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.
Spontaneous Reduction in ART-Conceived Twin Pregnancies: Risk Factors, Perinatal Outcomes, and a Prediction Model
Objective: To investigate the risk factors for spontaneous reduction (SR) in assisted reproductive technology (ART)-conceived twin pregnancies and compare perinatal outcomes between SR and non-SR pregnancies, and to develop and validate an SR risk prediction model in the dizygotic twin (DZT) cohort. Methods: This single-center retrospective cohort study enrolled patients who achieved clinical twin pregnancies following ART at the Reproductive Center of the First Affiliated Hospital of Anhui Medical University between January 2015 and December 2024. Participants were classified into monozygotic twins (MZT, n=505) and dizygotic twins (DZT, n=3,263) based on the number of gestational sacs and fetal heartbeats detected on early pregnancy ultrasound, and each cohort was further divided into SR and Non-SR groups. Baseline characteristics, treatment parameters, and perinatal outcomes were compared between groups. Univariable and multivariable logistic regression analyses were performed with SR as the dependent variable, incorporating nine core predictors. A predictive model for SR was constructed in the DZT cohort and internally validated; model performance was evaluated using the receiver operating characteristic (ROC) curve with area under the curve (AUC), calibration curve, Brier score, and decision curve analysis (DCA). Risk stratification was performed by tertiles of predicted probability. Results: In the DZT cohort, the SR group had significantly older maternal age, a higher proportion of advanced maternal age (≥35 years), and higher rates of blastocyst-stage transfer, intracytoplasmic sperm injection (ICSI), and frozen-thawed embryo transfer cycles than the Non-SR group (all P<0.05). No statistically significant differences were observed in any of these characteristics in the MZT cohort. Perinatal outcome trends were consistent across both cohorts: the SR group had later gestational age at delivery, lower rates of preterm birth and low birth weight, but higher rates of glucose metabolism abnormalities and lower rates of premature rupture of membranes. Multivariable logistic regression identified advanced maternal age (aOR=3.00), history of previous miscarriage (aOR=1.32), blastocyst-stage transfer (aOR=3.05), non-good-quality embryos (aOR=1.79), ICSI (aOR=1.56), and frozen-thawed cycles (aOR=3.33) as independent risk factors for SR, whereas secondary infertility (aOR=0.67) and transfer of ≥2 embryos (aOR=0.53) were associated with a reduced risk. The DZT-SR prediction model achieved an AUC of 0.857 on internal validation, with acceptable calibration and favorable net clinical benefit on DCA. SR incidence increased progressively across low-, intermediate-, and high-risk strata at 8.3%, 28.7%, and 77.9%, respectively. Conclusion: SR in ART-conceived twin pregnancies is closely associated with maternal age and multiple embryo- and cycle-related factors. The DZT-SR prediction model, built on nine routinely available clinical variables, demonstrated good internal validation performance and may serve as a practical tool for early pregnancy risk stratification and individualized follow-up planning.
Copyright (c) 2026 Life Conflux https://creativecommons.org/licenses/by/4.0
Clinicopathological Analysis of Succinate Dehydrogenase-Deficient Renal Cell Carcinoma
Objective: To investigate the clinicopathological features, immunophenotype, key diagnostic points and prognosis of succinate dehydrogenase (SDH)-deficient renal cell carcinoma in order to provide a reference for its clinical diagnosis, treatment and pathological diagnosis. Materials and Methods: The retrospective analysis was performed on 14 cases of SDH-deficient renal cell carcinoma, with a summary and evaluation of their clinicopathological, morphological, immunohistochemical features and prognosis. Results: Among the 14 patients, 10 were male and 4 were female. The age ranged from 43 to 78 years, with a median age of 52 years. 9 tumors were located in the left kidney and 5 in the right kidney. Tumor size ranged from 1.5 cm to 8.0 cm. Microscopically, the tumor cells exhibited diverse architectural patterns, including predominantly solid and nested growth, occasional microcystic and cystiic dilatation, and papillary architecture. The tumor cells had abundant cytoplasm, which was vacuolated or weakly eosinophilic. Immunohistochemical results showed that all 14 tumor cells were positive for vimentin and PAX-8, and negative for SDHB, CK7, CD117, and CA IX. The Ki-67 proliferation index ranged from 5% to 20%. Among the 14 patients, 1 was lost to follow-up, and 13 were followed up. Of the 13 followed patients, 12 were alive and 1 died. Conclusion: SDH-deficient renal cell carcinoma is a relatively rare subtype of renal cell carcinoma. Patients with low nuclear grade are generally younger, whereas those with high nuclear grade are mostly middle-aged or elderly and prone to metastasis. Loss of SDHB expression by immunohistochemical staining is helpful for the diagnosis of this type of tumor.
