Protective effect of LW-AFC against fear sensitization induced by traumatic stress / 军事医学

Objective To investigate the protective effects and underlying mechanisms of Liuwei Dihuang Glucoside(LW-AFC)against fear sensitization induced by traumatic stress.Methods Mice were divided into naive,control,stressed and LW-AFC administration groups.The LW-AFC treated group received LW-AFC(1.6 g/kg daily)via oral gavage for two weeks following exposure to traumatic stress.The non-associative memory dependent fear sensitization responses in mice subjected to trauma were investigated,including behavior in novel environments,social interaction,and observational fear tests.Z-score normalization method was employed to integrate and assess multiple behavioral variables such as travel distance,freezing time,and corner time,and comprehensively examined fear sensitization behaviors across the groups.Additionally,serum concentrations of adrenocorticotropic hormone,corticosterone,aldosterone,renin,angiotensin Ⅱ,and aldosterone were measured using ELISA.Results Compared to the control group,stressed mice exhibited significantly reduced travel distance(P<0.0001)and increased freezing time(P<0.0001)in the new context test.Integrated Z-scores indicated a significant increase in fear behavior among stressed mice during the new context test(P<0.0001).In the social interaction test,stressed mice demonstrated significantly reduced travel distance(P<0.0001),increased freezing time(P<0.0001),increased corner time(P<0.05),and higher integrated Z-scores(P<0.0001).In the observational fear test,stressed mice showed significantly reduced travel distance(P<0.05),increased freezing time(P<0.001),increased corner time(P<0.05),and higher integrated Z-scores(P<0.0001).Compared to the stressed group,mice in the LW-AFC treated group displayed trends toward improvement in travel distance,freezing time,corner time,and integrated Z-scores in the new context tests,albeit without statistical significance.In the social interaction test,the LW-AFC treated group exhibited a significant reduction in freezing time(P<0.05)and integrated Z-scores(P<0.05).In the observational fear test,the LW-AFC treated group showed a significant reduction in freezing time(P<0.05)and integrated Z-scores(P<0.01).Compared to the naive group,control and stressed groups exhibited an increased trend in renin and aldosterone levels after the fear sensitization test.Although there were no significant differences between stressed and control groups,renin and aldosterone levels significantly increased between stressed and naive groups(P<0.05,P<0.05).Following LW-AFC treatment,serum renin levels showed no significant change,while aldosterone levels significantly decreased(P<0.05).Conclusion Stressed mice exhibited significant fear sensitization behavior in new context,social interaction,and observational fear tests,possibly associated with partial activation of the renin-angiotensin-aldosterone system(RAAS)system.LW-AFC treatment significantly mitigated fear sensitization behavior of stressed mice in social interaction and observational fear test,potentially due to its regulatory effects on the RAAS system in mice subjected to traumatic stress.

Expression of platelet microparticles in patients with diabetic nephropathy and its relationship with renal damage / 中国输血杂志

【Objective】 To investigate the expression levels of platelet microparticles(PMPs) in patients with diabetic nephropathy (DN) and their relationship with renal injury. 【Methods】 Thirty DN patients, 30 T2DM patients without DN and 30 healthy controls were enrolled. Flow cytometry was used to detect the quantity and phenotype of PMPs, and ELISA was used to measure the levels of plasma renin, angiotensin Ⅱ (angiotoninⅡ, AngⅡ), vascular endothelial growth factor (vascular endothelial growth factor, VEGF) and transforming growth factor-β1(transforming growth factor-β1, TGF-β1). Kidney function was determined by blood biochemistry. 【Results】 The quantity of PMPs in the DN group was (1 564±346) particles/μL, which was significantly higher than that in the non-DN group (1 246±312) particles/μL and the control group (1 223±299) particles/μL (P<0.05). The PMPs in the DN group mainly expressed CD62P and CD41a, accounting for (76.5±12.3)%. Moreover, the levels and activation of PMPs increased with the progression of DN. The quantity of PMPs was positively correlated with renin and other factors (r=0.56-0.62, P<0.05), negatively correlated with the glomerular filtration rate (GFR) (r=-0.64, P<0.05), and positively correlated with the urinary albumin excretion rate (UAE) (r=0.66, P<0.05). PMPs were also an independent influencing factor of UAE (β=12.34, P<0.05). 【Conclusion】 PMPs expression is elevated in DN patients, which may be associated with renal injury, but it is insufficient to confirm its role in the pathogenesis of DN.

