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
Both geniposide （Ge） and natural borneol （NB） are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. ...Both geniposide （Ge） and natural borneol （NB） are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. The concentrations of Ge in plasma were determined by reversed-phase high-performance liquid chromatography （HPLC） after intranasal administration of Ge （4 mg/kg） alone and combined with different doses （0.08, 0.8, and 8 mg/kg） of NB. The intravenous administration was given as a reference （4 mg/kg of Ge and 8 mg/kg of NB）. Compared with the intravenous administration, the absolute bioavailability of Ge was 76.14% through intranasal administration combined with NB. Compared with the intranasal administration of Ge alone, Ge could be absorbed rapidly in the nasal cavity combined with NB; the peak time of Ge in the plasma became shorter （3-5 min vs. 40 min）; the peak concentration became higher （1.32-4.25 IJg/ml vs. 0.67 ug/ml）; and, the relative bioavailability of Ge combined with NB was 90.3%-237.8%. The enhancing effect was attenuated as the dose of NB decreased. The results indicated that NB can accelerate the absorption of Ge dose-dependently in the nasal cavity.展开更多
Tetrabromobisphenol A（TBBPA） and its derivatives are now being highly concerned due to their emerging environmental occurrence and deleterious effects on non-target organisms.Considering the potential neurotoxicity ...Tetrabromobisphenol A（TBBPA） and its derivatives are now being highly concerned due to their emerging environmental occurrence and deleterious effects on non-target organisms.Considering the potential neurotoxicity of TBBPA derivatives which has been demonstrated in vitro, what could happen in vivo is worthy of being studied. Tetrabromobisphenol A bis（2-hydroxyethyl ether）（TBBPA-BHEE）, a representative TBBPA derivative, was selected for a21-day exposure experiment on neonatal Sprague Dawley（SD） rats through intranasal administration. The neurobehavioral, histopathological changes, and differentially expressed genes based on RNA microarray were investigated to evaluate the neurological effects of this chemical. The results indicated that TBBPA-BHEE exposure significantly compromised the motor co-ordination performance and the locomotor activities（p 〈 0.05）. The neurobehavioral phenotype could be attributed to the obvious histopathological changes in both cerebrum and cerebellum, such as neural cell swelling, microglial activation and proliferation. A total of 911 genes were up-regulated, whereas 433 genes were down-regulated. Gene set enrichment analysis showed multiple signaling pathways, including ubiquitin-mediated proteolysis and wingless-int（Wnt） signaling pathway etc. were involved due to TBBPA-BHEE exposure. The gene ontology enrichment analysis showed the basic cellular function and the neurological processes like synaptic transmission were influenced. The toxicological effects of TBBPA-BHEE observed in this study suggested the potential neuronal threaten from unintended exposure,which would be of great value in the biosafety evaluation of TBBPA derivatives.展开更多
Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,...Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.展开更多
We report a case of recurrent glioblastoma (GBM) successfully treated with the Ras inhibitor monoterpene perillyl alcohol by intranasal administration. A 37-years-old white woman had been previously submitted to three...We report a case of recurrent glioblastoma (GBM) successfully treated with the Ras inhibitor monoterpene perillyl alcohol by intranasal administration. A 37-years-old white woman had been previously submitted to three neurosurgical procedures, in June 2000 for radical tumor excision of grade II astrocytoma;in July 2003 for first recurrence of type IV glioma and in August 2004 for GBM recurrence. After last surgery, patient started a new cycle of chemotherapy but was refractory to treatment, presented clinical adverse effects and resonance image scan showed no reduction of tumoral lesion. Patient was then considered out of therapeutic possibilities and indicated for supportive treatment. On March 2005 patient joined Phase I/II clinical trial for assess the efficacy of the monoterpene POH, a Ras inhibitor. POH was administered by intranasal route four times a day (268 mg daily) as single chemotherapy agent. Image scans performed 3 and 5 years later revealed marked reduction of enhancing lesion. This illustrative case demonstrates that intranasal administration of the monoterpene POH as a single agent was an effective therapeutic strategy capable to sustain long-term regression of recurrent glioma without clinical and laboratory toxicity.展开更多
Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were random...Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were randomly divided into two groups.The fate of drug in the serum of rats was monitered after intranasal and intragastic administration of Alprazolam 2 mg·kg-1.Serum levels of Alprazolam were determined by reversed-phase HPLC with Diode array detectors(DAD).Chromatographic conditions were adopted with ODS column as solid phase,methanaol-0.02 M ammonium acetate(pH=5.0)(60∶40)as mobile phase at a flow rate of 1.0 mL·min-1.The detection wavelength was 223 nm.The concentration-time data were analyzed using 3P87 program,and the pharmacokinetic parameters were compared by t-test.Results The pharmacokinetic characteristics were fit to two and one compartment opened model after intranasal and intragastic administration of Alprazolam,respectively.The drug absorption was quicker and the serum concentrations of Alprazolam