Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we "gliflozin" patients with kidney stone disease? / Inibidores de cotransportadores sódio-glicose-2 (SGLT2) na nefrolitíase - devemos "gliflozinar" os litiásicos?

ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?

RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?

Risk factors for acute kidney injury in patients hospitalized with COVID-19 / Fatores de risco para lesão renal aguda em pacientes hospitalizados com COVID-19

Abstract Introduction: Acute kidney injury (AKI) occurs frequently in COVID-19 patients and is associated with greater morbidity and mortality. Knowing the risks of AKI allows for identification, prevention, and timely treatment. This study aimed to identify the risk factors associated with AKI in hospitalized patients. Methods: A descriptive, retrospective, cross-sectional, and analytical component study of adult patients hospitalized with COVID-19 from March 1 to December 31, 2020 was carried out. AKI was defined by the creatinine criteria of the KDIGO-AKI guidelines. Information, regarding risk factors, was obtained from electronic medical records. Results: Out of the 934 patients, 42.93% developed AKI, 60.59% KDIGO-1, and 9.9% required renal replacement therapy. Patients with AKI had longer hospital stay, higher mortality, and required more intensive care unit (ICU) admission, mechanical ventilation, and vasopressor support. Multivariate analysis showed that age (OR 1.03; 95% CI 1.02-1.04), male sex (OR 2.13; 95% CI 1.49-3.04), diabetes mellitus (DM) (OR 1.55; 95% CI 1.04-2.32), chronic kidney disease (CKD) (OR 2.07; 95% CI 1.06-4.04), C-reactive protein (CRP) (OR 1.02; 95% CI 1.00-1.03), ICU admission (OR 1.81; 95% CI 1.04-3.16), and vasopressor support (OR 7.46; 95% CI 3.34-16.64) were risk factors for AKI, and that bicarbonate (OR 0.89; 95% CI 0.84-0.94) and partial pressure arterial oxygen/inspired oxygen fraction index (OR 0.99; 95% CI 0.98-0.99) could be protective factors. Conclusions: A high frequency of AKI was documented in COVID-19 patients, with several predictors: age, male sex, DM, CKD, CRP, ICU admission, and vasopressor support. AKI occurred more frequently in patients with higher disease severity and was associated with higher mortality and worse outcomes.

RESUMO Introdução: Lesão renal aguda (LRA) ocorre frequentemente em pacientes com COVID-19 e associa-se a maior morbidade e mortalidade. Conhecer riscos da LRA permite a identificação, prevenção e tratamento oportuno. Este estudo teve como objetivo identificar fatores de risco associados à LRA em pacientes hospitalizados. Métodos: Realizou-se estudo descritivo, retrospectivo, transversal e de componente analítico de pacientes adultos hospitalizados com COVID-19 de 1º de março a 31 de dezembro, 2020. Definiu-se a LRA pelos critérios de creatinina das diretrizes KDIGO-LRA. Informações sobre fatores de risco foram obtidas de prontuários eletrônicos. Resultados: Dos 934 pacientes, 42,93% desenvolveram LRA, 60,59% KDIGO-1 e 9,9% necessitaram de terapia renal substitutiva. Pacientes com LRA apresentaram maior tempo de internação, maior mortalidade e necessitaram de mais internações em UTIs, ventilação mecânica e suporte vasopressor. A análise multivariada mostrou que idade (OR 1,03; IC 95% 1,02-1,04), sexo masculino (OR 2,13; IC 95% 1,49-3,04), diabetes mellitus (DM) (OR 1,55; IC 95% 1,04-2,32), doença renal crônica (DRC) (OR 2,07; IC 95% 1,06-4,04), proteína C reativa (PCR) (OR 1,02; IC 95% 1,00-1,03), admissão em UTI (OR 1,81; IC 95% 1,04-3,16) e suporte vasopressor (OR 7,46; IC 95% 3,34-16,64) foram fatores de risco para LRA, e que bicarbonato (OR 0,89; IC 95% 0,84-0,94) e índice de pressão parcial de oxigênio arterial/fração inspirada de oxigênio (OR 0,99; IC 95% 0,98-0,99) poderiam ser fatores de proteção. Conclusões: Documentou-se alta frequência de LRA em pacientes com COVID-19, com diversos preditores: idade, sexo masculino, DM, DRC, PCR, admissão em UTI e suporte vasopressor. LRA ocorreu mais frequentemente em pacientes com maior gravidade da doença e associou-se a maior mortalidade e piores desfechos.

Importancia de la genómica en el diagnóstico de nuevas variantes asociadas a trastornos del tejido conectivo con solapamiento fenotípico

La Aracnodactilia Contractural Congénita  (ACC) es una enfermedad del tejido conectivo de herencia autosómica dominante, causada por variantes en el gen FBN2 que codifica la fibrilina-2. Tiene características específicas como contracturas congénitas, oreja con hélice superior arrugada, camptodactilia, pectus carinatum y complicaciones como escoliosis y la cifoescoliosis. Publicamos el caso de una paciente femenina de 19 años con historia de delgadez, velocidad de crecimiento acelerada, talla alta, pérdida de peso, contracturas articulares, hipotonía congénita, pubertad precoz, hábito marfanoide, pectus carinatum y leve aracnodactilia. Se sospecha de enfermedad del colágeno y se solicita secuenciación del exoma completo mediante NGS  (del inglés Next Generation Sequencing) + CNVs  (del inglés Copy Number Variations) genes relacionados con colagenopatías; se identificó una variante en el gen FBN2  (NM_001999.4): c.4394G>A; p.Cys1465Tyr; estado heterocigoto de significancia clínica probablemente patogénica. La ACC es fenotípicamente similar al síndrome de Marfán y se caracteriza por aracnodactilia, dolicostenomelia, escoliosis, contracturas congénitas múltiples y anomalías de los oídos externos. A diferencia del síndrome de Marfán; no tiene compromiso ocular ni afecta la raíz aórtica. Cuenta con variabilidad fenotípica que le dan la heterogeneidad que pueden interferir y retrasar el proceso diagnóstico y terapéutico específico al solaparse con otras condiciones médicas. Los avances en la medicina y la genómica con la utilización de nuevos métodos diagnósticos han permitido que cada día nos acerquemos más a la medicina 6P  (precisión, predicción, prevención, personalizada, participativa con enfoque poblacional) que impacta en el diagnóstico, tratamiento específico, seguimiento, pronóstico y adecuado asesoramiento genético de las enfermedades. (provisto por Infomedic International)

