Investigation of the effect and mechanism of nanocellulose on soy protein isolate- konjac glucomannan composite hydrogel system.

To enrich the application of nanocomposite hydrogels, we introduced two types of nanocellulose (CNC, cellulose nanocrystals; CNF, cellulose nanofibers) into the soy protein isolate(SPI)- konjac glucomannan (KGM) composite hydrogel system, respectively. The similarities and differences between the two types of nanocellulose as textural improvers of composite gels were successfully explored, and a model was developed to elaborate their interaction mechanisms. Appropriate levels of CNC (1.0 %) and CNF (0.75 %) prolonged SPI denaturation within the system, exposed more buried functional groups, improved molecular interactions, and strengthened the honeycomb structural skeleton formed by KGM. The addition of CNC resulted in greater gel strength (SKC1 2708.53 g vs. Control 810.35 g), while the addition of CNF improved the elasticity (SKF0.75 1940.24 g vs. Control 405.34 g). This was mainly attributed to the reinforcement of the honeycomb-structured, water binding and trapping, and the synergistic effect of covalent (disulfide bonds) and non-covalent interactions (hydrogen bonds, ionic bonds) within the gel network. However, the balance and interactions between proteins and polysaccharides were disrupted in the composite system with excessive CNF addition (≥0.75 %), which broken the stability of the honeycomb-like structure. We expect this study will draw attention on potential applications of CNC and CNF in protein-polysaccharide binary systems and facilitate the creation of novel, superior, mechanically strength-regulated nanofiber composite gels.

Effect of ultrasound treatment on thawing process of frozen tofu prepared with different salt coagulants.

This study investigated the effects of ultrasound-assisted water thawing (UWT) at different power levels (0, 100, 150, 200, and 250 W) on the thawing rate and gel properties of frozen tofu made using three different salt coagulants (CaCl2, CaSO4, and MgCl2). Tofu produced with CaCl2 and CaSO4 elicited gel structures with dense and homogeneous networks, while that with MgCl2 had rough pores and irregular networks. UWT treatment significantly decreased thawing time by 30.9-53.5% compared to the control. Water holding capacity and scanning electron microscopy analyses demonstrated that UWT-100, UWT-150, and UWT-200 should be used to increase the amount of fixed water for CaCl2, CaSO4, and MgCl2. These findings suggest that appropriate ultrasonic treatment could improve the water retention capacity of the tofu network and make the gel network structure more compact. Additionally, protein structural analysis showed a decrease in the exposure of hydrophobic groups and reduced protein denaturation when tofu prepared with all the coagulants were thawed with UWT energies of 100-200 W ultrasonication. These findings offer theoretical support for improving the frozen tofu thawing process while ensuring optimal final product quality.

Integrated Design from Microstructural Engineering to Binder Optimization Enabling a Practical Carbon Anode with Ultrahigh ICE and Efficient Potassium Storage.

Potassium-ion batteries (PIBs) are emerging as a powerful alternative to lithium-ion battery systems in large-scale energy storage owing to plentiful resources. Nevertheless, pursuing high-yield anode materials with high initial Coulombic efficiency (ICE) and superior rate capability is still one of the most critical challenges in practical application. Herein, an integrated electrode (PC-x) derived from a petroleum coke precursor (carbon residue rate as high as 89%) is regulated from microstructural engineering to binder optimization devoting to high ICE and efficient potassium storage. Excitingly, with a strong assist from a sodium carboxymethyl cellulose (CMC) binder, the PC-900 anode displays an ultrahigh ICE of 80.5%, one of the highest values reported for PIB carbon anodes. Simultaneously, the PC-900 anode submits a high capacity (304.3 mAh g-1), superb rate (138.2 mAh g-1 at 10C), and excellent stability. Furthermore, the full cell exhibits an outstanding rate and cycling performance (210.7 mAh g-1 at 0.5C), confirming its large-scale application prospects. The ultrahigh ICE and excellent performance are mainly attributable to the beneficial microstructures (low surface area, functional group content, and larger interlayer spacing) created by microstructural engineering. Meanwhile, binder optimization also plays a crucial role in reducing the irreversible capacity and interface impedance, further improving the ICE and rate capability. Importantly, mechanism analysis confirms two-stage K+ storage behavior: reversible adsorption at edges and defects (>0.25 V) and intercalation into crystalline layers (<0.25 V). This work provides an efficient and easily scalable electrode design strategy for future practical applications of PIBs.

