Research on Restricting Factors and Countermeasures of Balanced Development between Fairness and Efficiency of Basic Medical and Health Service in China / 中国医学伦理学

This paper analyzed the problems existing in China’s basic medical and health services from the perspective of fairness and efficiency, and the main restricting factors of balanced developmen. The main factors were: the far-reaching influence of "dual economic structure" between urban and rural areas, the government’s low-efficiency intervention in the allocation of health resources, the efficiency of hierarchical diagnosis and treatment system has not been fully released, the level of basic medical security needs to be improved, and the reform of the management and operation mechanism of medical institutions is lagging. It is proposed to adhere to the value concept of appropriate balance between fairness and efficiency, give full play to the functions of the government and the market, and take concrete measures to improve the financing mode, optimize the allocation of resources and improve the service system.

Relación estructura-función de la enzima uroporfirinógeno descarboxilasa: implicancias para la comprensión y el tratamiento de la porfiria cutánea tarda / Structure-function relationship of the enzyme uroporphyrinogen decarboxylase: implications for the understanding and treatment of porphyria cutanea tarda / Relação estrutura-função da enzima uroporfirinogênio descarbioxilase: implicações para a compreensão e tratamento da porfiria cutânea tardia / Reconocimiento a la trayectoria del Prof. Dr. Juan Miguel Castagnino†

Resumen La uroporfirinógeno descarboxilasa humana (UROD-h) es la quinta enzima del camino biosintético del hemo y su actividad deficiente, relacionada a mutaciones en su gen, se encuentra asociada a un subgrupo de porfirias. El objetivo de este trabajo fue estudiar la relación entre la dimerización de la enzima y su actividad enzimática y comprobar si la dimerización de UROD-h es imprescindible tanto para la primera etapa de la reacción (urogen→heptagen), como para la segunda etapa (heptagen→coprogen). Con ese objetivo, se expresó y purificó la UROD-h hasta homogeneidad, se analizó el comportamiento dímero-monómero bajo distintas condiciones que pudieran desplazar el equilibrio de dimerización y se evaluó la actividad enzimática en dichas condiciones. Los resultados obtenidos sugieren que la especie activa para la primera etapa de la reacción es el homodímero y que tanto el dímero como el monómero se comportan como especies activas para la segunda etapa de la reacción. Se propone que mutaciones clínicas como la Y311C, existentes en pacientes con porfiria cutánea tarda, podrían afectar la estabilidad del dímero y podrían ser el blanco para futuras terapias génicas.

Abstract Human uroporphyrinogen decarboxylase (UROD-h) is the fifth enzyme in the heme biosynthetic pathway and its deficient activity, related to mutations in its gene, is associated with a subset of porphyrias. The objective of this work was to study the relationship between the dimerisation of the enzyme and its enzymatic activity and to verify if the dimerisation of UROD-h is essential both for the first stage of the reaction (urogen→heptagen), and for the second stage (heptagen→ coprogen). With this objective, the UROD-h was expressed and purified to homogeneity, the dimer- monomer behaviour was analysed under different conditions, which could shift the dimerisation equilibrium, and the enzymatic activity was evaluated under these conditions. The results obtained suggest that the active species for the first stage of the reaction is the homodimer, and both the dimer and the monomer behaved as active species for the second stage of the reaction. It is proposed that clinical mutations such as Y311C, existing in porphyria cutanea tarda patients, could affect dimer stability and could be the target of future gene therapies.

Resumo A enzima uroporfirinogênio descarboxilase humana (UROD-h) é a quinta enzima da via biossintética do heme e sua atividade deficiente, relacionada com mutações em seu gene, está associada a um subgrupo de porfirias. O objetivo deste trabalho foi estudar a relação entre a dimerização da enzima e sua atividade enzimática e comprovar se a dimerização da UROD-h é imprescindível tanto para a primeira etapa da reação (urogênio→heptagênio), quanto para a segunda etapa (heptagênio→coprogênio). Com esse objetivo, a UROD-h foi expressa e purificada até a homogeneidade, o comportamento de dímero-monômero foi analisado sob diversas condições, que puderam deslocar o equilíbrio de dimerização, e a atividade enzimática foi avaliada em tais condições. Os resultados obtidos sugerem que a espécie ativa para a primeira etapa da reação é o homodímero, e tanto o dímero quanto o monômero se comportam como espécies ativas para a segunda etapa da reação. Propõe-se que mutações clínicas como Y311C, existentes em pacientes com porfiria cutânea tardia, poderiam afetar a estabilidade do dímero e poderiam ser o alvo de futuras terapias gênicas em porfiria cutânea tardia.

