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关键词： Mini-PCNL   Paediatric surgery   Paediatric urolithiasis   Renal stones   SWL   URS/RIRS  

摘要： Purpose: To evaluate outcomes and complications of different surgical approaches for 10–20 mm internal stones in children, based on bicentric real-world experience. Materials and methods: We retrospectively analysed 96 patients treated between 2009 and 2022 at two tertiary referral centres. Data included demographics, stone characteristics, treatment (extracorporeal shockwave lithotripsy -SWL, retrograde surgery -RIRS, percutaneous nephrolithotomy – PCNL, surgery), complications, and stone-free rates. The primary outcome was stone clearance;complications were graded according to the Clavien-Dindo classification. Categorical variables were compared using Chi-square of Fisher’s exact test. Results: Median age was 61 months (IQR 25–105). Nineteen patients (19.8%) had associated urological conditions. 50% had multiple stones. Treatments included SWL (17.7%), URS/RIRS (46.9%), PCNL (19.8%), and surgery (8.3%). Intraoperative complications occurred in 4.2%, early postoperative in 12.5%, and late complications in 11.5%. Stone clearance after the first procedure was achieved in 47.9%. Clearance rates were 58.8% for SWL, 47.8% for URS/RIRS, and 52.6% for PCNL. No statistically significant differences were observed in stone clearance or complication rates among treatments. Conclusions: All treatments demonstrated safety and efficacy for 10–20 mm pediatric intrarenal stones. Individualized treatment planning, considering stone burden and patient-specific factors, remains essential to optimize outcomes. © The Author(s) 2026.

关键词： Charcot–Marie–Tooth type 1A   Imaging mass spectrometry   Lipid metabolism   Peripheral myelin protein 22   Targeted metabolomics  

摘要： Charcot–Marie–Tooth Type 1 A (CMT1A) is a hereditary neuropathy caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. Emerging evidence suggests that lipid metabolism plays a central role in CMT1A pathology. This study investigated metabolic profiles in sciatic nerve tissue and plasma of PMP22 transgenic (TG) and wild-type (WT) rats at 2, 4, and 6 months of age. Utilizing targeted metabolomics, more than 600 metabolites covering central metabolic pathways and major lipid classes were analyzed, revealing distinct age-dependent changes in metabolic pathways. Alterations that emerged early and became increasingly pronounced with age were observed in sphingolipids and glycerophospholipids, while changes in other metabolic pathways, such as amino acids, storage lipids, bile acids, and nucleotide metabolism, were age-specific. Notably, in contrast to these age-dependent adaptive changes, three lipid signatures were identified that remained stable from the earliest age examined. These include: (1) an elevated ratio of hydroxylated to non-hydroxylated sphingolipids, (2) a reduced ratio of monounsaturated-containing to saturated fatty acid containing phosphatidylcholines, and (3) a decreased ratio of hexosylceramides to ceramides. Imaging mass spectrometry analyses confirmed disruptions in sphingolipid metabolism. These findings suggest a key regulatory role of PMP22 in lipid metabolism, as demonstrated by the early stabilization of specific lipid signatures compared to other metabolic changes that occurred in an age-dependent and adaptive manner. These observations provide valuable insights into the pathogenic mechanisms underlying CMT1A. © The Author(s) 2026.

关键词： Combined Positive Score   Immunohistochemistry analysis   PD-L1   Urothelial carcinoma  

摘要： Urothelial carcinoma (UC) is the commonest type of malignancy in the urinary system. The programmed death-ligand 1 (PD-L1) expression plays a key role in tumor immune evasion and could impact prognosis and treatment response, mainly to immune checkpoint inhibitors. This study was designed to assess PD-L1 expression using the Combined Positive Score (CPS) in UC cases from Basrah city and analyze its association with tumor grade, invasiveness, histological type, gender, and age. Fifty cases of UC were involved in this retrospective study. PD-L1 expression was evaluated using immunohistochemistry and quantified by CPS. The tumors were classified by histological grade (low or high), type (squamous or papillary), and invasiveness (invasive or noninvasive). Statistical analysis was performed with SPSS software. PD-L1 expression (CPS > 0) was found in 30% of cases, and it was strongly associated with tumor grade and invasiveness (p < 0.001), with higher-grade tumors and muscle-invasive tumors showing elevated levels of expression. These findings confirmed a significant association between PD-L1 expression in relation to tumor grade in UC, indicating its potential role as a prognostic marker and therapeutic target in high-grade tumors. Further studies on larger cohorts and clinical follow-up are recommended. © The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2026.

