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Background: The development of new health technologies – drugs has allowed to change the therapeutics of some diseases, however, despite the advantages in various clinical scenarios – prevention, prophylaxis, treatment, etc., there is evidence that adverse drug reactions (ADR) are a frequent but preventable cause of disease, disability, or death. Therefore, it is estimated that in some countries ADRs represent between the fourth and sixth cause of mortality. Objectives: To determine the prevalence and profile of ADRs in a reference center in Ecuador. Design and setting: This historical cohort study included patients aged ≥ 18 years with diagnosed Adverse Reaction to Medications in the period March 2018 – March 2019, at a reference center in Ecuador. Patients were divided into three groups: I) Adverse drug reaction; ii) medication error (ME); and iii) therapeutic failure, according to WHO and ARCSA definitions. Methods: Continuous variables were compared using t-test or Mann-Whitney test, when distributional assumptions were in doubt. Categories were compared via chi-square test or Fisher exact test, when needed. The analyses were conducted with IBM-SPSS version 25. P values Results: Antibiotics and analgesics - antipyretics were the pharmacological groups responsible for the highest number of cases of ADRs (accounting for 9.0% and 7.6% respectively) and EM (24.7% and 20.8% respectively). Conclusion: The ADRs, ME present an important prevalence, for this reason all health institutions have pharmacovigilance systems that allow early detection of these events within a public policy of quality and safety of care.

Enquadramento: O delirium nas Unidades de Cuidados Intensivos, é reconhecido como um problema de saúde que tem impacto a longo prazo não só para o doente, como também, no que respeita a encargos financeiros para os serviços de saúde, razões pelas quais, os enfermeiros assumem um papel preponderante na implementação de medidas preventivas de delirium. Objetivo: Identificar as recomendações da literatura científica para intervenções não farmacológicas preventivas de delirium em doentes adultos internados em Unidades de Cuidados Intensivos. Métodos: Foi realizada uma revisão da literatura em janeiro de 2022, em 11 bases de dados, partindo da questão de investigação “quais as recomendações existentes na evidência científica relativas às intervenções não farmacológicas preventivas do delirium em doentes adultos internados na Unidade de Cuidados Intensivos”? A pesquisa e a documentação foram realizadas de acordo com a metodologia PRISMA. Resultados: Como resultado obtivemos 11 artigos. A prevenção de delirium está associada a intervenções que estão organizadas neste estudo em sete categorias: comunicação, estimulação visual, estimulação auditiva, estimulação cognitiva, preservação do sono noturno, mobilização precoce e inclusão da família nos cuidados de saúde. As intervenções não farmacológicas podem efetivamente diminuir a incidência desta patologia e assim melhorar os resultados clínicos. Conclusões: Das sete categorias representativas das intervenções não farmacológicas preventivas do delirium resultantes desta revisão destacamos duas: a preservação do sono noturno e a estimulação auditiva, uma vez que, estiveram presentes com mais destaque, na quase totalidade dos artigos analisados. As intervenções identificadas neste estudo, revelam-se eficazes na sua maioria, sendo por isso de grande relevância para a prática clínica., Background: In the Intensive Care Unit, delirium is recognized as a health issue with a long term impact, not only for the patient, but also for the Health Service itself because of its financial charges. This is why nurses assume such a major role in the implementation of the delirium preventive ways. Objective: This study was conducted to Identify the recommendations for non-pharmacological interventions the prevention of delirium in adult patients admitted to the Intensive Care Unit in the scientific literature. Methods: A review was held in January 2022, in 11 based on the electronic data, based on the research question "what are the recommendations in the scientific evidence regarding non-pharmacological preventive interventions for delirium in adult patients admitted to the Intensive Care Unit? The research and documentation were carried out in accordance with the PRISMA methodology. Results: As a result, we obtained 11 articles. The prevention of the delirium is associated to measures that are categorized in this study, in seven areas: communication; visual stimulation; hearing stimulation; cognitive stimulation; nocturnal sleep preservation; early mobilization and family inclusion in the care process, which can reduce effectively the occurrence of this pathology, and, with this, improve clinic results. Conclusions: From the seven representative categories of nonpharmacological intervention for the prevention of delirium resulting from this review, we highlight two: night sleep preservation and hearing stimulation, since they were more prominently present in almost all of the articles analyzed. The interventions identified in this study had shown in its majority to be effective, being therefore, of great relevance for the practical clinic.

