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.

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.

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)

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.

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.

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.

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.

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.

Lesão renal aguda em pacientes adultos com COVID-19: revisão integrativa / Lesión renal aguda en pacientes adultos con COVID-19: revisión integradora / Acute kidney injury in adult patients with COVID-19: an integrative review

Resumo Objetivo Identificar a frequência de lesão renal aguda (LRA) em pacientes hospitalizados com COVID-19, as características associadas, a mortalidade e a letalidade. Métodos Revisão realizada nas bases de dados CINAHL, Embase, LILACS, Livivo, PubMed, SCOPUS, Web of Science e, na literatura cinzenta (Google Acadêmico) em 12 de janeiro de 2022. Foram incluídos artigos em inglês, espanhol e português, publicados a partir de novembro 2019 até janeiro de 2022, em pacientes maiores de 18 anos com COVID-19 hospitalizados e LRA conforme critério Kidney Disease Improving Global Outcomes (KDIGO). Os estudos selecionados foram lidos na íntegra para extração, interpretação, síntese e categorização conforme nível de evidência. Resultados 699 artigos encontrados e 45 incluídos. A idade avançada, sexo masculino, hipertensão, doença renal crônica, ventilação mecânica, aumento da proteína C reativa, uso de drogas vasoativas e de determinadas classes de anti-hipertensivos foram associados a LRA. A LRA está relacionada à maior frequência de mortalidade. Em 30% dos pacientes hospitalizados com COVID-19 houve LRA. A taxa de mortalidade por LRA foi de 5% e a letalidade de 18%. Conclusão Estes resultados ressaltam a relevância da LRA como uma complicação significativa da COVID-19 e sugerem que um controle mais cuidadoso e precoce dos fatores associados poderia potencialmente reduzir a mortalidade e a letalidade. É crucial intensificar a pesquisa nesse campo para esclarecer melhor os mecanismos envolvidos na lesão renal em pacientes com COVID-19, bem como identificar estratégias terapêuticas mais efetivas para sua prevenção e tratamento nesse contexto.

Resumen Objetivo Identificar la frecuencia de lesión renal aguda (LRA) en pacientes hospitalizados con COVID-19, las características relacionadas, la mortalidad y la letalidad. Métodos Revisión realizada en las bases de datos CINAHL, Embase, LILACS, Livivo, PubMed, SCOPUS, Web of Science y en la literatura gris (Google Académico) el 12 de enero de 2022. Se incluyeron artículos en inglés, español y portugués, publicados a partir de noviembre de 2019 hasta enero de 2022, con pacientes mayores de 18 años con COVID-19 hospitalizados y LRA de acuerdo con el criterio Kidney Disease Improving Global Outcomes (KDIGO). Los estudios seleccionados fueron leídos en su totalidad para extracción, interpretación, síntesis y categorización según el nivel de evidencia. Resultados Se encontraron 699 artículos y se incluyeron 45. Los factores relacionados con la LRA fueron: edad avanzada, sexo masculino, hipertensión, enfermedad renal crónica, ventilación mecánica, aumento de la proteína C reactiva, uso de drogas vasoactivas y de determinadas clases de antihipertensivos. La LRA está relacionada con mayor frecuencia de mortalidad. En el 30 % de los pacientes hospitalizados con COVID-19 hubo LRA. La tasa de mortalidad por LRA fue de 5 % y la letalidad de 18 %. Conclusión Estos resultados resaltan la relevancia de la LRA como una complicación significativa de COVID-19 y sugieren que un control más cuidadoso y temprano de los factores asociados podría reducir potencialmente la mortalidad y la letalidad. Es crucial intensificar la investigación en este campo para explicar mejor los mecanismos relacionados con la lesión renal en pacientes con COVID-19, así como identificar estrategias terapéuticas más efectivas para su prevención y tratamiento en este contexto.