Agenda governamental brasileira: prioridades e mudanças na dinâmica da atenção sobre a distribuição orçamentária da União (2000-2021) / Agenda del gobierno brasileño: prioridades y cambios en la dinámica de atención a la distribución del presupuesto federal (2000-2021) / Brazilian policy agenda: priorities and changes in the dynamics of attention on the federal budget distribution (2000-2021)

Resumo Os estudos sobre agenda governamental têm adotado diversos indicadores para mensurar a atenção e as prioridades dos governos, a fim de analisar os processos de formulação e mudança de políticas públicas. Com base nas prerrogativas da teoria do equilíbrio pontuado sobre os padrões de mudanças na dinâmica das políticas, a distribuição do orçamento público tem se destacado como um dos instrumentos que melhor expressam os níveis de atenção e as prioridades dos governos em diferentes setores. Nesse contexto, alinhado a uma agenda internacional, este estudo busca investigar o padrão da atenção governamental acerca da distribuição orçamentária no Brasil. Assim, o objetivo deste trabalho é mapear a dinâmica da atenção governamental sobre a disposição do orçamento aprovado da União ao longo das últimas duas décadas (2000-2021), identificando os níveis percentuais de atenção aos diferentes setores de políticas públicas ao longo do tempo e os fatores conjunturais e institucionais que balizam os níveis de atenção governamental na classificação orçamentária. Para isso, foi formulado um banco de dados do orçamento aprovado de 2000 a 2021, no qual as 814 combinações de funções e subfunções de gastos foram codificadas em 21 setores, conforme metodologia do comparative agenda project (CAP). Os resultados indicam que a atenção governamental sobre essa distribuição opera sob um padrão majoritariamente incremental no decorrer do tempo, mas permeado por pontuações no equilíbrio em políticas setoriais específicas, comprovando a teoria do equilíbrio pontuado (punctuated equilibrium theory [PET]) no cenário nacional. De igual modo, apontam para a necessidade de mais estudos setoriais que expliquem as causas e os efeitos das pontuações na atenção governamental, suas relações com mudanças na agenda legislativa e os impactos de momentos de crises institucionais na definição de prioridades na distribuição orçamentária, apontados como agendas futuras a partir deste trabalho.

Resumen Los estudios sobre la agenda gubernamental adoptaron varios indicadores para medir la atención y las prioridades de los gobiernos a los efectos de analizar los procesos de formulación y cambio de políticas públicas. Desde las prerrogativas de la teoría del equilibrio puntuado sobre los patrones de cambios en la dinámica de las políticas, la distribución del presupuesto público se ha destacado como uno de los instrumentos que mejor expresan los niveles de atención y las prioridades de los gobiernos de los diferentes sectores. En ese contexto, de acuerdo con una agenda internacional, este estudio busca investigar cuál es el patrón de atención gubernamental respecto a la distribución presupuestaria en Brasil. Así, el objetivo de este trabajo es mapear la dinámica de atención gubernamental sobre la distribución del presupuesto federal aprobado en las últimas dos décadas (2000-2021), identificando (i) cuáles son los niveles porcentuales de atención a los diferentes sectores de las políticas públicas a lo largo del tiempo y (ii) los factores coyunturales e institucionales que orientan los niveles de atención del gobierno en la clasificación presupuestaria federal. Para ello, se creó una base de datos del presupuesto aprobado de 2000 a 2021, en la que se codificaron las 814 combinaciones de funciones y subfunciones del gasto en 21 sectores, según la metodología del Proyecto de Agenda Comparada (CAP). Los resultados indican que la atención del gobierno sobre la distribución del presupuesto opera en un patrón mayoritariamente incremental en el tiempo, pero permeado por puntajes de equilibrio en políticas sectoriales específicas, demostrando así la teoría del equilibrio puntuado a nivel nacional. Asimismo, señalan la necesidad de mayores estudios sectoriales que expliquen las causas y efectos de los puntajes en la atención del gobierno, sus relaciones con los cambios en la agenda legislativa y los impactos de los momentos de crisis institucional en la definición de prioridades en la distribución presupuestaria, identificadas como futuras agendas a partir de este trabajo.

Abstract Studies on policy agenda have adopted several indicators to measure the attention and priorities of governments to analyze the processes of policy change and policy dynamics. Based on the Punctuated Equilibrium Theory (PET) applied on the patterns of policy change, the distribution of the public budget has stood out as one of the instruments that best express the levels of attention and priority for governments in different sectors. This study seeks to investigate the pattern of government attention on the federal budget distribution in Brazil. Thus, this work maps the dynamics of government attention on the distribution of the federal approved budget over the last two decades (2000-2021), identifying (i) what are the percentage levels of attention to the different sectors of public policies over time and (ii) the conjunctural and institutional factors that guide the levels of government attention in the budget distribution of the federal government in Brazil. A database of the federal approved budget from 2000 to 2021 was created, in which the 814 combinations of expenditure functions and subfunctions were coded into 21 sectors according to the methodology of the Comparative Agenda Project (CAP). The results indicate that government attention on the distribution of the Brazilian federal budget operates in a mostly incremental pattern over time, permeated by punctuations in specific sectoral policies, thus proving the Punctuated Equilibrium Theory at the national level. As for future research agenda, the study shows the need for further sectoral studies that explain the causes and effects of changes on government attention, their relationships with the legislative agenda, and the impacts of moments of institutional crisis in defining priorities in budget distribution.

