Postgraduate Medical Journal最新文献

{"title":"Causal relationship between gut microbiota and lung squamous cell carcinoma: a bidirectional two-sample Mendelian randomization study.","authors":"Weijian Song, Jianwei Shi, Minjun Du, Mei Liang, Boxuan Zhou, Linchuan Liang, Yushun Gao","doi":"10.1093/postmj/qgae184","DOIUrl":"https://doi.org/10.1093/postmj/qgae184","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to explore the potential causal relationship between gut microbiota and lung squamous cell carcinoma (LUSC).</p><p><strong>Methods: </strong>A bidirectional two-sample Mendelian randomization analysis was conducted using genome-wide association study (GWAS) data from gut microbiota and LUSC. Gut microbiota served as the exposure factor, with instrumental variables selected from a GWAS involving 18 340 participants. LUSC data were drawn from a European cohort including 29 266 LUSC cases and 56 450 controls. Inverse-variance weighted (IVW) method was used as the primary method, with the Benjamini-Hochberg method applied to adjust for multiple comparisons. An independent dataset (ieu-a-967, containing 3275 LUSC cases and 15 038 controls) was used for replication analysis to ensure robustness.</p><p><strong>Results: </strong>IVW analysis found that Butyricicoccus (OR = 0.79, 95% CI: 0.63-0.99, P = .042) and Coprobacter (OR = 0.85, 95% CI: 0.74-0.97, P = .018) were significantly protective against LUSC. In contrast, Victivallis (OR = 1.11, 95% CI: 1.00-1.23, P = .045) and Ruminococcus (OR = 1.28, 95% CI: 1.03-1.60, P = .028) increased LUSC risk. Replication analysis in the independent dataset confirmed significant associations for Ruminococcus and Coprobacter. No reverse causality or pleiotropy was detected.</p><p><strong>Conclusion: </strong>This study provides evidence of a causal relationship between specific gut microbiota and LUSC risk, highlighting new microbial targets for potential prevention and treatment strategies in lung cancer. Key messages What is already known on this topic?  Previous studies have suggested potential links between gut microbiota composition and the development of various cancers, including lung cancer. However, the exact causal relationship between specific gut microbiota and lung squamous cell carcinoma (LUSC) has remained unclear. Traditional observational studies have struggled to determine the direction of causality due to confounding factors, making further investigation necessary through more robust methods such as Mendelian randomization (MR). What this study adds?  This bidirectional MR study provides novel genetic evidence indicating that certain gut microbiotas are causally associated with LUSC risk. Specifically, Butyricicoccus appears to reduce the risk of LUSC, while Victivallis increases the risk. These findings highlight the role of the gut-lung axis in LUSC and open up new avenues for exploring gut microbiota as potential modulators of lung cancer risk. How this study might affect research, practice, or policy?  The implications of this study may significantly influence future research into cancer prevention strategies by targeting gut microbiota. Additionally, it could inform clinical practices aimed at modulating gut microbiota to lower the risk of LUSC, potentially influencing dietary or probiotic interventions to reduce cancer susceptibility. Furthermore, ","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847258","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":"Integrating bioinformatics and machine learning to unravel shared mechanisms and biomarkers in chronic obstructive pulmonary disease and type 2 diabetes.","authors":"Shen Jiran, Wang Jiling, Zhou Sijing, Zhang Binbin, Li Pulin, Han Rui, Fei Guanghe, Cao Chao, Wang Ran","doi":"10.1093/postmj/qgae186","DOIUrl":"https://doi.org/10.1093/postmj/qgae186","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) are on the rise. While there is evidence of a link between the two diseases, the pathophysiological mechanisms they share are not fully understood.</p><p><strong>Methods: </strong>In this study, the co-expressed genes of COPD and T2DM in Gene Expression Omnibus database were identified by bioinformatics method, and the functional enrichment analysis was performed. Machine learning algorithms were used to identify biomarkers. The diagnostic value of these biomarkers was assessed by receiver operating characteristic analysis, and their relationship to immune cells was investigated by immunoinfiltration analysis. Finally, real-time quantitative polymerase chain reaction was performed.