Abstract Objective To identify the frequency of acute kidney injury (AKI) in patients hospitalized with COVID-19, associated characteristics, mortality and lethality. Methods Integrative review carried out in the databases CINAHL, Embase, LILACS, Livivo, PubMed, SCOPUS, Web of Science and in the grey literature (Google Scholar) on January 12, 2022. Articles were included in English, Spanish and Portuguese, published from November 2019 to January 2022, in hospitalized patients over 18 years old with COVID-19 and AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The selected studies were read in full for extraction, interpretation, synthesis and categorization according to the level of evidence. Results A total of 699 articles were found and 45 included. Older age, male gender, hypertension, chronic kidney disease, mechanical ventilation, increased C-reactive protein, use of vasoactive drugs and certain classes of antihypertensives were associated with AKI. AKI is related to a higher frequency of mortality. AKI occurred in 30% of patients hospitalized with COVID-19. The mortality rate from AKI was 5% and the case fatality rate was 18%. Conclusion These results highlight the relevance of AKI as a significant complication of COVID-19 and suggest that more careful and early control of associated factors could potentially reduce mortality and lethality. It is crucial to intensify research in this field to better clarify the mechanisms involved in kidney injury in COVID-19 patients, as well as to identify more effective therapeutic strategies for its prevention and treatment in this context.

Xuebijing improves inflammation and pyroptosis of acute lung injury by up-regulating miR-181d-5p-mediated SPP1 inactivation

Abstract Background Xuebijing (XBJ) is widely applied in the treatment of Acute Lung Injury (ALI). This study focused on the potential mechanism of XBJ in Lipopolysaccharide (LPS)-induced ALI. Methods The rat ALI model was established by injection of LPS (10 mg/kg) and pretreated with XBJ (4 mL/kg) three days before LPS injection. BEAS-2B cell line was stimulated with LPS (1 μg/mL) and ATP (5 mM) to induce pyroptosis, and XBJ (2 g/L) was pretreated 24h before induction. The improvement effects of XBJ on pulmonary edema, morphological changes, and apoptosis in ALI lung tissue were evaluated by lung wet/dry weight ratio, HE-staining, and TUNEL staining. Inflammatory cytokines in lung tissue and cell supernatant were determined by ELISA. pyroptosis was detected by flow cytometry. Meanwhile, the expressions of miR-181d-5p, SPP1, p-p65, NLRP3, ASC, caspase-1, p20, and GSDMD-N in tissues and cells were assessed by RT-qPCR and immunoblotting. The relationship between miR-181d-5p and SPP1 in experimental inflammation was reported by dual luciferase assay. Results XBJ could improve inflammation and pyroptosis of ALI by inhibiting contents of inflammatory cytokines, and levels of inflammation- and pyroptosis-related proteins. Mechanistically, XBJ could up-regulate miR-181d-5p and inhibit SPP1 in ALI. miR-181d-5p can target the regulation of SPP1. Depressing miR-181d-5p compensated for the ameliorative effect of XBJ on ALI, and overexpressing SPP1 suppressed the attenuating effect of XBJ on LPS-induced inflammation and pyroptosis. Conclusion XBJ can regulate the miR-181d-5p/SPP1 axis to improve inflammatory response and pyroptosis in ALI.

Lesão renal aguda e COVID-19 em adultos jovens na terapia intensiva / Lesión renal aguda y COVID-19 en adultos jóvenes en cuidados intensivos / Acute kidney injury and COVID-19 in young adults in intensive care

