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Based on the general goal of the medium and long term development of basic science from 2021 to 2035 and the "14th Five-Year Plan" in China, combined with the national strategic needs, this paper discusses the five priority development areas of endemiology according to the development trends and characteristics of endemiology in the next 5 - 15 years. The five areas are study on the pathogenesis and prevention measures of endemic fluorosis; study on risk assessment, pathogenic mechanism and control strategy of environmental arsenic exposure; research on the basis and application transformation of the pathogenesis of iodine nutrition-related diseases; molecular mechanism and targeted intervention of cartilage injury in Kashin-Beck disease; precise prevention and treatment, preservation of biological samples and etiology study of Keshan disease. Combined with the scientific significance and national strategic needs of various field, the authors analyze its main study directions and core scientific issues.
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According to the general goal of long term development of basic science from 2021 to 2035 and the "14th Five-Year Plan" in China, starting from the reasearch characteristics and the basic situation of endemiology, this study discusses the strategic position, development law, development trend, development status and layout, development goals and realization ways of endemiology, combined with the strategic needs of the discipline, the important interdisciplinary research areas of endemiology are put forward. The purpose of this study is to promote the rapid development of basic research on endemic diseases, to provide reference for the scientific and technological layout and policy formulation of the endemiology, to provide reference for the "14th Five-Year Plan" in China, and to provide guarantee for the people in the sick area to seek health.
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Heart activity is highly dependent on adenosine triphosphate (ATP) produced via mitochondrial oxidative phosphorylation. Traditional therapeutics has developed drugs by repairing damaged mitochondrial DNA, reducing mitochondrial reactive oxygen species (ROS) production, and accelerating the degradation of damaged mitochondria and recycle. In recent years, however, mitochondrial replacement therapy has taken a different strategy, and has entered the clinical trial stage. This review will summarize the research progress of cardiovascular drugs targeting mitochondria and mitochondrial replacement therapy to provide a new perspective for addressing some relevant endemic diseases in China.
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The mitochondrial quality control system maintains mitochondrial homeostasis mainly through protein degradation, vesicle transport, and mitophagy. Mitochondrial biosynthesis, dynamics, and calcium ion play key regulative roles in mitochondrial quality control. Under normal conditions, the mitochondrial quality control system can work well. In recent years, studies have found that mitochondrial dysfunction is closely associated with the occurrence of heart failure. In order to understand mitochondrial function, this paper reviews mitochondrial quality control methods, regulatory factors and their potential therapeutic applications in heart failure.
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Recent studies have overturned the previous belief that adult cardiocyte had been thought to permanently withdraw from cell-cycle activity.At present,targeting cardiocyte proliferation is one of current major therapeutic strategies for myocardial injury and repair following injury.Therefore,the author review the research progress in cell-cycle regulation of cardiocyte proliferation by systematically searched the relevant studies.
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The mitochondrial quality control system maintains mitochondrial homeostasis mainly through protein degradation, vesicle transport, and mitophagy. Mitochondrial biosynthesis, dynamics, and calcium ion play key regulative roles in mitochondrial quality control. Under normal conditions, the mitochondrial quality control system can work well. In recent years, studies have found that mitochondrial dysfunction is closely associated with the occurrence of heart failure. In order to understand mitochondrial function, this paper reviews mitochondrial quality control methods, regulatory factors and their potential therapeutic applications in heart failure.
