J-shaped association between dietary zinc intake and new-onset hypertension: a nationwide cohort study in China / 医学前沿

We aimed to investigate the relationship of dietary zinc intake with new-onset hypertension among Chinese adults. A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey were included. Dietary intake was assessed by three consecutive 24-h dietary recalls combined with a household food inventory. Participants with systolic blood pressure ≽ 140 mmHg or diastolic blood pressure ≽ 90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up were defined as having new-onset hypertension. During a median follow-up duration of 6.1 years, 4269 participants developed new-onset hypertension. Overall, the association between dietary zinc intake and new-onset hypertension followed a J-shape (P for non-linearity < 0.001). The risk of new-onset hypertension significantly decreased with the increment of dietary zinc intake (per mg/day: hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.88-0.98) in participants with zinc intake < 10.9 mg/day, and increased with the increment of zinc intake (per mg/day: HR 1.14; 95% CI 1.11-1.16) in participants with zinc intake ≽ 10.9 mg/day. In conclusion, there was a J-shaped association between dietary zinc intake and new-onset hypertension in general Chinese adults, with an inflection point at about 10.9 mg/day.

Mineral and bone disorder and management in the China Dialysis Outcomes and Practice Patterns Study / 中华医学杂志(英文版)

BACKGROUND@#Despite a growing population of patients starting hemodialysis in China, little is known about markers of mineral bone disease (MBD) and their management. We present data on prevalence and correlates of hypocalcemia, hyperphosphatemia, and secondary hyperparathyroidism from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), with evaluation of whether these laboratory markers triggered changes in management.@*METHODS@#We compared the frequency of measurement and prevalence of poor control of MBD markers in China DOPPS with other DOPPS regions. We also used generalized estimating equations to assess correlates of MBD markers, and separate models to assess predictors of vitamin D and phosphate binder prescriptions in the China DOPPS.@*RESULTS@#Severe hyperphosphatemia (>7 mg/dL) and secondary hyperparathyroidism (>600 pg/mL) were common (27% and 21% prevalence, respectively); both were measured infrequently (14.9% and 3.2% of patients received monthly measurements in China). Frequency of dialysis sessions was positively associated with hyperphosphatemia; presence of residual kidney function was negatively associated with both hyperphosphatemia and secondary hyperparathyroidism. Laboratory measures indicating poor control of MBD were not associated with subsequent prescription of active vitamin D or phosphate binder.@*CONCLUSIONS@#There are substantial opportunities for improvement and standardization of MBD management in China. Development of country-specific guidelines may yield realistic targets and standardization of medication use accounting for availability and cost.

Acortatarin A inhibits high glucose-induced extracellular matrix production in mesangial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Various treatment regimens and combinations of therapies provide only partial renoprotection. Therefore new approaches are needed to retard the progression of DN. The aim of the present study was to evaluate the role of a novel spiroalkaloid from Acorus tatarinowii named acortatarin A (AcorA) in inhibiting high glucose-induced extracellular matrix accumulation in mesangial cells (MCs).</p><p><b>METHODS</b>The cytotoxity of AcorA on MCs was examined by 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay. The expression of fibronectin and collagen IV was examined by real time PCR and western blotting. The expression of p22(phox) and p47(phox) was detected by western blot. The interaction between p22(phox) and p47(phox) was examined by co-immunoprecipitation. The phosphorylation of p47(phox) was examined by immunoprecipitation. The phosphorylation of protein kinase C (PKC) α, PKCβ, phospholiase C gamma (PLCγ1), and the p85 subunit of PI3K was determined by Western blotting.</p><p><b>RESULTS</b>AcorA significantly inhibited high glucose-induced activation of NADPH oxidase, a ROS-generating enzyme, by increasing phosphorylation of p47(phox) and enhancing interaction between p22(phox) and p47(phox). Preincubation of AcorA with MCs inhibited high glucose-induced collagen IV and fibronectin production in a dose-dependent manner. Moreover, AcorA attenuated high glucose enhanced phosphorylation of PKCα, PKCβ, PLCγ1, and the p85 subunit of PI3K.</p><p><b>CONCLUSION</b>AcorA inhibits high glucose-induced extracellular matrix production via blocking NADPH oxidase activation.</p>

Role of reactive oxygen species in the renal fibrosis / 中华医学杂志(英文版)

