Diabetic kidney disease (DKD) is among the most common and severe complications of diabetes mellitus, with current treatments providing limited efficacy. Yi-Shen-Qu-Yu prescription (YSQYP), a traditional Chinese herbal formula, has demonstrated clinical efficacy in the treatment of DKD; however, its bioactive constituents and underlying mechanisms remain poorly defined. This study proposes a structure-based and deep learning-guided screening strategy to identify active compounds within YSQYP that target the vitamin D receptor (VDR). An integrated screening strategy was established, combining virtual screening using conventional docking methods and deep learning tools (CarsiDock and RTMScore), as well as biophysical validation through surface plasmon resonance (SPR). Subsequently, the protective effects of candidate compounds against high-glucose-induced podocyte injury were further validated using biological assays. Among the screened constituents, isorhamnetin, hederagenin, and (+)-catechin exhibited the strongest binding affinities for VDR. Functional assays confirmed their capacity to mitigate high-glucose-induced cytotoxicity and apoptosis in podocytes, with isorhamnetin showing the most potent protective effect. Collectively, this study establishes an efficient strategy for natural product screening and identifies promising VDR-targeting compounds from YSQYP, providing novel therapeutic candidates for the treatment of DKD.

Objective Renal fibrosis plays a pivotal role in the progression of renal dysfunction in diabetic kidney disease (DKD), with the macrophage-to-myofibroblast transition (MMT) serving as a central mechanism driving the advancement of renal fibrosis to end-stage renal disease (ESRD) in various chronic kidney conditions. Although the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (DAPA) slows renal function decline in DKD, its antifibrotic mechanisms remain unclear. This study aimed to elucidate whether DAPA ameliorates renal fibrosis by suppressing MMT, and the underlying molecular mechanisms. Methods We established a DKD model in male C57BL/6J mice by inducing them with a high-fat diet (HFD) followed by streptozotocin (STZ) injection. The effects of DAPA on renal function parameters (serum creatinine (Scr), urinary albumin-to-creatinine ratio (UACR)), and renal pathological injury, fibrosis markers (α-smooth muscle actin (α-SMA), type I collagen (Col-I)) were comprehensively evaluated. Immunofluorescence (IF) and Western blot were employed to analyze MMT progression (F4/80+/α-SMA+ double-positive cells) and TGF-β1-Smad3/7 pathway activity. Results DAPA significantly reduced blood glucose levels, mitigated weight loss, and effectively inhibited type 2 diabetes-induced increase in Scr (43.78 ± 3.84 vs. 33.93 ± 6.77 µmol/L, P < 0.05) and UACR (89.17 ± 16.33 vs. 52.51 ± 10.51 mg/g, P < 0.05) in DKD mice. DAPA significantly attenuated glomerular hypertrophy, mesangial hyperplasia, and vacuolar degeneration of the tubular epithelium in DKD mice, while concurrently reducing glomerular and tubular injury scores, as well as the renal interstitial fibrosis area (P < 0.05). IF revealed increased MMT within the renal tubulointerstitium in DKD mice, accompanied by elevated deposition of α-SMA and Col-I. DAPA treatment markedly reduced F4/80+ macrophage infiltration and F4/80+/α-SMA+ and F4/80+/Col-I+ double-positive MMT cells, with decreased α-SMA and Col-I expression (P < 0.05). Additionally, TGF-β1 and phosphorylated Smad3 (p-Smad3) expression were significantly upregulated in DKD mice, whereas Smad7 was downregulated (P < 0.05). DAPA treatment significantly reduced TGF-β1 and p-Smad3 levels and restored Smad7 expression, rebalancing the Smad3/Smad7 axis (P < 0.05). Therefore, we propose that DAPA likely alleviates renal fibrosis in DKD by modulating renal TGF-β1 activity and restoring the Smad3/Smad7 balance, thereby suppressing MMT. Conclusion This study is the first to reveal that DAPA is highly likely to exert anti-fibrotic effects through a novel mechanism involving targeted modulation of the TGF-β1-Smad3/7 axis to inhibit MMT, thereby laying a theoretical foundation and identifying a potential therapeutic target for precision treatment of DKD.

