Potential clinical benefits of probiotics in pediatric allergic rhinitis: a systematic review and network meta-analysis

Frontiers in Pediatrics · 2026-03-09

Objective This study aimed to evaluate potential clinical benefits and superior strains of probiotics for pediatric allergic rhinitis (AR) using meta-analysis and network meta-analysis. Methods A systematic search was conducted in databases including PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure up to July 31, 2025, to identify randomized controlled trials (RCTs). Inclusion criteria were pediatric patients with AR, probiotic interventions, control groups receiving placebo or standard treatment, and reported outcomes such as Total Nasal Symptom Score (TNSS), Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), Total Symptom Score (TSS), serum total IgE levels, or clinical efficacy. Study quality was assessed using the JADAD scale, with meta-analysis and network meta-analysis (NMA) performed via RevMan and R software, calculating standardized mean differences (SMD), relative risks (RR), and surface under the cumulative ranking curve (SUCRA) values. Results Eighteen RCTs were included, involving 1,789 patients (963 in the probiotic group and 826 in the control group). Meta-analysis showed that probiotics significantly reduced TNSS (SMD = −0.85, 95%CI [−1.25, −0.44], P < 0.05), improved PRQLQ scores (SMD = −2.53, 95% CI [−4.66, −0.40], P < 0.05) and enhanced clinical efficacy (RR = 1.16, 95%CI [1.07, 1.25], P < 0.05). However, no significant effects were observed on TSS (SMD = −1.79, 95%CI: [−4.06, 0.48], P = 0.12), or serum total IgE levels (SMD = −0.34, 95%CI [−0.84, 0.16], P = 0.18). Subgroup and NMA analyses indicated that mixed strains performed superiorly across multiple outcomes. Conclusions Probiotic supplementation, especially multi-strain formulations, may provide adjunctive benefits in pediatric AR, with potential for ameliorating nasal symptoms and enhancing quality of life, though further validation through rigorously designed trials is warranted.

Comprehensive modalities of kidney-sparing treatment in a carefully selected cohort of localized high-risk upper tract urothelial carcinoma: A potential paradigm shift.

Journal of Clinical Oncology · 2025-02-10

794 Background: This study aims to assess the efficacy and safety of comprehensive modalities of kidney-sparing treatment in a carefully selected cohort of patients with localized high-risk upper tract urothelial carcinoma (UTUC). Methods: This study was initiated in January 2019 and is ongoing. Selected localized high-risk UTUC patients, characterized by conditions such as solitary kidney, bilateral tumors, impending renal insufficiency or patient refusal/ineligibility for radical nephroureterectomy (RNU), were included. Systemic therapy regimens were tailored to patient characteristics, tumor pathology and biomarkers, and included platinum-based chemotherapy, Disitamab Vedotin, and immune checkpoint inhibitors (ICIs). After endoscopic biopsy and attempted laser ablation, patients received four cycles of systemic induction therapy, followed by maximal endoscopic laser ablation or segmental ureterectomy. Postoperatively, a one-year course of immunotherapy maintenance was administered. The co-primary endpoints were disease-free survival (DFS) and conversion-free survival (CFS). Secondary endpoints included metastasis-free survival (MFS), renal function changes, ureteral stricture and treatment safety. Results: 68 patients were enrolled, with a follow-up of 18 months. 54 patients underwent endoscopic thulium laser tumor ablation, while 14 underwent segmental ureterectomy. The induction therapy comprised Disitamab Vedotin for 32 patients, platinum-based chemotherapy for 9, and immunotherapy for 37. Urothelial tract recurrence was observed in 28 patients with a 1-yr DFS rate was 58.82%, who subsequently underwent repeat endoscopic laser ablation. Salvage RNU was performed in 9 patients, yielding a 1-yr CFS rate of 93.7% and a 2-yr CFS rate of 88.9%. No distal metastasis was reported. Postoperative renal function impairment was noted in 15 patients (22.06%). Mean eGFR improvements were observed at various time points: 3.15 ml/min/1.73m 2 at 1 months, 5.07 ml/min/1.73m 2 at 3 months, 2.41 ml/min/1.73m 2 at 6 months, and 3.97 ml/min/1.73m 2 at 12 months. Ureteral stricture on the affected side was a common complication, which was more likely to occur in patients who underwent 3 or more times of ureteroscopy (9/27). Notably, no grade 3 or higher systemic toxicities were observed. Conclusions: Preliminary findings indicate that our comprehensive modalities of kidney-sparing treatment demonstrated promising tumor control and satisfactory renal function preservation in a carefully selected cohort of localized high-risk UTUC. Its definite application strategy and value should be further evaluated in future clinical practice.

