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.

Diagnostic and management challenges in primary cutaneous anaplastic large cell lymphoma with necrosis,inflammation,and surgical intervention:A case report

BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)poses significant diagnostic difficulties due to its similarity in the appearance of skin lesions with chronic inflammatory disorders and other dermatological conditions.This study aims to investigate these challenges by conducting a comprehensive analysis of a case presenting with PC-ALCL,emphasizing the necessity of accurate differentiation for appropriate management.CASE SUMMARY An 89-year-old female patient with diabetes and hypertension presented with arm and abdominal ulcerated mass lesions.Diagnostic procedures included skin biopsies,histopathological assessments,and immunohistochemistry,complemented by advanced imaging techniques to confirm the diagnosis.The patient’s lesions were determined as PC-ALCL,characterized by necrosis,chronic inflammation,and a distinct immunophenotypic profile,including CD30,CD3,CD4,and EBER,CD56,MUM-1,Ki 67-positive in>80%of tumor cells,CD10,but negative for anaplastic lymphoma kinase,CD5,CD20,PAX-5,Bcl-2,Bcl-6,CD8,and CD15.Recurrence was not reported at the 6-month follow-up.CONCLUSION Accurate PC-ALCL differentiation from similar conditions is crucial for effective management and requires a multidisciplinary approach.

Ultrasound-guided peripheral nerve blocks for anterior cutaneous nerve entrapment syndrome after robot-assisted gastrectomy: A case report

BACKGROUND Anterior cutaneous nerve entrapment syndrome(ACNES)is a condition mani-festing with pain caused by strangulation of the anterior cutaneous branch of the lower intercostal nerves.This case report aims to provide new insight into the selection of peripheral nerve blocks for the ACNES treatment.CASE SUMMARY A 66-year-old woman manifested ACNES after a robot-assisted distal gastrec-tomy.An ultrasound-guided rectal sheath block was effective for pain triggered by the port scar.However,the sudden severe pain,which radiated laterally from the previous site,remained.A transversus abdominis plane block was performed for the remaining pain and effectively relieved it.CONCLUSION In this case,the trocar port was inserted between the rectus and transverse abdominis muscles.The intercostal nerves might have been entrapped on both sides of the rectus and transversus abdominis muscles.Hence,rectus sheath and transverse abdominis plane blocks were required to achieve complete pain relief.To the best of our knowledge,this is the first report on use of a combination of rectus sheath and transverse abdominis plane blocks for pain relief in ACNES.

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.

Clinical Study on the Effectiveness of Xian Fang Huo Ming Yin for Treating Cutaneous Infections and Promoting Wound Healing in Patients with Perianal Abscess

Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses who were admitted to our hospital(Xinghua City People’s Hospital)from May 2022 to May 2023 were selected and randomly divided into two groups,a control group(30 cases)and a study group(31 cases).Both groups received surgical treatment.The control group received conventional treatment and warm water fumigation,sitz bath,and surgical dressing change after surgery,while the research group received XFHM based on the control group.XFHM was taken orally and replaced with warm water for fumigation and sitz bathing.Both groups received treatment for 4 weeks but discontinued sitz bathing after 2 weeks.Various clinical indicators between the two groups were compared.Results:The total clinical effective rate and wound recovery rate of the study group were higher than that of the control group.There were differences in the wound pain scores,surrounding tissue edema,and wound secretions at different time points.Both groups experienced wound pain.The scores of wound pain,surrounding tissue edema,and wound secretions of the study group were lower than those of the control group,7 and 14 days after surgery.The serum interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)levels,and pH values of the study group were lower than those of the control group 10 days after surgery(P<0.05).Conclusion:The application of XFHM for treating cutaneous infections and promoting wound healing in patients with perianal abscesses improved the treatment outcome,alleviated clinical symptoms,and promoted healing.

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.

Endometriosis beyond the Pelvis: A Case Series of Cutaneous Endometriosis and Literature Review

Introduction: Cutaneous endometriosis is an uncommon but well-known skin disorder that represents about 0.5% to 1% of all endometriosis. The objective of this case series is to report clinical presentation, diagnosis, and management of various forms of cutaneous endometriosis. Material and Methods: It was an observational, retrospective and descriptive review of cases presenting with cutaneous endometriosis among Cameroonian women managed at the gynaecological outpatient department of Yaounde Gynaeco-Obstetric and Pediatric Hospital. All the following parameters were analysed: age, parity, previous pelvic surgery, presenting symptoms and duration, associated symptoms, localizations, imaging, size of the lesion, other localization of endometriosis, management and histopathological results. Results: we reported 4 cases of cutaneous endometriosis, with 3 umbilical endometriosis and 1 abdominal scar endometriosis. Patient age ranged from 28 to 39 years with an average of 33 years. All patients described infertility (two primary and two secondary) and two had a history of abdominal surgery. All patients presented local cyclical signs such as pain, swelling, color change and bleeding. The duration of symptoms varied from 2 to 3 years and the size of lesions ranged from 2 to 3.5 cm for umbilical lesions and was 9 cm for abdominal scar endometriosis. In all cases, no imaging was required for the diagnosis, which was suspected on the basis of patient’s history and the cyclical nature of local signs, followed by wide surgical excision and confirmation on histopathology. Conclusion: Cutaneaous endometriosis is a rare benign condition. Umbilical endometriosis seems to be the main cutaneous localization and can be described as primary or secondary. Even if its diagnosis must be confirmed by histopathology, it should be considered in patient with cutaneous cyclic signs such as pain, swelling or bleeding with or without history of abdominal surgery.

Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.

