Exploring the potential of omics technologies in medicinal plant research: a review in Colombia / Explorando el potencial de las tecnologías ómicas en la investigación de plantas medicinales: una revisión en Colombia

This review presents advances in the implementation of high - throughput se quencing and its application to the knowledge of medicinal plants. We conducted a bibliographic search of papers published in PubMed, Science Direct, Google Scholar, Scopus, and Web of Science databases and analyzed the obtained data using VOSviewer (versi on 1.6.19). Given that medicinal plants are a source of specialized metabolites with immense therapeutic values and important pharmacological properties, plant researchers around the world have turned their attention toward them and have begun to examine t hem widely. Recent advances in sequencing technologies have reduced cost and time demands and accelerated medicinal plant research. Such research leverages full genome sequencing, as well as RNA (ribonucleic acid) sequencing and the analysis of the transcr iptome, to identify molecular markers of species and functional genes that control key biological traits, as well as to understand the biosynthetic pathways of bioactive metabolites and regulatory mechanisms of environmental responses. As such, the omics ( e.g., transcriptomics, metabolomics, proteomics, and genomics, among others) have been widely applied within the study of medicinal plants, although their usage in Colombia is still few and, in some areas, scarce. (185)

El extracto de cloroformo (CE) y las fracciones obtenidas de las raíces de Aldama arenaria se evaluaron para determinar su actividad antiproliferativa in vitro contra 10 líneas ce lulares tumorales humanas [leucemia (K - 562), mama (MCF - 7), ovario que expresa un fenotipo resistente a múltiples fármacos (NCI/ADR - RES), melanoma (UACC - 62), pulmón (NCI - H460), próstata (PC - 3), colon (HT29), ovario (OVCAR - 3), glioma (U251) y riñón (786 - 0)]. CE presentó actividad antiproliferativa débil a moderada (log GI 50 medio 1.07), mientras que las fracciones 3 y 4, enriquecidas con diterpenos de tipo pimarane [ent - pimara - 8 (14), ácido 15 - dien - 19 - oico y ent - 8(14),15 - pimaradien - 3 ß - ol], presentaron activid ad moderada a potente para la mayoría de las líneas celulares, con un log GI 50 medio de 0.62 y 0.59, respectivamente. Los resultados mostraron una acción antiproliferativa in vitro prometedora de las muestras obtenidas de A. arenaria , con los mejores resul tados para NCI/ADR - RES, HT29 y OVCAR - 3, y valores de TGI que van desde 5.95 a 28.71 µg.mL - 1, demostrando que los compuestos de esta clase pueden ser prototipos potenciales para el descubrimiento de nuevos agentes terapéuticos

Sentimentos da mulher frente a gestação de alto risco / Sentimientos de la mujer frente al embarazo de alto riesgo / Women's feelings facing High-Risk pregnancy

Resumo Introdução: A gestação configura-se como um acontecimento único e memorável para a vida de uma mulher. A gravidez de alto risco é uma experiência estressante em razão dos riscos a que estão submetidos a mãe e o bebê e devido às mudanças que afetam negativamente o seu equilíbrio emocional. Objetivo: Identificar os sentimentos vivenciados pela gestante frente à gravidez de alto risco. Método: Descritivo e exploratório com abordagem qualitativa, com amostra por conveniência composta por mulheres com gestação de alto risco, selecionadas de acordo com a disponibilidade do serviço de internamento, até a saturação das entrevistas. A coleta dos dados foi realizada em um período de dois meses através de entrevistas guiadas por um roteiro. Os dados foram analisados por meio da técnica de análise de conteúdo segundo Minayo. Resultados: Fizeram parte 37 mulheres. Os resultados foram oeganizados nas categorias: Como se deu o diagnóstico de alto risco; Sentimentos ao descobrir que a gestação é/era de risco; Sentimentos em relação ao apoio familiar acerca da gestação de alto risco. Os sentimentos relatados pelas gestantes e puérperas que conviveram com a gravidez de alto risco, deixam evidentes os impactos que este evento traz não somente na saúde física sobretudo para a emocional, deixando as gestantes fragilizadas. Conclusão: Assim, o estudo nos permitiu perceber que os sentimentos vivenciados nesse processo podem interfir na vida dessas mulheres, e de forma negativa. Mas, que apesar dessa situação, estas expressam sentimentos ambíguos, pois mesmo com o risco gestacional, muitas mostram-se felizes pela dádiva de ser mãe.

Resumen Introducción: El embarazo se considera un evento único y memorable en la vida de una mujer. El embarazo de alto riesgo es una experiencia estresante debido a los riesgos a los que están expuestas tanto la madre como su bebé y a los cambios que afectan negativamente su equilibrio emocional. Objetivo: Identificar los sentimientos experimentados por las mujeres embarazadas frente a un embarazo de alto riesgo. Metodología: Descriptivo y exploratorio con enfoque cualitativo, con una muestra a conveniencia compuesta por mujeres con embarazos de alto riesgo, seleccionadas según la disponibilidad del servicio de hospitalización, hasta la saturación de las entrevistas. La recopilación de datos se llevó a cabo durante un período de dos meses a través de entrevistas guiadas. Los datos fueron analizados utilizando la técnica de análisis de contenido según Minayo. Resultados: Participaron 37 mujeres y los resultados se organizaron en las siguientes categorías: cómo se realizó el diagnóstico de alto riesgo; sentimientos al descubrir que el embarazo era de riesgo; sentimientos con respecto al apoyo familiar en relación con el embarazo de alto riesgo. Los sentimientos relatados por las mujeres embarazadas y posparto que vivieron un embarazo de alto riesgo evidencian los impactos que tiene este evento no solo en la salud física sino, especialmente, en el bienestar emocional, pues deja a las mujeres embarazadas en un estado de vulnerabilidad. Conclusión: El estudio nos permitió darnos cuenta de que los sentimientos experimentados en este proceso pueden interferir en la vida de estas mujeres de manera negativa. Sin embargo, a pesar de esta situación, muchas de ellas expresan sentimientos ambiguos, porque, incluso con el riesgo gestacional, están agradecidas por el regalo de la maternidad.

Abstract Introduction: Pregnancy is considered a unique and memorable event in a woman's life. High-risk pregnancy is a stressful experience due to the risks to which the mother and the baby are exposed, and due to the changes that negatively affect their emotional balance. Objective: To identify the feelings experienced by pregnant women facing high-risk pregnancy. Method: Descriptive and exploratory, employing a qualitative approach, the study featured a convenience sample of women with high-risk pregnancies, selected based on inpatient service availability, until interview saturation was achieved. Data collection was conducted over a two-month period through scripted interviews. Data analysis was performed utilizing Minayo's content analysis technique. Results: Thirty-seven women participated in the study. The results were categorized as follows: How the high-risk diagnosis was determined; Feelings upon discovering the pregnancy was high-risk; Feelings regarding family support regarding the high-risk pregnancy. The feelings reported by pregnant and postpartum women who experienced high-risk pregnancies clearly reveal the impacts this event has, not only on physical health, but especially on emotional well-being, leaving the pregnant women in a vulnerable state. Conclusion: The study allowed us to realize that the feelings experienced in this process can negatively interfere in the lives of these women. However, despite this situation, many of them express mixed feelings, because even with the gestational risk, they are grateful for the gift of motherhood.

