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.

Isquemia de mão de pacientes em terapia renal substitutiva: avaliação por termografia / Isquemia de mano de pacientes en terapia de reemplazo renal: evaluación por termografía / Hand ischemia in patients undergoing renal replacement therapy: assessment by thermography

Resumo Objetivo Avaliar a presença de isquemia na porção distal das mãos dos membros superiores com Fistula Arteriovenosa (FAV) de pacientes em Terapia Renal Substitutiva (TRS) através da termografia por infravermelho. Método Amostra composta por 15 pacientes em TRS por hemodiálise por meio de FAV que responderam um questionário elaborado pelos próprios autores com as seguintes variáveis: dados sociodemográficos, diagnóstico, sinais vitais e dados sobre a FAV. Para obtenção dos termogramas das mãos com e sem FAV foi utilizado uma câmera termográfica por infravermelho C5, FLIR Systems, fixada a 50 cm das mãos dos participantes, privilegiando o enquadramento bilateral enquadrando ambas as mãos. Os dados obtidos foram organizados em planilha de Excel 2011® e comparados estatisticamente utilizando o programa Microcal Origin 6.0, para avaliar se existia diferença entre as médias de temperatura. Resultados Com relação as variáveis sociodemográficas, o gênero masculino foi o predominante, faixa etária com média de 45 anos, ensino fundamental (incompleto/completo), casados e provenientes de outros municípios. A termografia demonstrou que há diferença de temperatura entre as mãos com FAV e sem FAV, com variação na temperatura de 1,78°C (± DP 1,99°C), menor para as mãos com FAV. Conclusão A análise da distribuição do sangue das mãos por meio da termografia pode fornecer evidências sobre a microcirculação periférica e orientar o diagnóstico precoce e o tratamento da isquemia induzida por FAV em indivíduos em TRS, como ferramenta inovadora de diagnóstico auxiliar das complicações dos acessos venosos de pacientes em hemodiálise.

Resumen Objetivo Evaluar la presencia de isquemia en la parte distal de las manos de los miembros superiores con fístula arteriovenosa (FAV) de pacientes en terapia de reemplazo renal (TRR) a través de la termografía infrarroja. Métodos Muestra compuesta por 15 pacientes en TRR por hemodiálisis mediante FAV que respondieron un cuestionario elaborado por los propios autores con las siguientes variables: datos sociodemográficos, diagnóstico, signos vitales y datos sobre la FAV. Para obtener los termogramas de las manos con y sin FAV, se utilizó una cámara termográfica infrarroja C5, FLIR Systems, ubicada a 50 cm de las manos de los participantes, favoreciendo el encuadramiento bilateral y encuadrando ambas manos. Los datos obtenidos se organizaron en una planilla de Excel 2011® y se compararon estadísticamente con el programa Microcal Origin 6.0, para evaluar si había diferencia entre los promedios de temperatura. Resultados Con relación a las variables sociodemográficas, el género masculino fue predominante, grupo de edad promedio de 45 años, educación primaria (incompleta/completa), casados y provenientes de otros municipios. La termografía demostró que hay diferencia de temperatura entre las manos con FAV y sin FAV, con una variación de temperatura de 1,78°C (± DP 1,99°C), menor en las manos con FAV. Conclusión El análisis de la distribución de la sangre de las manos por medio de termografía puede ofrecer evidencias sobre la microcirculación periférica y guiar el diagnóstico temprano y el tratamiento de la isquemia inducida por FAV en individuos en TRR, como una herramienta innovadora de diagnóstico auxiliar de las complicaciones de los accesos vasculares de pacientes en hemodiálisis.

Abstract Objective To assess the presence of ischemia in the distal portion of the hands of the upper limbs with arteriovenous fistula (AVF) in patients undergoing renal replacement therapy (RRT) using infrared thermography. Method The sample consisted of 15 patients on RRT via hemodialysis using an AVF who answered a questionnaire prepared by the authors themselves with sociodemographic data, diagnosis, vital signs and data on AVF. To obtain thermograms of hands with and without AVF, a C5 infrared thermographic camera, FLIR Systems, was used, fixed 50 cm from participants' hands, favoring bilateral framing of both hands. The data obtained were organized in an Excel 2011® spreadsheet and statistically compared using the Microcal Origin 6.0 program to assess whether there was a difference between temperature averages. Results Regarding sociodemographic variables, males were predominant, with a mean age of 45 years, (incomplete/complete) elementary school, married and from other municipalities. Thermography demonstrated that there is a difference in temperature between hands with AVF and without AVF, with a temperature variation of 1.78°C (± SD 1.99°C), lower for hands with AVF. Conclusion The analysis of hand blood distribution using thermography can provide evidence on peripheral microcirculation and guide the early diagnosis and treatment of AVF-induced ischemia in individuals undergoing RRT as an innovative auxiliary diagnostic tool for complications of venous access in hemodialysis patients.