Matrix stiffness drives squamous cell carcinoma progression via a Piezo1-mediated mechanotransduction feedback loop

Journal of Advanced Research · 2025-10-01 · 4 citations

• This work provides the first demonstration that increased matrix stiffness promotes SCC proliferation and invasion through the Piezo1-RCC2 (non-Hippo)-YAP signaling axis. • Our study reveals firstly that matrix stiffness-induced activation of Piezo1 in tumor cells can remodel fibroblasts via a paracrine mechanism, further enhancing matrix stiffness and establishing a positive feedback loop that exacerbates SCC progression. • This research establishes the inaugural evidence that Piezo1 serves as the pivotal mechano-decoder translating biomechanical cues into clinical outcomes, with its expression level independently predicting DFS in cutaneous SCC patients. Squamous cell carcinoma (SCC) is one of the most frequent solid tumor accounting for more than one million cancer deaths annually. Emerging evidence highlights the critical role of mechanical signaling in tumor progression, yet the mechanobiological interplay between extracellular matrix (ECM) stiffness and SCC pathogenesis remains poorly understood. This study aimed to investigate how matrix stiffness drives SCC progression via Piezo1-mediated mechanotransduction and its clinical implications. Atomic force microscopy quantified tissue stiffness in human cutaneous, oral, and lung SCC samples. Spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) analyzed ECM- and mechanoreceptor-related gene expression. In vitro models using tunable-stiffness gels assessed SCC cell proliferation, invasion, and Piezo1/YAP activity. Xenograft models evaluated Piezo1′s role in tumor growth and stiffness regulation. Clinical correlation studies analyzed Piezo1 expression and outcomes in a cutaneous SCC cohort (n = 53). SCC tissues exhibited elevated stiffness compared to adjacent normal tissues. Stiff matrices activated Piezo1, promoting proliferation and invasion in SCC cells via a non-canonical Hippo pathway involving RCC2. Piezo1 knockdown reduced tumor growth and stiffness in vivo. Mechanistically, Piezo1 activation induced TGFβ1 secretion, driving fibroblast-to-myofibroblast transition and collagen deposition, thereby reinforcing matrix stiffness. Clinically, high Piezo1 expression correlated with poor differentiation ( p = 0.0034), recurrence ( p = 0.047), and shorter disease-free survival (HR = 181.03, p = 0.01). This study identifies a self-reinforcing Piezo1-RCC2-YAP axis that translates mechanical cues into pro-tumorigenic signaling, fostering fibroblast-mediated ECM remodeling. Piezo1 emerges as a prognostic biomarker and therapeutic target to disrupt stiffness-driven SCC progression

Macrophage-mediated metabolic dysregulation in the pancreas: Insights from obesity

World Journal of Biological Chemistry · 2025-12-04

Obesity is a major contributor to metabolic dysfunction, and its impact on pancreatic health has garnered increasing attention. Macrophages, as key regulators of inflammation and metabolism, play a central role in mediating obesity-induced pancreatic damage. In obese individuals, excessive lipid accumulation and chronic low-grade inflammation drive the infiltration and polarization of macrophages within the pancreas. These macrophages, particularly the pro-inflammatory Macrophage, pro-inflammatory phenotype (M1) phenotype, secrete cytokines such as C-C motif ligand 2 (CCL2) and transforming growth factor beta (TGF-β), which disrupt pancreatic β-cell function and impair insulin secretion. Conversely, anti-inflammatory Macrophage, anti-inflammatory phenotype (M2) macrophages contribute to tissue repair but may also promote fibrotic changes under prolonged metabolic stress. Pancreatic macrophages are activated under high-fat diet conditions, promoting inflammation and impairing β-cell function through the SUCLA2-HIF-1α axis and mechanistic Target of Rapamycin Complex 1 (mTORC1)/PD-1 pathway, thereby establishing a self-perpetuating "metabolic-immunosuppressive" vicious cycle. Targeted intervention strategies against macrophages—such as SUCLA2 inhibitors can ameliorate metabolic dysregulation. Meanwhile, exosome-mediated interorgan communication [e.g. , via microRNA-155 (miR-155) and miR-30a] offers novel insights for multi-system synergistic therapies. Understanding the mechanisms by which macrophages mediate metabolic dysregulation in the pancreas under obese conditions provides critical insights into the pathogenesis of obesity-related pancreatic disorders.

