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.

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

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

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

Gerenciamento do protocolo de prevenção de lesão por pressão: construção de painel de bordo informatizado / Management of the pressure injury prevention protocol: construction of a computerized dashboard / Gestión del protocolo de prevención de lesiones por presión: construcción de panel informatizado

Objetivo: Relatar a construção e implantação de painel de bordo, desenvolvido por enfermeiros e profissionais da tecnologia da informação, para gerenciamento do Protocolo de Prevenção de Lesão por Pressão. Métodos: Trata-se de um relato de experiência sobre a construção e implantação de painel de bordo informatizado para gerenciamento de protocolo em um hospital privado universitário, localizado no interior do estado de São Paulo. Resultados: A construção do painel de bordo foi dividida nas seguintes etapas: revisão e atualização do protocolo, construção do modelo eletrônico e implementação. A divulgação foi realizada pela Comissão de Prevenção de Lesão por Pressão. Conclusão: O painel de bordo possibilitou a visualização rápida e em tempo real dos riscos dos pacientes, intervenções propostas e efetividade das medidas de prevenção, além de promover a integração e empoderamento dos profissionais na gestão do cuidado. (AU)

Objective: To report the construction and implementation of a dashboard, developed by nurses and information technology professionals, to manage the Pressure Injury Prevention Protocol. Methods: This is an experience report on the construction and implementation of a computerized dashboard for protocol management in a private university hospital, located in the interior of the state of São Paulo. Results: The construction of the dashboard was divided into the following steps: review and update of the protocol, construction of the electronic model and implementation. The Pressure Injury Prevention Commission disclosed the tool. Conclusion: The dashboard enabled the quick and real-time visualization of patient risks, proposed interventions and effectiveness of prevention measures, in addition to promoting the integration and empowerment of professionals in the management of care. (AU)

Objetivo: Informar la construcción e implementación de un panel, desarrollado por enfermeras y profesionales de tecnologías de la información, para gestionar el Protocolo de Prevención de Lesiones por Presión. Métodos: Se trata de un informe de experiencia sobre la construcción e implementación de un panel computarizado para la gestión del protocolo en un hospital universitario privado, en el interior del estado de São Paulo. Resultados: La construcción del panel se dividió en los siguientes pasos: revisión y actualización del protocolo, construcción del modelo electrónico e implementación. La divulgación fue realizada por la Comisión de Prevención de Lesiones por Presión. Conclusión: El panel permitió la visualización rápida y en tiempo real de los riesgos del paciente, las intervenciones propuestas y la efectividad de las medidas de prevención, además de promover la integración y el empoderamiento de los profesionales en la gestión del cuidado. (AU)

El humo del electrocauterio, el riesgo olvidado y minimizado de la cirugía / Smoke from electrocautery, the forgotten and minimized risk of surgery

Introducción. La nueva era de la cirugía es cada vez más dependiente de la tecnología, y un ejemplo de ello es el uso generalizado de electrocauterio como parte primordial de la práctica quirúrgica. El humo quirúrgico es un subproducto de la disección y la coagulación de los tejidos producidas por los equipos de energía, que representa múltiples riesgos potenciales para la salud del grupo quirúrgico, sin embargo, se han minimizado los peligros causados por la exposición de manera frecuente y acumulativa a este aerosol. Métodos. Se realizó un análisis crítico, desde una posición reflexiva de la información disponible, estableciendo los posibles riesgos relacionados con la exposición al humo quirúrgico. Discusión. Es visible la necesidad imperativa de establecer directrices nacionales, pautas normativas y recomendaciones estandarizadas para cumplir con las exigencias dadas por los sistemas de gestión en salud ocupacional y seguridad del trabajo, cuyo objetivo principal es hacer efectivo el uso de mascarillas quirúrgicas apropiadas, la implementación de programa de vigilancia epidemiológica ambiental en sala de cirugía, la priorización del uso constante de aspiradores y sistemas de evacuación, y la ejecución de programas educativos de sensibilización dirigidos al personal implicado. De igual manera, se abre la inquietud de la necesidad de nuevos estudios para definir con mayor precisión el peligro de este aerosol. Conclusión. Se recomienda de manera responsable utilizar todas las estrategias preventivas existentes para intervenir en salas de cirugía los riesgos minimizados y olvidados del humo quirúrgico.

