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Objective:To investigate the efficacy of Tanzhuo Decoction in the treatment of early diabetic nephropathy in patients with type 2 diabetes mellitus and its effect on cystatin C (Cys-C), C-reactive protein (CRP), urinary albumin excretion rate (UAER), and creatinine clearance rate (CCr). Methods:Eighty patients with type 2 diabetes mellitus complicated by early diabetic nephropathy who received treatment at Maanshan Hospital of Traditional Chinese Medicine from 2019 to 2021 were included in this randomized controlled study. They were divided into a control group ( n = 40) and a treatment group ( n = 40) using the random number table method. Patients in the control group received conventional therapy including blood glucose and blood pressure control, while those in the treatment group received Tangzhuo Decoction in addition to the same treatment as that given to the control group. Both groups of patients were treated for 30 days. The clinical efficacy as well as pre- and post-treatment Cys-C, CRP, UAER, and CCr were compared between the two groups. Results:The total response rate in the treatment group was 92.5% (37/40), which was significantly higher than 75.0% (30/40) in the control group ( χ2 = 4.50, P < 0.05). After treatment, Cys-C, CRP, and UAER in the treatment group were (2.04 ± 0.08) mg/L, (3.97 ± 1.71) mg/L, and (91.18 ± 18.68) μg/min, respectively, which were significantly decreased compared with those before treatment ( t = 12.14, 5.59, 4.73, all P < 0.05). After treatment, CCr in the treatment group was (56.3 ± 5.01) mL/min, which was significantly increased compared with that before treatment ( t = -8.56, P < 0.05). After treatment, Cys-C, CRP, and UAER in the control group were (2.17 ± 0.04) mg/L, (4.66 ± 1.47) mg/L, and (103.93 ± 22.62) μg/min, respectively, which were significantly decreased compared with those before treatment ( t = 4.05, 5.00, 2.24, all P < 0.05). After treatment, CCr in the control group was (45.9 ± 4.9) mL/min, which was significantly increased compared with that before treatment ( t = -3.98, P < 0.05). There were significant differences in Cys-C, UAER, and CCr between the treatment and control groups ( t = -7.42, -2.29, 7.82, all P < 0.05). Conclusion:Tanzhuo Decoction for the treatment of early diabetic nephropathy in patients with type 2 diabetes mellitus has a definite effect. It can effectively reduce levels of Cys-C and UAER, reduce inflammatory reactions, improve kidney function, and delay the progression of kidney injury.
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Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus. Cardiovascular disease often occurs in patients with DN. Patients with DN often experience changes in cardiac structure and function as proteinuria increases, glomerular filtration rate decreases, and blood creatinine levels increase, leading to the occurrence of cardiovascular disease. Additionally, inflammatory factors play a crucial role in cardiac structure and function. Understanding the pathological and physiological effects of inflammation on diabetic nephropathy-related cardiovascular disease and clarifying the relationship between cardiac structure and function in patients with DN are crucial for effective prevention and treatment of DN.
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Diabetic nephropathy is one of the most common and harmful microvascular complications of diabetes. In recent years, it has become a leading cause of end-stage renal disease due to its high incidence rate, challenging control, and poor prognosis. Studies have revealed that patients with diabetic nephropathy often exhibit imbalanced levels of sex hormones such as testosterone, dehydroepiandrosterone, estradiol, sex hormone binding globulin, and gonadotropin. Conversely, the imbalance of sex hormones can also influence the progression of diabetic nephropathy. Therefore, clarifying the potential relationship and interaction between sex hormones and diabetic nephropathy is essential for effective prevention and treatment of diabetic nephropathy. This warrants further research and consideration.
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Purpose To explore the clinical value of quantitative assessment of renal perfusion using ultrasound contrast imaging for the auxiliary diagnosis of type 2 diabetic nephropathy.Materials and Methods This prospective study was conducted from May 2017 to December 2019 at the First Medical Center of Chinese PLA General Hospital.A total of 41 patients with type 2 diabetes and renal function abnormalities,who were scheduled for renal biopsy,underwent contrast-enhanced ultrasound.Differences in contrast imaging parameters,including time to peak in the renal cortex,peak enhancement,mean transit time local,and area under the curve between diabetic nephropathy and focal segmental glomerulosclerosis were compared,and the correlation between imaging parameters and pathological results was analyzed.Results Among 41 patients,30 cases were diagnosed as diabetic nephropathy,and 11 cases were diagnosed as focal segmental glomerulosclerosis.The peak enhancement and area under the curve in the diabetic nephropathy group were significantly lower than those in the focal segmental glomerulosclerosis group[peak enhancement:3 837.16(2 449.16,5 929.16)vs.8 508.00(4 334.88,21 201.00),Z=-2.766,P=0.006;area under the curve:0.14±0.05 vs.0.19±0.05,t=-3.135,P=0.003].In the diabetic nephropathy group,peak enhancement showed a negative correlation with the global glomerulosclerosis rate(r=-0.489,P=0.006).Conclusion Contrast-enhanced ultrasound can quantitatively evaluate renal perfusion and has certain clinical value in assisting the diagnosis of type 2 diabetic nephropathy.
