Displaying publications 1 - 20 of 24 in total

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  1. Chen X, He Y, Deng Y
    PMID: 34457017 DOI: 10.1155/2021/1808081
    Betel nut, the fruit of Areca catechu L, has a long medical history in Southeast Asia. It is native to Malaysia and is cultivated and processed extensively in subtropical regions, such as South China and India. Betel nut almost appears as a "snack" in various occasions in most parts of China. Clinically, betel nut can play a certain pharmacology role and was used in malaria, ascariasis, arthritis, enterozoic abdominalgia, stagnation of food, diarrhea, edema, and beriberi. The nervous excitement of betel nut chewing has made it gradually become popular. However, chewing betel nut can induce oral submucosal fibrosis (OSF) and oral cancer (OC). At the same time, long-term chewing of betel nut also causes inhaled asthma, sperm reducing, betel quid dependence (BQD), and uterine and esophageal cancers. The main components of processed betel nut are the goal of this review. This study will mainly start from the pharmacological activity and toxicology study of betel nut in recent years, aiming to seek its advantages and disadvantages. In the meantime, this study will analyze and emphasize that betel nut and arecoline are the high-risk factors for oral cancer, which should arouse attention and vigilance of the public.
  2. Zong Z, Wang X, Deng Y, Zhou T
    J Med Microbiol, 2012 Oct;61(Pt 10):1483-1484.
    PMID: 22820689 DOI: 10.1099/jmm.0.041525-0
    A previously healthy Chinese male returned from working in the Malaysian jungle with a fever. A blood culture grew Gram-negative bacilli that were initially identified as Burkholderia cepacia by the VITEK 2 system but were subsequently found to be Burkholderia pseudomallei by partial sequencing of the 16S rRNA gene. The identification of B. pseudomallei using commercially available automated systems is problematic and clinicians in non-endemic areas should be aware of the possibility of melioidosis in patients with a relevant travel history and blood cultures growing Burkholderia spp.
  3. Peng L, Peng Y, Luo H, Deng Y
    PLoS One, 2023;18(5):e0285853.
    PMID: 37235592 DOI: 10.1371/journal.pone.0285853
    OBJECTIVE: Everyone in life will experience resource scarcity, which causes self-discrepancy. It is widely known that individuals participate in reactive consumption to solve the problems of self-discrepancy and resources scarcity. This kind of consumption may be symbolically related to the essence of the resource scarcity or may occur in an unrelated domain. This study proposes a theory for "filling up" one's resource scarcity through high-intensity sensory consumption (HISC).

    METHODS: We used different methods, including one-way analysis of variance (ANOVA), linear regression, mediating effect, and moderating effect, to test the four hypotheses. Four experiments in the study were conducted from May 2022 and August 2022 and involved undergraduates from a university and volunteers recruited online. All participants are adults and verbally agree to participate voluntarily. Study 1a (N = 96 (male 47, female 49), participants from a business school in China) measured resource scarcity in the laboratory experiments and verified the effect of resource scarcity on consumer HISC preference by using linear regression (H1). Study 1b (N = 191 (male 98, female 93), students and teachers from a university in China) measured resource scarcity in the laboratory experiments and manipulated positively and negatively valenced experiences. Using the PROCESS SPSS Mode l, we verified that negatively valenced stimuli also lead to higher levels of arousal, which in turn restores the self-discrepancy caused by resource scarcity (H2). Study 2 (an online experiment, N = 182 (male 91, female 91), participants from China) manipulated the resource scarcity in a color sensory stimulant context, replicating the preliminary effect and examined the mediating effect of the self-worth by using the PROCESS SPSS Mode 4 (H3). Study 3 (an online experiment, N = 251 (male 125, female 126), participants from China) manipulated resource scarcity and self-acceptance in the tactile sensory experience, and tested the moderating effect of self-acceptance by using the PROCESS SPSS Mode 8 (H4).

