Assessment of the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy

Objective:To study the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy.Methods:90 patients with early diabetic nephropathy treated in our hospital between June 2011 and November 2015 were collected and divided into observation group and control group (n=45) according to the single-blind randomized control method. Observation group received epalrestat combined with alprostadil treatment, control group received alprostadil treatment alone, and the treatment of both groups lasted for 3 months. Before treatment and after 3 months of treatment, turbidimetric immunoassay was used to detect the renal function indexes in peripheral blood, rate method was used to detect the renal function indexes in urine, and ELISA method was used to detect the levels of peroxidation indexes and inflammation indexes.Results:Before treatment, differences in renal function, peroxidation damage and inflammatory damage indexes were not statistically significant between two groups of patients (P>0.05). After 3 months of treatment, creatinine (Scr), cystatin C (CysC),β2 microglobulin (β2-MG), N-acetyl-β-D-glucosaminidase (NAG), reactive oxygen species (ROS), advanced protein oxidation products (AOPPs), interleukin-8 (IL-8), interleukin-27 (IL-27) and procalcitonin (PCT) levels of observation group were lower than those of control group while catalase (CAT), total superoxide dismutase (TSOD), interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13) levels were higher than those of control group (P<0.05). Conclusions:Epalrestat combined with alprostadil can protect the renal function and inhibit the peroxidation damage and inflammatory injury in patients with early diabetic nephropathy.

The Protective Role of Procyanidins and Lycopene Against Mercuric Chloride Renal Damage in Rats

Objective This study aims to investigate the protection of procyanidins and lycopene from the renal damage induced by mercuric chloride.Methods Rats were treated with either procyanidins or lycopene 2h before HgCl 2 subcutaneously injection,once daily treatment for 2 successive days.Results In comparison with HgCl 2 group,markers of renal function such as blood urea nitrogen in serum and urinary protein were decreased to （18.45±11.63） mmol/L and （15.93±9.36） mmol/L,（4.54±0.78） g/（g Cr） and （4.40±1.12） g/（g Cr）.N‐acetyl‐beta‐D‐glucosaminidase,lactate dehydrogenase,alkaline phosphatase in urine were depressed to （125.49±11.68） U/（g Cr）,（103.73±21.79） U/（g Cr）,（101.99±12.28） U/（g Cr）,and （113.19±23.74） U/（g Cr）,（71.14±21.80） U/（g Cr）,（73.64±21.51） U/（g Cr） in procyanidins and lycopene groups.Indicators of oxidative stress,for example,Glutathion was reduced to （45.58±9.89） μmol/（g pro） and （45.33±5.90） μmol/（g pro）,and antioxidant enzymes such as superoxide dismutase,glutathione‐peroxidase were enhanced to （43.07±10.97） U/（mg pro） and （39.94±6.04） U/（mg pro）,（83.85±18.48） U/（mg pro）,and （85.62±12.68） U/（mg pro）.Malondialdehyde was lowered to （0.95±0.12） （μmol/g pro） and （1.03±0.12） μmol/（g pro） in procyanidins and lycopene groups.ROS generation was decreased by 27.63% and 16.40% and apoptosis was also decreased in procyanidins and lycopene groups respectively.Pathological changes were much better as well.Conclusion Procyanidins and Lycopene play some protective role against mercury kidney damage.

Protective effect of antioxidant on renal damage caused by Doxorubicin chemotherapy in mice with hepatic cancer

Objective:To investigate the protective effects and mechanism of antioxidant TBHQ on renal damage caused by doxorubicin chemotherapy in mice with hepatic cancer.Methods:Cell H22 of mice with hepatic cancer which was subcultured for three times was subcutaneously transplanted to the groin of right lower limb of 45 SPF Kunming mice to establish the transplanted tumor model.The doxorubicin chemotherapy group and antioxidant intervention group received intraperitoneal injection of ADM(1 mg/kg·0.2 mL/2d).The model control group received normal saline(NS) of the same volume at the same time.1%TBHQ was added into the diet of mice of the antioxidant intervention group.Seven weeks later,morning urines and peripheral blood were randomly collected to detect UAIb,UCr,BUN,Scr and UAlb/Cr levels.All mice were beheaded.The renal tissues were made into homogenate,and SOD,T-AOC and MDA content in tissues were detected followed by cell lysis.All data were processed using SPSS 19.0.Results:The UAlb/Cr,BUN.Scr and MDA of doxorubicin chemotherapy group were significantly higher those of model control group and the activities of SOD,T-AOC in doxorubicin chemotherapy group were lower than those of model control group(P<0.01).The UAlb/Cr,BUN,Scr and MDA of antioxidant intervention group were lower than those of doxorubicin chemotherapy group and the activities of SOD,T-AOC of antioxidant intervention group were higher than those of doxorubicin chemotherapy group doxorubicin chemotherapy group(P<0.05).The BUN of model control group was higher than that of blank group,and T-AOC was lower than that of blank group,and difference was statistically significant(P<0.05).Conclusions:Doxorubicin chemotherapy could lead to abnormal antioxidant capacity and renal function of tumor-bearing mice with hepatic cancer.TBHQ antioxidant intervention could effectively improve the antioxidant capacity of renal tissue and reduce the renal damage caused by doxorubicin to some extent.