Contractural arachnodactyly congenita  (CCA) is an autosomal dominantly inherited connective tissue disease caused by variants in the FBN2 gene encoding fibrillin-2. It has specific features such as congenital contractures, wrinkled upper helix ear, camptodactyly, pectus carinatum and complications such as scoliosis and kyphoscoliosis. We publish the case of a 19-year-old female patient with a history of thinness, accelerated growth velocity, tall stature, weight loss, joint contractures, congenital hypotonia, precocious puberty, marfanoid habitus, pectus carinatum and mild arachnodactyly. Collagen disease was suspected and whole exome sequencing by NGS  (Next Generation Sequencing) + CNVs  (Copy Number Variations) genes related to collagenopathies was requested; a variant was identified in the FBN2 gene  (NM_001999.4): c.4394G>A; p.Cys1465Tyr; heterozygous state of probably pathogenic clinical significance. CCA is phenotypically similar to Marfan syndrome and is characterized by arachnodactyly, dolichostenomelia, scoliosis, multiple congenital contractures, and external ear anomalies. Unlike Marfan syndrome, it has no ocular involvement and does not affect the aortic root. It has phenotypic variability that gives it heterogeneity that can interfere and delay the specific diagnostic and therapeutic process by overlapping with other medical conditions. Advances in medicine and genomics with the use of new diagnostic methods have allowed us to get closer to 6P medicine  (precision, prediction, prevention, personalized, participatory with a population approach) that impacts on the diagnosis, specific treatment, follow-up, prognosis and adequate genetic counseling of diseases. (provided by Infomedic International)

Cobertura de vacunación contra COVID-19 e influenza en personal de salud y administrativo en Paraguay

Introducción: A nivel mundial, la cobertura de vacunación contra el COVID-19, así como contra la influenza es baja tanto en la población general como en los profesionales de la salud a pesar de que la vacuna es gratuita y obligatoria en el personal sanitario. Objetivo: Describir la cobertura de vacunación contra el COVID -19, y la influenza en personal de salud y administrativo de un hospital de referencia del Ministerio de Salud Pública y Bienestar Social en el periodo 2021-2022. Metodología: Estudio observacional descriptivo de corte trasverso. Se hizo la revisión de los registros del personal sanitario y administrativo del centro vacunatorio del Hospital Nacional de Itauguá de la campaña vacunal contra el COVID-19 y de anti-influenza en el periodo 2021- 2022. Resultados: De los 3.586 funcionarios, 999 (27,9 %) eran médicos, 1494 (41,7 %) personal de enfermería, 366 (10,2 %) otra categoría de personal sanitario, y 727 (20,3 %) personal administrativo. En forma global, el 86,5 % de los funcionarios recibió por lo menos las dos dosis que constituyen el esquema primario y el 73 % la dosis de refuerzo. El 2,1 % del personal no recibió ninguna dosis de vacuna anti covid-19, la cifra fue mayor en el personal administrativo (4,8 %). La cobertura de vacunación contra la influenza fue de 20 % en el 2021 y 25 % en el 2022. Discusión: Si bien cobertura de vacunación anti-COVID-19 fue comparable a otros países, la vacunación contra la influenza fue muy baja. Es urgente implementar estrategias dirigidas a aumentar la percepción de riesgo y aceptabilidad de las vacunas obligatorias para el personal sanitario.

Introduction: Worldwide, vaccination coverage against COVID-19, as well as against influenza, is low both in the general population and in health professionals, despite the fact that the vaccine is free and mandatory for health personnel. Objective: To describe the COVID -19 and influenza vaccination coverage in health and administrative personnel of a reference hospital of the Ministry of Public Health and Social Welfare in the period 2021-2022. Methods: Cross-sectional descriptive observational study. Charts of the health and administrative personnel of the vaccination center of the Itauguá National Hospital of the COVID-19 and influenza vaccination campaign in the period 2021-2022 were reviewed. Results: Of the 3,586 personnel, 999 (27.9%) were medical personnel, 1,494 (41.7%) nursing personnel, 366 (10.2%) other category of health personnel, and 727 (20.3%) administrative personnel. Overall, 86.5% of the employees received at least the two doses that constitute the primary schedule and 73% the booster dose; 2.1% of the staff did not receive any dose of the anti COVID-19 vaccine, which was higher in the administrative staff (4.8%). Influenza vaccination coverage was 20% in 2021 and 25% in 2022. Discussion: Even though the vaccination coverage of anti-COVID-19 was comparable to other countries, vaccination anti-influenza was very low. It is urgent to implement strategies aimed at increasing the perception of risk and acceptability of mandatory vaccines for health personnel.

Manifestaciones orales del COVID-19 en Paraguay: resultados de una encuesta en línea

Introducción: Estudios previos han reportado que pacientes infectados con el virus del COVID-19, podrían manifestar sintomatologías a nivel de la cavidad oral. Objetivo: Evaluar la frecuencia de manifestaciones orales asociadas a COVID-19 en un segmento de la población paraguaya y determinar cuáles son las más prevalentes. Metodología: Estudio descriptivo de corte transversal. Fue realizada una encuesta electrónica de enero a marzo del 2022. Los datos fueron presentados como frecuencias y porcentajes y analizados mediante la prueba de chi-cuadrado. El análisis estadístico se realizó con el software R versión 4.0.3. Resultados: La muestra estuvo compuesta por 478 personas. El 79,50 % correspondió al sexo femenino y el 45,19 % tenía entre 25 y 34 años. El 65,48 % informó haber experimentado al menos 1 síntoma o signo oral durante el curso de COVID-19. La pérdida de la sensación de sabores amargos, seguida de la alteración del sabor de los alimentos y la pérdida de la percepción dulce, fueron los síntomas más comunes. Se encontró una proporción significativamente mayor de manifestaciones orales en el rango de 18-24 años (χ²; p= 0,003). Entre las personas que desarrollaron COVID-19 de forma moderada a severa hubo mayor número de manifestaciones de síntomas orales (χ²; p= 0,044). Discusión: Se identificó una alta frecuencia de manifestaciones orales en pacientes con casos de moderados a severos de COVID-19, destacándose los trastornos del gusto como los más predominantes. Los individuos más jóvenes fueron los más afectados.

