Incidence of contrast-associated acute kidney injury: a prospective cohort / Incidência de lesão renal aguda associada ao contraste: uma coorte prospectiva

ABSTRACT Introduction: Contrast-associated acute kidney injury (CA-AKI) is a deterioration of kidney function that occurs after the administration of a iodinated contrast medium (ICM). Most studies that defined this phenomenon used older ICMs that were more prone of causing CA-AKI. In the past decade, several articles questioned the true incidence of CA-AKI. However, there is still a paucity of a data about the safety of newer ICM. Objective: To assess the incidence of CA-AKI in hospitalized patients that were exposed to computed tomography (CT) with and without ICM. Methods: Prospective cohort study with 1003 patients who underwent CT in a tertiary hospital from December 2020 through March 2021. All inpatients aged > 18 years who had a CT scan during this period were screened for the study. CA-AKI was defined as a relative increase of serum creatinine of ≥ 50% from baseline or an absolute increase of ≥ 0.3 mg/dL within 18 to 48 hours after the CT. Chi-squared test, Kruskal-Wallis test, and linear regression model with restricted cubic splines were used for statistical analyses. Results: The incidence of CA-AKI was 10.1% in the ICM-exposed group and 12.4% in the control group when using the absolute increase criterion. The creatinine variation from baseline was not significantly different between groups. After adjusting for baseline factors, contrast use did not correlate with worse renal function. Conclusion: The rate of CA-AKI is very low, if present at all, with newer ICMs, and excessive caution regarding contrast use is probably unwarranted.

RESUMO Introdução: Lesão renal aguda associada ao contraste (LRA-AC) é uma deterioração da função renal que ocorre após a administração de meio de contraste iodado (MCI). A maioria dos estudos que definiram esse fenômeno utilizaram MCI mais antigos, mais propensos a causar LRA-AC. Na última década, diversos artigos questionaram a verdadeira incidência de LRA-AC. Entretanto, ainda há escassez de dados sobre a segurança dos MCI mais novos. Objetivo: Avaliar a incidência de LRA-AC em pacientes hospitalizados expostos à tomografia computadorizada (TC) com e sem MCI. Métodos: Estudo de coorte prospectivo com 1.003 pacientes submetidos a TC em hospital terciário, de dezembro/2020 a março/2021. Todos os pacientes internados com idade ≥ 18 anos que realizaram TC nesse período foram selecionados. A LRA-AC foi definida como aumento relativo de creatinina sérica de ≥ 50% em relação ao valor basal ou aumento absoluto de ≥ 0,3 mg/dL dentro de 18 a 48 horas após a TC. Utilizamos o teste qui-quadrado, teste de Kruskal-Wallis e modelo de regressão linear com splines cúbicos restritos para análises estatísticas. Resultados: A incidência de LRA-AC foi 10,1% no grupo exposto ao MCI e 12,4% no grupo controle ao usar o critério de aumento absoluto. A variação da creatinina em relação ao valor basal não foi significativamente diferente entre os grupos. Após ajuste para fatores basais, o uso de contraste não se correlacionou com pior função renal. Conclusão: A taxa de LRA-AC é muito baixa, caso exista, com MCIs mais novos, e a cautela excessiva quanto ao uso de contraste provavelmente não se justifica.

Osteonecrosis de los Maxilares Asociada a Medicamentos y Anticuerpos Monoclonales. Revisión Sistemática de la Literatura y Propuesta para la Prevención y Manejo en un Procedimiento de Exodoncia

El objetivo de esta revisión sistemática consistió en la búsqueda de medidas preventivas y de tratamiento de osteonecrosis asociada a medicamentos y anticuerpos monoclonales para proponer un nuevo protocolo en caso de ser necesario. Esta revisión bibliográfica se realizó en PubMed/MedLine, Cochrane, SciELO y EBSCO; delimitando la búsqueda desde el 1 de enero de 2017 al 22 de septiembre de 2022. Se incluyeron un total de 8 artículos. A pesar de que se incluyó la mayor cantidad de evidencia certera se obtuvieron resultados no significativos, actualmente hay un protocolo de la Asociación Americana de Cirugía Oral y Maxilofacial sin embargo se necesita más evidencia clínica.

The objective of this systematic review was to search for preventive and treatment measures for osteonecrosis associated with medications and monoclonal antibodies to propose a new protocol if necessary. This literature review was conducted in PubMed/MedLine, Cochrane, SciELO, and EBSCO; limiting the search from January 1, 2017 to September 22, 2022. A total of 8 articles were included. Although the greatest amount of accurate evidence was included, non-significant results were obtained. There is currently a protocol from the American Association of Oral and Maxillofacial Surgery, however, more clinical evidence is needed.

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).