Cardiovascular Disease in Latin American Women Gaps and opportunities

Abstract Cardiovascular disease (CVD) remains the leading cause of death in women. This review will address the known disparities in cardiovascular care concerning diagnosing and treating of heart disease in Latin American (LA) women. Gender-specific differences regarding the incidence, treatment, and outcomes of common cardiovascular pathology are increasingly recognized. Today, we identify that women have cardiovascular risk factors (CRFs), specifying the traditional, emerging, unique, or sex-specific determinants and the social and biological determinants that play a leading role in the prevention of CVD. The purpose of this article is to review the literature on cardiovascular disease in LA women, focusing on ischemic heart disease (IHD), valve disease (VD), heart failure, and cardiac rehabilitation (CR), where disparities continue to affect outcomes. Understanding the unique cardiovascular risk profile and barriers to optimal treatment outcomes in women is imperative to eliminate the current disparities in CVD.

Open revascularization for chronic mesenteric ischemia in the endovascular era: a quaternary-center experience and management algorithm / Revascularização aberta na isquemia mesentérica crônica durante a era endovascular: experiência de um centro quaternário e um algoritmo de tratamento

Abstract Background Chronic mesenteric ischemia (CMI) is a debilitating disease with a heavy burden on quality of life. Stenting of the superior mesenteric artery (SMA) is the first option for treatment, but there is a lack of consensus defining precise indications for open revascularization (OR). Objectives To describe a series of 4 patients with CMI treated with OR and to present an algorithm for the management of this condition. Methods Three patients presented with typical intestinal angina and weight loss. One patient was subjected to prophylactic revascularization during open abdominal aortic aneurysm repair. Surgical techniques included: 1) Bypass from the infrarenal aorta to the SMA; 2) Bypass from an aorto-bifemoral polyester graft to the SMA; 3) Bypass from the right iliac artery to the SMA; 4) Bypass from the right graft limb of an aorto-biiliac polyester graft to the median colic artery at Riolan's arcade. PTFE was used in all surgeries. All grafts were placed in a retrograde configuration, tunneled under the left renal vein, making a smooth C-loop. A treatment algorithm was constructed based on the institution's experience and a review of recent literature. Results All patients demonstrated resolution of symptoms and recovery of body weight. All grafts are patent after mean follow-up of two years. Conclusions Open revascularization using the C-loop configuration is a valuable technique for CMI and may be considered in selected cases. The algorithm constructed may help decision planning in other quaternary centers.

Resumo Contexto A isquemia mesentérica crônica (IMC) é uma doença debilitante, com grave impacto na qualidade de vida. A literatura recomenda a angioplastia com stent da artéria mesentérica superior (AMS) como primeira opção de tratamento, mas há falta de consenso que defina indicações precisas para a revascularização aberta. Objetivos Descrever uma série de quatro pacientes com IMC, tratados com revascularização aberta, e apresentar um algoritmo para o manejo dessa condição. Métodos Três pacientes apresentaram angina intestinal típica e perda ponderal. Uma paciente foi submetida a reparo aberto de aneurisma da aorta abdominal e apresentava obstrução da AMS, que foi revascularizada profilaticamente. As técnicas cirúrgicas incluíram: 1) enxerto entre a aorta infrarrenal e a AMS; 2) enxerto entre o dácron utilizado em um enxerto aortobifemoral e a AMS; 3) enxerto entre a artéria ilíaca comum direita e a AMS; e 4) enxerto entre o ramo direito do dácron utilizado em um enxerto aorto-biilíaco e a artéria cólica média (ao nível da arcada de Riolan). Todos os enxertos foram feitos utilizando politetrafluoretileno em uma configuração retrógrada, tunelizados abaixo da veia renal esquerda, fazendo uma alça em C. Resultados Todos os pacientes demonstraram resolução dos sintomas e ganho ponderal. Todos os enxertos se mantiveram pérvios durante um seguimento médio de 2 anos. Conclusões A revascularização aberta para IMC utilizando-se a alça em C é uma técnica valiosa e pode ser considerada em pacientes selecionados. O algoritmo proposto pode auxiliar na decisão terapêutica em centros quaternários.