</p><p><strong>Results: </strong>A total of five overlapping genes were obtained, focusing on pathways associated with insulin resistance and inflammatory mediators. The machine learning method identified three biomarkers: matrix metalloproteinase 9, laminin α4, and differentially expressed in normal cells and neoplasia domain containing 4 C, all of which were shown to have high diagnostic values by receiver operating characteristic analysis. Immunoinfiltration analysis showed that it was associated with a variety of immune cells. In addition, the real-time quantitative polymerase chain reaction results confirmed agreement with our bioinformatics analysis.</p><p><strong>Conclusions: </strong>Our study sheds light on the common pathogenesis and biomarkers of both diseases, and these findings have potential implications for the development of new diagnostic and treatment strategies for COPD and T2DM. Key message What is already known on this topic?  Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) often coexist as comorbidities. However, the exact mechanistic link between the two diseases remains complex, multifactorial, and not fully understood. What this study adds?  Three biomarkers, including matrix metalloproteinase, laminin α4, and differentially expressed in normal cells and neoplasia domain containing 4 C, were identified as key co-expression hub genes in COPD and T2DM. How this study might affect research, practice or policy?  Future studies may benefit from incorporating a larger sample set to further explore and validate the diagnostic and therapeutic effects of these core genes.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847205","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":"Burnout among medical residents: key drivers and practical mitigating strategies.","authors":"Isaac K S Ng, Sarah Z L Tham, Kar Mun Chong, Wilson G W Goh, Christopher Thong, Kevin Soon Hwee Teo","doi":"10.1093/postmj/qgae179","DOIUrl":"https://doi.org/10.1093/postmj/qgae179","url":null,"abstract":"<p><p>Burnout is a prevalent phenomenon in medicine, affecting >50% of physicians and up to 60% of medical residents. This has negative consequences for both doctors' mental health and job satisfaction as well as patient care quality. While numerous studies have explored the causes, psychological effects, and workplace solutions, we aim to practicalize the issue from the perspectives of residents by discussing three key drivers of burnout and offering actionable, multipronged strategies that may be able to tackle these root causes effectively. From review of relevant literature and personal reflections/experiences, we identified three key factors that contribute to resident burnout, namely, (i) inherent physician attributes, (ii) mismatched expectations of the medical profession, and (iii) stressful nature of clinical work and residency training for junior physicians. We offer practical strategies that can be implemented by various stakeholders in a concerted manner to target these three areas, namely, to inculcate and foster accurate perception of the medical profession at the outset, develop psychological strength/resilience among medical residents, and make practical improvements to working and training environments.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838663","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":"Exploration oxidative stress underlying gastroesophageal reflux disease and therapeutic targets identification: a multi-omics Mendelian randomization study.","authors":"Jiaxin Shi, Bo Peng, Ran Xu, Xiaoyan Chang, Chenghao Wang, Xiang Zhou, Linyou Zhang","doi":"10.1093/postmj/qgae182","DOIUrl":"https://doi.org/10.1093/postmj/qgae182","url":null,"abstract":"<p><strong>Introduction: </strong>Gastroesophageal reflux disease (GERD) is a chronic inflammatory gastrointestinal disease, which has no thoroughly effective or safe treatment. Elevated oxidative stress is a common consequence of chronic inflammatory conditions.</p><p><strong>Methods: </strong>We employed Summary-data based MR (SMR) analysis to assess the associations between gene molecular characteristics and GERD. Exposure data were the summary-level data on the levels of DNA methylation, gene expression, and protein expression, which obtained from related methylation, expression, and protein quantitative trait loci investigations (mQTL, eQTL, and pQTL). Outcome data, Genome-wide association study (GWAS) summary statistics of GERD, were extracted from the Ong's study (discovery), the Dönertaş's study (replication), and the FinnGen study (replication). Colocalization analysis was performed to determine if the detected signal pairs shared a causative genetic mutation. Oxidative stress related genes and druggable genes were imported to explore oxidative stress mechanism underlying GERD and therapeutic targets of GERD. The Drugbank database was utilized to conduct druggability evaluation.