Preservation of residual kidney function (RKF) is critical for patients undergoing peritoneal dialysis (PD). However, the relationship between the rate of RKF decline (RKF slope) and PD technique failure remains incompletely understood, and a clinically actionable threshold is lacking. This was a single-centre, retrospective cohort study that included 539 patients who underwent peritoneal dialysis catheter placement at the hospital from 1 May 2006 to 31 December 2022. The primary analysis used pre‑specified Cox models to assess the association between RKF decline rate and technique failure (death or transfer to HD). RCS analysis and Kaplan‑Meier curves were also performed. During a median follow‑up of 30 months, 152 patients (28.2

Loss of immune homeostasis in Type 1 diabetes (T1D) leads to a dysregulated and autoreactive immune response that destroys pancreatic β cells, causing absolute insulin deficiency. Nevertheless, current strategies for restoring immune homeostasis remain limited. Inspired by our earlier research, we leveraged the single-cell RNA sequencing data from T1D patients, and unexpectedly found that STAT1 overrepresentation is much more prominent in dendritic cells (DCs) rather in CD4 T cells. Subsequently, we repurposed the clinically-applied STAT1 inhibitor fludarabine in T1D setting. To resolve the underlying mechanism, we employed a multipronged approach in animal studies, incorporating FACS, RNA-seq, ChIP-qPCR, Co-IP/MS, CESTA, TEM, Seahorse assay and Conditional gene knockout model. Furthermore, we investigated the significance of our data in human autoimmune diabetes. Other than directly targeting CD4+ effector T cells, fludarabine also elevated regulatory T cell (Treg) frequency, and therefore, its administration markedly alleviated T1D pathogenesis. Interestingly, fludarabine did not show a direct effect on Treg cells but indirectly fosters Treg program via inducing tolerogenic DCs (tolDCs). The fludarabine-reprogrammed tolDCs are featured by the metabolic shift towards mitochondrial oxidative respiration and exert protective effects on the adoptive transfer studies. Since the emergence of tolDCs could not be fully explained by STAT1 itself, we further explored whether fludarabine alters the STAT1 interactome. Notably, fludarabine binds to STAT1 and disrupts its interaction with the aryl hydrocarbon receptor (AhR), thereby facilitating AhR nuclear translocation. Activated AhR transcriptionally upregulated the expression of anti-inflammatory, anti-ferroptotic, and mitochondrial respiration genes to uphold the tolerogenic DC phenotype. Our findings identified that fludarabine could be a promising immunometabolic therapeutic candidate to restore immune tolerance, which may be a viable approach against T1D in clinical settings.

Background: Hypoxia is a key driver of cancer progression. However, its specific prognostic significance in gastric cancer (GC) remains insufficiently characterized. Methods: Single-sample gene set enrichment analysis (ssGSEA), weighted gene co-expression network analysis (WGCNA), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression were employed to identify a hypoxia-related prognostic signature. Subsequently, immune microenvironment profiling and single-cell RNA sequencing analyses were employed to further characterize the biological characteristics of the signature. In addition, quantitative real-time polymerase chain reaction (qPCR) was used to validate the expression levels of key hypoxia-associated genes in human GC tissues. Results: Elevated hypoxia levels were linked to worse survival outcomes in GC patients. Through integrated WGCNA, Cox, and LASSO analyses, a hypoxia-related prognostic signature (HYS) consisting of four genes-SPARC, AXL, NRP1, and VCAN-was established. Patients in the HYS-high group exhibited markedly poorer overall survival than their HYS-low counterparts [p = 0.000126, hazard ratio (HR) = 1.936]. Moreover, the HYS-high group exhibited increased infiltration of resting CD4(+) memory T cells, monocytes, M2 macrophages, and resting mast cells, as well as elevated expression of immunosuppressive molecules, including PDCD1LG2 and HAVCR2. Single-cell RNA sequencing analysis revealed that the signature genes were predominantly expressed in cancer-associated fibroblasts. Consistently, qPCR analysis in five paired GC and para-carcinoma tissues confirmed higher expression of these genes in tumor samples (p < 0.01). Conclusions: Our findings indicate that hypoxia is a critical determinant of prognosis in GC and is closely associated with an immunosuppressive tumor microenvironment, highlighting its potential value as a prognostic biomarker and therapeutic target.

