Prevalence of fatty liver disease and its risk factors in the population of South China

AIM: To investigate the population-based prevalence of fatty liver disease (FLD) and its risk factors in Guangdong Province,China. METHODS: A cross-sectional survey with multiple-stage stratified cluster and random sampling of inhabitants over 7-year-old was performed in 6 urban and rural areas of Guangdong Province,China. Questionnaires,designed by co-working of epidemiologists and hepatologists,included demographic characteristics,current medication use,medical history and health-relevant behaviors,i.e. alcohol consumption,smoking habits,dietary habits and physical activities. Anthropometric measurements,biochemical tests and abdominal ultrasonography were carried out. RESULTS: Among the 3543 subjects,609 (17.2%) were diagnosed having FLD (18.0% males,16.7% females,P > 0.05). Among them,the prevalence of confirmed alcoholic liver disease (ALD),suspected ALD and nonalcoholic fatty liver disease (NAFLD) were 0.4%,1.8%,and 15.0%,respectively. The prevalence rate (23.0%) was significantly higher in urban areas than (12.9%) in rural areas. After adjustment for age,gender and residency,the standardized prevalence of FLD in adults was 14.5%. Among them,confirmed ALD,suspected ALD and NAFLD were 0.5%,2.3%,and 11.7%,respectively,in adults and 1.3% (all NAFLD) in children at the age of 7-18 years. The overall prevalence of FLD increased with age in both genders to the peak of 27.4% in the group of subjects at the age of 60-70 years. The prevalence rate was significantly higher in men than in women under the age of 50 years (22.4% vs 7.1%,P < 0.001). However,the opposite phenomenon was found over the age of 50 years (20.6% vs 27.6%,P < 0.05). Multivariate and logistic regression analysis indicated that male gender,urban residency,low education,high blood pressure,body mass index,waist circumference,waist to hip ratio,serum triglyceride and glucose levels were the risk factors for FLD. CONCLUSION: FLD,especially NAFLD,is prevalent in South China. There are many risk factors for FLD.

Genetic and epigenetic variants influencing the development of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease （NAFLD） is common worldwide. The importance of genetic and epigen- eric changes in etiology and pathogenesis of NAFLD has been increasingly recognized. However, the ex- act mechanism is largely unknown. A large number of single nucleotide polymorphisms （SNPs） related to NAFLD has been documented by candidate gene studies （CGSs）. Among these genes, peroxisome pro- liferatoractivated receptor-γ, adiponectin, leptin and tumor necrosis factor-α were frequently reported. Since the introduction of genome-wide association studies （GWASs）, there have been significant advances in our understanding of genomic variations of NAFLD. Patatin- like phospholipase domain containing family member A3 （PNPLA3, SNP rs738409, encoding I148M）, also termed adiponutrin, has caught most attention. The evidence that PNPLA3 is associated with increased hepatic fat levels and hepatic inflammation has been validated by a series of studies. Epigenetic modification refers to phenotypic changes caused by an adaptive mechanism unrelated to alteration of primary DNA se- quences. Epigenetic regulation mainly includes microR- NAs （miRs）, DNA methylation, histone modifications and ubiquitination, among which miRs are studied most extensively, miRs are small natural single stranded RNA molecules regulating mRNA degradation or translation inhibition, subsequently altering protein expression of target genes. The miR-122, a highly abundant miR ac- counting for nearly 70% of all miRs in the liver, is sig- nificantly under-expressed in NAFLD subjects. Inhibition of miR-122 with an antisense oligonucleotide results in decreased mRNA expression of lipogenJc genes and improvement of liver steatosis. The investigation into epigenetic involvement in NAFLD pathogenesis is just at the beginning and needs to be refined. This review summarizes the roles of genetics and epigenetics in the development of NAFLD. The progress made in this field may provide novel diagnostic biomarkers and therapeu- tic targets for NAFLD management.

Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients

AIM: To investigate Fusobacterium nucleatum (F. nucleatum) abundance in colorectal cancer (CRC) tissues and its association with CRC invasiveness in Chinese patients.METHODS: The resected cancer and adjacent normal tissues (10 cm beyond cancer margins) from 101 consecutive patients with CRC were collected. Fluorescent quantitative polymerase chain reaction (FQ-PCR) was applied to detect F. nucleatum in CRC and normal tissues. The difference of F. nucleatum abundance between cancer and normal tissues and the relationship of F. nucleatum abundance with clinical variables were evaluated. Fluorescence in situ hybridization (FISH) analysis was performed on 22 CRC tissues with the highest F. nucleatum abundance by FQ-PCR testing to confirm FQ-PCR results.RESULTS: The median abundance of F. nucleatum in CRC tissues [0.242 (0.178-0.276)] was significantly higher than that in normal controls [0.050 (0.023-0.067)] (P < 0.001). F. nucleatum was over-represented in 88/101 (87.1%) CRC samples. The abundance of F. nucleatum determined by 2-ΔCT was significantly greater in tumor samples [0.242 (0.178, 0.276)] than in normal controls [0.050 (0.023, 0.067)] (P < 0.001). The frequency of patients with lymph node metastases was higher in the over-abundance group [52/88 (59.1%)] than in the under-abundance group [0/13 (0%)] (P < 0.005). No significant association of F. nucleatum with other clinico-pathological variables was observed (P > 0.05). FISH analysis also found more F. nucleatum in CRC than in normal tissues (median number 6, 25th 3, 75th 10 vs 2, 25th 1, 75th 5) (P < 0.01).CONCLUSION: F. nucleatum was enriched in CRC tissues and associated with CRC development and metastasis.