The Relationship Between the Energy Levels of Shock Waves and the Degree of Renal Damage After ESWL:A Prospective Clinical Matching Trail

In an attempt to understand the effects of high energy shock wave (HESW)on renal function, we studied prospectively 40 patients with nephrolithiasis in 4 groups,using same voltage with different numbers of shock wave therapy to identify the difference of effects on renal function. Stone burdens and posit ion were similar in these groups. Each group received 1500, 2000, 2500 or 3000 puises at 12. 5 KV on JT-3lithotripotor respectively. All the groups had significantly increased the levels of urinary NAG, β2MG, ALB and serum β2MG, which reached the highest values on 1-3days after ESWL (P<0. 001), and then decreased to the pre-ESWL levels except urinary NAG in group Cand D and serum β2MG which were still significantly higher (P<0.05) than those before-ESWL on the 7th day after ESWL. There was significant correlation between either urinary NAG (γ=0. 977, P<0. 05) or β2MG (γ=0. 933, P<0. 001) with the number of shock wave. In addition, urinary NAG and β2MG increased significantly when the number of shock waves was over 2500 shots.These above findings suggest that shock wave had induced acute changes in renal functions and transient renal tubular damages, although these functional changes recovered within one week, and the tubular damage might last longer than 7 days , In order to avoid serious renal damage, it’s necessary to limit the energy level of shock waves under 12. 5 KV×2500 shots by using JT-3 lithotriptor.

Metal magnetic memory testing for early damage assessment in ferromagnetic materials

In order to investigate the physical mechanism of metal magnetic memory testing, both the influences of earth magnetic field and applied stress on magnetic domain structure were discussed. Static tension and fatigue tests for low carbon steel plate specimens were carried out on hydraulic servo testing machine of MTS810 type and magnetic signals were measured during the processes by the type of EMS-2003 instrument. The results indicate that the initial magnetic signals of specimens are different before loading. The magnetic signals curves are transformed from initial random to regular pattern due to the effect of two types of loads. However, the shape and distribution of magnetic signal curves in the elastic region are different from that of plastic region in tension test. While in fatigue test those magnetic signals curves corresponding to different cycles are similar. The H_p(y) value of magnetic signals on the fracture zone increases dramatically at the breaking transient time and positive-negative magnetic poles occur on the two parts of fracture zone.

Ligliptin for treatment of type 2 diabetes mellitus with early renal injury: Efficacy and impact on endogenous hydrogen sulfide and endothelial function

BACKGROUND Diabetes is a clinically common chronic disease,and its incidence has been increasing in recent years.Diabetes is believed to accelerate the process of atherosclerosis in patients,and abnormal endothelial function is an important factor leading to diabetic kidney damage.AIM To investigate the efficacy of ligliptin in the treatment of type 2 diabetes mellitus(T2DM)with early renal injury and its effect on serum endogenous hydrogen sulfide(H2S),endothelial cell particles,and endothelial function.METHODS From January 2018 to April 2019,110 patients with T2DM and early kidney injury treated at our hospital were divided into an observation group(receiving ligliptin treatment,n=54)and a control group(receiving gliquidone therapy,n=56).Blood glucose and renal function before and after treatment were compared between the two groups.RESULTS The differences in fasting blood glucose,2 h blood glucose,and glycated hemoglobin were not statistically significant between the two groups after treatment.The urinary albumin excretion rate after treatment in the ligliptin group was 70.32±11.21μg/min,which was significantly lower than that of the gliquidone group(P=0.000).Serum endogenous H2S and endothelial cell microparticles of the ligliptin treatment group were 40.04±8.82 mol/L and 133.40±34.39,respectively,which were significantly lower than those of the gliquidone treatment group(P=0.000 for both);endothelin-dependent diastolic function and nitric oxide after treatment in the ligliptin group were 7.98%±1.22%and 190.78±30.32 mol/L,significantly higher than those of the gliquidone treatment group(P=0.000 for both).CONCLUSION Ligliptin treatment of T2DM with early renal injury has the same glucoselowering effect as gliquidone treatment.Ligliptin treatment has a better effect and it can significantly improve the renal function and vascular endothelial function of patients,and reduce serum endogenous H2S and endothelial cell particle levels.

