Medicine最新文献

{"title":"Efficacy of auricular bloodletting therapy for acute urticaria: A propensity score-matched retrospective cohort study.","authors":"Lan Xu, Xiujuan Xu, Yuejun Han, Ruyi Ju, Yueping Wang, Xuan Wu, Jiahui Zhou, Yi Cao","doi":"10.1097/MD.0000000000051145","DOIUrl":"https://doi.org/10.1097/MD.0000000000051145","url":null,"abstract":"<p><p>Acute urticaria is a common condition that can affect individuals across all age groups. Current pharmacological treatments primarily rely on antihistamines and corticosteroids. However, these therapies may be limited by suboptimal efficacy, dose- and time-dependence, and potential adverse effects. Therefore, the incorporation of effective adjunctive therapies is of considerable clinical value. This study aimed to evaluate the impact of auricular bloodletting (BL) therapy on the length of hospital stay in patients with acute urticaria. Poisson regression was used to compare differences in hospitalization duration between groups. Propensity score matching (PSM) was applied to minimize selection bias. Subgroup analyses by sex and age, as well as robustness checks using bootstrap resampling and Rosenbaum sensitivity analysis, were also performed. Before PSM, Poisson regression indicated that the bloodletting group had significantly shorter hospital stays. The effect was significant in the male, female, and adult subgroups. After PSM, the incidence rate ratios remained below 1 in all models, and statistical significance was observed. No significant differences were observed in the female or adult subgroups post-matching, whereas statistical significance was retained in the male subgroup. No adverse events were reported. Bootstrap and Rosenbaum sensitivity analyses confirmed the robustness of the findings. Patients who received auricular BL experienced shorter hospital stays. Post-matching results showed that statistical significance was retained in the male subgroup. Given the limited sample size in the intervention group, further prospective studies with larger cohorts are warranted to validate these findings and elucidate the underlying mechanisms.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 42","pages":"e51145"},"PeriodicalIF":2.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207059","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":"Integrated network toxicology, transcriptomic, and Mendelian randomization analyses explore potential molecular links between acrylamide exposure and clear cell renal cell carcinoma.","authors":"Shuwen Deng, Shuang Wang, Zhiqiang Zeng, Tao Li, Lunhong Zou, Yubo Zhou, Lei Lei, Tao Zhou","doi":"10.1097/MD.0000000000051254","DOIUrl":"https://doi.org/10.1097/MD.0000000000051254","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Acrylamide is a potential carcinogen widely encountered in occupational settings and heat-processed foods. However, the potential molecular relationships between acrylamide-associated targets and clear cell renal cell carcinoma remain poorly characterized. The toxicological characteristics of acrylamide were predicted using ProTox-3.0 and ADMETlab 3.0. Potential acrylamide-associated targets were identified using SwissTargetPrediction, the Similarity Ensemble Approach, and TargetNet and were intersected with clear cell renal cell carcinoma (ccRCC)-related genes obtained from GeneCards. Protein-protein interaction networks and functional enrichment analyses were performed using Search Tool for the Retrieval of Interacting Genes/Proteins, Cytoscape, and bioinformatics approaches to characterize the biological functions of the shared targets. Using The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma transcriptomic data, least absolute shrinkage and selection operator-Cox regression was applied to identify prognostic genes and construct a risk-prediction model. Two-sample Mendelian randomization analysis was subsequently conducted to evaluate associations between genetically predicted candidate-gene expression and kidney cancer risk. Representative immunohistochemical images from the Human Protein Atlas were examined as qualitative supporting evidence. Acrylamide was predicted to have potential carcinogenic properties. Among 161 putative acrylamide-associated targets and 1235 ccRCC-related genes, 50 overlapping targets were identified and were mainly enriched in chemical stress, oxidative stress, hypoxia-related processes, phosphoinositide 3-kinase-protein kinase B, hypoxia-inducible factor 1 (HIF-1), FoxO, and central carbon metabolism pathways. Least