We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
Comparative genome sequencing of indica and japonica rice reveals that duplication of genes and genomic regions has played a major part in the evolution of grass genomes
Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we used uniquely mapped reads to assemble a high-quality consensus sequence for 92% of the Asian individual's genome. We identified approximately 3 million single-nucleotide polymorphisms (SNPs) inside this region, of which 13.6% were not in the dbSNP database. Genotyping analysis showed that SNP identification had high accuracy and consistency, indicating the high sequence quality of this assembly. We also carried out heterozygote phasing and haplotype prediction against HapMap CHB and JPT haplotypes (Chinese and Japanese, respectively), sequence comparison with the two available individual genomes (J. D. Watson and J. C. Venter), and structural variation identification. These variations were considered for their potential biological impact. Our sequence data and analyses demonstrate the potential usefulness of next-generation sequencing technologies for personal genomics.
Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10−8, and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19–1.40) and P= 7.63 × 10−10. An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
It is evident that epigenetic factors, especially DNA methylation, play essential roles in obesity development. Using pig as a model, here we investigated the systematic association between DNA methylation and obesity. We sampled eight variant adipose and two distinct skeletal muscle tissues from three pig breeds living within comparable environments but displaying distinct fat level. We generated 1,381 gigabases (Gb) of sequence data from 180 methylated DNA immunoprecipitation (MeDIP) libraries, and provided a genome-wide DNA methylation map as well as a gene expression map for adipose and muscle studies. The analysis showed global similarity and difference among breeds, sexes and anatomic locations, and identified the differentially methylated regions (DMRs). The DMRs in promoters are highly associated with obesity development via expression repression of both known obesity-related genes and novel genes. This comprehensive map provides a solid basis for exploring epigenetic mechanisms of adipose deposition and muscle growth.
Information on the health-related quality of life (HRQoL) of patients with genital warts (GW) in populations in mainland China is still limited. The aim of the study was to use a generic instrument to measure the impact of genital warts on HRQoL in men and women in this setting.
A multi-centre hospital-based cross-sectional study across 18 centers in China was conducted to interview patients using the European quality of life-5 dimension (EQ-5D) instrument; respondents' demographic and clinical data were also collected.
A total of 1,358 GW patients (612 men, 746 women) were included in the analysis, with a mean age of 32.0 ± 10.6 years. 56.4% of the patients reported some problems in the dimension of Anxiety/Depression (highest), followed by Pain/Discomfort (24.7%) and Mobility (3.5%). The overall visual analogue scale (VAS) score of the study population was found to be 65.2 ± 22.0, and the EQ-5D index score was found to be 0.843 ± 0.129 using Japanese preference weights (the Chinese preference was unavailable yet). Patients with lower VAS means and EQ-5D index scores were more often female, living in urban area, and suffering multiple GW (all p values < 0.05), but the values did not differ notably by age (p values > 0.05).
The HRQoL of patients with GW was substantially lower, compared to a national representative general population in China (VAS = ~80); the findings of different subgroups are informative for future GW prevention and control efforts.
The polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is dysregulated in various cancers, and its upregulation strongly correlates with an invasive phenotype and poor prognosis in patients with nasopharyngeal carcinomas. However, the underlying mechanism of Bmi-1–mediated invasiveness remains unknown. In the current study, we found that upregulation of Bmi-1 induced epithelial-mesenchymal transition (EMT) and enhanced the motility and invasiveness of human nasopharyngeal epithelial cells, whereas silencing endogenous Bmi-1 expression reversed EMT and reduced motility. Furthermore, upregulation of Bmi-1 led to the stabilization of Snail, a transcriptional repressor associated with EMT, via modulation of PI3K/Akt/GSK-3β signaling. Chromatin immunoprecipitation assays revealed that Bmi-1 transcriptionally downregulated expression of the tumor suppressor PTEN in tumor cells through direct association with the PTEN locus. This in vitro analysis was consistent with the statistical inverse correlation detected between Bmi-1 and PTEN expression in a cohort of human nasopharyngeal carcinoma biopsies. Moreover, ablation of PTEN expression partially rescued the migratory/invasive phenotype of Bmi-1–silenced cells, indicating that PTEN might be a major mediator of Bmi-1–induced EMT. Our results provide functional and mechanistic links between the oncoprotein Bmi-1 and the tumor suppressor PTEN in the development and progression of cancer.
Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18X per individual. Genes showing population-specific allele frequency changes, which represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from EPAS1, a transcription factor involved in response to hypoxia. One SNP at EPAS1 shows a 78% frequency difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP’s association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus in genetic adaptation to high altitude.
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
LC3; autolysosome; autophagosome; flux; lysosome; phagophore; stress; vacuole
AIM: To determine whether and how magnetic resonance imaging (MRI)-based total liver volume (TLV) and diffusion weighted imaging (DWI) could predict liver fibrosis.
METHODS: Sixteen experimental mature mini-pigs (6 males, 10 females), weighing between 20.0 and 24.0 kg were prospectively used to model liver fibrosis induced by intraperitoneal injection of 40% CCl4 dissolved in fat emulsion twice a week for 16 wk, and by feeding 40% CCl4 mixed with maize flour twice daily for the subsequent 5 wk. All the survival animals underwent percutaneous liver biopsy and DWI using b = 300, 500 and 800 s/mm2 followed by abdominal gadolinium-enhanced MRI at the 0, 5th, 9th, 16th and 21st weekend after beginning of the modeling. TLV was obtained on enhanced MRI, and apparent diffusion coefficient (ADC) was obtained on DWI. Hepatic tissue specimens were stained with hematoxylin and Masson’s trichrome staining for staging liver fibrosis. Pathological specimens were scored using the human METAVIR classification system. Statistical analyses were performed to determine whether and how the TLV and ADC could be used to predict the stage of liver fibrosis.
RESULTS: TLV increased from stage 0 to 2 and decreased from stage 3 (r = 0.211; P < 0.001). There was a difference in TLV between stage 0-1 and 2-4 (P = 0.03) whereas no difference between stage 0-2 and 3-4 (P = 0.71). TLV could predict stage ≥ 2 [area under receiver operating characteristic curve (AUC) = 0.682]. There was a decrease in ADC values with increasing stage of fibrosis for b = 300, 500 and 800 s/mm2 (r = -0.418, -0.535 and -0.622, respectively; all P < 0.001). Differences were found between stage 0-1 and 2-4 in ADC values for b = 300, 500 and 800 s/mm2, and between stage 0-2 and 3-4 for b = 500 or 800 s/mm2 (all P < 0.05). For predicting stage ≥ 2 and ≥ 3, AUC was 0.803 and 0.847 for b = 500 s/mm2, and 0.848 and 0.887 for b = 800 s/mm2, respectively.
CONCLUSION: ADC for b = 500 or 800 s/mm2 could be better than TLV and ADC for b = 300 s/mm2 to predict fibrosis stage ≥ 2 or ≥ 3.
Magnetic resonance imaging; Total liver volume; Liver fibrosis; Apparent diffusion coefficient; Stage
To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million nonredundant microbial genes, derived from 576.7 Gb sequence, from faecal samples of 124 European individuals. The gene set, ~150 times larger than the human gene complement, contains an overwhelming majority of the prevalent microbial genes of the cohort and likely includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, suggesting that the entire cohort harbours between 1000 and 1150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions encoded by the gene set.
Artificial selection played an important role in the origin of modern Glycine max cultivars from the wild soybean Glycine soja. To elucidate the consequences of artificial selection accompanying the domestication and modern improvement of soybean, 25 new and 30 published whole-genome re-sequencing accessions, which represent wild, domesticated landrace, and Chinese elite soybean populations were analyzed.
A total of 5,102,244 single nucleotide polymorphisms (SNPs) and 707,969 insertion/deletions were identified. Among the SNPs detected, 25.5% were not described previously. We found that artificial selection during domestication led to more pronounced reduction in the genetic diversity of soybean than the switch from landraces to elite cultivars. Only a small proportion (2.99%) of the whole genomic regions appear to be affected by artificial selection for preferred agricultural traits. The selection regions were not distributed randomly or uniformly throughout the genome. Instead, clusters of selection hotspots in certain genomic regions were observed. Moreover, a set of candidate genes (4.38% of the total annotated genes) significantly affected by selection underlying soybean domestication and genetic improvement were identified.