Manejo de la vía aérea ante un caso de paro respiratorio en un escenario clínico simulado. Experiencia en una residencia de pediatría / Airway management during a respiratory arrest in a clinical simulation scenario. Experience at a pediatric residency program

Introducción. La insuficiencia respiratoria es la causa más común de paro cardíaco en pediatría; su reconocimiento y el manejo adecuado son cruciales. La simulación se utiliza para mejorar las habilidades médicas. El objetivo del trabajo fue determinar la proporción de residentes de pediatría que reconocieron un paro respiratorio (PR) pediátrico en un centro de simulación. Métodos. Se realizó un estudio observacional con 77 médicos residentes. Se utilizó un caso simulado de un paciente con dificultad respiratoria que progresa a PR. Resultados. De los 77 participantes, 48 reconocieron el paro respiratorio (62,3 %). El tiempo medio para reconocer el PR fue de 34,43 segundos. Conclusión. El 62,3 % de los participantes logró reconocer el paro respiratorio. Entre aquellos que lo identificaron, el tiempo promedio fue de 34,43 segundos. Se observaron graves deficiencias en algunas de las intervenciones esperadas.

Introduction. Respiratory failure is the most common cause of cardiac arrest in pediatrics. Recognizing and managing it adequately is critical. Simulation is used to improve medical skills. The objective of this study was to establish the proportion of pediatric residents who recognized a respiratory arrest in a child at a simulation center. Methods. This was an observational study in 77 residents. A simulation of a patient with respiratory distress that progressed to respiratory arrest was used. Results. Among the 77 participants, 48 recognized respiratory arrest (62.3%). The mean time to recognize respiratory arrest was 34.43 seconds. Conclusion. Respiratory arrest was recognized by 62.3% of participants. Among those who did so, the average time was 34.43 seconds. Severe failures were noted in some of the expected interventions.

Ligadura del trayecto fistuloso interesfinteriano. Nuestros resultados / Ligation of the intersphincteric fistulatract. Our results

Introducción: existen varias técnicas para el tratamiento quirúrgico de las fístulas anales, con variables resultados. La técnica de ligadura del trayecto fistuloso interesfinteriano (LIFT) consiste en la disección del espacio entre ambos esfínteres para localizar el trayecto fistuloso y proceder a su ligadura y sección. Objetivo: evaluar nuestros resultados con la técnica de LIFT para del tratamiento de las fístulas anales transesfinterianas. Diseño: retrospectivo, observacional de corte transversal. Materiales y métodos: Se incluyeron todos los pacientes con fístulas transesfinterianas tratados con LIFT desde enero de 2013 a diciembre 2020. El seguimiento postoperatorio se realizó hasta los 2 años. Resultados: se operaron 62 pacientes. El sexo predominante fue masculino. Hubo 47 pacientes con fístulas transesfinterianas bajas y 15 con fístulas transesfinterianas altas. En todos se identificó el trayecto fistuloso realizándose ligadura de ambos cabos del trayecto interesfinteriano y se procedió a un curetaje del trayecto a través del orificio externo. Cinco pacientes (8%) presentaron dehiscencia de piel a nivel de la incisión del espacio interesfinteriano, manejado en forma conservadora. Este grupo tuvo una cicatrización mas retardada de 4 semanas. Ocurrió recidiva en 22 (35,5%) pacientes. Conclusión: La técnica de LIFT parece una alternativa eficaz y segura para el tratamiento de las fístulas transesfinterianas bajas y altas ya que no altera la anatomía ni la continencia. (AU)

Introduction: there are various techniques for the surgical treatment of anal fistulas, with variable results. The ligation procedure of the intersphincteric fistulous tract (LIFT) consists of dissecting the space between both sphincters to locate the fistulous tract and proceed to its ligation and section. Objective: to evaluate our results with the LIFT procedure for the treatment of transsphincteric anal fistulas. Design: retrospective, cross-sectional observational study. Material and methods: all patients with transsphincteric fistulas treated with LIFT from January 2013 to December 2020 were included. Postoperative follow-up was carried out for up to 2 years. Results: sixty-two patients underwent surgery. The predominant sex was male. There were 47 patients with low transsphincteric fistulas and 15 with high transsphincteric fistulas. After identifying the fistulous tract in the intersphincteric groove, both ends were ligated and the tract was cut. Finally, curettage of the tract through the external orifice was performed. Five patients (8%) presented skin dehiscence at the level of the intersphincteric groove incision, managed conservatively. This group had a longer healing time of four weeks. Recurrence occurred in 22 (35.5%) patients. Conclusion: the LIFT procedure appears to be an effective and safe alternative for the treatment of low and high transsphincteric fistulas, since it does not alter the anatomy or continence. (AU)

Antioxidant activity, cytotoxicity, phenolic content, and phytochemical composition of Pithecellobium Diversifolium benth: a pilot study / Atividade antioxidante, citotóxica, conteúdo fenólico e composição fitoquímica de Pithecellobium Diversifolium benth: um estudo piloto / Actividad antioxidante, citotóxica, contenido fenólico y composición fitoquímica de Pithecellobium Diversifolium benth: un estudio piloto

Species of Pithecellobium (Fabaceae) are used in traditional medicine to treat diabetes, cough, bronchitis, and inflammation. This study aims to evaluate the content and determine the antioxidant activity, phenolic compounds content, and cytotoxicity of the extract and the fractions of Pithecellobium diversifolium. This is unprecedented research with an exotic species from the Caatinga, northeastern Brazil, using High-performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (HPLC-ESI-MS). The MeOH fractions of leaves and stem barks showed a high content of flavonoids (198.1 ± 106.50 and 542.7 ± 2.52 mg EqQ/g). The CH2Cl2 fraction of peels showed a high content of total phenolic compounds (516.7 ± 3.00 mg EqAG /g). The DPPH test showed that the CH2Cl2 fraction (leaves) held an EC50 of 0.08 ± 0.02, a higher value than that observed for the standards used in the test­Butylated hydroxyanisole (BHA), Butylated hydroxytoluene (BHT), and ascorbic acid. The AcOEt and MeOH fractions of peels presented moderate cytotoxicity with values below 500 µg/mL. The MeOH fraction of leaves showed seven major compounds: myricetin, quercetin, quercetin-arabinofuranoside, apigenin-triglycosides, and apigenin-diglucoside, being the last three unpublished in studies involving the genus. The tests conducted in this study show the potential of P. diversifolium as a promising source of biomolecules with therapeutic applicability.

Espécies de Pithecellobium (Fabaceae) são usadas na medicina tradicional para tratar diabetes, tosse, bronquite e inflamação. Este estudo teve como objetivo avaliar o teor e determinar a atividade antioxidante, o teor de compostos fenólicos e a citotoxicidade do extrato e das frações de Pithecellobium diversifolium, uma pesquisa inédita com uma espécie exótica da Caatinga do Nordeste do Brasil, utilizando a instrumentação Clae-IES. As frações MeOH das folhas e cascas do caule apresentaram alto teor de flavonoides (198,1 ± 106,50 e 542,7 ± 2,52 mg EqQ/g). A fração CH2Cl2 das cascas apresentou um elevado teor de compostos fenólicos totais (516,7 ± 3,00 mg EqAG/g). O teste DPPH mostrou que a fração CH2Cl2 (folhas) apresentou um EC50 de 0,08 ± 0,02, valor superior ao observado para os padrões utilizados no teste ­ Butil hidroxianisol (BHA), Butil hidroxitolueno (BHT) e ácido ascórbico. As frações AcOEt e MeOH das cascas apresentaram citotoxicidade moderada com valores inferiores a 500 µg/mL. A fração MeOH das folhas apresentou sete compostos majoritários: miricetina, quercetina, quercetina-arabinofuranosídeo, apigenina-triglicosídeos e apigenina-diglucosídeo, sendo os três últimos inéditos em estudos envolvendo o gênero. Os testes realizados demonstram o potencial de P. diversifolium, uma promissora fonte de biomoléculas com aplicabilidade terapêutica.

