Introduction: Lapatinib, a novel targeted anti-tumor drug in clinical use, demonstrates notable potential for liver cancer treatment. However, its mechanism of action in liver hepatocellular carcinoma (LIHC) remains poorly understood. This investigation sought to clarify the function of secreted phosphoprotein 1 (SPP1) in LIHC and investigate the anti-tumor effects of lapatinib on SPP1 expression. Methods: We analyzed data from normal liver and LIHC specimens obtained from The Cancer Genome Atlas (TCGA) and the GSE6764 dataset using R version 4.2.1. SPP1 protein expression in LIHC patients and its impact on patient prognosis were evaluated. Western blotting evaluated lapatinib-induced alterations in SPP1 protein levels in hepatoma cells. Cell Counting Kit-8 (CCK-8) assays measured lapatinib's impact on hepatoma cell growth and proliferation. Results and Discussion: SPP1 level was notably elevated in LIHC specimens versus normal liver tissues (P < 0.01). The survival outcomes were notably inferior in cases displaying elevated SPP1 levels versus those with reduced levels (P < 0.05). CCK-8 analyses demonstrated that a decrease in SPP1 expression leads to a significant inhibition of growth and proliferation in the LIHC cell line HepG2, while lapatinib can inhibit the survival of liver cancer cells. Western blotting analyses revealed that lapatinib treatment reduced SPP1 expression in HepG2 cells, increased the ratio of BAX/Bcl2, and triggered apoptosis in cells. Conclusion: These observations demonstrate that the expression of SPP1 is associated with disease progression and survival in patients with LIHC. Lapatinib exerts its anti-tumor effects in LIHC by downregulating SPP1 expression and promoting apoptosis in hepatoma cells.

Keshan disease (KD) is an endemic cardiomyopathy associated with selenium deficiency and distributed mainly along China’s low-selenium belt. Sporadic cases continue to occur in some historically endemic areas despite elimination efforts. The national-scale ecological spatial association between KD prevalence and serum selenium levels remains unclear. This study examined their spatial association in China to support targeted prevention and long-term surveillance. Using 2020 national surveillance data, we applied ordinary Kriging interpolation with an exponential model to map selenium distribution. Global and local bivariate spatial autocorrelation analyses were conducted in GeoDa to assess spatial associations between serum selenium and KD prevalence. Kriging identified a northeast-to-southwest belt of selenium deficiency overlapping KD-endemic areas. Global bivariate autocorrelation showed weak but statistically significant negative spatial associations between serum selenium and overall KD prevalence (Moran’s I = -0.047, P = 0.013) and latent Keshan disease (LKD) (Moran’s I = -0.063, P = 0.002), but not chronic Keshan disease (CKD). Given the small Moran’s I values, these results should be interpreted cautiously, as national-scale analysis may obscure local heterogeneity. Local analysis identified 67, 67, and 69 low–high clusters for KD, CKD, and LKD, respectively (203 in total across the three analyses). Serum selenium levels were weakly but significantly associated with KD prevalence spatial distribution in China. These findings indicate statistically detectable ecological spatial dependence, while no inference can be made regarding individual-level causality. The identified high–low clusters may be considered priority areas for targeted KD prevention and selenium monitoring.

The TKI-targeted agent lapatinib has been applied in clinical oncology for the management of multiple malignancies. Nonetheless, its therapeutic benefit is restricted by cardiotoxic effects that endanger patient survival, and the underlying molecular basis remains unclear. The GSE146096 dataset containing transcriptomic profiles of lapatinib-exposed human cardiomyocytes was analyzed to identify ferroptosis-related differentially expressed genes (DEGs). Protein expression of selected targets was subsequently confirmed by Western Blot. Reactive oxygen species (ROS) accumulation, Fe²⁺ levels, and mitochondrial membrane potential in AC16 cells exposed to lapatinib were examined using confocal microscopy. A microplate reader was employed to quantify alterations in malondialdehyde (MDA) and glutathione (GSH) levels in cardiomyocytes. Eight ferroptosis-associated genes were identified in lapatinib-treated cardiomyocytes, including the canonical regulator GPX4. siRNA interference and Western Blot analyses demonstrated marked induction of ATF4 expression and significant suppression of GPX4 expression following lapatinib exposure in AC16 cells. CCK-8 assays indicated dose-dependent cytotoxicity. Confocal microscopy and transmission electron microscopy (TEM) revealed altered mitochondrial morphology accompanied by a reduction in mitochondrial membrane potential. Intracellular MDA levels increased substantially, whereas GSH levels declined, indicating lipid peroxidation and subsequent ferroptosis. Treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1) or silencing of ATF4 expression effectively attenuated lapatinib-induced cytotoxicity. Lapatinib enhances ATF4 expression in cardiomyocytes, suppresses GPX4, triggers lipid peroxidation, induces ferroptosis, and thereby contributes to cardiotoxicity.

