Intranasal administration of stem cell-derived exosomes for central nervous system diseases

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.

Advances in Polysaccharide-Based Microneedle Systems for the Treatment of Ocular Diseases

The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance.Polysaccharidebased microneedles(PSMNs)have emerged as a transformative solution for ophthalmic drug delivery.However,a comprehensive review of PSMNs in ophthalmology has not been published to date.In this review,we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery.We provide a thorough analysis of PSMNs,summarizing the design principles,fabrication processes,and challenges addressed during fabrication,including improving patient comfort and compliance.We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios.Finally,we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.

Analysis of the Regulation System for Cosmetics Administration

This article uses the method of legal text analysis to systematically sort out the legal norms,administrative normative documents,and other normative documents in the regulation system of cosmetics.It focuses on discussing the definitions,legal attributes,sources,and effectiveness of laws,administrative regulations,departmental rules,administrative normative documents,standards,specification,and guiding principles.

Succession Plan for Nursing Academic Program Administrators

Leadership succession in nursing academic programs poses a significant challenge, primarily due to the limited availability of professionals with the competencies required for effective leadership [1]. This study aims to address this gap by investigating the critical factors in succession planning for nursing program administrators. The research objectives include identifying the competencies necessary for academic administrators, assessing the experience of current administrators, and developing a comprehensive succession plan framework. The research uses qualitative methods, including literature review, interviews with nursing administrators, and analysis of existing succession models. Results highlight the importance of integrating strategic planning into succession processes to ensure smooth transitions and organizational stability. Conclusions suggest that a formalized succession plan, incorporating mentorship and leadership development, can mitigate leadership gaps in nursing academia [2].

Research on Monitoring and Early-warning Standards of Ancient and Famous Trees Protection in the Humble Administrator's Garden

Based on the current situation and symptoms of the trees' growth in the Humble Administrator's Garden,this paper put forward corresponding monitoring and early-warning standards and technical measures of the ancient and famous trees protection in the Humble Administrator's Garden specifically.The aim of doing this is to establish a scientific basis for the protection of the ancient and famous trees in the Humble Administrator's Garden by setting up systematic fundamental data,dynamic protection standard grades and technique measures of protecting the trees.The main symptom of trees in the Humble Administrator's Garden is the erosion and decay of the tree trunks.Fifteen tree trunks need technical protection,which holds 65.22% of the total sum of trees in the Humble Administrator's Garden.Therefore,much more emphasis should be paid in strengthening technical protection procedures of monitoring and early warning of the tree trunks in the future protection of the ancient and famous trees in the garden.Besides,the rejuvenation technique of rooting zone and rooting system,tree pruning technique as well as tree supporting measures according to the specific condition and symptom of the trees should be concerned with in order to protect the ancient and famous trees in the Humble Administrator's Garden in a more scientific and effective way.

Effects of estradiol-17β and bisphenol A administered chronically to mice throughout pregnancy and lactation on the male pups＇ reproductive system

Aim： To assess the effect of estradiol-17β （E2） and bisphenol A （BPA） administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups＇ reproductive system in ICR mice. Methods： Female mice were implanted with a tube filled with 10 ng, 500 ng, 1 μg, or 10 μg of E2, or 100 μg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E2 was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 μg/day. Results： Most of the mice given 1 μg and 10 lag of E2 did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights （testes, epididymides and accessory reproductive glands） in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E2 and 5 mg of BPA than that in the control. Conclusion： Chronic exposure to E2 and BPA might disrupt spermatogenesis in male pups. （Asian JAndrol 2008 Mar; 10： 271-276）

Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism

Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain- containing 5 （FNDC5） protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue （WAT） and uncoupling protein I （UCP1） expression, leading to an increase in total body energy expenditure by augmented UCPl-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones, including growth plate, trabecular bone, cortical bone, articular cartilage, and bone-tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal （IP） administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-kB ligand （RANKL）- induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice.