Las especies de Pithecellobium (Fabaceae) se utilizan en la medicina tradicional para tratar diabetes, tos, bronquitis e inflamación. Este estudio tuvo como objetivo evaluar el contenido y determinar la actividad antioxidante, el contenido de compuestos fenólicos y la citotoxicidad del extracto y de las fracciones de Pithecellobium diversifolium, un estudio inédito con una especie exótica de la Caatinga de la región Nordeste de Brasil, que utilizó la instrumentación HPLC-ESI. Las fracciones MeOH de hojas y cortezas de tallo mostraron un alto contenido de flavonoides (198,1 ± 106,50 y 542,7 ± 2,52 mg EqQ/g). La fracción CH2Cl2 de las cortezas presentó un alto contenido de compuestos fenólicos totales (516,7 ± 3,00 mg EqAG/g). El ensayo DPPH mostró que la fracción CH2Cl2 (hojas) tenía EC50 de 0,08 ± 0,02, valor superior a lo observado para los estándares utilizados en el ensayo ­Butilhidroxianisol (BHA), butilhidroxitolueno (BHT) y ácido ascórbico. Las fracciones AcOEt y MeOH de las cortezas presentaron una citotoxicidad moderada con valores inferiores a 500 µ g/mL. La fracción MeOH de las hojas contiene siete compuestos principales: miricetina, quercetina, quercetina-arabinofuranosido, apigenina-triglucósidos y apigenina-diglucósido, de los cuales los tres últimos son inéditos en estudios sobre el género. Las pruebas realizadas demuestran el potencial de P. diversifolium, una fuente prometedora de biomoléculas con aplicabilidad terapéutica.

A rapid and sensitive High-Performance Liquid Chromatography method with fluorescence detection for quantification of melatonin in small volume rat plasma samples: application to a preclinical study to determine the oral pharmacokinetics of melatonin under gestational conditions

Abstract A novel, simple and sensitive high-performance liquid chromatography with fluorescence detection method was developed and validated for the characterization of the preclinical pharmacokinetics of melatonin under pregnant conditions. Plasma samples (25 µL) were treated with 30 µL of ethanol absolute (containing the internal standard, IS). After a centrifugation process, aliquots of supernant (5 µL) were injected into the chromatographic system. Compounds were eluted on a Xbridge C18 (150 mm x 4.6 mm i.d., 5 µm particle size) maintained at 30°C. The mobile phase consisted in a mixture of aqueous solution of 0.4% phosphoric acid and acetonitrile (70:30 v/v). The wavelengths were set at 305 nm (excitation) and 408 nm (emission) and the total analysis time was 8 min/sample. All validation tests were obtained with accuracy and precision, according to FDA guidelines, over the concentration range of 0.005-20 µg/mL. Pharmacokinetic study showed that melatonin systemic exposure increased from day 14, with a significant difference at 19 days of gestation compared to the control group. Our findings suggest a decreased metabolism of melatonin as result of temporary physiological changes that occur throughout pregnancy. However, other maternal physiological changes cannot be ruled out.

A percepção do estudante de medicina sobre a simulação realística em pediatria / The perception of the medical student about realistic simulation in pediatrics

Resumo Introdução: O uso de simulação realística em emergências pediátricas é particularmente valioso, pois permite o treinamento de habilidades técnicas, atitudinais e cognitivas, ajudando a garantir a segurança do paciente. Objetivo: Este estudo tem como objetivo descrever a percepção do aluno sobre o uso da Simulação Realista de Alta Fidelidade nos módulos de emergência pediátrica durante o internato de medicina. Métodos: Estudo observacional, descritivo, com abordagem quantitativa e qualitativa. Um questionário semiestruturado foi aplicado aos estudantes do sexto ano de medicina ao final dos módulos de internato pediátrico, com oito semanas de duração, de agosto a dezembro de 2020. Todos participaram de dois tipos de atividades sobre 14 temas: simulação de alta fidelidade (SRAF) e discussão estruturada de casos clínicos (DCC). Resultados: Dos 33 participantes, 29 responderam ao questionário. A média de idade foi de 24 ± 1,8 anos, sendo 58,6% do sexo feminino. Todos concordaram que a experiência com SRAF contribuiu para um desempenho mais seguro em emergências pediátricas, considerado ótimo por 76% e bom para os demais. A maioria achava que a associação de SRAF e DCC era o método ideal (96%). A análise de conteúdo das respostas sobre a SRAF destacou unidades temáticas em cinco categorias: aprendizagem significativa, contribuição para a formação profissional, habilidades, atitude/comportamento e qualidade da atividade. Conclusões: A reação dos estudantes ao uso da SRAF em emergências pediátricas foi muito positiva, e sua associação com a DCC foi considerada o método de ensino ideal. Conhecer as reações dos alunos ajuda os professores a planejarem suas atividades para melhorar o método de ensino-aprendizagem.

Abstract Introduction: The use of realistic simulation in pediatric emergencies is particularly valuable, as it allows the training of technical, attitudinal, and cognitive skills, helping to ensure patient safety. Objective: This study aims to describe the student's perception of using the High-Fidelity Realistic Simulation in the pediatric emergency modules during the internship. Methods: Observational, descriptive study with a quantitative and qualitative approach. A semi-structured questionnaire was applied to sixth-year medical students at the end of the pediatric internship modules, which lasted eight weeks, from August to December 2020. All of them participated in two types of activities on 14 topics: high-fidelity simulation (HFS) and structured discussion of clinical cases (SDCC). Results: Of the 33 participants, 29 answered the questionnaire. The mean age was 24 ± 1.8 years, and 58.6% were female. All agreed that the experience with HFS contributed to safer performance in pediatric emergencies, considered optimal by 76% and good for the remainder. Most thought the association of HFS and SDCC was the ideal method (96%). The content analysis of the responses on HFS highlighted thematic units in five categories: significant learning, contribution to professional training, skills, attitude/behavior, and quality of the activity. Conclusions: Students' reaction to using HFS in pediatric emergencies was very positive, and its association with SDCC was considered the ideal teaching method. Knowing the students' reactions helps teachers plan their activities to improve the teaching-learning method.

Práticas corporais e currículo: legitimação a partir da análise documental / Corporal practices and the curriculum: legitimization through document analysis / Prácticas corporales y currículo: legitimación basada en análisis documental

O estudo objetivou analisar o modo como os atos de currículo da Educação Física legitimam as práticas corporais no âmbito de 3 escolas de Ensino Médio de Simão Dias (SE) e as identidades projetadas. Para tanto, os respectivos projetos político-pedagógicos e planos de ensino do componente foram submetidos à análise de conteúdo. Notamos que as limitações dos espaços físicos condicionam a vivência de práticas corporais legitimadas na escola. Percebemos forte influência dos Parâmetros Curriculares Nacionais do Ensino Fundamental na organização do trabalho pedagógico e a vivência exaustiva dos esportes euro-estadunidenses. Fatores que parecem contribuir para a legitimação de determinadas práticas corporais em detrimento de outras tantas. O que também pode impactar nas identidades culturais e a forma com que os estudantes se relacionam com as diferentes manifestações.

The study aimed to analyze the way in which Physical Education curriculum acts legitimize bodily practices within 3 high schools in Simão Dias (SE) and the projected identities. To this end, the respective political-pedagogical projects and teaching plans for the component were subjected to content analysis. We note that the limitations of physical spaces condition the experience of legitimized bodily practices at school. We noticed a strong influence of the National Curricular Parameters for Elementary Education in the organization of pedagogical work and the exhaustive experience of Euro-American sports. Factors that seem to contribute to the legitimization of certain bodily practices to the detriment of many others. This can also impact cultural identities and the way students relate to different manifestations.

