End-stage renal disease (ESRD) patients exhibit a high prevalence of multidimensional frailty, yet its neurobiological correlates remain unclear. This study investigated neuroimaging correlates of frailty in ESRD and explored whether neuroanatomical measures statistically accounted for cross-sectional associations of aging and uremic markers with frailty severity. We enrolled 89 ESRD patients and 53 healthy controls (HC) assessed using the Tilburg Frailty Indicator. 3D T1-weighted images were processed to quantify regional gray matter volumes, and T2-weighted fluid-attenuated inversion recovery (FLAIR) images were processed to quantify white matter hyperintensity (WMH) volumes. Among the ESRD patients, 36.0% were frail. Frailty correlated with advancing age, elevated blood urea nitrogen (BUN), and psychosocial deficits. The ESRD patients had widespread lower cerebral volume and greater WMH burden, and the frail ESRD patients exhibited a marked reduction in left inferior parietal volume (Cohen’s d = − 0.70, FDR-q = 0.030) compared to non-frail ESRD patients, with no significant WMH differences between the two groups. Cross-sectional mediation models showed a significant indirect association involving age, left inferior parietal volume, and frailty severity (ACME = 0.0246, P = 0.016), whereas the indirect association involving BUN was not statistically significant. These findings identify reduced left inferior parietal volume as a key neuroanatomical correlate that statistically accounted for the age-frailty association in ESRD, while BUN was associated with frailty independently of left inferior parietal volume, which does not support the supposition that BUN contributes to frailty via cerebral structural alterations.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Given the limited therapeutic options, identifying novel differentially expressed genes and therapeutic targets is crucial for DN. We performed transcriptome sequencing of kidney tissue from DN patients and applied bioinformatics analyses to identify dysregulated pathways and candidate genes. Transcriptomic analysis revealed significant enrichment of the necroptosis pathway in DN kidney tissues, with Z-DNA binding protein 1 (ZBP1) showing the most pronounced differential expression among pathway-associated genes. Clinical and pathological data were collected from DN patients to evaluate the correlation between ZBP1 expression and key indicators of renal function and injury, thereby assessing its association with DN progression. Our results indicate that ZBP1 expression was significantly upregulated in DN kidney tissues compared to normal peritumour tissue, and correlated with renal tubule injury and renal function. Functional studies demonstrated that ZBP1 knockdown attenuated necroptosis, tubular injury, inflammation, and fibrosis in both db/db mice and high glucose/advanced glycation end products (HG/AGEs)-stimulated MTECs (mouse renal tubular epithelial cells). Mechanistically, ZBP1 directly interacts with receptor interacting protein kinase 3 (RIPK3) to promote necroptotic cell death. Furthermore, we identified ETS proto-oncogene 1 (ETS1) as a transcriptional activator of ZBP1 under HG conditions. In summary, this study identifies ZBP1 as a key mediator of tubular injury, inflammation and fibrosis in DN via RIPK3-dependent necroptosis, highlighting its potential as a therapeutic target.

Objective:To explore abnormal changes in brain entropy (BEN) and resting-state functional connectivity (RSFC) in peritoneal dialysis (PD) patients and their associations with cognitive impairment (CI). Methods:Fifty-three PD patients and 49 age-, gender-, and education-matched healthy controls (HCs) were enrolled. Resting-state functional magnetic resonance imaging (rs-fMRI) was performed to calculate BEN and RSFC. Neuropsychological assessments and clinical indicator collection were conducted. PD patients were divided into mild cognitive impairment (MCI) and non-cognitive impairment (NCI) groups using Montreal Cognitive Assessment (MoCA) scores. Correlation analyses were performed between BEN/RSFC values and neuropsychological/clinical indicators. Results:PD patients exhibited significantly poorer performance in multiple cognitive scales than HCs (all p < 0.001). Compared with HCs, PD patients had decreased BEN in the right middle occipital gyrus and left caudate nucleus, and increased BEN in the left middle temporal gyrus and right fusiform gyrus. Reduced RSFC was found between the right middle occipital gyrus and the right fusiform gyrus, right middle frontal gyrus, and right precuneus in PD patients. BEN and RSFC values were correlated with emotional scale scores, cognitive scale subscores, and clinical indicators (e.g., glycosylated hemoglobin, transferrin saturation). Conclusion:Patients with end-stage kidney disease undergoing peritoneal dialysis present abnormal brain entropy and functional connectivity patterns. These alterations are associated with systemic metabolic disorders, long-term dialysis treatment, and cognitive/emotional impairment.

