Skin barrier: new therapeutic targets for chronic kidney disease-associated pruritus - a narrative review.

The current incidence of chronic kidney disease-associated pruritus (CKD-aP) in patients with end-stage renal disease (ESRD) is approximately 70%, especially in those receiving dialysis, which negatively affects their work and private lives. The CKD-aP pathogenesis remains unclear, but uremic toxin accumulation, histamine release, and opioid imbalance have been suggested to lead to CKD-aP. Current therapeutic approaches, such as opioid receptor modulators, antihistamines, and ultraviolet B irradiation, are associated with some limitations and adverse effects. The skin barrier is the first defense in preventing external injury to the body. Patients with chronic kidney disease often experience itch due to the damaged skin barrier and reduced secretion of sweat and secretion from sebaceous glands. Surprisingly, skin barrier-repairing agents repair the skin barrier and inhibit the release of inflammatory cytokines, maintain skin immunity, and ameliorate the micro-inflammatory status of afferent nerve fibers. Here, we summarize the epidemiology, pathogenesis, and treatment status of CKD-aP and explore the possibility of skin barrier repair in CKD-aP treatment.

Modeling and Verification of Rolling Resistance Torque of High-Speed Rubber Track Assembly Considering Hysteresis Loss.

Due to the viscoelasticity of rubber materials, hysteresis loss due to deformation is the main reason for the rolling resistance of high-speed rubber tracks. Since the structure and material of high-speed rubber track assemblies are different from traditional tires and metal tracks, the rolling resistance theory of traditional wheeled and tracked vehicles is not applicable. Therefore, in order to determine the rolling resistance scientifically and accurately, the mechanism research of the rolling resistance of high-speed rubber track assembly is the key to the design of high-speed rubber crawler vehicles. In this paper, the stress-strain characteristics of rubber track under the action of compression, tension, bending, and driving were studied. The strain load spectrum of rubber tracks was established, and the strain cyclic load was extracted by the rainflow method. The temperature model of the rubber track was developed based on its dynamic characteristics. On the basis of energy conservation, the hysteresis loss of rubber is equivalent to the energy consumption of rolling resistance, and the theoretical model of rolling resistance of high-speed rubber track assembly is established. In accordance with the model above, the key influencing factors and changing trends of rolling resistance are analyzed, which provides a theoretical basis for the performance optimization of high-speed rubber track assembly.

A single-center cohort of mid-aortic syndrome among adults in China: Etiology, presentation and imaging features.

BACKGROUND: Mid-aortic syndrome (MAS), characterized by segmental stricture of the distal thoracic and abdominal aorta, is a heterogeneous clinical syndrome with multiple etiologies. METHODS: We retrospectively analyzed 143 consecutive patients (99 females and 44 males, mean age 40.93 ± 15.31 years) with MAS seen from January 1, 2010 to January 1, 2019. RESULTS: Takayasu arteritis (76.9%, 110/143) and atherosclerosis (19.6%, 28/143) were the most-common causes. There were also one patient with Behçet's disease and one with congenital MAS in the cohort. Hypertension was the most-common manifestation. Constitutional symptoms were mainly seen in Takayasu arteritis, and neurological, gastrointestinal and vascular symptoms were common in both Takayasu arteritis and atherosclerosis. The infrarenal segment was the most-commonly involved in atherosclerosis (89.3%, 25/28), whereas lesions were more distributed in Takayasu arteritis. The mean length of involved segments was longer (43.45 ± 23.64 mm vs. 30.68 ± 12.66 mm; P = 0.018) and the degree of stenosis was lower (80.20 ± 13.36% vs. 87.50 ± 13.95%, P = 0.004) in Takayasu arteritis than atherosclerosis. The most-common concurrently involved branch was the renal artery, followed by the celiac trunk and mesenteric arteries, in both Takayasu arteritis (51.8%, 32.7% and 27.3%, respectively) and atherosclerosis (53.6%, 25.0% and 17.9%, respectively). Concurrent artery involvement and coexisting lesions were absent in MAS caused by congenial coarctation of the abdominal aorta and Behçet's disease. CONCLUSIONS: Takayasu arteritis and atherosclerosis were the most-common causes of MAS among these adults. Imaging tests provided evidence of involved segments and luminal and mural changes, aiding conclusive diagnoses and etiological differentiation of MAS.