    RESULTS: Four studies suggest that not only do individuals facing resources scarcity prefer HISC but also that this consumption is mediated and moderated by self-worth and self-acceptance, respectively. This preference for HISC is negated when individuals have high self-acceptance traits. The findings are tested in the auditory domain (as evidenced by a propensity for louder volume), the visual domain (as evidenced by a propensity for more intense colors), and the tactile domain (as evidenced by a propensity for more intense need for touch). The findings also demonstrate that individual preferences for HISC is shown to operate regardless of the valence (positive valence vs. negative valence) of the sensory consumption.

    CONCLUSIONS: Across four experiments, we find that individuals who are subjected to resource scarcity show a preference for high-intensity sensory consumption in the auditory, visual, and tactile domains. We also find that both negatively and positively valenced sensory stimuli have the same impact on resource-scarce individuals' preference for HISC. Furthermore, we demonstrate that the sense of self-worth significantly mediates the effect of resource scarcity on HISC. Finally, we reveal that self-acceptance moderates the effect of resource scarcity on HISC preference.

  4. Zong Z, Wang X, Deng Y
    PMID: 27244959
    A previously healthy Chinese male working in Malaysia returned to China with high fever. A blood culture showed Burkholderia pseudomallei strain WCBP1. This isolate was sequenced, showing type, ST881, which appears to be present in Malaysia. WCP1 had unusual susceptibility to aminoglycosides and habored the Yersinia-like fimbrial gene cluster for virulence. The patient's condition deteriorated rapidly but he recovered after receiving meropenem and intensive care support. Melioidosis is a potential problem among Chinese imigrant workers with strains new to China being identified.
  5. Guo L, Malara D, Battaglia P, Waiho K, Davis DA, Deng Y, et al.
    Genome Biol Evol, 2024 Mar 02;16(3).
    PMID: 38408866 DOI: 10.1093/gbe/evae037
    The suppression of recombination is considered a hallmark of sex chromosome evolution. However, previous research has identified undifferentiated sex chromosomes and sex determination by single SNP in the greater amberjack (Seriola dumerili). We observed the same phenomena in the golden pompano (Trachinotus ovatus) of the same family Carangidae and discovered a different sex-determining SNP within the same gene Hsd17b1. We propose an evolutionary model elucidating the turnover of sex-determining mutations by highlighting the contrasting dynamics between purifying selection, responsible for maintaining W-linked Hsd17b1, and neutral evolution, which drives Z-linked Hsd17b1. Additionally, sporadic loss-of-function mutations in W-linked Hsd17b1 contribute to the conversion of W chromosomes into Z chromosomes. This model was directly supported by simulations, closely related species, and indirectly by zebrafish mutants. These findings shed new light on the early stages of sex chromosome evolution.
  6. Fu X, Norbäck D, Yuan Q, Li Y, Zhu X, Hashim JH, et al.
    Sci Total Environ, 2021 Jan 20;753:141904.
    PMID: 32890872 DOI: 10.1016/j.scitotenv.2020.141904
    Sick building syndrome (SBS) is a collection of nonspecific syndromes linked with the built environment. The occurrence of SBS is associated with humidity, ventilation, moulds and microbial compounds exposure. However, no study has reported the association between indoor microbiome and SBS. In this study, 308 students were surveyed for SBS symptoms from 21 classrooms of 7 junior high schools from Johor Bahru, Malaysia, and vacuum dust from floor, desks and chairs was collected. High throughput amplicon sequencing (16S rRNA gene and ITS region) and quantitative PCR were conducted to characterize the absolute concentration of bacteria and fungi taxa. In total, 326 bacterial and 255 fungal genera were detected in dust with large compositional variation among classrooms. Also, half of these samples showed low compositional similarity to microbiome data deposited in the public database. The number of observed OTUs in Gammaproteobacteria was positively associated with SBS (p = 0.004). Eight microbial genera were associated with SBS (p 
  7. Shang L, Xu Y, Leaw CP, Lim PT, Wang J, Chen J, et al.
    Sci Total Environ, 2021 Aug 01;780:146484.
    PMID: 33774286 DOI: 10.1016/j.scitotenv.2021.146484