was significantly higher in rats after intranasal administration group than that intragastic administration group(P<0.05).The eliminate parameters between the two groups were no significant difference(P>0.05).Means of pharmacokinetic parameters in intranasal and intragastic groups were:Ka 37.35±22.98 vs 11.57±12.47 h-1(P<0.05),t1/2ka0.025±0.013 vs 0.156±0.122 h(P<0.05),β(Ke)0.3131±0.1194 vs 0.3091±0.1216 h-1(P>0.05),t1/2β(t1/2Ke)2.51±0.99 vs 2.54±0.97 h(P>0.05),tmax 0.156±0.069 vs 0.618±0.414 h(P<0.01),Cmax 353.11±96.30 vs 62.09±35.08 μg·L-1(P<0.01),AUC 1111.6±473.2 vs 274.1±185.3 μg·L-1·h(P<0.01).Conclusions Alprazolam was absorbed quickly in rats after intranasal administration.And the serum concentration and bioavailability can be significantly increased after intranasal administration,which may be an effective preparation as nasal drug delivery system.展开更多
OBJECTIVE To evaluate the protective effects of resveratrol nanosuspensions loaded in situ hydrogel on Alzheimer disease model mice after intranasal administration. METHODS Resveratrol nanosuspensions were fabricated ...OBJECTIVE To evaluate the protective effects of resveratrol nanosuspensions loaded in situ hydrogel on Alzheimer disease model mice after intranasal administration. METHODS Resveratrol nanosuspensions were fabricated by antisolvent nano-precipitation method,and then dispersed into0.5% gellan gum to form resveratrol nanosuspenisons loaded ionic sensitive in situ hydrogel. The Alzheimer′s disease models were induced by lateral ventricle injection of Aβ_(25~35)and the protection and treatment effects of resveratrol nanosuspensions loaded in situ hydrogel on study and memory capability were performed after intranasal administration in water maze experiments. The analyses of the changes of cholinergic neurotransmitters in the brain were also determined according to the contents of acetylcholine(ACh),choline acetyltransferase(ChAT) and acetylcholinesterase(AChE). RESULTS Behavior assessment disclosed that in position navigation,escape latency test,each of experimental animals showed a decreased trend with swim training days increase,indicating that in the training process they had the ability of learning and memory in looking for the platform. Compared with the control group,average latency of model group significantly increased. While compared with the model group,treatment group′s average latency was significantly shorter. Space exploration experiment results showed that the times of model group across target quadrant of the platform is less than that of control group. But the crossing times of treatment group with resveratrol increased compared with the model group. As for the changes of cholinergic neurotransmitters,in AD mice brain ACh content decreased; the Ch AT activity decreased,while the activity of ACh E with the ability to hydrolysis acetylcholine increased. The administration of resveratrol can decrease the activity of ACh enzymes but increase Ch AT activity and the levels of acetylcholine. CONCLUSION Resveratrol nanosuspension loaded in situ gel can ameliorate the declining ability of learning and memory of AD model mice after intranasal administration. As a promising approach for the treatment of central nervous system(CNS) disease,intranasal administration route can effectively deliver to the brain and thus enhance the therapeutic effect.展开更多
Background:Intracerebral hemorrhage(ICH)poses a significant global health burden,characterized by high mortality rates and long-term disability.Despite advancements in stroke management,effective therapeutic strategie...Background:Intracerebral hemorrhage(ICH)poses a significant global health burden,characterized by high mortality rates and long-term disability.Despite advancements in stroke management,effective therapeutic strategies targeting secondary brain injury mechanisms post-ICH remain elusive.In this study,we explored the neuroprotective potential of edaravone(EDA)in a mouse model of ICH,with particular focus on the innovative approach of intranasal administration.Methods:A total of 96 C57BL/6 mice were randomly assigned to sham group(n=32),ICH+vehicle group(n=32)and ICH+EDA group(n=32).ICH was induced using 0.5μL bacterial collagenase VII.EDA(3 mg/kg)was administered intranasally starting 2 h after ICH and every 12 h thereafter(20μL per mouse;5μL per nostril every 5 min).The ICH+vehicle group received the identical solvent at an equivalent volume as the EDA group via intranasal administration.We evaluated neurological functions through mNSS,corner turn,and forelimb placement tests.Additionally,brain water content,immunofluorescence staining,western blot analysis,Evans blue extravasation assay,and TUNEL staining were utilized to examine the neuroprotective effects of EDA in ICH.Results:Our findings demonstrate that intranasal delivery of EDA significantly alleviated neurological deficits and reduced brain injury following ICH.This was evidenced by improvements in behavioral assessments,decreased brain water content,reduced lesion volume,and diminished cell death in the perihematomal region.Notably,intranasal EDA administration preserved blood-brain barrier integrity,suppressed microglia/macrophage activation,and mitigated oxidative stress,highlighting its multifaceted neuroprotective mechanisms.Conclusion:These outcomes underscore the therapeutic promise of intranasal administration of EDA as a prospective intervention for alleviating secondary brain injury post-ICH and advocate for further translational and clinical investigations to validate its efficacy and safety in ICH patients.展开更多
