Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epid...Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.展开更多
AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 20...AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 2017 to October 2021 were collected.The patients were divided into two groups:DME patients with DN(25 eyes),and DME patients without DN(29 eyes).General conditions were collected before treatment,laboratory tests include fasting blood glucose,HbA1c,microalbumin/creatinine,serum creatinine.Optical coherence tomography(OCT)was used to check the ellipsoidal zone(EZ)and external limiting membrane(ELM)integrity.Central macular thickness(CMT),best corrected visual acuity(BCVA),and retinal hyperreflective foci(HF)as well as numbers of injections were recorded.RESULTS:There were significant differences between fasting blood glucose,HbA1c,serum creatinine,urinary microalbumin/creatinine,and estimated glomerular filtration rate(eGFR)between the two groups(all P<0.05).EZ and ELM continuity in the DME+DN group was worse than that in the DME group(P<0.05).BCVA(logMAR)in the DME group was significantly better than that in the DME+DN group at the same time points during treatment(all P<0.05).CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points(all P<0.05)and significantly decreased in both groups with time during treatment.At 6mo after treatment,the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86,respectively.CONCLUSION:Conbercept has a significant effect in short-term treatment of DME patients with or without DN,and can significantly ameliorate BCVA,CMT and the number of HF,treatment efficacy of DME patients without DN is better than that of DME patients with DN.展开更多
AIM:To assess diabetic macular edema(DME)progression during the early phases of the COVID-19 pandemic,when severe societal restrictions raised the concern of possible deterioration of health in patients with systemic ...AIM:To assess diabetic macular edema(DME)progression during the early phases of the COVID-19 pandemic,when severe societal restrictions raised the concern of possible deterioration of health in patients with systemic conditions,particularly those requiring frequent office visits.METHODS:This is a multicenter retrospective chart review of 370 patients(724 eyes)with an established diagnosis of DME seen on 3 separate visits between January 2019 and July 2021.Period 1 was January 2019 to February 2020(considered pre-COVID-19),period 2 was March 2020 to December 2020(considered the height of the pandemic;highest level of pandemic-related clinical and societal regulations)and period 3 was January 2021 to July 2021(re-adjustment to the new“pandemic norms”).Main outcome measures included visual acuity,body mass index(BMI),blood pressure(BP),hemoglobin A1c(HbA1c),macular thickness,patient adherence to scheduled ophthalmology visits,and DME treatment(s)received at each visit.To facilitate measurement of macular thickness,each macula was divided into 9 Early Treatment Diabetic Retinopathy Study(ETDRS)-defined macular sectors as measured by OCT imaging.RESULTS:There was no change of BMI,systolic BP,and diastolic BP between any of the time periods.HbA1c showed a very small increase from period 1(7.6%)to period 2(7.8%,P=0.015)and decreased back to 7.6%at period 3(P=0.12).Macular thickness decreased for 100%of macular regions.The central macular thickness decreased across all 3 periods from 329.5 to 316.6μm(P=0.0045).After analysis of multiple variables including HbA1c,BMI,adherence to scheduled appointments,different clinic centers,and treatment interventions,there was no easily identifiable subgroup of patients that experienced the increase in DME.CONCLUSION:DME doesn’t worsen during the COVID-19 pandemic,instead sustaining a very small but statistically significant improvement.While identifying a mechanism behind our findings is beyond the scope of this study,potential explanations may include a delay in retinal changes beyond our study period,an unexpected increase in treatment frequency despite pandemic restrictions,and an unanticipated pandemic-related improvement in some lifestyle factors that may have had a positive impact on DME.展开更多
Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diab...Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.展开更多
Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of prot...Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.展开更多
●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A to...●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.展开更多
Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate t...Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg^(2+)promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated thealveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg^(2+)promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells,thus reducing theelevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg^(2+)promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondria metabolism.展开更多
Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,m...Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,myocardial hypertrophy,and impaired left ventricular diastolic function.While the clinical utility of the Jianpi Qinghua(JPQH)formula has been established in treating diabetes and insulin resistance,its potential efficacy in alleviating diabetic cardiomyopathy remains uncertain.This study aims to investigate the impact and underlying molecular mechanisms of the JPQH formula(JPQHF)in ameliorating myocardial injury in nonobese diabetic rats,specifically focusing on apoptosis and inflammation.Methods Wistar rats were assigned as the normal control group(CON),while Goto-Kakizaki(GK)rats were randomly divided into three groups:DM,DM treated with the JPQHF,and DM treated with metformin(MET).Following a 4-week treatment regimen,various biochemical markers related to glucose metabolism,cardiac function,cardiac morphology,and myocardial ultrastructure in GK rats were assessed.RNA sequencing was utilized to analyze differential gene expression and identify potential therapeutic targets.In vitro experiments involved high glucose to induce apoptosis and inflammation in H9c2 cells.Cell viability was evaluated using CCK-8 assay,apoptosis was monitored via flow cytometry,and the production of inflammatory cytokines was measured using quantitative real-time PCR(qPCR)and ELISA.Protein expression levels were determined by Western blotting analysis.The investigation also incorporated the use of MAPK inhibitors to further elucidate the mechanism at both the transcriptional and protein levels.Results The JPQHF group exhibited significant reductions in interventricular septal thickness at end-systole(IVSs)and left ventricular internal diameter at end-systole and end-diastole(LVIDs and LVIDd).JPQHF effectively suppressed high glucose-induced activation of IL-1βand caspase 3 in cardiomyocytes.Furthermore,JPQHF downregulated the expression of myocardial JunB/c-Fos,which was upregulated in both diabetic rats and high glucose-treated H9c2 cells.Conclusion The JPQH formula holds promise in mitigating diabetic myocardial apoptosis and inflammation in cardiomyocytes by inhibiting JunB/c-Fos expression through suppressing the MAPK(p38 and ERK1/2)pathway.展开更多
AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biolog...AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.展开更多
AIM:To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide(TA)in treating diabetic macular edema(DME)and to examine changes in growth factors and inflammatory mediator ...AIM:To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide(TA)in treating diabetic macular edema(DME)and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection.METHODS:Totally 67 DME patients(67 eyes)and 30 cataract patients(32 eyes)were enrolled as the DME group and the control group,respectively.The DME group was divided into the aflibercept group(34 cases)and the aflibercept combined with TA group(combined group,33 cases).The aqueous humor of both groups was collected during the study period.The aqueous levels of vascular endothelial growth factor(VEGF),monocyte chemoattractant protein-1(MCP-1),interleukin-6(IL-6),interleukin-8(IL-8),and interleukin-1β(IL-1β)were detected using a microsphere suspension array technology(Luminex 200TM).Aqueous cytokines,best-corrected visual acuity(BCVA),central macular thickness(CMT),and complications before and after treatment were compared between the aflibercept group and combined group.RESULTS:The concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group(all P<0.01).After 1mo of surgery,the concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group(all P<0.01).The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment(P<0.01).However,the difference was not statistically significant after 3mo of treatment(P>0.05).CONCLUSION:The cytokines VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor of DME patients are significantly increased.Aflibercept and aflibercept combined with TA have good efficacy in DME patients,can effectively reduce CMT,improve the patient’s vision,and have high safety.Aflibercept combined with TA can quickly downregulate the aqueous humor cytokines and help to relieve macular edema rapidly.However,the long-term efficacy is comparable to that of aflibercept alone.展开更多
Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes...Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.展开更多
Early screening of diabetes retinopathy(DR)plays an important role in preventing irreversible blindness.Existing research has failed to fully explore effective DR lesion information in fundus maps.Besides,traditional ...Early screening of diabetes retinopathy(DR)plays an important role in preventing irreversible blindness.Existing research has failed to fully explore effective DR lesion information in fundus maps.Besides,traditional attention schemes have not considered the impact of lesion type differences on grading,resulting in unreasonable extraction of important lesion features.Therefore,this paper proposes a DR diagnosis scheme that integrates a multi-level patch attention generator(MPAG)and a lesion localization module(LLM).Firstly,MPAGis used to predict patches of different sizes and generate a weighted attention map based on the prediction score and the types of lesions contained in the patches,fully considering the impact of lesion type differences on grading,solving the problem that the attention maps of lesions cannot be further refined and then adapted to the final DR diagnosis task.Secondly,the LLM generates a global attention map based on localization.Finally,the weighted attention map and global attention map are weighted with the fundus map to fully explore effective DR lesion information and increase the attention of the classification network to lesion details.This paper demonstrates the effectiveness of the proposed method through extensive experiments on the public DDR dataset,obtaining an accuracy of 0.8064.展开更多
