Incidence and Predictors of Acute Coronary Syndrome in Patients on Maintenance Hemodialysis: A Prospective Cohort Study.

Background: Cardiovascular diseases are the leading cause of death among patients on hemodialysis, with approximately 40% of the cardiovascular deaths linked to acute coronary syndrome. We aimed to investigate the incidence and risk factors of acute coronary syndrome in patients undergoing hemodialysis. Methods: Patients undergoing hemodialysis were prospectively enrolled from January 2018. Data regarding hospitalization due to acute coronary syndrome were collected at 3-month intervals through December 31, 2021. Cox regression model was used to estimate the association between baseline factors and incident acute coronary syndrome during follow-up. Results: Patients' mean age was 66 years, 48% were men, and 16% had a history of coronary artery disease at enrolment. Over a median follow-up of 1,187 days, 85 patients were hospitalized due to acute coronary syndrome. Left main or triple vessel disease was identified in 67 patients. Risk factors associated with incident acute coronary syndrome included aging, male sex, smoking, low diastolic blood pressure, and baseline comorbidities, in addition to dialysis factors including low urea clearance, central venous catheter use, and history of dialysis access dysfunction. After multivariate analysis, age, diabetes, hyperlipidemia, smoking, and frequent interventions for vascular access remained significant risk factors. Conclusions: A high acute coronary syndrome incidence was observed in our cohort, with traditional risk factors playing a consistent role with that in the general population. A history of frequent dialysis access dysfunction was also associated with incident acute coronary syndrome.

Studying the Roles of the Renin-Angiotensin System in Accelerating the Disease of High-Fat-Diet-Induced Diabetic Nephropathy in a db/db and ACE2 Double-Gene-Knockout Mouse Model.

Diabetic nephropathy (DN) is a crucial metabolic health problem. The renin-angiotensin system (RAS) is well known to play an important role in DN. Abnormal RAS activity can cause the over-accumulation of angiotensin II (Ang II). Angiotensin-converting enzyme inhibitor (ACEI) administration has been proposed as a therapy, but previous studies have also indicated that chymase, the enzyme that hydrolyzes angiotensin I to Ang II in an ACE-independent pathway, may play an important role in the progression of DN. Therefore, this study established a model of severe DN progression in a db/db and ACE2 KO mouse model (db and ACE2 double-gene-knockout mice) to explore the roles of RAS factors in DNA and changes in their activity after short-term (only 4 weeks) feeding of a high-fat diet (HFD) to 8-week-old mice. The results indicate that FD-fed db/db and ACE2 KO mice fed an HFD represent a good model for investigating the role of RAS in DN. An HFD promotes the activation of MAPK, including p-JNK and p-p38, as well as the RAS signaling pathway, leading to renal damage in mice. Blocking Ang II/AT1R could alleviate the progression of DN after administration of ACEI or chymase inhibitor (CI). Both ACE and chymase are highly involved in Ang II generation in HFD-induced DN; therefore, ACEI and CI are potential treatments for DN.

Timely thrombectomy can improve patency of hemodialysis arteriovenous fistulas.

OBJECTIVE: The urgency with which salvage of thrombosed vascular accesses for dialysis should be attempted remains unknown. We examined the effect of a timely thrombectomy approach on vascular access outcomes for dialysis. METHODS: A before-and-after study was conducted with patients on hemodialysis who had undergone endovascular thrombectomy. A timely thrombectomy initiative (ie, salvage within 24 hours of thrombosis diagnosis) was started in July 2015 at our institution. Data about thrombectomy procedures, performed within 1 year before and after the initiative was introduced, were abstracted from an electronic database. Immediate outcomes and patency outcomes were compared between the preinitiative (control) and postinitiative (intervention) groups. RESULTS: During the study period, 329 patients were enrolled, including 165 cases before and 164 cases after the initiative. The intervention group had more thrombectomy procedures performed within 24 hours (93% vs 55%; P < .01) and within 48 hours (97% vs 79%; P < .01) than the control group. No between-group differences in procedural success or clinical success rates were found. At 3 months, the intervention group had a higher postintervention primary patency rate than the control group, although this did not reach statistical significance (58% vs 48%; P = .06). After stratification into native or graft accesses, the patency benefit was observed in the native access group (68% vs 50%; P = .03) but not in the graft access group (50% vs 46%; P = .65). After adjusting for potential confounders, timely thrombectomy remained an independent predictor of postintervention primary patency (hazard ratio, 0.449; 95% confidence interval, 0.224-0.900; P = .02) for native dialysis accesses. CONCLUSIONS: Our results suggest that a timely thrombectomy approach, in which salvage is attempted within 24 hours of thrombosis diagnosis, improves postintervention primary patency of native but not graft accesses for dialysis.

