回回甘松饮治疗宁夏回族2型糖尿病肾病禀衰兼湿型158例临床观察

目的:基于回族医学"体质理论"中的"四性学说"与单于德教授的多年临床经验,探讨"回回甘松饮"对宁夏回族2型糖尿病肾病禀衰兼湿型的疗效。方法:选取2009年1月至2009年8月就诊于宁夏医科大学附属银川市中医院,符合西医诊断标准及纳入标准的宁夏回族2型糖尿病肾病患者158例,分为回回甘松饮组和西药组,以两种方案进行治疗。连续观察3个月。结果:①回回甘松饮组在糖尿病肾病几种理化指标方面的疗效优于西药组,且有统计学意义。②回回甘松饮组在相关主要中医证侯(禀衰兼湿型)改善方面优于西药组。结论:基于宁夏回族2型糖尿病肾病患者多属于"禀性衰败兼寒湿型",回回甘松饮以"香药"治疗宁夏回族2型糖尿病肾病取得了令人满意的疗效,为相关机制研究及回族医药保健品的开发奠定了基础。

Linggui Zhugan Decoction Improves High Glucose-Induced Autophagy in Podocytes

Objective To explore the influence of Linggui Zhugan Decoction(LGZGD) on high glucose induced podocyte autophagy.Methods LGZGD containing serum was prepared by intragastric administation of 4.2 g/kg(low dose), 8.4 g/kg(medium dose), and 12.6 g/kg(high dose) LGZGD into SD rats respectively. MPC5 and AB8/13 podocyte cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro. Both podocytes were divided into control group, high glucose group, low dose LGZGD group, medium dose LGZGD group, and high dose LGZGD group, respectively. For the three LGZGD groups, before LGZGD intervention, podocytes were treated with 60 mmol/L glucose for 3 days. After treated with LGZGD containing serum, cells were collected to analyze cell migration using Transwell assay, proliferation using CCK8, apoptosis and cell cycle using flow cytometry, autophagosome formation using transmission electron microscopy, and expression levels of Beclin-1, Atg5, LC3II/I, and P62 proteins using Western blot.Results Compared with the control group, the proliferation and migration of MPC5 and AB8/13 cells in the high glucose group slightly decreased, whereas these parameters restored after intervention with low and medium concentrations of LGZGD, with the medium dose LGZGD having the better effect(P < 0.05). Flow cytometry showed that the medium dose LGZGD group had a significantly lower apoptosis rate(P < 0.05) and higher survival rate(P > 0.05) compared to the high dose LGZGD group. High glucose arrested podocytes in G1 phase, whereas LGZGD shifted podocytes from being predominant in G1 phase to G2 phase. High dose LGZGD significanly reduced high glucose-increased autophagosome formation in both podocytes(P < 0.05). Western blot analysis showed that Beclin-1, Atg5, LC3II/I, and P62 expressions were increased in MPC5 cells treated with high glucose and reversed after adminstration of low and medium doses of LGZGD(P < 0.05).Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.

Correlation between podocyte excretion and proteinuria in diabetic nephropathy patients

Objective： To observe the podocyte injury in diabetic nephropathy （DN） patients by identifying the urinary podocytes and the situation of detached podocytes in glomeruli and to demonstrate the correlation between podocyte excretion and proteinuria, blood glucose, serum creatinine in different phases in DN patients. Methods： Urinary podocytes and the podocalyxin （PCX） expression state of podocytes in glomeruli were identified and observed by indirect immunofluorescent method. The DN patients were divided into three groups according to the volume of proteinuria, namely small, medium and large volume proteinuria groups. The podocytes in the urine of every group were calculated. The DN patients were divided into five groups according to the chronic kidney disease （CKD） phases, then the positive podocytes in urine were calculated. Meanwhile, the 24-hour protein in urine, fasting blood glucose （FBG） and the serum creatinine of DN patients were tested. The correlations among the proteinuria, serum creatinine, FBG and the number of positive podocytes in the urine of DN patients were statistically analyzed. Results： Urinary positive podocytes were found in 88% of the patients with DN, whereas podocytes were found in 0% of patients with minimal changed disease （MCD） and healthy cases. The expression of PCX was absent in DN patients. In contrast, PCX was expressed integrally in MCD patients. The positive podocytes was 1.49±0.95/ml in small-volume proteinuria group, 2.15±0.70/ml in the medium-volume proteinuria group, and 3.48±1.27/ml in the large-volume proteinuria group. There was no significant difference between the small- and medium- volume proteinuria groups, and there were significant differences between other groups （P〈0.05）. The positive podocyte number tended to increase as proteinuria was increased. By Pearson analysis, the correlation between podocyte number and proteinuria was podocytes in urine from different groups of DN patients, CKD pc I sitive statistically. The difference of the number of positive -V group was significant statistically. The correlation between serum creatinine of CKD Ⅰ -Ⅲ group and positive podocytes in urine was positive statistically. The correlation between serumcreatinine of CKD Ⅳ- Ⅴ group and positive podocytes in urine was not significant statistically. The correlation between FBG and positive podocytes in urine was not significant either. Conclusion： The mechanism of the podocyte injury in DN patients is present. The podocyte injury in DN may positively correlate to proteinuria and serum creatinine of CKD Ⅰ -ⅢDN patients, but not to the FBG and serum creatinine of CKD Ⅳ-Ⅴ patients.

