Molecular Mechanism of Nelumbinis Plumula Alkaloids in Prevention and Treatment of Non-Small Cell Lung Cancer： an Analysis Based on Network Pharmacology and Cell Experiment / 中国实验方剂学杂志

Objective:To explore the potential molecular mechanism of Nelumbinis Plumula alkaloids （NAPs） in the prevention and treatment of non-small cell lung cancer （NSCLC） based on network pharmacology and cell experiment. Method:The main active components of NAPs were obtained by searching Traditional Chinese Medicine System Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and their main targets were predicted and analyzed by employing Swiss Target Prediction. The main target genes of NSCLC were retrieved from GeneCards， Online Mendelian Inheritance in Man （OMIM） and DrugBank databases. The resulting common targets were imported into STRING platform for constructing the protein-protein interaction （PPI） network， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis based on Database for Annotation， Visualization， and Integrated Discovery （DAVID）. The NAPs-common target -pathway network was constructed by Cytoscape 3.7.1. After NSCLC cell line A549 was treated with isoliensinine， the cell morphology was observed under an inverted fluorescence microscope. The effect of isoliensinine on A549 vitality was detected by cell counting kit-8 （CCK-8） assay and the target protein changes were verified by Western blot. Result:The main active components for NAPs against NSCLC were lysicamine， liensinine， and isoliensinine. The phosphatidylinositol-3-kinase-protein kinase B （PI3K-AKT）， RAS-related protein 1 （Rap1）， epidermal growth factor family of receptor tyrosine kinases （ErbBs）， and hypoxia inducible factor-1 （HIF-1） pathways were mainly involved for binding adenosine triphosphate （ATP） and regulating protein kinase activity. The main targets included protein kinase B-1 （AKT1）， alpha catalytic subunit of phosphoinositol-3-kinase （PIK3CA）， cyclin-dependent kinase 2 （CDK2）， mitogen-activated protein kinase-1 （MAPK1）， epidermal growth factor receptor （EGFR）， adenosine triphosphate-binding cassette B1 （ABCB1）， mammalian target of rapamycin （mTOR）， tyrosine kinase （Src）， Janus kinase 1 （JAK1）， and G1-phase-specific gene cyclin-D₁ （CCND1）. The <italic>in vitro</italic> cell experiment also revealed that isoliensinine down-regulated the expression of phosphorylated AKT （p-AKT） and phosphorylated mTOR （p-mTOR） in a concentration- and time-dependent manner and inhibited the growth of A549 cells. Conclusion:NAPs exert the preventive and therapeutic effects against NSCLC through multiple components， multiple targets， and multiple pathways， especially the PI3K-AKT pathway.

Seguridad de la sedación con propofol administrado por gastroenterólogos en endoscopia digestiva / Safety of propofol sedation administered by gastroenterologists in digestive endoscopy

Resumen Objetivo: tradicionalmente, la sedación con propofol ha estado a cargo de especialistas en anestesiología; sin embargo, una extensa cantidad de información publicada ha demostrado que la sedación con propofol administrado por no anestesiólogos, es segura y eficaz. El estudio se realizó con el objetivo de evaluar la seguridad en la administración de propofol por gastroenterólogos, para la realización de procedimientos en endoscopia digestiva. Métodos: se hizo un estudio retrospectivo en el cual se revisaron los expedientes de 1135 pacientes sometidos a endoscopias digestivas diagnósticas y terapéuticas, en el período comprendido entre enero de 2016 y marzo de 2017. Los pacientes se organizaron por su: edad, género, clasificación de riesgo de la Sociedad Americana de Anestesiólogos, indicación para la endoscopia, y dosis utilizada de propofol. Se registraron los efectos adversos asociados al uso de Propofol, tales como: episodios de hipoxemia transitoria, complicaciones cardiopulmonares serias y muerte. Resultados: se incluyeron los datos de 1135 pacientes (56 % fueron mujeres) que se practicaron endoscopia digestiva bajo sedación con propofol administrado por gastroenterólogos, en un período de 14 meses. La dosis promedio utilizada de propofol fue de 154 +/- 66 mg. Según la clasificación de riesgo de la Sociedad Americana de Anestesiólogos, el 84 % de los pacientes corresponde a las clasificaciones I y II, un 14,8 % a pacientes con clasificación de riesgo III y un 1,1 %, riesgo IV. Los estudios efectuados fueron mayoritariamente gastroscopias (52,6 %) y según la indicación, el 79,6 % corresponde a estudios diagnósticos, seguido de un 12,1% para los sangrados digestivos altos de emergencia. En cuanto a las complicaciones documentadas, se identificaron 70 episodios de hipoxemia que corresponden a un 6,2 % de las sedaciones realizadas. (IC 95%, 4,7-7,6). Solamente un 3,7 % de los pacientes presentó un episodio de hipoxemia por debajo del 80 %. Todos los episodios de hipoxemia, excepto uno, resolvieron con maniobras simples, como la elevación del mentón. Durante el estudio no se presentaron complicaciones cardiopulmonares serias o muertes. Se identificaron, como factores de riesgo para la aparición de hipoxemia, una clasificación de riesgo de la Sociedad Americana de Anestesiólogos mayor a 3, y la realización del estudio endoscópico para dilatación esofágica o colocación de gastrostomía percutánea. Conclusiones: el uso de sedación con propofol administrado por no anestesiólogos en el estudio, no evidenció incremento en la aparición de complicaciones cardiopulmonares serias, ni en los episodios de hipoxemia.