    The dinoflagellate genus Alexandrium has been well known for causing paralytic shellfish poisoning (PSP) worldwide. Several non-PSP toxin-producing species, however, have shown to exhibit fish-killing toxicity. Here, we report the allelopathic activity of Alexandrium leei from Malaysia to other algal species, and its toxicity to finfish and zooplankton, via laboratory bioassays. Thirteen microalgal species that co-cultured with Al. leei revealed large variability in the allelopathic effects of Al. leei on the test algae, with the growth inhibition rates ranging from 0 to 100%. The negative allelopathic effects of Al. leei on microalgae included loss of flagella and thus the motility, damages of chain structure, deformation in cell morphology, and eventually cell lysis. The finfish experienced 100% mortality within 24 h exposed to the live culture (2000-6710 cells·mL-1), while the rotifer and brine shrimp exhibited 96-100% and 90-100% mortalities within 48 h when exposed to 500-6000 cells·mL-1 of Al. leei. The mortality of the test animals depended on the Al. leei cell density exposed, leading to a linear relationship between mortality and cell density for the finfish, and a logarithmic relationship for the two zooplankters. When exposed to the treatments using Al. leei whole live culture, cell-free culture medium, extract of algal cells in the f/2-Si medium, extract of methanol, and the re-suspended freeze-and-thaw algal cells, the test organisms (Ak. sanguinea and rotifers) all died at the cell density of 8100 cells·mL-1 within 24 h. Toxin analyses by HILIC-ESI-TOF/MS and LC-ESI-MS/MS demonstrated that Al. leei did not produce PSP-toxins and 13-desmethyl spirolide C. Overall, our findings demonstrated potent allelopathy and toxicity of Al. leei, which do not only pose threats to the aquaculture industry, fisheries, and marine ecosystems but may also play a part role in the population dynamics and bloom formation of this species.
  8. Demarchi B, Stiller J, Grealy A, Mackie M, Deng Y, Gilbert T, et al.
    Proc Natl Acad Sci U S A, 2022 Oct 25;119(43):e2109326119.
    PMID: 35609205 DOI: 10.1073/pnas.2109326119
    The realization that ancient biomolecules are preserved in "fossil" samples has revolutionized archaeological science. Protein sequences survive longer than DNA, but their phylogenetic resolution is inferior; therefore, careful assessment of the research questions is required. Here, we show the potential of ancient proteins preserved in Pleistocene eggshell in addressing a longstanding controversy in human and animal evolution: the identity of the extinct bird that laid large eggs which were exploited by Australia's indigenous people. The eggs had been originally attributed to the iconic extinct flightless bird Genyornis newtoni (†Dromornithidae, Galloanseres) and were subsequently dated to before 50 ± 5 ka by Miller et al. [Nat. Commun. 7, 10496 (2016)]. This was taken to represent the likely extinction date for this endemic megafaunal species and thus implied a role of humans in its demise. A contrasting hypothesis, according to which the eggs were laid by a large mound-builder megapode (Megapodiidae, Galliformes), would therefore acquit humans of their responsibility in the extinction of Genyornis. Ancient protein sequences were reconstructed and used to assess the evolutionary proximity of the undetermined eggshell to extant birds, rejecting the megapode hypothesis. Authentic ancient DNA could not be confirmed from these highly degraded samples, but morphometric data also support the attribution of the eggshell to Genyornis. When used in triangulation to address well-defined hypotheses, paleoproteomics is a powerful tool for reconstructing the evolutionary history in ancient samples. In addition to the clarification of phylogenetic placement, these data provide a more nuanced understanding of the modes of interactions between humans and their environment.
  9. Xie Z, Li Y, Xiong K, Tu Z, Waiho K, Yang C, et al.
    Environ Pollut, 2023 Aug 15;331(Pt 2):121921.
    PMID: 37263564 DOI: 10.1016/j.envpol.2023.121921
    Anthropologic activities caused frequent eutrophication in coastal and estuarine waters, resulting in diel-cycling hypoxia. Given global climate change, extreme weather events often occur, thus salinity fluctuation frequently breaks out in these waters. This study aimed to evaluate the combined effects of salinity and hypoxia on intestinal microbiota and digestive enzymes of Crassostrea hongkongensis. Specifically, we sequenced 16 S rRNA of intestinal microbiota and measured the digestive enzymes trypsin (TRS), lipase (LPS) and amylase (AMY) in oysters exposed for 28 days to three salinities (10, 25 and 35) and two dissolved oxygen conditions, normoxia (6 mg/L) and hypoxia (6 mg/L for 12 h, 2 mg/L for 12 h). Oysters in normoxia and salinity of 25 were treated as control. After 28-day exposure, for microbial components, Fusobacteriota, Firmicutes, Bacteroidota, Proteobacteria and Actinobacteriota comprised the majority for all experimental groups. Compared with the control group, the diversity and structure of intestinal microbiota tended to change in all treated groups. The species richness in C. hongkongensis intestine also changed. It was the most significant that high salinity increased Proteobacteria proportion while low salinity and hypoxia increased Fusobacteriota but decreased Proteobacteria, respectively. Additionally, Actinobacteriota was sensitive and changed under environmental stressor (P 
