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Ran Xu

Bio: Ran Xu is an academic researcher. The author has contributed to research in topics: Medicine & Immune system. The author has an hindex of 1, co-authored 1 publications receiving 3910 citations.

Papers
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Journal ArticleDOI
04 Oct 2012-Nature
TL;DR: MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance.
Abstract: Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.

4,981 citations

Journal ArticleDOI
TL;DR: In this article , the authors investigated the use of peripheral blood biomarkers as predictors of patient survival and found that low D-dimer level was significantly associated with better overall survival.
Abstract: The study objective was to investigate the use of peripheral blood biomarkers as predictors of patient survival. The aim of this study was to identify the baseline peripheral blood biomarkers associated with clinical outcome in patients with early lung cancer (stage I-II) treated with surgery.We included and analysed data from 376 patients with early-stage lung cancer who underwent a standard lobectomy. Univariate and multivariate Cox regression analyses were performed on all patients to assess the relationships between progression-free survival (PFS) and overall survival (OS) and the peripheral blood biomarker metrics measured before surgical treatment. The peripheral blood parameters included monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and dimeric fibrin fragment D (D-dimer).After univariate Cox regression analysis, low MLR, low NLR, low PLR and low D-dimer values were significantly associated with both better OS and PFS (all p < 0.05). In multivariate Cox regression analysis, a low MLR was significantly and independently associated with both better overall survival and better progression-free survival (both p <0.05). A low D-dimer level was significantly and independently associated with better overall survival (p <0.05). Furthermore, the categorization of patients according to the number of factors with favourable results revealed that those without favourable results had significantly worse outcomes than that of those patients with at least one.A baseline signature of low MLR, low NLR, low PLR, and low D-dimer values was associated with a better survival outcome for patients treated with surgery. Patients with more favourable results had better survival outcomes.

8 citations

Proceedings ArticleDOI
03 Aug 2022
TL;DR:
Abstract: Text-VQA aims at answering questions that require understanding the textual cues in an image. Despite the great progress of existing Text-VQA methods, their performance suffers from insufficient human-labeled question-answer (QA) pairs. However, we observe that, in general, the scene text is not fully exploited in the existing datasets -- only a small portion of the text in each image participates in the annotated QA activities. This results in a huge waste of useful information. To address this deficiency, we develop a new method to generate high-quality and diverse QA pairs by explicitly utilizing the existing rich text available in the scene context of each image. Specifically, we propose, TAG, a text-aware visual question-answer generation architecture that learns to produce meaningful, and accurate QA samples using a multimodal transformer. The architecture exploits underexplored scene text information and enhances scene understanding of Text-VQA models by combining the generated QA pairs with the initial training data. Extensive experimental results on two well-known Text-VQA benchmarks (TextVQA and ST-VQA) demonstrate that our proposed TAG effectively enlarges the training data that helps improve the Text-VQA performance without extra labeling effort. Moreover, our model outperforms state-of-the-art approaches that are pre-trained with extra large-scale data. Code is available at https://github.com/HenryJunW/TAG.

5 citations

Journal ArticleDOI
TL;DR: This study screened for genes associated with the prognosis of patients with lung adenocarcinoma and positively correlated with antigen-presenting cell infiltration and identified KLRG1 and CBFA2T3 as potential tumor antigens for mRNA vaccines in LUAD, providing a new perspective for mRNA vaccine treatment strategies for LUAD.
Abstract: Cancer vaccines are emerging as a viable strategy for cancer treatment. In the current study, we screened for genes associated with the prognosis of patients with lung adenocarcinoma and positively correlated with antigen-presenting cell infiltration and identified KLRG1 and CBFA2T3 as potential tumor antigens for mRNA vaccines in lung adenocarcinoma (LUAD). Further analyses of immune subtypes revealed that patients with early-stage LUAD, high immune cell infiltration, high immune checkpoint expression, and low tumor mutation burden might benefit from mRNA vaccination. Moreover, we identified four biomarkers that can be used to assess mRNA vaccination suitability. We also identified potentially sensitive anti-cancer drugs for populations not suitable for vaccination by means of anti-cancer drug susceptibility prediction. Overall, we provided a new perspective for mRNA vaccine treatment strategies for LUAD and emphasized the importance of precise and personalized treatments.