Resumo Objetivo Descrever a prevalência de lesão renal aguda em adultos jovens com diagnóstico da COVID-19 admitidos em unidade terapia intensiva. Métodos Estudo retrospectivo, quantitativo e analítico. A amostra foi de adultos jovens (20 a 40 anos) admitidos em unidades de terapia intensiva, com diagnóstico de infecção por SARS-CoV-2 entre março e dezembro de 2020. Os dados foram obtidos por meio do prontuário eletrônico, e a lesão renal aguda foi definida pelo valor da creatinina, segundo critérios das diretrizes da Kidney Disease Improving Global Outcomes. A significância estatística foi de p≤0,05. Resultados Foram internados 58 adultos jovens, sendo 63,8% do sexo masculino. A hipertensão arterial sistêmica esteve presente em 39,6%, a obesidade em 18,9% e o diabetes mellitus em 8,6%. A lesão renal aguda foi identificada em 55,1%, sendo o estágio 3 predominante em 43,1% deles. Nesses pacientes, o uso de ventilação mecânica e de drogas vasoativas foi significativo em 92%, assim como a disfunção orgânica respiratória (80%), seguida da renal (76%). Fatores de risco, como transplante renal ou doença renal crônica e obesidade, aumentaram em 12,3 e 9,0 vezes, respectivamente, a chance de desenvolver lesão renal aguda. Conclusão Este estudo demonstrou alta prevalência de lesão renal em adultos jovens e sua associação com comorbidades prévias. Obesidade, transplante renal e doença renal crônica elevaram a chance de o adulto jovem desenvolver lesão renal aguda, resultando em desfechos a favor da morbimortalidade.

Resumen Objetivo Describir la prevalencia de lesión renal aguda en adultos jóvenes con diagnóstico de COVID-19 admitidos en unidad de cuidados intensivos. Métodos Estudio retrospectivo, cuantitativo y analítico. La muestra fue de adultos jóvenes (20 a 40 años) admitidos en unidades de cuidados intensivos, con diagnóstico de infección por SARS-CoV-2 entre marzo y diciembre de 2020. Los datos se obtuvieron por medio de historias clínicas electrónicas, y la lesión renal aguda fue definida por el valor de la creatinina, de acuerdo con criterios de las directrices de la Kidney Disease Improving Global Outcomes. La significación estadística fue de p≤0,05. Resultados Hubo 58 adultos jóvenes internados, el 63,8 % de sexo masculino. La hipertensión arterial sistémica estuvo presente en el 39,6 %, la obesidad en el 18,9 % y la diabetes mellitus en el 8,6 %. Se identificó lesión renal aguda en el 55,1 %, de nivel 3 como predominante en el 43,1 % de los casos. En esos pacientes, el uso de ventilación mecánica y de drogas vasoactivas fue significativo en el 92 %, así como también la disfunción orgánica respiratoria (80 %), seguida de la renal (76 %). Los factores de riesgo, como trasplante renal o enfermedad renal crónica y obesidad, aumentaron 12,3 y 9,0 veces respectivamente la probabilidad de presentar lesión renal aguda. Conclusión Este estudio demostró alta prevalencia de lesión renal en adultos jóvenes y su asociación con comorbilidades previas. La obesidad, el trasplante renal y la enfermedad renal crónica aumentaron la probabilidad de que los adultos jóvenes presenten lesión renal aguda, lo que da como resultado desenlaces a favor de la morbimortalidad.

Abstract Objective To describe acute kidney injury prevalence in young adults diagnosed with COVID-19 admitted to the Intensive Care Unit. Methods This is a retrospective, quantitative and analytical study. The sample consisted of young adults (20 to 40 years old) admitted to Intensive Care Units, diagnosed with SARS-CoV-2 infection between March and December 2020. Data were obtained through electronic medical records, and kidney injury acute was defined by the creatinine value, according to the Kidney Disease Improving Global Outcomes guidelines criteria. Statistical significance was p≤0.05. Results A total of 58 young adults were hospitalized, 63.8% of whom were male. Hypertension was present in 39.6%, obesity in 18.9%, and diabetes mellitus in 8.6%. Acute kidney injury was identified in 55.1%, with stage 3 predominating in 43.1% of them. In these patients, the use of mechanical ventilation and vasoactive drugs was significant in 92% as well as respiratory organ dysfunction (80%), followed by renal organ dysfunction (76%). Risk factors such as kidney transplantation or chronic kidney disease and obesity increased by 12.3 and 9.0 times, respectively, the chances of developing acute kidney injury. Conclusion This study demonstrated a high kidney injury prevalence in young adults and its association with previous comorbidities. Obesity, kidney transplantation and chronic kidney disease increased the chance of young adults to develop acute kidney injury, resulting in outcomes in favor of morbidity and mortality.