ilustraciones El mundo evoluciona a pasos agigantados, la industria química no ha sido la excepción a ese desarrollo, y en una de sus ramas más importantes (supramolecular) cada vez se involucran más esfuerzos al reconocimiento de nuevos modelos, esto es posible gracias a la variedad de aplicaciones y a la versatilidad de las moléculas para adaptarse a un gran número de tareas dentro de los diferentes campos de la industria química, farmacéutica y ambiental. En ese sentido, en el presente estudio tiene por objeto caracterizar el uso de resorcinarenos como quimiosensores de neurotransmisores, dónde, en búsqueda de cumplir a entera cabalidad dicho objetivo, se ha empleado una metodología de investigación de tipo cualitativo, bajo un enfoque descriptivo, analítico y documental, pues se realizó una búsqueda y selección de información, con ayuda de diferentes bases de datos y gestores bibliográficos, como son Google Scholar, ScienceDirect, Scielo, EBSCO, Medline y similares, empleando criterios de búsqueda en palabras clave: resorcinarenes, resorcinarenes choline, resorcinarenes neurotrasmitters, chemosensor y chemosensor resorcinarene, y para ello, se ha tenido en cuenta el año de publicación de los artículos, ya que estos fueron ordenados, dependiendo de la función de los resorcinarenos dentro de los mismos, así como las particularidades con respecto a los neurotransmisores y técnicas trabajadas por los autores. (Texto tomado de la fuente) The world evolves by leaps and bounds, the chemical industry has not been the exception to this development, and in one of its most important branches (supramolecular) more and more efforts are involved in the recognition of new models, this is possible thanks to the variety of applications and the versatility of molecules to adapt to a large number of tasks within the different fields of the chemical industry, pharmaceutical and environmental. In this sense, the purpose of this study is to characterize the use of resorcinarenos as chemosensors of neurotransmitters, where, in search of fully fulfilling this objective, a qualitative research methodology has been used, under a descriptive, analytical and documentary approach, since a search and selection of information was carried out, with the help of different databases and bibliographic managers, such as Google Scholar, ScienceDirect, Scielo, EBSCO, Medline and similar, using search criteria in keywords: resorcinarenes, resorcinarenes choline, resorcinarenes neurotrasmitters, chemosensor and chemosensor resorcinarene, and for this, the year of publication of the articles has been taken into account, since these were ordered, depending on the function of the resorcinarenes within them, as well as the particularities with respect to neurotransmitters and techniques worked by the authors. Maestría Magíster en Ciencias - Química Para la realización del presente documento, se ha empleado una metodología de investigación de tipo cualitativo bajo un enfoque descriptivo, analítico y documental, pues se ha determinado mediante la investigación como el uso de resorcinarenos puede ser utilizado como quimiosensores de neurotransmisores, sin embargo, llegar a esa hipótesis ha demandado un análisis y síntesis de información extenso, sin mencionar que en el proceso de investigación, ha sido imprescindible utilizar únicamente fuentes que sean garantes de lo que publican para la temática involucrada, resaltando el uso de sitios web oficiales y de gobiernos nacionales, páginas certificadas y con dominios competentes. Asimismo, se ha empleado el uso de bases de datos científicas, siendo libres o por suscripción, resaltando entre ellas Google Scholar, ScienceDirect, EBSCO host, Scielo, Redalyc entre otras. El método de búsqueda de artículos e información ha funcionado bajo el uso de filtro de búsqueda por terminología MESH teniendo en cuenta palabras claves como (“resorcinarenes” AND “choline”), (“resorcinarenes” AND “neurotrasmitters”), (“chemosensor” AND “resorcinarene”), una vez se han obtenido los resultados, se procede a leer el título y aquellos que sean viables o que aporten al proyecto, se procede a leer su respectivo resumen, esto, con el fin de validar la utilidad del artículo, y si está orientada hacia el cumplimiento del objetivo del presente documento. Cabe resaltar que se aplican diversos filtros de las posibles investigaciones a utilizar respecto a las que no, por ejemplo, todos los artículos fueron tomados en cuenta respecto a su fecha de publicación, empleando solo aquellos que permitan agregar valor a la investigación, con datos actualizados o funcionales hasta la época, descartando aquellas publicaciones retrógradas o sin actualización. Los artículos cuyas temáticas tenidas en cuenta van desde las generalidades de los neurotransmisores y macrociclos, los usos y aplicaciones de resorcinarenos funcionalizados, sus características y forma de síntesis hasta sus sistemas de análisis, control y cuantificación de diferentes moléculas con grupos tetra-alquil amonio en sus estructuras, características de los quimiosensores, sus aplicaciones, así como artículos del trabajo experimental de análisis químico, las técnicas usadas y algunas recomendaciones dadas por los autores de los artículos

SUMMARY OBJECTIVE: To review the main physiological and pharmacological changes related to prematurity, to promote the evidence-based clinical practice. METHODS: This is a narrative review whose research was carried out in the ScienceDirect and Medline databases via PubMed, searching for articles in any language from January 2000 to February 2020. RESULTS: Premature newborns are born before completing the maturation process that prepares them for extrauterine life, which occurs especially in the last weeks of pregnancy. Therefore, they have their own characteristics in development. Several physiological peculiarities stand out, such as disturbances in glucose regulation, adrenal function, thermoregulation, immunity, in addition to changes in liver, renal and respiratory functions. Pharmacological aspects were also highlighted, involving pharmacokinetics and pharmacodynamics. CONCLUSIONS: Despite the recent advances in prematurity, it is still an area with many uncertainties, since several changes occur quickly and there are ethical issues that make studies difficult. Thus, it is clear that the therapeutic management of premature infants is still very much based on clinical practice.