absolute shrinkage and selection operator identified 8 prognostic genes: TP53, EGFR, PTEN, IL6, MTOR, SLC2A1, SCARB1, and IKBKB. The internally assessed 1-, 3-, and 5-year area under the curves were 0.688, 0.647, and 0.698, indicating moderate apparent discrimination. SLC2A1 was significantly upregulated in ccRCC, and genetically predicted higher SLC2A1 expression was associated with increased kidney cancer risk (odds ratio = 1.762, 95% confidence interval: 1.247-2.491, raw P = .001, false discovery rate-adjusted P = .006). TP53 showed a less robust inverse association (odds ratio = 0.506, 95% confidence interval: 0.291-0.881, raw P = .016, false discovery rate-adjusted P = .048), with evidence of directional horizontal pleiotropy. Representative Human Protein Atlas images provided qualitative support for the transcriptomic findings. This integrative analysis identified SLC2A1 as a prioritized candidate at the intersection of predicted acrylamide-associated targets and ccRCC-related biological processes. The convergent network, transcriptomic, and genetic findings provide a hypothesis for further investigation but do not establish that SLC2A1 or TP53 mediates an effect of acrylamide on rena","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 42","pages":"e51254"},"PeriodicalIF":2.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207183","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":"Feasibility and perceptions among hemophilia patients and doctors towards ultrasound for the assessment of subclinical abnormalities in hemophilic joints.","authors":"Ming Ye, Hong Zhou, Yuxin Zhao, Rong Chen, Hua Gao, Shen Gao, Lin Yang, Yaxi Li, Xin Zeng, Changyu Chen, Yang Zhou","doi":"10.1097/MD.0000000000051155","DOIUrl":"https://doi.org/10.1097/MD.0000000000051155","url":null,"abstract":"<p><p>This study explores the feasibility and perceptions of using ultrasound (US) for identifying subclinical abnormalities in hemophilic joints from the perspectives of both patients and medical practitioners. This was a single-center pilot follow-up study that included multidisciplinary medical professionals and severe hemophilia patients. The Hemophilia Early Arthropathy Detection with Ultrasound in China (HEAD-US-C) scale and Hemophilia Joint Health Score (HJHS) 2.1 were utilized to assess joint conditions. Inter-rater agreement for HEAD-US-C scoring on stored US images was evaluated. Data from 13 multidisciplinary doctors and 28 patients (112 joints: 40 elbows, 24 knees, 48 ankles) were analyzed. Among 40 joints without reported bleeding during follow-up, US total scores increased in 25.0% (10/40), whereas HJHS scores increased in 12.5% (5/40). Among the 78 joints with unchanged HJHS scores, US detected increased structural scores in 21.8% (17/78) of joints. Conversely, among the 66 joints with unchanged US scores, only 9.1% (6/66) exhibited HJHS score changes >0. At the joint level, HEAD-US-C scores were positively correlated with HJHS scores (repeated measures correlation coefficient = 0.757, 95% CI 0.648-0.835, P < .001). US was perceived as useful by 69.2% of doctors (38.5% very useful, 30.8% somewhat useful), and US-based visual explanations were perceived as useful by all patients. The overall linear weighted kappa for patient-level aggregated HEAD-US-C scores assigned by the 2 sonographers was 0.903 (95% CI 0.871-0.935). US assessment using the HEAD-US-C scale appeared feasible and was well accepted by doctors and patients. In this pilot study, US identified increased structural scores in some joints without corresponding HJHS changes, suggesting that it may provide complementary structural information to clinical joint assessment. The findings also showed a positive association between HEAD-US-C scores and HJHS scores and high inter-rater agreement for HEAD-US-C scoring on stored US images. However, this study was not designed to demonstrate superiority over HJHS, diagnostic performance, improved medication adherence, or complete reliability of the HEAD-US-C scoring system.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 42","pages":"e51155"},"PeriodicalIF":2.