Chirality-Driven Orbital Angular Momentum and Circular Dichroism in CoSi.

Chiral crystals and molecules were recently predicted to form an intriguing platform for unconventional orbital physics. Here, we report the observation of chirality-driven orbital textures in the bulk electronic structure of CoSi, a prototype member of the cubic B20 family of chiral crystals. Using circular dichroism in soft x-ray angle-resolved photoemission, we demonstrate the formation of a bulk orbital-angular-momentum texture and monopolelike orbital-momentum locking that depends on crystal handedness. We introduce the intrinsic chiral circular dichroism, icCD, as a differential photoemission observable and a natural probe of chiral electron states. Our findings render chiral crystals promising for spin-orbitronics applications.

Exploration of potential biomarkers and therapeutic targets for trauma-related acute kidney injury.

PURPOSE: Acute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury. Therefore, the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis. METHODS: Qualified datasets were selected from public databases, and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction (PPI) networks. Additionally, the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility. The raw data from both datasets were downloaded using R software (version 4.2.1) and processed with the "affy" package19 for correction and normalization. RESULTS: Our analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset, along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset. Concurrently, the establishment of the PPI network and subsequent topological analysis highlighted key hub genes, including CD44, CD163, TIMP metallopeptidase inhibitor 1, cytochrome b-245 beta chain, versican, membrane spanning 4-domains A4A, mitogen-activated protein kinase 14, and early growth response 1. Notably, their receiver operating characteristic curves displayed areas exceeding 75%, indicating good diagnostic performance. Moreover, our findings postulated a unique molecular mechanism underlying trauma-related AKI. CONCLUSION: This study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI, based on the identification of potential biomarkers and therapeutic targets. Additionally, this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.

Early life adverse exposures in irritable bowel syndrome: new insights and opportunities.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder worldwide. Extensive research has identified multiple factors contributing to its development, including genetic predisposition, chronic infection, gut dysbiosis, aberrant serotonin metabolism, and brain dysfunction. Recent studies have emphasized the critical role of the early life stage as a susceptibility window for IBS. Current evidence suggests that diet can heighten the risk of IBS in offspring by influencing the microbiota composition, intestinal epithelium structure, gene expression, and brain-gut axis. The use of antibiotics during pregnancy and the neonatal period disrupts the normal gut microbiota structure, aligning it with the characteristics observed in IBS patients. Additionally, early life stress impacts susceptibility to IBS by modulating TLR4, NK1, and the hypothalamic-pituitary-adrenal (HPA) axis while compromising the offspring's immune system. Formula feeding facilitates the colonization of pathogenic bacteria in the intestines, concurrently reducing the presence of probiotics. This disruption of the Th1 and Th2 cell balance in the immune system weakens the intestinal epithelial barrier. Furthermore, studies suggest that delivery mode influences the occurrence of IBS by altering the composition of gut microbes. This review aims to provide a comprehensive summary of the existing evidence regarding the impact of adverse early life exposures on IBS during pregnancy, intrapartum, and neonatal period. By consolidating this knowledge, the review enhances our understanding of the direct and indirect mechanisms underlying early life-related IBS and offers new insights and research directions from childhood to adulthood.

Family functioning and nicotine dependence among smoking fathers: a cross-sectional study.