AIM:To investigate the effects of Sonic hedgehog(Shh)gene-modified bone marrow mesenchymal stem cells(MSCs)on graft-induced retinal gliosis and retinal ganglion cells(RGCs)survival in diabetic mice.METHODS:Bone marrow...AIM:To investigate the effects of Sonic hedgehog(Shh)gene-modified bone marrow mesenchymal stem cells(MSCs)on graft-induced retinal gliosis and retinal ganglion cells(RGCs)survival in diabetic mice.METHODS:Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs(MSC-Shh).Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs(MSC-Gfp;control)were administered in diabetic mice.After 4wk,the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography,and markers of gliosis were examined by immunofluorescence and Western blotting.The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence.The mechanisms underlying the effects of MSC-Shh was investigated.RESULTS:A significant reduction of proliferative vitreoretinopathy(PVR)was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp.Significant downregulation of glial fibrillary acidic protein(GFAP)was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp.The extracellular signal-regulated kinase 1/2(ERK1/2),protein kinase B(AKT)and phosphatidylin-ositol-3-kinase(PI3K)pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp.Brain-derived neurotrophic factor(BDNF)and ciliary neurotrophic factor(CNTF)levels were significantly increased in the host retina,and RGCs loss was significantly prevented after MSC-Shh administration.CONCLUSION:MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice.The ERK1/2,AKT and PI3K pathways are involved in this process.MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.展开更多
BACKGROUND Stem cell therapy has shown great potential for treating diabetic foot(DF).AIM To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades,with the aim of ...BACKGROUND Stem cell therapy has shown great potential for treating diabetic foot(DF).AIM To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades,with the aim of depicting the current global research landscape,identifying the most influential research hotspots,and providing insights for future research directions.METHODS We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF.Bibliometric analysis was carried out using CiteSpace,VOSviewer,and R(4.3.1)to identify the most notable studies.RESULTS A search was conducted to identify publications related to the use of stem cells for DF treatment.A total of 542 articles published from 2000 to 2023 were identified.The United States had published the most papers on this subject.In this field,Iran’s Shahid Beheshti University Medical Sciences demonstrated the highest productivity.Furthermore,Dr.Bayat from the same university has been an outstanding researcher in this field.Stem Cell Research&Therapy is the journal with the highest number of publications in this field.The main keywords were“diabetic foot ulcers,”“wound healing,”and“angiogenesis.”CONCLUSION This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years.Current research findings suggested that the hotspots in this field include stem cell dressings,exosomes,wound healing,and adipose-derived stem cells.Future research should also focus on the clinical translation of stem cell therapies for DF.展开更多
AIM:To investigate systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),and plateletto-lymphocyte ratio(PLR)levels in patients with type 2 diabetes at different stages of diabetic retinopathy(DR...AIM:To investigate systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),and plateletto-lymphocyte ratio(PLR)levels in patients with type 2 diabetes at different stages of diabetic retinopathy(DR).METHODS:This retrospective study included 141 patients with type 2 diabetes mellitus(DM):45 without diabetic retinopathy(NDR),47 with non-proliferative diabetic retinopathy(NPDR),and 49 with proliferative diabetic retinopathy(PDR).Complete blood counts were obtained,and NLR,PLR,and SII were calculated.The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic(ROC)curves.The relationships between DR stages and SII,PLR,and NLP were assessed using multivariate logistic regression.RESULTS:The average NLR,PLR,and SII were higher in the PDR group than in the NPDR group(P=0.011,0.043,0.009,respectively);higher in the NPDR group than in the NDR group(P<0.001 for all);and higher in the PDR group than in the NDR group(P<0.001 for all).In the ROC curve analysis,the NLR,PLR,and SII were significant predictors of DR(P<0.001 for all).The highest area under the curve(AUC)was for the PLR(0.929 for PLR,0.925 for SII,and 0.821 for NLR).Multivariate regression analysis indicated that NLR,PLR,and SII were statistically significantly positive and independent predictors for the DR stages in patients with DM[odds ratio(OR)=1.122,95%confidence interval(CI):0.200–2.043,P<0.05;OR=0.038,95%CI:0.018–0.058,P<0.05;OR=0.007,95%CI:0.001–0.01,P<0.05,respectively).CONCLUSION:The NLR,PLR,and SII may be used as predictors of DR.展开更多