Background:There has been an annual rise in the incidence of primary membranous nephropathy (PMN), a common pathological type of nephrotic syndrome (NS). Obinutuzumab is a humanised, glycosylated, type II anti-CD20 monoclonal antibody. Characterised by its enhanced B-cell depletion capability compared with rituximab (RTX), obinutuzumab has demonstrated promising efficacy in the treatment of membranous nephropathy. Objective:This study aimed to investigate the efficacy and safety of obinutuzumab in treating various subtypes of PMN. Methods:A total of 94 PMN patients with NS were enrolled in this study. Based on their treatment history before receiving obinutuzumab, the patients were categorised into the Initial therapy group (group A, n=32), the Refractory group (group B, n=32), and the Remedial therapy group (group C, n=30). The efficacy and safety of obinutuzumab treatment after a 24-month follow-up period were observed and analysed in each group. The primary endpoint was the clinical remission rate (complete remission + partial remission) at 24 months, and the secondary endpoints were treatment safety and the incidence of treatment-emergent adverse events. Results:Following 24 months of obinutuzumab therapy, 95.74% (90/94) of the PMN patients achieved clinical remission, with 28.72% (27/94) reaching complete remission (CR) and 67.02% (63/94) achieving partial remission (PR). The Initial therapy group (group A) achieved a 100% (32/32) clinical remission rate: 37.5% (12/32) attained CR, and 62.5% (20/32) attained PR. The Refractory group (group B) achieved a 96.88% (31/32) clinical remission rate: 25% (8/32) attained CR, and 71.88% (23/32) attained PR. The Remedial therapy group (group C) achieved a 90% (27/30) clinical remission rate: 23.33% (7/30) attained CR, and 66.67% (20/30) attained PR. All 63 anti-PLA2R antibody-positive (>20 U/mL) patients and 16 anti-PLA2R antibody negativity but no immunological remission (2-20 U/mL) patients demonstrated declining antibody levels following obinutuzumab therapy, and 68.4% (54/79) attained complete immunological remission (<2 U/mL). Conclusion:Obinutuzumab demonstrates high clinical remission rates and acceptable safety in PMN patients, with good efficacy even in refractory and RTX-resistant patients.

Background:Under the Cardiovascular-Kidney-Metabolic (CKM) syndrome framework, insulin resistance (IR) is the core driver of renal damage. The triglyceride-glucose (TyG) index is a validated IR surrogate, but existing evidence is mostly limited to cross-sectional data or single-source databases, failing to clarify the longitudinal progression of renal injury and underlying mechanisms. Methods:This study integrated two independent prospective cohorts: the national community-based CHARLS cohort (4,476 middle-aged and elderly participants, 2011-2015 follow-up) and a hospital-based KDIGO 2012-defined CKD cohort (396 patients, median 1,019-day follow-up). We analyzed the association of TyG index with eGFR decline (CHARLS) and ESRD (CJFH), with pulse pressure as mediator, hypertension as moderator, via regression, mediation, survival and nonlinear analyses. Results:Elevated baseline TyG index was independently associated with renal function deterioration in both cohorts. Pulse pressure played a partial mediating role in this association, while baseline hypertension significantly amplified the adverse renal effect of TyG. The overall association was dominated by a negative linear trend with no significant risk threshold. Conclusion:TyG index is an independent risk factor for renal function deterioration, with its adverse effects partially mediated by elevated pulse pressure and amplified by hypertension. This study provides epidemiological evidence for the CKM "metabolism-vascular-renal" axis, supporting TyG-based early renal risk stratification in the general population and multi-dimensional interventions for CKD patients.