El estudio tuvo como objetivo analizar la forma en que los actos curriculares de Educación Física legitiman las prácticas corporales en 3 escuelas secundarias de Simão Dias (SE) y las identidades proyectadas. Para ello, se sometieron a análisis de contenido los respectivos proyectos político- pedagógicos y planes docentes del componente. Observamos que las limitaciones de los espacios físicos condicionan la experiencia de prácticas corporales legitimadas en la escuela. Notamos una fuerte influencia de los Parámetros Curriculares Nacionales para la Educación Primaria en la organización del trabajo pedagógico y la experiencia exhaustiva del deporte euroamericano. Factores que parecen contribuir a la legitimación de determinadas prácticas corporales en detrimento de muchas otras. Esto también puede afectar las identidades culturales y la forma en que los estudiantes se relacionan con las diferentes manifestaciones.

Acute physiological responses to "recovery intermittent hypoxia" in hiit / Respuestas agudas a la "hipoxia intermitente de recuperación" en el hiit / Respostas fisiológicas agudas à "hipóxia intermitente de recuperação" no hiit

ABSTRACT Introduction: Traditional intermittent hypoxia training improves sport performance after short periods of exposure, but acute exposure to intermittent hypoxia leads to decreased training intensity and technical quality. The solution to overcome these negative effects may be to perform efforts in normoxia and the intervals between efforts in hypoxia, maintaining the quality of training and the benefits of hypoxia. Objective: This study aimed to evaluate the acute physiological responses to hypoxia exposure during recovery between high intensity efforts. Materials and methods: Randomized, one-blind, placebo-controlled study. Sixteen men performed a graded exercise test to determine their maximal intensity and two sessions of high-intensity interval training. The training intervals could be in hypoxia (HRT), FIO2: 0.136 or normoxia (NRT), FIO2: 0.209. During the two-minute interval between the ten one-minute efforts, peripheral oxygen saturation (SpO2), heart rate (HR), blood lactate ([La]), blood glucose ([Glu]) were constantly measured. Results: There were differences in HR (TRN = 120 ± 14 bpm; TRH = 129 ± 13 bpm, p < 0.01) and SpO2 (TRN = 96.9 ± 1.0%; TRH = 86.2 ± 3.5%, p < 0.01). No differences in [La] and [Glu] TRN (4.4 ± 1.7 mmol.l-1; 3.9 ± 0.5 mmol.l-1) and TRH (5.2 ± 2.0 mmol.l-1; 4.0 ± 0.8 mmol.l-1, p = 0.17). Conclusion: The possibility of including hypoxia only in the recovery intervals as an additional stimulus to the training, without decreasing the quality of the training, was evidenced. Level of Evidence II; Randomized Clinical Trial of Minor Quality.

RESUMEN Introducción: El entrenamiento tradicional en hipoxia intermitente mejora el rendimiento deportivo tras cortos periodos de exposición, sin embargo, la exposición aguda a la hipoxia intermitente conduce a una disminución de la intensidad del entrenamiento y de la calidad técnica. La solución para superar estos efectos negativos puede ser realizar los esfuerzos en normoxia y los intervalos entre esfuerzos en hipoxia, manteniendo la calidad del entrenamiento y los beneficios de la hipoxia. Objetivo: Este estudio pretendía evaluar las respuestas fisiológicas agudas a la exposición a la hipoxia durante la recuperación entre esfuerzos de alta intensidad. Materiales y métodos: Estudio aleatorizado, a ciegas y controlado con placebo. Dieciséis hombres realizaron una prueba de ejercicio graduado para determinar su intensidad máxima y dos sesiones de entrenamiento por intervalos de alta intensidad. Los intervalos de entrenamiento podían ser en hipoxia (HRT), FIO2: 0,136 o normoxia (NRT), FIO2: 0,209. Durante el intervalo de dos minutos entre los diez esfuerzos de un minuto, se midieron constantemente la saturación periférica de oxígeno (SpO2), la frecuencia cardiaca (FC), el lactato en sangre ([La]) y la glucemia ([Glu]). Resultados: Hubo diferencias en la FC (TRN = 120 ± 14 lpm; TRH = 129 ± 13 lpm, p < 0,01) y la SpO2 (TRN = 96,9 ± 1,0%; TRH = 86,2 ± 3,5%, p < 0,01). No hubo diferencias en [La] y [Glu] TRN (4,4 ± 1,7 mmol.l-1; 3,9 ± 0,5 mmol.l-1) y TRH (5,2 ± 2,0 mmol.l-1; 4,0 ± 0,8 mmol.l-1, p = 0,17). Conclusión: Se evidenció la posibilidad de incluir hipoxia sólo en los intervalos de recuperación como estímulo adicional al entrenamiento sin disminuir la calidad del mismo. Nivel de Evidencia II; Ensayo Clínico Aleatorizado de Baja Calidad.

RESUMO Introdução: O treinamento de hipóxia intermitente tradicional melhora o desempenho esportivo após curtos períodos de exposição, porém a exposição aguda à hipóxia intermitente leva à diminuição da intensidade do treinamento e da qualidade técnica. A solução para superar esses efeitos negativos pode ser realizar esforços em normóxia e os intervalos entre os esforços em hipóxia, mantendo a qualidade do treinamento e os benefícios da hipóxia. Objetivo: Este estudo teve como objetivo avaliar as respostas fisiológicas agudas à exposição de hipóxia durante a recuperação entre esforços de alta intensidade. Materiais e métodos: Estudo aleatório e one-blinded, com efeito placebo controlado. Dezesseis homens realizaram um teste de exercício graduado para determinar sua intensidade máxima e duas sessões de treinamento intervalado de alta intensidade. Os intervalos de treinamento podem ser em hipóxia (TRH), FIO2: 0,136 ou normóxia (TRN), FIO2: 0,209. Durante os dois minutos de intervalo entre os dez esforços de um minuto, foram medidos constantemente a saturação periférica de oxigênio (SpO2), frequência cardíaca (FC), lactato sanguíneo ([La]), glicemia ([Glu]). Resultados: Houve diferenças na FC (TRN = 120 ± 14 bpm; TRH = 129 ± 13 bpm, p <0,01) e SpO2 (TRN = 96,9 ± 1,0%; TRH = 86,2 ± 3,5%, p <0,01). Sem diferenças em [La] e [Glu] TRN (4,4 ± 1,7 mmol.l-1; 3,9 ± 0,5 mmol.l-1) e TRH (5,2 ± 2,0 mmol.l-1; 4,0 ± 0,8 mmol.l-1, p = 0,17). Conclusão: Evidenciou-se a possibilidade de incluir a hipóxia apenas nos intervalos de recuperação como um estímulo adicional ao treinamento, sem diminuir a qualidade do treinamento. Nível de Evidência II; Estudo Clínico Randomizado de Menor Qualidade.

Macular dystrophies associated with Stargardt-like phenotypes / Distrofias maculares associadas a fenótipos Stargardt-like

ABSTRACT Purpose: Stargardt-like phenotype has been described as associated with pathogenic variants besides the ABCA4 gene. This study aimed to describe four cases with retinal appearance of Stargardt disease phenotypes and unexpected molecular findings. Methods: This report reviewed medical records of four patients with macular dystrophy and clinical features of Stargardt disease. Ophthalmic examination, fundus imaging, and next-generation sequencing were performed to evaluate pathogenic variants related to the phenotypes. Results: Patients presented macular atrophy and pigmentary changes suggesting Stargardt disease. The phenotypes of the two patients were associated with autosomal dominant inheritance pattern genes (RIMS1 and CRX) and in the other two patients were associated with recessive dominant inheritance pattern genes (CRB1 and RDH12) with variants predicted to be pathogenic. Conclusion: Macular dystrophies may have phenotypic similarities to Stargardt-like phenotype associated with other genes besides the classic ones.