AIM:To quantify changes in radial peripapillary capillary vessel density(ppVD)and the peripapillary retinal nerve fiber layer(pRNFL)in children with type 1 diabetes without clinical diabetic retinopathy by optical coh...AIM:To quantify changes in radial peripapillary capillary vessel density(ppVD)and the peripapillary retinal nerve fiber layer(pRNFL)in children with type 1 diabetes without clinical diabetic retinopathy by optical coherence tomography angiography(OCTA),providing a basis for early retinopathy in children with type 1 diabetes.METHODS:This was a retrospective study.A total of 30 patients(3–14y)with type 1 diabetes without clinical diabetic retinopathy(NDR group)were included.A total of 30 age-matched healthy subjects were included as the normal control group(CON group).The HbA1c level in the last 3mo was measured once in the NDR group.The pRNFL thickness and ppVD were automatically measured,and the mean pRNFL and ppVD were calculated in the nasal,inferior,temporal,and superior quadrants.The changes in ppVD and pRNFL in the two groups were analyzed.RESULTS:Compared with CON group,the nasal and superior ppVDs decreased in the NDR group(all P<0.01).The thickness of the nasal pRNFL decreased significantly(P<0.01),while the inferior,temporal and superior pRNFLs slightly decreased but not significant in the NDR group(all P>0.05).Person and Spearman correlation analysis of ppVD and pRNFL thickness in each quadrant of the NDR group showed a positive correlation between nasal and superior(all P<0.01),while inferior and temporal had no significant correlation(all P>0.05).There was no significant correlation between the HbA1c level and ppVD and pRNFL in any quadrant(all P>0.05).There was no significant correlation between the course of diabetes mellitus and ppVD and pRNFL in any quadrant(all P>0.05).CONCLUSION:ppVD and pRNFL decrease in eyes of children with type 1 diabetes before clinically detectable retinopathy and OCTA is helpful for early monitoring.展开更多
For years,foot ulcers linked with diabetes mellitus and neuropathy have significantly impacted diabetic patients’ health-related quality of life(HRQoL). Diabetes foot ulcers impact15% of all diabetic patients at some...For years,foot ulcers linked with diabetes mellitus and neuropathy have significantly impacted diabetic patients’ health-related quality of life(HRQoL). Diabetes foot ulcers impact15% of all diabetic patients at some point in their lives. The facilities and resources used for DFU detection and treatment are only available at hospitals and clinics,which results in the unavailability of feasible and timely detection at an early stage. This necessitates the development of an at-home DFU detection system that enables timely predictions and seamless communication with users,thereby preventing amputations due to neglect and severity. This paper proposes a feasible system consisting of three major modules:an IoT device that works to sense foot nodes to send vibrations onto a foot sole,a machine learning model based on supervised learning which predicts the level of severity of the DFU using four different classification techniques including XGBoost,K-SVM,Random Forest,and Decision tree,and a mobile application that acts as an interface between the sensors and the patient. Based on the severity levels,necessary steps for prevention,treatment,and medications are recommended via the application.展开更多
The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic mac...The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).展开更多
BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascu...BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.展开更多
AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl trans...AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.展开更多
基金supported by the National Natural Science Foundation of China,No.82122009 (to JX)Science Research Foundation ofAier Eye Hospital Group,No.AM2001D1 (to JX)the Natural Science Foundation of Hunan Province,No.2020JJ5002 (to SJ)。
文摘Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.
文摘AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 2017 to October 2021 were collected.The patients were divided into two groups:DME patients with DN(25 eyes),and DME patients without DN(29 eyes).General conditions were collected before treatment,laboratory tests include fasting blood glucose,HbA1c,microalbumin/creatinine,serum creatinine.Optical coherence tomography(OCT)was used to check the ellipsoidal zone(EZ)and external limiting membrane(ELM)integrity.Central macular thickness(CMT),best corrected visual acuity(BCVA),and retinal hyperreflective foci(HF)as well as numbers of injections were recorded.RESULTS:There were significant differences between fasting blood glucose,HbA1c,serum creatinine,urinary microalbumin/creatinine,and estimated glomerular filtration rate(eGFR)between the two groups(all P<0.05).EZ and ELM continuity in the DME+DN group was worse than that in the DME group(P<0.05).BCVA(logMAR)in the DME group was significantly better than that in the DME+DN group at the same time points during treatment(all P<0.05).CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points(all P<0.05)and significantly decreased in both groups with time during treatment.At 6mo after treatment,the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86,respectively.CONCLUSION:Conbercept has a significant effect in short-term treatment of DME patients with or without DN,and can significantly ameliorate BCVA,CMT and the number of HF,treatment efficacy of DME patients without DN is better than that of DME patients with DN.
