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1,2-Rhamnosyltransferase (1,2RhaT) catalyzes the final step of production of flavanone neohesperidoside (FNH) that is responsible for the primary bitter taste of citrus fruits. In this study, species-specific flavonoid profiles were determined in 87

Background Poor oral health may be a significant risk factor for gastric cancer (GC), however, previous results are not consistent. Here, we investigated the effect of oral health on GC and effect modification by other factors. Methods We conducted a population-based case-control study in Taixing, China. Participants aged between 40 and 85 years and who had lived in Taixing for at least 5 years were included. The GC cases were confirmed by endoscopy and pathological diagnosis, and the controls were randomly selected using the frequency-matching method. Unconditional logistic regression models were used to derive odds ratios (ORs) and 95% confidence intervals (CIs) of oral health for GC risk after adjusting for confounders and risk factors. Results Overall, 901 GC cases and 1972 controls were included. Tooth loss was not significantly associated with an increased risk of GC (yes vs. no, OR = 1.08, 95% CI 0.88-1.33). Compared with toothbrushing at least twice per day, toothbrushing once per day or less was associated with an increased risk of GC (OR = 2.39, 95% CI 1.94-2.94), and was more pronounced in esophagogastric junction cancer and intestinal-type GC. There was no significant interaction between the indicators of oral health and age, sex, tobacco smoking, alcohol drinking, and Helicobacter pylori seropositivity. Conclusion Poor oral hygiene behavior is associated with an increased risk of GC, and this positive association is consistent across all GC subgroups classified by anatomy and histology. Further studies are needed to explore the possible mechanisms behind this association. This article is protected by copyright. All rights reserved.

Background: To explore the relationship between family history of esophageal cancer, SNPs, and the risk of esophageal squamous cell carcinoma (ESCC), we performed a population-based case–control study and developed a genetic family history–related risk (GFR) score and non–family history-related risk (GnFR) score to quantify the cumulative number of risk genotypes carried by each individual. Methods: We used data of 700 patients with nonfamilial ESCC, 341 patients with familial ESCC, 1,445 controls without a family history of esophageal cancer, and 319 controls with a family history. We genotyped 87 genetic variants associated with the risk for ESCC, and constructed GFR and GnFR scores for cases and controls. Results: Our results show that ESCC risk increased with higher GFR score (Ptrend = 0.0096). Among the familial subgroup, we observed a nearly 7-fold [95% confidence interval (CI), 1.92–24.77] higher risk of ESCC in the highest GFR score group. The corresponding estimate was only 2-fold (95% CI, 1.41–3.93) higher risk of ESCC, in the stratum without a reported family history of esophageal cancer. Certain cell signaling pathways and immune-related pathways were enriched, specifically in familial ESCC. Results from a reconstructed cohort analysis demonstrated that cumulative risk to get esophageal cancer by age 75 years was 13.3%, 10.2%, 8.2%, and 5.1%, respectively, in four subgroups as defined by first-degree relatives of cases or controls with high or low genetic risk score. In particular, the cohort of relatives of ESCC cases with low genetic risk score exhibit a higher cumulative risk than the cohort of relatives of controls with high genetic risk score. It demonstrates that environmental factors play a major role in esophageal cancer. Conclusions: Further studies are warranted to dissect the mechanisms of shared environmental and genetic susceptibility affecting the risk of getting ESCC. Impact: Our study highlights that the need of preventive strategies to screen certain genetic polymorphisms, especially in individuals whose relatives had ESCC.

Distamycin (DST) is a well-characterized DNA minor groove binder with antivirus activity and antitumor potency. Two separate gene clusters (a 28-kb cluster and a 7-kb cluster) have recently been identified to coordinately encode the biosynthetic machinery of DST in Streptomyces netropsis. Here we report a gene cassette, which is linked to the aforementioned smaller dst gene cluster and plays an important role in the self-resistance to DST in S. netropsis. This cassette consists of three uncharacterized genes that might be implicated in DNA replication/repair. Knockout of the cassette led to the decrease in the production of DST, while heterologous expression of part of the cassette in S. lividans made it become resistant to both DST and mitomycin C, another DNA-binding agent. More interestingly, homologs of these three genes were found in genomes of other actinomyces that produce DNA-binding antibiotics, suggesting that a novel common mechanism in addition to pumping may enable these strains to resist the cytotoxic metabolites they produced.

The relationship between risk of esophageal squamous cell carcinoma (ESCC) and adult height, changes in individual body mass index (BMI) and body shape is not established. We performed a large population‐based case‐control study, which enrolled a total of 1414 ESCC cases and 1989 controls in a high‐incidence area in China. Using face‐to‐face interview with a structured questionnaire, information on participants' heights, weights, and perceived body shapes at 20 years of age was collected. Additionally, data on weight and perceived body shape among the same participants 10 years prior to ascertainment were collected using the same method. Odd ratios (ORs) of ESCC risk in relation to BMI and body shape were estimated using unconditional logistic regression models. The adjusted results indicated that ESCC risk in adults rapidly rose as height increased, plateauing at 170 cm among men and 157 cm among women. Among participants who were underweight, normal weight, or thinner than body shape 4, body weight loss was associated with increased risk of ESCC, and body weight gain was associated with decreased incidence of ESCC (ORs ranging from 0.40 to 0.76). Notably, however, changes in body weight did not significantly affect ESCC risk among participants who were overweight, obese, or larger than body shape 3. Maintaining a fit body shape and a reasonable BMI is advisable and of vital importance to reduce the risk of ESCC, especially in high‐risk areas.