Introduction. The new era of surgery is increasingly dependent on technology, and an example of this is the widespread use of electrocautery as a primary part of surgical practice. Surgical smoke is a byproduct of the dissection and coagulation of tissues produced by energy equipment, which represents multiple potential health risks for the surgical group; however, the dangers caused by cumulative exposure have been minimized. Methods. A critical analysis was carried out from a reflective position of the available information, establishing the possible risks related to exposure to surgical smoke. Discussion. The imperative need to establish national normative guidelines and standardized recommendations to comply with the demands given by the occupational health and work safety management systems, whose main objective is to make effective the use of appropriate surgical masks, implementation of environmental epidemiological surveillance program in the operating room, prioritizing the constant use of vacuum cleaners and evacuation systems, and carrying out educational awareness programs aimed at the personnel involved. Likewise, there is concern about the need for new studies to more precisely define the danger of this aerosol. Conclusion. It is recommended to responsibly use all existing preventive strategies to intervene in operating rooms to minimize the forgotten risks of surgical smoke.

Traumatismo anorrectal contuso. Reporte de un caso y revisión bibliográfica / Blunt anorectal trauma. Case reportand literature review

Introducción: El traumatismo anorrectal es una causa poco frecuente de consulta al servicio de emergencias, con una incidencia del 1 al 3%. A menudo está asociado a lesiones potencialmente mortales, por esta razón, es fundamental conocer los principios de diagnóstico y tratamiento, así como los protocolos de atención inicial de los pacientes politraumatizados. Método: Reportamos el caso de un paciente masculino de 47 años con trauma anorrectal contuso con compromiso del esfínter anal interno y externo, tratado con reparación primaria del complejo esfinteriano con técnica de overlapping, rafia de la mucosa, submucosa y muscular del recto. A los 12 meses presenta buena evolución sin incontinencia anal. Conclusión: El tratamiento del trauma rectal, basado en el dogma de las 4 D (desbridamiento, derivación fecal, drenaje presacro, lavado distal) fue exitoso. La técnica de overlapping para la lesión esfinteriana fue simple y efectiva para la reconstrucción anatómica y funcional. (AU)

Introduction: Anorectal trauma is a rare cause of consultation to the Emergency Department, with an incidence of 1 to 3%. It is often associated with life-threatening injuries, so it is essential to know the principles of diagnosis and treatment, as well as the initial care protocols for the polytrau-matized patient. Methods: We present the case of a 47-year-old man with a blunt anorectal trauma involving the internal and external anal sphincter, treated with primary overlapping repair of the sphincter complex and suturing of the rectal wall. At 12 months the patient presents good outcome, without anal incontinence. Conclusion: The treatment of rectal trauma, based on the 4 D ́s dogma (debridement, fecal diversion, presacral drainage, distal rectal washout lavage) was successful. Repair of the overlapping sphincter injury was simple and effective for anatomical and functional reconstruction. (AU)

Pediatric nephrologist-intensivist interaction in acute kidney injury / Interação nefro-intensivista pediátrica na lesão renal aguda

