Postgraduate Medical Journal最新文献

{"title":"Effects of miRNAs in inborn error of metabolism and treatment strategies.","authors":"Harun Bayrak, Parisa Sharafi, Ahmet Ç Özketen, Mustafa Kılıç","doi":"10.1093/postmj/qgae201","DOIUrl":"10.1093/postmj/qgae201","url":null,"abstract":"<p><p>Metabolism is the name given to all of the chemical reactions in the cell involving thousands of proteins, including enzymes, receptors, and transporters. Inborn errors of metabolism (IEM) are caused by defects in the production and breakdown of proteins, fats, and carbohydrates. Micro ribonucleic acids (miRNAs) are short non-coding RNA molecules, ⁓19-25 nucleotides long, hairpin-shaped, produced from DNA. They play key roles in regulating gene expression of target mRNAs at both transcriptional and post-transcriptional levels. Altered expression of miRNAs has emerged as an additional molecular mechanism implicated in the pathogenesis of many diseases, this altered miRNA expression is also present in inherited metabolic diseases. A single miRNA can regulate targets associated with similar cellular processes and pathways, making miRNAs powerful therapeutics to restore the impaired cellular functions seen in disease phenotypes by enhancing the cellular response. Although the miRNA research field has advanced significantly in recent years, studies in IEM are still limited. Further research on miRNA expression specifically related to IEM may allow the identification of new biomarkers for the diagnosis, progression, and prognosis of diseases. In this review, the literature studies between miRNAs and IEMs, diagnosis, prognosis, follow-up, and treatment possibilities of miRNAs were analyzed. We present recent advances on miRNAs in IEM and an overview of current miRNA therapeutics for the clinic.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":"101 1199","pages":"791-803"},"PeriodicalIF":2.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874848","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":"Application of the wireless wearable monitoring system improves the turnaround time in gastrointestinal endoscopy center.","authors":"Bo Zhu, Yu Huang, Yi Liu, Min Wang, Ling Liu","doi":"10.1093/postmj/qgaf103","DOIUrl":"10.1093/postmj/qgaf103","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate whether the wireless monitoring system can reduce the turnaround time in gastrointestinal endoscopy center.</p><p><strong>Methods: </strong>Enrolled patients were randomly allocated to the study or control group. The primary outcome was the turnaround time. The secondary outcomes included the total time from entering examination room to discharge (T1), the total time of monitoring mean arterial pressure (T5), incidences of hypotension, bradycardia, and hypoxia, evaluation of the medical staff, and rate of effective monitoring.</p><p><strong>Results: </strong>166 patients were analyzed. The turnaround time of study group was significantly shorter than that of control group (1.49 ± 1.82 vs. 4.78 ± 3.77 min, P < .001). The study group had a significantly shorter T1 (44.69 ± 4.54 vs. 49.49 ± 5.53 min, P < .001), but a longer T5 (44.39 ± 4.38 vs. 42.21 ± 4.97 min, P = .012). The medical staff gave higher scores to the wireless monitoring system in terms of practicability and application value (P < .05), but gave equally high evaluations on data reliability (P > .05). The rate of effective monitoring was acceptable in both groups.</p><p><strong>Conclusion: </strong>Application of the wireless monitoring system in an endoscopy center is feasible and acceptable, and improves the turnaround time.</p><p><strong>Trial registration: </strong>This study was registered at the Chinese Clinical Trial Registry on 19 April 2024 (ChiCTR2400083277).</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":"873-879"},"PeriodicalIF":2.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529398","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":"Diabetes and obesity susceptibility genes: a cross-sectional analysis of methylation patterns from Karachi, Pakistan.","authors":"Syeda Sadia Fatima, Asad Saulat Fatimi, Manzar Abbas, Unab I Khan","doi":"10.1093/postmj/qgaf016","DOIUrl":"10.1093/postmj/qgaf016","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose of study: &lt;/strong&gt;Environmental factors are pivotal in shaping disease outcomes for obesity, diabetes, and metabolic syndrome (MetS), especially in the Pakistani population. This study aimed to determine whether promoter methylation levels of 12 diabetes and obesity susceptibility genes are associated with MetS phenotypes and risk of T2DM in Pakistani