Introduction: Previous studies have reported that patients infected with the COVID-19 virus could manifest symptoms in the oral cavity. Objective: To evaluate the frequency of oral manifestations associated with COVID-19 in a segment of the Paraguayan population and determine the most prevalent ones. Methods: Descriptive cross-sectional study. An electronic survey was conducted from January to March 2022. The data were presented as frequencies and percentages and analyzed using the chi-square test. Statistical analysis was performed with R software version 4.0.3. Results: The sample consisted of 478 individuals. 79.50% were female, and 45.19% were between 25 and 34 years old. 65.48% reported having experienced at least 1 oral symptom or sign during the course of COVID-19. The loss of the sensation of bitter tastes, followed by the alteration of the taste of foods and the loss of sweetness perception, were the most common symptoms. A significantly higher proportion of oral manifestations was found in the 18-24 age range (χ²; p= 0.003). Among people who developed COVID-19 in a moderate to severe form, a greater number of oral symptom manifestations were observed (χ²; p= 0.044). Discussion: A high frequency of oral manifestations was identified in patients with moderate to severe cases of COVID-19, with taste disorders standing out as the most predominant. Younger individuals were the most affected.

Proporção de casos nosocomiais de COVID-19 no Brasil: análise de seus fatores associados em 1.631.47 registros de 2020 a 2022 / Proporción de casos nosocomiales de COVID-19 en Brasil: análisis de sus factores asociados en 1.631.47 registros de 2020 a 2022 / Proportionof nosocomial cases of COVID-19 in Brazil: analysisof1.631.47 case records from 2020 to 2022

Introdução: Infecções nosocomiais, adquiridas após a internação hospitalar, são o evento adverso mais comum que ameaça a saúde dos pacientes hospitalizados, sendo a pneumonia, incluindo a causada pelo SARS-Cov-2, responsável por mais de 80% das infecções nosocomiais. A pandemia declarada pela OMS em março de 2020 reflete o rápido aumento de casos, impulsionado pela disseminação do vírus através de gotículas e aerossóis. A transmissão nosocomial do SARS-Cov-2 foi observada desde o início do surto em Wuhan, representando um desafio adicional na qualidade de vida dos pacientes. Estudos internacionais em hospitais reportam incidências de infecção nosocomial por COVID-19 entre 11% e 44%.Objetivo: Identificar a proporção de infecção nosocomial por SARS-COV-2 no Brasil entre março de 2020 até dezembro de 2022.Metodologia:Trata-se de um estudo analítico, retrospectivo, de corte transversal, sobre a proporção de infecção nosocomial por Sars-Cov-2 no Brasil, através de dados secundários oriundos do Sistema de Informação da Vigilância Epidemiológica da Gripe. No presente estudo a variável dependente analisada foi a proporção de infecção nosocomial por Sars-cov-2. Como variáveis independentes exploratórias foram utilizadas: faixa etária, sexo, comorbidades e macrorregião de residência. Resultados: O estudo identificou uma proporção de casos nosocomiais de 2,58%, sendo maior no terceiro ano da pandemia 2022 (5,5%) na região Norte (7,57%), entre os indivíduos de 18-59 anos de idade (6,93%)Conclusões: Este estudo sobre casos nosocomiais de COVID-19 no Brasil revela uma proporção de 2,58% entre 2020 e 2022, com associações identificadas em relação à região, idade e comorbidades. Diferenças em relação a estudos internacionais sugerem questões metodológicas específicas. Essa pesquisa é de importância crítica, visto ser de abrangência nacional com grande amplitude, e estabelece uma base sólida para futuros estudos epidemiológicos (AU).

Introduction: Nosocomial infections, acquired after hospital admission, are the most common adverse events threatening patient health, with pneumonia, including that caused by SARS-CoV-2, responsible for over 80% of nosocomial infections. The pandemic declared by the WHO in March 2020 reflects the rapid rise in cases driven by the virus's spread through droplets and aerosols. Nosocomial transmission of SARS-CoV-2 has been observed since the outbreak's onset in Wuhan, posing an additional challenge to patient quality of life. International hospital studies report nosocomial COVID-19 infection rates between 11% and 44%. Objective: Identifying the proportion of nosocomial SARS-CoV-2 infection in Brazil between March 2020 and December 2022.Methodology:This is an analytical, retrospective, cross-sectional study on the proportion of nosocomial SARS-CoV-2 infection in Brazil, using secondary data from the Influenza Epidemiological Surveillance Information System. In this study, the analyzed dependent variable was the proportionof nosocomial SARS-CoV-2 infection. The exploratory independent variables included: age group, gender, comorbidities, and macro-region of residence.Results:The study identified a proportion of nosocomial cases of 2.58%, with a higher proportion in the third year of the pandemic, 2022 (5.5%) in the North region (7.57%), among individuals aged 18-59 years (6.93%). Conclusions: This study on nosocomial cases of COVID-19 in Brazil reveals a proportion of 2.58% between 2020 and 2022, with associations identified regarding region, age, and comorbidities. Differences compared to international studies suggest specific methodological issues. This research is of critical importance, given its national scope and broad coverage, and establishes a solid foundation for future epidemiological studies (AU).

