Diabetic wounds present challenges in clinical management due to persistent inflammation caused by excessive exudate infiltration.Inspired by the gradient wettability of cactus thorn,this study has devised a biomimeti...Diabetic wounds present challenges in clinical management due to persistent inflammation caused by excessive exudate infiltration.Inspired by the gradient wettability of cactus thorn,this study has devised a biomimetic Janus nanofiber membrane as a water diode,which endows with gradient wettability and gradient pore size,offering sustainable unidirectional self-drainage and antibacterial properties for enhanced diabetic wound healing.The Janus membrane is fabricated by depositing a hydrophilic polyacrylonitrile/chlorin e6 layer with smaller pore sizes onto a hydrophobic poly(ε-caprolactone)with larger pore sizes,thereby generating a vertical gradient in both wettability and pore structure.The incorporation of chlorin e6 in the upper layer enables the utilization of external light energy to generate heat for evaporation and produce reactive oxygen species,achieving a high sterilization efficiency of 99%.Meanwhile,the gradient structure of the Janus membrane facilitates continuous antigravity exudate drainage at a rate of 0.95 g cm^(−2) h^(−1).This dual functionality of effective exudate drainage and sterilization significantly reduces inflammatory factors,allows the polarization of macrophages toward the M2 proliferative phenotype,enhances angiogenesis,and accelerates wound healing.Therefore,this study provides a groundbreaking bioinspired strategy for the development of advanced wound dressings tailored for diabetic wound regeneration.展开更多
Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear....Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear.We measured HDGF levels in the aqueous humor and found that HDGF was increased in DR but decreased after anti-angiogenesis treatment.Using public single-cell RNA sequencing datasets,we found that elevated HDGF in DR was mainly produced by Müller cells and targeted microglia.Additionally,integrin beta 2(Itgb2),a target gene of HDGF that induces microglial activation,was significantly upregulated in DR.To verify these results,we performed enzyme-linked immunosorbent assays,quantitative reverse transcription-PCR,Western blotting,and fluorescence immunostaining in cultured Müller and microglial cells treated with HDGF or anti-HDGF,as well as in DR mice receiving intravitreal injections of HDGF or its antibody.Exogenous HDGF further promoted microglial activation,migration,and secretion of pro-inflammatory cytokines,while neutralization of HDGF suppressed these effects caused by high glucose.Furthermore,the HDGF receptor nucleolin was overexpressed in microglia under high glucose stimulation.Therefore,blocking HDGF from Müller cells in DR reduced the excessive inflammatory response in microglia,highlighting HDGF as a potential therapeutic target.展开更多
Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced ...Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced in rats using streptozotocin,after which full-thickness excisional wounds were created.Piceatannol was administered topically either as a raw hydrogel or formulated into a PIC-SNEDDS,which was prepared using an optimized oil-surfactant mixture and incorporated into a hydrogel for application.Wound healing activity was assessed through measurements of wound contraction,oxidative stress biomarkers,and collagen content,along with histological and immunohistochemical evaluation of inflammatory,angiogenic,and remodeling markers.Results:PIC-SNEDDS markedly enhanced diabetic wound healing by promoting epithelial regeneration,granulation tissue formation,epidermal proliferation,and keratinization.The formulation also reduced the expression of pro-inflammatory markers(interleukin-6,nuclear factor-kappa B,and tumor necrosis factor-α)while increasingα-smooth muscle actin,transforming growth factor-β1,vascular endothelial growth factor-A,and hydroxyproline levels.Additionally,it improved antioxidant status by lowering malondialdehyde levels and boosting superoxide dismutase and catalase activity,along with upregulation of COL1A1 mRNA expression.Conclusions:PIC-SNEDDS promotes the healing of diabetic wounds and exhibits anti-inflammatory,antioxidant,pro-collagen,and angiogenic properties.展开更多
Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-...Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-inflammatory,and immunomodulatory activities.However,its active constituents and mechanisms of action against diabetic foot remain to be elucidated.Methods:In this study,the chemical constituents of Sanhuang Oil were identified using UPLC-QE-Orbitrap-MS.Subsequently,the mechanism by which Sanhuang Oil promotes diabetic foot ulcer healing was predicted by integrating network pharmacology and molecular docking.Additionally,diabetic mouse model was established in ICR mice using a combination of a high-fat diet(HFD)and streptozotocin(STZ)chemical induction.A full-thickness skin defect was created on the dorsum of the mice.Wound healing and the healing rate were observed following Sanhuang Oil intervention.The mechanism underlying Sanhuang Oil’s promotion of diabetic ulcer healing was further investigated using transcriptomics and histopathological examination(H&E staining).Results:A total of 97 active ingredients were identified from Sanhuang Oil.Network pharmacology analysis predicted 543 common targets,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis identified 203 relevant pathways.Molecular docking further confirmed high binding affinity(binding energy≤−5.0 kcal/mol)between specific active components in Sanhuang Oil(e.g.,coptisine,phellodendrine,baicalein)and key targets associated with diabetic foot ulcers(e.g.,EGFR,AKT1,STAT3).In vivo experimental results demonstrated that the wound healing rate was significantly higher in Sanhuang Oil-treated groups compared to the model group(P<0.001).HE staining revealed that the high-dose Sanhuang Oil group exhibited more pronounced epithelial tissue coverage over the wound,reduced inflammatory cell infiltration,and increased collagen deposition and fibroblast proliferation.transcriptomic analysis identified Pdk4,Ttn,Csrp3,Actn2,Myoz2,Tnnc2,Myod1,Myog,Myot,and Myf6 as key regulatory proteins involved in promoting wound healing.Conclusion:Sanhuang Oil promotes wound healing in diabetic ulcer mice,potentially by mitigating inflammation and regulating key targets such as Pdk4 to enhance fibroblast function.These findings provide novel insights into the multi-target,multi-pathway mechanism of Sanhuang Oil for treating diabetic foot ulcers.展开更多