BACKGROUND: Nicotine dependence is a significant public health issue, and understanding the factors associated with nicotine dependence in this population is crucial for developing effective interventions. This study examined the association between family functioning and nicotine dependence levels of smoking fathers based on the McMaster model of family functioning (MMFF), providing evidence for future interventions. METHODS: In this study, we selected fathers of first- to fifth-grade students from 10 pilot elementary schools in Qingdao whose families smoked. We used the Fagerstrom test to assess nicotine dependence and the Family Assessment Device to evaluate family functioning. We performed univariate analysis to compare differences among those with different levels of nicotine dependence, and we used an ordinal logistic regression analysis to investigate the influences related to nicotine dependence. RESULTS: This study included 874 smokers, with 78.5% having mild nicotine dependence, 11.7% having moderate dependence, and 9.84% having severe dependence. Univariate analysis showed that smokers with severe dependence had lower education levels, higher prevalence of chronic diseases, more frequent alcohol consumption, and poorer family functioning compared to those with mild to moderate dependence. Ordinal logistic regression analysis showed that poorer general functioning scores (OR = 1.087, 95% CI: 1.008-1.173, P = 0.030), poorer behavioral control (OR = 1.124, 95% CI: 1.026-1.232, P = 0.012), more quit attempts, frequent alcohol consumption, and longer smoking duration may be associated with a higher likelihood of developing severe nicotine dependence. The older age of starting smoking and higher education level may be associated with a lower likelihood of developing severe nicotine dependence. However, it is important to note that the cross-sectional nature of this study precludes the determination of causal relationships. CONCLUSIONS: This study finds that heavy nicotine dependence in smoking fathers is associated with risky behaviors and demographics such as longer smoking duration and frequent alcohol consumption. Targeted smoking cessation interventions are crucial for this group, taking these specific factors into consideration. Family functioning, particularly general functioning and behavioral control, may also be linked to nicotine dependence, indicating the need for further research in this area.

Targeted VEGFA therapy in regulating early acute kidney injury and late fibrosis.

Damage to peritubular capillaries is a key process that contributes to acute kidney injury (AKI) progression. Vascular endothelial growth factor A (VEGFA) plays a critical role in maintaining the renal microvasculature. However, the physiological role of VEGFA in various AKI durations remains unclear. A severe unilateral ischemia‒reperfusion injury model was established to provide an overview of VEGFA expression and the peritubular microvascular density from acute to chronic injury in mouse kidneys. Therapeutic strategies involving early VEGFA supplementation protecting against acute injury and late anti-VEGFA treatment for fibrosis alleviation were analyzed. A proteomic analysis was conducted to determine the potential mechanism of renal fibrosis alleviation by anti-VEGFA. The results showed that two peaks of extraglomerular VEGFA expression were observed during AKI progression: one occurred at the early phase of AKI, and the other occurred during the transition to chronic kidney disease (CKD). Capillary rarefaction progressed despite the high expression of VEGFA at the CKD stage, and VEGFA was associated with interstitial fibrosis. Early VEGFA supplementation protected against renal injury by preserving microvessel structures and counteracting secondary tubular hypoxic insults, whereas late anti-VEGFA treatment attenuated renal fibrosis progression. The proteomic analysis highlighted an array of biological processes related to fibrosis alleviation by anti-VEGFA, which included regulation of supramolecular fiber organization, cell-matrix adhesion, fibroblast migration, and vasculogenesis. These findings establish the landscape of VEGFA expression and its dual roles during AKI progression, which provides the possibility for the orderly regulation of VEGFA to alleviate early acute injury and late fibrosis.

Transient upregulation of EGR1 signaling enhances kidney repair by activating SOX9+ renal tubular cells.

Background: Acute kidney injury (AKI) is associated with damage to the nephrons and tubular epithelial cells (TECs), which can lead to chronic kidney disease and end-stage renal disease. Identifying new biomarkers before kidney dysfunction will offer crucial insight into preventive and therapeutic options for the treatment of AKI. Early growth response 1 (EGR1) has been found to be a pioneer transcription factor that can sequentially turn on/off key downstream genes to regulate whole-body regeneration processes in the leopard worm. Whether EGR1 modulates renal regeneration processes in AKI remains to be elucidated. Methods: AKI models of ischemia-reperfusion injury (IRI) and folic acid (FA) were developed to investigate the roles of EGR1 in kidney injury and regeneration. To further determine the function of EGR1, Egr1-/- mice were applied. Furthermore, RNA sequencing of renal TECs, Chromatin Immunoprecipitation (ChIP) assay, and Dual-luciferase reporter assay were carried out to investigate whether EGR1 affects the expression of SOX9. Results: EGR1 is highly expressed in the kidney after AKI both in humans and mice through analysis of the Gene Expression Omnibus (GEO) database. Furthermore, we verified that EGR1 rapidly up-regulates in the very early stage of IRI and nephrotoxic models of AKI, and validation studies confirmed the essential roles of EGR1 in renal tubular cell regeneration. Further experiments affirmed that genetic inhibition of Egr1 aggravates the severity of AKI in mouse models. Furthermore, our results revealed that EGR1 could increase SOX9 expression in renal TECs by directly binding to the promoter of the Sox9 gene, thus promoting SOX9+ cell proliferation by activating the Wnt/ß-catenin pathway. Conclusions: Together, our results demonstrated that rapid and transient induction of EGR1 plays a renoprotective role in AKI, which highlights the prospects of using EGR1 as a potential therapeutic target for the treatment of AKI.