Identificación de Factores Clínicos Relacionados a una Mayor Mortalidad Asociada a Insuficiencia Renal Aguda en pacientes de Terapia Intensiva

La insuficiencia renal aguda (IRA) es una de las complicaciones más frecuentes en los pacientes hospitalizados, siendo un factor de riesgo de mortalidad. Es de suma importancia identificar la asociación de factores clínicos que empeoran la mortalidad en pacientes con IRA internados en una unidad de terapia intensiva (UTI). Se incluyeron 218 pacientes, de los cuales el 63,7% (n=139) correspondieron a hombres con un promedio de edad de 43±19 años. El análisis de correlación de variables de control, dependiente e independiente fue a través del coeficiente de Spearman y el OR fue analizado mediante regresión logística. De los 218 pacientes, falleció el 33% (n=72) de los pacientes internados en UTI. La IRA ocurrió en 28,4% (n=62) del total de pacientes y de estos, el 61,3% (n=38) fallecieron, con un OR de 4,94 (p 0,0001). La mayor proporción de fallecidos perteneció a la categoría AKIN 3. Las variables clínicas de ventilación mecánica (PR 3,57, IC 95%, 0,34-37,93), uso de drogas vasoactivas (PR 8,32, IC 95%, 3,20-21,64), puntuación APACHE III (PR 1,12, IC 95%, 1,03-1,23), edad (PR 1,01, IC 95%, 0,99-1,04) y los sometidos a cirugía (PR 0,28, IC 95%, 0,10-0,80) tuvieron asociación positiva y aumentaron la mortalidad. La presencia de variables clínicas de ventilación mecánica, la utilización de drogas vasoactivas, sepsis, el estudio APACHE III, la edad, la categoría AKIN 3, y el antecedente de cirugía previo al ingreso a UTI aumentan significativamente la mortalidad en pacientes con IRA en UTI.

Acute renal failure (ARF) is one of the most frequent complications in hospitalized patients and is a risk factor for mortality. It is extremely important to identify the association of clinical factors that worsen mortality in patients with ARF admitted to an intensive care unit (ICU). A total of 218 patients were included, of which 63.7% (n=139) were men with a mean age of 43±19 years. The correlation analysis of control, dependent, and independent variables was done through Spearman's coefficient and the OR was analyzed through logistic regression. Of the 218 patients, 33% (n=72) died in the ICU. ARF occurred in 28.4% (n=62) of all patients and of these, 61.3% (n=38) died, with an OR of 4.94 (p 0.0001). The highest proportion of deceased patients were in the AKIN 3 category. The clinical variables of mechanical ventilation (PR 3.57, 95% CI, 0.34-37.93), use of vasoactive drugs (PR 8.32, 95% CI, 3.20-21.64), APACHE III score (PR 1.12, 95% CI, 1.03-1.23), age (PR 1.01, 95% CI, 0.99-1.04) and those who underwent surgery (PR 0.28, 95% CI, 0.10-0.80) had a positive association and increased mortality. The presence of clinical variables of mechanical ventilation, the use of vasoactive drugs, sepsis, APACHE III stage, age, AKIN 3 category, and a history of surgery before admission to the ICU significantly increase mortality in patients with ARF in ICU.

Respiratory system parameters in children with low severity cystic fibrosis: is there early involvement in relation to healthy peers? / Parâmetros do sistema respiratório em crianças com fibrose cística de baixa gravidade: há acometimento precoce em relação a pares saudáveis?