Low-dose lipopolysaccharide as an immune regulator for homeostasis maintenance in the central nervous system through transformation to neuroprotective microglia

Microglia,which are tissue-resident macrophages in the brain,play a central role in the brain innate immunity and contribute to the maintenance of brain homeostasis.Lipopolysaccharide is a component of the outer membrane of gram-negative bacteria,and activates immune cells including microglia via Toll-like receptor 4 signaling.Lipopolysaccharide is generally known as an endotoxin,as administration of highdose lipopolysaccharide induces potent systemic inflammation.Also,it has long been recognized that lipopolysaccharide exacerbates neuroinflammation.In contrast,our study revealed that oral administration of lipopolysaccharide ameliorates Alzheimer’s disease pathology and suggested that neuroprotective microglia are involved in this phenomenon.Additionally,other recent studies have accumulated evidence demonstrating that controlled immune training with low-dose lipopolysaccharide prevents neuronal damage by transforming the microglia into a neuroprotective phenotype.Therefore,lipopolysaccharide may not a mere inflammatory inducer,but an immunomodulator that can lead to neuroprotective effects in the brain.In this review,we summarized current studies regarding neuroprotective microglia transformed by immune training with lipopolysaccharide.We state that microglia transformed by lipopolysaccharide preconditioning cannot simply be characterized by their general suppression of proinflammatory mediators and general promotion of anti-inflammatory mediators,but instead must be described by their complex profile comprising various molecules related to inflammatory regulation,phagocytosis,neuroprotection,anti-apoptosis,and antioxidation.In addition,microglial transformation seems to depend on the dose of lipopolysaccharide used during immune training.Immune training of neuroprotective microglia using lowdose lipopolysaccharide,especially through oral lipopolysaccharide administration,may represent an innovative prevention or treatment for neurological diseases;however more vigorous studies are still required to properly modulate these treatments.

Comparison of international mine reclamation bonding systems with recommendations for China

Mine reclamation bonds are used in countries with mineral mining to ensure that reclamation of the mined area is completed. The United States, Canada, and Australia are countries with established mine reclamation bond programs, with the United States coal system having been in place since 1977. China implemented a bonding system in 1998 and by 2013 all 31 provinces had established a system. An effective bonding system must be conditioned on fair and enforceable nationwide reclamation standard, stimulate companies to conduct reclamation by forming economic incentives rather than penalties that become a liability, and allow for full public participation. Based on these principles, this paper compares seven important factors for a successful reclamation bonding system： laws and regulations, administrative authority, bond types, bond size, calculation method, bond release, and public participation. The results show variation in policies and procedures for bonding among countries. Using principles and policies primarily from the United States, China should establish a national reclamation bonding system with legislation that forms a national authority to oversee and enforce reclamation standards and bond requirements. In addition, China can expand bond financial types and strategies, set the size of reclamation bonds at the level of a third-party reclamation cost, and set unified standards for calculation. Phased bond release should be established with specific reclamation criteria for each phase of release. Finally, bonding regulations should clearly identify opportunities for full public participation in the process.

A Continuable Political Administration System for World Countries （II）

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.

A Continuable Political Administration System for World Countries （I）

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.

Countries＇ Union and Political/Non-Political Administration Systems for the World Countries