ABSTRACT Introduction: Acute Kidney Injury (AKI) in the Intensive Care Unit (ICU) have concepts of diagnosis and management have water balance as their main point of evaluation. In our ICU, from 2004 to 2012, the nephrologist's participation was on demand only; and as of 2013 their participation became continuous in meetings to case discussion. The aim of this study was to establish how an intense nephrologist/intensivist interaction influenced the frequency of dialysis indication, fluid balance and pRIFLE classification during these two observation periods. Methods: Retrospective study, longitudinal evaluation of all children with AKI undergoing dialysis (2004 to 2016). Parameters studied: frequency of indication, duration and volume of infusion in the 24 hours preceding dialysis; diuresis and water balance every 8 hours. Non-parametric statistics, p ≤ 0.05. Results: 53 patients (47 before and 6 after 2013). There were no significant differences in the number of hospitalizations or cardiac surgeries between the periods. After 2013, there was a significant decrease in the number of indications for dialysis/year (5.85 vs. 1.5; p = 0.000); infusion volume (p = 0.02), increase in the duration of dialysis (p = 0.002) and improvement in the discrimination of the pRIFLE diuresis component in the AKI development. Conclusion: Integration between the ICU and pediatric nephrology teams in the routine discussion of cases, critically approaching water balance, was decisive to improve the management of AKI in the ICU.

RESUMO Introdução: Os conceitos sobre diagnóstico e conduta da Lesão Renal Aguda (LRA) na Unidade de Terapia Intensiva (UTI) tem como ponto primordial a avaliação do balanço hídrico. Em nossa UTI, de 2004 a 2012, a participação do nefrologista era sob demanda. A partir de 2013, a participação passou a ser contínua em reunião de discussão de casos. O objetivo deste estudo foi determinar como a maior interação nefrologista/intensivista influenciou a frequência de indicação de diálise, no balanço hídrico e na classificação pRIFLE durante esses dois períodos de observação. Método: Estudo retrospectivo, avaliação longitudinal de todas as crianças com LRA em diálise (2004 a 2016). Parâmetros estudados: frequência de indicação, tempo de duração e volume de infusão nas 24 horas precedendo a diálise; diurese e balanço hídrico a cada 8 horas. Estatística não paramétrica, p ≤ 0,05. Resultado: 53 pacientes (47 antes e 6 após 2013). Sem diferença significativa no número de internações e nem de cirurgias cardíacas entre os períodos. Após 2013, houve diminuição significativa no número de indicação de diálise/ano (5,85 vs. 1,5; p = 0,000); no volume de infusão (p = 0,02), aumento do tempo de duração da diálise (p = 0,002) e melhora da discriminação do componente diurese do pRIFLE na indicação de LRA. Conclusão: Integração entre equipes de UTI e nefrologia pediátrica na discussão rotineira de casos, abordando criticamente o balanço hídrico, foi determinante para a melhora na conduta da LRA na UTI.

Case fatality rate among COVID-19 patients treated with acute kidney replacement therapy / Letalidade entre pacientes com injúria renal aguda por COVID-19 tratados com suporte renal artificial

Abstract Introduction: Acute kidney injury (AKI) is a frequent complication of severe COVID-19 and is associated with high case fatality rate (CFR). However, there is scarcity of data referring to the CFR of AKI patients that underwent kidney replacement therapy (KRT) in Brazil. The main objective of this study was to describe the CFR of critically ill COVID-19 patients treated with acute kidney replacement therapy (AKRT). Methods: Retrospective descriptive cohort study. We included all patients treated with AKRT at an intensive care unit in a single tertiary hospital over a 15-month period. We excluded patients under the age of 18 years, patients with chronic kidney disease on maintenance dialysis, and cases in which AKI preceded COVID-19 infection. Results: A total of 100 out of 1479 (6.7%) hospitalized COVID-19 patients were enrolled in this study. The median age was 74.5 years (IQR 64 - 82) and 59% were male. Hypertension (76%) and diabetes mellitus (56%) were common. At the first KRT prescription, 85% of the patients were on invasive mechanical ventilation and 71% were using vasoactive drugs. Continuous veno-venous hemodiafiltration (CVVHDF) was the preferred KRT modality (82%). CFR was 93% and 81 out of 93 deaths (87%) occurred within the first 10 days of KRT onset. Conclusion: AKRT in hospitalized COVID-19 patients resulted in a CFR of 93%. Patients treated with AKRT were typically older, critically ill, and most died within 10 days of diagnosis. Better strategies to address this issue are urgently needed.