Dopamine Dynamics in the Amygdala Influence Emotional Changes in the Early Stage of Systemic Inflammatory Response Syndrome in Rats / La Dinámica de la Dopamina en la Amígdala Influye en los Cambios Emocionales en la Etapa Temprana del Síndrome de Respuesta Inflamatoria Sistémica en Ratas

SUMMARY: Systemic inflammatory response syndrome (SIRS) is a potentially fatal reaction to various forms of tissue damage and infections that cause damage to various organs. Furthermore, the brain is damaged earlier than other organs, resulting in diffuse brain dysfunction. The central clinical symptom of SIRS is delirium and emotional changes are involved in disease development. Although the amygdala is known to play a major role, the mechanisms underlying emotional changes in the early stages of SIRS have not been elucidated. Therefore, changes to dopamine levels in the amygdala were observed using an in vivo model of lipopolysaccharide (LPS)- induced SIRS to clarify the biochemical mechanisms activated in the early stages of SIRS. Extracellular dopamine was collected from the amygdala of free moving rats via microdialysis and then analyzed by high-performance liquid chromatography. In addition, emotional changes were assessed with the open field and sucrose preference tests. In the LPS group, dopamine release in the amygdala increased remarkably immediately after LPS administration, peaking at 120 min. Thereafter, dopamine release temporarily decreased, but then significantly increased again after 180 min. The present results suggest that diffuse brain dysfunction in the early stages of SIRS may involve altered dopamine levels in the amygdala.

El síndrome de respuesta inflamatoria sistémica (SRIS) es una reacción potencialmente fatal a diversas formas de daño tisular e infecciones que causan injuria a varios órganos. Además, el cerebro se daña antes que otros órganos, lo que provoca una disfunción cerebral difusa. El síntoma clínico central del SIRS es el delirio y los cambios emocionales están involucrados en el desarrollo de la enfermedad. Aunque se sabe que la amígdala desempeña un papel importante, no se han dilucidado los mecanismos que subyacen a los cambios emocionales en las primeras etapas del SRIS. Por lo tanto, en el estudio se provocaron cambios en los niveles de dopamina en la amígdala utilizando un modelo in vivo de SRIS inducido por lipopolisacáridos (LPS) para dilucidar los mecanismos bioquímicos activados en las primeras etapas del SRIS. La dopamina extracelular se recogió de la amígdala de ratas en movimiento libre mediante microdiálisis y luego se analizó mediante cromatografía líquida de alta resolución. Además, se evaluaron los cambios emocionales con las pruebas de campo abierto y de preferencia de sacarosa. En el grupo de LPS, la liberación de dopamina en la amígdala aumentó de manera notable inmediatamente después de la administración de LPS, alcanzando un máximo a los 120 minutos. A partir de entonces, la liberación de dopamina disminuyó temporalmente, pero luego volvió a aumentar significativamente después de 180 min. Los resultadosactuales sugieren que la disfunción cerebral difusa en las primeras etapas del SIRS puede implicar niveles alterados de dopamina en la amígdala.

Frequency of hand contact with hospital surfaces in hospitalized pediatric patients / Frecuencia de contacto de manos de pacientes pediátricos hospitalizados

Abstract Background: Hand hygiene (HH) is an important strategy for preventing health-care-associated infections (HAIs). Few programs focus on HH for family members and primary caregivers but fewer for patients. This study aimed to estimate the frequency with which hospitalized pediatric patients have hand contact with hospital surfaces. Methods: We conducted a cross-sectional descriptive observational study consisting of three phases: the first was the creation of an observation and data collection tool, the second was the training of the monitors, and the third was the observational study of hand contact and HH opportunities in hospitalized pediatric patients. Results: Over 3600 minutes of observation, 2032 HH opportunities were detected, averaging 33.8/h (SD 4.7) as determined by hand contact with hospital surfaces of hospitalized pediatric patients. In our study, infants and preschool children had the highest frequency of hand contact. Conclusion: The high frequency of hand contact of hospital surfaces by children suggests that hourly hand disinfection of patients and caregivers, objects and surfaces around the patients may be prevention measures that could be incorporated to reduce HAIs in pediatric hospitals.

Resumen Introducción: La higiene de manos es una estrategia importante para la prevención de infecciones asociadas a la atención sanitaria. Existen pocos programas centrados en la higiene de manos para los familiares y cuidadores primarios, y aún menos para el paciente. El objetivo de este estudio fue cuantificar la frecuencia con la que los pacientes pediátricos hospitalizados tienen contacto manual con superficies hospitalarias. Métodos: Se llevó a cabo un estudio observacional descriptivo transversal que constó de tres fases: la primera fue la creación de una herramienta de observación y registro de datos; la segunda fue la capacitación de los monitores y la tercera fue el estudio observacional del contacto manual y de las oportunidades de higiene de manos en pacientes pediátricos hospitalizados. Resultados: Durante los 3600 minutos de observación, se detectaron 2032 oportunidades, con una media de 33.8 (DE 4.7) por hora de oportunidades de higiene de manos establecidas por contacto manual con superficies de pacientes pediátricos hospitalizados. Los lactantes y los niños en edad preescolar presentaron la mayor frecuencia de contacto manual. Conclusiones: La alta frecuencia de contacto manual por parte del niño indica que medidas como la desinfección de las manos cada hora del paciente y del cuidador, así como de los objetos y superficies alrededor del paciente, podrían ser medidas útiles que deberían incluirse para prevenir las infecciones asociadas a la atención de la salud en los hospitales pediátricos.