Correlação entre o índice de resistência vascular e a arteriografia na avaliação do leito arterial distal na isquemia crítica dos membros inferiores / Correlation between the vascular resistance index and arteriography for assessment of the distal arterial bed in chronic limb threatening ischemia

Resumo Contexto Pacientes com isquemia crítica (IC) dos membros inferiores (MMII) precisam de arteriografia para o planejamento da cirurgia de revascularização. A ultrassonografia Doppler (UD) não é invasiva e, através da aferição do índice de resistência (IR), pode fornecer informações sobre as artérias distais. Objetivos Correlacionar a Classificação Angiográfica de Rutherford com o IR na avaliação do leito arterial distal dos MMII. Métodos Estudo transversal, realizado em hospital público terciário, com 120 pacientes portadores de IC dos MMII, entre setembro de 2019 a abril de 2022. Foi comparado o IR das artérias da perna passíveis de serem receptoras de revascularização com a imagem obtida através da arteriografia dessas artérias em acordo com a Classificação Angiográfica de leito distal de Rutherford. Resultados Foram avaliados 120 MMII em 120 pacientes com idade média de 68,6 anos. A amostra foi composta de 50,0% de pacientes do sexo masculino. Na amostra, 90,0% pacientes encontravam-se na classe cinco de Rutherford. Os valores do IR encontrados para as artérias de perna apresentaram uma correlação positiva, estatisticamente significativa, quando comparados com a Classificação de Rutherford (tibial anterior, p< 0,01; tibial posterior, p = 0,012 e fibular, p = 0,034 e artéria dorsal do pé, p < 0,001). Conclusões Neste estudo, os IRs das artérias da perna obtidos através da ultrassonografia Doppler apresentaram uma correlação positiva quando comparados à classificação de Rutherford. Em pacientes com isquemia crítica, esse índice pode ser útil na avaliação do leito arterial distal dos membros inferiores.

Abstract Background Patients with chronic limb threatening ischemia (CLTI) of the lower limbs (LL) undergo arteriography for revascularization surgery planning. Doppler ultrasound (DU) is non-invasive and can provide information about the distal arteries through measurement of the resistance index (RI). Objectives To correlate the Rutherford Angiographic Classification with the RI for assessment of the distal arterial bed of the LL. Methods A cross-sectional study, conducted at a public tertiary hospital with 120 patients with LL CLTI, from September 2019 to April 2022. The RI of arteries that were candidates for revascularization was compared with the images of the same arteries obtained using arteriography, using the Rutherford Angiographic Classification of the distal bed. Results A total of 120 LL were assessed in 120 patients with a mean age of 68.6 years. The sample was 50.0% male and 90.0% of the patients in the sample were classified as Rutherford category five. The RI values found for the arteries of the leg exhibited a statistically significant positive correlation with the Rutherford Classification (anterior tibial, p< 0.01; posterior tibial, p = 0.012 fibular, p = 0.034; and dorsalis pedis, p < 0.001). Conclusions In this study, RIs for the arteries of the leg measured using Doppler ultrasound exhibited a positive correlation with the Rutherford Classification. This index could be useful for assessment of the distal arterial bed of the lower limbs of patients with chronic limb threatening ischemia.

Feasibility of Goal-Directed Fluid Therapy in Patients with Transcatheter Aortic Valve Replacement - An Ambispective Analysis

ABSTRACT Introduction: Goal-directed fluid therapy (GDFT) has been shown to reduce postoperative complications. The feasibility of GDFT in transcatheter aortic valve replacement (TAVR) patients under general anesthesia has not yet been demonstrated. We examined whether GDFT could be applied in patients undergoing TAVR in general anesthesia and its impact on outcomes. Methods: Forty consecutive TAVR patients in the prospective intervention group with GDFT were compared to 40 retrospective TAVR patients without GDFT. Inclusion criteria were age ≥ 18 years, elective TAVR in general anesthesia, no participation in another interventional study. Exclusion criteria were lack of ability to consent study participation, pregnant or nursing patients, emergency procedures, preinterventional decubitus, tissue and/or extremity ischemia, peripheral arterial occlusive disease grade IV, atrial fibrillation or other severe heart rhythm disorder, necessity of usage of intra-aortic balloon pump. Stroke volume and stroke volume variation were determined with uncalibrated pulse contour analysis and optimized according to a predefined algorithm using 250 ml of hydroxyethyl starch. Results: Stroke volume could be increased by applying GDFT. The intervention group received more colloids and fewer crystalloids than control group. Total volume replacement did not differ. The incidence of overall complications as well as intensive care unit and hospital length of stay were comparable between both groups. GDFT was associated with a reduced incidence of delirium. Duration of anesthesia was shorter in the intervention group. Duration of the interventional procedure did not differ. Conclusion: GDFT in the intervention group was associated with a reduced incidence of postinterventional delirium.