Resumo Introdução: Injúria renal aguda (IRA) é uma complicação frequente da COVID-19 grave e está associada a alta taxa de letalidade (TL). Entretanto, há escassez de dados referentes à TL de pacientes com IRA submetidos a suporte renal artificial (SRA) no Brasil. O objetivo principal deste estudo foi descrever a TL de pacientes graves com IRA por COVID-19 tratados com SRA. Métodos: Estudo de coorte descritivo retrospectivo. Incluímos todos os pacientes tratados com SRA em unidade de terapia intensiva de um único hospital terciário por 15 meses. Excluímos pacientes menores de 18 anos, pacientes com doença renal crônica em diálise de manutenção e casos nos quais a IRA precedeu a infeção por COVID-19. Resultados: Incluímos neste estudo um total de 100 dos 1479 (6,7%) pacientes hospitalizados com COVID-19. A mediana de idade foi 74,5 anos (IIQ 64 - 82) e 59% eram homens. Hipertensão (76%) e diabetes mellitus (56%) foram comuns. Na primeira prescrição de SRA, 85% dos pacientes estavam em ventilação mecânica invasiva e 71% em uso de drogas vasoativas. A hemodiafiltração contínua foi a modalidade de SRA preferida (82%). A TL foi de 93% e 81 dos 93 óbitos (87%) ocorreram nos primeiros 10 dias do início da SRA. Conclusão: O SRA em pacientes hospi­talizados com IRA por COVID-19 resultou em TL de 93%. Os pacientes tratados com SRA eram geralmente idosos, gravemente enfermos e a maioria foi a óbito em até 10 dias após o diagnóstico. Estratégias melhores para abordar esse problema são urgentemente necessárias.

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Effect of Long-term Peripheral Nerve Stimulation on Neuro-Muscular Complex Morphologic Recovery in Experiment / Efecto de la Estimulación del Nervio Periférico a Largo Plazo sobre la Recuperación Morfológica del Complejo Neuromuscular en Experimento

SUMMARY: Peripheral nerve injury is an extremely important medical and socio-economic problem. It is far from a solution, despite on rapid development of technologies. To study the effect of long-term electrical stimulation of peripheral nerves, we used a domestically produced electrical stimulation system, which is approved for clinical use. The study was performed on 28 rabbits. Control of regeneration was carried out after 3 month with morphologic techniques. The use of long-term electrostimulation technology leads to an improvement in the results of the recovery of the nerve trunk after an injury, both directly at the site of damage, when stimulation begins in the early period, and indirectly, after the nerve fibers reach the effector muscle.

La lesión de los nervios periféricos es un problema médico y socioeconómico extremadamente importante. Sin embargo, y a pesar del rápido desarrollo de las tecnologías, aún no tiene solución. Para estudiar el efecto de la estimulación eléctrica a largo plazo de los nervios periféricos, utilizamos un sistema de estimulación eléctrica de producción nacional, que está aprobado para uso clínico. El estudio se realizó en 28 conejos. El control de la regeneración se realizó a los 3 meses con técnicas morfológicas. El uso de tecnología de electro estimulación a largo plazo conduce a una mejora en los resultados de la recuperación del tronco nervioso después de una lesión, tanto directamente en el lugar del daño, cuando la estimulación comienza en el período temprano, como indirectamente, después de que las fibras nerviosas alcanzan el músculo efector.

