Life Conflux
type: channel
description: Life Conflux (ISSN: 3078-4816) is an international, peer-reviewed, open-access journal focused on fundamental research and innovative applications in the field of medical informatics. The journal aims to publish high-quality research on digital health technologies, healthcare data analytics, clinical decision support systems, health information systems, and their applications in improving patient care and healthcare delivery. Spanning interdisciplinary areas such as artificial intelligence in medicine, telemedicine, electronic health records, biomedical data science, and healthcare technology implementation, Life Conflux explores how information technology transforms medical practice and healthcare systems. Through rigorous peer review and an open-access model, Life Conflux provides a vital platform for researchers, academics, healthcare professionals, and industry experts worldwide to share the latest discoveries in digital healthcare innovation and exchange scientific ideas on the integration of informatics solutions in clinical and public health settings.
publisher: Life Conflux Press
language: en
publication name: Life Conflux
issn: 3078-4816
items: Gut Microbiota Affects Cardiovascular Diseases via Inflammatory Cytokines: a Bidirectional Two-sample Mendelian Randomization Study and Mediation Analysis
items: Risk Factors of Reactive Cutaneous Capillary Endothelial Proliferation in Advanced Non-small Cell Lung Cancer Treated with Camrelizumab
items: Artificial Intelligence–Enabled Dissection of Regulatory T Cellsin the Tumor Immune Microenvironment:From Mechanistic Insight to Population-Scale Inference
items: Construction and Validation of a Clinical Model to Predict Lymph Node Metastasis in Early Hypopharyngeal Squamous Cell Carcinoma
items: High-risk Factors and a Nomogram Prediction Model for Pulmonary Fungal Infection in Elderly Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease
items: The Recent Changing Global Landscape of Cancer
items: Regulatory T Cells in Precision Immunotherapy: Mechanistic Insights and Translational Advances of Low-dose Interleukin-2
items: Puerarin Inhibits Gastric Cancer Cell Proliferationby Blocking the G2/M Phase Transition
items: Gut Microbiota and Hypertension: From Pathogenesis to Therapeutic Potential
items: The cGAS-STING Pathway: Insights into Regulatory Mechanisms, Disease Dysregulation, and Therapeutic Development
items: Trends and Cross-Country Inequalities of Melanoma andNon-Melanoma Skin Cancer from 1990 to 2021 and Predictive Trendsfrom 2022 to 2044: A Global Burden of Disease Study
items: Mendelian Randomization Reveals Height as a Risk Factor and Potential Therapeutic Target for Testicular Cancer
items: Do open access articles have a citation advantage? — a research based on European Urology Family
items: New Insights into Influenza Virus-Host Interactions, ImmuneResponses, and Vaccine Development at Single-Cell Resolution
items: Multidimensional Roles of EZH2 and Its Therapeutic Potential in Cancer Therapy
items: Exploring New Therapeutic Targets for Myasthenia Gravis: A Plasma and Cerebrospinal Fluid Proteomics Mendelian Randomization Study
items: Exploring the Causal Relationship Between Plasma Proteins and Systemic Lupus Erythematosus: A Mendelian Randomization Study
items: Tinnitus and Risk of Mortality in Normal-Hearing U.S. Adults: A Weighted Study Adjusted for Covariate Balance
items: The early stage of the COVID-19 Pandemic's Psychological Footprint: A Study on the Surge of Mental Health Concerns in China as Reflected by Baidu Index
items: The role of IL-17 family in the process of pulmonary fibrosis
items: Construction of prognostic model and tumor microenvironment landscape based on cuproptosis-related subtypes in melanoma
items: Forearm necrotizing fasciitis caused by freshwater fish in an immunocompromised patient with rheumatoid arthritis for 20 years: a case report and review of the literature
items: Causal Relationships between 1400 Serum Metabolite Traits,179 Plasma Lipids, and Hemorrhoids: A Mendelian Randomization Study and Meta-analysis
items: Causal Relationship between Chronic Gastritis and Sleep Apnea Syndrome: A Bidirectional and Two-step Mendelian Randomization Study
items: Dynamic Evolution of Hyperplastic Polyps in the Setting of Autoimmune Gastritis: An In-Depth Interpretation of Gastrin-Driven Patho-mechanisms in a Case
items: Mapping heterogeneous molecular subtypes of circadian misalignment underlying lung adenocarcinoma risk
items: ceerva81
items: Sphingomyelin mediates the association between natural killer cell receptor 2B4 (CD244) and head and neck cancer
items: Transthoracic pulmonary artery radiofrequency denervation (TPARFD) concomitantly with cardiac operations in adult atrial septal defect with pulmonary arterial hypertension: case report
items: Impact of heavy metals on allostatic load in adults: a NHANES study

Gut Microbiota Affects Cardiovascular Diseases via Inflammatory Cytokines: a Bidirectional Two-sample Mendelian Randomization Study and Mediation Analysis
type: item
description: Background: Cardiovascular diseases (CVDs) arise from complex interactions between genetic predisposition and environmental exposures, manifesting as persistent inflammatory disorders. Although accumulating evidence has implicated gut microbiota in the pathogenesis of CVDs, whether this association reflects a causal relationship remains to be firmly established. Therefore, the present study sought to examine the potential causal links between gut microbiota composition, circulating inflammatory cytokines, and susceptibility to CVDs. Methods: Summary statistics for 196 gut microbiota taxa, 91 cytokines, and 8 CVD subtypes were extracted from the largest published genome-wide association studies (GWAS) to conduct bidirectional two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used as the primary statistical approach. We investigated the causal associations between gut microbiota and 8 CVD subtypes, including coronary artery disease (CAD), coronary atherosclerosis (CAS), heart failure (HF), stroke, atrial fibrillation (AF), angina pectoris (AP), calcific aortic valve stenosis (CAVS), and aortic aneurysm. Multivariable MR (MVMR) analysis was further performed to explore the potential mediating role of cytokines in the causal pathways from gut microbiota to CVDs. Results: MR analysis identified causal associations between 58 gut microbiota taxa, 46 inflammatory cytokines, and CVDs. Specifically, 34 positive and 24 negative causal effects were observed between gut microbiota and CVDs, along with 16 positive and 30 negative causal effects between cytokines and CVDs. Additionally, mediation analysis identified C-C motif chemokine 25 (CCL25) level as a key mediator in the causal relationship from gut microbiota to CVDs. Conclusions: Our findings support a causal link between gut microbiota, inflammatory cytokines, and CVDs, with CCL25 mediating the protective effect of specific gut taxa against CAVS. These identified biomarkers …
subject: Biomedical Data Science and Analytics
  topic: section
subject: Gut microbiota
  topic: keywords
subject: Inflammatory Cytokines
  topic: keywords
subject: Cardiovascular diseases
  topic: keywords
subject: Mendelian randomization
  topic: keywords
creator: Xuekun Hou
creator: Yunxiao Meng
creator: Yuxuan Zhang
creator: Xianghan Zheng
creator: Hongqi Guo
creator: Yichen Zhang
creator: Hongmei Yuan
creator: Zefei Chu
rights: Copyright (c) 2026 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2026-04-21
publication date: 2026-04-21
starting page: e379
ending page: e379
doi: 10.71321/c18kt054

