Adult ; Cardiomyopathies ; epidemiology ; prevention & control ; Cardiomyopathy, Dilated ; epidemiology ; prevention & control ; Child ; China ; epidemiology ; Enterovirus Infections ; epidemiology ; prevention & control ; Environmental Monitoring ; Humans ; Male

Objective To observe the dilated cardiomyopathy ( DCM ) in non-Keshan disease areas in Shandong Province and assess scientifically the effectiveness of prevention and control measures on Keshan disease (KSD). Methods According to the scheme of DCM condition survey of our country in non-Keshan disease areas, seven representative counties(cities, areas) were chosen by their similarities in natural environment, production and life style to KSD areas; one or two townships ( towns ) were chosen in each county ( city , area ); one village was selected as a survey point in each township ( town ) . In each survey point , about four hundred and twenty natural populations were checked by asking detailed history, physical examination, and electrocardiography (ECG) tracings, and suspicious people were taken chest X-ray examination and cardiac ultrasound(UCG). The samples of inside and outside environmental were collected in partial residents and the selenium contents were detected by 2,3-diaminonaphthalene fluorometric method. At the same time the income, food of inhabitant and other basic information were collected. Results ① In 13 survey villages, sixty-four hundred and sixty-three residents were surveyed and 2 DCM cases and 111 similar potential KSD cases were detected, the detection rate was 1.75%(113/6 463). ② Sixty-four hundred and sixty-three residents were traced by ECG and the incidence of abnormal ECG was 20.4%(1 318/6 463), and sinus bradycardia, T-wave changes, sinus tachycardia, ST-T changes, occasional ventricular beating earlier, complete right bundle branch block, left anterior branch block, room premature beat, left ventricular high voltage, auriculo-ventricular block, et al were common. ③Samples of hair(260), wheat(260), corn (240) and soil (104) were collected, and the selenium contents were (0.353 ± 0.082), (0.035 ± 0.009), (0.024 ± 0.008) and (0.164 ± 0.019)mg/kg, respectively. Annual per capita income of each survey point was 2 500-8 670 yuan, and the residents’ main staple food was flour. Conclusion The results of DCM condition in non-Keshan disease areas of Shandong Province are stable and have provided a scientific basis for drawing up the national standard of eliminating KSD.

Objective To investigate the characteristics of chronic Keshan disease (CKD) and ischemic cardiomyopathy ( ICM ) and provide a basis for differential diagnosis . Methods Forty-two cases of CKD were randomly sampled from 6 Keshan disease districts in Sishui, Zoucheng, Juxian, Wulian, Yishui and Qingzhou Counties of Shandong Province, as CKD group. Thirty-one cases of ICM were selected from Qianfushan Hospital as ICM group. Echocardiography was used to analyze the cardiac morphology , hemodynamic and function. Results Left atrial internal diameter(LA), left ventricular(LV), end-diastolic internal diameter(LVd), right ventricular diameter(RV) and right atrial transverse diameter(RAtd) of the CKD group[(45.14 ± 6.93),(68.48 ± 6.24),(28.90 ± 3.14),(52.79 ± 6.62)mm] were higher than those of ICM group[(40.68 ± 5.12),(60.55 ± 4.07),(24.35 ± 2.12), (47.68 ± 8.53)mm , t = 3.03, 6.55, 7.38, 2.88, all P < 0.01]. In CKD group, several atrioventricular carities were enlarged, and the ventricular wall tended to become thin. In ICM group, left atrioventricular cavities were enlarged, and the apex of LV was thin spherical. The LV ejection fraction(LVEF) and fractional shortening of LV (LVFS) of the CKD group [(40.50 ± 10.68)%, (22.81 ± 6.24)%] were lower than those of the ICM group [(54.61 ± 6.58)%, (30.71 ± 4.29)%, t = - 6.957, - 5.976, all P < 0.01]. Diffuse hypokinetic motion of LV reduced in 85.7%(36/42) of CKD patients, and 83.9%(26/31) of ICM patients had segmental LV dyskinesia. Slight regurgitation of single valve was common in ICM group , but several regurgitation of multiple valves were more common in CKD group. Conclusion Echocardiography is a valuable noninvasive technology for differentiating CKD and ICM.

