Research progress on endogenous small-molecule phenolics and the proposal of "phenolomics" / 药学学报

Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

Clinical research progress and mechanism on myocardial injury in hearts from donors with stroke / 器官移植

At present, the heart of donor from donation after brain death are the primary organ sources for heart transplantation. After brain death, severe hemodynamic changes and a series of organ functional changes will occur, thereby leading to the functional damage or even loss of tissues and organs, especially the heart. Intimate relationship and interaction have been found in the physiology and pathophysiology between nervous and cardiovascular systems. After stroke, autonomic nervous disorder, neuroendocrine disorder and intense and persistent inflammatory reaction could be caused by the brain-heart axis reaction, leading to stroke-induced cardiac injuries, such as sympathetic storm, catecholamine storm, inflammatory storm, etc. In this article, research progresses on the mechanism of myocardial injury in heart from donors with stroke and the effect on clinical efficacy and prognosis after heart transplantation were reviewed, aiming to provide reference for clinical practice and subsequent research.

Intraoperative adenosine for pheochromocytoma with myocardial infarction and SARS-CoV-2. Case report / Adenosina intraoperatoria para feocromocitoma con infarto miocárdico y SARS-CoV-2. Reporte de caso

Abstract Pheochromocytomas are neuroendocrine tumors capable of synthetizing, storing and releasing catecholaminergic hormones that may lead to lifethreatening hemodynamic instability. The COVID-19 pandemic has increased the risks and perioperative complexity of the patients undergoing pheochromocytoma-associated adrenalectomy. This article discusses the use of adenosine for the management of hypertensive crisis during this intervention, as well as the need to individualize the suitable timing for surgery after recent COVID-19 infection. This article discusses the case of a patient with a finding of right adrenal incidentaloma; further studies determined a metanephrines secreting pheochromocytoma. Following hospital admission for preoperative optimization, the eve of the procedure the patient developed an acute myocardial infarction and subsequently SARS-CoV-2 symptomatic infection. Intraoperatively, hypertensive peaks were managed with continuous adenosine perfusion. The patient was discharged after 48 hours. Preoperative optimization positively influences the intraoperative management of patients with pheochromocytoma. The intraoperative use of adenosine allows for adequate and safe control of hypertensive crises. Each situation must be individualized in patients pending surgery, with a recent COVID-19 infection.

Resumen Los feocromocitomas son tumores neuroendocrinos capaces de sintetizar, almacenar y liberar hormonas catecolaminérgicas que pueden provocar inestabilidad hemodinámica con compromiso vital. La pandemia por COVID-19 ha aumentado los riesgos y la complejidad perioperatoria de los pacientes sometidos a adrenalectomía por feocromocitoma. Describimos el uso de adenosina para manejar las crisis hipertensivas durante esta intervención, así como establecer la necesidad de individualizar el momento quirúrgico idóneo tras infección reciente por COVID-19. Presentamos el caso de un paciente con hallazgo de incidentaloma suprarrenal derecho cuya ampliación de estudio se orientó como feocromocitoma secretor de metanefrinas. Tras ingreso hospitalario para optimización preoperatoria, el día previo al procedimiento presentó un infarto agudo de miocardio y posteriormente una infección sintomática por SARS-CoV-2. Intraoperatoriamente se manejaron los picos hipertensivos con perfusión continua de adenosina. Tras 48 horas recibió el alta hospitalaria. La optimización preoperatoria influye positivamente en el manejo intraoperatorio de los pacientes con feocromocitoma. El uso intraoperatorio de adenosina permite un adecuado y seguro control de las crisis hipertensivas. En pacientes pendientes de cirugía con infección reciente por COVID-19 se requiere individualizar cada situación.