Objective To identify latent subtypes of compassion fatigue among hemodialysis nurses and examine the differential associations of core competencies and work engagement with compassion satisfaction, burnout, and secondary traumatic stress across these subtypes. Methods A convenience sample of 3128 hemodialysis nurses from six provinces and municipalities in China was surveyed between January and March 2026 using a general information questionnaire, the Professional Quality of Life Scale (ProQOL-5), the Nurse Core Competency Scale, and the Work Engagement Scale. Latent profile analysis was used to identify compassion fatigue subtypes. Subtype-specific linear regression analyses were conducted to examine the associations of core competencies and work engagement with each dimension of compassion fatigue after controlling for demographic variables. Multinomial logistic regression was performed to evaluate the interaction between core competencies and work engagement in relation to subtype membership. Results Six subtypes were identified: low fatigue (10.10%), moderate-to-high fatigue (7.99%), moderate risk/high secondary traumatic stress (13.33%), high secondary traumatic stress/low compassion satisfaction (29.38%), high fatigue/high compassion satisfaction (paradoxical; 31.46%), and globally high-risk (7.74%). The associations of core competencies and work engagement with compassion fatigue differed across subtypes. No significant associations were observed in the low-fatigue subtype. Among the moderate-to-high fatigue and high secondary traumatic stress/low compassion satisfaction subtypes, higher work engagement was positively associated with burnout and secondary traumatic stress. In the moderate risk/high secondary traumatic stress subtype, work engagement was negatively associated with burnout but positively associated with secondary traumatic stress. In the paradoxical and global high-risk groups, both core competencies and work engagement were positively associated with compassion satisfaction, burnout, and secondary traumatic stress. Multinomial logistic regression showed that higher work engagement was associated with greater odds of membership in the higher secondary traumatic stress/low compassion satisfaction subtype and lower odds of membership in the paradoxical type. No significant interaction was observed between core competencies and work engagement. Conclusion The associations of core competencies and work engagement with the dimensions of compassion fatigue varied substantially across latent subtypes, suggesting a potential double-edged role of work engagement among nurses with more severe compassion fatigue. These findings support the development of subtype-specific interventions to improve the professional quality of life of hemodialysis nurses.

Treatments for secondary and tertiary hyperparathyroidism (SHPT/THPT) remain significant challenges in patients with end-stage renal disease. Thermal ablation (TA) has emerged as a minimally invasive, safe, and effective alternative to surgical resection (SR). However, technical variations and a lack of standardization have limited its widespread adoption. To address these challenges, an international expert panel developed consensus recommendations using a modified Delphi method, integrated with a systematic literature review. As a result, sixteen recommendations were formulated, addressing diagnosis, preoperative preparation, technical procedures, postoperative management, follow-up strategies, efficacy assessment, and complications associated with TA for SHPT/THPT. These recommendations aim to promote standardized treatment protocols, improve procedural safety, and provide evidence-based guidance for clinical practice and future research in ultrasound-guided TA for SHPT/THPT management.

BACKGROUND & AIMS:CD8+ T cells play a crucial role in antiviral immunity; however, hepatitis B virus (HBV)-specific CD8+ T cells become dysfunctional during chronic HBV (CHB) infection. Blocking inhibitory pathways only partially restores efficient antiviral responses, suggesting that the mechanism underlying CD8+ T-cell dysfunction is complicated. This study aimed to investigate whether HBV-specific CD8+ T cells undergo ferroptosis, examine its correlation with T-cell dysfunction, and elucidate the underlying mechanism and potential intervention strategies. METHODS:Analysis of CD8+ T cells from patients with CHB revealed ferroptosis markers via flow cytometry, electron microscopy, and single-cell RNA sequencing, and HBV-specific CD8+ T cells were identified using HBV-core antigen peptide-loaded major histocompatibility complex I tetramer. Flow cytometry, single-cell RNA sequencing, and additional experimental approaches were employed to investigate the ferroptosis-associated mechanisms in CD8+ T-cell dysfunction. RESULTS:Ferroptosis was observed in CD8+ T cells from patients with CHB, as indicated with increased lipid peroxidation, Fe2+ accumulation and mitochondrial atrophy, particular in HBV-specific CD8+ T cells. Downregulation of glutathione peroxidase 4 and upregulation of CD36 were found in CD8+ T cells with high level of lipid peroxidation. Furthermore, ferroptosis is accompanied by impaired antiviral ability. Mechanistically, palmitic acid upregulates CD36 expression, leading to lipid accumulation, whereas elevated serum transforming growth factor beta 1 in patients with CHB reduces GPX4 expression and impairs antioxidant capacity. These factors synergistically promote ferroptosis and dysfunction of CD8+ T cells. Treatment with selenium and liproxstain-1 enhanced cytotoxic cytokines production by CD8+ T cells, and subsequently improved antiviral efficacy in vivo. CONCLUSIONS:Our study demonstrates that ferroptosis drives CD8+ T-cell dysfunction in chronic HBV infection. Targeting ferroptosis pathways may offer a novel therapeutic strategy to restore antiviral immunity.