Analyzing the Local Electronic Structure of Co3O4 Using 2p3d Resonant Inelastic X-ray Scattering.

We present the cobalt 2p3d resonant inelastic X-ray scattering (RIXS) spectra of Co3O4. Guided by multiplet simulation, the excited states at 0.5 and 1.3 eV can be identified as the 4 T 2 excited state of the tetrahedral Co2+ and the 3 T 2g excited state of the octahedral Co3+, respectively. The ground states of Co2+ and Co3+ sites are determined to be high-spin 4 A 2(T d ) and low-spin 1 A 1g (Oh ), respectively. It indicates that the high-spin Co2+ is the magnetically active site in Co3O4. Additionally, the ligand-to-metal charge transfer analysis shows strong orbital hybridization between the cobalt and oxygen ions at the Co3+ site, while the hybridization is weak at the Co2+ site.

Deterministic Generation and Guided Motion of Magnetic Skyrmions by Focused He+-Ion Irradiation.

Magnetic skyrmions are quasiparticles with nontrivial topology, envisioned to play a key role in next-generation data technology while simultaneously attracting fundamental research interest due to their emerging topological charge. In chiral magnetic multilayers, current-generated spin-orbit torques or ultrafast laser excitation can be used to nucleate isolated skyrmions on a picosecond time scale. Both methods, however, produce randomly arranged skyrmions, which inherently limits the precision on the location at which the skyrmions are nucleated. Here, we show that nanopatterning of the anisotropy landscape with a He+-ion beam creates well-defined skyrmion nucleation sites, thereby transforming the skyrmion localization into a deterministic process. This approach allows control of individual skyrmion nucleation as well as guided skyrmion motion with nanometer-scale precision, which is pivotal for both future fundamental studies of skyrmion dynamics and applications.

Ketogenic diet-mediated steroid metabolism reprogramming improves the immune microenvironment and myelin growth in spinal cord injury rats according to gene and co-expression network analyses.

The ketogenic diet has been widely used in the treatment of various nervous system and metabolic-related diseases. Our previous research found that a ketogenic diet exerts a protective effect and promotes functional recovery after spinal cord injury. However, the mechanism of action is still unclear. In this study, different dietary feeding methods were used, and myelin expression and gene level changes were detected among different groups. We established 15 RNA-seq cDNA libraries from among 4 different groups. First, KEGG pathway enrichment of upregulated differentially expressed genes and gene set enrichment analysis of the ketogenic diet and normal diet groups indicated that a ketogenic diet significantly improved the steroid anabolic pathway in rats with spinal cord injury. Through cluster analysis, protein-protein interaction analysis and visualization of iPath metabolic pathways, it was determined that Sqle, Sc5d, Cyp51, Dhcr24, Msmo1, Hsd17b7, and Fdft1 expression changed significantly. Second, through weighted gene co-expression network analysis showed that rats fed a ketogenic diet showed a significant reduction in the expression of genes involved in immune-related pathways, including those associated with immunity and infectious diseases. A ketogenic diet may improve the immune microenvironment and myelin growth in rats with spinal cord injury through reprogramming of steroid metabolism.

Nomogram prediction model for renal anaemia in IgA nephropathy patients.