Fluoride has been identified as an important risk factor for cardiovascular disease, with endothelial cell dysfunction serving as a critical initiating event in its onset and progression. As cholesterol serves as an essential structural component of the endothelial cell membrane, alterations in cholesterol levels can significantly compromise endothelial function. However, the precise mechanisms underlying fluoride-induced cholesterol dysregulation in endothelial cells remain poorly understood. Through a well-established fluorosis mouse model, we observed that fluoride lead to significant detachment and pathological alterations of endothelial cells in mouse aorta. Transcriptomic profiling and enrichment analysis revealed that fluoride disrupted cholesterol biosynthesis pathway in HUVECs, particularly through downregulation of two key enzymes, HMGCR and CYP51A1. Subsequent validation experiments confirmed reductions in TC, HDL-C and LDL-C levels in mouse serum, accompanied by decreased expression of HMGCR and CYP51A1 in both mouse aortic endothelial cells and HUVECs. The reduction of cholesterol synthesis in fluoride induced endothelial injury was regulated by miR-200c-3p, a key regulator involved in fluorosis. To further substantiate the effect of fluoride on cholesterol levels, we conducted an epidemiological investigation and found a significant decrease in serum HDL-C levels and an elevated TG/HDL-C ratio in the population. In conclusion, this study demonstrated that fluoride exposure impaired endothelial cells by disrupting cholesterol synthesis, and fluoride induced dyslipidemia in populations may represent a potential mechanism underlying fluoride associated cardiovascular diseases, which may provide a new perspective on the mechanism of cardiovascular system injury caused by fluoride.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, influenced by both environmental and genetic factors. Single nucleotide polymorphism (SNP) in the human genome may influence the risk of developing COPD and the response to treatment. We assessed the effects of gene polymorphism of inflammatory and immune-active factors and gene-environment interaction on risk of COPD in middle-aged and older Chinese individuals. In this community-based case–control study, 471 patients with COPD and 485 controls aged 40–76 years in Heilongjiang Province, China were included. Face-to-face interviews, lung function tests, and multiplex polymerase chain reaction were used to obtain data. Logistic regression model, generalized multifactor dimensionality reduction and crossover analysis were used to analyse the effects of SNPs, gene–gene interactions, and gene-environment interactions on COPD. CRP gene[rs1130864-A allele (OR, 1.77; 95

While the TyG index has been studied in relation to stroke risk, there is a lack of research integrating fat distribution indicators like Body Roundness Index (BRI) and Fat Mass Index (FMI). Additionally, comparative studies across multiple regions are scarce. This study investigates the association between obesity-related parameters and stroke incidence, examining the mediation effects of multimorbidity, using data from rural areas in China and the United Kingdom. This cohort study included 60,685 participants (6,980 from China and 53,705 from UK). The obesity-related parameters were calculated using established formulas. The TyG index was determined as ln [TG (mg/dL) × GLU (mg/dL) / 2]. Additionally, composite indices were created by multiplying the TyG index by BMI, WC, FMI, and RBI to assess obesity-related risks. Cox regression analyses were employed on the relationship between Triglyceride Glucose index related parameters and stroke risk. Multiple mediation analysis was applied to assess the contributions of multimorbidity to obesity indicators in stroke occurrence. After excluding those who developed stroke within two years of enrollment, the Chinese cohort (6,638 subjects, median follow-up 4.33 years) had 237 ischemic and 21 hemorrhagic strokes. The UK cohort (53,631 subjects, median follow-up 13.85 years) had 742 ischemic and 316 hemorrhagic strokes. Chinese residents had lower BMI but higher visceral obesity (BRI), higher prevalence of multimorbidity, and higher stroke incidence compared to UK residents. Cox analyses demonstrated significant associations between BMI/TyG indices and ischemic stroke in both Chinese and UK populations, which diminished after adjusting for multimorbidity. In the Chinese rural cohort, only TyG-BRI (HR:1.13, 95