Succinate dehydrogenase-deficient renal cell carcinoma
Enhancing Early Sepsis Prediction with Temporal bias EHRs Data
Background: Sepsis prediction models using electronic health records (EHRs) are often challenged by temporal biases from irregular data entry and severe class imbalance. This study develops a novel deep learning (DL) framework to address these specific challenges for accurate and early sepsis detection. Methods: We propose a Feature-Wise Multi-Head Self-Attention Transformer (FW-MHSA-former) with an Adaptive Balance-Preserving Ensemble (ABPE). FW-MHSA-former mitigates temporal bias by applying self-attention across medical features to model correlations directly. ABPE resolves class imbalance by partitioning the majority class to train multiple models on balanced datasets, aggregating predictions via weighted voting. The framework was retrospectively validated on the MIMIC-IV dataset; Kaplan-Meier analysis assessed survival outcomes. Visualizing the attention-derived feature correlation matrix enhances interpretability. Results: The proposed framework achieved a peak Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.94. At this optimal performance, the model demonstrated a recall of 0.90 and an accuracy of 0.87. We compared our method with three classical models and three advanced attention/Transformer-based models. The proposed approach yielded consistently superior performance across all evaluation metrics, including accuracy and F1 score. The KM analysis confirmed that the model effectively stratified patients into high- and low-risk cohorts with statistically significant differences in survival outcomes (p < 0.001). Conclusions: The proposed framework effectively and robustly predicts early sepsis. By addressing timestamp irregularities and class imbalance, it achieves superior accuracy and provides an interpretable tool to enhance clinical decision support in critical care.
Gut Microbiota Affects Cardiovascular Diseases via Inflammatory Cytokines: a Bidirectional Two-sample Mendelian Randomization Study and Mediation Analysis
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 offer novel insights into the pathophysiological mechanisms of CVDs and may inform the development of novel strategies for CVD prevention, diagnosis, and treatment.
A Unique Case of Migraine Without Aura Triggered by Palpation ofV2-innervated Chronic Facial Folliculitis
Accumulating research suggests that peripheral pathological changes participate in the pathogenesis of migraine, and supporting evidence has been reported in many clinical cases. However, few cases have directly demonstrated the bidirectional interaction between migraine and peripheral pathological lesions. Here, we present a case of severe migraine without aura (MwoA) whose attacks were elicited by palpation of chronic folliculitis lesions around the unilateral nasal ala.This unique case reveals a distinct peripheral-central interaction in migraine, which may be mediated by neurogenic immunomodulation of the trigeminal system.
