Estimated glomerular filtration rate in clinical practice: Consensus positioning of the Brazilian Society of Nephrology (SBN) and Brazilian Society of Clinical Pathology and Laboratory Medicine (SBPC/ML) / Estimativa da taxa de filtração glomerular na prática clínica: posicionamento consensual da Sociedade Brasileira de Nefrologia (SBN) e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial (SBPC/ML)

ABSTRACT Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

RESUMO A doença renal crônica (DRC) representa um dos principais problemas de saúde pública da atualidade. A dosagem da creatinina sérica e a estimativa da taxa de filtração glomerular (TFG) são as principais ferramentas para avaliação da função renal. Para a estimativa da TFG, existem diversas equações, sendo a mais recomendada a CKD-EPI (Chronic Kidney Disease - Epidemiology). Existem ainda algumas controvérsias com relação à dosagem da creatinina sérica e da estimativa da TFG, uma vez que vários fatores podem interferir nesse processo. Uma importante mudança recente foi a retirada da correção por raça das equações para estimativa da TFG, que superestimavam a função renal, e consequentemente retardavam a implementação de tratamentos como diálise e transplante renal. Neste documento de consenso da Sociedade Brasileira de Nefrologia e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial são revisados os principais conceitos relacionados à avaliação da função renal, possíveis controvérsias existentes e recomendações para a estimativa da TFG na prática clínica.

Relationship of hemoglobin levels with outcomes in deceased donor kidney transplant: a retrospective cohort study / Relação dos níveis de hemoglobina com desfechos em transplante renal de doador falecido: um estudo de coorte retrospectivo

ABSTRACT Introduction: Anemia is frequent in patients undergoing replacement therapy for kidney failure. Anemia in the pre- and post-transplantation period might be related to kidney transplant outcomes. The current study therefore sought to assess the relationship between anemia, delayed allograft function (DGF), chronic kidney allograft dysfunction (CAD), and death from any cause following kidney transplantation from a deceased donor. Methods: This was a retrospective study with 206 kidney transplant patients of deceased donors. We analyzed deceased donors' and kidney transplant patients' demographic data. Moreover, we compared biochemical parameters, anemia status, and medicines between DGF and non-DGF groups. Afterward, we performed a multivariate analysis. We also evaluated outcomes, such as CAD within one year and death in ten years. Results: We observed a lower frequency of pre-transplant hemoglobin concentration (Hb) but higher frequency of donor-serum creatinine and red blood transfusion within one week after transplantation in the group with DGF. In addition, there was an independent association between Hb concentration before transplantation and DGF [OR 0.252, 95%CI: 0.159-0.401; p < 0.001]. There was also an association between Hb concentration after six months of kidney transplantation and both CAD [OR 0.798, 95% CI: 0.687-0.926; p = 0.003] and death from any cause. Conclusion: An association was found between pre-transplantation anemia and DGF and between anemia six months after transplantation and both CAD and death by any cause. Thus, anemia before or after transplantation affects the outcomes for patients who have undergone kidney transplantation from a deceased donor.

RESUMO Introdução: A anemia é frequente em pacientes submetidos à terapia substitutiva para insuficiência renal. A anemia nos períodos pré e pós-transplante pode estar relacionada aos desfechos do transplante renal. Portanto, o presente estudo buscou avaliar a relação entre anemia, função retardada do enxerto (FRE), disfunção crônica do enxerto renal (DCE) e óbito por qualquer causa após transplante renal de doador falecido. Métodos: Este foi um estudo retrospectivo com 206 pacientes transplantados renais de doadores falecidos. Analisamos dados demográficos de doadores falecidos e pacientes transplantados renais. Além disso, comparamos parâmetros bioquímicos, status de anemia e medicamentos entre os grupos FRE e não-FRE. Posteriormente, realizamos uma análise multivariada. Também avaliamos desfechos, como DCE em um ano e óbito em dez anos. Resultados: Observamos menor frequência de concentração de hemoglobina (Hb) pré-transplante, mas maior frequência de creatinina sérica do doador e transfusão de hemácias no período de uma semana após o transplante no grupo FRE. Além disso, houve associação independente entre a concentração de Hb antes do transplante e a FRE [OR 0,252; IC 95%: 0,159-0,401; p < 0,001]. Houve também associação entre a concentração de Hb após seis meses de transplante renal e ambos, DCE [OR 0,798; IC95%: 0,687-0,926; p = 0,003] e óbito por qualquer causa. Conclusão: Encontrou-se uma associação entre anemia pré-transplante e FRE e entre anemia seis meses após o transplante e ambos, DCE e óbito por qualquer causa. Assim, a anemia antes ou após o transplante afeta os desfechos de pacientes que foram submetidos a transplante renal de doador falecido.

Funcionamiento ejecutivo y metacognición en la alta capacidad intelectual / Executive functioning and metacognition in high intel lectual capacity

Resumen Introducción : Las funciones ejecutivas y la meta cognición se integran para la gestión de recursos inte lectuales, en estrecha relación con la inteligencia, su funcionamiento y resultados, especialmente interesan te para comprender la expresión y desarrollo, más o menos óptimos, de la alta capacidad intelectual (ACI). El Objetivo del trabajo es conocer la relación entre las funciones ejecutivas (y componentes) y la metacognición (y componentes) en escolares con ACI. Materiales y Métodos : Las medidas de funcionamien to y ejecutivo, metacognitivo y de perfeccionismo ex traídas en una muestra de n= 147 escolares con ACI son analizadas estadísticamente mediante el Path análisis. Resultados : Se obtiene un modelo ajustado en el que se relacionan los distintos componentes ejecutivos con los metacognitivos. Discusión : Se concluye y discute el modelo integrador entre función ejecutiva y metacognición y su papel me diador, como endofenotipo entre la dotación genética y la expresión de rendimiento de los recursos, sugiriendo la transferencia de resultados a la educación de la alta capacidad intelectual para la óptima y ética expresión del alto potencial.