文摘AIM:To assess diabetic macular edema(DME)progression during the early phases of the COVID-19 pandemic,when severe societal restrictions raised the concern of possible deterioration of health in patients with systemic conditions,particularly those requiring frequent office visits.METHODS:This is a multicenter retrospective chart review of 370 patients(724 eyes)with an established diagnosis of DME seen on 3 separate visits between January 2019 and July 2021.Period 1 was January 2019 to February 2020(considered pre-COVID-19),period 2 was March 2020 to December 2020(considered the height of the pandemic;highest level of pandemic-related clinical and societal regulations)and period 3 was January 2021 to July 2021(re-adjustment to the new“pandemic norms”).Main outcome measures included visual acuity,body mass index(BMI),blood pressure(BP),hemoglobin A1c(HbA1c),macular thickness,patient adherence to scheduled ophthalmology visits,and DME treatment(s)received at each visit.To facilitate measurement of macular thickness,each macula was divided into 9 Early Treatment Diabetic Retinopathy Study(ETDRS)-defined macular sectors as measured by OCT imaging.RESULTS:There was no change of BMI,systolic BP,and diastolic BP between any of the time periods.HbA1c showed a very small increase from period 1(7.6%)to period 2(7.8%,P=0.015)and decreased back to 7.6%at period 3(P=0.12).Macular thickness decreased for 100%of macular regions.The central macular thickness decreased across all 3 periods from 329.5 to 316.6μm(P=0.0045).After analysis of multiple variables including HbA1c,BMI,adherence to scheduled appointments,different clinic centers,and treatment interventions,there was no easily identifiable subgroup of patients that experienced the increase in DME.CONCLUSION:DME doesn’t worsen during the COVID-19 pandemic,instead sustaining a very small but statistically significant improvement.While identifying a mechanism behind our findings is beyond the scope of this study,potential explanations may include a delay in retinal changes beyond our study period,an unexpected increase in treatment frequency despite pandemic restrictions,and an unanticipated pandemic-related improvement in some lifestyle factors that may have had a positive impact on DME.
基金supported by the Projects of the National Key R&D Program of China,Nos.2021YFC2400803(to YO),2021YFC2400801(to YQ)the National Natural Science Foundation of China,Nos.82002290(to YQ),82072452(to YO),82272475(to YO)+5 种基金the Young Elite Scientist Sponsorship Program by Cast,No.YESS20200153(to YQ)the Sino-German Mobility Programme,No.M-0699(to YQ)the Excellent Youth Cultivation Program of Shanghai Sixth People’s Hospital,No.ynyq202201(to YQ)the Shanghai Sailing Program,No.20YF1436000(to YQ)the Medical Engineering Co-Project of University of Shanghai for Science and Technology,10-22-310-520(to YO)a grant from Shanghai Municipal Health Commission,No.202040399(to YO).
文摘Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.:82100801,81974096,81770711,81974097,and 81961138007).
文摘Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.
基金Supported by the National Key Research and Development Program of China(No.2016YFC0904800)National Natural Science Foundation of China(No.82101181)+1 种基金China Scholarship Council(No.201506230096)Shanghai Sailing Program(No.19YF1439700).
文摘●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.
基金supported by grants from the National Natural Science Foundation of China (No. 81901042)the Sichuan Science and Technology Program (No. 2022NSFSC1384)International Team for Implantology (No. 1477_2020)。
文摘Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg^(2+)promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated thealveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg^(2+)promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells,thus reducing theelevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg^(2+)promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondria metabolism.
基金supported by grants from the National Natural Science Foundation of China(No.81874434 and No.81804053)Yangtze River Delta Traditional Chinese Medicine Endocrinology and Metabolic Disease Specialist Alliance(No.ZY2021-2023-0302).