Plasma Donor-Derived Cell-Free DNA Levels Are Associated With the Inflammatory Burden and Macrophage Extracellular Trap Activity in Renal Allografts.

Recent studies have confirmed the role of plasma donor-derived cell-free DNA (ddcfDNA) as a reliable non-invasive biomarker for allograft injury after kidney transplantation. Whereas the variability of plasma ddcfDNA levels among recipients has limited their clinical use. This study aimed to explore the intrinsic factors associated with plasma ddcfDNA elevation by investigating the impact of Banff lesions and inflammatory infiltrates on ddcfDNA levels in kidney transplant recipients. From March 2017 to September 2019, a total of 106 kidney transplant recipients with matched allograft biopsies were included, consisting of 13 recipients with normal/nonspecific changes, 13 recipients with borderline changes, 60 with T cell-mediated rejection, and 20 with antibody-mediated rejection. Histologic classification was performed according to the Banff 2017 criteria by two experienced pathologists. Plasma ddcfDNA fractions ranged from 0.12% to 10.22%, with a median level of 0.91%. Banff histology subelements including glomerulitis, intimal arteritis, and severe interstitial inflammation were correlated with increased plasma ddcfDNA levels. The inflammatory cell infiltrate in the allografts was phenotyped by immunochemistry and automatically counted by digital image recognition. Pearson correlation analysis revealed a significant positive correlation between macrophage infiltrations in allografts and plasma ddcfDNA levels. Additionally, macrophage extracellular trap (MET) activity was significantly associated with the rise in plasma ddcfDNA levels. Our findings demonstrated that plasma ddcfDNA could reflect the inflammatory state in renal allografts and suggested the potential role of METs in the pathogenesis of allograft injury.

Association of serum levels of calcium, phosphate, and vitamin D with risk of developing aortic stenosis: the UK Biobank cohort.

AIMS: This study was aimed to investigate the associations of serum calcium, phosphate, and vitamin D levels with the risk of developing aortic stenosis (AS). METHODS AND RESULTS: We included 296 415 participants who were free of prior diagnosis of any valvular heart disease from the UK Biobank. Serum levels of phosphate, calcium, and vitamin D were measured. Incidental AS was determined by the records of hospital data. Cox regression was used to examine the association of serum mineral levels with incidental AS after adjustment for potential confounders. The mean age was 56.4 years (SD 8.14) and 53.3% of participants were women. During an average follow-up of 8.1 years, 1232 individuals developed AS. After adjustment, each 0.5-unit increase in serum phosphate level was associated with a 50% increase of AS risk (hazard ratio 1.50, 95% confidence interval 1.26-1.80). We observed no association of serum calcium and vitamin D levels with AS. CONCLUSION: Increased serum phosphate level, but not calcium or vitamin D, was associated with a higher risk of incident AS, this association did not differed substantially between patients with and without decreased kidney function. This finding implied that phosphate may be a potential interventional target for AS.

Urinary donor-derived cell-free DNA as a non-invasive biomarker for BK polyomavirus-associated nephropathy.

