A Case of 'Neptune's Fix Elixir': The Dangerous Consequences of Unregulated Use of Tianeptine in Over-the-Counter Products.

Tianeptine is an atypical tricyclic antidepressant approved for the treatment of major depressive disorder in some European, Asian, and Latin countries. Along with its serotonergic properties, tianeptine also acts as a full agonist at the mu-opioid receptor, creating sensations of euphoric highs and significant risks of addiction and withdrawal. For this reason, along with increased reports of adverse effects and fatalities, tianeptine has not been approved in the US. Despite this, tianeptine continues to be accessible through unregulated online stores and small retailers under street names such as Zaza, Tia, Tianna, 'gas-station dope', and a product not mentioned in the literature previously: Neptune's Fix Elixir. In this report, we discuss the case of a 34-year-old male who presented to the ED via EMS after being found unresponsive secondary to the ingestion of Neptune's Fix Elixir, whose main active ingredient is tianeptine.

A federated authentication schema among multiple identity providers.

Single Sign-On (SSO) methods are the primary solution to authenticate users across multiple web systems. These mechanisms streamline the authentication procedure by avoiding duplicate developments of authentication modules for each application. Besides, these mechanisms also provide convenience to the end-user by keeping the user authenticated when switching between different contexts. To ensure this cross-application authentication, SSO relies on an Identity Provider (IdP), which is commonly set up and managed by each institution that needs to enforce SSO internally. However, the solution is not so straightforward when several institutions need to cooperate in a unique ecosystem. This could be tackled by centralizing the authentication mechanisms in one of the involved entities, a solution raising responsibilities that may be difficult for peers to accept. Moreover, this solution is not appropriate for dynamic groups, where peers may join or leave frequently. In this paper, we propose an architecture that uses a trusted third-party service to authenticate multiple entities, ensuring the isolation of the user's attributes between this service and the institutional SSO systems. This architecture was validated in the EHDEN Portal, which includes web tools and services of this European health project, to establish a Federated Authentication schema.

A Network Pharmacology-based Study on the Anti-aging Properties of Traditional Chinese Medicine Sisheng Bulao Elixir.

BACKGROUND: Traditional Chinese Medicine (TCM) has a rich history of use in preventing senescence for millennia in China. Nonetheless, a systematic method to study the antiaging properties and the underlying molecular mechanism of TCM remains absent. OBJECTIVE: The objective of this study is to decipher the anti-aging targets and mechanisms of Sisheng Bulao Elixir (SBE) using a systematic approach based on a novel aging database and network pharmacology. METHODS: Bioactive compounds and target proteins in SBE were identified via the Traditional Chinese Medicine System Pharmacology (TCMSP) database. Aging-related proteins were uncovered through alignment with the Ageing Alta database. A compound-target (CT) protein network analysis highlighted key flavonoids targeting aging. Core aging-related proteins were extracted through protein-protein interaction (PPI) network analysis. Molecular docking validated binding activities between core compounds and aging-related proteins. The antioxidant activity of SBE was confirmed using an in vitro senescent cells model. RESULTS: A total of 39 active compounds were extracted from a pool of 639 compounds in SBE. Through a matching process with the Aging Alta, 88 target proteins associated with the aging process were identified. Impressively, 80 out of these 88 proteins were found to be targeted by flavonoids. Subsequently, an analysis using CT methodology highlighted 11 top bioactive flavonoids. Notably, core aging-related proteins, including AKT1, MAPK3, TP53, VEGFA, IL6, and HSP90AA1, emerged through the PPI network analysis. Moreover, three flavonoids, namely quercetin, kaempferol, and luteolin, exhibited interactions with over 100 aging-related proteins. Molecular docking studies were conducted on these flavonoids with their shared three target proteins, namely AKT1, HSP90AA1, and IL6, to assess their binding activities. Finally, the antioxidant properties of SBE were validated using an in vitro model of senescent cells. CONCLUSION: This study offers novel insights into SBE's anti-aging attributes, providing evidence of its molecular mechanisms. It enhances our understanding of traditional remedies in anti-aging research.

Active components and molecular mechanisms of Sagacious Confucius' Pillow Elixir to treat cognitive impairment based on systems pharmacology.

