| 1. |
- Zhang, Naiqi, et al.
(author)
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Combined Use of Aspirin and Selective Serotonin Reuptake Inhibitors Is Associated With Lower Risk of Colorectal Cancer : A Nested Case-Control Study
- 2021
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In: The American journal of gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 116:6, s. 1313-1321
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Chemoprevention against colorectal cancer (CRC) is greatly needed. As the development of CRC involves multiple dysfunctional pathways, it is thus reasonable to combine some agents that address several pathways to achieve better chemoprotection. We aimed to explore whether the use of aspirin and selective serotonin reuptake inhibitors (SSRIs)-either as monotherapy or combined-can have a clinical benefit against CRC.METHODS: We performed a nested case-control study using nationwide Swedish registers. We recruited 24,786 CRC cases and randomly matched to 74,358 controls conditional on birth year and sex using incidence-density sampling. The conditional logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, and multiplicative interaction was calculated by including a product term in the regression model.RESULTS: Both aspirin and SSRIs monotherapy were negatively associated with CRC risk, but the combined use of aspirin and SSRIs was associated with an even lower CRC risk (adjusted OR, 0.77, 95% CI, 0.67-0.89) than aspirin monotherapy (adjusted OR, 0.91, 95% CI, 0.87-0.97) or SSRI monotherapy (adjusted OR, 0.93, 95% CI, 0.86-1.00). A significant interaction was observed at the additive scale with a relative excess risk for interaction of -0.07 (P < 0.001), whereas no interaction was noted on the interactive scale. The inverse associations of CRC with aspirin and SSRIs showed a dose-dependent pattern.DISCUSSION: This study suggests that the use of aspirin and SSRIs-either as monotherapy or combined-was associated with a reduced risk of CRC. The stronger chemoprevention of combined use of aspirin and SSRIs is innovative and calls for further studies to confirm the underlying mechanisms and the plausibility of clinical recommendation.
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| 2. |
- Huang, Wuqing, et al.
(author)
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PDE5 inhibition mitigates heart failure in hyperlipidemia
- 2024
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In: Biomedicine and Pharmacotherapy. - 0753-3322. ; 175
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Journal article (peer-reviewed)abstract
- PDE5 inhibitors was reported to play a protective role in both regulating lipid metabolism and reducing heart failure (HF). This study aimed to clarify the effectiveness of PDE5 inhibitors against hyperlipidemia-related HF by combining evidence from population-based study and animal models. The nationwide cohort study found that post-diagnostic use of PDE5 inhibitors was associated with a significantly lower risk of HF compared with patients who used alprostadil, especially among individuals with hyperlipidemia (adjusted HR = 0.56, 95% CI = 0.40–0.78). In animal models, sildenafil significantly recovered the cardiac structure and function induced by AAB surgery, as well as reversed liver dysfunction and ameliorated hyperlipidemia induced by HFD via reducing the level of ALT, AST and serum lipids. Lipidomic analysis identified four lipid metabolites involved in sildenafil administration, including FA 16:3, LPC O-18:1, DG24:0_18:0 and SE28:1/20:4. This study revealed the protective effect of PDE5 inhibitors against HF in hyperlipidemia, indicating the potential of being repurposed as an adjuvant for HF prevention in patients with hyperlipidemia if these findings can be further confirmed in clinical trials.
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| 3. |
- Li, Yanni, et al.
(author)
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Association of Mitochondrial DNA Copy Number and Telomere Length with Prevalent and Incident Cancer and Cancer Mortality in Women : A Prospective Swedish Population-Based Study
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:15
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Journal article (peer-reviewed)abstract
- Changes in mitochondrial DNA copy number (mtDNA-CN) and telomere length have, separately, been proposed as risk factors for various cancer types. However, those results are conflicting. Here, mtDNA-CN and relative telomere length were measured in 3225 middle-aged women included in a large population-based prospective cohort. The baseline mtDNA-CN in patients with prevalent breast cancer was significantly higher (12.39 copies/µL) than cancer-free individuals. During an average of 15.2 years of follow-up, 520 patients were diagnosed with cancer. Lower mtDNA-CN was associated with decreased risk of genital organ cancer (hazard ratio (HR), 0.84), and shorter telomere length was associated with increased risk of urinary system cancer (HR, 1.79). Furthermore, mtDNA-CN was inversely associated with all-cause (HR, 1.20) and cancer-specific mortality (HR, 1.21) when considering all cancer types. Surprisingly, shorter telomere length was associated with decreased risk of cancer-specific mortality when considering all cancer types (HR, 0.85). Finally, lower mtDNA-CN and shorter telomere length were associated with increased risk of both all-cause and cancer-specific mortality in genital organ cancer patients. In this study population, we found that mtDNA-CN and telomere length were significantly associated with prevalent and incident cancer and cancer mortality. However, these associations were cancer type specific and need further investigation.