Objective To explore health-related quality of life (HRQOL) in patients with chronic Keshan disease in China and the influence factors.Methods According to the Diagnosis of Keshan Disease (WS/T 210-2011),146 patients with chronic Keshan disease were selected from the follow-up chronic Keshan disease patients with standard treatment in Shandong.The HRQOL was assessed in those patients by use of the Chinese version of SF-36.Correlation analysis and multiple linear regression were used to analyse the influence factors of HRQOL.Results All dimension scores were significantly lower than those of general population (t =-5.12--13.13,all P ＜ 0.01).There were significant differences in Role-Physical dimensions (RP,F =47.09,P ＜ 0.01) and Physiological Function dimension (PF,F =31.49,P ＜ 0.01) between patient groups with different severity of left ventricular ejectio,n fraction (LVEF),RP dimension (F =8.47,P ＜ 0.01) and Vitality dimension (VT,F =11.29,P ＜ 0.01) in patients varies with left ventricular end-diastolic dimension (LVEDD).The scores of some dimensions were correlated with age,family income,course of disease,LVEF and LVEDD,heart function grading,labor ability (r =-0.49-0.36,P ＜ 0.05 or ＜ 0.01).The multivariate linear regression analysis indicated that the influencing factors of physiological status were NYHA cardiac function classification,course of disease,family income and body mass index (BMI).The influencing factor of mental health states was NYHA cardiac function classification.The influencing factors of the total HRQOL score were NYHA cardiac function classification,course of disease and family income.Conclusions The HRQOL of patients with chronic Keshan disease is significantly declined as compared with the general population and the lowest is RP.NYHA functional class,course of disease and family income are relative dominant predictor of patients HRQOL among all variables.

Objective:To explore the predictors of recovery of normal left ventricular ejection fraction (LVEF) in patients with chronic Keshan disease (CKD) after standard anti-heart failure treatment.Methods:From June 2013 to October 2017, CKD patients were selected as the research subjects in 8 Keshan disease counties (cities) in Shandong Province. Demographic data and clinical indicators related to the recovery of normal LVEF were collected at the initial diagnosis, and the patients were given standard anti-heart failure treatment. Follow-up was carried out until October 2019 or until all-cause death. Patients were divided into recovery group and non-recovery group according to whether LVEF returned to normal (LVEF≥50% was normal) by group design, and multi-factor logistic regression was used to analyze the predictors of recovery of normal LVEF.Results:A total of 98 CKD patients were included in this study, their average age was (47.51 ± 12.84) years old; body mass index (BMI) was (23.18 ± 4.92) kg/m 2; LVEF was (39.54 ± 8.26)%; male accounted for 65.31% (64/98); the New York Heart Association (NYHA) heart function grade Ⅱ and grade Ⅲ accounted for 46.94% (46/98) and 53.06% (52/98), respectively. The median follow-up time was 26 months, the LVEF of 28 patients (28.57%) returned to normal, and the LVEF increased from (43.27 ± 7.85)% of the baseline to (58.74 ± 6.07)%, the difference was statistically significant ( t=8.25, P < 0.01); LVEF did not return to normal in 70 patients (71.43%), and the LVEF increased from (37.84 ± 6.93)% of the baseline to (42.94 ± 7.31)%, the difference was statistically significant ( t=4.24, P < 0.01). The median recovery time of 28 patients with normal LVEF recovery was 14 months, of which 4 patients (14.29%), 6 patients (21.43%) and 15 patients (53.57%) recovered at follow-up of 6, 12 and 18 months, respectively, and 27 patients (96.43%) recovered within 3 years. The results of multivariate logistic regression analysis showed that disease course [odds ratio ( OR)=0.81, 95% confidence interval ( CI): 0.70-0.95, P < 0.05], electrocardiogram QRS wave duration ( OR=0.88, 95% CI: 0.79-0.98, P < 0.05), LVEF ( OR=1.26, 95% CI: 1.13-1.42, P < 0.01), and left ventricular end-diastolic diameter (LVEDD, OR=0.79, 95% CI: 0.66-0.90, P < 0.01) were independent predictors of recovery of normal LVEF. Conclusions:LVEF can return to normal after anti-heart failure treatment in some CKD patients. Patients with shorter disease course, shorter electrocardiogram QRS wave duration, higher baseline LVEF and lower LVEDD are more likely to recover from LVEF.