individuals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design: &lt;/strong&gt;A cross-sectional study was undertaken whereby methylation-specific PCR assays were conducted on 203 adult subjects recruited from the community in Karachi, Pakistan. Participants were stratified into four groups based on their metabolic health and BMI (MOU n = 39, MHO n = 43, MUHNW n = 51, MHNW n = 70). Biochemical and biophysical data were statistically analyzed to determine the association of methylation levels with MetS phenotypes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Low chemerin promoter methylation was observed in metabolically unhealthy participants, irrespective of BMI, while higher methylation levels were observed for POMC and PCSK1. Unsupervised machine learning showed that the methylation status of Chemerin, IGF2, POMC, PCSK1 (P &lt; .001), and FNDC (P &lt; .05) was independently linked with the risk of developing MetS. Hierarchical clustering analysis revealed distinct genetic clusters that partially aligned with the original MetS and BMI categories, indicating the presence of unique genetic profiles and the potential misdiagnosis of high-risk individuals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Chemerin, IGF2, POMC, PCSK1, and FNDC's methylation status shows independently linked trends with the risk of developing MetS and obesity. Distinct genetic clusters for MUHNW and MHO exhibit similar phenotypic profiles, implying misdiagnosis risks and comparable risks of developing cardiometabolic disorders in the future. Large-scale methylation studies are needed to confirm the association. Key message What is already known on this topic:  Genetic susceptibility contributes significantly to complex disorders like obesity, diabetes, and MetS. Prior research has highlighted the role of genetic polymorphisms but hasn't extensively explored the influence of promoter methylation in Pakistani populations. Understanding genetic and epigenetic factors in disease etiology is crucial for tailored interventions, particularly in populations with diverse genetic backgrounds and environmental exposures. What this study adds:  Distinct trends of methylation patterns were observed in genes like Chemerin, IGF2, POMC, PCSK1, and FNDC, independently linked with MetS and obesity risk. Potential misdiagnosis risks and comparable risks of developing cardiometabolic disorders in individuals with metabolically unhealthy normal weight individuals and metabolically healthy phenotypes were observed. How this study might affect research, practice, or policy:  Incorporating epigenetic biomarkers into risk assessment algorithms could enhance disease prediction accuracy a","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":"854-862"},"PeriodicalIF":2.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390385","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":"Genetic insights into visceral obesity with health conditions, from disease susceptibility to therapeutic intervention.","authors":"Genshan Zhang, Baolin Han, Yanghui Chen, Wei Jiang, Jie Fu, Xiangshang Xu, Xuelai Luo, Zhixin Cao","doi":"10.1093/postmj/qgaf004","DOIUrl":"10.1093/postmj/qgaf004","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the relationship between visceral obesity and various disease traits, as well as to identify potential safe targets for the prevention and treatment of visceral obesity.</p><p><strong>Study design: </strong>Univariable and multivariable Mendelian randomization (MR) analyses were performed to examine the associations between visceral obesity and 1883 disease traits. Furthermore, we assessed the potential effect of 1684 protein expressions on visceral obesity using the available quantitative trait locus data for plasma proteins. To evaluate the potential safety profiles associated with biomarker intervention, we conducted phenome-wide MR using 1883 outcomes, focusing on the significant biomarkers.</p><p><strong>Results: </strong>Visceral obesity was significantly associated with elevated risks of 183 disease traits across multiple systems, such as endocrine, cardiovascular, respiratory, digestive, musculoskeletal, and genitourinary systems. Higher genetically predicted levels of GCKR, CYB5A, ITPKA, and ENTPD6 were found to increase the risk of visceral obesity, while 1433B, SEMA3G, FOXO3, and HAPLN4 were associated with a decreased risk of visceral obesity. The results of the phenome-wide MR analysis indicate that CYB5A, ENTPD6, 1433B, and HAPLN4 can potentially be safe and effective drug targets for visceral obesity treatment.