Dietary Quality and Relationships with Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) among United States Adults, Results from NHANES 2017-2018.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new definition for the evidence of hepatic steatosis and metabolic dysfunctions. The specific role of the dietary factors in the development and progress of the disease are not well illuminated. Thus, we conducted this study on the associations between dietary quality assessed by five dietary quality indexes (Dietary Inflammatory Index, DII; Mediterranean diet, MED; Dietary Approach to Stop Hypertension, DASH; Alternate Healthy Eating Index diet, AHEI; Healthy Eating Indices, HEI) and MAFLD phenotypes. This study was extracted from the latest NHANES 2017-2018 wave. Demographic information, health status, lifestyles, and dietary habits were reported in the questionnaire. Multivariate logistic regression and multivariate ordinal logistic regression methods were applied to explore the associations between dietary quality indexes and MAFLD or MAFLD with liver fibrosis. The weighted prevalence of Non-MAFLD, MAFLD without fibrosis, and MAFLD with fibrosis were 47.05%, 36.67%, and 16.28%, respectively, at the cutoff value of a median Controlled Attenuation Parameter (CAP) 248 dB/m and a median Liver Stiffness Measurement (LSM) 6.3 kPa. When the diagnostic cutoff values of CAP changed to 285 dB/m, the weighted prevalence of Non-MAFLD, MAFLD without liver fibrosis, and MAFLD with fibrosis turned to 64.62%, 22.08%, and 13.30%, respectively. All five dietary quality indexes, including DII, HEI-2015, AHEI, DASH, and MED, were all significantly associated with MAFLD phenotypes. DII was positively associated with MAFLD phenotypes, while other four dietary quality indexes, including HEI-2015, AHEI, DASH, and MED, were significantly associated with lower risk of MAFLD phenotypes. MAFLD is becoming a threatening public health concern among adult Americans and dietary quality is markedly associated with MAFLD phenotypes.

The effect of ambient temperature on in-hospital mortality: a study in Nanjing, China.

To reduce the inpatient mortality and improve the quality of hospital management, we explore the relationship between temperatures and in-hospital mortality in a large sample across 10 years in Nanjing, Jiangsu. We collected 10 years' data on patient deaths from a large research hospital. Distributed lag non-linear model (DLNM) was used to find the association between daily mean temperatures and in-hospital mortality. A total of 6160 in-hospital deaths were documented. Overall, peak RR appeared at 8 °C, with the range of 1 to 20 °C having a significantly high mortality risk. In the elderly (age ≥ 65 years), peak RR appeared at 5 °C, with range - 3 to 21 °C having a significantly high mortality risk. In males, peak RR appeared at 8 °C, with the range 0 to 24 °C having a significantly high mortality risk. Moderate cold (define as 2.5th percentile of daily mean temperatures to the MT), not extreme temperatures (≤ 2.5th percentile or ≥ 97.5th percentile of daily mean temperatures), increased the risk of death in hospital patients, especially in elderly and male in-hospital patients.

Associations between Serum Vitamin A and Metabolic Risk Factors among Eastern Chinese Children and Adolescents.

Vitamin A, a fat-soluble essential vitamin, is implicated in a large range of physiological processes. Up to now, the associations between vitamin A and metabolic syndrome (MetS) or other metabolic risk factors are controversial in children and adolescents. Thus, we aimed to dig into the relationship of vitamin A with MetS and many other metabolic risk factors. This was a cross-sectional study derived from the China National Nutrition and Health Surveillance of Children and Lactating Mothers. A total of 3025 school-aged (7-17 years) children and adolescents were selected by applying multistage stratified cluster random sampling methods in the Jiangsu Province of eastern China. Through enquiry survey, anthropometric measurement and laboratory examination, relevant information and blood biochemical indexes of the participants were collected in this study. MetS was identified according to the modified criteria of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Multivariate logistic analysis and the generalized additive model (GAM) were used to analyze the relationship between vitamin A and various metabolic risk factors. The overweight, obesity and MetS prevalence of children and adolescents in this study was 14.0%, 11.9% and 5.1%, respectively. The risk of prevalent MetS, general obesity, high low-density lipoprotein (LDL), high total cholesterol (TC) and hyperuricemia increased with vitamin A in a dose-dependent way. Logistic regression analysis showed that serum vitamin A Z scores were positively associated with MetS and central obesity, elevated blood pressure (BP) and elevated triglyceride (TG). Sex stratification analysis showed that both in male and female participants, the risk of prevalent MetS, general obesity, high LDL, high TC and hyperuricemia still increased with vitamin A levels. MetS was at a high prevalence level in children and adolescents in Jiangsu that were 7-17 years old. Vitamin A was positively associated with obesity, MetS, dyslipidemia and hyperuricemia. More public health measures and new visions should focus on the effects of retinol on children and adolescents.