Edema pulmonar por reexpansión. Reporte de Caso / Pulmonary edema due to re-expansion. Case Report

Introducción. El edema pulmonar por reexpansión es una complicación poco frecuente, secundaria a una rápida reexpansión pulmonar posterior al drenaje por toracentesis o toracostomía cerrada. Al día de hoy, se ha descrito una incidencia menor al 1 % tras toracostomía cerrada, con mayor prevalencia en la segunda y tercera década de la vida. Su mecanismo fisiopatológico exacto es desconocido; se ha planteado un proceso multifactorial de daño intersticial pulmonar asociado con un desequilibrio de las fuerzas hidrostáticas. Caso clínico. Presentamos el caso de un paciente que desarrolló edema pulmonar por reexpansión posterior a toracostomía cerrada. Se hizo una revisión de la literatura sobre esta complicación. Resultados. Aunque la clínica sugiere el diagnóstico, la secuencia de imágenes desempeña un papel fundamental. En la mayoría de los casos suele ser autolimitado, por lo que su manejo es principalmente de soporte; sin embargo, se han reportado tasas de mortalidad que alcanzan hasta el 20 %, por tanto, es importante conocer los factores de riesgo y las medidas preventivas. Conclusión. El edema pulmonar de reexpansión posterior a toracostomía es una complicación rara en los casos con neumotórax, aunque es una complicación que se puede presentar en la práctica diaria, por lo cual debe tenerse en mente para poder hacer el diagnóstico y un manejo adecuado.

Introduction. Re-expansion pulmonary edema is a rare complication secondary to rapid pulmonary re-expansion after drainage by thoracentesis and/or closed thoracostomy. As of today, an incidence of less than 1% has been described after closed thoracostomy, with a higher prevalence in the second and third decades of life. Its exact pathophysiological mechanism is unknown; a multifactorial process of lung interstitial damage associated with an imbalance of hydrostatic forces has been proposed. Clinical case. We present the case of a patient who developed pulmonary edema due to re-expansion after closed thoracostomy, conducting a review of the literature on this complication. Results. Although the clinic suggests the diagnosis, the sequence of images plays a fundamental role. In most cases, it tends to be a self-limited disease, so its management is mainly supportive. However, mortality rates of up to 20% have been recorded. Therefore, it is important to identify patients with major risk factors and initiate preventive measures in these patients. Conclusions. Re-expansion pulmonary edema after thoracostomy is a rare complication in cases with pneumothorax; however, it is a complication that can occur in daily practice. Therefore, it must be kept in mind to be able to make the diagnosis and an adequate management.

Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway

Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.

Trauma cerrado de aorta torácica, desde el servicio de urgencias hasta el quirófano: revisión narrativa / Blunt trauma of the thoracic aorta, from the emergency department to the operating room: narrative review / Trauma contuso da aorta torácica: do pronto-socorro ao centro cirúrgico, uma revisão narrativa

El trauma es la principal causa de muerte de la población en edad productiva. El abordaje del trauma torácico cerrado todavía es un desafío para el médico de urgencias. Aunque no es una entidad frecuente, se asocia con una alta mortalidad y resultados adversos. El diagnóstico del trauma cerrado de aorta torácica (LCAT) requiere un alto índice de sospecha, dado que los signos y síntomas no son específicos de esta enfermedad (dolor torácico, dolor interescapular, disnea, disfagia, estridor, disfonía). Es importante resaltar que la ausencia de inestabilidad hemodinámica no debe descartar una lesión aórtica. Para su diagnóstico imagenológico se debe tener en cuenta que los rayos X de tórax no tienen el rendimiento adecuado, el patrón de referencia es la angiotomografía y el ecocardiograma transesofágico (ETE) constituye una opción diagnóstica. El manejo incluye líquidos endovenosos y antihipertensivos como medida transitoria, manejo quirúrgico definitivo y, en algunos casos, manejo expectante o diferido. Los pacientes inestables o con signos de ruptura inminente deben ser llevados de manera inmediata a cirugía. El manejo quirúrgico temprano ha impactado en la mortalidad. A pesar de los avances en las técnicas quirúrgicas, la técnica quirúrgica abierta documenta mayor tasa de mortalidad que el manejo endovascular, el cual tiene numerosas ventajas al ser poco invasivo. Esta es una revisión narrativa que destaca algunos aspectos clave sobre los mecanismos de lesión, diagnóstico y manejo inicial del trauma cerrado aorta torácica. Por último, se propone un algoritmo de abordaje de trauma de aorta.