BK polyomavirus-associated nephropathy (BKPyVAN) is a common cause of allograft failure. However, differentiation between BKPyVAN and type I T cell-mediated rejection (TCMR) is challenging when simian virus 40 (SV40) staining is negative, because of the similarities in histopathology. This study investigated whether donor-derived cell-free DNA (ddcfDNA) can be used to differentiate BKPyVAN. Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function, 22 with type I TCMR, 21 with proven BKPyVAN, and 5 with possible PyVAN. We found that urinary ddcfDNA levels were upregulated in recipients with graft injury, whereas plasma ddcfDNA levels were comparable for all groups. The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients (10.4 vs. 6.1 ng/mL, P<0.001 and 68.4% vs. 55.3%, P=0.013, respectively). Urinary ddcfDNA fractions (not concentrations) were higher in the BKPyVAN-pure subgroup than in the BKPyVAN-rejection-like subgroup (81.30% vs. 56.64%, P=0.025). With a cut-off value of 7.81 ng/mL, urinary ddcfDNA concentrations distinguished proven BKPyVAN from type I TCMR (area under the curve (AUC)=0.848, 95% confidence interval (95% CI): 0.734 to 0.963). These findings suggest that urinary ddcfDNA is a non-invasive biomarker which can reliably differentiate BKPyVAN from type I TCMR.

Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in Mice.

BACKGROUND: After myocardial infarction, anti-inflammatory macrophages perform key homeostatic functions that facilitate cardiac recovery and remodeling. Several studies have shown that lactate may serve as a modifier that influences phenotype of macrophage. However, the therapeutic role of sodium lactate in myocardial infarction (MI) is unclear. METHODS: MI was established by permanent ligation of the left anterior descending coronary artery followed by injection of saline or sodium lactate. Cardiac function was assessed by echocardiography. The cardiac fibrosis area was assessed by Masson trichrome staining. Macrophage phenotype was detected via qPCR, flow cytometry, and immunofluorescence. Signaling proteins were measured by Western blotting. RESULTS: Sodium lactate treatment following MI improved cardiac performance, enhanced anti-inflammatory macrophage proportion, reduced cardiac myocytes apoptosis, and increased neovascularization. Flow-cytometric analysis results reported that sodium lactate repressed the number of the IL-6+, IL-12+, and TNF-α+ macrophages among LPS-stimulated bone marrow-derived macrophages (BMDMs) and increased the mRNA levels of Arg-1, YM1, TGF-ß, and IL-10. Mechanistic studies revealed that sodium lactate enhanced the expression of P-STAT3. Furthermore, a STAT3 inhibitor eliminated sodium lactate-mediated promotion macrophage polarization. CONCLUSION: Sodium lactate facilitates anti-inflammatory M2 macrophage polarization and protects against MI by regulating P-STAT3.

Activating transcription factor 4 regulates angiogenesis under lipid overload via methionine adenosyltransferase 2A-mediated endothelial epigenetic alteration.

Lipid overload is intimately connected with the change of endothelial epigenetic status which impacts cellular signaling activities and endothelial function. Activating transcription factor 4 (ATF4) is involved in the regulation of lipid metabolism and meanwhile an epigenetic modifier. However, the role of ATF4 in the angiogenesis under lipid overload is not well understood. Here, to induce lipid overload status, we employed high-fat diet (HFD)-induced obese mouse model in vivo and palmitic acid (PA) to stimulate endothelial cells in vitro. Compared with mice fed with normal chow diet (NCD), HFD-induced obese mice showed angiogenic defects evidenced by decline in (1) blood flow recovery after hind limb ischemia, (2) wound healing speed after skin injury, (3) capillary density in injured tissues and matrigel plugs, and (4) endothelial sprouts of aortic ring. ATF4 deficiency aggravated above angiogenic defects in mice while ATF4 overexpression improved the blunted angiogenic response. Mechanistically, lipid overload lowered the H3K4 methylation levels at the regulatory regions of NOS3 and ERK1 genes, leading to reduced angiogenic signaling activity. Methionine adenosyltransferase 2A (MAT2A) is identified as a target of ATF4 and formed complex with ATF4 to direct lysine methyltransferase 2A (MLL1) to the regulatory regions of both genes for the maintenance of the H3K4 methylation level and angiogenic signaling activity. Here, we uncovered a novel metabolic-epigenetic coupling orchestrated by the ATF4-MAT2A axis for angiogenesis. The ATF4-MAT2A axis links lipid overload milieu to altered epigenetic status of relevant angiogenic signaling in endothelial cells, suggesting a potential therapeutic target for angiogenesis impaired by lipid overload.