Trauma surgical intensive care unit (TSICU) patients frequently present with metabolic dysregulation. However, the combined prognostic value of the triglyceride-glucose–body mass index (TyG-BMI) and the stress hyperglycemia ratio (SHR) remains unclear. A retrospective cohort study was conducted using the MIMIC-IV database, with external validation in a TSICU cohort from Tongji Hospital. Adult patients admitted to the TSICU were classified into four groups based on joint TyG-BMI and SHR categories. The endpoints were 28-day and 180-day all-cause mortality. Cox regression, restricted cubic splines, Kaplan–Meier survival curves, and 33 machine learning models were employed to evaluate associations and predictive performance. A total of 872 patients were included in the training cohort and 525 in the validation cohort. Overall, 19.0

This study systematically analyzed 1,197 articles on the role of macrophages in systemic lupus erythematosus (SLE) published from 2016 to 2025 using bibliometric methods based on the Web of Science Core Collection. The analysis examined publication trends, collaborative networks, research themes, and the knowledge base to elucidate the current research landscape, core research forces, and frontier evolution in this field. The number of publications peaked at 154 in 2022, while annual citations increased overall from 184 in 2016 to 9,030 in 2025, indicating active and impactful research. China ranked first in publication volume (379 articles), whereas the United States led in total citations (18,838) and international collaboration centrality. Shanghai Jiao Tong University and Karolinska Institutet were the most productive institutions, with 23 articles each. Frontiers in Immunology (impact factor = 5.9; Journal Citation Reports quartile 1) was the most productive journal. Keyword timeline clustering identified 13 major research themes, including key components of innate immunity such as neutrophil extracellular traps, dendritic cells, and Toll-like receptors, as well as adaptive immunity involving T cells, B cells, and plasmacytoid dendritic cells. These themes also included core mechanisms such as macrophage polarization, the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, and apoptotic cell clearance, along with clinical hotspots such as lupus nephritis, macrophage activation syndrome, and rheumatoid arthritis. The evolution of research hotspots reflects a progression from early basic mechanisms of apoptotic cell and immune complex clearance to refined regulation of cytokines, innate immunity, and adaptive immunity, and finally to studies of signaling pathway-targeted therapy, clinical management, and multicenter validation, with "pathway" and "multicenter diagnosis" standing out as current research frontiers.

Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, involves immune complex deposition, inflammation, and kidney damage. Recent studies indicate that pyroptosis, a pro-inflammatory cell death process, drives renal injury in LN. This study intended to identify key pyroptosis-related genes in LN using datasets from the GEO database, encompassing glomerular, tubulointerstitial, and whole kidney tissues from LN patients. Identified differentially expressed genes related to pyroptosis and created a predictive model using univariate and LASSO regression analysis. LN patients were classified into subtypes through consensus clustering. Immune microenvironment characteristics and hallmark pathways were further analyzed. Using the WGCNA, key gene modules and hub genes were recognized, followed by an analysis of their clinical relevance and distribution patterns using the Nephroseq database and scRNA-seq data. Cellular experiments were conducted to validate the findings. We identified 26 differentially expressed pyroptosis-related genes in LN glomeruli and created a 10-gene model with high diagnostic accuracy (AUC: 0.968 for tubulointerstitium, 0.990 for whole kidney). Consensus clustering divided LN into two subtypes: subtype1, characterized by inflammation and immune activation, and subtype2, characterized by cellular metabolism. WGCNA highlighted the grey60 module linked to subtype1, and identified GBP2 and EIF2AK2 as hub genes. Cellular experiments showed that GBP2 and EIF2AK2 were upregulated in LPS-stimulated macrophages and glomerular endothelial cells, and their siRNA-mediated knockdown triggered a decline in pyroptosis-related marker expression, implying their possible role as therapeutic targets for modulating pyroptosis in LN. In conclusion, GBP2 and EIF2AK2 show potential as candidate molecules for targeted therapy in LN.

