Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway

Objective Keshan disease(KD)is a myocardial mitochondrial disease closely related to insufficient selenium(Se)and protein intake.PTEN induced putative kinase 1(PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body.This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury.Methods A low Se and low protein animal model was established.One hundred Wistar rats were randomly divided into 5 groups(control group,low Se group,low protein group,low Se+low protein group,and corn from KD area group).The JC-1 method was used to detect the mitochondrial membrane potential(MMP).ELISA was used to detect serum creatine kinase MB(CK-MB),cardiac troponin I(cTnI),and mitochondrial-glutamicoxalacetic transaminase(M-GOT)levels.RT-PCR and Western blot analysis were used to detect the expression of PINK1,Parkin,sequestome 1(P62),and microtubule-associated proteins1A/1B light chain 3B(MAP1LC3B).Results The MMP was significantly decreased and the activity of CK-MB,cTnI,and M-GOT significantly increased in each experimental group(low Se group,low protein group,low Se+low protein group and corn from KD area group)compared with the control group(P<0.05 for all).The mRNA and protein expression levels of PINK1,Parkin and MAP1LC3B were profoundly increased,and those of P62 markedly decreased in the experimental groups compared with the control group(P<0.05 for all).Conclusion Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

Efficacy of Long-term Selenium Supplementation in the Treatment of Chronic Keshan Disease with Congestive Heart Failure

Few effective treatments for chronic Keshan disease have been available till now.The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive.This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up.A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years.Of the 302 chronic Keshan disease patients,170(56.3%)were given selenium supplementation until the end point of follow-up.Cox proportional hazards regression models were used to identify the independent predictors of cardiac events.Our results showed that during the follow-up,there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group(101/170,59.4%)and 98 in non-selenium supplementation group(98/132,74.2%).Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death(HR 0.39,95%CI 0.28-0.53)after adjustment for baseline age,sex,cigarette smoking,family history of Keshan disease,body mass index(BMI),heart rate,electrocardiogram(ECG)abnonnalities,blood pressure,initial cardiothoracic ratio,left ventricular可ection fractions(LVEF)and whole-blood selenium concentration.Our ten-year follow-up analysis indicated that selenium supplementation,specifically combined with the use of angiotensinconverting cnzyme inhibitor and beta blocker therapy,improved the survival of patients with chronic Keshan disease with congestive heart failure.BMI,selenium deficiency,male,combined ECG abnonnalities,LVEF,and fast heart rate increased the risk of cardiac events.

Relationship Between Myocardial Injury and Expression of PGC-1α and Its Coactivators in Chronic Keshan Disease

Objective:Keshan disease(KD)is a mitochondrial cardiomyopathy.The present study explored the roles of peroxisome proliferator-activated receptor(PPAR)-y coactivator-la(PGC-la),the key regulator of mitochondrial structure and function,and its coactivators in myocardial injury in chronic KD.Furthermore,the usefulness of these molecules in the diagnosis of chronic KD was assessed.

THE STUDIES OF SERUM IL-6,INF-αAMONG CHRONIC KESHAN DISEASE PATIENTS

Objective To investigate the function of cytokine in the patients suffered from chronic Keshan disease. Methods Serum IL 6, INF α was tested among 55 patients of chronic Keshan disease and 30 health controls by the methods of ELISA, read in the unit of pg·mL -1 . Results The cytokine was significantly higher in Keshan disease patients than that in health control group. Conclusion Serum levels of IL 6, TNF α is higher in chronic Keshan disease patients than in health control group .It was showed that cytokine plays an important role during the etiopathology and the development in Chronic Keshan disease.