Effect and mechanism of angiotensin(1-7)supplementation combined with exercise therapy on cardiac remodeling in rats with renal hypertension / 中国组织工程研究

BACKGROUND:The renin-angiotensin system plays a key role in the occurrence and development of hypertension,in which angiotensin(1-7)has antihypertensive effect and reversely regulates the adverse effects of angiotensin Ⅱ.Exercise rehabilitation therapy is an important non-pharmaceutical means to prevent and treat hypertension;however,whether angiotensin(1-7)and exercise have a synergistic effect is not yet clear. OBJECTIVE:To explore the effect of angiotensin(1-7)supplementation combined with exercise therapy on cardiac remodeling in rats with renal hypertension and to investigate the possible mechanism of angiotensin(1-7)and its receptor signal axis. METHODS:Sixty male Sprague-Dawley rats were selected,of which 12 rats were randomly selected as normotensive group and the remaining 48 rats were used to make animal models of renal hypertension using two-kidney one-clip method and were then randomly divided into hypertension control group,hypertension exercise group,angiotensin(1-7)group and combined treatment group.One week after successful modeling,different interventions were given(for a period of 6 weeks)as follows:the hypertension exercise group was subjected to a running training on an electric treadmill,the angiotensin(1-7)group was perfused with angiotensin(1-7)by implanting Alzet microosmotic pump subcutaneously on the back of the rats,and the combined treatment group was perfused with angiotensin(1-7)after running training,while the normotensive group and hypertension control group were caged quietly.At 48 hours after the last training session,the tail artery blood pressure was measured with a non-invasive sphygmomanometer;the heart structure and function were detected by echocardiography;the left ventricular myocardium was taken for histopathological observation by hematoxylin-eosin and Masson staining,and the cardiomyocyte cross-sectional area and collagen volume fraction were obtained by image analysis software as markers of myocardial hypertrophy and fibrosis,respectively;the content of angiotensin(1-7)in the heart was detected by high performance liquid chromatography;the mRNA expression of cardiac embryonic genes,atrial natriuretic peptide and β-myosin heavy chain,was detected by real-time fluorescence quantitative PCR;and the protein expression of cardiac Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was measured by western blot assay. RESULTS AND CONCLUSION:Compared with the normotensive group,blood pressure increased(P<0.05),cardiac function had no significant changes(P>0.05),cardiomyocyte cross-sectional area and collagen volume fraction increased(P<0.05),mRNA expression of atrial natriuretic peptide and β-myosin heavy chain was upregulated(P<0.05),angiotensin(1-7)content and protein expression of Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was downregulated(P<0.05)in the hypertension control group.Compared with the hypertension control group,blood pressure decreased(P<0.05),cardiac function improved(P<0.05),collagen volume fraction decreased(P<0.05),cardiomyocyte cross-sectional area and angiotensin(1-7)content showed no significant changes(P>0.05),mRNA expression of atrial natriuretic peptide and β-myosin heavy chain was downregulated(P<0.05),and the protein expression of Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was upregulated(P<0.05)in the hypertension exercise group;except for an increase in myocardial angiotensin(1-7)content(P<0.05),other parameters had no statistical significance(P>0.05)in the hypertension angiotensin(1-7)group.Compared with the hypertension exercise group,blood pressure decreased(P<0.05),cardiomyocyte cross-sectional area and cardiac function had no significant changes(P>0.05),collagen volume fraction decreased(P<0.05),angiotensin(1-7)content increased(P<0.05),mRNA expression of atrial natriuretic peptide and β-myosin heavy chain was downregulated(P<0.05),and the protein expression of Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was upregulated(P<0.05)in the combined treatment group.To conclude,supplementation of angiotensin(1-7)alone cannot improve cardiac remodeling in rats with renal hypertension,but it can enhance the efficacy of exercise.The mechanism is related to the improvement of angiotensin(1-7)receptor deficiency and restoration of its signaling pathway function.