  10. Fu X, Norbäck D, Yuan Q, Li Y, Zhu X, Hashim JH, et al.
    Environ Int, 2020 05;138:105664.
    PMID: 32200316 DOI: 10.1016/j.envint.2020.105664
    Indoor microbial diversity and composition are suggested to affect the prevalence and severity of asthma by previous home microbiome studies, but no microbiome-health association study has been conducted in a school environment, especially in tropical countries. In this study, we collected floor dust and environmental characteristics from 21 classrooms, and health data related to asthma symptoms from 309 students, in junior high schools in Johor Bahru, Malaysia. The bacterial and fungal composition was characterized by sequencing 16s rRNA gene and internal transcribed spacer (ITS) region, and the absolute microbial concentration was quantified by qPCR. In total, 326 bacterial and 255 fungal genera were characterized. Five bacterial (Sphingobium, Rhodomicrobium, Shimwellia, Solirubrobacter, Pleurocapsa) and two fungal (Torulaspora and Leptosphaeriaceae) taxa were protective for asthma severity. Two bacterial taxa, Izhakiella and Robinsoniella, were positively associated with asthma severity. Several protective bacterial taxa including Rhodomicrobium, Shimwellia and Sphingobium have been reported as protective microbes in previous studies, whereas other taxa were first time reported. Environmental characteristics, such as age of building, size of textile curtain per room volume, occurrence of cockroaches, concentration of house dust mite allergens transferred from homes by the occupants, were involved in shaping the overall microbial community but not asthma-associated taxa; whereas visible dampness and mold, which did not change the overall microbial community for floor dust, was negatively associated with the concentration of protective bacteria Rhodomicrobium (β = -2.86, p = 0.021) of asthma. The result indicates complex interactions between microbes, environmental characteristics and asthma symptoms. Overall, this is the first indoor microbiome study to characterize the asthma-associated microbes and their environmental determinant in the tropical area, promoting the understanding of microbial exposure and respiratory health in this region.
  11. Sa N, Nie K, Ng YS, Deng T, Xu J, Wang W, et al.
    Nanotechnology, 2025 Feb 06;36(11).
    PMID: 39746220 DOI: 10.1088/1361-6528/ada4b7
    The graphitic carbon nitride (g-C3N4) is an important optoelectronic and photocatalytic material; however, its application is limited by the high recombination rate of the electron-hole (e--h+) pairs. In this work, we reported a novel strategy combining two-step annealing treatment and ionic-liquid (IL) gating technology for effectively regulating the properties of g-C3N4, especially largely reducing the recombination rate of the e--h+pairs, which is evidenced by a remarkable reduction of the photoluminescence (PL) intensity. Firstly, g-C3N4samples with typical layered structure were obtained by annealing melamine with temperature of 600 °C. Further annealing of the samples at 600 °C with much longer time (from 4 h to 12 h) were found to effectively reduce the imperfections or defects, and thus the PL intensity (49% reduction). This large reduction of PL intensity is attributed to the improved interconnection of triazine units, the shortened charge transfer diffusion distances, and the reduced interlayer spacing, which facilitate electron relocation on the g-C3N4surface. Secondly, by post-treating the annealed sample with IL, the PL intensities were found to be further reduced, mainly due to the passivation of charged defect centers by IL. Additionally, applying an external electric field in an IL environment can significantly enhance the charged defect passivation. Overall, by utilizing electric field-controlled IL gating, defect states in g-C3N4were passivated, leading to a significant reduction in PL intensity and an extension of PL lifetime, thereby effectively decreasing the e--h+recombination rate in the material. This study demonstrates a new approach for defect passivation, providing insights and strategies for modulating properties of advanced materials such as g-C3N4.
  12. Phua J, Joynt GM, Nishimura M, Deng Y, Myatra SN, Chan YH, et al.
    JAMA Intern Med, 2015 Mar;175(3):363-71.
    PMID: 25581712 DOI: 10.1001/jamainternmed.2014.7386
    Little data exist on end-of-life care practices in intensive care units (ICUs) in Asia.
  13. Phua J, Joynt GM, Nishimura M, Deng Y, Myatra SN, Chan YH, et al.
    Intensive Care Med, 2016 Jul;42(7):1118-27.
    PMID: 27071388 DOI: 10.1007/s00134-016-4347-y
    PURPOSE: To compare the attitudes of physicians towards withholding and withdrawing life-sustaining treatments in intensive care units (ICUs) in low-middle-income Asian countries and regions with those in high-income ones, and to explore differences in the role of families and surrogates, legal risks, and financial considerations between these countries and regions.