Risk Factors of Reactive Cutaneous Capillary Endothelial Proliferation in Advanced Non-small Cell Lung Cancer Treated with Camrelizumab
type: item
description: Background: Reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common cutaneous immune-related adverse event (irAE) of camrelizumab. The purpose of our research was to explore the risk factors associated with RCCEP and their predictive values. Methods: We conducted a retrospective investigation examining clinical records of advanced non-small cell lung cancer (NSCLC) patients treated with camrelizumab at our hospital between June 2022 and December 2024. Study participants were grouped based on whether they developed RCCEP. To pinpoint potential risk factors associated with RCCEP, we employed logistic regression analysis, while receiver operating characteristic (ROC) curve analysis helped determine the predictive values of our identified variables. Results: Among 194 patients, 94 (48.5%) developed RCCEP, of whom 92 cases developed grade 1-2 RCCEP, only 2 cases developed grade 3 RCCEP, with no grade 4-5 cases. Multivariate logistic regression analysis suggested that not using combined anti-angiogenic drugs (OR: 2.962, 95% CI 1.042-8.422, P = 0.042), high baseline albumin level (OR: 1.422, 95% CI 1.264-1.599, P < 0.001), and high baseline platelet count (OR: 1.018, 95% CI 1.010-1.026, P < 0.001) were significantly associated with RCCEP. ROC curve analysis showed that baseline albumin level, baseline platelet count, and their combination predicted RCCEP occurrence in advanced NSCLC patients receiving camrelizumab, with areas under the curve (AUCs) of 0.836 (95% CI 0.777-0.895), 0.778 (95% CI 0.709-0.847), and 0.874 (95% CI 0.823-0.924), respectively. The cutoff values for albumin and platelet were calculated using the maximum Youden index from the ROC curve, which were 36.85 g/L and 225×109/L, respectively. Conclusion: Not using combined anti-angiogenic drugs, high baseline albumin level, and high baseline platelet count were independent risk factors of camrelizumab-related RCCEP, and the combined indicator had higher predictive value. We recomme…
subject: Digital Health and Public Health Informatics
  topic: section
subject: Camrelizumab
  topic: keywords
subject: advanced non-small cell lung cancer (NSCLC)
  topic: keywords
subject: reactive cutaneous capillary endothelial proliferation (RCCEP)
  topic: keywords
subject: albumin
  topic: keywords
subject: platelet
  topic: keywords
subject: anti-angiogenic drugs
  topic: keywords
creator: Liuning Wang
creator: Shuxing Chen
creator: Siyu Sun
creator: Wenyi Li
creator: Congjun Zhang
rights: Copyright (c) 2026 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2026-03-06
publication date: 2026-03-06
starting page: e350
ending page: e350
doi: 10.71321/ncbcdv45

Artificial Intelligence–Enabled Dissection of Regulatory T Cellsin the Tumor Immune Microenvironment:From Mechanistic Insight to Population-Scale Inference
type: item
description: Background: Regulatory T cells (Tregs) are central regulators of immune tolerance in the tumor immune microenvironment (TIME) and are increasingly implicated in tumor immune evasion and immunotherapy resistance. While mechanistic studies have delineated pathways governing Treg recruitment and functional stability, extending these insights to spatial organization and population-level heterogeneity remains a major challenge. Methods: In this correspondence, we integrate recent advances in tumor immunology with emerging artificial intelligence (AI)–based analytical frameworks to highlight how Treg-driven immune programs can be interrogated at scale. We draw on representative experimental mechanisms and AI-enabled multimodal modeling approaches, including virtual tumor microenvironment reconstruction and vision–language foundation models, to illustrate a mechanism-informed computational perspective. Results: Evidence supports a layered model of tumor-driven Treg regulation, combining chemokine-mediated recruitment with intrinsic transcriptional stabilization within the TIME. AI-enabled approaches enable population-scale inference of Treg abundance, spatial distribution, and functional states, revealing clinically relevant heterogeneity and associations with differential immunotherapy responses that are difficult to capture using conventional experimental strategies alone. Conclusion: The convergence of mechanistic Treg biology and AI-driven TIME modeling offers a conceptual framework for bridging experimental insight with real-world tumor heterogeneity. Mechanism-informed AI has the potential to refine immune stratification and guide Treg-targeted therapeutic strategies, highlighting a translational path forward for precision immuno-oncology.
subject: Clinical Decision Support and AI in Medicine
  topic: section
subject: Artificial intelligence
  topic: keywords
subject: Regulatory T cells
  topic: keywords
subject: Tumor immune microenvironment
  topic: keywords
subject: Immunotherapy
  topic: keywords
subject: Precision oncology
  topic: keywords
creator: Xuexue Hao
creator: Muwei Li
creator: Tao Xiong
creator: Xiaoqiang Liu
rights: Copyright (c) 2026 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2026-02-08
publication date: 2026-02-08
starting page: e342
ending page: e342
doi: 10.71321/s2yhxp11

Construction and Validation of a Clinical Model to Predict Lymph Node Metastasis in Early Hypopharyngeal Squamous Cell Carcinoma
type: item
description: Background: Hypopharyngeal squamous cell carcinoma (HSCC) is the most frequent histologic subtype of hypopharyngeal carcinoma and has a poor prognosis. With the development of upper gastrointestinal endoscopy, an increasing number of early HSCC cases can be diagnosed and treated by endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). However, clinicians lack an effective tool to predict lymph node metastasis (LNM) of early HSCC. Methods: A total of 410 early HSCC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Clinical data (50 early HSCC patients) from our hospital were applied for external validation. Univariate and multivariate logistic regression analyses to filter the risk factors were performed. A nomogram model was built to predict LNM in early HSCC patients according to the multivariate logistic regression model. Results: HSCC patients with lymph node metastasis had worse overall survival rates and a higher risk of long-term mortality (P =0.016). The C-index and AUC of our predictive nomogram model were 0.674 and 0.623-0.726, respectively. The AUC, sensitivity, specificity, PPV, and NPV were 0.680 (95% CI: 0.525-0.835), 80.0%, 46.7%, 50.0%, and 77.8%, respectively, for the validation set. Conclusion: Our study resulted in a novel nomogram model for predicting LNM that can be a promising tool for assessing the feasibility of EMR/ESD in early HSCC. Impact: Our study provides a novel method for HSCC preoperative assessment before ESD.
subject: Digital Health and Public Health Informatics
  topic: section
subject: Metastasis
  topic: keywords
subject: Hypopharyngeal
  topic: keywords
subject: SEER
  topic: keywords
subject: Nomogram
  topic: keywords
subject: Prognosis
  topic: keywords
creator: Keshu Shan
creator: Chunxia Zhu
creator: Xueyou Lv
creator: Jianing Yan
creator: Qier Li
rights: Copyright (c) 2026 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2026-03-27
publication date: 2026-03-27
starting page: e337
ending page: e337
doi: 10.71321/ggvee953

High-risk Factors and a Nomogram Prediction Model for Pulmonary Fungal Infection in Elderly Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease
type: item
description: Background: Pulmonary fungal infection is a major risk factor for death and prolonged hospitalization in elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). At present, early recognition of these infections remains difficult. This study therefore collected clinical data to develop an early-prediction model for fungal pneumonia complicating AECOPD. Methods: We enrolled 404 elderly AECOPD patients admitted to the Department of Respiratory Medicine, First Affiliated Hospital of Anhui Medical University, from January to December 2023. The cohort was randomly split 7:3 into a training set (n =283) and a validation set (n =121). Univariate logistic regression was first performed in the training set; variables with p < 0.05 were entered into a multivariate model. Significant factors were used to construct a nomogram. Model performance was evaluated in both sets by the area under the receiver operating characteristic curve (AUC), calibration plots, and decision-curve analysis (DCA). Results: Smoking history, length of hospital stay, concomitant cardiovascular disease, glucocorticoid use, and the neutrophil-to-lymphocyte ratio (NLR) were independent risk factors for fungal infection during AECOPD (p < 0.05). The nomogram achieved AUCs of 0.884[95% CI: 0.838–0.930] in the training set and 0.879 [95% CI: 0.795–0.962] in the validation set. Calibration and DCA curves indicated good clinical utility. Conclusion: Smoking history, prolonged hospitalization, concurrent cardiovascular disease, glucocorticoid therapy, and elevated NLR are independent risk factors for fungal infection in AECOPD. The constructed nomogram exhibits strong predictive performance.
subject: Digital Health and Public Health Informatics
  topic: section
subject: elderly acute exacerbation of chronic obstructive pulmonary disease
  topic: keywords
subject: fungal infection
  topic: keywords
subject: risk factors
  topic: keywords
subject: nomogram
  topic: keywords
subject: prediction model
  topic: keywords
creator: Tiantian Zhang
creator: Siyu Sun
creator: Yingying Zhu
rights: Copyright (c) 2026 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2026-03-08
publication date: 2026-03-08
starting page: e327
ending page: e327
doi: 10.71321/d3zf3339

