Detection and analysis of signals of adverse events of memantine based on the US food and drug administration adverse event reporting system.

BACKGROUND: Despite its widespread use, the adverse effects (AEs) of memantine have not been well documented, and there is a need to find new ways to analyze the AEs of memantine. RESEARCH DESIGN AND METHODS: AEs in which the primary suspected drug was memantine were retrieved from the FAERS database. The proportional report ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM) were used to detect potential positive signals between memantine and AEs. SAS, MySQL, EXCEL, and R language software were used for data processing and statistical analysis. RESULTS: This study gathered a total of 5808 reports of AEs associated with memantine. Of these reports, a greater proportion of female patients (51.17%) than male patients (36.33%) had AEs. The AEs reported by FAERS were mainly in psychiatric category (n = 2157, IC025 = 2.69), various neurologic disorders (n = 1608, IC025 = 2.04), systemic disorders and various site reactions (n = 842, IC025 = 1.29). Unexpected ocular adverse events have been reported, ophthalmic vein thrombosis (n = 4, IC025 = 3.47) and scleral discolouration (n = 7, IC025 = 3.1), which may worsen glaucoma. CONCLUSIONS: This study observed conceivable new AEs signals and may supply important assist for scientific monitoring and threat identification of memantine.

Research advances and trends in anatomy from 2013 to 2023: A visual analysis based on CiteSpace and VOSviewer.

As the cornerstone of medicine, the development of anatomy is related to many disciplines and fields and has received extensive attention from researchers. How to integrate and grasp the cutting-edge information in this field quickly is a challenge for researchers, so the aim of this study is to analyze research in anatomy using CiteSpace and VOSviewer in order to identify research hotspots and future directions. To offer a fresh viewpoint for assessing the academic influences of researchers, nations, or institutions on anatomy, and to examine the development of hotspots in anatomical study and to forecast future trends. A total of 4637 anatomy-related publications from 2013 to 2023 were collected from Web of Science Core Collection databases. Their temporal distribution, spatial distribution, cited authors, co-cited journals, keywords, and disciplinary connections in the literature were analyzed using CiteSpace and VOSviewer, and a knowledge graph was constructed. The temporal distribution shows a general fluctuation in the amount of literature published from 2013 to 2023. In spatial distribution, the total number of published articles was highest in the United States, the United Kingdom, and China, the United States leading. Tubbs, Rhoton, Iwanaga, and LaPrade are important authors in anatomy. Clinical Anatomy, Surgical and Radiologic Anatomy, and Journal of Anatomy were the most highly cited journals. Analysis of keywords and citation emergence showed that the research hotspots and trends in anatomy focused mainly on anatomy education, digital technology, and surgical management. At the same time, anatomy showed a trend toward multidisciplinary crossover, developing closer relationships with molecular biology, immunology, and clinical medicine. Current research in anatomy focuses on innovative reform of the educational model and the application and promotion of digital technology. Also, multidisciplinary cross-fertilization is an inevitable trend for the future development of anatomy.

A real-world disproportionality analysis of the FDA adverse event reporting system events for ibuprofen.

INTRODUCTION: Ibuprofen is commonly used as an over-the-counter (OTC) antipyretic and analgesic. As the frequency of its use has increased, there has been a corresponding increase in reports of associated adverse events (AEs). However, these events have not been systematically reported in the literature. Meanwhile, the importance of effective pharmacovigilance in evaluating the benefits and risks of drugs is being recognized. METHODS: The data was obtained indirectly from FAERS using the OpenVigil 2 database, lexically mapped using software such as MySQL, Microsoft Excel, and the R language, and then subjected to four more rigorous algorithms to detect risk signals associated with ibuprofen AEs. RESULTS: By analyzing data from the past 18 years, 878 ibuprofen-related AEs were identified as primary AEs. Notably, unexpected reproductive system and breast diseases, etc., which were unexpected, were observed as important system organ classes (SOCs) associated with ibuprofen. Among the 651 preferred terms (PTs) that simultaneously satisfy the four arithmetic methods, renal tubular acidosis and lip oedema are proposed as new signals for ibuprofen AEs. CONCLUSION: This study explores the important and valuable potential AEs and ADRs of ibuprofen at the SOC and PT levels, respectively. To provide a reference on decision-making for ibuprofen to promote rational clinical dosing.