In this study, we focused on the influencing factors of renal anaemia in patients with IgA nephropathy and constructed a nomogram model. We divided 462 patients with IgA nephropathy diagnosed by renal biopsy into anaemic and non-anaemic groups. Then, the influencing factors of renal anaemia in patients with IgA nephropathy were analysed by least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression, and a nomogram model for predicting renal anaemia was established. Eventually, nine variables were obtained, which are easy to apply clinically. The areas under the receiver operating characteristic (ROC) curve and precision-recall (PR) curve reached 0.835 and 0.676, respectively, and the C-index reached 0.848. The calibration plot showed that the model had good discrimination, accuracy, and diagnostic efficacy. In addition, the C-index of the model following internal validation reached 0.823. Decision curve analysis suggested that the model had a certain degree of clinical significance. This new nomogram model of renal anaemia combines the basic information, laboratory findings, and renal biopsy results of patients with IgA nephropathy, providing important guidance for predicting and clinically intervening in renal anaemia.

Engineering MoxC nanoparticles confined in N,P-codoped porous carbon hollow spheres for enhanced hydrogen evolution reaction.

N,P-codoped porous carbon hollow nanosphere confining ultrafine molybdenum carbide nanoparticles are designed and prepared through a facile method. By virtue of the distinct composite and structure advantages, the resulting composite shows significantly enhanced electrocatalytic performance toward the hydrogen evolution reaction.

Synergistically enhanced hydrogen evolution reaction by ruthenium nanoparticles dispersed on N-doped carbon hollow nanospheres.

Ultrafine Ru nanoparticles dispersed on 3D N-doped carbon hollow nanospheres were firstly prepared by a feasible templating strategy. Due to the synergistic effect of the unique composite and structure, the resulting nanocomposite as a HER catalyst shows extraordinary electrocatalytic performance, superior to that of commercial Pt-C and most previously reported electrocatalysts.

Ruthenium Nanoparticles Anchored on Graphene Hollow Nanospheres Superior to Platinum for the Hydrogen Evolution Reaction in Alkaline Media.

The design and construction of highly efficient and stable Pt-free catalysts for the electrocatalytic hydrogen evolution reaction (HER) in alkaline media is extremely desirable. Herein, a novel hybrid of ruthenium (Ru) nanoparticles anchored on graphene hollow nanospheres (GHSs) is synthesized by a template-assisted strategy. The combination of ultrafine Ru nanoparticles and hollow spherical support endows the resultant Ru/GHSs an extraordinary catalytic performance with a low overpotential of 24.4 mV at a current density of 10 mA cm-2, a small Tafel slope of 34.8 mV dec-1, as well as long-term stability in 1.0 M KOH solution, which is, to our knowledge, superior to commercial 20% Pt-C catalyst and most of the state-of-the-art HER electrocatalysts reported. Remarkably, this work provides a new route for the development of other metal-based HER electrocatalysts for energy-related applications.

Diagnostic efficacy of serum anti-phospholipase A2 receptor antibodies for idiopathic membranous nephropathy in patients with diabetic kidney disease.

AIM: Serum anti-phospholipase A2 receptor (anti-PLA2R) antibodies are highly accurate in diagnosing idiopathic membranous nephropathy (IMN) in populations with kidney disease. However, the diagnostic value of anti-PLA2R antibodies for IMN in diabetic kidney disease (DKD) is unclear. The objective of this study is to determine the diagnostic efficacy and the optimal cut-off value of this marker in populations with DKD. METHODS: This study included 227 patients with type 2 diabetes who were admitted to the Department of Nephrology of the Chinese People's Liberation Army General Hospital from May 2016 to January 2018 and underwent pathological diagnosis by renal biopsy. Anti-PLA2R antibodies were detected by enzyme-linked immunosorbent assay in this population. According to the pathological results, the participants were divided into an IMN group and non-membranous nephropathy (non-MN) group. The clinical characteristics were analyzed, the diagnostic ability of anti-PLA2R antibodies was evaluated, and the receiver operating characteristic (ROC) curve was constructed to obtain the optimal cut-off value. RESULTS: There were 45 patients in the IMN group, accounting for 19.8% of the study sample. The patients in this group were older at the time of renal biopsy than the non-MN group and presented a shorter duration of diabetes, better glycemic control, lower blood pressure and uric acid, and better renal function; in addition, their clinical symptoms indicated nephrotic syndrome. The optimal cut-off value for anti-PLA2R antibodies for the diagnosis of IMN in DKD was 2.71 Ru/ml, sensitivity was 0.800, specificity was 0.951, positive predictive value was 0.800, negative predictive value was 0.951, accuracy was 0.921, and the Yoden index was 0.750. The area under the ROC curve was 0.87 (95% CI, 0.788-0.952) (p < 0.001). CONCLUSIONS: Patients in the IMN group were older, had better renal function and general condition, and the clinical symptoms indicated nephrotic syndrome. Anti-PLA2R antibodies had a good diagnostic performance for IMN in the population with DKD, and the optimal cut-off value was 2.71.