Analysis of Healthcare-associated Infections before and during the COVID-19 pandemic in a Colombian hospital

Introduction: Healthcare-associated infections pose a significant challenge, contributing to hospital morbidity and mortality. Objective: To describe the behavior of Healthcare Associated Infections before and during the pandemic reported to a high-complexity health institution in Colombia. Material and Methods: In our retrospective observational study on Healthcare-Associated Infections (HAIs), we analyzed data from all in-patients diagnosed with HAIs between 2018 and 2020. This included clinical, demographic, microbiological, and microbial susceptibility information collected from the Committee on Nosocomial Infections' prospective database. Data from 391 isolates were obtained using Whonet software for antimicrobial resistance surveillance. Results: We found 504 cases of HAIs (2018-2020) with an overall in-hospital infection rate of 2.55/1000 patient-days. The median age for pediatric patients was 5 years, and for adults, 56 years, with 57% male. The leading admission diagnoses were oncologic disease complications (31%). Bacteremia had a 30-day mortality rate of 13%, predominantly catheter-associated (37%). Gram-negative bacilli, notably Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa, represented 58% cases of HAI. Discussion: The critical need for specific interventions and antimicrobial management to control HAIs, especially given the challenges posed by the COVID-19 pandemic, is highlighted. Conclusions: This is the first report on HAIs incidence at a tertiary hospital in Bucaramanga, Santander (Colombia). Bacteremia was predominant; 75% of HAIs patients had comorbidities. Gram-negative bacilli prevailed; a notable rise in ICU respiratory infections occurred during the 2020 COVID-19 pandemic. Resistance to cephalosporins and carbapenems was prevalent.

Mortalidad intrahospitalaria de pacientes con COVID-19 complicados con neumonías bacterianas en asistencia respiratoria mecánica en Cuidados Intensivos de Adultos en un Hospital del Paraguay / In-hospital mortality of patients with COVID-19 complicated by bacterial pneumonia on mechanical ventilation in Adult Intensive Care in a Hospital in Paraguay

Introducción: los pacientes con COVID-19 ingresan en mayor proporción a asistencia respiratoria mecánica, aumentando: el riesgo de neumonía asociada a ventilador (NAV) las tasas de mortalidad, los días de permanencia en las unidades de terapia intensiva (UCI) y los costos sanitarios. Objetivo: determinar la Mortalidad intrahospitalaria de pacientes con COVID-19 complicados con neumonías bacterianas en asistencia respiratoria mecánica en Cuidados Intensivos de Adultos en un Hospital del Paraguay durante los años 2020 a 2021. Metodología: estudio analítico de tipo cohorte retrospectiva. Se registraron variables demográficas, comorbilidades, puntajes en scores de gravedad como el APACHE II al ingreso, la cifra más baja de oxigenación durante la internación expresado por la PaO2 / FIO2, días de ventilación, colocación en decúbito prono, traqueotomía, medidas terapéuticas farmacológicas y no farmacológicas, días de internación, así como las complicaciones y la mortalidad. Resultados: fueron incluidos 214 pacientes, 135 ingresaron a asistencia respiratoria mecánica (ARM) de los cuales 58 (42,9 %) desarrollaron NAV, con edad mediana de 52 años (40-60). Los microorganismos de NAV fueron cocos Gram negativos en 98,3 %, incluyendo Acinetobacter baumanii en 46,5 %, Klebsiella pneumoniae en 22,8 %, Pseudomona aeruginosa en 15,5 % y 5,2 % Stenotrophomona maltofilia. La mortalidad intrahospitalaria fue del 44,8 %. Los menores de 50 años tienen una sobrevida mayor que los mayores (34 días vs 22 días, con p de 0,026). Conclusión: la mortalidad intrahospitalaria fue del 44,8 %. La edad fue un factor de riesgo independiente para la mortalidad en pacientes con NAV, por lo que los profesionales de la salud deben estar atentos a la posibilidad de NAV en pacientes que requieren asistencia respiratoria mecánica, especialmente en pacientes mayores de 50 años.

Introduction: patients with COVID-19 are more likely to require mechanical ventilation, which increases the risk of ventilator-associated pneumonia (VAP), mortality rates, length of stay in intensive care units (ICUs), and healthcare costs. Objective: to determine the in-hospital mortality of patients with COVID-19 complicated by bacterial pneumonia on mechanical ventilation in Adult Intensive Care in a Hospital in Paraguay during the years 2020 to 2021. Methodology: this is a retrospective cohort analytical study. Demographic variables, comorbidities, severity scores such as APACHE II on admission, the worst oxygenation during hospitalization expressed by PaO2/FiO2, days of ventilation, prone position, tracheostomy, pharmacological and non-pharmacological therapeutic measures, days of hospitalization, as well as complications and mortality were recorded. Results: a total of 214 patients were included, 135 were admitted to mechanical ventilation (MRA), of which 58 (42.9%) developed VAP, with a median age of 52 years (40-60). VAP microorganisms were Gram-negative cocci in 98.3%, including Acinetobacter baumanii in 46.5%, Klebsiella pneumoniae in 22.8%, Pseudomona aeruginosa in 15.5%, and Stenotrophomona maltophilia in 5.2%. In-hospital mortality was 44.8%. Those under 50 years of age have a longer survival than those older (34 days vs. 22 days, with p of 0.026). Conclusion: the overall mortality rate was 44.8%. Age was an independent risk factor for mortality in patients with VAP, so healthcare professionals should be aware of the possibility of VAP in patients who require mechanical ventilation, especially in patients over 50 years of age.

