Association of food intake with a risk of metabolic dysfunction-associated fatty liver disease: a cross-sectional study.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease, the risk of which can be increased by poor diet. The objective of this study was to evaluate the associations between food items and MAFLD, and to propose reasonable dietary recommendations for the prevention of MAFLD. Methods: Physical examination data were collected from April 2015 through August 2017 at Nanping First Hospital (n = 3,563). Dietary intakes were assessed using a semi-quantitative food frequency questionnaire. The association between food intake and the risk of MAFLD was assessed by using the inverse probability weighted propensity score. Results: Beverages (soft drinks and sugar-sweetened beverages) and instant noodles were positively associated with MAFLD risk, adjusting for smoking, drinking, tea intake, and weekly hours of physical activity [adjusted odds ratio (ORadjusted): 1.568; P = 0.044; ORadjusted: 4.363; P = 0.001]. Milk, tubers, and vegetables were negatively associated with MAFLD risk (ORadjusted: 0.912; P = 0.002; ORadjusted: 0.633; P = 0.007; ORadjusted: 0.962; P = 0.028). In subgroup analysis, the results showed that women [odds ratio (OR): 0.341, 95% confidence interval (CI): 0.172-0.676] had a significantly lower risk of MAFLD through consuming more tubers than men (OR: 0.732, 95% CI: 0.564-0.951). Conclusions: These findings suggest that reducing consumption of beverages (soft drinks and sugar-sweetened beverages) and instant noodles, and consuming more milk, vegetables, and tubers may reduce the risk of MAFLD.

Esophageal mycobiome landscape and interkingdom interactions in esophageal squamous cell carcinoma.

Background: The study purpose was to characterize the mycobiome and its associations with the expression of pathogenic genes in esophageal squamous cell carcinoma (ESCC). Methods: Patients with primary ESCC were recruited from two central hospitals. We performed internal transcribed spacer 1 (ITS1) ribosomal DNA sequencing analysis. We compared differential fungi and explored the ecology of fungi and the interaction of bacteria and fungi. Results: The mycobiota diversity was significantly different between tumors and tumor-adjacent samples. We further analysed the differences between the two groups, at the species level, confirming that Rhodotorula toruloides, Malassezia dermatis, Hanseniaspora lachancei, and Spegazzinia tessarthra were excessively colonized in the tumor samples, whereas Preussia persica, Fusarium solani, Nigrospora oryzae, Acremonium furcatum, Golovinomyces artemisiae, and Tausonia pullulans were significantly more abundant in tumor-adjacent samples. The fungal co-occurrence network in tumor-adjacent samples was larger and denser than that in tumors. Similarly, the more complex bacterial-fungal interactions in tumor-adjacent samples were also detected. The expression of mechanistic target of rapamycin kinase was positively correlated with the abundance of N. oryzae and T. pullulans in tumor-adjacent samples. In tumors, the expression of MET proto-oncogene, receptor tyrosine kinase (MET) had a negative correlation and a positive correlation with the abundance of R. toruloides and S. tessarthra, respectively. Conclusion: This study revealed the landscape of the esophageal mycobiome characterized by an altered fungal composition and bacterial and fungal ecology in ESCC.

Genome-wide DNA methylation and RNA expression profiles identified RIPK3 as a differentially methylated gene in Chlamydia pneumoniae infection lung carcinoma patients in China.

Aim: To explore the relationship between Chlamydia pneumonia (Cpn) infection and lung cancer using integrative methylome and transcriptome analyses. Methods: Twelve primary lung cancer patients who were positive for Cpn and twelve patients who were negative were selected for demographic, clinicopathological, and lifestyle matching. Genomic DNA and RNA were extracted and DNA methylation and mRNA levels were detected using the Infinium Human Methylation 450 Beadchip array and mRNA + lncRNA Human Gene Expression Microarray. We identified differentially expressed methylation and genes profiles. Results: Integrative analysis revealed an inverse correlation between differentially expressed genes and DNA methylation. Cpn-related lung cancer methylated genes (target genes) were introduced into the gene ontology and KEGG, PID, BioCarta, Reactome, BioCyc and PANTHER enrichment analyses using a q-value cutoff of 0.05 to identify potentially functional methylation of abnormal genes associated with Cpn infection. Gene sets enrichment analysis was evaluated according to MsigDB. Levels of differentially expressed methylated sites were quantitatively verified. The promoter methylation sites of 62 genes were inversely related to expression levels. According to the quantitative analysis of DNA methylation, the methylation level of the RIPK3 promoter region was significantly different between Cpn-positive cancerous and adjacent tissues, but not between Cpn-negative cancerous and adjacent tissues. Conclusion:  Hypomethylation of the RIPK3 promoter region increases RIPK3 expression, leading to regulated programmed necrosis and activation of NF-κB transcription factors, which may contribute to the development and progression of Cpn-related lung cancer.