The clinicopathological features of drug-induced acute kidney injury-a single-center retrospective analysis.

BACKGROUND: This study aimed to analyze changes to the drug spectrum and clinicopathological features of drug-induced acute kidney injury (AKI) with recent medication habits changes. METHODS: A retrospective analysis of the characteristics of patients diagnosed with drug-induced AKI from January 2012 to October 2016 period at the First Affiliated Hospital of the Medical College of Zhejiang University was conducted. RESULTS: Between January 2012 and October 2016, 909 patients were diagnosed with AKI. Of these, 228 were diagnosed with drug-related AKI were engaged in this study, including 51 who underwent renal biopsies, 74 treated with antibacterial and antiviral drugs, and 63 who received nonsteroidal anti-inflammatory drugs (NSAIDs), and 17 who were treated with Chinese herbal medicine. AKI was most frequently associated with antibiotics and antiviral drugs, including cephalosporins, acyclovir, azithromycin, clindamycin, and levofloxacin. In those who underwent renal biopsy, 12 patients were diagnosed with allergic interstitial nephritis, 19 with interstitial nephritis, 8 with renal tubular epithelial cell injury, 2 with minimal change nephropathy, 2 with IgA nephropathy, and 2 with mild mesangial hyperplasia with glomerulosclerosis. The mean follow-up time was 437 days, ranging from 3 to 2,756 days. Among 228 patients, 165 recovered completely, 4 recovered partially, 8 did not recover, and 51 were lost to follow-up after discharge. CONCLUSIONS: The three main contributors to drug-induced AKI were antimicrobial agents, NSAIDs, and Chinese herbal medicines. The age distribution of the three different drug-induced AKI groups was significantly different. Allergic interstitial nephritis, interstitial nephritis, and tubular epithelial cell injury were the main pathological manifestations of drug-induced AKI. The novel predictive nomogram achieved a good performance of prediction recovery within 2 weeks in drug-induced AKI patients.

MARCH5 restores endothelial cell function against ischaemic/hypoxia injury via Akt/eNOS pathway.

MARCH5 is a critical regulator of mitochondrial dynamics, apoptosis and mitophagy. However, its role in cardiovascular system remains poorly understood. This study aimed to investigate the role of MARCH5 in endothelial cell (ECs) injury and the involvement of the Akt/eNOS signalling pathway in this process. Rat models of myocardial infarction (MI) and human cardiac microvascular endothelial cells (HCMECs) exposed to hypoxia (1% O2 ) were used in this study. MARCH5 expression was significantly reduced in ECs of MI hearts and ECs exposed to hypoxia. Hypoxia inhibited the proliferation, migration and tube formation of ECs, and these effects were aggravated by knockdown of MARCH5 but antagonized by overexpressed MARCH5. Overexpression of MARCH5 increased nitric oxide (NO) content, p-eNOS and p-Akt, while MARCH5 knockdown exerted the opposite effects. The protective effects mediated by MARCH5 overexpression on ECs could be inhibited by eNOS inhibitor L-NAME and Akt inhibitor LY294002. In conclusion, these results indicated that MARCH5 acts as a protective factor in ischaemia/hypoxia-induced ECs injury partially through Akt/eNOS pathway.

Prognostic value of the donor-derived cell-free DNA assay in acute renal rejection therapy: A prospective cohort study.