Abstract Introduction : Executive functions and Metacogni tion are integrated for the management of intellectual resources in close relation to intelligence its function ing and results; they are specially interesting for un derstanding the expression and development of high intellectual abilility (HIA). The aim of the study is to find out the relationship between executive functions (and components) and metacognition (and components) in schoolchildren with HIA. Materials and Method : Measures of executive and metacognitive functioning and perfectionism were ex tracted from a sample of n= 147 schoolchildren with HIA. Results : statistical analyses using Path analysis, of fered an adjusted model in which the different ex ecutive components are related to the metacognitive components. Discussion : We conclude and discuss the integrative model between executive function and metacognition and its mediating role as an endophenotype between genetic endowment and the expression of resource performance, suggesting the transfer of results to the education of high intellectual ability for the optimal and ethical expression of high potential.

An Assessment of Ankle Function, Oxidative Damage, and Inflammatory Factor Levels in Minimally Invasive Ankle Joint Fusion Surgery for the Treatment of Traumatic Ankle Osteoarthritis

SUMMARY: Traumatic ankle osteoarthritis is a degenerative condition resulting from traumatic injuries. The objective of this study was to evaluate the impact of minimally invasive ankle joint fusion surgery on ankle function, oxidative damage, and inflammatory factor levels in traumatic ankle osteoarthritis patients. A total of 112 traumatic ankle osteoarthritis patients treated in our hospital from January 2022 to January 2023 were enrolled. They were randomly rolled into a control group (Group C) and an experimental group (Group E), with the former undergoing conventional open ankle joint fusion surgery and the latter receiving minimally invasive ankle joint fusion surgery. A comparison was made between the two groups based on American Orthopedic Foot and Ankle Society (AOFAS), bony fusion rates, and visual analog scale (VAS) scores at pre-operation, and at 1, 2, and 3 months post-operation. Additionally, serum oxidative damage indicators and inflammatory factor levels were measured to evaluate the recovery effects in both groups. Relative to Group C, Group E showed drastically increased AOFAS scores and bony fusion rates (P<0.05), as well as greatly decreased VAS scores (P<0.05). Moreover, Group E exhibited more pronounced improvements in oxidative damage indicators and inflammatory factors versus Group C (P<0.05). Minimally invasive ankle joint fusion surgery drastically improves ankle function in traumatic ankle osteoarthritis patients and reduces levels of oxidative damage and inflammatory response. This provides an important clinical treatment option.

La osteoartritis traumática del tobillo es una afección degenerativa resultante de lesiones traumáticas. El objetivo de este estudio fue evaluar el impacto de la cirugía mínimamente invasiva de fusión de la articulación talocrural sobre la función del tobillo, el daño oxidativo y los niveles de factor inflamatorio en pacientes con osteoartritis traumática del tobillo. Se inscribieron un total de 112 pacientes con artrosis traumática de tobillo tratados en nuestro hospital desde enero de 2022 hasta enero de 2023. Fueron divididos aleatoriamente en un grupo de control (Grupo C) y un grupo experimental (Grupo E), donde el primero se sometió a una cirugía de fusión de la articulación talocrural abierta convencional y el segundo recibió una cirugía de fusión de la articulación talocrural mínimamente invasiva. Se realizó una comparación entre los dos grupos según la Sociedad Estadounidense de Ortopedia de Pie y Tobillo (AOFAS), las tasas de fusión ósea y las puntuaciones de la escala visual analógica (EVA) antes de la operación y 1, 2 y 3 meses después de la operación. Además, se midieron los indicadores de daño oxidativo sérico y los niveles de factor inflamatorio para evaluar los efectos de la recuperación en ambos grupos. En relación con el grupo C, el grupo E mostró puntuaciones AOFAS y tasas de fusión ósea drásticamente aumentadas (P <0,05), así como puntuaciones VAS muy disminuidas (P <0,05). Además, el grupo E exhibió mejoras más pronunciadas en los indicadores de daño oxidativo y factores inflamatorios en comparación con el grupo C (P <0,05). La cirugía de fusión de la articulación talocrural mínimamente invasiva mejora drásticamente la función del tobillo en pacientes con osteoartritis traumática del tobillo y reduce los niveles de daño oxidativo y la respuesta inflamatoria. Esto proporciona una importante opción de tratamiento clínico.

Parameters of pubertal growth spurt in children and adolescents living at high altitude in Peru

Abstract Objectives: The aim was to estimate the pubertal growth height of children and adolescents living in a high-altitude region of Peru using the Preece-Baines model 1 (1 PB). Methods: A cross-sectional study was conducted in schoolchildren from the department of Puno (Peru) between 3841 and 3874 masl. The age range was between 4 and 17 years. Standing height was evaluated. 1 PB was used to infer the mathematical and biological parameters of stature. Results: Mathematical parameters estimated by the 1 PB model reflected small residual standard error (RSE) values in both sexes (0.25 in boys and 0.27 in girls). In boys, the age at which peak velocity was reached (APHV) was estimated at 13.21 ± 0.33years. While in girls it was 9.96 ± 0.26years (p < 0.05). In general, girls reached APHV (y) 3.25 years earlier than boys. On the other hand, the growth velocity of maximum height [APHV (cm/y)] of boys was higher (6.33 ± 6.06 cm/y) relative to girls (6.06 ± 0.32 cm/y). Estimated final adult height (EFAH) in boys was reached at 166.020 ± 0.99 cm and height at maximum growth velocity (HPHV) was 153.07 ± 0.67 cm, while in girls they were significantly lower (EFAH; 153.74 ± 0.44 cm and HPHV: 139.73 ± 0.84 cm). Conclusions: This study showed that girls living in Puno at a high altitude in Peru reached APHV 3 years earlier than boys and at the same time reflected slower PHV. These results suggest that pubertal growth at high altitudes is slower in both sexes and especially in girls. Thus, modeling physical growth may be an important step in understanding the onset of puberty at different latitudes.