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| 4. |
- Li, Yanni, et al.
(author)
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Mitochondrial related genome-wide Mendelian randomization identifies putatively causal genes for multiple cancer types
- 2023
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In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 88
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Journal article (peer-reviewed)abstract
- BACKGROUND: Mitochondrial dysfunction is a hallmark of cancer. However, it is unclear whether it is a cause of cancer. This two-sample Mendelian randomization (MR) analyses, uses genetic instruments to proxy the exposure of mitochondrial dysfunction and cancer summary statistics as outcomes, allowing for causal inferences.METHODS: Summary statistics from 18 common cancers (2107-491,974 participants), gene expression, DNA methylation and protein expression quantitative trait loci (eQTL, mQTL and pQTL, respectively, 1000-31,684 participants) on individuals of European ancestry, were included. Genetic variants located within or close to the 1136 mitochondrial-related genes (in cis) and robustly associated with the mitochondrial molecular alterations were used as instrumental variables, and their causal associations with cancers were examined using summary-data-based MR (SMR) analyses. An additional five MR methods were used as sensitivity analyses to confirm the casual associations. A Bayesian test for colocalization between mitochondrial molecular QTLs and cancer risk loci was performed to provide insights into the potential regulatory mechanisms of risk variants on cancers.FINDINGS: We identified potential causal relationships between mitochondrial-related genes and breast, prostate, gastric, lung cancer and melanoma by primary SMR analyses. The sensitivity and the colocalization analyses further refined four genes that have causal effects on three types of cancer. We found strong evidence of positive association of FDPS expression level with breast cancer risk (OR per SD, 0.66; 95% CI, 0.49-0.83; P = 9.77 × 10-7), NSUN4 expression level with both breast cancer risk (OR per SD, 1.05; 95% CI, 1.03-1.07; P = 5.24 × 10-6) and prostate cancer risk (OR per SD, 1.06; 95% CI, 1.03-1.09; P = 1.01 × 10-5), NSUN4 methylation level with both breast and prostate cancer risk, and VARS2 methylation level with lung cancer risk.INTERPRETATIONS: This data-driven MR study demonstrated the causal role of mitochondrial dysfunction in multiple cancers. Furthermore, this study identified candidate genes that can be the targets of potential pharmacological agents for cancer prevention.FUNDING: This work was supported by Styrelsen för Allmänna Sjukhusets i Malmö Stiftelse för bekämpande av cancer (20211025).
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| 5. |
- Vats, Sakshi, et al.
