[Objectives]To evaluate the impact of nasal insulin administration on postoperative delirium(POD)through meta-analysis.[Methods]The Cochrane Library,PubMed,Embase,Web of Science,China National Knowledge Infrastructure...[Objectives]To evaluate the impact of nasal insulin administration on postoperative delirium(POD)through meta-analysis.[Methods]The Cochrane Library,PubMed,Embase,Web of Science,China National Knowledge Infrastructure(CNKI),Wanfang Database,and China Science and Technology Journal Database(CSTJ)were systematically searched for relevant literature published prior to February 27,2025.Literature screening and data extraction were conducted by two independent researchers in accordance with predetermined inclusion and exclusion criteria.The primary observation indicator was the incidence of POD across various treatment populations.The risk ratio for the primary outcome was calculated using the Mantel-Haenszel method.The secondary outcomes included the adverse effects associated with insulin treatment,which encompassed the glycemic variability indices,the incidence of nasal irritation symptoms following administration,hypoglycemic reactions,and insulin allergic reactions.The study protocol was registered on PROSPERO(CRD420250607492)before data extraction.[Results]A total of five randomized controlled trials involving 357 patients were included in the analysis.In the adult population undergoing surgical procedures,the administration of insulin via nasal delivery was found to significantly reduce the incidence of POD[RR=0.35,95%CI(0.23-0.53),P<0.001].The results of the subgroup analysis indicated that there were notable differences in the effectiveness of various doses of insulin administered nasally in preventing POD.Specifically,both the 20 U dose group[RR=0.45,95%CI:(0.29,0.70),P<0.001]and the 30 U dose group[RR=0.01,95%CI:(0.03,0.42),P<0.001]showed a significantly lower incidence of POD compared to the control group,with statistically significant conclusions.Conversely,the 40 U dose group[RR=0.47,95%CI:(0.17,1.34),P=0.16]yielded no statistically significant difference.Furthermore,the efficacy in preventing POD was found to be greater in the 30 U dose group compared to the 20 U dose group.Additionally,two cases of hypoglycemic reactions and increased nasal irritation symptom scores were reported in the 40 U dose group across the entire study population(P<0.05),suggesting potential adverse risks associated with this dosage.[Conclusions]The nasal administration of insulin significantly decreases the incidence of POD at a specific dosage,with optimal efficacy and high safety observed at a dosage of 30 U.展开更多
AIM:To study the expression of human insulin gene in gastrointestinal tracts of diabetic rats. METHODS: pCMV.Ins, an expression plasmid of the human insulin gene, wrapped with chitosan nanoparticles, was transfected t...AIM:To study the expression of human insulin gene in gastrointestinal tracts of diabetic rats. METHODS: pCMV.Ins, an expression plasmid of the human insulin gene, wrapped with chitosan nanoparticles, was transfected to the diabetic rats through lavage and coloclysis, respectively. Fasting blood glucose and plasma insulin levels were measured for 7 d. Reverse transcription polymerase chain reaction (RT-PCR) analysis and Western blot analysis were performed to confirm the expression of human insulin gene. RESULTS: Compared with the control group, the fasting blood glucose levels in the lavage and coloclysis groups were decreased significantly in 4 d (5.63 ± 0.48 mmol/L and 5.07 ± 0.37 mmol/L vs 22.12 ± 1.31 mmol/L, respectively, P < 0.01), while the plasma insulin levels were much higher (32.26 ± 1.81 μIU/mL and 32.79 ± 1.84 μIU/mL vs 14.23 ± 1.38 μIU/mL, respectively, P < 0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and coloclysis groups. CONCLUSION: Human insulin gene wrapped with chitosan nanoparticles can be successfully transfected to rats through gastrointestinal tract, indicating that chitosan is a promising non-viral vector.展开更多
Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is...Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.展开更多
The current global cybersecurity landscape, characterized by the increasing scale and sophistication of cyberattacks, underscores the importance of integrating Cyber Threat Intelligence (CTI) into Land Administration ...The current global cybersecurity landscape, characterized by the increasing scale and sophistication of cyberattacks, underscores the importance of integrating Cyber Threat Intelligence (CTI) into Land Administration Systems (LAS). LAS services involve requests and responses concerning public and private cadastral data, including credentials of parties, ownership, and spatial parcels. This study explores the integration of CTI in LAS to enhance cyber resilience, focusing on the unique vulnerabilities of LAS, such as sensitive data management and interconnection with other critical systems related to spatial data uses and changes. The approach employs a case study of a typical country-specific LAS to analyse structured vulnerabilities and their attributes to determine the degree of vulnerability of LAS through a quantitative inductive approach. The analysis results indicate significant improvements in identifying and mitigating potential threats through CTI integration, thus enhancing cyber resilience. These findings are crucial for policymakers and practitioners to develop robust cybersecurity strategies for LAS.展开更多
In recent years,the operational landscape of companies within the digital economy has experienced significant transformations.Embracing cutting-edge ideologies and digital innovations has not only created diverse aven...In recent years,the operational landscape of companies within the digital economy has experienced significant transformations.Embracing cutting-edge ideologies and digital innovations has not only created diverse avenues for growth but also led to substantial progress in certain areas while phasing out and optimizing several business models.Against this backdrop,employing effective and rational strategies to enhance corporate management standards is crucial.This is particularly important given the imperfections in current management systems,the shortage of specialized talent,and the need for digital capability improvements,all of which are vital for ensuring the long-term stability and success of enterprises.With this in mind,this paper explores corporate administration models and proposes several practical solutions to address challenges faced in business management under the digital economy,aiming to serve as a valuable resource for professionals and decision-makers alike.展开更多
Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory...Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.展开更多