Individual factors associated with postural adjustment during adaptive equilibrium / 中国康复理论与实践

ObjectiveTo investigate the individual factors of postural adjustment reaction time and movement time during adaptive equilibrium. MethodsFrom March to December, 2021, 126 healthy adults aged 18 to 80 years were recruited at the First Medical Center of the General Hospital of the Chinese PLA. The DE-A somatosensory balance detection system was used to detect their postural adjustment reaction time (RT) and movement time (MT) as the platform tilting in multiple directions during standing (static) or walking (dynamic). The ages, genders, body mass index (BMI) and physical activity level of them were investigated. ResultsThe age was the only factor independently associated with dynamic RT and MT in all the directions (β > 0.632, P < 0.05). For static MT, as the platform tilting forward, physical activity level (β = -0.143, P < 0.05), BMI (β = 0.154, P < 0.05) and age (β = 0.663, P < 0.05) were the independently associated factors; as the platform tilting leftward, gender (β = -0.173, P < 0.05) and age (β = 0.647, P < 0.05) were the independently associated factors; and age was the only independently associated factor for other directions (β > 0.571, P < 0.05). For the static RT, age was the only independently associated factor for all the directions (β > 0.615, P < 0.05). ConclusionAge is the most important independently factor related to postural adjustment during adaptive equilibrium, and aging may delay the postural adjustment after instability.

Determination of plasma protein binding rate of Shuganning Injection using equilibrium dialysis and UPLC-MS/MS / 中国中药杂志

Traditional Chinese medicine(TCM) compound preparations have complex compositions. As a widely used TCM injection, Shuganning Injection, its in vivo processes are not yet fully understood. Determining the plasma protein binding rate is of great significance for pharmacokinetic and pharmacodynamic studies. In this experiment, the equilibrium dialysis method combined with UPLC-MS/MS technology was used to determine the plasma protein binding rates of 10 components, including p-hydroxyacetophenone, caffeic acid, baicalein, oroxylin A, geniposide, baicalin, cynaroside, oroxylin A-7-O-β-D-glucuronide, scutellarin, and hyperoside, in Shuganning Injection in rat and human plasma to provide a theoretical basis for further elucidating the in vivo processes of Shuganning Injection and guiding clinical medication. The results showed that, except for baicalein and geniposide, the plasma protein binding rates of the other eight components were higher in human plasma than in rat plasma, and there were interspecies differences. In human plasma, except for geniposide, caffeic acid, and baicalin, the plasma protein binding rates of the remaining seven components were above 80%, with baicalein and oroxylin A exceeding 90%. All components exhibit a high level of binding to plasma proteins, with the exception of geniposide.

Applicability Analysis of Gender Selection in Mitochondrial Replacement Technology / 中国医学伦理学

Whether gender selection should be conducted is a controversial topic in ethical research on mitochondrial replacement technology. Scholars put forward different moral judgments based on different positions, and after reviewing these judgments, it was found that those who support gender selection mainly rely on the utility theory and rights theory, while those who oppose gender selection mainly rely on the dignity theory and community theory. It is not difficult to find that relying on traditional moral theory to defend moral judgments or actions often leads to endless debates among "moral strangers" , and does not provide effective guidance for solving specific problems. Principlism is a systematic and comprehensive analytical approach constructed with a series of clear and effective frameworks, which can reasonably solve the differences and disagreements between different value systems and cultural concepts. In the discussion of whether gender selection should be conducted in mitochondrial replacement technology, principlism refined and balanced it through the method of reflective equilibrium, and finally obtained the best judgment plan that allows for gender selection. To truly achieve the humane purpose of avoiding harm in gender selection, it is necessary to clearly limit the objects and stages of use, and regulate them from the dual dimensions of ethics and morality, as well as policy regulation.

Effects of Delay in Tumor-Immune System on Stability / 医用生物力学

Objective To study stability of the deterministic tumor-immune system with time delay by means of linear stability analysis method. Methods In tumor-immune system, since it took some time for immune cells to recognize tumor cells and respond appropriately, time delay was considered in this process, then the model was simplified by using Taylor expansion of small delay, and the equilibrium points were solved out. By linear stability analysis method, the stability of these equilibrium points was studied. Finally, the trajectory of the system and that around each equilibrium point were simulated by numerical calculation method, so as to verify the result of theoretical analysis. Results The system had four meaningful equilibrium points with small delay, including a stable focus, a stable node, and two saddles. Moreover, the type and stability of these equilibrium points were not affected by the delay. Numerical simulation demonstrated the conclusion from theoretical analysis. Conclusions Under the condition of small delay, the type and stability of equilibrium points in the system are notaffected by the delay. The results are helpful to further understand dynamic mechanisms of tumor immune response, and provide references for tumor growth and treatment

Control de la ventilación y regulación del estado ácido-base del pez al hombre / Control of ventilation and regulation of acid-base status from fish to man