(author)
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Oxidative stress-related genetic variation and antioxidant vitamin intake in intact and ruptured abdominal aortic aneurysm : a Swedish population-based retrospective cohort study
- 2024
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In: European Journal of Preventive Cardiology. - 2047-4881. ; 31:1, s. 61-74
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Journal article (peer-reviewed)abstract
- AIMS: The aim of this study is to investigate how genetic variations in genes related to oxidative stress, intake of antioxidant vitamins, and any potential interactions between these factors affect the incidence of intact abdominal aortic aneurysm (AAA) and its rupture (rAAA), accounting for sex differences where possible.METHODS AND RESULTS: The present retrospective cohort study (n = 25 252) uses baseline single-nucleotide polymorphisms (SNPs) and total antioxidant vitamin intake data from the large population-based, Malmö Diet and Cancer Study. Cumulative incidence of intact AAA was 1.6% and of rAAA 0.3% after a median follow-up of 24.3 years. A variant in NOX3 (rs3749930) was associated with higher rAAA risk in males [adjusted hazard ratio (aHR): 2.49; 95% confidence interval (CI): 1.36-4.35] and the overall population (aHR: 1.88; 95% CI: 1.05-3.37). Higher intakes of antioxidant vitamins, riboflavin, and folate were associated with 20% and 19% reduced intact AAA incidence, respectively. Interestingly, the inverse associations between riboflavin and vitamin D intake with intact AAA incidence were stronger in the individuals carrying the NOX3 variant as compared with the wild-type recessive genotype, i.e. by 60% and 66%, respectively (P for interaction < 0.05). Higher riboflavin intake was associated with a 33% male-specific intact AAA risk reduction, while higher intake of vitamin B12 intake was associated with 55% female-specific intact AAA risk increase; both these associations were significantly modified by sex (P for interaction < 0.05).CONCLUSIONS: Our findings highlight the role of oxidative stress genetic variations and antioxidant vitamin intake in AAA. Although a low AAA/rAAA sample size limited some analyses, especially in females, our findings highlight the need for future randomized controlled trials and mechanistic studies, to explore the potential benefits of antioxidant vitamins while accounting for genetic and sex differences.
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| 6. |
- Wang, Jin, et al.
(author)
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Multiagent and Bargaining-Game-Based Real-Time Scheduling for Internet of Things-Enabled Flexible Job Shop
- 2019
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In: IEEE Internet of Things Journal. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 2327-4662. ; 6:2, s. 2518-2531
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Journal article (peer-reviewed)abstract
- With the rapid advancement and widespread applications of information technology in the manufacturing shop floor, a huge amount of real-time data is generated, providing a good opportunity to effectively respond to unpredictable exceptions so that the productivity can be improved. Thus, how to schedule the manufacturing shop floor for achieving such a goal is very challenging. This paper addresses this issue and a new multiagent-based real-time scheduling architecture is proposed for an Internet of Things-enabled flexible job shop. Differing from traditional dynamic scheduling strategies, the proposed strategy optimally assigns tasks to machines according to their real-time status. A bargaining-game-based negotiation mechanism is developed to coordinate the agents so that the problem can be efficiently solved. To demonstrate the feasibility and effectiveness of the proposed architecture and scheduling method, a proof-of-concept prototype system is implemented with Java agent development framework platform. A case study is used to test the performance and effectiveness of the proposed method. Through simulation and comparison, it is shown that the proposed method outperforms the traditional dynamic scheduling strategies in terms of makespan, critical machine workload, and total energy consumption.
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| 7. |
- Xiao, Jun, et al.
(author)
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Association of genetically-predicted lipid traits and lipid-modifying targets with heart failure
- 2023
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In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 30:4, s. 358-366
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Journal article (peer-reviewed)abstract
- AIMS: To assess the association of genetically-predicted lipid traits and lipid-modification via licensed or investigational targets with heart failure (HF).METHODS AND RESULTS: Two-sample Mendelian randomization (MR) study was conducted using summary-level genome-wide association studies (GWASs) from UK Biobank and HERMES Consortium. Genetic variants obtained from UK Biobank GWAS data were selected as instrumental variables to predict the level of lipid traits (low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (ApoB) and apolipoprotein AI (ApoAI)) and lipid-modifying effect of eight drug targets (HMGCR, PCSK9, NPC1L1, PPARA, LPL, ANGPTL3, APOC3 and CETP). In this study, we observed that genetically-predicted LDL-C, TG, HDL-C or ApoB were significantly related to HF, which were mainly mediated by CHD. Drug target MR analyses identified PCSK9, CETP and LPL as potential targets to prevent HF. The genetic proxy of LDL-C and ApoB increase modified by PCSK9 showed similar evidence in increasing risk of HF (PLDL-C = 1.27*10-4; PApoB = 1.94*10-4); CETP played a role in HF risk via modifying all investigational lipid traits with the strongest evidence though ApoB (P = 5.87*10-6); LPL exerted effects on HF via modifying most lipid traits with the strongest evidence observed via modifying TG (P = 3.73*10-12).CONCLUSION: This two-sample MR study provided genetic evidence of the associations between lipid traits and HF risk, which were mostly mediated by CHD. Besides, drug target MR studies indicated that PCSK9 inhibition, CETP inhibition and LPL activation were effective in HF reduction.FUNDING INFORMATION: Start-up Fund for high-level talents of Fujian Medical University.