Abstract Aim: Traditionally, sedation with propofol has been approved exclusively for use by anethesiologists, however, an extensive amount of published information has shown that sedation with propofol administered by non-anesthesiologists is safe and effective. The present study was conducted with the objective of evaluating the safety in the administration of propofol by gastroenterologists for the performance of procedures in digestive endoscopy. Methods: A retrospective study was conducted in which the records of 1135 patients who underwent digestive and therapeutic digestive endoscopies were reviewed in the period between January 2016 and March 2017. The patients were classified by age, gender, risk classification of the American Society of Anesthesiologists (ASA), indication for endoscopy, and dose of propofol. The adverse effects associated with the use of propofol were recorded, such as episodes of transient hypoxemia, serious cardiopulmonary complications and death. Results: We included data from 1135 patients (56% were women) who underwent gastrointestinal endoscopy under sedation with propofol administered by gastroenterologist in a period of 14 months. The average dose used for propofol was 154 +/- 66 mg of propofol. According to the American Society of Anesthesiologists risk classification, 84% of the patients correspond to risk I and II, 14.8% to risk level III and 1.1% to risk level IV. The study carried out the most were gastroscopies (52.6%) and according to the indication, 79.6% corresponded to diagnostic studies, followed by 12.1% for upper gastrointestinal bleeding. Regarding the documented complications,70 episodes of hypoxemia were identified, corresponding to 6.2% of the sedations performed. (95% CI, 4.7-7.6). Only 3.7% of patients had an episode of hypoxemia below 80%. All episodes of hypoxemia, except one, resolved with simple maneuvers such as chin elevation. There were no serious cardiopulmonary complications or deaths during the study. We identified as risk factors for the appearance of hypoxemia a risk classification of the American Society of Anesthesiologists greater than 3 and performance of the endoscopic study for esophageal dilation or percutaneous gastrostomy placement. Conclusions: The use of sedation with propofol administered by non-anesthesiologists in the present study did not show an increase in the appearance of serious cardiopulmonary complications, or in episodes of hypoxemia.

Desempenho produtivo de frangos de corte e utilização de energia e nutrientes de dietas iniciais com milho classificado ou não e suplementadas com complexo enzimático / Broiler performance and energy and nutrient utilization of starter diets with classified corn or not and supplemented with enzymatic complexes

Dois experimentos foram conduzidos com o objetivo de avaliar o efeito da adição de um complexo enzimático em dietas iniciais elaboradas com milho classificado ou não por mesa densimétrica sobre o desempenho produtivo e a digestibilidade de nutrientes. Foram utilizados 1080 frangos de corte, machos, distribuídos em um delineamento inteiramente ao acaso, em esquema fatorial 2 x 3 (milho classificado ou não vs. dieta controle, dieta controle acrescida de complexo enzimático e dieta controle acrescida de enzimas e com redução de 150kcal de EM), totalizando seis repetições e 36 unidades experimentais. No ensaio de metabolismo, foram utilizadas 96 aves de 21 dias de idade, alojadas em baterias metálicas e distribuídas aos seis tratamentos, com oito repetições e 48 unidades experimentais. Dietas suplementadas com enzima, independentemente da classificação do milho, resultaram em maior (P<0,05) ganho de peso das aves aos 21 dias de idade. A adição de enzimas em dietas com milho classificado melhorou (P<0,05) a conversão alimentar. O CDPB foi maior (P<0,05) para dietas elaboradas com milho classificado, independentemente da suplementação do complexo enzimático, enquanto o CDEE de dietas à base de milho não classificado aumentou (P<0,05) quando as enzimas foram incluídas na deita. Dietas elaboradas à base de milho classificado e acrescidas de complexo enzimático comercial melhoraram (P<0,05) a EMA e a EMAn. As enzimas exógenas podem ser empregadas como ferramenta para melhorar a digestibilidade de nutrientes e de energia dos grãos de milho com variação nutricional.(AU)