Imbalanced plasma ACE and ACE2 level in the uremic patients with cardiovascular diseases and its change during a single hemodialysis session.

BACKGROUND: The renin-angiotensin system (RAS) has significant influences on heart and renal disease progression. Angiotensin converting enzyme (ACE) and angiotensin converting enzyme II (ACE2) are major peptidases of RAS components and play counteracting functions through angiotensin II (Ang II)/ATIR and angiotensin-(1-7) (Ang-(1-7))/Mas axis, respectively. METHODS: There were 360 uremic patients on regular hemodialysis (HD) treatment (inclusive of 119 HD patients with cardiovascular diseases (CVD) and 241 HD patients without CVD and 50 healthy subjects were enrolled in this study. Plasma ACE, ACE2, Ang II and Ang-(1-7) levels of the HD patients were determined. RESULTS: We compared pre-HD levels of plasma ACE, ACE2, Ang II and Ang-(1-7) in the HD patients with and without CVD to those of the controls. The HD patients, particularly those with CVD, showed a significant increase in the levels of ACE and Ang II, whereas ACE2 and Ang-(1-7) levels were lower than those in the healthy controls. Therefore, imbalanced ACE/ACE2 was observed in the HD patients with CVD. In the course of a single HD session, the plasma ACE, ACE/ACE2 and Ang II levels in the HD patients with CVD were increased from pre-HD to post-HD. On the contrary, ACE2 levels were decreased after the HD session. These changes were not detected in the HD patients without CVD. CONCLUSIONS: Pathogenically imbalanced circulating ACE/ACE2 was detected in the HD patients, particularly those with CVD. HD session could increase ACE/Ang II/AT1R axis and decrease ACE2/Ang-(1-7)/Mas axis activity in the circulation of HD patients with CVD.

Circulating Progenitor Cells Affect Thrombosis of Dialysis Arteriovenous Fistulas.

BACKGROUND: Arteriovenous fistula (AVF) thrombosis is a relevant cause of morbidity in hemodialysis (HD) patients. The number of circulating endothelial progenitor cells (EPCs) has been identified as a surrogate marker for vascular repair and health. Deficiency of EPCs has been demonstrated in dialysis patients to be associated with vascular events. Nonetheless, their role in thrombosis of AVFs remains unknown. METHODS: From January 2010 to May 2013, 147 HD patients with dysfunctional AVFs were enrolled. Surface makers including CD34, KDR and CD133 were used in combination to determine the number of circulating EPCs. All participants were prospectively followed at 6-month interval until December 2015. The primary outcome was thrombosis of dialysis AVFs. RESULTS: The median follow-up was 47 months, within which 42 patients experienced at least one episode of AVF thrombosis. Patients with AVF thrombosis had lower CD34+KDR+ cell counts compared with patients without thrombosis (median 5 vs. 13 per 150,000 mononuclear cells, p < 0.001). Kaplan-Meier analysis demonstrated an inverse relationship between CD34+KDR+ cell count tertiles and thrombosis-free patency (59, 69 and 86% for low, middle and high tertiles; p = 0.02). Using Cox regression analysis, AVF thrombosis was predicted by baseline CD34+KDR+ cell counts (hazards ratio (HR) 0.963, 95% CI 0.928-1.000, p = 0.05) and tertiles (high vs. low, HR 3.266, 95% CI 1.380-7.728, p < 0.01). In multivariate analysis, only CD34+KDR+ cell tertiles, C-reactive protein and lesion length remained independent predictors for thrombosis. CONCLUSION: Our study demonstrated an independently reverse association between circulating EPCs and thrombosis of dialysis AVFs. Further studies are warranted to ascertain whether EPCs serve as a marker or a therapeutic target for AVF thrombosis.

Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis.

BACKGROUND: Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) play important roles in the pathophysiology of renal diseases. Imbalanced MMPs/TIMPs are implicated in the vascular alterations of uremic patients on hemodialysis (HD). We have investigated the plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in uremic patients and the effects of a course of HD on the changes in these factors. METHODS: There were 382 uremic patients on regular HD treatment and 50 healthy controls enrolled in this study. The plasma MMP-2 and MMP-9 levels were detected by gelatin zymography, and TIMP-1 and TIMP-2 concentrations were determined by ELISA assay. RESULTS: Significantly higher plasma MMP-2 and MMP-9 and decreased TIMP-1 in the uremic patients were detected compared with those in the controls. Therefore, there were markedly higher MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in the uremic patients. In the course of a single HD session, the plasma MMP-2 level was significantly decreased from pre-HD to post-HD. TIMP-1 concentration was significantly increased from pre-HD to post-HD. Although the HD session did not have a significant effect on the levels of plasma MMP-9 and TIMP-2, both plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios were significantly decreased from pre-HD to post-HD levels. CONCLUSION: HD session could decrease MMP-2 and increase TIMP-1 level in the circulation of uremic patients. The physiological significance of reduced MMPs/TIMPs ratio due to a single HD session is required to further validate.

Effects of a Health Literacy Education Program on Mental Health and Renal Function in Patients With Chronic Kidney Disease: A Randomized Controlled Trial.

BACKGROUND: Chronic kidney disease (CKD) refers to permanent damage to the kidneys that occurs gradually over time. Further progression may be preventable depending on its stage. PURPOSE: This study was developed to evaluate the effect of a health literacy education program (HLEP) on mental health and renal functioning in patients with CKD. METHODS: A single-blind, randomized controlled trial study was conducted. Data were collected from March 25 to December 18, 2021. Participants were randomly assigned to either the experimental group (n = 42), which received multidisciplinary care and HLEP, or the control group (n = 42), which received multidisciplinary care only. Data were collected at baseline (T1), Month 3 (T2), and Month 6 (T3), and the data included patient characteristics, estimated glomerular filtration rate, and responses to the Mandarin Multidimensional Health Literacy Questionnaire and Beck Depression Inventory. RESULTS: After 6 months of the HLEP intervention, the results of generalized estimating equations analysis showed that, compared with the control group, the experimental group had significantly higher health literacy at Month 3 (ß = -3.37, 95% CI [-5.68, -1.06]), significantly improved depression at Month 3 (ß = -2.24, 95% CI [-4.11, -0.37]) and Month 6 (ß = -4.36, 95% CI [-6.60, -2.12]), and a significantly higher estimated glomerular filtration rate at Month 6 (ß = 5.87, 95% CI [1.35, 10.38]). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings of this study may provide a reference for healthcare providers to educate patients with Stage 3-4 CKD using the HLEP. Positive effects on health literacy, depression, and renal function in patients with Stage 3-4 CKD were observed in the short term. Findings from this study may facilitate the implementation of multidisciplinary and nurse-led strategies in primary care to reinforce patients' health literacy, self-care ability, and adjustment to CKD as well as delay disease progression.

Comparisons of clinical outcomes for thrombectomy devices with different mechanisms in hemodialysis arteriovenous fistulas.