BACKGROUND:Executive dysfunction is the most prominent feature of cognitive impairment in patients with end-stage renal disease (ESRD). The dorsolateral prefrontal cortex (DLPFC) is a central region for the regulation of executive functions. The aim of our study was to examine alterations in neural activity and functional connectivity (FC) of the DLPFC in relation to cognitive assessments and clinical indicators in patients with ESRD using the resting-state functional magnetic resonance imaging (rs-fMRI) technique, and to further predict cognitive-related brain damage in this population. METHODS:A total of 37 ESRD patients and 35 normal controls received MRI scans and neuropsychological assessments. Inter-group differences in fractional amplitude of low-frequency fluctuations (fALFF) and FC of the DLPFC were compared. Additionally, the relationships between DLPFC abnormalities and cognitive function were analyzed in ESRD patients, along with the clinical characteristics. Finally, we ascertained the potential of DLPFC abnormalities to predict cognitive-related brain damage using receiver operating characteristic (ROC) curve analysis. RESULTS:ESRD patients exhibited decreased fALFF in the bilateral DLPFC (p < 0.05, false discovery rate [FDR] corrected). These also showed abnormal FC with the frontoparietal cortex, cingulate cortex, cerebellar posterior lobe, inferior temporal gyrus, and rolandic operculum (p < 0.05, FDR corrected). Several alterations in the DLPFC were associated with cognitive assessments (p < 0.05) in ESRD patients, and were also correlated with the levels of uric acid and hemoglobin (p < 0.05). Importantly, ROC curve analysis showed the fALFF value of left DLPFC, and FC between right DLPFC and right middle frontal gyrus effectively predicted cognitive-related brain damage in patients with ESRD. CONCLUSIONS:This study demonstrated that the DLPFC is an important pathological brain region associated with the cognitive impairment of ESRD patients. Our results provide neuroimaging insights to further understand neural mechanisms of cognitive decline in this population.

Evidence suggests that hemoglobin-to-red blood cell distribution width ratio (HRR) is associated with many diseases. Nevertheless, the association between HRR and macroalbuminuria in patients with diabetic kidney disease (DKD) remains uncertain. Using NHANES data (1999-2018), DKD was clinically diagnosed as estimated glomerular filtration rate <60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio (UACR) ≥30 mg/g in patients with diabetes and divided into microalbuminuria and macroalbuminuria according to UACR. Propensity score matching (PSM), weighted logistics regression, restricted cubic spline, clinical subgroup and mediation analysis were performed to investigate the association between HRR and macroalbuminuria. Lasso regression and receiver operating characteristic curve were used to assess the diagnostic value. The HRR level in the macroalbuminuria group (0.96 ± 0.19) was significantly lower than that in the microalbuminuria group (1.01 ± 0.18, p < 0.001). Weighted binary logistic regression revealed that elevated HRR was associated with a significant decrease in UACR (95% confidence interval [CI]: 0.058-0.274, p < 0.001). Quartile analyses of HRR showed a significant trend across quartiles (Q4 vs. Q1, odds ratio in the fully adjusted model: 0.421, 95%CI: 0.284-0.620, p < 0.001). The restricted cubic spline curve demonstrated a graded decrease in the probability of macroalbuminuria with increasing HRR levels. Regression models including HRR had good detection value for macroalbuminuria. Low HRR is associated with macroalbuminuria in DKD in this cross-sectional study. HRR may be an effective inflammatory marker for identifying macroalbuminuria in DKD.