Influence of astragalus polysaccharide on kidney status and fibrosis indices of a ratmodel of streptozotocin-induced diabetic nephropathy

Object： To examine the effect of astragalus polysaccharide （APS） on kidney status and fibrosis indices of rats withdiabetic nephropathy. Methods： 72 male rats were randomly divided into three groups： negative control group （NC, n =24）; diabetic nephropathy model group （DNM, n = 24）; and diabetic nephropathy model with APS group （DNM ＋ APS,n = 24）. Rats of the DNM and DNM ＋ APS groups were subjected to both unilateral nephrectomy and administeredstreptozotocin （STZ） injection （65 mg/kg）. DNM ＋ APS group rats were administered 50 IU/kg/d APS by subcutaneousinjection from the first week after operation until death. The NC and DNM group rats were subcutaneously injected withan identical volume of physiological saline. At weeks 3, 8, and 13 after the operation, 6 rats from each group wererandomly sacrificed and blood was collected to measure serum creatinine and blood urea nitrogen. On the day beforesacrifice, the rats were placed in a metabolic cage for 24 h to collect urine. At week 14 after the operation, 6 rats fromeach group were randomly selected to measure body weight and kidney index. Blood was collected to measure bloodglucose. The kidneys were harvested to detect pathological changes by hematoxylin and eosin staining. Results：Histological assessment of DNM rats suggested damage symptoms as evidenced by hyperplasia of the glomerularmesangial matrix, atrophia of the kidney tubules, and thickening of the basement membrane. In contrast, STZ-induceddiabetic nephropathy rats treated with APS （50 IU/kg/d） showed significantly improved histological results, suggestingthat APS has beneficial effect on renal tissues in STZ-induced DNM rats. Our results also indicated that APS relievedrenal injury and effectively improved body weight in DNM rats. The ratio of kidney weight to body weight was reducedand the early stage of renal function damage was improved after APS treatment. In the later stages of the disease, the 24h urinary protein significantly decreased. Moreover, APS down-regulated TGF-β1 and α-SMA expression of the kidney.Conclusion： APS significantly improved renal tubular interstitial injury in DNM rats and the early stage of renalfunction damage. The mechanism may be related to downregulation of the expression of TGF-β1 and α-SMA whichdelays the progression of renal interstitial fibrosis in DNM rats.

Prolonged hypernatremia triggered by hyperglycemic hyperosmolar state with coma: A case report

A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus(NDI), presented with coma and hyperglycemic hyperosmolar state(HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 m Osm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with newonset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI.