OBJECTIVES: To compare clinical outcomes between mechanical thrombectomy devices with hydrodynamic mechanism and rotational mechanism. BACKGROUND: A number of advantages and concerns have been raised for different mechanical devices but the comparisons of clinical outcomes are absent, especially for the treatment of autogenous hemodialysis arteriovenous (AV) fistulas. METHODS: The authors retrospectively reviewed 275 percutaneous thrombectomy procedures in AV fistulas. Procedures included were thrombectomy using devices with hydrodynamic mechanism, the AngioJet rheolytic catheter (AngioJet) (n = 134) or devices with rotational mechanism, the Arrow-Trerotola percutaneous thrombectomy device (PTD) (n = 141). Measured outcomes included clinical success, complications and patency rates. RESULTS: Clinical success was achieved in 76% (102 of 134) of the AngioJet procedures and in 91% (128 of 141) of the PTD procedures (P = 0.002). The procedure time for the PTD method was significantly shorter than that of the AngioJet method (52 vs. 88 min, P < 0.001). Complications occurred in 14% of the AngioJet procedures and 11% of the PTD procedures. The post-intervention primary patency rates at 6 months were 45% for the AngioJet group and 43% for the PTD group (P = 0.70). The postintervention secondary patency rates at 1 year were 74% for the AngioJet group and 87% for the PTD group (P = 0.01). CONCLUSIONS: For the salvage of thrombosed AV fistulas, a device using rotational mechanism is more time-saving with a higher immediate success rate and secondary patency rate. However, the long-term patency results were not different.

Coexistence of neuroleptic malignant syndrome and a hyperosmolar hyperglycemic state.

Neuroleptic malignant syndrome (NMS) is a rare idiosyncratic disorder characterized by muscle rigidity, hyperthermia, autonomic dysfunction, and altered consciousness. Although the incidence of NMS is low, it may be fatal if early recognition is delayed. There are a variety of precipitating factors for NMS including systemic illness and dehydration. The combination of NMS with systemic illness can be difficult to diagnose because the systemic illness may mask the coexistence of NMS. We report a patient with hyperosmolar hyperglycemic state with coexistent NMS to remind physicians that hyperosmolar hyperglycemic state may precipitate the development of NMS in patients receiving neuroleptics.

Surface Modification of Biodegradable Mg-Based Scaffolds for Human Mesenchymal Stem Cell Proliferation and Osteogenic Differentiation.

Magnesium alloys with coatings have the potential to be used for bone substitute alternatives since their mechanical properties are close to those of human bone. However, the surface modification of magnesium alloys to increase the surface biocompatibility and reduce the degradation rate remains a challenge. Here, FHA-Mg scaffolds were made of magnesium alloys and coated with fluorohydroxyapatite (FHA). Human mesenchymal stem cells (hMSCs) were cultured on FHA-Mg scaffolds and cell viability, proliferation, and osteogenic differentiation were investigated. The results showed that FHA-Mg scaffolds display a nano-scaled needle-like structure of aggregated crystallites on their surface. The average Mg2+ concentration in the conditioned media collected from FHA-Mg scaffolds (5.8-7.6 mM) is much lower than those collected from uncoated, Mg(OH)2-coated, and hydroxyapatite (HA)-coated samples (32.1, 17.7, and 21.1 mM, respectively). In addition, compared with hMSCs cultured on a culture dish, cells cultured on FHA-Mg scaffolds demonstrated better proliferation and comparable osteogenic differentiation. To eliminate the effect of osteogenic induction medium, hMSCs were cultured on FHA-Mg scaffolds in culture medium and an approximate 66% increase in osteogenic differentiation was observed three weeks later, indicating a significant effect of the nanostructured surface of FHA-Mg scaffolds on hMSC behaviors. With controllable Mg2+ release and favorable mechanical properties, porous FHA-Mg scaffolds have a great potential in cell-based bone regeneration.

Plasma ADMA predicts restenosis of arteriovenous fistula.