Funções neuropsicológicas de meninas privadas de liberdade em unidade socioeducativa / Neuropsychological functions of girls deprived of liberty in socio-educational unit / Funciones neuropsicológicos de niñas privadas de libertad en unidad socioeducativa

OBJETIVO: A avaliação neuropsicológica tem alta relevância na adolescência e em situação de conflito com a lei, com privação de liberdade em instituições socioeducativas, pode auxiliar, compondo abordagens psicossociais que identifiquem as funções neuropsicológicas, situando-as a partir da historicidade do indivíduo. Deste modo, para compreender esse problema, foi objetivo desse estudo avaliar e descrever as funções neuropsicológicas de adolescentes meninas privadas de liberdade em instituição socioeducativa. MÉTODOS: As participantes foram 19 meninas avaliadas com os instrumentos: Barratt Scale, Inventário de Expressão de Raiva, teste Wisconsin de classificação de cartas, protocolo neuropsicológico, questionário para uso de drogas e Hare Psychopathy Checklist Revised. RESULTADOS: O uso de drogas na vida ocorreu em 80,0% dos casos. Verificaram-se altos escores de impulsividade total (M=75,8, DP=5,4), traço de raiva (M=24,5, DP=7,3) e respostas perseverativas (M =38,5, DP =19,9). Em conjunto com PCL-R total (M=17,5, DP=3,6) e com QI total (M=79,1, DP=16,2), esses níveis auxiliaram na caracterização das funções de autocontrole. CONCLUSÕES: Os dados foram interpretados como indicativos de baixo funcionamento executivo, altos níveis de raiva, de impulsividade, de uso de drogas e de traços de psicopatia. Foram relatadas adversidades durante a infância, o que pode ter contribuído para um desempenho prejudicado nas funções cognitivas e emocionais dessas meninas.

OBJECTIVE: Neuropsychological assessment is highly relevant in adolescence and in situations of conflict with the law, with deprivation of liberty in socio-educational institutions, it can help, composing psychosocial approaches that identify neuropsychological functions, situating them based on the individual's historicity. Therefore, to understand this problem, the objective of this study was to evaluate and describe the neuropsychological functions of adolescent girls deprived of liberty in a socio-educational institution. METHODS: The participants were 19 girls evaluated with the following instruments: Barratt Scale, Anger Expression Inventory, Wisconsin Card Sorting Test, Neuropsychological protocol, drug use questionnaire and Hare Psychopathy Checklist Revised. RESULTS: Lifetime drug use occurred in 80.0% of cases. There were high scores for total impulsivity (M=75.8, SD=5,4), trait anger (M=24.5, SD=7.3) and perseverative responses (M=38.5, SD=19.9). Together with total PCL-R (M=17.5, SD=3.6) and total IQ (M=79.1, SD=16), these levels helped to characterize self-control functions. CONCLUSIONS: The data were interpreted as indicating low executive functioning, high levels of anger, impulsivity, drug use and psychopathic traits. Adversities were reported during childhood, which may have contributed to impaired performance in the cognitive and emotional functions of these girls.

OBJETIVO: La evaluación neuropsicológica es de gran relevancia en la adolescencia y en las situaciones de conflicto con la ley, con privación de libertad en instituciones socioeducativas, puede ayudar, componiendo enfoques psicosociales que identifiquen funciones neuropsicológicas, las situando en función de la historicidad del individuo. Por tanto, para comprender esta problemática, el objetivo de este estudio fue evaluar y describir las funciones neuropsicológicas de niñas adolescentes privadas de libertad en una institución socioeducativa. MÉTODOS: Las participantes fueron 19 niñas evaluadas con los siguientes instrumentos: Escala de Barratt, Inventario de Expresión de Ira, Test de clasificación de cartas de Wisconsin, protocolo neuropsicológico, cuestionario de consumo de drogas y Lista de Verificación de Psicopatía de Hare Revisada. RESULTADOS: El consumo de drogas durante la vida ocurrió en el 80,0% de los casos. Hubo puntuaciones altas en impulsividad total (M = 75,8, DE = 5,4), rasgo de ira (M = 24,5, DE = 7,3) y respuestas perseverativas (M = 38,5, DE = 19,9). Junto con el PCL-R total (M=17,5, DE=3,6) y el CI total (M=79,1, DE=16,2), estos niveles ayudaron a caracterizar las funciones de autocontrol. CONCLUSIONES: Se interpretó que los datos indicaban un bajo funcionamiento ejecutivo, altos niveles de ira, impulsividad, consumo de drogas y rasgos psicopáticos. Se informaron adversidades durante la infancia, que pueden haber contribuido al deterioro del desempeño en las funciones cognitivas y emocionales de estas niñas.

