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.

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.

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.

Adjustment of Administrative Divisions and Upgrading of Industrial Structure in Hefei Metropolitan Area:Taking"Partitions of Chaohu"as a Quasi-natural Experiment

Administrative regions are an important environment for the operation of China's market economy.The relevant economic subjects cannot predict the policy of adjustment of administrative divisions and carry out conscious migration behavior,adjustment of administrative divisions can be regarded as a quasi-natural experiment.The three cities of Hefei,Wuhu,and Ma'anshan,which are directly related to the adjustment of the administrative division of Chaohu,are taken as the treatment group,and the seven adjacent cities of Lu'an,Huainan,Chuzhou,Bengbu,Anqing,Chizhou,and Tongling are taken as the control group.Differences-in-Differences method and relevant control variables affecting the upgrading of industrial structure are used to test.The test results show that"Partitions of Chaohu"has a significant industrial structure upgrading effect by promoting the optimization of spatial layout,the cross-regional flow of production factors and the effective management of Chaohu Lake Basin.At the same time,the increase of total retail sales of consumer goods,urban fixed assets investment,public utility expenses in science,education,culture and health,and population plays a significant positive role in promoting the upgrading of industrial structure,while foreign direct investment plays a certain inhibition role in the upgrading of industrial structure.In order to meet the ever-developing space demands and enhance the impact on surrounding areas,the Hefei metropolitan area should be driven by technological innovation,strengthen the integration of industrial chains,improve the business environment and transportation network,and continuously promote the upgrading of industrial structure and the formation and development of new productive forces.

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.

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.

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”

“行政”(administration)义考

"行政"一词是行政学的核心概念。作为一个学科,概念梳理和界定是一项基础性工作,如果概念特别是核心概念不清,学科发展必然会受到影响。本文从文字构成、词源、中英文对照的比较视角以及学科发展脉络对"行政"的含义进行考证和梳理。

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.

基于作者共被引的公共行政研究状况图谱分析——以《Public Administration Review》为研究对象

一门学科的发展离不开优秀专家学者的倾力支持,在公共行政学的形成和发展过程中,同样有一批优秀的公共行政学者推动了公共行政不同分支领域的衍生与发展。运用作者共被引和信息可视化方法,对权威期刊《公共行政评论》(Public Administration Review)于1975—2008年间发表的论文引文中被引频次前50名的学者进行分析。研究结果展现了公共行政领域的主要学术流派,并验证了公共行政研究确实是在沿着范式转移的轨迹更迭交替着。而这种变迁是相对的,大部分时间内,不同范式之间以及和其他学术流派之间是共存、互动甚至交融的。研究还发现,网络化治理正凭借其多中心和网络化的组织基础以及服务治理的先进理念迅速崛起,它将成为公共行政新的研究范式,而基于网络理论的公共行政理论大整合也将很有可能成为公共行政未来的研究热点。此外,实证结果与公共行政范式分类的高度相似性也充分表明了作者共被引和信息可视化方法的科学和有效,它的确为学科范式研究提供了一条定量研究的新思路和一个宏观分析的新视角。

“administration”的三大翻译之争

"administration"是一个用法极广、含义丰富的词汇,通常被翻译为"政府"、"管理"、"行政"等意思。本文主要围绕"administration"与"government"、"management"、"executive"等三词的翻译冲突,并较详细地探讨了它们之间的语义及语用区别。

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.

