Objective:To explore the clinical effect of low sodium hemodialysis(HD) combined with hemodiafiltration (HDF) on the blood pressure rhythm and calcium phosphorus metabolism of patients with resistant hypertension.Methods:62 uremia patients combined with resistant hypertension were randomly divided into two groups.The control group (n=31) was treated with traditional HD alone for 2h per time,3 times per week,and combined group (n=31) was treated with low sodium HD and HDF,once per week.The effect was evaluated at 3 months after treatment,the changes of blood pressure circadian rhythm,calcium phosphate metabolism before and after treatment as well as the incidence of adverse reactions during HD were compared between two groups.Results:The indicators of blood pressure rhythm including 24h systolic blood pressure (24hSBP),24h diastolic blood pressure (24hDBP),day systolic blood pressure (dSBP),day diastolic blood pressure (dSBP),night systolic blood pressure (nSBP),night diastolic blood pressure (nSBP) of treatment group were significantly reduced after treatment and were significantly lower than those of the control group (P<0.05).All the indicators of blood pressure rhythm except nSBP in control group showed no significant difference between before and after treatment (P>0.05).After treatment,the levels of blood Ca in the treatment group was obviously increased,the levels of blood P,PTH were obviously decreased compared with control group (P<0.05).The incidence of adverse reactions in treatment group and control group was 16.1% and 16.1% respectively,which showed no significant difference (P>0.05).Conclusions:Low sodium HD combined with HDF can effectively remove the toxic metabolites,promote the blood pressure rhythm recovery,regulate metabolism of calcium phosphate in treating the uremia patients with resistant hypertension.
The purpose of this review is to summarize cases of Chinese doctors who have committed suicides between years 2008 and 2016. Moreover, we would like to appeal to the government and the public to increase their efforts to reduce death among Chinese doctors. We have reviewed public reports from local media, medical websites, official documents, and articles published in PubMed, Google Scholar, China National Knowledge Infrastructure (CNKI), and www.dxy.cn (a popular medical web in China) between years 2008 and 2016. Identified articles were published in either English or Chinese. A total of 51 cases (16 females and 35 males) of doctor suicides were reported or published between 2008 and 2016. Most incidents of death occurred between 20-59-year-olds, with a higher number observed within the 30-39 age group. Notably, the Jiangsu province had the highest number of reported doctor suicides (9 cases). Furthermore, detailed analysis revealed that the department of pediatrics (18%, 9/51) topped the number of suicidal rates when compared to the other hospital units. Suicides occurred more often in the full-service, tertiary hospitals, accounting for 63% (32/51) of the reports. Jumping from a building was the most common way of death recorded, accounting for 55% (28/51) of total cases. Suicide is not just a medical issue but also a social concern. A key to reducing deaths by suicide in Chinese doctors should be a commitment of both the Chinese government and medical organizations to establish and implement a coordinated plan of action.
Background: Few studies have evaluated the prognostic value of dialysis dose in twice-weekly hemodialysis (HD). A single-pool Kt/V (spKt/V) over 1.70 may benefit patients receiving twice-weekly maintenance HD. Methods: This is a multicenter randomized controlled trial performed on 163 patients from 17 dialysis centers in Shanghai who were allocated to high- (n = 98) and standard-dose groups (n = 65) and followed through 96 weeks of study period. Therapeutic approaches were given to increase spKt/V to over 1.70 in the high-dose group. Data were collected every 12-24 weeks. The primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACEs) occurrence, and secondary outcomes included residual kidney function (RKF) and health-related quality of life (HR-QOL). Results: The spKt/V in high-dose and standard-dose groups were 1.80 ± 0.23 and 1.55 ± 0.19, respectively, after an 8-week intervention (p < 0.001). At the end of the study, SF-36 physical function and total score in high-dose group were 82 (69-90) and 74 (47-84), respectively, both of which were higher than those in the standard-dose group. Decline in urine volume was observed in both groups with no significant difference (p = 0.431). No difference was found in overall survival between the 2 groups (p = 0.580). The 1-year MACE-free survival for high-dose group was 84.49%, better than 76.72% for standard-dose group (p = 0.029). Conclusions: Higher spKt/V is also associated with MACE-free survival and better HR-QOL, especially in physical function aspect for twice-weekly dialysis patients. Increasing spKt/V over 1.70 in twice-weekly HD population does not cause loss of RKF.