Objectives: Epidemiological evidence has shown that genetics and environment are associated with the risk of hypertension. However, the specific SNP effects of a cluster of crucial genes in the RAAS system on the risk of hypertension are unclear. Methods: A case-control study was performed on the baseline participants of Environment and Chronic Disease in Rural Areas of Heilongjiang China (ECDRAHC) study. According to the inclusion and exclusion criteria, 757 subjects (428 hypertensive patients) were enrolled. A total of 32 SNP sites and related haplotypes, involved in AGT (angiotensinogen), ACE (angiotensin-converting enzyme), AGTR1, CYP11B2 (aldosterone-synthase), LDLR (low-density lipoprotein receptor), LRP5 (low-density lipoprotein receptor associated protein 5), LRP6 (low-density lipoprotein receptor associated protein 6), PPARG (peroxisome proliferator-activated receptor gamma) and ACE2 (angiotensin-converting enzyme 2) genes which exert important roles in renin-angiotensin-aldosterone system (RAAS) system were analyzed. Furthermore, a polygenic scoring model was established to assess individual risk of developing hypertension based on the comprehensive SNPs effects in genes related the RAAS system. Results: After controlling the impact of confounding factors, multivariate logistic regression analysis revealed that the distribution of AGT/rs5046, LRP6/rs12823243 and ACE2/rs2285666 was associated with susceptibility to essential hypertension. In genetic score model, the score >- 0.225 had a higher risk, the OR ( 95%CI) was 1.229 (1.110, 1.362). Conclusions: To the best of our knowledge, this is the first time a hypertension risk scoring model on RAAS associated gene cluster has been constructed, which will provide a novel approach for prevention and control of essential hypertension.

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.

BackgroundHypertension is a major public health concern that strongly influences the quality of life of people worldwide. Keshan disease (KD) is an endemic cardiomyopathy related to low selenium, threatening residents in rural areas of 16 provinces in China. Furthermore, the prevalence of hypertension in the KD-endemic areas has been increasing annually. However, hypertension research associated with KD has only focused on endemic regions, and no studies have compared hypertension prevalence between endemic and non-endemic areas. Therefore, this study investigated the prevalence of hypertension to provide a basis for preventing and controlling hypertension in the KD-endemic areas, even in rural areas.MethodsWe extracted blood pressure information from cardiomyopathy investigation data from a cross-sectional study of the KD-endemic and non-endemic areas. The hypertension prevalence between the two groups was compared using the Chi-square test or Fisher s exact test. Additionally, Pearson’s correlation coefficient was employed to evaluate the relationship between the per capita gross domestic product (GDP) and hypertension prevalence.ResultsThere was a statistically significant increase of hypertension prevalence in the KD-endemic areas (22.79%, 95% confidence interval [CI]: 22.30–23.27%) over the non-endemic areas (21.55%, 95% CI: 21.09–22.02%). In the KD-endemic areas, more men had hypertension than women (23.90% vs. 21.65%, P < 0.001). Furthermore, the hypertension prevalence was higher in the north than in the south in the KD-endemic areas (27.52% vs. 18.76%, P < 0.001), non-endemic areas (24.86% vs. 18.66%, P < 0.001), and overall (26.17% vs. 18.68%, P < 0.001). Finally, the prevalence of hypertension positively correlated with per capita GDP at province level.ConclusionsThe increasing hypertension prevalence is a public health problem in the KD-endemic areas. Healthy diets, such as high consumption of vegetables and seafoods, and foods that are rich in selenium, might help prevent and control hypertension in the KD-endemic areas and other rural areas in China.

Purpose Environmental factors such as long-term exposure to cold can increase the risk of chronic diseases. However, few studies have focused on the impact of environmental factors and lifestyle changes on chronic diseases. To fully explore the association between exposure to environmental factors and the prevalent risk of various chronic diseases, we conducted a large cohort study (Environment and Chronic Disease in Rural Areas of Heilongjiang, China (ECDRAHC)). The ECDRAHC collected detailed questionnaire data covering 10 sections, physical measurements and blood and urine samples. In this study, we describe the design and implementation of the cohort study and present the findings for the first 10 000 participants. Participants The ECDRAHC study was carried out in rural areas where the annual average temperature is 2.9°C, and aimed to recruit 40 000 participants who are long-term residents aged 35–74 years. The participants will be followed up every 5 years. Currently, ECDRAHC has reached 26.7% (n=10 694) of the targeted population. Findings to date A total of 10 694 adults aged 35–74 years were recruited, including 61.7% women. The prevalence of current smokers was 46.8% in men and 35.4% in women. The mean blood pressure was 140.2/89.9 mm Hg and 135.7/85.0 mm Hg in men and women, respectively. The mean body mass index was 24.74 kg/m 2 in men and 24.65 kg/m 2 in women, with >7.3% being obese (>30 kg/m 2 ). The main non-communicable diseases found in phase 1 were hypertension, diabetes, hypertriglyceridaemia and metabolic syndrome, with a higher prevalence of 51.0%, 21.6%, 46.8% and 42.6%, respectively. Future plans We plan to complete the follow-up for the first phase of the ECDRAHC in 2024. The second and third phase of the cohort will be carried out steadily, as planned. This cohort will be used to investigate the relationship between environmental factors, lifestyle, and genetic and common chronic diseases.