RESUMO Objetivo: Fenótipos Stargardt-like já foram asso-ciados a variantes patogênicas no gene ABCA4. O propósito desse estudo é descrever quatro pacientes com achados retinianos semelhantes a doença de Stargardt com resultados moleculares diferentes do esperado. Métodos: Esse relato fez a revisão de prontuários médicos de quatro pacientes com distrofia macular e achados clínicos sugestivos de doença de Stargardt. Foram realizados avaliação oftalmológica, exames de imagens e testes usando next generation sequencing para avaliar variantes patogênicas associadas aos fenótipos dos pacientes. Resultados: Os pacientes apresentavam atrofia macular e alterações pigmentares sugerindo achados clínicos de doença de Stargardt. Dois pacientes foram associados a genes com herança autossômica dominante (RIMS1 e CRX) e dois pacientes foram associados a genes com herança autossômica recessiva (CRB1 e RDH12) com variantes preditoras de serem patogênicas. Conclusão: Distrofias maculares podem ter similaridades fenotípicas com fenótipo de Stargardt-like associados a outros genes além dos classicamente já descritos.

Variabilidade de preços de aquisição de medicamentos do grupo 1B do Componente Especializado da Assistência Farmacêutica / Variability in Drug Procurement within Group 1B of the Pharmaceutical Specialized Scheme in Brazil

Resumo No Sistema Único de Saúde os medicamentos do grupo 1 do Componente Especializado da Assistência Farmacêutica (CEAF) são financiados pela União e adquiridos de forma centralizada (grupo 1A) ou por cada Unidade Federativa (UF) (grupo 1B). Diferentemente de outros países onde se negocia um preço fixo a ser praticado no sistema público, no Brasil as aquisições são realizadas por licitação, o que pode levar a diferentes preços. Para permitir a comparação de preços, foi pactuada a obrigatoriedade de registro das aquisições públicas no Banco de Preços em Saúde (BPS). O estudo teve como objetivo analisar a variabilidade dos preços de medicamentos do grupo 1B adquiridos pelas UF do Brasil em 2021. Foram obtidas as aquisições de medicamentos do grupo 1B realizadas pelas Secretarias de Estado das 27 UF por consulta ao BPS excluindo-se os medicamentos sem preço de ressarcimento estabelecido em dezembro/2021. Foi obtido do Sistema de Informações Ambulatoriais o ressarcimento para cada UF. Verificou-se grande variabilidade dos preços de aquisição para cada medicamento entre as UF e dentro da mesma UF. O estudo demonstrou potencial iniquidade de acesso ao CEAF, privilegiando com menores preços UF mais favorecidas (maior população e riqueza).

Abstract In the Brazilian Health System (SUS), drugs covered by the Specialized Pharmaceutical Scheme (CEAF) receive federal funding and can be procured either centrally (Group 1A) or by individual states (Federal Units - UF) (Group 1B). Unlike other countries where national procurement prices are negotiated centrally by the government, public procurement in Brazil follows a public auction procedure, potentially resulting in varying purchase prices. To facilitate price comparisons, it is a legal requirement to register public acquisitions in the Health Prices Registry (BPS). This study aimed to assess the variability in the procurement prices for Group 1B drugs across the 27 Brazilian states during 2021. Data on the acquisitions of Group 1B drugs by the 27 Health Secretariats were obtained from the BPS. Drugs with no reported reimbursement prices as of December 2021 were excluded from the analysis. The total reimbursement amount for each state was sourced from the SUS Ambulatory Information System. The findings revealed significant variability in drug procurement prices both across and within states. The study underscored a potential disparity in CEAF access, favoring wealthier states (those with larger populations and higher economic status) by securing lower drug prices.

A contribuição da Ergonomia para a segurança no trabalho / Ergonomics contribution to occupational safety

Resumo Introdução: processos de alto risco com elevadas taxas de acidentes desafiam a segurança. Por outro lado, sistemas ultrasseguros conquistaram ótimos indicadores. Em ambos, a prevenção parece ter chegado a um limite - em um deles, porque parece impotente para gerar prevenção; no outro, porque foi tão bem-sucedida que parece impossível avançar. Objetivo: evidenciar a contribuição da Ergonomia em prol da segurança, nas situações descritas, suas possibilidades ainda por explorar, entre elas a Ergonomia de concepção na integração homem-máquina (sistemas informatizados). Método: análise comparativa dos achados oriundos de estudos ergonômicos em sistemas de produção com altas taxas de acidentes e sistemas ultrasseguros. Discussão: a análise da atividade dos motofretistas mostrou que existem alternativas de ação ainda não exploradas entre as relações de trabalho desfavoráveis e a percepção de inevitabilidade dos acidentes. Nos sistemas ultrasseguros, o aparente limite pode ser superado com os avanços recentes na análise da ação e cognição situadas e na construção de espaços de debate que permitam o retorno da experiência de campo. Em sistemas informatizados, as práticas de projeto colaborativo, que se valem da experiência dos trabalhadores para alimentar as dinâmicas de aprendizagem e a confiabilidade técnica, são possibilidades ainda pouco praticadas na Engenharia de Segurança.

Abstract Introduction: while high-risk processes with high accident rates challenge safety, High Reliability Organization (HRO) achieve excellent indicators. In both cases, prevention seems to have reached a limit. In the former, because it seems powerless to generate prevention; in the latter, because it has been so successful that it seems impossible to reach greater levels. Objective: to highlight the contribution of Ergonomics to safety in these situations, pointing out unexplored possibilities such as design Ergonomics in man-machine integration (computerized systems). Method: comparative analysis of findings from ergonomic studies on production systems with high accident rates and HRO. Discussion: analysis of the motorcycle freight drivers' activity revealed alternatives yet to be explored between unfavorable work relations and the perceived inevitability of accidents. The apparent limit of HRO can be overcome with recent advances in the analysis of situated action and cognition and by building debate spaces based on field experience. Collaborative design practices, which draw on worker experience to feed learning dynamics and technical reliability, remains a poorly explored possibility in Safety Engineering when it comes to computerized systems.

High-intensity interval training in people with spinal cord injury: a systematic review / Entrenamiento por intervalos de alta intensidad en personas con lesiones medulares: una revisión sistemática / Treinamento intervalado de alta intensidade em pessoas com lesão da medula espinhal: revisão sistemática

ABSTRACT Objective: Analyze the effects of high-intensity interval training (HIIT) on cardiometabolic parameters, and cardiorespiratory fitness to compile the most used HIIT training types in adults with spinal cord injury (SCI). Methods: This is a systematic review of searches performed in the electronic databases PubMed / Medline, Science Direct, and Google Scholar. Studies included I) needed to apply HIIT training II) adults with SCI to analyze III) cardiometabolic aspects and cardiorespiratory fitness. Two independent reviewers selected the articles for inclusion, extracted their data, and assessed their methodological quality. Results: 654 studies were found. Thus, 12 studies, 11 pre- and post-intervention, and one control group (CG) with 106 participants were analyzed. Pre- and post-HIITT intervention results revealed significant improvement in cardiorespiratory fitness and cardiometabolic aspects (VO2peak, LDH, HDL, insulin resistance). In addition, GC results revealed significant improvement in cardiorespiratory fitness observed in the intervention group (HIIT) compared to the moderate-low intensity (GC) group. Seven studies used the arm ergometer as the primary exercise modality. Two studies described functional electrical stimulation (FES) performed with the arm ergometer plus electrical stimulation in the lower limbs. None reported heart rate dynamics during the study period. Conclusion: High-intensity interval training improves physical fitness and cardiometabolic health in adults with SCI. Evidence level II; Systematic Review of level II studies.