Donor-derived cell-free DNA (dd-cfDNA) is a promising biomarker for monitoring allograft status. However, whether dd-cfDNA can reflect real-time anti-rejection treatment effects remains unclear. We prospectively recruited 28 patients with acute renal rejection, including 5 with ABMR, 12 with type IA or type IB rejection, and 11 with type IIA or IIB rejection. dd-cfDNA levels in peripheral blood were measured using human single nucleotide polymorphism (SNP) locus capture hybridization. The percentage of dd-cfDNA (dd-cfDNA%) declined significantly from 2.566 ± 0.549% to 0.773 ± 0.116% (P < .001) after anti-rejection therapy. The dd-cfDNA% decreased steadily over the course of 3 days with daily methylprednisolone injections, but no significant difference in the dd-cfDNA% was observed between the end of anti-rejection therapy and 2 weeks later. Changes in the dd-cfDNA% (∆dd-cfDNA%) demonstrated a positive correlation with estimated glomerular filtration rates at 1 month (ρ = 2.570, P = .022), 3 months (ρ = 3.210, P = .027), and 6 months (ρ = 2.860, P = .019) after therapy. Thus, the dd-cfDNA assay shows prognostic capabilities in therapy outcome and allograft recovery; however, its ability is inhibited by methylprednisolone regardless of the types of rejection. Additionally, a reassessment of frequency intervals for testing is required.

Impact of initial dialysis modality on the survival of patients with ESRD in eastern China: a propensity-matched study.

BACKGROUND: There are conflicting research results about the survival differences between hemodialysis(HD) and peritoneal dialysis (PD). The present study estimated the survival and the relative mortality hazard for incident HD and PD patients with end stage renal disease (ESRD) in eastern China. METHODS: This study examined a cohort of patients with ESRD who initiated dialysis therapy in Zhejiang province between Jan of 2010 and Dec of 2014, followed up until the end of 2015. PD patients were matched in a 1:1 fashion with HD patients, and Kaplan-Meier analysis was used to explore the survival of them. The Cox proportional hazard regression model was applied to identify the factors that predict survival by treatment modality. Subgroup analyses were conducted by stratifying patients according to gender, age, causes of ESRD and comorbidities. RESULTS: Among a total of 22,379 enrolled patients (17,029 HD patients and 5350 PD patients), 5350 matched pairs were identified, and followed for a median of 29 months (3 ~ 72 months). Kaplan-Meier survival curve revealed that overall mortality rate was significantly higher in HD patients than in PD patients (log-rank test, P < 0.001), after adjusting by gender, age, primary causes of ESRD and comorbidities. HD was consistently associated with an increased risk for morality compared with PD in the matched cohort (adjusted hazard ratio (AHR): 1.140, 95%CI: 1.023 ~ 1.271). In subgroup analyses, male, younger patients, or nondiabetic patients aged less than 65 years after adjustment of covariates, initiating with PD was associated with a significantly lower mortality compared with HD. In the multivariate Cox proportional risks model, age, diabetic nephropathy (DN), other/unknown causes of ESRD, and patients with a history of cardiovascular disease or cancer showed statistical significance in explaining survival of incident ESRD patients. CONCLUSIONS: ESRD patients who initiated dialysis with PD yielded superior survival rates compared to HD. Increased use of PD as initial dialysis modality in ESRD patients could be encouraged in Chinese population.

ABO-incompatible living kidney transplantation.

ABO-incompatible living kidney transplantation is nowadays a routine procedure to expand living donor pool. The past decades have seen the evolution of desensitization protocol and immunosuppression regimen. Despite increased bleeding events, infectious complications, and rejection episodes reported in some studies, favorable graft and patient survival rate are now achieved, regardless of various protocols among transplant centers. Several issues such as the usage of rituximab and standardization of blood group antibody titration remain to be settled. The deposition of C4d is no longer the histopathologic hallmark of antibody-mediated rejection, which have inspired innovative strategies of peripheral molecular screening and the improvement of histological diagnosis of AMR (antibody-mediated rejection). The better understanding of the underlying mechanism might facilitate the distinction and therapeutic schemes of AMR.