ABSTRACT Objective: To compare and analyze pulmonary function and respiratory mechanics parameters between healthy children and children with cystic fibrosis. Methods: This cross-sectional analytical study included healthy children (HSG) and children with cystic fibrosis (CFG), aged 6-13 years, from teaching institutions and a reference center for cystic fibrosis in Florianópolis/SC, Brazil. The patients were paired by age and sex. Initially, an anthropometric evaluation was undertaken to pair the sample characteristics in both groups; the medical records of CFG were consulted for bacterial colonization, genotype, and disease severity (Schwachman-Doershuk Score — SDS) data. Spirometry and impulse oscillometry were used to assess pulmonary function. Results: In total, 110 children were included, 55 in each group. In the CFG group, 58.2% were classified as excellent by SDS, 49.1% showed the ΔF508 heterozygotic genotype, and 67.3% were colonized by some pathogens. Statistical analysis revealed significant differences between both groups (p<0.05) in most pulmonary function parameters and respiratory mechanics. Conclusions: Children with cystic fibrosis showed obstructive ventilatory disorders and compromised peripheral airways compared with healthy children. These findings reinforce the early changes in pulmonary function and mechanics associated with this disease.

RESUMO Objetivo: Comparar e analisar parâmetros de função pulmonar e de mecânica respiratória entre escolares saudáveis e com fibrose cística (FC). Métodos: Estudo transversal que incluiu escolares saudáveis (GES) e com FC (GFC), com idades entre seis e 13 anos, provenientes de instituições de ensino e de um centro de referência da FC em Florianópolis/SC, Brasil, pareados por idade e sexo, respectivamente. Inicialmente, conduziu-se avaliação antropométrica para pareamento e caracterização de ambos os grupos e, no GFC, consultou-se prontuário médico para registro dos dados de colonização bacteriana, genótipo e gravidade da doença (Escore de Schwachman-Doershuk — ESD). Para a avaliação da função pulmonar, realizou-se espirometria e a avaliação da mecânica respiratória foi conduzida por meio do sistema de oscilometria de impulso. Resultados: Participaram 110 escolares, 55 em cada grupo. No GFC, 58,2% foram classificados pelo ESD como excelentes, 49,1% apresentaram genótipo ∆F508 heterozigoto e 67,3% eram colonizados por alguma patógeno. Houve diferença significativa (p<0,05) na maioria dos parâmetros de função pulmonar e de mecânica respiratória entre os grupos. Conclusões: Escolares com FC apresentaram distúrbio ventilatório obstrutivo e com comprometimento de vias aéreas periféricas, em comparação aos escolares hígidos. Esse evento reforça o início precoce da alteração de função pulmonar e de mecânica respiratória nessa enfermidade, evidenciados pelos achados desta investigação.

Breviscapine alleviates myocardial ischemia-reperfusion injury in diabetes rats

Purpose: To investigate the protective effect of breviscapine on myocardial ischemia-reperfusion injury (MIRI) in diabetes rats. Methods: Forty rats were divided into control, diabetes, MIRI of diabetes, and treatment groups. The MIRI of diabetes model was established in the latter two groups. Then, the treatment group was treated with 100 mg/kg breviscapine by intraperitoneal injection for 14 consecutive days. Results: After treatment, compared with MIRI of diabetes group, in treatment group the serum fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycosylated hemoglobin levels decreased, the serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels decreased, the serum high-density lipoprotein cholesterol level increased, the heart rate decreased, the mean arterial pressure, left ventricular ejection fraction, and fractional shortening increased, the serum cardiac troponin I, and creatine kinase-MB levels decreased, the myocardial tumor necrosis factor α and interleukin-6 levels decreased, the myocardial superoxide dismutase level increased, and the myocardial malondialdehyde level decreased (all P < 0.05). Conclusions: For treating MIRI of diabetes in rats, the breviscapine can reduce the blood glucose and lipid levels, improve the cardiac function, reduce the myocardial injury, and decrease the inflammatory response and oxidative stress, thus exerting the alleviating effect.