Smoking is widely acknowledged for its harmful effects on multiple organs. However, its specific causal relationship with chronic kidney disease (CKD) remains uncertain. This study applied bivariate causal analysis and two-sample Mendelian randomization (MR) methods to examine the association between various smoking behaviors – initiation, cessation, age at initiation, cigarettes smoked per day, and lifetime smoking – and CKD, using genome-wide data. The inverse variance weighted (IVW) method was the primary analytical tool, supported by sensitivity analyses, pleiotropy assessments, and mediation analyses. External validation was conducted using independent datasets. The results revealed positive associations between CKD and smoking initiation (Pivw = 1.8 × 10−2, OR = 1.192), earlier age at initiation (Pivw = 2.3 × 10−3, OR = 1.481), cigarettes smoked per day (Pivw = 8.8 × 10−3, OR = 1.216), and lifetime smoking (Pivw = 2.3 × 10−7, OR = 2.445). In contrast, smoking cessation demonstrated a protective effect against CKD (Pivw = 4.0 × 10−12, OR = 0.791). External validation results aligned with the primary findings, and the absence of significant heterogeneity confirmed the robustness of the MR analysis. Additionally, the effect of smoking on CKD was mediated by factors such as body mass index, cardiovascular disease, hypertension, and type 2 diabetes. These findings identify smoking as a contributing factor to CKD and suggest that reducing smoking prevalence could significantly lower the incidence of CKD in the population.

Objectives In this study, we explored the mechanism by which DDIT4 influences the polarization phenotypic transformation of macrophages and inflammation through the regulation of mTOR signaling pathway, providing a new mechanism and target for the treatment of diabetic nephropathy.Methods The degree of inflammation and injury in renal tissues of diabetic kidney disease (DKD) animal model was evaluated using biochemical assays, renal pathology examinations, and Western blot tests. Podocytes and macrophages were isolated from renal tissues to observe the extent of podocyte injury and the quantity and polarization phenotype of macrophage infiltration. Subsequently, the activated M1 macrophage model was constructed and transfected with DDIT4 to evaluate the effect of DDIT4 on the polarization phenotype transformation of macrophages and the expression of inflammatory factors. Finally, the co-culture system of macrophages and podocytes was constructed to detect the cell apoptosis, and the morphology and subcellular structure of podocin were observed by transmission electron microscopy.Results In the DKD animal model, the expression levels of inflammatory factors in renal tissues were significantly higher than those in the control group. Additionally, there was significant damage to the renal podocytes. At the same time, there was a higher number of macrophage infiltrations, predominantly of the M1 polarized phenotype. In the constructed M1 polarized macrophage model, overexpression of DDIT4 can induce the decrease of M1 macrophages and reduce the expression level of inflammatory factors. In the co-culture system of macrophages and podocytes, overexpressed DDIT4 significantly reduced the proportion of podocyte apoptosis and protect the changes of morphology and subcellular structure.Conclusions The ability of DDIT4 to mediate the transformation of macrophage phenotype and reduce inflammation reveals its potential as an innovative drug discovery target for DKD. Further exploration and validation of the therapeutic potential of DDIT4 may provide effective interventions to address unaddressed clinical needs in the treatment of DKD.

Fabry disease is an inherited lysosomal storage disease that can be reversed, or the progression slowed, by enzyme replacement therapy in the early stage. However, whether patients receiving renal replacement therapy benefit from enzyme replacement therapy remains controversial, especially in regard to patients on hemodialysis, who additionally suffer from uremia and abnormal hemodynamics. Two male Han Chinese patients diagnosed with uremia prior to Fabry disease underwent renal transplantation and hemodialysis, respectively. At the ages of 27 and 32 years, they began receiving agalsidase-α, an enzyme replacement therapy drug, in February 2022, lasting for 1.5 years. Cardiac structural and functional parameters were obtained using the 6-minute walk test, along with serum biomarkers and electrocardiogram and ultrasound examinations. Changes in the cardiac parameters and the plasma globotriaosylsphingosine concentration before and after enzyme replacement therapy were evaluated. Both patients received enzyme replacement therapy for 18 months, which was uneventful. One patient maintained normal renal function, while the other received adequate dialysis. The level of globotriaosylsphingosine was reduced by approximately two-thirds after the first 3-month enzyme replacement therapy and remained stable during follow-up. No significant changes were detected in cardiac structure or function parameters, with the exception of the PR interval and left atrial reservoir strain. The PR interval of the renal transplant patient was prolonged from 108 to 128 milliseconds. Left atrial reservoir strain improved significantly in both patients, from 29.4