Garlic Extract Reverses Ischemic Heart Disease in Female Rats Exposed to Combined Oral Contraceptive Pills

Abstract Background Garlic is an herbal medicinal plant with several pharmacological properties used for the management of various ailments. However, its potential in the reversal of ischemic heart disease induced by combined oral contraceptive pills is not well reported. Objective This study investigated the cardioprotective potential of aqueous garlic extract against cardiotoxicity induced by oral contraceptive pills. Methods Forty-six rats were used for this study. Six were used to determine the lethal dose (LD50), and 40 rats were divided randomly into 5 groups of 8 rats each. Group A received feed and distilled water. Group B received 0.6 mg/kg of oral contraceptive pills. Group C received 500 mg/kg of garlic extract. Group D received 0.6 mg/kg of oral contraceptive pills + 500 mg/kg garlic extract. Group E received 0.6 mg/kg of oral contraceptive pills + 700 mg/kg garlic extract. The animals were sacrificed, and blood and tissue samples were collected for biochemical and histological analysis. Statistical analysis was done using SPSS, and p values < 0.05 were considered significant. Results The acute toxicity dose of combined oral contraceptive pills was 1.5 mg/kg for albino rats. Combined oral contraceptive pills induced ischemic necrosis as revealed by the photomicrographs, in addition to elevation of serum cardiac troponin-1, lactate dehydrogenase, creatine kinase, and malondialdehyde levels. Treatment with garlic extract demonstrated significant reduction in cardiac troponin-1 (p = 0.000), lactate dehydrogenase (p = 0.002), creatine kinase (p = 0.001), and malondialdehyde (p = 0.001) levels, as well as restoration of the cardiac cytoarchitecture changes caused by the combined oral contraceptive pills. Conclusion This study has demonstrated that aqueous garlic juice can reverse ischemic heart disease, lessen cytoarchitectural alterations of the heart caused by combined oral contraceptive pills, and thus ameliorate cardiac dysfunction.

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.

Arterialização venosa superficial com veia safena magna in situ: a experiência de um único centro / Superficial venous arterialization with the great saphenous vein in situ: a single-center experience

Resumo Contexto A arterialização do arco venoso dorsal do pé é uma técnica indicada em casos de isquemia crítica de membros inferiores sem leito distal adequado que possibilite tratamento convencional, como revascularização, angioplastia ou tratamento clínico. Objetivos O propósito do trabalho foi apresentar o resultado da arterialização do arco venoso do pé em 16 pacientes submetidos a essa técnica. Métodos Tratou-se de um estudo analítico descritivo retrospectivo transversal, baseado na revisão de prontuários de 16 pacientes submetidos à arterialização do arco venoso dorsal do pé para salvamento de membro, entre janeiro de 2016 a janeiro de 2021. Resultados Dos 16 pacientes submetidos à arterialização do arco venoso do pé, 25% (4) evoluíram para amputação maior durante a mesma internação, e 6,25% (1) pacientes evoluíram para amputação maior após 6 meses. Os demais pacientes (68,75%, 11) tiveram seus membros preservados, sendo que 10 foram submetidos a amputações menores (pododáctilos e antepé), e 1 paciente não necessitou de procedimento adicional. Conclusões A técnica de arterialização do arco venoso dorsal do pé deve ser considerada em casos selecionados. Trata-se de uma alternativa válida para a preservação do membro na impossibilidade de tratamento convencional.

Abstract Background Arterialization of the dorsal venous arch of the foot is a technique indicated in cases of critical lower limb ischemia that do not have a distal bed that is adequate to enable conventional treatment such as revascularization, angioplasty, or clinical treatment. Objectives The purpose of this study is to present the result of arterialization of the venous arch of the foot in 16 patients who underwent treatment with this technique. Methods This is a cross-sectional retrospective descriptive analytical study based on a review of the medical records of 16 patients who underwent arterialization of the dorsal venous arch of the foot for limb salvage from January 2016 to January 2021. Results Four (25%) of the 16 patients who underwent arterialization of the venous arch of the foot underwent a major amputation during the same hospital stay and one patient (6.25%) had a major amputation within 6 months. The other 11 patients (68.75%) had their limbs preserved, with 10 undergoing minor amputations (toes and forefoot) and one patient having no additional procedures. Conclusions We conclude that the technique of arterialization of the dorsal venous arch of the foot should be considered in selected cases. It is a valid alternative for limb salvage when conventional treatment is impossible.

