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  • BMJ  (6)
  • 1
    In: Gut, BMJ, Vol. 72, No. 5 ( 2023-05), p. 958-971
    Abstract: Innate immunity plays important roles in pancreatic ductal adenocarcinoma (PDAC), as non-T-cell-enriched tumour. Neutrophils are major players in innate immune system. Here, we aimed to explore the heterogeneity and pro-tumour mechanisms of neutrophils in PDAC. Design We analysed single-cell transcriptomes of peripheral blood polymorphonuclear leucocytes (PMNs) and tumour-infiltrating immune cells from five patients with PDAC, and performed immunofluorescence/immunohistochemistry staining, multi-omics analysis and in vitro experiments to validate the discoveries of bioinformatics analysis. Results Exploration of the heterogeneity of tumour-associated neutrophils (TANs) revealed a terminally differentiated pro-tumour subpopulation (TAN-1) associated with poor prognosis, an inflammatory subpopulation (TAN-2), a population of transitional stage that have just migrated to tumour microenvironment (TAN-3) and a subpopulation preferentially expressing interferon-stimulated genes (TAN-4). Glycolysis signature was upregulated along neutrophil transition trajectory, and TAN-1 was featured with hyperactivated glycolytic activity. The glycolytic switch of TANs was validated by integrative multi-omics approach of transcriptomics, proteomics and metabolomics analysis. Activation of glycolytic activity by LDHA overexpression induced immunosuppression and pro-tumour functions in neutrophil-like differentiated HL-60 (dHL-60) cells. Mechanistic studies revealed BHLHE40, downstream to hypoxia and endoplasmic reticulum stress, was a key regulator in polarisation of neutrophils towards TAN-1 phenotype, and direct transcriptional regulation of BHLHE40 on TAN-1 marker genes was demonstrated by chromatin immunoprecipitation assay. Pro-tumour and immunosuppression functions were observed in dHL-60 cells overexpressing BHLHE40. Importantly, immunohistochemistry analysis of PDAC tissues revealed the unfavourable prognostic value of BHLHE40 + neutrophils. Conclusion The dynamic properties of TANs revealed by this study will be helpful in advancing PDAC therapy targeting innate immunity.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 80128-8
    detail.hit.zdb_id: 1492637-4
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  • 2
    Online Resource
    Online Resource
    BMJ ; 2023
    In:  BMJ Global Health Vol. 8, No. 9 ( 2023-09), p. e012646-
    In: BMJ Global Health, BMJ, Vol. 8, No. 9 ( 2023-09), p. e012646-
    Abstract: Disparities in life expectancy between rural and urban populations are well established but how it varies with epidemics and pandemics remains poorly understood. We aimed to quantify the rural–urban differences in the mortality burden of COVID-19 and to contribute to understanding the disparity trends in life expectancy between 1987 and 2021 in China. Methods We used monthly death counts from death registration systems. Rural–urban gap estimation and decomposition were carried out using period life tables to calculate life expectancy, the Arriaga decomposition technique to break down into age-specific and cause-specific mortality, and the Lee-Carter forecasts to estimate the expected gap. Results The rural–urban gap increased to 22.7 months (95% credible interval (CI) 19.6 to 25.8) in 2020 and further to 23.7 months (95% CI 19.6 to 26.7) in 2021, and was larger than expected under the continuation of the prepandemic trends. Compared with that in the recent 2003 SARS-CoV-2 epidemic and the 2009 influenza epidemic, excess rural–urban gaps in the COVID-19 pandemic changed from urban disadvantage to rural disadvantage, and the contributions shifted toward old age groups and circulatory diseases. Variations in the rural–urban gap since 1987 were positively correlated with the rural–urban disparity in public health expenditures, especially among ages 〈 60 (p values 〈 0.005). Conclusions Our findings identified a widening rural–urban gap in life expectancy since COVID-19, and a shifting trend towards old ages and circulatory diseases, disrupting the diminishing trend of the gap over 35 years. The findings highlight the unequal impact of the pandemic on different communities in terms of mortality burdens.