Response features of nonlinear circumferential guided wave on early damage in inner layer of a composite circular tube

A theoretical model to analyze the nonlinear circumferential guided wave(CGW) propagation in a composite circular tube(CCT) is established. The response features of nonlinear CGWs to early damage [denoted by variations in third-order elastic constants(TOECs)] in an inner layer of CCT are investigated. On the basis of the modal expansion approach, the second-harmonic field of primary CGW propagation can be assumed to be a linear sum of a series of double-frequency CGW(DFCGW) modes. The quantitative relationship of DFCGW mode versus the relative changes in the inner layer TOECs is then investigated. It is found that the changes in the inner layer TOECs of CCT will obviously affect the driving source of DFCGW mode and its modal expansion coefficient, which is intrinsically able to influence the efficiency of cumulative second-harmonic generation(SHG) by primary CGW propagation. Theoretical analyses and numerical simulations demonstrate that the second harmonic of primary CGW is monotonic and very sensitive to the changes in the inner layer TOECs of CCT, while the linear properties of primary CGW propagation almost remain unchanged. Our results provide a potential application for accurately characterizing the level of early damage in the inner layer of CCT through the efficiency of cumulative SHG by primary CGW propagation.

Pterostilbene Ameliorates Renal Damage in Diabetic Rats by Suppressing Hyperglycemia with Inhibition of Inflammatory and Fibrotic Responses

Diabetes mellitus(DM) is a chronic metabolic disorder characterized by a combination of hyperglycemia, reduced insulin sensitivity, and/or relative impairment of insulin secretion[1]. Renal damage, which is a major microvascular complication of DM and a progressive kidney disease, has been considered the most common cause of end-stage renal disease[2]. Renal fibrosis is a common outcome of progressive renal damage.

Correlation of renal arterial ultrasound parameters with renal damage and placental hypoxia in patients with preeclampsia

Objective:To study the correlation of renal arterial ultrasound parameters with renal damage and placental hypoxia in patients with preeclampsia.Methods: A total of 56 cases of pregnant women who were diagnosed with preeclampsia in Mianyang People's Hospital between May 2014 and October 2016 were selected as the PE group of the research, and healthy pregnant women who received antenatal care during the same period were selected as the control group. Color Doppler diasonograph was used to determine renal arterial blood flow parameters, and enzyme-linked immunosorbent assay kits were used to determine the contents of renal damage and endothelial injury indexes in serum as well as the contents of apoptosis molecules caused by hypoxia in placenta.Results: Renal interlobar arterial Vs, Vd and AT levels in PE group were significantly higher than those in control group;CysC,β2-MG, sFlt-1, sEng, ET-1, AnnexinV and vWF contents in serum as well as KIM-1 and NGAL contents in urine of PE group were significantly higher than those of control group and positively correlated with renal interlobar arterial Vs, Vd and AT levels, and the ROS, CytC, Caspase-3 and Caspase-9 contents in placenta were significantly higher than those of control group and positively correlated with renal interlobar arterial Vs, Vd and AT levels.Conclusion: The change of renal arterial blood flow parameters in patients with preeclampsia can assess the extent of renal damage and placental hypoxia.

Protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms

Objective:To explore the protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms.Methods:A total of 50 patients with early diabetic nephropathy treated in our hospital between May 2012 and January 2016 were collected, and according to the random number table, the patients were divided into observation group (n=25) and control group (n=25). On the basis of conventional treatment, control group of patients received benazepril therapy, observation group of patients received calcium dobesilate combined with benazepril therapy, and the treatment lasted for 3 months. Before and after treatment, automatic biochemical analyzer was used to detect the levels of renal injury indexes in peripheral blood, RIA method was used to detect the levels of renal injury indexes in urine, ELISA method was used to detect the levels of renal fibrosis indexes and Western-blot method was used to detect the protein expression of TGF-β1/BMP-7 and Smad signaling pathway molecules in renal tissue. Results: Before treatment, differences in renal injury index levels, renal fibrosis index levels and signaling pathway molecule protein expression were not statistically significant between two groups of patients. After treatment, BUN, SCr andβ-TP levels in the peripheral blood as well as KIM-1 level in urine of observation group were lower than those of control group;renal fibrosis indexes TGF-β1, CTGF, TIMP-1, LN and HA levels in serum of observation group were lower than those of control group;TGF-β1 and Smad2/3 protein expression in renal tissue of observation group were lower than those of control group while Smad7 and BMP-7 protein expression were higher than those of control group.Conclusion: Calcium dobesilate combined with benazepril therapy can reduce the renal injury and inhibit the fibrosis process in patients with early diabetic nephropathy, and it achieves the above effect by regulating the TGF-β1/BMP-7 and Smad signaling pathway function.

Evaluation of renal function and oxidative stress after adjuvant epalrestat treatment of early diabetic nephropathy

Objective:To explore the influence of adjuvant epalrestat treatment of early diabetic nephropathy on renal function and oxidative stress.Methods:A total of 80 patients with early diabetic nephropathy who were treated in our hospital between January 2013 and February 2016 were collected and divided into observation group and control group according to single-blind parallel control. Control group of patients received routine therapy, and observation group of patients received adjuvant epalrestat treatment on this basis. After 8 weeks of treatment, automatic biochemical analyzer was used to detect the renal function indexes of two groups of patients;RIA method was used to detect the serum renal fibrosis index levels;enzyme-linked immunosorbent assay (ELISA) was used to detect serum oxidative stress index levels.Results:Before treatment, differences in serum renal function, renal fibrosis and oxidative stress index levels were not statistically significant between two groups of patients;after 8 weeks of treatment, serum renal function indexes Scr, BUN, CysC andβ2-MG levels of observation group were lower than those of control group, renal fibrosis indexes CⅣ, CTGF and TGF-β1 levels were lower than those of control group, oxidation indexes ROS, LHP and AOPPs levels were lower than those of control group, anti-oxidation indexes SOD, VitE, VitC and T-AOC levels were significantly higher than those of control group, and the differences were statistically significant.Conclusion:Adjuvant epalrestat therapy can optimize the renal function and reduce the systemic oxidative stress response in patients with early diabetic nephropathy.

Assessment of renal function and oxidative stress after alprostadil combined with valsartan treatment of early diabetic nephropathy

Objective:To analyze the renal function and oxidative stress after alprostadil combined with valsartan treatment of early diabetic nephropathy.Methods:A total of 230 patients with early diabetic nephropathy who were treated in our hospital between December 2011 and December 2015 were divided into control group (n=115) and observation group (n=115) according to random number table. Control group received valsartan treatment, observation group received alprostadil combined with valsartan treatment, and both lasted for one month. After treatment, renal blood flow parameters were evaluated by ultrasound contrast technique, renal function index levels in peripheral blood and urine were measured, and serum levels of oxidative stress indexes were detected.Results:After 1 month of treatment, area under curve (AUC) and time to peak (TTP) levels under ultrasound contrast of observation group were lower than those of control group while derived peak intensity (DPI) level was higher than that of control group;peripheral blood urea nitrogen (BUN) and serum creatinine (Scr) levels of observation group were lower than those of control group, albumin (Alb) level was higher than that of control group, and urine red blood cell (RBC) level was lower than that of control group;serum oxidative stress indexes malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels of observation group were lower than those of control group while superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) levels were higher than those of control group.Conclusion: Alprostadil combined with valsartan can optimize renal function and reduce systemic oxidative stress in patients with early diabetic nephropathy.

