Objectives The current work aimed to provide a comprehensive single-cell landscape of lupus nephritis (LN) kidneys, including immune and non-immune cells, identify disease-associated cell populations and unravel their participation within the kidney microenvironment. Methods Single-cell RNA and T cell receptor sequencing were performed on renal biopsy tissues from 40 patients with LN and 6 healthy donors as controls. Matched peripheral blood samples from seven LN patients were also sequenced. Multiplex immunohistochemical analysis was performed on an independent cohort of 60 patients and validated using flow cytometric characterisation of human kidney tissues and in vitro assays. Results We uncovered a notable enrichment of CD163⁺ dendritic cells (DC3s) in LN kidneys, which exhibited a positive correlation with the severity of LN. In contrast to their counterparts in blood, DC3s in LN kidney displayed activated and highly proinflammatory phenotype. DC3s showed strong interactions with CD4⁺ T cells, contributing to intrarenal T cell clonal expansion, activation of CD4⁺ effector T cell and polarisation towards Th1/Th17. Injured proximal tubular epithelial cells (iPTECs) may orchestrate DC3 activation, adhesion and recruitment within the LN kidneys. In cultures, blood DC3s treated with iPTECs acquired distinct capabilities to polarise Th1/Th17 cells. Remarkably, the enumeration of kidney DC3s might be a potential biomarker for induction treatment response in LN patients. Conclusion The intricate interplay involving DC3s, T cells and tubular epithelial cells within kidneys may substantially contribute to LN pathogenesis. The enumeration of renal DC3 holds potential as a valuable stratification feature for guiding LN patient treatment decisions in clinical practice.

Objective: The aim of this study was to evaluate the impact of peer role-playing on the clinical skills performance of pediatric trainees.Methods: Seventy-eight clinical medicine trainees were randomly divided into a role-playing group and a traditional teaching group, with 39 students in each group. The role-playing group alternated between the roles of clinicians and patients, while the traditional teaching group received the bedside teaching mode of verbal instruction. After two weeks traineeship, mini-Clinical Evaluation Exercise(Mini-CEX) was used to evaluate the trainees’ competence in physician-patient communication and clinical practice. A questionnaire was given to the role-playing group to assess their satisfaction with the method.Results: The Mini-CEX scores showed that the role-playing group had superior clinical skills (p < 0.05), including communication, history taking, professionalism, organization, clinical skills, and physical examination, compared to the traditional teaching group. Furthermore, trainee satisfaction was high with the role-playing method,and the satisfaction were more than 95%.Conclusion: The role-playing method effectively improved the clinical skills of pediatric trainees, developed clinical communication skills, and enhanced the application of medical knowledge in a simulated medical environment.

Background: Pathogenic variants of PAX2 cause autosomal-dominant PAX2-related disorder, which includes variable phenotypes ranging from renal coloboma syndrome (RCS), congenital anomalies of the kidney and urinary tract (CAKUT) to nephrosis. Phenotypic variability makes it difficult to define the phenotypic spectrum associated with genotype. Methods: We collected the phenotypes in patients enrolled in the China national multicenter registry who were diagnosed with pathogenic variant in PAX2 and reviewed all published cases with PAX2-related disorders. We conducted a phenotype-based cluster analysis by variant types and molecular modeling of the structural impact of missense variants. Results: Twenty different PAX2 pathogenic variants were identified in 32 individuals (27 families) with a diagnosis of RCS (9), CAKUT (11) and nephrosis (12) from the Chinese cohort. Individuals with abnormal kidney structure (RCS or CAKUT group) tended to have likely/presumed gene disruptive (LGD) variants (Fisher test, p < 0.05). A system review of 234 reported cases to date indicated a clear association of RCS to heterozygous loss-of-function PAX2 variants (LGD variants). Furthermore, we identified a subset of PAX2 missense variants in DNA-binding domain predicted to affect the protein structure or protein-DNA interaction associated with the phenotype of RCS. Conclusion: Defining the phenotypic spectrum combined with genotype in PAX2-related disorder allows us to predict the pathogenic variants associated with renal and ophthalmological development. It highlighted the approach of structure-based analysis can be applied to diagnostic strategy aiding precise and timely diagnosis.

Cold chain logistics, with its high carbon emissions and energy consumption, contradicts the current advocacy for a “low-carbon economy”. Additionally, in the real delivery process, customers often generate dynamic demand, which has the characteristic of being sudden. Therefore, to help cold chain distribution companies achieve energy-saving and emission-reduction goals while also being able to respond quickly to customer needs, this article starts from a low-carbon perspective and constructs a two-stage vehicle distribution route optimization model that minimizes transportation costs and refrigeration costs, alongside carbon emissions costs. This research serves to minimize the above-mentioned costs while also ensuring a quick response to customer demands and achieving the goals of energy conservation and emission reduction. During the static stage, in order to determine the vehicle distribution scheme, an enhanced genetic algorithm is adopted. During the dynamic optimization stage, a strategy of updating key time points is employed to address the dynamic demand from customers. By comparing the dynamic optimization strategy with the strategy of dispatching additional vehicles, it is demonstrated that the presented model is capable of achieving an overall cost reduction of approximately 17.13%. Notably, carbon emission costs can be reduced by around 17.11%. This demonstrates that the dynamic optimization strategy effectively reduces the usage of distribution vehicles and lowers distribution costs.

Renal interstitial fibrosis is an important mechanism in the progression of chronic kidney disease (CKD) to end-stage kidney disease. However, we lack specific treatments to slow or halt renal fibrosis. Ribosome profiling identified upregulation of a secreted micropeptide, C4orf48 (Cf48), in mouse diabetic nephropathy. Cf48 RNA and protein levels were upregulated in tubular epithelial cells in human and experimental CKD. Serum Cf48 levels were increased in human CKD and correlated with loss of kidney function, increasing CKD stage, and the degree of active interstitial fibrosis. Cf48 overexpression in mice accelerated renal fibrosis, while Cf48 gene deletion or knockdown by antisense oligonucleotides significantly reduced renal fibrosis in CKD models. In vitro, recombinant Cf48 (rCf48) enhanced TGF-β1–induced fibrotic responses in renal fibroblasts and epithelial cells independently of Smad3 phosphorylation. Cellular uptake of Cf48 and its profibrotic response in fibroblasts operated via the transferrin receptor. RNA immunoprecipitation–sequencing identified Cf48 binding to mRNA of genes involved in the fibrotic response, including Serpine1 , Acta2 , Ccn2 , and Col4a1 . rCf48 binds to the 3′UTR of Serpine1 and increases mRNA half-life. We identify the secreted Cf48 micropeptide as a potential enhancer of renal fibrosis that operates as an RNA-binding peptide to promote the production of extracellular matrix.