Objective:Peritoneal dialysis (PD) patients demonstrate distinct iron homeostasis imbalances. However, the relationship between brain iron and cognitive impairment in this population remains poorly elucidated. Methods:This study enrolled 52 PD patients and 49 healthy controls (HCs). Quantitative susceptibility mapping (QSM) was employed to quantify cerebral iron deposition. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and a comprehensive neuropsychological test battery. Dose-response relationships between iron metabolism parameters and cognitive performance were analyzed using generalized additive models (GAMs). Results:PD patients exhibited significantly higher iron deposition in the left amygdala and right putamen compared to HCs. Serum ferritin (SF) demonstrated an approximately inverted U-shaped relationship with MoCA scores, with an inflection point at 258.4 μg/L (p < 0.001). Every 100 μg/L increase in SF beyond this threshold was associated with a 3.1-point decrease in MoCA score. Iron deposition in the left amygdala showed significant correlations with scores on the Digit Symbol Test (DST), Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Verbal Fluency Test (VFT), but exhibited no direct association with peripheral iron metabolism parameters. Conclusion:In peritoneal dialysis patients, abnormal cerebral iron deposition predominantly localizes to limbic-basal ganglia regions. Iron accumulation in the left amygdala may specifically mediate the development of multi-domain cognitive impairment. QSM represents a sensitive technique for early detection of pathological iron accumulation.

BACKGROUND:The risk of cardiovascular events (CVEs) in peritoneal dialysis (PD) patients is high, but varies widely among individuals. Metabolic acidosis is prevalent in PD patients and may be involved in the development of CVEs. The aim of the study was to evaluate serum bicarbonate as a risk factor and derive a model of new CVE. METHODS:A predictive model was established by performing an observational study in 187 PD patients obtained from the First Affiliated Hospital of Anhui Medical University. The variables were extracted using least absolute shrinkage and selection operator (LASSO) regression, and the modeling was developed using multivariable Cox regression. RESULTS:Left ventricular hypertrophy (HR = 1.965, 95%CI 1.086-3.557) and history of CVEs (HR = 2.435, 95%CI 1.342-4.49) were risk parameters for a new CVE. Serum albumin (HR = 0.924, 95%CI 0.864-0.989) and bicarbonate levels (HR = 0.817, 95%CI 0.689-0.969) were protective parameters, in which the risk of CVEs was reduced by 7.6% and 18.3% for each 1-unit increase in serum albumin (g/L) and bicarbonate (mmol/L) levels, respectively. A nomogram based on the above predictive indicators was proposed with a C-statistic of 0.806, indicating good discrimination. Moreover, it successfully stratified patients into low-, intermediate-, and high-risk groups. CONCLUSIONS:We performed a risk prediction model for the development of CVEs in patients with PD, which may help physicians to evaluate the risk of new CVEs and provide a scientific basis for further interventions. Further studies are needed to externally validate current risk models before clinical application.

PurposeDiabetic kidney disease (DKD) is the primary reason of chronic kidney disease. Our objective was to discover potential autophagy-related biomarkers of tubulointerstitial injury in DKD and assess their clinical value.MethodsWe retrieved four datasets (GSE104954, GSE30122, GSE30529, and GSE99340) of renal tubule samples from Gene Expression Omnibus (GEO) and used two algorithms (LASSO and SVM-RFE) to screen for autophagy-related differentially expressed genes (ARDEGs) in DKD. Tripartite motif containing 22 (TRIM22) was identified for subsequent validation. Validation of TRIM22 and autophagic indicators expression in clinical samples and HK-2 cells stimulated by high glucose using immunohistochemistry, immunofluorescence, and western blot.ResultsWe identified four ARDEGs (TRIM22, PLK2, HTR2B, and FAS) using a diagnostic gene model. ROC curves further confirmed that TRIM22 had the best diagnostic efficacy for DKD. Both clinical samples and HK-2 cells stimulated by high glucose showed high protein expression of TRIM22. The correlation analysis revealed that TRIM22 correlates with SQSTM1, NGAL, and some clinical and pathological indicators in patients with DKD.ConclusionWe identified TRIM22 as a potential diagnostic biomarker for DKD, revealing its high diagnostic value in patients with DKD with moderate-to-severe interstitial fibrosis and tubular atrophy (IFTA). TRIM22 is involved in tubulointerstitial injury and autophagy dysregulation in DKD.