Objectives An altered microbiota, which can be described quantitatively, has been identified as playing a pivotal role in host vascular physiology, and it may contribute to various diseases. The aim of this study was to better understand the role of the gut microbiota in vascular physiology in a subclinical elderly population, and to investigate how lifestyle affects the composition of host gut microbiota to further impact the pathogenesis of vascular diseases. Methods We performed a population-based faecal metagenomic study over 569 elderly asymptomatic subclinical individuals in rural China. An association network was built based on clinical measurements and detailed epidemiologic questionnaires, including blood chemistry, arterial stiffness, carotid ultrasonography, and metagenomic datasets. Results By analyzing the breadth, depth and impact of each node of the association network, we found carotid arterial atherosclerosis indices, including intima-media thickness (IMT), were essential in the network, and were significantly associated with living habits, socio-economic status, and diet. Using mediation analysis, we found that higher frequency of eating fresh fruits and vegetables, and more exercise significantly reduced carotid atherosclerosis in terms of IMT, peak systolic velocity and end-diastolic velocity values through the mediation of Alistepes, Oligella and Prevotella. Gut microbes explained 16.5% of the mediation effect of lifestyle on the pathogenesis of carotid atherosclerosis. After adjustment, Faecalicatena [odds ratio (OR) = 0.12 ∼0.65] was shown to be protective against the formation of carotid atherosclerosis, independently, while Libanicoccus (OR = 1.46 ∼4.20 ) was associated with increased carotid arterial IMT. KEGG/KO Kyoto Encyclopedia of Genes and Genomes/ KEGG Orthology (KEGG/KO) analyses revealed a loss of anti-inflammation function in IMT subjects. Conclusion Our study revealed a Chinese population–wide phenotype–metagenomic association network and a mediation effect of gut microbiota on carotid artery atherosclerosis, hinting at potential therapeutic and preventive uses for microbiota in vascular diseases.

Background Early diagnosis of esophageal squamous cell carcinoma (ESCC) remains a challenge due to the lack of specific blood biomarkers. We aimed to develop a serum multi-protein signature for the early detection of ESCC. Methods We selected 70 healthy controls, 30 precancerous patients, 60 stage I patients, 70 stage II patients and 70 stage III/IV ESCC patients from a completed ESCC case-control study in a high-risk area of China. Olink Multiplex Oncology II targeted proteomics panel was used to simultaneously detect the levels of 92 cancer-related proteins in serum using proximity extension assay. Results We found that 10 upregulated and 13 downregulated protein biomarkers in serum could distinguish the early-stage ESCC from healthy controls, which were validated by the significant dose-response relationships with ESCC pathological progression. Applying least absolute shrinkage and selection operator (LASSO) regression and backward elimination algorithm, ANXA1 (annexin A1), hK8 (kallikrein-8), hK14 (kallikrein-14), VIM (vimentin), and RSPO3 (R-spondin-3) were kept in the final model to discriminate early ESCC cases from healthy controls with an area under curve (AUC) of 0.936 (95% confidence interval: 0.899 ~ 0.973). The average accuracy rates of the five-protein classifier were 0.861 and 0.825 in training and test data by five-fold cross-validation. Conclusions Our study suggested that a combination of ANXA1, hK8, hK14, VIM and RSPO3 serum proteins could be considered as a potential tool for screening and early diagnosis of ESCC, especially with the establishment of a three-level hierarchical screening strategy for ESCC control.

Additional file 1: Table S1. 92 proteins from the Olink multiplex Oncology II panel. Table S2. The general information of selected participants, controls and cases based on different cancer stages. Figure S1. The protein interaction of 23 preliminarily authenticated proteins. Each node represents a protein, and the gene name is marked at the top right of the node. Table S3. Gene ontology enrichment analysis of the identified 23 proteins that were differentially expressed between early ESCC and controls, covering three categories, i.e. molecular function, cellular component, and biological process. Top 5 gene ontologies in each enrichment category were selected. Data were obtained from the online ConsensusPathDB- human interaction network database http://cpdb.molgen.mpg.de/ . Table S4. Pathway enrichment analysis of the identified 23 proteins that were differentially expressed between early ESCC and controls. Top 7 enriched pathway were selected. Data were obtained from the online ConsensusPathDB- human interaction network database http://cpdb.molgen.mpg.de/ . Figure S2. An unsupervised hierarchical clustering analysis of 23 preliminarily authenticated proteins for discriminating early esophageal squamous cell carcinoma (ESCC) from healthy controls. Figure S3. The selection feature of least absolute shrinkage and selection operator (LASSO) via tenfold cross-validation based on area under the ROC curve (AUC). Selection of the tuning parameter (λ) in the LASSO model was via tenfold cross-validation based on minimum standard error. The y-axis indicates AUC. The lower x-axis indicates the log(λ). Numbers along the upper x-axis represent the average number of predictors. Red dots indicate average AUC values for each model with a given λ, and vertical bars through the red dots show the upper and lower values of AUC. The vertical black lines define the optimal values of λ, where the model provides its best fit to the data. Figure S4. A nomogram to predict individual ESCC risk based on the identified five-protein panel.

Additional file 1: Supplementary material. The questionnaire of upper gastrointestinal disease in Taixing, China.

Additional file 3: Table S2. OR with 95%CIs and nomogram points of candidate ESCC risk factors.

Additional file 2: Table S1. The age distribution of local residents in Taixing city and the weight of controls in our data analysis.

Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80–93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93–98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89–98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care., Patients whose disease is diagnosed in its early stages have better outcomes. In this study, the authors develop a non invasive blood test based on circulating tumor DNA methylation that can potentially detect cancer occurrence even in asymptomatic patients.

BackgroundMicrobiomic research has grown in popularity in recent decades. The widespread use of next-generation sequencing technologies, including 16S rRNA gene-based and metagenomic shotgun-based methods, has produced a wealth of microbiome data. At present, most software and analysis workflows for analysis and processing of microbiomic data are command line-based, which requires considerable computing time and makes interaction difficult.ResultsTo provide a command-line free, integrated, user interface friendly and online/local deployable microbiome analysis tool, we developed Microbiome Automated Analysis Workflows (MAAWf). The MAAWf assesses taxonomy, protein-coding genes, metabolic pathways, carbohydrate-active enzymes (CAZy) and antibiotic resistance genes (ARGs) for WMS, and clusters operational taxonomic units, alpha-/beta-diversity and functional annotations for 16S. MAAWf generates similar results to currently popular tools, but the running time was much shorter. MAAWf is freely accessible and source code available at http://www.maawf.com.ConclusionsMAAWf is a visual, integrated, rapid analysis tool that enables remote and local computing of microbiome data.