Circulating Adhesion Molecules in Patients with Keshan Disease and Their Relationship with Coxsackie B Virus Infection

This study determined the levels of serum soluble intercellular adhesion molecule-1 （sI-CAM-l） and soluble vascular cell adhesion molecular-1 （sVCAM-1） in patients with different types of Keshan disease （KD）, examined the relationship between Coxsackie B virus-specific IgM antibody （CBV-IgM） and slCAM-1 or sVCAM-1 in KD patients, and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications. The levels of serum slCAM-1, sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease （CKD）, 27 with latent Keshan disease （LKD） and 28 healthy controis. The subjects in different groups were adjusted for sex and age. Echocardiography was adopted to determine left ventricular ejection fraction （LVEF） in 22 patients with CKD. The results showed that CKD patients had significantly higher levels of slCAM-1 and sVCAM-1 than LKD patients and healthy controls （P〈0.01 for all）. And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls （P〈0.05）. A negative correlation was found between LVEF and slCAM-1 or sVCAM-1 in CKD patients. The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls. In CVB-specific IgM positive patients, the levels of serum slCAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart. It was concluded that the increase in the levels of slCAM-1 and sVCAM-1 suggests the progression of inflammation in KD. slCAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum slCAM-1 and sVCAM-1 in KD patients may be related to CBV infection.

THE STUDIES OF SERUM CVB-SPECIFIC IgM ANTIBODY AND NITRIC OXIDE AMONG THE PATIENTS WITH LATENT AND CHRONIC KESHAN DISEASE

Objective To investigate the serum coxsackie virus B(CVB) infection and nitric oxide (NO)level of the patients suffer from latent or chronic Keshan disease and their characteristics in the etiopathology of Keshan disease. Methods Sera were isolated from 30 patients with latent or chronic Keshan disease in Huangling county. Shaanxi Province, and the CVB-specific IgM antibody and NO were tested. Control groups were health subjects in Huangling county or Xi’an city, Shaanxi Province. Results The percentage of CVB-specific IgM positive in patients in Huangling county was significantly higher than that of both control groups in Huangling county and Xi’an city (P< 0.05). The serum level of NO In patients was significantly higher than that of the control group in Huangling county (P<0.05).however,compared with control group in Xi’an city. there was no difference (P>0.05). In CVB-specific IgM positive patients,the serum level of NO was significantly higher than that of CVB-specific 1gM negative group (P <0.05). Conclusion CVB infection and serum NO level might be related to the etiopathology and the development of Keshan disease.

Further Investigation on the Role of Selenium Deficiency in the Aetiology and Pathogenesis of Keshan Disease

Selenium supplements were not able to restore the ultrastructural changes in the myocardiurn of latent Keshan disease patients taken by using cardiac catheter endomyocardial biopsy. Observations on the changes of seleniurn status and the incidence of Keshan disease showed that new latent and naturally-occurring chronic cases were found in the endemic area even after selenium levels had been elevated in the residents to the levels typical in the non-endemic area. These results indicate that although selenium deficiency might be a primary pathogenetic geogen in the occurrence of Keshan disease, it is rather a conditional predisposing factor than a specific or initiative aetiologic factor for the occurrence of Keshan disease. Selenium supplmentation could apparently alleviate the higher platelet responsiveness of residents in the endemic area, which might contribute to eliminating the basis for the occurrence of the multifocal perivascular necroses in myocardium of acute and subacute Keshan disease

Research on Autoantibodies Against Myocardialβ_1-adrenergic and M_2 Cholinergic Receptors in Patients With Chronic Keshan Disease

Objectives To explore the relationship between serum autoantibodies against myocardial β1-adrenergic, M2-cholinergic receptors and chronic Keshan disease （CKD）. Methods The second extracellular loops of β1 and M2 receptors on human cardiomyocytes were used as the antigens. Enzyme linked immunosorbent assay （ELISA） was applied to determine serum autoantibodies against myocardial β1 and ME receptors in 32 CKD patients. 31 healthy subjects from endemic area were selected as the control. Results Positive rate of autoantibodies against myocardial β1 adrenergic （51.3%, 17/32） and M2 cholinergic （56.3% , 18/32） receptors were significantly higher than those in the control （9.7%, 3/ 31; 12.9%, 4/31） （both P〈 0.01）. Both positive rate and titers of above autoantibodies in NYHA Ⅱ - Ⅲ CKD patients were significantly higher than those in NYHA Ⅳ, demonstrating an apparently positive correlation between serum antibodies against myocardial β1 and M2 receptors （r=0.95）. Conclusions Autoantibodies against myocardial β1 and M2 receptors were found in sera of CKD patients; distribution of positive rate and titers of the autoantibodies in CKD patients in various NYHA are significantly different. classes of cardiac function