BACKGROUND: Sagacious Confucius' Pillow Elixir (SCPE) is a common clinical prescription to treat cognitive impairment (CI) in East Asia. OBJECTIVE: To predict the active components of SCPE, identify the associated signaling pathway, and explore the molecular mechanism using systems pharmacology and an animal study. METHODS: Systems pharmacology and Python programming language-based molecular docking were used to select and analyze the active components and targets. Senescence-accelerated prone 8 mice were used as a CI model. The molecular mechanism was evaluated using the water maze test, neuropathological observation, cerebrospinal fluid microdialysis, and Western blotting. RESULTS: Thirty active components were revealed by screening relevant databases and performing topological analysis. Additionally, 376 differentially expressed genes for CI were identified. Pathway enrichment analysis, protein-protein interaction (PPI) network analysis and molecular docking indicated that SCPE played a crucial role in modulating the PI3K/Akt/mTOR signaling pathway, and 23 SCPE components interacted with it. In the CI model, SCPE improved cognitive function, increased the levels of the neurotransmitter 5-hydroxytryptamine (5-HT) and metabolite 5-hydroxyindole acetic acid (5-HIAA), ameliorated pathological damage and regulated the PI3K/AKT/mTOR signaling pathway. SCPE increased the LC3-II/LC3-I, p-PI3K p85/PI3K p85, p-AKT/AKT, and p-mTOR/mTOR protein expression ratios and inhibited P62 expression in the hippocampal tissue of the CI model. CONCLUSION: Our study revealed that 23 active SCPE components improve CI by increasing the levels of the neurotransmitter 5-HT and metabolite 5-HIAA, suppressing pathological injury and regulating the PI3K/Akt/mTOR signaling pathway to improve cognitive function.

The ELIXIR Biodiversity Community: Understanding short- and long-term changes in biodiversity.

Biodiversity loss is now recognised as one of the major challenges for humankind to address over the next few decades. Unless major actions are taken, the sixth mass extinction will lead to catastrophic effects on the Earth's biosphere and human health and well-being. ELIXIR can help address the technical challenges of biodiversity science, through leveraging its suite of services and expertise to enable data management and analysis activities that enhance our understanding of life on Earth and facilitate biodiversity preservation and restoration. This white paper, prepared by the ELIXIR Biodiversity Community, summarises the current status and responses, and presents a set of plans, both technical and community-oriented, that should both enhance how ELIXIR Services are applied in the biodiversity field and how ELIXIR builds connections across the many other infrastructures active in this area. We discuss the areas of highest priority, how they can be implemented in cooperation with the ELIXIR Platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for a Biodiversity Community in ELIXIR and is an appeal to identify and involve new stakeholders.

Sagacious confucius' pillow elixir ameliorates Dgalactose induced cognitive injury in mice via estrogenic effects and synaptic plasticity.

Alzheimer's disease (AD) is a growing concern in modern society, and there is currently a lack of effective therapeutic drugs. Sagacious Confucius' Pillow Elixir (SCPE) has been studied for the treatment of neurodegenerative diseases such as AD. This study aimed to reveal the key components and mechanisms of SCPE's anti-AD effect by combining Ultra-high Performance Liquid Chromatography-electrostatic field Orbitrap combined high-resolution Mass Spectrometry (UPLC-LTQ/Orbitrap-MS) with a network pharmacology approach. And the mechanism was verified by in vivo experiments. Based on UPLC-LTQ/Orbitrap-MS technique identified 9 blood components from rat serum containing SCPE, corresponding to 113 anti-AD targets, and 15 of the 113 targets had high connectivity. KEGG pathway enrichment analysis showed that estrogen signaling pathway and synaptic signaling pathway were the most significantly enriched pathways in SCPE anti-AD, which has been proved by in vivo experiments. SCPE can exert estrogenic effects in the brain by increasing the amount of estrogen in the brain and the expression of ERα receptors. SCPE can enhance the synaptic structure plasticity by promoting the release of brain-derived neurotrophic factor (BDNF) secretion and improving actin polymerization and coordinates cofilin activity. In addition, SCPE also enhances synaptic functional plasticity by increasing the density of postsynaptic densified 95 (PSD95) proteins and the expression of functional receptor AMPA. SCPE is effective for treatment of AD and the mechanism is related to increasing estrogenic effects and improving synaptic plasticity. Our study revealed the synergistic effect of SCPE at the system level and showed that SCPE exhibits anti-AD effects in a multi-component, multi-target and multi-pathway manner. All these provide experimental support for the clinical application and drug development of SCPE in the prevention and treatment of AD.

Recommendations for the formatting of Variant Call Format (VCF) files to make plant genotyping data FAIR.