BACKGROUND:Keshan disease (KD) is strongly associated with selenium deficiency. Selenoprotein P (SELENOP) is a recognized molecular biomarker of selenoproteins and an important indicator of selenium nutrition. This study was aimed at providing geographically precisely visualized evidence of selenium nutrition at molecular level for assessing KD prevention, control, and elimination on the etiological perspective.METHODS:We used spatial ecological design for this study. The serum SELENOP levels of the residents were measured by ELISA. ArcGIS version 9.0 was used for spatial description, spatial autocorrelation analysis of SELENOP levels and spatial regression with per capita disposable income.RESULTS:The mean serum SELENOP levels of the 6,382 residents in 1,688 counties were 4.62 ± 1.82 μg/mL. The mean serum SELENOP levels of the residents living in the townships and rural areas of KD endemic counties were not statistically significantly lower than those of the KD non-endemic counties. The mean serum SELENOP levels were globally clustered (Moran's I = 0.03, z = 6.37, and P < 0.0001), and 99.3% (553/557) of the cold spots, identified by local autocorrelation analysis (Getis-Ord-Gi* analysis), were located in the KD endemic provinces of Shaanxi, Shanxi, Henan, Hebei, Shandong, Inner Mongolia, Gansu, Hubei, Chongqing, Yunnan, and Sichuan. The serum SELENOP level was positively correlated with per capita disposable income (t = 3.52, P = 0.0004).CONCLUSIONS:The results of this study were the geographically precisely visualized evidence of selenium nutrition at molecular level for assessing KD elimination on the etiological perspective. The cold spot counties found by Getis-Ord-Gi* analysis in the KD endemic provinces should be the high priority of KD precision prevention and control.

Purpose: To investigate the environmental, immune, and inflammatory factors associated with chronic obstructive pulmonary disease (COPD) in middle-aged and older Chinese individuals.Patients and Methods: A community-based case-control study was conducted among 471 patients with COPD and 485 controls. The information on COPD of the participants was collected through face-to-face interviews, and serum samples were measured at the laboratory. The main risk factors for COPD were analyzed using principal component analysis (PCA) and logistic regression.Results: Nine hundred and fifty-six respondents were included in the analysis. The results of the PCA-logistic regression analysis showed significant differences in the environmental factors, medical history, and serum C-reactive protein (CRP) levels between patients and controls. COPD was markedly more usual in those with smoking index >200 (OR, 1.42; 95% CI, 1.28-1.57); exposure to outdoor straw burning (OR, 1.64; 95% CI, 1.47-1.83); use of coal, wood, and straw indoors (OR, 2.31; 95% CI, 1.92-2.78); history of respiratory disease and coronary heart disease (OR, 3.58; 95% CI, 3.12-4.10), congestive heart failure (OR, 1.23; 95% CI, 1.09-1.38), and cerebrovascular disease (OR, 1.15; 95% CI,1.02-1.31); and higher serum level of CRP (OR, 1.20; 95% CI, 1.11-1.30). Compared to the logistic regression analysis, PCA logistic regression analysis identified more important risk factors for COPD.Conclusion: PCA-logistic regression analysis was first utilized to explore the influencing factors among rural residents in Northeast China Environmental aged 40 years and above, it was found that environmental factors, medical history, and serum CRP levels mainly affected the prevalence of COPD.