Diabetic kidney disease (DKD) is one of the common and serious complications of diabetes mellitus, with a complex pathogenesis and a lack of ideal treatment options in clinical practice. In recent years, the protective role of vitamin D and its receptor signaling pathway in DKD has garnered widespread attention. Vitamin D plays an important role in the onset and progression of DKD by participating in the regulation of insulin secretion, inhibiting inflammatory responses, attenuating podocyte injury, modulating the renin-angiotensin system (RAS), and inhibiting renal interstitial fibrosis through its receptor (VDR). Studies on the use of vitamin D and its receptors in DKD have increased gradually in recent years, with a focus on the development of vitamin D analogs and the clinical application of VDR activators. This study reviewed the mechanisms of vitamin D and its receptor in diabetic nephropathy, as well as the potential for therapeutic applications and associated adverse effects. It also analyzed current research hotspots and development trends based on bibliometrics. Future research should focus on further optimizing vitamin D-based therapeutic strategies to achieve better clinical efficacy and safety.

Cellular senescence and cellular reprogramming represent two fundamentally intertwined processes that profoundly influence aging and cancer. This paper explores how the permanent cell-cycle arrest of senescent cells and the identity-resetting capacity of reprogramming jointly shape biological outcomes in later life and tumor development. We synthesize recent findings to show that senescent cells, while halting the proliferation of damaged cells, can paradoxically promote tissue dysfunction and malignancy via their secretory phenotype. Conversely, induced reprogramming of somatic cells—exemplified by Yamanaka factors—resets cellular age and epigenetic marks, offering a potential to rejuvenate aged cells. Key findings highlight shared mechanisms (e.g., DNA damage responses and epigenetic remodeling) and bidirectional crosstalk between these processes: senescence signals can facilitate neighboring cell plasticity, whereas reprogramming attempts can trigger intrinsic senescence programs as a barrier. In aging tissues, transient (partial) reprogramming has been shown to erase senescence markers and restore cell function without inducing tumorigenesis, underlining a novel strategy to combat age-related degeneration. In cancer, we discuss how therapy-induced senescence of tumor cells may induce stem-cell-like traits in some cells and drive relapse, revealing a delicate balance between tumor suppression and tumor promotion. Understanding the interplay between senescence and reprogramming is crucial for developing innovative therapies. By targeting the senescence–reprogramming axis–for instance, via senolytic drugs, SASP inhibitors, or safe reprogramming techniques–there is significant therapeutic potential to ameliorate aging-related diseases and improve cancer treatment. Our findings underscore that carefully modulating cellular senescence and rejuvenation processes could pave the way for novel regenerative and anti-cancer strategies.

ObjectivesNephrotic syndrome (NS) in IgA nephropathy (IgAN) may indicate concurrent minimal change disease (MCD). This study characterized the IgAN-MCD overlap phenotype using anti-nephrin autoantibodies (IgG co-localization) in NS-IgAN patients, assessing its prevalence and therapeutic implications.MethodsWe conducted a retrospective analysis of 67 biopsy-confirmed NS-IgAN patients (2010-2024) with ≥1-year follow-up. Patients were stratified by treatment response into complete remission (CR, n = 24) and non-remission (NR, n = 26) groups. Renal biopsies were evaluated for anti-nephrin autoantibodies via IgG co-localization and podocyte ultrastructure. Longitudinal data were analyzed using repeated-measures ANOVA with Benjamini-Hochberg correction; time-to-remission was assessed by Kaplan-Meier and Cox regression analyses.ResultsCR patients showed significantly lower baseline serum albumin (18.8 ± 4.0 vs. 24.1 ± 4.2 g/L, P < 0.001) and higher eGFR (101 ± 29 vs. 62 ± 35 mL/min/1.73m², P < 0.001) compared to NR patients. Anti-nephrin IgG co-localization was detected in 54.2% of CR patients but absent in NR patients (P < 0.001). Cox regression identified anti-nephrin positivity as a strong predictor of faster remission (HR: 0.40, 95% CI: 0.17-0.90; P = 0.028). CR patients achieved rapid proteinuria remission (0.1 ± 0.1 vs. 7.0 ± 0.8 g/24h at 1 month, P < 0.001) with significant time×group interactions for proteinuria (P = 0.001) and serum albumin (P = 0.004). An estimated 35.8% of NS-IgAN cases represented IgAN-MCD overlap.ConclusionA significant subset (~36%) of NS-IgAN patients exhibit an IgAN-MCD overlap state identifiable by renal anti-nephrin IgG co-localization, demonstrating MCD-like pathology and excellent corticosteroid response. This biomarker integration can guide personalized therapy, enabling effective short-course treatment for overlap cases while avoiding unnecessary long-term immunosuppression in classic NS-IgAN.