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Objective To observe the intervention effect of vitamin C (Vit C) and adenosine triphosphate (ATP) on myocardial fibrosis in rats.Methods Forty male SD rats were selected,body weight were 125-140 g,and they were divided into 8 groups according to body weight using a random number table method.Four rats for control group,3 rats for model group,6 rats for Vit C early group,6 rats for ATP early group,6 rats for Vit C + ATP early group,5 rats for Vit C late group,5 rats for ATP late group,and 5 rats for Vit C + ATP late group.Rats in model group and these intervention groups were induced with doxorubicin (2 mg/kg each week) for 6 weeks,and control group was given the same amount of normal saline.All early groups were intragastrically administered with Vit C (200 mg·kg-1·d-1),ATP (45 mg·kg-1·d-1) and Vit C + ATP (200 mg·kg-1·d-1 + 45 mg·kg-1 ·d-1) in the fourth week;these late groups were intragastrically administered with the same dose in the sixth week;each group was continuously administered for 21 days.Three days after the last intervention,cardiac ultrasonography was performed in all surviving rats,and left ventricular end diastolic diameter (LVEDD),left ventricular end systolic diameter (LVESD),left ventricular ejection fraction (LVEF),and left ventricular fractional shortening (LVFS) were recorded.The rats were sacrificed and the hearts were taken.HE staining and Masson staining were used to observe the pathological changes of myocardial tissue and the collagen volume fraction (CVF) was calculate.Serum cardiac troponin Ⅰ (CTn-Ⅰ) and type Ⅰ procollagen amino terminal peptide (PINP) levels were determined by enzyme-linked immunosorbent assay (ELISA).Results Compared with control group [(3.65 ± 0.25) mm,(80.63 ± 3.03)％,(43.57 ± 2.54)％],LVESD [(5.07 ± 0.58),(4.06 ± 0.68),(4.71 ± 0.43),(4.87 ± 0.44),(4.79 ± 0.59),(5.07 ± 0.62),(4.97 ± 0.29) mm] of model group and each intervention groups were increased,LVEF [(62.17 ± 4.92)％,(71.28 ± 3.54)％,(65.03 ± 3.35)％,(59.81 ± 2.45)％,(60.42 ± 9.22)％,(60.15 ± 3.06)％,(60.65 ± 2.05)％],and LVFS [(30.05 ± 2.95)％,(36.44 ± 2.90)％,(31.63 ± 2.15)％,(26.95 ± 1.05)％,(28.35 ± 6.84)％,(27.79 ± 2.41)％,(28.38 ± 1.42)％] were decreased (P ＜ 0.05);compared with model group,LVESD was decreased,LVEF and LVFS were increased in Vit C early group (P ＜ 0.05).HE staining showed that the myocardial pathology of each early group improved to different degrees,such as cardiomyocyte degeneration,necrosis and fibrosis,inflammatory cell infiltration,moderate degree of interstitial edema,Vit C early group and Vit C + ATP early group were more pronounced.Masson staining showed significant improvement in fibrosis in the Vit C early group and Vit C + ATP early group,and collagen fibers were significantly reduced.Compared with the control group [(0.52 ± 0.14)％],the CVF [(27.11 ± 5.05)％,(9.80 ± 1.84)％,(16.55 ± 2.21)％,(5.06 ± 1.45)％,(12.11 ± 2.12)％,(15.71 ± 1.56)％,(16.93 ± 2.76)％] of myocardial tissue in model group and each intervention groups were significantly increased (P ＜ 0.05).There were no significant differences in CTn-Ⅰ and PINP levels between the eight groups (P ＞ 0.05).Conclusions Vit C can reduce myocardial fibrosis and improve cardiac function in the early stage.The effect of ATP alone to improve fibrosis is not obvious.
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With the huge advances in rural China since 1980s,rampant Keshan disease (KD)has been fading away,and therefore we set an ultimate goal at overall elimination.In recent years,the evaluation results showed that there were still some obstacles in achieving this goal.By explaining the pathogenesis and epidemic mechanism of KD and the factors regulating the fluctuation of the disease,as a kind of local lifestyle disease induced by poverty,the author think,it will be of very low possibility in breaking out again thanks to the long-term exchange of cereal commodities and current poverty relief program.And the next move is to revise the existing criteria for KD elimination and to maintain the state of elimination primarily through health education and social economic improvement in all affected areas.
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Heart failure is the leading cause of death in cardiovascular diseases.Despite effectiveness of current clinical treatment,it is not satisfactory in general,so more effective and optimal therapies are under seeking.All available evidences show that cardiac muscles have limited regenerative capacity in adult mammals,while some vertebrates,such as zebrafish and salamander,can completely recover through perfect regeneration following myocardial injury.In-depth investigation into underlying mechanism may facilitate the development of human heart's potential of scarless healing.In this review paper,we summarized recent progresses in distinct cardiac regenerative capacity and their main influencing factors of several model animals through comparative analysis.