    METHODS: Questionnaire study conducted in May-December 2012 on 847 physicians from 255 ICUs in 10 low-middle-income countries and regions according to the World Bank's classification, and 618 physicians from 211 ICUs in six high-income countries and regions.

    RESULTS: After we accounted for personal, ICU, and hospital characteristics on multivariable analyses using generalised linear mixed models, physicians from low-middle-income countries and regions were less likely to limit cardiopulmonary resuscitation, mechanical ventilation, vasopressors and inotropes, tracheostomy and haemodialysis than those from high-income countries and regions. They were more likely to involve families in end-of-life care discussions and to perceive legal risks with limitation of life-sustaining treatments and do-not-resuscitate orders. Nonetheless, they were also more likely to accede to families' requests to withdraw life-sustaining treatments in a patient with an otherwise reasonable chance of survival on financial grounds in a case scenario (adjusted odds ratio 5.05, 95 % confidence interval 2.69-9.51, P 

  14. Hu D, Zhu Z, Li S, Deng Y, Wu Y, Zhang N, et al.
    PLoS Pathog, 2019 06;15(6):e1007836.
    PMID: 31242272 DOI: 10.1371/journal.ppat.1007836
    Dengue is the most widespread vector-borne viral disease caused by dengue virus (DENV) for which there are no safe, effective drugs approved for clinical use. Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Immunogenetic analysis indicated that m366.6 is a germline-like mAb with very few somatic mutations from the closest VH and Vλ germline genes. Importantly, we demonstrated that it potently neutralized DENV both in vitro and in the mouse models of DENV infection without detectable antibody-dependent enhancement (ADE) effect. The epitope of m366.6 was mapped to the highly conserved regions on DIII, which may guide the design of effective dengue vaccine immunogens. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate.
  15. Jiang B, Li J, Liu L, Du X, Jiang H, Hu J, et al.
    Ann Hematol, 2025 Mar 10.
    PMID: 40063243 DOI: 10.1007/s00277-025-06235-y
    The COMMODORE study demonstrated the efficacy and safety of gilteritinib versus salvage chemotherapy (SC) treatment in a predominantly Asian population with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-mutated(mut+) acute myeloid leukemia (AML); here we present an exploratory analysis of the study stratified by region (China, South-East Asia and Russia). COMMODORE was a Phase 3, open-label, randomized (1:1), multicenter trial. There were 151, 50, and 33 patients in the China, South-East Asia, and Russia cohorts, respectively. Patients treated with gilteritinib had prolonged median overall survival (OS) versus SC-treated patients in all regions (China: 10.0 vs. 5.7 months, HR [95% CI]: 0.614 [0.385, 0.981]; South-East Asia: 7.8 vs. 4.7 months, HR [95% CI]: 0.887 [0.427, 1.843]; Russia: 8.8 vs. 2.6 months, HR [95% CI]: 0.271 [0.111, 0.662]). Improvements in event-free survival (EFS) were observed in the gilteritinib versus SC arms across all cohorts (China: 2.1 vs. 0.8 months; HR [95% CI]: 0.645 [0.427, 0.974]; South-East Asia 2.4 vs. 
  16. Gelabert P, Sandoval-Velasco M, Serres A, de Manuel M, Renom P, Margaryan A, et al.
    Curr Biol, 2020 01 06;30(1):108-114.e5.
    PMID: 31839456 DOI: 10.1016/j.cub.2019.10.066
    As the only endemic neotropical parrot to have recently lived in the northern hemisphere, the Carolina parakeet (Conuropsis carolinensis) was an iconic North American bird. The last surviving specimen died in the Cincinnati Zoo in 1918 [1]. The cause of its extinction remains contentious: besides excessive mortality associated to habitat destruction and active hunting, their survival could have been negatively affected by its range having become increasingly patchy [2] or by the exposure to poultry pathogens [3, 4]. In addition, the Carolina parakeet showed a predilection for cockleburs, an herbaceous plant that contains a powerful toxin, carboxyatractyloside, or CAT [5], which did not seem to affect them but made the birds notoriously toxic