Background: Early diagnosis of esophageal squamous cell carcinoma (ESCC) remains a challenge due to the lack of specific blood biomarkers. We aimed to develop a serum multi-protein signature for early detection of ESCC. Methods: We selected 70 healthy controls, 30 precancerous patients, 60 stage I patients, 70 stage II patients and 70 stage III/IV ESCC patients from a completed ESCC case-control study in a high-risk area of China. Olink Multiplex Oncology II targeted proteomics panel was used to simultaneously detect the levels of 92 cancer-related proteins in serum using proximity extension assay. Findings: We found that 10 upregulated and 13 downregulated protein biomarkers in serum could distinguish the early ESCC from healthy controls and their serum levels had significant dose-response relationships with ESCC progression. Applying least absolute shrinkage and selection operator (LASSO) regression and backward elimination algorithm, ANXA1 (annexin A1), hK8 (kallikrein-8), hK14(kallikrein-14), VIM (vimentin), and RSPO3 (R-spondin-3) were kept in final model to discriminate early ESCC cases from healthy controls with an area under curve (AUC) of 0.936 (95% confidence interval: 0.899~0.973). The average accuracy rates of the five-protein classifier were 0.861 and 0.825 in training and test data by five-fold cross-validation. Interpretation: Our study suggested that a combination of ANXA1, hK8, hK14, VIM and RSPO3 serum proteins could be considered as a potential tool for screening and early diagnosis of ESCC. Our results, however, need be confirmed in external case-control studies and prospective studies. Funding Statement: This work was supported by National Natural Science Foundation of China (81973116, 91846302, 81573229 and 81502870), National Key Research and Development program of China (2017YFC0907002 and 2017YFC0907003), International S&T Cooperation Program of China (2015DFE32790), European Research Council (682663), Medical and Health Technology Development Plan of Shandong Province (2018WS331). The funding sources had no role in the study design, interpretation of results, writing the manuscript or decision to submit the manuscript for the publication. The corresponding author has full access to all the data and assumes final responsibility for the decision to submit for publication. Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: The study protocol was approved by the Institutional Review Boards of the School of Life Sciences, Fudan University (date: February 19, 2009), Qilu Hospital, Shandong University (date: March 8, 2010), and Stockholm Ethical Vetting Board (2018/357-31). The study was carried out in accordance with the approved protocol, and all participants provided written informed consent.

Two meta-analysis of genome wide association studies identified two variants at adenylate cyclase 5 (ADCY5) associated with type 2 diabetes mellitus, fasting and 2-hour glucose in non-pregnant individuals of European descent. The objective of our study was to explore the role of common variants in ADCY5 on gestational glycemic traits, including plasma glucose, insulin values, β cell function and insulin resistance in the fasted state as well as plasma glucose 1 hour after a 50-gram glucose challenge test among Chinese Han women. Homoeostasis model assessment (HOMA) was used to quantify β cell function (HOMA1-β and HOMA2-β) and insulin resistance (HOMA1-IR and HOMA2-IR). Thirty-five single nucleotide polymorphisms (SNPs) in ADCY5 were genotyped in 929 unrelated Chinese Han women with singleton pregnancies. Three SNPs (rs6797915, rs9856662 and rs9875803) displayed evidence for association with plasma glucose 1 hour after a 50-gram glucose challenge test (P = 0.042, 0.018 and 0.018, respectively), one (rs6777397) displayed evidence for association with HOMA1-β (P = 0.014), and one (rs6762009) displayed evidence for association with HOMA1-IR (P = 0.033). These results provide additional insight into the effects of genetic variation within ADCY5 in glucose metabolism, especially during pregnancy and in non-European descent populations.

The objective of this study was to systemically and comprehensively evaluate the associations between smoking and disease outcomes in patients with ankylosing spondylitis (AS). Information on smoking, clinical features, and sociodemographic characteristics was collected by a questionnaire administered directly to the patient. Group differences were analyzed by t test or chi-square test. Logistic regression analysis was conducted with the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), C-reactive protein, and erythrocyte sedimentation rate as the dependent variables and different stratification of smoking duration, smoking intensity, and cumulative smoking as independent variables. In order to compare our results with previous studies, meta-analysis was performed to calculate standardized mean difference (SMD) for relationship between outcomes and smoking status. A total of 1178 AS patients were analyzed. Compared with non-smokers, the risk of having active disease (BASDAI ≥ 4) was higher in patients who smoked at least 15 years, or 15 cigarettes per day, or 15 pack-years (OR = 1.70 [1.06, 2.73], 1.75 [1.08, 2.82], and 1.97 [1.06, 3.67], respectively); and smokers had increasing risk of BASDAI ≥ 4 with increasing years of smoking, or cigarettes per day, or pack-years (p-trend = 0.010, 0.008 and 0.006, respectively). The risk of having active disease was higher in patients who smoked at least 15 cigarettes per day or 15 pack-years (OR = 1.74 [1.06, 2.84] and 2.89 [1.56, 5.35], respectively), with increasing number of cigarettes per day and pack-years. Smokers had an increased risk of BASFI ≥ 4 (p-trend = 0.040 and 0.007, respectively). By meta-analysis, current, former and ever smokers had significantly higher BASDAI (SMD = 0.34 [0.18, 0.48], 0.10 [0.01, 0.19], and 0.27 [0.20, 0.34], respectively) and BASFI (SMD = 0.35 [0.16, 0.55], 0.30 [0.22, 0.39], and 0.35 [0.21, 0.50], respectively) compared to non-smokers. Smoking is a risk factor for greater disease activity and worse functioning in AS patients.