RAAS in diabetic retinopathy: mechanisms and therapies

ABSTRACT Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.

Tumor de células yuxtaglomerulares (reninoma) como causa de hipertensión arterial en la adolescencia. A propósito de un caso / Juxtaglomerular cell tumor (reninoma) as a cause of arterial hypertension in adolescents. A case report

La hipertensión arterial (HTA) grave en pediatría responde fundamentalmente a causas secundarias. Presentamos una paciente adolescente de 14 años con HTA grave, alcalosis metabólica e hipopotasemia, secundaria a un tumor de células yuxtaglomerulares productor de renina, diagnosticado luego de dos años de evolución de HTA.

Severe arterial hypertension (HTN) in pediatrics is mainly due to secondary causes. Here we describe the case of a 14-year-old female adolescent with severe HTN, metabolic alkalosis, and hypokalemia, secondary to a renin-secreting juxtaglomerular cell tumor diagnosed after 2 years of HTN progression.

Biomechanical Effects of Angiotensin 1-7 in Diabetes Rats Femur / Efectos Biomecánicos de la Angiotensina 1-7 en el Fémur de Ratas Diabéticas

SUMMARY: It is known that diabetes mellitus has late complications, including microvascular and macrovascular diseases. Diabetes can affect bones through biochemical markers of bone structure, density, and turnover. This study aimed to biomechanically investigate the bone-protective effects of angiotensin 1-7 (Ang 1-7), one of the active peptides in the renin-angiotensin system, in rats with diabetes. Thirty male Wistar albino rats, three months old and weighing 250-300 g, were divided into four groups: diabetes, Ang 1- 7, diabetes plus Ang 1-7, and control. One month later, diabetes developed in rats; the rats were sacrificed, and their right femur was removed. Three-point bending biomechanical tests were performed on the femurs. The diabetic group had significantly higher bone fragility than the other groups (Pr >.05). Bone fragility was lower, and bone flexibility was higher in the Ang 1-7 groups (Pr>F value 0.05). As a result of our study, the effect of Ang 1-7 on the bones of rats with diabetes was investigated biomechanically. Ang 1-7 has a protective impact on the bones of rats with diabetes.

Se sabe que la diabetes mellitus tiene complicaciones tardías, incluyendo enfermedades microvasculares y macrovasculares. La diabetes puede afectar los huesos a través de los marcadores bioquímicos de la estructura, la densidad y el recambio óseo. Este estudio tuvo como objetivo investigar biomecánicamente los efectos protectores en los huesos de la angiotensina 1-7 (Ang 1-7), uno de los péptidos activos en el sistema renina-angiotensina, en ratas con diabetes. Treinta ratas albinas Wistar macho, de tres meses de edad y con un peso de 250-300 g, se dividieron en cuatro grupos: diabetes, Ang 1-7, diabetes más Ang 1-7 y control. Un mes después, se desarrolló diabetes en ratas; se sacrificaron los animales y se extrajo su fémur derecho. Se realizaron pruebas biomecánicas de flexión de tres puntos en los fémures. El grupo diabéticos tenía una fragilidad ósea significativamente mayor que los otros grupos (Pr > 0,05). La fragilidad ósea fue menor y la flexibilidad ósea fue mayor en los grupos Ang 1-7 (valor Pr>F 0,05). Como resultado de nuestro estudio, se determinó biomecánicamente el efecto de Ang 1-7 en los huesos de ratas con diabetes. Se concluye que Ang 1-7 tiene un impacto protector en los huesos de ratas diabéticas.

Short-term Effects of Garlic-Based Diets on mRNA Expression of Angiotensinogen, Angiotensin-1 Converting Enzyme, and Atrial Natriuretic Peptide in Cyclosporine-Induced Prehypertensive Rats

The short-term effects of garlic, Allium sativum L., on the mRNA expression of angiotensin-1 converting enzyme (ACE), angiotensinogen (AGT), and atrial natriuretic peptide (ANP) in cyclosporine-induced prehypertensive rats were investigated in this work. Seven (7) groups of animals totaling n=7 were created. Prehypertensive (induced with 25mg/kg cyclosporine) and normal rats were given 10% and 20% diets based on garlic for 7 days. Alteration of Na+ and K+ levels, increased systolic and diastolic blood pressures, and ACE, AGT & ANP mRNA expressions were all associated with cyclosporin-induced prehypertension. In rats placed on garlic-based diets, these effects were reversed.

