Science Letters: Proteomic analysis of the serum in patients with idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease of unknown etiology. The exact pathogenesis of pulmonary arterial hypertension is still not well known. In the past decades, many protein molecules have been found to be involved in the development of IPAH. With proteomic techniques, profiling of human plasma proteome becomes more feasible in searching for disease-related markers. In present study, we showed the protein expression profiles of the serum of IPAH and healthy controls after depleting a few high-abundant proteins in serum. Thirteen spots had changed significantly in IPAH compared with healthy controls and were identified by LC-MS/MS. Alpha-1-antitrypsin and vitronectin were down-regulated in IPAH and may be valuable candidates for further explorations of their roles in the development of IPAH.     

Influence of serum adiponectin level and SNP +45 polymorphism of adiponectin gene on myocardial fibrosis

Adiponectin plays an important role in the development of hypertension, atherosclerosis, and cardiomyocyte hypertrophy, but very little was known about the influence of serum adiponectin or the adiponectin gene polymorphism on myocardial fibrosis. Our study investigates the influence of the SNP +45 polymorphism of the adiponectin gene and serum levels of adiponectin on myocardial fibrosis in patients with essential hypertension. A case-control study was conducted on 165 hypertensive patients and 126 normotensive healthy controls. The genotypes of adiponectin gene polymorphisms were detected by the polymerase chain reaction (PCR) method. Serum concentrations of procollagen were measured by a double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in all subjects. The integrated backscatter score (IBS) was measured in the left ventricular myocardium using echocardiography. The serum levels of adiponectin in hypertensive patients were significantly lower than those in the normal control group ((2.69±1.0) μg/ml vs. (4.21±2.89) μg/ml, respectively, P<0.001). The serum levels of type-I procollagen carboxyl end peptide (PICP) and type-III procollagen ammonia cardinal extremity peptide (PIIINP) in the hypertension group were significantly higher than those in the control group. In the hypertension group, serum levels of adiponectin were significantly and negatively related to the average acoustic intensity and corrected acoustic intensity of the myocardium (r=0.46 and 0.61, respectively, P<0.05 for both). The serum levels of PICP and PIIINP were significantly different among the three genotypes of SNP +45 (P<0.01). Logistic regression analyses showed that sex and genotype (GG+GT) were the major risk factors of myocardial fibrosis in hypertensive patients (OR=5.343 and 3.278, respectively, P<0.05). These data suggest that lower levels of adiponectin and SNP +45 polymorphism of the adiponectin gene are likely to play an important role in myocardial fibrosis in hypertensive patients.     

Involvement of endothelial progenitor cells in the formation of plexiform lesions in broiler chickens: possible role of local immune/inflammatory response

Plexiform lesions (PLs), which are often accompanied by perivascular infiltrates of mononuclear cells, represent the hallmark lesions of pulmonary arteries in humans suffering from severe pulmonary arterial hypertension (PAH). Endothelial progenitor cells (EPCs) have been recently implicated in the formation of PLs in human patients. PLs rarely develop in rodent animal models of PAH but can develop spontaneously in broiler chickens. The aim of the present study was to confirm the presence of EPCs in the PLs in broilers. The immune mechanisms involved in EPC dysfunction were also evaluated. Lungs were collected from commercial broilers at 1 to 4 weeks of age. The right/total ventricle ratios indicated normal pulmonary arterial pressures for all sampled birds. Immunohistochemistry was performed to determine the expressions of EPC markers (CD133 and VEGFR-2) and proangiogenic molecule hepatocyte growth factor (HGF) in the lung samples. An EPC/lymphocyte co-culture system was used to investigate the functional changes of EPCs under the challenge of immune cells. PLs with different cellular composition were detected in the lungs of broilers regardless of age, and they were commonly surrounded by moderate to dense perivascular mononuclear cell infiltrates. Immunohistochemical analyses revealed the presence of CD133⁺ and VEGFR-2⁺ cells in PLs. These structures also exhibited a strong expression of HGF. Lymphocyte co-culture enhanced EPC apoptosis and completely blocked HGF-stimulated EPC survival and in vitro tube formation. Taken together, this work provides evidence for the involvement of EPCs in the development of PLs in broilers. It is suggested that the local immune cell infiltrate might serve as a contributor to EPC dysfunction by inducing EPC death and limiting their response to angiogenic stimuli. Broiler chickens may be valuable for investigating reversibility of plexogenic arteriopathy using genemodified inflammation-resistant EPCs.     