Objective By constructing the differential expression profile of lncRNA/mRNA in peripheral blood plasma of patients with Keshan disease (KSD) and dilated cardiomyopathy (DCM),to explore the commonality and characteristics of the two diseases in molecular mechanism.Methods Ten patients with chronic KSD were selected in the severe disease area of KSD in Shandong Province,and 10 cases of DCM and 10 healthy subjects (control group) were selected in non-KSD area.Blood of elbow vein was collected and plasma was separated.RNA-seq technology was used to construct the differential lncRNA/mRNA expression profile between KSD and control group,DCM and control group,and co-expression and specific expression of partial genes in KSD and DCM were analyzed through Wien analysis.The lncRNA-mRNA co-expression network maps of specific part of KSD,specific part of DCM and common part of the two diseases were constructed,and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to distinguish the biological function of the two diseases.Results Compared with control group,102 dysregulated mRNAs and 22 dysregulated lncRNAs showed the same trend in KSD and DCM.And 3 606 mRNAs and 451 lncRNAs were only differentially expressed in KSD group,217 mRNAs and 137 lncRNAs were only differentially expressed in DCM group.The differentially expressed lncRNA/mRNA shared between the KSD and DCM groups were mainly about viral transcription,immuno-inflammatory response,oxidative stress signaling pathways.The KSD specific lncRNA/mRNA mainly participated in cell membrane damage and viral myocarditis.The DCM specific lncRNA/mRNA mainly regulated mitochondrial structure and oxidative phosphorylation related enzymes.Conclusion The differentially expressed lncRNA/mRNA shared in KSD and DCM groups are mainly involved in viral transcription,oxidative stress signaling pathways;KSD specific lncRNA/mRNA are mainly related to cell membrane damage and viral myocarditis;DCM specific lncRNA/mRNA mainly regulate mitochondrial structure.