Diabetic retinopathy(DR)is a leading cause of vision loss among working-age populations,with early screening significantly reducing the risk of blindness.However,resource-limited regions often face challenges in DR sc...Diabetic retinopathy(DR)is a leading cause of vision loss among working-age populations,with early screening significantly reducing the risk of blindness.However,resource-limited regions often face challenges in DR screening due to a shortage of ophthalmologists.This study reports the implementation and outcomes of the Chinese local standard DB52/T 1726-2023,Regulations for the application of diabetic retinopathy screening artificial intelligence,in Cambodian healthcare institutions.A pilot DR screening program with independent operational capability is established by providing a non-mydriatic fundus camera and deploying a localized diabetic retinopathy artificial intelligence(DR-AI)screening platform at the Cambodia-Kingdom Friendship Hospital in Phnom Penh,along with comprehensive training.From January to August 2025,a total of 565 patients with type 2 diabetes were screened,yielding a DR detection rate of 26.0%(147 cases).Research findings demonstrate that applying mature Chinese DR-AI screening standards and technological solutions through international collaboration in regions with a scarcity of ophthalmic professionals is both feasible and effective.This project serves as a reference for promoting DR-AI in resource-constrained countries and regions,highlighting its significant potential to leverage AI in addressing the global burden of chronic diseases and advancing the modernization of health systems.展开更多
AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and...AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and vision data were compared between groups using an independent sample t-test.Resting-state functional magnetic resonance imaging(rs-fMRI)was used in all participants.fMRI data was obtained and analyzed using MRIcro and SPM8 software.Fractional amplitude of low-frequency fluctuation(fALFF)technology was used to measure regional spontaneous brain activity,and sensitivity was tested using receiver operating characteristic curves(ROCs).The fALFF values were analyzed using REST software and two-sample t-tests were used to compare values between groups.Hospital anxiety and depression scale(HADS)score was assessed in DVHs and Pearson’s correlation was used to test relationships between mean fALFF value and both HADS score and duration of DVH.RESULTS:Except for the best-corrected visual acuity(BCVA)in both eyes,which showed a statistically significant difference(P<0.05),there were no statistically significant differences in the other indicators(P>0.05)between the HCs and DVHs group.Compared with controls,fALFF value was higher in DVH in cerebellum posterior lobe(CPL)and lower in right anterior cingulate cortex(ACC)and right medial orbitofrontal cortex(OFC).In DVH patients,mean fALFF value of CPL was positively correlated with HADS score and duration of diabetes.However,no such correlation was found,for right ACC or right medial OFC.DVH may lead to abnormal activities in certain brain regions related to visual control and mood.CONCLUSION:Visual impairment caused by DVH may lead to adjustment in regional visual brain activities and may be related to depression or reward system processing in some brain regions.展开更多
Background:Inflammation,caused by prolonged hyperglycemia,plays a substantially more important part in the progression of diabetic peripheral neuropathy(DPN).Notably,the MAPK pathway that mediates the Nuclear Factor-k...Background:Inflammation,caused by prolonged hyperglycemia,plays a substantially more important part in the progression of diabetic peripheral neuropathy(DPN).Notably,the MAPK pathway that mediates the Nuclear Factor-kappa B(NF-κB)pathway contributes to inflammation-induced peripheral nerve damage,affecting cell survival.Juan Bi Tong Luo(JBTL),a traditional Chinese medicine(TCM),has demonstrated favorable results in alleviating pain and numbness in patients with DPN;however,whether JBTL exerts its effect through the MAPK mediating NF-κB pathway remains unclear.Methods:This study investigated whether JBTL modulates apoptosis in DPN models and Schwann cells cultured in 100 mM of glucose by MAPK/NF-κB.Results:The JBTL altered inflammation,reduced peripheral nerve tissue damage,and improved cell survival rates by down-regulating MAPK/NF-κB.Conclusion:Our findings demonstrate that the effect of JBTL on DPN is likely mediated by suppressing inflammation induced by the MAPK/NF-κB pathway,thus providing evidence for the clinical efficacy of JBTL in treating DPN.展开更多
BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the commo...BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments.AIM To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles(hAFSC-EVs)on the recovery of bladder dysfunction in DMA rats.METHODS Eighty rats were divided into normal control,streptozotocin-induced diabetic rats,diabetic rats subjected to arterial balloon endothelial injury of common iliac artery(DMA),and DMA rats treated with hAFSC-EVs(DMA+hAFSC-EVs).At 4 weeks and 12 weeks after DMA induction,levels of blood glucose,total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,homeostasis model assessment(HOMA)-insulin resistance,and HOMA-βwere measured.Cystometry,common iliac artery wall thickness,and bladder tumor necrosis factor(TNF)-α,interleukin(IL)-6,transforming growth factor(TGF)-β1,Smad3,connective tissue growth factor(CTGF)and fibronectin were also evaluated.RESULTS Bladder weight and blood glucose,triglyceride,HOMA-insulin resistance,common iliac artery intima thickness,voided volume,intercontraction interval,bladder capacity,and mRNA expression of TNF-α,IL-6,TGF-β1,Smad3,CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction,while the HOMA-βlevel decreased at 4 weeks and 12 weeks,and the high-density lipoprotein cholesterol level decreased at 12 weeks.hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose,thickness of common iliac arterial intima,voided volume,intercontraction interval and bladder capacity at 4 weeks.The mRNA expression of TNF-α,TGF-β1,and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks,while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks.CONCLUSION hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction,which is associated with lowered blood glucose levels,reduced arterial wall thickness,and decreased TNF-α,IL-6,TGF-β1,Smad3,and CTGF expression.展开更多
AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA scree...AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS:A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital,Sun Yat-sen University from 2022 to 2023 were included,including 95 first-diagnosed DR patients and 105 patients without DR,and all patients underwent OCTA examination and a collection of demographics and renal function parameters.After a quality check,automated measurements of the foveal avascular zone area,vessel density(VD),and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS:Using random forest and multivariate Logistic regression methods,we developed a diagnostic model for DR based on 12 variables(age,FBG,SBP,DBP,HbA1c,ALT,ALP,urea/Scr,DM duration,HUA,DN,and CMT).Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window,AUC=0.837 vs 0.819,P=0.03).In the study of DN patients,the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD;outer VD;full VD;outer PD;full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model.Meanwhile,compared with the 3 mm×3 mm window,the microvascular parameters in the 6 mm×6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.展开更多
Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic ...Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.展开更多
Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retin...Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.展开更多
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
Diabetic foot attack(DFA)is the most severe presentation of diabetic foot disease,with the patient commonly displaying severe sepsis,which can be limb or life threatening.DFA can be classified into two main categories...Diabetic foot attack(DFA)is the most severe presentation of diabetic foot disease,with the patient commonly displaying severe sepsis,which can be limb or life threatening.DFA can be classified into two main categories:Typical and atypical.A typical DFA is secondary to a severe infection in the foot,often initiated by minor breaches in skin integrity that allow pathogens to enter and proliferate.This form often progresses rapidly due to the underlying diabetic pathophysiology of neuropathy,microvascular disease,and hyperglycemia,which facilitate infection spread and tissue necrosis.This form of DFA can present as one of a number of severe infective pathologies including pyomyositis,necrotizing fasciitis,and myonecrosis,all of which can lead to systemic sepsis and multiorgan failure.An atypical DFA,however,is not primarily infection-driven.It can occur secondary to either ischemia or Charcot arthropathy.Management of the typical DFA involves prompt diagnosis,aggressive infection control,and a multidisciplinary approach.Treatment can be guided by the current International Working Group on the Diabetic Foot/Infectious Diseases Society of America guidelines on diabetic foot infections,and the combined British Orthopaedic Foot and Ankle Society-Vascular Society guidelines.This article highlights the importance of early recognition,comprehensive management strategies,and the need for further research to establish standardized protocols and improve clinical outcomes for patients with DFA.展开更多
This editorial offers insights from a minireview by Venkatesh et al,who explored pharmacological adjuvants for diabetic vitrectomy.Specifically,they synthesized current knowledge and evaluated the efficacy of various ...This editorial offers insights from a minireview by Venkatesh et al,who explored pharmacological adjuvants for diabetic vitrectomy.Specifically,they synthesized current knowledge and evaluated the efficacy of various adjunctive therapies in improving the outcomes of diabetic retinopathy and managing associated complications.Herein,we highlight the key roles of pharmacological adjuvants in optimizing surgical techniques,minimizing intraoperative challenges,and enhancing postoperative recovery.We further discuss the potential implications of this approach for clinical practice and future research directions in this evolving field.Overall,this editorial underscores the importance of incorporating pharmacological adjuvants into standard diabetic vitrectomy care to improve surgical outcomes and thus patients’quality of life.展开更多
Proliferative diabetic retinopathy(PDR)affects approximately 6%of diabetic patients globally.The overall prevalence of diabetic retinopathy is around 22%.Wet age-related macular degeneration(ARMD),the sight-threatenin...Proliferative diabetic retinopathy(PDR)affects approximately 6%of diabetic patients globally.The overall prevalence of diabetic retinopathy is around 22%.Wet age-related macular degeneration(ARMD),the sight-threatening type of ARMD,affects approximately 1.2%-1.3%of the general population and represents 15%of total ARMD cases.While intravitreal anti-vascular endothelial growth factor injections are still the mainstay therapy,there are a few challenges,such as frequent administration,cost burden,and compliance barriers that prompt the need for exploration into systemic oral alternative drugs like fenofibrate,candesartan,and vorolanib.These oral therapies have the advantage of being noninvasive and systemically accessible with few logistical burdens.This review highlights current evidence supporting the use of oral therapies in PDR and wet ARMD management,along with practical limitations and future prospects.展开更多
Diabetic neuropathy (DN) and impaired wound healing in diabetic foot ulcers(DFUs) are major complications of diabetes mellitus, driven by complex molecularmechanisms, including epigenetic modifications. Recent researc...Diabetic neuropathy (DN) and impaired wound healing in diabetic foot ulcers(DFUs) are major complications of diabetes mellitus, driven by complex molecularmechanisms, including epigenetic modifications. Recent research highlights therole of epigenetic markers including DNA methylation, histone modifications,and non-coding RNAs in regulating inflammatory responses, neuronal degeneration,and tissue repair. This review explores the epigenetics of DN and DFUs,emphasizing key regulatory pathways that influence disease progression andwound healing outcomes. Genome-wide DNA methylation studies reveal acceleratedepigenetic aging and metabolic memory effects in DN, contributing tosensory neuron dysfunction and neuropathic pain. Epigenetic dysregulation ofinflammatory mediators such as Toll-like receptors and the Nod-like receptorfamily, pyrin domain-containing 3 inflammasome further exacerbates neuronaldamage and delays wound healing. Additionally, histone deacetylases play apivotal role in oxidative stress regulation via the Nrf2 pathway, which is critical for both neuronal protection and angiogenesis in DFUs. Non-coding RNAs, particularly microRNAs (miRNAs),long non-coding RNAs (lncRNAs), and circular RNAs, are emerging as central regulators of the epigeneticcrosstalk between DN and DFUs. Several miRNAs, including miR-146a-5p and miR-518d-3p, are implicated inneuropathy severity, while lncRNAs such as nuclear enriched abundant transcript 1 modulate angiogenesis andwound repair. Cellular reprogramming of DFU fibroblasts has also been shown to induce pro-healing miRNAsignatures, offering potential therapeutic avenues. Furthermore, recent whole-genome and transcriptomic analysesof DFU-derived monocytes and Charcot foot lesions reveal unique epigenetic signatures that may serve as biomarkersfor early detection and personalized interventions. This epigenetic interplay between DN and DFUpathogenesis not only enhances our knowledge of disease mechanisms but also opens avenues for targetedepigenetic therapies to improve clinical outcomes.展开更多