The Recent Changing Global Landscape of Cancer
type: item
description: The good news, a 33% drop in U.S. cancer deaths since 1991, masks a troubling demographic shift revealed by the American Cancer Society’s newest statistics. As overall new cases rose from 1.96 million (2023) to 2.04 million (2025), leading to 618,120 expected deaths, the burden is falling unfairly. We’re seeing a rising incidence of breast, uterine corpus, and colorectal cancers in those under 55. For ages 50–64, women now lead men in new diagnoses. Crucially, significant racial gaps persist, with Native American and Black individuals facing two to three times the mortality rate for several cancer types. This evidence points to metabolic and inflammatory environments taking over as the main cancer drivers, moving past tobacco's historical dominance. Our next move must be to fully integrate precision prevention and equitable care access to shift the fight from treatment to early interception.
subject: Digital Health and Public Health Informatics
  topic: section
subject: Cancer trends
  topic: keywords
subject: Early-onset cancer
  topic: keywords
subject: Prevention
  topic: keywords
creator: Ilayda Karsidag
creator: Hengrui Liu
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-12-01
publication date: 2025-12-01
starting page: e312
ending page: e312
doi: 10.71321/e37ss652

Regulatory T Cells in Precision Immunotherapy: Mechanistic Insights and Translational Advances of Low-dose Interleukin-2
type: item
description: Regulatory T cells (Tregs) are the central guardians of immune tolerance, safeguarding against autoimmune and inflammatory damage through Foxp3-dependent transcriptional programs. Recent breakthroughs in precision immunotherapy have revived interest in low-dose interleukin-2 (Ld-IL-2), a cytokine-based strategy that selectively expands and activates Tregs via the high-affinity IL-2 receptor (CD25). This review summarizes emerging mechanistic insights into how Ld-IL-2 orchestrates multilevel immune rebalancing and highlights its translational progress from molecular engineering to clinical applications across autoimmune diseases. We integrated recent findings from cellular, metabolic, and systems immunology studies, together with our own multi-center clinical trial data, to outline the dynamic networks linking IL-2 signaling, Treg plasticity, and immune homeostasis. Ld-IL-2 exerts a dose-dependent biphasic effect on the immune system, selectively enhancing Treg survival and function while restraining pathogenic Th17, Tfh, and Teff subsets. Beyond classical STAT5-FOXP3 activation, recent studies reveal that IL-2 reprograms Treg metabolism toward oxidative phosphorylation, stabilizes Foxp3 epigenetic landscapes, and coordinates intercellular communication through exosomal and tissue-resident networks. Innovations in topologically engineered IL-2 variants and sustained-release delivery systems (e.g., polylactic-acid microsphere–exosome composites) further extend the precision and durability of Treg-directed therapy. Clinical evidence from SLE, Sjögren’s disease, and relapsing polychondritis confirms robust immune restoration and favorable safety profiles within defined dose windows. By selectively activating the Treg axis and reprogramming immune homeostasis, low-dose IL-2 represents a paradigm for precision immunotherapy. Integrating molecular engineering and targeted delivery strategies will enable next-generation cytokine therapies to achieve durable immune tolerance…
subject: Medical Informatics Cases, Reviews and Applications
  topic: section
subject: Regulatory T Cells
  topic: keywords
subject: Low-dose Interleukin-2
  topic: keywords
subject: Foxp3
  topic: keywords
subject: Immune tolerance
  topic: keywords
subject: Precision immunotherapy
  topic: keywords
subject: Translational medicine
  topic: keywords
creator: Ruiling Feng
creator: Bo Huang
creator: Xia Zhang
creator: Jing He
rights: Copyright (c) 2026 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2026-03-10
publication date: 2026-03-10
starting page: e307
ending page: e307
doi: 10.71321/xk8wzt47

Puerarin Inhibits Gastric Cancer Cell Proliferationby Blocking the G2/M Phase Transition
type: item
description: Background: Gastric cancer is a tumor with high morbidity and mortality with in the world, and according to the statistics of the World Health Organization (WHO), the incidence of gastric cancer is predominant in Asia, especially in East Asia, China and Japan are high-incidence areas, which is related to the special dietary habits of East Asians. Methods: In this study, we first investigated the effects of puerarin on the biological behaviors of two gastric cancer cell lines, HGC27 and AGS. To further explore the underlying mechanisms, we performed transcriptome sequencing, which revealed that puerarin primarily influences gastric cancer progression by regulating cell cycle transitions. To validate these findings, we examined the expression levels of cell cycle-related proteins and analyzed cell cycle distribution using flow cytometry. Results: This study demonstrated that puerarin significantly inhibits the proliferation, migration, and invasion of gastric cancer cells (HGC27 and AGS) while promoting their apoptosis. Transcriptome sequencing analysis revealed that puerarin primarily affects the biological behaviors of gastric cancer cells by regulating the G2-to-M phase transition. To validate this mechanism, we further employed flow cytometry to assess cell cycle distribution and analyzed the expression levels of cell cycle-related proteins, providing protein-level evidence that supports the G2/M phase transition regulation identified in the transcriptomic data. Conclusion: Puerarin effectively inhibits the proliferation and invasion of gastric cancer cells. Its mechanism is closely related to the regulation of the G2-to-M phase transition, thereby affecting cell cycle progression and proliferative capacity.
subject: Precision Medicine Informatics
  topic: section
subject: Puerarin
  topic: keywords
subject: Gastric cancer
  topic: keywords
subject: Cell cycle
  topic: keywords
creator: Jianye Han
creator: Weiwei Yuan
rights: Copyright (c) 2026 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2026-02-10
publication date: 2026-02-10
starting page: e301
ending page: e301
doi: 10.71321/zf32x172

Gut Microbiota and Hypertension: From Pathogenesis to Therapeutic Potential
type: item
description: Hypertension is a major global health burden with high morbidity. Beyond traditional genetic and metabolic factors, increasing evidence shows that gut microbiota dysbiosis plays an important role in the development and progression of hypertension. Clinical studies have revealed that hypertensive patients display reduced microbial diversity, decreased abundance of short-chain fatty acid (SCFA)–producing bacteria, and enrichment of pro-inflammatory taxa such as Prevotella and Klebsiella. These microbial alterations are associated with endothelial dysfunction, chronic inflammation, and activation of the sympathetic nervous system through the gut–brain and gut–kidney axis. Mechanistically, microbial metabolites such as SCFAs, lipopolysaccharide (LPS), and trimethylamine-N-oxide (TMAO) participate in blood pressure regulation by influencing vascular tone, immune responses, and renal sodium handling. Loss of SCFA-producing bacteria decreases nitric oxide bioavailability and impairs vasodilation, while accumulation of LPS and TMAO promotes vascular inflammation and oxidative stress. Disruption of intestinal barrier integrity further exacerbates systemic inflammation, creating a feedback loop that sustains elevated blood pressure. Therapeutically, modulation of gut microbiota through probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT) has shown promising antihypertensive effects in both animal and human studies. In addition, some antihypertensive drugs can remodel gut microbiota composition, suggesting potential synergistic benefits of combined treatment. In conclusion, the gut microbiota serves as a key and modifiable factor in hypertension pathogenesis. Understanding its mechanisms and therapeutic potential provides novel perspectives for developing microbiota-based and personalized strategies to improve blood pressure control and reduce cardiovascular risk.
subject: Medical Informatics Cases, Reviews and Applications
  topic: section
subject: Gut microbiota
  topic: keywords
subject: Hypertension
  topic: keywords
subject: Microbiota-targeted therapy
  topic: keywords
creator: Haitao Yang
creator: Jingkun Liu
rights: Copyright (c) 2026 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2026-03-07
publication date: 2026-03-07
starting page: e303
ending page: e303
doi: 10.71321/w9jjqk66

The cGAS-STING Pathway: Insights into Regulatory Mechanisms, Disease Dysregulation, and Therapeutic Development
type: item
description: The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, a central hub of the innate immune system, is a key mediator of immune surveillance against abnormal cytoplasmic dsDNA: cGAS recognizes such dsDNA to synthesize 2'3'-cGAMP, which activates STING and downstream signaling to drive IFN-I and proinflammatory cytokine expression for the maintenance of homeostasis. This mechanism enables the pathway to exert multidimensional roles in physiology and pathology. Its activity is fine-tuned by post-translational modifications and non-coding RNAs. Given its critical role in linking innate immunity to disease progression, it has become a promising therapeutic target. This review summarizes the pathway’s regulatory mechanisms and pathological implications, detailing its roles in immune activation, disease dysregulation, and therapeutic development. It also addresses existing challenges and proposes future directions, aiming to provide new insights for precision therapy against cGAS-STING-associated diseases.
subject: Medical Informatics Cases, Reviews and Applications
  topic: section
subject: cGAS
  topic: keywords
subject: STING
  topic: keywords
subject: Inflammation
  topic: keywords
subject: Tumor Immunity
  topic: keywords
subject: Diseases therapy
  topic: keywords
creator: Yunyong Wang
creator: Xiaohang Lu
creator: Jinna Tan
creator: Jiaqian He
creator: Hui Yin
creator: Peipei Chen
creator: Hemeng Wu
creator: Yuzhen Luo
creator: Mingfen Li
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-12-18
publication date: 2025-12-18
starting page: e300
ending page: e300
doi: 10.71321/dr57c347

