To investigate the regulatory role and mechanism of secreted phosphoprotein 1 (SPP1) on macrophage phenotype transformation in the early stage of ischemia-reperfusion induced acute kidney injury (AKI).

In this study, male C57BL/6J mice were used to establish a bilateral renal ischemia-reperfusion injury (IRI)-induced AKI model. Renal tissue injury, CD68⁺ macrophage infiltration, and SPP1 protein expression levels were evaluated by histopathological staining, immunostaining, and Western blotting. The mice bone marrow-derived macrophages were isolated and induced, and transcriptome sequencing was performed to analyze differentially expressed genes after stimulation with recombinant SPP1 protein. Furtherly RAW264.7 cells were stimulated with recombinant SPP1 protein, and the levels of IL-1β, TNF-α, CD86, inducible nitric oxide synthase, and reactive oxygen species were detected by qPCR and flow cytometry. For the in vivo intervention experiments, mice were randomly divided into three groups (n=6 per group): a sham group, an IRI+ IgG control group (treated with 10 mg/kg isotype IgG after IRI modeling), and an IRI+ anti-SPP1 group (treated with an equal dose of SPP1 neutralizing antibody after IRI modeling). Renal injury and inflammatory indicators were compared among the groups.

Significant tubular injury accompanied by increased CD68⁺ macrophage infiltration was observed in the renal corticomedullary junction after IRI modeling (P<0.05). SPP1 expression in proximal tubular epithelial cells was also significantly upregulated (P<0.05). Transcriptome analysis revealed that stimulation with exogenous recombinant SPP1 protein induced extensive alterations in the gene expression profile of macrophages. The 3, 141 differentially expressed genes identified were mainly enriched in inflammation- and immune-related pathways. In vitro experiments with RAW264.7 cells demonstrated that SPP1 promoted macrophage polarization towards a pro-inflammatory phenotype, as evidenced by increased mRNA expression of the aforementioned pro-inflammatory factors, a higher proportion of CD86⁺ cells, and elevated reactive oxygen species levels (all P<0.05). In vivo intervention experiments indicated that the SPP1 neutralizing antibody significantly attenuated renal tubular necrosis in the IRI mice and downregulated the expression of kidney injury molecule-1 and IL-1β (all P<0.05).

In the renal IRI, SPP1 expression was upregulated, promoting macrophage polarization towards a pro-inflammatory phenotype, enhancing oxidative stress, and thereby exacerbating renal inflammatory injury.

To investigate the effect of depleting renal natural killer (NK) cells on folic acid-induced acute kidney injury (AKI) in mice.

Male C57BL/6J mice aged 8-10 weeks old were selected and randomly divided into the following groups (n=5 per group): a model group (intraperitoneal injection of folic acid at 250 mg/kg), a model+ anti-mouse IgG2a antibody group (intraperitoneal injection of 200 μg IgG2a antibody for 2 consecutive days prior to modeling), a model+ anti-mouse NK1.1 antibody group (intraperitoneal injection of 200 μg anti-NK1.1 antibody for 2 consecutive days prior to modeling), and a control group (intraperitoneal injection of an equivalent volume of 0.3 M NaHCO₃). Mice of the control and model groups were sacrificed 2 days after modeling to evaluate serum creatinine, blood urea nitrogen, kidney-to-body weight ratio, and renal histopathological changes. Flow cytometry was performed to analyze the proportions of CD4⁺ T cells, CD8⁺ T cells, regulatory T cells, and NK cells in kidney tissues, as well as their capacity to secrete cytokines as interleukin-17A, interferon-γ, and tumor necrosis factor-α. For the model+ anti-mouse IgG2a antibody group and the model+ anti-mouse NK1.1 antibody group, the renal NK cells depletion efficiency was assessed by flow cytometry 2 days after modeling, along with the analysis of renal function and observation of renal pathological changes.

Compared with the control group, the model group showed significantly higher serum creatinine and blood urea nitrogen levels, as well as more severe renal tissue injury (all P<0.05), while the proportion of NK cells in the kidneys was also significantly increased (P<0.05), accompanied by decreased interferon-γ and increased tumor necrosis factor-α secretion (all P<0.05). In contrast, the proportions of CD4⁺ T cells, CD8⁺ T cells, and regulatory T cells, along with their associated cytokines, showed no significant changes in the renal tissues. Compared with the model+ anti-mouse IgG2a antibody group, the model + anti-mouse NK1.1 antibody group exhibited significant renal NK cells depletion, accompanied by lower serum creatinine and blood urea nitrogen levels and attenuated renal tissue injury (all P<0.05).

The use of anti-mouse NK1.1 antibody significantly depleted NK cells in renal tissues and attenuated folic acid-induced AKI in mice, suggesting that its protective mechanism is associated with reduced NK cells infiltration and decreased pro-inflammatory cytokines secretion in the kidneys.