Kidney transplantation from small pediatric donors may be feasible to those who developed chronic refractory dialysis hypotension: a single-center experience.

BACKGROUND: Chronic refractory dialysis hypotension (CRDH) is a serious issue in dialysis patients waiting for transplants. It leads to fatal clinical outcomes and disqualification from kidney transplantation. Kidney transplantation from pediatric donor to adult patient with lower blood pressure (BP) may be an option. No related study has been reported and we conducted this study to first evaluate the effect of pediatric donor kidney transplantation in CRDH recipients. METHODS: Ten single-kidney transplantations from small pediatric donors after cardiac death in our center between August 2016 and April 2018 were described. Half were CRDH recipients (group A) with intradialytic and interdialytic systolic blood pressure (SBP) below 100 mmHg. Each was paired with no-CRDH recipient (control, group B) from the same donor. The operation method of vascular anastomosis and ureterocystoneostomy was the same as that of adult donors. Clinical characteristics, post-operative treatment and outcomes of all recipients were retrieved. Postoperative BP, graft function and size were compared between two groups. The follow-up time was up to April 2019. RESULTS: There was no acute rejection (AR), graft loss or death in all recipients after transplantation. Their renal function was recovered despite three transient delayed graft function (DGF). There was no significant difference in serum creatinine (SCr) or graft size (P=0.84, 0.94) after transplantation between two groups. For all CRDH recipients, the postoperative SBP was above 100 mmHg (except one, 90-130 mmHg). The BP one year after transplantation was maintained at 110-125/70-85 mmHg. CONCLUSIONS: kidney transplantation from small pediatric donors may be feasible to CRDH recipients and their BP may return to normal after transplantation.

The relationship between hemodialysis mortality and the Chinese medical insurance type.

Objectives: In China, there are two major medical insurance models: the Urban Basic Medical Insurance (UBMI) and the New Cooperative Medical Scheme (NCMS). The aim of the present study was to evaluate the association of the medical insurance type of patients undergoing hemodialysis (HD) with their survival.Methods: We retrospectively analyzed the end-stage renal disease adult patients initiating HD between January 2010 and December 2014 in Zhejiang province, followed up through 31 December 2015. Patients who had received HD for over 3 months were separated into two groups, based on different medical insurance type. Demographic, clinical data, and clinical outcomes were analyzed. The survival rates were calculated by using the Kaplan-Meier method.Results: A total of 6779 patients (59 ± 16 years old, 4331 males (63.9%)) with UBMI and 7177 (59 ± 16 years old, 3778 males (52.8%)) with NCMS enrolled from 226 hemodialysis units. Compared with UBMI group, patients with NCMS had a smaller percentage of hypertensive nephropathy, diabetes mellitus and arteriovenous fistula, faced with more problems in anemia, hypoalbuminemia and metabolism of calcium and phosphorous. The 1-, 3- and 5-year survival rates were 95.4, 84.4, and 74.1% in UBMI group, 93.1, 79.7, and 67.7% in NCMS group, respectively. Patients with NCMS showed higher all-cause mortality compared with UBMI (p < 0.001). In multivariate Cox proportional hazards model, NCMS was independently associated with higher mortality (AHR = 1.53; 95% CI 1.38 ∼ 1.68).Conclusions: The medical insurance model was independently associated with HD patient survival, NCMS was associated with increased mortality among patients undergoing maintenance hemodialysis in China.

Transcatheter Aortic Valve Replacement in Patients with Aortic Stenosis Having Coronary Cusp Fusion versus Mixed Cusp Fusion Nonraphe Bicuspid Aortic Valve.