Isquemia mesentérica aguda: un desafío de la medicina. Reporte de un caso

La isquemia intestinal aguda es una emergencia vascular provocada por fenómenos oclusivos y no oclusivos de la circulación mesentérica arterial y venosa, de difícil diagnóstico y pronóstico ominoso. Su incidencia va en aumento paulatino con el decurso de los años, asociada fundamentalmente al envejecimiento de la población. La tasa de mortalidad es elevada a pesar de los avances en el campo de la imagenología. Suele diagnosticarse de forma tardía, cuando está establecido el daño isquémico intestinal de carácter irreversible. El elemento imprescindible e indispensable lo constituye el tiempo que trascurre hasta la cirugía, por lo que su diagnóstico sigue siendo un reto clínico. El tratamiento exige medidas médicas intensivas, al igual que cirugía de revascularización y resección del intestino necrosado. Por desdicha, el examen físico y los hallazgos de laboratorio no son sensibles ni específicos para su diagnóstico. Teniendo en cuenta estos elementos, se presenta el caso de una paciente de 38 años con clínica difusa de vómitos, diarrea y dolor abdominal progresivo, que requirió intervención quirúrgica de urgencia con diagnóstico transoperatorio de isquemia mesentérica aguda. Durante su estancia hospitalaria se relaparotomizó en dos ocasiones, mantuvo soporte ventilatorio e inotrópico por fallo multiorgánico en la Unidad de Cuidados Intensivos, mostrando una adecuada evolución posquirúrgica. El objetivo de esta presentación es enfatizar en la clínica como elemento fundamental para abordar de forma correcta esta entidad en un medio hospitalario de limitados recursos diagnósticos imagenológicos, al abordar conceptos teóricos recientes y facilitar una adecuada actuación en la toma de decisiones.

Acute intestinal ischemia is a vascular emergency caused by occlusive and non-occlusive phenomena of the mesenteric arterial and venous circulation of difficult diagnosis and ominous prognosis. Its incidence is gradually increasing over the years, mainly associated with the ageing of the population. The mortality rate is high despite advances in the field of imaging. It is usually diagnosed late, when irreversible ischemic intestinal damage is established. The essential and indispensable element is the time that elapses until surgery, so its diagnosis continues to be a clinical challenge. Treatment requires intensive medical measures, as well as revascularization surgery and resection of the necrotic intestine. Unfortunately, physical examination and laboratory findings are neither sensitive nor specific for its diagnosis. Taking these elements into account, the authors present the case of a 38-year-old female patient with diffuse symptoms of vomiting, diarrhea and progressive abdominal pain that required emergency surgery with intraoperative diagnosis of acute mesenteric ischemia. During her hospital stay, she underwent re-laparotomy twice, maintained ventilatory and inotropic support due to multi-organ failure in the Intensive Care Unit, showing an adequate post-surgical evolution. The objective of this presentation is to emphasize in the clinic as a fundamental element to correctly address this entity in a hospital environment with limited imaging diagnostic resources by addressing recent theoretical concepts and facilitating adequate action in decision-making.

Role of curcumin-mediated inhibition of inflammation in alleviating brain ischemia-reperfusion synaptic injury / 公共卫生与预防医学

Objective To investigate the potential effect and mechanism of curcumin in inhibiting synaptic injury in the cortex of rats with cerebral ischemia-reperfusion. Methods Sprague-Dawley rats were divided into sham-operated group, model group, low-dose curcumin (50 mg/kg) group, and high-dose curcumin (100 mg/kg) group. A model of middle cerebral artery occlusion for 2 hours and reperfusion for 24 hours was constructed, and curcumin was administered. Based on the neurological function score, the effects of curcumin on cerebral infarct volume, synaptic ultrastructure changes, inflammatory cell infiltration, and the expression of NLRP3, Caspase-1, Synapsin1, and CAMKⅡ were observed after the end of the animal treatment. Results The neurological function scores were 0, 3.25±0.43, 2.50±0.50, and 1.50±0.50 for the sham-operated group, model group, low-dose curcumin group, and high-dose curcumin group, respectively. The percentage of cerebral infarct volume was 0, (38.89±2.21)%, (33.48±1.77)%, and (23.69±2.19)%, respectively. Compared with the sham operation group, the model group had severe synaptic ultrastructure damage, extensive inflammatory cell infiltration, significantly increased expression of Caspase-1 and NLRP3 (P < 0.5), and significantly decreased expression of Synapsin1 and CAMKⅡ (P < 0.5). Curcumin treatment significantly inhibited synaptic damage, reduced inflammatory cell infiltration, decreased the expression of Caspase-1 and NLRP3 (P < 0.5), and increased the expression of Synapsin1 and CAMKII (P < 0.5), when compared with the model group. Conclusion Ischemia-reperfusion-mediated synaptic injury in rat brain triggers an inflammatory response in cortical nerve cells, and curcumin alleviates synaptic damage and reduces brain injury by inhibiting inflammatory factor levels.