Trends and Cross-Country Inequalities of Melanoma andNon-Melanoma Skin Cancer from 1990 to 2021 and Predictive Trendsfrom 2022 to 2044: A Global Burden of Disease Study
type: item
description: Background: Malignant skin melanoma (MSM) and non-melanoma skin cancer (NMSC) have imposed a significant health and economic burden globally. This study aims to explore the disease burden and temporal trends of MSM and NMSC to inform evidence-based prevention and control strategies. Methods: Data were derived from the Global Burden of Diseases (GBD) database, covering deaths, disability-adjusted life years (DALYs), incidence, and prevalence. Joinpoint regression, inequality analysis, decomposition analysis and age-period-cohort analysis identified trends and revealed the causes of burden changes from 1990 to 2021. Nordpred package in R projected the future trends of MSM and NMSC from 2022 to 2044. Results: From 1990 to 2021, global trends showed an increase in the number of deaths, DALYs, incidence, and prevalence for MSM, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). The disease burden was highest in high Socio-Demographic Index (SDI) regions, predominantly concentrated in New Zealand, Australia, and the United States. Among MSM, SCC and BCC, SCC experienced the most substantial increases in age-standardized incidence (AAPC = 1.62 [95% CI: 1.51 to 1.73]) and prevalence (AAPC = 1.90 [95% CI: 1.78 to 2.02]). The primary drivers of changes in DALYs were identified as population aging and population growth. Persistent health inequalities continue to exist in the global burden of skin cancer. In the future, the deaths, DALYs, incidence, and prevalence cases of MSM and NMSC may continue to increase. Conclusion: The disease burden associated with MSM and NMSC remains substantial. Primary prevention for the elderly should be given priority. In the prevention of skin cancer, particular attention should be directed toward SCC. Global medical resources should be appropriately tilted towards skin cancer.
subject: Digital Health and Public Health Informatics
  topic: section
subject: Trend
  topic: keywords
subject: Inequality
  topic: keywords
subject: Global burden of disease
  topic: keywords
subject: Melanoma
  topic: keywords
subject: Non-melanoma skin cancer
  topic: keywords
creator: Zhan Li
creator: Yuqin Tang
creator: Yuan Chen
creator: Yuxin Wang
creator: Yaping Feng
creator: Yue Li
creator: Yingying Yu
creator: Mingyi Zhang
creator: Fang Wang
rights: Copyright (c) 2026 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2026-01-04
publication date: 2026-01-04
starting page: e284
ending page: e284
doi: 10.71321/pykzbr95

Mendelian Randomization Reveals Height as a Risk Factor and Potential Therapeutic Target for Testicular Cancer
type: item
description: Objective To investigate the potential causal relationship between height and the risk of developing testicular cancer using Mendelian Randomization analysis. Methods We utilized phenotype data on height and testicular cancer from two European ancestry cohorts, integrating data from the IEU, FinnGen, and UK Biobank databases. Linkage Disequilibrium Score regression and SNP-associated gene enrichment analyses were initially conducted to assess the association between SNPs and the phenotypes. A two-sample MR approach was then applied to evaluate the causal relationship between height and testicular cancer risk. An additional cohort was analyzed for validation, followed by a meta-analysis to combine results. Reverse MR and colocalization analyses were performed to investigate potential reverse causality. Gene enrichment analysis was conducted to elucidate the biological mechanisms linking height to testicular cancer, and potential eQTL targets for testicular cancer were explored using summary-data-based MR and colocalization analysis. Results The Inverse Variance Weighted method revealed a significant association between genetically predicted height and testicular cancer risk, with an odds ratio of 1.372 (95% CI: 1.024-1.837, p-value < 0.05). Gene enrichment analysis suggested that the extracellular matrix-related pathway might underlie the increased risk of testicular cancer associated with height. PMF1 and SLC9B2 were identified as potential targets for testicular cancer from summary-data-based MR, colocalization, and gene expression analysis. Conclusions This Mendelian randomization study provides evidence supporting a causal relationship between height and the risk of developing testicular cancer, with PMF1 and SLC9B2 identified as potential targets for further investigation.
subject: Clinical Decision Support and AI in Medicine
  topic: section
subject: Height
  topic: keywords
subject: Testicular cancer
  topic: keywords
subject: Mendelian randomization
  topic: keywords
subject: Bayesian colocalization
  topic: keywords
subject: Susceptibility gene
  topic: keywords
creator: Yuanbo Xu
creator: Jieyu Xiong
creator: Yikun Wu
creator: Yuanlin Wang
creator: Hua Shi
creator: Shuxiong Xu
creator: Yuangao Xu
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e273
ending page: e273
doi: 10.71321/sqcqnh24

Do open access articles have a citation advantage? — a research based on European Urology Family
type: item
description: Background: Open access (OA), referring to the practice of providing unrestricted access to scholarly research outputs, has become a main publishing choice for authors. Previous studies have reported OA articles had a citation advantage compared to non-OA articles. Thus, this research aimed to further explore the impact of OA on article citations. Methods: We searched the Web of Science for research articles and reviews published in European Urology and its sub-journals in 2021. After data extraction, IBM SPSS Statistics 26 was used for statistical analysis, and binary logistic regression analysis was conducted to examine the influence of different variables, particularly OA, on article citation counts. Results: The study included 135 articles from European Urology, 183 articles from European Urology Focus, and 101 articles from European Urology Oncology. The analysis revealed a significant positive effect of OA on article citations in European Urology (OR = 0.391, 95%CI = 0.189-0.810, p = 0.011). However, OA did not have a statistically significant impact on article citations in European Urology Focus (p = 0.847) or European Urology Oncology (p = 0.83). Conclusion: Our analysis suggests OA significantly boosts citations in high-impact journals, but shows minimal effect in lower-impact venues.
subject: Medical Knowledge Intelligence
  topic: section
subject: open access
  topic: keywords
subject: European Urology
  topic: keywords
subject: regression analysis
  topic: keywords
creator: Jincong Li
creator: Shuangying Zhang
creator: Ruimeng Yue
creator: Chengxiang Tian
creator: Yuyao Jian
creator: Rui Chen
creator: Yang Liu
creator: Yun Peng
creator: Yuxuan Song
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e262
ending page: e262
doi: 10.71321/xpg76d58

New Insights into Influenza Virus-Host Interactions, ImmuneResponses, and Vaccine Development at Single-Cell Resolution
type: item
description: The integration of single-cell sequencing with spatial transcriptomics and multi-omics analyses has enabled a paradigm shift in biomedical research, thereby expanding its applicability and scientific impact. In the context of influenza virus studies, this technology has been instrumental in dissecting cellular heterogeneity, as demonstrated by its capacity to analyze differential transcriptomic profiles and reconstruct differentiation trajectories at the single-cell level following viral infection. These advances have provided mechanistic insights and a holistic understanding of influenza pathogenesis, surpassing the limitations of bulk-level analyses. This review provides a comprehensive dissection of cutting-edge applications of single-cell sequencing in elucidating influenza virus infection mechanisms, immune cell heterogeneity, and vaccine development. By highlighting the single-cell resolution of virus–host interactions and vaccine efficacy studies, this work offers novel perspectives for designing precision-targeted antiviral interventions.
subject: Clinical Decision Support and AI in Medicine
  topic: section
subject: Single-cell sequencing technology
  topic: keywords
subject: Influenza virus
  topic: keywords
subject: Cellular heterogeneity
  topic: keywords
subject: Immune cell subset differentiation
  topic: keywords
subject: Influenza vaccine
  topic: keywords
creator: Xingting Li
creator: Lingxi Gao
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-12-14
publication date: 2025-12-14
starting page: e259
ending page: e259
doi: 10.71321/dz9d7b09