The business environment directly impacts the level of regional economic development.As times change and society progresses,it is essential to create a favorable business environment for enterprises to better promote ...The business environment directly impacts the level of regional economic development.As times change and society progresses,it is essential to create a favorable business environment for enterprises to better promote economic growth and social civilization.This paper explores methods and strategies for optimizing the business environment from a public management perspective.By analyzing the significance of optimizing the business environment and addressing its current limitations,it offers practical recommendations aimed at comprehensively advancing business environment optimization and providing a solid foundation for the healthy development of enterprises.展开更多
With the gradual acceleration of information construction in colleges and universities,digital campus and smart campus have gradually become important means for colleges and universities to scientifically manage the c...With the gradual acceleration of information construction in colleges and universities,digital campus and smart campus have gradually become important means for colleges and universities to scientifically manage the campus.They have been applied to teaching,scientific research,student management,and other fields,improving the quality and efficiency of management.This paper mainly studies the intelligent educational administration management system based on data mining technology.Firstly,this paper introduces the application process of data mining technology,and builds an intelligent educational administration management system based on data mining technology.Then,this paper optimizes the application of the Apriori algorithm in educational administration management through transaction compression and frequent sampling.Compared with the traditional Apriori algorithm,the optimized Apriori algorithm in this paper has a shorter execution time under the same minimum support.展开更多
As the role of extracellular vesicles(EVs)in stem cell therapy is increasingly recognized,more researchers regard them as a promising new natural delivery system.When exerting therapeutic effects,EVs exhibit several a...As the role of extracellular vesicles(EVs)in stem cell therapy is increasingly recognized,more researchers regard them as a promising new natural delivery system.When exerting therapeutic effects,EVs exhibit several advantages,including low immunogenicity/cytotoxicity,the ability to traverse biological barriers,and high potential for engineering.However,several challenges remain in the clinical application of EVs.Their plasma half-life is relatively short,and they tend to accumulate in parenchymal organs(e.g.,liver and spleen)within a short time.Moreover,their targeting capabilities are neither precise nor highly effective.Additionally,EVs lack controlled and sustained release properties,necessitating the design of effective delivery strategies to ensure that therapeutic concentrations are achieved and maintained at the target site for an adequate duration.This review summarizes the latest drug delivery strategies involving EVs,focusing on systemic and local applications.It introduces various engineering approaches,administration strategies,and auxiliary delivery systems.Finally,the review discusses existing challenges in EV-based drug delivery and provides insights into the trends for future development in this field.展开更多
Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary informati...Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary information about adverse reactions is principally derived from clinical trials;however,there is a notable dearth of substantial real-world studies.Methods:In this research,an examination of the U.S.Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database was performed to evaluate the potential side effects of lenvatinib.The FAERS database revealed a total of 20,290 reported adverse events associated with lenvatinib.Different algorithms for repeated measure analysis were employed to ascertain the significance of these adverse reactions.Results:The study identified 170 instances of adverse events(AEs)induced by lenvatinib,incorporating several significant adverse reactions that the product label does not mention.The investigation also evaluated the onset periods of the adverse reactions,pinpointing a median time of 43 days.The majority of adverse reactions manifested within the initial month of lenvatinib use.Sex-specific analysis revealed disparities in high risk adverse reactions between females(vascular and lymphatic diseases,and neuronal organ diseases)and males(death and infectious diseases).Our data mining has unveiled adverse reactions beyond those mentioned within the instructions,such as osteonecrosis of the jaw,cholecystitis,cholangitis,dehydration,tumor lysis syndrome,type 1 diabetes,hyperammonemia,liver abscess,interstitial lung disease,pneumothorax,sudden death,and aortic dissection.Conclusion:The insights derived from these findings contribute significant nuances for optimizing lenvatinib use,enhancing its efficacy,and substantially mitigating potential side effects.These data elements will substantially enhance the implementation of the drug in a clinical environment.展开更多
Objective:The World Health Organization recommends annual preventive chemotherapy with a single dose of praziquantel at≥75%treatment coverage,but as of 2021,the national coverage rate in Nigeria among children falls ...Objective:The World Health Organization recommends annual preventive chemotherapy with a single dose of praziquantel at≥75%treatment coverage,but as of 2021,the national coverage rate in Nigeria among children falls below 10%.This qualitative study sought to explore the barriers and facilitators to implementing large-scale praziquantel mass drug administration(MDA)programs for school-aged children in Nigeria to delineate tools and strategies that could improve the scaling-up and effectiveness of school-based praziquantel MDA programs.Methods:An exploratory qualitative study was conducted with stakeholders with experience in MDAs involving praziquantel or related preventive chemotherapy drugs in Nigeria.Through snowball sampling,30 stakeholders with experience in praziquantel school-based MDA in Nigeria were interviewed.An inductive approach was used to generate broad themes based on the barriers and facilitators identified by the key informants.Results:A total of 45 barriers and 36 facilitators were identified and grouped inductively into eight themes:funding and resources,design and composition of praziquantel tablets,knowledge and awareness mobilization,government,nongovernmental organization,and school engagement,data management,logistics,training,and security.Conclusion:This qualitative study reveals a wide range of barriers and facilitators in the MDA of praziquantel in Nigeria and uncovered critical points along the implementation pathway based on the locus of the barriers and facilitators identified.Collaboration with national,international,and non-profit organizations,and drug education through promotional materials,were the most frequently mentioned facilitators of the MDA program.In addition,insufficient program funding,and the complexity of the supply chain were the most cited barriers.展开更多
Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigati...Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigation.The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain.The secondary aim was to determine whether sex is a confounding factor.Methods:Thirty adult Kramnik mice,divided equally into three groups,were ad-ministered CBD oil intrabuccally at three doses-10,20,and 30 mg/kg,euthanized 6 h later,and whole brain,urine,and blood samples were collected.Liquid chro-matography with tandem mass spectrometry was used to analyze the collected samples.Results:CBD and its three metabolites—7-carboxy cannabidiol(7-COOH-CBD),7-hydroxy cannabidiol(7-OH-CBD)and 6-hydroxy cannabidiol(6-OH-CBD),were identified and quantified in all samples.The 10 and 20 mg/kg doses of CBD produced similar results in the brain,but the group given the 10 mg/kg dose had the least vari-ation.The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples,but also the greatest variation.Sex only became a confounding factor at 30 mg/kg.Conclusions:This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples,with the least variation among the doses,and sex was not a confounder at 10 mg/kg.展开更多
BACKGROUND L-arginine(L-Arg)is one of the most widely used amino acids in dietary and pharmacological products.However,the evidence on its usefulness and dose limitations,especially in diabetics is still controversial...BACKGROUND L-arginine(L-Arg)is one of the most widely used amino acids in dietary and pharmacological products.However,the evidence on its usefulness and dose limitations,especially in diabetics is still controversial.AIM To investigate the effects of chronic administration of different doses of L-Arg on the cardiac muscle of type 2 diabetic rats.METHODS Of 96 male rats were divided into 8 groups as follows(n=12):Control,0.5 g/kg L-Arg,1 g/kg L-Arg,1.5 g/kg L-Arg,diabetic,diabetic+0.5 g/kg L-Arg,diabetic+1 g/kg L-Arg,and diabetic+1.5 g/kg L-Arg;whereas L-Arg was orally administered for 3 months to all treated groups.RESULTS L-Arg produced a moderate upregulation of blood glucose levels to normal rats,but when given to diabetics a significant upregulation was observed,associated with increased nitric oxide,inflammatory cytokines,and malonaldehyde levels in diabetic rats treated with 1 g/kg L-Arg and 1.5 g/kg L-Arg.A substantial decrease in the antioxidant capacity,superoxide dismutase,catalase,glutathione peroxidase,reduced glutathione concentrations,and Nrf-2 tissue depletion were observed at 1 g/kg and 1.5 g/kg L-Arg diabetic treated groups,associated with myocardial injury,fibrosis,α-smooth muscle actin upregulation,and disruption of desmin cardiac myofilaments,and these effects were not noticeable at normal treated groups.On the other hand,L-Arg could significantly improve the lipid profile of diabetic rats and decrease their body weights.CONCLUSION L-Arg dose of 1 g/kg or more can exacerbates the diabetes injurious effects on the myocardium,while 0.5 g/kg dose can improve the lipid profile and decrease the body weight.展开更多
Objective:To analyze the effectiveness of the matrix medical administration model in enhancing medical safety management.Method:A total of 39 medical incidents in the hospital from September 2020 to September 2022 wer...Objective:To analyze the effectiveness of the matrix medical administration model in enhancing medical safety management.Method:A total of 39 medical incidents in the hospital from September 2020 to September 2022 were selected as the reference group,implementing conventional medical administration.Another 39 medical incidents from October 2022 to October 2024 were chosen as the experimental group,adopting the matrix medical administration model.The practical indicators such as causes of medical disputes,dispute compensation,medical injury appraisal results,and diagnosis and treatment quality indicators were compared between the two groups.Results:In the experimental group,the primary reasons for medical disputes were patient-related,and most disputes resulted in no compensation.After medical injury appraisal,most cases were not considered medical injuries.The comparison between the two groups was statistically significant(P<0.05).The diagnosis and treatment quality indicators of the experimental group were superior to those of the reference group(P<0.05).Conclusion:The matrix medical administration model can reduce medical disputes caused by hospital factors,decrease the proportion of compensation and the incidence of medical injuries,and improve the quality of diagnosis and treatment,demonstrating high management effectiveness.展开更多
Fear memory,a predictive and protective mechanism in potentially hostile environments,elicits defensive behavioral responses that have evolved to help organisms avoid harm and ensure survival.However,excessive fear me...Fear memory,a predictive and protective mechanism in potentially hostile environments,elicits defensive behavioral responses that have evolved to help organisms avoid harm and ensure survival.However,excessive fear memories may contribute to the onset of various psychological disorders,such as panic disorder,phobias,and post-traumatic stress disorder(PTSD).展开更多
Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration,especially in orthodontic tooth movement.Abaloparatide(ABL),a synthetic analog of human PTHr P(1–34)and a clinical me...Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration,especially in orthodontic tooth movement.Abaloparatide(ABL),a synthetic analog of human PTHr P(1–34)and a clinical medication for treating osteoporosis,has recently demonstrated its potential in enhancing craniofacial bone formation.Herein,we show that intraoral submucosal injection of ABL,when combined with mechanical force,promotes in situ alveolar bone thickening.The newly formed bone is primarily located outside the original compact bone,implying its origin from the periosteum.RNA sequencing of the alveolar bone tissue revealed that the focal adhesion(FA)pathway potentially mediates this bioprocess.Local injection of ABL alone enhances cell proliferation,collagen synthesis,and phosphorylation of focal adhesion kinase(FAK)in the alveolar periosteum;when ABL is combined with mechanical force,the FAK expression is upregulated,in line with the accomplishment of the ossification.In vitro,ABL enhances proliferation,migration,and FAK phosphorylation in periosteal stem cells.Furthermore,the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor.In summary,abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis.Thus,we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation,which may prevent or repair the detrimental periodontal dehiscence,holding significant potential in dentistry.展开更多