Silent diabetic nephropathy

AIM： To examine the risk of renal events in patients with biopsy-proven diabetic nephropathy （DN） and its possible associated factors.METHODS： Clinical and histological data of 60 pa-tients diagnosed with diabetic nephropathy were retro-spectively collected. Patients with evidence or suspicion of other nephropathies were excluded from the study. The fnal event was defned as renal replacement ther-apy （RRT） initiation or progression of chronic kidney disease （CKD）, according to the KDIGO 2012 defnition of a decrease in CKD category and a decrease in GFR of 25% or more. RESULTS： A total of 45 patients with a follow-up of at least 3 mo were included. Most of the patients presented type 2 DM, with a mean age of 58.3 years old. The time of evolution of DM was 9.6 ± 7.8 years, al-though in 13 patients, it was less than 5 years. A total of 62% of patients reached the fnal event in a mean period of 3.4 years （95%CI： 2.1-4.7）, with 21 of them requiring dialysis. The factors that were indepen-dently associated with renal survival were estimated glomerular fltration rate （eGFR） at the time of biopsy, cardiovascular disease （CVD） history and HbA1c less than 7%. Therefore, for each 10 mL/min per 1.73 m2 reduction in eGFR, we obtained a DN progression risk of HR = 2 （1.3-3.0） （P = 0.001）; patients with CVD were at greater risk for DN progression （HR = 2.8, 1.1-7.1, P = 0.032）, and CKD patients with HbA1c 〈 7% demonstrated greater renal risk than patients with HbA1c ≥ 7%, with an HR of 2.9 （1.0-8.4） （P = 0.054）.CONCLUSION： A past history of CVD is a risk fac-tor for DN progression. Levels of HbA1c less than 7% could favor an eGFR decrease in these patients.

Effect of probucol on insulin resistance in patients with non-diabetic chronic kidney disease

Background Insulin resistance （IR） is present at all stages of chronic kidney disease （CKD） and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus （DM） patients. This study aimed to observe the effect of probucol on IR and kidney protection in non-diabetic CKD patients. Methods This was an open-label, non-placebo-controlled, randomized study. A total of 59 patients were randomized to the probucol group （0.5 g, twice daily） or the control group using a 1： 1 treatment ratio. IR was determined using a homeostatic model assessment-IR （HOMA-IR） index. An Excel database was established to analyze foUow-up data at weeks 0, 12, and 24. The primary outcome of interest was changes in the HOMA-IR, and the secondary outcomes of interest were changes in the estimated glomerular filtration rate （eGFR）, body mass index （BMI）, cholesterol, triglycerides, high-density lipoprotein （HDL）, low-density lipoprotein （LDL）, and 24-h urinary protein. Results The HOMA-IR index of the probucol group after 24 weeks was significantly decreased （P 〈 0.001） compared to the value before treatment （average decrease： 1.45; range： -2.90 to -0.43）. The HOMA-IR index in the control group increased （average increase： 0.54; range： -0.38 to 1.87）. For the secondary outcomes of interest, the changes between these two groups also exhibited significant differences in eGFR （P = 0.041）, cholesterol （P = 0.001）, fasting insulin （P 〈 0.001）, and fasting C-peptide （P = 0.001）. Conclusions Compared to angiotensin receptor blockers alone, the combination with probucol ameliorates IR in non-diabetic CKD patients and delays disease progression.

Antisense Smad2 inhibits high glucose-stimulated production of extracellular matrix in cultured rat glomerular mesangial cells

Objective：Hyperglycemia stimulates secretion of transforming growth factor-βl （TGF-βl） in cultured glomerular mesangial cells, thereby increases production of extracellular matrix （ECM）. We examined the effect of antisense mRNA for Smad2 on high glucose-induced ECM production in rat mesangial cells. Methods..A mammalian expression vector, pES2a, which expresses antisense Smad2 mRNA and green fluorescent protein （EGFP）, was transfected into mesangial cells. Following incubation in high glucose medium, EGFP expression and Smad2 mRNA level were determined by fluorescence microscopy and PCR, respectively. Secreted fibronectin and type IV collagen were assessed by enzyme-linked immunosorbent assay. Results ：Within 48 h of incubation in high glucose medium, Smad2 mRNA level significantly increased by 1.6 fold in association with increases in prodtaction of both fibronectin （from [45.86±2.73] to [84.19±6.81] ng/ml） and type IV collagen （from [16. 28±0. 90] to [55.27±4.75] ng/ml） in nontransfected cells （P〈0.05）. In pES2a-transfected cells, the high glucose-induced increase in Smad2 mRNA was abrogated completely, in parallel with significant suppression of the high glucose-indtmed increase in fibronectinproduction （[54.44±4.99] ng/ml） and type Ⅳ collagen （[20.96±2.47] ng/ml）. An empty vector was without effects. Coneluslon：These findings demonstrate that Smad2 plays a critical role in mediating high glucose-stimulated ECM production in mesangial cells, indicating that inhibition of Smad2 activity by antisense Smad2 mRNA may be an effective means to attenuate glomerular matrix accumulation in diabetic nephropathy.