[ES] Establecer el patrón de la oferta, el consumo y el coste de la terapia con Ansiolíticos (N05B) en Castilla y León en el periodo 2010-2020 y el efecto de la pandemia de la COVID-19. Para ello se pretende conocer la evolución de la oferta de ansiolíticos en España durante el periodo 2010-2015, analizar la evolución del consumo global de Ansiolíticos 2010-2015 en Dosis Diarias Definidas por 1000 habitantes y día (DHD), Diferenciar el consumo en DHD de especialidades farmacéuticas genéricas y especialidades farmacéuticas con nombre comercial en las distintas provincias y en Castilla y León, valorar la evolución del importe y gasto de ansiolíticos a nivel provincial y autonómico 2010-2015. Analizar la evolución y el patrón del consumo de Ansiolíticos 2015-2020 en envases por 1000 habitantes a nivel autonómico diferenciando entre los distintos principios activos y entre genéricos y marcas. Y observar el posible impacto de la COVID-19 en la utilización de Ansiolíticos.

Objective: To carry out a systematic review of studies with synthetic analogues of Aniba riparia, riparins A, B, C, D, E and F, in order to highlight the pharmacological potentials already elucidated. Methodology: Three databases were used to select the articles to be included in the Embase, Pubmed and Web of Science review, with the following simplified search strategy (Riparin or Aniba riparia), at the end of the selection, resulting in 10 articles for the elaboration of this work. Results: Publications of studies with synthetic derivatives were identified between the years 2014 to 2021. Most of the researches used riparin A, followed by B, and all were pre-clinical studies. Important pharmacological effects have been reported, such as antibacterial, antifungal, anti-inflammatory, antinociceptive, antitumor, immunomodulatory, antiprotozoal, antiparasitic, anxiolytic and antioxidant activities. Discussion: Studies carried out with synthetic analogues have placed them as possible therapeutic tools, considering the important pharmacological activities already reported. Conclusion: However, considering that the literature already reports six synthetic riparins, the number of articles published aimed at elucidating possible pharmacological activities seems small, even though they are promising candidates for the development of research aimed at discovering new drugs. Objetivo: Realizar una revisión sistemática de estudios con análogos sintéticos de Aniba riparia, riparinas A, B, C, D, E y F, con el fin de resaltar los potenciales farmacológicos ya dilucidados. Metodología: Se utilizaron tres bases de datos para seleccionar los artículos a incluir en la revisión Embase, Pubmed y Web of Science, con la siguiente estrategia de búsqueda simplificada (Riparin o Aniba riparia), al final de la selección, resultando en 10 artículos para la elaboración de este trabajo. Resultados: Se identificaron publicaciones de estudios con derivados sintéticos entre los años 2014 a 2021. La mayoría de las investigaciones utilizaron riparina A, seguida de B, y todas fueron estudios preclínicos. Se han reportado efectos farmacológicos importantes, tales como actividades antibacterianas, antifúngicas, antiinflamatorias, antinociceptivas, antitumorales, inmunomoduladoras, antiprotozoarias, antiparasitarias, ansiolíticas y antioxidantes. Discusión: Los estudios realizados con análogos sintéticos los han colocado como posibles herramientas terapéuticas, considerando las importantes actividades farmacológicas ya reportadas. Conclusión: Sin embargo, considerando que la literatura ya reporta seis riparinas sintéticas, el número de artículos publicados para dilucidar posibles actividades farmacológicas es pequeño, aunque son candidatos prometedores para el desarrollo de investigaciones dirigidas al descubrimiento de nuevos fármacos. Objetivo: Realizar uma revisão sistemática dos estudos com os análogos sintéticos da Aniba riparia, as riparinas A, B, C, D, E e F, com o intuito de evidenciar os potenciais farmacológicos já elucidados. Metodologia: Utilizou-se três bases de dados para seleção dos artigos a serem incluídos na revisão Embase, Pubmed e Web of Science, com a seguinte estratégia de busca simplificada (Riparin or Aniba riparia), ao final da seleção, resultou em 10 artigos para a elaboração deste trabalho. Resultados: As publicações dos estudos com derivados sintéticos foram identificadas entre os anos de 2014 a 2021. Sendo que a maioria das pesquisas utilizavam a riparina A, seguida pela B, e todos tratavam-se de estudos pré-clínicos. Foram relatados importantes efeitos farmacológicos, como as atividades antibacteriana, antifúngica, anti-inflamatória, antinociceptiva, antitumoral, imunomoduladora, antiprotozoário, antiparasitária, ansiolítica e antioxidante. Discussão: Os estudos realizados com os análogos sintéticos têm colocado as mesmas como possíveis ferramentas terapêuticas, considerando as importantes atividades farmacológicas já relatadas. Conclusão: Contudo, considerando que a literatura já relata seis riparinas sintéticas, o número de artigos publicados voltados para elucidação de possíveis atividades farmacológicas parece reduzido, mesmo sendo promissoras candidatas para o desenvolvimento de pesquisas direcionadas para descobertas de novos fármacos.

