El análisis estadístico implicativo y su uso en investigaciones de salud

Introducción: El análisis estadístico implicativo es un método basado en las técnicas estadísticas multivariadas, la teoría de la cuasi-implicación, la inteligencia artificial y el álgebra booleana. Se utiliza para modelar interrelaciones entre sujetos y variables que permiten la estructuración del conocimiento en forma de normas y reglas generalizadas. Objetivo: Caracterizar el análisis estadístico implicativo como herramienta del tratamiento de la información estadística en ciencias de la salud. Métodos: Se realizó una búsqueda de fuentes bibliográficas para caracterizar el método, y el uso en factores pronósticos y perfiles de organización funcional visual en patologías extrapolables a distintos tamaños de muestras. Desarrollo: El análisis estadístico implicativo organiza la información, favorece el tratamiento estadístico adecuado en el análisis de los datos y permite graficar los resultados. Igualmente, las reglas obtenidas conllevan a hipótesis de causalidad sin restringir el número de variables y el tamaño de la muestra. Su uso ha contribuido a estudios de factores pronósticos en patologías como el cáncer y de perfiles en el procesamiento visual en disléxicos. Conclusiones: El análisis estadístico implicativo crea hipótesis de causalidad a través de reglas metodológicas de relación entre las variables de estudio. Además, permite estructurar, analizar y comprender vínculos entre sujetos y variables de la investigación en salud.

Introduction: Implicative statistical analysis is a method based on multivariate statistical techniques, quasi-implication theory, artificial intelligence, and Boolean algebra. It is used to model interrelationships between subjects and variables that allow the structuring of knowledge in the form of generalized norms and rules. Objective: To characterize implicative statistical analysis as a tool for the processing of statistical information in health sciences. Methods: A search of bibliographic sources was carried out to characterize the method, and its use in prognostic factors and profiles of visual functional organization in pathologies that can be extrapolated to different sample sizes. Development: Implicative statistical analysis organizes information, favors the appropriate statistical treatment in the analysis of the data, and allows the results to be graphed. Likewise, the rules obtained lead to hypotheses of causality without restricting the number of variables and the size of the sample. Its use has contributed to studies of prognostic factors in pathologies such as cancer and profiles in visual processing in dyslexics. Conclusions: Implicative statistical analysis creates hypotheses of causality through methodological rules of relationship between study variables. In addition, it makes it possible to structure, analyze and understand links between subjects and variables of health research.

Urinary Metabolomics Aanlysis of Differences in Effect of Aconiti Coreani Radix and Typhonii Rhizoma on Gerbils with Stroke / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique， and then to clarify the mechanism of the two， as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group（CG）， model group（MG）， Aconiti Coreani Radix group（RA） and Typhonii Rhizoma group（RT）. Except for the CG， ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG， rats in the other groups received whole powder suspension（0.586 mg·g-1） was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0， 3， 7 and 14. After the end of administration， the serum， brain tissue and urine of gerbils in each group were collected， and the rate of cerebral infarction was detected by 2，3，5-triphenyltetrazolium chloride（TTC）， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， malondialdehyde（MDA）， superoxide dismutase（SOD）， glutathione（GSH）， and nitric oxide（NO） in serum and brain tissue were determined by enzyme-linked immunosorbent assay（ELISA）. The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， and the data were processed by multivariate statistical analysis， and differential metabolites were screened based on value of variable importance in the projection（VIP） of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG） database and Metaboanalyst 5.0. ResultCompared with the CG， the neurological deficit score was significantly increased in the MG（P<0.05）， compared with the MG， the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d（P<0.05）. Compared with the CG， the rate of cerebral infarction was significantly increased in the MG（P<0.05）， compared with the MG， the rates of cerebral infarction in the RA and RT were significantly reduced（P<0.05）. Compared with the CG， the levels of IL-6， TNF-α， and MDA in the serum and brain tissue of gerbils from the MG were significantly increased（P<0.05）， and the levels of SOD， GSH and NO were significantly reduced（P<0.05）. Compared with the MG， Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6， TNF-α and MDA， and up-regulated the levels of SOD， GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics， of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma， and could be used as potential biomarkers for both treatments in stroke gerbils， respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism， pyrimidine metabolism， and aminoacyl-tRNA biosynthesis. In addition， Aconiti Coreani Radix could also regulate riboflavin metabolism， Typhonii Rhizoma could also regulate purine metabolism， glycine， serine and threonine metabolism， arachidonic acid metabolism， biosynthesis of pantothenate and coenzyme A， and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke， with Aconiti Coreani Radix having stronger effects. From the metabolomics results， the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism， oxidative stress and so on， while Typhonii Rhizoma mainly involve amino acid metabolism， lipid metabolism， energy metabolism， etc.