Epicardial adipose tissue(EAT)is an active form of visceral adipose tissue that can affect myocardial function due to shared circulation with the myocardium.Given its rapid metabolic activity,EAT is considered a poten...Epicardial adipose tissue(EAT)is an active form of visceral adipose tissue that can affect myocardial function due to shared circulation with the myocardium.Given its rapid metabolic activity,EAT is considered a potential therapeutic target for medications that modulate fat and is a potent marker of metabolic changes including those observed in diabetic cardiomyopathy.Recent investigations propose an association between EAT accumulation and chronic diseases such as type 2 diabetes mellitus(T2DM),atrial fibrillation,and heart failure with preserved ejection fraction.According to the method first described by Iacobellis et al,EAT thickness is identified as the echo-free space between the outer wall of the myocardium and the visceral layer of the pericardium,measured in the parasternal short-and long-axis views at end-systole using ultrasound.Ultrasound of EAT is a safe,cost-effective,and readily available tool for cardiometabolic risk assessment.This minireview investigates the current role of echocardiography in the assessment of EAT thickness in patients with T2DM,regardless of the presence of overt heart failure.We also discuss whether changes in EAT thickness may be used as a significant marker of disease progression and if delta EAT thickness could serve as a surrogate of effective therapy.展开更多
BACKGROUND Gastroparesis may repeatedly induce diabetic ketoacidosis(DKA),and the differential diagnosis of these diseases is challenging because of similar gastrointestinal symptoms.If DKA is accompanied by gastropar...BACKGROUND Gastroparesis may repeatedly induce diabetic ketoacidosis(DKA),and the differential diagnosis of these diseases is challenging because of similar gastrointestinal symptoms.If DKA is accompanied by gastroparesis,patients present with persistent gastrointestinal symptoms without relief and may even experience recurrent DKA.Misdiagnosis results in poor treatment outcomes and prognosis.We hypothesized that biomarkers or screening tools can be identified by comparing the clinical data between DKA alone and DKA+gastroparesis to facilitate early screening.AIM To achieve early detection and diagnosis of DKA+gastroparesis to enable early treatment aimed at relieving gastrointestinal symptoms and preventing reinduction of DKA.METHODS We conducted a case-control study in which 15 patients hospitalized for DKA at the Endocrinology Department of Peking Union Medical College Hospital and diagnosed with DKA and gastroparesis between December 1999 and January 2023(DKA+gastroparesis group)were included.Then,we selected 60 DKA patients without DKA as a control group(DKA alone group)based on gender,age,disease course,and diabetes subtype in a 1:4 matching ratio.Clinical manifestations and physical and laboratory examination results were statistically compared between the groups.RESULTS The DKA+gastroparesis group was composed of nine males and six females,with a mean age of 35±11 years,while the DKA alone group included 34 males and 26 females,with a mean age of 34±17 years.In the DKA+gastroparesis group,urine ketone levels normalized,while gastrointestinal symptoms persisted despite treatment,and the tests indicated lower glycosylated hemoglobin levels(HbA1c;7.07%vs 11.51%,P<0.01),largest amplitude of glycemic excursions(5.86 vs 17.41,P<0.01),standard deviation of blood glucose(SDBG;2.69 vs 5.83,P<0.01),and coefficient of blood glucose variation(0.31 vs 0.55,P=0.014)compared with the DKA alone group.Probable gastroparesis was considered at HbA1c<8.55%.Besides,the patients in the DKA+gastroparesis group had lower body mass index(19.28 kg/m^(2) vs 23.86 kg/m^(2),P=0.02)and higher high density lipoprotein cholesterol level(2.34 mmol/L vs 1.05 mmol/L,P=0.019)compared to the DKA alone group,but no difference was observed in the remaining lipid profiles between the two groups.CONCLUSION Gastroparesis should be considered in DKA patients who fail to have improved gastrointestinal symptoms after ketone elimination and acidosis correction,particularly when the HbA1c level is<8.55%.展开更多
The management of diabetic ketoacidosis can be challenging in high-risk patients.Recent studies have reported a significant increase in diabetic ketoacidosis hospitalization rates.While managing this high-risk conditi...The management of diabetic ketoacidosis can be challenging in high-risk patients.Recent studies have reported a significant increase in diabetic ketoacidosis hospitalization rates.While managing this high-risk condition,patient factors and comorbidities should be given careful attention and consideration.Factors like pregnancy,renal disease,cardiac disease,older age,and use of sodium-glucose cotransporter-2 inhibitors all impact the treatment approach,and tailored management strategies are required.Particularly in children,specialized treatment and care during a diabetic ketoacidosis episode is necessary due to its long-term neurological consequences.However,guidelines often lack adequate recommendations about the approach to manage complex patients with specific conditions and comorbidities.Furthermore,there are still controversies around certain aspects of diabetic ketoacidosis management,and additional investigations are needed to determine the best management options.We aim to address these special conditions and provide an approach to manage complex patients with specific conditions and co-morbidities.展开更多
Diabetes mellitus ranks among the most prevalent non-communicable diseases worldwide,affecting a vast number of individuals.It can impact almost every organ in the body,leading to serious complications such as diabeti...Diabetes mellitus ranks among the most prevalent non-communicable diseases worldwide,affecting a vast number of individuals.It can impact almost every organ in the body,leading to serious complications such as diabetic retinopathy(DR),diabetic nephropathy,and diabetic neuropathy.Scientific literature indi-cates that patients with severely compromised kidney function may develop non-responsive DR.Moreover,anaemia in individuals with diabetic kidney disease(DKD)complicates DR and can contribute to significant health issues.Optical coherence tomography(OCT)is a widely used non-invasive imaging tool for diagnosing,managing,and predicting DR.OCT findings in patients with DR and DKD include cystoid macular oedema,diffuse retinal thickening,disruptions in the ellipsoid layer,hyperreflective dots,and damage to the external limiting membrane.The review examines OCT patterns of diabetic macular oedema in DKD,correlating these patterns with declines in kidney function and visual acuity.Additionally,we review various biomarkers linked to DR in DKD patients and the growing importance of novel imaging biomarkers in predicting and connecting the severity of DR with DKD.展开更多
基金All animal experiments were performed under the protocols approved by the Ethical Committee for Animal Care of Donghua University(DHUEC-NSFC-2019-20)financially supported by the National Key Research and Development Program of China(2021YFA1201304)+3 种基金the National Natural Science Foundation of China(52503082),China Postdoctoral Science Foundation(2024M750402)Postdoctoral Fellowship Program of CPSF(GZC20230419)Shanghai Anticancer Association EYAS PROJECT(SACA-CY23C05)The Fundamental Research Funds for the Central Universities(2232023D-03,2232024Y-01).