To utilize transcriptome sequencing datasets for exploring key cell clusters and specific transcriptional regulators during the fibrotic process, aiming to elucidate the mechanism by which sulforaphane ameliorates renal fibrosis in mice.

A single-cell RNA sequencing dataset (GSE175412) derived from a unilateral ureteral obstruction (UUO) renal fibrosis model was utilized. Cell clustering was performed using the Leiden algorithm, followed by manual annotation of the cell clusters. Cell-cell interaction analysis was performed using CellPhoneDB to identify key cell clusters involved in renal fibrosis. Subsequently, the RegDiffusion algorithm combined with AUCell scoring was employed to identify key cell-type-specific transcriptional regulators within each cluster. The bulk RNA-seq dataset of human polycystic kidney disease cells treated with sulforaphane (GSE141740) was utilized. The DESeq2 package was employed to analyze differentially expressed genes between the sulforaphane-treated group and the model group, aiming to identify potential downstream targets of sulforaphane. Subsequently, a UUO model was established by ligating the upper pole of the left ureter in 6 to 8-week-old male C57BL/6J mice to validate the anti-fibrotic effect of sulforaphane and its impact on the expression levels of potential downstream targets. The mice were divided into two groups (n=6 per group): the UUO model group and the UUO plus sulforaphane intervention group. The latter received intraperitoneal injections of sulforaphane [12.5 mg/(kg·d)] starting from the day after surgery. Real-time quantitative PCR was performed to verify the mRNA expression level of sex-determining region Y-related high-mobility-group box transcription factor 4 (Sox4). Masson′s trichrome staining was utilized to evaluate renal interstitial collagen deposition. Additionally, immunohistochemistry and Western blotting were employed to detect fibrotic markers, including vimentin, collagen I, and α-smooth muscle actin. One-way ANOVA was used for comparisons among multiple groups.

The results demonstrated that the proportion of proximal tubular epithelial cells decreased, while the proportion of injured tubular epithelial cells increased in the kidneys of UUO mice. Furthermore, injured tubular epithelial cells were found to interact with fibroblasts and pericytes via multiple pro-fibrotic pathways. Sox4 exhibited high specific activity and significantly elevated mRNA levels in the cluster of injured tubular epithelial cells. Furthermore, sulforaphane treatment significantly downregulated the mRNA expression of Sox4 in human polycystic kidney disease cells. In the UUO plus sulforaphane intervention group, Sox4 mRNA level was significantly downregulated (P<0.05), and renal interstitial collagen deposition was significantly reduced (P<0.05). Besides, the expression of collagen I, α-smooth muscle actin, and vimentin was also significantly decreased (all P<0.05).

Injured tubular epithelial cells served as a key cell cluster in the progression of UUO-induced renal fibrosis, with Sox4 acting as their specific transcriptional regulator. Sulforaphane may exert its anti-fibrotic effects by downregulating Sox4.

To investigate the effect of curcumin on renal necroptosis in diabetic kidney disease rats.

Adult male Sprague-Dawley (SD) rats were randomly divided into four groups (n=12 per group): a control group, a diabetic kidney disease (DKD) model group (intraperitoneal injection of a single dose of streptozotocin at 55 mg/kg), a DKD model+ curcumin group [daily intraperitoneal injection of curcumin suspension at 200 mg/(kg·d) via intragastric gavage after modeling], and a DKD model + carboxymethyl cellulose sodium (CMC-Na) group (daily intraperitoneal injection of an equal volume of 5% CMC-Na via intragastric gavage after modeling). General conditions of the rats were monitored throughout the study. Urine and blood samples were collected at weeks 8 and 12 to measure 24-h urinary protein, blood glucose, serum creatinine, and blood urea nitrogen (BUN). And bilateral kidneys were harvested for histopathological examination. Furthermore, the protein and mRNA expression levels of tumor necrosis factor-α (TNF-α), receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL), transforming growth factor-β (TGF-β), and interleukin-18 (IL-18) in renal tissues were detected using immunohistochemistry, Western blotting, and qRT-PCR, respectively.

Compared with the control group, rats in the DKD model group and the DKD model+ CMC-Na group exhibited poor general conditions, along with disordered glomerular structure and tubular swelling. Both blood and urinary biochemical indices were significantly elevated (all P<0.01). Furthermore, the expression levels of TNF-α, RIP1, RIP3, MLKL, TGF-β, and IL-18 in renal tissues were also significantly upregulated (P<0.01). Compared with the DKD model+ CMC-Na group, rats in the DKD model + curcumin group showed significant improvement in general conditions and alleviation of glomerular and tubular lesions. Both blood and urinary biochemical indices were significantly decreased (P<0.01). Moreover, the expression levels of TNF-α, RIP1, RIP3, MLKL, TGF-β, and IL-18 in renal tissues were also downregulated (P<0.01).