In this work, some important parts of the system, and the relation between the parts, and its connections with other systems are defined, explained briefly. With this respect, the nature of the person is defined with ...In this work, some important parts of the system, and the relation between the parts, and its connections with other systems are defined, explained briefly. With this respect, the nature of the person is defined with related parts. A new science branch called ＂information science＂ is defined. Importance of the political organizing of a political party is shortly explained. The necessity of the academies for public sector, private sector, and for political administration system is expressed. How to choose a person and how a person can be choose for any part of the system is defined. For both cases ＂good and/or correct＂ system criterions, determination of the criterions, and evaluation criterions are defined. New evaluation levels are defined based on the 8-basic senses in philosophical point of view to deepen the sensitivity of the evaluations. The importance of the situation notice and how to make it for each of the association are explained. The 10 main service parameters are defined to show the interactive relations between the ideology, services, person nature and others. Present and possible future problems of a country are expressed. Aims/targets are characterized with real approach for all related sides. Other systems which proposed to be connected to continuable political administration system are shortly defined and expressed. Way of system administration and administration types are shortly explained. The importance and ways of the decision making are expressed. The general ways, types of inspection are shortly explained. Official units that could be assign for the new system are defined. The importance of these units and of the persons that could be assign for these units are expressed together with the definition of the characteristics of the persons or groups that could be. The necessity of an action planning, possible supply and demand cases are defined scientifically. The importance and necessity of sense of justice is explained to make system continuable. The methods of determination of the policies/strategies are expressed.展开更多
In this work all the political/non-political ideologies, 168 religions/beliefs/sects, nearly 1,600 ethnic origin groups are synthesized to define continuable political construction. It is found that all the past feder...In this work all the political/non-political ideologies, 168 religions/beliefs/sects, nearly 1,600 ethnic origin groups are synthesized to define continuable political construction. It is found that all the past federations, confederations, empires, ideologies, political administration systems, thoughts and senses, doctrines, etc. are in fact each reflects a special functional processes within a general system of where the kinds of services, subjects of services, way of services, service types and persons are considered and placed as a factor in it and where these factors are arranged through different priorities, weights, and also taken under record with some rules. It is evaluated that each groups, communities, societies, countries are separate models, but at the same time each of them are factors which owns different beginning points to reach a correct country structure with five new separate groups （New Era Group, Progression of The Country Group, Unity of The Country Group, Values of The Country Group, Social Progression Group）. The continuable political administration system is defined here by considering the all possible parts and by considering the other systems eormected for a country. Possible forceful factors which can effect political system administration are given. To realize political construction, some political construction methods are defined： Political construction by putting together the values, political construction based on different value, Political construction based on the new defined values, Political construction which considers stepped transition and Ideal political construction which will carry the political points of views and other standards of judgement, points of views of persons to a same line are expressed. New ideologies are put forwarded and ideal political construction for a world country is given with details. Integration of the political groups, political ideologies to the new system is explained. Some methods of politics are mentioned. Persons related with politics are classified simply.展开更多
It is critical to ensure the safety and efficacy of human drugs through drug administration. Drug administration has a long history in developed countries, such as USA, European Union and Japan, and has achieved great...It is critical to ensure the safety and efficacy of human drugs through drug administration. Drug administration has a long history in developed countries, such as USA, European Union and Japan, and has achieved great success. In this study, we summarized the important changes in the practice of drug administration in USA, European Union and Japan since 1990s. We also discussed how these changes and experience could be applied in the reform plan in drug administration in China Food and Drug Administration （CFDA）. Our suggestions on future development of CFDA include improving post-market surveillance, advancing regulatory science, strengthening service-oriented regulation, and international cooperation.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
[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
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
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
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.
