This article reports a case of membranous nephropathy in an adolescent accompanied by monoclonal IgG1-κ deposition. The 16-year-old female patient was hospitalized for experiencing proteinuria and hematuria for more than 20 days. The patient had a history of mycoplasma infection and acute kidney injury, and renal pathology revealed glomerular membrane lesions accompanied by crescent formation. Electron microscopy showed electron dense deposits in the subepithelial and mesangial regions, and immunofluorescence demonstrated monotypic IgG1-κ deposits in the glomerulus. Bone marrow examination did not find any abnormal plasma cells, nor were there significant abnormalities in serum or urine free light chain κ/λ ratio. The diagnosis was proliferative glomerulonephritis characterized by membranous lesions with monoclonal IgG1-κ deposits. This disease is rare in children and adolescents, and currently there is limited understanding of its mechanism, with limited clinical treatment experience. This article aims to provide clinical insights through case analysis and literature review.

Tacrolimus is an immunosuppressant that was clinically used for organ transplantation in the 1990s. In the early 2000s, tacrolimus began to be used to treat pediatric kidney diseases in China. This article reviews the therapeutic effects, clinical dosages, and treatment methods of tacrolimus in the treatment of steroid-resistant, steroid-dependent, frequently relapsing, different pathological types, and monogenic mutation-related childhood nephrotic syndrome. It explores the clinical guiding role of machine learning in tacrolimus treatment for childhood nephrotic syndrome, aiming to provide references for the clinical research and application of tacrolimus in pediatric kidney diseases.

This article reports a case of membranous nephropathy in an adolescent accompanied by monoclonal IgG1-κ deposition. The 16-year-old female patient was hospitalized for experiencing proteinuria and hematuria for more than 20 days. The patient had a history of mycoplasma infection and acute kidney injury, and renal pathology revealed glomerular membrane lesions accompanied by crescent formation. Electron microscopy showed electron dense deposits in the subepithelial and mesangial regions, and immunofluorescence demonstrated monotypic IgG1-κ deposits in the glomerulus. Bone marrow examination did not find any abnormal plasma cells, nor were there significant abnormalities in serum or urine free light chain κ/λ ratio. The diagnosis was proliferative glomerulonephritis characterized by membranous lesions with monoclonal IgG1-κ deposits. This disease is rare in children and adolescents, and currently there is limited understanding of its mechanism, with limited clinical treatment experience. This article aims to provide clinical insights through case analysis and literature review.

Tacrolimus is an immunosuppressant that was clinically used for organ transplantation in the 1990s. In the early 2000s, tacrolimus began to be used to treat pediatric kidney diseases in China. This article reviews the therapeutic effects, clinical dosages, and treatment methods of tacrolimus in the treatment of steroid-resistant, steroid-dependent, frequently relapsing, different pathological types, and monogenic mutation-related childhood nephrotic syndrome. It explores the clinical guiding role of machine learning in tacrolimus treatment for childhood nephrotic syndrome, aiming to provide references for the clinical research and application of tacrolimus in pediatric kidney diseases.

Objective:To investigate the role of alkylation repair homolog 5(ALKBH5)-mediated N6-methyladenosine(m6A)modifi-cation in endometrial decidualization.Methods:The mouse models of pregnancy and pseudopregnancy were established,and quantita-tive real-time PCR and Western blot were used to measure the expression pattern of ALKBH5 in the endometrium.The mouse and cell models of artificially induced decidualization were established,and quantitative real-time PCR,Western blot,and immunohistochemis-try were used to measure the expression levels of decidualization-related markers.The EpiQuik m6A RNA methylation quantification kit was used to measure the level of m6A.The mouse and cell models of artificially induced decidualization with interference of ALKBH5 expression were established,and quantitative real-time PCR,Western blot,and immunohistochemistry were used to measure the expression levels of decidualization-related markers,cell proliferation marker molecules,and apoptosis molecules.Flow cytometry was used to measure cell apoptosis rate.Results:In the mouse model of pregnancy,the expression level of ALKBH5 at the uterine em-bryo implantation site was significantly higher than that adjacent to the implantation site,and in the mouse and cell models of artifi-cially induced decidualization,compared with the control group,the induction group had a significant increase in the expression level of ALKBH5 and a significant reduction in the level of m6A.Inhibiting the expression of ALKBH5 led to an increase in the level of m6A,which in turn inhibited the proliferation of stromal cells,induced cell apoptosis,and ultimately impaired the normal process of en-dometrial decidualization.Conclusion:ALKBH5 deficiency leads to an increase in the level of m6A and decidualization injury in the en-dometrium,which lays a foundation for the research on m6A modifi-cation in decidualization.

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.

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*