β2-microglobulin modified with advanced glycation end products modulates collagen synthesis by human fibroblasts

β2-microglobulin modified with advanced glycation end products modulates collagen synthesis by human fibroblasts. β2-microglobulin amyloidosis (Aβ2m) is a serious complication for patients undergoing long-term dialysis. β2-microglobulin modified with advanced glycation end products (β2m-AGE) is a major component of the amyloid in Aβ2m. It is not completely understood whether β2m-AGE plays an active role in the pathogenesis of Aβ2m, or if its presence is a secondary event of the disease. β2-microglobulin amyloid is mainly located in tendon and osteo-articular structures that are rich in collagen, and local fibroblasts constitute the principal cell population in the synthesis and metabolism of collagen. Recent identification of AGE binding proteins on human fibroblasts lead to the hypothesis that the fibroblast may be a target for the biological action of β2m-AGE. The present study demonstrated that two human fibroblast cell lines exhibited a decrease in procollagen type I mRNA and type I collagen synthesis after exposure to β2m-AGE for 72 hours. Similar results were observed using AGE-modified albumin. Antibody against the RAGE, the receptor for AGE, attenuated this decrease in synthesis, indicating that the response was partially mediated by RAGE. In addition, antibody against epidermal growth factor (EGF) attenuated the decrease in type I procollagen mRNA and type I collagen induced by β2m-AGE, suggesting that EGF acts as an intermediate factor. These findings support the hypothesis that β2m-AGE actively participates in connective tissue and bone remodeling via a pathway involving fibroblast RAGE, and at least one interposed mediator, the growth factor EGF

Acute and acute-on-chronic kidney injury of patients with decompensated heart failure: impact on outcomes

BACKGROUND: Acute worsening of renal function, an independent risk factor for adverse outcomes in acute decompensated heart failure (ADHF), occurs as a consequence of new onset kidney injury (AKI) or acute deterioration of pre-existed chronic kidney disease (CKD) (acute-on-chronic kidney injury, ACKI). However, the possible difference in prognostic implication between AKI and ACKI has not been well established. METHODS: We studied all consecutive patients hospitalized with ADHF from 2003 through 2010 in Nanfang Hospital. We classified patients as with or without pre-existed CKD based on the mean estimated glomerular filtration rate (eGFR) over a six-month period before hospitalization. AKI and ACKI were defined by RIFLE criteria according to the increase of the index serum creatinine. RESULTS: A total of 1,005 patients were enrolled. The incidence of ACKI was higher than that of AKI. The proportion of patients with diuretic resistance was higher among patients with pre-existed CKD than among those without CKD (16.9% vs. 9.9%, P = 0.002). Compared with AKI, ACKI was associated with higher risk for in-hospital mortality, long hospital stay, and failure in renal function recovery. Pre-existed CKD and development of acute worsening of renal function during hospitalization were the independent risk factors for in-hospital death after adjustment by the other risk factors. The RIFLE classification predicted all-cause and cardiac mortality in both AKI and ACKI. CONCLUSIONS: Patients with ACKI were at greatest risk of adverse short-term outcomes in ADHF. Monitoring eGFR and identifying CKD should not be ignored in patients with cardiovascular disease

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

An optimal-oriented quasi-droop control of interlinking converter in hybrid microgrid

In hybrid microgrid, interlinking converter (ILC) is a key component to connect the AC subgrid and DC subgrid. Its control strategy significantly affect the power flow management, power quality, system efficiency and stability. Traditionally, ILC is usually controlled as a current source, resulting in a poor dynamic stability when a remote weak AC subgird is connected by a large linking impedance. In this study, a quasi-droop control scheme is proposed to control ILC as a current controlled voltage source (CCVS). Not only a flexible power flow management is achieved, but an ancillary function of voltage support is also provided. Moreover, this simple quasidroop control enables ILC to synchronize with the AC subgrid autonomously without a phase-locked loop (PLL). Finally, simulations are presented to verify the system effectiveness.Accepted versio

β2-Microglobulin modified with advanced glycation end products delays monocyte apoptosis

