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Background: The utilization of antibiotic adjuvants presents a promising strategy for addressing bacterial resistance. Recently, the development of antibiotic adjuvants has attracted considerable attention from researchers in academia and industry. This study aimed to identify the most influential publications on antibiotic adjuvants and elucidate the hotspots and research trends in this field.Method: Original articles and reviews related to antibiotic adjuvants were retrieved from the Web of Science Core Collection database. The top 100 highly cited publications were selected and the visual analyses of publication outputs, countries, institutions, authors, journals, and keywords were conducted using Excel, VOSviewer, or CtieSpace software tools.Results: The top 100 cited publications concerning antibiotic adjuvants spanned the years 1977–2020, with citation counts ranging from 174 to 2,735. These publications encompassed 49 original articles and 51 reviews. The journal “Antimicrobial Agents and Chemotherapy” accounted for the highest number of publications (12%). The top 100 cited publications emanated from 39 countries, with the United States leading in production. Institutions in Canada and the United States exhibited the most substantial contributions to these highly cited publications. A total of 526 authors participated in these studies, with Robert E.W. Hancock, Laura J. V. Piddock, Xian-Zhi Li, Hiroshi Nikaido, and Olga Lomovskaya emerging as the most frequently nominated authors. The most common keywords included “E. coli”, “P. aeruginosa”, “S. aureus”, “in-vitro activity”, “antimicrobial peptide”, “efflux pump inhibitor” “efflux pump”, “MexAB-OprM” and “mechanism”. These keywords underscored the hotspots of bacterial resistance mechanisms and the development of novel antibiotic adjuvants.Conclusion: Through the bibliometric analysis, this study identified the top 100 highly cited publications on antibiotic adjuvants. Moreover, the findings offered a comprehensive understanding of the characteristics and frontiers in this field.

Introduction: Community-acquired pneumonia (CAP) is lethal in elderly individuals who are more vulnerable to respiratory failure and require more emergency ventilation support than younger individuals. Interleukin-6 (IL-6) plays a crucial role and has predictive value in CAP; high serum IL-6 concentrations in adults are associated with high respiratory failure and mortality rates. Early detection of IL-6 concentrations can facilitate the timely stratification of patients at risk of acute respiratory failure. However, conventional enzyme-linked immunosorbent assay (ELISA) IL-6 measurement is laborious and time-consuming.Methods: The IL-6 rapid diagnostic system combined with a lateral flow immunoassay-based (LFA-based) IL-6 test strip and a spectrum-based optical reader is a novel tool developed for rapid and sequential bedside measurements of serum IL-6 concentrations. Here, we evaluated the correlation between the IL-6 rapid diagnostic system and the ELISA and the efficacy of the system in stratifying high-risk elderly patients with CAP. Thirty-six elderly patients (median age: 86.5 years; range: 65–97 years) with CAP were enrolled. CAP diagnosis was established based on the Infectious Diseases Society of America (IDSA) criteria. The severity of pneumonia was assessed using the CURB-65 score and Pneumonia Severity Index (PSI). IL-6 concentration was measured twice within 24 h of admission.Results: The primary endpoint variable was respiratory failure requiring invasive mechanical or non-invasive ventilation support after admission. IL-6 rapid diagnostic readouts correlated with ELISA results (p < 0.0001) for 30 samples. Patients were predominantly male and bedridden (69.4%). Ten patients (27.7%) experienced respiratory failure during admission, and five (13.9%) died of pneumonia. Respiratory failure was associated with a higher mortality rate (p = 0.015). Decreased serum IL-6 concentration within 24 h after admission indicated a lower risk of developing respiratory failure in the later admission course (Receiver Operating Characteristic [ROC] curve = 0.696).Conclusion: Sequential IL-6 measurements with the IL-6 rapid diagnostic system might be useful in early clinical risk assessment and severity stratification of elderly patients with pneumonia. This system is a potential point-of-care diagnostic device for sequential serum IL-6 measurements that can be applied in variable healthcare systems.

BackgroundInterstitial pneumonia is a group of pathologies affecting the pulmonary interstitium, characterized by interstitial fibrosis and extensive alveolar consolidation. This disease can extend to the surrounding blood vessels and pulmonary interstitium, sometimes affecting the entire lung, resulting in functional limitations, including restrictive ventilatory defect, impaired gas exchange, and hypoxemia. Severe interstitial pneumonia can lead to death. Antitumor drugs can induce interstitial pneumonia. Sintilimab is an immune checkpoint inhibitor, a recombinant fully human immunoglobulin G-type programmed death protein-1 monoclonal antibody inhibitor. S-1 is a compound preparation consisting of gimeracil, oteracil potassium, and ftorafur. There have been cases of interstitial pneumonia caused by treatment with sintilimab or S-1 in clinical settings, but no cases of interstitial pneumonia caused by treatment with a combination of sintilimab and S-1 have been reported.Case reportA patient diagnosed with gastric cancer underwent nine courses of treatment using a chemotherapy regimen of combined oxaliplatin S-1., Due to severe bone marrow suppression and gastrointestinal adverse reactions, the treatment was switched to sintilimab in combination with S-1therapy., This change resulted in the development of interstitial pneumonia, as revealed by non-contrast chest Computed Tomography scans. Following a review of blood test results and a multidisciplinary consultation, we suspect that the interstitial pneumonia may have been caused either by Sintilimab alone or by the combined effects of sintilimab and S-1. The treatment was discontinued, and after receiving adequate glucocorticoid therapy, the pulmonary lesions showed slight improvement.ConclusionThis case provides a clinical reference, indicating that prior touse of sintilimab in combination with S-1 antitumor regimen, a comprehensive baseline assessment should be conducted, including blood routine examination, enzyme tests, and pulmonary imaging examination, with close monitoring of the patient’s pulmonary condition. If drug-induced lung injury is suspected, the medication should be discontinued immediately, and appropriate treatment should be initiated promptly.

BackgroundThe application of bioprinted hydrogels in the field of bone regeneration is garnering increasing attention. The objective of this study is to provide a comprehensive overview of the current research status, hotspots and research directions in this field through bibliometric methods, and to predict the development trend of this field.MethodsA search was conducted on 27 December 2024, for papers published on the Web of Science from 2010 to 2025. We used the bibliometrix package in the software program R to analyze the retrieved data and VOSviewer and CiteSpace to visualize hotspots and research trends in bioprinted hydrogels for bone regeneration.ResultsWe identified and reviewed 684 articles published in this field between 2010 and 2025. A total of 811 institutions and 1,166 researchers from 41 countries/regions contributed to these publications. Among them, China led in terms of the number of articles published, single-country publications (SCP), and multi-country publications (MCP). Our bibliometric-based visualization analysis revealed that the mechanical properties and osteogenic differentiation capacity of biomaterials have been a focal research topic over the past decade, while emerging research has also concentrated on the in vitro fabrication of stem cells for bone regeneration and osteogenic differentiation, particularly the precise application of in situ stem cell-loaded bioprinted organoids.ConclusionThis study provides an in-depth analysis of the research trajectory in the application of bioprinted hydrogels for bone regeneration. The number of research papers in this field is increasing annually, and the main research hotspots include bone regeneration, 3D printing, scaffolds, and hydrogels. Future research directions may focus on gelatin, additive manufacturing, and growth factors. Additionally, international collaboration is essential to enhance the effectiveness of bioprinted hydrogels in bone regeneration applications.