Given the uniqueness of the soybean germplasm sequenced, this study drew a clear picture of human-mediated evolution of the soybean genomes. The genomic resources and information provided by this study would also facilitate the discovery of genes/loci underlying agronomically important traits.
Artificial selection; Evolution; Genetic diversity; Population genomics; Soybean
Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8+, but not CD4+ T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.
Classical swine fever virus (CSFV) can evade the immune response and establish chronic infection under natural and experimental conditions. Some genes related to antigen processing and presentation and to cytokine regulation are known to be involved in this response, but the precise mechanism through which each gene responds to CSFV infection remains unclear.
In this study, the amplification standard curve and corresponding linear regression equations for the genes SLA-2, TAP1, SLA-DR, Ii, CD40, CD80, CD86, IFN-α, and IFN-β were established successfully. Real-time RT-PCR was used to quantify the immune response gene transcription in PK-15 cells post CSFV infection. Results showed that: (1) immune response genes were generally down-regulated as a result of CSFV infection, and (2) the expression of SLA-2, SLA-DR, Ii and CD80 was significantly decreased (p<0.001).
We conclude that in vitro infection with CSFV inhibits the transcription of host immune response genes. These findings may facilitate the development of effective strategies for controlling CSF.
Classical swine fever virus (CSFV); Immune response genes; Real-time RT-PCR
Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×10−19) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×10−8), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×10−4; rs455804: OR = 0.84, P = 6.92×10−3). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC.
Previous studies strongly suggest the importance of genetic susceptibility for hepatocellular carcinoma (HCC). However, the studies about genetic etiology on HBV–related HCC were limited. Our genome-wide association study included 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers for the discovery analysis. 2,112 HBV–positive HCC cases and 2,208 HBV carriers (the initial validation), and 1,021 cases and 1,491 HBV carriers (the second validation), were then analyzed for validation. The fourth independent samples of 1,298 cases and 1,026 controls were analyzed as replication. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 and rs455804 (GRIK1) on 21q21.3. HLA-DRB1 molecules play an important role in chronic HBV infection and progression to HCC. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC.
A recent genome-wide scan has identified two genetic variants in the HLA-DP region strongly associated with hepatitis B infection in Japanese. This study evaluates the effects of these risk variants in Chinese, where the HBV infection is the most popular in the world.
Methods and Findings
We have assessed the relationship between these two single nucleotide polymorphisms (rs3077 and rs9277535) and chronic hepatitis B infection in two independent case-control studies. The first population in Chinese Han included 736 patients and 782 spontaneously recovered controls. The second set was established in Chinese Zhuang minority of 177 patients and 208 controls. Both A alleles of rs3077 and rs9277535 significantly deceased the risk to CHB in Chinese Han (OR = 0.540, 95%CI: 0.464–0.628, P = 4.068×10−16 and OR = 0.696, 95%CI: 0.601–0.806, P = 1.062×10−6, respectively). Conceivably, rs9277535 was found to be associated with decreased risk of the disease in Chinese Zhuang, with an OR of 0.606 (95%CI, 0.441–0.833, P = 0.002).
Chronic hepatitis B susceptibility loci in HLA-DP region (rs3077 and rs9277535) identified by genome-wide scan in Japanese population were validated in Chinese population. These findings might provide clues to develop screening and surveillance strategies.
Previous studies support Beck's cognitive model of vulnerability to depression. However, the relationship between his cognitive triad and other clinical features and risk factors among those with major depression (MD) has rarely been systematically studied.
The three key cognitive symptoms of worthlessness, hopelessness and helplessness were assessed during their lifetime worst episode in 1970 Han Chinese women with recurrent MD. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression.