Multilevel Analysis of the Nutritional and Health Status among Children and Adolescents in Eastern China.

We aimed to identify multiple nutritional health problems and the relevant factors among children and adolescents aged 7-17 years. This study was part of the China Nutrition and Health Surveillance of Children and Lactating Mothers in 2016-2017, conducted in Jiangsu Province in eastern China. After sampling, 3025 school-age children and adolescents were enrolled into this study. Demographic information collections and anthropometric measurements were conducted by trained local Center for Disease Control and Prevention (CDC) staff. Venous blood in the amount of 6 mL was drawn from each participant in the morning and used for testing biochemical and nutritional indicators. Multivariate logistic regression analysis and Poisson regression analysis were used for overnutrition- and undernutrition-related disorders to test relevant personal, parental, and household factors. The prevalence of wasting, overweight, and obesity was 5.5%, 14.8%, and 12.7%, respectively. Metabolic syndrome (MetS) was prevalent among 5.1% of participants. Among the study participants, 29.5% had hyperuricemia. The overall prevalence of high low-density lipoprotein (LDL) and high total cholesterol (TC) of all participants was 4.8% and 7.4%, respectively. 0.9% of the participants had vitamin A deficiency (VAD) and 14.6% had marginal vitamin A deficiency; 25.1% had vitamin D deficiency (VDD) and 54.5% had inadequate vitamin D levels. Anemia was present in 4.0% of all participants. The prevalence of zinc deficiency was 4.8%. Demographic characteristics, behavioral characteristics, parents' characteristics, and family characteristics were associated with these multiple malnutrition disorders. The double burdens of malnutrition, which includes overnutrition- and undernutrition-related diseases, were prevalent among the school-age children and adolescents in Jiangsu Province in eastern China. There were various factors related to different nutritional problems. Thus, health education focusing on behavior intervention and nutrition education are necessary in containing nutritional problems among children.

Associations of Serum Uric Acid with Clustering of Cardiovascular Risk Factors and a 10-Year Atherosclerotic Cardiovascular Disease Risk Score in Jiangsu Adults, China.

PURPOSE: The relationship between serum uric acid (SUA) and Chinese characteristic 10-year atherosclerotic cardiovascular disease (ASCVD) risk score has not been well evaluated in Chinese populations. Aims of this cross-sectional study were to describe the correlation between SUA level and clustering of prevalent cardiovascular risk factors (CRFs) including overweight, central obesity, hypertension, diabetes and dyslipidemia, as well as the Chinese 10-year ASCVD risk score in adults from Jiangsu Province located in Eastern China. PATIENTS AND METHODS: A total of 7700 adults from 12 cities in Jiangsu Province were selected through multi-stage stratified cluster random sampling method in 2015. Face-to-face interviews, physical examinations and laboratory examinations were carried out to collect the information of the participants. Multivariate logistic analysis was used to analyze the relationship between SUA quartiles and various CVD risk factors. The nonlinear analysis was conducted to evaluate the relationship between SUA levels and the China-PAR 10-year ASCVD risk scores. RESULTS: The prevalence of hyperuricemia was 13.3% in all of the participants. By adjusting potential confounders, significant correlations were found between the SUA level and the overweight, central obesity, hypertension and dyslipidemia in both males and females. The clustering of CRFs was different across SUA quantiles (χ 2=607.685, P<0.001). After Gamma trend test (P < 0.001) and ordered logistic regression analysis, it was found out that with the increase of SUA quantiles, prevalent CRFs gradually gathered in both males and females. Furthermore, sex-specific difference was identified between SUA and 10-year ASCVD risk scores. CONCLUSION: The accumulation of CRFs increased with elevated SUA levels, whereas it was different between genders in the relationship between SUA and 10-year ASCVD risk scores. Tailored strategies should be taken when it came to males and females in managing SUA.

Association of antinuclear antibodies with the risk of intracranial arterial stenosis.