Efectividad de la Terapia Acuática en la Función Motora Gruesa en Población Infantojuvenil con Parálisis Cerebral. Una Revisión Narrativa / Effectiveness of Aquatic Therapy on Gross Motor Function in Children and Young People with Cerebral Palsy. A Narrative Review

Introducción. La parálisis cerebral (PC) es una de las principales causas de discapacidad en la población infantil, afectando diversas áreas del desarrollo como la función motora gruesa; equilibrio y marcha. Hay evidencia de los beneficios de la terapia acuática y de cómo puede complementar la rehabilitación. Objetivo. Describir la efectividad de las intervenciones acuáticas en personas con PC, determinar mejoras en la función motora gruesa uso de métodos, protocolos y dosificación. Métodos. Se analizaron 9 estudios aleatorizados controlados desde el 2012 a la fecha, seleccionados por un experto y cuyos sujetos tenían PC espástica, Gross Motor Function Classification System (GMFCS) I a IV, entre los 2 y 20 años. Post intervención acuática se reportan mejoras significativas en el promedio de los ítems medidos por Gross motor function measure (GMFM). De los métodos que contribuyeron a mejoras se encuentra Halliwick y ejercicios acuáticos sin un programa específico. Resultados. Se obtuvieron mejoras de 35 a 100 minutos, y de 12 a 30 sesiones en total. No se logra concluir el tipo de terapia más efectiva, ya que las medidas de resultado y las características de los sujetos eran diversas. Conclusión. Una dosificación mínima de 2 veces por semana, 35 minutos de intervención en un total de 16 sesiones (9,3 horas en total) pareciera mejorar la función motora gruesa, cuyos resultados son transferibles a las actividades en tierra inmediatamente, sin embargo, no se obtiene información si se mantienen a mediano o largo plazo.

Background. Cerebral palsy (CP) is one of the main causes of disability in the child population, affecting various areas of development such as gross motor function; balance and gait. There is evidence of the benefits of aquatic therapy and how it can complement rehabilitation. Objective. to describe the effectiveness of aquatic interventions in people with CP, to determine improvements in gross motor function using methods, protocols, and dosage. Methods. Nine randomized controlled studies were analyzed from 2012 to date, selected by an expert and whose subjects had spastic CP, Gross Motor Function Classification System (GMFCS) I to IV, between 2 and 20 years of age. Results. After the aquatic intervention, significant improvements were reported in the average of the Gross motor function measure (GMFM) items measured. Of the methods that contributed to improvements, there is Halliwick and aquatic exercises without a specific program. Results. Improvements were obtained from 35 to 100 minutes, and from 12 to 30 sessions in total. It is not possible to conclude the most effective type of therapy, since the outcome measures and the characteristics of the subjects were diverse. Conclusion. A minimum dosage of 2 times per week, 35 minutes of intervention in a total of 16 sessions (9.3 hours in total) seems to improve gross motor function, the results of which are immediately transferable to activities on land, however, it is not obtains information if they are maintained in the medium or long term.

Renal deficit and associated factors in children born with low birth weight / Déficit renal e fatores associados em crianças nascidas com baixo peso

ABSTRACT Introduction: Kidney problems may be due to low birth weight alone or may occur in association with other conditions. The objective this study was to evaluate the association between maternal and birth characteristics, anthropometric measurements, and kidney function deficit in low birth weight infants. Methods: Cross-sectional study with children who were born weighing < 2500 grams and were under outpatient follow-up. Maternal factors investigated were prenatal care and presence of hypertension, diabetes, and infection during pregnancy. The children's variables were sex, gestational age, birth weight, Apgar score, use of nephrotoxic medications, age, body weight at the time of evaluation, height, and serum creatinine and cystatin C dosages. The glomerular filtration rate (GFR) was estimated with the combined Zapittelli equation. Multivariate logistic regression model was used for identification of associated factors, with renal function deficit (GFR < 60 mL/min/1.73 m2) as the dependent variable. Results: Of the 154 children evaluated, 34.42% had kidney function deficit. Most of them had a gestational age > 32 weeks (56.6%), a mean birth weight of 1439.7 grams, and mean estimated GFR of 46.9 ± 9.3 mL/min/1.73 m2. There was a significant association of GFR < 60 mL/min/1.73 m2 with children's current weight and use of nephrotoxic drugs. Discussion: Children born with low birth weight had a high prevalence of kidney function deficit and current normal weight was a protective factor while the use of nephrotoxic drugs during perinatal period increased the chance of kidney deficit. These findings reinforce the need to evaluate the kidney function in these children, especially those who use nephrotoxic drugs.

RESUMO Introdução: Problemas renais podem ser devido apenas ao baixo peso ao nascer ou podem ocorrer em associação com outras condições. O objetivo deste estudo foi avaliar a associação entre características maternas e de nascimento, medidas antropométricas e déficit da função renal em bebês de baixo peso ao nascer. Métodos: Estudo transversal com crianças que nasceram com peso < 2500 gramas e estavam sob acompanhamento ambulatorial. Os fatores maternos investigados foram cuidados pré-natal e presença de hipertensão, diabetes e infecção durante a gravidez. As variáveis das crianças foram sexo, idade gestacional, peso ao nascer, índice Apgar, uso de medicamentos nefrotóxicos, idade, peso corporal no momento da avaliação, altura e dosagens séricas de creatinina e cistatina C. A taxa de filtração glomerular (TFG) foi estimada com a equação combinada de Zapittelli. Utilizou-se um modelo de regressão logística multivariada para identificação de fatores associados, com déficit da função renal (TFG < 60 mL/min/1,73 m2) como variável dependente. Resultados: Das 154 crianças avaliadas, 34,42% apresentaram déficit da função renal. A maioria tinha idade gestacional > 32 semanas (56,6%), peso médio ao nascer de 1439,7 gramas, e TFG média estimada de 46,9 ± 9,3 mL/min/1,73 m2. Houve uma associação significativa da TFG < 60 mL/min/1,73 m2 com o peso atual das crianças e o uso de medicamentos nefrotóxicos. Discussão: Crianças nascidas com baixo peso apresentaram alta prevalência de déficit da função renal e o peso atual normal foi um fator de proteção, enquanto o uso de medicamentos nefrotóxicos durante o período perinatal aumentou a chance de déficit renal. Estes achados reforçam a necessidade de avaliar a função renal destas crianças, especialmente aquelas que usam medicamentos nefrotóxicos.