Plasma levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide production, correlate with endothelial dysfunction and the development of cardiovascular events in patients with uremia. It is not known whether endothelial dysfunction contributes to the dysfunction of arteriovenous fistulas (AVFs) in hemodialysis patients. Here, we studied the predictive value of baseline plasma ADMA for symptomatic restenosis of an AVF after percutaneous transluminal angioplasty in dialysis patients. We obtained baseline plasma ADMA levels before percutaneous transluminal angioplasty in 100 consecutive patients with dysfunctional AVFs. Patients were followed up clinically for up to 6 mo after angioplasty for recurrent dysfunction. During the 6 mo after angioplasty, 46 patients experienced recurrent dysfunction of their AVF; of these, follow-up fistulography showed restenosis at the same location in 41, new stenosis at different locations in two, and no significant stenosis in three patients. Up to 60% of the patients with high levels of ADMA (>0.910 microM) had target lesion restenosis compared with 25% of those with low levels (<0.910 microM; P < 0.001). In multivariate analysis, plasma ADMA independently nearly tripled the risk for recurrent symptomatic stenosis of an AVF after percutaneous transluminal angioplasty (hazard ratio 2.65; 95% confidence interval 1.33 to 5.28). These results suggest a role for ADMA in the progression of symptomatic restenoses of AVFs after percutaneous transluminal angioplasty and call for preventive strategies that target ADMA and/or endothelial dysfunction to decrease the risk for AVF restenosis.

Effect of Hydrothermal (Sr)-Hydroxyapatite Coatings on the Corrosion Resistance and Mg2+ Ion Release to Enhance Osteoblastic Cell Responses of AZ91D Alloy.

The biomedical applications of Mg-based alloys are limited by their rapid corrosion rate in the body fluid. In this study, the hydrothermal synthesis is employed to produce protective bioactive hydroxyapatite coating (HAC) and strontium-substituted hydroxyapatite coating (Sr-HAC) to further enhance the corrosion resistance and in vitro biocompatibility of biodegradable AZ91D Mg alloy in physiological environments. For comparison, the brucite Mg(OH)2 prepared by the alkaline pre-treatment is designated as a control group. Experimental evidences of XRD and XPS analysis confirm that Sr2+ ions can be incorporated into HA crystal structure. It is noted that the hydrothermally synthesized Sr-HAC conversion coating composed of a specific surface topography with the nanoscaled flake-like fine crystallites is constructed on the AZ91D Mg alloy. The hydrophilicity of Mg substrate is effectively enhanced with the decrease in static contact angles after performing alkaline and hydrothermal treatments. Potentiodynamic polarization measurements reveal that the nanostructured Sr-HAC-coated specimens exhibit superior corrosion resistance than HAC and alkaline pre-treated Mg(OH)2. Moreover, immersion tests demonstrate that Sr-HAC provides favorable long-term stability for the Mg alloy with decreasing concentration of released Mg2+ ions in the SBF and the reduced corrosion rate during the immersion length of 30 days. The cells cultured on Sr-HAC specimens exhibit higher viability than those on the alkaline-pre-treated Mg(OH)2 and HAC specimens. The Sr-substituted HA coating with a nanostructured surface topography can help to stimulate the cell viability of osteoblastic cells.

Multiple screening of urolithic organic acids with copper nanoparticle-plated electrode: potential assessment of urolithic risks.

There is yet to be a reliable prediction of urolithiasis. To facilitate early diagnosis, a simple and rapid high performance liquid chromatography method with electrochemical detection using disposable copper-nanoparticle-plated electrodes (Cu(n)-SPE) was developed for multiple detection of creatinine and 4 urolithic organic acids. A total of 206 normal and urolithic human and canine urines and urolith samples were collected for direct analysis of creatinine, cystine, uric acid, oxalic acid, and citric acid without sample cleanup and derivatization processes. Urinary organic acids were separated in 11 min and were devoid of ascorbic acid interference. The detection limits (S/N>3) were at the nanomolar level with linear dynamic ranges spanning 2-3 orders of magnitude. Recoveries in urine ranged from 99.5% for creatinine to 86.5% for citric acid. The analytical variations (RSD) were less than 6.2% in phosphate buffer and 7.7% in urine. Important differences in organic acid levels/profiles between animal species and among normal and urolithic urines/urolith were unveiled and corresponded well (70-90%) with the urolithic risk in a retrospective assessment. The simplicity and reproducibility of this method using disposable Cu(n)-SPE has made routine urine analysis possible and can be of great clinical and diagnostic potential in the screening of urolithiasis and abnormal states related to excess secretion of organic acids and amino acids in humans and animals.