Coeficientes V de Aiken: diferencias en los juicios de validez de contenido / Aiken's V Coefficient: Differences in Content Validity Judgments / Coeficientes Aiken V: Diferenças nos julgamentos de validade do conteúdo

Resumen: Objetivo: Cuando es estudiada la validez de contenido en dos grupos independientes de jueces expertos, se requiere hacer una prueba formal de las diferencias entre sus juicios, dado que es posible obtener distintos juicios de validez de contenido. Pero, generalmente, la investigación de la validez de contenido no examina esta posible fuente de discrepancias. El presente reporte describe la implementación de un método para evaluar la diferencia de coeficientes V de Aiken aplicado al trabajo investigativo en ciencias del deporte. Metodología: El procedimiento aplica una adaptación para construir el intervalo de confianza de la diferencia entre coeficientes V de Aiken y también implementa un estimador estandarizado del tamaño de la distinción entre los coeficientes V, específicamente, la transformación arcoseno de coeficientes V. Resultados: Se desarrollan dos ejemplos, en un marco de análisis secundario de datos, y se demuestra la diferencia entre la conclusión con base impresionista y la conclusión con base empírica y evaluación formal. Se detectaron distinciones estadísticas no observadas previamente. Conclusiones e implicaciones: El método que estima diferencias de coeficientes de validez de contenido V de Aiken para la investigación permite un avance en la metodología que valida instrumentos de medición. Se valora la aplicabilidad de este procedimiento en el contexto de ciencias del deporte y ciencias de la educación, así como en el diseño de la investigación.

Abstract: Objective: When two independent groups of expert judges study content validity, a formal test of the differences between their judgments is required, since different content validity judgments can be obtained. But generally, content validity research does not examine this likely source of discrepancies. This report describes the implementation of a method to evaluate the difference in Aiken's V coefficients applied to research work in sports science. Methodology: The procedure applies an adaptation to construct the confidence interval of the difference between Aiken's V coefficients and also implements a standardized estimator of the size of the difference between the V coefficients, specifically the arcsine transformation of V coefficients. Results: In a secondary data analysis framework, two examples are developed, extracting data from both publications, and the difference between the impressionist-based conclusion and the empirical-based conclusion and formal evaluation is demonstrated. Statistical differences not previously observed were detected. Conclusions and implications: The method to estimate differences in Aiken's content validity coefficients for research allows an advance in the methodology to validate measurement instruments. The applicability of this procedure in the context of sports sciences and education sciences, as well as in the research design involved, is assessed.

Resumo: Objetivo: Quando a validade do conteúdo é estudada em dois grupos independentes de juízes especialistas, é necessário um teste formal das diferenças entre seus julgamentos, uma vez que é possível obter diferentes julgamentos de validade de conteúdo. Mas a pesquisa de validade do conteúdo geralmente não examina esta possível fonte de discrepâncias. Este relatório descreve a implementação de um método para avaliar a diferença dos coeficientes V de Aiken aplicada ao trabalho de investigação das ciências do desporto. Metodologia: O procedimento aplica uma adaptação para construir o intervalo de confiança da diferença entre os coeficientes V de Aiken, e também implementa um estimador estandardizado do tamanho da diferença entre os coeficientes V, especificamente a transformação arco-seno dos coeficientes V. Resultados: Dois exemplos são desenvolvidos em uma estrutura secundária de análise de dados, e a diferença entre a conclusão baseada no impressionismo e a conclusão baseada no empirismo com avaliação formal é demonstrada. Diferenças estatísticas não observadas anteriormente foram detectadas. Conclusões e implicações: O método para estimar as diferenças nos coeficientes de validade do conteúdo V de Aiken para a pesquisa permite um avanço na metodologia de validação dos instrumentos de medição. A aplicabilidade deste procedimento no contexto da ciência do esporte e da ciência educacional, assim como no projeto de pesquisa, é avaliada.

Análisis estadístico implicativo para identificar factores pronósticos de mortalidad por linfomas en niños y adolescentes

Fundamento: el análisis estadístico implicativo surgió en los años 80 para resolver problemas de la didáctica de las matemáticas. Recientemente se fundamentó su empleo en las Ciencias Médicas para identificar factores de riesgo y pronósticos. Objetivo: evaluar la utilidad del análisis estadístico implicativo en la identificación de los factores pronósticos que más inciden en la mortalidad por linfomas en niños y adolescentes. Método: se realizó un estudio de casos y controles en niños y adolescentes con diagnóstico de linfoma Hodgkin y no Hodgkin atendidos en el Hospital Docente Pediátrico Sur Dr. Antonio María Béguez César de Santiago de Cuba en el período de enero 2008 a enero 2021. Se analizó como variable dependiente el estado del paciente fallecido o vivo al momento del estudio y como covariables se tomaron: el estadio de mal pronóstico, la presencia de síntomas B, el subtipo histológico, la presencia de tres o más sitios extraganglionares, la metástasis, edad y presencia de masa tumoral. Se aplicaron dos técnicas estadísticas, la regresión logística binaria y el análisis estadístico implicativo. Resultados en los casos fue más frecuente el linfoma no Hodgkin mientras que en los controles predominó el Hodgkin. Ambas técnicas reconocieron el subtipo histológico y la afectación extraganglionar como factores pronósticos desfavorables. El análisis estadístico implicativo reconoció además el estadio y la presencia de metástasis. Conclusión: el análisis estadístico implicativo es una técnica que complementa la regresión logística binaria en la identificación de factores pronósticos, lo que permite mejor comprensión de la causalidad.