Induced acute hyperglycemia modifies the barrier function of the intestinal epithelium by tissue inflammation and tight junction disruption resulting in hydroelectrolytic secretion in an animal model

Abstract Diabetic-metabolic syndrome (MetS-D) has a high prevalence worldwide, in which an association with the rupture of the intestinal epithelium barrier function (IEBF) has been pointed out, but the functional and morphological properties are still not well understood. This study aimed to evaluate the impact of acute hyperglycemia diabetes on intestinal tight junction proteins, metabolic failure, intestinal ion and water transports, and IEBF parameters. Diabetes was induced in male Rattus norvegicus (200-310 g) with 0.5 mL of streptozotocin (70 mg/kg). Glycemic and clinical parameters were evaluated every 7 days, and intestinal parameters were evaluated on the 14th day. The MetS-D animals showed a clinical pattern of hyperglycemia, with increases in the area of villi and crypts, lactulose:mannitol ratio, myeloperoxidase (MPO) activity, and intestinal tissue concentrations of malondialdehyde (MDA), but showed a reduction in reduced glutathione (GSH) when these parameters were compared to the control. The MetS-D group had increased secretion of Na+, K+, Cl-, and water compared to the control group in ileal tissue. Furthermore, we observed a reduction in mRNA transcript of claudin-2, claudin-15, and NHE3 and increases of SGLT-1 and ZO-1 in the MetS-D group. These results showed that MetS-D triggered intestinal tissue inflammation, oxidative stress, complex alterations in gene regulatory protein transcriptions of intestinal transporters and tight junctions, damaging the IEBF and causing hydroelectrolyte secretion.

The duration-dependent and sex-specific effects of neonatal sevoflurane exposure on cognitive function in rats

Clinical studies have found that neonatal sevoflurane exposure can increase the risk of cognitive dysfunction. However, recent studies have found that it can exhibit neuroprotective effects in some situations. In this study, we aimed to explore the effects of sevoflurane neonatal exposure in rats. A total of 144 rat pups (72 males and 72 females) were assigned to six groups and separately according to sevoflurane exposure of different times on the seventh day after birth. Blood gas analysis and western blot detection in the hippocampus were conducted after exposure. The Morris water maze test was conducted on the 32nd to 38th days after birth. The expression of PSD95 and synaptophysin in the hippocampus was detected after the Morris water maze test. We found that neonatal exposure to sevoflurane promoted apoptosis in the hippocampus, and Bax and caspase-3 were increased in a dose-dependent manner. The 2-h exposure had the greatest effects on cognitive dysfunction. However, with the extension of exposure time to 6 h, the effects on cognitive function were partly compensated. In addition, sevoflurane exposure decreased synaptogenesis in the hippocampus. However, as the exposure time was extended, the suppression of synaptogenesis was attenuated. In conclusion, neonatal sevoflurane exposure exhibited duration-dependent effects on cognitive function via Bax-caspase-3-dependent apoptosis and bidirectional effects on synaptogenesis in rats.

Construction of Chinese Herbal Medicine Traceability System Based on Influencing Factors of Chinese Herbal Medicine Quality / 中国实验方剂学杂志

As a Chinese saying goes， "good Chinese medicinal material makes good medicine"， the quality of Chinese herbal medicines is related to the development prospect of Chinese medicine industry in China. With the rapid development of new technologies such as traceability methods and monitoring instruments， it is imperative to integrate and innovate traditional Chinese herbal medicines with new-generation information technology in view of the quality problems existing in the current production and circulation of Chinese herbal medicines， and it is of great significance for the construction of traceability system to ensure the quality and safety of Chinese herbal medicines and to promote the industry of Chinese herbal medicines to move towards high-quality development. This paper reviews the development history of the traceability system of Chinese herbal medicines in China， takes the influencing factors of the quality of Chinese herbal medicines as the entry point， and proposes that the construction of the traceability system should satisfy the traceability requirements of the characteristics of Chinese herbal medicines and their traditional medication experience. By analyzing the influencing factors of the quality of Chinese herbal medicines， it is pointed out that focusing on the influencing factors to build a traceability system is of great significance for targeting the problematic links at a later stage and exploring the interrelationship between environmental factors and the quality of Chinese herbal medicines. Based on the previous explorations， the author summarizes the system framework， functional modules and practical applications of the traceability system of Chinese herbal medicines， and looks forward to the development of a traceability system with risk early warning function and expert decision-making function in its functional development. Finally， based on the factors affecting the quality of Chinese herbal medicines， the author puts forward several thoughts on construction of the traceability system， and makes an in-depth analysis and puts forward a solution for the current situation that a unified， standardized and universal traceability system has not yet been built， with a view to providing ideas and references for the construction of traceability system of Chinese herbal medicines.