Multidimensional Roles of EZH2 and Its Therapeutic Potential in Cancer Therapy
type: item
description: Enhancer of zeste homolog 2 (EZH2), a core member of the Polycomb Group (PcG) family, is a pivotal epigenetic regulator. As the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), EZH2 mediates trimethylation of histone H3 lysine 27 (H3K27me3), leading to chromatin condensation and altered expression of downstream genes. This mechanism enables EZH2 to exert multidimensional roles in development, tumors, immunity, and the nervous system. Given its critical role in epigenetic regulation and multidimensional oncogenesis, EZH2 has emerged as a hot target for cancer therapy. This review summarizes EZH2's regulatory functions and specific pro-tumorigenic mechanisms, detailing its roles in epigenetic regulation, tumor proliferation and metastasis, tumor microenvironment, stemness maintenance, drug resistance, metabolic reprogramming, and dysregulated signaling pathways, aiming to inspire new perspectives in cancer treatment research.
subject: Precision Medicine Informatics
  topic: section
subject: EZH2
  topic: keywords
subject: epigenetic modification
  topic: keywords
subject: methylation
  topic: keywords
subject: H3K27me3
  topic: keywords
subject: cancer
  topic: keywords
creator: Hui Yin
creator: Jinna Tan
creator: Jiaqian He
creator: Mingfen Li
creator: Hongsheng Lin
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e252
ending page: e252
doi: 10.71321/q01vae55

Exploring New Therapeutic Targets for Myasthenia Gravis: A Plasma and Cerebrospinal Fluid Proteomics Mendelian Randomization Study
type: item
description: Background: Myasthenia Gravis (MG) is a chronic autoimmune neuromuscular disorder that severely impacts patients' quality of life. Identifying plasma and cerebrospinal fluid (CSF) proteins with a genetic causal relationship to MG may provide novel therapeutic targets. Methods: This study employed the Mendelian randomization (MR) approach, in combination with Bayesian colocalization analysis, to assess the causal relationship between 4,185 plasma proteins and 832 CSF proteins and the risk of MG. Sensitivity analyses were also performed to validate the robustness of the MR results. Additionally, protein–protein interaction networks and candidate drug predictions were utilized to elucidate the complex interactions between proteins and identify potential drug targets. Results: Three plasma proteins and five CSF proteins were significantly associated with MG risk. ALDH2, HSPA1A, PRSS8, MFRP, CTSH, SHBG, and TXNDC12 were found to increase MG risk, while IL36A was negatively correlated. Further colocalization analysis revealed strong evidence for the associations between PRSS8 and HSPA1A with MG (pph4 > 0.8), and substantial evidence for TXNDC12 and ALDH2 (0.8 > pph4 > 0.6). Conclusion: This study employed proteomics-based MR to identify several plasma and CSF proteins significantly associated with the risk of MG. Notably, PRSS8, HSPA1A, TXNDC12, and ALDH2 emerge as potential therapeutic targets for MG. While these findings offer valuable insights into the pathological mechanisms of MG and the development of novel therapeutic strategies, further research is required to evaluate the feasibility and clinical efficacy of these candidate proteins.
subject: Biomedical Data Science and Analytics
  topic: section
subject: Myasthenia Gravis
  topic: keywords
subject: Mendelian Randomization
  topic: keywords
subject: Proteomics
  topic: keywords
subject: Cerebrospinal Fluid Proteins
  topic: keywords
subject: Colocalization
  topic: keywords
subject: Therapeutic Target
  topic: keywords
creator: Hongmei Miao
creator: Yinying Chai
creator: Qianran Hong
creator: Yuxuan Song
creator: Yibo He
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e249
ending page: e249
doi: 10.71321/ybarkw62

Exploring the Causal Relationship Between Plasma Proteins and Systemic Lupus Erythematosus: A Mendelian Randomization Study
type: item
description: Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that severely impacts patient quality of life. Current treatments primarily manage symptoms rather than cure the disease, emphasizing the need for a deeper understanding of its pathogenesis and the discovery of novel therapeutic targets. Circulating proteins are thought to play a critical role in SLE risk, but their causal relationships remain underexplored. Methods: This study used pQTL and genome-wide association study (GWAS) data to perform a two-sample Mendelian randomization (MR) analysis to investigate the genetic causal relationships between circulating proteins and SLE. We identified proteins potentially associated with SLE risk and further analyzed their roles in immune regulation and inflammation using Protein-Protein Interaction (PPI) networks. Colocalization analysis was conducted to validate the associations of key proteins with SLE. Results: Our analysis identified 82 plasma proteins potentially causally linked to SLE risk (p < 0.05). Colocalization analysis confirmed the association of proteins such as TNFAIP3, PDHX, and CTSF with SLE, underscoring their critical role in disease pathogenesis. Additionally, PPI network analysis revealed that these proteins are involved in immune modulation and inflammatory pathways, further supporting their relevance as therapeutic targets. Conclusion: This study identifies 82 plasma proteins that may play a causal role in SLE, with TNFAIP3, PDHX, and CTSF emerging as promising therapeutic targets. These findings provide a foundation for future research aimed at developing precision therapies for SLE.
subject: Biomedical Data Science and Analytics
  topic: section
subject: Systemic Lupus Erythematosus
  topic: keywords
subject: Mendelian Randomization
  topic: keywords
subject: Circulating Proteins
  topic: keywords
subject: Colocalization Analysis
  topic: keywords
subject: Protein-Protein Interaction Network
  topic: keywords
creator: Xinzhen Zhao
creator: Yinying Chai
creator: Qianran Hong
creator: Yuxuan Song
creator: Yibo He
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e246
ending page: e246
doi: 10.71321/ma96k735

Tinnitus and Risk of Mortality in Normal-Hearing U.S. Adults: A Weighted Study Adjusted for Covariate Balance
type: item
description: Background: Tinnitus and hearing loss are both prevalent chronic conditions that can significantly impair quality of life. While prior studies have explored the association between tinnitus and mortality, many have failed to isolate the effect of tinnitus from that of coexisting hearing loss—a frequent comorbidity—which may have introduced confounding and biased the results. To investigate the association between tinnitus and both all-cause and cause-specific mortality among U.S. adults aged 20-69 years with normal hearing. Methods: We conducted a population-based cross-sectional analysis using data from five cycles of the National Health and Nutrition Examination Survey. Adults aged 20-69 years with audiometrically confirmed normal hearing were included. Tinnitus status was self-reported. Key covariates included demographic characteristics, comorbid conditions etc. We implemented propensity score matching and multivariable-adjusted Cox proportional hazards models to estimate the hazard ratios (HRs) for all-cause and cause-specific mortality. Results: Tinnitus was found to be significantly associated with an increased risk of all-cause mortality (HR: 1.84; 95% CI: 1.38-2.44). A particularly elevated risk was observed for cancer-specific mortality (HR: 2.11; 95% CI: 1.26-3.58). Importantly, these findings persisted after adjusting for multiple covariates in the matched cohort, highlighting the robustness of the results derived from a balanced comparison. Conclusions: Among U.S. adults with normal hearing, tinnitus was independently associated with increased risks of all-cause and cancer-specific mortality. These findings underscore the importance of recognizing tinnitus as not merely a benign symptom, but a potential marker of broader health risks, even in individuals without hearing impairment.
subject: Digital Health and Public Health Informatics
  topic: section
subject: tinnitus
  topic: keywords
subject: mortality
  topic: keywords
subject: balance
  topic: keywords
subject: normal hearing
  topic: keywords
subject: National Health and Nutrition Examination Survey (NHANES)
  topic: keywords
creator: Yuchen Zhang
creator: Yanqiang Zhang
creator: Ziyue Fu
creator: Chuanlu Shen
creator: Kaile Wu
creator: Yehai Liu
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e225
ending page: e225
doi: 10.71321/2eyyzr69