Performance evaluation of automated magnetic beads extraction method for the measurement of catecholamine metabolites analyzed by liquid chromatography tandem mass spectrometry / 中华检验医学杂志

Objective:To evaluate the performance of magnetic beads extraction method (MGE) for the measurement of catecholamine metabolites by liquid chromatography tandem mass spectrometry.Methods:This is a methodological evaluation study. The linearity, limit of quantitation, recovery, precision, and matrix effect of catecholamine metabolites 3-methoxyepinephrine (MN), 3-methoxynorepinephrine (NMN) and 3-methoxytyramine (3-MT) extracted by MGE method were evaluated according to CLSI C62-A. Consensus of method development and validation of liquid chromatography-tandem mass spectrometry in clinical laboratories and other guidelines, 132 clinical residual plasma samples were collected and extracted by automated MGE and traditional solid phase extraction (SPE) method to compare the harmonization of the two extraction methods.Results:The linearity of MN, NMN and 3-MT extracted by automated MGE was>0.99, and the LOQ for MN, NMN and 3-MT were 0.033 5 nmol/L, 0.054 7 nmol/L and 0.011 0 nmol/L, respectively. The repeatability of MN, NMN and 3-MT were 1.3%-5.1%, 2.2%-5.6% and 1.7%-7.1%, respectively. The total imprecision in the laboratory were 1.5%-8.2%, 2.2%-7.7%, 2.1%-11.2%. Although the absolute recovery is low, the average relative recoveries of MN, NMN and 3-MT were 91.5%-108.5%, 92.0%-108.6%, and 89.3%-104.1%, respectively, and the percentage deviation from the expected concentration was within 15%. After isotope internal standard correction, the relative matrix effect is close to 100%, which can compensate for the potential matrix effect. The results of MGE and SPE of MN, NMN and 3-MT showeda good correlation (correlation coefficient r>0.99). The average relative deviations of MN, NMN and 3-MT were 0.2%, -1.4% and 1.0%, respectively. Conclusion:The automatic MGE method hasa good performance in extracting catecholamine metabolites, and is expected to be used in high-throughput analysis of samples in clinical in the future.

Comparative study of dexmedetomidine vs. midazolam on plasma catecholamine levels and hemodynamics in patients with septic shock / 中华危重病急救医学

Objective:To compare the effects of dexmedetomidine (DEX) and midazolam on the endogenous plasma catecholamine levels and the dosage of exogenous norepinephrine (NE) to maintain blood pressure in patients with septic shock.Methods:From January 2018 to December 2019, patients admitted to the department of critical care medicine of the Affiliated Hospital of Guizhou Medical University who needed invasive mechanical ventilation and had a stay of more than 48 hours in the intensive care unit (ICU) for septic shock and received DEX or midazolam for sedation were enrolled in this study. The hemodynamic data, arterial blood lactic acid (Lac) level, arterial blood gas analysis and vasoactive drug dose at 0, 12, 24, 48, 72 hours after entering the ICU were dynamically recorded, and the plasma catecholamine levels at 0, 24, 48 hours after entering the ICU were recorded. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and sequential organ failure assessment (SOFA) score on ICU-admission were calculated. The parameters of prognosis were collected.Results:A total of 24 patients were enrolled, 12 in the DEX group and 12 in the midazolam group. There were similar dynamic trends in heart rate (HR), central venous pressure (CVP), venous-arterial carbon dioxide pressure difference (Pv-aCO 2), oxygenation index (PaO 2/FiO 2), and Lac level of patients between the two groups. Only the 12-hour CVP and 72-hour Pv-aCO 2 in the DEX group were significantly higher than those in the midazolam group [CVP (mmHg, 1 mmHg = 0.133 kPa): 13±3 vs. 10±3, Pv-aCO 2 (mmHg): 9.4±5.2 vs. 4.8±2.2, both P < 0.05], and the mean arterial pressure (MAP) of patients in the DEX group at 48 hours and 72 hours was significantly higher than that in the midazolam group (mmHg: 95±10 vs. 86±10, 96±9 vs. 88±7, both P < 0.05). There was no statistically significant difference in the duration of mechanical ventilation, ICU mortality or in-hospital mortality between the DEX group and the midazolam group [duration of mechanical ventilation (days): 5.6 (3.8, 9.5) vs. 10.5 (5.9, 15.0), ICU mortality: 16.7% vs. 33.3%, in-hospital mortality: 25.0% vs. 41.7%, all P > 0.05]. There was no significant difference in the dosage of propofol or sufentanil between the DEX group and the midazolam group [propofol (mg/kg): 0 (0, 9.35) vs. 4.07 (0, 13.75), sufentanil (μg/kg): 6.26 (4.90, 9.80) vs. 8.32 (3.52, 9.34), both P > 0.05]. The levels of plasma NE, dopamine and dobutamine in the DEX group at 48 hours were significantly lower than those in the midazolam group [NE (ng/L): 1 850.12 (342.16, 2 938.05) vs. 4 596.60 (3 310.56, 5 546.84), dopamine (ng/L): 119.10 (60.47, 200.71) vs. 275.40 (214.61, 418.88), dobutamine (ng/L): 51.20 (36.85, 75.59) vs. 98.97 (85.65, 107.10), all P < 0.05], but the amount of NE required to maintain MAP between 65 mmHg and 75 mmHg in the DEX group and the midazolam group was similar [μg/kg: 1 922 (1 170, 4 887) vs. 2 466 (2 043, 3 438), P > 0.05]. Conclusion:DEX can reduce plasma catecholamine levels in patients with septic shock more than midazolam, and does not increase the dose of exogenous NE, and has a smaller effect on hemodynamics in patients with septic shock than midazolam.