Trauma is the leading cause of death in the productive-age population. Addressing blunt chest trauma is still a challenge for the emergency physician. Although it is not a common entity, it is associated with high mortality and adverse outcomes. The diagnosis of blunt thoracic aortic trauma (LCAT) requires a high index of suspicion, given that the signs and symptoms are not specific to this disease (chest pain, interscapular pain, dyspnea, dysphagia, stridor, dysphonia). It is important to highlight that the absence of hemodynamic instability should not rule out aortic injury. For its imaging diagnosis, it must be taken into account that chest X-rays do not have adequate performance; the reference standard is angiotomography and transesophageal echocardiography (TEE) is a diagnostic option. Management includes intravenous fluids and antihypertensives as a temporary measure, definitive surgical management and, in some cases, expectant or deferred management. Unstable patients or patients with signs of imminent ruptura should be taken immediately to surgery. Early surgical management has impacted mortality. Despite advances in surgical techniques, the open surgical technique documents a higher mortality rate than endovascular management, which has numerous advantages as it is minimally invasive. This is a narrative review that highlights some key aspects about the mechanisms of injury, diagnosis and initial management of blunt thoracic aortic trauma. Finally, an algorithm for addressing aortic trauma is proposed.

O trauma é a principal causa de morte na população em idade produtiva. Abordar o trauma torácico contuso ainda é um desafio para o médico emergencista. Embora não seja uma entidade comum, está associada a alta mortalidade e resultados adversos. O diagnóstico de trauma fechado de aorta torácica (TACE) requer alto índice de suspeição, visto que os sinais e sintomas não são específicos desta doença (dor torácica, dor interescapular, dispneia, disfagia, estridor, disfonia). É importante ressaltar que a ausência de instabilidade hemodinâmica não deve descartar lesão aórtica. Para seu diagnóstico por imagem deve-se levar em consideração que a radiografia de tórax não apresenta desempenho adequado; o padrão de referência é a angiotomografia e a ecocardiografia transesofágica (ETE) é uma opção diagnóstica. O manejo inclui fluidos intravenosos e anti-hipertensivos como medida temporária, manejo cirúrgico definitivo e, em alguns casos, manejo expectante ou diferido. Pacientes instáveis ou com sinais de ruptura iminente devem ser encaminhados imediatamente para cirurgia. O manejo cirúrgico precoce impactou a mortalidade. Apesar dos avanços nas técnicas cirúrgicas, a técnica cirúrgica aberta documenta maior taxa de mortalidade do que o manejo endovascular, que apresenta inúmeras vantagens por ser minimamente invasivo. Esta é uma revisão narrativa que destaca alguns aspectos-chave sobre os mecanismos de lesão, diagnóstico e manejo inicial do trauma contuso da aorta torácica. Finalmente, é proposto um algoritmo para tratar o trauma aórtico.

Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics / 中华创伤杂志(英文版)

PURPOSE@#To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.@*METHODS@#This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.@*RESULTS@#Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.@*CONCLUSIONS@#Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Calcitonin gene-related peptide inhibits neuronal apoptosis in heatstroke rats via PKA/p-CREB pathway / 中华创伤杂志(英文版)

PURPOSE@#The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.@*METHODS@#We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant.@*RESULTS@#Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression.@*CONCLUSIONS@#CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Mechanism of Shikonin on spinal cord injury in rats based on TNFR/RIPK1 pathway / 中国骨伤