Background: the implicative statistical analysis arose in the 80s to solve problems in the didactics of mathematics. Its use in the Medical Sciences to identify risk factors and prognoses was recently founded. Objective: to evaluate the usefulness of the implicative statistical analysis in the identification of the prognostic factors that most affect mortality from lymphomas in children and adolescents. Method: a case-control study was carried out in children and adolescents diagnosed with Hodgkin and non-Hodgkin lymphoma treated at the Dr. Antonio María Béguez César Sur Pediatric Teaching Hospital in Santiago de Cuba from January 2008 to January 2021. The state of the deceased or alive patient at the time of the study was analyzed as the dependent variable and the following were taken as covariates: poor prognosis stage, presence of B symptoms, histological subtype, presence of three or more extranodal sites, metastasis, age and presence of tumor mass. Two statistical techniques were applied: binary logistic regression and implicative statistical analysis. Results: non-Hodgkin's lymphoma was more frequent in the cases, while Hodgkin's lymphoma predominated in the controls. Both techniques recognized the histological subtype and extranodal involvement as unfavorable prognostic factors. The implicative statistical analysis also recognized the stage and the presence of metastases. Conclusion: the implicative statistical analysis is a technique that complements the binary logistic regression in the identification of prognostic factors, which allows a better understanding of causality.

Proposta de modelo de acompanhamento dos gastos em saúde: uma análise para o câncer no período 2012 - 2021 / Proposal for health spending monitoring model: an analysis for cancer in the 2012 period ­ 2021

O câncer, como uma das principais causas de mortes no mundo, causa problemas econômicos para as nações. Seus gastos, além de críticos, pressionam o orçamento público, provocando, também, perda de produtividade devido aos afastamentos do trabalho, às mortes e aposentadorias prematuras. Apesar de todo o peso econômico e social do câncer, ainda são poucos os estudos sobre os gastos com essa doença. A ausência de informações mais dinâmicas impede um planejamento mais detalhado e eficiente do processo de gestão, de modo que uma visão mais aprofundada dessas correlações permitirá um planejamento e gestão mais eficientes numa área extremamente sensível da política de saúde no Brasil. O presente trabalho tem como objetivo a realização de uma análise econômica dos gastos com as internações no Sistema Único de Saúde (SUS) de 2012 a 2021. Para tal, utiliza uma metodologia que se inicia na extração de todos os dados públicos no período, considerando um subconjunto dos campos do Sistema de Internações Hospitalares (SIH/SUS) previamente escolhidos e todos os códigos de procedimentos relacionados ao câncer utilizados no Sistema de Gerenciamento da Tabela de Procedimentos, Medicamentos e Órteses, Próteses e Materiais Especiais do SUS (SIGTAP). Após a extração utilizando um programa desenvolvido em outro projeto no LEMAS/IMS/UERJ, os dados foram carregados numa aplicação de Business Intelligence (BI) denominada TABLEAU para análises e apresentação dos resultados, seguida de uma discussão que abrangeu comparações com outros dados nacionais e internacionais. Na sequência, esses dados extraídos foram carregados num sistema de banco de dados MySQL para futuras análises. (AU)

Cancer, as one of the main causes of deaths in the world, causes economic problems for nations. In addition to being critical, its expenses put pressure on the public budget, also causing loss of productivity due to absences from work, deaths and premature retirements. Despite all the economic and social weight of cancer, there are still few studies on the costs associated with this disease. The absence of more dynamic information prevents more detailed and efficient planning of the management process, so a more in-depth view of these correlations will allow for more efficient planning and management in an extremely sensitive area of health policy in Brazil. The objective of this work is to carry out an economic analysis of expenses with hospitalizations in the Unified Health System (SUS) from 2012 to 2021. To this end, it uses a methodology that begins with the extraction of all public data in the period, considering a subset of previously chosen Hospital Admissions System (SIH/SUS) fields and all cancer-related procedure codes used in the SUS Procedures, Medications and Orthoses, Prostheses and Special Materials Table Management System (SIGTAP). After extraction using a program developed in another project at LEMAS/IMS/UERJ, the data was loaded into a Business Intelligence (BI) application called TABLEAU for analysis and presentation of results, followed by a discussion that included comparisons with other national data and international. In sequence. these extracted data were loaded into a MySQL database system for future analysis. (AU)

Application of the multivariate and univariate analyses to estimate the feed efficiency in beef cattle