Advancements in the ERK1/2 Signaling Pathway Affecting Male Reproduction.

Male infertility, age-related changes, and tumors have been increasingly studied in the field of male reproductive health due to the emergence of environmental stressors, declining fertility rates, and aging populations. Numerous studies have demonstrated that the ERK1/2 signaling pathway plays a significant role in male reproduction. The ERK1/2 pathway is associated with several signaling pathways and has a complex interplay that influences the spermatogenic microenvironment, sperm viability, gonadal axis regulation, as well as resistance to testicular aging and tumors. Moreover, the ERK1/2 pathway directly or indirectly regulates testicular somatic cells, which are crucial for maintaining spermatogenesis and microenvironment regulation. Given the critical role of the ERK1/2 signaling pathway in male reproductive health, comprehensive exploration of its multifaceted effects on male reproduction and underlying mechanisms is necessary. This study aims to provide a solid foundation for in-depth research in the field of male reproduction and further enhance the reproductive health of males.

Metformin adverse event profile: a pharmacovigilance study based on the FDA Adverse Event Reporting System (FAERS) from 2004 to 2022.

BACKGROUND: Metformin has the potential for treating numerous diseases, but there are still many unrecognized and unreported adverse events (AEs). METHODS: We selected data from the United States FDA Adverse Event Reporting System (FAERS) database from the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2022 for disproportionality analysis to assess the association between metformin and related adverse events. RESULTS: In this study 10,500,295 case reports were collected from the FAERS database, of which 56,674 adverse events related to metformin were reported. A total of 643 preferred terms (PTs) and 27 system organ classes (SOCs) that were significant disproportionality conforming to the four algorithms simultaneously were included. The SOCs included metabolic and nutritional disorders (p = 0.00E + 00), gastrointestinal disorders (p = 0.00E + 00) and others. PT levels were screened for adverse drug reaction (ADR) signals such as acute pancreatitis (p = 0.00E + 00), melas syndrome, pemphigoid (p = 0.00E + 00), skin eruption (p = 0.00E + 00) and drug exposure during pregnancy (p = 0.00E + 00). CONCLUSION: Most of our results were consistent with the specification, but some new signals of adverse reactions such as acute pancreatitis were not included. Therefore, further studies are needed to validate unlabeled adverse reactions and provide important support for clinical monitoring and risk identification of metformin.

Global Status and Future Trends of Fascia and Pain Research in 2013-2022: Bibliometric Analysis Based on CiteSpace and VOSviewer.

Background: Fascial pathological pain is the main type of chronic pain in older adults today, and studying the relationship between fascia and pain can help in the clinical search for effective treatments. However, in the face of the vast amount of research findings, there is no systematic assessment of the relationship between fascia and pain in a bibliometric analysis. Therefore, the purpose of this study is to analyze studies on fascia and pain using CiteSpace and VOSviewer to identify research hotspots and future directions. Materials and Methods: A total of 744 papers related to fascia and pain from 2013 to 2022 were collected from the core collection database of Web of Science, and the authors, countries, institutions, keyword co-occurrence, keyword clustering, and keyword emergence were analyzed by CiteSpace and VOSviewer to construct a knowledge map. Results: Literature publication has shown an overall upward trend over the past decade, but there have been some fluctuations. Carmelo Pirri, Caterina Fede, and Raffaele De Caro are the top three authors with the most articles. The United States, China, and Spain are major contributors to fascial and pain research. The University of Padua, Universidad Complutense and Harvard Medical School are leading institutions in this field. However, it is noteworthy that the collaboration between authors, countries and institutions is not active. Keyword analysis showed that hot spots and trends in research on fascia and pain focused on hot diseases, major interventions, and mechanism exploration. Conclusion: This analysis identifies the most influential authors, institutions, and countries in the field of fascial and pain research and provides a reference for assessing their academic impact. The analysis of keywords and co-cited literature is useful for analyzing research hotspots and their evolution, as well as for predicting future trends.