Introducción: Las infecciones nosocomiales, adquiridas tras la hospitalización, son el evento adverso más común que amenaza la salud de los pacientes hospitalizados, siendo la neumonía, incluida la causada por el SARS-Cov-2, la responsable de más del 80% de las infecciones. La pandemia declarada por la OMS en marzo de 2020 refleja el rápido aumento de casos, impulsado por la propagación del virus a través de gotitas y aerosoles. La transmisión nosocomial del SRAS-Cov-2 se ha observado desde el inicio del brote en Wuhan, lo que supone un reto adicional para la calidad de vida de los pacientes. Estudios internacionales realizados en hospitales informan de incidencias de infecciones nosocomiales por COVID-19 de entre el 11% y el 44%. Objetivo: Identificar la proporción de infección nosocomial por SARS-CoV-2 en Brasil entre marzo de 2020 y diciembre de 2022. Metodología: Se trata de un estudio analítico, retrospectivo y transversal sobre la proporción de infección nosocomial por SARS-CoV -2 en Brasil, utilizando datos secundarios del Sistema de Información de Vigilancia Epidemiológica de Influenza. La variable dependiente analizada fue la proporción de infección nosocomial por SARS-CoV-2. Como variables independientes exploratorias se utilizaron: grupo de edad, sexo, comorbilidades y macrorregión de residencia. Resultados:El estudio identificó una proporción de casos nosocomiales del 2,58%, siendo mayor en el tercer año de la pandemia de 2022 (5,5%) en la región Norte (7,57%), entre individuos de 18 a 59 años (6,93%). Conclusiones:Este estudio de casos de COVID-19 hospitalizados en Brasil revela una proporción de 2,58% entre 2020 y 2022, con asociaciones identificadas en relación a la región, edad y comorbilidades. Las disparidades en relación a estudios internacionales sugieren la presencia de cuestiones metodológicas específicas. Esta investigación es de extrema importancia para orientar estrategias preventivas y mejorar el control de las infecciones hospitalarias (AU).

Control metabólico de pacientes diabéticos tipo 2 tratados con empagliflozina: serie de casos / Metabolic control in type 2 diabetic patients treated with empagliflozin: A case series

Introducción La diabetes mellitus tipo 2 es una enfermedad de alta prevalencia y está asociada a mayor morbimortalidad. Debido al bajo porcentaje de compensación, se han buscado nuevas estrategias de tratamiento farmacológico, como los inhibidores del cotransportador sodio-glucosa tipo 2. Objetivo Describir la evolución de pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor, ubicado en el sector poniente de la Región Metropolitana, Chile. El objetivo primario fue evaluar la eficacia del medicamento respecto a hemoglobina glicosilada A1c. Los objetivos secundarios fueron registrar el logro de hemoglobina glicosilada A1c igual o menor a 7,5% según análisis de supervivencia. Luego, consignar el cambio en la velocidad de filtración glomerular y en la excreción urinaria de albúmina post tratamiento. Métodos Revisión de ficha clínica de todos los pacientes tratados con empagliflozina desde noviembre de 2019 a junio de 2023. Media de seguimiento de 19 (de 16,3 a 40) meses. Para comparación entre valores de hemoglobina glicosilada A1c según rangos de seguimiento, se utilizó prueba T de Student de términos pareados o prueba de Wilcoxon. Resultados Se estudió a 58 pacientes, 15 hombres y 43 mujeres (74,1%). Edad 58,5 ± 9,2 años, rango de 35 a 75 años. Hemoglobina glicosilada A1c basal de 10,3 ± 1,6% y 8,98% ± 2,2 en un rango de seguimiento de 18 a 24 meses post tratamiento, resultando en un descenso de 1,27% (p = 0,002; intervalo de confianza 95%: 0,5 a 2,03). El efecto adverso más frecuente fue infección del tracto urinario. Conclusiones Los pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor lograron un mejor control glicémico con pocos efectos adversos.

Background Type 2 diabetes mellitus is a highly prevalent disease and is associated with increased morbidity and mortality. Due to the low percentage of adequate glycemic control, new strategies for the treatment of type 2 diabetes mellitus have been sought, including sodium-glucose cotransporter type 2 inhibitorss. Objective To describe the evolution of patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital. The primary objective was to evaluate the efficacy of the medication regarding glycosylated hemoglobin A1c (HbA1c). The secondary objectives were: 1) achievement of HbA1c equal to or less than 7.5% according to survival analysis. 2) Change in glomerular filtration rate and urinary albumin excretion post treatment. Methods Review of clinical records of all patients treated with empagliflozin from November 2019 to June 2023. Average follow-up of 19 (16.3 to 40) months. To compare HbA1c values according to follow-up ranges, the paired T test or Wilcoxon test was used. Results We included 58 patients, 15 men and 43 women (74.1%), with an average age of 58.5 ± 9.2 years, ranging from 35 to 75 years. Baseline HbA1c of 10.3 ± 1.6% and 8.98% ± 2.2 in a follow-up of 18 to 24 months post-treatment, resulted in a decrease of 1.27% (p = 0.002; confidence interval 95%: 0.5 to 2.03). The most common adverse effect was urinary tract infection. Conclusions Patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital achieved better glycemic control with few adverse effects.

Costo y porcentaje de gasto en salud por COVID-19 en primer nivel de atención / Cost and percentage of health spending by COVID-19 at the first level of care

Antecedentes. Ante la pandemia de COVID-19 el sistema de salud reasignó recursos económicos para la atención. Objetivo. Determinar el costo de la atención y el porcentaje del gasto en salud por COVID-19 en una unidad de medicina familiar de primer nivel de atención. Metodología. Estudio de costo y porcentaje de gasto en COVID-19 en una unidad de primer nivel de atención. Se identificaron los servicios generales y finales, para construir el costo fijo se utilizó la técnica de tiempos y movimientos, se identificaron el total de partidas presupuestales ejercidas en la unidad médica para cada uno de los servicios, para desagregar el gasto de los servicios generales a los finales se construyeron ponderadores. El costo variable se realizó con la técnica consenso de expertos y microcosteo. El costo promedio se relacionó con la productividad por servicio y con el total de pacientes atendidos por COVID-19, el resultado se relacionó con el presupuesto ejercido de la unidad. Resultados. El costo anual de la atención de COVID-19 en módulo respiratorio fue 158.597,25 dólares americanos, en medicina familiar fue 192.549,36 dólares americanos, el costo total ejercido en el año 2021 para atención de SARS COV 2 en una unidad de primera atención fue 351.146,61 dólares americanos. Esta cantidad representa el 9,6 % del gasto en salud. Conclusión. El costo en atención de COVID-19 y el porcentaje del gasto en salud en primer nivel de atención es elevado (AU)