Bloqueo del eje renina angiontensina aldosterona (RAAS) en la enfermedad renal diabética. Más allá del control de la hipertensión arterial / Renin angiotensin aldosterone system (RAAS) and its suppression in diabetic kidney disease. Control of arterial hypertension and beyond

La enfermedad renal diabética (ERD) es una comorbilidad con alta prevalencia a nivel mundial, siendo una de las complicaciones más frecuentes de la diabetes mellitus (DM). La ERD se relaciona con complicaciones cardiovasculares y progresión de la enfermedad renal crónica (ERC), por ello la identificación de factores modificables, como el control de la presión arterial, es uno de los pilares más importantes en el manejo integral. En esta revisión hacemos un recorrido sobre el papel de la hipertensión y el bloqueo del eje renina angiotensina aldosterona (RAAS) en el curso de la ERD y las estrategias terapéuticas orientadas a la reducción de la presión arterial (PA), el bloqueo RAAS y el impacto en resultados renales y cardiovasculares. El objetivo de este artículo es hacer una revisión de las intervenciones más importantes que actúan bloqueando el eje renina angiotensina aldosterona (RAAS) y determinar si estas medidas en los pacientes con ERD, solo tienen impacto en el control de la presión arterial o si también son estrategias de nefro y cardio-protección. Conclusión: La ERD es una de las complicaciones más frecuentes de la diabetes mellitus (DM). El control de la PA sigue siendo un pilar fundamental para lograr estos objetivos. Los bloqueadores del RAAS (iECAS y BRAs) son los antihipertensivos de elección con efecto terapéutico por el bloqueo RAAS y esto les permite tener además del control de la PA, efectos nefroprotectores y cardioprotectores importantes en pacientes con ERD, sobre todo cuando hay la presencia de albuminuria. Evaluamos que además de los inhibidores de la enzima convertidora de angiotensina (iECAs) y los bloqueadores del receptor de angiotensina (BRAs), vienen tomando importancia los antagonistas selectivos del receptor mineralocorticoide (ARM) como Finerenona.

Diabetic kidney disease (DKD) is a comorbidity with a high worldwide prevalence, and one of the most frequent complications of diabetes mellitus (DM). CKD is related to cardiovascular complications and the progression of chronic kidney disease (CKD), therefore the identification of modifiable factors, such as blood pressure control, is one of the most important pillars in comprehensive management. In this review, we will analyze the role of hypertension and the renin-angiotensin-aldosterone system (RAAS) and its suppression in the course of CKD, and therapeutic strategies aimed at reducing blood pressure (BP), RAAS blockade, and the impact on renal and cardiovascular outcomes. The objective of this article is to review the most important interventions that act by blocking the renin-angiotensin-aldosterone system (RAAS) and to determine if these measures in patients with CKD only have an impact on blood pressure control or if they are also nephron and cardio-protective strategies. Conclusion: DKD is one of the most frequent complications of diabetes mellitus (DM). BP control continues to be a fundamental pillar to achieve these objectives. RAAS blockers (iECAS and ARBs) are the first-line antihypertensive with a therapeutic effect due to RAAS blockade and this allows them to have, in addition to BP control, important nephroprotective and cardioprotective effects in patients with CKD, especially when there is albuminuria. We evaluated that in addition to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), selective mineralocorticoid receptor antagonists (MRA) such as Finerenone are gaining importance.