The aims of this study were to identify candidate pathways associated with serum urate and to explore the genetic effect of those pathways on the risk of gout. Pathway analysis of the loci identified in genome-wide association studies (GWASs) showed that the ion transmembrane transporter activity pathway (GO: 0015075) and the secondary active transmembrane transporter activity pathway (GO: 0015291) were both associated with serum urate concentrations, with PFDR values of 0.004 and 0.007, respectively. In a Chinese population of 4,332 individuals, the two pathways were also found to be associated with serum urate (PFDR = 1.88E-05 and 3.44E-04, separately). In addition, these two pathways were further associated with the pathogenesis of gout (PFDR = 1.08E-08 and 2.66E-03, respectively) in the Chinese population and a novel gout-associated gene, SLC17A2, was identified (OR = 0.83, PFDR = 0.017). The mRNA expression of candidate genes also showed significant differences among different groups at pathway level. The present study identified two transmembrane transporter activity pathways (GO: 0015075 and GO: 0015291) were associations with serum urate concentrations and the risk of gout. SLC17A2 was identified as a novel gene that influenced the risk of gout.

Socioeconomic status (SES) is suspected to influence the risk of esophageal squamous-cell carcinoma (ESCC) in China, however, the evidence is still inconclusive and the selection of SES indicators remains inconsistent. In current study, we examined the association between SES and risk of ESCC based on a population-based case-control study in Taixing, China, with 1298 histopathology-confirmed cases and 1900 controls recruited between October 2010 and September 2013. Data on SES indicators was collected using a structured questionnaire. We constructed a composite wealth score based on the ownership of a series of household appliances and other variables by using multiple correspondence analysis (MCA). We used unconditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of ESCC in association with SES indicators. SES was inversely associated with ESCC risk in current study. Higher education (secondary high school or above vs illiteracy, OR=0.60, 95%CI, 0.41-0.87), larger house area per person (>70 vs 5 years also had a lower ESCC risk. Whereas physical labor (very active vs sedentary, OR=1.69, 95%CI, 1.27-2.26) and larger families (≥6 vs

// Hui Zhang 1, * , Jing Liu 1, * , Zheng Dong 1, * , Yue Ding 2 , Qiaoxia Qian 2 , Jingru Zhou 2 , Yanyun Ma 2 , Zhendong Mei 1 , Xiangxiang Chen 1 , Yuan Li 1 , Ziyu Yuan 3 , Juan Zhang 3 , Yajun Yang 2, 3 , Xingdong Chen 1, 3 , Li Jin 1, 3 , Hejian Zou 4, 5 , Xiaofeng Wang 1, 3 and Jiucun Wang 1, 3, 5 1 State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China 2 Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China 3 Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China 4 Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China 5 Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China * These authors contributed equally to this work Correspondence to: Jiucun Wang, email: jcwang@fudan.edu.cn Xiaofeng Wang, email: xiaofengwang@fudan.edu.cn Keywords: serum urate, total bilirubin, mendelian randomization study Received: August 29, 2016 Accepted: October 03, 2017 Published: October 24, 2017 ABSTRACT Aim: A Mendelian randomization study (MRS) can be linked to a “natural” randomized controlled trial in order to avoid potential bias of observational epidemiology. We aimed to study the possible association between serum urate (SU) and total bilirubin (TBIL) using MRS. Materials and Methods: An observational epidemiological study using ordinary least squares (OLS) regression and MRS using two-stage least square (TLS) regression was conducted to assess the effect of SU on TBIL. The comparison between the OLS regression and the TLS regression was analyzed by the Durbin-Hausman test. If the p value is significant, it suggests that the OLS regression cannot evaluate the relationship between exposure and outcome, and the TLS regression is precise; while if the p value is not significant, there would be no significant difference between the two regressions. Results: A total of 3,753 subjects were analyzed. In OLS regression, there was no significant association between SU and TBIL in all subjects and subgroup analysis (all p > 0.05). However, MRS revealed a negative correlation between SU and TBIL after adjustment for confounders (beta = –0.021, p = 0.010). Further analysis was conducted in different SU subgroups, and results show that elevated SU was associated with a significant reduction in TBIL after adjustment for hyperuricemic subjects (beta = –0.053, p = 0.027). In addition, the results using the Durbin-Hausman test further confirmed a negative effect of SU on TBIL ( p = 0.002 and 0.010, respectively). Conclusions: This research shows for the first time that elevated SU was a potential causal factor in the reduction of TBIL and it provides strong evidence to resolve the controversial association between SU and TBIL.

Elevated plasma glucose levels in pregnancy increase adverse pregnancy outcomes. Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) has been shown to be involved in insulin secretion in pancreatic β cells. In this study, we investigated the impact of genetic variants in CDKAL1 on plasma glucose, insulin values, β cell function and insulin resistance in the fasted state as well as plasma glucose 1 h after the consumption of a 50-g oral glucose load between 24 and 28 weeks of pregnancy among 929 unrelated pregnant Han Chinese women. Seven common variants previously reported to associate with diabetes were genotyped. Insulin resistance and β cell function were assessed by homeostasis model assessment. The genetic impacts were analyzed using analysis of variance and analysis of covariance. The results showed that there was no significant association between any of the seven variants and those gestational glycemic traits. Therefore, this study suggests that the seven common variants in CDKAL1 are not significant factors for the variations of several gestational glycemic traits in the Han Chinese population. However, further well-designed studies with larger sample size, more ethnic groups and more CDKAL1 variants are required to validate the association between CDKAL1 and gestational glycemic traits.