RESUMEN Objetivo: Analizar los efectos del entrenamiento interválico de alta intensidad (HIIT) sobre los parámetros cardiometabólicos, fitness cardiorrespiratorio y recopilar los tipos de HIIT más utilizados en el entrenamiento en adultos con lesión medular (LME). Métodos: Se trata de una revisión sistemática, para lo cual se realizaron búsquedas en bases de datos electrónicas PubMed/Medline, Science Direct y Google Scholar. Se incluyeron estudios que I) necesitaban aplicar entrenamiento HIIT en II) adultos con SCI y analizar III) aspectos cardiometabólicos y aptitud cardiorrespiratoria. Dos revisores independientes seleccionaron los artículos para su inclusión, extrajeron sus datos y evaluaron su calidad metodológica. Resultados: De los 654 estudios encontrados, se analizaron 12 estudios, 11 pre y post intervención y 1 grupo control (GC) con un total de 106 participantes. Los resultados previos y posteriores a la intervención HIIT revelaron una mejora significativa en la aptitud cardiorrespiratoria y los aspectos cardiometabólicos (VO2pico, LDH, HDL, resistencia a la insulina). Los resultados de GC revelaron una mejora significativa en la aptitud cardiorrespiratoria observada del grupo de intervención (HIIT) en comparación con el grupo de intensidad moderada-baja (GC). Siete estudios utilizaron el ergómetro de brazo como la modalidad principal de ejercicio. Dos estudios describieron la estimulación eléctrica funcional (EEF) realizada con el ergómetro de brazo más la estimulación eléctrica en los miembros inferiores. Ninguno informó la dinámica de la frecuencia cardíaca durante el período de estudio. Conclusiones: El entrenamiento intervalos de alta intensidad mejora la condición física y la salud cardiometabólica en adultos con LME. Evidencia de nivel II; Revisión sistemática de estudios de nivel II.

RESUMO Objetivo: Analisar os efeitos do treinamento intervalado de alta intensidade (HIIT) nos parâmetros cardiometabólicos, aptidão cardiorrespiratória e compilar os tipos de HIIT mais utilizados no treinamento em adultos com lesão da medula espinhal (LME). Métodos: Trata-se de revisão sistemática, para a qual foram realizadas pesquisas nas bases de dados eletrônicas PubMed / Medline, Science Direct e Google Scholar. Foram incluídos estudos em que I) o treinamento HIIT era aplicado em II) adultos com LME e analisaram III) os aspectos cardiometabólicos e aptidão cardiorrespiratória. Dois revisores independentes selecionaram os artigos para a inclusão, extraindo seus dados e avaliarando a sua qualidade metodológica. Resultados: 654 estudos foram encontrados. Desses, 12 estudos, 11 pré e pós intervenção e 1 grupo controle (GC) com um total de 106 participantes foram analisados. Resultados pré e pós intervenção de HIIT revelaram significante melhora na aptidão cardiorrespiratória e aspectos cardiometabólicos (VO2pico, LDH, HDL, resistência à insulina). Resultados do GC revelaram uma significativa melhoria na aptidão cardiorrespiratória observada no grupo de intervenção (HIIT) em relação ao grupo de intensidade moderada-baixa (GC). Sete estudos usaram o ergômetro de braço como modalidade de exercício primária. Dois estudos descreveram a estimulação elétrica funcional (EEF) realizada com o ergômetro de braço adicionando estimulação elétrica nos membros inferiores. Nenhum relatou a dinâmica da frequência cardíaca durante o período do estudo. Conclusão: O treinamento intervalado de alta intensidade melhora a aptidão física e a saúde cardiometabólica em adultos com LME. Nível de evidência II; Revisão sistemática de Estudos de Nível II.

Efeitos da suplementação do cálcio sobre marcadores da pré-eclâmpsia: ensaio clínico randomizado / Efectos de los suplementos de calcio en marcadores de preeclampsia: ensayo clínico aleatorizado / Effects of calcium supplementation on markers of preeclampsia: randomized clinical trial

Resumo Objetivo Analisar os efeitos da suplementação de cálcio nos marcadores da pré-eclâmpsia ao longo do tempo, comparando o uso de cálcio em alta e baixa dosagem em mulheres grávidas com hipertensão. Métodos Trata-se de ensaio clínico randomizado com três grupos paralelos, placebo controlado, realizado no ambulatório de referência para o pré-natal de alto risco na Região Sul do Brasil, com análise de intenção de tratar e seguimento após quatro e oito semanas. A intervenção consistiu na ingestão de cálcio 500mg/dia, cálcio 1500mg/dia e placebo. Os dados foram analisados segundo um modelo generalizado de estimação de equações mistas adotando α 0,05. Resultados O efeito do cálcio em baixa e alta dosagem na evolução ao longo do tempo foi mantido entre os grupos, mesmo após o ajuste para os fatores de confusão. Houve diferença significativa nos parâmetros analisados na interação tempo e grupo (p <0,000) e diminuição nas médias de 12,3mmHg na PAS, 9,2 mmHg na PAD, 3,2 mg/dl creatinina e 7,2 mg/dl proteinúria para o grupo cálcio 500mg/dia. Os resultados foram semelhantes para o grupo com suplementação máxima. Conclusão O cálcio melhorou o prognóstico vascular em mulheres grávidas com hipertensão ao reduzir os níveis pressóricos e os marcadores da pré-eclâmpsia.

Resumen Objetivo Analizar los efectos de los suplementos de calcio en los marcadores de preeclampsia a lo largo del tiempo, comparando el uso de calcio en dosis altas y bajas en mujeres embarazadas con hipertensión. Métodos Se trata de un ensayo clínico aleatorizado con tres grupos paralelos, placebo controlado realizado en consultorios externos de referencia en el control prenatal de alto riesgo en la Región Sur de Brasil, con análisis de intención de tratar y seguimiento luego de cuatro y ocho semanas. La intervención consistió en la ingesta de calcio 500 mg/día, calcio 1500 mg/día y placebo. Los datos se analizaron de acuerdo con un modelo generalizado de estimación de ecuaciones mixtas adoptando α 0,05. Resultados El efecto del calcio en dosis bajas y altas en la evolución a lo largo del tiempo se mantuvo entre los grupos, inclusive después de los ajustes por los factores de confusión. Hubo diferencia significativa en los parámetros analizados en la interacción tiempo y grupo (p <0,000) y reducción de los promedios de 12,3 mmHg en la PAS, 9,2 mmHg en la PAD, 3,2 mg/dl creatinina y 7,2 mg/dl proteinuria en el grupo calcio 500 mg/día. Los resultados fueron parecidos en el grupo con suplemento en dosis máxima. Conclusión El calcio mejoró el pronóstico vascular en mujeres embarazadas con hipertensión al reducir los niveles de presión y los marcadores de preeclampsia. Registro Brasileiro de Ensaios Clínicos: RBR-9ngb95

Abstract Objective To analyze the effects of calcium supplementation on markers of preeclampsia over time by comparing the use of high- and low-dose calcium in hypertensive pregnant women. Methods This is a randomized clinical trial, placebo controlled, with three parallel groups carried out at the reference outpatient clinic for high-risk prenatal care in the South Region of Brazil, with intention-to-treat analysis and follow-up after four and eight weeks. The intervention consisted of ingesting calcium 500mg/day, calcium 1500mg/day and placebo. Data were analyzed according to a generalized mixed equation estimation model adopting α 0.05. Results The effect of low- and high-dose calcium on evolution over time was maintained between groups, even after adjustment for confounding factors. There was a significant difference in the parameters analyzed in the time and group interaction (p <0.000) and a decrease in the means of 12.3 mmHg in SBP, 9.2 mmHg in DBP, 3.2 mg/dl creatinine and 7.2 mg/dl proteinuria for the 500mg calcium/day group. The results were similar for the maximal supplementation group. Conclusion Calcium improved vascular prognosis in hypertensive pregnant women by reducing blood pressure levels and markers of preeclampsia. Brazilian Registry of Clinical Trials: RBR-9ngb95