Volumetric measurement techniques for assessment of cutaneous neurofibromas:A review

Cutaneous neurofibroma(cNF)is a prevalent clinical manifestation of neurofibromatosis type 1,significantly affecting the well-being and quality of life of the affected individuals.The adoption of reliable and reproducible volumetric measurement techniques is essential for precisely evaluating tumor burden and plays a critical role in the development of effective treatments for cNF.This study focuses on widely used volumetric measurement techniques,including vernier calipers,ultrasound,computed tomography,magnetic resonance imaging,and three-dimensional scanning imaging.It outlines the merits and drawbacks of each technique in assessing the cNF load,providing an overview of their current applications and ongoing research advancements in this domain.

A Case Report on Cutaneous Larva Migrans (CLM)

Cutaneous larva migrans (CLM) is a zoonotic hookworm infection of dogs and cats commonly found in low-income countries in the tropical and subtropical regions and travellers to these regions. It is caused by invasion of the skin by the parasitic larvae of hookworms which, after entry, move under the skin causing an inflammatory reaction resulting in a single or multiple tracks. Patients commonly present with a progressive, itchy, erythematous serpiginous skin rash, affecting the feet, although it can affect any other parts of the body. The diagnosis is mainly clinical, based on history and physical examination. Treatment of this condition can effectively be achieved with either albendazole or ivermectin. We present a case of a 7-year-old boy who was diagnosed with CLM after presenting to the hospital with a history of a progressive itchy rash with tracks on the left foot. Although CLM is a self-limiting disease, it causes a lot of suffering and, therefore, it is of public concern. There is a need to increase awareness of this disease among health workers, and to implement and promote preventive measures against the disease since the cause is known.

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.

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.

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.

Primary Cutaneous Apocrine Carcinoma of the Neck Involving the Parotid Gland: A Case Report and Review of the Literature

Introduction: Primary cutaneous apocrine carcinoma (PCAC) is a rare skin malignant tumor that originates from areas with a high concentration of apocrine glands. The incidence of PCAC in the neck is relatively low. The age of onset in PCAC ranges from 5 to 70 years old. Clinically, PCAC typically shows up as painless nodules or lumps. In immunohistochemistry, positive expression of CK-7, GCDFP-15, AR, and myoepithelial markers are helpful in the diagnosis of PCAC. This case report pertains to a 59-year-old male of Asian descent. Five years ago, a painless mass was discovered behind his right ear, which grew slowly. This patient was identified as PCAC based on clinical symptoms, pathology, immunohistochemistry, and imaging characteristics. PCAC involved the parotid gland in this case;it is easy to be misdiagnosed as a primary malignant tumor of the parotid gland on imaging. Furthermore, a thorough set of clinical, imaging, pathological, and immunohistochemical examinations must be performed to make a diagnosis because it is challenging to differentiate PCAC from metastatic breast carcinoma. Conclusion: A well-developed multidisciplinary examination is essential because PCAC can be challenging to diagnose and differentiate.

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.

Ultrasonographic identification of lateral femoral cutaneous nerve anatomical variation in persistent meralgia paresthetica:A case report

BACKGROUND Meralgia paresthetica(MP)is an entrapment mononeuropathy of the lateral femoral cutaneous nerve(LFCN).Although structural abnormalities in nerve tissues can be confirmed using ultrasonography,this is not routinely performed.CASE SUMMARY Herein,we present the case of a 52-year-old woman who developed MP after laparoscopic gynecological surgery.The patient was referred to our clinic from an obstetrics and gynecology clinic with symptoms of numbness and a tingling sensation in the left anterolateral thigh,which developed after surgery performed 5 mo earlier.Tests were performed to assess the disease status and determine the underlying causes.Ultrasonographic examination revealed an anatomical variation,where the left LFCN was entrapped within the inguinal ligament.This case suggests that performing ultrasonographic examination before and after surgery in the lithotomy position could help prevent MP.CONCLUSION This case demonstrates the value of ultrasonography in detecting anatomical variation and diagnosing persistent MP.Ultrasonography should be considered an adjunct to electromyography for optimal MP management.Further,this case would help other clinicians determine patient prognosis and decide on targeted treatment strategies.

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.

Anti-leishmanial,immunomodulatory and anti-oxidative activity of quercetin against cutaneous leishmaniasis caused by Leishmania major

Objective:To evaluate the in vitro and in vivo efficacy of quercetin and its immunomodulatory and anti-oxidative activity against Leishmania major(L.major).Methods:L.major promastigotes and amastigotes were incubated with different concentrations of quercetin to estimate EC_(50).For in vivo study,the base of tails of mice was infected with L.major.After developing ulcers in the inoculation site,mice were treated with 50 mg/kg quercetin orally for 28 consecutive days.The wound-healing potential of quercetin was evaluated by histopathological analysis of tissue sections stained by hematoxylin and eosin as well as Masson's trichrome.In addition,the levels of tumor necrosis factor-α,interleukin-6,malondialdehyde,and adiponectin,the ferric reducing ability of plasma,as well as superoxide dismutase and glutathione peroxidase activities were measured.Results:The EC_(50)values of quercetin against L.major promastigotes and intracellular amastigotes were 0.27 and 0.85μM,respectively.Histopathological analysis showed that fewer inflammatory cells,more fibroblasts,and more collagen deposition were observed in tissue sections of quercetin-treated mice.In addition,treatment with quercetin markedly increased glutathione peroxidase activity,the ferric reducing ability of plasma and adiponectin levels while decreasing malondialdehyde,interleukin-6,and tumor necrosis factor-αlevels.Conclusions:Quercetin shows anti-leishmanial activity,immunomodulatory,anti-oxidative,and anti-inflammatory effects.Therefore,it may be further explored as an effective drug in treating leishmaniasis.