We aimed to conduct a retrospective analysis to assess the efficacy and safety of finerenone in patients with membranous nephropathy (MN). This study conducted a retrospective analysis of patients with MN who were treated with finerenone for follow-up period ranging from 3 to 6 months. The study compared the estimated glomerular filtration rate (eGFR), urine total protein-to-creatinine ratio (PCR), urine albumin-to-creatinine ratio (ACR), serum creatinine concentration (SCr), blood pressure and serum potassium (K+) during the follow-up period. In this study, 20 patients with MN were treated with finerenone for a follow-up period of 3 to 6 months. Prior to treatment, the average eGFR was 65.15 mL/min/1.73 m2, the average PCR was 3643.63 mg/g, and the average ACR was 2489.44 mg/g. After 3 months of treatment, 80

Background Anaemia is a common comorbidity in patients with chronic kidney disease (CKD) and heart failure (HF). Roxadustat has been approved for the treatment of anaemia in patients with CKD. However, its efficacy and safety in treating anaemia in patients with both CKD and HF remain unclear. We conducted a retrospective study with propensity score matching (PSM) to evaluate the efficacy and safety of roxadustat in this population. Methods This retrospective study enrolled patients diagnosed with HF comorbid with CKD and anaemia. The patients were divided into two groups: a roxadustat group and a control group. One-to-one PSM was used to balance baseline characteristics between the groups. The primary endpoint was the change in haemoglobin (Hb) at week 8. Secondary endpoints included Hb response, changes in haematocrit, iron parameters, echocardiographic parameters, B-type natriuretic peptides and lipid levels. Exploratory endpoints were mortality and rehospitalization rates over 30 days-2 years. Safety endpoints included the incidence of hyperkalaemia, liver damage and thrombotic events. Results A total of 1055 patients were screened. After PSM, 206 patients were included. Baseline characteristics were comparable between the matched cohorts. At week 8, the roxadustat group experienced a greater increase in Hb than the control group, with a difference of 0.8 g/dl (95% confidence interval 0.3-1.3; P = .003). The roxadustat group also demonstrated a higher Hb response (60.2% versus 28.2%; P < .001) and a greater increase in haematocrit (4.7 +/- 0.9% versus 2.8 +/- 0.6%; P = .008) than the control group. No significant differences were observed for other secondary endpoints. Thrombotic events were similar between the two groups and there were no differences in the risks of mortality or rehospitalization. Conclusions Roxadustat was effective in correcting and maintaining Hb levels in patients with anaemia, HF and CKD. It did not increase thrombotic and other adverse events, mortality or rehospitalization risks, making it a promising treatment option for anaemia in this population.

BackgroundMembranous nephropathy (MN) is an autoimmune disease and represents the most prevalent type of renal pathology in adult patients afflicted with nephrotic syndrome. Despite substantial evidence suggesting a possible link between MN and cancer, the precise underlying mechanisms remain elusive.MethodsIn this study, we acquired and integrated two MN datasets (comprising a single-cell dataset and a bulk RNA-seq dataset) from the Gene Expression Omnibus database for differential expression gene (DEG) analysis, hub genes were obtained by LASSO and random forest algorithms, the diagnostic ability of hub genes was assessed using ROC curves, and the degree of immune cell infiltration was evaluated using the ssGSEA function. Concurrently, we gathered pan-cancer-related genes from the TCGA and GTEx databases, to analyze the expression, mutation status, drug sensitivity and prognosis of hub genes in pan-cancer.ResultsWe conducted intersections between the set of 318 senescence-related genes and the 366 DEGs, resulting in the identification of 13 senescence-related DEGs. Afterwards, we meticulously analyzed these genes using the LASSO and random forest algorithms, which ultimately led to the discovery of six hub genes through intersection (PIK3R1, CCND1, TERF2IP, SLC25A4, CAPN2, and TXN). ROC curves suggest that these hub genes have good recognition of MN. After performing correlation analysis, examining immune infiltration, and conducting a comprehensive pan-cancer investigation, we validated these six hub genes through immunohistochemical analysis using human renal biopsy tissues. The pan-cancer analysis notably accentuates the robust association between these hub genes and the prognoses of individuals afflicted by diverse cancer types, further underscoring the importance of mutations within these hub genes across various cancers.ConclusionThis evidence indicates that these genes could potentially play a pivotal role as a critical link connecting MN and cancer. As a result, they may hold promise as valuable targets for intervention in cases of both MN and cancer.