In this opinion article, we discuss the formatting of files from (plant) genotyping studies, in particular the formatting of (meta-) data in Variant Call Format (VCF) files. The flexibility of the VCF format specification facilitates its use as a generic interchange format across domains but can lead to inconsistency between files in the presentation of metadata. To enable fully autonomous machine actionable data flow, generic elements need to be further specified. We strongly support the merits of the FAIR principles and see the need to facilitate them also through technical implementation specifications. VCF files are an established standard for the exchange and publication of genotyping data. Other data formats are also used to capture variant call data (for example, the HapMap format and the gVCF format), but none currently have the reach of VCF. In VCF, only the sites of variation are described, whereas in gVCF, all positions are listed, and confidence values are also provided. For the sake of simplicity, we will only discuss VCF and our recommendations for its use. However, the part of the VCF standard relating to metadata (as opposed to the actual variant calls) defines a syntactic format but no vocabulary, unique identifier or recommended content. In practice, often only sparse (if any) descriptive metadata is included. When descriptive metadata is provided, proprietary metadata fields are frequently added that have not been agreed upon within the community which may limit long-term and comprehensive interoperability. To address this, we propose recommendations for supplying and encoding metadata, focusing on use cases from the plant sciences. We expect there to be overlap, but also divergence, with the needs of other domains.

Systems Biology in ELIXIR: modelling in the spotlight.

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR's future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.

Laniakea@ReCaS: exploring the potential of customisable Galaxy on-demand instances as a cloud-based service.

BACKGROUND: Improving the availability and usability of data and analytical tools is a critical precondition for further advancing modern biological and biomedical research. For instance, one of the many ramifications of the COVID-19 global pandemic has been to make even more evident the importance of having bioinformatics tools and data readily actionable by researchers through convenient access points and supported by adequate IT infrastructures. One of the most successful efforts in improving the availability and usability of bioinformatics tools and data is represented by the Galaxy workflow manager and its thriving community. In 2020 we introduced Laniakea, a software platform conceived to streamline the configuration and deployment of "on-demand" Galaxy instances over the cloud. By facilitating the set-up and configuration of Galaxy web servers, Laniakea provides researchers with a powerful and highly customisable platform for executing complex bioinformatics analyses. The system can be accessed through a dedicated and user-friendly web interface that allows the Galaxy web server's initial configuration and deployment. RESULTS: "Laniakea@ReCaS", the first instance of a Laniakea-based service, is managed by ELIXIR-IT and was officially launched in February 2020, after about one year of development and testing that involved several users. Researchers can request access to Laniakea@ReCaS through an open-ended call for use-cases. Ten project proposals have been accepted since then, totalling 18 Galaxy on-demand virtual servers that employ ~ 100 CPUs, ~ 250 GB of RAM and ~ 5 TB of storage and serve several different communities and purposes. Herein, we present eight use cases demonstrating the versatility of the platform. CONCLUSIONS: During this first year of activity, the Laniakea-based service emerged as a flexible platform that facilitated the rapid development of bioinformatics tools, the efficient delivery of training activities, and the provision of public bioinformatics services in different settings, including food safety and clinical research. Laniakea@ReCaS provides a proof of concept of how enabling access to appropriate, reliable IT resources and ready-to-use bioinformatics tools can considerably streamline researchers' work.

Electricity.

Quackery in medicine is as old as medicine. In times of crisis desperate patients believe in extraordinary claims. In the annals of pain killer quack medicine, elixirs, nostrums and liniments hold a special position. The College of Dentistry at NYU received a collection of 234 bottles of quack medicine dating from approximately 1850 through 1940.In this paper, the THIRD in a series of articles featuring "Elixirs of the Past", we focus on five particularly notable samples claiming to have "electric" properties: Electric Brand Oil Compound, Hunt's Lightening Oil, Electric Indian Liniment, Regent's Electric Liniment and Haven's Electro-magnetic Liniment. Needless to say, none of these contained electricity or even electrolytes for that matter. In 1906, Congress enacted The Pure Food and Drug Act to prohibit exaggerated or unsubstantiated claims in the marketing and labeling of household products and to control the use of potentially harmful ingredients. The modern-day use of internet advertisements to make unsupported claims is in some ways even more brazen than the advertisements from a century ago.

DETERMINATION OF SAFETY PROFILE OF REPARATIVE ACTIVITY OF THE NEW HYGIENIC PRODUCT "APIPROL".

