Postgraduate Medical Journal最新文献

{"title":"Identification of potential causal genes and drug targets in pulmonary hypertension based on transcriptomic analysis and Mendelian randomization.","authors":"Chengliang Liu, Fanliang Meng","doi":"10.1093/postmj/qgaf044","DOIUrl":"https://doi.org/10.1093/postmj/qgaf044","url":null,"abstract":"<p><strong>Purpose: </strong>Currently, there is no definitive treatment for pulmonary hypertension (PH). This study aims to utilize the GEO database and conduct Mendelian randomization (MR) analysis to identify new genetic targets for PH and investigate their potential pathogenic pathways and therapeutic drugs.</p><p><strong>Methods: </strong>We identified key genes by combining the findings from MR and bioinformatics analyses of GEO datasets. We performed enrichment analysis to explore the functional roles of these key genes. Then, we constructed protein-protein interaction (PPI) and miRNA-mRNA networks to identify interacting proteins and miRNAs. Drug prediction analysis was conducted to propose potential therapeutic drugs. Finally, we validated the results through the GEO dataset, RT-PCR, and western blot experiments.</p><p><strong>Results: </strong>The joint analysis utilizing GEO databases and MR analysis identified two key genes, ITGA2B and TSPAN9 that exhibited significance across both analytical methods. The enrichment analysis indicated that the key genes were involved in critical biological functions and pathways, including cell adhesion, platelet activation, and the PI3K-Akt signaling pathway. The PPI and miRNA-mRNA networks further highlighted the significance of the key genes in PH. Drug prediction analysis revealed the potential of the key genes as therapeutic targets. The RT-PCR and western blot experiments validated the above findings.</p><p><strong>Conclusion: </strong>By integrating bioinformatics and MR analysis, we found that ITGA2B and TSPAN9 have a causal relationship with PH. Our findings offer new insights into the molecular mechanism and potential treatment targets of PH, establishing a basis for future research and clinical applications.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing chikungunya vaccine equity: a Global Health imperative.","authors":"Amira M Taha, Cameron J Sabet, Dang Nguyen, Alfonso J Rodriguez-Morales","doi":"10.1093/postmj/qgaf036","DOIUrl":"https://doi.org/10.1093/postmj/qgaf036","url":null,"abstract":"","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One step forwards, two steps back: changes to Specialised Foundation Programme recruitment in England are counterproductive.","authors":"Andrew MacPhie, Adam Mallis, Callum Weston, Man Hei Marcus Kam","doi":"10.1093/postmj/qgaf040","DOIUrl":"https://doi.org/10.1093/postmj/qgaf040","url":null,"abstract":"","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of mindfulness and sleep quality on self-efficacy of clinical decision making among resident physicians: an observational study.","authors":"Mira M Abu-Elenin, Reham M Mounir, Walaa M Shehata","doi":"10.1093/postmj/qgaf031","DOIUrl":"https://doi.org/10.1093/postmj/qgaf031","url":null,"abstract":"<p><strong>Background: </strong>Mindfulness and sleep quality implicate the mental well-being of physicians; whose job demands high cognitive performance.</p><p><strong>Aim: </strong>This study aimed to measure the effect of sleep quality and mindfulness on residents to make timely proper clinical decisions.</p><p><strong>Methods: </strong>A cross-section study recruited 200 residents at Tanta University hospitals, in Egypt. Sleep quality was assessed using the Sleep Quality Scale, Mindfulness was measured by the Mindful Attention Awareness Scale, and clinical self-decision efficacy was determined by the Decision Self-efficacy Scale.</p><p><strong>Results: </strong>The study revealed that 22.5% of respondents had poor quality and 46.5% had low decision self-efficacy. A statistically significant high score of mindfulness was observed between residents of non-surgical specialties (3.1 ± 0.7). High capability of clinical decisions efficiently was statistically signficant and proportionally correlated with increased mindfulness scale (r = 0.4, P = 0.002). Lower self-efficacy was significantly associated with taking >3-night shifts/week and reduced break duration.</p><p><strong>Conclusion: </strong>There is remarkable low to moderate self-efficacy for clinical decision-making capability among the studied resident physicians, underpinned by the degree of mindfulness and hospital environmental factors.