Renal fibrosis is a common pathway of progressive renal diseases leading to end-stage renal disease regardless of the etiology. Accumulating evidence indicates that oxidative stress, resulting in generation of reactive oxygen species (ROS), plays a critical role in the initiation and progression of fibrotic diseases. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the predominant enzyme source for ROS generation and is now recognized as a key mediator of cell proliferation and matrix accumulation in renal disease. Multiple stimuli and agonists, such as transforming growth factor β1, tumor necrosis factor, platelet derived growth factor, angiotensin II, hyperglycemia, oxidized low-density lipoprotein and albumin have been shown to alter the activity or expression of the NADPH oxidase and ultimately increase ROS production. ROS directly incites damage to biologically important macromolecules and leads to generation of the so-called advanced oxidation protein products (AOPPs) and advanced glycation end products, which are not only markers of oxidative stress but also cause renal injury. Targeting NADPH oxidase and/or reducing AOPPs production might be a novel strategy for the therapeutic intervention of variety of fibrotic kidney disorders.

Current pattern of Chinese dialysis units: a cohort study in a representative sample of units / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Understanding the characteristics of Chinese dialysis patients and the current practice trends is the first step to evaluate the association between practice pattern and outcome in these populations. In the present study, we evaluated the status of medical treatment and characteristic features of chronic dialysis patients in China.</p><p><b>METHODS</b>Through a clustering sampling, we selected 9 centers from the largest dialysis facilities in 6 cities around China. All adult undergoing dialysis in the selected units were screened. A total of 2388 (1775 on hemodialysis (HD) and 613 on peritoneal dialysis (PD)) patients were finally enrolled. All data were collected at enrollment on the bases of review of medical records.</p><p><b>RESULTS</b>In this cohort, 1313 (55.0%) were male. The mean age was 54 years old. The median time for dialysis was 26 months (12 - 51 months). Seventy-five percent of patients were on HD and 25.0% on PD. Among PD patients, about 21% patients did not receive dialysis adequacy. For HD patients, about 14.0% of them did not achieve dialysis adequacy when the target of kt/V was set as 1.2. Only 44.7% of patients achieved blood pressure target of 140/90 mmHg. About 60% of patients did not reach the hemoglobin target of 110 g/L even though 85.0% of them were treated with erythropoietin. In addition, 48.5% of the patients had uncontrolled mineral metabolism revealed by the high calcium-phosphate product. Compared with HD patients, higher level of serum glucose, triglyceride, and total and low density lipoprotein cholesterol were more common in PD patients.</p><p><b>CONCLUSIONS</b>This observational study suggests that many Chinese dialysis patients did not achieve the therapeutic target, particularly in blood pressure control, anemia correction, and mineral balance. PD patients were more likely to suffer metabolic disturbance.</p>

Coronary stenting does not improve the long-term cardiovascular outcome of patients with mild to moderate renal insufficiency / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Several studies have shown that coronary stenting reduces the frequency of clinical and angiographic restenosis in patients with mild to moderate renal insufficiency. However, less is known about the long-term benefits of stent use in this population. This study was aimed to determine the impact of coronary stenting on extended (5 years) long-term outcomes of patients with chronic renal insufficiency.</p><p><b>METHODS</b>The study included 602 consecutive patients who underwent successful percutaneous coronary intervention with stenting. Renal insufficiency was defined as an estimated glomerular filtration rate < 60 ml x min(-1) x 1.73 m(-2). The major adverse cardiac events were compared for patients with (n = 160) and without (n = 442) renal insufficiency.</p><p><b>RESULTS</b>After the third year of follow-up, nonfatal myocardial infarction and revascularization rates were significantly increased in patients with renal insufficiency compared with those without renal dysfunction (16.9% vs 7.7%, P = 0.001; 29.4% vs 15.8%, P < 0.001). In patients who had recurrent cardiovascular events, a significantly higher rate of de novo stenosis revascularization was found in patients with renal insufficiency than without renal insufficiency (57.7% vs 22.7%, P < 0.001), while there was no significant difference in target lesion revascularization between the groups (51.9% vs 43.6%, P = 0.323). Multivariate analysis demonstrated an independent impact of the presence of renal insufficiency on the major adverse cardiac events (hazard ratio: 1.488, 95% confidence interval: 1.051 - 2.106, P = 0.025) and de novo stenosis (hazard ratio: 5.505, 95% confidence interval: 2.151 - 14.090, P < 0.001).</p><p><b>CONCLUSIONS</b>The late major adverse cardiac events, after successful coronary stenting, is increased in patients with an estimated glomerular filtration rate < 60 ml x min(-1) x 1.73 m(-2). This might be associated with increased risk of de novo stenosis in this population.</p>