文摘Diabetic wounds present challenges in clinical management due to persistent inflammation caused by excessive exudate infiltration.Inspired by the gradient wettability of cactus thorn,this study has devised a biomimetic Janus nanofiber membrane as a water diode,which endows with gradient wettability and gradient pore size,offering sustainable unidirectional self-drainage and antibacterial properties for enhanced diabetic wound healing.The Janus membrane is fabricated by depositing a hydrophilic polyacrylonitrile/chlorin e6 layer with smaller pore sizes onto a hydrophobic poly(ε-caprolactone)with larger pore sizes,thereby generating a vertical gradient in both wettability and pore structure.The incorporation of chlorin e6 in the upper layer enables the utilization of external light energy to generate heat for evaporation and produce reactive oxygen species,achieving a high sterilization efficiency of 99%.Meanwhile,the gradient structure of the Janus membrane facilitates continuous antigravity exudate drainage at a rate of 0.95 g cm^(−2) h^(−1).This dual functionality of effective exudate drainage and sterilization significantly reduces inflammatory factors,allows the polarization of macrophages toward the M2 proliferative phenotype,enhances angiogenesis,and accelerates wound healing.Therefore,this study provides a groundbreaking bioinspired strategy for the development of advanced wound dressings tailored for diabetic wound regeneration.
基金supported by National Natural Science Foundation of China(Grant No.81900873 to A.Q.)the Jiangsu Provincial Key Research and Development Programme-social development(Grant No.BE2023777 to W.Z.)+1 种基金the Key Medical Research Project of Jiangsu Commission of Health(Grant No.H2022185 to W.Z.)the Clinical Capacity Enhancement Project of Jiangsu Province Hospital(Grant No.JSPH-MB-2023-18 to W.Z.)。
文摘Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear.We measured HDGF levels in the aqueous humor and found that HDGF was increased in DR but decreased after anti-angiogenesis treatment.Using public single-cell RNA sequencing datasets,we found that elevated HDGF in DR was mainly produced by Müller cells and targeted microglia.Additionally,integrin beta 2(Itgb2),a target gene of HDGF that induces microglial activation,was significantly upregulated in DR.To verify these results,we performed enzyme-linked immunosorbent assays,quantitative reverse transcription-PCR,Western blotting,and fluorescence immunostaining in cultured Müller and microglial cells treated with HDGF or anti-HDGF,as well as in DR mice receiving intravitreal injections of HDGF or its antibody.Exogenous HDGF further promoted microglial activation,migration,and secretion of pro-inflammatory cytokines,while neutralization of HDGF suppressed these effects caused by high glucose.Furthermore,the HDGF receptor nucleolin was overexpressed in microglia under high glucose stimulation.Therefore,blocking HDGF from Müller cells in DR reduced the excessive inflammatory response in microglia,highlighting HDGF as a potential therapeutic target.
基金funded by the Deanship of Scientific Research at King Abdulaziz University,Jeddah,under Grant No.G:534-140-1443.
文摘Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced in rats using streptozotocin,after which full-thickness excisional wounds were created.Piceatannol was administered topically either as a raw hydrogel or formulated into a PIC-SNEDDS,which was prepared using an optimized oil-surfactant mixture and incorporated into a hydrogel for application.Wound healing activity was assessed through measurements of wound contraction,oxidative stress biomarkers,and collagen content,along with histological and immunohistochemical evaluation of inflammatory,angiogenic,and remodeling markers.Results:PIC-SNEDDS markedly enhanced diabetic wound healing by promoting epithelial regeneration,granulation tissue formation,epidermal proliferation,and keratinization.The formulation also reduced the expression of pro-inflammatory markers(interleukin-6,nuclear factor-kappa B,and tumor necrosis factor-α)while increasingα-smooth muscle actin,transforming growth factor-β1,vascular endothelial growth factor-A,and hydroxyproline levels.Additionally,it improved antioxidant status by lowering malondialdehyde levels and boosting superoxide dismutase and catalase activity,along with upregulation of COL1A1 mRNA expression.Conclusions:PIC-SNEDDS promotes the healing of diabetic wounds and exhibits anti-inflammatory,antioxidant,pro-collagen,and angiogenic properties.
基金supported by the Natural Science Foundation of Hubei Provincial Department of Education(D20232101)Shandong Second Medical University 2024 Affiliated Hospital(Teaching Hospital)Scientific Research Development Fund Project(2024FYQ026)+3 种基金the innovative Research Programme of Xiangyang No.1 People’s Hospital(XYY2023ZY01)Faculty Development Grants of Xiangyang No.1 People’s Hospital Affiliated to Hubei University of Medicine(XYY2023D05)Joint supported by Hubei Provincial Natural Science Foundation and Xiangyang of China(2025AFD091)Traditional Chinese Medicine Scientific Research Project of Hubei Provincial Administration of Traditional Chinese Medicine(ZY2025D019).
文摘Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-inflammatory,and immunomodulatory activities.However,its active constituents and mechanisms of action against diabetic foot remain to be elucidated.Methods:In this study,the chemical constituents of Sanhuang Oil were identified using UPLC-QE-Orbitrap-MS.Subsequently,the mechanism by which Sanhuang Oil promotes diabetic foot ulcer healing was predicted by integrating network pharmacology and molecular docking.Additionally,diabetic mouse model was established in ICR mice using a combination of a high-fat diet(HFD)and streptozotocin(STZ)chemical induction.A full-thickness skin defect was created on the dorsum of the mice.Wound healing and the healing rate were observed following Sanhuang Oil intervention.The mechanism underlying Sanhuang Oil’s promotion of diabetic ulcer healing was further investigated using transcriptomics and histopathological examination(H&E staining).Results:A total of 97 active ingredients were identified from Sanhuang Oil.Network pharmacology analysis predicted 543 common targets,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis identified 203 relevant pathways.Molecular docking further confirmed high binding affinity(binding energy≤−5.0 kcal/mol)between specific active components in Sanhuang Oil(e.g.,coptisine,phellodendrine,baicalein)and key targets associated with diabetic foot ulcers(e.g.,EGFR,AKT1,STAT3).In vivo experimental results demonstrated that the wound healing rate was significantly higher in Sanhuang Oil-treated groups compared to the model group(P<0.001).HE staining revealed that the high-dose Sanhuang Oil group exhibited more pronounced epithelial tissue coverage over the wound,reduced inflammatory cell infiltration,and increased collagen deposition and fibroblast proliferation.transcriptomic analysis identified Pdk4,Ttn,Csrp3,Actn2,Myoz2,Tnnc2,Myod1,Myog,Myot,and Myf6 as key regulatory proteins involved in promoting wound healing.Conclusion:Sanhuang Oil promotes wound healing in diabetic ulcer mice,potentially by mitigating inflammation and regulating key targets such as Pdk4 to enhance fibroblast function.These findings provide novel insights into the multi-target,multi-pathway mechanism of Sanhuang Oil for treating diabetic foot ulcers.