OBJECTIVE: The aim: To prove safety of the new elixir and determine the effect on regenerative processes under conditions of the experimental trauma. PATIENTS AND METHODS: Materials and methods: The formula of the new dental elixir "Apiprol" includes biologically active components of bee products (propolis, comb capping wax), plant origin compounds. The elixir was single administered, intragastrally to white nonlinear mice weighing (22±2) g at doses at 50 mg/kg, 500 mg/kg, 5000 mg/kg. Acute toxicity of the new hygienic product "Apiprol" was investigated by a single application at the rate of 1000 and 5000 mg/kg animal weight. Subacute (chronic) toxicity was studied when elixir was applied to the skin of 10 mice at a single daily dose of 500 mg/kg for one month. A local irritant effect of the elixir on the oral mucosa was examined in 14 white rats daily after application for 3-5 min. The study of reparative activity was carried out on an experimental model of the wound process. RESULTS: Results: The elixir's components promote tissues regeneration, rapid epithelialization and wound surfaces healing, having a highly immune stimulating activity and antibacterial properties. CONCLUSION: Conclusions: The performed study proved a complete safety of the new elixir "Apiprol" and indicated a necessity of the further development of this preparation in order to create a greater variety of dental means produced in Ukraine.

Opium.

Quackery in medicine is as old as medicine itself. In times of crisis, desperate patients often believe extraordinary claims. In the annals of pain-killer quack medicine, elixirs, nostrums and liniments hold a prominent position. NYU College of Dentistry (NYUCD) has a collection of 234 bottles of such medicines dating from the mid-1800s through 1940. This paper is the second in a series of articles featuring "Elixirs of the Past" in which we bring to light five more samples containing opium: Dr. B.J. Kendall's Instant Relief for Pain, Dr. Munn's Elixir of Opium, Dill's Balm of Life, Foley's Pain Relief, and Brown's Instant Relief for Pain. These are just five examples out of countless syrups, nostrums, balm or liniments that contained narcotics and were linked to overdose, addiction and sometimes death. In 1906, Congress enacted The Pure Food and Drug Act to stop unsubstantiated medicinal claims and control the use of addictive substances. The modern-day use of internet advertisements to make unsupported claims is in some ways even more brazen than the advertisements from a century ago. Indeed, the recent widespread use of prescription painkillers, along with the resulting epidemic in opiate addiction that has caused upwards of 50,000 deaths is a case in point.

Proteomics Software in bio.tools: Coverage and Annotations.

The large diversity of experimental methods in proteomics as well as their increasing usage across biological and clinical research has led to the development of hundreds if not thousands of software tools to aid in the analysis and interpretation of the resulting data. Detailed information about these tools needs to be collected, categorized, and validated to guarantee their optimal utilization. A tools registry like bio.tools enables users and developers to identify new tools with more powerful algorithms or to find tools with similar functions for comparison. Here we present the content of the registry, which now comprises more than 1000 proteomics tool entries. Furthermore, we discuss future applications and engagement with other community efforts resulting in a high impact on the bioinformatics landscape.

Factors affecting serum phenobarbital concentration changes in pediatric patients receiving elixir and powder formulations.

BACKGROUND: Phenobarbital (PB) is commonly used as elixir and powder formulations in pediatric care. Its dose adjustment is performed based on individual drug concentration monitoring. Few studies have comprehensively analyzed the variation factors for serum PB concentration. In this study, we retrospectively investigated the factors that influence serum PB concentration and assessed the impacts of dosage formulation and administration route. METHODS: This retrospective cohort study covered clinical data from January 2007 to September 2019 at Mie University Hospital. The present study included 60 pediatric patients administered the elixir and powder of PB through oral route and enteral tube. Simple and multiple linear regression analyses were performed to identify the risk factors that affect the weight-corrected PB serum concentration/dose (C/D) ratio in pediatric patients. Six subgroups were also established according to the concomitant use of drugs that potentially inhibit PB metabolism, dosage formulation, and administration route to investigate the difference in the PB C/D ratio among the subgroups. RESULTS: A significant regression equation to predict the PB C/D ratio was found through simple and multiple linear regression analyses, with an adjusted coefficient of determination of 0.53 (p < 0.001). Further, the concomitant uses of valproic acid (VPA) or amiodarone, which were the only two drugs seen in this study as potential inhibitors of PB, was found to have the greatest effect on the PB C/D ratio (standardized partial regression coefficient (ß) = 0.543, p < 0.001). Furthermore, a significant difference in the PB C/D ratio was found between the subgroups classified by the concomitant use of VPA or amiodarone (p = 0.002). However, there were no significant correlations between the PB C/D ratio, dosage formulation, and administration route. CONCLUSIONS: The most influential factor on the PB C/D ratio was the concomitant use of VPA or amiodarone with PB. This result could provide an important perspective in pediatric drug therapy where elixir and powder formulations are administered via the oral route and enteral tube.