慢性肺心病急性发作期患者血液流变学测定的临床意义

目的探讨慢心肺心病患者在急性发作期的血液流变学测定的临床应用价值．方 法采用全自动血液粘度快测议测定５８例患者和５２例对照组的血液粘度．结果 除纤维 蛋白原外，其它六项指标明显高于对照组，Ｐ＜０．００１．结论 本法具有快速、特异、实用等 特点，为临床在肺心病患者急性发作期合理用药提供一种有效方法．     

血清胱抑素C对高血压早期肾损伤诊断价值的研究

目的探讨血清胱抑素C（Cystainc）水平在原发性高血压早期肾损伤临床诊断中的价值。方法高血压病1。2级患者共41例作为观察组,同时选择41例健康体检者作为对照组,分别检测两组治疗前后Cystain C、尿微量白蛋白（mAlb）、血清肌酐（Scr）、尿素氮（BUN）、内生肌酐清除率（Ccr）等。结果观察组与对照组间Cystain C、24hmAlb、Ccr有显著性差异（P〈0．01）、Scr差异无显著性（P〉0．05）;结论血清Cystain C的浓度比BUN、Scr浓度更能够反映肾小球滤过功能的损害,是早期诊断肾小球滤过功能受损的敏感指标之一。     

透明质酸检测对肝病及非肝病患者的诊断价值

血清透明质酸是近年来在临床上应用较广泛的肝病及非肝病的检测指标.本文用放射免疫学方法对82例正常献血员,134例肝病患者血清及慢性阻塞性肺病、肺心病、冠心病、肾病、类风湿性关节炎和系统性红斑狼疮等非肝病患者透明质酸进行了检测.结果表明肝病患者血清透明质酸明显高于对照组,非肝病各组明显高于正常对照组（p<0.01）,具有一定的临床诊断意义.因此,血清透明质酸对肝病的诊断、分型、病情进展以及非肝病诊断有一定价值.     

VEGFmRNA and eNOSmRNA expression in immature rabbits with bleomycin-induced pulmonary hypertension

INTRODUCTION Pulmonary hypertension is not rare in humanwith some heart and lung diseases. Chronic pul-monary hypertension leads to structural alterationsof the lung vessels. The pathophysiology of thisremodeling process is still poorly understood.Furthermore, the structural damage of the lungvessels limits the clinical success of vasodilatortreatment. Assuming genetic susceptibility, shearstress and inflammation are the principal pathoge-netic factors involved in lung vessel remode…     

Do race,neglect, and childhood poverty predict physical health in adulthood? A multilevel prospective analysis

Childhood neglect and poverty often co-occur and both have been linked to poor physical health outcomes. In addition, Blacks have higher rates of childhood poverty and tend to have worse health than Whites. This paper examines the unique and interacting effects of childhood neglect, race, and family and neighborhood poverty on adult physical health outcomes. This prospective cohort design study uses a sample (N = 675) of court-substantiated cases of childhood neglect and matched controls followed into adulthood (M_age = 41). Health indicators (C-Reactive Protein [CRP], hypertension, and pulmonary functioning) were assessed through blood collection and measurements by a registered nurse. Data were analyzed using hierarchical linear models to control for clustering of participants in childhood neighborhoods. Main effects showed that growing up Black predicted CRP and hypertension elevations, despite controlling for neglect and childhood family and neighborhood poverty and their interactions. Multivariate results showed that race and childhood adversities interacted to predict adult health outcomes. Childhood family poverty predicted increased risk for hypertension for Blacks, not Whites. In contrast, among Whites, childhood neglect predicted elevated CRP. Childhood neighborhood poverty interacted with childhood family poverty to predict pulmonary functioning in adulthood. Gender differences in health indicators were also observed. The effects of childhood neglect, childhood poverty, and growing up Black in the United States are manifest in physical health outcomes assessed 30 years later. Implications are discussed.     