The Level of Serum Intact Terminal Peptide of Procollagen and Its Clinical Significance in Patients with Chronic Keshan Disease

Objectives To evaluate the changes of serum intact terminal peptide of procollagen in patients with chronic Keshan disease (KD) and investigate their clinical significance. Methods The concentrations of serum intact N-terminal peptide of type procollagen (P NP) and intact N-terminal peptide of type procollagen were measured by radioimmunoassay in 35 patients with chronic KD and 31 normal control. Doppler ultrasounds was used to determine several parameters of left ventricular systole and diastole functions. Results The concentration of serum P NP (74.07±16.74)μg/L and the ratio of P NP/ P NP (18.02 ±4.60) in chronic KD were significantly increased as compared to the control (39.63±12.07 μg/L, 12.12±4.24; P< 0.001). Serum P NP (4.19±0.64)μg/L in chronic KD was higher than that in the control (3.36±0.65 μg/L,P < 0.001) too. The higher of serum concentration of P NP and the ratio of P NP/ P NP, the worse of cardiac function in patients with chronic KD. A negative correlation was found between serum P NP/ P NP, P NP and VE/VA, LVEF (γ=-0.4502, -0.4608, P< 0.01 and γ=-0.3936, -0.3904, respectively; P<0.05). Conclusions These findings suggested that tissue synthesis of collagen type and type was abnormally increased in chronic KD. On the other hand, our results indicated that P NP and P NP were related to several functional alterations of the left ventricle. Serum procollagen peptide measurements might therefore provide indirectly diagnostic information on myocardial fibrosis associated with chronic KD.

Serum level of galectin-3 and its clinical significance in patients with chronic Keshan disease

Objective: Keshan disease (KD) is a fatal endemic dilated cardiomyopathy with unclear etiology and pathogenesis, and a high mortality in China. Pathologic studies confirmed that different degree of myocardial fibrosis existed in various types of KD. Myocardial fibrosis is an important contributor to the pathophysiology of left ventricular remodeling. Recently, galectin-3 (Gal-3) as a marker of cardiac fibrosis and heart failure was approved by the US FDA. The aim of this study was to evaluate the changes of serum level of Gal-3 in chronic KD (CKD) and their clinical implications. Methods: The levels of serum Gal-3 were measured by using enzyme-linked immunosorbent assay (ELISA) in 37 CKD patients and 32 healthy controls. Echocardiography was used to determine parameter of left ventricular ejection fraction (LVEF) and left ventricular end-diastolic dimension (LVEDD). Results: The serum concentration of Gal-3 ([95.81±18.99] ng/ml versus [48.16±11.09] ng/ml, t=6.906, P<0.001) and LVEDD ([60.46±7.63] mm versus (42.69±10.66) mm, t=3.61, P<0.01) were significantly higher, while LVEF ([42.69±10.66]% versus [62.16±6.38]%, t=4.679, P<0.01) were significantly lower in CKD patients compared with healthy controls. A negative correlation was found between elevated Gal-3 and lower LVEF (r=-0.882, P<0.001) and a positive correlation was found between elevated Gal-3 levels and enlarged LVEDD (r=0.834, P<0.001) or higher NYHA class (r=0.854, P<0.01) in CKD patients. Conclusion: Serum concentration of Gal-3 is strongly correlated with poorer left ventricular systolic function, enlarged LVEDD and higher New York Heart Association (NYHA) class, which may provide indirectly diagnostic information on myocardial fibrosis and heart function in CKD patients.