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Endemic diseases include iodine deficiency disorders,fluorosis,arsenicosis,Keshan disease and Kaschin-Beck disease,which have been well under controlled or basically eliminated so far in China thanks to the great efforts made by our governments and medical staffs over the past decades.We are entering into a new era for consolidation of the achievements.Meanwhile,unprecedented social changes are happening in the diseases affected rural areas of China,which features:first of all,younger generation left and permanent population aging;second,severely polluted natural environment and better housing conditions;third,social transformation from self-sufficient natural economy to commodity economy with improved living standard,but still leaving a certain number of poor farmers and;lastly,backward social security system.However,there are some preferential policies issued in recent years for agriculture,alleviating grass-root social conflicts.All these changes may exert positive or negative influences on combating endemic disease,at least through disease incidence,control measures and surveillance,and further investigations are needed.
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Objective To explore expression level of circulating microRNA (miR)-133a and Galectin-3 and their potential clinical application in differential diagnosis between patients with chronic Keshan disease and dilated cardiomyopathy.Methods Twenty-eight patients with chronic Keshan disease and 28 cases of age-and sex-matched healthy people as control from the same severe historical endemic areas of Keshan disease in Heilongjiang Province,and another 28 patients with dilated cardiomyopathy from non-affected areas were chosen for the study.All the subjects were asked for disease history and did physical examination,examined by Doppler echocardiography for left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD),and collected fasting venous blood specimen (elbow vein).The plasma miR-133a and the serum Galectin-3 were determined by Real-time PCR and enzyme-linked immunosorbent method,respectively.Meanwhile,the correlation was analyzed between miR-133a,galectin-3,LVEF and LVEDD.Results The miR-133a and Galectin-3 levels in different groups were statistically different (F =48.789,9.485,P ＜ 0.01).The plasma miR-133a level in chronic Keshan disease group and dilated cardiomyopathy group [median (quartile):0.394 (0.271,0.770),1.665 (0.943,2.713)] were both significantly lower than those in control group [2.382 (1.502,3.302],P ＜ 0.01 or ＜ 0.05],and the plasma miR-133a level in chronic Keshan disease group was lower than that in dilated cardiomyopathy group (P ＜ 0.01).There was no significant difference of serum Galectin-3 level between chronic Keshan disease group and dilated cardiomyopathy group [17.710 (9.624,27.799),12.692 (9.376,26.290) μg/L,P ＞ 0.05],but both were significantly higher than those in control group [8.070 (7.135,9.308) μg/L,P ＜ 0.01].The miR-133a was positively correlated with LVEF (rs =0.297,P ＜ 0.01),while negatively correlated with LVEDD,and Galectin-3 (rs =-0.271,-0.318,P ＜ 0.05 or ＜ 0.01);the serum Galectin-3 was negatively correlated with LVEF (rs =-0.392,P ＜ 0.01),and positively correlated with LVEDD (rs =0.385,P ＜ 0.01).Conclusion The combined application of miR-133a,Galectin-3,LVEF and LVEDD may provide assistance in clinical differential diagnosis of chronic Keshan disease and dilated cardiomyopathy.