Efficacy of partial and complete resuscitative endovascular balloon occlusion of the aorta in the hemorrhagic shock model of liver injury / 世界急诊医学杂志（英文）

@#BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) can temporarily control traumatic bleeding. However, its prolonged use potentially leads to ischemia-reperfusion injury (IRI). Partial REBOA (pREBOA) can alleviate ischemic burden; however, its security and effectiveness prior to operative hemorrhage control remains unknown. Hence, we aimed to estimate the efficacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic gun. METHODS: Twenty Landrace pigs were randomized into control (no aortic occlusion) (n=5), intervention with complete REBOA (cREBOA) (n=5), continuous pREBOA (C-pREBOA) (n=5), and sequential pREBOA (S-pREBOA) (n=5) groups. In the cREBOA and C-pREBOA groups, the balloon was inflated for 60 min. The hemodynamic and laboratory values were compared at various observation time points. Tissue samples immediately after animal euthanasia from the myocardium, liver, kidneys, and duodenum were collected for histological assessment using hematoxylin and eosin staining. RESULTS: Compared with the control group, the survival rate of the REBOA groups was prominently improved (all P<0.05). The total volume of blood loss was markedly lower in the cREBOA group (493.14±127.31 mL) compared with other groups (P<0.01). The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups (P<0.05). At 120 min, the S-pREBOA group showed higher alanine aminotransferase (P<0.05) but lower blood urea nitrogen compared with the cREBOA group (P<0.05). CONCLUSION: In this trauma model with liver injury, a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure, despite persistent hemorrhage. Extended tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures, and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.

Evolution and innovation of preservation fluid for donor liver / 器官移植

Organ preservation fluid could mitigate cold ischemia injury and maintain normal function of the grafts. At present, how to reduce a series of injury caused by cold ischemia of donor liver and improve the preservation quality of grafts are the hot and challenging spots in this field. Currently, preservation fluid in clinical practice has not achieved ideal preservation effect, especially for the protection of marginal donor organs. In the context of severe donor shortage, the key solution is still to explore the optimal preservation protocol for donor liver to prevent grafts from cold ischemia injury. In this article, the mechanism of donor liver injury during cold ischemia, the classification and evolution of donor liver preservation fluid were summarized, the development direction and challenges of donor liver preservation fluid were discussed, aiming to provide novel ideas and references for the research and development of donor liver preservation fluid.

Construction of competitive endogenous RNA network mediated by lung ischemia-reperfusion core genes / 器官移植

Objective To analyze the core genes of lung ischemia-reperfusion injury and construct a competitive endogenous RNA (ceRNA) network. Methods Original data of GSE145989 were downloaded from the Gene Expression Omnibus (GEO) database as the training set, and the GSE172222 and GSE9634 datasets were used as the validation sets, and the differentially-expressed genes (DEG) were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) network was constructed, and the core genes were screened, and the diagnostic values of these core genes and the immune infiltration levels of immune cells were evaluated. The ceRNA network was constructed and validated. The targeted drugs based on ceRNA network were assessed. Results A total of 179 DEG were identified, including 61 down-regulated and 118 up-regulated genes. GO analysis showed that DEGs were associated with multiple biological processes, such as cell migration, differentiation and regulation, etc. They were correlated with cell components, such as vesicle membrane, serosa and membrane raft, etc. They were also associated with multiple molecular functions, such as chemokine receptor, G protein-coupled receptor, immune receptor activity and antigen binding, etc. KEGG pathway enrichment analysis revealed that DEG were involved in tumor necrosis factor (TNF), Wnt, interleukin (IL)-17 and nuclear factor (NF)-κB signaling pathways, etc. PPI network suggested that CD8A, IL2RG, STAT1, CD3G and SYK were the core genes of lung ischemia-reperfusion injury. The ceRNA network prompted that miR-146a-3p, miR-28-5p and miR-593-3p were related to the expression level of CD3G. The miR-149-3p, miR-342-5p, miR-873-5p and miR-491-5p were correlated with the expression level of IL-2RG. The miR-194-3p, miR-512-3p, miR-377-3p and miR-590-3p were associated with the expression level of SYK. The miR-590-3p and miR-875-3p were related to the expression level of CD8A. The miR-143-5p, miR-1231, miR-590-3p and miR-875-3p were associated with the expression level of STAT1. There were 13 targeted drugs for CD3G, 4 targeted drugs for IL-2RG, 28 targeted drugs for SYK and 3 targeted drugs for lncRNA MUC2. No targeted drugs were identified for CD8A, STAT1 and other ceRNA network genes. Conclusions CD8A, IL2RG, STAT1, CD3G and SYK are the core genes of lung ischemia-reperfusion injury. The research and analysis of these core genes probably contribute to the diagnosis of lung ischemia-reperfusion injury and providing novel research ideas and therapeutic targets.