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between body roundness index and stroke incidence among middle-aged and older adults in China: a longitudinal analysis of the CHARLS data.","authors":"Lanqing Peng, Zhiguo Wen, Cong Xia, Yawei Sun, Yifan Zhang","doi":"10.1093/postmj/qgaf043","DOIUrl":"https://doi.org/10.1093/postmj/qgaf043","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the association between body roundness index (BRI) and stroke risk in middle-aged and elderly Chinese population.</p><p><strong>Methods: </strong>This retrospective cohort study utilized data from the China Health and Retirement Longitudinal Study (CHARLS), including participants aged ≥45 years. BRI was the exposure variable, and stroke incidence was the outcome. Weighted Cox regression models analyzed the association and evaluated the threshold effect of BRI on stroke risk.</p><p><strong>Results: </strong>Among 7651 participants, 519 stroke cases were identified. A one-unit increase in BRI was associated with a 15.8% elevated stroke risk [hazard ratio (HR) = 1.158, 95% confidence interval (CI): 1.158-1.159, P < 0.00001]. Quartile analysis revealed that the highest BRI quartile group had an 80.3% increased stroke risk compared to the lowest quartile (HR = 1.803, 95%CI: 1.800-1.806, P < 0.00001). A threshold effect was observed: when BRI was <5.94, a 1-unit increase was associated with an 18% increased stroke risk (HR = 1.18, 95%CI: 1.08-1.29, P = 0.0002). However, when BRI was >5.94, a 1-unit increase was associated with a non-significant 13% decreased risk (HR = 0.87, 95%CI: 0.68-1.12, P = 0.2944).</p><p><strong>Conclusion: </strong>BRI is significantly and positively associated with stroke risk in middle-aged and elderly Chinese population, with a threshold effect observed. BRI may serve as a valuable marker for stroke prediction and prevention, particularly at lower levels. Further research is needed to investigate BRI's applicability in diverse populations and its potential in developing stroke prevention strategies. Key message What is already known on this topic.  Stroke remains a leading cause of death and disability, particularly in China, emerging body shape indices warrant investigation as cardiovascular predictors, extending beyond the cross-sectional associations documented in previous studies. What this study adds.  In this first longitudinal study of Chinese adults aged 45 and older, we identified four distinct BRI trajectory patterns over a 10-year follow-up, revealing that consistently high and rapidly increasing trajectories were associated with elevated stroke risk, with notable gender differences. How this study might affect research, practice, or policy.  Our findings support BRI trajectory monitoring as a valuable stroke risk assessment tool, emphasizing the importance of gender-specific prevention strategies, stable body shape maintenance, and early intervention for unfavorable patterns.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically predicted effects of COVID-19 on 2272 traits: exploring through a phenome-wide Mendelian randomization study.","authors":"Junyu Zhou, Yi Ge, Jing Yu, Yu Zhang","doi":"10.1093/postmj/qgaf037","DOIUrl":"https://doi.org/10.1093/postmj/qgaf037","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic has significantly impacted global health, making it essential to understand its genetic effects on various traits.</p><p><strong>Method: </strong>Leveraging the extensive FinnGen dataset comprising 500 000 individuals, we performed a Mendelian randomization (MR) phenome-wide association study. COVID-19-related phenotypes obtained from the COVID-19 Host Genetics Initiative GWAS (release 7). We employed four distinct approaches, including MR-Egger, weighted median, random-effect inverse variance weighted (IVW), and weighted mode, to conduct the MR analysis.</p><p><strong>Results: </strong>Two hundred fifty-five potential causal effects of COVID-19 were observed for a diverse range of outcomes using the IVW method, including cardiovascular disorders, respiratory conditions, autoimmune diseases, and metabolic disorders. Apart from a few that can be classified as \"other traits,\" the majority of the traits are disease-related traits. We have also identified 31 traits, wherein all four distinct MR analyses yielded a P-value of less than 0.05. Only one trait remained statistically significant after multiple testing correction using the conservative Bonferroni threshold (P < 2.2E-5).