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207198","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":"Cirrhotic cardiomyopathy: A comprehensive review of pathophysiology, diagnosis, and management.","authors":"Li Zhang, Jing Yi","doi":"10.1097/MD.0000000000051200","DOIUrl":"https://doi.org/10.1097/MD.0000000000051200","url":null,"abstract":"<p><p>Cirrhotic cardiomyopathy (CCM) is a prevalent yet frequently underrecognized cardiac complication of liver cirrhosis, characterized by impaired myocardial contractile reserve, diastolic dysfunction, and electrophysiological abnormalities. Despite its clinical significance, particularly in the setting of liver transplantation, CCM remains largely overlooked. We performed a narrative review of the literature on CCM published up to December 2025, covering pathophysiology, diagnostic criteria, imaging modalities, biomarkers, and management strategies. Depending on the diagnostic criteria used, the prevalence of CCM ranges from 29% to 67.2%. Advanced imaging techniques, particularly global longitudinal strain and cardiac magnetic resonance, enable early detection of subclinical systolic dysfunction. A \"toxic triangle\" comprising systemic inflammation, metabolic derangements, and neurohormonal activation represents an integrated pathophysiological model that drives myocardial fibrosis and dysfunction. Beta-blockers and aldosterone antagonists remain mainstays of pharmacological management, while liver transplantation is currently the only definitive therapy. CCM is an underrecognized condition with substantial clinical implications. Standardized diagnostic criteria, validated biomarkers, and large-scale prospective studies are urgently needed to improve patient outcomes.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 42","pages":"e51200"},"PeriodicalIF":2.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207212","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":"A quality appraisal of clinical practice guidelines for herpes zoster and postherpetic neuralgia using the AGREE II instrument: A systematic review.","authors":"YeEun Hong, JungGun Park, Jaehyun Yoo, Kyuseok Kim","doi":"10.1097/MD.0000000000051100","DOIUrl":"https://doi.org/10.1097/MD.0000000000051100","url":null,"abstract":"<p><strong>Background: </strong>This study systematically assesses the methodological quality of both Western and traditional medicine clinical practice guidelines (CPGs) for herpes zoster (HZ) and postherpetic neuralgia (PHN) using the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument.</p><p><strong>Methods: </strong>A systematic search was conducted up to January 10, 2025 to identify CPGs for HZ or PHN, regardless of whether they were based on Western or traditional medicine. All CPGs addressing diagnosis, evaluation, treatment, prevention, and management were included. Two evaluators independently screened the records and extracted the data. The quality of the CPGs was independently assessed by 5 evaluators using the AGREE II instrument. The intraclass correlation coefficient (ICC) was calculated to assess inter-rater reliability.</p><p><strong>Results: </strong>Eleven CPGs were included, consisting of ten from Western medicine and 1 from traditional medicine. The AGREE II domain scores were as follows: The \"Clarity of Presentation\" domain received the highest score (76.2%), whereas \"Editorial Independence,\" \"Stakeholder Involvement,\" and \"Applicability\" scored below 30%, with \"Applicability\" receiving the lowest score (10.9%). Inter-rater reliability was excellent, with ICCs for the AGREE II domains ranging from 0.927 to 0.990. Four CPGs were rated as Moderate quality (Recommended with modifications), and 6 CPGs were of Low quality (Not recommended). Among the Western medicine CPGs, JASP 2021 was the only 1 rated as High quality (Recommended), whereas CACMS 2013, the only traditional medicine CPG, was rated as Low quality (Not recommended).</p><p><strong>Conclusion: </strong>The findings reveal considerable variability in quality, with overall low-to-moderate quality observed in the guidelines for HZ and PHN. These results highlight the need to address the domains with consistently low scores identified by the AGREE II instrument by adopting a multidisciplinary approach, strengthening applicability, and ensuring rigor in the development process to improve guideline quality.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 42","pages":"e51100"},"PeriodicalIF":2.