Commuting Dual Toeplitz Operators on the Polydisk

We completely characterize commutativity of S and Sψ on La2(Dn)⊥ for bounded pluriharmonic symbols and ψ on Dn, and prove that SSψ = Sψ if and only if is analytic or ψˉ is analytic.

Exercise-induced albuminuria and circadian blood pressure abnormalities in type 2 diabetes

AIMTo investigate the relationship between circadian vari-ations in blood pressure （BP） and albuminuria at rest, and during exercise in non-hypertensive type 2 diabetes （T2D） patients.METHODSWe conducted a cross-sectional study in well controlled T2D patients, non-hypertensive, without clinical pro-teinuria and normal creatinine clearance. In each parti-cipant, we recorded the BP using ambulatory bloodTankeu AT et al . Exercise-induced albuminuria and BP in T2DMpressure monitoring （ABPM） for 24-h, and albuminuria at rest and after a standardized treadmill exercise.RESULTSWe enrolled 27 type 2 patients with a median age of 52; and a mean duration of diabetes and HbA1c of 3.6 ± 0.8 years and 6.3% ± 0.5% respectively. Using a 24-h ABPM, we recorded a mean diurnal systolic blood pressure （SBP） of 128 ± 17 mmHg vs nocturnal of 123 ± 19 mmHg （ P = 0.004）, and mean diurnal diastolic blood pressure （DBP） of 83 ± 11 mmHg vs nocturnal 78 ± 14 mmHg （ P = 0.002）. There was a signifcant difference between albuminuria at rest [median = 23 mg, interquartile range （IQR） = 10-51] and after exercise （median = 35 mg, IQR = 23-80, P 〈 0.001）. Patients with exercise induced albuminuria had an increase in nocturnal BP values on all three components （128 mmHg vs 110 mmHg, P = 0.03 for SBP; 83 mmHg vs 66 mmHg, P = 0.04; 106 vs 83, P = 0.02 for mean arterial pressure）, as well as albuminuric patients at rest. Moreover, exercise induced albuminuria detect a less increase in nocturnal DBP （83 vs 86, P = 0.03） than resting albuminuria.CONCLUSIONExercise induced albuminuria is associated with anincrease in nocturnal BP values in T2D patients.

Mechanisms of Dihuang(Rehmanniae Radix)in treating diabetic nephropathy complicated with depression based on network pharmacology

Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanniae Radix)were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP),Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and relevant literature.The component targets were detected by combining the SwissTargetPrediction and Pub Chem databases.Disease targets were collected from the Therapeutic Target Database(TTD),Dis Ge NET,and Ensembl databases with“diabetic nephropathy”and“depression”as keywords.The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets.A protein-protein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database and Cytoscape 3.7.2.The co-expression genes of the key targets were collected based on the COXPRESdb 7.3.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for potential targets using R language.Target-component docking was verified and evaluated using Discovery Studio 4.5.Results According to the databases and literature reports,Dihuang(Rehmanniae Radix)contained 65 active components,and had 155 related targets for the treatment of DN complicated with depression.PPI screening showed that the key targets included serine/threonine protein kinase 1(AKT1),signal transducer and activator transcription 3(STAT3),interleukin 6(IL-6),mitogen-activated protein kinase 1(MAPK1),and vascular endothelial growth factor A(VEGFA),etc.GO enrichment analysis mainly involved biological processes,such as lipid metabolism,protein secretion regulation,cell homeostasis,and phosphatidylinositol 3 kinase activity.KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements,insulin resistance(IR),neurotrophin signal path,Toll-like receptor signaling pathway,relaxin signaling pathway,epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),etc.Molecular docking showed that the target had high affinity for stachyose,manninotriose,verbascose,nigerose,etc.Conclusion Based on network parmacology,this study preliminarily predict the effects of Dihuang(Rehmanniae Radix)in treating DN complicated with depression by regulating inflammation,glucose metabolism,nution nerve,etc.