基金supported by the National Natural Science Foundation of China (No. 81073057)the Key New Drug Creation and Development Programme of China (Nos. 2009ZX09502-008 and 2009ZX09308-003)the Doctoral Fund of the Ministry of Education of China(No. 20090013110007)
文摘Both geniposide （Ge） and natural borneol （NB） are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. The concentrations of Ge in plasma were determined by reversed-phase high-performance liquid chromatography （HPLC） after intranasal administration of Ge （4 mg/kg） alone and combined with different doses （0.08, 0.8, and 8 mg/kg） of NB. The intravenous administration was given as a reference （4 mg/kg of Ge and 8 mg/kg of NB）. Compared with the intravenous administration, the absolute bioavailability of Ge was 76.14% through intranasal administration combined with NB. Compared with the intranasal administration of Ge alone, Ge could be absorbed rapidly in the nasal cavity combined with NB; the peak time of Ge in the plasma became shorter （3-5 min vs. 40 min）; the peak concentration became higher （1.32-4.25 IJg/ml vs. 0.67 ug/ml）; and, the relative bioavailability of Ge combined with NB was 90.3%-237.8%. The enhancing effect was attenuated as the dose of NB decreased. The results indicated that NB can accelerate the absorption of Ge dose-dependently in the nasal cavity.
基金supported by the Major International (Regional) Joint Project (No. 21461142001)the National Basic Research Program of China (No. 2015CB453102)+2 种基金the National Natural Science Foundation of China (Nos. 21621064, 21477153)the Strategic Priority Research Program of the Chinese Academy of Science (No. 14040302)the Chinese Academy of Sciences (No. QYZDJ-SSW-DQC017)
文摘Tetrabromobisphenol A（TBBPA） and its derivatives are now being highly concerned due to their emerging environmental occurrence and deleterious effects on non-target organisms.Considering the potential neurotoxicity of TBBPA derivatives which has been demonstrated in vitro, what could happen in vivo is worthy of being studied. Tetrabromobisphenol A bis（2-hydroxyethyl ether）（TBBPA-BHEE）, a representative TBBPA derivative, was selected for a21-day exposure experiment on neonatal Sprague Dawley（SD） rats through intranasal administration. The neurobehavioral, histopathological changes, and differentially expressed genes based on RNA microarray were investigated to evaluate the neurological effects of this chemical. The results indicated that TBBPA-BHEE exposure significantly compromised the motor co-ordination performance and the locomotor activities（p 〈 0.05）. The neurobehavioral phenotype could be attributed to the obvious histopathological changes in both cerebrum and cerebellum, such as neural cell swelling, microglial activation and proliferation. A total of 911 genes were up-regulated, whereas 433 genes were down-regulated. Gene set enrichment analysis showed multiple signaling pathways, including ubiquitin-mediated proteolysis and wingless-int（Wnt） signaling pathway etc. were involved due to TBBPA-BHEE exposure. The gene ontology enrichment analysis showed the basic cellular function and the neurological processes like synaptic transmission were influenced. The toxicological effects of TBBPA-BHEE observed in this study suggested the potential neuronal threaten from unintended exposure,which would be of great value in the biosafety evaluation of TBBPA derivatives.
基金supported by KAKENHI under grant number 23K08535,22K09274(to MK)。
文摘Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.
文摘We report a case of recurrent glioblastoma (GBM) successfully treated with the Ras inhibitor monoterpene perillyl alcohol by intranasal administration. A 37-years-old white woman had been previously submitted to three neurosurgical procedures, in June 2000 for radical tumor excision of grade II astrocytoma;in July 2003 for first recurrence of type IV glioma and in August 2004 for GBM recurrence. After last surgery, patient started a new cycle of chemotherapy but was refractory to treatment, presented clinical adverse effects and resonance image scan showed no reduction of tumoral lesion. Patient was then considered out of therapeutic possibilities and indicated for supportive treatment. On March 2005 patient joined Phase I/II clinical trial for assess the efficacy of the monoterpene POH, a Ras inhibitor. POH was administered by intranasal route four times a day (268 mg daily) as single chemotherapy agent. Image scans performed 3 and 5 years later revealed marked reduction of enhancing lesion. This illustrative case demonstrates that intranasal administration of the monoterpene POH as a single agent was an effective therapeutic strategy capable to sustain long-term regression of recurrent glioma without clinical and laboratory toxicity.