Decreased fragile histidine triad expression in colorectal cancer and its association with apoptosis inhibition

AIM： To detect the expression of fragile histidine triad （FHIT） in normal colorectal tissue, colorectal adenoma and colorectal cancer （CRC） tissue, and to analyze its relationship with the clinicopathological features of CRC, and apoptosis-associatecl proteins （Bcl-2, Bax, survivin） and apoptosis in colorectal cancer. METHODS： FHIT mRNA analysis was performed by nested reverse transcription-polymerase chain reaction （RT-PCR） assay. Tissue microarray （TMA） was established to detect the expression of FHIT, Bcl-2, Bax and survivin genes in 80 CRC tissue specimens, 16 colorectal adenoma tissue specimens and 16 hemorrhoid （PPH） tissue specimens during the same period of time as the control. Citrate-microwave-SP was used as immunohistochemical method. The relationship between clinicopathological factors, such as differentiation grades and 5-year survival rate was observed. TUNEL assay was used to detect the apoptosis index in 80 CRC tissue specimens. RESULTS： Ten out of 26 （38.5%） CRC tissue specimens expressed aberrant FHIT transcripts, none of the aberrant FHIT transcripts was observed in the matchednormal tissue and colorectal adenoma tissue by nested RT-PCR assay. The positive rate of FHIT gene expression in normal colorectal tissue, colorectal adenoma and carcinoma tissue was 93.75%, 68.75% and 46.25%, respectively. Clinicopathological analysis of patients showed that the decreased FHIT gene expression was not associated with age, sex, serum CEA levels, tumor site and size, histological classification. However, the expression of FHIT was correlated with differentiation grades, pathological stages, lymph node metastases and 5-year survival rate after operation. The positive rate of apoptosis-associated proteins （Bax, Bcl-2 and survivin） in CRC tissue was 72.50%, 51.25% and 77.50%, respectively. The expression of these apoptosisassociated proteins in CRC tissue was correlated with the expression of FHIT. The mean apoptosis index in FHIT negative tumors was significantly lower than that in FHIT- positive tumors （5.41 ± 0.23 vs 0.56 ± 0.10, P 〈 0.01）. CONCLUSION： The FHIT gene plays an important role in the regulation of apoptosis and decreased FHIT expression plays a key role in the initiation and progression of colorectal carcinoma.

Nur-related receptor 1 gene polymorphisms and alcohol dependence in Mexican Americans

AIM： To investigate the association of polymorphisms of nur-related receptor 1 （Nurrl） and development of alcohol dependence in Mexican Americans. METHODS： Peripheral blood samples were collected from 374 alcoholic and 346 nonalcoholic Mexican Amer- icans; these two groups were sex- and age-matched. Sample DNA was extracted and genomic DNA was amplified by polymerase chain reaction. The -2922（C） 2-3 polymerase chain reaction products were digested with Sau96I, alleles of 1345（G/C）, and -1198（C/G） in the regulatory region as well as Ex＋132 （G/T/A/C） and Ex＋715（T/-） in exon 3 were studied by sequencing. RESULTS： The C2/C2, C2/C3, C3/C3 genotype distribu- tion of -2922（C） 2-3 was 34.4%, 38.2% and 27.5% in the nonalcoholic group compared to 23.3%, 51.2% and 25.4% in the alcoholic group （P = 0.001）. The C/C, C/G ,G/G genotype distribution of -1198（C/6） was 23.5%, 46.1% and 30.3% in the nonalcoholic group compared to 13.9%, 50.9% and 35.3% in the alcoholic group （P = 0.007）. However, the -1345 （G/C）, Ex3＋132（G/T/A/C） and Ex3＋715（T/-） alleles were not polymorphic in Mex- ican Americans, and all those studied had G/G, G/G and T/T genotype for these three alleles, respectively. The -2922（C） 2-3 did not show allele level difference be- tween alcoholic and nonalcoholic individuals, but -1198 （C/G） showed a significant allele frequency difference between alcoholic （39.3%） and nonalcoholic （46.6%） populations （P = 0.005）. Excluding obese individuals, significant differences were found at both genotypic and allelic levels for the -2922（C） 2-3 polymorphism （P = 0.000 and P = 0.049） and the -1198 （C/G） polymor- phism （P = 0.008 and P = 0.032） between nonobese alcoholics and nonobese controls. Excluding smokers, a significant difference was found only at the genotypic level for the -2922（C） 2-3 polymorphism （P = 0.037） between nonsmoking alcoholics and nonsmoking con- trols, but only at the allelic level for the -1198（C/G） polymorphism （P = 0.034）. CONCLUSION： Polymorphisms in the regulatory region of Nurrl are implicated in pathogenesis of alcohol de- pendence and the Nurrl/dopamine signaling pathway might be important for this dependence development in Mexican Americans.