Gastrointestinal motility disorders (GIMDs) are prevalent conditions with heterogeneous symptoms and limited long term therapeutic efficacy. Increasing evidence indicates that gut dysbiosis contributes to the development and persistence of these disorders by impairing mucosal barrier function, inducing low-grade inflammation, and disrupting signaling within the enteric nervous system and the gut brain axis. Consequently, microbiota targeted interventions including probiotics, prebiotics, synbiotics, and postbiotics have attracted growing interest. This review summarizes recent advances across these four microecological strategies and integrates mechanistic insights relevant to multiple motility phenotypes. Probiotics regulate gastrointestinal motility through strain specific mechanisms involving reshaping of microbial communities and metabolic outputs, reinforcement of barrier integrity, modulation of immune inflammatory responses, and regulation of enteric neural and neuroendocrine pathways. Prebiotics selectively promote beneficial bacteria such as Bifidobacterium and Lactobacillus and increase the production of short chain fatty acids, thereby optimizing the intestinal microenvironment to support motility recovery. Synbiotics combine microbial strains with fermentable substrates to accelerate ecological restoration and often provide broader benefits on intestinal transit, barrier function, and neuroimmune regulation. Postbiotics enable targeted interventions independent of live colonization by directly influencing metabolism, barrier homeostasis, immune signaling, and smooth muscle function. Despite promising evidence, clinical translation is challenged by patient heterogeneity, variable study design, and limited comparative trials. Future research should emphasize mechanism driven precision strategies supported by multi omics stratification and rigorously designed multicenter randomized studies.

BACKGROUND & AIMS:Malnutrition is a significant health issue in hospital settings, with persistent diagnostic challenges. Despite the Global Leadership Initiative on Malnutrition (GLIM) criteria providing a standardised approach, nationwide validation and implementation remain limited. We aimed to estimate the national prevalence of GLIM-defined malnutrition among Chinese adult inpatients and assess the predictive value of the GLIM criteria for short-term clinical outcomes. METHODS:We conducted the China Nutrition Fundamental Data 2022 project among adult inpatients from 322 sites across 31 provinces in China between February and October 2023. Malnutrition was defined using the GLIM criteria through a standardised two-step process. The clinical outcomes included discharge outcomes, length of stay, hospitalisation costs, and 30-day mortality. We used logistic and multiple linear regression analyses to examine the association between malnutrition severity and clinical outcomes. RESULTS:The final analysis included 61,283 individuals. Malnutrition was prevalent in 24.6 % of the inpatients (moderate malnutrition: 13.8 %; severe malnutrition: 10.8 %). A dose-response relationship was observed between malnutrition severity and adverse clinical outcomes: moderate and severe malnutrition increased the risk of ineffective discharge outcomes by 1.533 (95 % CI: 1.362-1.725) and 2.200 (1.958-2.473) times, respectively, and 30-day mortality by 1.875 times (1.408-2.496) and 3.065 (2.332-4.028) times, respectively. Additionally, moderate and severe malnutrition were linked to a 0.97-day and 1.20-day increases in hospital stays, respectively. CONCLUSIONS:Malnutrition is prevalent among adult Chinese inpatients and strongly associated with adverse clinical outcomes. GLIM-based assessments and interventions are essential to reduce the burden of malnutrition.

Malnutrition substantially contributes to adverse clinical outcomes. However, no national survey has been conducted to characterize its epidemiology in hospital settings in China. We conducted the China Nutrition Fundamental Data 2020 project among a multistage stratified cluster sample of adult inpatients from 291 study sites across 30 provinces, autonomous regions and municipalities (except for Hong Kong, Macao, Taiwan Province, and the Xizang Autonomous Region, please see MATERIALS AND METHODS for details of the causes) of China to generate reliable data on the prevalence of malnutrition and explore the associated risk factors. We collected information on participants’ sociodemographic characteristics, physical examinations, and laboratory test results. Malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. The standardized prevalence of malnutrition was calculated, and factors associated with malnutrition were examined using logistic regression analyses. We included 54,652 individuals with seven systemic diseases who completed all the survey documents in the final analysis. The overall prevalence of malnutrition was 12.5