</p><p><strong>Conclusions: </strong>This phenome-wide MR study provides valuable insights into the genetically predicted effects of COVID-19 on a comprehensive range of traits. The identified associations contribute to our understanding of the complex interplay between the impact of the post-COVID-19 era on healthcare and may have implications for the development of targeted therapeutic strategies and public health interventions. Key messages What is already known on this topic - COVID-19 has a high mortality rate, and patients often have many sequelae, including myocarditis, acute respiratory distress syndrome, and neurological and hematologic complications. What this study adds Most of the current relevant studies lack large-scale phenotype-group ranging Mendelian randomization (MR) studies on the outcome of COVID-19 due to their small sample sizes. Therefore, this study performed a full phenotypic group MR analysis in the FinnGen dataset to investigate the relationship between COVID-19 and thousands of outcome variables. How this study might affect research, practice or policy- The study identified a set of traits that are strongly associated with genetic susceptibility to the long-term effects of COVID-19.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges towards medical writing in a developing country: a post-graduate resident's perspective.","authors":"Ahsan Tameez-Ud-Din","doi":"10.1093/postmj/qgaf042","DOIUrl":"https://doi.org/10.1093/postmj/qgaf042","url":null,"abstract":"","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helmet continuous positive airway pressure as noninvasive ventilation for COVID-19 patients; a systematic review and meta-analysis of randomized trials.","authors":"Yongke Zheng, Shihan Zhou, Nanyuan Gu, Xiaokang Zeng, Hayat Khizar, Longhuan Zeng","doi":"10.1093/postmj/qgaf038","DOIUrl":"https://doi.org/10.1093/postmj/qgaf038","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic has challenged healthcare systems globally, highlighting the need for effective respiratory support strategies. Helmet continuous positive airway pressure (CPAP) has emerged as a potential noninvasive ventilation (NIV) method for COVID-19 patients.</p><p><strong>Methods: </strong>We searched PubMed, EMBASE, the Cochrane Library, and Scopus from December 1, 2019, to June 1, 2024. Randomized controlled trials (RCTs) comparing helmet CPAP therapy with standard oxygen therapy or other forms of NIV in COVID-19 patients with acute hypoxemic respiratory failure were included. Random effects meta-analyses were performed to calculate pooled risk ratios (RRs) with 95% confidence intervals (95% CIs).</p><p><strong>Results: </strong>Three RCTs involving 580 patients were included in this analysis. There was no significant differences (P > 0.05) in mortality at 28 d (RR, 1.20; 95% CI, 0.84-1.71), 60-90 d (1.02, 95% CI, 0.75-1.37), or 180 d (0.98, 95% CI, 0.76-1.25) between the helmet CPAP group and the control group as well as similar intubation rates (RR 0.90; 95% CI, 0.73-1.10) and times to intubation. However, helmet CPAP was associated with significantly shorter ICU stays and hospital stays. The adverse event rates were similar between the groups. Patient comfort, as measured by the EQ-VAS, was significantly better with the CPAP helmet.</p><p><strong>Conclusion: </strong>The use of helmet CPAP for the treatment of respiratory failure in patients with COVID-19 showed comparable intubation rates and shorter ICU and hospital stays without increasing mortality or adverse events. Key messages What is already known about this topic?  Noninvasive ventilation (NIV) methods, such as helmet CPAP, treat patients with acute hypoxemic respiratory failure. The effectiveness of helmet CPAP for COVID-19 patients is unknown. What this study adds?  This study shows that helmet CPAP has similar intubation and mortality rates to standard treatments in COVID-19 acute respiratory failure patients. It also highlights how helmet CPAP reduces ICU and hospital stays and improves patient comfort. How this study might affect research, practice, or policy?  The findings of this study could lead to future research into helmet CPAP approaches for COVID-19 and other respiratory failure patients. They could also influence clinical practice and healthcare policy by emphasizing helmet CPAP as a preferable noninvasive ventilation technique for similar patient populations.