β2-Microglobulin modified with advanced glycation end products delays monocyte apoptosis.BackgroundA local inflammatory reaction to β2-microglobulin (β2m) amyloid deposits by monocytes/macrophages is a characteristic histologic feature of dialysis-related amyloidosis (DRA). Since β2m modified with advanced glycation end products (AGE-β2m) is a major constituent of amyloid in DRA, we tested the hypothesis that AGE-β2m affects apoptosis and phenotype of human monocytes.MethodsHuman peripheral blood monocytes were incubated with or without in vitro-derived AGE-β2m, and their viability, extent of apoptosis, morphology, and function examined over the subsequent four days.ResultsAGE-modified but not unmodified β2m significantly delayed spontaneous apoptosis of human peripheral blood monocytes in adherent and nonadherent cultures. The effect of AGE-β2m on monocytes apoptosis was time- and dose-dependent and was attenuated by a blocking antibody directed against the human AGE receptor (RAGE). There was no difference in effect between AGE-β2m and that of AGE-modified human serum albumin. Culture of monocytes with AGE-β2m did not alter membrane expression of Fas or Fas ligand. Monocytes cultured with AGE-β2m underwent substantial changes in morphology similar to those observed when monocytes differentiate into macrophages. The cultured cells increased in size and vacuolization, and their content of β-glucuronidase and acid phosphatase increased by 5- to 10-fold at day 4. Expression of the monocyte–macrophage membrane antigens HLA-DR, CD11b, and CD11c also increased at day 4. Although exhibiting phenotypic characteristics of macrophages, monocytes cultured with AGE-β2m functioned differently than macrophages cultured with serum. Superoxide production in response to phorbol myristic acetate was maintained in monocytes cultured with AGE-β2m, but declined with time in cells cultured with serum. Constitutive synthesis of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and prostaglandin E2 (PGE2) increased in monocytes cultured for four to six days with AGE-β2m.ConclusionsThese findings support a novel role for AGE-modified proteins such as AGE-β2m that may contribute to the development of a local inflammatory response, with predominant accumulation of monocytes/macrophages, in DRA

Habitual Fish Oil Supplementation and Incident Chronic Kidney Disease in the UK Biobank

Background: To explore the relation of habitual fish oil use with the risk of chronic kidney diseases (CKD). Methods: 408,023 participants (54.2% female) without prior CKD and with completed information regarding their consumption of major food groups and fish oil in the UK Biobank were enrolled. Fish oil use and dietary intakes were assessed by touch screen questionnaire and food frequency questionnaire, respectively. Incident CKD was recorded from hospital inpatient records. Results: At baseline, 128,843 (31.6%) participants reported taking fish oil supplements. During a median follow-up period of 12.0 years, a total of 10,782 (2.6%) participants developed CKD. With adjustments for important confounders, habitual fish oil use was associated with a significantly lower hazard of incident CKD (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87–0.95), compared with non-use. Consistently, participants reporting ≥2 servings/week of oily fish (HR, 0.86; 95% CI, 0.79–0.94) and nonoily fish (HR, 0.86; 95% CI, 0.77–0.97) consumption had a lower hazard of incident CKD compared to those reporting no consumption ever. Additionally, among the 97,914 participants with data on plasma fatty acid, there were significant inverse relationships of plasma omega-3 polyunsaturated fatty acid (PUFA) (per SD increment, HR, 0.89, 95% CI, 0.84–0.94) and eicosatetraenoic acid (per SD increment, HR, 0.91, 95% CI, 0.87–0.96) with incident CKD. Conclusions: Habitual fish oil use was associated with a lower hazard of CKD, which was further confirmed by the consistent inverse relations between fish consumption and circulating omega-3 PUFA concentration with incident CKD

Hepatitis C Prevalence, Incidence, and Treatment in Chinese Hemodialysis Patients: Results From the Dialysis Outcomes and Practice Patterns Study-China (2019–21)

Prior work from the Dialysis Outcomes and Practice Patterns Study (DOPPS) showed HCV prevalence in China in 2012–2015 being in the upper third and HCV incidence the 2nd highest among 15 different countries/regions investigated. The goal of the present investigation was to: (1) determine if HCV prevalence and incidence has changed, and (2) collect detailed data to understand how HCV is treated, monitored, and managed in Chinese HD facilities and non-dialysis chronic kidney disease (CKD) clinics