Effects of Zhuyu Pill （茱萸丸） and its Ingredient on Aortic Plaque and the NLRP3/Asc/Caspase-1 Signaling Pathway in Aortic Tissue of Mice in Atherosclerosis Model / 中医杂志

ObjectiveTo investigate the possible mechanism of action and combination of medicinals of Zhuyu Pill （茱萸丸） in the treatment of atherosclerosis. MethodsThirteen normal C57BL/6J mice were used as blank group， and 40 ApoE-/- mice of the same strain were randomly divided into model group， Huanglian （Coptis chinensis Franch.） group， Wuzhuyu （Tetradium ruticarpum） group， and Zhuyu Pill group， with 10 mice in each group. Except the blank group， the other groups were fed with high-fat diet for modeling， and the total modeling cycle was 12 weeks. After modelling， Huanglian group was given Huanglian solution 143.34 mg/（kg·d）， Wuzhuyu group with Wuzhuyu solution 301.78 mg/（kg·d）， Zhuyu Pill group with 261.07 mg/（kg·d） of Zhuyu Pill solution， blank group and model group were given 0.3ml of normal saline. Mice in all groups were gavaged for 12 weeks. The levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C） and fasting blood glucose were measured by biochemical method； fasting insulin in serum was detected by enzyme-linked immunosorbent assay （ELISA） and insulin resistance index was calculated； HE staining was used to observe the pathological and morphological changes of aortic tissue， liver and epididymal fat in mice， and oil red O staining was used to observe the lipid deposition of aortic tissue in mice， and the percentage of positive area of aortic HE staining， the percentage of positive area of aortic oil red O staining， the non-alcoholic fatty liver activity score （NAS） score， and the cross-sectional area of epididymal fat were calculated； serum levels of interleukin 1β （IL-1β） and interleukin 18 （IL-18） were detected by ELISA； protein expression of nucleotide-binding oligomerisation structural domain-like receptor family pyridoxal structural domain protein 3 （NLRP3） in aortic tissues was detected by Western blot； and immunofluorescence was used to detect the levels of apoptosis-associated granulocyte-like protein （ASC）， which contains the CARD structural domain （ASC） and cysteine-containing aspartic protease 1 （Caspase-1） protein expression； and real-time fluorescence PCR was used to detect NLRP3， ASC， Caspase-1， IL-1β， and IL-18 mRNA expression in mouse aortic tissues. ResultsCompared with blank group， serum TC， TG and LDL-C were increased， insulin was decreased， fasting blood glucose and insulin resistance index were increased in model group （P＜0.01）. Aortic plaque area increased， liver lipid deposition increased， epididymal fat cells volume increased， liver NAS score increased， and epididymal fat cross-sectional area increased. Serum IL-1β and IL-18 increased， and the expression levels of NLRP3， ASC， Caspase-1 protein and mRNA in aortic tissue increased （P＜0.01）. Compared with model group， serum TC， TG and LDL-C in Huanglian group， Wuzhuyu group and Zhuyu Pill group decreased， fasting insulin increased， fasting blood glucose and insulin resistance index decreased （P＜0.01）； aortic plaque area decreased significantly， liver lipid deposition decreased， liver NAS score decreased， epididymal fat cell volume decreased， epididymal fat cross section area decreased， serum IL-1β and IL-18 were decreased， the expression levels of NLRP3， ASC， Caspase-1 protein and mRNA in aortic tissue were decreased （P＜0.01）， and the improvement of all indexes in the Zhuyu Pill group was better than that in Huanglian and Wuzhuyu groups （P＜0.01）. ConclusionZhuyu Pill has a good therapeutic effect on atherosclerosis in mice， and the combination of Huanglian and Wuzhuyu has a synergistic effect， the mechanism of which may be related to regulation of the NLRP3/ASC/Caspase-1 aortic signaling pathway， and thus reducing the vascular inflammatory response.

