To investigate the impact of gender differences on the prognosis of elderly patients with IgA nephropathy （IgAN） by examining their clinical indices and pathological characteristics.
Methods
A retrospective analysis of primary IgAN patients aged ≥ 60 years diagnosed by renal biopsy at the First Medical Center of PLA General Hospital from January 2004 to August 2022.The follow-up deadline was September 2023.The endpoint events were end-stage renal disease （ESRD）， regular renal replacement therapy， or decrease of eGFR by no less than 50%.The effective follow-up duration was 1 year.The clinical and pathological characteristics of the patients were observed.Kaplan-Meier survival analysis method was used to compare the differences in renal survival rate between the male and female elderly patients with IgAN.And Cox regression model was used to analyze the prognostic factors of the elderly patients with IgAN.
Results
This study included 135 patients with a median age of 64 years， among whom there were 81 males and 54 females.Compared with the female patients， the male patients showed higher levels of serum creatinine， blood urea nitrogen， blood uric acid， mesangial cell proliferation， and tubular atrophy/interstitial fibrosis， but lower levels of serum IgA， triglycerides， and total cholesterol （all P＜0.05）.During a median follow-up of 58 months， a total of 32 patients （23.7%） had endpoint events， including 23 males （28.3%）and 9 females （16.7%）.Kaplan-Meier survival analysis showed that the renal survival rate of the male patients was significantly lower than that of the female patients （P=0.01）.Cox regression analysis showed that the male gender （HR=3. 689， 95%CI： 1. 517-8. 977， P= 0.004） was a risk factor for the poor prognosis of the elderly patients with IgAN.
Conclusion
The male gender was an independent risk factor for the poor prognosis in the elderly patients with IgAN.
To explore the predictive role of neutrophil to lymphocyte ratio （NLR） in cardiovascular disease （CVD） morality risk of peritoneal dialysis （PD） patients with diabetes mellitus（DM）.
Methods
A retrospective analysis of clinical data of DM patients who underwent PD catheterization at the General Hospital of Northern Theater Command from January 2013 to September 2021 was conducted.By using receiver operating characteristic （ROC） curves to determine the optimal cutoff value for NLR， the study subjects were divided into low NLR and high NLR groups.Kaplan-Meier method was used for survival analysis， and a multivariate Cox regression proportional hazards model was used to analyze the risk factors affecting CVD mortality of the patients.
Results
A total of 201 PD patients with DM were included.The ROC curve showed that the optimal cut-off value of NLR for predicting CVD morality was 3.36.Therefore，the subjects were divided into a low NLR group （n=52） and a high NLR group （n=149）.Compared with the low NLR group， the high NLR group had higher level of neutrophils but lower levels of body mass index（BMI） and lymphocytes.Kaplan-Meier curve analysis showed that the overall survival rate of patients in the high NLR group was lower than that in the low NLR group （16.70% vs. 71.90%， χ2=5.765， P=0.016）.After adjusting for confounding factors， the results of the multivariate Cox regression model analysis showed that NLR （HR= 1. 082， 95%CI： 1. 013-1. 155， P= 0.019） was an independent risk factor for CVD mortality risk in the DM patients undergoing PD， while BMI （HR=0. 847， 95%CI： 0. 770-0. 933， P=0.001） was a protective factor.
Conclusion
NLR was an independent risk factor for CVD mortality risk in the DM patients undergoing PD， which may have certain reference value for clinical work.
To explore the feasibility of establishing a microfluidic technology for detecting potassium in finger blood of hemodialysis patients.
Methods
Eighteen hemodialysis patients were enrolled， from each of whom 100 μl of finger blood was collected for potassium detection using the microfluidic technology， and 2 ml of venous blood was sent to the laboratory for potassium detection.The difference and correlation between the blood potassium concentrations measured by the two methods were analyzed.The receiver operating characteristic （ROC） curves were drawn to analyze the diagnostic and therapeutic value of finger blood potassium ＞5.0 mmol/L for dialysis patients.
Results
The difference between the finger blood potassium concentration detected by microfluidic technology and the venous blood potassium concentration measured by the laboratory was about 10% （r=0.774， P＜0.05）.The area under the ROC curve with the finger blood potassium＞5.0 mmol/L being the indicator was 0.938.
Conclusion
The finger blood potassium concentration detected by microfluidic technology was linearly correlated to the venous blood potassium concentration detected by the laboratory.The finger blood potassium detection method based on microfluidic technology may have certain value for monitoring the blood potassium concentration of dialysis patients.
To establish and compare three animal models of acute kidney disease（AKD） to provide basic research evidence for investigating the pathophysiological mechanisms of AKD.