Diabetic kidney disease (DKD) is one of the major causes of end-stage renal disease and one of the significant complications of diabetes. This study aims to identify the main differentially expressed genes in DKD from transcriptome sequencing results and analyze their diagnostic value. The present study sequenced db/m mouse and db/db mouse to determine the ALOX12 genetic changes related to DKD. After preliminary validation, ALOX12 levels were significantly elevated in the blood of DKD patients, but not during disease progression. Moreover, urine ALOX12 was increased only in macroalbuminuria patients. Therefore, to visualize the diagnostic efficacy of ALOX12 on the onset and progression of renal injury in DKD, we collected kidney tissue from patients for immunohistochemical staining. ALOX12 was increased in the kidneys of patients with DKD and was more elevated in macroalbuminuria patients. Clinical chemical and pathological data analysis indicated a correlation between ALOX12 protein expression and renal tubule injury. Further immunofluorescence double staining showed that ALOX12 was expressed in both proximal tubules and distal tubules. Finally, the diagnostic value of the identified gene in the progression of DKD was assessed using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) value for ALOX12 in the diagnosis of DKD entering the macroalbuminuria stage was 0.736, suggesting that ALOX12 has good diagnostic efficacy. During the development of DKD, the expression levels of ALOX12 in renal tubules were significantly increased and can be used as one of the predictors of the progression to macroalbuminuria in patients with DKD.

IntroductionCognitive impairment in patients with end-stage renal disease (ESRD) is associated with brain structural damage. However, no prior studies have investigated the relationship between brain texture features and the cognitive function in ESRD patients. This study aimed to investigate changes in brain texture features in ESRD patients and their relationships with cognitive function using voxel-based 3D brain texture analysis (TA), and further predict individual cognitive-related brain damage in ESRD patients.MethodsForty-seven ESRD patients and 45 control subjects underwent whole-brain high-resolution 3D T1-weighted imaging scans and neuropsychological assessments. The voxel-based 3D brain TA was performed to examine inter-group differences in brain texture features. Additionally, within the ESRD group, the relationships of altered texture features with neuropsychological function and clinical indicators were analyzed. Finally, receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of brain texture features for cognitive-related brain damage in ESRD patients.ResultsCompared to the control group, the ESRD group exhibited altered texture features in several brain regions, including the insula, temporal lobe, striatum, cerebellum, and fusiform gyrus (p < 0.05, Gaussian random-field correction). Some of these altered texture features were associated with scores from the Digit Symbol Substitution Test and the Trail Making Test Parts A (p < 0.05), and showed significant correlations with serum creatinine and calcium levels within the ESRD group (p < 0.05). Notably, ROC curve analysis revealed that the texture features in the right insula and left middle temporal gyrus could accurately predict cognitive-related brain damage in ESRD patients, with the area under the curve values exceeding 0.90.ConclusionAberrant brain texture features may be involved in the neuropathological mechanism of cognitive decline, and have high accuracy in predicting cognitive-related brain damage in ESRD patients. TA offers a novel neuroimaging marker to explore the neuropathological mechanisms of cognitive impairment in ESRD patients, and may be a valuable tool to predict cognitive decline.