The up-regulation of miR-221-3p by tumor-associated macrophages may be involved in the metastasis of prostate cancer / 现代泌尿外科杂志

【Objective】 To investigate the mechanism by which the up-regulation of miR-221-3p by tumor-associated macrophages (TAMs) may be involved in promoting the malignant metastasis of prostate cancer (PCa). 【Methods】 The microRNAs (miRNAs) expression profiles of 6 cases of metastatic PCa tissues were sequenced and analyzed.The primary TAMs were isolated.The expression of miR-221-3p was determined with qPCR.The miR-221-3p mimic or miR-221-3p inhibitor was transfected into RAW264.7 macrophages in vitro, and co-cultured with human prostate cancer PC3 cells.The proliferation, apoptosis, invasion and migration of PC3 cells were detected with CCK-8, flow cytometry (FCM), Transwell assay, respectively.Expressions of epithelial-mesenchymal transformation (EMT) related protein factors were determined with Western blot. 【Results】 In the 6 cases of metastatic PCa, hsa-miR-221-3p was significantly up-regulated in TAMs-derived from PCa tissues with positive lymph node metastasis (P<0.05).In the co-cultured system, compared with Mimic-NC group, miR-221-3p mimic group had significantly up-regulated proliferation, migration, invasion and EMT-related protein factors (except E-Cadherin) (P<0.05).Compared with Inhibitor-NC group, miR-221-3p inhibitor group had significantly up-regulated apoptosis rate, but down-regulated proliferation, migration, invasion and EMT-related protein factors (except E-Cadherin) (P<0.05). 【Conclusion】 The miR-221-3p expression up-regulate by TAMs may participate in the malignant metastasis of prostate cancer.

Effects of PATL1 on the proliferation and migration of gastric cancer cells and its mechanism of action / 安徽医科大学学报

Objective @#Objective @*Methods @#The expression levels of PATL1 in pancar- cinoma，gastric cancer and normal tissues were analyzed by TCGA database．The expression level of PATL1 in 40 human gastric cancer tissues and paired adjacent tissues was evaluated by quantitative real-time PCR (RT-qPCR) . The Kaplan-Meier Plotter database was used to analyze the prognosis of PATL1 in gastric cancer patients．The gas- tric cancer cell line AGS was transfected with PATL1 interference vector，and the interference effect was evaluated by RT-qPCR. The effects of PATL1 on the proliferation and migration of AGS were detected by cell counting kit-8 ( CCK-8) ，Transwell test and scratch healing test．The effects of interference with PATL1 on the expression of cel- lular-myelocytomatosis viral oncogene ( c-Myc) and autophagy related 7 ( ATG7) proteins in gastric cancer cells were detected by Western blot assay. @*Results @#RT-qPCR showed that the expression of PATL1 in human gastric cancer tissue was higher than that in normal gastric tissue (P＜0. 001) ，and PATL1 was correlated with the progno- sis of patients with enteric gastric cancer (P＜0. 000 1) ．After PATL1 was knocked down，the number of prolifera- ting and migrating gastric cancer cells decreased (P＜0. 05) ．Western blot test results showed that the expression level of ATG7 protein decreased after PATL1 was knocked down (P＜0. 05) ．@*Conclusion @#PATL1 may inhibit the proliferation and migration of gastric cancer cells through crosstalk with c-Myc and ATG7 .

Analysis on integrity of target nucleic acid in recombinant adeno-associated virus / 中国生物制品学杂志

@#Objective To explore a method for detecting the integrity of target nucleic acid in recombinant adeno-associated virus(rAAV),and establish a preliminary analysis algorithm.Methods The free DNA fragment of rAAV was digested,and the virus genome was extracted.Five pairs of overlapping primers were designed,using the orthogonal array method,which were detected by digital PCR respectively,with conventional conditions:20 μL reaction system with EveGreen and4 μL template,and digital PCR conditions:95 ℃ 5 min;95 ℃ 15 s,55 ℃ 30 s,72 ℃ 90 s for 45 cycles.The enhancement condition of ultra-long nucleic acid fragment was 25 μL reaction system with Mix B-2 000 bp and 2 μL template,and the quantitative analysis was performed by using the software attached to the instrument.Using the least square method,the number of full-length fragments was fitted and analyzed,and then the integrity distribution of target nucleic acid was interpreted.Results The fragments with the distance between primers of no more than 1 200 nt were amplified effectively,and a series of effective copies of fragments with a length of about 1 000 nt were obtained by systematic analysis.The copy number of common fragments was fitted and analyzed by the least square method.It was estimated that the full-length fragments in the sample were no more than 1 234 copies/μL,and there was a signficant difference(P < 0.05)between this value and the maximum measured value of 1 443 copies/μL,with the difference of approximately 16.9%.Conclusion A preliminary detection method for the integrity of target nucleic acid in rAAV has been developed,and a certain amount of incomplete target nucleic acids were analyzed in the test sample,laying a foundation for further in-depth research.