In this work, the author noticed that some/most of the problems in the world countries, are because of the past/present differences, disputes about ethnic origins, federation systems, political and/or religious ideologies, organizations, mythologies, religions/sects, organs of governments, party systems, political systems, basic senses, administrations, and others. Purpose of this work, is to solve these problems for all related sides in a country and/or in the world to obtain continuable （political/non-political） administrative system（s） for the world countries by considering countries＇ union theory. The author considered the ＂synthesis＂ method and evaluated, generally/specifically, all these subjects also related philosophy branches, present political ideology spectrums, power sources and structures, public administrations, science branches by considering nearly 12,000 years written historical period. The author also considered his personal contacts with nearly 80,000 people from different political/non-political groups, and from all different position levels of persons, directly/indirectly. The author defined 21 dimensions of the synthesis to categorise the problems, related solutions, and theories he found. General points that can be evaluate as positive and/or negative about each side are expressed. Basic important concepts and definitions about political/non-political administrations of a world country are defined. General types of organizations and administrations in the world are expressed together with some related problems in the present systems. Good and/or correct perspective that must be behind administration（s） is described. Categories and types of interacted sides are explained. Subjects of services mandatory for a world country are defined. Necessity of the new system（s） for two or more sides is expressed. General types of needs for each world country are defined and categorized due to the domestic and international needs and due to possible interaction between two or more sides. As a conclusion, new political/non-political methods are defined to solve general and specific administrative problems between sides in a world country or between different countries. Theory of countries＇ union system is defined. General principles and sense of justice which are necessary for establishing countries＇ union between any two countries are defined.

New Administration Systems for the World Countries and Sense of Justice ＆ Continuity in the System Administration

In this work, some of the results of the synthesis about the administration systems are expressed. The Author defined four new case theories and 23 main methods, and defined five general political/non-political administration system categories for the world countries. Each system is defined with the related 12 sub blocs to solve the general and specific problems of communities, territories, states and/or countries. Each bloc includes presidency, council, committees, associations and R-autonomous construction. For each of these five administration system categories, and for each of their sub blocs, general/specific system administration construction is defined with its 21 blocs. Importance of both sense of justice and continuity/sustainability are described with the related 21 categories defined for each of these perspective. Types of system administration are defined for five categories of administration systems. General and specific characteristics and possible fundamental and representative duties of country presidency system are defined. Ideal political constructions are defined for each of five general administration system categories. Specific way of integration of the past and present politic/non-politic groups into the ideal political construction is defined in multi dimensional form. Constructional centrism, R-Centrism, R-Continuity, R-Democracy, R-Ideology, R-Philosophy, R-Progressive, R-Religion, R-Science, Progressive Religion, ideal stability chart and some other concepts are defined as constructional and/or complementary basics of the systems. Author defined a criterion to measure the value of a country. Effective weight function of a world country is defined as a mathematical function to inspect, observe the performance and progression of a country inside, and/or in the region, and/or in the world. Basic forms of government are re-constructed and/or re-defined as hybrid-powers for each of these five categories of administration systems and general comparison made with the past/present ones. New political constructions are proposed for different party systems, different federation systems in the world. Applications and realization of the four new case theories and 23 main methods are expressed for all world countries. Author defined new or re-constructed 20 regional unions for the world due to new case theories, and one of them （SEAEU） is already officially declared.

Long-term versus Short-term Introvesical Chemotherapy in Patients with Non-muscle-invasive Bladder Cancer:A Systematic Review and Meta-analysis of the Published Results of Randomized Clinical Trials

In order to assess the effect of long-term versus short-term intravesical chemotherapy in preventing the recurrence of patients with non-muscle-invasive bladder cancer, we searched several da- tabases with words as mesh terms and free text words to find all eligible randomized clinical trials （RCTs） for the Comparison of the two strategies of instillation durations. ＂Observed-Expected events re- search （O-E）＂ and ＂Variance （V）＂ for calculating hazard ratio （HR） were used in Revman 5.2 software recommended by Cochrane Collabration for data analysis. Sensitivity and subgroup analysis were se- lected to minish heterogeneity. GRADEpro 3.6 profile recommended by Cochrane Collabration was employed for quality assessment of analyses. Finally, 13 eligible RCTs with 4216 patients were in- eluded in this review and 16 comparisons from 13 trials were involved for analysis. The pooled analysis revealed no significant difference between long-term and short-term duration [HR=0.99, 95% CI （0.89, 1.11）, P=-0.89]. Within the subgroup analysis, patients benefited from long-term instillations with a start regimen of one immediate instillation [HR=0.83, 95% CI （0.69, 1.00）, P=-0.05]. But patients were not suitable to receive long-term instillations with epirubicin （EPI） [HR=1.01, 95% CI （0.91, 1.13）, P=0.78] The progression rate was not reduced after long-term instillations [HR=0.96, 95% CI （0.66, 1.39）, P=0.82]. From our results, patients should not receive introvesical chemotherapy more than half a year. In contrast, patients with one immediate instillation are preferred to have a long-term duration at least one year. Long-term instillations can not reduce the progression rate.