Euodiae Fructus (EF) is the dried and nearly ripe fruit of Euodia rutaecarpa, first recorded in Shen Nong’s Herbal Classic. EF is a versatile Traditional Chinese Medicine (TCM) known for the effects of dispelling colds and alleviating pain, suppressing adverse qi to relieve vomiting, and boosting yang to mitigate diarrhea. However, it should be noted that EF possesses mild toxicity. In TCM prescriptions, EF is employed to treat various ailments, including abdominal pain, diarrhea, chronic non-atrophic gastritis, irritable bowel syndrome, and primary dysmenorrhea. This review collected the literature published before September 2024 on EF. An exhaustive analysis of EF literature was conducted utilizing multiple sources, namely classic TCM books and various scientific databases like Web of Science, PubMed, Elsevier, ACS, ResearchGate, Google Scholar, and Chinese National Knowledge Infrastructure. So far, more than 300 metabolites have been extracted and identified from EF, exhibiting various pharmacological effects, such as cardiovascular protection, gastrointestinal protection, neuroprotection, anti-inflammation, analgesia, anti-tumor, glucose and lipid metabolism regulation, etc. It also exhibits diverse toxicological properties and poses specific toxic risks to the liver, heart, and kidney. Nonetheless, research is scarce regarding the toxicology of EF, especially on its cardiotoxicity and nephrotoxicity. Further in-depth research is necessary to explore the mechanisms underlying EF’s pharmacological and toxicological mechanisms and to develop strategies for quality control and toxicity mitigation. The toxicity of EF can be reduced by processing, but this aspect is rarely discussed, and the quality control needs to be further standardized. Evodiamine, rutaecarpine, and limonin are the effective metabolites of EF and are also one of the causes of EF toxicity. The pharmacological effects of evodiamine and rutaecarpine have been intensely studied, but there are few studies on limonin and other metabolites of EF. Therefore, this paper focuses on the botanical characteristics, traditional applications, processing methods, phytochemistry, quality control, pharmacology, and toxicology of EF. We hope this paper provides a theoretical basis for the future high-value and high-connotation development of EF.

IntroductionPatients with advanced hepatocellular carcinoma (HCC) have very limited treatment options, among which transarterial radioembolization (TARE) receives increasing attention, relying on its promising efficacy and fewer side effect. However, a bibliometric analysis of TARE for HCC is still lacking. This study employed bibliometric methods to analyze the related articles over the past three decades, and aimed to identify trends in clinical research comparing TARE to other treatments.MethodsArticles related with TARE for HCC were obtained from the Web of Science (WoS). After screening, the R package Bibliometrix was employed to explore the primary bibliometric characteristics. The number of publications was analyzed and mathematically fitted to a curve using Microsoft Excel 2021 and SPSS 25, and then was plotted in the graph using GraphPad Prism 8.0. VOSviewer, SCImago Graphica, and Pajek were utilized for the analysis of researchers’ co-authorship, co-occurrence, and visualization. Keywords citation burst was detected by CiteSpace software.ResultsA total of 1,110 articles from 1993 to 2023 were included in our final analysis, among which the United States not only ranked the first in term of the number of published articles, also was at the forefront in other important indicators, including the total number of article citations and the average citation frequency. Riad Salem from Northwestern University, also being the organization with the greatest number of research papers, was the most active author and has published 96 papers. The keywords were classified into three clusters: 90Y microspheres for TARE, Basic research on TARE, and Clinical trial of TARE for HCC. Furthermore, we identified the most frequently cited keywords with strong citation bursts since 2020 were “multicenter,” “overall survival” and “PET/CT.”ConclusionOur study employed a bibliometric approach to achieve the visualization research on TARE for HCC, and further revealed the trends and frontiers of TARE research, providing valuable information for researchers to identify the critical and persistent challenges and select potential partners in related area. Based on our analysis, future research focus include the clinical comparative studies on the effect of TARE and TACE combined with immunotherapies or targeted therapy, dosimetry, and personalized TARE therapy for HCC.

Pharmacogenomics (PGx) is a powerful tool for clinical optimization of drug efficacy and safety. However, due to many factors affecting drugs in the real world, PGx still accounts for a small proportion of actual clinical application scenarios. Therefore, based on the information software, pharmacists use their professional advantages to integrate PGx into all aspects of pharmaceutical care, which is conducive to promoting the development of personalized medicine. In this paper, the establishment of an information software platform is summarized for the optimization of a personalized medication program based on PGx. Taking colorectal cancers (CRC) as an example, this paper also discusses the role of PGx in different working modes and participation in drug management of CRC patients by pharmacists with the help of information systems. Finally, we summarized the recommendations of different PGx guidelines to provide reference for the follow-up personalized pharmaceutical care.

Apigenin (C15H10O5, API) is a natural flavonoid widely found in vegetables, fruits, and plants such as celery, oranges, and chamomile. In recent years, API has attracted considerable attention as a dietary supplement due to its low toxicity, non-mutagenic properties and remarkable therapeutic efficacy in various diseases. In particular, evidence from a large number of preclinical studies suggests that API has promising effects in the prevention and treatment of a variety of liver diseases, including multifactorial liver injury, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, liver fibrosis and liver cancer. This paper provides a comprehensive review of the progress of research into the therapeutic applications of API in liver diseases as of August 2024, based on literature retrieved from databases such as Web of Science, PubMed, CNKI, Google Scholar and ScienceDirect. The hepatoprotective effects of API involve multiple molecular mechanisms, including inhibition of inflammation, alleviation of hepatic oxidative stress, amelioration of insulin resistance, promotion of fatty acid oxidation, inhibition of liver cancer cell proliferation and differentiation, and induction of tumour cell apoptosis. More importantly, signaling pathways such as Nrf2, NF-κB, PI3K/Akt/mTOR, NLRP3, Wnt/β-catenin, TGF-β1/Smad3, AMPK/SREBP, PPARα/γ, MAPKs, and Caspases are identified as key targets through which API exerts its beneficial effects in various liver diseases. Studies on its toxicity and pharmacokinetics indicate that API has low toxicity, is slowly metabolized and excreted in vivo, and has low oral bioavailability. In addition, the paper summarises and discusses the sources, physicochemical properties, new dosage forms, and current challenges and opportunities of API, with the aim of providing direction and rationale for the further development and clinical application of API in the food, pharmaceutical and nutraceutical fields.

BackgroundIn recent years, the incidence of depression, recognized as a serious psychological disorder, has escalated rapidly. Rehmannia glutinosa DC. (Scrophulariaceae; Rehmanniae Radix, Crude drug) and Lilium lancifolium Thunb. (Liliaceae; Lilii bulbus, Crude drug) constitute a classic anti-depressant combination, exhibiting pharmacological effects that include anti-depressive, anti-anxiety, and anti-inflammatory properties. Current clinical studies have demonstrated that Baihe Dihuang Decoction, a traditional Chinese herbal compound, is effective in treating depression. However, the majority of scholars have predominantly examined Rehmannia glutinosa and Lilium in isolation, and a comprehensive elucidation of their principal active metabolites and pharmacological mechanisms remains lacking.MethodsA comprehensive literature search was conducted as of 29 September 2024, utilizing databases such as PubMed, CNKI, Wanfang Data, Baidu Scholar, and Google Scholar. Additionally, classical texts on Chinese herbal medicine, the Chinese Pharmacopoeia, as well as doctoral and master’s theses, were included in the collected materials. The search employed specific terms including “R. glutinosa,” “Lilium,” “Baihe Dihuang decoction,” “application of Baihe Dihuang decoction,” “pathogenesis of depression,” and “pharmacological action and mechanism of depression.ResultsThis paper reviewed the traditional applications and dosages of the R. glutinosa-Lilium as documented in Chinese medical classics, thereby establishing a foundation for the contemporary development and clinical application of the classical formula Baihe Dihuang Decoction. Additionally, recent years have seen a comprehensive review of the pharmacological effects and mechanisms of R. glutinosa-Lilium and its principal metabolites in the context of depression.ConclusionThis paper has reviewed the active metabolites of R. glutinosa-Lilium and demonstrated its efficacy in the treatment of depression, as well as its role in modulating the underlying mechanisms of the disorder. The findings aim to serve as a reference for further research into the mechanisms of depression, its clinical applications, and the development of novel therapeutic agents.