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207245","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 differential associations of reminiscence and exploratory travel with late-life psychological well-being: A prospective cohort study.","authors":"Ruyue Li, Nana Zhao","doi":"10.1097/MD.0000000000051140","DOIUrl":"https://doi.org/10.1097/MD.0000000000051140","url":null,"abstract":"<p><p>Leisure travel has been associated with better mental health in older adults, but it is unclear whether different travel motivations (remembering the past vs seeking new experiences) are differentially associated with anxiety and feelings of meaning in life, respectively. This study aimed to explore whether there are prospective associations between nostalgia-oriented and exploration-oriented travel motivations and follow-up anxiety symptoms and the sense of meaning in life among older adults and examine the possible underlying psychological pathways. This prospective cohort study included 5482 older adults from southern China. Latent class analysis was used to classify participants into 4 types based on baseline travel motivation: nostalgia-dominant, exploration-dominant, mixed-active, and inactive. Anxiety and a sense of meaning in life were assessed in a follow-up survey. Linear regression, structural equation modeling, subgroup analysis, and predictive analysis were used. Because baseline anxiety and meaning in life were not assessed, all outcome models estimate follow-up levels rather than within-person change. Mixed-active travel was most strongly associated with lower levels of anxiety (β = -1.22, 95% CI: -1.55 to - 0.89) and higher levels of meaning in life (β = 0.58, 95% CI: 0.35 to 0.81). Exploration-dominant travel was significantly associated with lower levels of anxiety (β = -0.92, 95% CI: -1.24 to - 0.60), and this association was partly statistically mediated by psychological capital (33.7%). Nostalgia-dominant travel was significantly associated with higher follow-up meaning in life (β = 0.27, 95% CI: 0.05 to 0.49), and self-continuity partly statistically mediated this association. The association between active travel and lower anxiety was strongest among older adults with low social support. A model that combined travel type and psychosocial factors showed predictive performance for subsequent clinically significant anxiety (area under the curve = 0.78). The associations of later-life travel with mental health depended on travel motivation. Exploration-oriented travel was prospectively associated with lower anxiety, partly statistically mediated by psychological capital, whereas nostalgia-oriented travel was prospectively associated with higher meaning in life, partly statistically mediated by self-continuity. Given the observational design and lack of baseline outcome measures, these findings should be interpreted as associations rather than causal effects.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 42","pages":"e51140"},"PeriodicalIF":2.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207304","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":"Trends in HIV-related mortality by sex, race, age, and region in the United States, 1999-2023: A retrospective CDC WONDER database study.","authors":"Feng Jiang, Ming-Jie Jia, Ying-Lu Ma, Fei-Qing Liang, Weiwei Zeng","doi":"10.1097/MD.0000000000050986","DOIUrl":"10.1097/MD.0000000000050986","url":null,"abstract":"<p><p>Although antiretroviral therapy has improved human immunodeficiency virus (HIV) prognosis, mortality and demographic disparities remain critical public health issues in the United States (US). This study analyzed long-term trends in HIV-related mortality from 1999 to 2023 using Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research data. This retrospective database study analyzed death certificate data for HIV-related deaths in the US from 1999 to 2023. Crude and age-adjusted mortality rates were calculated. Joinpoint regression was used to assess trends using annual percent change (APC) and average APC (AAPC), stratified by sex, race/ethnicity, age group, census region, and urbanization level. A total of 221,831 HIV-related deaths occurred from 1999 to 2023. Annual deaths declined from 14,499 in 1999 to 4719 in 2023, representing a 67.45% reduction. The age-adjusted mortality rate decreased from 8.05 to 1.92 per 100,000 population, with an AAPC of -5.73. The decline was fastest from 2007 to 2011 (APC = -10.99) but slowed from 2019 to 2023 (APC = -2.79). Mortality rates remained higher among men, non-Hispanic Black individuals, and residents of the Southern US. Although mortality declined in both metropolitan and nonmetropolitan areas, the decline was slower in nonmetropolitan areas than in metropolitan areas (AAPC = -3.92 vs -6.54). Mortality increased among older age groups, particularly those aged 75 to 84 years. HIV-related mortality in the US decreased substantially from 1999 to 2023, but the pace of decline slowed in recent years. Persistent racial, geographic, urban-rural, and age-related disparities highlight the need for targeted interventions, improved access to HIV care, and strategies addressing the growing burden among older adults.