Effect of Direct-acting Antivirals Treatment on Renal Function Among HCV-infected Patients / 中山大学学报(医学科学版)

； ObjectiveTo explore the effect of direct-acting antiviral treatment on renal function in patients with chronic hepatitis C. MethodsA total of 123 HCV-infected patients receiving DAAs treatment at the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2021 were included in this study. To explore the renal function in patients with chronic hepatitis C treated with direct-acting antivirals， serum creatinine values were collected before， during and after the treatment， which were used to estimate the eGFR by the MDRD equation to assess the changes in renal function. ResultsOf the 123 patients enrolled， 67.5%（n=83）were male， and the mean age of participants was （50±11） years old. The mean follow-up period was 24 weeks . Comorbidities included cirrhosis in 26.8%， and diabetes in 10.6%. Meanwhile， 11.4% of the cohort had eGFR < 60 mL/（min ·1.73 m2）， 33.3% of the cohort had eGFR 60 to 90 mL/（min ·1.73 m2）， and 55.3% had eGFR≥90 mL/（min ·1.73 m2）. No decrease in renal function was seen among all the HCV-infected patients at the end of treatment or the follow-up period after treatment. However， compared with the eGFR at the baseline， eGFR in CKD2 patients in the follow-up period was improved 【（88.65±15.52） mL/（min ·1.73 m2）vs （78.12 ±7.60） mL/（min ·1.73 m2）， P< 0.001】. And 14.6% （n=18） of patients experienced progressive deterioration of renal function. Logistic regression analysis showed that diabetes could predict the deterioration of renal function （OR=4.663， P=0.016）. ConclusionsOur study shows renal function is not impair among HCV-infected patients following DAAs treatment， and renal function in CKD2 patients have improvements. However， HCV-infected patients with diabetes mellitus are at a high risk of renal impairment and closely monitoring of renal function is still needed.

Clinical significance of benign liver function abnormality / 临床肝胆病杂志

Biochemical liver function tests are important methods to determine liver function in clinical practice， but abnormal liver biochemical parameters are not completely equivalent to liver damage. Some genetic and immune factors can also cause abnormal liver biochemical parameters， but with good prognosis in most cases. This article summarizes the causes of some benign abnormal liver biochemical parameters， so as to help clinicians to broaden their thinking of diagnosis and treatment， take into account genetic and immune factors， and avoid misdiagnosis and mistreatment.

Effect of microparticles derived from bone marrow mesenchymal stem cells on cardiomyocyte hypertrophy and its mechanism / 中国生物制品学杂志

@#Objective To investigate the effect of microparticles(MPs)derived from bone marrow mesenchymal stem cells(BMSCs) on myocardial hypertrophy and its mechanism.Methods The osteogenic differentiation and adipogenic differentiation of mesenchymal stem cells(MSCs) were induced. After isolation and purification,the morphological characteristics were observed by transmission electron microscope,and the MPs surface antigen was identified by flow cytometry. Myocardial hypertrophy model was induced by using isoprenaline(ISO)in rats,which were measured for the cardiac structure and function by echocardiography,and then detected for various indexes of the heart and isolated left ventricle. Single ventricular myocytes of rats were acutely isolated and divided into control group(Control group),cardiomyocyte hypertrophy group(ISO group),MPs group(MPs group),and MPs supernatant group(Supernatant group). The mRNA expressions of atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)were detected by qRTPCR. The expression levels of calmodulin-dependent protein kinaseⅡ（CaMKⅡ）and phosphorylated calmodulin-dependent protein kinaseⅡ（p-CaMKⅡ）were detected by ELISA. The L-type calcium current(LCa-L)in single ventricular myocyte of various groups was recorded by whole-cell patch clamp.Results The bone nodules of MSCs osteogenic differentiation turned red after alizarin red staining,and lipid droplets of adipogenic differentiation turned red after oil red O staining;Under transmission electron microscope,MPs membrane had a complete structure,a clear outline and a diameter of about200 nm;The positive rates of CD29 and CD90 on the surface of MPs were(98. 24 ± 0. 82)% and(97. 69 ± 1. 83)%,respectively. Compared with Control group,the left ventricular end diastolic dimension(LVEDD)reduced signifi-cantly(t =5. 065,P < 0. 05),while the interventricular septum end-diastolic dimension(IVSd),left ventricular posterior wall dimension(LVPWd),heart weight to body weight ratio(HW/BW),and heart weight to tibial length ratio(HW/Tibia)significantly increased in ISO group(t = 4. 013,2. 368,4. 392,5. 043 and 6. 120,respectively,each P < 0. 05),indicating that the hypertrophic model was successfully established. The expression levels of ANP and BNP mRNA in hypertrophic cardiomyocytes of rats in ISO group were significantly higher than those in Control group(t = 25. 120 and18. 261,respectively,each P < 0. 01);While the expression levels of ANP and BNP mRNA in MPs group significantly reduced after incubation with 48 μg/mL MPs for 48 h compared with ISO group(t = 12. 110 and 3. 526,respectively,each P < 0. 05);The expression levels of CaMK Ⅱand p-CaMKⅡ in ISO group were significantly higher than those in Control group(t = 3. 278 and 4. 181,respectively,each P < 0. 05),while the expression of p-CaMK Ⅱ in MPs group decreased significantly(t = 5. 420,P < 0. 05);The calcium current density in ISO group was significantly higher than that in Control group(t = 15. 261,P < 0. 01),while that in MPs group was significantly lower than that in ISO group(t =6. 216,P < 0. 05).Conclusion MSC-MPs can significantly inhibit ISO-induced cardiomyocyte hypertrophy in rats,which is related to its down-regulation of cardiomyocyte CaMKⅡ and inhibition of L-type calcium channel.