Respiratory muscles: structure, function and relationship with the ACE gene: a brief morphofunctional communication / Músculos respiratorios: estructura, función y relación con el gen de la ECA: una breve comunicación morfofuncional

SUMMARY: Pulmonary ventilation is a mechanical process in which the respiratory muscles act in coordination to maintain the oxygenation of the organism. Any alteration in the performance of these muscles may reduce the effectiveness of the process. The respiratory muscles differ from the other skeletal muscles in the vital support that they provide through rhythmiccontractions. The structure and energy system of the muscles are specially adapted to perform this function. The composition of the respiratory muscles is exceptional; they are small, and present an abundant capillary network, endowing them with a high aerobic level and resistance to fatigue. Coordinated regulation of the local renin-angiotensin system provides proper blood flow and energy supply in the myofibrils of the skeletal muscle tissue. Specifically, this performance will depend to a large extent on blood flow and glucose consumption, regulated by the renin-angiotensin system. The angiotensin converting enzyme is responsible for degrading kinins, which finally regulate muscle bioenergy and glucose between the blood vessel and the skeletal muscle. The objective of this review is to describe the structure of the respiratory muscles and their association with the angiotensin converting enzyme gene.

La ventilación pulmonar es un proceso mecánico en el que los músculos respiratorios actúan coordinadamente para mantener la oxigenación en el organismo. Así, cualquier alteración en el desempeño de estos músculos puede reducir la efectividad del proceso. Los músculos respiratorios se diferencian de otros músculos esqueléticos, debido al apoyo vital que brindan a través de sus contracciones rítmicas. La estructura y el sistema energético de estos músculos están especialmente adaptados para realizar esta función. La composición de los músculos respiratorios es especial; son pequeñas y presentan una abundante red capilar, lo que les otorga un alto nivel aeróbico y resistencia a la fatiga. La regulación coordinada del sistema renina-angiotensina local, proporciona un adecuado flujo sanguíneo y suministro de energía a las miofibrillas del músculo esquelético. En concreto, este rendimiento dependerá en gran medida del flujo sanguíneo y del consumo de glucosa, regulado por el sistema renina-angiotensina. Aquí, la enzima convertidora de angiotensina es responsable de degradar las kininas, que finalmente regulan la bioenergía muscular y la glucosa entre el vaso sanguíneo y el músculo esquelético. El objetivo de esta breve comunicación es describir la estructura de los músculos respiratorios y su asociación con el gen de la enzima convertidora de angiotensina.

Efficacy of alfacalcidol on liver and kidney function，inflammatory cytokines and RAS activity in hypertensive patients with renal impairment / 中国药房

OBJECTIVE To explore the efficacy of alfacalcidol combined with conventional antihypertensive and lipid- lowering drugs on liver and kidney function， serum inflammatory cytokines and renin-angiotensin system（RAS） in hypertensive patients with renal impairment. METHODS A total of 200 hypertensive patients with renal impairment who were treated in the department of nephrology in our hospital from December 2017 to December 2020 were selected and randomly divided into control group and observation group， with 100 cases in each group. Both groups of patients were treated with conventional antihypertensive and lipid-lowering drugs for a total of 14 weeks， patients in the observation group were additionally treated with oral alfacalcidol after 2 weeks of treatment （0.25 μg each time， once a day， for a total of 12 weeks）. The levels of liver function indexes [aspartate aminotransferase （AST）， alanine aminotransferase （ALT）]， renal function indexes [blood calcium， blood phosphorus， blood urea nitrogen （BUN）， cystatin C （Cys-C）， serum creatinine （Scr）， urine microalbumin （mAlb）， β2-microglobulin （β2-MG）， urinary N- acetyl β-D-glucosaminidase （NAG）， 24 h urinary protein]， inflammatory factors [serum interleukin 6 （IL-6）， tumor necrosis factor α （TNF-α）， hypersensitive C-reactive protein （hs-CRP）] and RAS activity indexes [renin， angiotensin Ⅰ（Ang Ⅰ）， Ang Ⅱ and aldosterone] were observed in 2 groups before and after treatment， and the occurrence of adverse drug reactions was recorded during treatment. RESULTS There was no statistical significance in the levels of detection indexes between 2 groups before treatment （P＞0.05）. After treatment， the level of blood calcium in the observation group was significantly higher than before treatment （P＜0.05）， but remained at clinically normal level. Compared with before treatment， the levels of Cys-C， Scr， BUN， urine mAlb， β2-MG， NAG and 24 h urinary protein， hs-CRP， IL-6， TNF-α， renin， Ang Ⅰ， Ang Ⅱ and aldosterone were significantly decreased in the observation group after treatment （P＜0.05）. After treatment， the level of blood calcium in observation group was significantly higher than control group （P＜0.05）. Additionally， the levels of Cys-C， Scr， BUN，urine mAlb， β2-MG， NAG， 24 h urinary protein， hs-CRP， IL-6， TNF-α， renin， Ang Ⅰ， Ang Ⅱ and aldosterone were significantly lower than control group （P＜0.05）. There was no statistical significance in the incidence of adverse drug reactions between 2 groups during treatment （P＞0.05）. CONCLUSIONS Alfacalcidol combined with routine therapy of antihypertensive and lipid-lowering drugs could effectively improve liver and renal functions， inhibit inflammation and RAS activity in hypertensive patients with renal impairment， with a favorable safety.