This study aimed to compare the univariate analyses (relationship between dry matter intake (DMI) and average daily gain (ADG), Kleiber ratio, and residual feed intake) and multivariate analysis (bionutritional index [BNI]) to determine feed efficiency. Were used a total of 160 cattle (individual data) and the analyzed variables were dry matter intake, weight gain, and body weight of the animals. We used five methods to evaluate feed efficiency, the BNI, FE, corrected feeding efficiency (corFE), Kleiber ratio (KR), and residual feed intake (RFI). Study 1 demonstrated that only the FE (p=0.0472) was significant, although the FE after the transformation of Box-Cox (corFE) (p=0.0642) showed a statistical trend. In studies 2, 3, and 5, we observed that BNI was the best biological efficiency indicator. In the study 4, we observed that the best indicators were FE (0.110; p=0.0281), corFE (0.380; p=0.0429), and RFI (0.465; p=0.0340) for the genders. However, corFE decreased the coefficient of variation in all studies. In conclusion, the use of the Box-Cox transformation is as efficient as the multivariate analysis in discriminating experimental groups (genetic groups, different levels of concentrate in the diet, and genders) concerning the other univariate analyzes.

Statistical analysis logic and expression specifications of cohort and case-control studies / 中华麻醉学杂志

Cohort and case-control studies are important types of study design in clinical and epidemiological researches. Although they are both methods to study associations between an exposure and a disease, their core logic is completely different.In order to evaluate the association between an exposure and an outcome, cohort studies group the populations by the research factor (exposure or not), and compare the event rate of the outcome in exposure and control groups through follow-up. Cohort studies are sequential from cause to effect. On the contrary, case-control studies derive cause from effect. Case-control studies group the populations by the outcome (occurrence or not), and compare the distributions of the exposure in case and control groups through retrospective investigation or collection of exposure information from historical records. This paper declares the logic that should be followed in statistical analysis of these two types of studies, as well as the specifications that should be followed in formulating statistical analysis plans and reporting results. The aim of this paper is to enhance the scientific nature of the research and improve the readability of the literature.

Study on quality standard of Yi medicine Gynura japonica and quality evaluation of medicinal materials from different producing areas / 中国药房

OBJECTIVE To improve the quality standard of Yi medicine Gynura japonica， and to evaluate its quality. METHODS Using 15 batches of G. japonica from different producing areas as samples， the contents of water， total ash， acid- insoluble ash and water-soluble extract were determined according to the method stated in part Ⅳ of Chinese Pharmacopoeia （2020 edition）. The contents of total alkaloid （calculated by senecionine） was determined by UV spectrophotometry. The contents of senecionine and seneciphylline were determined by HPLC. Using above 7 indexes as evaluation indexes， cluster heat map analysis， principal component analysis （PCA） and entropy weight approximation ideal ranking （TOPSIS） were used to evaluate the quality of medicinal material comprehensively. RESULTS Among 15 batches of G. japonica， the moisture contents were 8.88%-12.60%， the total ash contents were 4.43%-11.02%， the acid-insoluble ash contents were 0.56%-3.45%， the water-soluble extract contents were 21.71%-53.91%， the total alkaloid contents （calculated by senecionine） were 0.15%-0.39%， and the contents of senecionine and seneciphylline were 0.01% -0.05% and 0.01%-0.06% respectively. According to the results of various indicators， it was preliminarily proposed that the water content in the sample of G. japonica should not exceed 13.00%， the total ash content should not exceed 11.50%， the acid-insoluble ash content should not exceed 3.70%， the water-soluble extract should not be less than 20.70%， the total alkaloid content should not be less than 0.15%， the contents of senecionine and seneciphylline should not be less than 0.01% both. The results of cluster heat map analysis showed that the 15 batches of samples could be divided into four categories； the results of PCA and TOPSIS showed that the samples with high-quality ranking were jsq-2， jsq-5， jsq-6 and jsq-10， and the samples with low-quality ranking were jsq-4， jsq-13 and jsq-14. CONCLUSIONS In this study， the quantitative analysis method of total alkaloids （calculated by senecionine）， senecionine and seneciphylline in G. japonica is established， and the limits of each index are preliminarily determined. Among 15 batches of samples， the qualities of medicinal material collected from Linza Village of Ganluo County of Liangshan Yi Autonomous Prefecture， Machangping Village of Luojishan Town of Puge County of Liangshan Yi Autonomous Prefecture and other places are better.