Effect of intraoperative fluid administration on perioperative outcomes in patients undergoing McKeown esophagogastrectomy

Objective: Fluid therapy is one of the key components of perioperative management. However, evidence of intraoperative fluid(IOF) administration affecting clinical outcomes following McKeown esophagogastrectomy remains limited. This study investigated the impact of IOF on clinical outcomes after McKeown esophagogastrectomy.Methods: Patients who underwent McKeown esophagogastrectomy between July 2013 and July 2016 were identified. Preoperative, intraoperative and postoperative variables for each eligible patient were retrospectively collected from our electronic medical records and anesthetic records. IOF rates were determined and their relationships to postoperative clinical outcomes were compared.Results: A total of 546 patients were enrolled in the analysis. The median IOF rate was 8.87 mL/kg/h. We divided the patients into two groups: a low fluid volume group(LFVG <8.87 mL/kg/h, n=273) and a high fluid volume group(HFVG ≥8.87 mL/kg/h, n=273). No statistically significant differences in postoperative clinical outcomes were found between LFVG and HFVG either before or after propensity score matching.Conclusions: No effect of IOF administration on clinical outcomes in patients undergoing McKeown esophagogastrectomy was identified. Further high-quality studies examining the influence of IOF administration on clinical outcomes following McKeown esophagogastrectomy are still needed.

Genetic factors for individual administration of immunosuppressants in organ transplantation

BACKGROUND: The immunosuppressive drugs used worldwide have a narrow therapeutic index, which results in a need to individualize the dose regimen for different recipients. The oxidative enzymes cytochrome P450 (CYP)3A and the drug efflux pump P-glycoprotein (P-gp) are two potential factors in the processes of metabolism. Pharmacogenetic study of immunosuppressive drugs has focused on these two enzymes. This review was undertaken to assess the role of single nuclear polymorphisms (SNPs) of these two enzymes in the individual administration of immunosuppressive drugs. DATA SOURCES: An English-language literature search was made using MEDLINE for articles on CYP3A and P-gp in organ transplantation. RESULTS: The SNPs of CYP3A and P-gp are closely correlated to the large variations of cyclosporine and tacrolimus dosage between different patients, although conflicting results were obtained by some authors. CONCLUSIONS: More studies should be conducted to elucidate further the pharmacogenetics of immunosuppressive drugs in organ transplantation, a deep understanding of which would provide an important step toward drug regimen individualization in the posttransplant therapy.

Subcutaneous versus Intravenous Bortezomib Administration for Multiple Myeloma Patients：a Meta-analysis

Bortezomib,the first potent therapeutic proteasome inhibitor,has been suggested as a standard care in patients with newly diagnosed and relapsed multiple myeloma（MM）.However,evidence bearing on the efficacy and safety of subcutaneous（SC） versus intravenous（IV） administration of bortezomib for MM patients is controversial.Randomised controlled trials（RCTs） and observational studies were enrolled in our meta-analysis to investigate the efficacy and safety of bortezomib via SC vs.IV administration on MM patients.Sixteen trials with a total of 2575 patients with MM（SC,n=1191;IV,n=1384） were included in our meta-analysis.There were no significant differences between these two arms regarding overall response rate（ORR）,complete response（CR）,or very good partial response（VGPR）.The pooled RRs for rate of adverse events（AEs）,such as thrombocytopenia and bortezomib-induced peripheral neuropathy（BIPN）,were 0.79（95% CI：0.68–0.92） and 0.63（95% CI：0.51–0.79）,respectively.Moreover,there was much more largely decreased incidence of grade 3 and higher thrombocytopenia and BIPN in bortezomib SC administration than IV route.In general,alternative SC administration should be considered instead of IV administration in use of bortezomib for patients with MM.

Timing, method and discontinuation of hydrocortisone administration for septic shock patients