VEGFmRNA and eNOSmRNA expression in immature rabbits with bleomycin-induced pulmonary hypertension

Objective: To investigate the evolution of pulmonary hypertension, the pathological changes of pulmonaryarteries, and the expression of VEGFmRNA and eNOSmRNA of pulmonary arterial endothelial cells in immature rabbitstreated with intratracheal bleomycin (BLM). Methods: Immature rabbits were divided into control and BLM group. Twoand four weeks after intratracheal normal saline or BLM injection, the systolic, diastolic and mean pulmonary arterypressure (PASP, PADP, MPAP) were measured by micro-catheter; the pathological changes and the expression ofVEGFmRNA and eNOSmRNA of endothelial cells in pulmonary arteries were evaluated by HE and in situ hybridization.Results: Two and four weeks after intratracheal injection of BLM, the PASP, PADP and MPAP increased 53%, 49%, 52%in 2 weeks, and 43%, 89%, 56% in 4 weeks; the wall thickness increased and the cavity in middle and small pulmonaryarteries became narrow; the Thickness Index (TI) and Area Index (AI) increased 25%, 14% in 2 weeks, and 22%, 24% in 4weeks; the level of VEGFmRNA and eNOSmRNA expression decreased 46%, 43% in 2 weeks, and 43%, 51% in 4 weeks.There was no significant difference between 2 weeks and 4 weeks BLM groups. Conclusion: The pulmonary artery pressurewas elevated, the thickness of wall increased and the cavity became narrow in middle and small pulmonary arteries, and thelevel of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in immature rabbitsafter 2 weeks and 4 weeks of intratracheal 4 U/kg BLM injection.     

Molecular hydrogen is a promising therapeutic agent for pulmonary disease

Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ for gas exchange, the lungs are constantly exposed to various harmful environmental irritants. Short- or long-term exposure to these harmful substances often results in lung injury, causing respiratory and lung diseases. Acute and chronic respiratory diseases have high rates of morbidity and mortality and have become a major public health concern worldwide. For example, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.     

Effect of nebulized nitroglycerin on children with ventricular septal defect and pulmonary hypertension

In order to find a safe, simple, effective and selective pulmonary vasodilator, we tested the effectiveness and safety of inhalation of nebulized nitroglycerin (Neb-NTG) by children with ventricular septal defect and pulmonary hypertension (VSD-PH). Twenty μg/kg Neb-NTG was inhaled by seven children with VSD-PH using face mask during cardiac catheterization. The pulmonary artery pressure (PAP), systemic arterial pressure (SAP) and methemoglobin (MetHb) concentration were measured before and after inhalation of Neb-NTG. After inhalation of Neb-NTG, the PAP and pulmonary-to-systemic pressure ratio (Pp/Ps) decreased significantly; There was no significant decrease in SAP. The systolic and diastolic PAP decreased respectively 13±4% and 9±7% in 5 min, 21±3% and 13±17% in 10 min, 24±3% and 16±19% in 15 min. The Pp/Ps decreased 12±4% in 5 min, 21±9% in 10 min and 24±6% in 15 min. There was no significant increase in the MetHb level after inhalation of 20 μg/kg of Neb-NTG. The MetHb level was below 1.5%. Neb-NTG is a safe, simple, effective and selective pulmonary vasodilator.     