Role of β-adrenergic receptors in development of breast cancer / 中国药理学通报

; β-adrenergic receptors (β-ARs) are widely found in organs of the human body and play an important role in regulating heart function, blood vessel dilation, energy metabolism, etc. Studies have shown that β-ARs are abnormally high in breast cancer cells, which can promote the occurrence and development of breast cancer by affecting the growth and metabolism of breast cancer, invasive metastasis, and angiogenesis. Clinical studies have shown that blocking β-ARs signaling improves the prognosis of breast cancer patients, so β-ARs may be a potential treatment target for breast cancer. This paper summarizes the role of β-ARs in the development of breast cancer, with a view to providing some reference for follow-up research and clinical treatment.

Bilateral Pheochromocytoma Masquerading as Acute Severe Congestive Heart Failure in a Juvenile Male Subject: A Case Report and Review of Literature

Introduction: Pheochromocytomas are rare neuroendocrinetumours of the adrenal medulla that do not always presentwith classical triad of headache, palpitations and diaphoresisalong with paroxysmal or sustained hypertension. Herein wepresent a case of young boy with pheochromocytoma whopresented initially with congestive cardiac failure with noother significant manifestation.Case report: A 17 -year-old boy was admitted in ouremergency with 2 months history of unevaluated headacheand one day history of breathlessness along with syncopalattacks. His initial clinical evaluation was suggestive ofcongestive cardiac failure (CCF) with hypotension. Afterinitial stabilization he was shifted to intensive care unit (ICU)where his echocardiography revealed dilated cardiomyopathywith severe mitral regurgitation. Because of young ageof presentation and no past significant medical historyneuroendocrine cause for cardiac illness was suspected.Further investigations revealed grossly elevated levels ofnormetanephrines in 24-hour urine collection. Imaging studiesincluding ultrasonography followed by computed tomographyof abdomen and I123 MIBG confirmed presence of bilateralpheochromocytoma. An open bilateral adrenalectomywas performed successfully after initial stabilisation.Patient was discharged after one-month postoperative care.Patient is presently in our follow up on low dose steroids,mineralocorticoids along with betablocker and has shownmarked improvement in biochemical and clinical parameters.Conclusion: Pheochromocytoma though a rare catecholamineproducing tumour but if not timely intervened can lead tolife-threatening consequences. Our case report highlights theimportance of high clinical suspicion of pheochromocytomaeven in young adolescent patients who present first time withacute severe CCF with dilated cardiomyopathy

Changes of vasoactive substances and adrenergic beta receptors in rabbit models of neurogenic pulmonary edema / 中国小儿急救医学