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 42","pages":"e50986"},"PeriodicalIF":2.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207056","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 characteristics of depression and sleep among Chinese high school students: A cross-sectional study.","authors":"Herun Han, Ziwen Mu, Qiran Li, Hongtao Zeng, Yixuan Ma, Zhihua Liu, Chen Li, Yuxuan Zhou, Zhiguang Guo, Meng Lv, Xiao Zhou","doi":"10.1097/MD.0000000000051117","DOIUrl":"10.1097/MD.0000000000051117","url":null,"abstract":"<p><p>Mental health and sleep problems are among the most significant burdens of illnesses for adolescents in China. This study aimed to investigate the characteristics of depression and sleep quality among high school students and compare sleep quality across students with varying levels of depression. A cross-sectional study was performed to collect data on depression and sleep quality using a paper questionnaire including a self-rating depression scale (SDS) and Pittsburgh Sleep Quality Index (PSQI). Among all the 537 high school students, 57.0% (306 participants) experienced depression and 47.5% (255 participants) suffered from poor sleep quality. Males showed significantly greater SDS scores than females (55.2 ± 7.2 vs 53.8 ± 6.8, P = .027). Significantly greater PSQI score in high school students with moderate-to-severe depression than those with mild depression and nondepression (5.2 ± 2.7 vs 5.3 ± 2.4 vs 6.2 ± 2.3, F = 3.5, P = .032). In contrast, an adjusted logistic regression model indicated that depression severity was not an independent significant predictor of poor sleep quality after adjusting for age, sex, and BMI (all P > .05). Overall, high school students exhibited a high prevalence of depression and poor sleep quality, with those experiencing moderate-to-severe depression showing the poorest sleep quality in unadjusted comparisons. However, depression severity did not remain an independent significant predictor of poor sleep quality after adjustment. Depression and sleep problems among high school students should receive greater attention, particularly for high school students with moderate-to-severe depression.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 42","pages":"e51117"},"PeriodicalIF":2.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207294","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 effects of antihypertensive drugs on thyroid diseases: A trans-ancestry drug-target Mendelian randomization study.","authors":"Xiao-Hong Wang, Yue-Yang Zhang, Qin Wan","doi":"10.1097/MD.0000000000051090","DOIUrl":"10.1097/MD.0000000000051090","url":null,"abstract":"<p><p>Thyroid disorders frequently coexist with cardiovascular disease, including hypertension, but whether long-term modulation of antihypertensive drug targets influences thyroid disease risk remains uncertain. We aimed to evaluate the associations of 7 antihypertensive drug-target classes with thyroid diseases in European and East Asian populations using a trans-ancestry drug-target Mendelian randomization (MR) framework. We performed a two-sample, trans-ancestry drug-target MR analysis of 7 antihypertensive target classes. Target-proximal single-nucleotide polymorphisms associated with systolic blood pressure (SBP) were used as genetic proxies. Estimates were scaled per 1-mm Hg genetically predicted increase in SBP; the putative effect of target inhibition that lowers SBP was therefore interpreted in the opposite direction. Summary statistics were obtained for 4 primary thyroid diseases, benign thyroid tumors where available, and 3 thyroid-related proteins in European and East Asian datasets. Hypertension was used as a positive-control outcome. Random-effects inverse-variance weighting was the primary method, with Wald ratio estimation for single-nucleotide polymorphism instruments and weighted-median, Cochran's Q, MR-Egger, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier analyses as sensitivity assessments. Within the European populace, genetic surrogates for β-blockers exhibit (odds ratio = 0.93; 95% confidence interval = 0.87-0.99) a close association with heightened susceptibility to thyroid carcinoma, whereas KCNH2 (1.15; 1.01-1.32) demonstrates an inverse correlation with thyroid cancer risk. Moreover, calcium channel blockers exhibit a