Dietary patterns, BCMO1 polymorphisms, and primary lung cancer risk in a Han Chinese population: a case-control study in Southeast China.

BACKGROUND: We investigated whether BCMO1 variants and dietary patterns are associated with lung cancer risk. METHODS: Case-control study including 1166 lung cancer cases and 1179 frequency matched controls was conducted for three BCMO1 variants (rs6564851, rs12934922, and rs7501331) and four dietary patterns were investigated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: The rs6564851, rs12934922, and rs7501331 were not found to be associated with lung cancer risk (P > 0.05). In multivariable-adjusted models, compared to the lowest quartile of the score on the "fruits and vegetables" pattern, the highest quintile was associated with a 78.4% decreased risk (OR Q4 vs. Q1 = 0.216; 95% CI, 0.164-0.284; P for trend < 0.001). Other patterns were not found the association. The "fruits and vegetables" pattern was associated with a reduced risk of lung cancer with all 3 SNPs irrespective of genotypes (all P for trend< 0.001). The association for the "Frugal" pattern was associated with increased risk of lung cancer among smokers (P for interaction = 0.005). The protective effects of the "cereals/wheat and meat" pattern was more evident for squamous cell carcinoma and other histological type. CONCLUSIONS: We did not observe associations of BCMO1 variants and lung cancer. Diets rich in fruits and vegetables may be protective against lung cancer.

Independent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China.

BACKGROUND: The purpose of this study was to explore the effects of CYP2C19 gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population. METHODS: A 1:2 frequency-matched case control study of 285 patients and 570 controls was conducted from June 2010 to May 2011 in AnXi of Fujian province, China. Environmental factors were investigated using a self-administered questionnaire and genotypes were determined using polymerase chain reaction restriction fragment length polymorphism based methods. Unconditional logistic regression models were used for statistical evaluation. RESULTS: Current or former smoking, consumption of pickled vegetables or hot beverages/food, having a first degree relative with ESCC and history of reflux esophagitis were significantly associated with increased ESCC risk, whereas tea drinking and consumption of fresh vegetables and fruits were significantly associated with decreased risk. The CYP2C19*2 GA/AA genotype was significantly more prevalent in ESCC patients and individuals with at least one copy of the CYP2C19*2 A allele had a 3.19-fold increased risk (adjusted 95% confidence interval (CI): 2.21-4.61, P < 0.001) of ESCC compared with those without this allele. We found no significant associations between CYP2C19*3 genotypes and ESCC. The Cyp2C19*2 polymorphism appeared to have a multiplicative joint effect with tea drinking and hot beverage/food consumption (gene-tea drinking: P(interaction) = 0.042; hot beverage/food consumption: P(interaction) = 6.98 × 10(-6)) and an additive joint effect with pickled vegetable consumption (interaction contrast ratio = 1.96, 95% CI: 0.12-3.80). CONCLUSIONS: Our findings suggest that the CYP2C19*2 polymorphism plays an important role in the development of ESCC in the Chinese population, modified by tea drinking and consumption of pickled vegetables or hot beverages/food. Further studies are warranted to confirm our results.

NQO1 609C>T polymorphism interaction with tobacco smoking and alcohol drinking increases colorectal cancer risk in a Chinese population.

BACKGROUND: NAD (P)H:quinone oxidoreductase (NQO1) catalyzes the activation of some environmental procarcinogens present in tobacco smoke or the diet. We conducted a hospital-based case-control study to evaluate the potential association between NQO1 609C>T polymorphisms and colorectal cancer risk in a Chinese population. METHODS: The study population comprised 672 histologically confirmed colorectal cancer patients and 672 frequency-matched control subjects without cancer or systemic illness. We used PCR restriction fragment length polymorphism-based methods for genotyping analyses and unconditional logistic regression model for statistical evaluations. RESULTS: The risk of colorectal cancer increased with the level of smoking and decreased with the consumption of tea, fresh fruits, and vegetables. In addition, we found that the NQO1 609 CT and TT genotypes were associated with an increased risk of colorectal cancer (CT: adjusted OR=2.02, 95% CI=1.55-2.57; TT: adjusted OR=2.51, 95% CI=1.82-3.47), compared with the CC genotype. Moreover, NQO1 609C>T appeared to have a multiplicative joint effect with both tobacco smoking and alcoholic drinking (P for multiplicative interactions were 0.0001 and 0.013, respectively) on colorectal cancer risk. CONCLUSION: Our findings suggest that the NQO1 609C>T polymorphism plays an important role in the development of colorectal cancer in the Chinese population, which is strengthened by alcohol drinking or tobacco smoking.