Level of asymmetric dimethylarginine and carotid atherosclerosis in patients with chronic kidney disease / 中南大学学报(医学版)

OBJECTIVE@#To determine the association between asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, with atherosclerosis in patients with chronic kidney disease (CKD).@*METHODS@#One hundred thirty-eight CKD patients were enrolled in this study. Serum levels of L-arginine, ADMA, and SDMA were measured by high-performance liquid chromatography (HPLC). Common carotid arteries intimae-medial thickness (CCA-IMT), cross-sectional calculated intimae-medial thickness (cIM area) and atherosclerotic plaque were detected by noninvasive high-resolution B-mode ultrasonography.@*RESULTS@#Serum levels of ADMA and SDMA were significantly increased in CKD patients (n=138) compared with age matched healthy subjects (n=42, P<0.01). ADMA and SDMA levels increased with the progression of renal dysfunction and were negatively related to creatinine clearance (Ccr) in pre-dialysis patients (r=-0.315, P<0.05; r=-0.426, P<0.01). Serum levels of ADMA and SDMA in dialysis patients (n=74) were significantly higher than those in pre-dialysis patients (P<0.05). Patients with carotid artery plaques showed significantly higher levels of ADMA compared with those without plaques. Serum levels of ADMA closely correlated with the mean IMT (r=0.471, P<0.01) and cIM area value (r=0.430, P<0.01). These correlations remained significant even after adjusting GFR, age, gender ,and other risk factors for atherosclerosis in the multiple regression analysis.@*CONCLUSION@#Serum levels of ADMA increased with the progression of CKD and may play a role in the pathogenesis of accelerated atherosclerosis in CKD patients.

Effect of advanced oxidation protein products on nitric oxide production in mouse peritoneal macrophages / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of advanced oxidation protein products (AOPP) on nitric oxide (NO) production in mouse peritoneal macrophages (MPMs).</p><p><b>METHODS</b>MPMs were incubated in the absence or presence of lipopolysaccharide (LPS) with AOPP-modified bovine serum albumin (BSA) prepared by exposure of BSA to hypoclorous acid or pre-treated with AOPP-BSA and subsequent stimulation with LPS. NO production in the supernatants of the culture media was determined spectrophotometrically using Griess method. The cell viability was measured by MTT assay.</p><p><b>RESULTS</b>BSA induced significant NO production in MPMs. AOPP modification of BSA significantly inhibited NO production, and AOPP-BSA exhibited time- and dose-dependent inhibition of NO production induced by LPS in MPMs incubated together with LPS or pre-treated before LPS stimulation.</p><p><b>CONCLUSION</b>AOPP-BSA is capable of inhibiting inducible NO production in MPMs.</p>

Mechanism of advanced glycation end products-induced hyperpermeability in endothelial cells / 生理学报

The purpose of the present study was to investigate the effects of advanced glycation end products (AGEs) modified protein on the permeability of endothelium monolayers and morphological changes of actin cytoskeleton. The roles of receptor for AGEs (RAGE), oxidant stress and the activation of p38 MAPK pathway in this pathological procedure were elucidated. Human umbilical vein endothelial cells (HUVECs)-derived cell line (ECV304) were incubated with AGEs modified human serum albumin (AGE-HSA) in concentrations of 12.5, 25, 50, and 100 microg/ml respectively, for 2, 4, 8, 12 and 24 h. As control, HSA of the same concentration was administered to cells. Then TRITC-albumin was added to evaluate Pa value that reflects the permeability of endothelial monolayer. Furthermore, to visualize the morphological changes of actin cytoskeleton, the treated cells were incubated with rhodamine-phalloidin to stain F-actin. The results showed that the trans-endothelial membrane flux of albumin was significantly increased in a concentration- and time-dependent manner upon the stimulation of AGE-HSA, accompanying with actin reorganization. The blockage of AGE and RAGE binding with anti-RAGE IgG and the pharmacological inhibition of NADPH oxidase or p38 MAP kinase greatly attenuated the AGE-induced hyperpermeability response, respectively. These results indicate that RAGE, NADPH oxidase and p38 MAPK are possibly involved in the mediation of AGEs-induced barrier dysfunction and actin cytoskeleton reorganization in endothelial cells.