The study aimed to determine whether unique clinical patterns of AS may exist in China, specifically to explore the different clinical manifestations caused by gender, HLA-B27 status, and age at disease onset. The multicenter cross-sectional survey was conducted and 1251 patients were enrolled across China, representing a broad spectrum of Chinese AS patients. The mean age at onset and diagnosis were 29.2 (11.4) and 33.5 (12.6) years, respectively. The male/female ratio was 2.7:1. Acute anterior uveitis (AAU) was experienced in 10.3% of AS patients and 9.1% patients had juvenile-onset AS (JoAS). Men were significantly younger at onset and diagnosis and showed a higher frequency of HLA-B27 positivity, JoAS, and AAU than women. HLA-B27-positive patients had a younger age of onset than HLA-B27-negative patients. HLA-B27-positive patients were nearly three times as likely to develop AAU than negative patients (P = 0.04). JoAS patients had a family history of AS more often than adult-onset AS (AoAS) patients, and 4.9% of JoAS patients underwent surgical treatments, a rate more than six times that of AoAS patients (P = 0.01). Men had higher levels of C-reactive protein than women, as did HLA-B27 positives compared to negative patients, and JoAS compared to AoAS (all P

Distamycin (DST) is a well-characterized DNA minor groove binder with antivirus activity and antitumor potency. Two separate gene clusters (a 28-kb cluster and a 7-kb cluster) have recently been identified to coordinately encode the biosynthetic machinery of DST in Streptomyces netropsis. Here we report a gene cassette, which is linked to the aforementioned smaller dst gene cluster and plays an important role in the self-resistance to DST in S. netropsis. This cassette consists of three uncharacterized genes that might be implicated in DNA replication/repair. Knockout of the cassette led to the decrease in the production of DST, while heterologous expression of part of the cassette in S. lividans made it become resistant to both DST and mitomycin C, another DNA-binding agent. More interestingly, homologs of these three genes were found in genomes of other actinomyces that produce DNA-binding antibiotics, suggesting that a novel common mechanism in addition to pumping may enable these strains to resist the cytotoxic metabolites they produced.

Asymptomatic brain abnormalities are common incidental findings on brain MRI in the elderly population and can be regarded as imaging markers of early stroke and dementia. We initiated the Taizhou Imaging Study (TIS) to examine the prevalence and correlates of incidental findings using brain MRI among an elderly population residing in a rural area of China. A total of 562 individuals, at the age of 55 to 65 years, participated in the TIS study with a response rate of 90%. The prevalence of lacunes, white matter hyperintensity (WMH), cerebral microbleeds (CMB), perivascular space, and intracranial arterial stenosis was 26.69%, 10.68%, 18.51%, 27.76%, and 12.81%, respectively. Age and hypertension were the major correlates of these incidental findings. Per each year increase in age, the risks of WMH and CMB increased by 15% and 14%. Compared to individuals with normal blood pressure, individuals with hypertension had an increased risk of all incidental findings, with the adjusted odds ratios of 2.28 to 5.45. Correlations of age, gender and body mass index with brain gray matter fraction were also observed. The high prevalence of these findings indicates a need of preventative strategy to help prevent future stroke and dementia in this population.

Background Cerebral microbleeds (CMBs) are considered to be risk factors for cognitive dysfunction. The specific pathology and clinical manifestations of CMBs are different based on their locations. We investigated the association between CMBs at different locations and cognitive dysfunction and explored the potential underlying pathways in a rural Han Chinese population. Methods We used baseline data from 562 community-dwelling adults (55–65 years old) in the Taizhou Imaging Study between 2013 and 2015. All individuals underwent multimodal brain magnetic resonance imaging (MRI) and 444 subjects completed neuropsychological tests: the Mini-Mental Status Examination and the Montreal Cognitive Assessment. Multinomial logistic regression was used to estimate the association between CMBs and cognitive dysfunction. The volume of brain regions and white matter microstructure were analyzed using Freesurfer and tract-based spatial statistics, respectively. Results CMBs were detected in 104 individuals (18.5%) in our study. Multinomial logistic regression found deep/mixed CMBs were associated with global cognitive dysfunction (OR 3.52; 95% CI 1.21 to 10.26), whereas lobar CMBs (OR 1.76; 95% CI 0.56 to 5.53) were not. Quantification of multimodal brain MRI showed that deep/mixed CMBs were accompanied by decreased thalamic volume and loss of fractional anisotropy of bilateral anterior thalamic radiations. Conclusion Deep/mixed CMBs were associated with cognitive dysfunction in this Chinese cross-sectional study. Disruption of thalamocortical connectivity might be a potential pathway underlying this relationship., Highlights • Cerebral microbleeds (CMBs) are found in 18.5% of middle-aged Chinese population. • Deep/mixed CMBs, not lobar CMBs, are associated with cognitive dysfunction. • Atrophy and fiber connectivity disruption might be the underlying neural pathways.

To further examine the association between oral hygiene and esophageal squamous cell carcinoma (ESCC) risk and the effect modification of other exposures, we conducted a population-based case-control study between 2010 and 2012 in Taixing, China, a high-risk area for ESCC. Cases were primarily recruited from endoscopy units at local hospitals, supplemented by linkage to the local Cancer Registry. Control subjects were frequency matched to cases by sex and age (5-year groups) and were randomly selected from the Taixing Population Registry. For the current analysis, data from 616 histopathologically confirmed cases and 770 controls with complete information on oral hygiene were analyzed. Unconditional logistic regression models, including oral hygiene indicators and potential behavioral confounders, were used to derive odds ratios (ORs) and 95% confidence intervals (CIs). Tooth loss was only marginally significantly associated with ESCC risk (yes vs no, OR=1.29, 95% CI 0.94-1.74). However, the excess risk increased with increasing numbers of lost teeth (more than 6 teeth lost vs none, OR=1.48, 95% CI 1.04-2.11). Tooth brushing once or less per day, compared with tooth brushing twice or more per day, was associated with a 1.81-fold increased risk of ESCC. In the stratification analyses, the increased risks associated with these indicators of oral health were more pronounced in older subjects (age ≥ 70 years), women, non-smokers, and non-drinkers. Further studies are warranted to verify these findings and to explore the underlying mechanisms, e.g., changed oral microbiota, associated with poor oral hygiene. This article is protected by copyright. All rights reserved.