Objective To establish an animal model of neurogenic pulmonary edema (NPE),and to study the role of catecholamine and beta receptors in the occurrence of NPE. Methods The NPE model was established by injecting fibrinogen and thrombin into the cerebellum medullary pool of the rabbits. Twenty-four rabbits were divided into the control group,the saline group and the experimental group by random num-ber table. In the control group,only cerebellar medullary cistern puncture was carried out,and no drug was in-jected. Cerebrospinal fluid was drew out and the same amount of saline was injected into the cerebellum me-dullary pool in the saline group. Fibrinogen and thrombin were injected into the cerebellum medullary pool in the experimental group. The animals were intubated by tracheotomy,the femoral artery and the internal jugu-lar vein were dissected and connected with the PiCCO instrument to detect the blood pressure,heart rate,and respiratory rate before puncture and at 1 min,10 min,30 min after puncture. Serum samples were collected for the determination of epinephrine,norepinephrine,acetylcholine,endothelin-1,cardiac troponin I,brain natri-uretic peptide and neuropeptide Y levels before puncture and at 1 min,10 min after puncture. The rabbits weresacrificed at 3 hours after successful modeling,the pathological examination of lung was performed. Myocar-dial samples were taken to detect adrenergic beta receptors mRNA. Results (1)The heart rate,respiratory rate and mean arterial pressure at 1 min and 10 min after puncture in experimental group were significantly higher than those in control group and saline group. (2) The pathological examination of the rabbits′ lungs in experimental group found that the lung tissue was swollen and dark red in appearance with large areas of con-gestion. Under the microscope,the lung tissue was edema,bleeding,and inflammatory cells were infiltrated in the alveolar cavity,which was consistent with characteristics of NPE. (3)There was no difference in epineph-rine and norepinephrine concentration in all groups before the cerebellar medullary pool puncture. The concen-tration of epinephrine and norepinephrine at 1 min after puncture time were (200. 0 ± 251. 7)μg/ L,(448. 9 ± 356. 7)μg/ L in the experimental group,whcih were significantly higher than those of control group[(15. 4 ± 3. 4)μg/ L,(15. 9 ± 9. 7)μg/ L] and saline group[(17. 1 ± 3. 8) μg/ L,(29. 6 ± 18. 4) μg/ L] (P < 0. 05). The concentration of epinephrine and norepinephrine at 10 min after puncture were (397. 0 ± 797. 7)μg/ L, (221. 4 ± 173. 7)μg/ L in the experimental group,whcih were significantly higher than those of control group [(23. 3 ± 6. 4) μg/ L,(18. 8 ± 3. 9) μg/ L] and saline group[(16. 7 ± 9. 1) μg/ L,(20. 3 ± 6. 5) μg/ L] (P < 0. 05). (4)There was no significant difference in the levels of serum neuropeptide Y,acetylcholine and endothelin-1 among the three groups. (5)The mRNA of adrenergic beta-1 receptor in the experimental group was 0. 37 ± 0. 12,which was significantly lower than those in the control group (0. 54 ± 0. 13) and saline group (0. 56 ± 0. 14) (P < 0. 05). There was no significant difference in adrenergic beta-3 receptor mRNA among the three groups. Conclusion The NPE animal model was constructed by injecting fibrinogen and thrombin into the cerebellum medullary pool of the rabbits. Catecholamine and beta-1 receptor play a role in the occurrence of NPE rabbit model. There is no significant correlation between neuropeptide Y,acetylcholine,en-dothelin-1 and the occurrence of NPE in rabbits.

Advances in immunomodulatory effects of catecholamines in critical illness / 中华危重病急救医学

Immune disorders are common in critically ill patients. Catecholamines play a crucial role in theimmune regulation and modulation. Immune cells can synthesize catecholamines and express adrenergic receptors. Catecholamine has a wide-ranging regulatory effect on innate immunity such as neutrophils, monocyte macrophages, dendritic cells, natural killer cells, and lymphocyte-mediated acquired immunity. Catecholamines exert different immunomodulatory effects by binding to α receptors, β receptors, and dopamine receptor subtypes on immune cells. In-depth study of the effect and mechanism of catecholamine on immune function in critically ill patients will provide new ideas for the prevention and treatment of immune dysfunction in critical illness.