Effects of Intestinal Flora and Local Renin-angiotensin System on Diabetic Nephropathy and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN） is a common clinical complication of diabetes， the main cause of end-stage renal disease （ESRD）， and a key determinant of survival in diabetic patients. The pathogenesis of DN is complex， and it is currently believed to be associated with hemodynamic abnormalities， intestinal flora disturbances， glucose and lipid metabolism disorders， oxidative stress， genetic susceptibility， and protein non-enzymatic glycosylation. The local renin-angiotensin system （RAS） has always been the core of the pathogenic and progressive changes of DN. Once activated， it will induce the massive release of oxygen free radicals in the blood vessels， damage the endothelial function， and affect the microcirculation of the body. The recent studies demonstrate that intestinal flora and its metabolites may affect the occurrence and development of DN by activating or antagonizing the local RAS. Compared with western medicine treatment， traditional Chinese medicine （TCM） has the advantages of multiple targets and little toxic and side effects. Many TCM scholars have found that single herbs， their active ingredient extracts， and TCM compound prescriptions can improve kidney function by regulating the local RAS or intestinal flora. Specifically， the Chinese medicinal materials tonifying spleen （Codonopsis Radix， Dioscoreae Rhizoma， Atractylodis Macrocephalae Rhizoma， and Poria）， replenishing kidney （Rehmanniae Radix Praeparata， Corni Fructus， and Pseudostellariae Radix）， and activating blood， resolving stasis， and dredging collaterals （Hirudo， Salviae Miltiorrhizae Radix et Rhizoma， and Angelicae Sinensis Radix） have the regulatory effect. This article summarizes the roles of intestinal flora and local RAS in the occurrence and development of DN， and analyzes the animal experiments or clinical trials of TCM intervention in DN in recent years， aiming to provide more therapies and a theoretical basis for the treatment of DN with integrated TCM and Western medicine.

Correlation analysis between renin-angiotensin system and bone mineral density in children with glucocorticoid-induced osteoporosis / 中华内分泌外科杂志

Objective:To investigate the relationship between renin-angiotensin system (RAS) and bone mineral density in children with glucocorticoids-induced osteoporosis (GIOP) .Methods:From Apr. 2020 to May. 2021, 53 children with GIOP were recruited in the Children’s Hospital of Taiyuan Maternal and Child Health Hospital and included in the observation group, and 47 children who received glucocorticoid therapy but did not suffer from GIOP were included in the control group. The levels of serum RAS components and bone mineral density of the two groups of pediatric patients were detected and compared, and the risk clinical indicators affecting bone mineral density and GIOP were analyzed.Results:There were no significant differences between the observation group and the control group in terms of gender, age, BMI, disease type, type of glucocorticoid use, use of anti-osteoporosis (OP) drugs, expression levels of Angiotensin converting enzyme 2 (ACE2) or angiotensin II (Ang Ⅱ) (all P>0.05) . The bone density value of the observation group was lower than those of the control group, and the levels of angiotensin converting enzyme (ACE) (1.19±0.23) , angiotensin receptor 1 (AT1R) (1.24±0.24) , angiotensin receptor 2 (AT2R) (1.14±0.17) , and Mas receptor (MasR) (1.11±0.28) were significantly higher than those of the control group (1.00±0.23, 1.00±0.25, 1.00±0.21, 1.00±0.20) , and the differences were statistically significant (all P<0.05) . Pearson analysis showed that bone mineral density was negatively correlated with the levels of ACE ( r=-0.34, P=0.013) , AT1R ( r=-0.41, P=0.002) and AT2R ( r=-0.34, P=0.014) , and stepwise regression model showed that ACE ( t=-2.21, P=0.032) and AT1R ( t=-2.92, P=0.005) were the main factors affecting bone mineral density. Logistic regression model analysis showed that bone mineral density ( OR=0.85, P<0.001) , Ang Ⅱ ( OR=0.53, P=0.041) and AT2R ( OR=2.00, P=0.024) were independent clinical risk factors affecting GIOP (all P<0.05) . Conclusion:RAS components ACE and AT1R are independent risk factors affecting bone mineral density in children with GIOP, and are significantly correlated with bone mineral density in children.