Clinical and pathological factors of renal anaemia in patients with IgA nephropathy in Chinese adults: a cross-sectional study.

OBJECTIVE: Few studies with large sample populations concerning renal anaemia and IgA nephropathy have been reported worldwide. The purpose of this cross-sectional study was to examine the clinical and pathological characteristics and influencing factors associated with renal anaemia in patients with IgA nephropathy, which is the most common aetiology of chronic kidney disease. METHODS: A total of 462 hospitalised patients with IgA nephropathy confirmed by renal biopsy who met the inclusion criteria were consecutively recruited from January 2014 to January 2016. Their general information, routine blood test results, blood chemistries, estimated glomerular filtration rates (eGFRs) and renal pathologies were collected. The Oxford classification was used to characterise the renal pathologies. Univariable and multivariate logistic regression models were used to analyse the influencing factors of anaemia associated with IgA nephropathy. RESULTS: The incidence of renal anaemia was 28.5% (132/462 patients) in our study (21.3% in males and 38.9% in females). The anaemia type was primarily normocytic and normochromic. The rate of anaemia in patients with eGFR values of 30-59 mL/min/1.73 m2 was higher than that in patients with an eGFR >60 mL/min/1.73 m2 (42.9% vs 17.8%, p<0.001). Notably, in the group with eGFR values <15 mL/min/1.73 m2, the anaemia rate was 100%. Logistic regression analysis showed that factors affecting anaemia in patients with IgA nephropathy included being female (OR 3.02, 95% CI 1.76 to 5.17), low albumin levels (OR 0.87, 95% CI 0.82 to 0.93), reduced eGFR values (OR 0.98, 95% CI 0.97 to 0.99) and renal tubulointerstitial lesions >50% (OR 2.57, 95% CI 1.22 to 5.40). CONCLUSIONS: The female sex, hypoalbuminaemia, reduced eGFR levels and severe renal tubulointerstitial lesions were correlated with renal anaemia in patients with IgA nephropathy. These results provide new insight into our understanding of anaemia in IgA nephropathy and may improve the management and treatment of clinical renal anaemia.

Protective Effects and Mechanisms of Shenhua Tablet () on Toll-Like Receptors in Rat Model of Renal Ischemia-Reperfusion Injury.

OBJECTIVES: To investigate the protective effects and potential mechanisms of Shenhua Tablet (, SHT) on the toll-like receptors (TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injury (IRI). METHODS: Sixty male Wistar rats were randomly divided into 5 groups: sham surgery, model control, astragaloside (150 mg•kg-1•d-1), low- and high-dose SHT (1.5 and 3.0 g•kg-1•d-1, repectively) groups. One week after drug treatment, rats underwent surgery to establish the IRI models. At 24 h and 72 h after the modeling, serum creatinine (Scr) and blood urea nitrogen (BUN) were analyzed; pathological damage were scored after periodic acid-Schiffstaining. TLR2, TLR4 and myeloid differentiation factor 88 (MyD88) protein and mRNA expressions were detected by inmmunohistochemistry, Western blot and qPCR. Tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) protein expressions were detected by enzyme linked immunosorbent assay. RESULTS: Compared with the sham group, the model group exhibited severe change in renal function (Scr: 189.42±21.50, P<0.05), pathological damage (damage score: 4.50±0.55, P<0.05), and the expression levels of TLR2, TLR4, MyD88, TNF-α, IL-6 were significantly higher than other groups. Meanwhile, the levels of TLRs in model group showed upward tendency from 24 to 72 h, unparalleled with pathological and functional changes. The aforementioned parameters were alleviated to a certain extent, and, in addition to TLRs, presented the obvious downward trending from the 24 to 72 h after the intervention in the SHT and astragaloside groups relative to the model (P<0.05); in particular, the most significant mitigation of these changes was observed in the SHT-H group (P<0.05). CONCLUSION: TLRs may be an important spot to treat and research in acute kidney injury. SHT could effectively mitigate renal injuries and promote recovery of IRI injuries through suppression of degeneration induced by up-regulation of TLR2 and TLR4 expression levels in the MyD88-dependent signaling pathway and exhibit some dose dependence.

