IL-18,and NLRP3 and impeded the expression of VEGF and SCG3 in AGEs-damaged hRMECs.These results showed that genipin can reverse high glucose induced damage with regard to cell proliferation and apoptosis in vitro,while reducing energy metabolism,oxidative stress,and inflammatory injury caused by high glucose.In addition,ROS levels and glucose uptake levels were higher in the retina from the untreated eye than in the genipin-treated eye of STZ mice.The expression of inflammatory cytokines and pathway protein in the untreated eye compared with the genipin-treated eye was significantly increased,as measured by Western blot.These results showed that IOI of genipin reduced the expression of CHGA,UCP2,and GLUT1,maintained the retinal structure,and decreased ROS,glucose uptake,and inflammation levels in vivo.In addition,we found that SCG3 expression might have a higher sensitivity in DR than VEGF as a diagnostic marker at the protein level.CONCLUSION Our study suggested that genipin ameliorates AGEs-induced hRMECs proliferation,apoptosis,energy metabolism,oxidative stress,and inflammatory injury,partially via the CHGA/UCP2/GLUT1 pathway.Control of advanced glycation by IOI of genipin may represent a strategy to prevent severe retinopathy and vision loss.
基金Supported by the National Natural Science Foundation of China(No.81970832No.81870650)+2 种基金the Key Project of the Chongqing Health Commission(No.2018MSXM003No.2018GDRC008)Natural Science Foundation of Chongqing Science and Technology Bureau(No.cstc2021jcyj-msxmX0967).
文摘AIM:To evaluate the safety,effectiveness,and predictability of small incision lenticule extraction(SMILE)for the treatment of anisometropia,and to explore the personalized design scheme of SMILE in correcting adult myopia anisometropia based on the nomogram.METHODS:It’s a prospective cohort study.Patients with anisometropic myopia of refractive difference≥2.0 diopters(D)who underwent SMILE between September 2020 and March 2021 were enrolled.Clinical features and visual function were assessed preoperatively and at 1wk,1,3,and 6mo after the operation.The examination included tests for uncorrected distance visual acuity(UDVA),corrected distance visual acuity(CDVA),refractive errors,effectiveness index(preoperative CDVA/postoperative UDVA),safety index(postoperative CDVA/preoperative CDVA),nomogram and stereoscopic function.Paired t-test,Wilcoxon signed-rank test and repeated-measures analyses of variance were used for continuous variables,and Pearson Chi-squared test was used for categorical variables.RESULTS:The study involved 45 consecutive patients(average age:25.0±6.9y;82 out of 90 eyes underwent SMILE,while 8 eyes were not operated).The average preoperative spherical equivalent(SE)was-4.74±0.22 D.Six months after surgery,the effectiveness index was 1.05±0.12,and the safety index was 1.09±0.11.Seventy eyes(85.4%)exhibited SE correction error within±0.5 D.The percentage of eyes with Titmus stereoscopic function equal to or less than 200”significantly increased from 55.6%preoperatively to 88.9%postoperatively(P<0.05).There was statistically significant difference between higher myopia eyes and contralateral eyes in average nomogram value/spherical refraction ratio.CONCLUSION:SMILE is safe,effective and predictable in correcting myopic anisometropia,and it improves stereoscopic visual function of anisometropia patients.The precise and individualized design of the nomogram is a vital element to ensure the balance of both eyes after SMILE.
基金Supported by the National Natural Science Foundation of China,No.81870650,No.81570832,and No.81300794Science and Technology Program Chongqing,China,No.2018GDRC008.