RELATION OF HYPERTENSION TO DIABETIC NEPHROPATHY IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES MELLITUS—A PAIR-MATCHED CASE-CONTROL STUDY

To assess the role of hypertension and family history of hypertensio n in the development of nephropathy in patients with non insulin dependent dia betes mellitus (NIDDM).Methods. A retrospective analysis was done on 2 groups of NIDDM patients, one g roup without proteinuria (urine protein< 300mg/24h, n=106) and the other group w ith proteinuria (urine protein≥500mg/24h, n=106). The 2 groups were matched by age(≤±3yrs), sex, ethnic and resident place. Some information of these subject s including demographic; history of disease, family history of diseases, lifesty le and behavior style variables was obtained by questionnaire; some variables w ere measured, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), quantity of protein in 24h urine. Then condi tional logistic regression analysis was performed.Results. Some factors, including history of hypertension, longer duration of hy pertension, higher levels of the past highest SBP and DBP, were independently as sociated with the occurrence risk of diabetic nephropathy (DN). Their correspond ing odd ratios (OR) with 95% confidence intervals (CI) were 2.00(1.17～3.43), 1 .25(1.08～1.46), 1.38(1.15～1.66), and 1.33(1.09～1.62) respectively, but family history of hypertension was not significantly associated with the development o f DN. When the above mentioned relations were respectively adjusted by some pos sible confounding factors, they still existed.Conclusions. History of hypertension, longer duration of hypertension, higher l evels of the past highest SBP and DBP are independent risk factors for DN in Chi nese NIDDM patients.

IDENTIFICATION OF GLUCOSE TRANSPORTER- 1 AND ITS FUNCTIONAL ASSAY IN MOUSE GLOMERULAR MESANGIAL CELLS CULTURED IN VITRO

To evaluate the role of glucose transporter- l (GLUT1) in the glucose uptake of glomerular mesangial cells. Methods. Cultured C57/SJL mouse mesangial cells were used in the study. The expression of GLUT1 mRNA was detected by RT- PCR. The expression of GLUT1 protein was detected by immunofluorescence and flow cytometry. The uptake of glucose and its kinetics were determined by 2- deoxy- [3H]- D- glucose uptake. Results. Both GLUT1 mRNA and protein were found in mouse glomerular mesangial cells. 2- deoxy- D- glucose uptake and kinetics assay showed that this glucose transporter had high affinity for glucose and the glucose uptake specificity was further confirmed by phloretin. Conclusion. Functional GLUT1 did present in mouse mesangial cells cultured in vitro and it might be the predominant transporter mediated the uptake of glucose into mesangial cells.

Effects of angiotensin-Ⅱ receptor blockers on β-catenin expression in a rat model of experimental streptozotocin-induced early-stage of diabetic nephropathy

Objective： Diabetic nephropathy （DN） is one of the most common causes of end-stage renal failure. The pathogenesis of progressive renal injury is multifactorial and the mechanism by which hyperglycemia causes microangiopathy is still poorly understood. The WNT pathway is activated in DN and regulating β-catenin protein levels is referred to as the canonical Wntβ-catenin pathway. Because the renin angiotensin system has been reported to be an important contributory factor in the pathophysiology of DN, exogenous administration of angiotensin Ⅱ receptor antagonist may be beneficial in counteracting some biochemical or functional changes of DN. The aim of the study was to determine the β-catenin expression and the possible protective effects of irbesartan, an angiotensin Ⅱ type 1 receptor blocker （ARB） in a rat model of streptozotocin（STZ）-induced diabetic nephropathy. Methods： STZ-induced DN in rats was assessed biochemically by measuring urine volume, protein and creatinine clearance as well as Kidney weight/body weight （KW/BW） and the index of mesangial expansion. Three groups of male Sprague-dawley rats were used. The first group consisted of non-diabetic control rats （control）. The second group was the untreated diabetic rats（STZ＋vehicle）. The third group consisted of diabeti rats treated with irbesartan, 50 mg/kg for 12 weeks （STZ＋irbesartan）. Immunohistochemical stainings and real time PCR for β-catenin were performed in renal cortex of rat modals. Results： Marked hyperglycemia, polyuria, proteinuria, renal hypertrophy, mesangial matrix expansion and glomerular hyperfiltration were observed in STZ diabetic rats. The levels of microalbuminuria and KW/BW in the STZ＋irbesartan group were lower than those in the STZ＋vehicle group （P〈0.05）. The up-regulated immunostaining and mRNA expression of β-catenin were decreased in renal cortic of the Irbesartan-treated diabetic group, but there was no significant difference compared to the untreated diabetic group. Conclusion： The data suggest that irbesartan ameliorates proteinuria and renal hypertrophy, charactered damages of STZ-induced early-stage DN in rats, but its effective drug target is not to inhibit the up-regulated expressions of β-catenin.