Radial artery approach for endovascular salvage of occluded autogenous radial-cephalic fistulae.

BACKGROUND: The endovascular salvage of occluded autogenous radial-cephalic fistulae is a more challenging procedure than that for stenotic fistulae. To obtain an access to the fistula is one of the keys to success. Both retrograde venous approach and brachial artery approach have some disadvantages. The radial artery approach has been used in the endovascular therapy of fistula dysfunction, but few data focused on their feasibility and safety for the totally occluded fistulae. METHODS: We retrospectively reviewed the patients with occluded autogenous radial-cephalic fistulae receiving endovascular salvage via the radial artery approach in our institution. From January 2004 to July 2007, 48 patients fulfilling the above criteria were enrolled. Balloon maceration was used for patients with small clots. Mechanical thrombectomy with an Arrow-Trerotola percutaneous thrombolytic device or an AngioJet rheolytic catheter was used for patients with large clot burden. Outcome variables included anatomic and clinical success, complications and primary and secondary patency. RESULTS: All the transradial punctures were successful. Anatomic and clinical success was achieved in 96% of the cases. The post-interventional primary patency rates were 92%, 77%, 55% and 44% at 1, 3, 6 and 12 months, respectively. The post-interventional secondary patency rates were 96%, 93%, 89% and 89% at 1, 3, 6 and 12 months, respectively. The 12-month primary patency of the short-segment thrombus group was better than that of the long-segment thrombus group (57% versus 19%, P = 0.005). The complication rate was 4%. No puncture-site-related complications were noted, and all the radial arteries were palpable at follow-up. CONCLUSIONS: An endovascular intervention through the radial artery approach is a safe and feasible strategy choice for restoring occluded autogenous radial-cephalic fistulae.

Weibull Statistical Analysis of Strength Fluctuation for Failure Prediction and Structural Durability of Friction Stir Welded Al⁻Cu Dissimilar Joints Correlated to Metallurgical Bonded Characteristics.

In this paper, dissimilar Al⁻Cu joints of AA1050H/C1100-Cu, AA6061-T6/C1100-Cu, and AA1050H/C2600-brass are successfully welded by a friction stir welding (FSW) process. The aim of the present study is not only to examine the tensile strength, but also to investigate the reliability, durability, and failure behaviors of joints as correlated with the metallurgical bonded microstructures of varied Al⁻Cu joints. Experimental evidence confirms that good welding quality for an FSW Al⁻Cu dissimilar joint is obtained when pure Cu and brass plates are positioned at the advancing side. Cross-sectional microstructures reveal that the AA6061-T6/C1100-Cu joint exhibits an extensive metallurgical bonded region with significant onion rings in the welding zone, whereas the AA1050H/C2600-brass joint generally displays a clear mechanical kissing bonded boundary at the joint interface. Al2Cu, Al4Cu9, and γ-Cu5Zn8 are major intermetallic compounds (IMCs) that are formed within the metallurgical bonded welding zone. The Weibull model provides a statistical method for assessing the failure mechanism of FSW Al⁻Cu joints. Better welding reliability and tensile properties with ductile dimpled ruptures are obtained for the Al⁻Cu joints with a typical metallurgical bonded zone. However, a mechanical kissing bonded interface and thick interfacial IMCs result in the deterioration of tensile strength with a brittle fracture and a rapid increase in the failure probability of Al⁻Cu joints.

A randomized feasibility study of the effect of ascorbic acid on post-angioplasty restenosis of hemodialysis vascular access (NCT03524846).