Objective The echocardiography of patients with chronic Keshan disease (CKD) in the plateau and plain areas was compared,to analyze the specific manifestations of echocardiography in patients with high altitude CKD,to provide a reference for imaging diagnosis.Methods From October 2014 to December 2016,34 patients with CKD were selected in the Tibet Autonomous Region [18 males,16 females,aged (44.5 ± 5.6) years old] as plateau group;45 patients with CKD were selected in Shandong Province [21 males,24 females,age (47.3 ± 6.9) years old] as a plain group.Echocardiography was performed on the observed subjects,and cardiac morphology,hemodynamics and cardiac function were analyzed.Results The left atrial diameter (LAD),left ventricular end diastolic diameter (LVEDD),and left ventricular mass (LVM) of the plateau group were (39.2 ± 4.8),(56.5 ± 6.3) mm and (232.4 ± 40.2) g,respectively,which were lower than those of the plain group [(48.3 ± 5.7),(65.2 ± 7.8) mm,(283.7 ± 38.3) g,t =-7.52,-5.30,-5.74,P ＜ 0.01].The right atrial transverse diameter (RATD),right ventricular transverse diameter (RVTD) and right ventricular lateral wall thickness (RVWT) of the plateau group were (47.6 ± 8.5),(50.4 ± 7.3) and (4.8 ± 1.1) mm,respectively,which were higher than those of the plain group [(42.3 ± 7.2),(42.7 ± 6.8),(3.3 ± 0.7) mm,t =2.99,4.81,7.36,P ＜ 0.01].The early diastolic filling velocity (E),the early diastolic peak velocity of the mitral annular (Em) of the plateau group were lower than those of the plain group,E/Em of the plateau group was higher than that of the plain group (t =-2.64,-2.35,2.07,P ＜ 0.05).The fractional area change (FAC) of right ventricular,tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity (S') of the plateau group [(24.9 ± 2.8)％,(13.2 ± 1.2) mm,(6.8 ± 1.0) cm/s] were lower than those of the plain group [(26.3 ± 3.2)％,(14.5 ± 1.3) rmm,(7.5 ± 1.2) cm/s,t =-2.02,-4.53,-2.74,P ＜ 0.05 or ＜ 0.01].The tricuspid annular diastolic velocity (e') of the plateau group was lower than that of the plain group,and tricuspid annular blood flow early diastolic filling velocity maximum (e)/e'was higher than that of the plain group (t =-2.07,2.09,P ＜ 0.05).The systolic pulmonary artery pressure (SPAP) of the plateau group [(48.5 ± 12.3) mmHg,1 mmHg =0.133 kPa] was higher than that of the plain group [(41.6 ± 13.3) mmHg,t =2.34,P ＜ 0.05].Conclusion Compared with CKD patients in plain area,CKD patients in plateau area have showed more obvious right heart enlargement and right ventricular failure,and combined with higher SPAP.

Objective:Through differential miRNA expression profiles and bioinformatics in the peripheral blood of patients with Keshan disease (KD) and healthy control, to explore the possible pathogenesis of KD.Methods:Ten patients with chronic KD (KD group) were selected in the severe disease area of KD in Wulian County, and 10 healthy subjects (control group) were selected in non-KD area of Dongchangfu District, Shandong Province. Blood sample of elbow vein was collected and plasma was separated. RNA-seq technology was used to construct the differential expression profiles of miRNA in KD and control groups. Target mRNAs were screened using Starbase, miRTarBase, miRDB and TargetScan. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to investigate the possible pathogenesis of KD.Results:Compared the control group and KD group, 132 differentially expressed miRNAs were screened out, including 90 upregulated and 42 downregulated miRNAs. Through Starbase, miRTarBase, miRDB and TargetScan, 53 miRNAs were obtained, 737 targeted mRNAs were obtained. GO analysis showed that the differential genes were mainly involved in the biological processes of Ras protein signal transduction, transmembrane transport, cell cycle regulation, cell adhesion, etc. KEGG pathway analysis showed that the differential genes were mainly involved in viral infection, endocytosis, adhesion spot and actin regulation.Conclusion:In this study, RNA-seq technology is used to obtain differential miRNA expression profiles of KD patients and healthy control, and target pathogenic genes and signaling pathways that may be related to KD are screened out.

Objective:To investigate the spatial distribution characteristics of Keshan disease in Shandong Province, and to provide evidence for prevention and control of Keshan disease.Methods:The incidence data of Keshan disease in Shandong Province from 1960 to 2018 were collected from Shandong Provincial Institute for Endemic Disease Control and Prevention, and a spatial database was built. Global and local spatial autocorrelation (Moran's I) were analyzed by ArcGIS 10.2 and GeoDa 1.14 softwares, respectively. Local indicators on spatial association (LISA) aggregation graph was drawn. This allowed us to investigate the spatial autocorrelation and cluster range of the distribution of Keshan disease in Shandong Province. Results:A total of 4 172 cases of Keshan disease were reported in Shandong Province with an annual incidence rate of 0 to 51.4/10 000 of the population at the township-level from 1960 to 2018. Global spatial autocorrelation analysis on the incidence of Keshan disease at the township-level showed that global Moran's I values ranged from 0.020 to 0.429 in 1962 - 1964, 1969 - 1985, 1989, 1995, 1998 - 2001 and 2004 - 2016 ( P < 0.05), thus indicating significant spatial autocorrelation overall. LISA analysis further revealed that high-high clusters of Keshan disease existed in 1960, 1962 - 1964, 1969 - 1985, 1989, 1998 - 2000 and 2002 - 2016. These clusters were predominantly distributed in three areas: Zoucheng City, Pingyi County and Sishui County in the southwest of Shandong Province; Wulian County and Ju County in the southeast of Shandong Province; and Qingzhou City, Linqu County and Yishui County in the central and middle-south of Shandong Province. Conclusions:Keshan disease exhibits significant spatial autocorrelation in Shandong Province. High-high clusters are mainly located in certain townships in the southwest, southeast, central and middle-south of Shandong Province.