Compared to patients who did not endorse the cognitive trio, those who did had a greater number of DSM-IV A criteria, more individual depressive symptoms, an earlier age at onset, a greater number of episodes, and were more likely to meet diagnostic criteria for melancholia, postnatal depression, dysthymia and anxiety disorders. Hopelessness was highly related to all the suicidal symptomatology, with ORs ranging from 5.92 to 6.51. Neuroticism, stressful life events (SLEs) and a protective parental rearing style were associated with these cognitive symptoms.
During the worst episode of MD in Han Chinese women, the endorsement of the cognitive trio was associated with a worse course of depression and an increased risk of suicide. Individuals with high levels of neuroticism, many SLEs and high parental protectiveness were at increased risk for these cognitive depressive symptoms. As in Western populations, symptoms of the cognitive trio appear to play a central role in the psychopathology of MD in Chinese women.
Cognitive trio; Han Chinese women; major depression; suicide; symptoms
The relationship between suicidality and major depression is complex. Socio- demography, clinical features, comorbidity, clinical symptoms, and stressful life events are important factors influencing suicide in major depression, but these are not well defined. Thus, the aim of the present study was to assess the associations between the above-mentioned factors and suicide ideation, suicide plan, and suicide attempt in 6008 Han Chinese women with recurrent major depression (MD). Patients with any suicidality had significantly more MD symptoms, a significantly greater number of stressful life events, a positive family history of MD, a greater number of episodes, a significant experience of melancholia, and earlier age of onset. Comorbidity with dysthymia, generalized anxiety disorder (GAD), social phobia, and animal phobia was seen in suicidal patients. The present findings indicate that specific factors act to increase the likelihood of suicide in MD. Our results may help improve the clinical assessment of suicide risk in depressed patients, especially for women.
To investigate liver lobe volumes and the ratios of liver lobe volumes to spleen volume measured with magnetic resonance imaging (MRI) for quantitatively monitoring and staging liver fibrosis.
Animal study was approved by Institutional Animal Care and Use Committee. Sixteen minipigs were prospectively used to model liver fibrosis, and underwent abdominal gadolinium-enhanced MRI on 0, 5th, 9th, 16th and 21st weekend after modeling this disease staged by biopsy according to METAVIR classification system. On MRI, volume parameters including left lateral liver lobe volume (LLV), left medial liver lobe volume (LMV), right liver lobe volume (RV), caudate lobe volume (CV), and spleen volume (SV) were measured; and LLV/SV, LMV/SV, RV/SV and CV/SV were calculated. Statistical analyses were performed for staging this fibrosis.
LLV and CV increased with increasing stage of fibrosis (r = 0.711, 0.526, respectively; all P < 0.05). RV and LMV increased from stage 0 to 2 and decreased from 2 to 4; and RV/SV decreased from 0 to 1, increased from 1 to 2, and decreased from 3 to 4 (all P > 0.05). LLV/SV, LMV/SV and CV/SV decreased from stage 0 to 4 (r = -0.566, -0.748 and -0.620, respectively; all P < 0.05). LLV, CV, LLV/SV, LMV/SV, RV/SV, and CV/SV could distinguish stage 0–1 from 2–4 and 0–2 from 3–4 (all P < 0.05). Among these parameters, LLV and LMV/SV could best classify stage ≥2 and ≥3, respectively (area under receiver operating characteristic curve = 0.893 and 0.946, respectively).
LLV and LMV/SV complement each other in staging liver fibrosis, and both parameters should be used to stage this disease.
Background Drinking alcohol has a long tradition in Chinese culture. However, data on the prevalence and patterns of alcohol consumption in China, and its main correlates, are limited.
Methods During 2004–08 the China Kadoorie Biobank recruited 512 891 men and women aged 30–79 years from 10 urban and rural areas of China. Detailed information on alcohol consumption was collected using a standardized questionnaire, and related to socio-demographic, physical and behavioural characteristics in men and women separately.
