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.

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.

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.

Long-term follow-up of intravesical abobotulinumtoxinA (Dysport®) injections in women with idiopathic detrusor overactivity

Objective:Only a few numbers of studies have been published on the use of abobotulinumtoxinA(Dysport®)in idiopathic detrusor overactivity(IDO).This study reported the long-term follow-up of women with IDO who were treated with intravesical Dysport®injections.Methods:Two hundred and thirty-six patients with IDO who had failed first-line conservative and antimuscarinic therapy received 500-900 units of Dysport®between April 2014 and July 2015.All patients were followed up for 5 years after their initial injection and interviewed on the phone.Results:A total of 236 women with IDO aged from 18 years to 84 years(mean±standard deviation:49.6±15.9 years)were included in our study.The median follow-up time for patients was 36.5(range:10-70)months,and the median recovery time after injection was 18.5(range:0-70)months.A total of 83(35.2%)patients stated that they had subjective improvement of their symptoms whereas 84(35.6%)patients did not report any improvement in symptoms.The initial International Consultation on Incontinence Questionnaire Overactive Bladder mean score was 6.9(standard deviation 3.4).There was a positive association between the median recovery time and the components of the International Consultation on Incontinence Questionnaire Overactive Bladder questionnaire.Conclusion:In a sub-population of overactive bladder patients with IDO who have failed first-line therapy,a single intravesical Dysport®injection can resolve patient symptoms completely or reduce the symptoms to an acceptable level that can be controlled with antimuscarinics or re-injection on demands.

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.

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.

“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。