DETECTION OF CYTOMEGALOVIRUS(CMV) IMMEDIATE EARLY ANTIGEN IN KIDNEY BIOPSIES AND TRANSPLANT NEPHRECTOMIES

Objective To investigate the relationship between CMV infection and renal allograft rejection. Methods 39 kidney biopsies and transplant nephrectomies were collected and investigated for CMV immediate early antigen by immunohistochemistry. Results In 14 out of 39 tissue specimens CMV immediate early antigen were found. 8 biopsies from normal donor kidneys were negative; only 1 (10%) in 10 tissue specimens with early stage acute rejection was positive; 5(55.6%) in 9 biopsies with late stage acute rejection and 8 (66.7%) in 12 tissue blocks with chronic rejection were positive. Compared with normal kidney tissues, the infections in tissues with early stage acute rejection didn't increase obviously, but increased obviously in kidney tissue specimens with late stage rejection and with chronic rejection (P< 0.05). Conclusion CMV infection appears to contribute to late stage acute rejection and chronic rejection after renal transplantation.

Combined early fluid resuscitation and hydrogen inhalation attenuates lung and intestine injury

AIM:To study the effects of combined early fluid resuscitation and hydrogen inhalation on septic shockinduced lung and intestine injuries.METHODS:Wistar male rats were randomly divided into four groups:control group(Group A,n = 15);septic shock group(Group B,n = 15);early fluid resuscitation-treated septic shock group(Group C,n = 15);and early fluid resuscitation and inhalation of 2% hydrogentreated septic shock group(Group D,n = 15).The activity of hydroxyl radicals,myeloperoxidase(MPO),superoxide dismutase(SOD),diamine oxidase(DAO),and the concentration of malonaldehyde(MDA) in the lung and intestinal tissue were assessed according to the corresponding kits.Hematoxylin and eosin staining was carried out to detect the pathology of the lung and intestine.The expression levels of interleukin(IL)-6,IL-8,and tumor necrosis factor(TNF)-α in lung and intestine tissue were detected by enzyme-linked immunosorbent assay method.The expression levels of Fas and Bcl2 in lung tissues were determined by immunohistochemistry and Western blotting.RESULTS:Septic shock elicited a significant increase in the levels of MDA(10.17 ± 1.12 nmol/mg protein vs 2.98 ± 0.64 nmol/mg protein) and MPO(6.79 ± 1.02 U/g wet tissue vs 1.69 ± 0.14 U/g wet tissue) in lung tissues.These effects were not significantly decreased by Group C pretreatment,but were significantly reduced by Group D pretreatment(MDA:4.45 ± 1.13 nmol/mg protein vs 9.56 ± 1.37 nmol/mg protein;MPO:2.58 ± 0.21 U/g wet tissue vs 6.02 ± 1.16 U/g wet tissue).The activity of SOD(250.32 ± 8.56 U/mg protein vs 365.78 ± 10.26 U/mg protein) in lung tissues was decreased after septic shock,and was not significantly increased by Group C pretreatment,but was significantly enhanced by Group D pretreatment(331.15 ± 9.64 U/mg protein vs 262.98 ± 5.47 U/mg protein).Histological evidence of lung hemorrhage,neutrophil infiltration and overexpression of IL-6,IL-8,and TNF-α was observed in lung tissues,all of which were attenuated by Group C and further alleviated by Group D pretreatment.Septic shock also elicited a significant increase in the levels of MDA,MPO and DAO(6.54 ± 0.68 kU/L vs 4.32 ± 0.33 kU/L) in intestinal tissues,all of which were further increased by Group C,but significantly reduced by Group D pretreatment.Increased Chiu scoring and overexpression of IL-6,IL-8 and TNF-α were observed in intestinal tissues,all of which were attenuated by Group C and further attenuated by Group D pretreatment.CONCLUSION:Combined early fluid resuscitation and hydrogen inhalation may protect the lung and intestine of the septic shock rats from the damage induced by oxidative stress and the inflammatory reaction.

Effect of sitagliptin combined with Yiqi yangyin huoxue decoction on clinical efficacy and hemorheology in early diabetic nephropathy