Establishment and validation of a method for determination of interesting protein expression level in cells infected with recombinant adeno-associated virus / 中国生物制品学杂志

@#Objective To establish and validate a method for the determination of the interesting protein expression level of recombinant adeno-associated virus(rAAV)infected cells,so as to monitor the product quality in different stages of rAAV9production process.Methods After incubation of serial diluted rAAV samples with infection enhancer Envirus-AAV,the human malignant glioblastoma cells(U87-MG)pretreated with hydroxyurea(HU)were infected.Using rAAV9 reference as the standard,the expression level of glutaryl-CoA dehydrogenase(GCDH)was detected by ELISA,and the specificity,accuracy,precision,linear range,limit of quantitation(LOQ)and durability of the method were verified.Eight batches of rAAV9 samples were detected by the established method.Results The A_(450)-A_(630) value of the sample buffer was 0.3,which was slightly lower than the lowest dilution point(1 ng/mL)of the four-parameter standard curve for protein quantification.The average recoveries of samples with 150%,100% and 50% theoretical relative titer levels were in the range of 100.0%-107.3%.The RSDs of the target protein expression level of the samples with three theoretical relative titer levels detected by the same experimenter three times and different experimenters were all less than 25%.There was a good linear relationship between rAAV9 samples and the target protein expression levels in the range of 50%-150% theoretical relative titer levels,and the linear regression equation was y = 1.077 x-0.022,R~2= 0.984.The LOQ of the method was 0.59,namely 6.0×10~(12) vg/mL.After U87-MG cells were incubated with HU for different time(18,21,24 h),and the culture supernatant was stored under different conditions(room temperature for 0.5 h,below-60 ℃ for 12 h,below-60 ℃ for 24 h).The RSDs of target protein expression levels were all less than 25%.The target protein expression levels of 1-8 batches of rAAV9 samples were 111%,121%,72%,65%,86%,75%,102% and 91%,respectively.Conclusion The established method for the determination of the target protein expression level after rAAV infection has good specificity,accuracy,precision and durability,and can be used for the quality control of products in different stages of rAAV9 production.

A systematic review on the effectiveness of N-acetylcysteine in children with dengue-associated liver injury

Objectives@#This study aimed to determine the effectiveness of N-acetylcysteine (NAC) in reversal of liver enzyme abnormalities among pediatric patients with dengue induced liver injury.@*Materials and Methods@#The preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P 2020) declaration was used to create this systematic review. The study population included children (<18 years old) diagnosed with dengue-associated Liver Injury and given NAC. The outcome of interest was full recovery. A search was performed in PubMed/MEDLINE, EMBASE, Google Scholar, HERDIN PLUS, WPRIM, clinicaltrials.gov, and Cochrane databases on March 2023. The New Castle-Ottawa Quality Assessment Scale was adapted for risk of bias assessment for cohort studies.@*Results@#Three case series and one pre-post cohort study published from 2013 to 2022 were included. The studies were of acceptable quality. In two studies with overall 10 pediatric patients given NAC for dengue-related ALF, all recovered without adverse events. In one study with 4 patients given NAC, half survived with their liver function tests returning to normal values. Finally, in one comparative study, the durations of time before the liver function tests returned to normal levels, and the mortality rates between those treated with and without N-acetyl cysteine were not significantly different. All studies reported no occurrence of adverse drug reaction related to NAC. @*Conclusion@#This systematic review shows limited evidence on the effectiveness of NAC in the reversal of liver enzymes among pediatric patients because of the low incidence of dengue induced liver injury seen in observational studies. Given that NAC is reported by all four studies to be accessible, effective, and with no attributable adverse events, its use can be considered. However, clinicians must still be cautioned given the limited available evidence.

Relationship between serum lncRNA XIST and SIRT1 levels with diabetic retinopathy and their diagnostic value / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To detect the expression levels of long non-coding RNA(lncRNA)X-inactive specific transcript(XIST)and silencing information regulatory factor 2 associated enzyme 1(SIRT1)in serum of patients with type 2 diabetes mellitus(T2DM), and to explore their correlation with diabetic retinopathy(DR)and their diagnostic value. METHODS: Prospective study. A total of 214 patients with T2DM admitted to our hospital from January 2022 to February 2023 were selected as the research subjects. Based on whether retinopathy occurred, they were divided into 126 cases(126 eyes)in the non-DR group and 88 cases(88 eyes)in the DR group. An additional 130 healthy individuals who underwent a physical examination during the same period were selected as the control group. The serum levels of lncRNA XIST and SIRT1 in the three groups were measured and compared. The relationship between lncRNA XIST and SIRT1 expression with DR was analyzed using Pearson's method. The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum lncRNA XIST, SIRT1, and their combination for DR. Multivariate Logistic regression analysis was performed to investigate the factors affecting the occurrence of DR in T2DM patients.RESULTS: Compared with the control group, the levels of serum lncRNA XIST and SIRT1 in the non-DR group and DR group were successively decreased(all P&#x003C;0.05). The levels of serum lncRNA XIST and SIRT1 were positively correlated in DR patients(r=0.639, P&#x003C;0.05). ROC analysis showed that the area under the curve(AUC)for predicting DR by combining serum lncRNA XIST and SIRT1 was 0.940, which was higher than the AUC by serum lncRNA XIST and SIRT1 alone(0.855, 0.875). Logistic regression analysis showed that lncRNA XIST(OR=0.752)and SIRT1(OR=0.694)were influencing factors for the occurrence of DR(both P&#x003C;0.01).CONCLUSION: The serum levels of lncRNA XIST and SIRT1 are both lower in DR patients, and the combination of lncRNA XIST and SIRT1 has a better assessment capacity for the occurrence of DR.