Prevalence of high-risk human papillomavirus genotypes among apparently healthy women with normal and abnormal cervical cytology in Kaduna State, Nigeria

Background: About 99.7% of cervical dysplasia and cancer cases are caused by persistent genital high-risk human papillomavirus (hrHPV) infection. Most HPV infections are subclinical and self-limiting but may persists in about 5 to 10% of infected women, resulting in pre-cancerous lesions that can progress to invasive cancer years later. This study is aimed at detecting hrHPV among apparently healthy women of reproductive age in Kaduna State, thus providing more information for effective control of HPV and cervical cancer in Nigeria. Methodology: Cervical smears were taken from 515 randomly selected apparently healthy women across selected secondary and tertiary facilities from 3 Local Government Areas (LGAs) in each Senatorial Zone of Kaduna State, Nigeria. Liquid-based cytology (LBC) technique was used to collect cervical smears and prepare smears for cytology study, while the remaining samples were stored at -80oC for molecular studies. HPV DNA were extracted from the samples and amplified by convectional PCR using specific hrHPV (HPV 16,18,31 and 45) primer sets and a broad spectrum MY09/11 and GP5+/6+ primers for a wider range of HPV genotypes. Data were analysed using the Statistical Package for Social Sciences (SPSS) version 23.0 and relationship between prevalence of hrHPV and socio-demographic factors such as age and marital status were determined using Chisquare or Fisher Exact test with p<0.05 considered statistically significant. Results: The prevalence of total HPV and hrHPV infections in the study population was 11.8% (61/515) and 9.3% (48/515) respectively. A total of 100 HPV genotypes were detected by PCR in the 61 positive smears, with 66 hrHPV types from 48 women, and 34 other HPV types from 13 women. The frequency of hrHPV genotypes detected was HPV 31 (5.8%, n=30), HPV 45 (4.1%, n=21), HPV 16 (1.7%, n=9), and HPV 18 (1.2%, n=6), with other HPV genotypes (6.6%, n=34). The frequency of cervical dysplasia was 6.4% (33/515), which was significantly associated with all HPV genotypes except HPV 16. Single HPV infection was seen in 31 (51.8%) women while multiple infections were seen in 30 (49.2%), with double infection in 21 (34.4%) and triple infections in 9 (14.7%). Conclusion: The prevalence of hrHPV infection was high among women in Kaduna State, Nigeria. DNA-based screening for hrHPV genotypes and production of new vaccine that will protect against the predominant hrHPV genotypes are thus recommended for the prevention of cervical cancer in Nigeria, Africa and beyond.

Comparison of Quality Change During Processing Process of Achyranthis Bidentatae Radix from Different Origins Based on Color-component Correlation Analysis / 中国实验方剂学杂志

ObjectiveTaking Achyranthis Bidentatae Radix（ABR） from different origins as samples， to quantitatively analyze the chemical composition and chromaticity of ABR with different processing degrees， and clarify the correlation and change law between color and composition in the processing process of ABR， so as to provide reference for the quality evaluation of processed products of ABR. MethodThe colorimeter is used to measure the chromaticity values of three kinds of processing degrees of ABR in different origins to show the color value change trend during the processing process， and the color parameters of wine-processed and salt-processed products of ABR with different processing degrees were analyzed by principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA） and other analysis methods. The contents of eight representative components of ABR were measured by high performance liquid chromatography（HPLC）， the correlation between chromaticity and each representative component was analyzed by Pearson correlation analysis， and the applicability of the selected eight representative components was further verified by Fisher linear discriminant analysis， and the wine-processed and salt-processed products of ABR with different processing degrees were grouped according to the degree of processing， and 48 samples of wine-processed and salt-processed products with different processing degrees were used as training samples. Taking the contents of 5-hydroxymethylfurfural， polypodine B， β-ecdysterone， 25R-inokosterone， 25S-inokosterone， ginsenoside Ro， chikusetsusaponin Ⅳa and polysaccharides as variables， the discriminant function was established respectively， and 12 samples of wine-processed and salt-processed products of ABR with different processing degrees were back-tested to verify the discriminant function and test the reliability of the function. ResultPCA and OPLS-DA results showed that ABR samples with different processing degrees were classified into clusters， and the results could significantly distinguish different processed products. During the process of wine and salt processing， the contents of 5-hydroxymethylfurfural， ginsenoside Ro， and chikusetsusaponin Ⅳa gradually increased with the deepening of the processing degree， while the contents of polypodine B， β-ecdysterone， 25R-inokosterone， 25S-inokosterone and polysaccharides showed a gradual decreasing trend， indicating these 8 components increased and decreased to different degrees in the process of wine and salt processing. The results of Pearson correlation analysis showed that the 5-hydroxymethylfurfural content of the samples with different processing degrees of wine-processed and salt-processed products were negatively correlated with the brightness value（L*） and the total color difference value（E*ab）（P<0.01）， and positively correlated with the red-green value（a*） and the yellow-blue value（b*）（P<0.01）， and that the content of polypodine B and polysaccharides were positively correlated with L* and E*ab（P<0.01）. The discriminant functions of wine-processed and salt-processed products of ABR were established by Fisher linear discriminant analysis， and their accuracy rates in the training samples were 93.75% and 95.83%， respectively. Twelve test samples of wine-processed and salt-processed products with different processing degree were back substitution， and the correct rate was 100%. ConclusionThe trend of composition and color changes of ABR with different processing degrees in different production areas is relatively consistent， and the color value can better distinguish ABR with different processing degrees， and the color of ABR is related to some representative components in the processing process， indicating that the color can provide reference for the identification of the processing degree of ABR and the prediction of component content.

Determination and Mechanism Prediction of Potential Active Ingredients in Erdongtang Based on UHPLC-QqQ-MS and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo establish an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry（UHPLC-QqQ-MS） for determination of the active ingredients in Erdongtang， and to predict the targets and pathways of anti-insulin resistance action of this formula. MethodThe analysis was performed on an ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-3 min， 90%-87%A； 3-6 min， 87%-86%A； 6-9 min， 86%-83%A； 9-11 min， 83%-75%A； 11-18 min， 75%-70%A； 18-19 min， 70%-52%A； 19-22 min， 52%A； 22-25 min， 52%-5%A； 25-27 min， 5%-90%A； 27-30 min， 90%A）. The contents of active ingredients in Erdongtang was detected by electrospray ionization（ESI） and multiple reaction monitoring（MRM） mode under positive and negative ion modes. On this basis， network pharmacology was applied to predict the targets and pathways of Erdongtang exerting anti-insulin resistance effect. ResultThe 20 active ingredients in Erdongtang showed good linear relationships within a certain mass concentration range， and the precision， stability， repeatability and recovery rate were good. The results of determination showed that the ingredients with high content in 15 batches of samples were baicalein（1 259.39-1 635.78 mg·L-1）， baicalin（1 078.37-1 411.52 mg·L-1）， the ingredients with medium content were mangiferin（148.59-217.04 mg·L-1）， timosaponin BⅡ（245.10-604.89 mg·L-1）， quercetin-3-O-glucuronide（89.30-423.26 mg·L-1）， rutin（46.91-1 553.61 mg·L-1）， glycyrrhizic acid（55.97-391.47 mg·L-1）， neomangiferin（37.45-127.03 mg·L-1）， nuciferine（0.89-63.48 mg·L-1）， hyperoside（6.96-136.78 mg·L-1）， liquiritin（30.89-122.78 mg·L-1）， liquiritigenin（26.64-110.67 mg·L-1）， protodioscin（58.57-284.26 mg·L-1）， the ingredients with low content were wogonin（7.16-20.74 mg·L-1）， pseudoprotodioscin（5.49-22.96 mg·L-1）， ginsenoside Rb1（7.31-23.87 mg·L-1）， ginsenoside Rg1（10.78-28.33 mg·L-1）， ginsenoside Re（7.78-24.76 mg·L-1）， ophiopogonin D（2.08-4.29 mg·L-1）， methylophiopogonanone A（0.74-1.67 mg·L-1）. The results of network pharmacology indicated that the mechanism of anti-insulin resistance exerted by Erdongtang might be related to the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway. ConclusionThe established UHPLC-QqQ-MS has the advantages of simple sample processing， strong exclusivity and high sensitivity， and can simultaneously determine the contents of the main ingredients from seven herbs in Erdongtang， which can lay the foundation for the development of Erdongtang compound preparations. The results of the network pharmacology can provide a reference for the mechanism study of Erdongtang in the treatment of type 2 diabetes mellitus.