Background This study aimed to investigate the intrinsic mechanisms of Qishen granules (QSG) in the treatment of HF, and to provide new evidence and insights for its clinical application. Material/Methods Information on QSG ingredients was collected from Traditional Chinese medicine systems pharmacology (TCMSP), TCM@Taiwan, TCMID, and Batman, and input into SwissTargetPrediction to identify the compound targets. HF-related targets were detected from Therapeutic Target Database (TTD), Disgenet-Gene, Drugbank database, and Online Mendelian Inheritance in Man (OMIM) database. The overlap targets of QSG and HF were identified for pathway enrichment analysis by utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The protein-protein interaction (PPI) network of QSG-HF was constructed, following by the generation of core targets, construction of core modules, and KEGG analysis of the core functional modules. Results There were 1909 potential targets predicted from the 243 bioactive compounds in QSG which shared 129 common targets with HF-related targets. KEGG pathway analysis of common targets indicated that QSG could regulated 23 representative pathways. In the QSG-HF PPI network analysis, 10 key targets were identified, including EDN1, AGT, CREB1, ACE, CXCR4, ADRBK1, AGTR1, BDKRB1, ADRB2, and F2. Further cluster and enrichment analysis suggested that neuroactive ligand-receptor interaction, cGMP-PKG signaling pathway, renin secretion, vascular smooth muscle contraction, and the renin-angiotensin system might be core pathways of QSG for HF. Conclusions Our study elucidated the possible mechanisms of QSG from a systemic and holistic perspective. The key targets and pathways will provide new insights for further research on the pharmacological mechanism of QSG.

BACKGROUND Epimedii Herba is a traditional Chinese herbal medicine used to treat central nervous system diseases such as Alzheimer's disease in China. However, the pharmacological mechanism is unclear. To investigate the mechanisms of Epimedii Herba in the treatment of Alzheimer's disease, we assessed effective compounds, corresponding targets, and related pathways of Epimedii Herba in the treatment of Alzheimer's disease based on network pharmacology. MATERIAL AND METHODS The active components and targets of Epimedii Herba were obtained through the TCMSP database and the DrugBank database. The DisGeNET database and GeneCards database were used to search for Alzheimer's disease targets. The common targets of components and disease were obtained by Wayne diagram. Gene ontology (GO) analysis and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed using the DAVID database. The component-target-pathway interaction network model was constructed using Cytoscape software. Auto Duck Vina software was used for molecular docking to analyze the affinity of the key ingredients and the main targets. RESULTS We screened 17 active ingredients and 27 key targets of Epimedii Herba in the treatment of Alzheimer's disease, which were related to the HIF-1 signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, NF-kappaB signaling pathway, VEGF signaling pathway, and sphingolipid signaling pathway. CONCLUSIONS Based on network pharmacology, the multi-component, multi-target, and multi-pathway characteristics of Epimedii Herba in the treatment of Alzheimer's disease were explored. Our results provide new ideas for future pharmacological and experimental research on Epimedii Herba in the treatment of Alzheimer's disease.

RESUMO Objetivo: Investigar a efetividade da vancomicina contra Gram-positivos com concentração inibitória mínima de 1mg/L em pacientes pediátricos com base na razão entre área sob a curva e concentração inibitória mínima > 400. Métodos: População de 22 pacientes pediátricos (13 meninos) internados no centro de terapia intensiva pediátrica, com função renal preservada, que foram distribuídos em dois grupos (G1 < 7 anos e G2 ≥ 7 anos). Após a quarta dose de vancomicina (10 - 15mg/kg a cada 6 horas), duas amostras de sangue foram colhidas (terceira e quinta horas), seguidas da dosagem sérica por imunoensaios para investigação da farmacocinética e da cobertura do antimicrobiano. Resultados: Não se registrou diferença entre os grupos com relação à dose, ao nível de vale ou ainda na área sob a curva. A cobertura contra Gram-positivos com concentração inibitória mínima de 1mg/L ocorreu em apenas 46% dos pacientes em ambos os grupos. A farmacocinética se mostrou alterada nos dois grupos diante dos valores de referência, mas a diferença entre grupos foi registrada pelo aumento da depuração total corporal e pelo encurtamento da meia-vida biológica, mais pronunciados nos pacientes mais novos. Conclusão: A dose empírica mínima de 60mg/kg ao dia deve ser prescrita ao paciente pediátrico de unidade de terapia intensiva com função renal preservada. A utilização da razão entre área sob a curva e concentração inibitória mínima na avaliação da cobertura da vancomicina é recomendada para se atingir o desfecho desejado, uma vez que a farmacocinética está alterada nesses pacientes, podendo impactar na efetividade do antimicrobiano. Abstract Objective: To investigate the vancomycin effectiveness against gram-positive pathogens with the minimum inhibitory concentration of 1mg/L in pediatric patients based on the area under the curve and the minimum inhibitory concentration ratio > 400. Methods: A population of 22 pediatric patients (13 boys) admitted to the pediatric intensive care unit with preserved renal function was stratified in two groups (G1 < 7 years and G2 ≥ 7 years). After the fourth dose administered of vancomycin (10 - 15mg/kg every 6 hours) was administered, two blood samples were collected (third and fifth hours), followed by serum measurement by immunoassays to investigate the pharmacokinetics and antimicrobial coverage. Results: There was no difference between the groups regarding dose, trough level or area under the curve. Coverage against gram-positive pathogens with a minimum inhibitory concentration of 1mg/L occurred in only 46% of patients in both groups. The pharmacokinetics in both groups were altered relative to the reference values, and the groups differed in regard to increased total body clearance and shortening of the biological half-life, which were more pronounced in younger patients. Conclusion: A minimum empirical dose of 60mg/kg per day should be prescribed for pediatric patients in intensive care units with preserved renal function. The use of the ratio between the area under the curve and minimum inhibitory concentration in the evaluation of vancomycin coverage is recommended to achieve the desired outcome, since the pharmacokinetics are altered in these patients, which may impact the effectiveness of the antimicrobial.