Distribution characteristics of plasma renin concentration in patients with aldosterone-producing adenoma / 中华内科杂志

Objective:To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis.Methods:In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed.Results:The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 2<PRC≤4 mU/L. PRC was not suppressed (PRC>8.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome.Conclusions:Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

The effects of high-intensity interval training on the renin-angiotensin system in spontaneously hypertensive rats / 中华物理医学与康复杂志

Objective:To observe any effect of high-intensity interval training on the blood pressure and renal function of Wistar-Kyoto rats modeling spontaneous hypertension (SHR) and to explore the mechanism of the renal renin-angiotensin system′s (RAS′s) role in this process.Methods:Twenty male SHR were randomly divided into a sedentary group and an exercise group, each of 10. Another 10 Wistar-Kyoto rats formed a normotensive control group. The rats in the normotensive and hypertensive sedentary groups were fed quietly in their cage, while the hypertensive exercise group performed high-intensity interval training for 8 weeks. After the last exercise, blood pressure, renal function, the kidney levels of nitric oxide and interleukin-6 (IL-6) and the protein expressions of angiotensin converting enzyme (ACE), ACE2, angiotensin type 1 receptor (AT1R), AT2R and Mas receptor (MasR) were measured.Results:Compared with the normotensive group, the hypertensive sedentary group showed a significant increase in average blood pressure, IL-6, ACE and AT1R protein and the ratio of AT1R to AT2R. There was a significant decrease in the renal function, the average NO level and the expression of ACE2, AT2R and MasR protein. That group also showed a significant decrease in blood pressure, IL-6, ACE and AT1R protein expression and the AT1R: AT2R ratio compared with the hypertensive sedentary group, but a significant increase in renal function, average NO content and the expression of ACE2, AT2R and MasR protein.Conclusion:Eight weeks of high-intensity interval training has a protective effect on the kidneys by regulating the renin-angiotensin system, at least in rats.

Kidney xenotransplantation: status quo and development trend of physiological research / 器官移植

Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D3 of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.

Construction of a clinical-radiomic nomogram model for the differential diagnosis of adrenal adenoma and small diameter pheochromocytoma / 现代泌尿外科杂志

【Objective】 To effectively differentiate adrenal adenoma (AA) and small diameter pheochromocytoma (PCC) by establishing a clinical-radiomic nomogram model before surgery. 【Methods】 A total of 132 pathologically confirmed patients (45 PCC cases, 87 AA cases) were enrolled. After the features of enhanced CT were assessed, the radiomic features and related clinical indicators were extracted. Based on multiple Logistic regression, a clinical-radiomic nomogram with radiomic features and independent clinical predictors was developed. The area under the receiver operating characteristic (ROC) curve (AUC) was used for internal evaluation to compare the diagnostic effectiveness of the three models. The clinical effectiveness of the nomogram was verified with decision curve analysis (DCA). 【Results】 One of the 108 candidate features was used to construct the radiological feature score. Individualized clinical-radiomic nomogram included independent clinical factors (24 h urinary vanmandelic acid/renin/angiotensin I) and original first-order median radiological feature scores. Internal evaluation of the prediction model showed that the AUC was 0.945 (95%CI:0.906-0.984), superior to the single clinical model or radiological model in precise differentiation. DCA showed that the nomogram had the best clinical use. 【Conclusion】 The clinical-radiomic nomogram model can effectively differentiate adrenal adenoma from small diameter pheochromocytoma, which can improve the preoperative differential diagnosis and preparation.