The Optimal Allocation of Investment between Antivirals and Vaccines for Influenza Pandemic Preparedness Planning

Objectives To investigate that given a fixed amount of financial resources,what is the optimal combination of vaccine and antiviral stockpiles in terms of minimizing the attack rate.Methods Mathematic modeling was used to simulate the dynamics that with fixed influenza pandemic budget.Different budget conditions were observed if the combination changed.Framework between vaccines and antivirals was introduced by taking into account the uncertainty in vaccine and antiviral efficacy.Results Given a fixed budget,different budget allocations between vaccines and antivirals stockpile gave different attack rates.When the price of vaccine was lower than or similar with the antivirals,the attack rate increased with increasing investment in antiviral.But if the price of the vaccine was higher than the antivirals,the attack rate may not decrease with increasing investment in vaccine.Fixed the vaccine effectiveness,higher effectiveness of antiviral got a lower attack rate.When both antiviral and vaccine were with 50%probability of effectiveness,the attack rate changed by antiviral stockpile with a same pattern as they were with 100%efficacy probability,even it has a higher attack rate.Conclusions Assume the antivirals have 100%probability to be effective,budget was limited to a fix number,then in any event,population should stockpile a small amount of antivirals such that if the post-vaccination reproductive number turns out to be near 1,the additional intervention may further reduce the reproductive number to <1 and prevent the epidemic.Under the fixed budget,the price of the vaccines and antivirals will strongly affect the strategy of the stockpile allocation.When the price of vaccine is comparative lower,more investment of vaccine is better for the pandemic control,but if the vaccine price is too high then more investment in antiviral may be better.We found that attack rates and the optimal budget allocation depend on the probability to be effective of vaccine and antivirals.

Diagnostic Performance of Intestinal Fusobacterium nucleatum in Colorectal Cancer： A Meta-Analysis

Background： Increasing evidence has supported the link of intestinal Fusobacterium nucleatum infection to colorectal cancer （CRC）. However, the value of F. nucleatum as a biomarker in CRC detection has not been fully defined. In order to reduce the random error and bias of individual research, this meta-analysis aimed to evaluate the diagnostic performance of intestinal F. nucleatum in CRC patients and provide evidence-based data to clinical practice. Methods： An article search was performed from PubMed, Embase, Cochrane Library, and Web of Science databases up to December 2017, using the following key words： ＂Fusobacterium nucleatum＂, ＂Fusobacterium spp.＂, ＂Fn＂, ＂colorectal cancer（s）＂, ＂colorectal carcinoma（s）＂, ＂colorectal neoplasm（s）＂, and ＂colorectal tumor（s）＂. Articles on relationships between E nucleatum and CRC were selected according to the preestablished inclusion and exclusion criteria. This meta-analysis was performed using STATA 12.0 software, which included mapping of lbrest plots, heterogeneity tests, recta-regression, subgroup analysis, sensitivity analysis, and publication bias. The sensitivity, specificity, positive likelihood ratio （LR）, negative LR, diagnostic odds ratio （DOR）, and their corresponding 95% confidence interval （CI） of each eligible study were summarized. Results： Finally, data for 1198 participants （629 CRC and 569 healthy controls） in 10 controlled studies from seven articles were included. The summary receiver operator characteristic curve was mapped. The diagnostic performance of intestinal E nucleatum infection on CRC was as follows： the area under the curve： 0.86 （95% CI： 0.83-0.89）, the pooled sensitivity： 0.81 （95% CI：0.64 0.91 ）, specificity： 0.77 （95% CI： 0.59-0.89）, and DOR： 14.00 （95% CI： 9.00 -22.00）. Conclusion： Intestinal E nucleatum is a valuable marker for CRC diagnosis.

Association of MSI2 Gene Polymorphism with Age-at-Onset of Schizophrenia in a Chinese Population

Dear Editor,Schizophrenia is one of the most complicated and challenging mental disorders psychiatrists and mental health caregivers confront.It is a heavy burden for the patients and usually occurs during adulthood.With a peak age-atonset of 18–25 years,schizophrenia results in the loss of productivity,poses a considerable burden on the relatives,and causes high medical and social costs.In the general population worldwide,the life risk for schizophrenia is