Circular RNAs (circRNAs) are special non-coding RNA (ncRNA) molecules that play a significant role in many diseases. However, the biogenesis and regulation of circRNAs in diabetic nephropathy (DN) are largely unknown. Here, we investigated the expression profile of circRNAs in kidney of DN mice through circular RNA sequencing (circRNA-seq). The renal biopsy samples of patients with DN had low circ -0,000,953 expression, which was significantly associated with renal function. Furthermore, loss-of-function and gain-of-function experiments were carried out to prove the role of circ -0,000,953 in DN. Podocyte conditional knockin (cKI) or systemic overexpression of circ -0,000,953 alleviated albuminuria and restored macroautophagy/autophagy in kidney of diabetic mice. However, circ -0,000,953 knockdown exacerbated albuminuria and podocyte injury. Mechanistically, we found circ -0,000,953 directly binds to Mir665-3p-Atg4b to perform its function. Silencing of Mir665-3p or overexpression of Atg4b recovered podocyte autophagy both in vitro and in vivo. To examine the cause of circ -0,000,953 downregulation in DN, bioinformatics prediction found that circ -0,000,953 sequence has a high possibility of containing an m6A methylation site. Additionally, METTL3 was proved to regulate the expression and methylation level of circ -0,000,953 through YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). In conclusion, this study revealed that circ -0,000,953 regulates podocyte autophagy by targeting Mir665-3p-Atg4b in DN. Therefore, circ -0,000,953 is a potential biomarker for prevention and cure of DN.

ObjectiveDiabetic kidney disease (DKD) is the most common cause of the end-stage renal disease, which has limited treatment options. Rutaecarpine has anti-inflammatory effects, however, it has not been studied in DKD. Pyroptosis is a newly discovered mode of podocyte death related to inflammation. This study aimed to explore whether Rutaecarpine can ameliorate DKD and to clarify its possible mechanism.MethodsIn this study, we investigated the effects of Rutaecarpine on DKD using diabetic mice model (db/db mice) and high glucose (HG)-stimulated mouse podocyte clone 5 (MPC5) cells. Quantitative reverse transcription polymerase chain reaction and western blot were performed to detect the related gene and protein levels. We applied pharmacological prediction, co-immunoprecipitation assay, cellular thermal shift assay, surface plasmon resonance to find the target and pathway of the substances. Gene knockdown experiments confirmed this view in HG-stimulated MPC5 cells.ResultsRutaecarpine significantly reduced proteinuria, histopathological damage, and pyroptosis of podocytes in a dose-dependent manner in db/db mice. Rutaecarpine also protected high glucose induced MPC5 injury in vitro experiments. Mechanistically, Rutaecarpine can inhibit pyroptosis in HG-stimulated MPC5 by reducing the expression of VEGFR2. VEGFR2 is a target of Rutaecarpine in MPC5 cells and directly binds to the pyroptosis initiation signal, NLRP3. VEGFR2-knockdown disrupted the beneficial effects of Rutaecarpine in HG-stimulated MPC5 cells.ConclusionRutaecarpine inhibits renal inflammation and pyroptosis through VEGFR2/NLRP3 pathway, thereby alleviating glomerular podocyte injury. These findings highlight the potential of Rutaecarpine as a novel drug for DKD treatment.

Purpose: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) worldwide. Elucidation of the molecular mechanisms underlying ferroptosis and immunity in DKD could aid the development of potentially effective therapeutics. This study aimed to perform an integrated analysis of ferroptosis and immune-related differentially expressed mRNAs (DEGs) in DKD. Materials and Methods: Gene expression profiles of samples obtained from patients with DKD and controls were downloaded from the Gene Expression Omnibus (GEO) database. The potential differentially expressed genes (DEGs) were screened using R software, and ferroptosis immune-related differentially expressed genes (FIRDEGs) were extracted from the DEGs. We performed functional enrichment analyses, and constructed protein-protein interaction (PPI) networks, transcription factor (TFs)-gene networks, and gene drug networks to explore their potential biological functions. Correlation analysis and receiver operating characteristic curves were used for evaluating the FIRDEGs. We used the CIBERSORT algorithm to examine the composition of immune cells and determine the relationship between FIRDEG signatures and immune cells. Finally, the RNA expression of six FIRDEGs was validated in animal kidney samples using RT-PCR.Results: We identified 80 FIRDEGs and performed their functional analyses. We identified six hub genes (Ccl5, Il18, Cybb, Fcgr2b, Myd88, and Ccr2) using PPI networks and predicted potential TF gene networks and gene-drug pairs. Immune cells, including M2 macrophages, resting mast cells, and gamma-delta T cells, were altered in DKD; the FIRDEGs (Fcgr2b, Cybb, Ccr2, and Ccl5) were closely correlated with the infiltration abundance of M2 macrophages and gamma-delta T cells. Finally, the hub genes were verified in mouse kidney samples.Conclusion: We identified six hub FIRDEGs (Ccl5, Il18, Cybb, Fcgr2b, Myd88, and Ccr2) in DKD, and predicted the potential transcription factor gene networks and possible treatment targets for future research.