RESUMEN Este artículo analiza ciertos aspectos evolutivos en el intercambio gaseoso, el desa rrollo pulmonar, la bomba respiratoria, el estado ácido-base y el control de la ventila ción en relación con un evento trascendente: el pasaje de la vida acuática a la terres tre. Su estudio puede permitir comprender ciertos aspectos con los que lidiamos en la práctica clínica: ¿Por qué las personas con debilidad muscular respiratoria extrema respiran como ranas (respiración frog)?, ¿Por qué los recién nacidos con dificultad respiratoria tienen aleteo nasal y quejido espiratorio?, ¿cómo es posible que los mús culos abdominales, típicamente espiratorios, asistan a la inspiración en casos de la parálisis diafragmática?, ¿por qué en la insuficiencia respiratoria el patrón respiratorio tiene menos variabilidad y se torna más rígido? y, por último, ¿es posible imaginar un pH neutro que no tenga el valor de 7,0, para qué sirve este conocimiento y como se deben interpretar los gases en hipotermia? La transición del agua a la tierra es una de las más importantes e inspiradoras de las grandes transiciones en la evolución de los vertebrados. Ante la sorprendente diversi dad de organismos vivos, es tentador imaginar una cantidad enorme de adaptaciones evolutivas para resolver los diferentes desafíos que cada especie tiene para la vida en la tierra. Hay desarrollos tempranos que comparten algunos factores cruciales y algunas de las redes genéticas regulatorias cercanas y lejanas están conservadas. Somos testigos de hallazgos clínicos que son el testimonio de especies que han vivido en épocas remotas y nos han legado su historia evolutiva.

ABSTRACT This article analyzes certain evolutionary aspects of gas exchange, lung development, the respiratory pump, the acid-base status and control of ventilation in relation to a significant event: the passing from aquatic to terrestrial life. By studying this, we can understand certain aspects that are present in the clinical practice: Why do people with extreme respiratory muscle weakness breathe as frogs? (frog breathing); why do newborns with breathing difficulties have nasal flaring and expiratory grunting?; how is it possible that abdominal muscles, which are typically expiratory, assist with inspira tion in cases of diaphragmatic paralysis?; why does the breathing pattern of respiratory failure has less variability and becomes more rigid? and, finally, is it possible to imagine a neutral pH that doesn't have the 7.0 value?; what's the use of this knowledge, and how should gases in hypothermia be interpreted? Water-to-land transition is one of the most important and inspiring major transitions of vertebrate evolution. Given the amazing diversity of living organisms, it is tempting to imagine an enormous amount of evolutionary adaptation processes to solve the different challenges of living on earth faced by each species. There are certain early development processes that share some crucial factors, and some of the close and distant gene regulatory networks are conserved. We are witnesses of clinical findings that serve as testimony of the species that lived in remote times and left us their evo lutionary history.

Effects of Plasma-Lyte® and 0. 9% saline in renal function after deceased-donor kidney transplant: a randomized controlled trial

Abstract Background The influence of different crystalloid solutions infused during deceased-donor kidney transplant on the incidence of delayed graft function remains unclear. We investigated the influence of Plasma-Lyte® vs. 0.9% saline on the incidence of delayed graft function in deceased-donor kidney transplant recipients. Methods We conducted a single-blind randomized controlled trial of 104 patients aged 18 to 65 years who underwent deceased-donor kidney transplant under general anesthesia. Patients were randomly assigned to receive either Plasma-Lyte® (n = 52) or 0.9% saline (n = 52), at the same infusion volume, for intraoperative fluid replacement. The primary outcome was the occurrence of delayed graft function. Secondary outcomes included metabolic and electrolytic changes at the end of surgery. Results Two patients in the Plasma-Lyte® group and one in the 0.9% saline group died postoperatively and were not included for analysis. The incidence of delayed graft function in Plasma-Lyte® and 0.9% saline groups were 60.0% (95% Confidence Interval [95% CI 46.2-72.4]) and 74.5% (95% CI 61.1-84.4), respectively (p= 0.140). Mean (standard deviation) values of immediate postoperative pH and serum chloride levels in Plasma-Lyte® and 0.9% saline groups were 7.306 (0.071) and 7.273 (0.061) (p= 0.013), and 99.6 (4.2) mEq.L-1 and 103.3 (5.6) mEq.L-1, respectively (p< 0.001). All other postoperative metabolic and electrolyte variables were not statistically different at the immediate postoperative period (p> 0.05). Conclusion In deceased-donor kidney transplant recipients, the incidence of delayed graft function is not influenced by Plasma-Lyte® or 0.9% saline used for intraoperative fluid replacement.

Physiological variables of the "metabolic component" of acid-base balance and mortality in intensive care patients / Variables fisiológicas del "componente metabólico" del estado ácido base y mortalidad en pacientes de cuidados intensivos