Background. In the COVID-19 pandemic, the health system reallocated financial resources for care. Objetive. To determine the cost of care and the percentage of health spending due to COVID-19 in a first level care family medicine unit. Metodology. Study of the cost and percentage of spending on COVID-19 in a first-level care unit. The general and final services were identified, to construct the fixed cost, the technique of times and movements was used, the total budget items exercised in the medical unit for each of the services were identified, to disaggregate the expense of general services to the endings were constructed weights. Variable costing was performed using the expert consensus technique and microcosting. The average cost was related to productivity per service and to the total number of patients treated for COVID-19, the result was related to the budget used by the unit. Results. The annual cost of COVID-19 care in the respiratory module was 158.597,25 US dollars, in family medicine it was 192.549,36 US dollars, the total cost incurred in 2021 for SARS COV 2 care in a unit of first attention was 351.146,61 US dollars. This amount represents 9,6% of health spending. Conclusion. The cost of COVID-19 care and the percentage of health spending at the first level of care is high (AU)

Láser CO2 vaginal, indicaciones y aplicaciones / Vaginal CO2 laser, indications and applications

El síndrome genitourinario es una entidad hoy en día cada vez más frecuente en la mujer posmenopáusica, con signos y síntomas muy característicos que llevan a la pérdida de calidad de vida de las pacientes, generados por la disminución de estrógenos. Su diagnóstico se realiza mediante una buena historia clínica, exámenes hormonales, estudios urodinámicos y de pH vaginal. Su clínica varía desde sequedad vaginal, atrofia de la misma, vaginitis a repetición, pérdida de orina al esfuerzo, nicturia y dispareunia. A los largo de los años se han protocolizado diferentes tratamientos como reemplazos hormonales, lubricantes y cirugías invasivas vaginales. Pero en los últimos años ha aparecido una nueva terapéutica de láser CO2 fraccionado. Materiales y método. Se realizó un estudio retrospectivo de seis años de evolución, entre los años 2017 y 2023, con más de 300 pacientes tratadas con tecnología láser CO2 fraccionado, con criterios de inclusión y exclusión, protocolizando 3 sesiones cada 30 días y controles hasta los 6 meses. Resultados. Para evaluar los resultados se diseñó una encuentra de satisfacción de 5 puntos, la cual fue presentada luego de cada sesión, encontrando un alto grado de satisfacción en la mejoría clínica a medida que transcurrían las sesiones, con un muy bajo índice de complicaciones. También biopsias con mejorías histológicas que demuestran resultados. Discusión. La aplicación de esta nueva tecnología láser nos abre una posibilidad terapéutica segura, rápida y efectiva para mejorar la sintomatología y calidad de vida de nuestras pacientes con síndrome genitourinario, sumando una nueva terapéutica a todo el arsenal de tratamientos médico-quirúrgicos disponibles a la fecha. Conclusiones. El síndrome genitourinario es una entidad prácticamente inevitable, con síntomas desde leves a graves, que afecta la calidad de vida personal, sexual y social. Los tratamientos hasta la fecha hormonales, tópicos o quirúrgicos han dado mediocres resultados sin estar exentos de complicaciones, por lo que la aparición de la tecnología láser CO2 fraccionada nos ha dado el plus necesario para aportar un tratamiento seguro, eficaz, con mínimas complicaciones y una curva de aprendizaje pequeña

Genitourinary syndrome is an increasingly frequent entity in postmenopausal women today, with very characteristic signs and symptoms that lead to a loss of quality of life in patients, generated by estrogen depletion, whose diagnosis is made through a good clinical history, hormonal tests, urodynamic and vaginal pH studies. Its symptoms vary from vaginal dryness, vaginal atrophy, repeated vaginitis, loss of urine on exertion, nocturia and dyspareunia. Over the years, different treatments have been protocolized, such as hormone replacements, lubricants, and invasive vaginal surgeries. But in recent years a new fractionated CO2 laser therapy has appeared. Materials and method. A retrospective study of six years of evolution was carried out, between the years 2017 and 2023, with more than 300 patients treated with fractionated CO2 laser technology, with inclusion and exclusion criteria, protocolizing 3 sessions every 30 days and controls until the 6 months. Results. To evaluate the results, a 5-point satisfaction score was designed, which was presented after each session, finding a high degree of satisfaction in the clinical improvement as the sessions progressed with a very low indication of complications. Also biopsies with histological improvements that demonstrate results. Discussion. The application of this new laser technology opens up a safe, fast and effective therapeutic possibility to improve the symptoms and quality of life of our patients with genitourinary syndrome, adding a new therapeutic option to the arsenal of medical-surgical treatments available to date. Conclusions. Genitourinary syndrome is a practically inevitable entity, with symptoms ranging from mild to severe, affecting the quality of personal, sexual and social life. The hormonal, topical or surgical treatments to date have given mediocre results, not being free of complications, so the appearance of fractionated CO2 laser technology has given us the necessary extra to provide a safe, effective treatment, with minimal complications. and a small learning curve.

Celecoxib: Antiangiogenic and Antitumoral Action / Celecoxib: Acción Antiangiogénica y Antitumoral

SUMMARY: Angiogenesis, a process by which new blood vessels are generated from pre-existing ones, is significantly compromised in tumor development, given that due to the nutritional need of tumor cells, pro-angiogenic signals will be generated to promote this process and thus receive the oxygen and nutrients necessary for its development, in addition to being a key escape route for tumor spread. Although there is currently an increase in the number of studies of various anti-angiogenic therapies that help reduce tumor progression, it is necessary to conduct a review of existing studies of therapeutic alternatives to demonstrate their importance.

La angiogénesis, proceso por el cual se generan nuevos vasos sanguíneos a partir de otros preexistentes, se encuentra comprometida de forma importante en el desarrollo tumoral, dado que por necesidad nutritiva de las células tumorales se generarán señales pro angiogénicas para promover este proceso y así recibir el oxígeno y los nutrientes necesarios para su desarrollo, además de ser una ruta de escape clave para la diseminación tumoral. Si bien, actualmente existe un aumento en la cantidad de estudios de diversas terapias anti angiogénicas que ayudan a reducir el avance tumoral, es necesario realizar una revisión de los estudios existentes de alternativas terapéuticas para demostrar su importancia.

Overexpression SPRY2 Suppresses Esophageal Squamous Cell Carcinoma Progression Via Inactivation of ERK/AKT Signaling / La Sobreexpresión SPRY2 Suprime la Evolución del Carcinoma de Células Escamosas de Esófago Mediante la Inactivación de la Señalización ERK/AKT

SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.