Preparation and In Vitro Bioactivity Study of a Novel Hollow Mesoporous Bioactive Glass Nanofiber Scaffold.

In this study, a novel three-dimensional hollow mesoporous bioactive glass nanofiber scaffold has been synthesized with a template-assisted sol-gel method using bacterial cellulose (BC) as a template and nonionic triblock copolymer (P123) as a pore-directing agent, ethyl orthosilicate (TEOS), calcium nitrate tetrahydrate (CN), and triethyl phosphate (TEP) as glass precursors. Scanning and transmission electron microscopies, X-ray diffraction, nitrogen adsorption-desorption, and nuclear magnetic resonance method were applied to characterize the morphology, crystal structure, and chemical structure of the mesoporous bioactive glass nanofiber scaffold. Furthermore, the in vitro bioactivity and biocompatibility were also explored. The obtained scaffold depicted nanofiber-like morphology and interconnected three-dimensional network structure that replicated the BC template. The scaffold showed a large specific surface area (230.0 cm2 g-1) and pore volume (0.2 m3 g-1). More importantly, the scaffold exhibited excellent apatite-forming ability and cellular biocompatibility. We believe that the hollow mesoporous bioactive glass nanofiber scaffold has great potential application in bone tissue regeneration.

The optimal exercise modality and intensity for hemodialysis patients incorporating Bayesian network meta-analysis and systematic review.

Background: Physical inactivity is highly prevalent in patients with hemodialysis, and a large body of evidence reported the positive effect of different exercise modalities on their health outcomes. However, the effective dosage of exercise for hemodialysis patients still requires verification. Objective: We aimed to determine the most effective exercise intensity and modality for improvements in physical function, blood pressure control, dialysis adequacy, and health-related quality of life for hemodialysis patients. Design: Systematic review with network meta-analysis of randomized trials. Data sources: Five electronic databases (PubMed, EMBASE, Web of Science, Cochrane CENTRAL, and Scopus) were searched for randomized controlled trials. Data extraction and quality appraisal were conducted by two authors independently. Data were analyzed by the R (version.3.6.2) and the Stata (version.15.0). Result: We included 1893 patients involving four exercise modalities and six exercise intensities. Combined training (aerobic exercise plus resistance exercise) has been the top-ranking exercise modality for improving the 6-min walk test (6MWT) (surface under the cumulative ranking curve analysis (SUCRA) score, 90.63), systolic blood pressure control (SUCRA score, 77.35), and diastolic pressure control (SUCRA score, 90.56). Moreover, the top-ranking exercise intensity was moderate-vigorous for 6MWT (SUCRA score, 82.36), systolic blood pressure (SUCRA score, 77.43), and diastolic blood pressure (SUCRA score, 83.75). Regarding dialysis adequacy and health-related quality of life, we found no exercise modality or intensity superior to the placebo. Conclusion: This network meta-analysis indicated that combined training and moderate-vigorous intensity might be the most effective interventions to improve 6MWT and blood pressure control. This finding helps further guide clinical exercise prescriptions for hemodialysis patients. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021268535].

Roxadustat Attenuates the Disruption of Epithelial Tight Junction in Caco2 Cells and a Rat Model of CKD Through MicroRNA-223.