Vascular response to vasodilator treatment in microalbuminuric diabetic kidney disease

Under common practice, the conventional diagnostic marker such as microalbuminuria determination does not recognized early stage of diabetic kidney disease （normoalbuminuria, chronic kidney disease stage 1, 2）; due to the insensitiveness of the available marker. Treat-ment at later stage （microalbuminuria） simply slows the renal disease progression, but is rather diffcult to restore the renal perfusion. Intrarenal hemodynamic study in these patients revealed an impaired renal per-fusion and abnormally elevated renal arteriolar resis-tances. Treatment with vasodilators such as angiotensin converting enzyme inhibitor and angiotensin receptor blocker fails to correct the renal ischemia. Recent study on vascular homeostasis revealed a defective mecha-nism associated with an impaired nitric oxide production which would explain the therapeutic resistance to va-sodilator treatment in microalbuminuric diabetic kidney disease. This study implies that the appropriate thera-peutic strategy should be implemented at earlier stage before the appearance of microalbuminuria.

A Meta-analysis of angitensin-converting enzyme inhibitors on normotensive early diabetic renal diseases

Objective: To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinical experiments published on MEDLINE from January 1990 to April 1999 and on China Biological Medicine were reviewed for studying the effects of ACE-inhibitors on normotensive patients with early diabetic renal diseases. Based on the inclusion criteria, 10 studies were selected. Their results were combined and analyzed with RevMan3. I software. Results: The pooled effect of urinary microalbumin excretion rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were -77.502 mg/24 h (-100.748 to-54.256), -5.002 mmHg [-9.630 to 0.685],-2.949 mmHg (-4.005 to 1.892). -4.284 mmHg (-5.444 to 3.123) respectively. Using clinical albuminuria as the end-point, the pooled odd ratio was 0.27 [95% CI 0.18 0.40]. The sub-group analysis showed that those results had no difference between type 1 and type 2 diabetes. There was no significant correlation between the pooled effects of urinary micro-albuminuria excretion rate and systolic blood pressure. diastolic blood pressure or mean arterial blood pressure. Conclusion: ACE inhibitors can decline urinary micro-albuminuria excretion rate in normotensive patients with early diabetic renal disease and delay the progression of early diabetic renal disease to clinical albuminuria. These effects may not be dependent on its blood pressure-reduction effect.

Serum metrix metalloproteinase-9 combined with homocysteine, IL-6, TNF-α, CRP, HbA11c and lipid profile in the incipient diabetic nephropathy with or without macrovascular diseases

Objective ： To evaluate the changes of serum matrix metalloproteinase-9 （romp-9） in patients of incipient diabetic nephropathy with or without macrovascular disease and to analyze the factors associated with homocysteine（hcy）, interleukin-6（IL-6）, tumor necrosis factor-alpha （TNF-α）, highly sensitive C-reactive protein （hsCRP）, HbAlc and lipid profile in those patients in order to know whether this marker or other factors are more important to induce diabetic macrovascular disease. Methods： Type 2 diabetes mellitus（T2DM） subjects with incipient diabetic nephropathy with or without macrovascular disease were selected for participation and divided into 2 groups. The patients in group 1 （n= 38） used insulin, and patients in group 2 （n=34） were treated with an oral antidiabetic drug. Then serum mmp-9, hey, IL-6 and TNF-α in these patients were measured, and compared to the healthy subjects as control （n= 16）. The results were analyzed by SPSS13. Results： Serum romp-9 and hcy of the patients having incipient diabetic nephropathy with macrovascular disease were higher than that of patients without macrovascular disease （P〈0.01）. For insulin-injected patients, whether they accompanied with macrovascular diseases or not, the serum levels of romp-9, hcy, IL-6 and TNF-α were all lower, but no significant statistics compared with non-insulin used patients or the healthy subjects. The serum level of romp-9 was more correlated with the serum hcy in antidiabetic drug used patients. （P〈0. 000） Conclusion： The serum level of romp-9 plays an important role of pathogenesis in the macrovascular disease in the incipient diabetic patients, and the serum level of hcy also can reflect the severely degree of macrovascular disease in these patients, insulin can reduce these markers.