El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.

Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up

Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

Evidencias del efecto del grano integral en las enfermedades crónicas no transmisibles

Los cereales integrales son una categoría de alimentos fundamental para la dieta humana y representan una fuente invaluable de carbohidratos, proteínas, fibras, fitoquímicos, minerales y vitaminas. Muchos estudios han demostrado que el consumo de cereales integrales está relacionado con un menor riesgo de enfermedades crónicas no transmisibles. Sin embargo, varios de sus efectos positivos para la salud parecen desaparecer cuando se refinan los cereales. La pregunta de investigación es cuál sería el efecto de los cereales integrales en la prevención de enfermedades crónicas no transmisibles. Este artículo describe los efectos positivos del consumo de cereales integrales en la prevención de estas enfermedades. Para ello, se realiza una descripción narrativa que revisa los antecedentes disponibles sobre: a) situación epidemiológica en Chile y su relación con la alimentación; b) consumo de cereales integrales en el mundo y en Chile; y c) el efecto del consumo de cereales integrales en la reducción del riesgo de enfermedad cardiovascular. obesidad, diabetes tipo 2 y cáncer. Los antecedentes generales son muy alentadores sobre el efecto positivo del consumo de cereales integrales sobre determinadas enfermedades, especialmente las de origen metabólico. Sin embargo, la incertidumbre de algunas asociaciones negativas merece mayor atención.

Whole grains are a fundamental food category for the human diet and represent an invaluable source of carbohydrates, proteins, fibers, phytochemicals, minerals and vitamins. Many studies have shown that consumption of whole grains is linked to a lower risk of chronic non-communicable diseases. However, several of its positive health effects seem to disappear when grains are refined. The research question is what would be the effect of whole grains in the prevention of Chronic Non-Communicable Diseases. This article describes the positive effects of whole grain consumption in these diseases.To this end, a narrative description is made that reviews the available background on: a) epidemiological situation in Chile and its relationship with diet; b) consumption of whole grains in the world and in Chile; and c) the effect of whole grain consumption on reducing the risk of cardiovascular disease. obesity, type 2 diabetes, and cancer. The general background is very encouraging for a positive effect of whole grain consumption on certain diseases, especially those of metabolic origin. However, the uncertainty of some negative associations deserves further attention.

Lineamientos técnicos para la vacunación contra el SARS-CoV-2 / Technical guidelines for vaccination against SARS-CoV-2

El objetivo general de los presentes lineamientos es establecer las disposiciones técnicas para la realización de las acciones para continuar la vacunación de la población contra el SARS-CoV-2. La priorización vacunal es una estrategia para proteger poblaciones de riesgo, evitando caer en el error de no vacunar a otros grupos cuyo riesgo puede ser bajo, pero que pueden generar enfermedad severa, complicaciones, hospitalizaciones y muerte asociada a COVID-19. En razón de lo anterior se actualizan los esquemas de vacunación frente a COVID-19, a partir de priorización de grupos poblacionales

The general objective of these guidelines is to establish technical provisions for the implementation of actions to continue the vaccination of the population against SARS-CoV-2. Vaccine prioritization is a strategy to protect at-risk populations, avoiding the error of not vaccinating other groups whose risk may be low, but which can lead to severe disease, complications, hospitalizations and death associated with VOCID-19. In view of the foregoing, vaccination schemes against VOCID-19 are updated, based on the prioritization of population groups

Telemedicine for diagnosis or treatment during Covid-19: systematic review

OBJECTIVE: To describe the use of telemedicine by health professionals for diagnosis or treatment of patients during the Covid-19 pandemic. METHOD: This is a systematic literature review of observational studies. Five databases were used. The assessment of the studies methodological quality occurred individually among the revisors and the Joanna Briggs Institute (JBI) tool was used. RESULTS: The reviewers selected 22 articles from 6,180 works. The services provided through telemedicine were consultation/screening, consultation/follow-up or monitoring, test reports, medication prescriptions and case discussions. The technological resources used were platforms using video and telephone (audio and video). The use of telemedicine made it possible to reduce their exposure to Covid-19, reduce social panic and anxiety, quickly medical specialties access and the possibility of access to diagnosis and treatment of patients with chronic and acute diseases. CONCLUSION: Telemedicine can be an important tool in healthcare, keeping patients and healthcare professionals safe during the Covid-19 pandemic.

Mecanismo y diseño de vacunas para el sars-cov-2, revisión narrativa / Mechanism and design of vaccines against sars-cov-2, narrative review / Mecanismo e desenho de vacinas para sars-cov-2, revisão narrativa

La infección por el virus SARS-CoV-2, conocida como COVID-19, ha causado alta morbilidad y mortalidad en el mundo. Después de haber descifrado el código genético del virus y haber desarrollado un gran trabajo investigativo en la creación de vacunas, con diversas estrategias de acción, se ha logrado disminuir la morbi mortalidad. Fue necesario acelerar el proceso de producción de vacunas, lo cual estuvo facilitado por el avanzado conocimiento científico en el campo de la genética y la virología, para brindar a la especie humana una protección eficaz y segura contra la agresiva y progresiva infección. Las vacunas se clasifican de acuerdo con su mecanismo de acción, existen vacunas basadas en vectores virales que no se replican, vacunas recombinantes, otras basadas en virus atenuados y virus inactivos, y (la gran novedad de la ciencia actual) las vacunas basadas en ARN mensajero y ADN. Estas últimas han demostrado una gran eficacia y seguridad en la prevención de la infección por el SARS-CoV-2, también han impactado de manera fuerte, por lo que han reducido la infección y la mortalidad en la población. En consecuencia, cada día que pasa desde que se inició el periodo de vacunación mundial, se evidencia una reducción en la curva de contagio y mortalidad por COVID-19.