Curcumin may attenuate renal inflammation and injury in DKD rats by inhibiting TNF-α expression, thereby partially suppressing the activation of the necroptosis pathway and the release of inflammatory cytokines.

To investigate the stratification value of combined scoring of procalcitonin (PCT) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) on the efficacy of methylprednisolone combining integrated blood purification in children with severe sepsis.

A retrospective analysis was conducted on children with severe sepsis who received methylprednisolone combined with integrated blood purification from January 2024 to December 2025. Based on organ function and perfusion status at 72 hours post-treatment, the patients were divided into a treatment response group and a non-response group. Baseline characteristics were compared between the two groups, and a combined PCT and NT-proBNP scoring model was constructed. Multivariate logistic regression was used to analyze independent factors influencing treatment response, while receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis were employed to evaluate the predictive performance and clinical utility of the combined markers.

A total of 117 children patients were included, comprising 68 in the treatment response group and 49 in the non-response group. Compared with the non-response group, the treatment response group exhibited significantly lower baseline pediatric sequential organ failure assessment scores, lactate, PCT, NT-proBNP, and combined scores (all P<0.05). A higher combined score was identified as an independent risk factor for poor treatment response (OR=4.150, 95%CI: 1.892-9.102, P<0.01). According to the stratification of the optimal cut-off value of 0.85, children with higher combined scores exhibited lower treatment response rates, higher 28-day mortality, slower organ function recovery, and longer pediatric intensive care unit (all P<0.05). Based on the combined scoring prediction model, the area under the curve for predicting treatment response was 0.842, with good calibration. Additionally, decision curve analysis demonstrated a high clinical net benefit within reasonable threshold ranges.

Baseline combined PCT and NT-proBNP scoring is associated with the 72-hour early treatment response and 28-day mortality risk in children with severe sepsis treated with methylprednisolone and integrated blood purification. The prediction model constructed based on this score demonstrates favorable discrimination and calibration, suggesting it could serve as a valuable reference for early risk stratification and management.

Renal ischemia-reperfusion injury is often irreversible, and effective clinical treatments remain scarce. Recent studies have demonstrated that ferroptosis is a critical mechanism mediating renal tubular epithelial cell death in renal ischemia-reperfusion injury, making it a prominent research hotspot. This review summarizes the molecular mechanisms of ferroptosis and the progress in identifying novel targets in renal ischemia-reperfusion injury, and also discusses the current status and future prospects of developing drugs that target ferroptosis.

To investigate the application effect of project-based learning in improving the mastery of basic experimental techniques, literature comprehension, and scientific thinking among nephrology postgraduate students.

Research-type postgraduate students majoring in nephrology enrolled in 2022 and 2023 at the Senior Department of Nephrology, Chinese PLA General Hospital, were selected as the study subjects. They were randomly divided into an experimental group (project-based learning) and a control group (traditional mentoring learning). The scores for experimental techniques, literature reading, and the scientific research thinking ability scale were compared between the two groups to evaluate the teaching effectiveness.

A total of 40 postgraduate students were included, with 20 in the experimental group and 20 in the control group. After the teaching practice, the experimental group demonstrated significantly higher excellence rates in basic experimental technique assessments (90% vs. 50%), literature review scores [(92.1±3.2) vs. (80.5±4.8)], and scientific research competence scale scores [(89.5±4.1) vs. (75.8±5.6)] compared to the control group (all P<0.05).

Project-based learning can effectively improve nephrology postgraduate students′ mastery of basic experimental techniques, deepen their understanding of professional literature, and significantly promote their establishment of scientific thinking.

To evaluate the effectiveness of the "student-led case presentation" teaching mode for nephrology residents in standardized training.

Resident physicians undergoing standardized training in the Department of Nephrology, First Medical Center of Chinese PLA General Hospital from November 2024 to December 2024 were enrolled as study subjects and randomly divided into an observation group and a control group. The control group received traditional teaching, while the observation group was taught with the "student-led case presentation" mode. After the same duration of training, both groups were assessed. The two groups were compared to evaluate the effectiveness of the two teaching methods, and the participants′ satisfaction with the training course was analyzed.

A total of 36 resident physicians were enrolled with 18 in each group. The observation group achieved significantly higher theoretical and practical examination scores than the control group (92.4±3.1 vs. 83.6±4.2, 91.8±2.5 vs. 82.9±3.8, respectively; all P<0.001). The observation group also showed greater satisfaction than the control group in overall course satisfaction (94.4%), teaching format (88.9%), understanding of theoretical knowledge (88.9%), and cultivation of clinical thinking (83.3%) (all P<0.05).

The application of the "student-led case presentation" teaching mode for nephrology residents in standardized training can effectively improve the participants′ theoretical and practical examination scores as well as their satisfaction.