GC-MS Analysis of Effect of Different Processing Conditions on Irritation of Magnoliae Officinalis Cortex / 中国实验方剂学杂志

ObjectiveTo investigate the key compounds affecting the irritation and to clarify the effect of heating and the addition of ginger juice as the auxiliary material during the processing on the irritation of Magnoliae Officinalis Cortex（MOC） by comparing the irritation and composition of volatile oil in MOC and its different processed products. MethodVolatile oil in raw products， water-processed products， ginger-dried products， ginger-fried products（the amounts of ginger were 10%， 50%， respectively） of MOC were extracted by steam distillation and subjected to rabbit eye irritation experiment， and the volatile components of each sample were detected by gas chromatography-mass spectrometry（GC-MS）. Principal component analysis（PCA）and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to analyze the data of each sample by SIMCA 14.1. The relative contents of different processed products were compared two by two with those of and raw products or ginger-fried products， and the markers that might be related to the irritation were sorted out according to the principles of variable importance in the projection（VIP） value >1 and P<0.05， and the factors influencing the differences in irritation were analyzed. ResultCompared with the blank group， the administration groups all had irritation to the eyes of rabbits， and the degree of irritation was in the order of raw products>water-processed products>ginger-dried products>ginger-fried products（10%）>ginger-fried products（50%）. The results of PCA and OPLS-DA showed that there were differences in the volatile oil from raw products and different processed products. According to VIP value>1 and P<0.05， and combined with the results of eye irritation experiment， ten volatile compounds related to irritation changes were screened out. Among them， cis-cinnamaldehyde was only detected in raw products， the relative contents of β-caryophyllene， （+）-delta-cadinene， α-humulene， γ-muurolene， （-）-isoledene and citral all increased to different degrees， the contents of p-cymene， 1（10）-4-cadinadien-15-ol and β-eudesmol all decreased to different degrees. ConclusionThe irritation of MOC is reduced after heating and processing with ginger juice， and the synergistic effect of both is more effective for reducing irritation. Among the differential markers associated with changes in irritation， the increase in the relative content of citral is closely related to the addition of ginger juice， while the decrease in the relative contents of cis-cinnamaldehyde， p-cymene， 1（10）-4-cadinadien-15-ol is related to heating， and the changes of other components may be related to the synergistic effect of heating and ginger juice.

Data verification and sensitivity analysis of statistical analysis in bioequivalence studies / 药学实践杂志

Objective To sort out the key points, problems and countermeasures of data verification through data verification of statistical analysis in 18 bioequivalence studies, and provide reference for improving the statistical analysis reports of related research. Methods SAS and WinNonlin software was used to illustrate that whether the random number tables, main pharmacokinetic parameters and bioequivalence data could reproduce the corresponding results in the original statistical analysis reports. Results Among the 18 studies, sensitivity analysis was supplemented or re-performed for 5 studies due to sampling time deviation of individual subjects or adjustment of sensitivity data sets, resulting in differences in pharmacokinetic parameters from the original statistical analysis report, but same for the bioequivalence evaluation. Other verified data was consistent with the original statistical analysis reports. Conclusions The verification of statistical analysis data of bioequivalence studies is extremely important, and the problems found in this paper should be fully considered when writing such statistical analysis reports.

Differential analysis of coumarins in Angelica dahurica from different origins / 中国药房

OBJECTIVE To screen the differential components of coumarins in Angelica dahurica from two origins （A. dahurica cv.‘ Hangbaizhi’； A. dahurica cv.‘ Qibaizhi’）. METHODS Non-targeted metabolomics technique of UPLC-Q-Exactive- MS/MS was used to analyze the coumarins in 6 batches of A. dahurica cv. ‘Hangbaizhi’ and 12 batches of A. dahurica cv. ‘Qibaizhi’. The differential components were screened by principal component analysis， partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis. Cluster analysis was performed on differential components. RESULTS A total of 41 coumarins were identified in 18 batches of samples， in which 23 coumarins were differential components. Therein， 6 differential components were higher in content in A. dahurica cv.‘ Hangbaizhi’， while 17 differential components were higher in content in A. dahurica cv.‘ Qibaizhi’. The content of marmesin galactoside in A. dahurica cv.‘ Hangbaizhi’ was significantly higher than that in A. dahurica cv.‘ Qibaizhi’. Based on 23 differential components， A. dahurica cv.‘ Hangbaizhi’ and A. dahurica cv. ‘Qibaizhi’ could be grouped into one category， respectively. CONCLUSIONS The screened differential components of coumarins can be used to distinguish A. dahurica cv. ‘Hangbaizhi’ from A. dahurica cv. ‘Qibaizhi’， especially marmesin galactoside contributed the most， which can be used to identify A. dahurica cv.‘ Hangbaizhi’ and A. dahurica cv.‘ Qibaizhi’.