The early stage of the COVID-19 Pandemic's Psychological Footprint: A Study on the Surge of Mental Health Concerns in China as Reflected by Baidu Index
type: item
description: Background: The outbreak of COVID-19 has posed an enormous threat to the health of people worldwide, both physically and mentally. We aimed to investigate the impact of COVID-19 on Chinese people’s mental health via the Baidu Index, especially during the early period of the outbreak. Methods: We collected people’s search data regarding mental illness and COVID-19 from the Baidu index. Spearman’s correlation analysis was applied to explore the correlations among mental illness search index values, COVID-19 search index values, and the number of confirmed cases in China. We implemented a dynamic series analysis to show the changing trend of Baidu index search values. Gender, age, and regional distribution of search values were also observed. Internet searches for mental illness increased significantly after the quarantine measures were implemented. Results: The number of COVID-19 cases were positively correlated to the overall search index values for mental illnesses (rs=0.766, p=1.041×10-12), and negatively correlated to search index values for COVID-19 (rs=-0.236, p=0.023). The searches for COVID-19 was positively correlated to the daily growth of cases (rs=0.861, p=2.310×10-18). No lag pattern exists between Internet searches for mental illness and the number of confirmed cases. Male and people over 50 years old searched less than other groups. Besides, the highest search behaviors appeared in southeastern China. Public search behaviors indicate that since the outbreak of COVID-19, the psychological problems of the Chinese people have been extremely prominent. Conclusion: Baidu Index offers a valuable tool for guiding effective intervention and prevention efforts aimed at mitigating psychological stress. Its ability to reflect public search behaviors allows for the timely provision of mental health support during the COVID-19 pandemic and could serve as a model for responding to the mental health challenges posed by future large-scale infectious disease outbreaks.
subject: Digital Health and Public Health Informatics
  topic: section
subject: COVID-19
  topic: keywords
subject: Mental illness
  topic: keywords
subject: Psychological stress
  topic: keywords
subject: Baidu index
  topic: keywords
creator: Nana Meng
creator: Yuan Chen
creator: Danna Zhao
creator: Dingtao Hu
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e219
ending page: e219
doi: 10.71321/62xm7s05

The role of IL-17 family in the process of pulmonary fibrosis
type: item
description: Pulmonary fibrosis is a serious lung disease characterized by the destruction of alveolar structures and excessive proliferation of fibrous tissue. The interleukin-17 (IL-17) family consists of six members (IL-17A-17F), which play a crucial role in the occurrence and development of pulmonary fibrosis. The IL-17 family drives pulmonary fibrosis through multiple mechanisms such as pro-inflammatory cytokines, immune cell recruitment, and fibroblast activation. IL-17A is the core molecule, while other members participate in the disease process through synergistic or independent pathways. Targeting the IL-17 signaling axis provides a new strategy for the treatment of pulmonary fibrosis. This article summarizes the effects of IL-17 on pulmonary inflammation response and fibrosis process through literature review, as well as its possible involvement in signal transduction molecular mechanisms, and explores its potential as a therapeutic target, providing theoretical basis for future research aimed at regulating IL-17 expression and function to treat related diseases.
subject: Precision Medicine Informatics
  topic: section
subject: interleukin-17 (IL-17) family
  topic: keywords
subject: IL-17 receptor
  topic: keywords
subject: pulmonary fibrosis
  topic: keywords
creator: Ge Zhou
creator: Amin Li
creator: Ruikai Wang
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e217
ending page: e217
doi: 10.71321/tg620c27

Construction of prognostic model and tumor microenvironment landscape based on cuproptosis-related subtypes in melanoma
type: item
description: Background: Melanoma, known for its aggressive nature and poor prognosis, may be impacted by cuproptosis, a recently discovered form of programmed cell death. Despite its unclear mechanisms, preliminary studies suggested a link between cuproptosis and cancer progression and metastasis. We aimed to investigate the association between cuproptosis-related genes (CRGs) and melanoma to enhance prognostic and therapeutic strategies. Method: In this study, we downloaded transcriptome RNA-seqs and clinical information of all melanoma patients from The Cancer Genome Atlas (TCGA) database, selected a dataset from Gene Expression Omnibus (GEO) databases, and merged the two datasets. After univariate regression analysis, all the samples were categorized into three groups based on expression levels of CRGs. Differential expression analysis was carried out for three CRG clusters to obtain the significant differentially expressed genes (DEGs). After univariate Cox regression analysis, multivariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm were performed on DEGs, the prognosis related genes were screened to establish a prognosis prediction model. The model's accuracy was validated through Kaplan-Meier analysis, receiver operating characteristic (ROC) curve, nomogram, and independent prognostic analysis. Additionally, we compared the immune scores of the tumor microenvironment, tumor mutation burden, tumor immune dysfunction and exclusion, and drug sensitivity between high-risk and low-risk groups. Results: Through algorithm analysis, eight genes significantly related to prognosis were identified, among which SLFN13, CAMK4, TLR8, EIF4E3, and CLEC2B were low-risk genes, OCA2, NAIP, and SAMD9 were high-risk genes. Using these genes, we established a prognostic model that effectively distinguishes between different survival outcomes, with the low-risk group showing a markedly higher long-term survival rate. Conclusion: In conclusi…
subject: Biomedical Data Science and Analytics
  topic: section
subject: melanoma
  topic: keywords
subject: cuproptosis
  topic: keywords
subject: tumor microenvironment
  topic: keywords
subject: differentially expressed genes
  topic: keywords
subject: risk score
  topic: keywords
subject: bioinformatics analysis
  topic: keywords
creator: Zishen Xia
creator: Nan Gao
creator: Jianwen Wang
creator: Lizhao Yan
creator: Cong Ma
creator: Kangwei Wang
creator: Yuxiong Weng
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e214
ending page: e214
doi: 10.71321/vxy0xd87

Forearm necrotizing fasciitis caused by freshwater fish in an immunocompromised patient with rheumatoid arthritis for 20 years: a case report and review of the literature
type: item
description: Necrotizing fasciitis (NF) is a life-threatening soft tissue infection typically associated with marine pathogens such as Vibrio vulnificus in cases involving fish-related injuries. This case report describes a rare instance of NF caused by Aeromonas sobria following a freshwater fish (Chinese carp) injury in a 58-year-old immunocompromised woman with a 20-year history of rheumatoid arthritis on long-term immunosuppressive therapy. The patient presented with rapid-onset swelling, pain, and septic shock, requiring intensive care, vasopressor support, and four surgical debridements with negative pressure wound therapy. Wound cultures confirmed Aeromonas sobria, contrasting with the more common marine-acquired Vibrio infections. Despite delayed diagnosis, aggressive multimodal management—including broad-spectrum antibiotics (piperacillin-tazobactam followed by meropenem) and repeated surgical interventions—resulted in survival after 41 days of hospitalization. This case highlights the importance of considering freshwater pathogens in NF, particularly in immunocompromised patients, and underscores the critical role of early surgical debridement and empiric antimicrobial coverage for atypical organisms. Clinicians should maintain a high suspicion for NF in fish-related injuries, even without marine exposure, to prevent fatal outcomes.
subject: Digital Health and Public Health Informatics
  topic: section
subject: Necrotizing fasciitis
  topic: keywords
subject: Aeromonas sobria
  topic: keywords
subject: Immunocompromised host
  topic: keywords
subject: Septic shock
  topic: keywords
creator: Zhengnan Zhao
creator: Peng Wang
creator: Lei Ma
creator: Yang Wang
creator: Jiaping Guo
creator: Chenglong Yao
creator: Zefan Sun
creator: Xiu Wang
creator: Jiabao Yang
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e204
ending page: e204
doi: 10.71321/t6symt70

