BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by...BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.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
Objective:To study the effect of Chongcao Bushen Capsules on bone turnover markers in patients with diabetic osteoporosis.Methods:107 patients with diabetic osteoporosis treated in the Hospital from December 2016 to N...Objective:To study the effect of Chongcao Bushen Capsules on bone turnover markers in patients with diabetic osteoporosis.Methods:107 patients with diabetic osteoporosis treated in the Hospital from December 2016 to November 2019were enrolled.They were divided into a control group(n=54)and an observation group(n=53)by random number table.The control group was treated with calcium carbonate,and the observation group was treated with Chongcao Bushen Capsules.The treatment effects,TCM syndrome scores,and bone turnover markers[including osteocalcin,type 1 procollagen amino-terminal propeptide(tP1NP),parathyroid hormone(PTH),25-hydroxyvitamin D,andβ-isomerized c-terminal peptide(β-CTx)],and the incidence of adverse reactions in the two groups were observed and compared.Results:After treatment,the total effective rate of treatment in the observation group(94.44%)was higher than that in the control group(73.58%),and the difference was statistically significant(P<0.05).The scores of symptoms including waist and knee weakness,back and waist pain,lower limb weakness,fatigue and tiredness,difficult walking and dizziness in the observation group were shown to be lower than the control group,and the difference was statistically significant(P<0.05).The levels of osteocalcin,PTH,tP1NP,andβ-CTx in the observation group were lower than those in the control group,and the difference was statistically significant(P<0.05).The 25-hydroxyvitamin D in the observation group was higher than the control group,and the difference was statistically significant(P<0.05).Bone density in both male and female in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Conclusion:For patients with diabetic osteoporosis,Chongcao Bushen Capsule can help improve their clinical symptoms,bone density and the level of bone turnover markers.展开更多
Diabetic osteoporosis(DOP) is the leading complication continuously threatening the bone health of patients with diabetes. A key pathogenic factor in DOP is loss of osteocyte viability. However, the mechanism of osteo...Diabetic osteoporosis(DOP) is the leading complication continuously threatening the bone health of patients with diabetes. A key pathogenic factor in DOP is loss of osteocyte viability. However, the mechanism of osteocyte death remains unclear. Here, we identified ferroptosis, which is iron-dependent programmed cell death, as a critical mechanism of osteocyte death in murine models of DOP. The diabetic microenvironment significantly enhanced osteocyte ferroptosis in vitro, as shown by the substantial lipid peroxidation, iron overload, and aberrant activation of the ferroptosis pathway. RNA sequencing showed that heme oxygenase-1(HO-1) expression was notably upregulated in ferroptotic osteocytes. Further findings revealed that HO-1 was essential for osteocyte ferroptosis in DOP and that its promoter activity was controlled by the interaction between the upstream NRF2 and c-JUN transcription factors. Targeting ferroptosis or HO-1 efficiently rescued osteocyte death in DOP by disrupting the vicious cycle between lipid peroxidation and HO-1 activation, eventually ameliorating trabecular deterioration. Our study provides insight into DOP pathogenesis, and our results provide a mechanism-based strategy for clinical DOP treatment.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
Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2...Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.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
Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture,which increases patient susceptibility to fragile fractures.The intricate mechanisms governing...Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture,which increases patient susceptibility to fragile fractures.The intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles(EVs),which play crucial roles in both pathological and physiological contexts.EVs derived from various sources exert distinct effects on osteoporosis.Specifically,EVs released by osteoblasts,endothelial cells,myocytes,and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins,miRNAs,and cytokines.Conversely,EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone formation.Furthermore,the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is promising.Here,we review the current understanding of the impact of EVs on bone homeostasis,including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in osteoporosis.Furthermore,we present an overview of the latest research progress on diagnosing and treating osteoporosis by using EVs.Finally,we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.展开更多
Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has re...Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis,with sex-specific differences in epidemiology and pathogenesis.Specifically,females are more susceptible than males to osteoporosis,while males are more prone to disability or death from the disease.To date,sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells.Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men.This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis,mainly in a population of aging patients,chronic glucocorticoid administration,and diabetes.Moreover,we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men.Additionally,the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.展开更多
Introduction: Predictions on the prevalence of diabetes mellitus, according to the International Diabetes Federation, indicated 9.3% in 2019 and nearly 10.9% of the general population in 2045. In Benin, the increase i...Introduction: Predictions on the prevalence of diabetes mellitus, according to the International Diabetes Federation, indicated 9.3% in 2019 and nearly 10.9% of the general population in 2045. In Benin, the increase in this prevalence, according to the World Health Organization (WHO), is constantly increasing. Diabetic foot is one of its most common complications. The aim of this work was to study the prognostic factors of diabetic foot in the Department of Endocrinology, Metabolism and Nutrition of the CNHU-HKM of Cotonou. Patients and method: This is a descriptive and analytical retrospective study of the prognostic factors of diabetic foot over a period of 3 years from January 2019 to December 2021 in patients who have been hospitalized or followed on an outpatient basis for diabetic foot in the Endocrinology, Metabolism and Nutrition Department of the CNHU-HKM of Cotonou. Results: A total of 112 patients were included in this study. The average age of the patients was 59.70 ± 2.10 years. A male predominance was noted with a sex ratio (M/F) of 1.7. Mixed gangrene and phlegmons were the most common lesions. According to the classification of diabetic feet according to the University of Texas, 59.1% of patients had a 100% risk of amputation. Ten patients died from sepsis (8.9%). The average blood glucose on admission was 2.74 ± 0.23 g/l, reflecting the glycemic imbalance in these patients. There is a statistically significant association between the duration of progression of diabetes, the type of lesion and amputation. Patients whose diabetes has lasted more than 30 years and patients who are not monitored have a greater risk of death. Conclusion: Diabetic patients most often consulted at a late stage, compromising conservative treatment. The duration of diabetes and the type of lesion on admission were the main factors leading to amputation, thus compromising the functional prognosis. As for death, it was mainly linked to irregular monitoring of diabetes and the duration of diabetes. Effective prevention and management of diabetic feet requires patient education about the diabetic foot and systematic screening of at-risk feet in consultation.展开更多
Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the devel...Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.展开更多
Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-...Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.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 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
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
Introduction: Macroangiopathy plays an important role, with a high prevalence of morbidity and mortality in diabetic patients. The aim was to study the epidemiological, clinical, paraclinical, therapeutic and evolutio...Introduction: Macroangiopathy plays an important role, with a high prevalence of morbidity and mortality in diabetic patients. The aim was to study the epidemiological, clinical, paraclinical, therapeutic and evolutionary profile of macroangiopathy in diabetic patients in the internal medicine department of the Abass Ndao hospital. Patients and methods: This was a descriptive and analytical cross-sectional study. Our investigations were recruited over a 7-year period (January 1, 2016 to December 31, 2022). Results: Three hundred and fifty-nine (359) patients (10.22%) were enrolled. The mean age was 62.83 years, with extremes ranging from 17 to 98 years. The [60 - 69] age group was more representative (37.32%). Women accounted for 180 cases (50.1%), with a sex ratio (m/f) of 0.99. The average duration of diabetes was 11.86 years. Average consultation time was 38.07 days, with extremes ranging from 1 to 368 days. Average hospital stay was 7.65 days. Inaugural diabetes was noted in 12 cases (3.34%). Type 2 diabetes accounted for 95.82% (n = 344) of patients. Hypertension was present in 150 patients (41.8%). Patients with 2 risk factors accounted for 173 cases (48.18%). Nineteen patients had already had a stroke (5.29% of cases). Fourteen (14) patients (4.2%) were amputees. Obliterative arteriopathy of the lower limbs (AOMI) was noted in 193 patients (54%). Stroke was noted in 101 patients (28%). Ischemic heart disease (IHD) was noted in 38 patients (11%). AOMI was more common in males (110 patients, 57%) than in females (43%). Seventy-three (73) patients (20.3%) died. Predictors of death were age over 60 and the existence of more than two cardiovascular risk factors. Conclusion: Diabetic macroangiopathy is a major cause of morbidity and mortality. The development and implementation of a prevention and management program is essential.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
Introduction: Cardiovascular disease is the leading cause of death in diabetics. The objective of our study was to investigate the echocardiographic aspects of type 2 diabetics. Patients and Method: Descriptive a...Introduction: Cardiovascular disease is the leading cause of death in diabetics. The objective of our study was to investigate the echocardiographic aspects of type 2 diabetics. Patients and Method: Descriptive and cross-sectional study of 12 months from June 2020 to June 2021. We included hospitalized type 2 diabetics who underwent transthoracic cardiac ultrasound in the Department of Medicine and Endocrinology at the Mali Hospital. Results: We collected 128 type 2 diabetics. The predominance was male with a sex ratio of 1.2. The mean age of patients was 60.06 ± 11.54 years with extremes of 28 and 84 years. Echocardiographic abnormalities were dominated by abnormal relaxation of left ventricle in 62.5%, increased of left ventricle mass in 54.7% and left atrium dilation in 28.1%. Patients with type 2 diabetes mellitus and hypertension had more left atrium dilation with a p of 0.02. Disorders of global kinetics and systolic dysfunction were more prevalent in smoking patients with statistically significant associations, respectively, p = 0.02;p = 0.03. Dyslipidemia had a statistically significant association with segmental kinetic disorders with a p of 0.008. Duration of diabetes greater than 5 years was associated with left atrium dilation and p-value was 0.04. Conclusion: Diabetes is responsible for cardiovascular manifestations that can be identified with transthoracic echocardiography. Its performance in diabetic patients makes it possible to refine the patient’s management.展开更多
Introduction: Type 1 diabetes can have acute complications, sometimes requiring hospitalization. The aim of this study was to describe the epidemiological, clinical and evolutionary aspects of type 1 diabetes in patie...Introduction: Type 1 diabetes can have acute complications, sometimes requiring hospitalization. The aim of this study was to describe the epidemiological, clinical and evolutionary aspects of type 1 diabetes in patients at the Abass Ndao National Hospital in Dakar. Patients and Methods: This was a cross-sectional, descriptive and analytical study conducted from January 01, 2010 to December 31, 2021. It focused on hospitalized type 1 diabetic patients. Epidemiological, clinical and evolutionary data were evaluated. Results: Six hundred and fifty-nine (659) patients were enrolled, representing a frequency of 11.5%. The mean age was 29.47 years, giving a sex ratio (m/f) of 0.95. Average hospital stay was 6.1 days. One hundred and forty-four (144) patients (21.8%) had inaugural diabetes. The average consultation time was 14.89 days. Acute metabolic complications were ketoacidosis in 353 patients (56%), and hypoglycemia in 1.2%. Simple hyperglycemia was noted in 113 patients (18.0%). Infection was present in 522 patients (58.3%), of whom 95 (28.2%) had a skin infection.55 patients (16.3%) had a respiratory infection. 12.3% had a dietary imbalance.176 cases (27.7%) had no imbalance.26 patients (3.9%) died, with infectious pathologies accounting for the majority of decompensation factors among the deceased (57.7%). Conclusion: Type 1 diabetes is a cause of morbidity and mortality. It is essential to develop and implement a prevention and management program.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
基金Supported by the National Natural Science Foundation of China,No.81471094 and No.82202743.
文摘BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.