OBJECTIVE:Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Since there are limited therapeutic options available for the prevention of DN progression, it is imperative to explore novel differentially expressed genes and therapeutic targets for DN. METHODS:In this study, mice kidney tissue were subjected to transcriptome sequencing and the results were analysed using bioinformatics methods. Interleukin 17 receptor E (IL-17RE) was screened from the sequencing data and its expression was validated in the animal tissues and a cross-sectional clinical study. Fifty-five DN patients were enrolled and further subdivided into two groups based on the urinary albumin-to-creatinine ratio (UACR). Two control groups were used for comparison (minimal change disease group, 12 patients; normal control group, 6 patients). Correlation analysis was conducted to study the relationship between IL-17RE expression and the clinicopathological indices. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to evaluate the diagnostic value. RESULTS:IL-17RE expression was significantly higher in db/db mice and the kidney tissues of DN patients than the control group. IL-17RE protein levels in the kidney tissues were strongly correlated with neutrophil gelatinase-associated lipocalin (NGAL) levels, UACR, and certain clinicopathological indices. IL-17RE levels, total cholesterol (TC) levels, and glomerular lesions were independent risk factors for macroalbuminuria. ROC curves showed a good detection value for IL-17RE in macroalbuminuria (area under the curve = 0.861). CONCLUSION:The results of this study provide novel insights into DN pathogenesis. Kidney IL-17RE expression levels were associated with DN disease severity and albuminuria.

ETHNOPHARMACOLOGICAL RELEVANCE:Paeonia lactiflora Pall has been used in Chinese Medicine for thousands of years, especially having anti-inflammatory, sedative, analgesic and other ethnic pharmacological effects. Moreover, Paeoniflorin is the main active ingredient of the Paeonia lactiflora Pall, and most are used in the treatment of inflammation-related autoimmune diseases. In recent years, studies have found that Paeoniflorin has a therapeutic effect on a variety of kidney diseases. AIM OF THE STUDY:Cisplatin (CIS) is limited in clinical use due to its serious side effects, such as renal toxicity, and there is no effective method for prevention. Paeoniflorin (Pae) is a natural polyphenol which has a protective effect against many kidney diseases. Therefore, our study is to explore the effect of Pae on CIS-induced AKI and the specific mechanism. MATERIALS AND METHODS:Firstly, CIS induced acute renal injury model was constructed in vivo and in vitro, and Pae was continuously injected intraperitoneally three days in advance, and then Cr, BUN and renal tissue PAS staining were detected to comprehensively evaluate the protective effect of Pae on CIS-induced AKI. We then combined Network Pharmacology with RNA-seq to investigate potential targets and signaling pathways. Finally, affinity between Pae and core targets was detected by molecular docking, CESTA and SPR, and related indicators were detected in vitro and in vivo. RESULTS:In this study, we first found that Pae significantly alleviated CIS-AKI in vivo and in vitro. Through network pharmacological analysis, molecular docking, CESTA and SPR experiments, we found that the target of Pae was Heat Shock Protein 90 Alpha Family Class A Member 1 (Hsp90AA1) which performs a crucial function in the stability of many client proteins including Akt. RNA-seq found that the KEGG enriched pathway was PI3K-Akt pathway with the most associated with the protective effect of Pae which is consistent with Network Pharmacology. GO analysis showed that the main biological processes of Pae against CIS-AKI include cellular regulation of inflammation and apoptosis. Immunoprecipitation further showed that pretreatment with Pae promoted the Hsp90AA1-Akt protein-protein Interactions (PPIs). Thereby, Pae accelerates the Hsp90AA1-Akt complex formation and leads to a significant activate in Akt, which in turn reduces apoptosis and inflammation. In addition, when Hsp90AA1 was knocked down, the protective effect of Pae did not continue. CONCLUSION:In summary, our study suggests that Pae attenuates cell apoptosis and inflammation in CIS-AKI by promoting Hsp90AA1-Akt PPIs. These data provide a scientific basis for the clinical search for drugs to prevent CIS-AKI.