OBJECTIVES: We aimed to assess the procedural and clinical results of transcatheter aortic valve replacement (TAVR) for nonraphe bicuspid aortic stenosis (AS) with coronary vs mixed cusp fusion. BACKGROUND: It remains unclear whether cusp fusion morphology affects TAVR outcomes in patients with nonraphe bicuspid AS. METHODS: This retrospective study enrolled consecutive patients with severe symptomatic AS and type-0 bicuspid aortic valve, who underwent TAVR at our institution between 2012 and 2017. TAVR outcomes were defined based on the Valve Academic Research Consortium-2 recommendations. RESULTS: Compared to patients with mixed cusp fusion (44/71), those with coronary cusp fusion (27/71) had a larger ellipticity index for the aortic annulus (21.9% ± 9.0% vs 15.6% ± 9.3%, p=0.007) and increased left ventricular outflow tract obstruction (31.1% ± 9.4% vs 26.9% ± 7.5%, p=0.04) but comparable rates of second valve implantation (15.9% vs 14.8%), mild paravalvular leakage (PVL, 38.5% vs 30.2%), permanent pacemaker implantation (PPM, 25.9% vs 15.9%), and 30-day mortality (7.4% vs 6.8%). Use of a first-generation transcatheter heart valve was associated with higher risk for mild PVL (odds ratio (OR) = 4.37; 95% confidence interval (95% CI) = 1.14-16.75; p=0.03) but not PPM (OR = 0.77; 95% CI = 0.22-2.62; p=0.67), whereas a larger oversizing ratio tended to be associated with a higher PPM rate (OR = 1.49; 95% CI = 0.46-4.86; p=0.51) but lower incidence of mild PVL (OR = 0.51; 95% CI = 0.19-1.35; p=0.17). CONCLUSIONS: In AS patients with type-0 bicuspid valves, cusp fusion morphology does not affect the procedural or clinical results of TAVR. Use of second-generation transcatheter heart valves may provide more favorable results in such patients. This trial is registered with NCT01683474.

The relationship between hemodialysis mortality and the Chinese medical insurance type.

Objective: In China, there are two major medical insurance models: the Urban Basic Medical Insurance (UBMI) and the New Cooperative Medical Scheme (NCMS). The aim of the present study was to evaluate the association of the medical insurance type of patients undergoing hemodialysis (HD) with their survival. Methods: We retrospectively analyzed the end-stage renal disease adult patients initiating HD between January 2010 and December 2014 in Zhejiang province, followed up through 31 December 2015. Patients who had received HD for over 3 months were separated into two groups, based on different medical insurance type. Demographic, clinical data, and clinical outcomes were analyzed. The survival rates were calculated by using the Kaplan-Meier method. Results: A total of 6779 patients (59 ± 16 years old, 4331 males (63.9%)) with UBMI and 7177 (59 ± 16 years old, 3778 males (52.8%)) with NCMS enrolled from 226 hemodialysis units. Compared with UBMI group, patients with NCMS had a smaller percentage of hypertensive nephropathy, diabetes mellitus and arteriovenous fistula, faced with more problems in anemia, hypoalbuminemia and metabolism of calcium and phosphorous. The 1-, 3- and 5-year survival rates were 95.4%, 84.4%, and 74.1% in UBMI group, 93.1%, 79.7%, and 67.7% in NCMS group, respectively. Patients with NCMS showed higher all-cause mortality compared with UBMI (p < .001). In multivariate Cox proportional hazards model, NCMS was independently associated with higher mortality (AHR = 1.53; 95% CI 1.38 ∼ 1.68). Conclusions: The medical insurance model was independently associated with HD patient survival, NCMS was associated with increased mortality among patients undergoing maintenance hemodialysis in China.

The bifunctional SDF-1-AnxA5 fusion protein protects cardiac function after myocardial infarction.