Potential role of adenosine deaminase in the diagnosis of adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is a systemic inflammatory autoimmune disorder of unknown etiology and pathogenesis. There are no specific laboratory tests for AOSD. To investigate the potential role of adenosine deaminase (ADA) in the diagnosis of AOSD and analyze the correlation among ADA, LDH and WBC (white blood cell count), the serum levels of ADA and LDH in 26 patients with active untreated AOSD, 40 patients with active systemic lupus erythematosus (SLE) as disease control and 48 healthy volunteers as healthy control were determined using automatic biochemical analyzer (Olympus AU2700, Japan). WBC was examined by automatic blood cell analyzer (Beckman Coulter Hmx, America). Significantly higher levels of serum ADA, LDH and WBC were found in active untreated AOSD patients than in active SLE patients and healthy volunteers (F = 27.823; P = 0.000; F = 28.458, P = 0.000; F = 51.929, P = 0.000). Serum ADA were related to LDH level in patients with AOSD patients (r = 0.786, P = 0.000 < 0.01). Both ADA and LDH were not related to WBC (r = 0.244, P = 0.229 > 0.01; r = 0.054, P = 0.794 > 0.01). This is the first study to show that serum ADA could play an important role in AOSD and may be an important biomarker for the diagnosis of AOSD. Serum ADA could be another diagnostic marker independent from whole blood WBC.

[Construction and identification of small interfering RNA expression vector targeting ATF-2 gene].

AIM: To construct an eukaryotic expression vector for RNA interference targeting activating transcription factor 2 (ATF-2) gene, and explore its effect on proliferation and apoptosis of HepG2 cells. METHODS: Two complementary oligonucleotides were synthesized based on ATF-2 mRNA sequence. The annealed fragment was inserted into the vector PBA-siU6. The recombinant plasmid PBA-siATF-2 was confirmed by DNA sequencing and transfected into HepG2 cells mediated by liposome. After transfection, ATF-2 protein was detected by Western blotting. The cellular growth activity and apoptosis rate were measured by MTT assay and flow cytometry, respectively. RESULTS: Recombinant plasmid expressing siRNA targeting ATF-2 gene was confirmed by DNA sequencing. Plasmid transfection down-regulated the level of ATF-2 protein in HepG2 cells, which blocked cellular growth and induced cell apoptosis. CONCLUSION: The eukaryotic expression vector for RNA interference targeting ATF-2 gene was constructed successfully, which inhibits HepG2 cell proliferation and induces cell apoptosis.

Role of Kasai procedure in surgery of hilar bile duct strictures.

AIM: To assess the application of the Kasai procedure in the surgical management of hilar bile duct strictures. METHODS: Ten consecutive patients between 2005 and 2011 with hilar bile duct strictures who underwent the Kasai procedure were retrospectively analyzed. Kasai portoenterostomy with the placement of biliary stents was performed in all patients. Clinical characteristics, postoperative complications, and long-term outcomes were analyzed. All patients were followed up for 2-60 mo postoperatively. RESULTS: Patients were classified according to the Bismuth classification of biliary strictures. There were two Bismuth III and eight Bismuth IV lesions. Six lesions were benign and four were malignant. Of the benign lesions, three were due to post-cholecystectomy injury, one to trauma, one to inflammation, and one to inflammatory pseudotumor. Of the malignant lesions, four were due to hilar cholangiocarcinoma. All patients underwent Kasai portoenterostomy with the placement of biliary stents. There were no perioperative deaths. One patient experienced anastomotic leak and was managed conservatively. No other complications occurred perioperatively. During the follow-up period, all patients reported a good quality of life. CONCLUSION: The Kasai procedure combined with biliary stents may be appropriate for patients with hilar biliary stricture that cannot be managed by standard surgical methods.

[The effects of microcystin-LR on the mRNA expression levels of base excision repair genes and genes related to apoptosis].