松辽盆地克山地区航放异常特征及铀成矿条件分析

为了筛选铀成矿有利地段,探索克山地区铀成矿前景,通过开展1:5万高精度航空放射性测量异常查证工作,并结合收集整理的相关地质资料,从航放异常特征、地质特征、能谱特征及土壤氡浓度特征等几个角度,对克山地区进行铀成矿条件分析。结果表明:该地区靠近小兴安岭地区,且盆地盖层具有较高的初始铀含量,铀源条件优良;地层宽缓,断裂发育,是深部烃类向上运移的通道,地表局部剥蚀强烈,形成构造天窗,成矿有利砂体大规模发育,并伴有后生改造作用和铀富集。克山地区航放异常集中分布,航磁推断构造发育,深部放射性信息突出,为砂岩型铀矿找矿提供了有益线索,为圈定找矿有利区段提供了依据。

Keshan disease and mitochondrial cardiomyopathy

Keshan disease (KD) is a potentially fatal form of cardiomyopathy (disease of the heart muscle) endemic in certain areas of China. From 1984 to 1986, a national comprehensive scientific investigation on KD in Chuxiong region of Yunnan Province in the southwest China was conducted. The investigation team was composed of epidemiologists, clinic doctors, pathologists, biochemists, biophysicists and specialists in ecological environment. Results of pathological, biochemical and biophysical as well as clinical studies showed: an obvious increase of enlarged and swollen mito- chondria with distended crista membranes in myocardium from patients with KD; significant reduc- tions in the activity of oxidative phosphorylation (succinate dehydrogenase, cytochrome oxidase, succinate oxidase, H+-ATPase) of affected mitochondria; decrease in CoQ, cardiolipin, Se and GSHPx activity, while obvious increase in the Ca2+ content. So, it was suggested that mitochondria are the predominant target of the pathogenic factors of KD. Before Chuxiong KD survey only a few cases of mitochondrial cardiomyopathy were studied. During the multidisciplinary scientific investiga- tion on KD in Chuxiong a large amount of samples from KD cases and the positive controls were examined. On the basis of the results obtained it was suggested that KD might be classified as a “Mitochondrial Cardiomyopathy” endemic in China. This is one of the achievements in the three years’ survey in Chuxiong and is valuable not only to the deeper understanding of pathogenic mechanism of KD but also to the study of mitochondrial cardiomyopathy in general. Keshan disease is not a genetic disease, but is closely related to the malnutrition (especially mi- croelement Se deficiency). KD occurs along a low Se belt, and Se supplementation has been effective in prevention of such disease. The incidence of KD has sharply decreased along with the steady raise of living standard and realization of preventive measures. At present, patients of KD are very sparse. In recent years the research on the non-KD mitochondrial cardiomyopathy has progressed rapidly. Given the advances in this aspect a minireview is written to evaluate the classification of KD as a kind of mitochondrial cardiomyopathy.

松嫩平原北部全新世黑土剖面孢粉组合及其对环境演化的制约

古气候和古环境演化是研究黑土形成演化最关键的问题之一。重建古植被、古气候、古环境,预测黑土区气候环境的演变已成为黑土地研究的热点。在松嫩平原北部克山县典型黑土剖面中采集到15件孢粉样品进行孢粉学研究,并对部分相同层位土壤样品中总有机碳进行了AMS ^(14)C测年。系统分析、鉴定和研究表明,克山县黑土剖面自下而上可划分为3个孢粉组合,下部孢粉组合以Planted Poaceae-Echinate Asteraceae-Tamarix-Polypodiaceae为代表,中部孢粉组合以Tamarix-Chenopodium-Polypodiaceae-Echinate Asteraceae为代表,上部孢粉组合以Pinus-Chenopodium为代表。综合第四纪地质地貌、孢粉、AMS ^(14)C、元素地球化学分析认为,典型黑土主要形成于中全新世7500 a B.P.以来的大暖期,形成于松嫩平原温暖半湿润的气候环境,植被为以草本灌木为主的草原植被。新构造运动是控制典型黑土区自然环境演变的主要内动力,晚更新世黄土状亚粘土为克山县典型黑土的成土母质,黑土发育过程即为成土母质黑化的过程。

Comparing gene expression profiles of Kashin-Beck and Keshan diseases occurring within the same endemic areas of China