BACKGROUND This study used a network pharmacology approach to identify the pharmacological mechanisms of a traditional Chinese medicine derived from Trachelospermum jasminoides (Lindl.) Lem. in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS Known compounds of T. jasminoides were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the Shanghai Institute of Organic Chemistry of Chinese Academy of Science, Chemistry (CASC) database, and a literature search. Putative targets of identified compounds were predicted by SwissTargetPrediction. RA-related targets were achieved from the Therapeutic Target database, Drugbank database, Pharmacogenomics Knowledgebase, and Online Mendelian Inheritance in Man database. The protein-protein interaction (PPI) network was built by STRING. CluGO was utilized for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis. RESULTS A total of 354 potential targets were predicted for the 17 bioactive compounds in T. jasminoides; 69 of these targets overlapped with RA-related targets. A PPI network was composed and 2 clusters of 59 and 42 nodes each were excavated. GO and KEGG enrichment analysis of the overlapping targets and the 2 clusters was mainly grouped into immunity, inflammation, estrogen, anxiety, and depression processes. CONCLUSIONS Our study illustrated that T. jasminoides alleviates RA through the interleukin-17 signaling pathway, the tumor necrosis factor signaling pathway, and other immune and inflammatory-related processes. It also may exert effects in regulating cell differentiation and potentially has anti-anxiety, anti-depression, and estrogen-like effects.

BACKGROUND Nasopharyngeal carcinoma (NPC) is a common head and neck cancer epidemic in southern China and southeast Asia. LeiGongTeng has been widely used for the treatment of cancers. The purpose of this study was to determine the pharmacological mechanism of action of LeiGongTeng in the treatment of NPC using a network pharmacological approach. MATERIAL AND METHODS The traditional Chinese medicine systems pharmacology (TCMSP) database was used to identify active ingredients and associated target proteins for LeiGongTeng. Cytoscape was utilized to create a drug-disease network and topology analysis was conducted to analyze the degree of each ingredient. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) online tool was applied for the construction and analysis of the protein-protein interaction (PPI) network, while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) functional analyses were utilized to determine drug-disease common genes. RESULTS 22 active ingredients including kaempferol, nobiletin, and beta-sitosterol, and 30 drug-disease common genes including VEGFA, CASP3, ESR1, and RELA were identified. GO analysis indicated that 94 biological processes, including RNA polymerase II, apoptotic process, response to drug, cell adhesion, and response to hypoxia, were found to be associated with NPC. The KEGG enrichment analysis showed that 58 pathways, including the PI3K-Akt signaling pathway, microRNAs in cancer, tumor necrosis factor (TNF) signaling pathway and pathways in cancer were found to be associated with NPC. CONCLUSIONS LeiGongTeng exerts its therapeutic effect through various biological processes and signaling pathways since it acts on several target genes. Systematic pharmacology can be used to predict the underlying function of LeiGongTeng and its mechanism of action in NPC.

BACKGROUND This study used network pharmacology method and cell model to assess the effects of Radix Astragali (RA) on cholangiocarcinoma (CCA) and to predict core targets and molecular mechanisms. MATERIAL AND METHODS We performed an in vitro study to assess the effect of RA on CCA using CCK8 assay, the Live-Cell Analysis System, and trypan blue staining. The components and targets of RA were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and genes associated with CCA were retrieved from the GeneCards and OMIM platforms. Protein-protein interactions were analyzed with the STRING platform. The components-targets-disease network was built by Cytoscape. The TIMER database revealed the expression of core targets with diverse immune infiltration levels. GO and KEGG analyses were performed to identify molecular-biology processes and signaling pathways. The predictions were verified by Western blotting. RESULTS Concentration-dependent antitumor activity was confirmed in the cholangiocarcinoma QBC939 cell line treated with RA. RA contained 16 active compounds, with quercetin and kaempferol as the core compounds. The most important biotargets for RA in CCA were caspase 3, MAPK8, MYC, EGFR, and PARP. The TIMER database revealed that the expression of caspase3 and MYC was related with diverse immune infiltration levels of CCA. The results of Western blotting showed RA significantly influenced the expression of the 5 targets that network pharmacology predicted. CONCLUSIONS RA is an active medicinal material that can be developed into a safe and effective multi-targeted anticancer treatment for CCA.