Effect of targeted CXCL5 silencing on biological function of laryngeal squamous cell carcinoma cell line AMC-HN-8 and its regulation analysis / 中国生物制品学杂志

@#Objective To investigate the effects of targeted silencing of CXCL5 on the related biological functions of laryngeal squamous cell carcinoma(LSCC)cell line AMC-HN-8,and analyze the regulation through TCGA database.Methods RNA-seq data related to LSCC were obtained from TCGA database,and the expression differences of CXCL5 gene in LSCC and the adjacent tissues were analyzed. Total 60 samples of LSCC and the adjacent tissues from January 2019 to December 2020 were selected from the First Hospital of Shanxi Medical University,and the expression of CXCL5 protein in LSCC tissues was detected by immunohistochemical staining. Human LSCC cell line AMC-HN-8 was cultured and the mRNA transcription level of CXCL5 in AMC-HN-8 cells was detected by qPCR. Two groups of SiRNA with high knock-down efficiency were screened,CCK8 assay was used to detect the cell proliferation,Transwell test was used to measure the cell invasion and migration,and flow cytometry was used to detect the cell cycle and apoptosis. The correlation between CXCL5and tumor immune invasion level of LSCC was analyzed by ssGSEA,and CXCL5 co-expression gene network was constructed and analyzed for GO and KEGG enrichment.Results Compared with the adjacent tissues and the cells in control group,the expression of CXCL5 in LSCC tissues and cells increased,which was consistent with the analysis of TCGA database;Inhibition of CXCL5 expression in AMC-HN-8 cells inhibited the proliferation,invasion and migration of tumor cells,and promoted the apoptosis through inhibiting the cell cycle in G1 phase;The immune cell scores in DC,neutrophils,NK and TH17 cells were different.Conclusion CXCL5gene is highly expressed in LSCC tissues,which might be one of the targets of LSCC targeted therapy.

Advances in antitumor research of bifunctional small molecule inhibitors targeting heat shock protein 90 / 药学学报

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.

Effects of Guben Fangxiao Beverage （固本防哮饮） on Lung Tissue Oxidative Stress and AMPK/Nrf2/HO-1 Pathway in Mice with Bronchial Asthma in Remission / 中医杂志

ObjectiveTo investigate the possible mechanism of Guben Fangxiao Beverage （固本防哮饮） for the prevention and treatment of chronic airway inflammation during asthma remission. MethodsThirty-six female Balb/c mice were randomly divided into normal group， model group， low-， medium-， and high-dose of Guben Fangxiao Beverage group and montelukast sodium group， with 6 mice in each group. Except for the normal group， ovalbumin and respiratory syncytial virus were used in other groups to establish a mouse model of bronchial asthma in remission stage. After molding， the low-， medium-， and high-dose groups of Guben Fangxiao Beverage were respectively given 12， 24， and 36 g/（kg·d）， the montelukast sodium group was given montelukast sodium granule 2.6 mg/（kg·d）， and the mice in the normal group and model group were given 20 ml of double-distilled water， all by gavage， once a day for 28 days. The levels of interleukin 4 （IL-4） and interleukin 5 （IL-5） in the lung tissue of mice were detected； HE staining was used to observe the pathology of the lung tissue and to score the inflammation； DHE staining was used to observe the level of reactive oxygen species （ROS） in the lung tissue， and the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， Ⅳ， and Ⅴ in the lung tissue were detected； the levels of serum superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA） and adenosine triphosphate （ATP） were detected； the protein expression levels of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， nuclear factor erythroid 2-related factor 2 （Nrf2）， haem oxygenase 1 （HO-1） and cAMP responsive element binding protein （CREB） in the lung tissues of the model group were detected by Western blot. ResultsCompared with the normal group， the histopathological results of the lungs of mice in the model group showed an increase in inflammatory cells around the airways and an increase in inflammatory score； DHE staining showed an increase in the level of ROS， and an increase in the levels of IL-4 and IL-5 in the lung tissues； the levels of serum SOD， CAT， and ATP were reduced， and the level of MDA was elevated； the activities of the mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， Ⅳ， and Ⅴ of the lung tissues were reduced， and the activities of p-AMPK， Nrf2， CREB protein expression decreased （P＜0.05）. Compared with the model group， the lung tissue inflammatory cells and inflammation scores of mice in each Guben Fangxiao Beverage dose group and montelukast sodium group were reduced； the levels of ROS， IL-4 and IL-5 in the lung tissue were reduced； the levels of CAT and ATP in the serum increased， and the content of MDA was reduced； and the activities of mitochondrial respiratory chain complexes Ⅰ and Ⅱ， as well as the expression of CREB protein， were elevated in the lung tissue （P＜0.05）. Compared with the high-dose group， the MDA level of the medium-dose Guben Fangxiao Beverage group decreased （P＜0.05）. The activity of mitochondrial respiratory chain complex V in the medium-dose group was higher than that in the montelukast sodium group， and the activity of mitochondrial respiratory chain complex Ⅳ in the medium- and high-dose groups was higher than that in the low-dose group （P＜0.05）. ConclusionGuben Fangxiao Beverage can inhibit oxidative stress and improve mitochondrial function to relieve chronic airway inflammation in bronchial asthma model mice during asthma remission， and its mechanism may be related to the activation of AMPK/Nrf2/HO-1 signaling pathway.