</p><p><strong>Results: </strong>After multi-omics SMR analysis and colocalization analysis, we identified seven key genes for GERD, which were SUOX and SERPING1, DUSP13, SULT1A1, LMOD1, UBE2L6, and PSCA. SUOX was screened out to be the mediator, which suggest that GERD is related to oxidative stress. SERPING1, SULT1A1, and PSCA were selected to be the druggable genes.</p><p><strong>Conclusions: </strong>These findings offered strong support for the identification of GERD treatment targets in the future as well as for the study of the oxidative stress mechanism underlying GERD.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822665","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":"The 2024 revision of the Declaration of Helsinki: a modern ethical framework for medical research.","authors":"Boyuan Wen, Guochao Zhang, Chang Zhan, Chen Chen, Hang Yi","doi":"10.1093/postmj/qgae181","DOIUrl":"https://doi.org/10.1093/postmj/qgae181","url":null,"abstract":"<p><p>The Declaration of Helsinki, established in 1964, remains a foundational document in medical research ethics. This review examines the 2024 revision, endorsed by the 75th World Medical Association (WMA) Assembly, highlighting its impact on modern clinical research. Major updates include the shift from \"subjects\" to \"participants,\" promoting autonomy and active involvement, and the introduction of dual ethical review requirements for cross-border studies to strengthen accountability. New guidelines for data privacy address AI-related ethical concerns, while enhanced community engagement fosters transparency and shared decision-making. Additionally, standards for environmental sustainability encourage research practices that minimize ecological impacts. In response to global health crises such as COVID-19, the revised Declaration sets forth ethical protections to balance participant safety with research urgency during emergencies. Despite these advances, areas for improvement remain, especially in AI ethics, emergency research protocols, and the extension the Declaration's scope to include forensic and specimen research. The 2024 revision thus strengthens the Declaration's role as an adaptive, relevant framework for safeguarding participant rights and research integrity in a changing landscape.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821748","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":"Comprehensive multi-omics approach reveals potential therapeutic targets and agents for osteoarthritis.","authors":"Qingxia Gao, Dawei Yao, Zuozhen Yin, Gongchang Yu, Bin Shi, Jiaying Wang","doi":"10.1093/postmj/qgae176","DOIUrl":"https://doi.org/10.1093/postmj/qgae176","url":null,"abstract":"<p><strong>Background: </strong>The mechanisms underlying osteoarthritis (OA) remain unclear, and effective treatments are lacking. This study aims to identify OA-related genes and explore their potential in drug repositioning for OA treatment.</p><p><strong>Methods: </strong>Transcriptome-wide association studies (TWAS) were performed using genome-wide association studies summary data and expression quantitative trait loci data from the Genotype-Tissue Expression project. Differentially expressed genes between OA patients and healthy controls were identified using four datasets from the Gene Expression Omnibus database. Gene ontology and pathway enrichment analyses identified potential hub genes associated with OA. A network-based drug repositioning approach was applied to discover potential therapeutic drugs for OA.</p><p><strong>Results: </strong>Through TWAS and mRNA expression profiling, 7 and 167 OA-related genes were identified, respectively. From these, 128 OA-related genes were selected based on common biological processes. Using the maximal clique centrality algorithm, 10 core-related genes (JUN, VEGFA, FN1, CD44, PTGS2, STAT1, MAP 2K7, GRB2, EP300, and PXN) were identified for network-based drug repositioning. Consequently, 24 drugs were identified based on 128 OA-related genes and 23 drugs based on 10 core OA-related genes. Some identified drugs, such as dexamethasone, menadione, and hyaluronic acid, have been previously reported for OA and/or rheumatoid arthritis treatment. Network analysis also indicated that spironolactone, lovastatin, and atorvastatin may have potential in OA treatment.</p><p><strong>Conclusion: </strong>This study identified potential OA-related genes and explored their roles in drug repositioning, suggesting the repurposing of existing drugs and the development of new therapeutic options for OA patients. Key message What is already known on this topic The exact pathogenesis of osteoarthritis (OA) remains unclear, and currently, there are no approved drugs that can prevent, halt, or inhibit the progression of OA. What this study adds We identified 128 OA-related genes and 10 core-related genes based on common biological processes revealed by TWAS and mRNA expression profiling. Using these genes, we discovered potential drugs for OA through the Network-based drug repositioning method. How this study might affect research, practice, or policy This study provides recommendations for repositioning existing drugs and developing new treatment options for patients with OA.