In this study, differentially expressed genes in peripheral blood from patients with Kashin-Beck disease and Keshan disease were compared to further investigate the etiology and pathogenesis of both diseases, which occur in a common endemic area of China. Twenty Kashin-Beck disease patients and 12 healthy controls, and 16 Keshan disease patients and 16 healthy controls, were grouped into four pairs. Patients and controls were selected from common endemic areas for the two diseases. Total RNA was isolated from peripheral blood mononuclear cells from all patients and controls, and gene expression profiles analyzed by oligonucleotide microarrays. Sixteen genes differentially expressed in both Kashin-Beck disease and Keshan disease (versus controls) were identified, and comprised nine genes showing synchronous and seven asynchronous expression. The Comparative Toxicogenomics Database shows that expression and biological function of these genes can be affected by multiple environmental factors, including mycotoxin and selenium content, potential environmental risk factors for the two diseases. Thus, these shared differentially expressed genes may contribute to the distinct organ lesions, caused by common environmental risk factors of Kashin-Beck disease and Keshan disease.

基于SWOT分析的克山马铃薯品牌建设研究

随着农产品市场竞争日渐激烈,农产品品牌建设逐渐成为提升市场竞争力的重要途径。农产品品牌建设不仅能增加优质绿色农产品供给,同时又可以推动区域经济发展。本文通过运用SWOT分析方法,围绕优势、劣势、机遇、威胁4个方面,对克山马铃薯品牌的发展现状进行了分析阐述,并结合克山马铃薯品牌建设的实际状况,提出强化品牌意识、延伸产业链、深化落实数商兴农、加强品牌宣传等对策,为克山马铃薯产业发展持续注入新动能,为品牌建设提供强有力的支持。

提高食物链硒通量防治大骨节病和克山病示范研究

本研究在黄土高原的陕西省彬县大骨节病和克山病重病区，进行小麦、蔬菜的叶面喷Ｓｅ和主食加Ｓｅ防治地方病的示范研究。结果显示，喷Ｓｅ小麦含Ｓｅ量达０．０８１μｇ／ｇ，明显高于未喷Ｓｅ的小麦（０．００９μｇ／ｇ）；示范点膳食含Ｓｅ达０．０７６μｇ／ｇ，显著高于对照点（０．０１４μｇ／ｇ）；示范点人均日摄Ｓｅ量由１３．４０μｇ／ｇ提高到６０．３９μｇ／ｇ；大骨节病Ｘ线阳性检出率由４３．３３％下降到６．４５％，达到国家控制标准。

2004年全国克山病病情监测汇总分析

目的掌握2004年全国克山病患病及发病趋势。方法根据《克山病监测》标准(WS/T78-1996)及《克山病诊断标准》(GB17021-1997)对监测点区居民进行普查,随访2003年在册的克山病病例,对克山病发病相关因素进行调查。结果18个监测点区潜在型、慢型克山病检出率分别为3.5%和0.7%,估计全国有491万￣600万克山病病例,其中慢型克山病患者65万￣117万。潜在型、慢型克山病发病率分别为1.8‰和0.1‰,估计新发潜在型13万～39万例,新检出慢型病例最高可达4.3万例。人均发硒0.365mg/kg。粮硒平均0.020mg/kg。结论克山病仍然是一个严重的地方性公共卫生问题,工作重点应放在克山病监测、患者管理和硒预防等方面。

云南省地方性猝死的临床分析

目的调查云南省地方性猝死(YunnanEndemicSuddenDeath,YESD)的死亡性质,为有效地防治提供依据。方法访问患者家属及医务人员,调查死者发病与死亡经过。对患者家属及对照人群作全面查体、心电图、X线检查。以发现各村、屯的现有病人,为分析与确定死亡原因提供重要依据。结果调查的163例病区居民,查出各型克山病16例:轻症急型2例、慢型2例、潜在型12例。8例死者从临床表现和流行病特点符合克山病急性泵或电衰竭(严重或恶性心律紊乱)致死,故诊断为克山病。结论死亡8例地方性猝死病人的临床性质,为急型克山病急性心衰死亡(1例是慢型克山病,因心源性休克急型发作致死)。贯彻对克山病行之有效的综合防治措施,做到早期发现及时报告、早诊断、早治疗,云南“地方性猝死”是完全可防可治的。