To investigate the vancomycin effectiveness against gram-positive pathogens with the minimum inhibitory concentration of 1mg/L in pediatric patients based on the area under the curve and the minimum inhibitory concentration ratio400.A population of 22 pediatric patients (13 boys) admitted to the pediatric intensive care unit with preserved renal function was stratified in two groups (G17 years and G2 ≥ 7 years). After the fourth dose administered of vancomycin (10 - 15mg/kg every 6 hours) was administered, two blood samples were collected (third and fifth hours), followed by serum measurement by immunoassays to investigate the pharmacokinetics and antimicrobial coverage.There was no difference between the groups regarding dose, trough level or area under the curve. Coverage against gram-positive pathogens with a minimum inhibitory concentration of 1mg/L occurred in only 46% of patients in both groups. The pharmacokinetics in both groups were altered relative to the reference values, and the groups differed in regard to increased total body clearance and shortening of the biological half-life, which were more pronounced in younger patients.A minimum empirical dose of 60mg/kg per day should be prescribed for pediatric patients in intensive care units with preserved renal function. The use of the ratio between the area under the curve and minimum inhibitory concentration in the evaluation of vancomycin coverage is recommended to achieve the desired outcome, since the pharmacokinetics are altered in these patients, which may impact the effectiveness of the antimicrobial.Investigar a efetividade da vancomicina contra Gram-positivos com concentração inibitória mínima de 1mg/L em pacientes pediátricos com base na razão entre área sob a curva e concentração inibitória mínima400.População de 22 pacientes pediátricos (13 meninos) internados no centro de terapia intensiva pediátrica, com função renal preservada, que foram distribuídos em dois grupos (G17 anos e G2 ≥ 7 anos). Após a quarta dose de vancomicina (10 - 15mg/kg a cada 6 horas), duas amostras de sangue foram colhidas (terceira e quinta horas), seguidas da dosagem sérica por imunoensaios para investigação da farmacocinética e da cobertura do antimicrobiano.Não se registrou diferença entre os grupos com relação à dose, ao nível de vale ou ainda na área sob a curva. A cobertura contra Gram-positivos com concentração inibitória mínima de 1mg/L ocorreu em apenas 46% dos pacientes em ambos os grupos. A farmacocinética se mostrou alterada nos dois grupos diante dos valores de referência, mas a diferença entre grupos foi registrada pelo aumento da depuração total corporal e pelo encurtamento da meia-vida biológica, mais pronunciados nos pacientes mais novos.A dose empírica mínima de 60mg/kg ao dia deve ser prescrita ao paciente pediátrico de unidade de terapia intensiva com função renal preservada. A utilização da razão entre área sob a curva e concentração inibitória mínima na avaliação da cobertura da vancomicina é recomendada para se atingir o desfecho desejado, uma vez que a farmacocinética está alterada nesses pacientes, podendo impactar na efetividade do antimicrobiano.

BACKGROUND Paeonia lactiflora is the main active ingredient of peony decoction, which is used to treat ulcerative colitis (UC) in traditional Chinese medicine (TCM). Network pharmacology indicates the multiple interactions among genes, proteins, and metabolites associated with diseases and drugs from the network perspective, which shows the multi-component and multi-target attributes of TCM. This study predicted the pharmacological mechanism of Paeonia lactiflora in the treatment of UC by network pharmacological method. MATERIAL AND METHODS Chemical constituents of Paeonia lactiflora were searched from TCMSP data, gene names of target sites were extracted from UniProt database, and disease targets of ulcerative colitis were obtained from the CTD disease database. Use Venny online tools to obtain common targets for drugs and diseases. The DAVID database was used to enrich GO and KEGG for the common target, and the related functions and pathways were obtained. Cytoscape 3.7.1 was used to construct the 'drug-compound-target-disease' network. RESULTS There are 70 common target genes between Paeonia lactiflora and UC. GO analysis showed that the biological functions of the common target genes of Paeonia lactiflora and UC include response to lipopolysaccharide, response to estradiol, response to drug, positive regulation of nitric oxide biosynthetic process, and steroid hormone-mediated signaling pathway. Enrichment of the KEGG signaling pathway mainly involves signaling pathways, including Pathways in cancer, TNF signaling pathway, Tuberculosis, Hepatitis B, and Toxoplasmosis. CONCLUSIONS The network pharmacology intuitively shows the multi-component, multi-target, and multi-channel pharmacological effects of Paeonia lactiflora on UC, and provides a scientific basis for studying the mechanism of the effect of Paeonia lactiflora on UC.