Restenosis remains a significant problem after angioplasty of hemodialysis vascular access. Both experimental and clinical studies have shown a protective effect of antioxidants against post-angioplasty restenosis. A prospective, randomized, feasibility study was conducted to investigate the effect of ascorbic acid to prevent restenosis. Ninety-three hemodialysis patients were randomized into three groups after angioplasty: placebo (n = 31), 300 mg ascorbic acid (n = 31), and 600 mg ascorbic acid (n = 31), treated intravenously 3 times per week for 3 months. Eighty-nine completed the clinical follow-up, and 81 had angiographic follow-up. In the angiographic follow-up, the mean (stand deviation) late loss of luminal diameter for the placebo, 300 mg, and 600 mg groups were 3.15 (1.68) mm, 2.52 (1.70) mm (P = 0.39 vs. placebo group), and 1.59 (1.67) mm (P = 0.006, vs. placebo group), with corresponding angiographic binary restenosis of 79%, 67% (P = 0.38 vs. placebo group), and 54% (P = 0.08 vs. placebo group). The post-interventional primary patency rates at 3 months were 47%, 55% (P = 0.59 vs. placebo group), and 70% (P = 0.18 vs. placebo group) for placebo, 300 mg, and 600 mg groups. Our results demonstrated that intravenous 600 mg ascorbic acid was a feasible therapy and might attenuate restenosis after angioplasty; however, its effect on post-interventional primary patency was modest.

Renal chymase-dependent pathway for angiotensin II formation mediated acute kidney injury in a mouse model of aristolochic acid I-induced acute nephropathy.

Angiotensin-converting enzyme (ACE) is the primary enzyme that converts angiotensin I (Ang I) to angiotensin II (Ang II) in the renin-angiotensin system (RAS). However, chymase hydrates Ang I to Ang II independently of ACE in some kidney diseases, and it may play an important role. The present study investigated whether chymase played a crucial role in aristolochic acid I (AAI)-induced nephropathy. C57BL/6 mice were treated with AAI via intraperitoneal injection for an accumulated AAI dosage of 45 mg/kg body weight (BW) (15 mg/kg BW per day for 3 days). The animals were sacrificed after acute kidney injury development, and blood, urine and kidneys were harvested for biochemical and molecular assays. Mice exhibited increased serum creatinine, BUN and urinary protein after the AAI challenge. Significant infiltrating inflammatory cells and tubular atrophy were observed in the kidneys, and high immunocytokine levels were detected. Renal RAS-related enzyme activities were measured, and a significantly increased chymase activity and slightly decreased ACE activity were observed in the AAI-treated mice. The renal Ang II level reflected the altered profile of RAS enzymes and was significantly increased in AAI-treated mice. Treatment of AAI-induced nephropathic mice with an ACE inhibitor (ACEI) or chymase inhibitor (CI; chymostatin) reduced renal Ang II levels. The combination of ACEI and CI (ACEI+CI) treatment significantly reversed the AAI-induced changes of Ang II levels and kidney inflammation and injuries. AAI treatment significantly increased renal p-MEK without increasing p-STAT3 and p-Smad3 levels, and p-MEK/p-ERK1/2 signalling pathway was significantly activated. CI and ACEI+CI treatments reduced this AAI-activated signaling pathway. AAI-induced nephropathy progression was significantly mitigated with CI and ACEI+CI treatment. This study elucidates the role of RAS in the pathogenesis of AAI-induced nephropathy.

Hydrothermal treatment and butylphosphonic acid derived self-assembled monolayers for improving the surface chemistry and corrosion resistance of AZ61 magnesium alloy.

The hydrothermal treatment followed by a self-assembled monolayer (SAM) of 1-butylphosphonic acid through the tethering by aggregation and growth (T-BAG) method was employed to produce protective surface coatings on the Mg-6Al-1Zn alloy (AZ61) for reducing the degradation rate in physiological environments. Potentiodynamic polarization measurements revealed that the organic self-assembled monolayer and Mg(OH)2 coating can further enhance the surface chemical stability and corrosion resistance of Mg alloys. SAM-treated Mg(OH)2 coatings can be served as a more passive surface layer as a result of their much higher charge transfer resistance and the presence of Warburg impedance in electrochemical impedance spectroscopy measurement.

Monocyte Chemoattractant Protein-1 Levels and Postangioplasty Restenosis of Arteriovenous Fistulas.