Methods
Ninety healthy male C57BL/6J mice aged 6-8 weeks were selected， and divided into model groups and control groups （15 mice/group） to establish three AKD models： folic acid model group （given intraperitoneal injection of 0.5% folic acid at 250 mg/kg）， folic acid control group （given intraperitoneal injection of the same amount of 0.3 M sodium bicarbonate）， unilateral ureteral obstruction （UUO） model group （given unilateral ureteral obstruction）， UUO control group （given sham operation）， unilateral ischemia-reperfusion （UIR） model group （given clamping of unilateral renal pedicle for 30 minutes）， and UIR control group （given sham operation）.On day 2， day 8， and day 14 after the modeling， samples were collected to measure serum creatinine， blood urea nitrogen， and proteinuria levels.Renal tissue pathology was observed， and renal injury and collagen deposition were assessed.Western blotting was used to detect the expressions of fibrosis-related proteins such as vimentin and α-smooth muscle actin.RT-qPCR was used to detect renal mRNA expressions of kidney injury molecule-1 （KIM-1） and inflammatory factors including TNF-α， IL-1β， IL-8， and IFN-γ）.
Results
In the folic acid model group， serum creatinine and blood urea nitrogen significantly increased at day 8 after the modeling （both P＜0.05）， while the KIM-1 expression was higher than those in the other two model groups at day 2 after the modelings.At day 8 after the modelings， the expression of KIM-1 in the UUO model group was higher than those in the other two model groups （all P＜0.05）.The tubular injury scores and collagen deposition in the three model groups showed a time-dependent increase， and were all higher than those in their respective control groups.At day 14 after modeling， the UUO model group showed higher tubular injury scores and collagen deposition， as well as higher expressions of vimentin and α-smooth muscle actin than the other two model groups （all P＜0.05）.At day 8 after the modelings， the mRNA expressions of IL-8， IL-1β， TNF-α， and IFN-γ in the three model groups were all higher than those in their respective control groups （all P＜0.05）， while the expressions of these inflammatory factors in the UUO model group were higher than those in the other two model groups （all P＜0.05）.
Conclusion
The folic acid model， UUO model， and UIR model of mice AKD were all established at day8after the modeling operations， among which the renal fibrosis during the disease progression was more severe in the UUO model.
This study employed transcriptomic sequencing and bioinformatics analyses to identify differentially expressed genes （DEGs） in mesenchymal stem cells （MSCs） treated with ginsenoside Rb1， in order to uncover key genes with potential therapeutic effects on acute kidney injury（AKI）， thereby providing novel insights for AKI treatment.
Methods
In this study， R4.4.2 software was employed to analyze the GSE207667 dataset for identifying DEGs in MSCs after ginsenoside Rb1 treatment.AKI-related key genes were then selected via Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses.The selected key genes were further examined through functional annotations， literature review， and database analysis.
Results
From the MSCs treated with ginsenoside Rb1， 2969 DEGs were identified， comprising 1567 upregulated genes and 1402 downregulated genes（|log2FC|＞0.585）.GO enrichment analysis revealed that these DEGs were primarily about biological and molecular functions， including the positive regulation of cell population proliferation and apoptotic cell clearance.KEGG analysis further indicated significant enrichment of DEGs in pathways of cytokine-cytokine receptor interaction， IL-17 signaling， ferroptosis， cell senescence， and efferocytosis （P＜0.05）.Based on functional annotations， this study identified 43 potential key genes related to AKI intervention， and discussed focusing on genes of BMP2， MMP13， ATG5， PTN， and NGF.These genes were implicated in critical biological processes as cell proliferation， apoptosis， inflammation， and tissue repair， and may be closely linked to the mechanism in which MSCs pretreated by ginsenoside Rb1 modulated AKI.
Conclusion
Ginsenoside Rb1 may exert therapeutic effects on AKI by modulating biological processes of cell proliferation and apoptosis in MSCs.The five key genes identified in this study （BMP2， MMP13， ATG5， PTN， and NGF） may offer potential targets for the application of ginsenoside Rb1-treated MSCs in AKI therapy.
To investigate the role of histone lactylation in peritoneal inflammation induced by high-glucose peritoneal dialysate.
