Background:The risks and benefits of colchicine use among patients with atherosclerotic cardiovascular disease (ASCVD) have been widely reported. Our umbrella review aimed to systematically analyse and synthesise the available causal evidence on the therapeutic effects and safety profile of colchicine in patients with ASCVD. Methods:We searched PubMed, Embase, Web of Science, and Cochrane Library from database inception to December 4, 2024, to identify systematic reviews and meta-analyses of randomised controlled trials (RCTs) investigating colchicine use among patients with ASCVD. The primary endpoints were physical adverse events, MACEs, and CV disorder. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Risk of bias was evaluated using Cochrane Systematic Review criteria. Inconsistency was flagged if heterogeneity (I 2 ) exceeded 50%, or 75% without explanation. Publication bias was detected via funnel plot asymmetry or Egger's test. Subgroup analyses were done according to colchicine dose, treatment duration, geographical region, participant age and disease of patients. This study is registered with PROSPERO (CRD 42025631311). Findings:This review analysed 47 unique outcomes from 48 systematic reviews and meta-analyses of RCTs. Among 271 associations, 95 were supported by high-certainty evidence. For primary outcomes, compared with placebo treatment, colchicine exhibited therapeutic efficacy in coronary heart disease [relative risk (RR): 0.73, 95% confidence interval (CI): 0.64-0.83, I 2 : 0%] and acute coronary syndromes (OR: 0.72, 95% CI: 0.58-0.89, I 2 : 0%), demonstrating secondary prevention benefits in major adverse cardiovascular events (RR: 0.56, 95% CI: 0.47-0.67, I 2 : 0%). Common adverse effects included gastrointestinal reactions and hepatic toxicity, with dose-dependent associations of drug discontinuation (RR: 4.63, 95% CI: 2.06-10.38, I 2 : 36%). Evidence of publication bias was identified in 18 of 271 tested associations. Subgroup analyses indicated that optimal clinical application required consideration of patient age, geographic variance in pharmacogenomics, and protocol adjustments (recommended dose ≤0.5 mg/day for more than a month) to balance efficacy-risk profiles. Interpretation:High-certainty evidence supported the therapeutic and secondary preventive benefits of colchicine in patients with ASCVD when dose and duration were appropriately controlled. Future studies could focus on identifying ASCVD subgroups with pharmacogenomic and ethnographic predictors of colchicine response heterogeneity to guide precision therapy. Funding:This work was supported by the Liaoning Revitalization Talents Program, Outstanding Youth Scientific Talent Project of Dalian, and Outstanding Scientific Fund of Shengjing Hospital.

ABSTRACT Background The precise mechanisms responsible for renal injury in IgA nephropathy (IgAN) are not fully understood. Our study employed an extensive scRNA‐seq analysis of kidney biopsies obtained from individuals with IgAN, with a specific emphasis on investigating the involvement of renal endothelial cells. Methods We obtained data from the Gene Expression Omnibus database and conducted bioinformatics analysis, which included enrichment analysis of differentially expressed genes, AUCell analysis, and high‐dimensional weighted gene co‐expression network analysis (hdWGCNA). The results of these analyses were further validated using human renal glomerular endothelial cells (HRGECs). Results The ScRNA‐seq data uncovered notable variations in gene expression between IgAN and control kidney tissues. The enrichment analysis using AUCell demonstrated a high presence of adhesion molecules and components related to the mitogen‐activated protein kinase signaling pathway within the renal endothelial cells. Furthermore, through hdWGCNA analysis, it was discovered that interleukin (IL)‐6, Rac1, and cadherin exhibited associations with the renal endothelial cells. Stimulation of HRGECs with IL‐6/IL‐6 receptor resulted in a significant reduction in VE‐cad expression while inhibiting Rac1 led to a substantial decrease in Rac1‐GTP levels and an increase in VE‐cad expression. Conclusion This study presents novel findings regarding the contribution of renal endothelial cells to the development of IgAN, as it demonstrates that IL‐6 negatively regulates VE‐cad expression in HRGECs via Rac1. These results highlight the significant involvement of renal endothelial cells in the pathogenesis of IgAN.

Objective: Glomerular hyperfiltration is an early indicator of obesity-related glomerular disease. However, in adolescents, there are no quantifiable indicators of obesity and glomerular hyperfiltration. This study investigates the association between visceral adipose tissue and glomerular hyperfiltration in adolescents. Methods: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES; 2011-2018), and adolescents aged 12-17 years were included. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) formed the independent variables while estimated glomerular filtration rate (eGFR) acted as the dependent variable. Their association was assessed using unadjusted and multivariate regression analyses, as well as subgroup and interaction analyses. Results: Multivariate regression analysis revealed that VAT was positively associated with eGFR and glomerular hyperfiltration among adolescents. The incidence of glomerular hyperfiltration increased by 99 % in boys and 56 % in girls per 100 g of VAT increase. Additionally, VAT and eGFR exhibited a linear relationship in both boys (beta = 5.63, p < 0.001) and girls (beta = 2.72, p < 0.001). Conclusions: In US adolescents aged 12-17 years, VAT was positively correlated with eGFR and glomerular hyperfiltration.