基金funded by the Chronic Disease Management Research Project of National Health Commission Capacity Building and Continuing Education Center 2025(GWJJMB202510024146)the Post-Subsidy Project for Standard Development of Guizhou Provincial Market Supervision and Administration Bureau 2025(DB52/T1726-2023)the Guizhou Provincial Health Commission Science and Technology Fund Project(gzwkj2024-076,gzwkj2026-146).
文摘Diabetic retinopathy(DR)is a leading cause of vision loss among working-age populations,with early screening significantly reducing the risk of blindness.However,resource-limited regions often face challenges in DR screening due to a shortage of ophthalmologists.This study reports the implementation and outcomes of the Chinese local standard DB52/T 1726-2023,Regulations for the application of diabetic retinopathy screening artificial intelligence,in Cambodian healthcare institutions.A pilot DR screening program with independent operational capability is established by providing a non-mydriatic fundus camera and deploying a localized diabetic retinopathy artificial intelligence(DR-AI)screening platform at the Cambodia-Kingdom Friendship Hospital in Phnom Penh,along with comprehensive training.From January to August 2025,a total of 565 patients with type 2 diabetes were screened,yielding a DR detection rate of 26.0%(147 cases).Research findings demonstrate that applying mature Chinese DR-AI screening standards and technological solutions through international collaboration in regions with a scarcity of ophthalmic professionals is both feasible and effective.This project serves as a reference for promoting DR-AI in resource-constrained countries and regions,highlighting its significant potential to leverage AI in addressing the global burden of chronic diseases and advancing the modernization of health systems.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Zhejiang Traditional Chinese Medicine Science and Technology Plan Project(No.2025ZR172).
文摘AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and vision data were compared between groups using an independent sample t-test.Resting-state functional magnetic resonance imaging(rs-fMRI)was used in all participants.fMRI data was obtained and analyzed using MRIcro and SPM8 software.Fractional amplitude of low-frequency fluctuation(fALFF)technology was used to measure regional spontaneous brain activity,and sensitivity was tested using receiver operating characteristic curves(ROCs).The fALFF values were analyzed using REST software and two-sample t-tests were used to compare values between groups.Hospital anxiety and depression scale(HADS)score was assessed in DVHs and Pearson’s correlation was used to test relationships between mean fALFF value and both HADS score and duration of DVH.RESULTS:Except for the best-corrected visual acuity(BCVA)in both eyes,which showed a statistically significant difference(P<0.05),there were no statistically significant differences in the other indicators(P>0.05)between the HCs and DVHs group.Compared with controls,fALFF value was higher in DVH in cerebellum posterior lobe(CPL)and lower in right anterior cingulate cortex(ACC)and right medial orbitofrontal cortex(OFC).In DVH patients,mean fALFF value of CPL was positively correlated with HADS score and duration of diabetes.However,no such correlation was found,for right ACC or right medial OFC.DVH may lead to abnormal activities in certain brain regions related to visual control and mood.CONCLUSION:Visual impairment caused by DVH may lead to adjustment in regional visual brain activities and may be related to depression or reward system processing in some brain regions.
基金funded by grants from the Suzhou Gusu Health Talents Project(grant No.GSWS2024050 to Liu W)Natural Science Foundation Project of Nanjing University of Chinese Medicine(grant No.XZR2021043 to Liu W and grant No.XZR2023021 to Huang F)+1 种基金Suzhou Science Education Health Youth Project(grant No.KJXW2021046 to Liu W)Suzhou Major Disease Multi-center Clinical Research Project(grant No.DZXYJ202410 to Huang F).
文摘Background:Inflammation,caused by prolonged hyperglycemia,plays a substantially more important part in the progression of diabetic peripheral neuropathy(DPN).Notably,the MAPK pathway that mediates the Nuclear Factor-kappa B(NF-κB)pathway contributes to inflammation-induced peripheral nerve damage,affecting cell survival.Juan Bi Tong Luo(JBTL),a traditional Chinese medicine(TCM),has demonstrated favorable results in alleviating pain and numbness in patients with DPN;however,whether JBTL exerts its effect through the MAPK mediating NF-κB pathway remains unclear.Methods:This study investigated whether JBTL modulates apoptosis in DPN models and Schwann cells cultured in 100 mM of glucose by MAPK/NF-κB.Results:The JBTL altered inflammation,reduced peripheral nerve tissue damage,and improved cell survival rates by down-regulating MAPK/NF-κB.Conclusion:Our findings demonstrate that the effect of JBTL on DPN is likely mediated by suppressing inflammation induced by the MAPK/NF-κB pathway,thus providing evidence for the clinical efficacy of JBTL in treating DPN.
基金the Ministry of Science and Technology Taiwan,No.MOST 109-2314-B-182A-091,No.NSTC 112-2314-B-182A-062, No.NSTC 113-2314-B-182A-125.