The prevalence of intracranial arterial stenosis (IAS) as well as antinuclear antibody (ANA) positivity was found to be higher in Asians than that in the Western population. To investigate the relation of ANAs with IAS in patients with acute ischemic cerebrovascular disease, we enrolled 2492 patients with acute ischemic stroke or transient ischemic attack into the study. All the patients were categorized into 3 groups according to the IAS burden. Multinomial logistic regression analyses were used in statistical analysis. The positive rate of ANAs in the IAS ≥ 2 group was higher than that in the single IAS group and the no IAS group (p<0.001). The adjusted odds ratio (OR) for IAS ≥ 2 in ANAs-positive patients was 3.737 (95%CI=2.676-5.220, p<0.001) compared with the ANAs-negative patients. ANAs were associated with multiple IAS rather than single IAS in both male and female subgroups. Besides, ANAs were significantly associated with single and multiple IAS in individuals ≤ 60 years. However, ANAs were only associated with two or more IAS in two age groups (between 61 to 75 years and >75 years old). In summary, ANAs are associated with IAS in patients with acute ischemic cerebrovascular disease.

Cell-free plasma hypermethylated CASZ1, CDH13 and ING2 are promising biomarkers of esophageal cancer.

Identifying sensitive and specific biomarkers for early detection of cancer is immensely imperative for early diagnosis and treatment and better clinical outcome of cancer patients. This study aimed to construct a specific DNA methylation pattern of cancer suppressor genes and explore the feasibility of applying cell-free DNA based methylation as a biomarker for early diagnosis of esophageal squamous cell carcinoma (ESCC). We recruited early stage ESCC patients from Yangzhong County, China. The Illumina Infinium 450K Methylation BeadChip was used to construct a genome-wide DNA methylation profile. Then, differentiated genes were selected for the validation study using the Sequenom MassARRAY platform. The frequency of methylation was compared between cancer tissues, matched cell-free DNAs and normal controls. The specific methylation profiles were constructed, and the sensitivity and specificity were calculated. Seven CG sites in three genes CASZ1, CDH13 and ING2 were significantly hypermethylated in ESCC as compared with normal controls. A significant correlation was found between the methylation of DNA extracted from cancer tissues and matched plasma cell-free DNA, either for individual CG site or for cumulative methylation analysis. The sensitivity and specificity reached 100% at an appropriate cut-point using these specific methylation biomarkers. This study revealed that aberrant DNA methylation is a promising biomarker for molecular diagnosis of esophageal cancer. Hypermethylation of CASZ1, CDH13 and ING2 detected in plasma cell-free DNA can be applied as a potential noninvasive biomarker for diagnosis of esophageal cancer.

Accumulated promoter methylation as a potential biomarker for esophageal cancer.

We performed a two-stage molecular epidemiological study to explore DNA methylation profiles for potential biomarkers of esophageal squamous cell carcinoma (ESCC) in a Chinese population. Infinium Methylation 450K BeadChip was used to identify genes with differentially methylated CpG sites. Sixteen candidate genes were validated by sequencing 1160 CpG sites in their promoter regions using the Illumina MiSeq platform. When excluding sites with negative changes, 10 genes (BNIP3, BRCA1, CCND1, CDKN2A, HTATIP2, ITGAV, NFKB1, PIK3R1, PRDM16 and PTX3) showed significantly different methylation levels among cancer lesions, remote normal-appearing tissues, and healthy controls. PRDM16 had the highest diagnostic value with the AUC (95% CI) of 0.988 (0.965-1.000), followed by PIK3R1, with the AUC (95% CI) of 0.969 (0.928-1.000). In addition, the methylation status was higher in patients with advanced cancer stages. These results indicate that aberrant DNA methylation may be a potential biomarker for the diagnosis of ESCC.

Preventive use of a hepatoprotectant against anti-tuberculosis drug-induced liver injury: A randomized controlled trial.

BACKGROUND AND AIM: Hepatoprotectants are routinely prescribed in China to prevent anti-tuberculosis drug-induced liver injury (ATLI). However, their biological mechanisms have not yet been clearly demonstrated. This study aims to evaluate the preventive effects of Silybum marianum against drug-induced liver injury among tuberculosis patients and to provide clinical guidelines for tuberculosis management in China. METHODS: A randomized controlled trial was performed in Jiangsu, China. Tuberculosis patients were randomly allocated to the experimental group (anti-tuberculosis therapy plus S. marianum capsule) or the control group (anti-tuberculosis therapy plus vitamin C tablet). The primary outcomes were the occurrence of probable and possible ATLI, the peak aspartate aminotransferase/alanine aminotransferase ratio and the maximum altered alkaline phosphatase or gamma-glutamyl transferase. RESULTS: The final analysis comprised 183 cases in the experiment group and 187 cases in the control group. The risk of developing probable ATLI was not significantly different between the two groups. During the follow-up period, 43.72% of cases in the experiment group and 35.83% of cases in the control group were determined to have possible ATLI (relative risk = 1.23, 95% confidence interval: 0.94-1.54). When using a more strict definition of possible ATLI, the adjusted relative risk (95% confidence interval) was 1.76 (1.14-2.56). The risks of adverse drug reactions, prolonged treatment length, taking second-line tuberculosis drugs, and the clearance of tuberculosis bacteria were similar between the two groups. CONCLUSIONS: No significant preventive effect of silymarin was found for either lowering the risk of liver injury or boosting the positive outcomes. Worse, we even found a potential risk of liver damage caused by the hepatoprotectant.