Application of bensulfuron-methyl produced a stimulative effect on growth and heterocyst formation at low concentrations but an inhibition effect at high concentrations. Presence of the sulfonylurea herbicide bensulfuron-methyl at 0.001 to 10 mg/L affected the growth and cell morphology of the nitrogen-fixing cyanobacteria (Anabaena azotica), high concentration of bensulfuron-methyl (1 mg/L and 10 mg/L) obviously inhibited the growth of A.azotica, especially vegetative cells and heterocyst. And at the same time lots of cell disintegrated and inclusions dissolved. Presenting in 0.001 to 0.1 mg/L, the effect of bensulfuron-methyl on cell morphology was not significant. Cells can grow well and vegetative cell and heterocyst number increased notly. Our findings support the view that low concentrations stimulate growth and cell maintain good morphological structure while high dose inhibited.
OBJECTIVE To explore the renoprotective effects of (-)-epigallocatechin-3-gallate (EGCG) and its potential mechanism in type 2 diabetic db/db mice. METHODS 8-week-old db/db mice (6 h fasting plasma glucose >16.7 mmol/L) were allocated randomly into Control group (non-intervention group, n=8), EGCG A group (50 mg·kg(-1)·d(-1,)n=8), EGCG B group (100 mg·kg(-1)·d(-1,)n=8). Before the study and after the intervention (in the 4(th)and 8(th)week), the body weight, the level of fasting plasma glucose, oral glucose tolerance test (OGTT) were measured and 24 h urine samples were collected. 24 h proteinuria was measured by routine chemical method. The levels of angiotensin Ⅱ(AngⅡ), fasting plasma insulin and urinary 8-OHdG were measured with enzyme-linked immunosorbent assay (ELISA). The protein expression levels of angiotensin Ⅱ type 1 receptor (AT-1R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit P22-phox, NADPH oxidase subunit P47-phox, phospho-extracellular regulated protein kinases (p-Erk1/2), phospho-P38 mitogen-activated protein kinase (p-P38MAPK), phospho -phosphatidylinositol 3-hydroxy kinase (p-PI3K) and phospho-protein kinase B (p-AKT) were determined by Western blot. The renal pathological changes were examined by the method of PAS (periodic acid-Schiff stain). RESULTS After 8 weeks of treatment with EGCG, the level of fasting plasma glucose decreased[(14.4±1.0) mmol/L, (14.2±0.7) mmol/L vs. (17.2±0.8) mmol/L]; the level of fasting plasma insulin increased[(13.2±1.2)mU/L, (13.4±1.3) mU/L vs. (9.9±1.0) mU/L]; the area under the curve (AUC) of OGTT decreased[(49.3±1.8) mmol·L(-1)·h(-1,)(44.8±0.7) mmol·L(-1)·h(-1)vs. (60.0±0.8) mmol·L(-1)·h(-1)]; the level of 24 h proteinuria[(8.8±1.0) mg, (8.6±1.1) mg vs. (11.7±1.3) mg]and urinary 8-OHdG[(90±5) ng/d, (78±5) ng/d vs. (118±10) ng/d]decreased; the level of serum Ang-Ⅱ[(498±23) ng/L, (511±19) ng/L vs. (688±17) ng/L]and renal cortex AngⅡ[(367±5) ng/L, (384±10) ng/L vs. (406±7) ng/L]decreased; the expression levels of AT-1R, P22-phox, P47-phox, p-Erk1/2, p-P38MAPK downregulated obviously and the expression levels of p-PI3K, p-AKT increased significantly (P<0.05), and renal pathology improved as compared with the control group. After 8 weeks of treatment with EGCG, the level of urinary 8-OHdG decreased (P=0.007) and the AUC of OGTT also decreased (P=0.01) in EGCG B group when compared with the EGCG A group. CONCLUSION EGCG protects the kidney in diabetic db/db mice via anti-oxidative stress pathway, as well as inhibiting Erk1/2-P38MAPK pathway and improving PI3K-AKT signaling transduction pathway.