BackgroundNo spatial analysis of hair selenium and Keshan disease (KD) on a nationwide county-level has been performed. Selenium deficiency is a recognized environmental risk factor for KD. Hair selenium is one of the recognized biomarkers of selenium nutrition. This study aimed to perform a geographically precise and visualized assessment of the achievement of KD prevention and control at the level of selenium nutrition in terms of etiology.MethodsA spatial ecological study was conducted. The hair selenium content of the residents was assayed using an atomic fluorescence spectrometer. The spatial analysis was performed using ArcGIS.ResultsThe median of the hair selenium levels of the 3,028 participants in the 1,174 counties was 0.38 mg/kg, and the content of inhabitants in KD endemic counties was significantly lower than that in KD non-endemic counties (0.34 vs. 0.39 mg/kg, z = −10.03, P < 0.0001). The proportion of Se-deficient and Se-marginal counties in KD endemic counties was significantly higher than that in KD non-endemic counties (59.4 vs. 29.0%, z = −7.45, P < 0.0001). The global autocorrelation analysis was not statistically significant (Moran's I = 0.0005, P = 0.68). Local autocorrelation analysis identified 174 low-low clusters of hair selenium levels, 83 (47.7%) of which are KD endemic counties located in KD endemic provinces of Henan, Gansu, Shaanxi, Inner Mongolia, Jilin, and Heilongjiang. The hair selenium featured a positive correlation with per capita GDP (rs = 0.20, P < 0.0001).ConclusionThe median of the hair selenium levels of inhabitants living in KD endemic counties was significantly lower than that in KD non-endemic counties. All the 83 KD endemic counties with low-low clusters of hair selenium levels should be prioritized in KD precision prevention and control. These findings are geographically precise and visualized evidence of the assessment of the effectiveness of KD prevention and control at the level of selenium nutrition in terms of etiology.

Few nationwide investigations on hair selenium (Se) and Keshan disease (KD) have been conducted. KD is closely associated with Se deficiency. Hair Se is an important biomarker for selenium nutrition. This research aimed to provide evidence for assessment of KD prevention, control, and elimination at the molecular level from the etiological perspective of selenium nutrition. The hair Se of the residents living in the KD endemic and non-endemic areas were determined through atomic fluorescence spectrometer. The median of the hair Se levels of the inhabitants living in KD endemic counties was significantly lower than that in KD non-endemic counties (0.34 vs 0.39 mg/kg, U = −10.03, P < 0.0001). The proportion of Se-deficient or Se-marginal residents in KD endemic counties was significantly higher than that in KD non-endemic counties (56.9% vs 36.6%, U = −9.57, P < 0.0001). The medians of the hair Se levels in KD endemic provinces of Shannxi, Heilongjiang, and Gansu were the lowest (0.35mg/kg), and in the category of Se-marginal status. The hair Se level featured a positive Spearman correlation with per capita disposable income (rs = 0.20, P < 0.0001). In conclusion, the median of the hair Se contents of residents living in KD endemic counties was significantly lower than that in KD non-endemic counties. The hair Se contents of nearly 57% of inhabitants living in KD endemic regions were in Se-deficient or Se-marginal status. The KD endemic provinces of Shannxi, Heilongjiang, and Gansu should be given high priority in KD prevention and control.

Purpose: The prevalence of Keshan disease (KD) is low and has reached controlled or eliminated levels even in counties that had a high KD prevalence in the past. Few nationwide surveys on selenium levels in KD areas have been conducted in the past 2 decades. We conducted a cross-sectional study to investigate the selenium levels and their association with KD control and prevention in areas where KD is prevalent. Methods: We collected 2143 human-hair, 698 soil, 701 rice, 607 flour, 521 corn, and 330 other-food samples from 49 counties with KD and 19 non-KD counties of nine KD provinces of China. The selenium content of samples was examined with hydride generation atomic fluorescence spectrometry. The difference in selenium levels between the KD and non-KD areas was analyzed. Cochran-Armitage trend tests were used to evaluate the association between selenium levels and KD control. Results: The selenium levels in human hair, soil, staple foods, and other foods in the KD areas (0.2996 mg/kg, 0.1380 mg/kg, 0.0190 mg/kg and 0.0076 mg/kg, respectively) were lower than those in the non-KD areas (0.3700 mg/kg, 0.1930 mg/kg, 0.0240 mg/kg and 0.0165 mg/kg, respectively). The Cochran-Armitage tests showed that there was a trend for the selenium standard ratio in the counties to increase in the order of KD uncontrolled, to controlled, to eliminated (Z = 2.229, P < 0.05). Conclusion: The residents in the KD areas were found to be selenium-deficient. Improving the supply of staple foods containing selenium levels exceeding 0.025 mg/kg and abundant foodstuffs might contribute to KD control and prevention.