Introduction: Increasing evidence supports the idea that the disruption of epithelial tight junction proteins (TJPs) caused by accumulation of uremia toxins, such as homocysteine (Hcy), is one of the most important mechanisms underlying the damage of intestinal barrier function (IBF) in chronic kidney disease (CKD). Since the decrease of hypoxia inducible factor-1α (HIF-1α) is reported to be involved in Hcy-induced cell injury, and the upregulation of microRNA-223 (miR-223) plays a vital protective role in the impairment of IBF in the experimental colitis, we investigated the effect of HIF-1α stabilizer roxadustat on the disruption of TJPs induced by Hcy and CKD and the underlying mechanism. Methods: Chronic kidney disease was induced in rats via 5/6 nephrectomy. In a series of experiments, the rats were treated orally with roxadustat of different doses. The expression of tight junction proteins, HIF-1α, and miR-223 was analyzed in different groups by western blotting analysis, RT-qPCR techniques and immunofluorescence. A series of experiments with cultured Caco2 cells was performed. Results: The results showed that the expression of TJPs (occludin, claudin-1, and ZO-1) decreased significantly, accompanied by the reduction of HIF-1α and miR-223 in Hcy-treated Caco2 cells and colonic mucosa of uremic rats. The reduction of HIF-1α and miR-223 was reversed by roxadustat and the decrease of TJPs expression was attenuated in both Caco2 cells induced by Hcy and colon tissue of CKD rats. Furthermore, transfection with miR-223 mimics increased the expression of TJPs, while transfection with miR-223 inhibitor decreased their expression in Caco2 cells. MiR-223 inhibitor applied before roxadustat treatment partly diminished the effect of roxadustat on TJPs expression in Caco2 cells. Conclusion: These results indicated that roxadustat attenuated the disruption of epithelial TJPs induced by Hcy in Caco2 cells and the damage of colonic epithelium in CKD rats through the upregulation of miR-223 induced by HIF-1α. A novel insight into the IBF dysfunction in CKD was provided, and it suggests a potential therapeutic use of roxadustat for the IBF dysfunction besides anemia in CKD.

Concurrent Primary Aldosteronism and Renal Artery Stenosis: An Overlooked Condition Inducing Resistant Hypertension.

To explore the clinical features of coexisting primary aldosteronism (PA) and renal artery stenosis (RAS), we retrospectively analyzed records from 71 patients with PA with RAS and a control group of 121 patients with PA without RAS. Aldosterone-to-renin concentration ratio tests and computerized tomography (CT) scanning of the adrenal and renal arteries were routinely conducted to screen for PA and RAS. Color Doppler flow and/or magnetic resonance imaging were used as substitute testing of patients for whom CT was contraindicated. Standard percutaneous renal arteriography (PTRA) was considered for patients with RAS exceeding 70% based on non-invasive tests and for those without PTRA contraindications. The patients with PA with RAS were further divided into severe (RAS>70%) and moderate (50% < RAS <70%) RAS groups. The prevalence of RAS among PA patients was 6.9% (71/1,033), including 3.2% (33/1,033) with severe RAS. Compared with the PA without RAS group, the severe RAS group showed higher levels of systolic blood pressure (SBP) (171.82 ± 18.24 vs. 154.11 ± 18.96 mmHg; P < 0.001) and diastolic BP(DBP) (110.76 ± 15.90 vs. 91.73 ± 12.85 mmHg; P < 0.001) and prevalence of resistant hypertension (RH) (90.9 vs. 66.9%; P = 0.008), whereas the moderate RAS group merely showed higher DBP (98.63 ± 14.90 vs. 91.73 ± 12.85 mmHg; P = 0.006). The direct renin concentrations (DRCs) (5.37 ± 3.94 vs. 3.71 ± 2.10 µU/mL; P < 0.001) and false-negative rate (33.8 vs. 3.3%; P < 0.01) of PA screening tests were significantly higher in the PA with RAS group than in the control group, but only in severe RAS group, in subgroup analysis. Among patients who underwent successful treatment for severe RAS, mean DRC decreased from 11.22 ± 9.10 to 3.24 ± 2.69 µIU/mL (P < 0.001). Overall, the prevalence of RH decreased from 81.7 to 2.8% (P < 0.001) when both PA and RAS were treated with standard methods. PA with concurrent severe RAS is a condition that induces RH. PA can be easily missed in patients with coexisting RAS. RAS patients with RH after successful revascularization for RAS should be evaluated for coexisting PA.

Effect of probiotics on the intestinal microbiota of hemodialysis patients: a randomized trial.