Effects of echinacoside on renal injury in uremia rats and its mechanism / 中国药房

OBJECTIVE To investigate the effects of echinacoside （ECH） on renal injury in uremia （URE） rats and its mechanism. METHODS URE model of the rat was established by 5/6 nephrectomy. Successfully modeled rats were grouped into uremia group （URE group）， ECH low-dose [10 mg/（kg·d）] group， ECH medium-dose [20 mg/（kg·d）] group， ECH high-dose [40 mg/（kg·d）] group， ECH high-dose+anisomycin [p38 mitogen-activated protein kinase （p38 MAPK） pathway activator] group [ECH-H+Ani group， 40 mg/（kg·d） ECH +2 mg/（kg·d） anisomycin]， with a sham operation group， 12 mice in each group. Each drug group was given corresponding ECH intragastrically， while ECH-H+Ani group was further injected with anisomycin via the tail vein， once a day， for 8 consecutive weeks. The serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， blood urea nitrogen （BUN）， β2-microglobulin （β2-MG）， serum creatinine （Scr）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， cystatin C （Cys-C） and 24 h urine protein （24 h UP） as well as the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） activity in renal tissue were all detected； pathological changes of renal tissue were observed； the rate of positive expression of α-smooth muscle protein （α-SMA） and E-cadherin， and the phosphorylation of p38 MAPK and nuclear factor-κB （NF-κB） p65 were determined in renal tissue of rats. RESULTS Compared with URE group， glomerular swelling， damage and necrosis of renal tubular epithelial cells and inflammatory cell infiltration were relieved significantly in ECH groups. The renal injury score， levels of TNF-α， IL-1β， IL-6， BUN， Scr， β2-MG， 24 h UP， NGAL， KIM- 1， Cys-C and MDA， the positive expression rate of α-SMA in renal tissue， the phosphorylation of p38 MAPK and NF-κB p65 were decreased in dose-dependent manner， while SOD activity and the positive expression rate of E-cadherin were obviously increased in dose-dependent manner （P＜0.05）. Anisomycin significantly attenuated the improvement effect of high-dose ECH on renal injury in URE rats （P＜0.05）. CONCLUSIONS ECH may inhibit inflammation and oxidative stress， enhance renal function， and improve renal injury in uremic rats by inhibiting the activation of p38 MAPK/NF-κB signaling pathway.

Effects of GW501516 on the injury of pulmonary artery endothelial cells induced by hypoxia and its mechanism / 中国药房

OBJECTIVE To investigate the effects of the peroxisome proliferator-activated receptors δ （PPARδ） agonist GW501516 on the injury of pulmonary artery endothelial cells （PAECs） induced by hypoxia and its mechanism. METHODS The cytotoxic effects of GW501516 were observed by detecting the relative survival rate of PAECs； the protein expression of PPARδ was determined by Western blot assay. The cellular model of PAECs injury was established under hypoxic conditions； using antioxidant N-acetylcysteine （NAC） as positive control， the effects of GW501516 on cell injury and reactive oxygen species （ROS） production were investigated by detecting cell apoptotic rate， cell viability， lactate dehydrogenase （LDH） activity and ROS levels. Using nuclear factor erythroid 2-related factor 2（Nrf2） activator dimethyl fumarate （DMF） as positive control， PAECs were incubated with GW501516 and/or Nrf2 inhibitor ML385 under hypoxic conditions； the mechanism of GW501516 on PAECs injury induced by hypoxia was investigated by detecting cell injury （cell apoptosis， cell viability， LDH activity）， the levels of superoxide dismutase （SOD）， glutathione peroxidase （GPx）， catalase （CAT）， malondialdehyde （MDA） and ROS， the expressions of Nrf2， heme oxygenase-1 （HO-1） and cleaved-caspase-3 （C-caspase-3） protein. RESULTS The results demonstrated that hypoxia inhibited the protein expression of PPARδ （P＜0.05）， while GW501516 promoted the protein expression of PPARδ in hypoxia- exposed PAECs without obvious cytotoxic effects. GW501516 inhibited the apoptosis of PAECs， improved cell viability， and reduced LDH activity and ROS levels. GW501516 could up-regulate the protein expression of HO-1 in PAECs and the levels of SOD， GPx and CAT， while down-regulated the levels of MDA and ROS by activating the Nrf2 pathway （P＜0.05）； but Nrf2 inhibitor ML385 could reverse the above effects of GW501516 （P＜0.05）. GW501516 exerted similar effects to Nrf2 activator DMF in down-regulating the expression of C-caspase-3 and inhibiting the injury of PAECs under conditions of hypoxia （P＜0.05）. Moreover， Nrf2 inhibitor ML385 reversed the 163.com inhibition effects of GW501516 on PAECs injury （P＜0.05）. CONCLUSIONS GW501516 can relieve the hypoxia-induced injury of PAECs via the inhibition of oxidative stress， the mechanism of which may be associated with activating Nrf2.