Development and application of a closed-loop medication administration system in University of Hongkong-Shenzhen Hospital

Objective： This study aimed to develop and apply a closed-loop medication administration system in a hospital in order to reduce medication administration errors （MAEs）.Methods： The study was implemented in four pilot general wards. We used a before-and-after design to collect oral medication administration times before and after the implementation of the closed-loop medication administration system, evaluated MAE alert logs after the intervention, and conducted a survey of the nurses1 satisfaction with the system in the pilot wards.Results： （a） Nursing time of oral medication administration： before the adoption of the closed-loop medication administration system, the average nursing time was 31.56 ± 10.88 minutes （n = 78）; after the adoption of the system, the time was 18.74 ± 5.60 minutes （n = 54）. Independent sample Mests showed a significant difference between two groups（t= 8.85, P 〈0.00）. （b） Degree of nurses’ satisfaction with the closed-loop medication administration system： 60.00% （n = 42） of nurses considered the system to be helpful for their work and nearly half of the nurses （47.14%, n = 33） believed that the system could facilitate clinical work and reduce workload; 51.43% {n = 36） believed that the system could reduce checking time and enhance work efficiency; 82.86% （n = 58） believed that the system was helpful in improving checking accuracy to reduce MAEs and ensure patient safety. More than 60% of the nurses considered the system to be a method that could help to track MAEs to improve nursing quality, （c） The MAE alert logs during observation period： it revealed only 27 alerts from the repeated scans of 3,428 instances of medication administration.Conclusions： The nurses were satisfied with the closed-loop medication administration system because it improved their work efficiency and reduced their workload. The current investigation was limited by time; therefore, further research is needed to more closely examine the relationship between the system and MAEs.

Research of University Educational Administration System Bottlenecks and Overall Optimization Scheme

This paper analyzes of the bottleneck to influence the running efficiency of educational administration system in universities and colleges,and from the system deployment architecture, server configuration, database SQL statement optimization and other aspects, it puts forwards the optimization scheme.

Wildlife Export Quota and Its Administrative System

The authors discussed the administrative system of export quota and its method of calculation in the international wildlife trade. Three methods for determining wildlife export quota in China was put forvvard, based on the trend and status, domestic use, and historical export of wildlife resources. They include the single factor method, the double factor method, and the multiple faCtor method. In addition, the approaches and measures to establish and carry out the administrative system of wildlife export quota in China were discussed in this paper.

Information Network Systems and Information Sharing on Administrative Websites

In Japanese 'e-government' policy, called 'e-Japan', the 'administrative document management system' is functioning as information searching systems. On the other hand, this system has also generated the problem that it is not fully functioning as a means for the information sharing in a governmental agency. So, the purpose of this research is to find how the administrative document management system can function as information sharing in administrative organization. For this purpose, this paper considers the current status and some problems firstly. And secondary, this paper proposes the idea and constructs some information systems using administrative official Website. This is the method and approach of this research. As a conclusion, this proposal information system junctions as information sharing support systems.

Recent advances in particulate drug delivery systems: Oral, pulmonary, and ophthalmic administrations

Colloidal drug carriers such as liposomes,lipid emulsions,and polymeric nanoparticles have great potential to deliver drugs effectively.Preparation of nano-crystals of API has also received much attention to design dosage forms to complete effective drug delivery.A variety of investigations have been carried out toward the design of an optimal particulate system.