Experiences of ZHAO Yonghou in Differentiation and Staged Treatment of Schizophrenia Using the Theory of Ti （Character， 体） and Yong （Function， 用） in Mental Illness / 中医杂志

Based on the theory of ti （character， 体） and yong （function， 用） in mental illness， ZHAO Yonghou's clinical experience in staged differentiation and treatment of schizophrenia is summarized. According to the theory， the core disease location of schizophrenia is in the brain， which is closely related to the organs， qi， and blood. It is proposed to interpret the pathogenesis of schizophrenia from the perspective of “zang-fu organs-qi and blood-brain and spirit”， that is， dysfunction of the zang-fu organs， disharmony of qi and blood， and malnourishment of the brain ti lead to dysfunction of the spirit ti and yong. In clinical practice， treatment of schizophrenia can be divided into four stages， for which the method of treating ti and yong simultaneously is suggested. In the prodromal stage， Liuwei Dihuang Decoction combined with Sini San （六味地黄汤合四逆散） with modifications is used to nourish the kidney and boost marrow， soothe the liver and rectify the spleen. For acute exacerbation with binding of phlegm and heat syndrome， Zhaoshi Yikuang Decoction （赵氏抑狂汤） with modifications is used to clear heat and dispel phlegm， awaken the brain and calm the mind. For phlegm-heat damaging yin pattern， Mengshi Guntan Pill combined with Zengye Decoction （礞石滚痰丸合增液汤） with modifications is used to clear heat and dispel phlegm， enrich yin and calm the mind. For the chronic treatment stage， Yudian Decoction （愈癫汤） with modifications is used to disperse phlegm and dissolve stasis， move qi and awaken the mind. For the rehabilitation and regulation stage， Shenan Pill （神安丸） with modifications is used to boost qi and nourish yin， and tranquilize the mind.

Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment" / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases （COPD） and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups， with 10 rats in each group， and the groups were control group， model group， acute syrup group （10 g·kg-1·d-1）， and low， medium， and high-dose groups （10， 15， 20 g·kg-1·d-1） of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method， and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively， while the rest groups were controlled by saline gavage， and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （IgA） in colon tissue were measured by enzyme-linked immunosorbent assay （ELISA）. The biochemical indexes such as serum diamine oxidase （DAO）， D-lactic acid， and malondialdehyde （MDA） were measured. Immunohistochemistry was used to detect the expression of tight junction protein （Occludin） in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue， and the expression of α-actin （α-SMA） and colonic atresia small band protein-1 （ZO-1） were determined by immunofluorescence. The protein expression of p-NF-κB p65， NF-κB p65， p-p38 MAPK， and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group， the model group had pulmonary dysfunction， reduced forced vital capacity （FVC）， arterial partial oxygen pressure （PaO2）， arterial oxygen saturation （SaO2）， and dynamic lung compliance （Cdyn） （P<0.01）， and the pathological changes in the lung and intestine were obvious. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were increased （P<0.05，P<0.01）， and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA， Occludin， and ZO-1 in colon tissue decreased （P<0.05，P<0.01）. Compared with the model group， the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved， and the FVC， PaO2， SaO2， and Cdyn were increased （P<0.05， P<0.01）. The pathological changes in the lung and intestine were significant. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were decreased （P<0.05，P<0.01）， and the expressions of F4/80 positive macrophages in lung tissue were decreased （P<0.01）. The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased （P<0.01）， and the expression of IgA， Occludin， and ZO-1 in colon tissue increased （P<0.01）. ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats， and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.

Repair effect of ephedrine on lipopolysaccharide-induced microglia function injury and its mechanism / 中国药房

OBJECTIVE To study the repair effect of ephedrine on lipopolysaccharide （LPS）-induced microglia function injury and its mechanism. METHODS Human microglia cells （HMC3） were used as research objects to investigate the effects of different concentrations of ephedrine （75， 150， 300， 600 μg/mL） on the viability and apoptosis of HMC3 cells. HMC3 cells were divided into control group （without drug intervention）， LPS group （1 μg/mL）， ephedrine group （1 μg/mL LPS+300 μg/mL ephedrine）， BAY11-7082 group [1 μg/mL LPS+5 μmol/L nuclear factor-κB （NF-κB） pathway inhibitor BAY11-7082]， inhibitor group （1 μg/mL LPS+300 μg/mL ephedrine+5 μmol/L BAY11-7082） and activator group （1 μg/mL LPS+300 μg/mL ephedrine+1 μmol/L NF-κB pathway activator Prostratin）. After 24 hours of drug treatment， cell migration， the levels of soluble interleukin-6（sIL-6）， interleukin-10（IL-10）， superoxide dismutase（SOD）and malondialdehyde（MDA）， and the expressions of NF-κB pathway-related proteins were all detected. RESULTS The viability of HMC3 cells could be increased significantly by 300 μg/mL ephedrine， while the apoptotic rate was decreased significantly （P＜0.05）. Compared with the control group， the number of migrating cells was increased significantly in the LPS group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were increased significantly， while the levels of IL-10 and SOD were decreased significantly （P＜0.05）. Compared with the LPS group， the above indexes were reversed significantly in the ephedrine group and BAY11-7082 group （P＜0.05）. Compared with the ephedrine group， the number of migrating cells was decreased significantly in the inhibitor group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were decreased significantly， while the levels of IL-10 and SOD were increased significantly （P＜0.05）. The above indexes were reversed significantly in the activator group （P＜0.05）can repair cell injury by inhibiting LPS induced apoptosis， migration， inflammation and oxidant stress of HMC3 cells， the mechanism of which may be associated with inhibiting the activity of the NF-κB signaling pathway.