BACKGROUND Early diabetic nephropathy(DN)is a complication of diabetes mellitus.It mainly affects kidney microvessels and glomerular function,and its timely and effective treatment is critical for early DN.However,the effects of treatments comprising simple Western medicine are not optimal.With the promotion and implementation of integrated Chinese and western medicine treatments,remarkable results have been achieved for many diseases.To this end,we explored the clinical efficacy of integrated traditional Chinese and western medicines for the treatment of early DN.AIM To investigate the effect of sitagliptin tablets combined with Yiqi yangyin huoxue decoction on clinical efficacy and hemorheology in patients with early DN.METHODS Through a retrospective analysis,123 patients with early DN were admitted to the endocrinology clinic of the Changzhou NO.7 People’s Hospital from January 2021 to October 2022 and were selected as study subjects.After rigorous screening,100 patients with early DN were enrolled.The control group(CG,n=50)and the observation group(OG,n=50)were divided according to the treatment method.The CG were treated with sitagliptin,and the OG were treated with sitagliptin plus the Yiqi yangyin huoxue decoction.Both groups were treated for 3 mo.For both groups,the baseline data and clinical efficacy were compared,and changes in blood glucose levels,lipid levels,renal function,and hematological indicators before(T0)and after(T1)treatment were assessed.RESULTS The total effective rate for the OG was 94.00%and that of the CG was 80.00%(P<0.05).After treatment(T1),the levels of fasting blood glucose,2 h postprandial glucose,total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol in OG patients were obviously lower than those in the CG(P<0.05),and cystatin C,homocysteine,urinary microalbumin,and blood creatinine values in OG patients were also obviously lower than those in the CG(P<0.05);erythrocyte deposition,plasma viscosity,whole blood high shear viscosity,and whole blood low shear viscosity were markedly lower in OG patients than in the CG(P<0.05).CONCLUSION Sitagliptin combined with Yiqi yangyin huoxue decoction has a remarkable effect when used to treat patients with early DN.Further,it is helpful in improving hemorheological indices and controlling disease progression.

Advance on Chinese Medicine for Hypertensive Renal Damage:Focus on the Complex Molecular Mechanisms

Hypertensive renal damage(HRD)is a major cause of end-stage renal disease.Among the causes of end-stage renal disease,HRD accounts for nearly 34%of the total number of cases.Antihypertensive treatment is primarily drug-based,but therapeutic efficacy is less effective and can have serious side effects.Chinese medicine(CM)has significant advantages in the treatment of HRD.CM is rich in various active ingredients and has the property of targeting multiple targets and channels.Therefore,the regulatory network of CM on disease is complex.A large number of CM have been employed to treat HRD,either as single applications or as part of compound formulations.The key possible mechanisms of CM for HRD include regulation of the renin-angiotensin-aldosterone system,antioxidation,anti-inflammation,rescue of endothelial function,regulation of vasoactive substance secretion and obesity-related factors,etc.This review summarized and discussed the recent advance in the basic research mechanisms of CM interventions for HRD and pointed out the challenges and future prospects.

Effect of Traditional and Integrative Regimens on Quality of Life and Early Renal Impairment in Elderly Patients with Isolated Systolic Hypertension

Objective：To observe the effect of Chinese medical regimen and integrative medical regimen on quality of life and early renal impairment in elderly patients with isolated systolic hypertension（EISH）.Methods： A multi-center,randomized,double-blinded controlled trail was adopted.A total of 270 cases of EISH were randomly divided into 3 groups：Chinese medicine group（CM）,combination group and Western medicine group （WM）.The course of treatment was 4 weeks.The clinical blood pressure,integral of quality of life（SF-36 scale）, immunoglubin G（IgG）,microalbumin（mALB）,β_2-microglobulin（β_2-MG）,transferrin（TRF）and N-acetyl-β＇- D-glucosa-minidase（NAG）in urine were determined before and after the treatment.Results：After treatment, systolic blood pressure depressed significantly in each group（P〈0.05）,and the combination group was superior to CM or WM group in depressing SBP（P〈0.05）; in each group,integral of quality of life improved in different degree,and combination group was superior to WM group in all 8 dimensions（P〈0.05）.The level of mALB andβ_2-MG in urine decreased in all groups（P〈0.05）,and the combination group was superior to CM group or WM group in decreasing mALB（P〈0.05）.Conclusions：Chinese medical regimen has affirmative effect in treating EISH patients,and could lower the systolic blood pressure,improve quality of life and early renal impairment of the patients,and integrative medical regimen has superiority on account of cooperation,and deserves further study.