Objective Analyze the microbiological effectiveness, based on the pharmacokinetics/pharmacodynamics correlation of vancomycin in pediatric patients, and to propose dose adjustment. Methods This is an observational, cross-sectional study, conducted in a pediatric hospital, over a 1-year period (2016 to 2017). Children of both sexes, aged 2 to 12 years, were included in the study; burn children, and children in renal replacement therapy were excluded. For the pharmacokinetic analysis, two samples of 2mL of whole blood were collected, respecting the 2-hour interval between each withdrawal. Results Ten pediatric patients with median age of 5.5 years and interquartile range (IQR) of 3.2-9.0 years, median weight of 21kg (IQR: 15.5-24.0kg) and median height of 112.5cm (IQR: 95-133cm), were included. Only one child achieved trough concentrations between 10µg/mL and 15µg/mL. Conclusion The empirical use of vancomycin in the children studied did not achieve the therapeutic pharmacokinetic/pharmacodynamic target for minimum inhibitory concentration of 1µg/mL. RESUMO Objetivo Analisar a efetividade microbiológica considerando a correlação farmacocinética/farmacodinâmica de vancomicina em crianças e propor uma estimativa de ajuste na dose. Métodos Trata-se de um estudo observacional, transversal, realizado em hospital pediátrico, no período de 1 ano (2016 a 2017). Foram incluídas crianças de 2 a 12 anos de ambos os sexos, tendo sido excluídas crianças queimadas ou submetidas à terapia renal substitutiva. Para análise farmacocinética, foram coletadas duas amostras de 2mL de sangue total, respeitando o intervalo de 2 horas entre cada coleta. Resultados Foram incluídos dez pacientes pediátricos com idade de 5,5 anos (mediana) e intervalo interquartil (IQ) de 3,2-9,0 anos, peso de 21kg (mediana; IQ: 15,5-24,0kg) e altura de 112,5cm (mediana; IQ: 95-133cm). Apenas uma criança alcançou concentrações mínimas entre 10µg/mL e 15µg/mL. Conclusão A utilização empírica de vancomicina na população de crianças não alcançou o alvo farmacocinético/farmacodinâmico terapêutico para concentração inibitória mínima de 1μg/mL.

BACKGROUND Cornus officinalis (CO), also known as 'Shanzhuyu', is one of the most common traditional Chinese herbs used against osteoporosis. Although previous studies have found that CO has beneficial effects in alleviating osteoporosis, its mechanisms remain unclear. MATERIAL AND METHODS In this study, we applied system bioinformatic approaches to investigate the possible therapeutic mechanisms of CO against osteoporosis. We collected the active ingredients of CO and their targets from the TCMSP, BATMAN-TCM, and ETCM databases. Next, we obtained the osteoporosis targets from differentially expressed mRNAs from the Gene Expression Omnibus (GEO) gene series (GSE35958). Next, the shared genes of the CO pharmacological targets and osteoporosis-related targets were selected to construct the protein-protein interaction network, based on the results from the STRING database. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out by using the clusterProfiler package in R software. RESULTS In all, there were 58 unique CO compounds and 518 therapeutic targets. Based on the GO and KEGG enrichment results of 98 common genes, we selected the top 25 terms, based on the terms' P values. We found that the anti-osteoporotic effect of CO may mostly involve the regulation of calcium metabolism and reactive oxygen species, and the estrogen signaling pathway and osteoclast differentiation pathway. CONCLUSIONS We found the possible mechanisms of CO in treating osteoporosis may be based on multiple targets and pathways. We also provided a theoretical basis and promising direction for investigating the exact anti-osteoporotic mechanisms of CO.

BACKGROUND Intracerebral hemorrhage (ICH), a fatal type of stroke, profoundly affects public health. Yi-Qi-Huo-Xue decoction (YQHXD), a traditional Chinese medicine (TCM) prescription, is verified to be an efficient method to treat ICH stroke among the Chinese population. Nevertheless, the pharmacological mechanisms of YQHXD have been unclear. MATERIAL AND METHODS We used a strategy based on network pharmacology to explore the possible multi-component, multi-target, and multi-pathway pattern of YQHXD in treating ICH. First, candidate targets for YQHXD were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Then, these candidate YQHXD targets were used in combination with the known targets for the treatment of ICH stroke to construct the core network (cPPI) using data on protein-protein interaction (PPI). We calculated 5 topological parameters for identification of the main hubs. Pathway enrichment and GO biological process enrichment analyses were performed after the incorporation of the main hubs into ClueGO. RESULTS In total, 55 candidate YQHXD targets for ICH were recognized to be the major hubs in accordance with their topological importance. As suggested by enrichment analysis, the YQHXD targets for ICH were roughly classified into several biological processes (related to redox equilibrium, cell-cell communication, adhesion and collagen biosynthesis, cytokine generation, lymphocyte differentiation and activation, neurocyte apoptosis and development, neuroendocrine system, and vascular development) and related pathways (VEGF, mTOR, NF-kappaB, RAS/MAPK, JAK/STAT and cytokine-cytokine receptors interaction), indicating those mechanisms underlying the therapeutic effect of YQHXD. CONCLUSIONS The present results may serve as a pharmacological framework for TCM studies in the future, helping to promote the use of YQHXD in clinical treatment of ICH.

Narcolepsy is a chronic neurological sleep disorder with potentially disabling symptoms ranging from occupational concerns to mental health difficulties. Recent advances related to the neurobiological basis of narcolepsy have led to newer pharmacological treatment options and adjunctive behavioral techniques that support symptom management. This article outlines evidence-based pharmacologic therapies, behavioral techniques, and psychosocial costs related to narcolepsy. Psychosocial factors, although frequently acknowledged, deserve further attention and awareness from researchers and providers. The American Academy of Sleep Medicine's (AASM) Quality Measure Drivers and potential future treatment options are also discussed.