BACKGROUND: Intestinal dysbiosis contributes to the progression of renal failure and cardiovascular diseases in patients with chronic kidney disease. Probiotics is a promising intervention to improving intestinal dysbiosis. A double-blind clinical trial to investigate the ability of probiotics to modulate gut microbiota compositions in patients receiving hemodialysis (HD) was undertaken. METHODS: Fifty HD patients were enrolled and randomized, receiving either probiotics or placebo for 6 months. The responses to the interventions on gut microbiome, serum and fecal metabolome, serum albumin and endotoxin, endothelial activation markers and inflammatory markers were assessed. RESULTS: Totally, 22 in the probiotics group (11 males; 14 non-diabetic) and 23 in the placebo group (13 males; 17 non-diabetic) completed the study. Compared to that in the placebo group, probiotics did not significantly alter species diversity of the fecal microbiome. Probiotics did, however, restore the community composition, with particular significance in non-diabetic HD patients (P = 0.007 by Adonis analysis). Specifically, according to the results of linear discriminate analysis effect size, probiotics raised the proportions of family Bacteroidaceae and Enterococcaceae, and reduced Ruminococcaceae, Halomonadaceae, Peptostreptococcaceae, Clostridiales Family XIII. Incertae Sedis and Erysipelotrichaceae in non-diabetic HD patients. Additionally, probiotics reduced the abundances of several uremic retention solutes in serum or feces, including indole-3-acetic acid-O-glucuronide, 3-guanidinopropionic acid, and 1-methylinosine (P < 0.05). In the probiotic arm, no significant changes were observed in other secondary outcomes. CONCLUSIONS: Taken together, outcomes from this study suggest that probiotics do have benefits on improving intestinal imbalances and lowering exposure to several uremic toxins in HD patients.

D-site binding protein regulates cell proliferation through mediating cell cycle progression in rat mesangial cells.

Over proliferation of glomerular mesangial cells (MCs) disturbs mesangial homeostasis and leads to renal damage in mesangioproliferative glomerulonephritis. It is documented that transcriptional factors may be involved in the proliferation of MCs. This study aims to identify the key transcriptional factor that prevents the MCs from over proliferation and to clarify its regulatory mechanism. Microarray analysis of glomeruli isolated from Sprague-Dawley rats (SD rats) with or without anti-Thy1 nephritis (anti-Thy1N) showed that the cell cycle pathway was the most enriched pathway in anti-Thy1N model, and the D-site binding protein (DBP) ranked first in the cluster of transcription factors. Compare with normal rats, DBP is markedly decreased accompanied by an over proliferation of MCs in rats with anti-Thy1N. The cell proliferative capacity was measured by 5-Ethynyl-2'-deoxyuridine (EdU) assay in primary rat MCs with DBP knockdown or overexpression, respectively. The results showed that the knockdown of DBP significantly promoted the proliferation of MCs, whereas the overexpression of DBP inhibited the MCs' proliferation, compared to that of the control cells. Further study indicated that DBP arrested G1/S-phase transition by inhibiting the expression of p21, p27 and inducing the Cyclin D1 expression in MCs. The current data suggest that DBP effectively inhibits the proliferation of MCs through G1 phase arrest, and the decrease of DBP may induce mesangial over proliferation in rats with anti-Thy1N.

Homocysteine induces human mesangial cell apoptosis via the involvement of autophagy and endoplasmic reticulum stress.

