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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.

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.

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.

Objective: The causes of “delayed-on” and “no-on” phenomena in Parkinson disease (PD) are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. Case Description: A 69-year-old man with PD presented with “delayed-on” and “no-on” phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an “off” state. Videofluoroscopic examination of swallowing in an “off” state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of “delayed-on” and “no-on” phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG) was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of “no-on” phenomena decreased. Conclusion: In PD patients, the “no-on” phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.

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 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.