Background/Aim. Data on phytochemical and pharmacological investigations of genus Cirsium Mill. (Asteraceae) are scarce. Some data suggest that decoctions or infusions prepared from these plants are used in folk medicine as tonics, particularly in inflammatory, liver and stomach diseases. So far there have been no pharmacological investigations related to Cirsium ligulare (C. ligulare) Boiss. Accordingly, the aim of this study was to estimate antioxidative, anti-inflammatory and gastroprotective activities of aqueous extracts of C. ligulare herb prepared as 5% and 10% decoctions. Methods. Antioxidative activity was determined using the method of 2,2-diphenyl-1- picrylhydrazyl (DPPH) radical scavenging. Investigations of anti-inflammatory (a model of systemic inflammatory response induced by endotoxin of Escherichia coli and carrageenaninduced rat paw oedema model for local inflammatory response), as well as gastroprotective effects (a model of stress-ulcer induced by absolute ethanol), were conducted in adult female Wistar rats that were given the aqueous extracts of C. ligulare herb per os. Indomethacin and ranitidine were used as reference drugs for evaluation of local anti-inflammatory and gastroprotective effects, respectively. Results. The results demonstrated that aqueous extracts of C. ligulare herb produced strong antioxidative activity, diminished body weight loss induced by endotoxin, significantly reduced carrageenan-induced paw oedema, and prevented the ulcerogenic action of absolute ethanol. Both anti-inflammatory and gastroprotective activities of the extract tested were comparable to those of the reference drugs. Conclusion. Presented results justify the traditional use of C. ligulare herb decoctions and further phytochemical and pharmacological investigations are warranted. Uvod/Cilj. Biljke roda Cirsium su hemijski i farmakološki nedovoljno ispitane. Tradicionalno se dekokti ili infuzi ovih biljaka koriste kao tonici, naročito kod zapaljenjskih procesa, kao i kod bolesti jetre i želuca. Vrsta Cirsium ligulare (C. ligulare) Boiss. do sada nije farmakološki ispitivana. Stoga je cilj ovog istraživanja bio da se proceni antioksidantna, antiinflamatorna i gastroprotektivna aktivnost vodenog ekstrakta herbe C. ligulare izrađenog kao 5% i 10% dekokt. Metode. Ispitivanje antioksidantne aktivnosti vršeno je testom neutralizacije 2,2-diphenyl-1-picrylhydrazyl (DPPH) radikala. Ispitivanje antiinflamatornog (model sistemskog inflamatornog odgovora indukovan endotoksinom bakterije Escherichia coli i karageninom-indukovani edem šape pacova kao model lokalne inflamcije), kao i gastroprotektivnog efekta (model ulkusa indukovanog apsolutim etanolom), sprovedeno je na odraslim ženkama pacova Wistar soja, kojima su per os dati vodeni ekstrakti herbe C. ligulare. Kao referentni lekovi prilikom ispitivanja lokalnog antiinflamatornog i gastroprotektivnog delovanja, primenjeni su indometacin i ranitidin, redom. Rezultati. Rezultati pokazuju da su ispitivani vodeni ekstrakti herbe C. ligulare ispoljili jaku antioksidantnu aktivnost, smanjili gubitak telesne mase indukovan endotoksinom, značajno redukovali karageninom indukovani edem šape pacova i spečili ulcerogeni efekat apsolutnog etanola. Antiinflamatorna i gastroprotektivna aktivnost ispitivanih ekstrakata bila je uporediva sa aktivnošću referentnih lekova. Zaključak. Dobijeni rezultati u značajnoj meri opravdavaju tradicionalnu primenu dekokta herbe C. ligulare, a planiraju se i dodatna hemijska i farmakološka ispitivanja ove droge.

BACKGROUND This study aimed to explore the therapeutic effect of external application of ligustrazine combined with holistic nursing on pressure sores, as well as the underlying mechanism. MATERIAL AND METHODS From February 2014 to March 2015, a total of 32 patients with Phase II and Phase III pressure sores were enrolled and randomly assigned to an experimental group or a control group. The clinical data were comparable between the 2 groups. In addition to holistic nursing, the patients in the experimental group received 4 weeks of continuous external application of ligustrazine, whereas patients in the control group received compound clotrimazole cream. Therapeutic effect and healing time were recorded. HaCaT cells were used as an in vitro model for mechanism analysis of the effect of ligustrazine in treating pressure sores. After culturing with different concentrations of ligustrazine or the inhibitor of AKT (LY294002) for 72 h, cell viability, clone formation numbers, and levels of phosphatidyl inositol 3-kinase (PI3K), p-AKT, and p-mammalian target of rapamycin (mTOR) were determined. RESULTS Compared to the control group, the total effective rate in the experimental group was significantly higher, and the healing time was significantly reduced. Cell viability and clone formation numbers were significantly upregulated by ligustrazine in a dose-dependent manner. Both the cell viability and clone formation numbers were significantly inhibited by application of LY294002. CONCLUSIONS Our results suggest that ligustrazine combined with holistic nursing is an effective treatment of pressure sores. The protective effect may be associated with the promotion of cell growth by activation of the PI3K/AKT pathway.