Introduction:Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within the VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery.Methods:Transcriptome data from the Gene Expression Omnibus Database were analyzed to assess the expression of mTOR and VDR expression in human renal tissues. Clinical samples from DKD patients and minimal change disease (MCD) controls were examined, and a DKD animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection was employed to modulate the VDR-mTOR pathway, with its components evaluated using immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA).Results:Changes in the expression of the VDR-mTOR pathway were observed in both DKD patients and the animal model. Overexpression of DDIT4 increased VDR expression and decreased levels of mTOR, p70s6k, and 4E-BP1. Furthermore, DDIT4 treatment regulated autophagy by upregulating LC3I expression and downregulating LC3II expression. Notably, DDIT4 alleviated oxidative stress by reducing the levels of lipid peroxidation product MDA, while simultaneously increasing the levels of superoxide dismutase (SOD) and glutathione (GSH), underscoring the role of DDIT4 in the pathological process of DKD and its potential as a therapeutic target.Conclusion:Unraveling DDIT4’s involvement in the VDR-mTOR pathway provides insights for innovative DKD drug discovery, emphasizing its potential as a therapeutic target for future interventions.

Background To investigate the efficacy and safety of rituximab (RTX) with or without glucocorticoid (GC) in inducing remission of minimal change disease (MCD) in adults.Methods Twenty-one adult MCD patients were included in the study. The patients were assigned to the following three groups according to their background before RTX treatment: an RTX single drug direct induction treatment group (Group A; n = 9), a short-term, low-dose GC combined with RTX induction treatment group (Group B; n = 4), and a short-term, adequate-dose GC-induced remission and RTX maintenance treatment group (Group C; n = 8). The primary endpoints were the time to induction of remission and the rate of clinical remission at 12 months.Results All patients achieved clinical remission, with 19 (90.48%) achieving complete remission (CR), and the median remission time was 4 (2.5, 12) weeks. Eight (88.89%) patients in Group A achieved CR, and the median remission time was 3 (2.25, 14) weeks. In Group B, three (75.00%) patients achieved CR, with a median remission time of 4 (4, 10) weeks. In Group C, eight (100.00%) patients achieved CR, and the median remission time was 3.5 (2, 4) weeks.Conclusions In MCD patients without acute kidney injury, adequate RTX alone or short-term combined treatment with low-dose GCs can effectively induce and maintain MCD remission. Adequate short-term GCs combined with RTX maintenance may be an effective alternative for MCD patients in context of acute kidney injury. There is a need to investigate different induction therapy regimens for the remission of MCD patients with different backgrounds.

The development of omics technologies has driven a profound expansion in the scale of biological data and the increased complexity in internal dimensions, prompting the utilization of machine learning (ML) as a powerful toolkit for extracting knowledge and understanding underlying biological patterns. Kidney disease represents one of the major growing global health threats with intricate pathogenic mechanisms and a lack of precise molecular pathology-based therapeutic modalities. Accordingly, there is a need for advanced high-throughput approaches to capture implicit molecular features and complement current experiments and statistics. This review aims to delineate strategies for integrating multi-omics data with appropriate ML methods, highlighting key clinical translational scenarios, including predicting disease progression risks to improve medical decision-making, comprehensively understanding disease molecular mechanisms, and practical applications of image recognition in renal digital pathology. Examining the benefits and challenges of current integration efforts is expected to shed light on the complexity of kidney disease and advance clinical practice.