Virological features of chronic hepatitis B patients with metabolic associated fatty liver disease： A stratified analysis / 临床肝胆病杂志

ObjectiveTo investigate the virological features of patients with chronic hepatitis B （CHB） and metabolic associated fatty liver disease （MAFLD） through a stratified analysis. MethodsA retrospective analysis was performed for 131 patients with CHB and MAFLD and 168 patients with CHB alone who underwent percutaneous liver biopsy and did not receive antiviral therapy or withdrew from drugs for more than 6 months in Beijing YouAn Hospital， Capital Medical University， from January 1， 2013 to December 31， 2019. The two groups were compared in terms of general data， biochemical parameters， and virological parameters. The patients in the two groups were stratified according to liver inflammation grade （G） and liver fibrosis stage （S）， and the patients with CHB and MAFLD were further analyzed based on the degree of hepatic steatosis and NAFLD activity score （NAS）. Virological features （the serum levels of HBV DNA and HBV HBsAg） were compared between groups. The Wilcoxon test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups； the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the CHB group， the CHB+MAFLD group had a significantly higher proportion of male patients， a significantly higher proportion of patients with hypertension or type 2 diabetes mellitus， and significantly higher levels of the blood biochemical parameters of triglyceride， low-density lipoprotein cholesterol， apolipoprotein B， alanine aminotransferase， gamma-glutamyl transpeptidase， uric acid， and fasting blood glucose （all P<0.05）， as well as significantly lower levels of high-density lipoprotein cholesterol， apolipoprotein A1， and HBV DNA （all P<0.05）. The stratified analysis based on liver fibrosis stage showed that for both the patients with CHB alone and those with CHB and MAFLD， the significant fibrosis （S2‍ ‍—‍ ‍4） group had a significantly lower level of HBV DNA than the non-significant fibrosis （S0‍ ‍—‍ ‍1） group （P<0.05）， and for the patients with CHB alone， the significant fibrosis （S2‍ ‍—‍ ‍4） group had a significantly lower level of HBsAg than the non-significant fibrosis （S0‍ ‍—‍ ‍1） group （P<0.05）. The stratified analysis based on inflammation grade showed that for the patients with CHB and MAFLD， the high inflammation grade （G3） group had a significantly higher level of HBV DNA than the low inflammation grade （G1‍ ‍—‍ ‍2） group （P<0.05）， and in the low inflammation grade （G1‍ ‍—‍ ‍2） group， the patients with CHB and MAFLD had a significantly lower level of HBsAg than the patients with CHB alone （P<0.05）. The stratified analysis based on the degree of hepatic steatosis showed that the level of HBV DNA gradually decreased with the increase in the degree of steatosis， and the severe steatosis group had a significantly lower level of HBV DNA than the mild group （P<0.05）， while there was no significant difference in HBsAg level between the groups with different degrees of hepatic steatosis （P>0.05）. The stratified analysis based on NAS score showed that the NAS≥4 group had significantly higher levels of HBV DNA and HBsAg than the NAS<4 group （both P<0.05）. ConclusionPatients with CHB and MAFLD have significant abnormalities in metabolic markers and aminotransferases， while virological indicators show different features in stratified analyses based on various indicators.

Brain Targeted Strategies of Oligonucleotide Drug for Aging-associated Diseases Therapy / 生物化学与生物物理进展

Oligonucleotide drugs have experienced accelerated development in the past 10 years, and some of them have been used in clinical treatment. Because of its convenient design, flexible sequence, and high specificity, it is expected to solve the “undruggable” challenge of many targets which are difficult in drug development. Moreover, its clinical transformation period and cost are relatively low, which makes oligonucleotide drug become the frontier of emerging biotechnology drug discovery. Brain diseases include a series of incurable diseases, such as neurodegenerative diseases, glioma, and motor neuron diseases. Many of them are age-related and regarded as aging-associated brain diseases. Due to the complex etiology, many targets are difficult to be drugged. At the same time, the existence of the barrier system “blood-brain barrier” in the brain makes most drugs unable to achieve effective accumulation at brain lesions, and many small molecule drugs have failed in clinical transformation. The specificity and sequence flexibility of oligonucleotide acid drugs provide new possibilities for drug development, but they also face the challenge of brain delivery. Although a variety of oligonucleotide drugs have been used in the medical market, brain-targeted oligonucleotide drugs are still extremely rare. This article reviewed recent advances and discussed key topics and clinical transformation challenges in this field, such as clinical approval cases, bottlenecks of brain-targeted delivery and current strategies, as well as potential targets for aging-related brain diseases.