Homocysteine (Hcy) level characterizes a progressive increase in chronic kidney disease (CKD). In fact, Hcy accumulation is considered to be a crucial biochemical culprit in CKD progression, but the mechanism underlying this remains poorly understood. This study investigated the role of Hcy in glomerular mesangial cell (MC) apoptosis and the potential involvement of autophagy and endoplasmic reticulum (ER) stress in this process, shedding light on Hcy toxicity in kidney disease. Human mesangial cells (HMCs) were incubated with different concentrations of Hcy for different times. Flow cytometry was used to determine the proportion of apoptotic cells and western blotting was used to analyze protein levels after the administration of Hcy, endoplasmic reticulum inhibitor 4-phenylbutyric acid (4-PBA), and Atg5 siRNA. The results demonstrated that the cell viability gradually decreased and the proportion of HMCs undergoing apoptosis increased with increasing Hcy concentration and prolonged incubation time. Meanwhile, levels of the apoptosis-related proteins Bax and cleaved caspase-3 were significantly increased, while ER stress-related proteins such as ATF4, CHOP, GRP78, and phospho-eIF2α significantly increased. Levels of cleaved LC3, and beclin1 and Atg5 proteins also increased, accompanied by p62 degradation, indicating autophagy activation. 4-PBA effectively inhibited ER stress and reversed Hcy-induced apoptosis and autophagy. Moreover, Atg5 siRNA alleviated Hcy-induced apoptosis. Taken together, these results suggest that Hcy induces HMC apoptosis in a dose- and time-dependent manner via the activation of Atg5-dependent autophagy triggered by ER stress. This study suggests a novel strategy against Hcy toxicity in kidney injury and should help in clarifying the pathogenesis of CKD.

[Application evaluation of failure mode and effect analysis in optimization of vascular recanalization process].

OBJECTIVE: To investigate the clinical application and effect evaluation of failure mode and effect analysis (FMEA) in the optimization of vascular recanalization in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 389 STEMI patients admitted to the emergency department of the Fifth Central Hospital in Tianjin from January 2014 to January 2015 were served as the control group, and 398 STEMI patients admitted to the chest pain center of the Fifth Central Hospital in Tianjin from January 2016 to October 2017 were served as the experimental group. In the control group, routine emergency treatment was used. At the same time, the intervention room was 24-hour prepared for emergency vascular recanalization. The experimental group used FMEA. Through the usage of FMEA, the main factors those caused the delay in revascularization treatment were determined, and the revascularization process was optimized for these influencing factors, thereby shortening the "criminal" blood vessel opening time of patients. The door-to-balloon dilatation time (D-to-B time), troponin testing time, placement time of the catheterization room, initiation of the catheterization room to balloon dilatation time, and preoperative and 1 week postoperative N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, heart function parameters [left ventricular ejection fraction (LVEF), left ventricular short axis shortening rate (FS), left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD)] within 1 week, 3 months and 6 months after intervention, and the incidence of main cardiovascular adverse events within 1 month after intervention, hospital mortality, the length of hospital stay, and readmission within 1 year in the patients of two groups were recorded. RESULTS: D-to-B time (minutes: 70.6±3.6 vs. 79.4±8.7), troponin testing time (minutes: 17.1±2.3 vs. 65.2±6.5), placement time of the catheterization room (minutes: 28.9±9.8 vs. 52.3±12.2) and activation of the catheterization room to balloon expansion time (minutes: 47.3±9.3 vs. 65.1±7.2) in the experimental group were significantly shorter than those in the control group (all P < 0.01). The NT-proBNP levels at 1 week after intervention in the two groups were lower than the preoperative levels, slightly lower in the experimental group, but the difference was not statistically significant. There was no significant difference in cardiac function at 1 week and 3 months after intervention between the two groups. The LVEF and FS at 6 months after intervention in the experimental group were significantly higher than those in the control group [LVEF: 0.622±0.054 vs. 0.584±0.076, FS: (38.1±4.3)% vs. (35.4±6.2)%, both P < 0.01], and LVESD and LVEDD were decreased significantly [LVESD (mm): 31.2±3.8 vs. 34.7±4.2, LVEDD (mm): 49.2±5.3 vs. 52.4±5.6, all P < 0.01]. The length of hospital stay in the experimental group was significantly shorter than that in the control group (days: 8.3±3.2 vs. 13.2±6.8, P < 0.01), the incidence of major cardiovascular adverse events within 1 month after intervention [13.6% (54/398) vs. 19.8% (77/389)], hospital mortality [1.8% (7/398) vs. 4.9% (19/389)], and readmission rate within 1 year [9.5% (38/398) vs. 14.5% (56/389)] in the experimental group were significantly lower than those in the control group (all P < 0.05). CONCLUSIONS: The usage of FMEA to optimize the vascular recanalization procedure can shorten the emergency treatment time of STEMI patients, reduce the occurrence of adverse events, and improve the prognosis.