As a prominent mode of variability in the tropical stratosphere on the interannual timescale,the Quasi-Biennial Oscillation(QBO)can significantly influence global atmospheric circulation and weather patterns.This stud...As a prominent mode of variability in the tropical stratosphere on the interannual timescale,the Quasi-Biennial Oscillation(QBO)can significantly influence global atmospheric circulation and weather patterns.This study explores the dynamic processes of QBO disruptions using the integrated climate model of the China Meteorological Administration(CMA)by nudging the tropical zonal winds toward observations.A comparative analysis with ERA5 reanalysis data shows that the nudged runs accurately replicate the general characteristics of the QBO,including the alternating QBO wind regimes and QBO disruption events.The evolution of the QBO winds is diagnosed using empirical orthogonal function and root-mean-square difference analyses,and the rarity of the disruption events is confirmed in the CMA model.Different aspects of the QBO disruptions and the relevant dynamics are present in the model.Firstly,the momentum budget analysis highlights the crucial roles of extratropical Rossby waves and non-orographic gravity waves in the transition from westerly to easterly winds during a disruption.Secondly,Kelvin waves and non-orographic gravity waves explain much of the transition from easterly to westerly winds near 40 hPa.Thirdly,the positive tendency from enhanced vertical advection further accelerates westerly momentum development via secondary meridional circulation.These findings underscore the importance of nudging techniques in understanding QBO dynamics,which provides valuable insights for future climate model improvements toward better forecasting QBO-related climate variability.Notably,due to model limitations,no QBO disruptions were simulated in the free-run experiments.展开更多
BACKGROUND Managing sudden deafness(SD)in patients with diabetes mellitus(DM)is partic-ularly challenging due to the heightened risk of adverse effects associated with systemic drug administration.This study explores ...BACKGROUND Managing sudden deafness(SD)in patients with diabetes mellitus(DM)is partic-ularly challenging due to the heightened risk of adverse effects associated with systemic drug administration.This study explores the potential of retroauricular subperiosteal injection as a localized drug delivery method for a more effective and safe treatment.AIM To compare the efficacy of retroauricular subperiosteal injection vs systemic intravenous glucocorticoid(GC)administration for SD in patients with DM and assess the effects on blood glucose levels.METHODS A total of 128 cases of type 2 DM(T2DM)with SD diagnosed and treated in Zibo Central Hospital from February 2021 to July 2023 were divided into two groups:An observation group(66 cases receiving retroauricular subperiosteal injection of methylprednisolone)and a control group(62 cases receiving systemic intravenous administration of methylprednisolone).The two groups were compared in terms of therapeutic efficacy,hearing recovery,blood glucose level changes,and incidence of adverse reactions.Binary logistic regression was used to analyze the factors affecting therapeutic efficacy.RESULTS The observation group showed a significantly higher total effective rate(90.91%)compared with the control group(75.81%,P<0.05).Additionally,pure-tone hearing threshold,fasting plasma glucose,and 2-hour postprandial blood glucose were significantly lower in the observation group compared with the control group(P<0.05).The incidence of adverse reactions was also lower in the observation group than in the control group(7.58%vs 22.58%,P<0.05).A T2DM course longer than 5 years and systemic intravenous GC administration were identified as independent risk factors for treatment inefficacy(P<0.05).INTRODUCTION Sudden deafness(SD)is a clinical emergency characterized by rapid-onset hearing loss that is often accompanied by clinical symptoms such as tinnitus and vertigo[1].Although its pathogenesis remains unclear,it is supposedly associated with factors,including inner ear microcirculation disorders,autoimmune diseases,and viral infections[2,3].Patients with diabetes are particularly susceptible to microvascular complications due to poor long-term glycemic control,affecting the ear’s microcirculation,subsequently increasing the risk of SD[4].Type 2 diabetes mellitus(T2DM),a chronic metabolic disease,causes multiple microvascular damages throughout the body,complicating SD treatment in patients with diabetes[5,6].Inner ear microcirculation disturbances in patients with diabetes may exacerbate the risk of SD,and its pathological process may be related to vascular endothelial dysfunction,inflammatory reactions,and hemorrhological changes caused by diabetes mellitus(DM)[7].Current SD treatments include glucocorticoids(GCs),vasodilators,and hyperbaric oxygen therapy[8].GCs are widely used due to their anti-inflammatory and immunosuppressive effects[9].However,systemic GCs may cause blood glucose(BG)fluctuations and even increase the risk of complications in patients with DM,limiting their clinical use in this population[10].Therefore,there is a compelling and immediate need for a local alternative solution that minimally affects the metabolic mechanisms.In recent years,retroauricular subperiosteal injection has emerged as a localized administration modality for treating SD[11].This method allows drugs to directly act on the inner ear,avoiding the side effects of systemic administration and having a minor impact on BG levels,providing a potentially effective treatment for patients with diabetes[12].However,there is limited clinical evidence to compare the efficacy and glycaemic effects of retroauricular subperiosteal injection vs systemic intravenous GC administration in patients with SD and diabetes.This study aimed to explore the efficacy of retroauricular subperiosteal injection and systemic intravenous GC administration for treating patients with SD and DM and their effects on BG,providing a safer and more effective clinical treatment approach.展开更多
Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central com...Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.展开更多
The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors ...The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors to cognitive decline.Insulin resistance impairs neuronal metabolism and synaptic function,fostering neurodegeneration as observed in Alzheimer’s disease and Down syndrome.Indeed,Down syndrome,characterized by the triplication of the APP gene,represents a valuable genetic model for studying early-onset Alzheimer’s disease and accelerated aging.Building on the link between metabolic dysfunctions and neurodegeneration,innovative strategies addressed brain insulin resistance as a key driver of cognitive decline.Intranasal insulin has shown promise in improving cognition in early Alzheimer’s disease and type 2 diabetes,supporting the concept that restoring insulin sensitivity can mitigate neurodegeneration.However,insulin-based therapies risk desensitizing insulin signaling,potentially worsening the disease.Incretins,particularly glucagon-like peptide 1 receptor agonists,offer neuroprotective benefits by enhancing insulin sensitivity,metabolism,and synaptic plasticity while reducing oxidative distress and neuroinflammation.This review focuses on current knowledge on the metabolic and molecular interactions between insulin resistance,mitochondrial dynamics(including their roles in energy metabolism),and oxidative distress regulation,as these are pivotal in both Alzheimer’s disease and Down syndrome.By addressing these interconnected mechanisms,innovative treatments may emerge for both metabolic and neurodegenerative disorders.展开更多
