Objective To systematic analyze the risk factors for new-onset urethral stricture after transurethral holmium laser enucleation of the prostate(HoLEP)in the treatment of benign prostatic hyperplasia(BPH).Methods A case-control study was conducted on 746 BPH patients undergoing HoLEP treatment in Department of Urology of the Third Medical Center of Chinese PLA General Hospital from November 2021 to August 2024.After 23 cases were excluded because of complication of prostate cancer,finally 723 patients were included.General clinical data such as age,height,weight,history of smoking and drinking,perioperative parameters,and follow-up data at 1,3 and 6 months after operation were collected.Univariate and multivariate logistic regression analyses were used to identify the clinical risk factors for new-onset urethral stricture after HoLEP.Results The subjected patients had a median age of 66.5(64.0,75.0)years,and a preoperative median prostate volume of 66(45,92)mL,and a median indwelling catheter time of 4(4,5)d.The incidence of new urethral stricture after operation was 5.8%(42/723),with membranous part of the urethra(61.9%)the most common site,followed by the external urethral orifice(21.4%)and the bladder neck(7.1%).Risk factor analysis indicated that low BMI(<18.5 kg/m2)(OR=4.682,P=0.037),young age(OR=0.946,P=0.005),and postoperative urinary tract infection(OR=4.513,P=0.001)were independent risk factors for new-onset urethral stricture after surgery.Prostate volume and indwelling time of urinary catheter had no significant association with the occurrence of new urethral stricture after surgery.Conclusion The occurrence of new-onset urethral stricture after HoLEP is significantly correlated with BMI,age and urinary tract infection.The above 3 factors can be used as better predictors of new-onset urethral stricture after HoLEP.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To conduct a comprehensive review on application status and future development prospects of proton therapy for pediatric medulloblastoma.Methods A total of 218 literatures were retrieved from PubMed and CNKI database using the search terms"pediatric medulloblastoma,proton therapy,radiotherapy"(English)and"儿童髓母细胞瘤,质子治疗,放射治疗"(Chinese),with a publication timeframe from January 1,2004,to June 1,2025.Inclusion criteria were as follow:(1)proton therapy for pediatric medulloblastoma;(2)radiotherapy for pediatric medulloblastoma;(3)proton therapy for pediatric brain tumors;(4)development and applications of proton therapy.Exclusion criteria were as follow:(1)outdated literatures;(2)redundant or highly similar studies.After screening,89 literatures met the inclusion criteria.Results Compared with conventional treatments such as surgery,photon therapy,and chemotherapy,proton therapy for pediatric medulloblastoma significantly reduced acute toxicity and long-term side effects including cognitive dysfunction,endocrine disorders,and hearing loss.Additionally,proton therapy exhibited favorable cost-effectiveness.In the future,the therapeutic outcomes would be further enhanced through the optimization of proton therapy techniques,treatment planning,and equipment.Conclusion With ongoing technological advancements and growing clinical experience,proton therapy is expected to become one of the standard treatment modalities for pediatric medulloblastoma.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Knee osteoarthritis(KOA)is a chronic joint disease characterized by degeneration of articular cartilage and joint pain.Its pathogenesis is complex,involving cell death,inflammatory responses and the interaction of various signaling pathways.Apoptosis is activated by Caspase family proteins and DNA endonucleases,leading to cellular dysfunction and promoting the degeneration of articular cartilage.Pyroptosis is a form of programmed cell death triggered by inflammasome activation,involving the activation of nucleotide-binding oligomeric domain-like receptor protein 3 inflammasome,which leads to the release of pro-inflammatory cytokines such as interleukin(IL)-6,IL-1 β and tumor necrosis factor-α.This release intensifies local inf/lammation and accelerates the progression of the disease.Ferroptosis is driven by iron-catalyzed lipid peroxidation,which induces the rupture of chondrocyte cell membranes and the degradation of matrix,thereby promoting joint degeneration.In addition,autophagy plays a dual role in KOA:moderate autophagy supports chondrocyte repair,while excessive autophagy may promote joint destruction,cartilage matrix degradation and subchondral bone sclerosis.The PI3K/AKT,NF-κB,Wnt/β-catenin and Hedgehog signaling pathways can regulate the growth,differentiation,proliferation,migration and apoptosis of articular chondrocytes.Single-cell RNA sequencing technology has provided new insights into the cellular heterogeneity and molecular mechanisms in the pathogenesis of KOA.This review explores the mechanisms of cell death in KOA,with a focus on the roles of pro-inflammatory cytokines,signaling pathway,and single-cell RNA sequencing techniques in the occurrence and progression of KOA.