Aberrant promoter methylation of cancer-related genes in human breast cancer.

The clinical relevance of aberrant DNA methylation is being increasingly recognized in breast cancer. The present study aimed to evaluate the promoter methylation status of seven candidate genes and to explore their potential use as a biomarker for the diagnosis of breast cancer. A total of 70 Chinese patients with breast cancer were recruited, and matched with 20 patients with benign breast disease (BBD). Methylation-specific polymerase chain reaction was performed to measure the methylation status of selected genes. The protein expression of candidate genes was determined by immunohistochemistry. Hypermethylation of Breast cancer 1, early onset; DNA repair associated (BRCA1), glutathione S-transferase pi 1 (GSTP1), cyclin dependent kinase inhibitor 2A, O-6-methylguanine-DNA methyltransferase, phosphatase and tensin homolog, retinoic acid receptor beta 2 and cyclin D2 was observed to be more common in cancerous tissues (24.3, 31.4, 40.0, 27.1, 48.6, 55.7 and 67.1%, respectively) as compared with BBD controls (0.0, 0.0, 20.0, 25.0, 40.0, 40.0 and 45.0%, respectively). Immunohistochemical analysis demonstrated a correlation between the methylation of the target gene and downregulation of protein expression. When BRCA1 and GSTP1 were combined as the biomarker, the area under the receiver operating characteristic curve reached 0.721 (95% confidence interval, 0.616-0.827). The present findings indicated that promoter methylation of cancer-related genes was frequently observed in patients with breast cancer and was associated with various clinical features. Hypermethylation of BRCA1 and GSTP1 may be used as promising biomarkers for breast cancer.

Massive Endoscopic Screening for Esophageal and Gastric Cancers in a High-Risk Area of China.

OBJECTIVE: This study aims to describe the findings from a massive endoscopic screening program in a high-risk area of China and to evaluate the prognosis of patients diagnosed through endoscopic screening compared with those diagnosed at usual hospital visits because of illness. METHODS: In 2006, an early detection and treatment program was initiated in Yangzhong county, China. Local residents aged 40-69 years were eligible for free endoscopic screening. Endoscopic examination was performed with Lugol's iodine staining, followed by biopsies. Patients diagnosed with esophageal or gastric cancer were referred for treatment and followed to assess their long-term survival status. RESULTS: From 2006 through 2012, we screened 12453 participants, including 5334 (42.8%) men and 7119 (57.2%) women. The average age was 52.8 ± 8.0 years. We detected 166 patients with upper digestive tract cancers, including 106 cancers in the esophagus (detection rate: 0.85%) and 60 cancers in the stomach (detection rate: 0.48%). Of these patients, 98.11% with esophageal cancer and 100% with gastric cancer were defined as at the early stage. In the process of follow-up, 17 patients died from cancer-related causes, and the median survival time was greater than 85 months. The overall survival rates for 1, 3 and 5 years were 98.0%, 90.0% and 89.0%, respectively. A significant positive effect was observed for the long-term survival of patients diagnosed through massive endoscopic screening. CONCLUSIONS: In a high-risk population, massive endoscopic screening can identify early stage carcinoma of esophageal and gastric cancers and improve patients' prognosis through early detection and treatment.

Is tuberculosis treatment really free in China? A study comparing two areas with different management models.

OBJECTIVE: China has implemented a free-service policy for tuberculosis. However, patients still have to pay a substantial proportion of their annual income for treatment of this disease. This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. METHODS: There are three tuberculosis management models in China: the tuberculosis dispensary model, specialist model and integrated model. We selected Zhangjiagang (ZJG) and Taixing (TX) as the study sites, which correspond to areas implementing the integrated model and dispensary model, respectively. Patients diagnosed and treated for tuberculosis since January 2010 were recruited as study subjects. A total of 590 patients (316 patients from ZJG and 274 patients from TX) were interviewed with a response rate of 81%. The economic burden attributed to tuberculosis, including direct costs and indirect costs, was estimated and compared between the two study sites. The Mann-Whitney U Test was used to compare the cost differences between the two groups. Potential factors related to the total out-of-pocket costs were analyzed based on a step-by-step multivariate linear regression model after the logarithmic transformation of the costs. RESULTS: The average (median, interquartile range) total cost was 18793.33 (9965, 3200-24400) CNY for patients in ZJG, which was significantly higher than for patients in TX (mean: 6598.33, median: 2263, interquartile range: 983-6688) (Z = 10.42, P < 0.001). After excluding expenses covered by health insurance, the average out-of-pocket costs were 14304.4 CNY in ZJG and 5639.2 CNY in TX. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs. CONCLUSION: Under the current "free of diagnosis and treatment" policy, the financial burden remains heavy on tuberculosis patients. Policy makers need to consider appropriate steps to lessen the burden of out-of-pocket costs for tuberculosis patients in China and how best to improve service delivery for poor patients.

