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.

Building a Smart Management System for the Field Training Course at the Faculty of Specific Education-Mansoura University

Field training is the backbone of the teacher-preparation process.Its importance stems from the goals that colleges of education aim to achieve,which include bridging the gap between theory and practice and aligning with contemporary educational trends during teacher training.Currently,trainee students attendance in field training is recordedmanually through signatures on attendance sheets.However,thismethod is prone to impersonation,time wastage,and misplacement.Additionally,traditional methods of evaluating trainee students are often susceptible to human errors during the evaluation and scoring processes.Field training also lacks modern technology that the supervisor can use in case of his absence from school to monitor the trainee students’implementation of the required activities and tasks.These shortcomings do not meet the needs of the digital era that universities are currently experiencing.As a result,this paper presents a smart management system for field training based on Internet of Things(IoT)and mobile technology.It includes three subsystems:attendance,monitoring,and evaluation.The attendance subsystem uses an R307 fingerprint sensor to record trainee students’attendance.The Arduino Nano microcontroller transmits attendance data to the proposed Android application via an ESP-12F Wi-Fi module,which then forwards it to the Firebase database for storage.The monitoring subsystem utilizes Global Positioning System(GPS)technology to continually track trainee students’locations,ensuring they remain at the school during training.It also enables remote communication between trainee students and supervisors via audio,video,or text by integrating video call and chat technologies.The evaluation subsystem is based on three items:an online exam,attendance,and implementation of required activities and tasks.Experimental results have demonstrated the accuracy and efficiency of the proposed management system in recording attendance,as well as in monitoring and evaluating trainee students during field traiing.

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.

Subtle skills: Using objective structured clinical examinations to assess gastroenterology fellow performance in system based practice milestones

BACKGROUND System based practice(SBP) milestones require trainees to effectively navigate the larger health care system for optimal patient care. In gastroenterology training programs, the assessment of SBP is difficult due to high volume, high acuity inpatient care, as well as inconsistent direct supervision. Nevertheless,structured assessment is required for training programs. We hypothesized that objective structured clinical examination(OSCE) would be an effective tool for assessment of SBP.AIM To develop a novel method for SBP milestone assessment of gastroenterology fellows using the OSCE.METHODS For this observational study, we created 4 OSCE stations: Counseling an impaired colleague, handoff after overnight call, a feeding tube placement discussion, and giving feedback to a medical student on a progress note. Twentysix first year fellows from 7 programs participated. All fellows encountered identical case presentations. Checklists were completed by trained standardized patients who interacted with each fellow participant. A report with individual and composite scores was generated and forwarded to program directors to utilize in formative assessment. Fellows also received immediate feedback from a faculty observer and completed a post-session program evaluation survey.RESULTS Survey response rate was 100%. The average composite score across SBP milestones for all cases were 6.22(SBP1), 4.34(SBP2), 3.35(SBP3), and 6.42(SBP4)out of 9. The lowest composite score was in SBP 3, which asks fellows to advocate for cost effective care. This highest score was in patient care 2, which asks fellows to develop comprehensive management plans. Discrepancies were identified between the fellows’ perceived performance in their self-assessments and Standardized Patient checklist evaluations for each case. Eighty-seven percent of fellows agreed that OSCEs are an important component of their clinical training,and 83% stated that the cases were similar to actual clinical encounters. All participating fellows stated that the immediate feedback was "very useful." One hundred percent of the fellows stated they would incorporate OSCE learning into their clinical practice.CONCLUSION OSCEs may be used for standardized evaluation of SBP milestones. Trainees scored lower on SBP milestones than other more concrete milestones. Training programs should consider OSCEs for assessment of SBP.

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.

Dexamethasone does not affect endolymphatic hydrops(EH)in patients with Meniere's disease within 24 h,and intratympanic administration of gadolinium plus dexamethasone simplifies high-quality imaging of EH using a novel protocol of 7 min

Background:Intratympanic administration of gadolinium chelate allows for a better visualization of endolymphatic hydrops(EH)using MRI than intravenous injection and was recently further improved to facilitate high-quality imaging of EH in 7 min.The aim of the present study was to simplify the intratympanic administration protocol by mixing gadolinium chelate with therapeutic dexamethasone and to evaluate the effects of this mixture on the visualization of EH in MRI.Materials and methods:In an in vitro study,the potential impact of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)on the stability of dexamethasone was evaluated by analyzing dynamic changes in dexamethasone with high-performance liquid chromatography(HPLC)after mixing with GdDTPA.Ten patients with definite Meniere's disease(MD)were recruited to study the potential interference of dexamethasone on MRI visualization of EH,and 49 patients with MD were recruited to evaluate the effect of intratympanic injection of Gd-DTPA mixed with dexamethasone on MRI of EH using a 3T MR machine and a novel heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed using a magnitude plus zero-filled interpolation(hT2FLAIR-MZFI)sequence.Results:The retention times and peak area of dexamethasone in HPLC were not modified by the addition of Gd-DTPA.EH grading in the cochlea and vestibule was not influenced in any ear by intratympanic injection of dexamethasone.Excellent inner ear images were obtained from all patients,and EHs with various grades were displayed.There were significant correlations between diagnosis and cochlear EH(p<0.01,Spearman's Rho),between diagnosis and vestibular EH(p<0.01,Spearman's Rho),and between cochlear and vestibular EH(p<0.01,Spearman's Rho).The distribution of Gd-DTPA plus dexamethasone negatively correlated with the grade of vestibular EH.Injury of the endolymph-perilymph barrier was detected in one cochlea and three vestibules of 59 inner ears with MD.Conclusions:Intratympanic administration of Gd-DTPA plus dexamethasone yielded high-quality MRI images of EH in patients with MD using a novel 7-min protocol and simplified the clinical application.Intratympanic administration of Gd-DTPA plus dexamethasone might be used to test its therapeutic effect in future work.