Development and verification of a reversed phase high-performance liquid chromatography method for purity determination of recombinant Mycobacterium tuberculosis Ag85b protein stock solution / 中国生物制品学杂志

@#Objective To develop and verify a reversed phase high-performance liquid chromatography method for the determination of the purity of recombinant Mycobacterium tuberculosis(Mtb)Ag85b protein stock solution.Methods Fourfactor,three-level orthogonal test was designed,with the area,trailing factor,peak area and peak area RSD as the evaluation indexes to explore the optimal detection conditions. The methodology verification of specificity,linear range,precision and durability was conducted in accordance with the general principles of Chinese Pharmacopoeia(Volume Ⅳ,2020 edition)9101.Results The results of all the evaluation indexes were good when the elution ratio of organic phase was30% ～ 95%,the detection temperature was 35 ℃,the sample volume was 3 μg,and the elution time of 95% organic phase was 15 min. The method had the linear correlation coefficient(R2)of 0. 998 5,the linear range of 1. 8 ～ 4. 2 μg,the reproducibility RSD of 0. 01%,and the intermediate precision RSD of 0. 16%,with good durability under slight changes of column temperature and flow rate.Conclusion The reversed phase high-performance liquid chromatography method for the purity determination of recombinant Mtb Ag85b protein stock solution was developed,which has good specificity,precision and durability,and can be used for the quality control of recombinant Mtb Ag85b protein stock solution.

Development and verification of a high performance liquid chromatography method for determination of aluminium adjuvant content in vaccine / 中国生物制品学杂志

@#Objective To develop a high performance liquid chromatography(HPLC)method for determination of aluminium adjuvant content in vaccine,and verify and preliminarily apply the method.Methods The 8-hydroxyquinoline derivatization method was used for determination. The chromatographic column was phenyl-hexyl column[Luna 5u PhenylHexyl(250 mm × 4. 6 mm)],and the mobile phase was composed of ammonium acetate solution-acetonitrile(with 8-hydroxyquinoline)(60 ∶ 40)containing 20 mg/L ascorbic acid,while eluted at a flow rate of 1. 0 mL/min with the isocratic eluent. The excitation wavelength and the emission wavelength of the fluorescence detector were 380 nm and 520 nm respectively. The column temperature was 40 ℃,and the sample injection was 50 μL. The developed method was verified for the specificity,linear range,accuracy,repeatability,stability and durability,and used to determine the aluminum content in 12 batches of vaccines. The results were compared with those determined by titration in general principle 3106of Chinese Pharmacopoeia(VolumeⅢ,2020 edition).Results No interference peaks appeared in the sample chromatogram,and the non-aluminum adjuvant vaccine components and phosphate buffer had no interference with the determination. The linearity of aluminum standard was good in the concentration range of 6. 25 ～ 100 μg/mL,r = 0. 999 6. The average results of spike recoveries of aluminum content in inactivated hepatitis A vaccine,recombinant hepatitis B vaccine,adsorbed acellular DTP vaccine and inactivated enterovirus 71 vaccine were 98. 32%,100. 85%,101. 09% and 99. 31%,respectively in the verification for accuracy. The relative standard deviations(RSDs) of the determination results of aluminum content in the solution of six samples of the four vaccines in the same batch were 1. 09%,1. 42%,0. 97% and1. 30%,respectively. The RSDs of aluminum content of four vaccine samples stored at room tempe-rature for 0,2,4,6 and8 h were 0. 82%,0. 73%,0. 40% and 0. 48%,respectively. When the ratio of ammonium acetate solution to 8-hydroxyquinoline acetonitrile solution in mobile phase changed within 5%,the fluctuation range of aluminum content of four vaccines was less than 2%. There was no significant difference between the developed HPLC method and the titration method of Chinese Pharmacopoeia(VolumeⅢ,2020 edition)for determination of aluminum content in the 12 batches of vaccine samples.Conclusion A HPLC method for determination of aluminum adjuvant content in vaccines has been successfully established with good specificity,linearity,accuracy,repeatability,stability and durability,simple operation,high degree of automation and less interference of manual factors. It can realize the determination of aluminium content in single dose,which provides an effective means for the rapid and large-scale determination of aluminum content in vaccine products and monitoring the dispensing of semi-final products in the production process.

Improvement effects of glycyrrhizin on Helicobacter pylori-associated gastritis in rats and its mechanism / 中国药房

OBJECTIVE To investigate the improvement effects of glycyrrhizin （GL） on Helicobacter pylori （HP）-associated gastritis in rats and its mechanism. METHODS HP-associated gastritis rat model was induced by inoculating with 1×109 cfu/mL HP. The model rats were randomly divided into model group， positive control group （HP standard quadruple group）， GL low-dose， medium-dose and high-dose groups （5， 20， 50 mg/kg）， with 12 rats in each group. Another 12 healthy rats were selected as normal control group. Except the normal control group and model group were given constant volume of normal saline intragastrically， the other groups were given corresponding drugs intragastrically， once a day， for 30 consecutive days. After administration， rats received 13C urea breath test， and delta-over-baseline （DOB） was recorded； the pathological and cellular morphological changes of gastric mucosa in rats were observed， and pathological scoring was performed； the levels of interleukin-8 （IL-8）， IL-1β， tumor necrosis factor-α （TNF-α）， reactive oxygen species （ROS） and malondialdehyde （MDA） were detected in gastric mucosa of rats； mRNA expressions of high mobility group box-1 protein （HMGB1） and nuclear factor-κ-B （NF-κB）， relative expressions of nitric oxide synthases （iNOS） and HMGB1， the phosphorylation level of NF- κBp65 were also detected in rats. RESULTS Compared with normal control group， the DOB value， histopathological score of gastric mucosa， the levels of IL-8， IL-1β， TNF-α， ROS and MDA， relative expressions of HMGB1 and NF- κB mRNA， relative expressions of iNOS and HMGB1 protein and the phosphorylation level of NF-κB p65 were all increased significantly in model group （P＜0.05）； the epithelial cells of gastric mucosa in rats were incomplete in structure and decreased in the number， with an increase in cell fragments and vacuoles， and significant cell pyknosis. Compared with model group， the changes of the above indexes in GL groups and positive control group were significantly reversed （P＜0.05）； the changes in the above indicators in the GL high-dose group were more significant than GL low-dose and medium-dose groups （P＜0.05）； the pathological changes of gastric mucosal cells in rats had all improved. CONCLUSIONS GL may inhibit inflammation and oxidative stress by inhibiting the activation of HMGB1/NF-κB pathway， thus relieving HP-induced gastric mucosal injury.