Down-regulation of XBP1s alleviates the senescence of renal tubular epithelial cells induced by hypoxia/reoxygenation through Sirt3/SOD2/mtROS signaling pathway / 器官移植

Objective To investigate the role and mechanism of spliced X-box binding protein 1 (XBP1s) in the senescence of primary renal tubular epithelial cells induced by hypoxia/reoxygenation (H/R). Methods Primary renal tubular epithelial cells were divided into the normal control group (NC group), H/R group, empty adenovirus negative control group (Ad-shNC group), targeted silencing XBP1s adenovirus group (Ad-shXBP1s group), empty adenovirus+H/R treatment group (Ad-shNC+H/R group) and targeted silencing XBP1s adenovirus+H/R treatment group (Ad-shXBP1s +H/R group), respectively. The expression levels of XBP1s in the NC, H/R, Ad-shNC and Ad-shXBP1s groups were measured. The number of cells stained with β-galactosidase, the expression levels of cell aging markers including p53, p21 and γH2AX, and the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were determined in the Ad-shNC, Ad-shNC+H/R and Ad-shXBP1s+H/R groups. Chromatin immunoprecipitation was employed to verify Sirtuin 3 (Sirt3) of XBP1s transcription regulation, and the expression levels of Sirt3 and downstream SOD2 after down-regulation of XBP1s were detected. Mitochondrial reactive oxygen species (mtROS) were detected by flow cytometry. Results Compared with the NC group, the expression level of XBP1s was up-regulated in the H/R group. Compared with the Ad-shNC group, the expression level of XBP1s was down-regulated in the Ad-shXBP1s group (both P<0.001). Compared with the Ad-shNC group, the number of cells stained with β-galactosidase was increased, the expression levels of p53, p21 and γH2AX were up-regulated, the levels of ROS, MDA and mtROS were increased, the SOD activity was decreased, the expression level of Sirt3 was down-regulated, and the ratio of Ac-SOD2/SOD2 was increased in the Ad-shNC+H/R group. Compared with the Ad-shNC+H/R group, the number of cells stained with β-galactosidase was decreased, the expression levels of p53, p21 and γH2AX were down-regulated, the levels of ROS, MDA and mtROS were decreased, the SOD activity was increased, the expression level of Sirt3 was up-regulated and the ratio of Ac-SOD2/SOD2 was decreased in the Ad-shXBP1s+H/R group (all P<0.05). Conclusions Down-regulation of XBP1s may ameliorate the senescence of primary renal tubular epithelial cells induced by H/R, which probably plays a role through the Sirt3/SOD2/mtROS signaling pathway.

Research progress on association between macrophages and ischemia-reperfusion injury / 器官移植

Ischemia-reperfusion injury (IRI) is an extremely complicated pathophysiological process, which may occur during the process of myocardial infarction, stroke, organ transplantation and temporary interruption of blood flow during surgery, etc. As key molecules of immune system, macrophages play a vital role in the pathogenesis of IRI. M1 macrophages are pro-inflammatory cells and participate in the elimination of pathogens. M2 macrophages exert anti-inflammatory effect and participate in tissue repair and remodeling and extracellular matrix remodeling. The balance between macrophage phenotypes is of significance for the outcome and treatment of IRI. This article reviewed the role of macrophages in IRI, including the balance between M1/M2 macrophage phenotype, the mechanism of infiltration and recruitment into different ischemic tissues. In addition, the potential therapeutic strategies of targeting macrophages during IRI were also discussed, aiming to provide reference for alleviating IRI and promoting tissue repair.

Research progress of traditional Chinese medicine in regulating Nrf2/HO-1 signaling pathway to interfere with myocardial ischemia-reperfusion injury / 中国药房

Myocardial ischemia-reperfusion injury （MIRI） is a serious complication of revascularization in patients with myocardial infarction. The nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway plays an important role in the pathological process of MIRI. Currently，research has found that traditional Chinese medicine has a good effect on myocardial injury caused by ischemia-reperfusion. Based on the Nrf2/HO-1 signaling pathway，this article summarizes the action mechanism of traditional Chinese medicine formulas and monomers in intervening with MIRI. It is found that traditional Chinese medicine formulas （Yixin formula，Wenyang tongmai formula，Dingxin formula Ⅰ），monomers such as terpenoids （ginkgolides， astragaloside Ⅳ，ginsenosides），phenols （brazilin，hematoxylin A，resveratrol） and quinones （aloe，emodin） can alleviate MIRI by activating the Nrf2/HO-1 signaling pathway，inhibiting oxidative stress and inflammatory reactions，etc.