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814137","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":"The causal relationship between negative emotions and inflammatory dermatoses: a bidirectional Mendelian randomization study.","authors":"Keyi Zhang, Mingwei Zeng, Li Lei, Chuhan Fu, Jiangfeng Huang, Shu Zhou, Yaqing Wen, Jinhua Huang, Jing Chen, Qinghai Zeng","doi":"10.1093/postmj/qgae173","DOIUrl":"https://doi.org/10.1093/postmj/qgae173","url":null,"abstract":"<p><strong>Purpose: </strong>Observational studies have suggested a potential link between emotions and inflammatory dermatoses. However, research on the causal relationship between different types of emotions and inflammatory dermatoses is lacking. This study is aimed to investigate the causal relationship between negative emotions and inflammatory dermatoses through Mendelian randomization (MR) analysis.</p><p><strong>Methods: </strong>Summary data of seven negative emotions were obtained from a genome-wide association study (GWAS) conducted by the MRC-IEU consortium. Seven inflammatory dermatoses including vitiligo, psoriasis, systemic lupus erythematosus, eczema, atopic dermatitis, acne, and rosacea were obtained from published GWAS. The MR analysis primarily employed the Inverse variance weighted (IVW) method, and supplemented by MR-Egger and other three MR methods.</p><p><strong>Results: </strong>The IVW method revealed that guilty feelings have potential to increase the risk of psoriasis (OR = 1.02, 95% CI: 1.00-1.05, P = 0.019), while worrier/anxious feelings have a potential risk effect on eczema (OR = 1.07, 95% CI: 1.00-1.13, P = 0.042). Psoriasis could increase the occurrence of miserableness (OR = 1.41, 95% CI: 1.18-1.68, P = 0.0001), worrier/anxious feelings (OR = 1.26, 95% CI: 1.02-1.57, P = 0.033), nervous feelings (OR = 1.25, 95% CI: 1.05-1.49, P = 0.012), and loneliness/isolation (OR = 1.19, 95% CI: 1.04-1.36, P = 0.009). Eczema might cause an increased incidence of worrier/anxious feelings (OR = 1.038, 95% CI: 1.007-1.070, P = 0.014).</p><p><strong>Conclusion: </strong>This MR study revealed bidirectional causality between worrier/anxious feelings and eczema. It also found that guilty feelings may elevate the risk of psoriasis, and individuals with psoriasis may experience increased rates of miserableness, worrier/anxious feelings, nervous feelings, and loneliness/isolation.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807767","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":"Beyond medicine: how Dr. Smarajit Jana transformed public health for India's most vulnerable.","authors":"Atanu Chandra, Rupak Chatterjee, Sugata Dasgupta, Shatavisa Mukherjee","doi":"10.1093/postmj/qgae177","DOIUrl":"https://doi.org/10.1093/postmj/qgae177","url":null,"abstract":"","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807756","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":"International medical graduates face insurmountable obstacles in accessing academic training in the United Kingdom.","authors":"Hareesha Rishab Bharadwaj, Arkadeep Dhali, Rick Maity","doi":"10.1093/postmj/qgae178","DOIUrl":"https://doi.org/10.1093/postmj/qgae178","url":null,"abstract":"","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807763","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":"Fibrosis mechanisms in systemic sclerosis and new potential therapies.","authors":"Raffaele Barile, Cinzia Rotondo, Valeria Rella, Antonello Trotta, Francesco Paolo Cantatore, Addolorata Corrado","doi":"10.1093/postmj/qgae169","DOIUrl":"https://doi.org/10.1093/postmj/qgae169","url":null,"abstract":"<p><p>Systemic sclerosis is a rare rheumatic disease characterized by immune cell activation, tissue fibrosis, and endothelial dysfunction. Extracellular matrix synthesis disorder causes widespread fibrosis, primarily in skin and internal organs. Various factors such as TGFβ, VEGF, Galectin-3, and signaling pathways like Wnt/β-catenin are involved in pathophysiological processes. Treatment lacks a unified approach but combines diverse modalities tailored to disease subtype and progression. Current therapeutic strategies include biologics, JAK inhibitors, and IL-6 pathway modulators. Monoclonal antibodies and hypomethylating agents demonstrate potential in fibrosis inhibition. This review focuses on emerging therapeutic evidence regarding drugs targeting collagen, cytokines, and cell surface molecules in systemic sclerosis, aiming to provide insight into potential innovative treatment strategies.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829657","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}