BackgroundCardiovascular diseases (CVD) pose a significant threat to human health due to their high mortality and morbidity rates. Despite advances in treatments, the prevalence and impact of cardiovascular disease continue to increase. Sodium-glucose transporter 2 inhibitors (SGLT2i), initially approved for the treatment of type 2 diabetes, have important research value and promising applications in reducing CVD risk, especially in heart failure (HF) and atherosclerosis patients with cardiovascular disease (ASCVD). This study aims to comprehensively review the latest progress, research trends, cutting-edge hot spots, and future development directions of SGLT2i in the field of CVD through bibliometric analysis.MethodsArticles related to MSCs in cardiovascular diseases were sourced from the Web of Science. The bibliometric analysis was conducted using CiteSpace and VOSviewer, and a knowledge map was created based on the data obtained from the retrieved articles.ResultsIn this article, we screened 3,476 relevant studies, including 2,293 articles and 1,183 reviews. The analysis found that the number of papers related to the application of SGLT2i in CVD has generally increased, peaking in 2022. The United States and China contributed the largest number of papers, with the United States accounting for 36.97% of the total and also ranking first in terms of the number of citations. However, China’s high-quality papers are slightly lacking and need further improvement. Keyword analysis showed that empagliflozin, dapagliflozin, diabetes, and heart failure were the most common terms, reflecting the main research interests in currently published papers in this field.ConclusionBibliometric analysis showed a robust and growing interest in the application of SGLT2i for treating CVD. By summarizing the latest progress of SGLT2i in the field of CVD, exploring research hotspots, and looking forward to future research development trends, this article provides valuable insights for thinking about research prospects.

BackgroundMulti-organ metastasis has been the main cause of death in patients with Gastric cancer (GC). The prognosis for patients with metastasized GC is still very poor. Long noncoding RNAs (lncRNAs) always been reported to be closely related to cancer metastasis.MethodsIn this paper, the aberrantly expressed lncRNA CADM2-AS1 was identified by lncRNA-sequencing in clinical lymph node metastatic GC tissues. Besides, the role of lncRNA CADM2-AS1 in cancer metastasis was detected by Transwell, Wound healing, Western Blot or other assays in vitro and in vivo. Further mechanism study was performed by RNA FISH, Dual-luciferase reporter assay and RT-qPCR. Finally, the relationship among lncRNA CADM2-AS1, miR-5047 and NOTCH4 in patient tissues was detected by RT-qPCR.ResultsIn this paper, the aberrantly expressed lncRNA CADM2-AS1 was identified by lncRNA-sequencing in clinical lymph node metastatic GC tissues. Besides, the role of lncRNA CADM2-AS1 in cancer metastasis was detected in vitro and in vivo. The results shown that overexpression of the lncRNA CADM2-AS1 promoted GC metastasis, while knockdown inhibited it. Further mechanism study proved that lncRNA CADM2-AS1 could sponge and silence miR-5047, which targeting mRNA was NOTCH4. Elevated expression of lncRNA CADM2-AS1 facilitate GC metastasis by up-regulating NOTCH4 mRNA level consequently. What’s more, the relationship among lncRNA CADM2-AS1, miR-5047 and NOTCH4 was further detected and verified in metastatic GC patient tissues.ConclusionsLncRNA CADM2-AS1 promoted metastasis in GC by targeting the miR-5047/NOTCH4 signaling axis, which may be a potential target for GC metastasis.

BackgroundEpigenetics denotes heritable alterations in gene expression patterns independent of changes in DNA sequence. Epigenetic therapy seeks to reprogram malignant cells to a normal phenotype and has been extensively investigated in oncology. This study conducts a bibliometric analysis of epigenetic therapy in cancer, providing a comprehensive overview of current research, identifying trends, and highlighting key areas of investigation.MethodsPublications concerning epigenetic inhibitors in cancer spanning 2004 to 2023 were retrieved from the Web of Science Core Collection (WoSCC). Co-occurrence analysis using VOSviewer assessed current status and focal points. Evolutionary trends and bursts in the knowledge domain were analyzed using CiteSpace. Bibliometrix facilitated topic evolution and revealed trends in keywords. National, institutional, and author affiliations and collaborations were also examined.ResultsA total of 2,153 articles and reviews on epigenetic therapy in oncology were identified, demonstrating a consistent upward trend over time. The United States (745 papers), University of Texas MD Anderson Cancer Center (57 papers), and Stephen B. Baylin (27 papers) emerged as the most productive country, institution, and author, respectively. Keyword co-occurrence analysis identified five primary clusters: tumor, DNA methylation, epigenetic therapy, expression, and immunotherapy. In the past 5 years, newly emerging themes with increased centrality and density include “drug resistance,” “immunotherapy,” and “combination therapy.” The most cited publication reviewed current understanding of potential causes of epigenetic diseases and proposed future therapeutic strategies.ConclusionIn the past two decades, the importance of epigenetic therapy in cancer research has become increasingly prominent. The United States occupies a key position in this field, while China, despite having published a large number of related papers, still has relatively limited influence. Current research focuses on the “combination therapy” of epigenetic drugs. Future studies should further explore the sequencing and scheduling of combination therapies, optimize trial designs and dosing regimens to improve clinical efficacy.

There is substantial evidence from clinical and preclinical studies suggesting an association between metformin use and a reduced risk of cancer. However, the effects of metformin use on cancers have not yet been subjected to bibliometric analysis. The goal of this study was to explore the potential effects of metformin use on cancers and to conduct a comprehensive assessment of research hotspots related to the use of metformin on cancers. The results of the literature analysis were visualized using various tools such as Adobe Illustrator CC 2018, VOSviewer, CiteSpace, and the R package “bibliometric.” The average annual publications from 2013 to 2023 was 372. In terms of journals and co-cited journals, a total of 1,064 journals published 1958 papers, and Oncotarget published the highest number of papers (n = 153, 7.81%), while Cancer Research (Co-citation = 5,125) was the most frequently cited journal. A total of 25,665 authors participated in the research on metformin use on cancers. Metformin has demonstrated improved outcomes in various types of cancer, including breast cancer (BC), lung cancer (LC), colorectal cancer (CRC), prostate cancer (PC), and pancreatic cancer. This bibliometric analysis reviews the current literature on the clinical data on metformin use on cancers and describes the preclinical evidence illustrating the potential mechanisms of metformin use on various cancers directly or indirectly.

Zika Virus (ZIKV) is a positive-strand RNA virus that can lead to Guillain-Barré syndrome or encephalitis in some individuals and hence presents a serious public health risk. Since the first outbreak of ZIKV in Brazil in 2015, no effective clinical inhibitors have been developed, making the development of effective ZIKV drugs an urgent issue that needs to be addressed. ZIKV belongs to the Flaviviridae family, and its structure includes three structural proteins, namely, capsular (C), premembrane (prM), and envelope (E) proteins, as well as seven nonstructural proteins, namely, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. To provide a reference for the development of future ZIKV drugs, this paper reviews the structure of the ZIKV based on recent literature reports, analyzes the potential therapeutic targets of various proteins, and proposes feasible drug design strategies. Additionally, this paper reviews and classifies the latest research progress on several protease inhibitors, such as E protein inhibitors, NS2B-NS3 inhibitors, and NS5 inhibitors, so that researchers can quickly understand the current status of development and the interconnections among these inhibitors.

Despite extensive preclinical research over the years, a significant gap remains in our understanding of the specific effects of methamphetamine (METH) and amphetamine (AMPH) withdrawal. Understanding these differences could be pivotal to unveiling the unique pathophysiology underlying each stimulant. This may facilitate the development of targeted and effective treatment strategies tailored to the specific characteristics of each substance. Following PRISMA guidelines, this systematic review was conducted to examine alterations in spontaneous locomotor activity, specifically horizontal activity, in animals experiencing withdrawal from extended and repeated administration of AMPH or METH. Original articles were retrieved from four electronic databases, supplemented by a review of the references cited in the published papers. A total of thirty-one full-length articles (n = 31) were incorporated in the analysis. The results indicated that six studies documented a significant increase in horizontal activity among animals, seven studies reported decreased locomotion, and eighteen studies (8 AMPH; 10 METH) reported no significant alterations in the animals’ locomotor activity. Studies reporting heightened locomotion mainly employed mice undergoing withdrawal from METH, studies reporting diminished locomotion predominantly involved rats undergoing withdrawal from AMPH, and studies reporting no significant changes in horizontal activity employed both rats and mice (12 rats; 6 mice). Drug characteristics, routes of administration, animal models, dosage regimens, duration, and assessment timing seem to influence the observed outcomes. Despite more than 50% of papers enlisted in this review indicate no significant changes in the locomotion during the stimulant withdrawal, the unique reactions of animals to withdrawal from METH and AMPH reported by some underscore the need for a more nuanced understanding of stimulant withdrawal.