关键词： Anti-CTLA-4   Dacarbazine   Ipilimumab   Melanoma   Temozolomide  

摘要： Many patients with advanced melanoma eventually stop responding to PD-1 immunotherapy, and effective treatments are limited. Recent studies suggest that older chemotherapy drugs such as dacarbazine and temozolomide may work better after prior PD-1 therapy and can stimulate the immune system when combined with CTLA-4 blockade (ipilimumab). This review summarises clinical evidence and biological mechanisms supporting these combinations, including how chemotherapy-induced DNA damage can release tumour antigens, activate interferon pathways, and reawaken exhausted T cells. Because these regimens are relatively safe, inexpensive, and widely available, they may provide a realistic treatment option for patients in health systems where modern cell-based therapies are not accessible. Further clinical trials with integrated biomarker research are needed to identify which patients benefit most from this approach. © The Author(s) 2026.

关键词： Bladder   Cancer   FGFR3   IL-1β   Polymorphism   Rs28931614  

摘要： Bladder cancer (BCa) is a prevalent malignancy. It ranks as the seventh most common cancer, and the 13th most common cause of cancer mortality, particularly in Egypt, where it has been the most common cancer for the past 50 years. Genetic and inflammatory factors may influence its risk and prognosis. To evaluate the association of FGFR3 gene polymorphisms (rs28931614) and interleukin-1β (IL-1β) serum levels with BCa risk and survival in Egyptian patients. A case–control study included 100 BCa patients from Mansoura University Urology and Nephrology Center and 100 healthy controls. It evaluated risk, diagnosis, and prognosis of BCa. FGFR3 genotyping was performed using PCR-ARMS, and IL-1β levels were measured via ELISA. BCa patients showed significantly higher frequencies of FGFR3 GA, AA genotypes, dominant and recessive models, and A allele compared to controls (P-values ranging from 0.003 to 0.039). Median IL-1β levels were elevated in BCa patients (14.35 pg/mL) versus controls (8.9 pg/mL, P < 0.001). Stratification by FGFR3 genotypes and IL-1β levels revealed that patients with low IL-1β and wild-type FGFR3 had the highest overall survival (OS) probability (97.6%), while high IL-1β with variant FGFR3 or low IL-1β with variant FGFR3 indicated poorer prognosis. The AA genotype and high IL-1β were linked to shorter OS. FGFR3 rs28931614 polymorphisms and elevated IL-1β levels are associated with increased BCa risk and reduced survival, suggesting their potential as diagnostic and prognostic biomarkers. © The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2026.

关键词： Gut microbiota   Immune homeostasis   Schizophyllan   Selenium nanoparticles   Toll-Like receptor 4/Nuclear factor kappa b pathway   Type 1 diabetes mellitus  

摘要： Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic β-cells. Growing evidence indicates that immune dysregulation along the gut–lung axis contributes to its pathogenesis. This study aimed to develop a selenium-loaded sustained-release Schizophyllan (Se/s-SPG) composite and investigate its mechanism of action in alleviating T1DM-associated inflammatory immune responses through modulation of the gut microbiota and the Toll-like receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) signaling pathway. A T1DM model was established using non-obese diabetic (NOD)/LtJ mice. Comprehensive analyses were performed, including 16 S rRNA sequencing, RNA sequencing (RNA-seq), Western blot (WB), Enzyme-linked immunosorbent assay (ELISA), and Flow Cytometry to assess the effects of Se/s-SPG on gut microbial diversity, pancreatic structure and function, immune cell subset distribution, and inflammatory signaling pathways. The results demonstrated that Se/s-SPG significantly improved glucose metabolism, restored intestinal and pulmonary barrier integrity, and regulated T cell subset differentiation as well as macrophage polarization. This study proposes a novel intervention strategy targeting the gut–lung axis for T1DM and highlights its potential for clinical translation. © The Author(s) 2026.

摘要： Radiotherapy is constricted by collateral normal tissue injury during treatment, particularly the gastrointestinal tracts, which is usually referred as radiation-induced gastrointestinal syndrome (RIGS). Currently, there is no FDA-approved agent for the prevention or treatment of RIGS. By using a mice model of RIGS, we demonstrated that 1,2-propanediol (1,2-PD) prevents radiation-induced fatal intestinal injury and significantly increases mice survival following lethal doses of radiation. 1,2-PD pretreatment also enhanced the survival of Lgr5⁺ISCs and improved crypts regeneration after radiation. Moreover, we confirmed 1,2-PD induces dormant cell cycle arrest in enterocytes and ameliorates DNA damage both in vitro and in vivo. Although we did have observed 1,2-PD pretreatment inhibiting P53-PUMA signal pathway, but fail to prove its relation with radiation resistance. In RNA sequencing, we have observed 1,2-PD pretreatment significantly upregulates the Hif-2α, Hif-3α and PPARα target gene ACOX2, whilst downregulating the cell cycle drivers E2f3 and Cyclin D2. These results demonstrate that ISCs play a key role in radiation-induced intestinal regeneration and that 1,2-PD acts as a potent intestinal radioprotector © The Author(s) 2026.