Renal cell carcinoma (RCC) remains a significant clinical challenge due to delayed diagnosis and multidrug resistance, necessitating innovative strategies to enhance early detection and therapeutic efficacy. This review evaluates the role of lipid-based nanoparticles (LNPs), including liposomes, micelles, nanoemulsions, solid lipid nanoparticles, and nanostructured lipid carriers, as advanced drug delivery systems in providing innovative solutions for RCC diagnosis and treatment. These LNPs exhibit unique advantages of great biocompatibility, biodegradability, extended circulation, and tumor-targeting capabilities, which enable precise drug delivery, controlled release, and circumvention of drug resistance mechanisms. After integrating recent advancements, it is highlighted that formulations such as Liposome@Sunitinib can enhance tumor accumulation, two-drug-loaded liposomes can activate immune responses, and RNA therapy in combination with immunomodulators can reverse drug resistance. Current findings underscore the transformative potential of lipid-based nanotechnology in addressing RCC-specific challenges, particularly in overcoming biological barriers and refining personalized treatment approaches. In the future, multifunctional nano platforms, precision therapies based on patient genes, advanced materials engineering, combination therapies, and sustainable manufacturing can be developed to promote the application of LNPs in the treatment of RCC and realize personalized nanomedicine.

Acute kidney injury (AKI) can progress to renal fibrosis and chronic kidney disease (CKD), which reduces quality of life and increases the economic burden on patients. However, the molecular mechanisms underlying renal fibrosis following AKI remain unclear. This study tested the hypothesis that the Kruppel-like factor 4 (KLF4)/miR-101/Collagen alpha-1X (COL10A1) axis could inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis after AKI in a mouse model of ischemia-reperfusion (I/R)-induced renal fibrosis and HK-2 cells by gene silencing, overexpression, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, dual-luciferase reporter assay, fluorescence in situ hybridization (FISH) and ELISA. Compared with the Sham group, I/R induced renal tubular and glomerular injury and fibrosis, and increased the levels of BUN, serum Scr and neutrophil gelatinase-associated lipocalin (NGAL), Col10a1 and Vimentin expression, but decreased E-cadherin expression in the kidney tissues of mice at 42 days post-I/R. Similarly, hypoxia promoted fibroblastic morphological changes in HK-2 cells and enhanced NGAL, COL10A1, Vimentin, and alpha-SMA expression, but reduced E-cadherin expression in HK-2 cells. These pathological changes were significantly mitigated in COL10A1-silenced renal tissues and HK-2 cells. KLF4 induces miR-101 transcription. More importantly, hypoxia upregulated Vimentin and COL10A1 expression, but decreased miR-101, KLF4, and E-cadherin expression in HK-2 cells. These hypoxic effects were significantly mitigated or abrogated by KLF4 over-expression in the HK-2 cells. Our data indicate that KLF4 up-regulates miR-101 expression, leading to the downregulation of COL10A1 expression, inhibition of EMT and renal fibrosis during the pathogenic process of I/R-related renal fibrosis.

Objective: Cathepsin S (CTSS) is an important lysosomal cysteine protease. This study aimed at investigating the clinical significance of CTSS and underlying mechanism in immunoglobulin A nephropathy (IgAN). Methods: This study recruited 25 children with IgAN and age-matched controls and their serum CTSS levels were measured by enzyme-linked immunosorbent assay (ELISA). Following induction of IgAN in rats, their kidney CTSS expression, IgA accumulation and serum CTSS were characterized by immunohistochemistry, immunofluorescence, and ELISA. The impact of IgA1 aggregates on the proliferation of human mesangial cells (HMCs) was determined by Cell Counting Kit-8 and Western blot analysis of Ki67. Results: Compared to the non-IgAN controls, significantly up-regulated CTSS expression was detected in the renal tissues, particularly in the glomerular mesangium and tubular epithelial cells of IgAN patients, accompanied by higher levels of serum CTSS (P < 0.05), which were correlated with the levels of 24-h-urine proteins and microalbumin and urine erythrocytes and grades of IgAN Lee's classification in children with IgAN (P < 0.01 for all). Following induction of IgAN, we detected inducible IgA accumulation and increased levels of CTSS expression in the glomerular mesangium and glomerular damages in rats, which were mitigated by LY3000328, a CTSS-specific inhibitor. Treatment with LY3000328 significantly mitigated the Ki67 expression in the kidney of IgAN rats (P < 0.01) and significantly minimized the IgA1 aggregate-stimulated proliferation of HMCs and their Ki67 expression in vitro (P < 0.01). Conclusions: CTSS promoted the proliferation of glomerular mesangial cells, contributing to the pathogenesis of IgAN and may be a new therapeutic target for intervention of aberrant mesangial cell proliferation during the process of IgAN.