Objective: Use of prolonged nocturnal or daytime hemodialysis (PHD, more than 12 h per week) is associated with improvement of some clinical parameters relative to conventional hemodialysis (CHD, 4 h sessions, thrice weekly), but the effect on survival is unclear. The purpose of this meta-analysis is to determine whether PHD improves survival of patients undergoing maintenance HD. Design: Systematic review of observational studies by meta-analysis. Data Sources: Electronic searches in MEDLINE (PubMed, 1966-2012), EMBASE (1974-2012), www.clinicaltrials.gov, and the Cochrane Controlled Clinical Trials Register Database. Eligibility Criteria for Selecting Studies: All prospective or retrospective studies were considered eligible if they were cohort studies or observational studies that compared CHD with PHD (more than 12 h of HD per week due to more HD sessions or increased duration of HD sessions) and the final outcome was all-cause death or mortality. Results: Thirteen studies with a total of 85,722 participants (10,285 PHD patients, 75,437 CHD patients) met the inclusion criteria. Summary estimates indicated that PHD was associated with decreased risk of mortality (OR = 0.72, 95% CI 0.64-0.81, p < 0.00001). Analysis of residual confounders of pooled results from six retrospective studies indicated that PHD patients were less likely to have low hemoglobin (11.7 vs. 11.2 g/dl, p < 0.01), younger (51.2 vs. 58.8 years, p < 0.01), less likely to have diabetes (27.1 vs. 40.8%, p < 0.01), and less likely to use a catheter (18.4 vs. 27.1%, p < 0.01), so these may have affected the outcome measure in these studies. Conclusions: PHD is associated with improved survival relative to CHD, although residual confounders have affected this relationship in observational studies. Large, multicenter randomized, controlled trials are needed to confirm our results. (C) 2013 S. Karger AG, Basel
Hypertension is a serious worldwide public health problem. The aim of this study is to design anti-hypertension angiotensin II (Ang II) vaccine using molecular biology and immunological method. This novel anti-hypertension vaccine, which is a chimeric protein named pHAV-4Ang IIs, presents four successive repeated Ang IIs as the functional epitope on the surface of the hepatitis A virus-like particle (HAVLP). In this study, pHAV-4Ang IIs was expressed using Bac-to-Bac Baculovirus Expression System. With the RT-PCR analysis, SDS-PAGE, western blot, IFA, electron microscope methods for identification of expression products, these results confirmed that stable expression of pHAV-4Ang IIs can be effectively achieved in infected sf9 cells. Spontaneous hypertensive rats (SHRs) were immunized with pHAV-4Ang IIs to test immunogenicity and pharmacodynamic action. The results showed that this anti-hypertension vaccine can induce high titer Ang II-specific IgG antibody for almost 10 weeks. When antibody titer reached the peak at 8th week, the mean systolic blood pressure (SBP) degraded approximately 23 mmHg compared with the PBS control group, and the mean diastolic blood pressure (DBP) degraded approximately 12 mmHg compared with the PBS control group. These results suggest that this anti-hypertension vaccine has good immunogenicity and good effect on reduction of blood pressure in SHRs, which provide reliable base for large-scale preparation of this hypertension vaccine in the future, and a new direction of exploration for the development of anti-hypertension therapeutic vaccine.
Objective To investigate the effects of L-carnitine supplementation on insulin resistance in nondiabetic hemodialysis patients.Method 41 non-diabetic patients undergoing hemodialysis were divided into two groups:therapy group(n=20) was treated with iv L-carnitine 1.0g twice per week after hemodialysis session for 6 months,21 matched non-diabetic hemodialysis patients no received L-carnitine served as control.Fasting blood glucose,insulin,insulin resistance index(HOMA-IR),and the inflammation marker-C-reactive protein(CRP) were assessed at baseline and 6 months after therapy.Results 6 monthst reatment of L-carnitine supplementation significantly decreased fasting insulin and HOMA-IR in therapy group as compared with control group,the change from baseline to 6month value was-10(-35,20) vs-1(-15,20),P=0.03;(-2.80.6) vs(-0.40.5),P < 0.01,respectively.Moreover the inflammation marker,CRP was decreased in L-carnitine group when compared with control group,the change from baseline to the end of therapy was(-5.91.2) vs(-0.10.1).The relative assessment showed that CRP was positively associated with insulin levels(r=0.56,P< 0.01) and HOMA-IR(r=0.46,P < 0.05).Conclusion L-carnitine therapy may significantly improve insulin resistance in non-diabetic patients on hemodialysis,which is associated with the improvement of micro-inflammation as indicated by decreased CRP.Our study will provide broader insight into the role of L-carnitine in the treatment of insulin resistance in maintenance hemodialysis patients.