Acute kidney injury (AKI) is a prevalent and critical clinical condition characterized by high morbidity and mortality. Recently, numerous studies have implicated ferroptosis, an iron-dependent programmed cell death process, in the pathophysiology of AKI. Despite this, the mechanism underlying the widespread occurrence of ferroptosis in AKI remains elusive. To address this, our study analyzed snRNA-seq data from AKI and healthy renal tissues. The analysis revealed notable differences in ferroptosis activity within proximal tubule (PT) cells of AKI patients, specifically highlighting a strong correlation between ferroptosis and the expression of genes GPX4, FTH1, and FTL. Spatial transcriptomics confirmed that the genes GPX4, FTH1, and FTL play a crucial role in driving ferroptosis propagation in AKI. Furthermore, utilizing a mouse model of bilateral renal ischemia-reperfusion injury, we validated the emergence of ferroptosis mediated by these key genes following AKI. The findings from our in vivo experiments were consistent with the spatial transcriptomics data. Chromatin accessibility and transcription factor analysis identified KLF6 as a repressor of ferroptosis-related genes. An in-depth analysis of PT revealed a subpopulation closely associated with ferroptosis. The cellular microenvironment within this subpopulation may regulate ferroptosis through the SPP1 signaling pathway, ultimately influencing the outcome of PT following AKI. In conclusion, this study elucidates the crucial role of GPX4, FTH1, and FTL in ferroptosis propagation during AKI and underscores the potential therapeutic benefits of targeting ferroptosis in the management of AKI.

This study aims to explore the varying association of different bilirubin levels on the prognosis of peritoneal dialysis patients, with particular emphasis on the relationship between the initial occurrence of peritonitis and bilirubin levels, which has not been well elucidated in existing literature. This single-center retrospective study enrolled end-stage renal disease patients who underwent peritoneal dialysis catheter placement at Tongji Hospital from January 1, 2009, to December 31, 2023. Follow-up was conducted until October 31, 2024. To explore the relationship between the development of peritonitis and bilirubin levels, we utilized Cox proportional hazards regression models, Spearman correlation analysis, and restricted cubic spline plots. This study included 426 patients, with the sum of 106 episodes of peritonitis were documented, of which 57 were first-time occurrences, making for an incidence rate of 0.09 episodes per patient-year. Patients with total bilirubin (TBil) levels below 3.69 µmol/L (P = 0.008, HR = 1.919, 95

A low-protein diet is essential for the nutritional management of chronic kidney diseases as it can reduce renal burden. However, the effect of low-protein diets on dialysis patients compared to pre-dialysis patients remains unclear. This study aims to compare residual renal function among dialysis patients following a low-protein diet versus a normal diet, offering valuable insights into the optimal nutritional strategy for preserving residual renal function. This meta-analysis has been registered on PROSPERO, an international registry of prospective systematic reviews. We conducted a comprehensive and systematic literature search using PubMed, Cochrane Library and Web of Science (WOS). Our search strategy was designed to discover all relevant studies investigating the influence of low-protein diets on residual renal function among dialysis patients. Four studies met the inclusion criteria. Heterogeneity was discussed through subgroup analysis of dialysis method, the addition of ketoacid and other relevant factors. We included four prospective studies of low-protein diets among dialysis patients, each of which included at least 40 participants. Individuals receiving a 12-months low-protein diet had a higher GFR (MD = 1.37 ml/min; 95

OBJECTIVES:Dietary supplements have gained attention among people with diabetes as an alternative and complementary treatment, yet there is a limited understanding of supplement use and the motivations behind it. METHODS:Data from the National Health and Nutrition Examination Survey (NHANES) from the 2009-2020 period were analyzed, including data on 5784 people with diabetes aged 20 years or older. Dietary supplement use was self-reported. Trends in supplement use were examined across three periods: 2009-2012, 2013-2016, and 2017-2020. Statistical analyses were conducted while considering NHANES's complex survey design to provide nationally representative estimates for the general noninstitutionalized population of the United States. RESULTS:A total of 61.72% of individuals reported using dietary supplements with a notable increase over time. Supplement users were generally older, more likely to be female, better educated, and had superior blood glucose control with lower smoking rates compared to non-users. Common supplements included multivitamins, multimineral supplements, vitamin D, calcium, zinc, vitamin C, and fish oil. Only 44.58% of individuals used dietary supplements based on medical advice, with the rest opting for self-directed usage. The primary specific health reasons for supplement use were to improve bone health and heart health and enhance the immune system. CONCLUSIONS:Dietary supplement use is prevalent among people with diabetes, and most diabetic supplement use is self-directed, which reflects a growing trend toward complementary therapies. Healthcare providers are encouraged to inquire about patients' use of supplements and offer appropriate guidance as an integral component of comprehensive diabetes management.