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood biomarkers of Alzheimer's disease: findings from proteomics.","authors":"Yuye Wang, Xiaoqian Niu, Weizhe Zhen, Bin Zhang, Leian Chen, Yuchen Liu, Wei Sun, Dantao Peng","doi":"10.1093/postmj/qgaf039","DOIUrl":"https://doi.org/10.1093/postmj/qgaf039","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease, the most prevalent cause of dementia, is a worldwide health problem. Proteomics is the systematic study of proteins and peptides to provide comprehensive descriptions. Aiming to obtain a more accurate and convenient clinical diagnosis, researchers are working on blood biomarkers.</p><p><strong>Method: </strong>This review synthesizes findings from previous studies investigating blood biomarkers for Alzheimer's disease using proteomic approaches.</p><p><strong>Results: </strong>We summarized the application of blood proteomics as diagnostic biomarkers and associations with clinical indicators such as neuropsychological performances, Aβ deposition and brain atrophy in Alzheimer's disease, and mild cognitive impairment.</p><p><strong>Conclusion: </strong>In summary, blood proteomics is suggested to be promising in biomarkers of Alzheimer's disease.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MVPA as the most influential factor for myocardial infarction through Bayesian Mendelian randomization among 11 behaviors.","authors":"Lei Pu, Peng Sun","doi":"10.1093/postmj/qgaf041","DOIUrl":"https://doi.org/10.1093/postmj/qgaf041","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;The causal associations between behavioral factors (BF) and myocardial infarction (MI), as well as the potential mediators and dose-response relationships, are incompletely clear. Therefore, this study aimed to evaluate the association of 11 BF with MI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We used two-sample Mendelian randomization (2SMR) to investigate he associations between BF and MI and applied a two-sample multivariable MR approach based on Bayesian model averaging (MR-BMA) to prioritize the BF identified by 2SMR. For significant BF, we conducted extra conducted mediation analysis and restricted cubic spline (RCS) analysis to reveal potential mediating pathways and their dose-response relationships. Furthermore, we conducted replication analysis and meta-analysis to further support the results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 11 BF, 2SMR identified 3 BF that were significantly associated with MI. Among them, MR-BMA identified moderate to vigorous intensity physical activity (MVPA) (Marginal inclusion probability (MIP) = 0.77) as the most influential factor. A potential mechanism underlying the MVPA-MI association was waist-hip ratio (WHR, 7.26%). RCS analysis further revealed that an MVPA of 1094-2043 MET minutes/week was associated with the lowest risk of MI. Finally, replication analysis and meta-analysis further supported the 3 BF and identified an extra association between tea intake and MI risk (Meta: OR = 0.991, P = .003).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Of the 11 BF, MVPA was the most influential factor independently associated with the reduced risk of MI, with WHR mediating this association. At least 39 minutes of MVPA per day is recommended to reduce the risk of MI. In addition, tea intake is a potential protective factor for MI that warrants further investigation. Key messages What is already known on this topic?  Previous studies have shown an association between behavioral factors and the risk of myocardial infarction (MI). However, the exact causal relationship, which behavioral factors is most influential for MI, and the potential dose-response relationship are incompletely clear. Mendelian randomization can provide genetic evidence of causal associations and reveal the underlying mechanisms. What this study adds?  This study provides novel genetic evidence that smoking initiation, leisure sedentary time, and moderate to vigorous intensity physical activity (MVPA) are associated with MI. MVPA is the most influential factor. Only MVPA is independently associated with MI, and waist-to-hip ratio mediated the association. In addition, we found that at least 39 minutes of MVPA per day resulted in the greatest reduction in MI. Finally, we also found a potential protective effect of tea drinking on MI. How this study might affect research, practice, or policy?  This study suggests that MVPA is independently associated with MI. In addition, this provides a basis for clinical exercise intervention. Final","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}