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.

The Development Trend of Enterprise Business Administration and the Innovation of Management Mode

In the context of the new period,the continuous growth of social and economic levels and the rapid update of information technology have significantly impacted the business management of Chinese enterprises,presenting substantial challenges.The intensification of market competition exerts development pressure on many enterprises,and coupled with the unstable strength of some businesses,numerous problems in business management arise.These issues hinder the smooth execution of various business activities.Therefore,it is crucial to ensure effective business administration to conduct different business activities in an orderly manner,promptly avoid adverse risks,and strengthen control over multiple factors.The innovation and improvement of business administration are of great significance for enhancing the management level and market competitiveness of modern enterprises,accelerating their healthy development,and creating numerous opportunities.Consequently,this paper analyzes and explores the development trends of enterprise business administration and the innovation of management models for reference.

Exploring Corporate Tax Compliance in the Era of Digital Tax Collection and Administration:Insights from the“Golden Tax Phase Four”Project

This article primarily examines the current state of tax collection and management,alongside other associated issues.It integrates insights from China’s“14th Five-Year Plan”and anticipates the imminent implementation of the“Golden Tax Phase Four.”With this backdrop,the article offers recommendations for advancing the reform of the tax collection and management system,fostering the development of intelligent taxation,and accelerating the modernization of tax collection and management in China.

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.

America’s Policy towards China under Two Administrations in the Context of Great Changes: Difference, Influence and Enlightenment

Under the great changes unseen in a century,comprehensive containment and suppression of China in the name of strategic competition has become a crossparty consensus in the United States,with the Republican Trump administration initiating the process of containing and suppressing China and the Democratic Biden administration continuing and developing such a strategy.In the process of implementing this strategy,there are some diff erences in the goals and means of the two American administrations.The Trump administration was trying to“crush China”with the super strength of the United States,with more extreme and tougher means,being more unilateralist and even going so far as to launch a“new Cold War”against China.The Biden administration,on the other hand,emphasizes long-term competition with China,and focuses on“managing competition”while suppressing China,accustomed to being double-handed and using both carrot and stick.When it comes to addressing global challenges,the Republican Party completely lacks the will to cooperate with China,while the Democratic Party has a certain need for cooperation and action.

Application of Information Technology in Institutions and Challenges of Human Resources-Case Study: Administration of the Municipality of Ferizaj

This study aims to investigate how information technology is applied in the administration of the municipality of Ferizaj and what are the challenges with human resources, the work was carried out through a case study in the municipality. This paper highlights that the use of information technology provides higher efficiency for the performance of daily work in the municipality, thus also the provision of better services to citizens. However, the level of use of information technology in the Municipality of Ferizaj leaves much to be desired in terms of efficiency because a significant number of employees have not attended adequate training for the effective and efficient use of various IT applications and have not are still adapted to the digital environment in the municipality. Therefore, the recommendation derived from this paper is that the information technology environment in the municipality of Ferizaj needs to be improved by providing staff with adequate qualifications, while for those who are currently engaged in the municipality and who do not have adequate qualifications, training should be provided in a way that all users of IT applications are fully integrated into the digitized environment in order to be effective and efficient in providing services to citizens. This simultaneously gives the municipal staff job security and motivation for better services for citizens. Also, information technology enables a better control over the activity of the municipality because every action is recorded as data which can then be used to analyze the performance of the municipality.

Value of Tongue Color Combined with Sublingual Microcirculation in Predicting the Severity of Mild to Moderate Acute Cerebral Infarction