</p><p><strong>Conclusions: </strong>This study indicates visceral obesity is associated with an increased risk of diseases within various physiological systems, such as cardiovascular, respiratory, and endocrine systems. The circulatory proteome reveals eight novel biomarkers for visceral obesity intervention, with CYB5A, ENTPD6, 1433B, and HAPLN4 displaying particular potential as safe and effective drug targets.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":"804-813"},"PeriodicalIF":2.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010292","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 basal metabolic rate and infectious diseases: a Mendelian randomization study.","authors":"Zhanbin Li, Yicheng Ma, Qiuhui Xuan, Zhenyu Yao, Qiaoran Liu","doi":"10.1093/postmj/qgaf018","DOIUrl":"10.1093/postmj/qgaf018","url":null,"abstract":"<p><strong>Background: </strong>The causal relationship between basal metabolic rate (BMR) and infectious diseases remains elusive. This study aims to clarify this association.</p><p><strong>Methods: </strong>This study analyzed genome-wide association studies (GWASs) data from the UK Biobank and FinnGen cohorts to investigate the association between BMR and infectious diseases in European populations. Mendelian randomization (MR) analysis was initially employed, followed by multivariable Mendelian randomization (MVMR) to account for potential confounders. Mediation analysis further confirmed significant relationships. Sensitivity analyses were conducted to validate the study findings.</p><p><strong>Results: </strong>Using two sample MR, genetically predicted BMR was positively linked to skin and soft tissue infections (SSTIs) (OR: 1.31, 95% CI: 1.18-1.47, P < .001), osteomyelitis (OR: 1.95, 95% CI: 1.36-2.80, P < .001) (1.36 ± 2.80), all-cause infections (OR: 1.36, 95% CI: 1.26-1.48, P < .001) and sepsis (OR: 1.36, 95% CI: 1.23-1.51, P < .001). MVMR analysis confirmed BMR's direct causal effect on SSTIs, osteomyelitis, all-cause infections, and sepsis, except for BMI and other factors affecting osteomyelitis. Mediation analysis revealed VAT as a mediator in the linkage between BMR and SSTIs and all-cause infections. HbA1c mediated the path from BMR to osteomyelitis, while CRP and BMI exhibited mediation effects in the BMR-all-cause infections relationship.</p><p><strong>Conclusion: </strong>The study revealed a significant link between increased BMR and elevated risks of SSTIs, osteomyelitis, and bacterial infections, highlighting the intricate BMR-immune connection and its implications for disease control. Key message What is already known on this topic:  High BMR is positively correlated with COVID-19 and associated with proinflammatory and immunological activation, but the relationship between BMR and other infectious diseases remains largely unexplored. What this study adds:  Higher BMR significantly raises the risk of SSTIs, osteomyelitis, all-cause infections, and sepsis. VAT, HbA1c, CRP, and BMI may mediate the BMR-infection relationship. How this study might affect research, practice, or policy:  A higher BMR may be a valuable indicator associated with an increased risk for SSTIs, osteomyelitis, and sepsis. Modulating BMR might hold promise as a clinically relevant intervention to prevent specific infectious diseases.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":"836-844"},"PeriodicalIF":2.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190282","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":"Transforming the NHS through AI-driven solutions: a new era of digital health.","authors":"Mohamed A Imam, Ahmed Elgebaly, Adam Zumla, Shyam Kolvekar, Rizwan Ahmed, Alimuddin Zumla","doi":"10.1093/postmj/qgaf023","DOIUrl":"10.1093/postmj/qgaf023","url":null,"abstract":"","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":"777-778"},"PeriodicalIF":2.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425964","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":"Academic pressure behind the suicide crisis of doctoral students at the Indian Institute of Technology: rethinking doctoral education policies.","authors":"Bo Gao","doi":"10.1093/postmj/qgaf030","DOIUrl":"10.1093/postmj/qgaf030","url":null,"abstract":"","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":"884-885"},"PeriodicalIF":2.