Lentivirus-mediated downregulation of α-synuclein reduces neuroinflammation and promotes functional recovery in rats with spinal cord injury.

BACKGROUND: The prognosis of spinal cord injury (SCI) is closely related to secondary injury, which is dominated by neuroinflammation. There is evidence that α-synuclein aggregates after SCI and that inhibition of α-synuclein aggregation can improve the survival of neurons after SCI, but the mechanism is still unclear. This study was designed to investigate the effects of α-synuclein on neuroinflammation after SCI and to determine the underlying mechanisms. METHOD: A T3 spinal cord contusion model was established in adult male Sprague-Dawley rats. An SNCA-shRNA-carrying lentivirus (LV-SNCA-shRNA) was injected into the injury site to block the expression of α-synuclein (forming the SCI+KD group), and the SCI and sham groups were injected with an empty vector. Basso-Beattie-Bresnahan (BBB) behavioural scores and footprint analysis were used to detect motor function. Inflammatory infiltration and myelin loss were measured in the spinal cord tissues of each group by haematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining, respectively. Immunohistochemistry, Western blot analysis, and RT-qPCR were used to analyse protein expression and transcription levels in the tissues. Immunofluorescence was used to determine the morphology and function of glial cells and the expression of matrix metalloproteinase-9 in the central canal of the spinal cord. Finally, peripheral serum cytokine levels were determined by enzyme-linked immunosorbent assay. RESULTS: Compared with the SCI group, the SCI+KD group exhibited reduced inflammatory infiltration, preserved myelin, and functional recovery. Specifically, the early arrest of α-synuclein inhibited the pro-inflammatory factors IL-1ß, TNF-α, and IL-2 and increased the expression of the anti-inflammatory factors IL-10, TGF-ß, and IL-4. The neuroinflammatory response was regulated by reduced proliferation of Iba1+ microglia/macrophages and promotion of the shift of M1-polarized Iba1+/iNOS+ microglia/macrophages to M2-polarized Iba1+/Arg1+ microglia/macrophages after injury. In addition, compared with the SCI group, the SCI+KD group also exhibited a smaller microglia/astrocyte (Iba1/GFAP) immunostaining area in the central canal, lower MMP-9 expression, and improved cerebrospinal barrier function. CONCLUSION: Lentivirus-mediated downregulation of α-synuclein reduces neuroinflammation, improves blood-cerebrospinal barrier function, promotes functional recovery, reduces microglial activation, and promotes the polarization of M1 microglia/macrophages to an M2 phenotype to confer a neuroprotective immune microenvironment in rats with SCI.

Valsartan Alleviates Insulin Resistance in Skeletal Muscle of Chronic Renal Failure Rats.

BACKGROUND Studies on insulin resistance (IR) in chronic kidney disease (CKD) patients are rare, and its exact mechanism remains unclear. In this study, we explored the molecular mechanism of IR with chronic renal failure (CRF) and interventions to alleviate IR in patients with CRF. MATERIAL AND METHODS In vivo and in vitro models of CRF were established by 5/6 nephrectomy and urea stimulation C2C12 cells, respectively. Based on the CRF model, angiotensin II (Ang II) and valsartan groups were established to observe the effect of drug intervention on IR. Western blot assays were performed to detect the expression and phosphorylation of IRS-1 and Akt, which are 2 critical proteins in the insulin signaling pathway. RESULTS Both urea stimulation and 5/6 nephrectomy induced glucose uptake disorder in skeletal muscle cells (P<0.01). Skeletal muscle IR was aggravated in the Ang II group (P<0.05) but alleviated in the valsartan group (P<0.01). Regardless of the experimental method (in vivo or in vitro), tyrosine phosphorylation of IRS-1 and Akt were significantly lower (P<0.01) and serine phosphorylation was significantly higher (P<0.01) in the model group than in the sham/control group. Compared to the model group, additional Ang II aggravated abnormal phosphorylation (P<0.05); conversely, additional valsartan alleviated abnormal phosphorylation to some extent (P<0.05). CONCLUSIONS There is skeletal muscle insulin resistance in the presence of CRF. This phenomenon can be aggravated by Ang II and partially relieved by valsartan. One of the mechanisms of IR in CRF patients may be associated with the critical proteins in the IRS-PI3k-Akt pathway by changing their phosphorylation levels.