Patients with type 2 diabetes lose beta cells, but the underlying mechanisms are incompletely understood. Glucose-6-phosphate dehydrogenase (G6PD) is the principal source of the major intracellular reductant, NADPH, which is required by many enzymes, including enzymes of the antioxidant pathway. Previous work from our laboratory has shown that high glucose impairs G6PD activity in endothelial and kidney cells, which leads to decreased cell survival. Pancreatic beta cells are highly sensitive to increased ROS. This study aimed to determine whether G6PD and NADPH play central roles in beta-cell survival. Human and mouse islets, MIN6 cell line, and G6PD deficient mice were studied. High glucose inhibited G6PD expression and activity. Inhibition of G6PD with siRNA led to increased ROS and apoptosis, decreased proliferation, and impaired insulin secretion. High glucose decreased insulin secretion, which was improved by overexpressing G6PD. G6PD-deficient mice had smaller islets and impaired glucose tolerance compared with control mice, which suggests that G6PD deficiency per se leads to beta-cell dysfunction and death. G6PD plays an important role in beta-cell function and survival. High-glucose-mediated decrease in G6PD activity may provide a mechanistic explanation for the gradual loss of beta cells in patients with diabetes.
Objective To investigate the effects of serum of patients with maintenance hemodialysis(HD),conventional dialysate(CD) and high purity dialysate(HPD) on apoptosis of adipocytes. Methods Blood samples of 20 patients with HD(ten were treated with CD and ten were treated with HPD) were collected,and serum was isolated for detection of tumor necrosis factor-α(TNF-α) by ELISA.Mature 3T3-L1 adipocytes induced in vitro were treated with hemodialysis patient serum(HDPS group),HDPS combined with CD(HDPS+CD group) and HDPS combined with HPD(HDPS+HPD group),respectively,and cells were harvested 48 h later.Morphological changes were observed by Hoechst33258 fluorescence staining,and cell apoptosis was detected by Annexin-V-FITC/PI double staining.Bacterial DNA from CD and HPD was assayed by PCR. Results It was revealed by ELISA that the serum level of TNF-α from patients with HD treated by CD was significantly higher than that from patients with HD treated by HPD(P0.05).Typical apoptotic morphology changes were observed by fluorescence microscopy in HDPS group and HDPS+CD group,and the apoptosis rates in these two groups were significantly higher than that in HDPS+HPD group(P0.05).PCR revealed that there were significant differences between the expression of bacterial DNA in CD and that in HPD(902.79±60.57 vs 454.87±32.22)(P0.05). Conclusion HDPS may induce apoptosis of 3T3-L1 adipocytes,which may be related to the increased serum level of TNF-α.Compared with intervention by HDPS and CD,intervention by HDPS and HPD may yield lower apoptosis rate of adipocytes,and there may be lower expression of bacterial DNA in HPD.
Objective To investigate the effects of different dialysates on expression of protein kinase C-δ (PKCδ) and apoptosis of U937 cell line. Methods Different dialysates were added into culture fluid with U937 cell line at exponential phase of growth, and groups were divided: fluid A+fluid B group (dialysate A+dialysate B), fluid A+fluid B+rottlerin (PKCδ specific inhibitor)group, fluid A+powder B group (dialysate A+powder B) and fluid A+powder B + rottlerin group. Besides, blank control group and normal control group were established. Cells were harvested 24 h and 48 h after treatment, morphological changes were observed by Hoechst33258 fluorescence staining, cell apoptosis was measured by Annexin-V-FITC/PI double staining, and expression of PKCδ mRNA and protein was detected by RT-PCR and Western blotting, respectively. Results Cell apoptosis significantly increased in fluid A+powder B group, with typical morphology of apoptosis. After treatment for 24 h and 48 h, cell apoptosis rates in fluid A+powder B group were significantly higher than those at corresponding time points in blank control group, normal control group and fluid A+powder B+rottlerin group (P0.05). Compared with normal control group, blank control group and fluid A+powder B+rottlerin group, the expression of PKCδ mRNA and protein of U937 cells in fluid A+powder B group were significantly increased (P0.05). There was no significant difference in cell apoptosis rates and expression of PKCδ mRNA and protein between fluid A+fluid B group and blank control group, normal control group and fluid A+fluid B+rottlerin group (P0.05). Conclusion Fluid A+powder B can significantly increase apoptosis of U937 cell line, the mechanism of which may be associated with the up-regulation of expression of PKCδ. Compared with fluid A+powder B, fluid A+fluid B is superior in reducing apoptosis of peripheral blood monouclear cells.