Medical Informatics Cases, Reviews and Applications
Association of Peritoneal Dialysis Effluent Interleukin-17 with Peritoneal Functional Decline and Clinical Significance: A Prospective Cohort Study
Background: Long-term peritoneal dialysis (PD) frequently induces chronic peritoneal inflammation, fibrosis, and increased peritoneal solute transport rate (PSTR). This study assessed whether effluent interleukin-17 (IL-17) predicts increased PSTR and relates to peritoneal fibrosis. Methods: This prospective cohort enrolled 130 PD patients, of whom 115 completed 1-year follow-up. Effluent IL-17, transforming growth factor-β (TGF-β), and fibronectin (FN) were measured by enzyme-linked immunosorbent assay (ELISA). Peritoneal function was assessed by dialysate-to-plasma creatinine ratio (D/P Cr) at baseline and 1 year. We used correlation analysis, multivariable regression, interaction analysis, and Receiver operating characteristic (ROC) analysis to evaluate the predictive value of effluent IL-17 for increased PSTR. A mouse peritoneal fibrosis model was used to evaluate local IL-17 expression by immunohistochemistry and real-time quantitative PCR (RT-qPCR). Results: Effluent IL-17 was higher in patients with increased PSTR and correlated positively with TGF-β, FN, and ΔD/P Cr. Multivariable analysis showed that IL-17 independently predicted 1-year D/P Cr after adjustment for baseline D/P Cr and clinical covariates. PD vintage significantly modified the association between IL-17 and increased PSTR. Adding IL-17 to baseline D/P Cr and peritoneal creatinine clearance improved prediction of increased PSTR, with the AUC increasing from 0.705 to 0.789. Furthermore, immunohistochemical and qPCR results showed that IL-17 expression was elevated in fibrotic peritoneal tissues of PF mice compared with control mice. Conclusion: Effluent IL-17 is associated with peritoneal fibrosis and longitudinal PSTR increase, supporting its potential as a noninvasive biomarker for early risk stratification in PD patients.
Clinical Decision Support and AI in Medicine
Risk Factors of Reactive Cutaneous Capillary Endothelial Proliferation in Advanced Non-small Cell Lung Cancer Treated with Camrelizumab
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 recommend increasing clinical attention and personalizing management for patients with the above risk factors for RCCEP to improve patient compliance and achieve long-term treatment outcomes.
Digital Health and Public Health Informatics
advanced non-small cell lung cancer (NSCLC)
reactive cutaneous capillary endothelial proliferation (RCCEP)
The Relationship between Blood Pressure Response Index and Acute Kidney Injury in Patients with Septic Shock: A Retrospective Study Based on the MIMIC-IV Database
Background: The blood pressure response index (BPRI) is the ratio of mean arterial pressure (MAP) to the vasoactive-inotropic score (VIS). It accurately reflects the response to vasoactive drugs in patients with septic shock and assesses the patient's vascular status. However, the relationship between BPRI and the occurrence of acute kidney injury (AKI) in patients with septic shock has never been studied. Methods: This study retrospectively analyzed patients diagnosed with sepsis and using vasoactive drugs in the MIMIC-IV database. The patients were divided into four groups according to the BPRI level. The primary outcome is whether AKI occurs after the diagnosis of sepsis. The association between BPRI and outcome was assessed by constructing logistic regression models and plotting restricted cubic spline (RCS) curves. The predictive value of the BPRI for outcome was evaluated by plotting receiver operating characteristic (ROC) curves and comparing areas under the curves (AUC). Results: 5524 patients with septic shock were finally included. The median age of the patients was 68.8 years, and 84.3% developed AKI after the diagnosis of sepsis. In a fully adjusted model, BPRI and the development of AKI were significantly correlated (OR [95%CI], 0.988 [0.979, 0.996], P=0.006). The results of the RCS curves suggested an "L"-shaped association and the inflection point was located at the level of 3.98. On the left side of the inflection point, there was a decreasing trend in the risk of AKI in patients as BPRI levels increased (OR [95%CI], 0.82 [0.747, 0.9], P<0.001). On the right side of the inflection point, there was no statistically significant association (OR [95%CI], 0.995 [0.985, 1.01], P=0.212). In addition, the BPRI showed favorable predictive value for outcome (AUC [95% CI], 0.624 [0.601, 0.639]). Conclusion: We identified a distinct non-linear association between BPRI and AKI risk in septic shock, characterized by a critical inflection point at 3.98. Below this threshold, the likelihood of AKI rises sharply as BPRI decreases. Integrating perfusion pressure and vasopressor load, the BPRI serves as a readily available metric to stratify renal risk and recognize vascular hyporesponsiveness.