to most predators [3]. To explore the demographic history of this bird, we generated the complete genomic sequence of a preserved specimen held in a private collection in Espinelves (Girona, Spain), as well as of a close extant relative, Aratinga solstitialis. We identified two non-synonymous genetic changes in two highly conserved proteins known to interact with CAT that could underlie a specific dietary adaptation to this toxin. Our genomic analyses did not reveal evidence of a dramatic past demographic decline in the Carolina parakeet; also, its genome did not exhibit the long runs of homozygosity that are signals of recent inbreeding and are typically found in endangered species. As such, our results suggest its extinction was an abrupt process and thus likely solely attributable to human causes.
  17. Wu J, Danko D, Afshinnekoo E, Bezdan D, Bhattacharyya M, Castro-Nallar E, et al.
    Environ Res, 2022 May 01;207:112183.
    PMID: 34637759 DOI: 10.1016/j.envres.2021.112183
    In urban ecosystems, microbes play a key role in maintaining major ecological functions that directly support human health and city life. However, the knowledge about the species composition and functions involved in urban environments is still limited, which is largely due to the lack of reference genomes in metagenomic studies comprises more than half of unclassified reads. Here we uncovered 732 novel bacterial species from 4728 samples collected from various common surface with the matching materials in the mass transit system across 60 cities by the MetaSUB Consortium. The number of novel species is significantly and positively correlated with the city population, and more novel species can be identified in the skin-associated samples. The in-depth analysis of the new gene catalog showed that the functional terms have a significant geographical distinguishability. Moreover, we revealed that more biosynthetic gene clusters (BGCs) can be found in novel species. The co-occurrence relationship between BGCs and genera and the geographical specificity of BGCs can also provide us more information for the synthesis pathways of natural products. Expanded the known urban microbiome diversity and suggested additional mechanisms for taxonomic and functional characterization of the urban microbiome. Considering the great impact of urban microbiomes on human life, our study can also facilitate the microbial interaction analysis between human and urban environment.
  18. Ryon KA, Tierney BT, Frolova A, Kahles A, Desnues C, Ouzounis C, et al.
    iScience, 2022 Nov 18;25(11):104993.
    PMID: 36299999 DOI: 10.1016/j.isci.2022.104993
    The MetaSUB Consortium, founded in 2015, is a global consortium with an interdisciplinary team of clinicians, scientists, bioinformaticians, engineers, and designers, with members from more than 100 countries across the globe. This network has continually collected samples from urban and rural sites including subways and transit systems, sewage systems, hospitals, and other environmental sampling. These collections have been ongoing since 2015 and have continued when possible, even throughout the COVID-19 pandemic. The consortium has optimized their workflow for the collection, isolation, and sequencing of DNA and RNA collected from these various sites and processing them for metagenomics analysis, including the identification of SARS-CoV-2 and its variants. Here, the Consortium describes its foundations, and its ongoing work to expand on this network and to focus its scope on the mapping, annotation, and prediction of emerging pathogens, mapping microbial evolution and antibiotic resistance, and the discovery of novel organisms and biosynthetic gene clusters.
  19. Chia JWK, Segelov E, Deng Y, Ho GF, Wang W, Han S, et al.
    Lancet Gastroenterol Hepatol, 2025 Mar;10(3):198-209.
    PMID: 39824200 DOI: 10.1016/S2468-1253(24)00387-X
    BACKGROUND: Aspirin is a simple, globally available medication that has been shown to reduce the incidence of colorectal cancer. We aimed to evaluate the safety and efficacy of aspirin in the secondary prevention of colorectal cancer.