Revealing the Mechanisms of Byu dMar 25 in the Treatment of Alzheimer's Disease through Network Pharmacology, Molecular Docking, and In Vivo Experiment.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease, severely reducing the cognitive level and life quality of patients. Byu dMar 25 (BM25) has been proved to have a therapeutic effect on AD. However, the pharmacological mechanism is still unclear. Therefore, this study aims to reveal the potential mechanism of BM25 affecting AD from the perspective of network pharmacology and experimental validation. METHODS: The potential active ingredients of BM25 were obtained from the TCMSP database and literature. Possible targets were predicted using SwissTargetPrediction tools. AD-related genes were identified by using GeneCards, OMIM, DisGeNET, and Drugbank databases. The candidate genes were obtained by extraction of the intersection network. Additionally, the "drug-target-disease" network was constructed by Cytoscape 3.7.2 for visualization. The PPI network was constructed by the STRING database, and the core network modules were filtered by Cytoscape 3.7.2. Enrichment analysis of GO and KEGG was carried out in the Metascape platform. Ledock software was used to dock the critical components with the core target. Furthermore, protein levels were evaluated by immunohistochemistry. RESULTS: In this study, 112 active components, 1112 disease candidate genes, 3084 GO functions, and 277 KEGG pathways were obtained. Molecular docking showed that the effective components of BM25 in treating AD were ß-asarone and hydroxysafflor yellow A. The most important targets were APP, PIK3R1, and PIK3CA. Enrichment analysis indicated that the Golgi genetic regulation, peroxidase activity regulation, phosphatidylinositol 3-kinase complex IA, 5-hydroxytryptamine receptor complexes, cancer pathways, and neuroactive ligand-receptor interactions played vital roles against AD. The rat experiment verified that BM25 affected PI3K-Akt pathway activation in AD. CONCLUSIONS: This study reveals the mechanism of BM25 in treating AD with network pharmacology, which provides a foundation for further study on the molecular mechanism of AD treatment.

Research Progress on the Effect of Autophagy and Exosomes on Liver Fibrosis.

Chronic liver disease is a known risk factor for the development of liver cancer, and the development of microRNA (miRNA) liver therapies has been hampered by the difficulty of delivering miRNA to damaged tissues. In recent years, numerous studies have shown that hepatic stellate cell (HSC) autophagy and exosomes play an important role in maintaining liver homeostasis and ameliorating liver fibrosis. In addition, the interaction between HSC autophagy and exosomes also affects the progression of liver fibrosis. In this paper, we review the research progress of mesenchymal stem cell-derived exosomes (MSC-EVs) loaded with specific miRNA and autophagy, and their related signaling pathways in liver fibrosis, which will provide a more reliable basis for the use of MSC-EVs for therapeutic delivery of miRNAs targeting the chronic liver disease.

To Explore the Molecular Mechanism of Acupuncture Alleviating Inflammation and Treating Obesity Based on Text Mining.

Objective: To explore the related mechanism of acupuncture affecting obesity by regulating inflammation using bioinformatics methods. Methods: The genes related to obesity, inflammation, and acupuncture and inflammation were mined using GenCLiP 3, and the intersecting genes were extracted using Venn diagram. The DAVID database was employed for pathway enrichment analysis and functional annotation of coexpressed genes. Then, the protein-protein interaction (PPI) network was constructed with the STRING database and visualized by the Cytoscape software and screened out important hub genes. Finally, the Boxplot and Survival Analysis of the hub genes in various cancers were performed by GEPIA. Results: 755 genes related to obesity and inflammation and 38 genes related to acupuncture and inflammation were identified, and 24 coexpressed genes related to obesity, inflammation, and acupuncture were extracted from the Venn diagram. Eight hub genes including interleukin-6 (IL-6), interleukin-10 (IL-10), Toll-like receptor 4 (TLR4), signal transduction and transcriptional activation factor 3 (STAT3), C-X-C motif chemokine 10 (CXCL10), interleukin-17A (IL-17A), prostaglandin peroxide synthesis-2 (PTGS2), signal transistors, and transcriptional activation factor 6 (STAT6) were identified by gene ontology (GO), Kyoto Encyclopedia of Genes (KEGG), and PPI network analysis. Among them, IL-6 is suggested to play an essential role in the treatment of obesity and inflammation by acupuncture, and IL-6 was significant in both Boxplot and Survival Analysis of pancreatic cancer (PAAD). Therefore, in this study, the core gene, IL-6 was used as the breakthrough point to explore the possible mechanism of acupuncture in treating obesity and pancreatic cancer by regulating IL-6. Conclusion: (1) Acupuncture can regulate the expression of IL-6 through the TLR4/nuclear factor-κB (NF-κB) pathway, thereby alleviating inflammation, which can be used as a potential strategy for the treatment of obesity. (2) IL-6/STAT3 is closely related to the occurrence, development, and metastasis of pancreatic cancer. Acupuncture affecting pancreatic cancer through TLR4/NF-κB/IL-6/STAT3 pathway may be a potential method for the treatment of pancreatic cancer.