文摘[Objectives]To evaluate the impact of nasal insulin administration on postoperative delirium(POD)through meta-analysis.[Methods]The Cochrane Library,PubMed,Embase,Web of Science,China National Knowledge Infrastructure(CNKI),Wanfang Database,and China Science and Technology Journal Database(CSTJ)were systematically searched for relevant literature published prior to February 27,2025.Literature screening and data extraction were conducted by two independent researchers in accordance with predetermined inclusion and exclusion criteria.The primary observation indicator was the incidence of POD across various treatment populations.The risk ratio for the primary outcome was calculated using the Mantel-Haenszel method.The secondary outcomes included the adverse effects associated with insulin treatment,which encompassed the glycemic variability indices,the incidence of nasal irritation symptoms following administration,hypoglycemic reactions,and insulin allergic reactions.The study protocol was registered on PROSPERO(CRD420250607492)before data extraction.[Results]A total of five randomized controlled trials involving 357 patients were included in the analysis.In the adult population undergoing surgical procedures,the administration of insulin via nasal delivery was found to significantly reduce the incidence of POD[RR=0.35,95%CI(0.23-0.53),P<0.001].The results of the subgroup analysis indicated that there were notable differences in the effectiveness of various doses of insulin administered nasally in preventing POD.Specifically,both the 20 U dose group[RR=0.45,95%CI:(0.29,0.70),P<0.001]and the 30 U dose group[RR=0.01,95%CI:(0.03,0.42),P<0.001]showed a significantly lower incidence of POD compared to the control group,with statistically significant conclusions.Conversely,the 40 U dose group[RR=0.47,95%CI:(0.17,1.34),P=0.16]yielded no statistically significant difference.Furthermore,the efficacy in preventing POD was found to be greater in the 30 U dose group compared to the 20 U dose group.Additionally,two cases of hypoglycemic reactions and increased nasal irritation symptom scores were reported in the 40 U dose group across the entire study population(P<0.05),suggesting potential adverse risks associated with this dosage.[Conclusions]The nasal administration of insulin significantly decreases the incidence of POD at a specific dosage,with optimal efficacy and high safety observed at a dosage of 30 U.
文摘AIM:To study the expression of human insulin gene in gastrointestinal tracts of diabetic rats. METHODS: pCMV.Ins, an expression plasmid of the human insulin gene, wrapped with chitosan nanoparticles, was transfected to the diabetic rats through lavage and coloclysis, respectively. Fasting blood glucose and plasma insulin levels were measured for 7 d. Reverse transcription polymerase chain reaction (RT-PCR) analysis and Western blot analysis were performed to confirm the expression of human insulin gene. RESULTS: Compared with the control group, the fasting blood glucose levels in the lavage and coloclysis groups were decreased significantly in 4 d (5.63 ± 0.48 mmol/L and 5.07 ± 0.37 mmol/L vs 22.12 ± 1.31 mmol/L, respectively, P < 0.01), while the plasma insulin levels were much higher (32.26 ± 1.81 μIU/mL and 32.79 ± 1.84 μIU/mL vs 14.23 ± 1.38 μIU/mL, respectively, P < 0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and coloclysis groups. CONCLUSION: Human insulin gene wrapped with chitosan nanoparticles can be successfully transfected to rats through gastrointestinal tract, indicating that chitosan is a promising non-viral vector.
基金supported by the National Natural Science Foundation of China[31872674]the Jilin Talent Development Foundation Grant[20200301018RQ]the Fundamental Research Funds for the Central Universities[CGZH202206].
文摘Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.
文摘The current global cybersecurity landscape, characterized by the increasing scale and sophistication of cyberattacks, underscores the importance of integrating Cyber Threat Intelligence (CTI) into Land Administration Systems (LAS). LAS services involve requests and responses concerning public and private cadastral data, including credentials of parties, ownership, and spatial parcels. This study explores the integration of CTI in LAS to enhance cyber resilience, focusing on the unique vulnerabilities of LAS, such as sensitive data management and interconnection with other critical systems related to spatial data uses and changes. The approach employs a case study of a typical country-specific LAS to analyse structured vulnerabilities and their attributes to determine the degree of vulnerability of LAS through a quantitative inductive approach. The analysis results indicate significant improvements in identifying and mitigating potential threats through CTI integration, thus enhancing cyber resilience. These findings are crucial for policymakers and practitioners to develop robust cybersecurity strategies for LAS.
文摘In recent years,the operational landscape of companies within the digital economy has experienced significant transformations.Embracing cutting-edge ideologies and digital innovations has not only created diverse avenues for growth but also led to substantial progress in certain areas while phasing out and optimizing several business models.Against this backdrop,employing effective and rational strategies to enhance corporate management standards is crucial.This is particularly important given the imperfections in current management systems,the shortage of specialized talent,and the need for digital capability improvements,all of which are vital for ensuring the long-term stability and success of enterprises.With this in mind,this paper explores corporate administration models and proposes several practical solutions to address challenges faced in business management under the digital economy,aiming to serve as a valuable resource for professionals and decision-makers alike.
基金supported by the National Natural Science Foundation of China (32471188,32170984,82301787)。
文摘Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.
文摘The business environment directly impacts the level of regional economic development.As times change and society progresses,it is essential to create a favorable business environment for enterprises to better promote economic growth and social civilization.This paper explores methods and strategies for optimizing the business environment from a public management perspective.By analyzing the significance of optimizing the business environment and addressing its current limitations,it offers practical recommendations aimed at comprehensively advancing business environment optimization and providing a solid foundation for the healthy development of enterprises.