Study on the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) in patients with Helicobacter pylori Infection

Objective: To evaluate the interaction between serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and Helicobacter pylori (H. pylori) infection in patients with chronic gastritis and peptic ulcer. Methods: The serum levels of sICAM-1 in 205 patients with chronic gastric diseases were detected by ELISA method and the status of H. pylori was determined by histologic examination, RUT, 14C - UBT, and serology. The sera obtained from 18 healthy volunteers served as controls. Results: The serum levels of sICAM-1 were significantly higher in patients with H. pylori positive than those of H. pylori negative (889.43±32.52 ng/ml vs. 747.07±30.45 ng/ml, P<0.05). The serum levels of sICAM-1 in patients with mild, moderate and severe infection of H. pylori were 841.68±72.36 ng/ml, 905.43±37.59 ng/ml and 1012.54±49.34 ng/ml,respectively (P<0.05). The serum levels of sICAM-1 proved to be significantly correlated with the density of H. pylori colonization in gastric mucosa (rs =0.316, P<0.001). The serum levels of sICAM-1 in patients with chronic gastritis and peptic ulcer were significantly higher than those in healthy controls (P<0.05). Conclusions: These results indicated that H. pylori infection up-regulates the expression of sICAM-1.     

Correlation of serum arylesterase activity on phenylacetate estimated by the integrated method to common classical biochemical indexes of liver damage

The correlation of serum arylesterase (PON1) activity on phenylacetate determined by an integrated method to classical biochemical indexes of liver damage was investigated for the use of PON1 activity to evaluate liver damage. PON1 reaction curve as absorbance at 270 nm for 0.20 mmol/L phenylacetate hydrolysis was analyzed by the integrated method to determine maximal PON1 reaction rate. Classical biochemical indexes of liver damage were determined routinely. The 95% confidence threshold of PON1 activity in sera from healthy individuals was 2.12 mkat/L [(4.73±1.31) mkat/L, n=105]. PON1 activity in clinical sera was closely correlated to serum albumin, total protein and the ratio of albumin to globulins, but was weakly correlated to both direct and total bilirubin in serum. There were no correlations of PON1 activity to γ-glutamyltransferase, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. Among 127 clinical sera with PON1 activity＞2.12 mkat/L, there were 92% healthy individuals examined by albumin, 90% healthy individuals examined by total protein, 88% healthy individuals examined by total bilirubin, 86% healthy individuals examined by direct bilirubin and 64% healthy individuals examined by the ratio of albumin to globulins, respectively. In each group of healthy individuals judged by classical biochemical indexes of close correlation to PON1 activity, percentage of healthy individuals examined by PON1 activity was always ＞80%. These results suggested PON1 activity on phenylacetate estimated by the integrated method was also suitable for the evaluation of liver damage.     

Serum macrophage migration inhibitory factor as a potential biomarker to evaluate therapeutic response in patients with allergic asthma: an exploratory study

Background: Previous studies have shown that macrophage migration inhibitory factor(MIF) is involved in the pathogenesis of asthma. This study aimed to investigate whether serum MIF reflects a therapeutic response in allergic asthma.Methods: We enrolled 30 asthmatic patients with mild-to-moderate exacerbations and 20 healthy controls, analyzing the parameter levels of serum MIF, serum total immunoglobulin E(tIgE), peripheral blood eosinophil percentage(EOS%), and fractional exhaled nitric oxide(FeNO). Lung function indices were used to identify disease severity and therapeutic response.Results: Our study showed that all measured parameters in patients were at higher levels than those of controls. After one week of treatment, most parameter levels decreased significantly except for serum tIgE. Furthermore, we found that serum MIF positively correlated with EOS% as well as FeNO, but negatively correlated with lung function indices. Receiver operator characteristic(ROC) curve analysis indicated that among the parameters, serum MIF exhibited a higher capacity to evaluate therapeutic response. The area under the curve(AUC) of MIF was 0.931, with a sensitivity of 0.967 and a specificity of 0.800.Conclusions: Our results suggested that serum MIF may serve as a potential biomarker for evaluating therapeutic response in allergic asthma with mild-to-moderate exacerbations.     