This article forms part of a series on “openness,” “non-linearity,” and “embodied-health” in the post-physical, informational (virtual) era of society. This is vital given that the threats posed by advances in artificial intelligence call for a holistic, embodied approach. Typically, health is separated into different categories, for example, (psycho)mental health, biological/bodily health, genetic health, environmental health, or reproductive health. However, this separation only serves to undermine health; there can be no separation of health into subgroups (psychosomatics, for example). Embodied health contains no false divisions and relies on “optimism” as the key framing value. Optimism is only achieved through the mechanism/enabling condition of openness. Openness is vital to secure the embodied health for individuals and societies. Optimism demands that persons become active participants within their own lives and are not mere blank slates, painted in the colors of physical determinism (thus a move away from nihilism—which is the annihilation of freedom/autonomy/quality). To build an account of embodied health, the following themes/aims are analyzed, built, and validated: (1) a modern re-interpretation and validation of German idealism (the crux of many legal–ethical systems) and Freud; (2) ascertaining the bounded rationality and conceptual semantics of openness (which underlies thermodynamics, psychosocial relations, individual autonomy, ethics, and as being a central constitutional governmental value for many regulatory systems); (3) the link between openness and societal/individual embodied health, freedom, and autonomy; (4) securing the role of individualism/subjectivity in constituting openness; (5) the vital role of nonlinear dynamics in securing optimism and embodied health; (6) validation of arguments using the methodological scientific value of invariance (generalization value) by drawing evidence from (i) information and computer sciences, (ii) quantum theory, and (iii) bio-genetic evolutionary evidence; and (7) a validation and promotion of the inalienable role of theoretic philosophy in constituting embodied health, and how modern society denigrates embodied health, by misconstruing and undermining theoretics. Thus, this paper provides and defends an up-to-date non-physical account of embodied health by creating a psycho-physical–biological–computational–philosophical construction. Thus, this paper also brings invaluable coherence to legal and ethical debates on points of technicality from the empirical sciences, demonstrating that each field is saying the same thing.

Due to the similarity and diversity among kinases, small molecule kinase inhibitors (SMKIs) often display multi-target effects or selectivity, which have a strong correlation with the efficacy and safety of these inhibitors. However, due to the limited number of well-known popular databases and their restricted data mining capabilities, along with the significant scarcity of databases focusing on the pharmacological similarity and diversity of SMIKIs, researchers find it challenging to quickly access relevant information. The KLIFS database is representative of specialized application databases in the field, focusing on kinase structure and co-crystallised kinase-ligand interactions, whereas the KLSD database in this paper emphasizes the analysis of SMKIs among all reported kinase targets. To solve the current problem of the lack of professional application databases in kinase research and to provide centralized, standardized, reliable and efficient data resources for kinase researchers, this paper proposes a research program based on the ChEMBL database. It focuses on kinase ligands activities comparisons. This scheme extracts kinase data and standardizes and normalizes them, then performs kinase target difference analysis to achieve kinase activity threshold judgement. It then constructs a specialized and personalized kinase database platform, adopts the front-end and back-end separation technology of SpringBoot architecture, constructs an extensible WEB application, handles the storage, retrieval and analysis of the data, ultimately realizing data visualization and interaction. This study aims to develop a kinase database platform to collect, organize, and provide standardized data related to kinases. By offering essential resources and tools, it supports kinase research and drug development, thereby advancing scientific research and innovation in kinase-related fields. It is freely accessible at: http://ai.njucm.edu.cn:8080.

Herb compatibility is the soul of traditional Chinese Medicine prescriptions. Coptidis rhizoma (CR) (Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao, or Coptis teeta Wall.; family Ranunculaceae), is a well-known herb. The bitter and cold nature of CR can irritate the spleen and stomach, and certain ingredients in CR may trigger allergic reactions. Herb combinations can help alleviate the side effects caused by CR. Through data analysis and literature research, there are many herbs combined with CR have a high frequency, but only a few are currently used as formulae in clinical practice. The results showed that these six herb pairs are usually widely studied or used as prescriptions in the clinic. This paper describes the six herb pairs from the key traditional uses, changes in bioactive constituents, and compatibility effects, especially with Euodiae fructus (family Rutaceae), Scutellariae radix (family Lamiaceae), Magnoliae Officinalis cortex (family Magnoliaceae), Glycyrrhizae radix et rhizoma (family Fabaceae), Ginseng radix et rhizoma (family Araliaceae), and Aucklandiae radix (family Asteraceae), and found that herbs are more effective when used in combination. Therefore, it is feasible to establish some methods to study herb pairs comprehensively from different perspectives. This paper aims to provide the latest and most comprehensive information on the six herb pairs and summarize the pattern of CR compatibility effects. It aims to attract more attention, and further experimental studies will be conducted to investigate and evaluate the effects of herb pairs containing CR. These data can also provide valuable references for researchers and also provide more possibilities for future applications in clinical practice and new drug development.

Introduction: This paper describes the peculiarities of the plasma-derived medicinal product (PDMP) market and illustrates the results of a review of the literature on policies aimed at counteracting the shortage of PDMPs.Characteristics of PDMPs: Plasma is primarily used for the industrial production of blood products (80%). The demand for PDMPs, particularly immunoglobulins (IGs), is increasing. However, the production of PDMPs is complex, long (7–12 months), and expensive, accounting, according to US estimates, for 57% of the total costs of PDMPs compared to 14% for small molecules.PDMP market: Unexpected increases in clinical need cannot be addressed in the short term. Once the demand for some diseases is satisfied, the collection and fractionation of plasma will only be used to supply some specific patients. Hence, the full weight of the marginal costs, which remain constant, are borne by a few products. According to last liter economics, the industry stops producing when the marginal revenue equals the marginal cost, thereby reducing the convenience of producing the most commonly used PDMPs (albumin and IG). The imbalance between the demand and supply of PDMPs was exacerbated by the COVID-19 pandemic, which further increased the cost of plasma collection.Shortage issue and possible solutions: Policies to counteract this imbalance have also been discussed. If the demand is inappropriate, it should be reduced. If the demand is appropriate and supply cannot be increased, the demand should be prioritized for patients for whom PDMPs are the only available treatment. If the shortage depends on insufficient supply and technical and allocative efficiency, both production and supply should be improved, together with incentives for all stakeholders involved in the PDMP market to increase the sustainability of production/supply. The paper is focused on this second issue, that is supply-driven unbalance.

IntroductionIn recent years, graph neural network has been extensively applied to drug discovery research. Although researchers have made significant progress in this field, there is less research on bibliometrics. The purpose of this study is to conduct a comprehensive bibliometric analysis of graph neural network applications in drug discovery in order to identify current research hotspots and trends, as well as serve as a reference for future research.MethodsPublications from 2017 to 2023 about the application of graph neural network in drug discovery were collected from the Web of Science Core Collection. Bibliometrix, VOSviewer, and Citespace were mainly used for bibliometric studies.Results and DiscussionIn this paper, a total of 652 papers from 48 countries/regions were included. Research interest in this field is continuously increasing. China and the United States have a significant advantage in terms of funding, the number of publications, and collaborations with other institutions and countries. Although some cooperation networks have been formed in this field, extensive worldwide cooperation still needs to be strengthened. The results of the keyword analysis clarified that graph neural network has primarily been applied to drug-target interaction, drug repurposing, and drug-drug interaction, while graph convolutional neural network and its related optimization methods are currently the core algorithms in this field. Data availability and ethical supervision, balancing computing resources, and developing novel graph neural network models with better interpretability are the key technical issues currently faced. This paper analyzes the current state, hot spots, and trends of graph neural network applications in drug discovery through bibliometric approaches, as well as the current issues and challenges in this field. These findings provide researchers with valuable insights on the current status and future directions of this field.