文摘Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,myocardial hypertrophy,and impaired left ventricular diastolic function.While the clinical utility of the Jianpi Qinghua(JPQH)formula has been established in treating diabetes and insulin resistance,its potential efficacy in alleviating diabetic cardiomyopathy remains uncertain.This study aims to investigate the impact and underlying molecular mechanisms of the JPQH formula(JPQHF)in ameliorating myocardial injury in nonobese diabetic rats,specifically focusing on apoptosis and inflammation.Methods Wistar rats were assigned as the normal control group(CON),while Goto-Kakizaki(GK)rats were randomly divided into three groups:DM,DM treated with the JPQHF,and DM treated with metformin(MET).Following a 4-week treatment regimen,various biochemical markers related to glucose metabolism,cardiac function,cardiac morphology,and myocardial ultrastructure in GK rats were assessed.RNA sequencing was utilized to analyze differential gene expression and identify potential therapeutic targets.In vitro experiments involved high glucose to induce apoptosis and inflammation in H9c2 cells.Cell viability was evaluated using CCK-8 assay,apoptosis was monitored via flow cytometry,and the production of inflammatory cytokines was measured using quantitative real-time PCR(qPCR)and ELISA.Protein expression levels were determined by Western blotting analysis.The investigation also incorporated the use of MAPK inhibitors to further elucidate the mechanism at both the transcriptional and protein levels.Results The JPQHF group exhibited significant reductions in interventricular septal thickness at end-systole(IVSs)and left ventricular internal diameter at end-systole and end-diastole(LVIDs and LVIDd).JPQHF effectively suppressed high glucose-induced activation of IL-1βand caspase 3 in cardiomyocytes.Furthermore,JPQHF downregulated the expression of myocardial JunB/c-Fos,which was upregulated in both diabetic rats and high glucose-treated H9c2 cells.Conclusion The JPQH formula holds promise in mitigating diabetic myocardial apoptosis and inflammation in cardiomyocytes by inhibiting JunB/c-Fos expression through suppressing the MAPK(p38 and ERK1/2)pathway.
基金Supported by the National Natural Science Foundation in China(No.81671641)Jiangsu Provincial Medical Innovation Team(No.CXTDA2017039)Gusu Health Talents Program(No.GSWS 2022018).
文摘AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.
基金Supported by the Shenzhen Science and Technology Innovation Committee,China(No.JCYJ20220530164600002)Scientific Research Program of Xiangjiang Philanthropy FoundationScience Research Grant of Aier Eye Hospital Group(No.AF2201D06).
文摘AIM:To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide(TA)in treating diabetic macular edema(DME)and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection.METHODS:Totally 67 DME patients(67 eyes)and 30 cataract patients(32 eyes)were enrolled as the DME group and the control group,respectively.The DME group was divided into the aflibercept group(34 cases)and the aflibercept combined with TA group(combined group,33 cases).The aqueous humor of both groups was collected during the study period.The aqueous levels of vascular endothelial growth factor(VEGF),monocyte chemoattractant protein-1(MCP-1),interleukin-6(IL-6),interleukin-8(IL-8),and interleukin-1β(IL-1β)were detected using a microsphere suspension array technology(Luminex 200TM).Aqueous cytokines,best-corrected visual acuity(BCVA),central macular thickness(CMT),and complications before and after treatment were compared between the aflibercept group and combined group.RESULTS:The concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group(all P<0.01).After 1mo of surgery,the concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group(all P<0.01).The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment(P<0.01).However,the difference was not statistically significant after 3mo of treatment(P>0.05).CONCLUSION:The cytokines VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor of DME patients are significantly increased.Aflibercept and aflibercept combined with TA have good efficacy in DME patients,can effectively reduce CMT,improve the patient’s vision,and have high safety.Aflibercept combined with TA can quickly downregulate the aqueous humor cytokines and help to relieve macular edema rapidly.However,the long-term efficacy is comparable to that of aflibercept alone.
基金This research was financially supported by the National Key R&D Program of China(2019YFA0110600)the National Natural Science Foundation of China(82370932,81970917,82370929,81970916,81800947,82101077)+2 种基金the Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202102,RD03202302)Sichuan Science and Technology Program(2022NSFSC0002)Sichuan Province Youth Science and Technology Innovation Team(2022JDTD0021).
文摘Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.
基金supported in part by the Research on the Application of Multimodal Artificial Intelligence in Diagnosis and Treatment of Type 2 Diabetes under Grant No.2020SK50910in part by the Hunan Provincial Natural Science Foundation of China under Grant 2023JJ60020.