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Objective To carry out a pilot investigation into fungus diversity in corn samples harvested from Keshan disease areas and obtain the information of dominant fungi,to predict possible secondary toxins in future study.Methods In Keshan disease areas (Heshui County and Zhengning County of Gansu Province,Yuanbao Town of Heilongjiang Province) and non-Keshan disease area (Harbin suburbs of Heilongjiang Province),5 samples of newly harvested corn from local plants were collected via the simple random sampling method,and the samples (n =20) were put in a sterile bags and sealed,numbered and transported to laboratory,placed in the incubator for cultivating mould fungi,cuhured for 2 weeks,and fungal DNA was extracted.The DNA samples were sent to Beijing Auwegene Technology Co Ltd for quality inspection,and sequencing analysis of fungal internal transcribed spacer 1 (ITS1) region was done using modern high-throughput DNA sequencing technique and MiSeq PE3000 platform,the rationality of sequencing data was analyzed through the rarefaction curve and the Shannon-Wiener curve trend to be gentle or not,and the true condition of the fungal community in the sample was tested by species composition Coverage ＞ 99％ or not,the difference in fungal community was studied between Keshan disease group and non-Keshan disease group based on the relative abundance of the fungal species in each group.Results A total of 513 869 high quality sequences were obtained,and 528 operational taxonomic unit (OTU) classifications were produced.The trend of rarefaction curve and Shannon-Wiener curve were gradually flattening,they showed that the sequences of the data were reasonable;and coverage ＞ 99％ showed that data could reflect the true situation of the fungal community.Analysis of species composition showed that there was a great overlap of fungal species between Keshan disease group and non-Keshan disease group,the relative abundance of the genus Wickerhamomyces,Candida and Aspergillus in Keshan disease group were higher than that of non-Keshan disease group.Conclusion Genus Wickerhamomyces,Candida and Aspergillus may be the dominant fungi associated with Keshan disease,it can be considered for secondary toxins studies.
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Keshan disease (KD),an endemic cardiomyopathy liable to affect preschool children and young women with high disability and mortality,occurs in some rural areas of mainland China.However,the cause of KD remains unclear except for a number of plausible hypotheses proposed,which have puzzled scientists for nearly a hundred years since 1935.In this paper,we systematically reviewed KD etiological studies in@@literature,and classified them into five key historical times as follows:preliminary investigation stage (from Manchuria to the early days of new China),blossom research stage the 20th century (from the late 1950s through the 1960s),broad collaboration stage (from the 1970s through the mid-1980s),key research stage for selenium compounding factors (from the late 1980s through the mid-1990s),and radical innovation research stage (since the late 1990s).In the past century,several risk factors including unbalanced diet,selenium deficiency,enterovirus infection and mildew cereals,have been proved to be closely related to KD occurrence and development,but their etiological necessity and relationship are yet to be clarified.We highly recommend that the lack of study subjects could be overcome by referring to the major clues identified in literature,by using experimental animal models,and by establishing a core biological specimen bank of KD patients as well.
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Myocardial fibrosis is a pathological process characterized by fibroblast proliferation and collagen deposition,which occurs in the normal structure of the myocardium.MicroRNAs (miRNAs) are a class of endogenous,non-coding RNA of approximately 22 nucleotides in length,regulating gene expression at posttranscriptional level by complementary pairing with the target gene mRNA.Recent studies have showed that miRNAs play an important role in the formation of myocardial fibrosis,therefore,much attention has been paid to miRNAs as they may serve as targets for prevention and treatment of myocardial fibrosis.
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Objective In this paper,major issues for all those who have been selected in China national treatment program for patients with chronic Keshan disease (CNTP-CKD) were uncovered through evaluation of the annually reported data from participating provinces,in order to improve the performance quality of the program.Methods The datasets 2005-2012 were merged after cleaning them,and the composition of the treated patients was statistically analyzed,including gender and age distribution,diagnosis evidence for chronic Keshan disease (ECG,cardiothoracic ratio by X-ray,heart function grade of NYHA),and proportion of cases who had received treatment more than once.Results ①A total of 2 649 patients participated in the treatment,of them 1 115 patients were males accounting for 42.1％ (1 115/2 649),1 534 patients were females accounting for 57.9％ (1 534/2 649).Age of the patients were mainly distributed in 41 to 70 years old,and 24 CKD patients under 10 years accounting for 0.9％ (24/2 649).②2 313 cases of the involved patients were diagnosed with sufficient evidence,accounting for 81.9％ (2 313/2 823) and 121 cases with full misdiagnosis,accounting for 18.1％ (121/2 823).③There were 881 patients been treated for more than once,accounting for 38.3％ (881/2 301) of the number of treatment.Conclusions ① Diagnosis for CKD remains a key problem,suggesting that medical record for each patient diagnosed by province-level doctors' needs to be built up as early as possible.The rate of patient treatment for more than once is low which is not beneficial to the patients.② Treatment period for CKD patients is highly recommended to expand to at least one year,and the disease should be enrolled in the free cost list of the new rural cooperative medical system (NCMS).