文摘BACKGROUND Optical coherence tomography angiography(OCTA)is a new and reliable machine used to evaluate retinal structure and macular perfusion in children.The use of OCTA under bad condition such as high altitude,low atmospheric oxygen,and low humidity,in children is rarely.AIM To quantify the macular micro-vasculature in healthy children of various ages using OCTA in Qamdo.METHODS Design:Prospective cross-sectional,school-based study.Three hundred and fortyseven normal students from 9 schools in 4 different areas in Qamdo were included.OCTA was performed on a 3 mm×3 mm area centered on the macular region and macular cube 512×128 showed details in macular.Early treatment of diabetic retinopathy study Vessel Flow Density(VD)of the macular central vascular plexus density(CVD),inner vascular plexus density(IVD),full vascular plexus density(FVD),and the size of the foveal avascular zone(FAZ)were measured.All these results corrected by t/s=3.382×0.01306×(axial length-1.82).The differences were compared among various ages,sexes and living environments.RESULTS The mean FAZ area in all eyes was 0.27 mm^(2)±0.12 mm^(2).The mean foveal thickness(MFT)in the macular cube was 227.64μm±23.51μm.Compared with girls,boys had a lager FAZ(P=0.0029).Among the different age groups,MFT(P<0.001)and FVD(P<0.0001),IVD(P<0.0001),and CVD(P=0.0050)increased with age.FAZ areas were not correlated with age(P=0.8853)or others(MFT,area).CONCLUSION OCTA can use to evaluate macular perfusion in children.Our data bridge the gap between structural OCT and perfusion density in children in high altitude.Even though these were not a longitudinal study,it may provide us with hints about retina development during puberty and clinical implications of OCTA in children.
基金National Natural Science Foundation of China (No.81070753)Fundamental Research Funds of State Key Laboratory of Ophthalmology,China(No.2010C02)
文摘AIM: To investigate the distribution of bone morphogenetic protein receptors (BMPRs) in human scleral fibroblsasts (HSFs) and in human sclera. METHODS: Primary HSFs were cultured in vitro . The mRNA levels of BMP-2 and BMPRs in HSFs were assayed by reverse transcription-polymerase chain reaction (RT-PCR). The protein distributions of BMP-2 and BMPRs in HSFs were further detected by immunocytofluorescence and western blot. Their protein expression was also detected in frozen human posterior scleral sections by immunohistofluorescence. RESULTS: BMP-2 and BMPRs were expressed in both HSFs and human sclera not only at mRNA level but also at protein level. The expressions of BMPRIA and BMPRII were higher than that of BMPRIB in the cytoplasm and cell membrane of HSFs in vitro. Western blot further verified the results of immunocytofluorescence. In human sclera, BMP2, BMPR IB and BMPR II were found to be expressed in the cytomatrix of HSF, and weak signal was detected about BMPRIA. CONCLUSION: BMP-2 and all three subtypes of BMPRs were found in HSFs and may play a role in scleral remodeling.
基金National Natural Science Foundation of China(51788104,51390471,51527803 and 51761135131)National 973 Project of China(2015CB654902)National Key Research and Development Pro gram(2016YFB0700402)。
文摘Two TiAl alloys,Ti-47.5Al-3.7(Cr,V,Zr)and Ti-47.5Al-3.7(Cr,V,Zr)-0.1C(at.%),were prepared by cold crucible levitation melting to couple the hard-oriented directional lamellar microstructure with carbon microalloying strengthening.The creep behavior and mechanism for the improvement in creep properties by carbon addition were investigated by mechanical tests and electron microscopy characterizations.The results show that obvious improvements on the creep properties at 760°C and 276 MPa are achieved by 0.1 at.%C addition into TiAl alloy with directional lamellar microstructure,which promotes the creep strain and minimum creep rate decreasing with a large content.The minimum creep rate is reduced from 4.37×10^(-8) to 3.97×10^(-9) s^(-1),and the duration entering into creep acceleration is prolonged for more than 10 times.The mechanism for creep property improvement by 0.1%C addition is attributed to two aspects.The first one is that Ti_(2) AlC is found to be strong obstacles of 1/2[110]dislocations when moving across the lamellar interface in the carbon containing alloy.The other one is that the in terfacial dislocatio ns are effectively impeded and the release process is hindered by dynamic precipitation of Ti_(3) AlC,which is proposed to be the special mechanism for creep resistance improvement of this hard-oriented directional lamellar microstructure.