Correlation between blood pressure and level of catecholamine in children with obstructive sleep apnea hypopnea syndrome / 上海交通大学学报（医学版）

Objective • To investigate the correlation between blood pressure and catecholamine levels in children with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods • From January 2014 to December 2014, children and adolescents aged 2 to 12 years old who complained mainly of snoring during sleep were admitted to Department of Otolaryngology-Head and Neck Surgery, Shanghai Children's Hospital and underwent surgery. Allnight polysomnography (PSG) was used to monitor and measure the systolic blood pressure (SBP) and diastolic blood pressure (DBP) in conscious state. According to the blood pressure reference standard of Chinese children and adolescents in 2010, the children with OSAHS were divided into normal blood pressure group, SBP increased group, DBP increased group, and SBP and DBP increased group. The children with OSAHS were divided into light, moderate and severe OSAHS subgroups according to the apnea hypopnea index (AHI) and the lowest oxygen saturation (LSpO2). The correlation between blood pressure and the level of catecholamine was analyzed in the children with OSAHS. Results • Two hundred and twenty-three subjects were included in the analysis. The average SBP was (100.3±9.8) mmHg (1 mmHg=0.133 kPa) and the average DBP was (63.0±9.8) mmHg. There were 50 cases (22.42%) diagnosed as hypertension, in which 20 cases (8.97%) were severe hypertension. The 223 children with OSAHS were divided into mild OSAHS subgroup (n=59), moderate OSAHS subgroup (n=127) and severe OSAHS subgroup (n=37) according to OSAHS grades. The difference of adrenaline level between the normal blood pressure group and the DBP increased group was statistically significant (P=0.032). The difference of LSpO2 between the DBP increased group and the SBP and DBP increased group was statistically significant (P=0.031). There were no significant differences in dopamine and noradrenaline levels among the four groups. There were significant differences in SBP and adrenaline level between OSAHS mild subgroup and moderate subgroup (P=0.038, P=0.000), but there were no significant differences between the moderate OSAHS subgroup and the severe OSAHS subgroup. There were no significant differences in dopamine and noradrenaline levels among the three OSAHS subgroups. Conclusion • The increase of plasma catecholamine level in children with OSAHS can lead to the increase of SBP, which will increase with the development of OSAHS. Therefore, early diagnosis and treatment of OSAHS should be taken into consideration.

Recognition of neurogenic myocardial injury / 中国实用内科杂志

Transient,reversible myocardium injury can occur in patients with brain injury.Several pathophysiological mechanisms are involved in the development of such neurogenic myocardium injury.Excess catecholamine release plays a major role during myocardial injury.The clinical features include abnormal electrocardiographic,echocardiographic features and elevated biomarkers.In some patients stunned myocardium can be observed which may lead to hemodynamic instability or even cardiogenic shock.Inotropic agents and mechanical support are useful in improving cardiac function.β-adrenergic blockade is likely to attenuate the catecholamine toxicity but its use remains controversial.

Advances in immunomodulatory effects of catecholamines in critical illness / 中华危重病急救医学

Immune disorders are common in critically ill patients. Catecholamines play a crucial role in theimmune regulation and modulation. Immune cells can synthesize catecholamines and express adrenergic receptors. Catecholamine has a wide-ranging regulatory effect on innate immunity such as neutrophils, monocyte macrophages, dendritic cells, natural killer cells, and lymphocyte-mediated acquired immunity. Catecholamines exert different immunomodulatory effects by binding to α receptors, β receptors, and dopamine receptor subtypes on immune cells. In-depth study of the effect and mechanism of catecholamine on immune function in critically ill patients will provide new ideas for the prevention and treatment of immune dysfunction in critical illness.

Advances in immunomodulatory effects of catecholamines in critical illness / 中华危重病急救医学

Immune disorders are common in critically ill patients. Catecholamines play a crucial role in theimmune regulation and modulation. Immune cells can synthesize catecholamines and express adrenergic receptors. Catecholamine has a wide-ranging regulatory effect on innate immunity such as neutrophils, monocyte macrophages, dendritic cells, natural killer cells, and lymphocyte-mediated acquired immunity. Catecholamines exert different immunomodulatory effects by binding to α receptors, β receptors, and dopamine receptor subtypes on immune cells. In-depth study of the effect and mechanism of catecholamine on immune function in critically ill patients will provide new ideas for the prevention and treatment of immune dysfunction in critical illness.