Causal Relationships between 1400 Serum Metabolite Traits,179 Plasma Lipids, and Hemorrhoids: A Mendelian Randomization Study and Meta-analysis
type: item
description: Background: Hemorrhoids is a common anorectal disorder that significantly impacts patients' quality of life over the long term and imposes a substantial economic burden. However, the potential link between HD and serum metabolites and lipids has been scarcely studied, and its pathogenesis remains unclear. Methods: The causal relationships between serum metabolite traits, plasma lipids, and HD were evaluated using Mendelian Randomization. Inverse Variance Weighted was the most important analysis approach. Sensitivity analysis was used to assess the robustness of the results. Enrichment analysis was applied to the metabolites obtained from the results of MR analysis and meta-analysis. Results: The risk factors included Citramalate levels (OR = 1.487, 95%CI = 1.172-1.888, P = 0.001), P-cresol sulfate levels (OR = 1.476, 95%CI = 1.111-1.961, P = 0.007), and Triacylglycerol (53:3) levels (OR = 1.262, 95%CI = 1.049-1.518, P = 0.014). The protective factors included Imidazole lactate levels (OR = 0.865, 95%CI = 0.756-0.989, P = 0.034), 1-(1-enyl-stearoyl)-GPE (p-18:0) levels (OR = 0.722, 95%CI = 0.552-0.944, P = 0.017), and Phosphatidylethanolamine (18:1_18:1) levels (OR = 0.803, 95%CI = 0.666-0.969, P = 0.022). Enrichment analysis showed that risk factors were enriched in Alanine Metabolism (Holm P = 0.0039), Cysteine Metabolism (Holm P = 0.0146), Urea Cycle (Holm P = 0.0181), and Ammonia Recycling (Holm P = 0.0245). Protective factors were enriched in the Urea Cycle (Holm P = 0.00754), Ammonia Recycling (Holm P = 0.0102), Aspartate Metabolism (Holm P = 0.0147), Glutamate Metabolism (Holm P = 0.038), Arginine and Proline Metabolism (Holm P = 0.0479), and Malate-Aspartate Shuttle (Holm P = 0.0495). Conclusion: Previous studies often focused on the causal relationships between a few potential risk factors and HD in a single population. Our study is the first to address this gap by integrating a broad range of 1400 metabolites and 179 lipids with HD across diverse population…
subject: Biomedical Data Science and Analytics
  topic: section
subject: Serum Metabolites
  topic: keywords
subject: Plasma Lipids
  topic: keywords
subject: Hemorrhoids
  topic: keywords
subject: Mendelian Randomization
  topic: keywords
subject: Meta-analysis
  topic: keywords
creator: Lu Hu
creator: Danyang Wang
creator: Chang You
creator: Ziyan Zhao
creator: Wanlin Zheng
creator: Luyao Wang
creator: Yutong Li
creator: Liangzhe Dai
creator: Hongkai Yu
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e202
ending page: e202
doi: 10.71321/8s70we60

Causal Relationship between Chronic Gastritis and Sleep Apnea Syndrome: A Bidirectional and Two-step Mendelian Randomization Study
type: item
description: Background: Sleep apnea syndrome (SAS) and chronic gastritis are prevalent in middle-aged and elderly people. Although clinical observations suggest an association between the two diseases, the causal relationship between them has not been clarified. This study aims to explore the causal relationship between SAS and chronic gastritis and to elucidate the possible mediating mechanisms. Methods: The causal relationship between SAS and chronic gastritis was assessed using five methods, primarily utilizing the Inverse Variance Weighted (IVW) approach, with other methods categorized as sensitivity analyses. A two-step Mendelian randomization study was conducted using a genome-wide association study (GWAS) dataset to evaluate the mediating role of signatures in immune cell and inflammatory proteins. Sensitivity analyses were conducted to determine the robustness of the results. To systematically address horizontal pleiotropy, we employed the CAUSE framework, which distinguishes causal effects from confounding by comparing genetic architectures under competing causal and shared confounding models, while accounting for both linkage disequilibrium-related and independent pleiotropic pathways. The STROBE-MR guidelines were followed for MR results reporting. Results: Through two-sample MR analysis, we identified significant bidirectional causal relationships between sleep apnea syndrome (SAS) and chronic gastritis (forward: OR = 1.131, 95% CI: 1.031-1.240, p = 0.009; reverse: OR = 1.065, 95% CI: 1.007-1.128, p = 0.028). Simulation studies confirmed CAUSE's superior specificity in controlling false positives through its dual-model framework that explicitly accounts for pleiotropic pathways. Two-step MR analysis revealed that the changes in the level of PD-L1 expressed by CD14+CD16+ monocytes played a significant mediating role in the effect of chronic gastritis on SAS. Conclusion: The bidirectional causal relationship between SAS and chronic gastritis was confirmed through two-…
subject: Biomedical Data Science and Analytics
  topic: section
subject: sleep apnea syndrome
  topic: keywords
subject: chronic gastritis
  topic: keywords
subject: a two-step Mendelian Randomization Study
  topic: keywords
subject: a two-sample Mendelian randomization
  topic: keywords
creator: Ziyan Zhao
creator: Yanyu Zhu
creator: Chang You
creator: Yan Wang
creator: Tianchi Zhuang
creator: Yingqi Yang
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e180
ending page: e180
doi: 10.71321/zrtsfk74

Dynamic Evolution of Hyperplastic Polyps in the Setting of Autoimmune Gastritis: An In-Depth Interpretation of Gastrin-Driven Patho-mechanisms in a Case
type: item
description: Through longitudinal clinical follow-up of a 75-year-old male with autoimmune gastritis (AIG) complicated by gastric hyperplastic polyps (GHPs), this study systematically investigated the critical regulatory role of gastrin signaling networks in gastric mucosal remodeling. The case demonstrated that within the established pathological cascade of AIG (from parietal cell destruction to gastric acid deficiency and hypergastrinemia), GHPs exhibited short-term volumetric growth. This observation challenges traditional views about the indolent nature of hyperplastic polyps. Our findings highlight the dual role of proton-pump inhibitor (PPI) therapy in AIG management while alleviating mucosal inflammation, it paradoxically induces G-cell hypersensitivity that elevates gastrin levels beyond biological thresholds (332 increasing to 770 U/L), creating a critical driver for GHP progression. This case redefines clinical management paradigms for AIG complications and offers translational insights for gastrointestinal tumor surveillance.
subject: Medical Informatics Cases, Reviews and Applications
  topic: section
subject: autoimmune gastritis
  topic: keywords
subject: gastric hyperplastic polyp
  topic: keywords
subject: proton-pump inhibitor
  topic: keywords
creator: Yimin Song
creator: Jianing Yan
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e168
ending page: e168
doi: 10.71321/19f3bp17

Mapping heterogeneous molecular subtypes of circadian misalignment underlying lung adenocarcinoma risk
type: item
description: Background: The circadian rhythm coordinates multiple physiological and behavioral processes. Substantial evidence illustrates that circadian rhythm disruption (CRD) dramatically influences tumor initiation, progression, and the tumor immune microenvironment remodeling. However, there is a dearth of exploration for CRD heterogeneity’s underlying clinical significance in lung adenocarcinoma (LUAD). Methods: 2090 LUAD patients and 79 immunotherapy patients were enrolled from nine public independent datasets. The nonnegative matrix factorization (NMF) was applied to develop molecular classification after collecting CRD-related genes. Subsequently, the reliability and robustness of classification were evaluated through the nearest template prediction (NTP) method. Furthermore, clinical outcomes, functional characteristics, genomic alterations, and immune landscape were explored. The efficacy of clinical common treatment was detected for the specific classification. Results: Three heterogeneous LUAD subtypes were identified based on the expression profile of CRD-related genes. Different expression characteristics and clinical outcomes of distinct subtypes were revealed. Relative similar clinical outcomes and proportion of each subtype were verified in multiple independent cohorts, which indicated the reliability of classification. Distinguish features of three subtypes were further explored: (i) C1, the poorest prognosis, significant cell proliferation, and highest genomic instability. (ii) C2, the best outcome, elevated lipid metabolic function, favorable regulation of circadian rhythm, and (iii) C3, copious immune infiltration, immunosuppressive microenvironment, and conspicuous intratumor heterogeneity. The evaluation of treatment strategies suggested that C1 patients might benefit from chemotherapeutics agents, including docetaxel and paclitaxel, patients in C2 were suitable for glucocorticoids, whereas C3 patients were recommended to accept immunotherapy. Conclusion…
subject: Precision Medicine Informatics
  topic: section
subject: Circadian Rhythm Disruption
  topic: keywords
subject: Lung Adenocarcinoma
  topic: keywords
subject: Molecular Subtype
  topic: keywords
subject: Immunotherapy
  topic: keywords
subject: Tumor Immune Microenvironment
  topic: keywords
creator: Ruhao Wu
creator: Kaisaierjiang Kadier
creator: Shuai Xu
creator: Peiyu Yuan
creator: Yu Yang
creator: Pengyuan Xu
creator: Xufeng Huang
creator: Shujing Zhou
creator: Song-Bin Guo
creator: Haonan Zhang
creator: Shiqian Zhang
creator: Chaoyang Yu
creator: Teng Li
creator: Ge Zhang
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e137
ending page: e137
doi: 10.71321/fy14v342