AIM To characterize the prescribing patterns for hydrocortisone for patients with septic shock and perform an exploratory analysis in order to identify the variables associated with better outcomes.METHODS This prospective cohort study included 59 patients with septic shock who received stress-dose hydrocortisone.It was performed at 2 critical care units in academic hospitals from June 1st, 2015, to July 31 st, 2016. Demographic data, comorbidities, medical management details, adverse effects related to corticosteroids, and outcomes were collected after the critical care physician indicated initiation of hydrocortisone. Univariate comparison between continuous and bolus administration of hydrocortisone was performed, including multivariate analysis, as well as Kaplan-Meier analysis to compare the proportion of shock reversal at 7 d after presentation. Receiver operating characteristic(ROC) curves determined the best cut-off criteria for initiation of hydrocortisone associated with the highest probability of shock reversal. We addressed the effects of the taper strategy for discontinuation of hydrocortisone, noting risk of shock relapse and adverse effects.RESULTS All-cause 30-d mortality was 42%. Hydrocortisone was administered as a continuous infusion in 54.2% of patients; time to reversal of shock was 49 h longer in patients who were given a bolus administration [59 h(range, 47.5-90.5) vs 108 h(range, 63.2-189); P = 0.001]. The maximal dose of norepinephrine after initiation of hydrocortisone was lower in patients on continuous infusion [0.19 μg/kg per minute(range, 0.11-0.28 μg)] compared with patients who were given bolus [0.34 μg/kg per minute(range, 0.16-0.49); P = 0.004]. Kaplan-Meier analysis revealed a higher proportion of shock reversal at 7 d in patients with continuous infusion compared to those given bolus(83% vs 63%; P = 0.004). There was a good correlation between time to initiation of hydrocortisone and time to reversal of shock(r = 0.80; P < 0.0001); ROC curve analysis revealed that the best criteria for prediction of shock reversal was a time to initiation of hydrocortisone of ≤ 13 h after administration of norepinephrine, with an area under the curve of 0.81(P < 0.001). The maximal dose of norepinephrine at initiation of hydrocortisone with the highest association with shock reversal was ≤ 0.28 μg/kg per minute, with an area under the curve of 0.75(P = 0.0002). On a logistic regression model, hydrocortisone taper was not associated with a lower risk of shock relapse(RR = 1.29; P = 0.17) but was related to a higher probability of hyperglycemia [odds ratio(OR), 5.3; P = 0.04] and hypokalemia(OR = 10.6; P = 0.01). CONCLUSION Continuous infusion of hydrocortisone could hasten the resolution of septic shock compared to bolus administration. Earlier initiation corresponds with a higher probability of shock reversal. Tapering strategy is unnecessary.

Oral Administration Following Subcutaneous Administration of FCV Vaccines Enhances Vaccine Efficacy against Challenge of a Highly Virulent Vs Feline Calicivirus

Feline calicivirus (FCV) is a common cause of upper respiratory and oral disease in cats. Highly virulent systemic strains of FCV (vs FCV) have been described. These vs FCV isolates cause characteristic edema, cutaneous ulcers and other clinical signs typically associated with FCV infection. Vs FCV isolates also cause high mortality even in previously vaccinated cats. We reported previously that the FCV serum cross-neutralization profile of cat serum generated using the oralnasal route of administration is broader than with subcutaneous administration (SC), as measured with a 26-FCV viral panel (Rong et al., Virus Research 122:95-108, 2006). In this report, we tested the in vivo ef- ficacy of the FCV vaccine, in a 4-way (FCV-FHV-FPV-FCp) format, by using a highly virulent vs FCV- 33585 as the challenge virus. Vaccines were administered as 2-dose subcutaneouly (SC/SC), or subcutaneously followed by orally (SC/Oral). The mortality induced by vs FCV-33585 in unvaccinated control cats was 78% (7 out of 9 cats). The mortality decreased to 44% (4 out of 9 cats) with cats vaccinated with the 4-way vaccine given SC/SC. However, when this vaccine was given SC/Oral, the mortality decreased to 10% (1 out of 10 cats). The clinical scores, calculated based on frequency and severity of various clinical signs, correlated with mortality data. These results demonstrated that oral administration of FCV vaccines, as the second dose following the first dose of subcutaneious administration, ehances FCV efficacy against challenge of a highly virulent vs FCV. We propose that not only oral vaccination offers convenience and needle-free inoculation, it also enhances FCV vaccine efficacy.