文摘With the gradual acceleration of information construction in colleges and universities,digital campus and smart campus have gradually become important means for colleges and universities to scientifically manage the campus.They have been applied to teaching,scientific research,student management,and other fields,improving the quality and efficiency of management.This paper mainly studies the intelligent educational administration management system based on data mining technology.Firstly,this paper introduces the application process of data mining technology,and builds an intelligent educational administration management system based on data mining technology.Then,this paper optimizes the application of the Apriori algorithm in educational administration management through transaction compression and frequent sampling.Compared with the traditional Apriori algorithm,the optimized Apriori algorithm in this paper has a shorter execution time under the same minimum support.
基金Supported by the Natural Science Foundation of Sichuan Province,No.24NSFSC0679State Key Clinical Department of Oral&Maxillofacial Surgery.
文摘As the role of extracellular vesicles(EVs)in stem cell therapy is increasingly recognized,more researchers regard them as a promising new natural delivery system.When exerting therapeutic effects,EVs exhibit several advantages,including low immunogenicity/cytotoxicity,the ability to traverse biological barriers,and high potential for engineering.However,several challenges remain in the clinical application of EVs.Their plasma half-life is relatively short,and they tend to accumulate in parenchymal organs(e.g.,liver and spleen)within a short time.Moreover,their targeting capabilities are neither precise nor highly effective.Additionally,EVs lack controlled and sustained release properties,necessitating the design of effective delivery strategies to ensure that therapeutic concentrations are achieved and maintained at the target site for an adequate duration.This review summarizes the latest drug delivery strategies involving EVs,focusing on systemic and local applications.It introduces various engineering approaches,administration strategies,and auxiliary delivery systems.Finally,the review discusses existing challenges in EV-based drug delivery and provides insights into the trends for future development in this field.
基金The 2022 Educational Teaching Reform and Research Project of Guangxi University of Traditional Chinese Medicine(2022C032).
文摘Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary information about adverse reactions is principally derived from clinical trials;however,there is a notable dearth of substantial real-world studies.Methods:In this research,an examination of the U.S.Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database was performed to evaluate the potential side effects of lenvatinib.The FAERS database revealed a total of 20,290 reported adverse events associated with lenvatinib.Different algorithms for repeated measure analysis were employed to ascertain the significance of these adverse reactions.Results:The study identified 170 instances of adverse events(AEs)induced by lenvatinib,incorporating several significant adverse reactions that the product label does not mention.The investigation also evaluated the onset periods of the adverse reactions,pinpointing a median time of 43 days.The majority of adverse reactions manifested within the initial month of lenvatinib use.Sex-specific analysis revealed disparities in high risk adverse reactions between females(vascular and lymphatic diseases,and neuronal organ diseases)and males(death and infectious diseases).Our data mining has unveiled adverse reactions beyond those mentioned within the instructions,such as osteonecrosis of the jaw,cholecystitis,cholangitis,dehydration,tumor lysis syndrome,type 1 diabetes,hyperammonemia,liver abscess,interstitial lung disease,pneumothorax,sudden death,and aortic dissection.Conclusion:The insights derived from these findings contribute significant nuances for optimizing lenvatinib use,enhancing its efficacy,and substantially mitigating potential side effects.These data elements will substantially enhance the implementation of the drug in a clinical environment.
基金the Flourish Collective,a Cluster of Scholarly Prominence at the University of Toronto,Scarborough。
文摘Objective:The World Health Organization recommends annual preventive chemotherapy with a single dose of praziquantel at≥75%treatment coverage,but as of 2021,the national coverage rate in Nigeria among children falls below 10%.This qualitative study sought to explore the barriers and facilitators to implementing large-scale praziquantel mass drug administration(MDA)programs for school-aged children in Nigeria to delineate tools and strategies that could improve the scaling-up and effectiveness of school-based praziquantel MDA programs.Methods:An exploratory qualitative study was conducted with stakeholders with experience in MDAs involving praziquantel or related preventive chemotherapy drugs in Nigeria.Through snowball sampling,30 stakeholders with experience in praziquantel school-based MDA in Nigeria were interviewed.An inductive approach was used to generate broad themes based on the barriers and facilitators identified by the key informants.Results:A total of 45 barriers and 36 facilitators were identified and grouped inductively into eight themes:funding and resources,design and composition of praziquantel tablets,knowledge and awareness mobilization,government,nongovernmental organization,and school engagement,data management,logistics,training,and security.Conclusion:This qualitative study reveals a wide range of barriers and facilitators in the MDA of praziquantel in Nigeria and uncovered critical points along the implementation pathway based on the locus of the barriers and facilitators identified.Collaboration with national,international,and non-profit organizations,and drug education through promotional materials,were the most frequently mentioned facilitators of the MDA program.In addition,insufficient program funding,and the complexity of the supply chain were the most cited barriers.
基金National Research Fund of South Africa(grant number:137792).
文摘Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigation.The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain.The secondary aim was to determine whether sex is a confounding factor.Methods:Thirty adult Kramnik mice,divided equally into three groups,were ad-ministered CBD oil intrabuccally at three doses-10,20,and 30 mg/kg,euthanized 6 h later,and whole brain,urine,and blood samples were collected.Liquid chro-matography with tandem mass spectrometry was used to analyze the collected samples.Results:CBD and its three metabolites—7-carboxy cannabidiol(7-COOH-CBD),7-hydroxy cannabidiol(7-OH-CBD)and 6-hydroxy cannabidiol(6-OH-CBD),were identified and quantified in all samples.The 10 and 20 mg/kg doses of CBD produced similar results in the brain,but the group given the 10 mg/kg dose had the least vari-ation.The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples,but also the greatest variation.Sex only became a confounding factor at 30 mg/kg.Conclusions:This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples,with the least variation among the doses,and sex was not a confounder at 10 mg/kg.