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Traditional Chinese medicine research project of Hebei administration of traditional Chinese medicine(No.2016092)。
文摘Objective:To study the effect of Chongcao Bushen Capsules on bone turnover markers in patients with diabetic osteoporosis.Methods:107 patients with diabetic osteoporosis treated in the Hospital from December 2016 to November 2019were enrolled.They were divided into a control group(n=54)and an observation group(n=53)by random number table.The control group was treated with calcium carbonate,and the observation group was treated with Chongcao Bushen Capsules.The treatment effects,TCM syndrome scores,and bone turnover markers[including osteocalcin,type 1 procollagen amino-terminal propeptide(tP1NP),parathyroid hormone(PTH),25-hydroxyvitamin D,andβ-isomerized c-terminal peptide(β-CTx)],and the incidence of adverse reactions in the two groups were observed and compared.Results:After treatment,the total effective rate of treatment in the observation group(94.44%)was higher than that in the control group(73.58%),and the difference was statistically significant(P<0.05).The scores of symptoms including waist and knee weakness,back and waist pain,lower limb weakness,fatigue and tiredness,difficult walking and dizziness in the observation group were shown to be lower than the control group,and the difference was statistically significant(P<0.05).The levels of osteocalcin,PTH,tP1NP,andβ-CTx in the observation group were lower than those in the control group,and the difference was statistically significant(P<0.05).The 25-hydroxyvitamin D in the observation group was higher than the control group,and the difference was statistically significant(P<0.05).Bone density in both male and female in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Conclusion:For patients with diabetic osteoporosis,Chongcao Bushen Capsule can help improve their clinical symptoms,bone density and the level of bone turnover markers.
基金supported by National Natural Science Foundation of China(NSFC)grants 92068205,81802679,and 82002328supported by China Postdoctoral Science Foundation grants 2018M632136 and 2019T120348。
文摘Diabetic osteoporosis(DOP) is the leading complication continuously threatening the bone health of patients with diabetes. A key pathogenic factor in DOP is loss of osteocyte viability. However, the mechanism of osteocyte death remains unclear. Here, we identified ferroptosis, which is iron-dependent programmed cell death, as a critical mechanism of osteocyte death in murine models of DOP. The diabetic microenvironment significantly enhanced osteocyte ferroptosis in vitro, as shown by the substantial lipid peroxidation, iron overload, and aberrant activation of the ferroptosis pathway. RNA sequencing showed that heme oxygenase-1(HO-1) expression was notably upregulated in ferroptotic osteocytes. Further findings revealed that HO-1 was essential for osteocyte ferroptosis in DOP and that its promoter activity was controlled by the interaction between the upstream NRF2 and c-JUN transcription factors. Targeting ferroptosis or HO-1 efficiently rescued osteocyte death in DOP by disrupting the vicious cycle between lipid peroxidation and HO-1 activation, eventually ameliorating trabecular deterioration. Our study provides insight into DOP pathogenesis, and our results provide a mechanism-based strategy for clinical DOP treatment.
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funded by the National Key Research and Development Program of China(2020YFD0900902)Zhejiang Province Public Welfare Technology Application Research Project(LGJ21C20001)Zhejiang Provincial Key Research and Development Project of China(2019C02076 and 2019C02075)。
文摘Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.
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.
基金This study was supported by the National Natural Science Foundation of China(Grant numbers 11932014,12372315 and 32301089)the Sichuan Science and Technology Program(Grant numbers 2022NSFSC0765 and 2022ZYD0079).
文摘Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture,which increases patient susceptibility to fragile fractures.The intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles(EVs),which play crucial roles in both pathological and physiological contexts.EVs derived from various sources exert distinct effects on osteoporosis.Specifically,EVs released by osteoblasts,endothelial cells,myocytes,and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins,miRNAs,and cytokines.Conversely,EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone formation.Furthermore,the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is promising.Here,we review the current understanding of the impact of EVs on bone homeostasis,including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in osteoporosis.Furthermore,we present an overview of the latest research progress on diagnosing and treating osteoporosis by using EVs.Finally,we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.