Polymer-based nanomaterials have exhibited promising alternative avenues to combat the globe challenge of multidrug-resistant bacterial infection. However, most of the reported polymeric nanomaterials have facially linear amphiphilic structures with positive net charges, which may lead to nonspecific binding, high hemolysis, and uncontrollable self-organization, limiting their practical applications. In this contribution, we report a one-dimensional glyconanorod (GNR) through self-assembly of well-defined β-cyclodextrin-based glycoconjugates (RMan) featuring hydrophobic carbon-based chains and amide rhodamines with an adenosine triphosphate (ATP)-recognition site and targeted and hydrophilic mannoses and positively net-charged ethylene amine groups. The GNRs show superior targeting sensing and killing for Gram-negative Escherichia coli (E. coli) dominantly through the multivalent recognition between mannoses on the nanorod and the lectin on the surface of E. coli. Moreover, red fluorescence was light on due to the hydrogen bonding between amide rhodamine and ATP. Benefiting from the designs, the GNRs are capable of possessing a higher therapeutic index and of encapsulating other antibiotics. They exhibit an enhanced effect against E. coli strains. Intriguingly, the GNRs displayed a more reduced hemolysis effect and lower cytotoxicity compared to that of ethylene glyco-modified nanorods. These results reveal that the glyconanomaterials not only feature superior and targeted bacterial sensing and antibacterial activity, but also better biocompatibility compared with the widely used PEG-covered nanomaterials. Furthermore, the in vivo studies demonstrate that the targeted and ATP-responsive GNRs complexed with antibiotics showed better treatment using a mouse model of abdominal sepsis following intraperitoneal E. coli infection. The present work describes a targeted and effective sensing and antibacterial platform based on glycoconjugates that have potential applications for the treatment of infections caused by pathogenic microorganisms.

目的:研究持续非卧床腹膜透析患者的营养状态的影响因素.方法:回顾性分析2019年6月-2022年4月安徽医科大学第一附属医院收治的169例CAPD患者的临床资料.运用老年营养风险指数评估患者营养状态,将其分为营养正常组及营养不良组,比较两组患者的差别,分析各个变量与营养不良的相关性,并利用多因素logistic回归分析进行结果分析.结果:通过老年营养风险指数评估结果得出营养正常组83例(49.1％),营养不良组86例(50.9％).两组年龄、血清白蛋白、血红蛋白、舒张压、碳酸氢根、尿酸、C反应蛋白、转铁蛋白饱和度水平比较,差异均有统计学意义(P<0.05).多因素分析结果显示,血清白蛋白、碳酸氢根、尿酸为营养不良发生的保护因素,年龄为营养不良发生的独立危险因素(P<0.05).结论:持续非卧床腹膜透析营养不良的发生率高,年龄是患者发生营养不良的独立危险因素,血清白蛋白、碳酸氢根、尿酸为患者发生营养不良的保护因素.