Objective:To explore the value of tongue color combined with sublingual microcirculation in predicting the severity of mild to moderate acute cerebral infarction(ACI).Methods:From January to December 2022,90 patients with ACI were admitted to the Department of Neurology of Jiangsu Provincial Hospital of Integrated Traditional Chinese and Western Medicine.According to the NHISS score on the 5th day of admission,the patients were divided into mild group(35 cases)and moderate group(55 cases).The changes of tongue color and arterial lactate on the 5th day of admission were observed and monitored.Side-stream dark field imaging(SDF)was used to determine the total vascular density(TVD),perfused vascular density(PVD),perfused vascular ratio(PPV)and microvascular flow index(MFI).The multivariate logistic regression analysis was used to screen the risk factors for the severity of ACI,and the receiver operating characteristic curve(ROC)to evaluate their values in predicting ACI severity.Results:There was no significant difference in lactate between the two groups(P>0.05),and the frequency of red tongue in the mild group was higher,and the frequency of red tongue in the moderate group was significantly higher in the dark tongue group(P<0.05).The multivariate logistic regression analysis showed that PVD and PPV were independent risk factors for the severity of mild to moderate ACI(P<0.05).The ROC curve analysis showed that an area under the curve of 0.832 was achieved by the combination of PVD and PPV,which was larger than that of a single factor.Conclusion:Tongue color combined with sublingual microcirculation can be combined to predict the severity of mild to moderate ACI.

Status, Transition, and Impact of the Yoon Suk-yeol Administration’s Trade Policy with China

China is Korea’s main trade partner in East Asia and one of its key economic and trade partners worldwide.The two countries have complementary industrial structure and a long history of trade exchanges.However,against the backdrop of a return to global trade protectionism and the politicization of international affairs with Yoon Suk-yeol coming to power,South Korea has undertaken a strong trade shift toward the United States(US),triggering a change in the pattern of economic cooperation in East Asia and challenging the regional trade structure.A review of the trade policy agenda of the Yoon Suk-yeol administration toward the US and China,along with a comparative review of Korea’s foreign trade stance under Moon Jae-in,allows for an analysis of the turnaround and characteristics of Yoon’s trade policy toward China during his tenure.The implications for global trade governance and regional security are further analyzed with an aim of finding a Nash equilibrium in trade cooperation among East Asian countries.

Design of an E-Administration Platform and Its Cryptography-Based Security Model

E-administration is performing administrative works via computer and its associated technologies such as the Internet. It is administrative efforts that center on the exchange of information and providing services to people and the business sector at high speed and low cost through computers and networks with the assurance of maintaining information security. It is based on the positive investment in information technology and communication in administrative practices. This paper presents the design of the e-administration platform that adopts the concept of cryptography for identity management. The architectural framework of the platform comprises subcomponents for service and forms identification, business process redesign, service architecture, amalgamation, and deployment. The cryptography model for securing the platform was designed based on the combination of authentication criteria presented in the Rijndael-Advanced Encryption Standard (AES), Lattice-based cryptography (LBC), and Secure Hash Algorithm (SHA512). It is required that a record be encrypted prior to its commitment to the database via a double encryption method. The AES algorithm-based encryption’s output will form the input to the LBC algorithm to obtain the final output.

Pharmacokinetics and Absolute Bioavailability of the Sublingual Naloxone Hydrochloride Tablet in Dogs

The pharmacokinetics and absolute bioavailability of the sublingual naloxone tablet were studied with HPLC-electrochemical detection. Eight male dogs received single 5 mg dose of naloxone intravenously, the plasma concentration-time curves could be fitted to two-compartment open model, with 12.0 min of t1/2( , 143.4 min of t1/2( and 7.92 mg(min/L of AUC. The same eight dogs received 5 mg dose of the sublingual naloxone tablet after an interval of a week. The main pharmacokinetic parameters were: t1/2ka = 11.0 min, t1/2( = 15.4 min, t1/2( = 164.1 min, Tmax = 27.7 min, Cmax = 34.2 ng / ml, and AUC = 6.79 mg(min / L, respectively. The plasma concentration-time curves were fitted to the first order absorption two-compartment open model also. The mean absolute bioavailability of the sublingual naloxone tablet was 86.8 ( 10.9%. No statistically significant differences were found with t1/2(, t1/2(, ( and ( between the two routes of administration. These results indicated that the course of disposition for naloxone in dogs was similar for the two routes of administration, and the absolute bioavailability of the sublingual naloxone tablet was high. Thus satisfactory clinical effects could be expected.