基金This work received support from the following sources:the National Natural Science Foundation of China(Grants 82170844 and 82270613)the Sichuan Science and Technology Program(Grants 2022YFH0045 and 2022YFH0102)+4 种基金the 111 Project(Grant B18035),the 1·3·5 project for Disciplines of Excellence at West China Hospital,Sichuan University(Grant ZYGD22007 and ZYJC21004)Ningbo Top Medical and Health Research Program(No.2023030514)Ningbo Medical and Health Brand Discipline(Grant No.PPXK2018-02)Ningbo Clinical Research Center for Otolaryngology Head and Neck Disease(Grant No.2022L005)the Ministry of Education,Singapore,(Grant MOE-000395-00)to LYC.
文摘Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis,with sex-specific differences in epidemiology and pathogenesis.Specifically,females are more susceptible than males to osteoporosis,while males are more prone to disability or death from the disease.To date,sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells.Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men.This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis,mainly in a population of aging patients,chronic glucocorticoid administration,and diabetes.Moreover,we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men.Additionally,the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.
文摘Introduction: Predictions on the prevalence of diabetes mellitus, according to the International Diabetes Federation, indicated 9.3% in 2019 and nearly 10.9% of the general population in 2045. In Benin, the increase in this prevalence, according to the World Health Organization (WHO), is constantly increasing. Diabetic foot is one of its most common complications. The aim of this work was to study the prognostic factors of diabetic foot in the Department of Endocrinology, Metabolism and Nutrition of the CNHU-HKM of Cotonou. Patients and method: This is a descriptive and analytical retrospective study of the prognostic factors of diabetic foot over a period of 3 years from January 2019 to December 2021 in patients who have been hospitalized or followed on an outpatient basis for diabetic foot in the Endocrinology, Metabolism and Nutrition Department of the CNHU-HKM of Cotonou. Results: A total of 112 patients were included in this study. The average age of the patients was 59.70 ± 2.10 years. A male predominance was noted with a sex ratio (M/F) of 1.7. Mixed gangrene and phlegmons were the most common lesions. According to the classification of diabetic feet according to the University of Texas, 59.1% of patients had a 100% risk of amputation. Ten patients died from sepsis (8.9%). The average blood glucose on admission was 2.74 ± 0.23 g/l, reflecting the glycemic imbalance in these patients. There is a statistically significant association between the duration of progression of diabetes, the type of lesion and amputation. Patients whose diabetes has lasted more than 30 years and patients who are not monitored have a greater risk of death. Conclusion: Diabetic patients most often consulted at a late stage, compromising conservative treatment. The duration of diabetes and the type of lesion on admission were the main factors leading to amputation, thus compromising the functional prognosis. As for death, it was mainly linked to irregular monitoring of diabetes and the duration of diabetes. Effective prevention and management of diabetic feet requires patient education about the diabetic foot and systematic screening of at-risk feet in consultation.
基金supported by the National Natural Science Foundation of China (81921002,81900970,82130027)Innovative Research Team of High-Level Local Universities in Shanghai (SHSMUZLCX20212400)+1 种基金Young Physician Innovation Team Project (QC202003)of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghai“Rising Stars of Medical Talent”Youth Development Program is also acknowledged。
文摘Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.
基金supported by the National Natural Science Foundation of China(Grant No.81673996,81904220)the Jiangmen Association for Science and Technology-Youth science and technology talent lifting project(Grant No.2022-2023).
文摘Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.
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.
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.
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.