Methods
Thirty-two male C57BL/6 mice， aged 8 weeks and weighing 20-25 grams， were used to develop a peritoneal inflammation model by employing 4.25% glucose peritoneal dialysate and methylglyoxal （MGO） as inflammatory agents， but rotenone （ROT） and oxalate（OXA） as lactylation enhancer and inhibitor， respectively.The mice were divided into four groups： the control group， high-glucose dialysate group， high-glucose dialysate with ROT group （ROT group）， and high-glucose dialysate with OXA （OXA group）.The control group received no treatment， while the other three groups received daily intraperitoneal injection of 4.25% glucose dialysate （0.1 ml/g） and MGO（50 μg/g）.Additionally， the ROT group and OXA group also received 1 mg/kg ROT and 750 mg/kg OXA， respectively.The experimental period lasted for two weeks， after which the parietal peritoneal tissues were collected from the mice for evaluating the thickness of the peritoneal tissue， observing the pathological changes of the peritoneal tissue by PAS staining， and assessing the inflammatory response by immunohistochemical staining.For cell experiments， a cell line of human peritoneal mesothelial cells（HPMCs） was utilized.The cells were also divided into four groups： control culture group， high-glucose culture group， high-glucose culture plus ROT group， and high-glucose culture plus OXA group.Apart from the control culture group， the other three groups were treated with high-glucose of 50% glucose （10.8 μl/ml）， high-glucose plus ROT （0.012 mg/ml）， and high-glucose plus OXA （0.45 mg/ml）， respectively.After 48 hours of treatment， the cell groups were analyzed for mRNA levels of glycolytic enzymes， glycolytic rate， and ATP concentration.Both mice peritoneal tissues and HPMCs underwent immunoprecipitation for detecting histone lactylation， ELISA for detecting lactate and proteins of inflammatory factors， and real-time PCR for detecting mRNAs of inflammatory factors.
Results
Animal experiments showed that the levels of mice peritoneal thickness， lactate level， and histone H3 lactylation level， as well as the infiltration of inflammatory cells （macrophages and neutrophils） in the peritoneal tissues and the expression of inflammatory factors （IL-1β and IL-6）， were higher in the high-glucose dialysate group than in the control group， and even higher in the ROT group than in the high-glucose dialysate group， but lower in the OXA group than in the high-glucose dialysate group （all P＜0.05）.Cell experiments showed that compared with the control culture group， the high-glucose culture group had significantly higher levels of key glycolytic enzymes， glycolytic rate， lactate， histone H3 lactylation， and inflammatory factors （IL-1β and IL-6）， but less ATP production （all P ＜0.05）.Further studies found that the levels of the mRNA and protein expressions of the inflammatory factors （IL-1β and IL-6） were significantly higher in the high-glucose culture plus ROT group， but lower in the high-glucose culture plus OXA group， than in the high-glucose culture group （all P＜0.05）.
Conclusion
High-glucose peritoneal dialysate may promote peritoneal fibrosis by inducing histone lactylation modification and aggravating the peritoneal inflammatory response.Inhibiting the histone lactylation modification may attenuate the inflammatory response induced by high-glucose peritoneal dialysate， providing a new idea for the clinical prevention and treatment of peritoneal fibrosis.
Chronic kidney disease-mineral and bone disorder （CKD-MBD） is one of the most common and important complications of chronic kidney disease.With the progression of renal failure， the patients' calcium and phosphorus regulation becomes imbalanced.The patients may experience vitamin D deficiency， hyperphosphatemia， hypocalcemia， secondary hyperparathyroidism， and calcification of blood vessels and soft tissues.These conditions increase the risk of fractures and cardiovascular events， reduce quality of life， and increase the risk of death.Active treatment of secondary hyperparathyroidism， prevention and treatment of osteoporosis and vascular calcification， and control of blood phosphorus are important measures in the treatment of CKD-MBD.This article reviewed the new progress in research on the drug treatment of CKD-MBD.
For a long time， the diagnosis of acute kidney injury （AKI） has mainly relied on serum creatinine and estimated glomerular filtration rate， but the lag in detection often leads to missed optimal diagnosis and treatment opportunities in clinical practice.Contemporary nanotechnology and biomedical developments have brought hope for the early diagnosis of AKI.Point-of-care testing （POCT） for biomarkers such as kidney injury molecule-1， neutrophil gelatinase-associated lipocalin， and microRNAs may make the diagnostic process of AKI faster， simpler， and of lower-cost.This article reviewed the significance of early biomarkers for AKI as well as the current status of their POCT research， and looked ahead to the future challenges and application prospects.
In recent years， significant advances in understanding the pathophysiological mechanisms of membranous nephropathy （MN） have revealed its underlying pathogenesis， primarily characterized by the interaction between autoantibodies and podocyte target antigens.Concurrently， the epidemiological features of MN have demonstrated regional variations and dynamic trends， offering novel insights for disease prevention and clinical management.This review systematically summarizes the latest progress in MN research， with a particular focus on the discovery of target antigens and innovative therapeutic approaches represented by targeted therapy，including anti-CD20 monoclonal antibodies， complement inhibitors， and proteasome inhibitors， in order to provide reference for the follow-up research and clinical diagnosis and treatment of membranous nephropathy.