OBJECTIVE@#To explore the effect of shikonin on the recovery of nerve function after acute spinal cord injury(SCI) in rats.@*METHODS@#96 male Sprague-Dawley(SD)rats were divided into 4 groups randomly:sham operation group (Group A), sham operation+shikonin group (Group B), SCI+ DMSO(Group C), SCI+shikonin group (Group D).The acute SCI model of rats was made by clamp method in groups C and D . After subdural catheterization, no drug was given in group A. rats in groups B and D were injected with 100 mg·kg-1 of shikonin through catheter 30 min after modeling, and rats in group C were given with the same amount of DMSO, once a day until the time point of collection tissue. Basso-Beattie-Bresnahan(BBB) scores were performed on 8 rats in each group at 6, 12, and 3 d after moneling, and oblique plate tests were performed on 1, 3, 7 and 14 d after modeling, and then spinal cord tissues were collected. Eight rats were intraperitoneally injected with propidine iodide(PI) 1 h before sacrificed to detection PI positive cells at 24 h in each group. Eight rats were sacrificed in each group at 24 h after modeling, the spinal cord injury was observed by HE staining.The Nissl staining was used to observe survivor number of nerve cells. Western-blot technique was used to detect the expression levels of Bcl-2 protein and apoptosis related protein RIPK1.@*RESULTS@#After modeling, BBB scores were normal in group A and B, but in group C and D were significantly higher than those in group A and B. And the scores in group D were higher than those in group C in each time point (P<0.05). At 12 h after modeling, the PI red stained cells in group D were significantly reduced compared with that in group C, and the disintegration of neurons was alleviated(P<0.05). HE and Nissl staining showed nerve cells with normal morphology in group A and B at 24h after operation. The degree of SCI and the number of neuronal survival in group D were better than those in group C, the difference was statistically significant at 24h (P<0.05). The expression of Bcl-2 and RIPK1 proteins was very low in group A and B;The expression of RIPK1 was significantly increased in Group C and decreased in Group D, with a statistically significant difference (P<0.05);The expression of Bcl-2 protein in group D was significantly higher than that in group C (P<0.05).@*CONCLUSION@#Shikonin can alleviate the pathological changes after acute SCI in rats, improve the behavioral score, and promote the recovery of spinal nerve function. The specific mechanism may be related to the inhibition of TNFR/RIPK1 signaling pathway mediated necrotic apoptosis.

Analysis of the causes of cage subsidence after oblique lateral lumbar interbody fusion / 中国骨伤