    METHODS: This phase 3, randomised, double-blind, placebo-controlled trial was conducted at 66 centres across 11 countries and territories (ten in Asia-Pacific; one in the Middle East). The trial included patients aged 18 years and older with Dukes' C or high-risk Dukes' B colon cancer or Dukes' B or C rectal cancer who had undergone resection and had completed standard adjuvant therapy (at least 3 months of chemotherapy). Patients with contraindications to aspirin, familial syndromes of colorectal cancer, recent other cancers, and clinically significant history of cardiovascular disease or stroke were excluded. Patients were randomly assigned (1:1) to aspirin 200 mg daily or placebo for 3 years, and were followed up for 5 years. Randomisation was stratified by study centre, tumour site and stage, and inclusion of oxaliplatin in adjuvant chemotherapy. The patients, study team, and sponsor were masked to treatment assignment. The primary endpoint was disease-free survival. The primary analysis used a stratified Cox model in those commencing study treatment (modified intention-to-treat population), analysing all events to March 31, 2023. Safety was analysed in the same population. This trial is registered at ClinicalTrials.gov (NCT00565708). The primary analysis has been completed, but translational studies of putative aspirin sensitivity biomarkers are ongoing.

    FINDINGS: Between Feb 25, 2009, and June 30, 2021, 1587 patients underwent randomisation, of whom 1550 were included in the modified intention-to-treat analysis: 791 (51%) in the aspirin group and 759 (49%) in the placebo group. Of these patients, the median age was 57 years (IQR 48-65); 897 (58%) were male and 653 (42%) female; 271 (17%) had Dukes' B colon cancer, 770 (50%) Dukes' C colon cancer, and 509 (33%) rectal cancer. Median follow-up at data cutoff was 59·2 months (IQR 36·7-60·0). 5-year disease-free survival was 77·0% (95% CI 73·6-80·0) in the aspirin group and 74·8% (71·3-77·9) in the placebo group (hazard ratio of 0·91 [95% CI 0·73-1·13]; p=0·38). Any-grade adverse events were reported in 390 (49%) of 791 patients in the aspirin group versus 386 (51%) of 759 in the placebo group. Serious adverse events were reported in 95 (12%) patients in the aspirin group versus 107 (14%) in the placebo group. There were no treatment-related deaths in either group. Among adverse events of special interest, there were no cases of acute myocardial infarction in the aspirin group versus two in the placebo group; no ischaemic cerebrovascular events in the aspirin group versus two in the placebo group; and three major gastrointestinal bleeds in the aspirin group versus one in the placebo group.

    INTERPRETATION: In patients with colorectal cancer, aspirin 200 mg daily for 3 years after completion of standard adjuvant therapy was well tolerated but did not significantly improve disease-free survival.

    FUNDING: SingHealth Foundation, National Medical Research Council Singapore, National Cancer Centre Research Fund, Rising Tide Foundation, Lee Foundation, Lee Kim Tah Foundation, Duke-NUS Khoo Bridge Funding Award, Terry-Fox Run, Silent Foundation, Cancer Australia, Bowel Cancer Australia, and Cancer Council NSW.

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