关键词： Downward propagation   Planetary wave   Sudden stratospheric warming   Zonal wavenumber 1  

摘要： To elucidate dynamics of significant downward propagation (SDP) events of zonal wavenumber 1 (WN1) planetary waves from the stratosphere after sudden stratospheric warming (SSW) events and their influence on the extratropical troposphere, a case study of an SDP event in March 2023 and composite analyses for SDP events with and without SSW using JRA-3Q reanalysis are conducted. The March 2023 event is characterized by the equatorward propagation of enhanced WN1 components in the troposphere, which follows the WN1 downward propagation after the SSW. Exceptionally warm anomalies in East Asia including Japan in early March are associated with the equatorward propagation. A statistical investigation on the timing of all SDP and SSW events reveals that an SDP event is significantly more likely to occur after an SSW. The composite of the SDP event with SSW is characterized by stratospheric easterlies, in contrast to that without SSW, in which westerlies prevail in the stratosphere. Downward propagated WN1 components in the troposphere propagate equatorward and produce temperature anomalies in the extratropics, depending on the WN1 phase at high latitudes for both SDP events. When the WN1 ridge is positioned around the date line in SDP events with SSW, cold anomalies tend to cover East Asia including Japan. The WN1 component during the March 2023 event has the largest amplitude among SDP events with SSW and a ridge location around 90°W, which is far apart from the rest. These peculiar characteristics of the WN1 component would contribute to the extraordinary warm anomalies near Japan. © The Author(s) 2026.

关键词： Peritoneal dialysis   Children   Peritoneal function   Genetic polymorphism  

摘要： BackgroundAquaporins (AQPs) are a class of proteins that transport water molecules across membranes, which can promote water transport in cells. We aimed to explore the correlation between different polymorphisms of AQP1 and peritoneal function in children on peritoneal dialysis (PD).MethodsChildren who underwent PD at the Children's Hospital of Fudan University from January 1, 2014, to December 31, 2023, were included. The AQP1 genotypes of the four polymorphisms were rs2075574 (TT, CT, CC), rs1049305 (GG, CG, CC), rs10253374 (TT, CT, CC) and rs17159702 (TT, CT, CC).ResultsA total of 187 children on chronic PD were included in the study. We found that the TT group with rs2075574 exhibited a lower baseline peritoneal equilibration test (PET) ultrafiltration level than the CC group (302 +/- 129 vs. 408 +/- 168 ml/m2, P = 0.015). For rs1049305, the CC group had a higher pKT/V than both the GG (2.71 +/- 1.25 vs. 2.27 +/- 0.79, P = 0.04) and CG groups (2.71 +/- 1.25 vs. 2.24 +/- 0.88, P = 0.03). Additionally, at 12-month follow-up, the CC (410 +/- 160 ml/m2, P = 0.04) and CG (393 +/- 174 ml/m2, P = 0.04) groups of rs1049305 showed higher PET ultrafiltration than the GG group (239 +/- 288 ml/m2). No significant correlation was observed between the four genotypes and adverse ***1 rs2075574 and rs1049305 polymorphisms might be associated with ultrafiltration and urea transport in children with *** AbstractA higher resolution version of the Graphical abstract is available as Supplementary information

关键词： PBCV-1   Viral capsid assembly   Vp54   major capsid protein   membrane-capsid coupling   cryo-EM   molecular dynamics simulations   electrostatic interactions  

摘要： Giant double-stranded DNA (dsDNA) viruses such as Paramecium bursaria chlorella virus 1 (PBCV-1) exhibit complex assembly pathways shaped by global protein symmetry, local asymmetry and an internal membrane scaffold. Cryo-electron microscopy has resolved the T =169 d lattice and unique vertex architecture of the PBCV-1 capsid, while structural and lipidomic studies highlight the contribution of the internal membrane to infection and virion stability. Yet, the dynamic processes through which thousands of Vp54 trimers and membrane components coalesce into a complete virion remain poorly understood. Computational methods, including electrostatics, molecular dynamics, coarse-grained modeling and multiscale simulations, have emerged as powerful tools to complement experimental findings and elucidate the physicochemical rules of assembly. In this review, we synthesize current structural and functional knowledge of PBCV-1, emphasize emerging computational advances and integrate cross-system examples to outline transferable principles. Together, these perspectives chart a roadmap toward predictive modeling of giant virus assembly and the coupling between membranes and capsids.