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| 8. |
- Yi, Huan, et al.
(author)
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Association of Levonorgestrel-Releasing Intrauterine Device with Gynecologic and Breast Cancers: National Cohort Study in Sweden
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In: American Journal of Obstetrics and Gynecology. - 1097-6868.
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Journal article (peer-reviewed)abstract
- BackgroundThe levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive.ObjectiveWe aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer.Study DesignA total of 514719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1544157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios and 95% confidence intervals. Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model.ResultsThe use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99) and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P < 0.002), and 1.63 additional cases per 10,000 person-years.ConclusionsThe risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It's important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.
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| 9. |
- Zhang, Huimin, et al.
(author)
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Integration of Learning-Based Testing and Supervisory Control for Requirements Conformance of Black-Box Reactive Systems
- 2018
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In: IEEE Transactions on Automation Science and Engineering. - : IEEE. - 1545-5955 .- 1558-3783. ; 15:1, s. 2-15
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Journal article (peer-reviewed)abstract
- A fundamental requirement of the supervisory control theory (SCT) of discrete-event systems is a finite automaton model of the plant. The requirement does not hold for black-box systems whose source code and logical model are not accessible. To apply SCT to black-box systems, we integrate automaton learning technology with SCT and apply the new method to improve the requirements conformance of software reuse. If the reused software component does not satisfy a requirement, the method adds a supervisor component to prevent the black-box system from reaching ''faulty sections.'' The method employs learning-based testing (LBT) to verify whether the reused software meets all requirements in the new context. LBT generates a large number of test cases and iteratively constructs an automaton model of the system under test. If the system fails the test, the learned model is applied as the plant model for control synthesis using SCT. Then, the supervisor is implemented as an executable program to monitor and control the system to follow the requirement. Finally, the integrated system, including the supervisory program and the reused component, is tested by LBT to assure the satisfiability of the requirement. This paper makes two contributions. First, we innovatively integrate LBT and SCT for the control synthesis of black-box reactive systems. Second, software component reuse is still possible even if it does not satisfy user requirements at the outset.
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| 10. |
- Zhang, Naiqi, et al.
(author)
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An Increasing Trend in the Prevalence of Polypharmacy in Sweden : A Nationwide Register-Based Study
- 2020
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In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 11
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Journal article (peer-reviewed)abstract
- Aim: Polypharmacy is becoming a global health problem. The aims of this study were to evaluate the temporal trends in the prevalence of polypharmacy in Sweden and to explore polypharmacy disparities by age, gender, education, and immigration status. Methods: Polypharmacy and excessive polypharmacy were evaluated using data extracted from the Swedish Prescribed Drug Register between 2006 and 2014. Polypharmacy was defined as being exposed to five or more drugs and excessive polypharmacy was defined as being exposed to 10 or more drugs during 1 month respectively. Average annual percent change (AAPC) was calculated using Joinpoint Statistical Software. Results: The prevalence of polypharmacy increased from 16.9% in 2006 to 19.0% in 2014 with an AAPC of 1.3; the prevalence of excess polypharmacy increased from 3.8% in 2006 to 5.1% in 2014 with an AAPC of 3.4. The prevalence of polypharmacy and excessive polypharmacy increased dramatically with age and peaked up to 79.6% and 36.4% in individuals aged 90 and above respectively. Females and individuals with lower education level were associated with a higher rate of polypharmacy and excessive polypharmacy. Immigrants from Middle-Eastern countries had the highest rate of polypharmacy and excessive polypharmacy, whereas individuals from Western Europe countries had the lowest rate. Conclusion: The prevalence of polypharmacy has increased gradually in Sweden during the past decade. Individuals with older age, female sex, or lower education have a higher rate of polypharmacy and excessive polypharmacy. Immigrants from Middle-Eastern countries showed a higher rate of polypharmacy.
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