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.

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.

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.

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.