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458968","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 reduction of medical resident duty hours for the benefit of patient safety.","authors":"Alison Hager","doi":"10.1093/postmj/qgaf014","DOIUrl":"10.1093/postmj/qgaf014","url":null,"abstract":"<p><p>Since the case of Libby Zion spurred the first duty hour restrictions placed upon medical residents, the impact of fatigue and the importance of duty hour restrictions have been hotly debated. This paper discusses the history of duty hour restrictions as well as the documented impact of fatigue both on the medical profession and other industries upon which the federal government has imposed hours restrictions due to the danger fatigue has been found to pose. It then takes this information and applies it to the American Medical Association's 'Code of Medical Ethics' to determine if residents can truly adhere to these principles and prioritize patient safety while working hours shaped by current duty hour limits.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":"925-930"},"PeriodicalIF":2.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190284","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 Kafkaesque odyssey of securing study leave: a trainee's satirical take.","authors":"Ibraheem Alghamdi","doi":"10.1093/postmj/qgaf011","DOIUrl":"10.1093/postmj/qgaf011","url":null,"abstract":"","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":"880-881"},"PeriodicalIF":2.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391515","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":"Causal association between telomere length and female cancers: a two-sample Mendelian randomization study.","authors":"Yangyang Shi, He Huang, Rui Zhang, Ling Yin","doi":"10.1093/postmj/qgaf028","DOIUrl":"10.1093/postmj/qgaf028","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the causal associations between genetically predicted telomere length and gynecologic and breast cancers.</p><p><strong>Methods: </strong>This Mendelian randomization study used data from genome-wide association studies on telomere length and breast (BC), cervical cancer, endometrial (EC), and ovarian (OC) cancers. The primary analysis was performed using the inverse variance weighted (IVW) method, with confirmation using the weighted median, weighted mode, and MR-Egger methods. Heterogeneity was detected using Cochran's Q-test, horizontal pleiotropy using MR-Egger regression, outliers using MR-PRESSO, and discordant single-nucleotide polymorphisms using the leave-one-out method.</p><p><strong>Results: </strong>The genetic prediction results indicated causal associations between the risk of telomere length and EC [IVW; OR = 1.29, 95% confidence interval (95%CI): 1.05-1.59, P = .02], leukocyte telomere length and EC (IVW; OR = 1.23, 95%CI: 1.01-1.51, P = .04), telomere length and OC (IVW; OR = 1.27, 95%CI: 1.01-1.60, P = .04), telomere length and BC (IVW; OR = 1.12, 95%CI: 1.01-1.23, P = .03), and leukocyte telomere length and BC (IVW; OR = 1.12, 95%CI: 1.02-1.24, P = .02). Cochran's Q-test revealed heterogeneity for telomere length and BC (P < .001), leukocyte telomere length and BC (P < .001), and B-cell telomere length and BC (P = .012). The MR-Egger regression results suggest that the analyses of telomere length and BC (P = .014) and leukocyte telomere length and BC (P = .044) were influenced by horizontal pleiotropy. The MR-PRESSO analysis indicated the presence of outliers in the analyses of telomere length and BC and leukocyte telomere length and breast cancer. After removing the outliers, the statistical significance remained.</p><p><strong>Conclusion: </strong>This MR study suggests a causal association between telomere length and BC, EC, and OC, warranting additional study. Key message What is already known on this topic?  Previous research has indicated an association between telomere length and the risk of various cancers, including breast and gynecologic cancers. However, the causal relationship remained unclear, necessitating further exploration to establish whether telomere length could be a modifiable risk factor for these cancers. What this study adds?  This study provides robust evidence of a causal relationship between genetically predicted telomere length and an increased risk of breast cancer, endometrial cancer, and ovarian cancer, with specific odds ratios indicating a significant association. It highlights that both leukocyte and overall telomere length are important factors in cancer risk. How this study might affect research, practice, or policy?  The findings could inform future research into telomere length as a biomarker for cancer risk, promote investigations into telomere-targeting interventions, and influence guidelines on screening and preventive strategies for at-risk popula","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":"863-872"},"PeriodicalIF":2.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441770","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}