Effects of Polygonum cuspidatum on AMPK-FOXO3α Signaling Pathway in Rat Model of Uric Acid-Induced Renal Damage

Objective: To observe the effects of Chinese medicine(CM) Polygonum cuspidatum(PC) on adenosine 5'-monophosphate-activated protein kinase(AMPK), forkhead box O3α(FOXO3α), Toll-like receptor-4(TLR4), NACHT, LRR and PYD domains-containing protein 3(NLRP3), and monocyte chemoattractant protein-1(MCP-1) expression in a rat model of uric acid-induced renal damage and to determine the molecular mechanism. Methods: A rat model of uric acid-induced renal damage was established, and rats were randomly divided into a model group, a positive drug group, and high-, medium-, and low-dose PC groups(n=12 per group). A normal group(n=6) was used as the control. Rats in the normal and model groups were administered distilled water(10 m L·kg^(–1)) by intragastric infusion. Rats in the positive drug group and the high-, medium-, and low-dose PC groups were administered allopurinol(23.33 mg·kg^(–1)), and 7.46, 3.73, or 1.87 g·kg^(–1)·d^(–1) PC by intragastric infusion, respectively for 6 to 8 weeks. After the intervention, reverse transcription polymerase chain reaction, Western blot, enzyme linked immunosorbent assay, and immunohistochemistry were used to detect AMPK, FOXO3α, TLR4, NLRP3, and MCP-1 m RNA and protein levels in renal tissue or serum. Results: Compared with the normal group, the m RNA transcription levels of AMPK and FOXO3α in the model group were significantly down-regulated, and protein levels of AMPKα1, pAMPKα1 and FOXO3α were significantly down-regulated at the 6 th and 8 th weeks(P<0.01 or P<0.05). The m RNA transcription and protein levels of TLR4, NLRP3 and MCP-1 were significantly up-regulated(P<0.01 or P<0.05). Compared with the model group, at the 6 th week, the mRNA transcription levels of AMPK in the high-and medium-dose groups, and protein expression levels of AMPKα1, p AMPKα1 and FOXO3α in the high-dose PC group, AMPKα1 and p AMPKα1 in the mediumdose PC group, and p AMPKα1 in the low-dose PC group were significantly up-regulated(P<0.01 or P<0.05); the m RNA transcription and protein levels of TLR4 and NLRP3 in the 3 CM groups, and protein expression levels of MCP-1 in the medium-and low-dose PC groups were down-regulated(P<0.01 or P<0.05). At the 8 th week, the m RNA transcription levels of AMPK in the high-dose PC group and FOXO3α in the medium-dose PC group, and protein levels of AMPKα1, p AMPKα1 and FOXO3α in the 3 CM groups were significantly up-regulated(P<0.01 or P<0.05); the m RNA transcription levels of TLR4 in the medium-and low-dose PC groups, NLRP3 in the high-and low-dose PC groups and MCP-1 in the medium-and low-dose PC groups, and protein expression levels of TLR4, NLRP3 and MCP-1 in the 3 CM groups were down-regulated(P<0.01 or P<0.05). Conclusion: PC up-regulated the expression of AMPK and its downstream molecule FOXO3α and inhibited the biological activity of TLR4, NLRP3, and MCP-1, key signal molecules in the immunoinflammatory network pathway, which may be the molecularmechanism of PC to improve hyperuricemia-mediated immunoinflammatory metabolic renal damage.

Diagnostic Value of Sensitive Biomarkers for Early Kidney Damage in Diabetic Patients with Normoalbuminuria

To the Editor:Diabetic kidney disease (DKD)is the most common cause of end-stage renal disease (ESRD);however,the onset of DKD is difficult to detect.[1]When persistent microalbuminuria becomes detectable,DKD has already progressed to the third disease stage,and finding biomarkers that are more sensitive than microalbuminuria is therefore necessary to indicate kidney damage at an earlier stage of DKD.[2]Both glomerular and tubulointerstitial damages have been repeatedly demonstrated to be important factors in the pathophysiology of DKD.[3] Therefore,we investigated the expression levels of six markers closely related to the glomerulus and renal tubule.

Early renal failure as a cardiovascular disease:Focus on lipoprotein(a) and prothrombotic state

Patients with renal failure are at increased risk of cardiovascular events even at the earliest stages of disease. In addition to many classic cardiovascular risk factors, many conditions that are commonly identified as emerging risk factors might contribute to occurrence of cardiovascular disease. Changes in circulating levels of many of these emerging risk factors have been demonstrated in patients with early stages of renal failure caused by different types of renal disease and have been associated with detection of cardiovascular complications. However, for most of these factors evidence of benefts of correction on cardiovascular outcome is missing. In this article, we comment on the role of lipoprotein（a） and prothrombotic factors as potential contributors to cardiovascular events in patients with early renal failure.