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Knee osteoarthritis(KOA)is a chronic joint disease characterized by degeneration of articular cartilage and joint pain.Its pathogenesis is complex,involving cell death,inflammatory responses and the interaction of various signaling pathways.Apoptosis is activated by Caspase family proteins and DNA endonucleases,leading to cellular dysfunction and promoting the degeneration of articular cartilage.Pyroptosis is a form of programmed cell death triggered by inflammasome activation,involving the activation of nucleotide-binding oligomeric domain-like receptor protein 3 inflammasome,which leads to the release of pro-inflammatory cytokines such as interleukin(IL)-6,IL-1 β and tumor necrosis factor-α.This release intensifies local inf/lammation and accelerates the progression of the disease.Ferroptosis is driven by iron-catalyzed lipid peroxidation,which induces the rupture of chondrocyte cell membranes and the degradation of matrix,thereby promoting joint degeneration.In addition,autophagy plays a dual role in KOA:moderate autophagy supports chondrocyte repair,while excessive autophagy may promote joint destruction,cartilage matrix degradation and subchondral bone sclerosis.The PI3K/AKT,NF-κB,Wnt/β-catenin and Hedgehog signaling pathways can regulate the growth,differentiation,proliferation,migration and apoptosis of articular chondrocytes.Single-cell RNA sequencing technology has provided new insights into the cellular heterogeneity and molecular mechanisms in the pathogenesis of KOA.This review explores the mechanisms of cell death in KOA,with a focus on the roles of pro-inflammatory cytokines,signaling pathway,and single-cell RNA sequencing techniques in the occurrence and progression of KOA.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective To conduct a comprehensive review on application status and future development prospects of proton therapy for pediatric medulloblastoma.Methods A total of 218 literatures were retrieved from PubMed and CNKI database using the search terms"pediatric medulloblastoma,proton therapy,radiotherapy"(English)and"儿童髓母细胞瘤,质子治疗,放射治疗"(Chinese),with a publication timeframe from January 1,2004,to June 1,2025.Inclusion criteria were as follow:(1)proton therapy for pediatric medulloblastoma;(2)radiotherapy for pediatric medulloblastoma;(3)proton therapy for pediatric brain tumors;(4)development and applications of proton therapy.Exclusion criteria were as follow:(1)outdated literatures;(2)redundant or highly similar studies.After screening,89 literatures met the inclusion criteria.Results Compared with conventional treatments such as surgery,photon therapy,and chemotherapy,proton therapy for pediatric medulloblastoma significantly reduced acute toxicity and long-term side effects including cognitive dysfunction,endocrine disorders,and hearing loss.Additionally,proton therapy exhibited favorable cost-effectiveness.In the future,the therapeutic outcomes would be further enhanced through the optimization of proton therapy techniques,treatment planning,and equipment.Conclusion With ongoing technological advancements and growing clinical experience,proton therapy is expected to become one of the standard treatment modalities for pediatric medulloblastoma.

Objective:To analyze the clinicopathological features and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement, aiming enhance its recognition and prevent misdiagnosis.Methods:The clinicopathological features, immunophenotype, and fluorescence in situ hybridization (FISH) results of six cases diagnosed with IRF4 rearrangement-positive B-cell lymphoma at the Affiliated Hospital of Xuzhou Medical University from 2015 to 2023 were retrospectively analyzed. Additionally, a comprehensive review of the literature was conducted.Results:Six patients with IRF4 rearrangement-positive large B-cell lymphoma were included. Patients 1 to 5 included three males and two females with a median age of 19 years ranging from 11 to 34 years. Four patients presented with head and neck lesions, while the other one had a breast nodule; all were in clinical Ann Arbor stages I to Ⅱ. Morphologically, entirely diffuse pattern was present in two cases, purely follicular pattern in one case, and diffuse and follicular patterns in other two cases. The tumor cells, predominantly centroblasts mixed with some irregular centrocytes, were of medium to large size, with a starry sky appearance observed in two cases. Immunophenotyping revealed all cases were positive for bcl-6 and MUM1, with a Ki-67 index ranging from 70% to 90%, and CD10 was positive in two cases. IRF4 rearrangement was confirmed in all cases by FISH analysis, with dual IRF4/bcl-6 rearrangements identified in two cases, leading to a diagnosis of LBCL-IRF4. Case 6, a 39-year-old female with a tonsillar mass and classified as clinical Ann Arbor stage Ⅳ, displayed predominantly diffuse large B-cell lymphoma (DLBCL) morphology with 20% high-grade follicular lymphoma characteristics. Immunohistochemistry showed negative CD10 and positive bcl-6/MUM1, with a Ki-67 index of approximately 80%. Triple rearrangements of IRF4/bcl-2/bcl-6 were identified by FISH, leading to a diagnosis of DLBCL with 20% follicular lymphoma (FL). All six patients achieved complete remission after treatment, with no progression or relapse during a follow-up period of 31-100 months.Conclusions:Large B-cell lymphoma with IRF4 rearrangement is a rare entity with pathological features that overlap with those of FL and DLBCL. While IRF4 rearrangement is necessary for diagnosing LBCL-IRF4, it is not specific and requires differentiation from other aggressive B-cell lymphomas with IRF4 rearrangement.