文摘Early screening of diabetes retinopathy(DR)plays an important role in preventing irreversible blindness.Existing research has failed to fully explore effective DR lesion information in fundus maps.Besides,traditional attention schemes have not considered the impact of lesion type differences on grading,resulting in unreasonable extraction of important lesion features.Therefore,this paper proposes a DR diagnosis scheme that integrates a multi-level patch attention generator(MPAG)and a lesion localization module(LLM).Firstly,MPAGis used to predict patches of different sizes and generate a weighted attention map based on the prediction score and the types of lesions contained in the patches,fully considering the impact of lesion type differences on grading,solving the problem that the attention maps of lesions cannot be further refined and then adapted to the final DR diagnosis task.Secondly,the LLM generates a global attention map based on localization.Finally,the weighted attention map and global attention map are weighted with the fundus map to fully explore effective DR lesion information and increase the attention of the classification network to lesion details.This paper demonstrates the effectiveness of the proposed method through extensive experiments on the public DDR dataset,obtaining an accuracy of 0.8064.
基金Supported by the Natural Science Foundation of Guangdong Province(No.2018A0303130293,No.2023A1515012470).
文摘AIM:To investigate the effects of Sonic hedgehog(Shh)gene-modified bone marrow mesenchymal stem cells(MSCs)on graft-induced retinal gliosis and retinal ganglion cells(RGCs)survival in diabetic mice.METHODS:Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs(MSC-Shh).Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs(MSC-Gfp;control)were administered in diabetic mice.After 4wk,the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography,and markers of gliosis were examined by immunofluorescence and Western blotting.The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence.The mechanisms underlying the effects of MSC-Shh was investigated.RESULTS:A significant reduction of proliferative vitreoretinopathy(PVR)was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp.Significant downregulation of glial fibrillary acidic protein(GFAP)was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp.The extracellular signal-regulated kinase 1/2(ERK1/2),protein kinase B(AKT)and phosphatidylin-ositol-3-kinase(PI3K)pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp.Brain-derived neurotrophic factor(BDNF)and ciliary neurotrophic factor(CNTF)levels were significantly increased in the host retina,and RGCs loss was significantly prevented after MSC-Shh administration.CONCLUSION:MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice.The ERK1/2,AKT and PI3K pathways are involved in this process.MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.
基金Supported by:The study was funded by the National Natural Science Foundation of China(82274528)Construction Task Book for the Three-Year Action Plan for Accelerating the Inheritance and Innovative Development of Traditional Chinese Medicine in Shanghai(2021-2023)(ZY(2021-2023)-0211)+4 种基金Shanghai Municipal Health Commission Scientific Research Programme Mission Statement(202240228)Special Youth Project for Clinical Research of Shanghai Municipal Health Commission(20234Y0162)Clinical Research Talent Training Program of Shanghai University of Traditional Chinese Medicine Affiliated Hospital(2023LCRC06)Four Bright Foundations of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine(SGKJ-202301)Shanghai Pudong New Area Health and Family Planning Commission’s Pudong Famous TCM Cultivation Program project(PWRZM2020-18).
文摘BACKGROUND Stem cell therapy has shown great potential for treating diabetic foot(DF).AIM To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades,with the aim of depicting the current global research landscape,identifying the most influential research hotspots,and providing insights for future research directions.METHODS We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF.Bibliometric analysis was carried out using CiteSpace,VOSviewer,and R(4.3.1)to identify the most notable studies.RESULTS A search was conducted to identify publications related to the use of stem cells for DF treatment.A total of 542 articles published from 2000 to 2023 were identified.The United States had published the most papers on this subject.In this field,Iran’s Shahid Beheshti University Medical Sciences demonstrated the highest productivity.Furthermore,Dr.Bayat from the same university has been an outstanding researcher in this field.Stem Cell Research&Therapy is the journal with the highest number of publications in this field.The main keywords were“diabetic foot ulcers,”“wound healing,”and“angiogenesis.”CONCLUSION This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years.Current research findings suggested that the hotspots in this field include stem cell dressings,exosomes,wound healing,and adipose-derived stem cells.Future research should also focus on the clinical translation of stem cell therapies for DF.
基金Affiliated Jinling Hospital,Medical School of Nanjing University(No.22JCYYYB29).