目的 探讨钙离子非依赖型磷酸酯酶A2β(iPLA2β)在高糖诱导的人肾小管上皮细胞(HK-2细胞)中的表达,iPLA2β与铁死亡的关系以及iPLA2β对高糖诱导的HK-2细胞损伤的保护机制.方法 用30 mmol/L葡萄糖刺激HK-2细胞,iPLA2β质粒转染构建过表达模型,铁死亡抑制剂Fer-rostatin-1(Fer-1)和铁死亡激活剂erastin作为铁死亡对照组.干预36 h后,试剂盒检测细胞内超氧化物歧化酶(SOD)、丙二醛(MDA)、铁含量,DCF免疫荧光检测细胞内活性氧(ROS)水平.Western blot法检测铁死亡指标ACSL4、GPX4、LPCAT3、TFR1的表达.结果 高糖刺激可以降低HK-2细胞内iPLA2β 的表达,HK-2细胞内ROS、MDA水平升高,GSH、SOD水平降低.Western blot结果显示ACSL4、LP-CAT3、TFR1表达增高,GPX4表达降低.Fer-1干预后上述指标改善.过表达iPLA2β后,可降低KIM-1表达,减轻HK-2细胞损伤.进一步研究发现,过表达iPLA2β后可抑制高糖诱导的HK-2细胞的氧化应激和铁死亡.另外,erastin减弱了iPLA2β对高糖诱导的HK-2细胞损伤的保护作用.结论 iPLA2β通过调控铁死亡减轻高糖诱导的HK-2细胞损伤.

Background End-stage renal disease (ESRD) patients have functional and structural brain abnormalities. The cerebellum also showed varying degrees of damage. However, no studies on cerebellar-cerebral functional connectivity (FC) have been conducted in ESRD patients. This study aimed to investigate the changes in cerebellar-cerebral FC in ESRD patients and its relationship with neuropsychological and clinical indexes. Methods Resting-state functional magnetic resonance imaging and neuropsychological assessment were performed on 37 ESRD patients and 35 control subjects. Seed-based FC analysis was performed to investigate inter-group differences in cerebellar-cerebral FC. In addition, the relations of altered FC with the neuropsychological function and clinical indicators were analyzed in ERSD patients. Results ESRD patients exhibited alterations in cerebellar-cerebral FC involving the executive control network, default mode network, and affective-limbic network compared to control subjects (False discovery rate-corrected, p < 0.05). The altered cerebellar-cerebral FC was associated with the Montreal Cognitive Assessment Scale score (p < 0.05), and correlated with serum creatinine and uric acid levels within the ESRD group (p < 0.05). Conclusions The study indicates that cerebellar-cerebral FC is involved in the neural substrates of cognitive impairment in ESRD patients. The findings may provide clinically relevant new neuroimaging biomarkers for the neuropathological mechanisms underlying cognitive impairment of ESRD.

目的 探究维持性腹膜透析(MPD)患者肺动脉高压(PAH)与细胞外水(ECW)/身体总水(TBW)水平的关系.方法 回顾性分析2019年5月至2022年5月安徽医科大学第一附属医院收住院的125例MPD患者临床资料,根据超声心动图检查肺动脉压力值分为PAH组(肺动脉压力≥35 mmHg)75例和非PAH组(肺动脉压力＜35 mmHg)50例,比较两组的一般资料、实验室指标、超声心动图参数、人体成分分析参数.采用线性回归分析、平滑曲线拟合、受试者工作特征(ROC)曲线等方式探讨MPD患者ECW/TBW水平与PAH的相关性.结果 PAH组和非PAH组的体重指数(BMI)、收缩压、血红蛋白(HGB)、脑钠肽(BNP)、细胞外水(ECW)/身体总水(TBW)、射血分数(EF)、左室质量分数(LVMI)差异均有统计学意义(P＜0.05).多因素logistic逐步回归分析结果显示,ECW/TBW(×10-2)[OR=1.127,95%CI:1.005～1.265,P=0.041]是MPD患者发生PAH的独立影响因素.以PAH为状态变量,ECW/TBW(×10-2)为检验变量绘制ROC曲线,ECW/TBW预测PAH发生的ROC曲线下面积为0.739,其临界点为47.1×10-2.ECW/TBW(×10-2)每升高1×10-2,PAH发生率升高12.7%.结论 MPD患者的PAH发生与容量状态关系密切,ECW/TBW水平升高可导致PAH的发生.