Abstract Introduction: Metabolic acidosis is a frequent pathophysiological condition in critically ill patients. It can be assessed using different physiological variables, but their prognostic value has not yet been well established. Objective: To evaluate the association between the variables that allow assessing the metabolic component of acid-base balance (ABB) and 28-day mortality in patients admitted to an intensive care unit (ICU) in Bogotá, D.C., Colombia. Materials and methods: Prospective cohort study conducted in 122 patients admitted to an ICU between January and June 2013 and with a stay >24 hours. On admission to the ICU, blood samples were taken, and an arterial blood gas test was performed in order to calculate the following variables: anion gap (AG), corrected anion gap (AGc), standard base excess (BEst), metabolic H+, base excess-unmeasurable anions (BEua), arterial pH, arterial lactate, standard HCO3-st, and strong ion difference (SID). APACHE II and SOFA scores were also calculated. A bivariate analysis was performed in which ORs and their respective 95%CI were calculated, and then a multivariate analysis was conducted using a logistic regression model to identify the variables associated with 28-day mortality; a significance level of p<0.05 was considered. Results: Out of the 122 patients, 33 (27.05%) died at 28 days and 51 (48.80%) were women. Participants' mean age was 46.5 years (±15.7). The following variables were significantly associated with 28-day mortality in the bivariate analysis: SID (OR=1.150; p=0.008), BEua (OR=0.897; p=0.023), AG (OR=1.231; p=0.002), AGc (OR=1.232; p=0.003), blood pH (OR=0.001; p=0.023), APACHE II (OR=1.180; p=0.001), HCO3-st (OR=0.841; p=0.015). In the multivariate analysis, only the APACHE II score variable was significantly associated with 28-day mortality (OR=1.188; p=0.008). Conclusion: The physiological variables that allow assessing the metabolic component of ABB, both from the Henderson model and the Stewart model, were not significantly associated with 28-day mortality.

Resumen Introducción. La acidosis metabólica es una condición fisiopatológica frecuente en pacientes críticamente enfermos. Esta alteración es evaluada mediante diferentes variables fisiológicas; sin embargo, su valor pronóstico aún no está bien definido. Objetivo. Evaluar la asociación entre, por una parte, las variables del componente metabólico que permiten valorar el estado ácido base (EAB) y, por la otra, la mortalidad a 28 días en pacientes hospitalizados en una unidad de cuidados intensivos (UCI) en Bogotá D.C., Colombia. Materiales y métodos. Estudio de cohorte prospectivo realizado en 122 pacientes hospitalizados en una UCI entre enero y junio de 2013 y con una estancia mayor a 24 horas. Se tomaron muestras sanguíneas y gases arteriales de ingreso a UCI para el cálculo de las siguientes variables: anion gap (AG), anion gap corregido (AGc), base exceso estándar (BEst), H+ metabólicos, base exceso-aniones no medibles (BEua), pH arterial, lactato arterial, HCO3-st y brecha de iones fuertes (BIF). También se calcularon el puntaje APACHE II y el puntaje SOFA. Se realizó un análisis bivariado en el que se calcularon OR y sus respectivos IC95%, y luego uno multivariado, mediante un modelo de regresión logística, para identificar las variables asociadas con la mortalidad a 28 días; se consideró un nivel de significancia de p<0.05 Resultados. De los 122 pacientes, 33 (27.05%) fallecieron a 28 días y 51 (48.80%) eran mujeres. La edad promedio fue 46.5 años (±15.7). En el análisis bivariado, las siguientes variables se asociaron significativamente con la mortalidad a 28 días: BIF (OR=1.150; p=0.008), BEua (OR=0.897; p=0.023), AG (OR=1.231; p=0.002), AGc (OR=1.232; p=0.003), pH arterial (OR=0.001; p=0.023), APACHE II (OR=1.180;p=0.001), HCO3-st (OR=0.841;p=0.015). En el análisis multivariado, solo el puntaje APACHE II se asoció significativamente con la mortalidad a 28 días (OR=1.188; p=0.008). Conclusión. Las variables fisiológicas que permiten evaluar el componente metabólico del EAB, tanto las del modelo de Henderson, como las del modelo de Stewart, no se asociaron significativamente con la mortalidad a 28 días.

Chemical denaturants induced folding unfolding pathway of the recombinant zebrafish dihydrofolate reductase

Denaturation of proteins plays a crucial part in cellular activities. In this study, we have investigated the folding unfolding pathways of zebrafish dihydrofolate reductase (zDHFR) in presence of different chemical denaturants which were found to be an influential factor for the refolding yield by UV-visible spectrophotometric analysis. The activity change of zDHFR has been observed in presence of three different denaturants like Acetic Acid (AcOH), Sodium Dodecyl Sulphate (SDS), and Ethanol (C2H5OH). Spectrophotometric analysis reveals that protein unfolded completely at different concentrations and times by these denaturants. The spontaneous refolding experiments of chemically denatured zDHFR were also conducted to verify the spontaneous refolding yield. These investigations have helped us to decipher a picture about the denaturants contributing to achieving the refolding yield. We observed that acetic acid is a stronger denaturant among all, and the spontaneous refolding yields were higher from SDS denaturation. In the light of the above findings, higher spontaneous refolding yields were obtained from the low concentration of denaturants.

Levels and variation of radon equilibrium factor in an office of Nanning city / 中华放射医学与防护杂志

Objective:To study the levels and variation of equilibrium factor in indoor environment.Methods:A one-year continuous measurement of radon concentration and equilibrium equivalent radon concentration was carried out in an indoor office building of Nanning city. The effective data acquisition rates of radon gas and radon progeny were 99.9% and 86.7%, respectively.Results:The annual average activity concentration and equilibrium equivalent radon concentration in indoor environment were (50.9±20.7)and (15.5±10.1)Bq/m 3, both of which had the same diurnal and seasonal variation. The average annual value of equilibrium factor was 0.30±0.12, showing no obvious diurnal variation. The distribution of monthly mean value of equilibrium factor showed a similar trend to that of radon and radon progeny. The highest and the lowest value appeared in November and June, respectively, with 0.47±0.24 and 0.19±0.06. Conclusions:Due to the large variation range of monthly mean value of equilibrium factor in indoor environment, when annual effective dose of radon exposure was estimated based on radon gas concentration, attention should be paid to choose the quantity value of equilibrium factor and the uncertainty caused by the change of equilibrium factor should be considered.