conspicuous linkage with an elevated incidence of hyperthyroidism (0.97; 0.96-0.99) alongside a diminished likelihood of thyroid cancer (1.07; 1.03-1.10). CYP17A1 exerts a protective influence against hyperthyroidism (1.04; 10.1-1.07) and Graves disease (1.10; 1.05-1.16) but manifests a pathogenic effect concerning hypothyroidism (0.99; 0.97-1.00) and thyroid cancer (0.92; 0.86-0.98). Conversely, KCNJ11 demonstrates a proximate correlation between diminished hypothyroidism risk and augmented thyroid cancer susceptibility (0.83; 0.73-0.95). Analogous estimations were noted for CYP17A1 within the East Asian cohort. Genetically proxied perturbation of several antihypertensive drug targets was associated with thyroid disease risk, with CYP17A1 showing the broadest cross-ancestry pattern. These estimates reflect lifelong target-proximal genetic effects rather than the clinical effects of prescribed drugs and should be considered hypothesis-generating pending replication, pharmacoepidemiological studies, and randomized clinical trials.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 42","pages":"e51090"},"PeriodicalIF":2.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207223","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":"Completed clinical trials of p53-targeted therapeutic strategies in cancer: A cross-sectional ClinicalTrials.gov registry analysis.","authors":"Nasser M Alorfi, Nouf M Alourfi","doi":"10.1097/MD.0000000000050949","DOIUrl":"10.1097/MD.0000000000050949","url":null,"abstract":"<p><p>The tumor suppressor gene TP53 is one of the most frequently altered genes in human cancers and plays a central role in regulating cell cycle arrest, apoptosis, and genomic stability. Therapeutic strategies targeting the p53 pathway have been investigated to restore or exploit p53 function in human malignancies. However, the characteristics, reporting completeness, and clinical development patterns of completed trials evaluating p53-targeted therapeutic strategies have not been comprehensively summarized. This study aims to characterize the design, therapeutic strategies, reporting completeness, and primary objectives of completed clinical trials investigating p53-targeted therapeutic strategies for cancer. A cross-sectional registry analysis of ClinicalTrials.gov was conducted using the search terms \"Cancer\" AND \"p53 gene therapy.\" Completed studies available as of 1 July 2025 were screened for eligibility. Trials investigating p53-targeted therapeutic strategies, including p53 gene therapy and other therapeutic approaches directly targeting the p53 pathway, were included. Data extracted included study design, cancer type, therapeutic strategy, clinical phase, enrollment, and primary outcome measures. Descriptive statistics were used to summarize study characteristics; no inferential statistical analyses were performed. Twenty-three completed studies met the eligibility criteria, including 20 (87.0%) interventional and 3 (13.0%) observational studies. The included studies evaluated diverse p53-targeted therapeutic strategies, including adenoviral vector-mediated p53 gene therapy, chemotherapy combinations, immunotherapeutic approaches, biomarker-guided treatment strategies, and molecularly targeted therapies. Early-phase clinical development predominated, with Phase I studies accounting for the largest proportion of completed trials. Enrollment information was available for 17 (73.9%) studies, whereas six (26.1%) did not report participant numbers. Primary outcome measures were reported for 15 (65.2%) studies, while eight (34.8%) lacked clearly defined primary outcomes. Five studies (21.7%) had publicly posted study results on ClinicalTrials.gov, whereas 18 (78.3%) had no posted results available. Reported primary endpoints predominantly focused on safety, dose escalation, treatment feasibility, and biomarker evaluation. Completed clinical trials investigating p53-targeted therapeutic strategies remain predominantly in the early stages of clinical development and have primarily focused on evaluating safety, feasibility, and preliminary biological activity rather than definitive treatment efficacy. Variability in registry reporting, including incomplete enrollment, primary outcome, and study result reporting, limits comprehensive assessment of the current evidence base.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 42","pages":"e50949"},"PeriodicalIF":2.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207208","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}