Effect of Guipitang on ERK1/2 and p38 MAPK in Rats with Myocardial Ischemia / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg-1） groups， and a trimetazidine group （0.002 g·kg-1）. By intragastric administration of vitamin D3 and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

Trombosis venosa mesentérica y portal como causa infrecuente de obstrucción e isquemia intestinal en paciente joven. Reporte de caso / Mesenteric and Portal Venous Thrombosis as an infrequent cause of intestinal Obstruction and Ischemia in young patients. A case report

Resumen La isquemia mesentérica aguda se asocia a una mortalidad de entre el 50 y el 100%, la causa más rara de esta es la trombosis venosa de los vasos mesentéricos (5%) y portal (1%). Las manifestaciones clínicas son diversas, siendo el dolor abdominal el principal síntoma. La tomografía computarizada con contraste intravenoso en fase portal es la imagen más precisa para el diagnóstico. El tratamiento en fase aguda se basa en anticoagulación, fluidos intravenosos, antibióticos profilácticos, descanso intestinal y descompresión. La laparotomía de control de daños, incluida la resección intestinal y el abdomen abierto, pueden estar justificados en última instancia para pacientes con necrosis intestinal y sepsis. Caso clínico: Hombre de 35 años, sin antecedentes de importancia, solo tabaquismo desde hace 15 años. Refirió que 5 días previos comenzó a presentar dolor en el epigastrio tipo cólico, de intensidad moderada, posteriormente refirió que el dolor se generalizó y aumentó de intensidad, acompañado de náusea, vómito, intolerancia a la vía oral y alza térmica. Al examen físico tuvo datos de respuesta inflamatoria sistémica, estaba consciente y orientado, con abdomen doloroso a la palpación superficial y profunda a nivel generalizado, pero acentuado en el flanco derecho, rebote positivo con resistencia, timpanismo generalizado, peristalsis ausente. Se ingresó a quirófano a laparotomía exploradora, encontrando lesión a intestinal isquémica-necrótica a 190-240 cm del ángulo de Treitz, y 400 cc de líquido hemático; se realizó resección de la parte intestinal afectada, con entero-enteroanastomosis término-terminal manual. Se envió pieza a patología, y se reportó un proceso inflamatorio agudo con necrosis transmural y congestión vascular. Ante estos hallazgos se realizó angiotomografía abdominal que reportó defecto de llenado en la vena mesentérica superior, secundario a trombosis que se extendía hasta la confluencia y la vena porta. Conclusión: La trombosis venosa mesentérica y portal es una patología muy infrecuente en pacientes jóvenes sin factores de riesgo en los que se presenta dolor abdominal. El diagnóstico es complejo debido a que los datos clínicos y de laboratorio son poco específicos. Sin embargo, debemos tenerla en cuenta en el diagnóstico diferencial de etiologías de dolor abdominal.

Abstract Acute Mesenteric Ischemia is associated with a mortality rate between 50% and 100%; the rarest cause of this is venous thrombosis of the mesenteric (5%) and portal (1%) vessels. The clinical manifestations are diverse, with abdominal pain being the main symptom. Computed tomography with intravenous contrast in the portal phase is the most accurate image for diagnosis. Treatment in the acute phase is based on anticoagulation, intravenous fluids, prophylactic antibiotics, intestinal rest, and decompression. Damage control laparotomy, including bowel resection and open abdomen, may ultimately be warranted for patients with bowel necrosis and sepsis. Clinical case: 35-year-old man, with no significant history, only smoking for 15 years. For 5 days before, he reported crampy epigastric pain of moderate intensity. He subsequently reported that the pain became generalized and increased in intensity, accompanied by nausea, vomiting, oral intolerance, and temperature rise. The physical examination showed signs of a systemic inflammatory response, conscious and oriented, abdomen painful on superficial and deep palpation at a generalized level but accentuated on the right flank, positive rebound with resistance, generalized tympanism, absent peristalsis. The operating room was entered for exploratory laparotomy, finding an ischemic-necrotic intestinal lesion at 190 - 240 cm from the angle of Treitz, and 400cc of blood fluid. Resection of the affected intestinal part is performed, with entire manual terminal end anastomosis. The specimen was sent to pathology, reporting an acute inflammatory process with transmural necrosis and vascular congestion. Given these findings, abdominal CT angiography was performed, which reported a filling defect in the superior mesenteric vein, secondary to thrombosis that extended to the confluence and the portal vein. Conclusion: Mesenteric and portal venous thrombosis is a very rare pathology in young patients without risk factors in whom abdominal pain occurs. The diagnosis is complex because the clinical and laboratory data are not very specific. However, we must take it into account in the differential diagnosis of abdominal pain etiologies.