BACKGROUND AND OBJECTIVES: Inflammation is relevant in restenosis of atherosclerotic vascular diseases, but its role in dialysis arteriovenous fistula remains unknown. In animal studies, upregulation of monocyte chemoattractant protein-1 has been shown in venous segments of arteriovenous fistula. We, therefore, aimed to investigate serial changes in circulating monocyte chemoattractant protein-1 after percutaneous transluminal angioplasty of dialysis arteriovenous fistulas and its relation to restenosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fifty-nine patients with dysfunctional arteriovenous fistulas that were referred for percutaneous transluminal angioplasty were enrolled prospectively between January of 2010 and July of 2012. Three of them were excluded due to percutaneous transluminal angioplasty failure or acute infection. Blood was sampled from arteriovenous fistulas at baseline, 2 days, 2 weeks, and 3 months after percutaneous transluminal angioplasty. Clinical follow-up was continued monthly for 3 months. Angiographic follow-up was arranged at the end of 3 months. Seventeen patients without significant stenosis were enrolled as the control group. RESULTS: Fifty-six patients completed clinical follow-up. Significant increases in monocyte chemoattractant protein-1 were observed at 2 days and 2 weeks (both P<0.001) after percutaneous transluminal angioplasty. Twenty-three (41%) patients had symptomatic restenosis. The restenosis group had a higher percentage change in monocyte chemoattractant protein-1 levels at 2 days (median =47%; interquartile range, 27%-65% versus median =17%; interquartile range, 10%-25%; P<0.001) after percutaneous transluminal angioplasty compared with the patent group. Fifty-two patients completed angiographic follow-up. A positive correlation between relative luminal loss and monocyte chemoattractant protein-1 increase at 2 days after percutaneous transluminal angioplasty was found (r=0.53; P<0.001). In multivariate analysis, postangioplasty monocyte chemoattractant protein-1 increase at 2 days was an independent predictor of restenosis. Using receiver operator characteristic analysis, >25% postangioplasty increase of monocyte chemoattractant protein-1 was significantly associated with restenosis after percutaneous transluminal angioplasty (hazard ratio, 5.36; 95% confidence interval, 1.81 to 15.8). CONCLUSIONS: Circulating monocyte chemoattractant protein-1 levels were elevated 2 days and 2 weeks after percutaneous transluminal angioplasty. Early postangioplasty increase of monocyte chemoattractant protein-1 level was associated with restenosis of arteriovenous fistulas.

An integrative transcriptomic analysis reveals bisphenol A exposure-induced dysregulation of microRNA expression in human endometrial cells.

Bisphenol A (BPA) are commonly used in the manufacture of polycarbonate plastics. Higher BPA exposure levels have been found in patients with endometrial hyperplasia that is one of risk factors of endometrial cancer (EC). Aberrant microRNAs (miRNAs) regulation has been observed in the development of cancer. Thus, this study investigated whether BPA exposure can disrupt miRNA regulation and its gene expression regarding to EC carcinogenic progress. Microarray experiments of miRNA and mRNA were performed in human endometrial cancer RL95-2 cells with treatment of low-to-moderate (10, 103 and 105nM) BPA to explore the aberrant genes corresponding to human EC progression. According to the analysis of KEGG pathway and Cytoscape gene network, this study identified that BPA exposure reduced miR-149 expression to down-regulate DNA repair gene ARF6 (ADP-ribosylation factor 6) and tumor protein p53 (TP53), and up-regulate CCNE2 (cyclin E2) potentially to interrupt cell cycle. BPA also increased miR-107 to suppress hedgehog signaling factors, suppressor of fused homolog (SUFU) and GLI family zinc finger 3 (GLI3) to activate hedgehog signaling for cell proliferation underlying carcinogenesis. Furthermore, the BPA-induced cell proliferation was attenuated by transfection with miR-149 mimic and miR-107 inhibitor. These findings provided an insight into potential epigenetic mechanism of BPA exposure on the risk of endometrial carcinogenesis.