Simultaneous determination of LY3214996,abemaciclib,and M2 and M20 metabolites in human plasma,cerebrospinal fluid,and brain tumor by LC-MS/MS / 药物分析学报

A sensitive and rapid liquid chromatography tandem mass spectrometry(LC-MS/MS)method was established for the quantification of total and unbound concentrations of LY3214996,an extracellular signal-regulated kinase inhibitor;abemaciclib,a cyclin-dependent kinase 4/6 inhibitor;and abemaciclib active metabolites,M2 and M20,in human plasma,brain tumor,and cerebrospinal fluid samples.The method was validated over a concentration range of 0.2-500 nM within a total run time of 3.8 min using isocratic elution on a Kinetex? Fs column.Detection was performed on a Sciex QTRAP 6500+mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization.The intra-and inter-batch accuracy as well as the precision of the method for all matrices was within±20％and≤20％at the lower limit of quantification,and within±15％and≤15％for other quality control levels for all analytes.The unbound fractions of drugs and metabolites in spiked and patient samples were determined using an optimized equilibrium dialysis.The validated method was successfully applied in a phase 0/2 clinical trial to assess the central nervous system penetration of LY3214996 and abemaciclib.

Study on effect of restoring mitochondrial dynamics on NK2 activation of NK cells / 中国药理学通报

Aim To explore the internal mechanism of NK2 activation of NK cells from the perspective of "mitochondrial dysfunction-abnormal cell activation".Methods NK-92MI cells were divided into blank group, TSLP group, 1, 5, and 10 μmol·L-1 Mdivi-1 dose groups.The levels of IL-4, IL-5, and IFN-γ in the supernatant of each group were determined by ELISA; The expression of p-Drp1 and MnSOD protein in each group was determined by Western blotting; the ROS level of each group was detected by DHE staining and flow cytometry; mitochondrial morphology was observed by confocal laser in each group of cells.Results ELISA showed that compared with control group, the levels of IL-4 and IL-5 in cell supernatant of TSLP group significantly increased, and the level of IFN-γ was down-regulated(P<0.05); Compared with TSLP group, the levels of IL-4 and IL-5 in cell supernatant of 5 and 10 μmol·L-1 Mdivi-1 group decreased, and the IFN-γ concentration of the 10 μmol·L-1 Mdivi-1 group rose(P<0.05).DHE staining and flow cytometry showed that ROS level of cells in TSLP group was significantly higher than control group.Compared with TSLP group, ROS level of the 5 and 10 μmol·L-1 Mdivi-1 groups decreased(P<0.05).The laser confocal results showed that after TSLP stimulation, a large number of spherical mitochondria were formed in cells.This phenomenon was improved to a certain extent after the intervention of 5, 10 μmol·L-1 Mdivi-1.Western blot analysis showed that the p-Drp1 level of NK-92MI cells in TSLP group was significantly up-regulated, and the expression of MnSOD decreased, while the intervention of Mdivi-1 effectively reversed the changes in the expression of the above-mentioned molecules.Conclusions Mitochondrial dynamic imbalance may be one of the internal mechanisms of abnormal activation of NK cells, and it may be an important target for regulating NK2 activation of NK cells and improving the allergic inflammatory response mediated by it.

Establishment and application of a method for the determination of plasma protein binding rate of imatinib and its metabolite / 中国药房

OBJECTIVE To establish a method for the determination of plasma protein binding rate of imatinib and its metabolite（N-desmethyl imatinib ）and apply it to patients with gastrointestinal stromal tumor （GIST）.METHODS Using imatinib - d8 as the internal standard ，after being deproteinized methanol ，the sample was determined by equilibrium dialysis combined with liquid chromatography -tandem mass spectrometry . The free concentrations of imatinib and its metabolites in plasma of GIST patients were detected by the same method . RESULTS The protein binding rates of imatinib with albumin ，α1-acid glycoprotein and globulin at 120 ng/mL and 4 000 ng/mL were （92.5±1.0）% and（91.7±0.4）%，（56.6±2.0）% and（62.6±2.6）%，（56.3±3.1）% and （68.0±8.6）% ，respectively. The protein binding rates of N-desmethyl imatinib with albumin ，α1-acid glycoprotein and globulin at 60 ng/mL and 2 000 ng/mL were （90.6±3.5）% and（91.3±1.5）%，（54.1±5.1）% and（63.7±1.3）%，（56.2±7.6）% and（67.5±7.3）%，respectively. Compared with the low concentration group of imatinib （120 ng/mL）and its metabolite （60 ng/mL），the plasma protein binding rate of high concentration of imatinib （4 000 ng/mL）and its metabolite （2 000 ng/mL）with α1-acid glycoprotein and globulin was significantly increased （P＜ Δ基金项目 国家自然科学基金资助项目（No.81503160）；江苏省 0.05），but there was no signifi -cant difference with albumin 卫生健康发展研究中心 2021年度开放课题（No.JSHD2021004）；江苏 （P＞0.05）. In blank plasma ，the protein binding rates of imatinib（4 000 ng/mL）at high concentration and its metabolites（2 000 ng/mL）were significantly lower than those of low （120， 60 ng/mL） and medium （750， 375 ng/mL）concentration （P＜0.01）. Average protein binding rates of imatinib and its metabolite in plasma of GIST patients were （99.0±0.3）% and（99.2±0.3）%，respectively；the correlation coefficients between the concentrations of imatinib and its metabolites and the protein binding rates were －0.298 5 and －3.332 3，respectively（all P＜0.05）. CONCLUSIONS The method for determining the plasma protein binding rates of imatinib and its metabolites is successfully established . The plasma protein binding rates of imatinib and its metabolites in patients with GIST are negatively correlated with drug concentration .