    Type of Medium: Online Resource
    ISSN: 2059-7908
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2851843-3
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  • 3
    In: BMJ Open Diabetes Research & Care, BMJ, Vol. 10, No. 3 ( 2022-05), p. e002720-
    Abstract: There is absence of national data to estimate the prevalence of long-term diabetic complications among inpatients with diabetes in tertiary hospitals in China. Research design and methods Using the national Hospital Quality Monitoring System database, inpatients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) were identified by the International Classification of Diseases-10 code, and the temporal trends of microvascular and macrovascular complications 2013–2017 were calculated, and then the risk factors were analysed by multivariate regression analysis. Results A total of 92 413 inpatients with T1DM and 6 094 038 inpatients with T2DM were identified in 2013–2017. The proportions of inpatients with microvascular complications in inpatients with T1DM and T2DM increased from 29.9% and 19.0% in 2013 to 31.6% and 21.0% in 2017, respectively. The proportions of inpatients with macrovascular complications in inpatients with T1DM and T2DM increased from 7.3% and 14.5% in 2013 to 13.2% and 18.4% in 2017, respectively. Hypertension and hyperlipidemia were risk factors for both microvascular and macrovascular complications. Among inpatients with T1DM, the adjusted ORs of microvascular complications increased in 40–49 age group and Northeast region, while older age, male and North region were risks factor for macrovascular complications. Among inpatients with T2DM, the ORs of microvascular complications increased in 40–49 age group, female, urban and North region, while older age, male, urban and Southwest region were risks factor for macrovascular complications. Conclusions The proportions of long-term complications of inpatients with diabetes in China increased in 2013–2017. Efforts are needed to improve the management of patients with diabetes in China.
    Type of Medium: Online Resource
    ISSN: 2052-4897
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2732918-5
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  • 4
    Online Resource
    Online Resource
    BMJ ; 2012
    In:  Heart Vol. 98, No. Suppl 2 ( 2012-10), p. E88.3-E89
    In: Heart, BMJ, Vol. 98, No. Suppl 2 ( 2012-10), p. E88.3-E89
    Type of Medium: Online Resource
    ISSN: 1355-6037 , 1468-201X
    Language: English
    Publisher: BMJ
    Publication Date: 2012
    detail.hit.zdb_id: 1303417-0
    detail.hit.zdb_id: 1475501-4
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  • 5
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 12, No. 1 ( 2024-01), p. e008040-
    Abstract: Immunotherapies targeting immune checkpoints have gained increasing attention in cancer treatment, emphasizing the need for predictive biomarkers. Circular RNAs (circRNAs) have emerged as critical regulators of tumor immunity, particularly in the PD-1/PD-L1 pathway, and have shown potential in predicting immunotherapy efficacy. Yet, the detailed roles of circRNAs in cancer immunotherapy are not fully understood. While existing databases focus on either circRNA profiles or immunotherapy cohorts, there is currently no platform that enables the exploration of the intricate interplay between circRNAs and anti-tumor immunotherapy. A comprehensive resource combining circRNA profiles, immunotherapy responses, and clinical outcomes is essential to advance our understanding of circRNA-mediated tumor-immune interactions and to develop effective biomarkers. Methods To address these gaps, we constructed The Cancer CircRNA Immunome Atlas (TCCIA), the first database that combines circRNA profiles, immunotherapy response data, and clinical outcomes across multicancer types. The construction of TCCIA involved applying standardized preprocessing to the raw sequencing FASTQ files, characterizing circRNA profiles using an ensemble approach based on four established circRNA detection tools, analyzing tumor immunophenotypes, and compiling immunotherapy response data from diverse cohorts treated with immune checkpoint blockades (ICBs). Results TCCIA encompasses over 4,000 clinical samples obtained from 25 cohorts treated with ICBs along with other treatment modalities. The database provides researchers and clinicians with a cloud-based platform that enables interactive exploration of circRNA data in the context of ICB. The platform offers a range of analytical tools, including browse of identified circRNAs, visualization of circRNA abundance and correlation, association analysis between circRNAs and clinical variables, assessment of the tumor immune microenvironment, exploration of tumor molecular signatures, evaluation of treatment response or prognosis, and identification of altered circRNAs in immunotherapy-sensitive and resistant tumors. To illustrate the utility of TCCIA, we showcase two examples, including circTMTC3 and circMGA, by employing analysis of large-scale melanoma and bladder cancer cohorts, which unveil distinct impacts and clinical implications of different circRNA expression in cancer immunotherapy. Conclusions TCCIA represents a significant advancement over existing resources, providing a comprehensive platform to investigate the role of circRNAs in immuno-oncology.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    Language: English
    Publisher: BMJ
    Publication Date: 2024
    detail.hit.zdb_id: 2719863-7
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  • 6
    Online Resource
    Online Resource
    BMJ ; 2012
    In:  Heart Vol. 98, No. Suppl 2 ( 2012-10), p. E162.2-E163
    In: Heart, BMJ, Vol. 98, No. Suppl 2 ( 2012-10), p. E162.2-E163
    Type of Medium: Online Resource
    ISSN: 1355-6037 , 1468-201X
    Language: English
    Publisher: BMJ
    Publication Date: 2012
    detail.hit.zdb_id: 1303417-0
    detail.hit.zdb_id: 1475501-4
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