ELIXIR and Toxicology: a community in development.

Toxicology has been an active research field for many decades, with academic, industrial and government involvement. Modern omics and computational approaches are changing the field, from merely disease-specific observational models into target-specific predictive models. Traditionally, toxicology has strong links with other fields such as biology, chemistry, pharmacology and medicine. With the rise of synthetic and new engineered materials, alongside ongoing prioritisation needs in chemical risk assessment for existing chemicals, early predictive evaluations are becoming of utmost importance to both scientific and regulatory purposes. ELIXIR is an intergovernmental organisation that brings together life science resources from across Europe. To coordinate the linkage of various life science efforts around modern predictive toxicology, the establishment of a new ELIXIR Community is seen as instrumental. In the past few years, joint efforts, building on incidental overlap, have been piloted in the context of ELIXIR. For example, the EU-ToxRisk, diXa, HeCaToS, transQST, and the nanotoxicology community have worked with the ELIXIR TeSS, Bioschemas, and Compute Platforms and activities. In 2018, a core group of interested parties wrote a proposal, outlining a sketch of what this new ELIXIR Toxicology Community would look like. A recent workshop (held September 30th to October 1st, 2020) extended this into an ELIXIR Toxicology roadmap and a shortlist of limited investment-high gain collaborations to give body to this new community. This Whitepaper outlines the results of these efforts and defines our vision of the ELIXIR Toxicology Community and how it complements other ELIXIR activities.

Magnetism.

Quackery in medicine is as old as medicine itself. In times of crisis desperate patients often believe extraordinary claims. In the annals of pain killer quack medicine, elixirs, nostrums and liniments hold a special position. The College of Dentistry at NYU received a collection of 234 bottles of nostrums and liniments dating from approximately 1850 through 1940. In this paper, the FOURTH in a series of articles featuring "Elixirs of the Past" we bring to light four more samples claiming to have magnetic properties: Dr. J.R. Miller's Magnetic Balm, Havens' Electromagnetic Liniment, Headman's Magnetic Liniments, and Magnetic Cream. It goes without saying that none of these had any magnetic properties. In 1906, Congress enacted The Pure Food and Drug Act to prohibit exaggerated or unsubstantiated claims in the marketing and labeling of household products and to control the use of potentially harmful ingredients. The modern-day use of internet advertisements to make unsupported claims is in some ways even more brazen than the advertisements from a century ago.

Snake Oil and Indian Liniment.

Quackery in medicine is as old as medicine itself. In times of crisis, desperate patients often believe extraordinary claims. In the annals of pain-killer quack medicine, snake oil, elixirs, nostrums and Indian liniments hold a special position. NYU College of Dentistry (NYUCD) has a collection of 234 bottles of such medicines dating from the mid-1800s through 1940. This paper is the fifth in a series of articles featuring "Elixirs of the Past" in which we bring to light six more samples with claims to traditional Chinese or American Indian medicine using snake oil: Virex Compound, Rattlesnake Bill's Oil, Electric Indian Liniment, The King of All Indian Oils, Millerhaus Antiseptic Oil and Celebrated Indian Lotion. The six examples are just a few quack medications linked to fraud, overdose, addiction or death. In 1906, Congress enacted The Pure Food and Drug Act and reinforced it with the Federal Food, Drug and Cosmetic Act of 1938, to stop unsubstantiated medicinal claims and control the use of addictive and dangerous substances. The modern-day use of social media to advertise quack medicine is in some ways even more brazen than selling patent medicine a century ago.

A community proposal to integrate structural bioinformatics activities in ELIXIR (3D-Bioinfo Community).