Estimation of peach supply response in Colombia using a Vector Error Correction Model / Estimación de la respuesta de la oferta de durazno en Colombia mediante el modelo de vector de corrección de errores / Estimativa da resposta de fornecimento de pêssego na Colômbia usando um Modelo de Correcção de Erros Vectoriais

ABSTRACT An empirical study of peach supply response to own-price and yield in Colombia using time series data from 2000 to 2018 was undertaken. A quantitative, correlational and non-experimental research design was selected and the Johansen's co-integration as well as the vector error correction framework were employed. The Augmented Dickey-Fuller test showed that the time series were integrated of order one and the Johansen's co-integration confirmed the existence of a long-term relationship between the variables. Moreover; the short and long run coefficients for own-price and yield were statistically significant and presented the expected signs, however estimated own-price elasticity was below unit suggesting it is not an important factor in peach supply response. Furthermore, the vector error correction coefficient (-0.32) was negative and in line with theory which showed that in the long-run, the model converges towards equilibrium, however at a relatively slow pace. Therefore, it can be concluded that, overall, the proposed model contributes to the understanding of the dynamics in peach output supply

RESUMEN Se realizó un estudio empírico sobre la respuesta a la oferta de durazno con relación a su precio y rendimiento agr'cola en Colombia, utilizando datos de series de tiempo para el per'odo comprendido entre 2000 y 2018. Se seleccionó un diseño de investigación cuantitativo, correlacional y no experimental y se empleó la cointegración de Johansen y el modelo de vector de corrección de errores. Los resultados de la a prueba de Aumentada de Dickey-Fuller demostraron que las series temporales estaban integradas en el orden uno y la cointegración de Johansen confirmó la existencia de una relación a largo plazo entre las variables. Además, los coeficientes del precio y rendimiento a largo y corto plazo fueron estadísticamente significativos y presentaron los signos esperados. Sin embargo, la elasticidad precio estimada fue inferior a la unidad, lo cual sugiere que no es un factor importante en la respuesta de la oferta de durazno. Asimismo, el coeficiente de corrección de error del vector (-0.32) fue negativo y en línea con la teoría, denostando que, a largo plazo, el modelo converge hacia al equilibrio, pero a una velocidad relativamente lenta. Por lo tanto, se puede concluir que, en general, el modelo propuesto, contribuye a la comprensión de la dinámica de la respuesta de la oferta de durazno.

RESUMO Realizou-se um estudo empírico da resposta da oferta de pêssego em função do seu preço e rendimento agrícola na Colômbia, usando dados de séries temporais para o período entre 2000 a 2018. O estudo usou um desenho de pesquisa quantitativa, correlacional e não experimental assim como a cointegração de Johansen e o modelo Vetorial de Correção de Erro. Os resultados do teste Aumentado de Dickey-Fuller demonstraram que as séries são integradas de ordem um e a cointegração de Johansen confirmou a existência de uma relação de longo prazo entre as variáveis. Além disso, os coeficientes do curto e longo prazo para preço e rendimento foram estatisticamente significantes e apresentaram os sinais esperados; no entanto, a elasticidade estimada do preço foi menor que a unidade, sugerindo que não é um fator importante na resposta da oferta de pêssego. Além disso, o coeficiente de correção de erros vetoriais (-0,32) foi negativo e alinhado à teoria, que mostrou que, a longo prazo, o modelo converge para o equilíbrio, porém a um ritmo relativamente lento. Portanto, pode-se concluir que, de maneira geral, o modelo proposto contribui para entender a dinâmica da oferta de produção de pêssego.