文摘AIM:To investigate systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),and plateletto-lymphocyte ratio(PLR)levels in patients with type 2 diabetes at different stages of diabetic retinopathy(DR).METHODS:This retrospective study included 141 patients with type 2 diabetes mellitus(DM):45 without diabetic retinopathy(NDR),47 with non-proliferative diabetic retinopathy(NPDR),and 49 with proliferative diabetic retinopathy(PDR).Complete blood counts were obtained,and NLR,PLR,and SII were calculated.The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic(ROC)curves.The relationships between DR stages and SII,PLR,and NLP were assessed using multivariate logistic regression.RESULTS:The average NLR,PLR,and SII were higher in the PDR group than in the NPDR group(P=0.011,0.043,0.009,respectively);higher in the NPDR group than in the NDR group(P<0.001 for all);and higher in the PDR group than in the NDR group(P<0.001 for all).In the ROC curve analysis,the NLR,PLR,and SII were significant predictors of DR(P<0.001 for all).The highest area under the curve(AUC)was for the PLR(0.929 for PLR,0.925 for SII,and 0.821 for NLR).Multivariate regression analysis indicated that NLR,PLR,and SII were statistically significantly positive and independent predictors for the DR stages in patients with DM[odds ratio(OR)=1.122,95%confidence interval(CI):0.200–2.043,P<0.05;OR=0.038,95%CI:0.018–0.058,P<0.05;OR=0.007,95%CI:0.001–0.01,P<0.05,respectively).CONCLUSION:The NLR,PLR,and SII may be used as predictors of DR.
基金Supported by Xi’an Municipal Health Commission Scientific Research Project(No.2023yb22)Hospital Level Project of Xi’an Children’s Hospital(No.2021H12No.2022F08).
文摘AIM:To quantify changes in radial peripapillary capillary vessel density(ppVD)and the peripapillary retinal nerve fiber layer(pRNFL)in children with type 1 diabetes without clinical diabetic retinopathy by optical coherence tomography angiography(OCTA),providing a basis for early retinopathy in children with type 1 diabetes.METHODS:This was a retrospective study.A total of 30 patients(3–14y)with type 1 diabetes without clinical diabetic retinopathy(NDR group)were included.A total of 30 age-matched healthy subjects were included as the normal control group(CON group).The HbA1c level in the last 3mo was measured once in the NDR group.The pRNFL thickness and ppVD were automatically measured,and the mean pRNFL and ppVD were calculated in the nasal,inferior,temporal,and superior quadrants.The changes in ppVD and pRNFL in the two groups were analyzed.RESULTS:Compared with CON group,the nasal and superior ppVDs decreased in the NDR group(all P<0.01).The thickness of the nasal pRNFL decreased significantly(P<0.01),while the inferior,temporal and superior pRNFLs slightly decreased but not significant in the NDR group(all P>0.05).Person and Spearman correlation analysis of ppVD and pRNFL thickness in each quadrant of the NDR group showed a positive correlation between nasal and superior(all P<0.01),while inferior and temporal had no significant correlation(all P>0.05).There was no significant correlation between the HbA1c level and ppVD and pRNFL in any quadrant(all P>0.05).There was no significant correlation between the course of diabetes mellitus and ppVD and pRNFL in any quadrant(all P>0.05).CONCLUSION:ppVD and pRNFL decrease in eyes of children with type 1 diabetes before clinically detectable retinopathy and OCTA is helpful for early monitoring.
文摘For years,foot ulcers linked with diabetes mellitus and neuropathy have significantly impacted diabetic patients’ health-related quality of life(HRQoL). Diabetes foot ulcers impact15% of all diabetic patients at some point in their lives. The facilities and resources used for DFU detection and treatment are only available at hospitals and clinics,which results in the unavailability of feasible and timely detection at an early stage. This necessitates the development of an at-home DFU detection system that enables timely predictions and seamless communication with users,thereby preventing amputations due to neglect and severity. This paper proposes a feasible system consisting of three major modules:an IoT device that works to sense foot nodes to send vibrations onto a foot sole,a machine learning model based on supervised learning which predicts the level of severity of the DFU using four different classification techniques including XGBoost,K-SVM,Random Forest,and Decision tree,and a mobile application that acts as an interface between the sensors and the patient. Based on the severity levels,necessary steps for prevention,treatment,and medications are recommended via the application.
基金supported by Science and Technology Research Project of Jilin Provincial Department of Education,No.JJKH20220072KJ(to XL)Science and Technology Development Program of Jilin Province,No.20200201495JC(to YL)。
文摘The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).
基金The study was reviewed and approved by the First People’s Hospital of Wenling(Approval No.KY-2023-2034-01).
文摘BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.
基金Supported by grant from Fundamental Research Grant Scheme by Ministry of Higher Education(MoHE)600-IRMI/FRGS 5/3(101/2019).
文摘AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.