Liquid Chromatography/Mass Spectrometry Reveals the Effect of Lactobacillus Treatment on the Faecal Metabolite Profile of Rats with Chronic Renal Failure.

BACKGROUND/AIM: Chronic kidney disease is accompanied by changes in the gut microbiome and by an increase in the number of gut pathogenic bacteria. The aim of this study was to investigate the difference of the faecal metabolic profiles in rats with uremia, and to determine whether the altered metabolites in the rats with uremia can be restored by Lactobacillus. METHODS: Thirty rats were randomly divided into 3 groups: sham, uremia and uremia + probiotic (UP) groups. The rats in uremia and UP groups were prepared through surgical renal mass 5/6 ablation. The rats in the UP group received Lactobacillus LB (1 ml, 109 CFU/ml) through gavage every day for 4 weeks. The rats were fed with a standard diet. Faecal samples were analysed through ultra performance liquid chromatography/mass spectrometry. Statistical analyses were performed using MetaboAnalyst and MATLAB. RESULTS: A total of 99, 324 and 177 significantly different ion peaks were selected between sham and uremia groups; sham and UP groups; and uremia and UP groups, respectively. In the 3 groups, 35 significantly altered metabolites were identified; of the 35 metabolites, 27 initially increased and then decreased; by contrast, 8 metabolites initially decreased and then increased. The 35 metabolites were subjected to pathway analysis in MetaboAnalyst. CONCLUSIONS: Faecal metabolites were significantly altered in rats with uremia; these changes were partially reversed by Lactobacillus.

[Plasma scavenger receptor BI and CD36 expression change and susceptibility of atherosclerosis in patients post liver transplantation].

OBJECTIVE: To explore the association between expression changes of plasma macrophages scavenger receptor (SR)-BI and CD36 and risk of arteriosclerosis in end-stage liver disease (ESLD) patients post liver transplantation. METHODS: A total of 20 liver transplantation patients were included. Clinical data including blood pressure, blood lipid, blood glucose, incidence of new-onset cardiovascular events were obtained. Plasma macrophages scavenger receptor SR-BIand CD36 expressions were detected by polymerase chain reaction (RT-PCR) and Western-blot before and at 1 year after liver transplantation. RESULTS: The serum levels of TC [(5.34 ± 0.87) mmol/L vs. (4.27 ± 0.91) mmol/L], TG [(2.47 ± 0.81) mmol/L vs. (1.02 ± 0.49) mmol/L] and LDL-C [(3.36 ± 0.67) mmol/L vs. (2.14 ± 0.74) mmol/L] were significantly increased (P < 0.05) while the serum level of HDL-C [(0.98 ± 0.84) mmol/L vs. (1.58 ± 0.34) mmol/L] was significantly reduced (P < 0.05) at 1 year post transplantation compared to before-transplantation levels. One patient developed non-ST segment elevation myocardial infarction and treated with percutaneous coronary intervention, another patient developed atrial fibrillation at one year after transplantation. The plasma mRNA expression of SR-BI was reduced (20.44 ± 0.60 vs. 23.12 ± 0.69, P < 0.05) while the expression of CD36 mRNA was upregulated (20.91 ± 0.35 vs. 18.55 ± 0.62, P < 0.05) at 1 year after liver transplantation compare with that of before the transplantation. Similarly, the plasma protein expression of SR-BIwas reduced (0.21 ± 0.13 vs. 0.64 ± 0.28, P < 0.05) while the protein expression of CD36 was upregulated (0.94 ± 0.13 vs. 0.42 ± 0.19, P < 0.05) at 1 year after liver transplantation compare with that of before the transplantation. CONCLUSION: Plasma expression changes of SR-BI and CD36 might contribute to the dyslipidemia and contribute to the atherosclerosis susceptibility after liver transplantation.