Stromal cell-derived factor-1 (SDF-1) is a well-characterized cytokine that protects heart from ischaemic injury. However, the beneficial effects of native SDF-1, in terms of promoting myocardial repair, are limited by its low concentration in the ischaemic myocardium. Annexin V (AnxA5) can precisely detect dead cells in vivo. As massive cardiomyocytes die after MI, we hypothesize that AnxA5 can be used as an anchor to carry SDF-1 to the ischaemic myocardium. In this study, we constructed a fusion protein consisting of SDF-1 and AnxA5 domains. The receptor competition assay revealed that SDF-1-AnxA5 had high binding affinity to SDF-1 receptor CXCR4. The treatment of SDF-1-AnxA5 could significantly promote phosphorylation of AKT and ERK and induce chemotactic response, angiogenesis and cell survival in vitro. The binding membrane assay and immunofluorescence revealed that AnxA5 domain had the ability to specifically recognize and bind to cells injured by hypoxia. Furthermore, SDF-1-AnxA5 administered via peripheral vein could accumulate at the infarcted myocardium in vivo. The treatment with SDF-1-AnxA5 attenuated cell apoptosis, enhanced angiogenesis, reduced infarcted size and improved cardiac function after mouse myocardial infarction. Our results suggest that the bifunctional SDF-1-AnxA5 can specifically bind to dead cells. The systemic administration of bifunctional SDF-1-AnxA5 effectively provides cardioprotection after myocardial infarction.

Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation: a single-center pilot study.

Donor-derived cell-free DNA (ddcfDNA) is reported to be a promising noninvasive biomarker for acute rejection in organ transplant. However, studies on monitoring ddcfDNA dynamics during the early periods after organ transplantation are scarce. Our study assessed the dynamic variation in ddcfDNA in early period with various types and status of kidney transplantation. Target region capture sequencing used identifies ddcfDNA level in 21 kidney transplant recipients. Median ddcfDNA level was 20.69% at the initial time post-transplant, and decreased to 5.22% on the first day and stayed at the stable level after the second day. The ddcfDNA level in DCD (deceased donors) group (44.99%) was significantly higher than that in LDRT (living donor) group (10.24%) at initial time, P < 0.01. DdcfDNA level in DGF (delayed graft function) recipients was lower (23.96%) than that in non-DGF (47.74%) at the initial time, P = 0.89 (19.34% in DGF and 4.46% in non-DGF on the first day, P = 0.17). DdcfDNA level at initial time significantly correlated with serum creatinine (r2  = 0.219, P = 0.032) and warm ischemia time (r2  = 0.204, P = 0.040). Plasma ddcfDNA level decreased rapidly follow an L-shaped curve post-transplant, and level in DGF declined slower than non-DGF. The rebound of ddcfDNA level may indicate the occurrence of acute rejection.

[Bicyclol protects rat thoracic aorta from superoxide anion-induced inhibition of vascular relaxation].

OBJECTIVE: To investigate the effect of bicyclol on vascular oxidative stress injury induced by superoxide anion. METHODS: Rat thoracic aortic rings were isolated for isometric tension recording using organ bath technique. Superoxide arterial injury was induced by pyrogallol exposure, and the effect of bicyclol on endothelium-dependent relaxation was evaluated. RESULTS: Bicyclol (10(-8) - 10(-5) mol/L) relaxed endothelium-intact aortic rings precontracted by phenylephrine. This effect was abolished by L-NAME, an inhibitor of nitric oxide synthase and indomethacin, an inhibitor of cyclooxygenase. Exposure to pyrogallol (500 micromol/L) resulted in decrease of acetylcholine(ACh)-induced endothelium-dependent relaxation in aortic rings, and pre-incubation of bicyclol (10(-5) mol/L) for 45 min improved the relaxation attenuated by pyrogallol. In aortic rings pre-treated with indomethacin, bicyclol increased the ACh-induced relaxation that was inhibited by pyrogallol (500 micromol/L). This effect was not found in aortic rings pre-treated with L-NAME. CONCLUSION: Bicyclol has endothelium-dependent vasodilating effect on rat thoracic aorta and improves vascular function by attenuating oxidative stress. Nitric oxide from endothelium is involved in the anti-oxidative effect of bicyclol.