The infection produced by the SARS-CoV-2 virus, known as COVID-19, has caused high morbidity and mortality across the world. After having deciphered the virus's genoma and carried out investigative endeavors that led to the creation of a variety of vaccines with different mechanisms of action, it has been possible to decrease the morbidity and mortality associated with the virus. It was necessary to accelerate the vaccine production process, which was facilitated by advanced scientific knowledge within the disciplines of genetics and virology, in order to provide the human species with a safe and effective form of protection against the aggressive and progressive infection. Vaccines are classified differently depending on their action mechanisms: there are some based on non-replicating viral vectors, recombinant vaccines, ones that are based on attenuated or inactivated viruses, and (the greatest novelty of current scientific developments) vaccines based on DNA and messenger RNA. The latter has demonstrated significant efficacy and safety in the prevention of the SARS-CoV-2 infection as observed in preliminary studies, and they have meaningfully impacted the population by reducing the rates of infection and mortality. As a result, decreased levels of spread of and mortality from COVID-19 have been evidenced across the globe following the beginning of the vaccine distribution period.

A infecção pelo vírus SARS-CoV-2, conhecido como COVID-19, tem causado elevada morbidade e mortalidade no mundo. Depois de ter decifrado o código genético do virus e de ter realizado um grande trabalho de investigação na criação de vacinas, com diversas estratégias de ação, a morbilidade e a mortalidade foram reduzidas. Foi necessário acelerar o processo de produção de vacinas, facilitado por conhecimentos científicos avançados no domínio da genética e da virologia, para proporcionar à espécie humana uma proteção eficaz e segura contra a infecção agressiva e progressiva. As vacinas são classificadas de acordo com seu mecanismo de ação, existem vacinas baseadas em vetores virais que não se replicam, vacinas recombinantes, outras baseadas em virus atenuados e vírus inativos, e (a grande novidade da ciência atual) vacinas baseadas em RNA mensageiro e ADN. Estas últimas demonstraram grande eficácia e segurança na prevenção da infecção por SARS-CoV-2, mas também tiveram um forte impacto, razão pela qual reduziram a infecção e a mortalidade na população. Consequentemente, a cada dia que passa desde o início do período global de vacinação, fica evidente uma redução na curva de contágio e mortalidade por COVID-19.

Role of Histone Methyltransferase in Fibrosis and Traditional Chinese Medicine Treatment： A Review / 中国实验方剂学杂志

Fibrosis， a tumor-like lesion between benign tissue and malignant tumor， mostly occurs in the liver， kidney， heart， lung， bone marrow and other organs and tissues. It can affect almost every organ and eventually induce multiple organ failure and cancers， seriously endangering human life. It will be of great importance to prevent cancer if the disease can be opportunely blocked in the fibrotic stage. The pathogenesis of fibrosis is still not completely clear. It is of great clinical significance to study the occurrence， development， and mechanism of fibrosis as well as to screen new therapeutic targets. Enhancer of zeste homolog 2 （EZH2） is mainly located in the nucleus and involved in the formation of the polycomb repressive complex 2. EZH2 is a methyltransferase which makes the lysine on position 27 of histone H3 （H3K27me3） undergo trimethyl modification induces gene silencing through classical or nonclassical actions， so as to inhibit or activate transcription. EZH2 plays a critical role in cell growth， proliferation， differentiation， and apoptosis， which is regulated by different targets and signaling pathways. EZH2 regulates the transformation of myofibroblasts and participates in the fibrosis of multiple organs. Recent studies have shown that EZH2 plays a role in fibrosis-related pathophysiological processes such as epithelial-mesenchymal transition， oxidative stress， and inflammation. EZH2 as the target of fibrosis， EZH2 inhibitors， and EZH2-related traditional Chinese medicine （TCM） formula and active compounds have gradually become hot research directions. EZH2 may be a powerful target for organ fibrosis. Exploring the structure， function， and distribution of EZH2， the role of EZH2 in fibrosis， the EZH2 inhibitors， and TCM formulas and active components targeting EZH2 has great meanings. This paper reviews the research progress in EZH2 and fibrosis， providing new ideas for the diagnosis， treatment， and drug development of fibrosis.

Compatibility Theory of Yiqi Zengmian Prescription as Vaccine Adjuvant / 中国实验方剂学杂志

ObjectiveThis study explored the application of Yiqi Zengmian prescription as a vaccine adjuvant， aiming to provide a new scheme for the prevention and control of corona virus disease 2019（COVID-19） with traditional Chinese medicine （TCM）. By analyzing the compatibility and efficacy， this paper examines the compatibility effect of Yiqi Zengmian prescription， which is modified from the classic tonifying agent Si Junzitang， as a vaccine adjuvant. MethodUsing the Database of Ancient Classical Prescriptions， this paper analyzed the composition of Yiqi Zengmian prescription and probed into the theoretical basis for the compatibility of this prescription from the properties， medicine combination， and efficacy. Furthermore， the compatibility effect of this prescription with vaccines was analyzed. ResultAs a TCM prescription， Yiqi Zengmian prescription focuses on the lung and spleen and enhances the Qi in the two organs. The lung governs Qi movement. The body breathes fresh air through the lungs and exchanges the turbid gas in the lungs， and the gas circulates alternately in the lungs to ensure the normal breathing of the human body. The spleen governing transportation and transformation is the hub for Qi movement， and Qi is the embodiment of metabolic function. By regulating qi movement and enhancing the functions of Qi and blood， Yiqi Zengmian prescription can enhance the immunogenicity of the vaccine， which provides a theoretical basis for enhancing the immune effects of vaccines. ConclusionYiqi Zengmian prescription has the effects of replenishing Qi and invigorating spleen， regulating Qi and drying dampness， and enhancing immunity. The in-depth analysis of the TCM theory of Yiqi Zengmian prescription as a vaccine adjuvant and the results of clinical and laboratory studies suggest that Yiqi Zengmian prescription may enhance the induction of immune response after vaccination and maintain the immune memory. However， the mechanism of Yiqi Zengmian prescription in regulating the complex immune network remains to be elucidated.