Structural bioinformatics provides the scientific methods and tools to analyse, archive, validate, and present the biomolecular structure data generated by the structural biology community. It also provides an important link with the genomics community, as structural bioinformaticians also use the extensive sequence data to predict protein structures and their functional sites. A very broad and active community of structural bioinformaticians exists across Europe, and 3D-Bioinfo will establish formal platforms to address their needs and better integrate their activities and initiatives. Our mission will be to strengthen the ties with the structural biology research communities in Europe covering life sciences, as well as chemistry and physics and to bridge the gap between these researchers in order to fully realize the potential of structural bioinformatics. Our Community will also undertake dedicated educational, training and outreach efforts to facilitate this, bringing new insights and thus facilitating the development of much needed innovative applications e.g. for human health, drug and protein design. Our combined efforts will be of critical importance to keep the European research efforts competitive in this respect. Here we highlight the major European contributions to the field of structural bioinformatics, the most pressing challenges remaining and how Europe-wide interactions, enabled by ELIXIR and its platforms, will help in addressing these challenges and in coordinating structural bioinformatics resources across Europe. In particular, we present recent activities and future plans to consolidate an ELIXIR 3D-Bioinfo Community in structural bioinformatics and propose means to develop better links across the community. These include building new consortia, organising workshops to establish data standards and seeking community agreement on benchmark data sets and strategies. We also highlight existing and planned collaborations with other ELIXIR Communities and other European infrastructures, such as the structural biology community supported by Instruct-ERIC, with whom we have synergies and overlapping common interests.

"Possible mechanisms underlying treatment of Alzheimer's disease with Traditional Chinese Medicine: active components, potential targets and synthetic pathways of Bulao Elixir".

OBJECTIVE: To elucidate the mechanisms underlying the treatment of Alzheimer's disease (AD) with Traditional Chinese Medicine (TCM), by examining the active components, potential targets and synthetic pathways of Bulao Elixir (BLE). METHODS: The Absorption, Distribution, Metabolism, Excretion (ADME) / Toxicology (T) calculation was used to screen the active components of Bulao Elixir. Based on the TCM Systems Pharmacology Analysis Platform (TCMSP database) and a text mining tool (GoPubMed database), we predicted and screened the active components of Bulao Elixir and its therapeutic targets for AD. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID), we obtained the targets for AD. Cytoscape software was used to establish a network map of the active component-target and target-pathway of Bulao Elixir. Gene function, related biological processes and signaling pathways were analyzed using the DAVID database. RESULTS: Twelve active components were selected from 196 components of Bulao Elixir. Among 2209 targets, 102 effective targets were selected, and 30 important targets were identified via matching with the disease targets. After further analysis, 14 core targets were identified. Enrichment analysis revealed that most of these important targets were involved in multiple biological processes, including apoptosis, inflammatory reactions, and cell regulation cycles. The synthetic pathways for AD treatment were identified after analyzing and confirming the relevant pathways, providing potentially useful information for diagnosis and treatment methods for AD. CONCLUSION: The current study elucidated the potential treatment mechanisms of Bulao Elixir in AD using network pharmacology, providing a foundation for further clarification of its treatment targets.

Study protocol for efficacy and safety of steroid-containing mouthwash to prevent chemotherapy-induced stomatitis in women with breast cancer: a multicentre, open-label, randomised phase 2 study.

INTRODUCTION: Stomatitis is a frequent adverse event in patients undergoing chemotherapy for breast cancer. Stomatitis can hamper oral nutrition resulting in malnutrition, reduce quality of life and introduce the need for dose reductions and interruption of chemotherapy; however, there is currently no standard approach for preventing chemotherapy-induced stomatitis. We aimed to assess the safety and efficacy of a dexamethasone-based elixir mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. METHODS AND ANALYSIS: In this multicenter, randomised, controlled phase 2 trial, we will randomly assign 120 women with early breast cancer undergoing chemotherapy to use of a dexamethasone-based elixir or standard oral care, to compare their preventive effects on chemotherapy-induced stomatitis. Patients will be assigned in a 1:1 ratio. Patients in the intervention group will receive chemotherapy, oral care and a dexamethasone-based elixir (10 mL 0.1 mg/mL; swish for 2 min and spit, four times daily for 9 weeks), and patients in the control group will receive chemotherapy and oral care. The primary endpoint is the difference in incidence of stomatitis between the two groups. The sample size allows for the detection of a minimum difference of 20% in the incidence of stomatitis between the two groups. Secondary endpoints are severity of stomatitis, duration of stomatitis, completion rate of chemotherapy and adverse events. ETHICS AND DISSEMINATION: All participants signed a written consent form, and the study protocol has been reviewed and approved by the Clinical Research Review Board of Nagasaki University (CRB7180001). TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000030489).