Two experiments were performed with the aim of evaluating the effect of inclusion of enzymatic complexes in starter diets containing classified corn or not on the productive performance of poultry and nutrient digestibility. In the performance test 1080 broilers were used, distribuited in a completely randomized design in a factorial 2 x 3 (classified corn or not and corn control diet, control diet plus enzyme complex, and control diet plus enzymes and reduction of 150kcal of ME) and consisting of six replicates and 36 experimental units. In the metabolism trial 96 21-day-old birds were used, housed in metal cages, distributed to six treatments with eight replicates of 48 experimental units. Diets supplemented with enzyme, regardless of the corn classification, resulted in higher (P<0.05) weight gain of birds at 21 days of age. The addition of enzymes in diets with classified corn improved (P<0.05) feed conversion ratio. The CDPB was higher (P<0.05) for diets formulated with classified corn, regardless of the supplementation of the enzyme complex, while the CDEE of not classified corn-based diets increased (P<0.05) when the enzymes were included. Diets formulated with classified corn plus commercial enzymatic complex, improved (P 0.05) the AME and AMEn. Exogenous enzymes may be employed as a tool to improve the digestibility of nutrients and energy of corn with nutritional variation.(AU)

Distributions and associations between duration of sleep, daytime naps and insomnia symptoms among Chinese adults / 中华流行病学杂志

Objective To investigate the distribution of sleep duration,daytime naps habits,and insomnia-related symptoms among participants from the China Kadoorie Biobank (CKB) study,and to examine the associations between the sleep-associated factors.Methods A self-designed computer-based questionnaire was adopted to collect social-demographic information and lifestyle-related factors of the participants.A total of 452 829 Chinese adults aged 30-79 years,without self-reported histories of coronary heart disease,stroke,chronic obstructive pulmonary diseases or cancer,were included in this study.General linear regression and multinomial logistic regression models were used to estimate the distributions on duration of sleep,daytime naps habits,and insomnia-related symptoms in different populations,after adjusted for gender,age,and residential regions.Gender-specific logistic regression model was adopted to examine the associations between the above mentioned sleep-related factors.Results The average sleep duration of the participants was 7.41 hours per day,with 20.3％ of them having daytime naps all year round,but 40.1％ only had daytime naps in summer,and 39.6％ had no habits of daytime naps.11.0％,10.0％,and 2.1％ of the participants reported having had symptoms as difficulty in falling asleep,waking up too early or with daytime dysfunction,respectively.There were significant differences on the distributions in sleep-related factors between participants with different gender,age,residential areas,education levels,household income,and marital status (P＜0.05).Results from the logistic regression showed that longer sleep duration was associated with lower risks of insomnia-related symptoms trend (P＜0.001).Factor as without habits of daytime naps seemed to be associated with higher risks of insomnia-related symptoms (P＜0.05).Participants with longer sleep duration were more likely to have the habit of taking daytime naps (P＜0.05).Conclusions The distributions of sleep duration,habits on daytime naps and insomnia-related symptoms varied according to the differences on social-demographic factors.There were associations existed between the sleeping-related factors,which would influence the promotion on optimal sleep duration and better quality of sleep.

Distributions and associations between duration of sleep, daytime naps and insomnia symptoms among Chinese adults / 中华流行病学杂志

Objective To investigate the distribution of sleep duration,daytime naps habits,and insomnia-related symptoms among participants from the China Kadoorie Biobank (CKB) study,and to examine the associations between the sleep-associated factors.Methods A self-designed computer-based questionnaire was adopted to collect social-demographic information and lifestyle-related factors of the participants.A total of 452 829 Chinese adults aged 30-79 years,without self-reported histories of coronary heart disease,stroke,chronic obstructive pulmonary diseases or cancer,were included in this study.General linear regression and multinomial logistic regression models were used to estimate the distributions on duration of sleep,daytime naps habits,and insomnia-related symptoms in different populations,after adjusted for gender,age,and residential regions.Gender-specific logistic regression model was adopted to examine the associations between the above mentioned sleep-related factors.Results The average sleep duration of the participants was 7.41 hours per day,with 20.3％ of them having daytime naps all year round,but 40.1％ only had daytime naps in summer,and 39.6％ had no habits of daytime naps.11.0％,10.0％,and 2.1％ of the participants reported having had symptoms as difficulty in falling asleep,waking up too early or with daytime dysfunction,respectively.There were significant differences on the distributions in sleep-related factors between participants with different gender,age,residential areas,education levels,household income,and marital status (P＜0.05).Results from the logistic regression showed that longer sleep duration was associated with lower risks of insomnia-related symptoms trend (P＜0.001).Factor as without habits of daytime naps seemed to be associated with higher risks of insomnia-related symptoms (P＜0.05).Participants with longer sleep duration were more likely to have the habit of taking daytime naps (P＜0.05).Conclusions The distributions of sleep duration,habits on daytime naps and insomnia-related symptoms varied according to the differences on social-demographic factors.There were associations existed between the sleeping-related factors,which would influence the promotion on optimal sleep duration and better quality of sleep.