文摘BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments.AIM To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles(hAFSC-EVs)on the recovery of bladder dysfunction in DMA rats.METHODS Eighty rats were divided into normal control,streptozotocin-induced diabetic rats,diabetic rats subjected to arterial balloon endothelial injury of common iliac artery(DMA),and DMA rats treated with hAFSC-EVs(DMA+hAFSC-EVs).At 4 weeks and 12 weeks after DMA induction,levels of blood glucose,total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,homeostasis model assessment(HOMA)-insulin resistance,and HOMA-βwere measured.Cystometry,common iliac artery wall thickness,and bladder tumor necrosis factor(TNF)-α,interleukin(IL)-6,transforming growth factor(TGF)-β1,Smad3,connective tissue growth factor(CTGF)and fibronectin were also evaluated.RESULTS Bladder weight and blood glucose,triglyceride,HOMA-insulin resistance,common iliac artery intima thickness,voided volume,intercontraction interval,bladder capacity,and mRNA expression of TNF-α,IL-6,TGF-β1,Smad3,CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction,while the HOMA-βlevel decreased at 4 weeks and 12 weeks,and the high-density lipoprotein cholesterol level decreased at 12 weeks.hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose,thickness of common iliac arterial intima,voided volume,intercontraction interval and bladder capacity at 4 weeks.The mRNA expression of TNF-α,TGF-β1,and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks,while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks.CONCLUSION hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction,which is associated with lowered blood glucose levels,reduced arterial wall thickness,and decreased TNF-α,IL-6,TGF-β1,Smad3,and CTGF expression.
文摘AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS:A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital,Sun Yat-sen University from 2022 to 2023 were included,including 95 first-diagnosed DR patients and 105 patients without DR,and all patients underwent OCTA examination and a collection of demographics and renal function parameters.After a quality check,automated measurements of the foveal avascular zone area,vessel density(VD),and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS:Using random forest and multivariate Logistic regression methods,we developed a diagnostic model for DR based on 12 variables(age,FBG,SBP,DBP,HbA1c,ALT,ALP,urea/Scr,DM duration,HUA,DN,and CMT).Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window,AUC=0.837 vs 0.819,P=0.03).In the study of DN patients,the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD;outer VD;full VD;outer PD;full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model.Meanwhile,compared with the 3 mm×3 mm window,the microvascular parameters in the 6 mm×6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.
基金Supported by the King Salman Center for Disability Research,No.KSRG-2023-407.
文摘Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.
文摘Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.
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Diabetic foot attack(DFA)is the most severe presentation of diabetic foot disease,with the patient commonly displaying severe sepsis,which can be limb or life threatening.DFA can be classified into two main categories:Typical and atypical.A typical DFA is secondary to a severe infection in the foot,often initiated by minor breaches in skin integrity that allow pathogens to enter and proliferate.This form often progresses rapidly due to the underlying diabetic pathophysiology of neuropathy,microvascular disease,and hyperglycemia,which facilitate infection spread and tissue necrosis.This form of DFA can present as one of a number of severe infective pathologies including pyomyositis,necrotizing fasciitis,and myonecrosis,all of which can lead to systemic sepsis and multiorgan failure.An atypical DFA,however,is not primarily infection-driven.It can occur secondary to either ischemia or Charcot arthropathy.Management of the typical DFA involves prompt diagnosis,aggressive infection control,and a multidisciplinary approach.Treatment can be guided by the current International Working Group on the Diabetic Foot/Infectious Diseases Society of America guidelines on diabetic foot infections,and the combined British Orthopaedic Foot and Ankle Society-Vascular Society guidelines.This article highlights the importance of early recognition,comprehensive management strategies,and the need for further research to establish standardized protocols and improve clinical outcomes for patients with DFA.
文摘This editorial offers insights from a minireview by Venkatesh et al,who explored pharmacological adjuvants for diabetic vitrectomy.Specifically,they synthesized current knowledge and evaluated the efficacy of various adjunctive therapies in improving the outcomes of diabetic retinopathy and managing associated complications.Herein,we highlight the key roles of pharmacological adjuvants in optimizing surgical techniques,minimizing intraoperative challenges,and enhancing postoperative recovery.We further discuss the potential implications of this approach for clinical practice and future research directions in this evolving field.Overall,this editorial underscores the importance of incorporating pharmacological adjuvants into standard diabetic vitrectomy care to improve surgical outcomes and thus patients’quality of life.
文摘Proliferative diabetic retinopathy(PDR)affects approximately 6%of diabetic patients globally.The overall prevalence of diabetic retinopathy is around 22%.Wet age-related macular degeneration(ARMD),the sight-threatening type of ARMD,affects approximately 1.2%-1.3%of the general population and represents 15%of total ARMD cases.While intravitreal anti-vascular endothelial growth factor injections are still the mainstay therapy,there are a few challenges,such as frequent administration,cost burden,and compliance barriers that prompt the need for exploration into systemic oral alternative drugs like fenofibrate,candesartan,and vorolanib.These oral therapies have the advantage of being noninvasive and systemically accessible with few logistical burdens.This review highlights current evidence supporting the use of oral therapies in PDR and wet ARMD management,along with practical limitations and future prospects.
文摘Diabetic neuropathy (DN) and impaired wound healing in diabetic foot ulcers(DFUs) are major complications of diabetes mellitus, driven by complex molecularmechanisms, including epigenetic modifications. Recent research highlights therole of epigenetic markers including DNA methylation, histone modifications,and non-coding RNAs in regulating inflammatory responses, neuronal degeneration,and tissue repair. This review explores the epigenetics of DN and DFUs,emphasizing key regulatory pathways that influence disease progression andwound healing outcomes. Genome-wide DNA methylation studies reveal acceleratedepigenetic aging and metabolic memory effects in DN, contributing tosensory neuron dysfunction and neuropathic pain. Epigenetic dysregulation ofinflammatory mediators such as Toll-like receptors and the Nod-like receptorfamily, pyrin domain-containing 3 inflammasome further exacerbates neuronaldamage and delays wound healing. Additionally, histone deacetylases play apivotal role in oxidative stress regulation via the Nrf2 pathway, which is critical for both neuronal protection and angiogenesis in DFUs. Non-coding RNAs, particularly microRNAs (miRNAs),long non-coding RNAs (lncRNAs), and circular RNAs, are emerging as central regulators of the epigeneticcrosstalk between DN and DFUs. Several miRNAs, including miR-146a-5p and miR-518d-3p, are implicated inneuropathy severity, while lncRNAs such as nuclear enriched abundant transcript 1 modulate angiogenesis andwound repair. Cellular reprogramming of DFU fibroblasts has also been shown to induce pro-healing miRNAsignatures, offering potential therapeutic avenues. Furthermore, recent whole-genome and transcriptomic analysesof DFU-derived monocytes and Charcot foot lesions reveal unique epigenetic signatures that may serve as biomarkersfor early detection and personalized interventions. This epigenetic interplay between DN and DFUpathogenesis not only enhances our knowledge of disease mechanisms but also opens avenues for targetedepigenetic therapies to improve clinical outcomes.