Albuminuria and Endothelial Dysfunction in Patients with Non-Diabetic Chronic Kidney Disease.

BACKGROUND Albuminuria has been associated with cardiovascular events, but whether such an association can be explained by endothelial dysfunction is not fully understood. In this study, we examined the relationship between the urine albumin-to-creatinine ratio (UACR) and biomarkers of endothelial function in patients with chronic kidney disease (CKD). MATERIAL AND METHODS The cross-sectional associations of renal dysfunction and UACR with procoagulant and inflammatory factors were evaluated for 151 consecutive CKD (stage 3-5) patients. Subjects were grouped by UACR (≤300 mg/g or >300 mg/g) and estimated glomerular filtration rate (eGFR) (30≤ eGFR <60, 15≤ eGFR <30, or eGFR <15 ml/min per 1.73 m²). RESULTS A higher UACR level was associated with an increase in von Willebrand factor antigen (vWF: Ag) levels, vWF activity, factor VIII, interleukin-2, and log (interleukin-6), even after adjustment for risk factors. Linear regression analysis indicated that for every 88.5 mg/g increase in UACR, the vWF activity and factor VIII were elevated by 8.3% and 6.3%, respectively. The factorial design ANOVA data showed no statistically significant interaction between UACR and CKD stage with procoagulant and inflammatory factors. CONCLUSIONS Our study shows an eGFR-independent association of higher UACR with elevations in markers of endothelial dysfunction and inflammatory factors in CKD patients.

Blood coagulation system in patients with chronic kidney disease: a prospective observational study.

OBJECTIVES: Thromboembolic events are the major factor affecting the prognosis of patients with chronic kidney disease (CKD). Haemostatic alterations are possible causes of these complications, but their roles remain poorly characterised. In the prospective observational study, we investigated the entire coagulation process in patients with CKD to elucidate the mechanisms of their high thromboembolic risk. METHODS: A total of 95 patients with CKD and 20 healthy controls who met the inclusion criteria were consecutively recruited from September 2015 to March 2016. The platelet count, platelet aggregation, von Willebrand factor antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), fibrinogen, factor V (FV), FVII, FVIII, antithrombin III, protein C, protein S, D-dimer, standard coagulation tests and thromboelastography were measured in patients with CKD and controls. Associations between the estimated glomerular filtration rate (eGFR) and haemostatic biomarkers were tested using multivariable linear regression. RESULTS: The adjusted and unadjusted levels of vWF:Ag, vWF:RCo, fibrinogen, FVII, FVIII and D-dimer were significantly higher in patients with CKD than that in the healthy controls, and were elevated with CKD progression. However, after adjustment for baseline differences, platelet aggregation and thromboelastography parameters showed no significant differences between patients with CKD and healthy controls. In the correlation analysis, vWF:Ag, vWF:RCo and FVIII were inversely associated with eGFR (r=-0.359, p<0.001; r=-0.391, p<0.001; r=-0.327, p<0.001, respectively). During the 1-year of follow-up, one cardiovascular event occurred in patients with CKD 5 stage, whereas no thromboembolic event occurred in the CKD 3 and 4 and control groups. CONCLUSIONS: Patients with CKD are characterised by endothelial dysfunction and increased coagulation, especially FVIII activity. The abnormal haemostatic profiles may contribute to the elevated risk of thrombotic events but further longer-term study with large samples is still required to more precisely determine the relationship between the elevation of procoagulant factors and clinical outcomes.