BackgroundQuercetin, a widespread polyphenolic flavonoid, is known for its extensive health benefits and is commonly found in the plant kingdom. The natural occurrence and extraction methods of quercetin are crucial due to its bioactive potential.PurposeThis review aims to comprehensively cover the natural sources of quercetin, its extraction methods, bioavailability, pharmacokinetics, and its role in various cell death pathways and liver fibrosis.MethodsA comprehensive literature search was performed across several electronic databases, including PubMed, Embase, CNKI, Wanfang database, and ClinicalTrials.gov, up to 10 February 2024. The search terms employed were “quercetin”, “natural sources of quercetin”, “quercetin extraction methods”, “bioavailability of quercetin”, “pharmacokinetics of quercetin”, “cell death pathways”, “apoptosis”, “autophagy”, “pyroptosis”, “necroptosis”, “ferroptosis”, “cuproptosis”, “liver fibrosis”, and “hepatic stellate cells”. These keywords were interconnected using AND/OR as necessary. The search focused on studies that detailed the bioavailability and pharmacokinetics of quercetin, its role in different cell death pathways, and its effects on liver fibrosis.ResultsThis review details quercetin’s involvement in various cell death pathways, including apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis, with particular attention to its regulatory influence on apoptosis and autophagy. It dissects the mechanisms through which quercetin affects these pathways across different cell types and dosages. Moreover, the paper delves into quercetin’s effects on liver fibrosis, its interactions with hepatic stellate cells, and its modulation of pertinent signaling cascades. Additionally, it articulates from a physical organic chemistry standpoint the uniqueness of quercetin’s structure and its potential for specific actions in the liver.ConclusionThe paper provides a detailed analysis of quercetin, suggesting its significant role in modulating cell death mechanisms and mitigating liver fibrosis, underscoring its therapeutic potential.

Siraitia grosvenorii (Swingle) C. Jeffrey (S. grosvenorii), a perennial indigenous liana from the Cucurbitaceae family, has historically played a significant role in southern China’s traditional remedies for various ailments. Its dual classification by the Chinese Ministry of Health for both medicinal and food utility underscores its has the potential of versatile applications. Recent research has shed light on the chemical composition, pharmacological effects, and toxicity of S. grosvenorii. Its active ingredients include triterpenoids, flavonoids, amino acids, volatile oils, polysaccharides, minerals, vitamins, and other microconstituents. Apart from being a natural sweetener, S. grosvenorii has been found to have numerous pharmacological effects, including alleviating cough and phlegm, preventing dental caries, exerting anti-inflammatory and anti-allergic effects, anti-aging and anti-oxidative, hypoglycemic, lipid-lowering, anti-depression, anti-fatigue, anti-schizophrenic, anti-Parkinson, anti-fibrotic, and anti-tumor activities. Despite its versatile potential, there is still a lack of systematic research on S. grosvenorii to date. This paper aims to address this gap by providing an overview of the main active components, pharmacological efficacy, toxicity, current status of development and application, development dilemmas, and strategies for intensive exploitation and utilization of S. grosvenorii. This paper aims to serve as a guide for researchers and practitioners committed to exploiting the biological resources of S. grosvenorii and further exploring its interdisciplinary potential.

Introduction:Head and neck cancer is one of the most common tumors worldwide. However, drug resistance in its treatment has become a major factor limiting the efficacy. This study aims to comprehensively understand the current status of research in this field.Methods:The study analyzes papers related to therapeutic resistance in head and neck cancer published between 2000 and 2023 in the Web of Science Core Collection To achieve the research objectives, we searched the WoSCC for research and review papers on therapeutic resistance in head and neck cancer from 2000 to 2023, screened the English literature, and analyzed the research hotspots, academic collaborations, and trends in detail using tools such as Citespace, SCImago Graphica, and VOS viewer.Results:This study summarizes 787 head and neck cancer treatment resistance publications from WoSCC. The analysis showed that China and the United States are the major contributors in this field, and Grandis Jennifer R and Yang Jai-Sing are the key scholars. Keyword analysis showed that “cisplatin resistance” is a continuing focus of attention, while “Metastasis” and “Ferroptosis” may be emerging research hotspots. Literature clustering analysis pointed out that “Ferroptosis”, “Immunotherapy” and “ERK signaling” were the recent hotspots that received extensive attention and citations. Finally, we discuss the current status and challenges in drug-resistant therapies for head and neck cancer.Conclusion:This study is the first comprehensive bibliometric analysis of drug resistance in head and neck cancer. Reveals current trends and helps researchers grasp cutting-edge hotspots in the field.

For over 170 years, general anesthesia has played a crucial role in clinical practice, yet a comprehensive understanding of the neural mechanisms underlying the induction of unconsciousness by general anesthetics remains elusive. Ongoing research into these mechanisms primarily centers around the brain nuclei and neural circuits associated with sleep-wake. In this context, two sophisticated methodologies, optogenetics and chemogenetics, have emerged as vital tools for recording and modulating the activity of specific neuronal populations or circuits within distinct brain regions. Recent advancements have successfully employed these techniques to investigate the impact of general anesthesia on various brain nuclei and neural pathways. This paper provides an in-depth examination of the use of optogenetic and chemogenetic methodologies in studying the effects of general anesthesia on specific brain nuclei and pathways. Additionally, it discusses in depth the advantages and limitations of these two methodologies, as well as the issues that must be considered for scientific research applications. By shedding light on these facets, this paper serves as a valuable reference for furthering the accurate exploration of the neural mechanisms underlying general anesthesia. It aids researchers and clinicians in effectively evaluating the applicability of these techniques in advancing scientific research and clinical practice.

Legionella is a significant pathogen responsible for community-acquired pneumonia and, less commonly, for hospital-acquired pneumonia. Legionella pneumophila, the most prevalent species within the Legionella genus, accounts for 80%–90% of human infections, and often leads to severe pneumonia complicated by multi-organ dysfunction. Omadacycline, a novel tetracycline, has demonstrated in vitro activity against atypical pathogens, including L. pneumophila; however evidence regarding its application in severe Legionella pneumonia remains limited. In this paper, we report 3 cases of successful treatment of severe Legionella pneumonia with omadacycline in patients who initially did not respond to empirical treatment with moxifloxacin, aiming to provide clinical experience and guidance for the use of omadacycline.

BackgroundOsteoporosis and diabetes mellitus (DM) are both prevalent chronic conditions associated with significant morbidity, particularly in aging populations. Patients with DM are at increased risk of developing osteoporosis due to complex pathophysiological interactions between glucose metabolism and bone health. Although pharmacological interventions have been used to prevent and manage osteoporosis in individuals with DM, variability in reported outcomes across studies hinders evidence synthesis and meta-analyses. A standardized Core Outcome Set (COS) is required to harmonize outcome reporting in clinical trials, improving comparability and clinical relevance. This paper outlines the protocol for developing a COS for pharmacological interventions targeting osteoporosis among patients with DM.MethodsThe development of the COS will follow a five-phase approach. Phase 1 involves a systematic review to identify key outcomes in clinical trials of osteoporosis pharmacotherapy in diabetic populations. Phase 2 consists of a modified Delphi process involving international experts in endocrinology, bone metabolism, and diabetes care, as well as patients and public representatives. This will be followed by Phase 3, where consensus meetings will be held to finalize the essential outcomes for inclusion. Phase 4 will focus on identifying appropriate outcome measurement tools based on a systematic review and additional consensus-building meetings. Finally, Phase 5 will involve dissemination and implementation activities to ensure broad adoption of the COS in future research and clinical trials. Patient and Public Involvement (PPI) will be integrated throughout all phases of the project to ensure the relevance of selected outcomes.ConclusionThe resulting COS will provide a standardized framework for reporting outcomes in pharmacological intervention studies of osteoporosis in patients with DM. By facilitating meta-analyses and data pooling, this COS will improve the comparability of clinical trials, enhance research efficiency, and reduce outcome reporting bias. Ultimately, the COS will support better clinical decision-making, fostering the development of targeted and effective therapies for osteoporosis in the context of diabetes.