Comprehensive quality evaluation of Periploca forrestii produced in Guizhou using multi-index components combined with multivariate statistical analysis / 中国药房

OBJECTIVE To establish comprehensive quality evaluation method based on multi-index components combined with multivariate statistical analysis， and to comprehensively evaluate the quality of Periploca forrestii. METHODS Taking 11 batches of P. forrestii medicinal materials from different areas in Guizhou as samples， the contents of neochlorogenic acid， cryptochlorogenic acid， chlorogenic acid， procyanidin A2， isochlorogenic acid A and isochlorogenic acid C were determined by HPLC. Clustering heat map analysis， grey correlation analysis（GRA） and technique for order preference by similarity to ideal solution（TOPSIS） were used to evaluate the quality of P. forrestii. RESULTS The results of methodological investigation of content determination were in accordance with the relevant regulations， and the linear relationship and accuracy of each component were good in their respective sampling range. The contents of chlorogenic acid， cryptochlorogenic acid， neochlorogenic acid， procyanidin A2， isochlorogenic acid A and isochlorogenic acid C in 11 batches of samples were 3.650-7.302， 0.888-2.575， 1.371- 2.386， 0.947-1.469， 0.084-0.169 and 0.725-1.067 mg/g， respectively. The content of each component was significantly different， with the highest content of chlorogenic acid and the lowest content of isochlorogenic acid A. The comprehensive results of cluster heat map， GRA and TOPSIS analysis showed that the comprehensive quality of S5 and S10 was relatively good. CONCLUSIONS The established method is accurate， stable and simple. Combined with multivariate statistical analysis method， it can be used for quality evaluation of P. forrestii. The quality of samples from Jiuzhou Town and Caiguan Town of Xixiu District in Anshun City of Guizhou Province are relatively good among 11 different origin samples.

Quality evaluation of Cnidii Fructus in commodity grade based on theory of "quality evaluation through morphological identification" / 中国中药杂志

From the perspective of market classification of Cnidii Fructus, this paper revealed the scientific connotation of evaluating the quality grade of Cnidii Fructus by its appearance traits. Thirty batches of Cnidii Fructus in different grades were selected as the research objects. The canonical correlation analysis and principal component analysis(PCA) were used to explore the measurement values of 15 appearance traits and intrinsic content indexes. The results of correlation analysis showed that except the aspect ratio, the 5 appearance trait indexes(length, width, 1 000-grain weight, broken grain weight proportion, and chroma) and 9 internal content indexes(the content of moisture, total ash, acid insoluble ash, osthole, imperatorin, 5-methoxy psoralen, isopimpinellin, xanthotoxin, and xanthotol) showed significant correlation to varying degrees. In addition, there was a significant positive correlation between the first typical variable U_1 composed of appearance traits and the first typical variable V_1 composed of internal content indexes(CR_1=0.963, P<0.01). The results of PCA showed that the classification results of appearance traits for 30 batches of Cnidii Fructus were consistent with the actual information of the samples. Under the same analysis conditions, 30 batches of Cnidii Fructus were reclassified by 9 groups of internal content indexes, and the analysis results were consistent. From the classification standard of the appearance traits of the system study, the statistical results of 6 appearance traits of Cnidii Fructus showed a correlation with grades. There was a good correlation between the appearance and the internal content of Cnidii Fructus, and the appearance quality effectively predicted the level of the internal content. There is a certain scientific basis for the quality classification of Cnidii Fructus by main appearance traits. Appearance classification can replace quality grading to realize the "quality evaluation through morphological identification" of Cnidii Fructus.

Discrimination of cultivation modes of Dendrobium nobile based on content of mineral elements and ratios of nitrogen stable isotopes / 中国中药杂志

This study explored the feasibility of mineral element content and ratios of nitrogen isotopes to discriminate the cultivation mode of Dendrobium nobile in order to provide theoretical support for the discrimination of the cultivation mode of D. nobile. The content of 11 mineral elements(N, K, Ca, P, Mg, Na, Fe, Cu, Zn, Mn, and B) and nitrogen isotope ratios in D. nobile and its substrate samples in three cultivation methods(greenhouse cultivation, tree-attached cultivation, and stone-attached cultivation) were determined. According to the analysis of variance, principal component analysis, and stepwise discriminant analysis, the samples of different cultivation types were classified. The results showed that the nitrogen isotope ratios and the content of elements except for Zn were significantly different among different cultivation types of D. nobile(P<0.05). The results of correlation analysis showed that the nitrogen isotope ratios, mineral element content, and effective component content in D. nobile were correlated with the nitrogen isotope ratio and mineral element content in the corresponding substrate samples to varying degrees. Principal component analysis can preliminarily classify the samples of D. nobile, but some samples overlapped. Through stepwise discriminant analysis, six indicators, including δ~(15)N, K, Cu, P, Na, and Ca, were screened out, which could be used to establish the discriminant model of D. nobile cultivation methods, and the overall correct discrimination rates after back-substitution test, cross-check, and external validation were all 100%. Therefore, nitrogen isotope ratios and mineral element fingerprints combined with multivariate statistical analysis could effectively discriminate the cultivation types of D. nobile. The results of this study provide a new method for the identification of the cultivation type and production area of D. nobile and an experimental basis for the quality evaluation and quality control of D. nobile.