Endoplasmic reticulum stress (ERS) is strongly associated with acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Huaier extract (HE) protects against kidney injury; albeit, the underlying mechanism is unknown. We hypothesized that HE reduces kidney injury by inhibiting ERS. In this study, using an AKI-CKD mouse model of ischemia-reperfusion injury (IRI), we evaluated the effect of HE on AKI-CKD transition. We also explored the underlying molecular mechanisms in this animal model and in the HK-2 human kidney cell line. The results showed that HE treatment improved the renal function, demonstrated by a significant decrease in serum creatinine levels after IRI. HE appreciably reduced the degree of kidney injury and fibrosis and restored the expression of the microRNA miR-1271 after IRI. Furthermore, HE reduced the expression of ERS markers glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and inhibited apoptosis in the IRI group. This in vivo effect was supported by in vitro results in which HE inhibited apoptosis and decreased the expression of CHOP and GRP78 induced by ERS. We demonstrated that CHOP is a target of miR-1271. In conclusion, HE reduces kidney injury, probably by inhibiting apoptosis and decreasing the expression of GRP78 and CHOP via miR-1271 upregulation.

Cathepsin S (Cat S) is an important member of the cysteine cathepsin protease family.It is a lysosomal protease,which has been shown to be expressed in inflammatory conditions and autoimmune diseases.It has more specific roles such as antigen presentation,tissue repair,cell proliferation and apoptosis.It contributes to a variety of clinical diseases.In this review,we summarize the structure,characteristics and functions of cathepsin S in kidney and rheumatic diseases.

目的 探讨α-干扰素(IFN-α)对慢性乙型肝炎患儿的疗效及影响因素.方法 选取2017年6月至2018年10月本院收治的慢性乙型肝炎患儿140例,随机分为观察组(80例)和对照组(60例).对照组患儿给予胸腺肽注射液25～50 mg,皮下注射,每2d注射1次;观察组患儿给予IFN-α(3～6)×106 IU/d,皮下注射,连用4w后改为3次/w;两组均连续治疗6个月.全自动生化分析仪检测两组患儿的谷丙转氨酶、乙肝表面抗原(HBsAg)、乙型肝炎E抗原(HBeAg)水平;分子杂交和聚合酶链反应检测乙肝病毒的脱氧核糖核酸(HBV-DNA)水平.结果 治疗6个月后,观察组HBeAg转阴率和HBV-DNA转阴率分别为40.00％和77.50％,明显高于对照组(10.00％,6.67％),差异均有统计学意义(均P＜0.01).不同年龄、性别、病程、血清胆红素及HBV-DNA水平的患儿HBeAg转阴率和HBV-DNA转阴率之间比较差异均有统计学意义(均P＜0.05).结论 IFN-α对慢性乙型肝炎患儿的近期疗效较佳,但其疗效受患儿年龄、性别、病程、血清胆红素及HBV-DNA水平的影响,应予以重视.

Aim The aim of the present study was to screen and verify downstream genes involved in the epithelial mesenchymal transition (EMT) induced by paired box 2 (PAX2) in NRK-52E cells. Methods NRK-52E cells were transfected with lentivirus carrying PAX2 gene or no-load virus respectively. Total RNA was isolated 72 h after transfection from PAX2-overexpressing cells and control cells. Isolated RNA was then hybridized with the Rat OneArray Plus expression profile chip. The chips were examined by Agilent 0.1 XDR to screen for differentially expressed genes, which were further analyzed to investigate complement-related genes as genes of interest. Results In NRK-52E cells, PAX2 overexpression promoted EMT followed by upregulation of 298 genes and downregulation of 293 genes. KEGG analysis indicated the differential expression of genes related to cytokines and their receptors, extracellular matrix (ECM), MAPKs, local adhesion, cancer, the complement cascade, and coagulation. Gene oncology analysis screened out genes related to molecular functions (e.g., hydrolase activity, phospholipase activity, components of the ECM) and biological processes (e.g., cell development, signal transduction, phylogeny), and cell components (e.g., cytoplasm, cell membrane, and ECM). Analysis of the complement system revealed upregulation of C3 and downregulation of CD55 and complement regulator factor H (CFH). Conclusion PAX2 overexpression upregulates EMT in vitro and may regulate C3, CD55, and CFH.