Xiaorong Yang,1,2 Yingchun Ni,2 Ziyu Yuan,3,4 Hui Chen,1 AmeliePlymoth,5 Li Jin,3,4 Xingdong Chen,3,4 Ming Lu,1,2,4 Weimin Ye4,5 1Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China; 2Department of Epidemiology, School of Public Health, Shandong University, Jinan, China; 3State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China; 4Fudan University Taizhou Institute of Health Sciences, Taizhou, China; 5Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Background: Previous studies on the association between green tea drinking and esophageal squamous cell carcinoma (ESCC) risk show inconsistent results.Materials and methods: We conducted a large population-based case–control study from 2010 to 2013 in a high-risk area of China, in which 1,355 ESCC cases and 1,962 controls were recruited. Information on lifelong tea drinking was collected via face-to-face interviews using an electronic structured questionnaire. ORs with 95% CIs were estimated using unconditional logistic regression models.Results: Most tea drinkers were males and consumed exclusively green tea. After adjustment for potential confounders, among men the OR of ever green tea drinking for ESCC risk was 1.52 (95% CI: 1.24–1.85), compared with never tea drinking. The excess risk increased monotonically with earlier age at starting, longer duration, more intensity, and accumulation of tea drinking. The OR of drinking very hot green tea for ESCC risk was 2.15 (95% CI: 1.52–3.05), compared with never drinking tea. For accumulation of tea drinking and the risk of ESCC, a non-linear relationship was observed. Before the accumulation of tea drinking reached 5 L/day*years, drinking tea showed a mild protective effect; then the ORs sharply increased to around 2.0 from 5 L/day*years to 25 L/day*years, and leveled off thereafter. The non-linear relationship was further modified by tea temperature. The joint effect of tea drinking and alcohol consumption on ESCC risk was also significant (P=0.019).Conclusion: Very hot tea drinking significantly increases the risk of ESCC among Chinese men, which is particularly evident among alcohol drinkers. Keywords: green tea, high temperature, esophageal squamous cell carcinoma, risk factor, case–control studyA Letter to the Editor has been received and published for this article.&nbsp

Introduction Studies have reported alcohol consumption and genetic variants as major contributing factors for esophageal squamous cell carcinoma (ESCC). However, the complicated interactions between alcohol and genetic factors involved in alcohol metabolism have not been well elucidated with respect to augmented risk of ESCC. Methods We performed a large population-based case-control study in a Chinese city with a high ESCC incidence by enrolling 1190 case patients and 1883 controls. We integrated candidate single-nucleotide polymorphism data, detailed alcohol consumption records, gene-alcohol interactions, and single-nucleotide polymorphism functional information to untangle the complicated relationship between alcohol, variants of genes encoding alcohol metabolism enzymes, and ESCC risk. The gene-alcohol interaction was tested by including their product term in a multivariable logistic regression model. Synergy index and ratio of ORs were calculated to assess interaction on additive and multiplicative scale, respectively. Results We confirmed two ESCC susceptibility loci, rs671 in aldehyde dehydrogenase 2 family member gene (ALDH2) and rs1042026 in alcohol dehydrogenase 1B (class I), beta polypeptide gene (ADH1B), that significantly altered alcohol consumption behavior and subsequently modified the association between alcohol consumption and ESCC risk. The rs671(A) allele was associated with ESCC risk in alcohol drinkers (adjusted odds ratio =1.98, 95% confidence interval [CI]: 1.51–2.60) but not in nondrinkers. Healthy individuals who carry different ALDH2 and ADH1B genotypes exhibit diversified drinking behavior, with the proportion of drinkers varying between 23.7% and 54.3%. Among individuals with a fast ethanol oxidization rate, we observed a strong interaction between heavy alcohol consumption and ethanal oxidization rate on both the additive scale (synergy index 4.80 [95% CI: 1.82–12.68]) and the multiplicative scale (ratio of ORs 2.93, 95% CI: 1.39–6.35). Conclusions Our observation highlights the need for preventing excessive use of alcohol, especially in individuals harboring active alcohol dehyrogenase and inactive ALDH2 variants.

Objectives: Loss of bone mass may affect the progression of atherosclerosis. We investigated the relationship between low bone mineral density (BMD) and subclinical atherosclerosis in rural China. Methods: In total, 333 men and 421 postmenopausal women aged 55–65 years were enrolled. BMD was measured in the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. Subclinical atherosclerosis was defined as increased carotid artery intima-media thickness (CIMT ≥0.9 mm), the presence of carotid plaques, high brachial-ankle pulse wave velocity (baPWV ≥1,400 cm/s), and low ankle-brachial index (ABI ≤1). Binary logistic regression analyses were used to estimate the association between low BMD and subclinical atherosclerosis. Results: There was no significant difference in BMD between the normal group and the subclinical atherosclerosis group. After full adjustment for the relevant covariates, a boundary significant association was found between low BMD in the femoral neck and baPWV in postmenopausal women (odds ratio = 1.77, p = 0.049). After full adjustment, neither BMD nor low BMD were significantly associated with subclinical atherosclerosis in men or postmenopausal women. Conclusions: Low BMD is not associated with subclinical atherosclerosis in Chinese individuals aged 55–65 years resident in rural China.

Background: Asymptomatic brain abnormalities are common incidental findings on brain MRI in the elderly population and can be regarded as imaging markers of early stroke and dementia. We initiated the Taizhou Imaging Study (TIS) to examine the prevalence and correlates of incidental findings using brain MRI among an elderly population residing in a rural area of China. Methods: A total of 562 individuals, at the age of 55 to 65 years, participated in the TIS study with a response rate of 90%. The primary findings included lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMB), perivascular space (PVS), intracranial arterial stenosis (ICAS), and others (venous angioma, etc.). The brain parenchymal fraction and the brain gray matter fraction (BGMF) were also estimated. Findings: The prevalence of lacunes, WMH, CMB, PVS, and ICAS was 26.69%, 10.68%, 18.51%, 27.76%, and 12.81%, respectively. Age and hypertension were the major correlates of these incidental findings. Per each year increase in age, the risks of WMH and CMB increased by 15% and 14%. Compared to individuals with normal blood pressure, individuals with hypertension had an increased risk of all incidental findings, with the adjusted odds ratios of 2.28 to 5.45. Correlations of age, gender and BMI with BGMF were also observed. Interpretation: The prevalence of MRI incidental findings was high in the rural Chinese population at the age of 55-65 years. The high prevalence of these findings indicates a need of preventative strategy to help prevent future stroke and dementia in this population. Funding: The project was supported by the International Science and Technology Cooperation Program of China (grant number: 2014DFA32830), the Key Research and Development Plans of Jiangsu Province (grant number: BE2016726), the key basic research grants from Science and Technology Commission of Shanghai Municipality (grant number: 16JC1400500), the Karolinska Institutet (Senior Researcher Award and Strategic Research Area in Epidemiology), and the National Key Research and Development program of China (grant number: 2017YFC0907002, 2017YFC0907501). Declaration of interests: We declare no competing interests. Ethical Approval Statement: This study was approved by the Human Ethics Committee of School of Life Sciences of Fudan University (number of Institutional Review Board approval: 469).