Objective To analyze the difference of echocardiography in patients with chronic Keshan disease (CKD) at different altitudes areas,explore the effects of altitude on the structure and functional of right heart in CKD patients,and provide a reference for imaging diagnosis of CKD.Methods According to the three step distribution of the terrain in China,30 cases of CKD patients in the first step (altitude ＞ 4 000 m) of Tibet autonomous region were randomly selected as the Tibetan plateau group.In the second step (altitude:1 000-2 000 m),31 cases were randomly selected in Gansu Province as the Loess plateau group.In the third step (altitude ＜ 500 m),42 cases were randomly selected in Shandong Province as the plain group.Echocardiography was used to analyze the morphology,hemodynamics and function of right heart.Results Right atrial transverse diameter (RATD),right ventricular transverse diameter (RVTD),right ventricular lateral wall thickness (RVWT) and main pulmonary artery diameter (MPAD) of the Tibetan plateau group,the Loess plateau group and the plain group (mm:49.75 ± 8.40,45.64 ± 7.63,43.56 ± 7.34;50.89 ± 7.13,46.56 ± 5.62,43.27 ± 6.01;4.75 ± 1.02,3.53 ± 0.61,3.37 ± 0.51;32.87 ± 3.62,28.93 ± 2.12,28.44 ± 2.71) were significant differences among the three groups (F =5.36,12.91,37.08,23.33,P ＜ 0.01).The above indexes of the Tibetan plateau group were higher than those of the Loess plateau group and the plain group (P ＜ 0.05).RVTD of Loess plateau group was higher than that of plain group (P ＜ 0.05).The fractional area change [FAC,(24.85 ± 2.75)％,(26.26 ± 3.42)％,(26.73 ± 3.14)％],tricuspid annular plane systolic excursion [TAPSE,(12.87 ± 1.12),(14.59 ± 1.63),(14.13 ± 1.31) mm] of the Tibetan plateau group,the Loess plateau group and the plain group were significant differences among the three groups (F =3.36,13.47,P ＜ 0.05 or ＜ 0.01);the above indexes of the Tibetan plateau group were lower than those of the Loess plateau group and the plain group (P ＜ 0.05).Tei index (0.87 ± 0.18,0.78 ± 0.16,0.71 ± 0.14),tricuspid flap diastolic maximum filling speed/tricuspid annulus early diastolic peak velocity (E/E',9.48 ± 1.22,8.64 ± 0.91,8.12 ± 1.13),systolic pulmonary artery pressure [SPAP,(49.58 ± 11.76),(44.35 ± 11.41),(42.67 ± 12.13) mmHg,1 mmHg =0.133 kPa] of the Tibetan plateau group,the Loess plateau group and the plain group were significant differences among the three groups (F =12.89,13.99,3.12,P ＜ 0.01 or ＜ 0.05);the Tei index and E/E'of the Tibetan plateau group were higher than those of the Loess plateau group and the plain group (P ＜ 0.05).Tei index,E/E'of the Loess plateau group were higher than those of the plain group (P ＜ 0.05).Conclusions The right heart structure and function of CKD patients are affected by the altitude of their residence.With the increase of altitude,the right heart is enlarged,the right ventricular systolic and diastolic functions are decreased,and SPAP is increased in CKD patients.