Association between angiotensinogen M235T gene polymorphism and risk of hypertension: A case control study among Ethiopian patients

Background: Hypertension is a major public health problem in both developing and developed nations because it is highly prevalent and is associated with complications. Numerous enviromnental and genetic variables are linked to the occurrence of the disease. It may be influenced by the renin-angiotensin-aldosterone system, M'hich preserves bodily homeostasis. The angiotensinogen gene 11235T polymorphisms that has an effect on the activity of the renin-angiotensin-aldosterone system are related to the high hvpertension risk. The aim of this study was to find out the association between angiotensinogen Nf235T gene polymorphism and the risk of developing hypertenMon. Methods: A total of 306 samples - 153 patients Il'ith hvpertension and 153 age- and ser-matched healthy controls were selected using a simple random sampling technique. Clinical and biochemical variables were measured to assess the associated riskfactors. Blood samples from the patients and matched controls were used to isolate deoxyribonucleic acid. The AGT 11235T genotypes u:ere identified using polymerase chain reaction and analyzed by agarose gel electrophoresis. Logistic regression with a 95% confidence interval (CI) was employed to assess the risk correlations ofAGT gene M235Tpolymorphisms with hypertension. Results: Our analysis showed that the AGT-TT genotype (odds ratio [OR] = 3.11, 95% CL = 1.67­5.79, P< 0.001) and T allele (OR = 2.18, 95% CL = 1.56­3.04, P< 0.001) are considerably higher in hypertensive patients than in healthy controls. Our study also identified the clinical risk factors for hypertension, such as, total cholesterol, triglycerol, low density lipoprotein-cholesterol, and high density lipoprotein-cholesterol Inels, which were significantly higher in patients compared to controls (P< 0.001). Conclusion: The A GT M235T genes of the TT genotype and the T allele are associated with an increased risk of hypertension among the Ethiopian patients. A population-based epidemiological study is needed corroborate the association between AGT and HTN

Ang-(1-7) attenuates podocyte injury induced by high glucose in vitro

ABSTRACT Objective: The incidence of diabetic nephropathy (DN) is gradually increasing worldwide. Podocyte injury, such as podocyte apoptosis and loss of the slit diaphragm (SD)-specific markers are early pathogenic features of DN. Materials and methods: The cultured mouse podocytes were separated into a high glucose-treated (HG, 30mM) group to mimic DN in vitro, a low glucose-treated (LG, 5mM) group as a control and HG+ angiotensin-(1-7)(Ang-(1-7)) and HG+Ang-(1-7) + D-Ala7-Ang-(1-7) (A779, Ang-(1-7)/Mas receptor antagonist) experimental groups. The Cell Counting Kit-8 (CCK-8) method and flow cytometry was used to detect podocyte activity and podocyte apoptosis respectively. The expression of angiotensin type 1 receptor (AT1R), Mas receptor (MasR) and podocyte-specific markers were examined by q-PCR and Western blot, respectively. Results: The results showed that the decrease in podocyte activity; the increase in podocyte apoptosis; the decreased mRNA and protein expression of nephrin, podocin, WT-1 and MasR; and the upregulated expression of AT1R induced by HG could be reversed by Ang-(1-7). However, these effects were blocked by A779. The possible mechanisms of the Ang-(1-7)-mediated effect depended on MasR. In addition, the protective effect of Ang-(1-7) on podocyte activity was dose-dependent and most obvious at 10 µM. A779 had the greatest antagonistic action against Ang-(1-7) at a concentration of 10 μM. Conclusion: This study reveals that binding of Ang-(1-7) to its specific receptor MasR may counteract the effects of Ang II mediated by AT1R to significantly attenuate podocyte injury induced by high glucose. Ang-(1-7)/MasR targeting in podocytes may be a therapeutic approach to attenuate renal injury in DN.