In 2003, Sabate’s World Health Organisation report defined medication nonadherence as a phenomenon where individuals’ behaviour does not correspond to prescribed treatment recommendations from their healthcare provider. This concept of nonadherence evolved beyond a categorisation of patients as adherent or nonadherent. Rather, nonadherence varies within the same individual and treatment over time, and between treatments and individuals. The type and patterns of nonadherence are key determinants of outcome with individuals with the same percentage nonadherence having different outcomes depending on their pattern of nonadherence. Often the poorest clinical outcomes occur in individuals who do not initiate medication or discontinue early, but much of the nonadherence literature remains focused on implementation. This paper provides a nuanced discussion of nonadherence which has been enabled in part by the growing availability of technologies such as electronic nonadherence monitors, new biomarkers for adherence and greater access to ‘big data’ (e.g., on prescription refills). These allow granular assessment of nonadherence that can be linked with biophysical markers captured using technologies such as wearables. More validated self-report measures have also become available to profile nonadherence in research and practice. Together, in-depth data on dosing and clinical measures provide an opportunity to explore complex interactions between medications, therapeutic effects and clinical outcomes. This variation in measurement and definition means that there is a more fine-grained understanding of the prevalence of nonadherence and a greater recognition of the prevalence of nonadherence, with growing evidence suggesting that approximately a fifth of patients do not initiate treatment, of those initiating treatment approximately 30%–50% of patients do not implement their treatment as prescribed and that, over long follow-up periods in some conditions 80%–100% of patients discontinue. There is potential too to better understand causes of nonadherence. New behavioural models synthesise determinants of nonadherence previously considered separately. Frameworks like the COM-B (considering individual capability, opportunity, and motivation factors) and MACO (focusing on Medication Adherence Contexts and Outcomes) emphasize the multifaceted nature of nonadherence determinants. Greater focus on dynamic processes with interplay between individual, social, and environmental influences is needed. Addressing these complexities could lead to more effective and personalised support for patients.

As a traditional Chinese herbal medicine, Draconis Resina (DR) has garnered significant attention due to its efficacy in treating various clinical diseases. Notably, it demonstrates remarkable therapeutic effects in cardiovascular diseases, such as atherosclerosis, coronary heart disease, and myocardial ischemia-reperfusion injury. A comprehensive understanding of the potential therapeutic mechanisms of DR in cardiovascular diseases can positively influence their prevention and treatment. Therefore, through a thorough literature review, this paper summarizes the primary mechanisms of DR in managing cardiovascular diseases, which include the prevention of thrombosis, inhibition of inflammatory responses, alleviation of oxidative stress, enhancement of endothelial function, and mitigation of myocardial fibrosis. There may remain many untapped therapeutic applications of DR that need further exploration. This review aims to give readers a deeper understanding of the DR and offer new perspectives.

Colorectal cancer (CRC) is a common malignant tumor of the digestive system, and the pathogenic mechanism is still unclear, mostly related to genetics, immunity, inflammation, and abnormal activation of tumor-related signaling pathways. MAPK belongs to the Ser/Thr kinase family, which plays an important role in complex cellular programs such as the regulation of cell proliferation, differentiation, apoptosis, angiogenesis, and tumor metastasis. Increasing evidence supports that MAPK activation is highly correlated with the risk of CRC. Targeting MAPK may be a therapeutic strategy, and natural products show great therapeutic potential in regulating MAPK-related proteins. In this paper, we searched PubMed, Web of Science and CNKI databases with keywords “colorectal cancer, natural products, MAPK pathway, ERK, P38, JNK” for relevant studies in the last 14 years from 2010 to 2024. This work retrieved 47 studies, aiming to provide new therapeutic strategies for CRC patients and lay the foundation for new drug development.

Formononetin (FMN) is a common natural metabolite that can be extracted and isolated from some common botanical drugs. In recent years, FMN has garnered increasing attention due to its beneficial biological activities. In this paper, we systematically summarize the sources of FMN and provide a comprehensive review of its pharmacological activities and molecular mechanisms, co-administration, toxicity, derivatives, and drug delivery systems in the last 5 years. The study results found that FMN has a wide range of pharmacological activities in neurological disorders, organ damage and cancer, showing great potential for clinical application and broad prospects. Researchers are exploring various types of delivery systems, including nanoparticle carriers, ligand modifications and polymer microspheres. These advanced delivery systems can enhance the stability of FMN, prolong its release time in vivo, and improve targeting, thereby optimizing its therapeutic efficacy and reducing side effects, and greatly improving its bioavailability. In conclusion, FMN is a natural metabolite with considerable research value, and its diverse biological activities make it a promising candidate for drug development and medical research.

BackgroundUnderstanding students’ preferences is crucial for developing targeted teaching strategies and improving educational outcomes. This study aimed to investigate Chinese undergraduate pharmacy students’ preferences for case-based learning (CBL).MethodsWe conducted a discrete choice experiment (DCE) to quantify preferences for CBL. Six key attributes associated with CBL preferences were identified: case modality, provider type, group size, case authenticity, case complexity, and examination format. An online questionnaire was administered to undergraduate pharmacy students from two universities in China. The data were analyzed using a mixed logit model to estimate preference weights, assess the relative importance of the attributes, and predict uptake rates. Additionally, interaction effects and subgroup analysis were employed to identify heterogeneity in preferences among different student groups.ResultsA total of 613 participants completed the questionnaire and 482 participants were included in the analysis. The most influential attribute was case modality, with scenario simulation strongly preferred over paper modality. Case authenticity and provider type were also significant factors, followed by group size and case complexity. Examination format did not significantly affect preferences. We found heterogeneity in preferences between different groups of students. The highest uptake was achieved when cases were presented in scenario simulations by clinical instructors in small groups, using real cases of low complexity alongside the traditional written examination.ConclusionThe study highlights the importance of case modality with scenario simulation, case authenticity, and provider by clinical instructors among Chinese undergraduate pharmacy students for CBL, and suggests the need for personalized CBL approaches to accommodate different preferences.

BackgroundNanomedicine has received much attention for its potential applications in the diagnosis and treatment of liver cancer. However, no bibliometric evaluation has been conducted to present an assessment of scientific progress in the field. The aim of this study is to comprehensively catalog the cooperation and influence of journals, countries, institutions, and authors in the field of nanomedicine in liver cancer from the perspective of bibliometrics, evaluate the clustering evolution of knowledge structure, and uncover hot topics and emerging themes.MethodsArticles and reviews related to nanomedicine and liver cancer were retrieved from the Web of Science Core Literature Library using Topic Search. #1 T= (“Hepatic Neoplasm*” OR “Liver Neoplasm” OR “Liver Cancer*” OR “Hepatocellular Cancer*” OR “Hepatic Cancer*“), #2 T= “nano*“, the search strategy is set as #1 AND #2 limited to Science Citation Index Expanded database source, with no limitation of publication types and language/time. Bibliometric studies were conducted using CiteSpace and VOSviewer.Results2,648 articles and reviews were included from 2000 to 2024. The number of articles regarding nanomedicine in liver cancer showed an increasing trend. Analysis of the most productive journals shows that most are specialized in nanoscience and nanotechnology, pharmacology and pharmacy, and chemistry and multidisciplinary. These publications mainly come from 8,782 institutions in 297 countries led by China and the United States of America. Shao D published the most papers among the publications, while Jemal A had the most co-citations. The macroscopical sketch and micro-representation of the whole knowledge field are realized through co-citation analysis. Hepatocellular carcinoma, targeted delivery, sorafenib nanoparticles, and others are current and developing areas of study. The keywords “nanocrystals,” “biodistribution,” and “particles” also may be the focus of new trends and future research.ConclusionIn this study, bibliometrics and visual methods were used to review the research of nanomedicine in liver cancer comprehensively. The article will help scholars to gain a better understanding of the dynamic evolution of nanomedicine applications in liver cancer and point the directions for future research.

Female gonadal hormones, particularly estrogen and progesterone, are not only central to reproductive health but also play a crucial role in regulating mood, cognition, and overall brain health. These hormones have a significant impact on the central nervous system, influencing key processes such as neurotransmission, neuroplasticity, and brain development. Increasing evidence shows that hormonal fluctuations contribute to the onset and progression of mental health disorders that disproportionately affect women, particularly premenstrual dysphoric disorder (PMDD), postnatal depression (PND), and menopausal depression. This paper explores the current evidence regarding the neurobiological effects of female hormones on the brain and discusses the therapeutic approaches in conditions such as PMDD, PND, and menopausal depression.