OBJECTIVE: To explore the effects of microcystin-LR (MCLR) on the expression of base excision repair genes and genes related to apoptosis. METHODS: The BRL-3A cells were exposed to different concentrations of MCLR for various periods of time and the cell viability was measured by MTT. The mRNA expression was determined with the quantitative real-time polymerase chain reaction (QRT-PCR). RESULTS: The viability of BRL-3A cells significantly reduced in a concentration- and time-dependent manner. In 30 µg/ml group, the mRNA expression level (1.327 ± 0.028) of p53 increased significantly at 24 h after exposure, as compared with the other groups (1.005 ± 0.117, 0.862 ± 0.154, 1.028 ± 0.056 and 1.015 ± 0.091) (P < 0.05). The mRNA expression levels (5.080 ± 0.729, 5.820 ± 0.373, 6.018 ± 0.359 and 6.183 ± 0.515) of Bax in all exposure groups were significantly higher than that (1.024 ± 0.277) in control group at 24 h after exposure. However, the Bax mRNA expression level (0.604 ± 0.146) in the 30 µg/ml group at 72 h after exposure was significantly lower than those (1.004 ± 0.107, 0.811 ± 0.142, 0.855 ± 0.101 and 0.814 ± 0.056) in other groups (P < 0.05). When compared with control group (1.006 ± 0.132) and 1 µg/ml group (1.034 ± 0.241), the mRNA expression level (0.488 ± 0.147) of PARP1 in 30 µg/ml group at 48 h after exposure decreased significantly (P < 0.05). Furthermore, the mRNA expression levels (0.594 ± 0.180, 0.491 ± 0.015 and 0.305 ± 0.091) of JWA, XRCC1 and PARP1 in 30 µg/ml group at 72 h after exposure decreased significantly, as compared with the other groups (P < 0.05). CONCLUSION: The induction of gene expression is a transient phenomenon that occurred at different times of exposure for different genes. Inhibition of MCLR on the base excision repair gene expression may play important role in the course of MCLR promoting liver tumor.

[Relationship between genetic polymorphism of ERCC1 and susceptibility to liver cancer].

OBJECTIVE: To investigate the association between genetic polymorphisms of ERCC1-C8092A and susceptibility to liver cancer, as well as the gene-environmental interaction on the etiology of liver cancer in Fuzhou. METHODS: A case-control study was conducted to collect the information on environmental exposure while genetic polymorphism of ERCC1 was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. General relative risk regression models were further applied to fit the interaction between genetic polymorphisms of ERCC1-C8092A and the environmental factors of liver cancer. RESULTS: ERCC1-C8092A variant genotypes were associated with significant increasing risk of liver cancer adjusted odds ratio (OR = 3.789, 95%CI: 2.792 - 5.142), compared to the wild-type homozygote. Data from the analysis of interaction showed that genetic polymorphism of ERCC1-8092A appeared super-additive interaction with drinking pond-ditch or with hepatitis B, and super-multiplicative interaction with eating moldy food. CONCLUSION: The point mutation in ERCC1-8092A was possibly susceptible to liver cancer, and related synergistically with other risk factors in hepatocelluar carcinogenesis in Fuzhou.

[Effects of microcystins on expression of apoptosis-associated hepatocyte genes].

OBJECTIVE: To deeply explore the effects of microcystins (MC-LR) on Bax and Bcl-2 during the course of MC-LR promoting liver tumor. METHODS: applied to set up the animal model, and the effect of MC-LR promoting liver tumor was evaluated by the Albertgamma-GT methods. And then, the immunohistochemical technique, RT-PCR and image analysis were used to study the expression of the Bcl-2 and Bax during the course of promoting tumor. RESULTS: (1) MC-LR might enhance the positive reaction rate of GGT. The positive reaction rate of GGT in DEN + pure toxin group was 100%, it was significantly higher than the DEN control group 22.22% (P < 0.05). (2) The intension and areas of the protein expression of Bcl-2 in DEN + pure toxin group were 0.0977 and 0.0315, and in DEN control group were 0.0460 and 0.0205, respectively. The expression level of Bcl-2 protein in DEN + pure toxin group were significantly higher than in DEN control group (P < 0.05). Simultaneously, the protein expression of Bax was significantly decreased by MC-LR (P < 0.05). The intension and areas of the expression of Bax in DEN + pure toxin group were 0.0283 and 0.0073, and in DEN control group were 0.0655 and 0.0244 respectively. (3) The mRNA expression of Bcl-2 was significantly increased by MC-LR. The intension of Bcl-2 mRNA expression in DEN + pure toxin group was 2.244, being significantly higher than in the other groups (P < 0.05). However, the mRNA expression of Bax showed no significant difference between DEN + pure toxin and the other groups. CONCLUSION: The expression change of Bcl-2 and Bax should possibly play an important role in the course of MC-LR promoting liver tumor.