OBJECTIVE@#To observe the cage subsidence after oblique lateral interbody fusion (OLIF) for lumbar spondylosis, summarize the characteristics of the cage subsidence, analyze causes, and propose preventive measures.@*METHODS@#The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively analyzed. There were 43 males and 101 females, and the age ranged from 20 to 81 years old, with an average of (60.90±10.06) years old. Disease types:17 patients of lumbar intervertebral disc degenerative disease, 12 patients of giant lumbar disc herniation, 5 patients of discogenic low back pain, 33 patients of lumbar spinal stenosis, 26 patients of lumbar degenerative spondylolisthesis, 28 patients of lumbar spondylolisthesis with spondylolisthesis, 11 patients of adjacent vertebral disease after lumbar internal fixation, 7 patients of primary spondylitis in the inflammatory outcome stage, and 5 patients of lumbar degenerative scoliosis. Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis, and 87 patients of normal bone density. The number of fusion segments:124 patients of single-segment, 11 patients of two-segment, 8 patients of three-segment, four-segment 1 patient. There were 40 patients treated by stand-alone OLIF, and 104 patients by OLIF combined with posterior pedicle screw. Observed the occurrence of fusion cage settlement after operation, conducted monofactor analysis on possible risk factors, and observed the influence of fusion cage settlement on clinical results.@*RESULTS@#All operations were successfully completed, the median operation time was 99 min, and the median intraoperative blood loss was 106 ml. Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients. The mean follow-up was (14.57±7.14) months from 6 to 30 months. During the follow-up, except for the patients of primary lumbar interstitial inflammation and some patients of lumbar spondylolisthesis with spondylolisthesis, the others all had different degrees of cage subsidence. Cage subsidence classification:119 patients were normal subsidence, and 25 patients were abnormal subsidence (23 patients were gradeⅠ, and 2 patients were gradeⅡ). There was no loosening or rupture of the pedicle screw system. The height of the intervertebral space recovered from the preoperative average (9.48±1.84) mm to the postoperative average (12.65±2.03) mm, and the average (10.51±1.81) mm at the last follow-up. There were statistical differences between postoperative and preoperative, and between the last follow-up and postoperative. The interbody fusion rate was 94.4%. The low back pain VAS decreased from the preoperative average (6.55±2.2 9) to the last follow-up (1.40±0.82), and there was statistically significant different. The leg pain VAS decreased from the preoperative average (4.72±1.49) to the final follow-up (0.60±0.03), and the difference was statistically significant (t=9.13, P<0.000 1). The ODI index recovered from the preoperative average (38.50±6.98)% to the latest follow-up (11.30±3.27)%, and there was statistically significant different. The complication rate was 31.3%(45/144), and the reoperation rate was 9.72%(14/144). Among them, 8 patients were reoperated due to fusion cage subsidence or displacement, accounting for 57.14%(8/14) of reoperation. The fusion cage subsidence in this group had obvious characteristics. The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group, Stand-alone OLIF group, 2 or more segments fusion group, and endplate injury group was higher than that in the normal bone mass group, OLIF combined with pedicle screw fixation group, single segment fusion group, and no endplate injury group, and the comparison had statistical differences.@*CONCLUSION@#Cage subsidence is a common phenomenon after OLIF surgery. Preoperative osteopenia or osteoporosis, Stand-alone OLIF, 2 or more segments of fusion and intraoperative endplate injury may be important factors for postoperative fusion cage subsidence. Although there is no significant correlation between the degree of cage subsidence and clinical symptoms, there is a risk of cage migration, and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence, including reoperation.

Research progress on mechanism of traumatic brain injury promoting fracture healing / 中国修复重建外科杂志

OBJECTIVE@#To summarize the research progress on the mechanism related to traumatic brain injury (TBI) to promote fracture healing, and to provide theoretical basis for clinical treatment of fracture non-union.@*METHODS@#The research literature on TBI to promote fracture healing at home and abroad was reviewed, the role of TBI in fracture healing was summarized from three aspects of nerves, body fluids, and immunity, to explore new ideas for the treatment of fracture non-union.@*RESULTS@#Numerous studies have shown that fracture healing is faster in patients with fracture combined with TBI than in patients with simple fracture. It is found that the expression of various cytokines and hormones in the body fluids of patients with fracture and TBI is significantly higher than that of patients with simple fracture, and the neurofactors released by the nervous system reaches the fracture site through the damaged blood-brain barrier, and the chemotaxis and aggregation of inflammatory cells and inflammatory factors at the fracture end of patients with combined TBI also differs significantly from those of patients with simple fracture. A complex network of humoral, neural, and immunomodulatory networks together promote regeneration of blood vessels at the fracture site, osteoblasts differentiation, and inhibition of osteoclasts activity.@*CONCLUSION@#TBI promotes fracture healing through a complex network of neural, humoral, and immunomodulatory, and can treat fracture non-union by intervening in the perifracture microenvironment.

Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/mTOR Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway.@*METHODS@#Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR.@*RESULTS@#The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01).@*CONCLUSIONS@#EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.

Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism.@*METHODS@#Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis.@*RESULTS@#DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01).@*CONCLUSIONS@#DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.

Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.@*METHODS@#A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed.@*RESULTS@#FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05).@*CONCLUSION@#FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.