AimThis study aimed to establish a prediction model in peritoneal dialysis patients to estimate the risk of technique failure and guide clinical practice.MethodsClinical and laboratory data of 424 adult peritoneal dialysis patients were retrospectively collected. The risk prediction models were built using univariate Cox regression, best subsets approach and LASSO Cox regression. Final nomogram was constructed based on the best model selected by the area under the curve.ResultsAfter comparing three models, the nomogram was built using the LASSO Cox regression model. This model included variables consisting of hypertension and peritonitis, serum creatinine, low-density lipoprotein, fibrinogen and thrombin time, and low red blood cell count, serum albumin, triglyceride and prothrombin activity. The predictive model constructed performed well using receiver operating characteristic curve and area under the curve value, C-index and calibration curve.ConclusionThis study developed and verified a new prediction instrument for the risk of technique failure among peritoneal dialysis patients. imageConclusionThis study developed and verified a new prediction instrument for the risk of technique failure among peritoneal dialysis patients. image Technique failure is a significant obstacle for peritoneal dialysis (PD), which may be the main reason for relatively poor PD retention rates worldwide. This study aimed to establish a prediction model in PD patients to estimate the risk of technique failure and guide clinical practice. image

OBJECTIVE:This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia. METHODS:A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with polysaccharide-iron complex, and those in the experimental group were administered Jianpi Shengxue tablet. After 8 weeks of continuous treatment, the therapeutic outcomes regarding anemia were compared between the two groups. RESULTS:After treatment, the red blood cell (RBC) count, hematocrit (HCT), reticulocyte percentage (RET), ferritin (SF), serum iron (SI), transferrin saturation (TSAT), and serum albumin (ALB) all increased (P<0.01), and the clinical symptom score and total iron binding capacity decreased (P<0.01) in the experimental group. Moreover, the improvements in RBC, HCT, RET, SF, SI, TAST, ALB, and clinical symptoms (fatigue, anorexia, dull skin complexion, numbness of hands and feet) in the experimental group were significantly greater than those in the control group (P<0.05). The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group (P<0.01). CONCLUSION:The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia, leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

AbstractNeuropilin-1 (NRP1), a co-receptor for various cytokines, including TGF-β, has been identified as a potential therapeutic target for fibrosis. However, its role and mechanism in renal fibrosis remains elusive. Here, we show that NRP1 is upregulated in distal tubular (DT) cells of patients with transplant renal insufficiency and mice with renal ischemia-reperfusion (I-R) injury. Knockout of Nrp1 reduces multiple endpoints of renal injury and fibrosis. We find that Nrp1 facilitates the binding of TNF-α to its receptor in DT cells after renal injury. This signaling results in a downregulation of lysine crotonylation of the metabolic enzyme Cox4i1, decreases cellular energetics and exacerbation of renal injury. Furthermore, by single-cell RNA-sequencing we find that Nrp1-positive DT cells secrete collagen and communicate with myofibroblasts, exacerbating acute kidney injury (AKI)-induced renal fibrosis by activating Smad3. Dual genetic deletion of Nrp1 and Tgfbr1 in DT cells better improves renal injury and fibrosis than either single knockout. Together, these results reveal that targeting of NRP1 represents a promising strategy for the treatment of AKI and subsequent chronic kidney disease.

Background: Obstructive nephropathy (ON), resulting from hindered urine flow, significantly contributes to both acute kidney injury (AKI) and chronic kidney disease (CKD). Research has consistently highlighted increased lymphatic vessels (LVs) density in diverse kidney diseases. However, the precise involvement of LVs in ON remains unclear. Methods: Patients diagnosed with ON were enrolled in this study from January 2020 to December 2023. LVs and histological pathology in renal biopsy tissues were detected through immunohistochemistry and Periodic Acid-Schiff staining. Patients were categorized into two cohorts based on their estimated glomerular filtration rate (eGFR) levels: one cohort included patients with eGFR < 90, while the other encompassed those with eGFR ≥ 90. Univariate and multivariable logistic regression analyses were conducted to determine the odds ratio (OR) and 95% confidence interval (CI) for the association between the two cohorts. Results: 239 patients were enrolled in the study. The density of LVs was elevated in ON, with even higher densities observed in patients with severe renal impairment. Additionally, several risk factors contributing to the deterioration of renal function in ON patients have been identified, including age, ureteral calculi (UC), alanine aminotransferase (ALT), and uric acid (UA). Furthermore, by leveraging LVs density, multiple robust models have been established to predict severe renal impairment in ON. Conclusions: Lymphatic vessels density is significantly elevated in ON, serving as an independent risk factor for the decline in renal function.