Previous results regarding the associations between esophageal squamous-cell carcinoma (ESCC) risk and smoking/alcohol drinking in high-risk areas are inconsistent. We performed a large population-based case-control study from 2010 to 2013 in a high-incidence area of China, and enrolled 1353 ESCC cases and 1961 controls. Data regarding smoking and alcohol drinking were collected via face-to-face interviews using a structured questionnaire. Odd ratios (ORs) with 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. After adjusting for alcohol drinking and other potential confounders, male heavy smokers (i.e., those who started smoked more than 20 cigarettes per day or 40 pack-years, or started smoking early), showed a moderately increased risk for ESCC; however, current smoking was not associated with an increased risk. Alcohol drinking among males significantly increased the risk for ESCC (OR = 2.20, 95%CI:1.79~2.70). We observed increasing excess ESCC risks with decreasing age at behavior initiation as well as with increasing duration and intensity of alcohol intake, which were particularly evident among current smokers. In contrast, neither smoking nor alcohol drinking was not associated with ESCC risk among females. In conclusion, alcohol drinking shows a monotonic dose-response relationship with ESCC risk among men, and this relationship is particularly evident among smokers.

Traffic-related air pollution is known to be associated with skin aging manifestations. We previously found that the use of fossil fuels was associated with skin aging, but no direct link between indoor air pollutants and skin aging manifestations has ever been shown. Here we directly measured the indoor PM2.5 exposure in 30 households in Taizhou, China. Based on the directly measured PM2.5 exposure and questionnaire data of indoor pollution sources, we built a regression model to predict the PM2.5 exposure in larger datasets including an initial examination group (N = 874) and a second examination group (N = 1003). We then estimated the association between the PM2.5 exposure and skin aging manifestations by linear regression. In the initial examination group, we showed that the indoor PM2.5 exposure levels were positively associated with skin aging manifestation, including score of pigment spots on forehead (12.5% more spots per increase of IQR, P-value 0.0371), and wrinkle on upper lip (7.7% more wrinkle on upper lip per increase of IQR, P-value 0.0218). The results were replicated in the second examination group as well as in the pooled dataset. Our study provided evidence that the indoor PM2.5 exposure is associated with skin aging manifestation in a Chinese population.

High levels of serum uric acid can predict the progression of stage I and II chronic kidney disease (CKD), but whether serum urate is an independent risk factor or has causal impact on serum creatinine (SCr) and renal function remains unclear. Mendelian randomization was used to determine whether serum uric acid had a causal effect on renal function, represented by estimated glomerular filtration rate (eGFR), with potential confounding factors, in 3734 subjects from the Taizhou Longitudinal Study. In the two-stage least squares method of Mendelian randomization, serum uric acid level was selected as the exposure, genetic risk score of uric acid transporters was selected as the instrumental variable, and SCr and eGFR were selected as the outcomes. The result of the analysis showed that increased serum uric acid was not a causal effect on renal function, but it was a causal effect on reducing estimated glomerular filtration rate in both the female population and the subjects who were under 65 years old. We also found that increased serum uric acid levels led to impaired renal function only in the subjects with normal eGFR values. In addition, the serum uric acid was a risk factor for renal function in the subjects with relatively high levels of fasting glucose or who were currently smokers. Although serum urate is not an independent risk factor for renal dysfunction, it has a causal effect on renal dysfunction in either female or individuals of under 65, or normal eGFR, or high level of fasting glucose, or current smokers.

Recent studies suggested that maternal and placental leptin receptor (LEPR) may be involved in maternal glucose metabolism in pregnancy. To identify maternal and fetal LEPR common variants influencing gestational glycemic traits, we performed association study of 24-28-week maternal fasting glucose, glucose 1 hour after the consumption of a 50-g oral glucose load, fasting insulin and indices of beta-cell function (HOMA-β) and insulin resistance (HOMA-IR) in 1,112 unrelated women and their children. Follow-up of 36 LEPR loci identified 3 maternal loci (rs10889567, rs1137101 and rs3762274) associated with fasting glucose, these 3 fetal loci associated with fasting insulin and HOMA1-IR, as well as these 3 maternal-fetal loci combinations associated with HOMA2-β. We also demonstrated association of maternal locus rs7554485 with HOMA2-β and HOMA2-IR, maternal locus rs10749754 with fasting glucose, fetal locus rs10749754 with HOMA2-IR. However, these associations were no longer statistically significant after Bonferroni correction. In conclusion, our results first revealed multiple associations between maternal and fetal LEPR common variants and gestational glycemic traits. These associations did not survive Bonferroni correction. These corrections are overly conservative for association studies. We therefore believe the influence of these nominally significant variants on gestational glycometabolism will be confirmed by additional studies.