文摘Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were randomly divided into two groups.The fate of drug in the serum of rats was monitered after intranasal and intragastic administration of Alprazolam 2 mg·kg-1.Serum levels of Alprazolam were determined by reversed-phase HPLC with Diode array detectors(DAD).Chromatographic conditions were adopted with ODS column as solid phase,methanaol-0.02 M ammonium acetate(pH=5.0)(60∶40)as mobile phase at a flow rate of 1.0 mL·min-1.The detection wavelength was 223 nm.The concentration-time data were analyzed using 3P87 program,and the pharmacokinetic parameters were compared by t-test.Results The pharmacokinetic characteristics were fit to two and one compartment opened model after intranasal and intragastic administration of Alprazolam,respectively.The drug absorption was quicker and the serum concentrations of Alprazolam was significantly higher in rats after intranasal administration group than that intragastic administration group(P<0.05).The eliminate parameters between the two groups were no significant difference(P>0.05).Means of pharmacokinetic parameters in intranasal and intragastic groups were:Ka 37.35±22.98 vs 11.57±12.47 h-1(P<0.05),t1/2ka0.025±0.013 vs 0.156±0.122 h(P<0.05),β(Ke)0.3131±0.1194 vs 0.3091±0.1216 h-1(P>0.05),t1/2β(t1/2Ke)2.51±0.99 vs 2.54±0.97 h(P>0.05),tmax 0.156±0.069 vs 0.618±0.414 h(P<0.01),Cmax 353.11±96.30 vs 62.09±35.08 μg·L-1(P<0.01),AUC 1111.6±473.2 vs 274.1±185.3 μg·L-1·h(P<0.01).Conclusions Alprazolam was absorbed quickly in rats after intranasal administration.And the serum concentration and bioavailability can be significantly increased after intranasal administration,which may be an effective preparation as nasal drug delivery system.
基金The project supported by the National Training Program of Innovation and Entrepreneurship for Undergraduates(201610439108)
文摘OBJECTIVE To evaluate the protective effects of resveratrol nanosuspensions loaded in situ hydrogel on Alzheimer disease model mice after intranasal administration. METHODS Resveratrol nanosuspensions were fabricated by antisolvent nano-precipitation method,and then dispersed into0.5% gellan gum to form resveratrol nanosuspenisons loaded ionic sensitive in situ hydrogel. The Alzheimer′s disease models were induced by lateral ventricle injection of Aβ_(25~35)and the protection and treatment effects of resveratrol nanosuspensions loaded in situ hydrogel on study and memory capability were performed after intranasal administration in water maze experiments. The analyses of the changes of cholinergic neurotransmitters in the brain were also determined according to the contents of acetylcholine(ACh),choline acetyltransferase(ChAT) and acetylcholinesterase(AChE). RESULTS Behavior assessment disclosed that in position navigation,escape latency test,each of experimental animals showed a decreased trend with swim training days increase,indicating that in the training process they had the ability of learning and memory in looking for the platform. Compared with the control group,average latency of model group significantly increased. While compared with the model group,treatment group′s average latency was significantly shorter. Space exploration experiment results showed that the times of model group across target quadrant of the platform is less than that of control group. But the crossing times of treatment group with resveratrol increased compared with the model group. As for the changes of cholinergic neurotransmitters,in AD mice brain ACh content decreased; the Ch AT activity decreased,while the activity of ACh E with the ability to hydrolysis acetylcholine increased. The administration of resveratrol can decrease the activity of ACh enzymes but increase Ch AT activity and the levels of acetylcholine. CONCLUSION Resveratrol nanosuspension loaded in situ gel can ameliorate the declining ability of learning and memory of AD model mice after intranasal administration. As a promising approach for the treatment of central nervous system(CNS) disease,intranasal administration route can effectively deliver to the brain and thus enhance the therapeutic effect.