Results Overall, 76% of men and 36% of women reported drinking some alcohol during the past 12 months, with 33% of men and 2% of women drinking at least weekly; the prevalence of weekly drinking in men varied from 7% to 51% across the 10 study areas. Mean consumption was 286 g/week and was higher in those with less education. Most weekly drinkers habitually drank spirits, although this varied by area, and beer consumption was highest among younger drinkers; 37% of male weekly drinkers (12% of all men) reported weekly heavy drinking episodes, with the prevalence highest in younger men. Drinking alcohol was positively correlated with regular smoking, blood pressure and heart rate. Among male weekly drinkers, each 20 g/day alcohol consumed was associated with 2 mmHg higher systolic blood pressure. Potential indicators of problem drinking were reported by 24% of male weekly drinkers.
Conclusion The prevalence and patterns of drinking in China differ greatly by age, sex and geographical region. Alcohol consumption is associated with a number of unfavourable health behaviours and characteristics.
Alcohol; drinking; cohort study; descriptive analysis; China
Some syphilis patients remain in a serologically active state after the recommended therapy. We currently know too little about the characteristics of this serological response.
We conducted a cohort study using the clinical database from Zhongshan Hospital, Medical College of Xiamen. In total, 1,327 HIV-negative patients with primary, secondary, latent, and tertiary syphilis were enrolled. Bivariate and multivariate analyses were utilised to identify factors associated with a serological cure and serofast state in syphilis patients one year after therapy. Chi-square tests were used to determine the differences in the serological cure rate across different therapy time points.
One year after the recommended therapy, 870 patients achieved a serological cure, and 457 patients (34.4%) remained in the serofast state. The serological cure rate increased only within the first 6 months. The bivariate analysis indicated that male or younger patients had a higher likelihood of a serological cure than female or older patients. Having a baseline titre ≤1∶2 or ≥1∶64 was associated with an increased likelihood of a serological cure. The serological cure rate decreased for the different disease stages in the order of primary, secondary, latent, and tertiary syphilis. A distinction should be drawn between early and late syphilis. The multivariate analysis indicated that a serological cure was significantly associated with the disease phase, gender, age, and baseline rapid plasma reagin (RPR) titre.
The serofast state is common in clinical work. After one year of the recommended therapy, quite a few syphilis patients remained RPR positive. The primary endpoint of the study indicated that disease phase, gender, age and baseline RPR titre were crucial factors associated with a serological cure.
In this study, we examined anti-fungal and anti-inflammatory effects of the synthetic melanocortin peptide (Ac-Cys-Lys-Pro-Val-NH2)2 or (CKPV)2 against Candida albicans vaginitis. Our in vitro results showed that (CKPV)2 dose-dependently inhibited Candida albicans colonies formation. In a rat Candida albicans vaginitis model, (CKPV)2 significantly inhibited vaginal Candida albicans survival and macrophages sub-epithelial mucosa infiltration. For mechanisms study, we observed that (CKPV)2 inhibited macrophages phagocytosis of Candida albicans. Meanwhile, (CKPV)2 administration inhibited macrophage pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) release, while increasing the arginase activity and anti-inflammatory cytokine IL-10 production, suggesting macrophages M1 to M2 polarization. Cyclic AMP (cAMP) production was also induced by (CKPV)2 administration in macrophages. These above effects on macrophages by (CKPV)2 were almost reversed by melanocortin receptor-1(MC1R) siRNA knockdown, indicating the requirement of MC1R in the process. Altogether, our results suggest that (CKPV)2 exerted anti-fungal and anti-inflammatory activities against Candida albicans vaginitis probably through inducing macrophages M1 to M2 polarization and MC1R activation.
For years, emerging infectious diseases have appeared worldwide and threatened the health of people. The emergence and spread of an infectious-disease outbreak are usually unforeseen, and have the features of suddenness and uncertainty. Timely understanding of basic information in the field, and the collection and analysis of epidemiological information, is helpful in making rapid decisions and responding to an infectious-disease emergency. Therefore, it is necessary to have an unobstructed channel and convenient tool for the collection and analysis of epidemiologic information in the field.