Papel de la alimentación en la respuesta a infecciones respiratorias altas en atletas de élite / Role of nutrition in the response to upper respiratory infections in elite athletes

Las infecciones de las vías respiratorios altas (IVRA), son debilitantes para el potencial deportivo de los atletas de élite. El ejercicio físico activa múltiples vías moleculares y bioquímicas relacionadas con el sistema inmune, sensibles a influencias nutricionales. Sobre este contexto, la inmunonutrición está adquiriendo una nueva dirección orientada a conseguir el equilibrio inmunológico, contraponiéndose con algunas de las teorías que han sentado las bases de la inmunología del ejercicio durante las últimas décadas. Objetivo. Investigar los aspectos nutricionales que puedan mejorar la respuesta inmunológica en deportistas de elite. Estudiar los posibles beneficios del equilibrio inmunológico para mejorar el rendimiento, analizar los factores nutricionales que contribuyan al equilibrio de la respuesta inmunológica y extrapolar la evidencia actual en recomendaciones prácticas de alimentación/suplementación para mejorar la homeostasis de la respuesta inmunológica en atletas de élite, teniendo en cuenta las limitaciones existentes.Resultados. La evidencia científica apunta que se puede potenciar el equilibrio inmunológico y la respuesta inmune a través de la modificación de factores nutricionales. Dentro de los cuales, la vitamina D, los probióticos, la vitamina C y el cinc son los que cuentan con mayor evidencia. Conclusión. Los avances científicos resultan prometedores y de interés para los atletas de élite, debido a que pueden disminuir la incidencia de IVRA, mejorando el éxito deportivo de los mismos. Se requieren más estudios para su validación y aplicación(AU)

Upper respiratory tract infections (URTI) are debilitating for the athletic potential of elite athletes. Physical exercise in elite athletes activates multiple molecular and biochemical pathways related to the immune system, which, at the same time, are sensitive to nutritional influences. Based on this context, immunonutrition is taking a new direction aimed at achieving the immunological balance. Objective. To investigate the nutritional aspects that can improve the immune response in elite athletes. To study the potential benefits of immune balance to improve performance, to analyse nutritional factors that contribute to the balance of the immune response and to extrapolate current evidence into practical dietary/supplementation recommendations to improve the homeostasis of the immune response in elite athletes, considering existing limitations. Results. Scientific evidence suggests that immune balance and immune response can be enhanced through the modification of nutritional factors. Among which, vitamin D, probiotics, vitamin C and zinc are the micronutrients with most evidence. Conclusion. Scientific advances in this field are promising and of great interest to elite athletes since it could decrease the incidence of URTI and, as a consequence, it could improve their sporting success. However, more studies are still required for its validation and application(AU)

Preparation, characterization and improved solubility of ticagrelor salts / 药学学报

Four salts of ticagrelor, ticagrelor-3,5-dinitrobenzoic acid, ticagrelor-pyrazinamide, ticagrelor-D-proline and ticagrelor-L-proline were prepared by solvent suspension and liquid-assisted grinding to improve the solubility of ticagrelor. The compounds were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, elemental analysis, and the intermolecular salt-bonding forces were analyzed. The equilibrium solubility of salts and pure drug in hydrochloride buffer pH 1.2 and phosphate buffer pH 6.8 were measured by high-performance liquid chromatography. Ticagrelor was salted with 3,5-dinitrobenzoic acid, pyrazinamide, D-proline, L-proline all in a stoichiometric ratio of 1∶1; with the exception of ticagrelor-D-proline, the solubility of the other three salts provided significantly improved solubility in hydrochloride buffer pH 1.2, and the equilibrium solubility of ticagrelor-3,5-dinitrobenzoic acid was increased by approximately 1.7 folds as compared to pure drug. Salt-forming technology is convenient and can improve the solubility of ticagrelor.

Princípios analíticos da gasometria arterial / Analytical principles of arterial gasometry

Gasometria arterial (GA) é um exame que permite avaliar a condição respiratória e metabólica do paciente, sendo uma das formas mais comuns de investigação clínica em casos emergenciais e de cuidados críticos. É utilizada para medir as concentrações de oxigênio e também para avaliação do distúrbio do equilíbrio ácido-base, da oxigenação do sangue arterial e da ventilação alveolar. O presente estudo tem como objetivo apontar e avaliar os princípios da técnica de gasometria arterial, fases analíticas, principais doenças em que se utiliza o exame e inovações da técnica ao longo dos anos, baseado em dados de artigos científicos e banco de dados do Scielo (Scientific Eletronic Library Online) e Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde). A coleta de sangue arterial para gasometria ocorre através de um procedimento invasivo realizado por intermédio de uma punção arterial. Tal procedimento é executado pelo profissional enfermeiro e exige qualificações técnicas e científicas. O estudo mostrou que as informações acerca do exame constituem uma importante ferramenta para que se possam compreender a complexidade da técnica bem como os distúrbios ácido-base envolvidos na clínica do paciente.

Arterial blood gas (GA) is an exam that allows the assessment of respiratory and metabolic condition, being one of the most common forms of clinical investigation in emergency cases and critical care. It is used to measure oxygen concentrations, as well as for evaluation of acid-base balance disorder, arterial blood oxygenation and alveolar ventilation. This study aims to point out and evaluate the principles of arterial blood gas technique, analytical phases, main diseases in which the examination is used and innovations of the technique over the years, based on data from scientific articles and SciELO database (Scientific Electronic Library Online) and Lilacs (Latin American and Caribbean Health Sciences Literature). The collection of arterial blood for blood gas analysis occurs through an invasive procedure in which an arterial puncture is performed. Such procedure is performed by the professional nurse and requires technical and scientific qualifications. The study showed that the information about the exam is an important tool to understand the complexity of the technique, as well as the acid-base disorders involved in the patient's clinic.