The role of catecholamine in the severe hand, foot and mouth disease in children / 中国小儿急救医学

Objective To study the levels of plasma catecholamine( norepinephrine,epinephrine and dopamine) in children with severe hand,foot and mouth disease( HFMD) ,and to assess the influence of cate-cholamine on the pathogenesis of severe HFMD. Methods A collaborative study group was established, including Children′s Hospital of Fudan University, Jiangxi Provincial Children′s Hospital, Anhui Provincial Children′s Hospital,Linyi People′s Hospital and No. 2 People′s Hospital of Fuyang City. Blood samples from children with severe HFMD were collected from April 2014 to October 2016. The levels of blood epineph-rine,norepinephrine,dopamine were measured at 2 h,24 h and 48 h after diagnosis for HFMD. Results The level of epinephrine at 24 h after diagnosis was ( 213. 0 ± 139. 8 ) ng/L in children with pulmonary edema, which was significantly higher than that of children without pulmonary edema[(137. 8 ± 45. 5)ng/L)](P=0. 022). The level of epinephrine at 24 h after diagnosis was (373. 2 ± 298. 1)ng/L in the dead children,and was (144. 2 ± 42. 5)ng/L in the survival children. The concentration of norepinephrine at 24 h after diagnosis was (1935. 7 ± 1824. 1)ng/L in the dead children,and was (858. 3 ± 212. 7)ng/L in the survival children. The levels of epinephrine and norepinephrine of those who died from HFMD were significantly higher than those of survival children at 24 h after diagnosis. There were no significant differences in catecholamine con-centrations among stage 2,3,4 HFMDs at 2 h,24 h and 48 h after diagnosis. Sex and enterovirus 71 virus infection had no significant influences on plasma catecholamine concentrations in children with severe HFMD. Conclusion Plasma epinephrine levels increase in children with HFMD complicated with pulmonary edema. Epinephrine and norepinephrine may play an important role in the death of children with severe HFMD.

Adverse reactions of catecholamines in shock treatment / 中国小儿急救医学

Catecholamines is an important part of the treatment of shock.Its best goal is not only to maintain the patient′s blood pressure,but also to increase the effective perfusion of tissues and organs, improve microcirculation and prevent multiple organ dysfunction. But in the current clinical practice, catecholamines are often"double-edged sword". Therefore,focusing on the benefits of each catecholamine while taking into account the adverse reactions of the drug may be the key to finding the best solution.

Use of vasoactive agents in different shock / 中国小儿急救医学

Circulatory failure recognition and treatment represents an important issue in critically ill infants and children.Improvement of cardiocirculatory disability and stabilization of hemodynamic is the key step.Hemodynamic variations among different types of shocks,such as hypovolemic,cardiogenic,distributive and obstructive shock,are different.When fluid administration fails to restore adequate arterial pressure and organ perfusion,vasoactive agents should be considered.The key to selecting among vasoactive agents is to consistent with the context of the goals of therapy.Despite the complex pathophysiology of shock,choose of right vasoactive agents for hemodynamic support of patients with shock can be guided by acknowledged pathological changes,mechanisms of vasoactive agents and current studies.