Research Progress on Cancer-Associated Fibroblasts in Hepatocellular Carcinoma / 肿瘤防治研究

Hepatocellular carcinoma (HCC) is one of the cancers with the highest incidence and mortality rates in China and often presents with insidious early clinical manifestations. This frequency results in the majority of patients being diagnosed at middle and advanced stage of the disease, thereby missing the opportunity for potentially curative surgical interventions. For patients who are ineligible for radical surgical resection, a variety of therapeutic approaches, including systemic antitumor therapy, local radiotherapy, interventional treatment, and liver transplantation, have been employed. Moreover, neoadjuvant therapies have transformed a subset of initially unresectable HCC cases into operable ones. Nevertheless, many patients fail to benefit from these treatments, underscoring the urgent need for novel therapeutic targets. Cancer-associated fibroblasts (CAFs), a principal component of the solid tumor microenvironment, play a pivotal role in the proliferation, migration, invasion, and treatment resistance of cancer cells. This review delineates the origins of CAFs and their mechanisms of action in the pathogenesis and progression of HCC and discusses potential therapeutic strategies targeting CAFs.

Current situation of healthcare-associated infection management of fever clinics in Wuhan medical institutions / 公共卫生与预防医学

Objective To analyze the current situation of healthcare-associated infection (HCAI) management of fever clinics among different levels of medical institutions in Wuhan, and to provide a scientific basis for improving hospital infection management. Methods In January 2023, a network questionnaire survey was conducted on medical institutions with fever clinics in Wuhan. Results A total of 72 medical institutions were investigated, of which 58.33% had CT, and 48.61% had fever clinics for children. The total qualified rate of HCAI management was 78.28%. The qualified rates of four primary indicators, including hospital management, diagnosis and treatment environment protection, training and education, and implementation of infection control measures, were 82.27%, 71.49%, 75.93%, and 81.31%, respectively. There were statistical differences among different levels of medical institutions (all P<0.01). Among the 13 secondary indicators, the qualified rates of 7 indicators were more than 80%, with the highest being medical item management (93.06%), medical waste disposal (89.72%), and personnel management (83.33%), and the lowest being facilities and equipment (66.32%), and patients and accompanying personnel education (66.67%). Among the 65 tertiary indicators, 30 had a pass rate great than 80%. Conclusion Wuhan actively promotes the construction of fever clinics in medical institutions, and the overall situation of HCAI management is good. However, there are still some problems to varying degrees, especially in the layout procedures, hand hygiene, and staff training of fever clinics in secondary and lower medical institutions, which should be further strengthened.

Characterization analysis of capsid protein of recombinant adeno-associated virus 6 using reversed phase liquid chromatography-mass spectrometry / 中国生物制品学杂志

@#Objective To characterize the capsid proteins of recombinant adeno-associated virus 6(rAAV6)vectors by reversed phase liquid chromatography-mass spectrometry(RPLC-MS),including primary structure and post-translational modification(PTM).Methods The mobile phase A consisted of 0. 1% aqueous solution of difluoroacetic acid(DFA),while the mobile phase B was 0. 1% DFA acetonitrile solution. The column temperature was maintained at 80 ℃,and the gradient elution lasted for 10 min(0→10 min,mobile phase B 15%→45%). The ESI-Q-TOF mass spectrometry detection operated in positive ion mode with the scanning range of 400-4 000 m/z,the scanning frequency of 2 Hz,the cone voltage at 80 V,the capillary voltage at 3. 0 kV,and the ion source temperature at 120 ℃.Results The measured relative molecular mass of the AAV capsid proteins VP1,VP2,and VP3 was 81 255. 9,66 062. 9,and 59 488. 6,respectively. The deviations from the theoretical values were 8. 1 ppm for VP1,3. 8 ppm for VP2,and 36 ppm for VP3. Mass peptide profile analysis of the enzymatically digested rAAV6 sample indicated a sequence coverage of about 89% with detected PTMs mainly including deamidation,N-terminal acetylation,ubiquitination,and phosphorylation;no glycosylation modification sites were found. Tandem mass spectrometry confirmed the N-terminal and C-terminal sequences of the rAAV6 capsid protein as well as the N-terminal PTM.Conclusion The complete relative molecular mass of rAAV6 capsid protein was analyzed by RPLCMS technique,and the PTM of rAAV6 capsid protein was analyzed by tandem mass spectrometry at the peptide level,which has a certain significance for the quality control of AAV gene therapy products and the improvement of production process.

qPCR在重组腺相关病毒产品大片段宿主细胞残留DNA检测中的应用 / 中国生物制品学杂志

@#Objective To investigate the feasibility of using quantitative PCR(qPCR)technology to detect large fragments of host cell residual DNA(HCD)in recombinant adeno-associated virus(rAAV)gene therapy products.Methods Four different serotypes of rAAV were extracted for the nucleic acids,two fragment sequences of 244 bp and 562 bp within the long terminal repeat sequence(LTR)in the genome of host cells HEK293 were specifically quantified by qPCR,and the proportion of HCD in the total nucleic acids was calculated.Results Large fragments of HCD in qPCR quantifiable range were detected in four different serotype rAAV products,with the abundance ranging from 0. 3% to 5. 4%. As the length of the detected fragment increased,the abundance of HCD fragments showed a decreasing trend.Conclusion qPCR technology can be used to determine the presence of large fragments of HCD in rAAV products.