Effects of Oral Administration of Propylene Glycol and Ca-P-Mg Mixture on Milk Quality and SCC of Dairy Cows after Birth

In order to further study the postpartum care technology of dairy cows,the effects of oral administration of propylene glycol or Ca-P-Mg mixture and compound oral rehydration salts on milk quality and SCC of dairy cows after birth were investigated. The results showed that the milk fat and dry matter contents in the dairy cows administered with Ca-P-Mg mixture and compound oral rehydration salts were higher than those in the dairy cows administered with propylene glycol（P 〈0.05）. However, there were no significant differences in milk sugar and protein contents and SCC between the two administration groups.

c-Fos expression within the L_5 spinal cord dorsal horn after spinal nerve ligation in rats Is intraplantar administration of glutamate different from intrathecal administration?

BACKGROUND： Injection of glutamate （Glu） in normal animals can cause neuronal c-Fos expression; however, whether Glu can induce spinal neuronal c-Fos expression in pain models is unclear. OBJECTIVE： To examine the effects of intraplantar and intrathecal injection of Glu on c-Fos expression in the L5 spinal cord dorsal horn Ⅰ/Ⅱ and Ⅲ/Ⅳ layers after spinal nerve ligation, and to study the effects of the N-methyI-D-aspartic acid （NMDA） receptor antagonist, D-2-amino-5-phosphonopentanoate （D-AP5）, and a selective group I mGluR antagonist, 7-hydroyiminocyclo propan[a]chromen-lacarboxylic acid ethyl ester （cpccoEt）. DESIGN, TIME AND SETTING： A randomized, controlled animal study was performed at the Department of Pharmacology, Oral Anatomy, and Neurobiology, Osaka University Graduate School of Dentistry, from December 2005 to December 2006. MATERIALS： Glu （5 μmol）, D-AP5 （50 nmot） and cpccoEt （250 nmol） were provided by Wako Pure Chemical Industries, Osaka, Japan, and diluted in saline （50 μL）. The pH of all solutions was adjusted to 7.4. METHODS： Twelve rats were randomly divided into sham operation （n = 6） and spinal nerve ligation （SNL; n = 6） groups for behavioral assessments of neuropathic pain after ligation surgery of the left L5-6 nerve segment. Another 60 rats were randomly divided into sham operation, SNL, saline-intraplantar, saline-intrathecal, Glu-intraplantar, Glu-intrathecal, D-AP5-intrathecal, Glu-D-AP5-intrathecal, cpccoEt-intrathecal, and Glu-cpccoEt-intrathecal groups, with 6 rats in each group. All groups except sham operation group received a similar SNL. On day 14, rats received a 50-μL injection of saline, Glu, D-AP5, and/or cpccoEt into the left intraplantar or intrathecal L5-4 segments. MAIN OUTCOME MEASURES： The number of c-Fos positive neurons in both Ⅰ/Ⅱ and Ⅲ/Ⅳ spinal layers at L6 was observed using immunohistochemistry 2 hours after administration. RESULTS： （1） SNL increased the level of c-Fos expression in two sides of the spinal cord, particularly on Ⅲ/Ⅳ spinal layers of the ligated side. （2） Intraplantar or intrathecal administration of saline significantly increased the c-Fos labeled neurons in Ⅰ/Ⅱ spinal layers of the ligated side, compared with SNL alone （P 〈 0.01）. （3） Intraplantar Glu （5 μmol） increased the number of c-Fos positive neurons in Ⅰ/Ⅱ spinal layers compared with intraplantar saline （P〈 0.01）. （4） The number of c-Fos neurons in Ⅰ/Ⅱ spinal layers on both the ipsilateral and contralateral side after intraplantar Glu was lower than intrathecal Glu （P〈 0.01）, with a 3-fold higher induction by intrathecal Glu. （5） Co-administration of D-AP5 or cpccoEt reduced the effects of intrathecal Glu （P 〈 0.01）. CONCLUSION： Intrathecal Glu increases c-Fos expression more than intraplantar Glu. Antagonists of NMDA and group I mGluRs block this effect.