Effect of processing method on chemical constituents of Rehmanniae Radix: based on UHPLC-LTQ-Orbitrap MS / 中国中药杂志

This study aims to explore the chemical composition of Rehmanniae Radix braised with mild fire and compare the effect of processing method on the chemical composition of Rehmanniae Radix. To be specific, ultra-high performance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to screen the chemical constituents of Rehmanniae Radix. The chemical constituents were identified based on the relative molecular weight and fragment ions, literature information, and Human Metabolome Database(HMDB). The ion peak area ratio of each component before and after processing was used as the index for the variation. SIMCA was employed to establish principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) models of different processed products. According to the PCA plot, OPLS-DA plot, and VIP value, the differential components before and after the processing were screened out. The changes of the content of differential components with the processing method were analyzed. A total of 66 chemical components were identified: 57 of raw Rehmanniae Radix, 55 of steamed Rehmanniae Radix, 55 of wine-stewed Rehmanniae Radix, 51 of repeatedly steamed and sundried Rehmanniae Radix Praeparata, 62 of traditional bran-braised Rehmanniae Radix, and 63 of electric pot-braised Rehmanniae Radix. Among them, the 9 flavonoids of braised Rehmanniae Radix were from Citri Reticulatae Pericarpium. PCA suggested significant differences in the chemical composition of Rehmanniae Radix Praeparata prepared with different processing methods. OPLS-DA screened out 32 chemical components with VIP value >1 as the main differential components. Among the differential components, 9 were unique to braised Rehmanniae Radix(traditional bran-braised, electric pot-braised) and the degradation rate of the rest in braised(traditional bran-braised, electric pot-braised) or repeatedly steamed and sundried Rehmanniae Radix was higher than that in the steamed or wine-stewed products. The results indicated the chemical species and component content of Rehmanniae Radix changed significantly after the processing. The 32 components, such as rehmapicrogenin, martynoside, jionoside D, aeginetic acid, hesperidin, and naringin, were the most important compounds to distinguish different processed products of Rehmanniae Radix. The flavonoids introduced by Citri Reticulatae Pericarpium as excipient may be the important material basis for the effectiveness of braised Rehmanniae Radix compared with other processed products.

Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum / 中国中药杂志

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.

Quality evaluation of Huocao based on UPLC fingerprint and multi-component content determination / 中国中药杂志

Huocao(a traditional Chinese herbal medicine) moxibustion is a characteristic technology in Yi medicine suitable for cold-dampness diseases. Huocao, as the moxibustion material, is confusedly used in clinical practice and little is known about its quality control. In this study, UPLC method was used to establish the chemical fingerprint of non-volatile components in Huocao, and the contents of eight phenolic acids such as chlorogenic acid were determined. Multivariate statistical analysis was performed to obtain the indicator components of Huocao for quality evaluation, and thus a comprehensive evaluation system for the quality of Huocao was built. The UPLC fingerprints of 49 batches of Huocao were established, and there were 20 common peaks, of which eight phenolic acids including neochlorogenic acid and chlorogenic acid were identified. Except for three batches of Huocao, the similarity of the other 46 batches was higher than 0.89, suggesting that the established fingerprint method could be used for quality control of the medicinal herb. The correlation coefficient between entropy weight score of the eight phenolic acids and comprehensive fingerprint score in Huocao was 0.875(P<0.01), which indicated that the eight phenolic acids could be used as indicator components for the quality evaluation of Huocao. Furthermore, in multivariate statistical analysis on the common peaks of fingerprint and the contents of the eight phenolic acids, chlorogenic acid, isochlorogenic acid A and isochlorogenic acid C were screened to be the indicator components. The results revealed that the proposed method achieved a simple and accurate quality control of Huocao based on UPLC fingerprint and multi-component content determination, which provided useful data for establishing the quality standard of Huocao.

Quality Marker （Q-marker） of Tinosporae Radix Associated with Efficacy of "Relieving Sore Throat" / 中国实验方剂学杂志

ObjectiveTo study the potential quality marker （Q-marker） of Tinosporae Radix associated with efficacy of "relieving sore throat" based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， multivariate statistical analysis （MSA）， and network pharmacology. MethodUPLC-Q-TOF-MS was used to identify the main chemical components in 18 batches of Tinosporae Radix. On this basis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were employed to screen out the main marker components that caused differences between groups. Moreover， network pharmacology technology was applied to predict the potential "sore throat-relieving" components， and the molecular docking between the common components resulting from MSA and network pharmacology and the core targets was carried out to verify the marker components. ResultA total of 17 compounds， including alkaloids， diterpenoid lactones， and sterols， were identified by UPLC-Q-TOF-MS. Five main differential components were found by MSA： Columbamine， jatrorrhizine， palmatine， menisperine， and columbin. Network pharmacology analysis yielded six compounds： tetrahydropalmatine， palmatine， menisperine， fibleucin， neoechinulin A， and columbin which were selected as potential "sore throat-relieving" components of Tinosporae Radix. They may relieve sore throat by acting on interleukin-6， epidermal growth factor receptor， prostaglandin G/H synthase 2， matrix metalloproteinase-9， proto-oncogene tyrosine-protein kinase Src and other targets， and regulating Hepatitis B， influenza A， human T-cell virus infection， human cytomegalovirus infection， coronavirus disease-2019， and other signaling pathways. The common active components in Tinosporae Radix resulting from MSA and network pharmacology analysis were palmatine， menisperine， and columbin， which had high binding affinity with six core targets and can be used as the Q-marker components of Tinosporae Radix in "relieving sore throat". ConclusionThis study predicts the "sore throat-relieving" Q-marker of Tinosporae Radix， which lays a basis for developing the quality standard of Tinosporae Radix based on the efficacy and improving the quality evaluation system of the medicinal.