Dissolvable microneedles based on active components of Chinese Herbal Medicine for enhanced treatment of skin diseases

Journal of Biomaterials Science Polymer Edition · 2025-07-22

According to World Health Organization (WHO) estimates, around 900 million people globally are affected by various skin diseases, which cause significant physical and psychological distress and place a heavy economic burden on healthcare systems. The primary challenges in treating skin diseases include the limited transdermal drug absorption due to the skin barrier, the side effects associated with medications, and the recurring nature of these conditions that lead to prolonged patient suffering. Microneedles (MNs) have emerged as a promising transdermal drug delivery technology, able to painlessly penetrate the stratum corneum and deliver medications directly to the affected area. Various types of MNs technology have been developed, including dissolvable MNs (DMNs), solid MNs, coated MNs, hollow MNs, and hydrogel-based MNs. DMNs, especially, offer non-invasive drug delivery with sustained release through their dissolvable nature. Combining active ingredients from Chinese Herbal Medicine (CHM), known for their natural anti-inflammatory and antibacterial properties with minimal side effects, with DMNs provides an effective approach for treating skin diseases. This review aims to provide a comprehensive overview of the application of CHM-based DMNs in treating psoriasis, acne, hypertrophic scars, keloids, melanoma, atopic dermatitis, and other skin conditions. Additionally, it will introduce the manufacturing methods for CHM-based DMNs, explore strategies for integrating CHM with MNs, and summarize the broad translational potential and challenges of this technology in the field of dermatology.

Development and validation of a nomogram combining cytokines with traditional clinical parameters in predicting the risk of postoperative sepsis after ureteroscopic lithotripsy

Renal Failure · 2025-06-23

BACKGROUND: Sepsis is one of the most severe complications of ureteroscopic lithotripsy (URSL) surgery and is the main cause of death in hospitalized patients. Traditional preoperative patient management and risk assessment systems need to be updated urgently to reduce the occurrence of postoperative sepsis. This study aimed to construct a novel nomogram to preoperatively predict the risk of septic complications after URSL. METHOD: We retrospectively reviewed the records of patients who underwent URSL between January and December 2023 and divided them into the control and sepsis groups according to their postoperative outcomes. Baseline data, routine blood and urine parameters, and blood cytokine concentrations were collected for analysis. Independent predictive factors for the onset of postoperative sepsis were selected using univariate and multivariate logistic regression analyses. A nomogram was constructed, and its clinical effectiveness was validated using receiver operating characteristic (ROC) curve and decision curve analyses (DCA). RESULTS: Three hundred and thirty-three patients were included in the analysis; 293 were discharged smoothly and divided into a control group, and 40 patients developed postoperative sepsis. Day of preoperative antibiotic use, C-reactive protein, albumin, lactate dehydrogenase, interleukin (IL)-6, IL-8, IL-10, interferon-γ, and urine protein were entered into the nomogram. Our nomogram demonstrated strong discriminative ability, with an area under the ROC curve of 0.981. Further validation of the DCA showed that the nomogram was clinically useful in evaluating the risk of postoperative septic complications. CONCLUSIONS: We developed a nomogram combining traditional blood and urine parameters with cytokine concentrations to predict the risk of postoperative septic complications after URSL. Validation using decision curve analysis revealed satisfactory discrimination, indicating its potential clinical utility. This may aid in surgical risk assessment and clinical decision-making.

Incidence of major urological cancers in patients on dialysis: a systematic review and meta-analysis