Hypoalbuminemia, defined as serum albumin levels below 35 g/L, is common in patients with conditions such as nephrotic syndrome, cirrhosis, or sepsis. This review examines the impact of hypoalbuminemia on the pharmacokinetics of selected drugs—such as antibiotics, immunosuppressants, antifungals, or anticonvulsants—emphasizing its role in drug efficacy and safety. Albumin is the main drug transporter and key binding protein, which influences the free drug concentration and drug activity. The review includes all studies available in the scientific literature found in the PubMed, Scopus, and Cochrane databases. The paper emphasizes the importance of therapeutic drug monitoring (TDM) in patients with hypoalbuminemia to avoid subtherapeutic or toxic drug levels. Many drugs need for dose adjustments to achieve therapeutic levels, especially in critically ill patients. The results of studies emphasize the need for individualized dosing regimens based on TDM to optimize drug therapy in patients with hypoalbuminemia. Our review is the first article to summarize the influence of hypoalbuminemia on the pharmacokinetic parameters of drugs and may be a useful tool for clinicians in their daily work.

The fruit of Sclerocarya birrea (A. Rich.) Hochst., commonly known as the marula, is widely appreciated for its nutritious pulp and edible nuts. The pulp has a higher vitamin C than those of other fruits, including pineapple, guava, and oranges. In addition, fresh marula fruits are often used to produce delicious sweets, wine and flavorings: it is perhaps best known as the flavor of Amarula liqueur. In vitro and in vivo studies indicate that the various parts of marula have pro-health properties, such as antioxidant, antibacterial, antifungal, antidiabetic activities. This paper reviews the current state of knowledge regarding the marula fruit and its products, with a special emphasis on their chemical composition, biological activity and pro-health potential.

Gastric cancer (GC) is a prevalent malignant tumor that originates from the epithelial cells of the gastric mucosa, predominantly in the form of adenocarcinoma. Extensive research has confirmed the significant role of autophagy in the initiation, progression, and chemoresistance of GC. The potential of traditional Chinese medicine (TCM) to exert anti-tumor effects by modulating autophagy has been demonstrated, particularly in the context of GC prevention and treatment. Natural products (NPs) have great therapeutic potential in the prevention and treatment of GC by targeting autophagy-related genes and signaling pathways to intervene in the biological behaviors of gastric cancer cells such as proliferation, metastasis, invasion and death. This article describes the molecular mechanisms and key markers of tumor autophagy, the signaling pathways involved in GC-associated autophagy (PI3K/AKT/mTOR, AMPK, MAPK, p53), and summarizes the mechanism of autophagy and Helicobacter pylori infection in GC, how autophagy interacts with apoptotic and iron-death processes and the wide-ranging influences that these factors play in the process. Finally, this paper systematically summarizes the natural compounds of terpenoids, polyphenols, alkaloids, saponins, and polysaccharides that modulate autophagy-related signaling pathways and potential targets for the treatment of GC, and evaluates the toxic effects of NPs, providing a more compelling rationale and direction for GC therapy.

The process of drug discovery and development is both lengthy and intricate, demanding a substantial investment of time and financial resources. Bioinformatics techniques and tools can not only accelerate the identification of drug targets and the screening and refinement of drug candidates, but also facilitate the characterization of side effects and the prediction of drug resistance. High-throughput data from genomics, transcriptomics, proteomics, and metabolomics make significant contributions to mechanics-based drug discovery and drug reuse. This paper summarizes bioinformatics technologies and tools in drug research and development and their roles and applications in drug research and development, aiming to provide references for the development of new drugs and the realization of precision medicine.

Atrial fibrillation (AF) causes a heavy socio-economic burden on healthcare systems around the globe. Identification of new preventive, diagnostic, and treatment methods is imperative. In recent years, special attention has been paid to microRNAs (miRNAs) as potential regulators of AF pathogenesis. Through post-transcriptional regulation of genes, miRNAs have been shown to play crucial roles in AF-related structural and electrical atrial remodeling. Altered expression of different miRNAs has been related to proarrhythmic changes in the duration of action potentials and atrial fibrosis. In clinical studies, miRNA changes have been associated with AF, whereas in experimental studies miRNA manipulation has emerged as a potential therapeutic approach. It would appear that, with the advent of miRNAs, we may have found the Holy Grail, and that efficient and personalized AF therapy may be one step away. Yet, the clinical relevance of miRNA evaluation and manipulation remains questionable. Studies have identified numerous miRNAs associated with AF, but none of them have shown sufficient specificity for AF. MicroRNAs are not gene-specific but regulate the expression of a myriad of genes. Cardiac and non-cardiac off-target effects may thus occur following miRNA manipulation. A Pandora’s box might thus have opened with the advent of these sophisticated molecules. In this paper, we provide a critical analysis of the clinical and experimental, epidemiological and mechanistic data linking miRNAs to AF, we discuss the most promising miRNA therapeutic approaches, we emphasize a number of questions that remain to be answered, and we identify hotspots for future research.

The release of intracellular DNA into the extracellular area occurs via two pathways: cell death and active secretion by cells. The DNA, which is free in the extracellular space, is commonly known as Cell-Free DNA (cfDNA). In healthy people, the levels of cfDNA in the circulation are notably minimal. Within a healthy organism, cfDNA undergoes swift elimination and filtration upon release, ensuring a persistently low concentration in the bloodstream. Conversely, individuals suffering from diverse illnesses like stroke, trauma, myocardial infarction, and various cancers show markedly higher levels of cfDNA in their blood plasma or serum. Further research has shown that cfDNA is associated with a wide range of human diseases and may have a feedback relationship with inflammation, potentially serving as a non-invasive, accurate, sensitive, and rapid biomarker for clinical applications in disease differential diagnosis, activity monitoring, and prognosis assessment. Studies dating back to the 1970s have indicated elevated cfDNA concentrations in SLE. Currently, increased levels of cfDNA are noted in a range of rheumatic disorders. Inflammatory damage in patients with rheumatic diseases promotes the release of cfDNA, while potential abnormalities in cfDNA metabolism further increase its levels. Elevated concentrations of cfDNA are recognized by DNA receptors, initiating immune-inflammatory reactions which subsequently accelerate the progression of disease. Reducing excess cfDNA may help improve inflammation. Additionally, several trials have demonstrated a correlation between cfDNA concentrations and the activity of rheumatic diseases, indicating the potential of cfDNA, a novel marker for inflammation, in conjunction with C-creative protein (CRP), Erythrocyte Sedimentation Rate (ESR) to monitor disease activity in rheumatic conditions. This paper provides an overview of cfDNA and summarizes current research advancements in cfDNA in rheumatic diseases, aiming to offer new perspectives for researchers.

IntroductionTraditional Chinese medicine (TCM) prescriptions are generally formulated by experienced TCM researchers based on their expertise and data statistical methods.MethodsIn order to predict TCM formulas for diabetes more accurately, this paper proposes a novel multi-source ensemble prediction method that combines machine learning ensemble techniques and multi-source data. In this method, the multi-source data contain datasets based on the components and targets (DPP-4 and GLP-1). Gradient boosting decision tree (GBDT), flexible neural tree (FNT), and Light Gradient Boosting Machine (LightGBM) algorithms are trained using these two types of datasets, respectively. The compound dataset from the TCMSP database is then used as testing data to predict and screen the active ingredients. The frequencies of occurrences of medicinal herbs corresponding to these three algorithms are obtained, each containing an active ingredient list. Finally, the frequencies of occurrences of the medicinal herbs obtained from the three algorithms using the component and target datasets are integrated to select duplicate drugs as the candidate drugs for diabetes treatment.ResultsThe identification results reveal that theproposed ensemble method has higher accuracy than GBDT, FNT, and LightGBM. The medicinal herbs predicted include Lycii fructus, Amygdalus communis vas, Chrysanthemi flos, Hippophae fructus, Mori folium, Croci stigma, Maydis stigma, Ephedrae herba, Cimicifugae rhizoma, licorice, and Epimedii herba, all of which have been proven effective in the treatment of diabetes.DiscussionsThe results of network pharmacology show that myrrha can play a role in treating diabetes through multiple targets and pathways.

The liver performs crucial roles in energy metabolism, detoxification, and immune regulation. Hepatic diseases, including hepatitis, liver fibrosis, and liver cancer, have posed a significant threat to global health, emphasizing the critical need for the development of novel and effective treatment approaches. Nanotechnology, an emerging technology, has been extensively researched in medicine. Among the many types of nanomaterials, polymeric nanoparticles (NPs) are widely used in drug delivery systems. Compared to traditional therapies, they offer significant advantages in the treatment of liver disease by improving outcomes and reducing side effects. This review introduced the development of liver disease and discussed the application of natural polymers and synthetic polymers in their management. Furthermore, this paper reviewed the application of polymeric nanoparticles -mainly chitosan (CS), hyaluronic acid (HA), polyethylene glycol (PEG) and poly (lactic-co-glycolic acid) (PLGA)-in liver disease treatment, focusing on their use in various delivery systems for pure bioactive compounds of natural origin, drugs, nucleic acids, peptides, and others. Finally, the challenges and future perspectives of the NPs were discussed to provide guidance for further research directions, with the aim of promoting the clinical application of nanotherapeutics in treating hepatic diseases.