文摘Epicardial adipose tissue(EAT)is an active form of visceral adipose tissue that can affect myocardial function due to shared circulation with the myocardium.Given its rapid metabolic activity,EAT is considered a potential therapeutic target for medications that modulate fat and is a potent marker of metabolic changes including those observed in diabetic cardiomyopathy.Recent investigations propose an association between EAT accumulation and chronic diseases such as type 2 diabetes mellitus(T2DM),atrial fibrillation,and heart failure with preserved ejection fraction.According to the method first described by Iacobellis et al,EAT thickness is identified as the echo-free space between the outer wall of the myocardium and the visceral layer of the pericardium,measured in the parasternal short-and long-axis views at end-systole using ultrasound.Ultrasound of EAT is a safe,cost-effective,and readily available tool for cardiometabolic risk assessment.This minireview investigates the current role of echocardiography in the assessment of EAT thickness in patients with T2DM,regardless of the presence of overt heart failure.We also discuss whether changes in EAT thickness may be used as a significant marker of disease progression and if delta EAT thickness could serve as a surrogate of effective therapy.
基金Supported by National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-015the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences,No.2021-I2M-C&T-B-003.
文摘BACKGROUND Gastroparesis may repeatedly induce diabetic ketoacidosis(DKA),and the differential diagnosis of these diseases is challenging because of similar gastrointestinal symptoms.If DKA is accompanied by gastroparesis,patients present with persistent gastrointestinal symptoms without relief and may even experience recurrent DKA.Misdiagnosis results in poor treatment outcomes and prognosis.We hypothesized that biomarkers or screening tools can be identified by comparing the clinical data between DKA alone and DKA+gastroparesis to facilitate early screening.AIM To achieve early detection and diagnosis of DKA+gastroparesis to enable early treatment aimed at relieving gastrointestinal symptoms and preventing reinduction of DKA.METHODS We conducted a case-control study in which 15 patients hospitalized for DKA at the Endocrinology Department of Peking Union Medical College Hospital and diagnosed with DKA and gastroparesis between December 1999 and January 2023(DKA+gastroparesis group)were included.Then,we selected 60 DKA patients without DKA as a control group(DKA alone group)based on gender,age,disease course,and diabetes subtype in a 1:4 matching ratio.Clinical manifestations and physical and laboratory examination results were statistically compared between the groups.RESULTS The DKA+gastroparesis group was composed of nine males and six females,with a mean age of 35±11 years,while the DKA alone group included 34 males and 26 females,with a mean age of 34±17 years.In the DKA+gastroparesis group,urine ketone levels normalized,while gastrointestinal symptoms persisted despite treatment,and the tests indicated lower glycosylated hemoglobin levels(HbA1c;7.07%vs 11.51%,P<0.01),largest amplitude of glycemic excursions(5.86 vs 17.41,P<0.01),standard deviation of blood glucose(SDBG;2.69 vs 5.83,P<0.01),and coefficient of blood glucose variation(0.31 vs 0.55,P=0.014)compared with the DKA alone group.Probable gastroparesis was considered at HbA1c<8.55%.Besides,the patients in the DKA+gastroparesis group had lower body mass index(19.28 kg/m^(2) vs 23.86 kg/m^(2),P=0.02)and higher high density lipoprotein cholesterol level(2.34 mmol/L vs 1.05 mmol/L,P=0.019)compared to the DKA alone group,but no difference was observed in the remaining lipid profiles between the two groups.CONCLUSION Gastroparesis should be considered in DKA patients who fail to have improved gastrointestinal symptoms after ketone elimination and acidosis correction,particularly when the HbA1c level is<8.55%.
文摘The management of diabetic ketoacidosis can be challenging in high-risk patients.Recent studies have reported a significant increase in diabetic ketoacidosis hospitalization rates.While managing this high-risk condition,patient factors and comorbidities should be given careful attention and consideration.Factors like pregnancy,renal disease,cardiac disease,older age,and use of sodium-glucose cotransporter-2 inhibitors all impact the treatment approach,and tailored management strategies are required.Particularly in children,specialized treatment and care during a diabetic ketoacidosis episode is necessary due to its long-term neurological consequences.However,guidelines often lack adequate recommendations about the approach to manage complex patients with specific conditions and comorbidities.Furthermore,there are still controversies around certain aspects of diabetic ketoacidosis management,and additional investigations are needed to determine the best management options.We aim to address these special conditions and provide an approach to manage complex patients with specific conditions and co-morbidities.
文摘Diabetes mellitus ranks among the most prevalent non-communicable diseases worldwide,affecting a vast number of individuals.It can impact almost every organ in the body,leading to serious complications such as diabetic retinopathy(DR),diabetic nephropathy,and diabetic neuropathy.Scientific literature indi-cates that patients with severely compromised kidney function may develop non-responsive DR.Moreover,anaemia in individuals with diabetic kidney disease(DKD)complicates DR and can contribute to significant health issues.Optical coherence tomography(OCT)is a widely used non-invasive imaging tool for diagnosing,managing,and predicting DR.OCT findings in patients with DR and DKD include cystoid macular oedema,diffuse retinal thickening,disruptions in the ellipsoid layer,hyperreflective dots,and damage to the external limiting membrane.The review examines OCT patterns of diabetic macular oedema in DKD,correlating these patterns with declines in kidney function and visual acuity.Additionally,we review various biomarkers linked to DR in DKD patients and the growing importance of novel imaging biomarkers in predicting and connecting the severity of DR with DKD.