World Journal of Surgical Oncology · 2025-04-04 · 4 citations

BACKGROUND: Studies have demonstrated an elevated risk of urological malignancies in individuals undergoing dialysis, which consequently leads to unfavorable prognoses and diminished quality of life for patients with end-stage kidney disease. Nevertheless, the absence of standardized recommendations for cancer screening and limited utilization of conventional screening methods within the dialysis population remain prevalent issues. METHODS: A meta-analysis was conducted on cohort studies published prior to June 2024, aiming to quantify the cancer risk among individuals undergoing dialysis. Random-effects meta-analyses were employed to combine standardized incidence rates (SIRs) along with their corresponding 95% confidence intervals, considering a p-value of less than 0.05 or an I² value exceeding 50%. Subgroup analyses, heterogeneity tests, and sensitivity analyses were performed as well. RESULTS: A total of 10 studies, consisting of 12 cohort studies, were ultimately identified, encompassing a collective patient population of 1,362,196 individuals. Compared to the general population, the pooled SIRs for all cancers except non-melanoma skin cancer (NMSC), major urological cancers (MUCs), cancers of the kidney/renal pelvis, bladder cancers and prostate cancers were 1.40 (95% CI: 1.28-1.54), 1.76 (95% CI: 1.45-2.14), 4.73 (95% CI: 3.96-5.64), 1.89 (95% CI: 1.61-2.21) and 0.94 (95% CI: 0.79-1.11), respectively. The cancer risk was notably elevated in specific subgroups of women, younger patients (age at first dialysis, 0-34 years), during the initial year of dialysis, and among Asian patients. SIRs differed when considering different primary renal diseases. However, high heterogeneity was observed among the studies investigating cancers during dialysis, while this heterogeneity did not have a substantial impact on the pooled SIRs for overall cancer, as determined through sensitivity analysis. CONCLUSIONS: Compared with the general population, the dialysis population had a significantly increased risk of developing urological malignancies, particularly cancers of the kidney/renal pelvis. Our findings indicate a substantial increase in risks among female, young, Asian patients, during the first year of dialysis and highlight variations in SIRs based on primary renal disease. These results suggest the potential for adopting a more personalized approach to cancer screening in chronic dialysis patients. Given the considerable heterogeneity observed, further rigorous investigations are warranted to enhance our understanding in this area.

Endoscopic Thulium Laser Ablation with Disitamab Vedotin and Immunotherapy in High-risk Upper Tract Urothelial Carcinoma: A Prospective Pilot Study of a Novel Kidney-sparing Strategy

European Urology Oncology · 2025-10-17 · 3 citations

BACKGROUND AND OBJECTIVE: Kidney-sparing treatment (KST) is an emerging alternative to radical nephroureterectomy for selected patients with upper tract urothelial carcinoma (UTUC), particularly those with imperative indications. Our aim was to evaluate the efficacy and safety of a novel KST approach combining endoscopic thulium laser ablation (TLA) with perioperative systemic therapy (disitamab vedotin [DV] and an immune checkpoint inhibitor [ICI]; toripalimab or tislelizumab) in a carefully selected cohort of patients with localized high-risk UTUC. METHODS: This single-center prospective pilot study conducted from June 2021 to February 2024 and enrolled patients with localized high-risk UTUC with HER2 expression. Patients underwent multimodal treatment comprising sequential induction therapy, endoscopic TLA, consolidation therapy, and maintenance therapy. Co-primary endpoints were local recurrence-free survival (LRFS) and conversion-free survival (CFS). Secondary endpoints included overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), intravesical recurrence-free survival (IVRFS), renal function benefits, and therapy-related adverse events (TRAEs). KEY FINDINGS AND LIMITATIONS: A total of 33 patients were enrolled. Median follow-up was 23 mo for those without death or salvage surgery. LRFS rates were 67% at 1 yr and 64% at 2 yr. HER2 positivity was identified as a candidate protective factor for local recurrence within the first year (odds ratio 0.12, 95% confidence interval 0.01-0.95; p = 0.042). The 2-yr survival rates were 94% for CFS, 88% for IVRFS,100% for MFS, 94% for OS, and 100% for CSS. A renal function benefit was observed within the first year after ablation. The 1-yr ureteral stricture rate was 12% and no grade >3 TRAEs were observed. CONCLUSIONS AND CLINICAL IMPLICATIONS: The combination of endoscopic TLA with perioperative systemic therapy demonstrated promising efficacy and manageable safety in selected patients with localized high-risk UTUC. Our results suggest that there is potential for a paradigm shift in the management of this challenging patient population.

Cepharanthine may inhibit the proliferation of prostate cells by blocking the EGFR/PI3K/AKT signaling pathway: comprehensive network analysis, molecular docking, and experimental evaluation