基金The Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia, No. IF2/PSAU/2022/03/23339.
文摘BACKGROUND L-arginine(L-Arg)is one of the most widely used amino acids in dietary and pharmacological products.However,the evidence on its usefulness and dose limitations,especially in diabetics is still controversial.AIM To investigate the effects of chronic administration of different doses of L-Arg on the cardiac muscle of type 2 diabetic rats.METHODS Of 96 male rats were divided into 8 groups as follows(n=12):Control,0.5 g/kg L-Arg,1 g/kg L-Arg,1.5 g/kg L-Arg,diabetic,diabetic+0.5 g/kg L-Arg,diabetic+1 g/kg L-Arg,and diabetic+1.5 g/kg L-Arg;whereas L-Arg was orally administered for 3 months to all treated groups.RESULTS L-Arg produced a moderate upregulation of blood glucose levels to normal rats,but when given to diabetics a significant upregulation was observed,associated with increased nitric oxide,inflammatory cytokines,and malonaldehyde levels in diabetic rats treated with 1 g/kg L-Arg and 1.5 g/kg L-Arg.A substantial decrease in the antioxidant capacity,superoxide dismutase,catalase,glutathione peroxidase,reduced glutathione concentrations,and Nrf-2 tissue depletion were observed at 1 g/kg and 1.5 g/kg L-Arg diabetic treated groups,associated with myocardial injury,fibrosis,α-smooth muscle actin upregulation,and disruption of desmin cardiac myofilaments,and these effects were not noticeable at normal treated groups.On the other hand,L-Arg could significantly improve the lipid profile of diabetic rats and decrease their body weights.CONCLUSION L-Arg dose of 1 g/kg or more can exacerbates the diabetes injurious effects on the myocardium,while 0.5 g/kg dose can improve the lipid profile and decrease the body weight.
文摘Objective:To analyze the effectiveness of the matrix medical administration model in enhancing medical safety management.Method:A total of 39 medical incidents in the hospital from September 2020 to September 2022 were selected as the reference group,implementing conventional medical administration.Another 39 medical incidents from October 2022 to October 2024 were chosen as the experimental group,adopting the matrix medical administration model.The practical indicators such as causes of medical disputes,dispute compensation,medical injury appraisal results,and diagnosis and treatment quality indicators were compared between the two groups.Results:In the experimental group,the primary reasons for medical disputes were patient-related,and most disputes resulted in no compensation.After medical injury appraisal,most cases were not considered medical injuries.The comparison between the two groups was statistically significant(P<0.05).The diagnosis and treatment quality indicators of the experimental group were superior to those of the reference group(P<0.05).Conclusion:The matrix medical administration model can reduce medical disputes caused by hospital factors,decrease the proportion of compensation and the incidence of medical injuries,and improve the quality of diagnosis and treatment,demonstrating high management effectiveness.
基金supported by the National Natural Science Foundation of China(82104138)the Zhejiang Provincial Natural Science Foundation of China(LY24H310003).
文摘Fear memory,a predictive and protective mechanism in potentially hostile environments,elicits defensive behavioral responses that have evolved to help organisms avoid harm and ensure survival.However,excessive fear memories may contribute to the onset of various psychological disorders,such as panic disorder,phobias,and post-traumatic stress disorder(PTSD).
基金supported by the National Natural Science Foundation of China(NSFC)(82371003)the Elite Research Grant of the International Orthodontics Foundation 2022。
文摘Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration,especially in orthodontic tooth movement.Abaloparatide(ABL),a synthetic analog of human PTHr P(1–34)and a clinical medication for treating osteoporosis,has recently demonstrated its potential in enhancing craniofacial bone formation.Herein,we show that intraoral submucosal injection of ABL,when combined with mechanical force,promotes in situ alveolar bone thickening.The newly formed bone is primarily located outside the original compact bone,implying its origin from the periosteum.RNA sequencing of the alveolar bone tissue revealed that the focal adhesion(FA)pathway potentially mediates this bioprocess.Local injection of ABL alone enhances cell proliferation,collagen synthesis,and phosphorylation of focal adhesion kinase(FAK)in the alveolar periosteum;when ABL is combined with mechanical force,the FAK expression is upregulated,in line with the accomplishment of the ossification.In vitro,ABL enhances proliferation,migration,and FAK phosphorylation in periosteal stem cells.Furthermore,the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor.In summary,abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis.Thus,we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation,which may prevent or repair the detrimental periodontal dehiscence,holding significant potential in dentistry.
基金funded by the National Natural Science Foundation of China(Grant No.42275056).
文摘As a prominent mode of variability in the tropical stratosphere on the interannual timescale,the Quasi-Biennial Oscillation(QBO)can significantly influence global atmospheric circulation and weather patterns.This study explores the dynamic processes of QBO disruptions using the integrated climate model of the China Meteorological Administration(CMA)by nudging the tropical zonal winds toward observations.A comparative analysis with ERA5 reanalysis data shows that the nudged runs accurately replicate the general characteristics of the QBO,including the alternating QBO wind regimes and QBO disruption events.The evolution of the QBO winds is diagnosed using empirical orthogonal function and root-mean-square difference analyses,and the rarity of the disruption events is confirmed in the CMA model.Different aspects of the QBO disruptions and the relevant dynamics are present in the model.Firstly,the momentum budget analysis highlights the crucial roles of extratropical Rossby waves and non-orographic gravity waves in the transition from westerly to easterly winds during a disruption.Secondly,Kelvin waves and non-orographic gravity waves explain much of the transition from easterly to westerly winds near 40 hPa.Thirdly,the positive tendency from enhanced vertical advection further accelerates westerly momentum development via secondary meridional circulation.These findings underscore the importance of nudging techniques in understanding QBO dynamics,which provides valuable insights for future climate model improvements toward better forecasting QBO-related climate variability.Notably,due to model limitations,no QBO disruptions were simulated in the free-run experiments.