Administration与Government文化语义辨析及其翻译

本文分析了英语（尤其是美国英语）中administration与government的文化语义差异，认为administration的词义核心是“行政分芰”，将administration翻译为汉语的“政府”不够妥当，该词的恰当汉译为“行府”，而government的汉译是“政府”

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.

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.

Current Issues and Development Strategies of Building the Discipline of Pharmacy Administration at Pharmacy Schools in China

The history and current status of Pharmacy Administration discipline atpharmacy schools in China are illustrated. Several current issues are explored including: (1)insufficient teaching organizations and curriculum, (2) faculty deficiency both in quantity andquality, and (3) much improvement needed in the scope, methodology, and sophistication of research.Several development strategies are formulated such as (1) integrating native education resources inorder to better foster quality professionals, (2) accelerating inter-university cooperation both inteaching and research, and (3) studying the regularites of discipline development and enhancinginternational exchange.

A Comparative Analysis of the Administration of Oral Hypoglycemic Drugs in Second Affiliated Hospital of Guiyang Medical College during 2012-2014

[Objective] This study aimed to analyze the application and administration of oral hypoglycemic drugs in Second Affiliated Hospital of Guiyang Medical College,aiming at providing guidance and reference for clinical medication for treatment of diabetes.[Method] The main types,dosages and prices of oral hypoglycemic drugs in Second Affiliated Hospital of Guiyang Medical College during 2012-2014 were compared and analyzed using the computer network system.[Result] During 2012-2014,sales quantity and sales amount of oral hypoglycemic drugs in Second Affiliated Hospital of Guiyang Medical College demonstrated an upward trend.[Conclusion] Integrative medicine can significantly improve symptoms of diabetes complications.Certain achievements have been made in diabetes treatment by Second Affiliated Hospital of Guiyang Medical College.

Fifty-six Cases of Stubborn Eczema Treated by Oral Administration and Topical Application of Herbal Medicine

Eczema is a kind of very common dermatopathy. The cases with a long course of illness and hard to be cured are termed as stubborn eczema. We have obtained good results in its treatment since 1995 with the Chu Shi Tang (除湿汤Dampness-Clearing Decoction) for oral intake and the Fu Fang Ku Shen Xi Ye (复方苦参洗液) for topical application. The following is a clinical report for treating 56 patients with stubborn eczema.

Single-allergen Sublingual Immunotherapy versus Multi-allergen Subcutaneous Immunotherapy for Children with Allergic Rhinitis

It has always been controversial whether a single allergen performs better than multiple allergens in polysensitized patients during the allergen-specific immunotherapy. This study aimed to examine the clinical efficacy of single-allergen sublingual immunotherapy(SLIT) versus multi-allergen subcutaneous immunotherapy(SCIT) and to discover the change of the biomarker IL-4 after 1-year immunotherapy in polysensitized children aged 6–13 years with allergic rhinitis(AR) induced by house dust mites(HDMs). The AR polysensitized children(n=78) were randomly divided into two groups: SLIT group and SCIT group. Patients in the SLIT group sublingually received a single HDM extract and those in the SCIT group were subcutaneously given multiple-allergen extracts(HDM in combination with other clinically relevant allergen extracts). Before and 1 year after the allergen-specific immunotherapy(ASIT), the total nasal symptom scores(TNSS), total medication scores(TMS) and IL-4 levels in peripheral blood mononuclear cells(PBMCs) were compared respectively between the two groups. The results showed that the TNSS were greatly improved, and the TMS and IL-4 levels were significantly decreased after 1-year ASIT in both groups(SLIT group: P<0.001; SCIT group: P<0.001). There were no significant differences in any outcome measures between the two groups(for TNSS: P>0.05; for TMS: P>0.05; for IL-4 levels: P>0.05). It was concluded that the clinical efficacy of single-allergen SLIT is comparable with that of multi-allergen SCIT in 6–13-year-old children with HDM-induced AR.