Effect of Polysaccharides and n-Butanol Fractions of Atractylodis Rhizoma Stir-fried with Bran on Metabonomics in Rats with Spleen Deficiency / 中国实验方剂学杂志

ObjectiveTo explore the regulatory effect of polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran on the plasma metabolites of spleen-deficient rats， and then to elucidate their mechanisms of spleen-enhancing effects. MethodForty male SD rats were randomly divided into the blank group， model group， polysaccharide group （FD group， 0.075 6 g·mL-1·d-1）， n-butanol fractions group （FZ group， 0.012 1 g·mL-1·d-1）， with 10 rats in each group. Except the blank group， the other three groups used the compound factors of overwork， dietary disorders and intragastric administration of Sennae Folium decoction to replicate the rat model of spleen deficiency. After the end of modeling， the FD group and FZ group were given the corresponding medicinal solution by gavage for 7 d， meanwhile， the blank group and model group were given an equal volume of saline. The plasma samples from rats in the blank， model， FZ and FD groups were analyzed by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap-MS）， multivariate statistical methods were used to process the data and screen differential metabolites， and metabolic pathway enrichment analysis of the screened differential metabolites was performed using the Kyoto Encyclopedia of Genes and Genomes （KEGG)）database and MetaboAnalyst 5.0. ResultThe results of multivariate statistical analysis showed that there were significant differences in plasma metabolites between the model group and blank group， FZ group and model group， FD group and model group. There were 380 differential metabolites between the blank group and the model group， of which 78 and 57 were called back by polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran， respectively. Metabolic pathway enrichment results showed that the n-butanol fractions mainly affected glycine， serine and threonine metabolism， alanine， aspartate and glutamate metabolism， D-arginine and D-ornithine metabolism， which were summarized as amino acid metabolism， while the polysaccharides mainly affected glycine， serine and threonine metabolism， alanine， aspartate and glutamate metabolism， tricarboxylic acid cycle， biotin metabolism and thiamine metabolism. ConclusionBoth of polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran have significant regulating effects on the metabolic abnormalities in spleen-deficient rats， in which the n-butanol fractions is mainly involved in amino acid metabolism， and the polysaccharides are involved in energy metabolism and cofactor and vitamin metabolism in addition to regulating amino acid metabolism.

Rapid determination of microbial contamination of Bupleurum chinense DC. decoction slices by ATP bioluminescence technology combined with statistical analysis methods / 药学学报

This study focuses on the microbial quality control of the Chinese herbal decoction pieces. In view of the shortcomings of traditional culture methods such as slow detection speed and inability to detect unculturable microorganisms, a new method based on ATP bioluminescence technology combined with statistical analysis methods was established to rapidly predict and quantitatively detect the total aerobic microbial count (TAMC) and total yeast and mold count (TYMC) contaminated Bupleurum chinense DC. decoction pieces. Based on the optimized ATP bioluminesence detection system, accurate detection of pure bacterial solution of Escherichia coli, Bacillus subtilis and Staphylococcus aureus can be achieved, with detection limits of 47.86, 89.13 and 1 862.09 CFU·mL-1, respectively. The detection time was 6.5 h, and the detection cost was as low as 2 yuan/time. The upper and lower warning limits of TAMC were determined by the misjudgment rates of 10% and 20%, respectively. And the warning limit of TYMC was determined by the misjudgment rate of 20%. The proposed crossing method could quickly predict the amount of microbial contamination in Bupleurum chinense DC. decoction pieces. The constructed partial least squares regression (PLSR) model could accurately quantify the quantity of microbial contamination in Bupleurum chinense DC. decoction pieces. The optimal PLSR prediction model for TAMC had a correction coefficient (R2) of 0.826, a root mean square error of correction set (RMSEE) of 0.468 and a root mean square error of cross-validation set (RMSECV) of 0.465. The R2, RMSEE and RMSECV in the prediction model of TYMC were 0.778, 0.543 and 0.541, respectively. The aim of this study is to establish a kind of rapid detection method and prediction models for the microbial limit of traditional Chinese medicine and Chinese herbal decoction pieces, and to provide a more convenient and sensitive detection technology for the microbial quality process control of traditional Chinese medicine products.