Frontiers in Pharmacology · 2025-11-24

Introduction Pharmacological studies have confirmed that Cepharanthine (CEP) can exert anti-inflammatory, antioxidant and anti-fibrotic effects. However, there is no systematic study on whether CEP targets and regulates the core pathological link of benign prostatic hyperplasia (BPH) - matrix hyperplasia. Methods First, the CEP structure was obtained through PubChem. Combined with BPH targets from the GeneCards/OMIM/TTD database, potential targets were obtained by intersection using Venny 2.1. Then, the PPI network was constructed using STRING, and top 20 core targets were identified using Cytoscape 3.9.1. GO/KEGG enrichment analysis was performed using the DAVID database. Based on the CB-Dock platform, CEP was molecularly docked with key targets, the protein structure was derived from AlphaFold2 and PDB, and the binding energy was calculated by the VINA algorithm. Furthermore, human prostate stromal cells WPMY-1 and benign prostatic hyperplasia cells BPH-1 were used as a model. The Celigo full-field scanning system dynamically monitored proliferation from 0 to 96 h, DNA synthesis was quantified by EdU staining, and apoptosis was detected by Annexin V-APC/PI or Annexin V-FITC/PI double staining flow cytometry. Finally, the effect of CEP on the expression of key target genes was analyzed by Western blot. Results Network analysis showed that 96 cross-targets were significantly enriched in the PI3K-AKT, MAPK and HIF-1 pathways. Molecular docking confirmed that CEP strongly bound to EGFR (−9.2 kcal/mol), AKT1 (−7.7 kcal/mol), and FN1 (−9.6 kcal/mol). In vitro experiments showed that CEP inhibited WPMY-1 (IC 50 = 6.396 μM) and BPH-1 (IC 50 = 2.355 μM) proliferation in a dose-dependent manner. Treatment of BPH-1 and WPMY-1 cells with 2.5 μM and 5 μM CEP for 48 h, respectively, significantly reduced the proportion of EdU + cells in both cell lines. Celigo counting revealed a significant decrease in both cell lines after 24–96 h of CEP treatment. Flow cytometry revealed a significant increase in the total apoptotic rate of both WPMY-1 and BPH-1 cells after CEP treatment. Western blot analysis revealed that CEP inhibited EGFR and AKT phosphorylation and FN1 expression in WPMY-1 and BPH-1 cells in a dose-dependent manner. Conclusion This study confirmed for the first time the effectiveness of CEP in targeted regulation of prostatic hyperplasia. However, the in vivo efficacy needs to be verified in testosterone-induced animal models in the future.

Toxicological Impacts and Mechanistic Insights of Bisphenol a on Clear Cell Renal Cell Carcinoma Progression: A Network Toxicology, Machine Learning and Molecular Docking Study

Biomedicines · 2025-11-13 · 2 citations

Background: Clear cell renal cell carcinoma (ccRCC) is a prevalent urological malignancy, accounting for approximately 1.6% of all cancer-related deaths in 2022. While endocrine-disrupting chemicals (EDCs) have been implicated as risk factors for ccRCC, the toxicological profiles and immune mechanisms underlying Bisphenol A (BPA) exposure in ccRCC progression remain inadequately understood. Materials and Methods: Protein–protein interaction (PPI) analysis and visualization were performed on overlapping genes between ccRCC and BPA exposure. This was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to elucidate potential underlying mechanisms. Subsequently, 108 distinct machine learning algorithm combinations were evaluated to identify the optimal predictive model. An integrated CoxBoost and Ridge regression model was constructed to develop a prognostic signature, the performance of which was rigorously validated across two independent external datasets. Finally, molecular docking analyses were employed to investigate interactions between key genes and BPA. Results: A total of 114 overlapping targets associated with both ccRCC and BPA were identified. GO and KEGG analyses revealed enrichment in cancer-related pathways, including pathways in cancer, endocrine resistance, PD-L1 expression and PD-1 checkpoint signaling, T-cell receptor signaling, endocrine function, and immune responses. Machine learning algorithm selection identified the combined CoxBoost-Ridge approach as the optimal predictive model (achieving a training set concordance index (C-index) of 0.77). This model identified eight key genes (CHRM3, GABBR1, CCR4, KCNN4, PRKCE, CYP2C9, HPGD, FASN), which were the top-ranked by coefficient magnitude in the prognostic model. The prognostic signature demonstrated robust predictive performance in two independent external validation cohorts (C-index = 0.74 in cBioPortal; C-index = 0.81 in E-MTAB-1980). Furthermore, molecular docking analyses predicted strong binding affinities between BPA and these key targets (Vina scores all <−6.5 kcal/mol), suggesting a potential mechanism through which BPA may modulate their activity to promote renal carcinogenesis. Collectively, These findings suggested potential molecular mechanisms that may underpin BPA-induced ccRCC progression, generating hypotheses for future experimental validation. Conclusions: These findings enhance our understanding of the molecular mechanisms by which BPA induces ccRCC and highlight potential targets for therapeutic intervention, particularly in endocrine and immune-related pathways. This underscores the need for collaborative efforts to mitigate the impact of environmental toxins like BPA on public health.