文摘Background:Intracerebral hemorrhage(ICH)poses a significant global health burden,characterized by high mortality rates and long-term disability.Despite advancements in stroke management,effective therapeutic strategies targeting secondary brain injury mechanisms post-ICH remain elusive.In this study,we explored the neuroprotective potential of edaravone(EDA)in a mouse model of ICH,with particular focus on the innovative approach of intranasal administration.Methods:A total of 96 C57BL/6 mice were randomly assigned to sham group(n=32),ICH+vehicle group(n=32)and ICH+EDA group(n=32).ICH was induced using 0.5μL bacterial collagenase VII.EDA(3 mg/kg)was administered intranasally starting 2 h after ICH and every 12 h thereafter(20μL per mouse;5μL per nostril every 5 min).The ICH+vehicle group received the identical solvent at an equivalent volume as the EDA group via intranasal administration.We evaluated neurological functions through mNSS,corner turn,and forelimb placement tests.Additionally,brain water content,immunofluorescence staining,western blot analysis,Evans blue extravasation assay,and TUNEL staining were utilized to examine the neuroprotective effects of EDA in ICH.Results:Our findings demonstrate that intranasal delivery of EDA significantly alleviated neurological deficits and reduced brain injury following ICH.This was evidenced by improvements in behavioral assessments,decreased brain water content,reduced lesion volume,and diminished cell death in the perihematomal region.Notably,intranasal EDA administration preserved blood-brain barrier integrity,suppressed microglia/macrophage activation,and mitigated oxidative stress,highlighting its multifaceted neuroprotective mechanisms.Conclusion:These outcomes underscore the therapeutic promise of intranasal administration of EDA as a prospective intervention for alleviating secondary brain injury post-ICH and advocate for further translational and clinical investigations to validate its efficacy and safety in ICH patients.
文摘In this work, some important parts of the system, and the relation between the parts, and its connections with other systems are defined, explained briefly. With this respect, the nature of the person is defined with related parts. A new science branch called ＂information science＂ is defined. Importance of the political organizing of a political party is shortly explained. The necessity of the academies for public sector, private sector, and for political administration system is expressed. How to choose a person and how a person can be choose for any part of the system is defined. For both cases ＂good and/or correct＂ system criterions, determination of the criterions, and evaluation criterions are defined. New evaluation levels are defined based on the 8-basic senses in philosophical point of view to deepen the sensitivity of the evaluations. The importance of the situation notice and how to make it for each of the association are explained. The 10 main service parameters are defined to show the interactive relations between the ideology, services, person nature and others. Present and possible future problems of a country are expressed. Aims/targets are characterized with real approach for all related sides. Other systems which proposed to be connected to continuable political administration system are shortly defined and expressed. Way of system administration and administration types are shortly explained. The importance and ways of the decision making are expressed. The general ways, types of inspection are shortly explained. Official units that could be assign for the new system are defined. The importance of these units and of the persons that could be assign for these units are expressed together with the definition of the characteristics of the persons or groups that could be. The necessity of an action planning, possible supply and demand cases are defined scientifically. The importance and necessity of sense of justice is explained to make system continuable. The methods of determination of the policies/strategies are expressed.
文摘In this work all the political/non-political ideologies, 168 religions/beliefs/sects, nearly 1,600 ethnic origin groups are synthesized to define continuable political construction. It is found that all the past federations, confederations, empires, ideologies, political administration systems, thoughts and senses, doctrines, etc. are in fact each reflects a special functional processes within a general system of where the kinds of services, subjects of services, way of services, service types and persons are considered and placed as a factor in it and where these factors are arranged through different priorities, weights, and also taken under record with some rules. It is evaluated that each groups, communities, societies, countries are separate models, but at the same time each of them are factors which owns different beginning points to reach a correct country structure with five new separate groups （New Era Group, Progression of The Country Group, Unity of The Country Group, Values of The Country Group, Social Progression Group）. The continuable political administration system is defined here by considering the all possible parts and by considering the other systems eormected for a country. Possible forceful factors which can effect political system administration are given. To realize political construction, some political construction methods are defined： Political construction by putting together the values, political construction based on different value, Political construction based on the new defined values, Political construction which considers stepped transition and Ideal political construction which will carry the political points of views and other standards of judgement, points of views of persons to a same line are expressed. New ideologies are put forwarded and ideal political construction for a world country is given with details. Integration of the political groups, political ideologies to the new system is explained. Some methods of politics are mentioned. Persons related with politics are classified simply.
文摘It is critical to ensure the safety and efficacy of human drugs through drug administration. Drug administration has a long history in developed countries, such as USA, European Union and Japan, and has achieved great success. In this study, we summarized the important changes in the practice of drug administration in USA, European Union and Japan since 1990s. We also discussed how these changes and experience could be applied in the reform plan in drug administration in China Food and Drug Administration （CFDA）. Our suggestions on future development of CFDA include improving post-market surveillance, advancing regulatory science, strengthening service-oriented regulation, and international cooperation.
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[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.
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.