Anatomy of the Cun Position at Wrist and Its Application in Pulse Diagnosis.

Information on anatomy of the Cun position at wrist is lacking; whether the blood vessel taking pulse in Cun is the radial artery or the superficial palmar branch is also clinically controversial. The objective was to investigate the boundaries and contents, and the vascular distribution and their pulse points in Cun. Thirty-two upper extremities of 16 human cadavers were investigated for dissection and observation. The boundaries, contents, and blood vessel distribution in Cun were observed; the location of pulse points in Cun was identified; the length of the superficial palmar branch in wrist pulse (L1), the pulp width of the index finger (L2), and the angle between the radial artery and the superficial palmar branch were measured. The results showed that the Cun was located in the region formed by the bulge of the prominent bone proximal to the palm, the radial flexor tendon, the tubercle of scaphoid, and the abductor longus muscle tendon. In this area, the radial artery could be pulsed part in the medial side of the abductor longus muscle tendon, while the superficial palmar branch lied near the surface and was easy to pulse in the lateral side of the radial flexor tendon and the medial side of the tubercle of scaphoid. The ratio of L1 to L2 was 1.2±0.8, and the angle was 23.3±9.9°. The results suggested that it could not be generalized that the blood vessel taking pulse in Cun was the radial artery or the superficial palmar branch; it might depend on the vascular distribution in Cun, the region of finger positioning, and the patient's pulse condition.

Fascia and Primo Vascular System.

The anatomical basis for the concept of acupuncture points/meridians in traditional Chinese medicine (TCM) has not been resolved. This paper reviews the fascia research progress and the relationship among acupuncture points/meridians, primo vascular system (PVS), and fascia. Fascia is as a covering, with common origins of layers of the fascial system despite diverse names for individual parts. Fascia assists gliding and fluid flow and holds memory and is highly innervated. Fascia is intimately involved with nourishment of all cells of the body, including those of disease and cancer. The human body's fascia network may be the physical substrate represented by the meridians of TCM. The PVS is a newly found circulatory system; recent increased interest has led to new research and new discoveries in the anatomical and functional aspects of the PVS. The fasciology theory provides new insights into the physiological effects of acupuncture needling on basic cellular mechanisms including connective tissue mechanotransduction and regeneration. This view represents a theoretical basis and means for applying modern biomedical research to examining TCM principles and therapies, and it favors a holistic approach to diagnosis and treatment.

Transplanted Adipose-Derived Stem Cells Ameliorate Testicular Dysfunction In A D-Galactose-Induced Aging Rat Model.

Glycation product accumulation during aging of slowly renewing tissues may be an important mechanism underlying aging of the testis. Adipose-derived stem cells (ADSCs) have shown promise in a novel tissue regenerative technique and may have utility in treating sexual dysfunction. ADSCs have also been found to be effective in antiaging therapy, although the mechanism underlying their effects remains unknown. This study was designed to investigate the anti-aging effect of ADSCs in a D-galactose (D-gal)-induced aging animal model and to clarify the underlying mechanism. Randomly selected 6-week-old male Sprague-Dawley rats were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, D-gal-induced aging rats were randomized to receive caudal vein injections of 3 × 10(6) 5-bromo 2'deoxy-uridine-labeled ADSCs or an equal volume of phosphate-buffered saline. Serum testosterone level, steroidogenic enzymes (3-ß-hydroxysteroid dehydrogenase), and superoxide dismutase (SOD) activity decreased significantly in aging rats compared with the control group; serum lipid peroxidation, spermatogenic cell apoptosis, and methane dicarboxylic aldehyde (MDA) expression increased significantly. ADSCs increased the SOD level and reduced the MDA level in the aging animal model and restored levels of serum testosterone, steroidogenic enzymes, and spermatogenic cell apoptosis. These results demonstrate that ADSCs can contribute to testicular regeneration during aging. ADSCs also provide functional benefits through glycation suppression and antioxidant effects in a rat model of aging. Although some ADSCs differentiated into Leydig cells, the paracrine pathway seems to play a main role in this process, resulting in the reduction of apoptosis.