The rapid advancements in regenerative medicine (RM), including cell therapies, gene therapies, tissue-engineered products, and combined RM advanced therapies, require the development of regulatory frameworks. The global landscape of regulatory frameworks presents diverse approaches to the oversight of these therapies, posing challenges in the global application of RM. This paper reviews the regulatory frameworks for RM across the United States, European Union, Japan, Canada, Australia, Taiwan, and South Korea and compares the unique features of the respective legislations.

Psoralea corylifolia L. (PCL) is an annual herb of the genus Psoralea in the family Fabaceae, and its mature fruit can be used medicinally as a precious medicinal herb to tonify muscles and bones. With the deepening of research, its applications to various industries, including food, agriculture, and cosmetics, with products being developed in countries such as Vietnam, India, and Japan. A total of 321 metabolites, including coumarins, flavonoids, meroterpenes, benzofurans, and dimers, were identified in PCL. PCL and related products have demonstrated therapeutic effects, such as antiosteoporosis effects, estrogen-like effects, anti-inflammatory properties, neuroprotection, antitumor activity, and vitiligo treatment. The expression mechanisms of these pharmacological effects are closely related to the regulation of the immune system, the inhibition of oxidative stress, and the induction of apoptosis. This paper summarizes the latest research on the ethnobotany, phytochemistry, processing technology, pharmacology, and hepatotoxicity of PCL. Furthermore, bibliometric analysis was used to systematically analyze the research hotspots and trends in PCL, which have never been addressed in previous reviews of PCL. In the future, it will be necessary to focus on the active metabolites of PCL, analyze its targets and signaling pathway network to address potential toxicity and side effects in clinical applications, and further expand the potential application of PCL in medicine.

Hyperactivation of blood platelets, one of the causes of heart attack, and other cardiovascular diseases (CVDs), is influenced by various dietary components, including phenolic compounds from vegetables, fruits, teas, wines, cocoa and its products, including chocolate. The present paper sheds new light on the effect of cocoa and its products, especially dark chocolate, on the number and function of blood platelets, and the anti-platelet activity of their constituent phenolic compounds. A review was performed of papers identified in various electronic databases, including PubMed, Science Direct, Scopus, Web of Knowledge, and Google Scholar, with the aim of determining whether their anti-platelet activity may serve as part of a sweet strategy in countering CVDs. Various studies demonstrate that cocoa consumption, especially in the form of dark chocolate, with a high flavanol concentration, has anti-platelet activity and may play a significant role in cardioprotection; they also note that cocoa consumption may be a good strategy in diminishing cardiovascular risk, including hyperactivation of blood platelets.

Despite its millennial existence and empirical documentation, the ethnological knowledge of herbs is a more recent phenomenon. The knowledge of their historical uses as food, medicine, source of income and small-scale businesses, and the sociological impacts are threatened due to the slow ethnobotanical research drive. Species of the genus Solanum have long been extensively used in folk medicine to treat various illnesses of humans since the dawn of civilization. All data were systematically obtained from papers, monographs, and books written in Uzbek, Russian, and English through various scientific online databases, including Google, Google Scholar, PubMed, Scopus, Semantic Scholar, Science Direct, and Web of Science using specific keywords focused on eight Solanum species. Eight native and non-native Solanum species as S. dulcamara L., S. lycopersicum L., S. melongena L., S. nigrum L., S. rostratum Dunal., S. sisymbriifolium Lam., S. tuberosum L., and S. villosum Mill. have been recorded in Uzbekistan of Central Asia. In this article we presented recently obtained data on the diversity, morphological characteristics, global distribution, habitat, population status, phenology, reproduction, pharmacology and phytochemistry of these Solanum species in Uzbekistan. Furthermore, relying on a combination of literature reviews and analyses from various scientific papers, we focus on food consumption coupled with global ethnobotanical and ethnopharmacological uses in human diseases of the Solanum species growing in Uzbekistan. Since the dawn of civilization, these eight cultivated and non-cultivated species of Solanum have provided sustainable resources of medicinal plants in Uzbekistan to prevent and treat various human diseases. Based on the collected data, it was shown that Solanum species have not been studied ethnobotanically and ethnomedicinally in Uzbekistan and it is necessary to conduct phytochemical and biotechnological research on them in the future. Traditional uses and scientific evaluation of Solanum indicate that S. nigrum, S. sisymbriifolium and S. tuberosum are one of the most widely used species in some parts of the world. Although considerable progress has been made to comprehend the chemical and biological properties of S. nigrum and S. tuberosum species, more research on the pharmacology and toxicology of these species is needed to ensure the safety, efficacy, and quality of their biologically active extracts and isolated bioactive compounds. Additionally, conducting additional research on the structure-activity relationship of certain isolated phytochemicals has the potential to enhance their biological efficacy and advance the scientific utilization of traditional applications of Solanum taxa.

This paper explores the socio cultural and institutional determinants of irresponsible prescription and use of antibiotics which has implications for the rise and spread of antimicrobial resistance (AMR). This study describes the patterns of prescription of antibiotics in a public facility in India and identifies the underlying institutional, cultural and social determinants driving the irresponsible use of antibiotics. The analysis is based on an empirical investigation of patients’ prescriptions that reach the in-house pharmacy following an outpatient department (OPD) encounter with the clinician. The prescription analysis describes the factors associated with use of broad-spectrum antibiotics, and a high percentage of prescriptions for dental outpatient department prescribed as a precautionary measure. This paper further highlights the need for future research insights in combining socio-cultural approach with medical rationalities, to further explore questions our analysis highlights like higher antibiotic prescription, etc., Along with the recommendations for further research.

All disease, but especially non-communicable diseases, are related to dysfunction of one or more regulatory systems. In developing countries, long-term management of patients with chronic diseases has many challenges and is generally not financially viable, but Africa in particular, which is rich in diverse ethnomedicines presents a more feasible long-term therapeutic approach in this niche. However, despite comprehensive preclinical investigations on numerous plant-derived candidate medicines, only a small portion of these reach the patient as recognised medicines. In this review, we use the example of rooibos (Aspalathus linearis (Burm.f.) R. Dahlgren)–which is globally consumed as aromatic, caffeine-free tea–to illustrate the hurdles that need to be overcome in the low-to middle-income countries, before progression of ethnomedicines to official treatment regimens can be achieved. In terms of methodology, regulatory system focused rooibos papers indexed on PubMed for the past three decades (n = 112) were accessed. Papers reporting duplication of previous results were excluded, as well as review papers. Topics covered includes the high standard of ethnomedicine drug discovery and efficacy testing research performed in Africa (and South Africa in particular in the case of rooibos), the potential bias in terms of preclinical research focus, ethnomedicine ownership and the requirement for independent clinical trial coordination and/or management.

Introduction: Advanced Therapy Medicinal Products are a type of therapies that, in some cases, hold great potential for patients without an effective current therapeutic approach but they also present multiple challenges to payers. While there are many theoretical papers on pricing and reimbursement (P&R) options, original empirical research is very scarce. This paper aims to provide a comprehensive international review of regulatory and P&R decisions taken for all ATMPs with centralized European marketing authorization in March 2022.Methods: A survey was distributed in July 2022 to representatives of 46 countries.Results: Responses were received from 20 countries out of 46 (43.5%). 14 countries reimbursed at least one ATMP. Six countries in this survey reimbursed no ATMPs.Conclusion: Access to ATMPs is uneven across the countries included in this study. This arises from regulatory differences, commercial decisions by marketing authorization holders, and the divergent assessment processes and criteria applied by payers. Moving towards greater equality of access will require cooperation between countries and stakeholders, for example, through the WHO Regional Office for Europe’s Access to Novel Medicines Platform.