Novel Solution Based on Face Recognition to Address Identity Theft and Cheating in Online Examination Systems

The main objective of this research is to provide a solution for online exam systems by using face recognition to authenticate learners for attending an online exam. More importantly, the system continuously (with short time intervals), checks for learner identity during the whole exam period to ensure that the learner who started the exam is the same one who continued until the end and prevent the possibility of cheating by looking at adjacent PC or reading from an external paper. The system will issue an early warning to the learners if suspicious behavior has been noticed by the system. The proposed system has been presented to eight e-learning instructors and experts in addition to 32 students to gather feedback and to study the impact and the benefit of such system in e-learning environment.

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.

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.

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.

A Study on System Availability Vs System Administration Efforts with Mathematical Models

Two mathematical models are developed in this paper to study the effectiveness of system administration efforts on the improvement of system availability, based on the assumption that there exists a transitional state for a computer system in operation before it is brought down by some hardware or software problems and with intensified system administration efforts, it is possible to discover and fix the problems in time to bring the system back to normal state before it is down. Markov chain is used to simulate the transition of system states. A conclusion is made that increasing system administration efforts may be a cost-effective way to meet the requirements for moderate improvement on system availability, but higher demand on this aspect still has to be met by advanced technologies.

A Study on the Reform of China's Agricultural Administration System

After various reforms,China's agricultural administration system has been changing functions and improving structure,and it has basically met the requirements of agricultural and rural economic development,but in some areas,it can not be adapted to modern agricultural development. Based on the analysis of the necessity of improving agricultural administration system and the problems in current agricultural administration system,this paper comes up with the viable path choice of China's agricultural administration system reform.

ISHD:Intelligent Standing Human Detection of Video Surveillance for the Smart Examination Environment

In the environment of smart examination rooms, it is important to quickly and accurately detect abnormal behavior(human standing) for the construction of a smart campus. Based on deep learning, we propose an intelligentstanding human detection (ISHD) method based on an improved single shot multibox detector to detect thetarget of standing human posture in the scene frame of exam room video surveillance at a specific examinationstage. ISHD combines the MobileNet network in a single shot multibox detector network, improves the posturefeature extractor of a standing person, merges prior knowledge, and introduces transfer learning in the trainingstrategy, which greatly reduces the computation amount, improves the detection accuracy, and reduces the trainingdifficulty. The experiment proves that the model proposed in this paper has a better detection ability for the smalland medium-sized standing human body posture in video test scenes on the EMV-2 dataset.

Impact of Bar-Code Medication Administration and Electronic Medication Administration Record System in Clinical Practice for an Effective Medication Administration Process

Clinical innovations are ideations resulting from collective experiences that enhance the “norm” and embrace an avenue for change with an invention. As such, collective data that were suggestive of increased medication errors that compromised patient safety initiated the exploration of methods that could reduce multifactorial human errors. The pursuit for an appropriate system followed with the discovery of barcode medication administration system (BCMA) and electronic medication administration system (e-MAR). Prior to the adoption of BCMA and e-MAR, it was crucial to assess the impact of the new medication administration system and the rate of medication administration errors recorded, specifically those that resulted in harm. The purpose of the study was to evaluate BCMA and e-MAR usage outcomes, clinical practices, policies, and processes impacting nurses administering medications in the clinical environment using BCMA and e-MAR system. Thus, an annotated literature review was conducted prior to the implementation of the innovation which analyzed various studies that elaborated on their study methods, data collection and analysis that deliberated on the advantages and disadvantages of barcode medication administration system. It is evident in the researched journals that increased compliance was observed with appropriate guidance, processes and policies in place. There was also a significant reduction in reported errors. The incorporation of barcode technology with electronic medication administration record (e-MAR) had greatly improved the efficiency of the BCMA system. BCMAs method was one of the proposed solutions to medication administration errors and to enhance patient safety measures. As such, the innovation could significantly reduce medication error resulting from intrinsic and extrinsic factors. This paper will further elaborate on the advantages and disadvantages of BCMA and e-MAR, the strategies assumed in the development of BCMA and e-MAR system and its implementation process by identifying and overcoming potential challenges that may arise.

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.