Artificial Intelligence–Enabled Dissection of Regulatory T Cellsin the Tumor Immune Microenvironment:From Mechanistic Insight to Population-Scale Inference
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.
Construction and Validation of a Clinical Model to Predict Lymph Node Metastasis in Early Hypopharyngeal Squamous Cell Carcinoma
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.
The Mechanism of Platelet-Rich Plasma Added to Skin FlapPostoperative for the Influence of Skin Flap Survival
Background: This study investigated the effects of postoperative platelet-rich plasma (PRP) supplementation on skin flap survival in a rat model. Methods: A random-pattern skin flap model was established in rats. During surgery, PRP injection combined with platelet-rich gel (PRG) application was performed. On postoperative day 3, PRP or PRG was supplemented into the flap via uniform point injections. Necrotic area was recorded at postoperative day 7. Flap defect length and terminal edema severity were assessed by contrast-enhanced ultrasonography. Tissue specimens were collected for histopathological and immunohistochemical analysis. Relative expression levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and cluster of differentiation 34 (CD34) were measured. Results: The group receiving intraoperative PRP injection combined with PRG application, followed by postoperative PRG supplementation, showed significantly shorter tissue defect lengths and less terminal tissue edema compared to other groups (P<0.01). Relative expression levels of VEGF, PDGF, and CD34 were significantly higher than those in other groups (P<0.01). Conclusion: Postoperative PRP and PRG supplementation reduced flap defect length and edema severity, increased growth factor expression, and improved flap survival. PRG supplementation produced the most pronounced benefits.
High-risk Factors and a Nomogram Prediction Model for Pulmonary Fungal Infection in Elderly Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease
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.
elderly acute exacerbation of chronic obstructive pulmonary disease
The Recent Changing Global Landscape of Cancer
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.
Copyright (c) 2025 Life Conflux https://creativecommons.org/licenses/by/4.0
Regulatory T Cells in Precision Immunotherapy: Mechanistic Insights and Translational Advances of Low-dose Interleukin-2
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 across autoimmune and inflammatory disorders.
Puerarin Inhibits Gastric Cancer Cell Proliferationby Blocking the G2/M Phase Transition
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.
Gut Microbiota and Hypertension: From Pathogenesis to Therapeutic Potential
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.
The cGAS-STING Pathway: Insights into Regulatory Mechanisms, Disease Dysregulation, and Therapeutic Development
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.
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
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.
Mendelian Randomization Reveals Height as a Risk Factor and Potential Therapeutic Target for Testicular Cancer
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.
Do open access articles have a citation advantage? — a research based on European Urology Family
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.
New Insights into Influenza Virus-Host Interactions, ImmuneResponses, and Vaccine Development at Single-Cell Resolution
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.
Multidimensional Roles of EZH2 and Its Therapeutic Potential in Cancer Therapy
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.
Exploring New Therapeutic Targets for Myasthenia Gravis: A Plasma and Cerebrospinal Fluid Proteomics Mendelian Randomization Study
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.
Exploring the Causal Relationship Between Plasma Proteins and Systemic Lupus Erythematosus: A Mendelian Randomization Study
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.
Tinnitus and Risk of Mortality in Normal-Hearing U.S. Adults: A Weighted Study Adjusted for Covariate Balance
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.
National Health and Nutrition Examination Survey (NHANES)
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
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.
The role of IL-17 family in the process of pulmonary fibrosis
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.
Construction of prognostic model and tumor microenvironment landscape based on cuproptosis-related subtypes in melanoma
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 conclusion, based on the research of cuproptosis subtypes, we identify the DEG with predictive potential and establish a prognosis prediction model. This study may provide a reference for the prognosis and clinical treatment of melanoma patients from the perspective of cuproptosis.
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
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.
Causal Relationships between 1400 Serum Metabolite Traits,179 Plasma Lipids, and Hemorrhoids: A Mendelian Randomization Study and Meta-analysis
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 populations, and identifying specific metabolic pathways involved in HD development.