To further examine the association between oral hygiene and esophageal squamous cell carcinoma (ESCC) risk and the effect modification of other exposures, we conducted a population-based case-control study between 2010 and 2012 in Taixing, China, a high-risk area for ESCC. Cases were primarily recruited from endoscopy units at local hospitals, supplemented by linkage to the local Cancer Registry. Control subjects were frequency matched to cases by sex and age (5-year groups) and were randomly selected from the Taixing Population Registry. For the current analysis, data from 616 histopathologically confirmed cases and 770 controls with complete information on oral hygiene were analyzed. Unconditional logistic regression models, including oral hygiene indicators and potential behavioral confounders, were used to derive odds ratios (ORs) and 95% confidence intervals (CIs). Tooth loss was only marginally significantly associated with ESCC risk (yes vs. no, OR = 1.29, 95% CI 0.94-1.74). However, the excess risk increased with increasing numbers of lost teeth (more than 6 teeth lost vs. none, OR = 1.48, 95% CI 1.04-2.11). Tooth brushing once or less per day, compared with tooth brushing twice or more per day, was associated with a 1.81-fold increased risk of ESCC. In the stratification analyses, the increased risks associated with these indicators of oral health were more pronounced in older subjects (age ≥ 70 years), women, non-smokers, and non-drinkers. Further studies are warranted to verify these findings and to explore the underlying mechanisms, e.g., changed oral microbiota, associated with poor oral hygiene.

The aim of this study is to investigate the relationship between sleep duration and hypertension in a middle-aged Chinese population. Cross-sectional data of 20,505 individuals aged 35–64 years from Taizhou longitudinal study was used. Logistic regression models were used to calculate odds ratios (ORs) for the risk of pre-hypertension and hypertension in association with sleep duration. Short sleep duration was associated with high systolic and diastolic blood pressure in comparison with sleep duration of 7–8 h in females. Short sleep duration was also associated with an increased risk of hypertension in females. Age-stratified analysis showed that as compared with sleep duration of 7–8 h, sleep duration

There are controversies in reports on the association of the angiotensinogen (AGT) gene polymorphisms with the risk of developing pre-eclampsia (PE). We performed a meta-analysis to examine the association between the AGT polymorphisms and PE risk: M235T (31 studies involving 2555 patients and 6114 controls) and T174M (six studies involving 681 patients and 2076 controls). For the M235T polymorphism, the TT genotype increased the PE risk as compared to the MM genotype (odds ratio 1.61, 95% confidence intervals 1.22-2.14, P= 0.001). When stratified by ethnicity, the TT genotype remained significantly associated with higher PE risk in Caucasians and Mongolians but not in Africans. Similar results were also obtained under all three genetic models of the M235T polymorphism. For the T174M polymorphism, no significant association was found in the comparisons (MT vs. TT and MM vs. TT) and under any genetic models. The analysis excluding the highly significant Hardy-Weinberg equilibrium-violating studies and sensitivity analysis further strengthened the validity of these associations. No publication bias was observed in this study. This meta-analysis demonstrates that the AGT M235T polymorphism is significantly associated with PE whereas the T174M polymorphism is not.

Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC). We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3-V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of each genus was compared by means of multivariate-adjusted odds ratios derived from logistic regression model. Relative abundance was compared using Metastats method. Beta diversity was estimated using Unifrac and weighted Unifrac distances. Principal coordinate analysis (PCoA) was applied to ordinate dissimilarity matrices. Multinomial logistic regression was used to compare the coordinates between different groups. ESCC subjects had an overall decreased microbial diversity compared to control and dysplasia subjects (P

A population-based case-control was performed to explore familial aggregation of esophageal squamous cell carcinoma (ESCC). Family history of cancer was assessed by a structured questionnaire and from which 2 cohorts of relatives of cases and controls were reconstructed. Unconditional logistic regression and Cox proportional hazards regression were applied for case-control design and reconstructed cohort design, respectively. We observed a close to doubled risk of ESCC associated with a positive family history of esophageal cancer among first degree relatives (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.42–2.41), after adjusting age, sex, family size and other confounders. The excess risks of ESCC increased with the increasing of first-degree relatives affected by esophageal cancer (p

To study the relationship between socioeconomic status (SES) and esophageal squamous cell carcinoma (ESCC) in Taixing city,Jiangsu province.A population-based case-control study was carried out to collect data including demography, socioeconomic status indicators and possible risk factors. Unconditional logistic regression was used to compare different SES indicators and composite wealth scores constructed between cases and controls, using the principal component analysis methodology.Factors as:having received high school or higher education (OR = 0.66, 95% CI:0.46-0.96), living space over 67 m2 per-capita (OR = 0.71, 95% CI: 0.54-0.94), drinking tap water longer than 5 years (OR = 0.76, 95% CI:0.59-0.98) and wealth score0.93 (OR = 0.63, 95%CI:0.48-0.83)were associated with increased risk of ESCC. Compared to those worked in farming, forestry, animal husbandry, fishery and water conservancy, the individuals who worked in business-service industry were at lower risk of ESCC(OR = 0.65, 95%CI:0.43-0.97).An inverse association of low SES and ESCC were found in Taixing people that called for further explanation.

There are controversies in reports on the association of the angiotensinogen (AGT) gene polymorphisms with the risk of developing pre-eclampsia (PE). We performed a meta-analysis to examine the association between the AGT polymorphisms and PE risk: M235T (31 studies involving 2555 patients and 6114 controls) and T174M (six studies involving 681 patients and 2076 controls). For the M235T polymorphism, the TT genotype increased the PE risk as compared to the MM genotype (odds ratio 1.61, 95% confidence intervals 1.22-2.14, P= 0.001). When stratified by ethnicity, the TT genotype remained significantly associated with higher PE risk in Caucasians and Mongolians but not in Africans. Similar results were also obtained under all three genetic models of the M235T polymorphism. For the T174M polymorphism, no significant association was found in the comparisons (MT vs. TT and MM vs. TT) and under any genetic models. The analysis excluding the highly significant Hardy-Weinberg equilibrium-violating studies and sensitivity analysis further strengthened the validity of these associations. No publication bias was observed in this study. This meta-analysis demonstrates that the AGT M235T polymorphism is significantly associated with PE whereas the T174M polymorphism is not.