The efficacy and safety of Chinese herbal medicine combined with ACEI/ARB fortreatment of incipient diabetic nephropathy： Ameta-analysis

Objective： This meta- analysis evaluated the efficacy and safety of Chinese herbal medicine （CHM） combined withangiotensin-converting enzyme inhibitors （ACEIs） and/or angiotensin-receptor blockers （ARBs）for treatment ofincipient diabetic nephropathy（IDN）. Methods： Nine data bases were searched for randomized controlled trials ofChinese herbal medicine（CHM） and ACEI/ARB for treatment of IDN. Included articles were published betweenJanuary2006 and December 2016. All studies were divided into prescriptions containing both Astragali Radix andRehmanniae Radix （i subgroup）, Astragali Radix（Huangqi） or Rehmanniae Radix（Dihuang） （ii subgroup）, neitherAstragali Radix nor Rehmanniae Radix （iii subgroup）. Review Manager 5.3 was used for subgroup analysis.Results： In total, 28 RCTs with 2017 patients were included. The results showed 1）the urinary albumin excretionrate （UAER） can be reduced significantly using CHM with ACEI or ARB for treatment of IDN compared to ACEIor ARB alone, and reduction of the UAER of the i subgroup was superior to that of the other two subgroups;2）serum creatinine （Scr） levels can be reduced significantly using CHM combined with ACEI or ARB, andreduction of Scr in the ii subgroup was superior to that in the iii subgroup; 3）reduction of BUN in group A was notbetter than that in group B. Conclusion： In summary, CHMs combined with ACEI/ARB can decrease UAER andScr significantly compared to the use of ACEI/ARB during IDN treatment. The effect was more significant in theCHM group containing Astragali Radix or Rehmanniae Radix. The application of Astragali Radix and RehmanniaeRadix should be emphasized in third stage diabetic nephropathy.

Mechanism analysis of Traditional Chinese Medicine in treatment of Diabetic Nephropathy based on network pharmacology and Traditional Chinese Medicine inheritance support system

Diabetic nephropathy is one of the most serious complications of diabetes mellitus. In the early stage, edema and proteinuria are the main clinical manifestations. In the later stage, glomerulosclerosis and interstitial fibrosis will occur. And the prognosis is poor. Nowadays, traditional Chinese medicine has a remarkable curative effect in the treatment of diabetic nephropathy. There are more and more studies on the treatment of diabetic nephropathy with traditional Chinese medicine, but most of them focus on the syndromes of diabetic nephropathy, which are short of in-depth research and summary on the mechanism of Chinese herbal prescriptions. In this paper, the traditional Chinese medicine inheritance support system and network pharmacology BATMAN-TCM software were used to collect and analyze the relevant literature. It was found that the core compatibility of Shanzhuyu, Fuling and Shuyu in the treatment of diabetic nephropathy is closely related to the signal transduction pathway and target of diabetic nephropathy, and has a positive effect on the improvement of clinical symptoms such as proteinuria, glycometabolism disorder, edema, etc. This paper explores the core compatibility of Shanzhuyu, Fuling and Shuyu on diabetic nephropathy, in order to provide reference for clinical treatment.

Neuroprotective Effect of Bu-Shen-Huo-Xue Extract against High Glucose-induced Apoptosis in PC12 Cells

Objective： To investigate the neuroprotective effect of Bu-Shen-Huo-Xue （BSHX） extract, a polyherbal formula, against High Glucose （HG）-induced neurotoxicity in PC12 cells. Methods： Cell viability assay, Lactate Dehydrogenase （LDH） assay, Reactive Oxygen Species （ROS） detection, Hoechst 33258, Acridine Orange （AO）/Ethidium Bromide （EB） double stain and Mitochondrial Membrane Potential （MMP） assay were performed. In addition, Bax, Bcl-2, caspase-3, cleaved caspase-3, PARP, cleaved PARP, cytochrome c and Mitogen-Activated Protein Kinases （MAPKs） were detected by western blot. Results： BSHX extract increased cell viability and decreased LDH leakage in a concentration-dependent manner in HG-induced PC12 cells. Moreover, BSHX extract decreased the level of intracellular ROS, increased mitochondrial membrane potential, regulated the expressions of Bax and Bcl-2, and inhibited the release of cytochrome c from mitochondria. Furthermore, BSHX extract attenuated the activation of caspase-3 and PARP, and inhibited the phosphorylations of c-Jun N-terminal kinase （JNK） and p38 MAPKs. Conclusion： BSHX extract exhibited significant neuroprotective effect on HG-induced apoptosis in PC12 cells. This effect may be associated with the suppression of ROS generation as well as mitochondria-mediated caspase and JNK/p38 MAPK signaling pathways.