Objective: To clarify the urinary arsenic metabolism characteristics in individuals with essential hypertension and to analyze the relationship between lipid metabolism gene polymorphisms and susceptibility to essential hypertension in individuals in high-arsenic areas in western China. Methods: A case-control study was conducted and involved individuals exposed to high arsenic levels (in this study, the arsenic content in the pressurized well water was 0-510.2 mu g/L, and that in the mechanical well water was 167 mu g/L) in two adjacent high-arsenic areas in Shanxi Province and the Inner Mongolia Autonomous Region, China. A total of 699 samples were collected, including 192 case samples (patients with hypertension) and 507 control samples (no hypertension). Blood pressure measurement data obtained from an epidemiological survey were used to determine whether the subjects had hypertension, and a logistic regression model was used to analyze the association between lipid metabolism gene polymorphisms and hypertension susceptibility. Blood and urine samples were collected based on epidemiological methods, single nucleotide polymorphisms (SNPs) were genotyped using a SNPscanTM multiple SNP typing kit, and urinary arsenic concentrations were determined using the hydride generation atomic fluorescence method (HG-AFS). Results: ADIPOQ/rs266729 was the dominant genetic model [(GC + GG) vs CC = 0.686:1, 95 % CI = 0.478-0.983], and FABP2/rs1799883 was the recessive genetic model [TT vs (CC + TC) = 1.690:1, 95 % CI = 1.014-2.816]. The distribution of the urinary arsenic secondary methylation ratio (SMR) [dimethylated arsenic (DMA)/monomethylated arsenic (MMA)] was different between hypertensive patients and controls. Conclusion: ADIPOQ/rs266729 and FABP2/rs1799883 polymorphisms affect susceptibility to essential hypertension in individuals exposed to high levels of arsenic; there was a clear difference in the urinary arsenic metabolism pattern between hypertensive patients and controls.

Objective:To master the new cases and the condition of Keshan disease (KD) in key endemic areas and provide scientific basis for updating control strategies.Methods:In 2017, sentinel surveillance was carried out in some counties with substandard KD or serious historical KD. Two to three villages with more KD patients and the total population of 1 000 were chosen to investigate. All of the inhabitants were checked by physical examination and electrocardiography. Suspected KD patients were examined by echocardiography. KD was identified according to "Diagnosis of Keshan Disease" (WS/T 210-2011). The confirmed cases were followed up.Results:A total of 70 008 people were examined in 86 counties of 14 provinces. The ratio of male to female was 1.0 ∶ 1.2 (31 720/38 288). The total number of KD patients identified was 308, including 68 chronic KD and 240 latent KD. The detection rates were 44/10 000, 10/10 000 and 34/10 000, respectively. Totally 198 cases of chronic KD and 115 cases of latent KD were followed up, and the follow-up mortality was 8.1% (16/198) and 7.0% (8/115), respectively. In this year, 29 cases of latent KD and 5 cases of chronic KD were newly diagnosed.Conclusion:There are still a number of KD patients including new cases in endemic areas with high prevalence nowadays or in the past indicating the prevention and control of KD should be maintained.

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.

The exposure/biotransformation of inorganic arsenic (iAs) may perturb DNA methylation patterns and subsequently influence disease risk by altering the expression of key genes. Interindividual variation in patterns of DNA methylation can be explained by the influence of environmental, genetic, and stochastic factors. Here, we examined promoter DNA methylation levels with urinary arsenical concentrations and investigated the genetic and nongenetic determinants of DNA methylation in 105 samples collected from populations in Shanxi Province, China, with high levels of arsenic in drinking water. Arsenic concentrations in water were determined by atomic absorption spectrophotometry (AA-6800, Shimadzu Co., Kyoto, Japan). Urine samples were measured using an atomic absorption spectrophotometer with an arsenic speciation pretreatment system (ASA-2sp, Shimadzu Co. Kyoto, Japan) for detection. Gene-specific (CDH1, EREG, ERCC2, GSTP1, and MGMT) DNA methylation was quantified by targeted bisulfite sequencing. Single-nucleotide polymorphism (SNP) genotyping was performed using a custom-by-design 2 × 48-Plex SNPscan™ Kit. These results revealed CDH1 with promoter DNA methylation levels associated with iAs. After the exclusion of confounding factors, age was correlated with increased methylation of the CDH1 gene. The susceptibility of the CDH1 and GSTP1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs2424932) GA genotype, and the susceptibility of the CDH1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs6087990) TC genotype. Although the above results must still be replicated in larger samples, the findings improve our understanding of the pathogenesis of arsenic and may highlight certain DNA methylation markers as attractive surrogate markers for prevention research.