Protective effects of esmolol on lung function in septic rat / 中华急诊医学杂志

Objective To explore the protective effects of short-acting β31 receptor blocker esmolol on lung injury in septic rats and explore its mechanism.Methods Fifty-four male SpragueDawley rats were randomly(random number) divided into three groups (n=18 in each),namely sham operation group(Sham),sepsis group(Spesis),esmolol group(ES).Each group were further divided into three subgroups of 6 h,12 h and 24 h(n=6 in each subgroup).The sepsis models were established with cecal ligation and puncture (CLP) in rats of Sepsis group and ES group,while rats of SH group were treated with laparotomy without CLP.Dwelled cannulation in the left internal jugular vein was performed after the model establishment.Saline in the rate of 1 mL/h was continuously pumped intravenously into the rats of SH group and Sepsis group by micro pump for 6 h,and esmolol solution in the rate of 1 mL/h [15 mg/(kg·h)]was continuously pumped into the rats of ES group for 6h.Rats in each subgroup were sacrificed at 6h,12h and 24 h after modeling,separately.The levels of catecholamine (CA) in plasma and levels of NF-κB in lung tissue were measured by ELISA.The protein levels of TLR4 and NF-κB in lung tissue were detected by Western Blot.The protein content of alveolar lavage fluid,wet/dry weight ratio(W/D) of lung tissue,lung coefficient and lung water content were measured.The pathological changes of lung tissues were observed under an optical microscope.Results (①) The levels of CA in plasma in Sepsis and ES groups at 6 h after modeling was significantly increased compared with Sham group (P＜0.05),and the level of CA in plasma increased significantly in ES group compared with Sham and Sepsis groups (P＜0.05).At 12 h after modeling,level of CA in plasma was still significantly increased in ES group compared with SH group (P＜0.05);At 24 h after modeling,level of CA in plasma was increased significantly in ES group compared with Sepsis group (P＜0.05).(②) At 6 h,12 h and 24 h after modeling,levels ofNF-κ B in lung tissue were significantly increased in Sepsis group and ES group compared with SH group (P＜0.05),and levels of NFκ B in lung tissue in ES group were also significantly lower than those in Sepsis group at given intervals (P＜0.05).③ At 6 h,12 h and 24 h after modeling,protein content of alveolar lavage fluid,wet/dry weight ratio (W/D) in lung tissue,lung coefficient and lung water content in Sepsis group and ES group were significantly increased compared with SH group (P＜0.05),and protein content of alveolar lavage fluid,wet/ dry weight ratio (W/D) in lung tissue,lung coefficient and lung water content in ES group also significantly lower than those in Sepsis group at given intervals (P＜0.05).④ Western Blot revealed at 6 h,12 h and 24 h after modeling,the protein levels of TLR4 and NF-κ B in lung tissue in Sepsis group and ES group were significantly increased compared with SH group (P＜0.05),and the protein levels of TLR4 and NF-κ B in lung tissue of ES group were also significantly lower than those in Sepsis group at all given intervals (P＜0.05).⑤ The lightest degree of pathological change was observed in SH group,the most serious degree of pathological change was found in Sepsis group,and the pathological change was significantly alleviated in ES group compared with Sepsis group whereas the pathological change was significantly increased compared with SH group at all given intervals.Conclusions Esmolol can promote the secretion of catecholamine,inhibit the release of inflammatory cytokines,reduce lung permeability,reduce pulmonary edema,and thus play an important role in protecting the lungs.The mechanism may be that esmolol improves the responsiveness of β-adrenergic receptor to catecholamine,and regulates the level of inflammatory cytokines by inhibiting TLR4-NF-κB-TNF-α signaling pathways,thus exerting protective effect on the lungs.

Correlation analysis of stress indicators of blood growth differentiation factor-15, catecholamine,heat shock protein and acute coronary syndrome / 中华急诊医学杂志

Objective To analyze the correlation between acute coronary syndrome (ACS) and stress differentiation factors (GDF-15), catecholamines, and heat shock proteins (HSP-70). Methods A total of 40 patients with ACS were selected from the Emergency Department of the PLA General Hospital from September 10, 2016 to October 10, 2016. 40 healthy volunteers were selected as the control group. The information of age, gender, history of smoking, drinking, hyperlipidemia, hypertension and diabetes. Inspection indicators of blood biochemistry (Creation kinase Isoenzyme, Total cholesterol, Triglyceride, High-density lipoprotein, Blood glucose, Total bilirubin, Direct bilirubin), serum level of GDF-15, catecholamine (Adrenaline,norepinephrine,dopamine)and HSP-70 were collected. Evaluation of Coronary Stenosis used with Coronary Artery Lesions and Gensini Score. Statistical analysis using SPSS 17.0 statistical software, measurement data are expressed as mean ± standard deviation (x±s),count data to the number of cases and percentage, measurement using t test, count data using chisquare test. Results Serum levels of GDF-15[(21.94±14.23) vs. (7.06±5.53), P=0.007],catecholami ne[(46592.15±30931.27) vs. (5507.14±2083.28), P<0.01], HSP-70 [(369.56±300.44) vs. (07.76±54.23),P<0.001],all higher than the control group. GDF-15 serum levels of Gensini scores> 40 compare with <20group was significantly higher [(324.27 ± 198.81) vs. (77.43 ± 699.22), P=0.035], serum catecholaminelevels of > 40 group compare with <20 group significantly increased [(18.71 ± 7.32) vs. (18.6±46.1),P=0.017], GDF-15 levels were significantly higher in the multi-vessel stenosis group than in the doublevessel stenosis group[ (618.40±434.42) vs. (292.07±219.65), P=0.033]. Conclusions GDF-15,catecholamine and HSP-70 are correlated with ACS, as well as the severity of coronary artery lesions.