几种因素对人体动脉血压的影响

对衡水学院大学生,在肢体运动、冰水、不同体重指数等情况下和安静状态下的动脉血压采用常规方法进行测量、记录数据并进行统计学处理.结果表明,血压与肢体运动、冰水及体重指数等因素有非常明显的联系（P〈0.01）,这些都会影响人体血压;控制体重、饮食、多进行有氧运动以及养成良好的生活习惯是预防和减少大学生高血压的主要措施.     

缺铁性贫血患者血清蛋白变化的研究

本文报告90例IA患者及52例健康人血清总蛋白及血清白蛋白的测定结果,结果显示IA患者的血清总蛋白及血清白蛋白水平明显低于正常对照,且贫血越明显降低越显著。     

Association between non-alcoholic fatty liver disease and arterial stiffness in the non-obese,non-hypertensive,and non-diabetic young and middle-aged Chinese population

Background and objective: Non-alcoholic fatty liver disease (NAFLD) is associated with arterial stiffness in the general population. Age, obesity, hypertension, and diabetics are risk factors for arterial stiffness. In this study, we aimed to investigate the association between NAFLD and arterial stiffness as measured by brachial-ankle pulse wave velocity (baPWV) in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population. Methods: A cross-sectional study with 1296 non-obese, non-hypertensive, and non-diabetic young and middle-aged (20–65 years) subjects undergoing routine medical check-ups in the International Health Care Center of the Second Affiliated Hospital of School of Medicine of Zhejiang University was carried out. Fatty liver was diagnosed by ultrasonography, and baPWV was measured using an automatic waveform analyzer. The subjects were classified into two groups according to the presence of NAFLD, and divided into a further two groups according to their baPWV. Results: The overall incidence of NAFLD was 19.0%, and NAFLD patients had a significantly higher level of baPWV than the controls ((1321±158) cm/s vs. (1244±154) cm/s; P<0.001). The incidence of NAFLD was clearly higher in the increased baPWV group than in the normal baPWV group (29.3% vs. 16.9%; P<0.001), and the incidence increased in line with the increase of baPWV quartiles in the normal range as well as with the severity of arterial stiffness (both P for trend <0.001). Multiple linear logistic regression analysis showed that the presence of NAFLD was positively and independently associated with baPWV. Conclusions: Our results suggest that the presence of NAFLD is associated with arterial stiffness as measured by baPWV in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population.     

超声对高血压病患者颈动脉声像图的分析

目的探讨各级高血压病与颈动脉硬化之间的关系。方法对558例高血压病患者的颈动脉内膜中层厚度（IMT）、斑块发生率进行检查分析,并与209例健康成人对照。结果各级高血压患者颈动脉IMT与对照组相比均有明显增加;各级高血压病患者颈动脉IMT之间进行比较亦显示出显著性差异;颈动脉IMT随高血压分级增加而逐渐增厚。结论血压增高与高血压病患者颈动脉变化密切相关,颈动脉超声检测对于防治高血压及其并发症具有重要意义。     

血清和唾液中尿素氮、肌酐、尿酸测定的相关性研究

本文主要探讨唾液与血清中BUN、Cr、UA的相关性和临床应用价值。住院肾脏病患者73例和健康人42例,检测血清和唾液中的尿素氮、肌酐及尿酸浓度。肾脏病患者唾液和血清BUN、Cr、UA有较好的相关性。肾脏病患者唾液BUN、Cr、UA含量均比健康人高。健康人唾液和血清BUN有较好的相关性,Cr无相关性。唾液UA浓度随血清UA浓度的增加而升高。唾液中BUN、Cr、UA可用于判定肾脏功能障碍病人的疾病损害程度。     

尿微量蛋白联合尿酶测定对高血压病肾损害的临床意义

[目的]探讨尿微量蛋白的检测对高血压病早期肾损害的诊断价值.[方法]分别对高血压病组与健康对照组做尿微量蛋白mAlb,IgG以及NAG的测定,结果两组作对比.[结果]高血压病组的尿微量蛋白mAlb,IgG,NAG明显高于对照组(P<0.01).[结论]尿微量蛋白联合尿酶测定可作为高血压病早期肾损伤诊断的敏感指标.