Baseline information for each county in mainland China was collected and a database was established by geo-coding information on a digital map of county boundaries throughout the country. Google Maps was used to display geographic information and to conduct calculations related to maps, and the 3G wireless network was used to transmit information collected in the field to the server. This study established a decision support system for the response to infectious-disease emergencies based on WebGIS and mobile services (DSSRIDE). The DSSRIDE provides functions including data collection, communication and analyses in real time, epidemiological detection, the provision of customized epidemiological questionnaires and guides for handling infectious disease emergencies, and the querying of professional knowledge in the field. These functions of the DSSRIDE could be helpful for epidemiological investigations in the field and the handling of infectious-disease emergencies.
The DSSRIDE provides a geographic information platform based on the Google Maps application programming interface to display information of infectious disease emergencies, and transfers information between workers in the field and decision makers through wireless transmission based on personal computers, mobile phones and personal digital assistants. After a 2-year practice and application in infectious disease emergencies, the DSSRIDE is becoming a useful platform and is a useful tool for investigations in the field carried out by response sections and individuals. The system is suitable for use in developing countries and low-income districts.
The aim of this study was to determine whether and how the diameter of the vein that gives rise to the inflowing vein of the esophageal and gastric fundic varices secondary to posthepatitic cirrhosis, as measured with multidetector-row computed tomography, could predict the varices and their patterns.
A total of 106 patients with posthepatitic cirrhosis underwent multidetector-row computed tomography. Patients with and without esophageal and gastric fundic varices were enrolled in Group 1 and Group 2, respectively. Group 1 was composed of Subgroup A, consisting of patients with varices, and Subgroup B consisted of patients with varices in combination with portal vein-inferior vena cava shunts. The diameters of the originating veins of veins entering the varices were reviewed and statistically analyzed.
The originating veins were the portal vein in 8% (6/75) of patients, the splenic vein in 65.3% (49/75) of patients, and both the portal and splenic veins in 26.7% (20/75) of patients. The splenic vein diameter in Group 1 was larger than that in Group 2, whereas no differences in portal vein diameters were found between groups. In Group 1, the splenic vein diameter in Subgroup A was larger than that in Subgroup B. A cut-off splenic vein diameter of 8.5 mm achieved a sensitivity of 83.3% and specificity of 58.1% for predicting the varices. For discrimination of the varices in combination with and without portal vein-inferior vena cava shunts, a cut-off diameter of 9.5 mm achieved a sensitivity of 66.7% and specificity of 60.0%.
The diameter of the splenic vein can be used to predict esophageal and gastric fundic varices and their patterns.
Portal Hypertension; Esophageal and Gastric Fundic Varices; Originating Vein; Computed Tomography
AIM: To investigate contrast-enhanced computed tomography (CECT) for discriminating esophageal squamous cell carcinoma (ESCC) from normal esophagus and evaluating outcomes within tumors after chemoradiotherapy (CRT).
METHODS: Sixty-four patients with surgical ESCC served as group A, and underwent thoracic contrast-enhanced scan with 16-section multidetector row CT 1 wk before surgery. Thirty-five patients with advanced ESCC receiving 4-wk CRT and showing response to CRT served as group B, and underwent CT scans similar with group A 4 wk after completion of CRT. In group A, differences in CT attenuation values (in HU) between the preoperative ESCC and background normal esophageal wall (delta CT1), or between different background normal esophageal walls (delta CT2) were compared. Furthermore, delta CT1 between group A and B was also compared.
RESULTS: In group A, mean delta CT1 was higher than delta CT2 (23.86 ± 10.59 HU vs 6.24 ± 3.06 HU, P < 0.05). When a delta CT1 of 10.025 HU was employed at a cut-off value to discriminate ESCC from normal esophagus, a sensitivity of 89.1% and specificity of 90.6% were achieved. Mean delta CT1 was lower in group B than in group A (9.25 ± 10.86 vs 23.86 ± 10.59, P < 0.05), and a delta CT1 of 15.45 HU was obtained at a cut-off value to assess the CRT changes with a sensitivity of 76.6% and specificity of 77.1%.
CONCLUSION: CECT might be a clinical technique for discriminating ESCC from normal esophagus, and evaluating outcome in the tumors treated with CRT.
Esophagus; Squamous cell carcinoma; Multidetector row computed tomography; Attenuation value; Chemoradiotherapy