Protective effects of blueberry drink on cognitive impairment induced by chronic mild stress in adult rats

BACKGROUND/OBJECTIVES: Stress-induced cognitive impairment is related to the suppression of hippocampal neurogenesis that results from an increase of oxidative stress. Therefore, the aim of this study was to investigate the effects of administration of a blueberry drink, having a high antioxidant power, on the cognitive performance of adult rats exposed to chronic mild stress. MATERIALS/METHODS: Twelve-week-old male Sprague-Dawley rats (n = 48) were randomly divided into four groups: control (CO), stress (ST), control + 5% blueberry drink (CO + B), and stress + 5% blueberry drink (ST + B). After eight weeks, the cognitive performance was assessed using a multiple T-maze water test. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and ascorbic acid were measured in the brain, and catecholamine concentrations were measured in plasma. RESULTS: The brain weights of the rats from the ST and ST + B groups were significantly lower than those of the rats from the CO and CO + B groups. The cognitive performance of the ST group was impaired when compared to that of the CO group. This impairment was significantly improved by the blueberry drink supplementation (P < 0.05). The brain SOD and CAT concentrations were not influenced by the stress or by the blueberry drink. However, the brain levels of GPx and ascorbic acid were significantly lower in the ST group than those in the CO group and were increased by the blueberry drink supplementation. The plasma catecholamine concentrations were affected by chronic mild stress and by the blueberry drink. The plasma norepinephrine and dopamine concentrations were decreased by the chronic stress and improved by the blueberry drink supplementation. The plasma epinephrine level was only influenced by the stress. CONCLUSION: These findings suggest that the blueberry drink may protect against the cognitive impairment induced by chronic mild stress.

The influence of sildenafil on myocardial catecholamine level in a swine model of ventricular fibrillation / 中华急诊医学杂志

Objective To reveal the changes of catecholamine and lactate levels in myocardial interstitial fluid during cardiopulmonary resuscitation in order to prove the protective effects of sildenafil pretreatment on post-resuscitation myocardial function in swine model of ventricular fibrillation (VF).Methods Twenty-four swine were randomly (random number) divided into three groups:saline group,sildenafil group and shame operation group.Sildenafil in dose of 0.5 mg/kg dissolved in 40 mL of saline was given to swine once intraperitoneally 40 min prior to VF in sildenafil group.The equivalent volume of saline (0.9％ NaC1) alone was administered instead in saline groups.There was no treatment in shame operation group.After ventricular fibrillation untreated for 8 min,open-chest cardiopulmonary resuscitation was initiated.The hemodynamic variables were recorded at baseline,4 min,1 h and 6 h after restoration of spontaneous circulation (ROSC).The interstitial fluid from the left ventricle wall was collected by using the microdialysis tubes at given intervals,in which the levels of dopamine,norepinephrine,epinephrine,and lactate were measured.The samples for pathological examination were taken at 24 hours after ROSC.Results The levels of catecholamine and lactate in the sildenafil group were lower than those in saline group at all different intervals (P ＜ 0.05 or P ＜ 0.01).The cumulative defibrillation energy was lower in the sildenafil group than that in the saline group (P ＜ 0.05).The hemodynamic changes and myocardial histological damage in sildenafil group were milder than those in saline group (P ＜ 0.05).The pathologic changes of myocardium and mitochondria in saline group were more severe than those in sildenafil group.Conclusions Sildenafil pretreatment prior to VF can effectively reduce endogenous catecholamine secretion and lactate levels in myocardial tissue,protecting the myocardium and improving post-resuscitation myocardial function.