Genetic polymorphisms of IFNG and IFNGR1 in association with the risk of pulmonary tuberculosis.

OBJECTIVE: Genetic host factors play an important role in controlling individual's susceptibility to the pathogen. This study aims to explore the single and joint effect of genetic polymorphisms of interferon-gamma (IFNG) and its receptor (IFNGR1) in association with the pulmonary tuberculosis in a Chinese Han population. METHODS: This population-based case control study consisted of 1434 pulmonary tuberculosis patients and 1412 healthy controls. Six tag SNPs in IFNG/IFNGR1 were genotyped using TaqMan allelic discrimination technology. The logistic regression model was carried out to analyze the associations between the genotypes and haplotypes and the risk of tuberculosis by calculating the odds ratio (OR) and 95% confidence interval (CI). RESULTS: After the Bonferroni correction for multiple comparisons, three SNPs (rs2234711, rs1327475 and rs7749390) in IFNGR1 gene were observed to be significantly associated with the altered risks of tuberculosis. For the SNP rs2234711, individuals carrying C allele (vs. T) showed a decreased risk, with the adjusted OR(95% CI) of 0.82(0.76-0.91). The additive model revealed that each additional allele contributed about 14% decreased risk (OR: 0.86, 95% CI: 0.77-0.95). Moreover, we observed a strong linkage disequilibrium between rs2234711 and rs3799488. Compared with the common rs2234711C-rs3799488C haplotype, the haplotype rs2234711T-rs3799488C contributed to a significant increase in the risk of tuberculosis (adjusted OR: 1.24, 95% CI: 1.09-1.41). CONCLUSIONS: Our results suggest that genetic polymorphisms in IFNGR1 gene are involved in the risk of tuberculosis in the Chinese population. Future studies should include a comprehensive sequencing analysis to identify the specific causative sequence variants underlying the observed associations.

Promoter methylation of BRCA1 in the prognosis of breast cancer: a meta-analysis.

The inactivation of BRCA1 by epigenetic alterations is a critical event in breast tumorigenesis, which may potentially be used as a prognostic marker for patients with breast cancer. The present study systematically reviewed the promoter methylation of BRCA1 and its relationship to the clinical outcomes of breast cancer patients. We performed a meta-analysis following the PRISMA guideline. Relevant articles were identified by searching PubMed, Web of Science and Embase database until August 2013. The pooled hazard ratio (HR) and 95 % confidence interval (CI) were applied to estimate the effect of BRCA1 methylation. Random or fixed effect model was chosen based on the heterogeneity analysis. A total of 3,205 patients from nine eligible studies were included in the meta-analysis. BRCA1 methylation was found to be significantly correlated with a poor overall survival of breast cancer, with the combined HR (95 % CI) of 2.02 (1.35-3.03). After adjusting for potential confounders using the Cox regression model, the pooled HR (95 % CI) of BRCA1 methylation on patients' overall survival was 1.38 (1.04-1.84). If we used the disease-free survival as the outcome, the combined HR (95 % CI) was 2.89 (1.73-4.83) for univariate analysis and 3.92 (95 % CI 1.49-10.32) for multivariate analysis, respectively. Subgroup analysis of specimen types revealed that the pooled HR (95 % CI) for overall survival was 1.48 (1.22-1.81) when using formalin-fixed paraffin-embedded (FFPE) specimen and 1.38 (0.16-11.84) when using fresh frozen tissues. As for the disease-free survival, the pooled HR (95 % CI) was 2.47 (1.33-4.58) when using FFPE specimen and 2.78 (1.47-5.28) when using fresh frozen tissues. As a conclusion, the present meta-analysis provides evidence that BRCA1 methylation is associated with a poor survival of breast cancer patients. Our findings underscore the clinical relevance of aberrant epigenetic alteration as a promising biomarker for the prognosis of human cancers.