Progress on the relationship of aldehyde dehydrogenase 2 with human diseases and its small-molecule activators / 药学实践杂志

Aldehyde dehydrogenase 2 (ALDH2) is one of important factors against from the damage under oxidative stress in human body. A high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also have found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value of clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.

Clinical Study of Modified Shenqi Pill （肾气丸） Plus Tongdu Tiaoshen Acupuncture （通督调神针刺） for Neurogenic Bladder After Spinal Cord Injury of Kidney-Yang Deficiency Syndrome / 中医杂志

ObjectiveTo observe the clinical efficacy of modified Shenqi Pill （肾气丸） plus Tongdu Tiaoshen Acupuncture （通督调神针刺） in the treatment of neurogenic bladder after spinal cord injury of kidney-yang deficiency syndrome. MethodsForty-six patients were randomly divided into 23 cases each in the control group and the treatment group. Both groups were given conventional treatment， i.e. oral methylcobalamin tablets （0.5 mg each time， 3 times a day） and paraplegic conventional acupuncture （once a day， 6 consecutive days a week）. The control group was given simple bladder function rehabilitation training on the basis of the conventional treatment； and the treatment group was given modified Shenqi Pill orally （1 dose a day， 150 ml each time， taken warmly in morning and evening） and Tongdu Tiaoshen Acupuncture （once a day， 6 consecutive days per week） in addition to what were given to the control group. The treatment course lasted for 4 weeks. The 24 h urination frequency， 24 h urine leakage frequency， 24 h single urine volume， bladder residual urine volume， international lower urinary tract symptom （LUTS） score， traditional Chinese medicine （TCM） syndrome score were compared between the two groups， and clinical effectiveness and TCM syndrome effectiveness were compared between the two groups after treatment. ResultsTwenty patients in each group were finally analyzed in this study. The number of 24 h urination， the number of 24 h urine leakage， bladder residual urine volume， LUTS score， and the TCM syndrome scores decreased after treatment in both groups， and the 24 h single urine volume increased （P＜0.01）； and much more improvement was found of each index in the treatment group than in the control group （P＜0.05 or P＜0.01）. The total clinical effectiveness and TCM syndrome effectiveness in the treatment group was 85.00% （17/20） respectively， which were statistically significantly higher than 45.00% （the total clinical effectiveness， 9/20） and 60.00% （TCM syndrome effectiveness， 12/20） in the control group （P＜0.01）. ConclusionModified Shenqi Pill plus Tongdu Tiaoshen Acupuncture can signi-ficantly improve the clinical symptoms of neurogenic bladder patients after spinal cord injury of kidney-yang deficiency syndrome， having better effectiveness than simple bladder function rehabilitation training， and its mechanism may be related to the improvement of the injured nerve function innervating the bladder.