文摘Introduction: Macroangiopathy plays an important role, with a high prevalence of morbidity and mortality in diabetic patients. The aim was to study the epidemiological, clinical, paraclinical, therapeutic and evolutionary profile of macroangiopathy in diabetic patients in the internal medicine department of the Abass Ndao hospital. Patients and methods: This was a descriptive and analytical cross-sectional study. Our investigations were recruited over a 7-year period (January 1, 2016 to December 31, 2022). Results: Three hundred and fifty-nine (359) patients (10.22%) were enrolled. The mean age was 62.83 years, with extremes ranging from 17 to 98 years. The [60 - 69] age group was more representative (37.32%). Women accounted for 180 cases (50.1%), with a sex ratio (m/f) of 0.99. The average duration of diabetes was 11.86 years. Average consultation time was 38.07 days, with extremes ranging from 1 to 368 days. Average hospital stay was 7.65 days. Inaugural diabetes was noted in 12 cases (3.34%). Type 2 diabetes accounted for 95.82% (n = 344) of patients. Hypertension was present in 150 patients (41.8%). Patients with 2 risk factors accounted for 173 cases (48.18%). Nineteen patients had already had a stroke (5.29% of cases). Fourteen (14) patients (4.2%) were amputees. Obliterative arteriopathy of the lower limbs (AOMI) was noted in 193 patients (54%). Stroke was noted in 101 patients (28%). Ischemic heart disease (IHD) was noted in 38 patients (11%). AOMI was more common in males (110 patients, 57%) than in females (43%). Seventy-three (73) patients (20.3%) died. Predictors of death were age over 60 and the existence of more than two cardiovascular risk factors. Conclusion: Diabetic macroangiopathy is a major cause of morbidity and mortality. The development and implementation of a prevention and management program is essential.
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.
文摘Introduction: Cardiovascular disease is the leading cause of death in diabetics. The objective of our study was to investigate the echocardiographic aspects of type 2 diabetics. Patients and Method: Descriptive and cross-sectional study of 12 months from June 2020 to June 2021. We included hospitalized type 2 diabetics who underwent transthoracic cardiac ultrasound in the Department of Medicine and Endocrinology at the Mali Hospital. Results: We collected 128 type 2 diabetics. The predominance was male with a sex ratio of 1.2. The mean age of patients was 60.06 ± 11.54 years with extremes of 28 and 84 years. Echocardiographic abnormalities were dominated by abnormal relaxation of left ventricle in 62.5%, increased of left ventricle mass in 54.7% and left atrium dilation in 28.1%. Patients with type 2 diabetes mellitus and hypertension had more left atrium dilation with a p of 0.02. Disorders of global kinetics and systolic dysfunction were more prevalent in smoking patients with statistically significant associations, respectively, p = 0.02;p = 0.03. Dyslipidemia had a statistically significant association with segmental kinetic disorders with a p of 0.008. Duration of diabetes greater than 5 years was associated with left atrium dilation and p-value was 0.04. Conclusion: Diabetes is responsible for cardiovascular manifestations that can be identified with transthoracic echocardiography. Its performance in diabetic patients makes it possible to refine the patient’s management.
文摘Introduction: Type 1 diabetes can have acute complications, sometimes requiring hospitalization. The aim of this study was to describe the epidemiological, clinical and evolutionary aspects of type 1 diabetes in patients at the Abass Ndao National Hospital in Dakar. Patients and Methods: This was a cross-sectional, descriptive and analytical study conducted from January 01, 2010 to December 31, 2021. It focused on hospitalized type 1 diabetic patients. Epidemiological, clinical and evolutionary data were evaluated. Results: Six hundred and fifty-nine (659) patients were enrolled, representing a frequency of 11.5%. The mean age was 29.47 years, giving a sex ratio (m/f) of 0.95. Average hospital stay was 6.1 days. One hundred and forty-four (144) patients (21.8%) had inaugural diabetes. The average consultation time was 14.89 days. Acute metabolic complications were ketoacidosis in 353 patients (56%), and hypoglycemia in 1.2%. Simple hyperglycemia was noted in 113 patients (18.0%). Infection was present in 522 patients (58.3%), of whom 95 (28.2%) had a skin infection.55 patients (16.3%) had a respiratory infection. 12.3% had a dietary imbalance.176 cases (27.7%) had no imbalance.26 patients (3.9%) died, with infectious pathologies accounting for the majority of decompensation factors among the deceased (57.7%). Conclusion: Type 1 diabetes is a cause of morbidity and mortality. It is essential to develop and implement a prevention and management program.
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.