Comparison on Ameliorating Effect of Arisaematis Rhizoma and Arisaematis Rhizoma Preparatum on Allergic Asthma in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effects and difference in the effects of Arisaematis Rhizoma （AR） before and after processing （i.e.， Arisaematis Rhizoma Preparatum， ARP） with Zingiberis Rhizoma Recens-Alumen on allergic asthma in rats and to provide a basis for the theory of processing improving the efficacy. MethodA rat model of allergic asthma was established in 70 SD rats by intraperitoneal injection of ovalbumin （OVA）-aluminum hydroxide. The rats were administrated with the aqueous extracts of AR （1.2， 0.3 g∙kg-1） and ARP （1.2， 0.3 g∙kg-1） aqueous extracts by gavage， and montelukast sodium （0.001 g∙kg-1） was used as the positive drug. The T helper cell type 1/type 2 （Th1/Th2） ratio in the serum and bronchoalveolar lavage fluid （BALF） and percentages of inflammatory cells in BALF were determined. Polymerase chain reaction （PCR） was employed to determine the mRNA level of mucin 5AC （MUC5AC） in the lung tissue. The pathological changes in the lung tissue were observed by hematoxylin-eosin （HE） staining and PAS staining. Immunohistochemical assay was employed to measure the expression of c-Jun amino-terminal kinase （JNK）， extracellular signal regulated protein kinase （ERK）， and p38 mitogen-activated protein kinase （p38 MAPK） in rat lung tissue. Western blot was employed to determine the protein levels of ERK， p-ERK， JNK， p-JNK， p38， p-p38 in the lung tissue. The effects of AR and ARP were compared based on overall desirability. ResultCompared with the blank group， the levels of interleukin-12 （IL-12） and γ interferon （IFN-γ） in serum and BALF of rats in the model group were significantly lower （P<0.05， P<0.01）， and the levels of interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） were significantly higher （P<0.05， P<0.01）. Compared with the model group， the serum and BALF contents of IL-12 and IFN-γ in rats in the montelukast sodium group， high-dose AR group and high-dose ARP group were significantly higher （P<0.05， P<0.01）， and the contents of IL-4， IL-5 and IL-13 were significantly lower （P<0.05， P<0.01）， and the serum contents of IFN-γ in rats in the low-dose AR group and low-dose ARP group were in BALF was significantly higher （P<0.05） and IL-4 and IL-13 were significantly lower （P<0.05， P<0.01）， the percentages of macrophages， lymphocytes， neutrophils， and eosinophils were reduced in BALF， and the expression of JNK/ERK/p38 MAPK signaling pathway and MUC5AC protein was inhibited in lung tissues. Overall assessment of the normalized analysis revealed that the ARP group was slightly more potent than the AR group after administration of the same dose. ConclusionAR and ARP can effectively treat allergic asthma by inhibiting JNK/ERK/p38 MAPK signaling pathway， and the effect is better after concoction， which can provide data support for its "concoction efficiency".

Tongxie Yaofang Regulates Expression of NKG2DL to Enhance Anti-tumor Effect of NK Cells in Colon Cancer under Chronic Stress / 中国实验方剂学杂志

ObjectiveTo observe the effect of Tongxie Yaofang on the function of tumor-related natural killer （NK） cells under chronic stress and explore the possible molecular mechanism. MethodFifty SPF-grade BABL/C male mice were randomized into normal， model， and low-， medium-， and high-dose （6.825， 13.65， and 27.3 g·kg-1， respectively） Tongxie Yaofang groups， with 10 mice in each group. Other groups except the blank group were subjected to 7 days of chronic restraint stress， and then forced swimming and tail suspension tests were carried out to evaluate the modeling performance. After the successful modeling， rats in Tongxie Yaofang groups were administrated with low-， medium-， and high-doses of Tongxie Yaofang by gavage， while those in the other groups were administrated with normal saline by gavage. After 14 days， each group of mice was inoculated with subcutaneous colon cancer to establish the model of colon cancer under chronic stress. The pathological changes of the tumor tissue in each group of mice were observed using hematoxylin-eosin （HE） staining. The content of CD49b-positive cells in the peripheral blood and tumor tissue of mice was measured by flow cytometry. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the content of molecules associated with NK cell activation in the peripheral blood. Western blot was employed to determine the protein levels of major histocompatibility complex class Ⅰ polypeptide-related sequences A and B （MICA+MICB） and UL-16-binding protein 1 （ULBP1） in the tumor tissue. ResultCompared with the normal group， the model group showed a decrease in 5-hydroxytryptamine （5-HT） content and an increase in corticosterone （CORT） content in the serum （P<0.05）. Compared with the model group， Tongxie Yaofang increased the 5-HT content and decreased the CORT content （P<0.05， P<0.01）. Compared with the normal group， the modeling increased the tumor volume and weight （P<0.05）， while Tongxie Yaofang inhibited such increases with no statistical significance. The tumor cells in the model group presented neat arrangement， irregular shape， uneven size， obvious atypia， common nuclear division， and small necrotic area， and blood vessels were abundant surrounding the tumor cells. Compared with the model group， Tongxie Yaofang groups showed sparse arrangement of tumor cells， different degrees of patchy necrosis areas in the tumor， and karyorrhexis， dissolution， and nuclear debris in the necrotic part. Compared with the normal group， the model group showed reduced CD49b-positive cells in the peripheral blood and tumor tissue （P<0.01）. Compared with the model group， Tongxie Yaofang increased CD49b-positive cells （medium dose P<0.01， high dose P<0.05， P<0.01）. Compared with the normal group， the modeling lowered the serum levels of granzymes-B （Gzms-B）， perforin （PF）， interferon （IFN）-γ， and tumor necrosis factor （TNF）-α （P<0.05， P<0.01）. Compared with the model group， low-dose Tongxie Yaofang elevated the serum levels of PF， Gzms-B， and TNF-α （P<0.05， P<0.01）， and medium-dose Tongxie Yaofang elevated the serum levels of Gzms-B， PF， IFN-γ， and TNF-α （P<0.05， P<0.01）. In addition， high-dose Tongxie Yaofang elevated the serum levels of PF， IFN-γ， and TNF-α （P<0.01）. Compared with the normal group， the model group presented down-regulated protein level of ULBP1 （P<0.05）. Compared with the model group， low-， medium-， and high-dose Tongxie Yaofang up-regulated the protein level of ULBP1 （P<0.05， P<0.01）， and medium- and high-dose Tongxie Yaofang up-regulated the protein level of MICA+MICB （P<0.05， P<0.01）. ConclusionTongxie Yaofang may promote NK cell activation by up-regulating the expression of MICA+MICB and ULBP1， thereby delaying the progression of colon cancer under chronic stress.