文摘BACKGROUND Managing sudden deafness(SD)in patients with diabetes mellitus(DM)is partic-ularly challenging due to the heightened risk of adverse effects associated with systemic drug administration.This study explores the potential of retroauricular subperiosteal injection as a localized drug delivery method for a more effective and safe treatment.AIM To compare the efficacy of retroauricular subperiosteal injection vs systemic intravenous glucocorticoid(GC)administration for SD in patients with DM and assess the effects on blood glucose levels.METHODS A total of 128 cases of type 2 DM(T2DM)with SD diagnosed and treated in Zibo Central Hospital from February 2021 to July 2023 were divided into two groups:An observation group(66 cases receiving retroauricular subperiosteal injection of methylprednisolone)and a control group(62 cases receiving systemic intravenous administration of methylprednisolone).The two groups were compared in terms of therapeutic efficacy,hearing recovery,blood glucose level changes,and incidence of adverse reactions.Binary logistic regression was used to analyze the factors affecting therapeutic efficacy.RESULTS The observation group showed a significantly higher total effective rate(90.91%)compared with the control group(75.81%,P<0.05).Additionally,pure-tone hearing threshold,fasting plasma glucose,and 2-hour postprandial blood glucose were significantly lower in the observation group compared with the control group(P<0.05).The incidence of adverse reactions was also lower in the observation group than in the control group(7.58%vs 22.58%,P<0.05).A T2DM course longer than 5 years and systemic intravenous GC administration were identified as independent risk factors for treatment inefficacy(P<0.05).INTRODUCTION Sudden deafness(SD)is a clinical emergency characterized by rapid-onset hearing loss that is often accompanied by clinical symptoms such as tinnitus and vertigo[1].Although its pathogenesis remains unclear,it is supposedly associated with factors,including inner ear microcirculation disorders,autoimmune diseases,and viral infections[2,3].Patients with diabetes are particularly susceptible to microvascular complications due to poor long-term glycemic control,affecting the ear’s microcirculation,subsequently increasing the risk of SD[4].Type 2 diabetes mellitus(T2DM),a chronic metabolic disease,causes multiple microvascular damages throughout the body,complicating SD treatment in patients with diabetes[5,6].Inner ear microcirculation disturbances in patients with diabetes may exacerbate the risk of SD,and its pathological process may be related to vascular endothelial dysfunction,inflammatory reactions,and hemorrhological changes caused by diabetes mellitus(DM)[7].Current SD treatments include glucocorticoids(GCs),vasodilators,and hyperbaric oxygen therapy[8].GCs are widely used due to their anti-inflammatory and immunosuppressive effects[9].However,systemic GCs may cause blood glucose(BG)fluctuations and even increase the risk of complications in patients with DM,limiting their clinical use in this population[10].Therefore,there is a compelling and immediate need for a local alternative solution that minimally affects the metabolic mechanisms.In recent years,retroauricular subperiosteal injection has emerged as a localized administration modality for treating SD[11].This method allows drugs to directly act on the inner ear,avoiding the side effects of systemic administration and having a minor impact on BG levels,providing a potentially effective treatment for patients with diabetes[12].However,there is limited clinical evidence to compare the efficacy and glycaemic effects of retroauricular subperiosteal injection vs systemic intravenous GC administration in patients with SD and diabetes.This study aimed to explore the efficacy of retroauricular subperiosteal injection and systemic intravenous GC administration for treating patients with SD and DM and their effects on BG,providing a safer and more effective clinical treatment approach.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC)+6 种基金STI2030-Major Projects(2021ZD0202700,to HY)the National Natural Science Foundation of China(32241004,to HY)the Natural Science Foundation of Zhejiang Province of China(LR24C090001,to HY)Key R&D Program of Zhejiang Province(2024SSYS0017,to HY)CAMS Innovation Fund for Medical Sciences(2019-12M-5-057,to HY)Fundamental Research Funds for the Central Universities(226-2022-00193,to HY)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-01,to HY)。
文摘Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.
基金supported by Fondi Ateneo grants funded by Sapienza University (#RM120172A3160B53) to EBfunds from Jerome-Lejeune Foundation (#1887-2019b) to EBthe European Union–Next Generation EU (Project ECS 0000024Rome Technopole,–CUP B83C22002820006, NRPMission 4 Component 2 Investment 1.5 to LRR)
文摘The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors to cognitive decline.Insulin resistance impairs neuronal metabolism and synaptic function,fostering neurodegeneration as observed in Alzheimer’s disease and Down syndrome.Indeed,Down syndrome,characterized by the triplication of the APP gene,represents a valuable genetic model for studying early-onset Alzheimer’s disease and accelerated aging.Building on the link between metabolic dysfunctions and neurodegeneration,innovative strategies addressed brain insulin resistance as a key driver of cognitive decline.Intranasal insulin has shown promise in improving cognition in early Alzheimer’s disease and type 2 diabetes,supporting the concept that restoring insulin sensitivity can mitigate neurodegeneration.However,insulin-based therapies risk desensitizing insulin signaling,potentially worsening the disease.Incretins,particularly glucagon-like peptide 1 receptor agonists,offer neuroprotective benefits by enhancing insulin sensitivity,metabolism,and synaptic plasticity while reducing oxidative distress and neuroinflammation.This review focuses on current knowledge on the metabolic and molecular interactions between insulin resistance,mitochondrial dynamics(including their roles in energy metabolism),and oxidative distress regulation,as these are pivotal in both Alzheimer’s disease and Down syndrome.By addressing these interconnected mechanisms,innovative treatments may emerge for both metabolic and neurodegenerative disorders.