ceerva81
type: item
title: Correlation Analysis between Spontaneous Nystagmus Characteristics and Semicircular Canal Dysfunction in Patients with Vestibular Neuritis: A Quantitative Study Using Electronystagmography and Video Head Impulse Test
description: Objective: To compare the characteristics of spontaneous nystagmus (SN) in patients with vestibular neuritis (VN) at different disease stages and to investigate its correlation with semicircular canal dysfunction. Methods: A total of 115 VN patients were enrolled, who were divided into acute phase (1 – 7 days), subacute phase (8 – 30 days) and chronic phase (>30 days) according to the course of disease. Quantitative assessment of SN was performed using electronystagmography (ENG), with particular focus on the slow phase velocity (SPV) in the horizontal plane. Simultaneously, vestibular-ocular reflex function was systematically evaluated through video head impulse test (vHIT), with quantitative measurements of angular vestibulo-ocular reflex (aVOR) gain and asymmetry of the affected semicircular canals. Results: Among 115 patients, 67 (58.3%) were in acute phase, 29 (25.2%) in subacute phase and 19 (16.5%) in chronic phase. The mean age of patients in the acute phase was significantly lower than that in the chronic phase (p = 0.028), while there was no significant difference between the subacute phase and the other two groups. 98 patients (85.2%) had SN, 62 patients (92.5%) in acute phase, 26 patients (89.7%) in subacute phase and 10 patients (52.6%) in chronic phase. SPV in acute phase was significantly higher than that in subacute phase (p = 0.003) and chronic phase (p < 0.001), but there was no significant difference between chronic phase and subacute phase. In 112 patients with VN, the horizontal semicircular canals were affected, and the mean aVOR gain and asymmetry of the damaged side were 0.47 ± 0.14 and 0.35 ± 0.14, respectively. The aVOR gain of injured side in chronic phase was significantly higher than that in acute phase (p < 0.001) and subacute phase (p = 0.007), but there was no significant difference between acute phase and subacute phase (p = 0.950). The asymmetry in chronic phase was significantly lower than that in acute phase (p = 0.001) and subacu…
subject: Digital Health and Public Health Informatics
  topic: section
subject: vestibular neuritis
  topic: keywords
subject: spontaneous nystagmus
  topic: keywords
subject: video head impulse test
  topic: keywords
creator: Jun Cao
creator: Jingye Wang
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-03-30
publication date: 2025-03-30
starting page: e149
ending page: e149
doi: 10.71321/ceerva81

Sphingomyelin mediates the association between natural killer cell receptor 2B4 (CD244) and head and neck cancer
type: item
description: Objective: To investigate the causal link between natural killer (NK) cell receptor CD244 and head and neck cancer (HNC), and to evaluate sphingomyelin (SM) as a potential mediator of this relationship. Methods: A two-sample Mendelian randomization (MR) analysis was conducted using genome-wide association study (GWAS) summary statistics from European cohorts (NCD244=14,735; NHNC=2,131; NSM=8,260). Instrumental variables (32 SNPs for CD244, 79 SNPs for HNC) were selected at genome-wide significance (P<5×10⁻⁸/5×10⁻⁶) after rigorous linkage disequilibrium clumping. Causal estimates were generated using inverse variance weighting (IVW), MR-Egger, and weighted median methods. Mediation analysis quantified SM's contribution to CD244-HNC associations. Results: Genetically predicted CD244 levels showed a protective effect against HNC (IVW OR=0.82 per SD, 95% CI:0.71-0.94, P<0.01), while elevated CD244 was associated with reduced SM levels (IVW OR=0.92, 95% CI:0.86-0.98, P<0.05). Conversely, SM demonstrated risk-enhancing effects on HNC (IVW OR=1.20, 95% CI:1.01-1.41, P=0.03). Mediation analysis revealed that SM accounted for 7.3% of the total CD244-associated HNC risk. Conclusion: This study establishes a causal protective role of CD244 in HNC pathogenesis, partially mediated through SM. The findings highlight CD244 and SM metabolism as potential targets for HNC immunomodulatory therapies. Future research should validate these mechanisms in diverse populations and explore additional mediators.
subject: Biomedical Data Science and Analytics
  topic: section
subject: NK cell
  topic: keywords
subject: CD244
  topic: keywords
subject: Head and Neck Cancer
  topic: keywords
subject: Sphingomyelin
  topic: keywords
subject: Mendelian Randomization
  topic: keywords
creator: Boxuan Han
creator: Shaokun Liu
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-03-30
publication date: 2025-03-30
starting page: e145
ending page: e145
doi: 10.71321/cdx1k098

Transthoracic pulmonary artery radiofrequency denervation (TPARFD) concomitantly with cardiac operations in adult atrial septal defect with pulmonary arterial hypertension: case report
type: item
description: Pulmonary arterial hypertension (PAH) is a life-threatening progressive disorder caused by increased resistance in the pulmonary vasculature. The condition may lead to right-sided heart failure and death. A 56-year-old woman was referred for pulmonary arterial hypertension (PAH) with atrial septal defect, mitral regurgitation, and tricuspid regurgitation. Hemodynamic parameters were obtained by right heart catheterization. She underwent transthoracic pulmonary artery radiofrequency denervation (TPARFD), to relieve the pulmonary artery pressure, while concomitantly undergoing mitral valvuloplasty with 28 # Sorin ring, patch closure of atrial septal defect, and tricuspid annuloplasty with 28 # Edwards MC3 ring. Her hemodynamic parameters and functional capacity showed marked improvement after TPARFD.
subject: Medical Informatics Cases, Reviews and Applications
  topic: section
subject: Pulmonary artery radiofrequency denervation
  topic: keywords
subject: Pulmonary arterial hypertension
  topic: keywords
subject: Congenital heart disease
  topic: keywords
creator: Wenpeng Dong
creator: Shenglin Ge
creator: Min Lin
creator: Weida Zhang
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-10-20
publication date: 2025-10-20
starting page: e135
ending page: e135
doi: 10.71321/89fykb91

Impact of heavy metals on allostatic load in adults: a NHANES study
type: item
description: Background: Allostatic load, defined as the cumulative strain resulting from the chronic stress response, is associated with adverse health outcomes. Heavy metals, prevalent in various environmental pollutants, exert cumulative effects on the human body through exposure via water or food sources. However, the relationship between heavy metals and allostatic load remains poorly understood. The aim of this study is to examine the association between urinary metal concentrations and allostatic load. Methods: This study analyzed data from 4,231 adult participants in the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2010. We employed linear regression analysis, Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS), and quantile g-computation (qgcomp) to investigate the associations between twelve urinary metals and allostatic load. Additionally, we developed K-nearest neighbors (KNN), random forest (RF), and XGBoost models to predict allostatic load scores (ALS). Results: Linear regression analysis indicated that the combined effects of the twelve urinary metals were negatively correlated with allostatic load. WQS, qgcomp, and BKMR analyses identified cesium (Cs), molybdenum (Mo), lead (Pb), platinum (Pt), and cobalt (Co) as the primary influencing factors (all p-values < 0.05). Furthermore, when predicting ALS based on heavy metal exposure, the random forest model outperformed the other machine learning algorithms, with a root mean square error (RMSE) of 2.377428, compared to 2.501523 for KNN and 2.377733 for XGBoost. Conclusion: Our findings indicate that urinary metal concentrations are negatively associated with allostatic load, with Cs, Mo, Pt, Pb, and Co showing the most significant negative correlations. Further research is necessary to explore the causal relationships and underlying mechanisms. Additionally, our analysis demonstrated that the random forest model was the most effective for ALS prediction.
subject: Digital Health and Public Health Informatics
  topic: section
subject: Urinary metals
  topic: keywords
subject: Allostatic load score
  topic: keywords
subject: National health and nutrition examination survey
  topic: keywords
subject: Machine Learning
  topic: keywords
creator: Yiyin Rong
creator: Shenglin Luo
creator: Cong Wu
creator: Haozhe Huang
creator: Ming Chen
creator: Xingyu Liu
creator: Shaobo Wu
rights: Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
date: 2025-03-30
publication date: 2025-03-30
starting page: e133
ending page: e133
doi: 10.71321/3b9xjm29