4 citations

Journal ArticleDOI
TL;DR: NLRC5, LCP2, TMEM229B, and FCRL4 are potential antigens for ESCC mRNA vaccines, and such vaccines may be more suitable for IS2 patients, as well as two immune subtypes that showed different drug sensitivities to common anti-tumor drugs.
Abstract: Purpose: The applicability of mRNA vaccines against esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we identified potential antigens for developing mRNA vaccines against ESCC and characterized immune subtypes to select appropriate patients for vaccination. Methods: RNA-seq, genetic alteration data, and corresponding clinical information of ESCC patients were obtained from the Cancer Genome Atlas (TCGA) database. The RNA-seq data of normal esophageal tissue were obtained from the Genotype-Tissue Expression (GTEx) database. Potential tumor antigens were screened by analyzing differentially expressed and mutated genes and potential antigens with significant differences in prognosis were screened using the Kaplan-Meier method. The proportion of immune cell infiltration in the tumor microenvironment was estimated using CIBERSORT and MCPcounter, and the correlation of potential antigens with antigen-presenting cells and major histocompatibility complex class II was analyzed. Subsequently, immune subtypes were constructed using consensus clustering analysis and characterized by single-sample gene set enrichment analysis and weighted gene co-expression network analysis (WGCNA). The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to analyze the drug sensitivity of different immune subtypes. Results: Four overexpressed and mutated tumor antigens associated with antigen presentation and poor prognosis were identified in ESCC, including NLRC5, FCRL4, TMEM229B, and LCP2. By consensus clustering, we identified two immune-associated ESCC subtypes, immune subtype 1 (IS1) and immune subtype 2 (IS2); the prognosis of the two subtypes was statistically different. In addition, the two immune subtypes had distinctly different cellular, molecular, and clinical characteristics. IS1 patients have a distinct immune “hot” phenotype with strong immune tolerance, whereas patients with IS2 have an immune “cold” phenotype. Differential expression of immune checkpoints and immunogenic cell death modulators was observed between the different immune subtypes. Finally, we found that IS1 and IS2 patients showed different drug sensitivities to common anti-tumor drugs, possibly facilitating the development of individualized treatment regimens for patients. Conclusion: NLRC5, LCP2, TMEM229B, and FCRL4 are potential antigens for ESCC mRNA vaccines, and such vaccines may be more suitable for IS2 patients. This study provides a theoretical basis for mRNA vaccines against ESCC, by identifying the critical characteristics to predict ESCC prognosis and select suitable patients for vaccination.

3 citations


Cited by
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Journal ArticleDOI
TL;DR: An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics and the appropriate use and scope of the term probiotic.
Abstract: An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.

5,114 citations

Journal ArticleDOI
29 Aug 2013-Nature
TL;DR: The authors' classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.
Abstract: We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.

3,448 citations

Journal ArticleDOI
TL;DR: Substantial insight is provided into the intricate mechanisms of bacterial regulation of the cross-talk between the host and gut microbiota and provides a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
Abstract: Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.

3,263 citations

Journal ArticleDOI
27 Mar 2014-Cell
TL;DR: In high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses.

3,257 citations

Journal ArticleDOI
TL;DR: An updated view of the global epidemiology of type 2 diabetes mellitus, as well as dietary, lifestyle and other risk factors for T2DM and its complications are provided.
Abstract: Globally, the number of people with diabetes mellitus has quadrupled in the past three decades, and diabetes mellitus is the ninth major cause of death. About 1 in 11 adults worldwide now have diabetes mellitus, 90% of whom have type 2 diabetes mellitus (T2DM). Asia is a major area of the rapidly emerging T2DM global epidemic, with China and India the top two epicentres. Although genetic predisposition partly determines individual susceptibility to T2DM, an unhealthy diet and a sedentary lifestyle are important drivers of the current global epidemic; early developmental factors (such as intrauterine exposures) also have a role in susceptibility to T2DM later in life. Many cases of T2DM could be prevented with lifestyle changes, including maintaining a healthy body weight, consuming a healthy diet, staying physically active, not smoking and drinking alcohol in moderation. Most patients with T2DM have at least one complication, and cardiovascular complications are the leading cause of morbidity and mortality in these patients. This Review provides an updated view of the global epidemiology of T2DM, as well as dietary, lifestyle and other risk factors for T2DM and its complications.

2,763 citations