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Objective:To investigate interleukin-37 (IL-37) expression in patients with diabetic kidney disease (DKD), and to assess the regulation of exogenous IL-37 on CD8 + T cell function in DKD patients. Methods:A cross-section study was carried out. Twenty healthy controls, thirty-six patients with diabetes mellitus type 2 (T2DM), and forty-seven DKD patients were enrolled in the study. Peripheral blood was collected. Plasma and peripheral blood mononuclear cells were isolated. IL-37 and soluble IL-1 receptor 8 (IL-1R8) levels in the plasma were measured by enzyme-linked immunosorbent assay (ELISA). IL-18 receptor α chain (IL-18Rα), IL-1R8 and immune checkpoint molecules levels in CD8 + T cells were measured by flow cytometry. CD8 + T cells were purified, and were stimulated with recombinant IL-37. CD8 + T cells were co-cultured with HEK293 cells in either direct contact or indirect contact manner. Levels of perforin, granzyme B, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The proportion of target cell death was assessed by measuring lactate dehydrogenase level. Results:Plasma IL-37 levels in DKD patients [(63.42±23.30) ng/L] were significant lower than those in healthy controls [(143.02±50.67) ng/L] and T2DM patients [(87.88±40.62) ng/L] ( t=8.848, P<0.001; t=3.456, P<0.001). Plasma IL-37 level had good predictive values for T2DM in health individuals and for DKD in T2DM patients [the area under the curve was 0.797 (95% CI 0.676-0.917, P<0.001) and 0.691 (95% CI 0.576-0.807, P=0.003), respectively]. Plasma IL-37 level was negatively correlated with urea nitrogen ( r=-0.313, P=0.032) and creatinine ( r=-0.477, P<0.001), and positively correlated with estimated glomerular filtration rate (eGFR) ( r s=0.478, P<0.001) in DKD patients. IL-1R8 + CD8 + cell proportion in DKD patients (33.60%±9.47%) was significantly higher compared to healthy controls (16.29%±5.97%) and T2DM patients (17.13%±4.85%) ( t=7.545, 9.516, both P<0.001), but did not correlate with fast blood glucose, urea nitrogen, creatinine, or eGFR (all P>0.05). There were no statistical differences of IL-18Rα + CD8 + cell proportion, soluble IL-1R8 level, or immune checkpoint molecule proportion in CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). Perforin and granzyme B secretions by CD8 + T cells were significantly elevated in DKD patients compared with healthy controls [(108.78±12.42) ng/L vs. (94.60±10.07) ng/L, t=3.096, P=0.005; (261.34±48.79) ng/L vs. (166.28±30.80) ng/L, t=3.387, P=0.002] and T2DM patients [(108.78±12.42) ng/L vs. (92.58±14.71) ng/L, t=3.263, P=0.003; (261.34±48.79) ng/L vs. (170.66±39.24) ng/L, t=2.627, P=0.014]. There were no significant differences of either IFN-γ or TNF-α secretions by CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). In direct contact co-culture manner, CD8 + T cell-induced HEK293 cell death was down- regulated (13.03%±4.97% vs. 17.88%±5.19%, t=2.235, P=0.037). The levels of perforin [(222.02±25.79) ng/L vs. (294.30±25.58) ng/L, t=6.603, P<0.001], granzyme B [(416.27±90.24) ng/L vs. (524.71±115.53) ng/L, t=2.454, P=0.023], IFN-γ [(23.66±4.20) ng/L vs. (35.18±8.51) ng/L, t=4.026, P<0.001] and TNF-α [(1.62±0.29) μg/L vs. (2.09±0.57) μg/L, t=2.302, P=0.034] were also reduced as well. In indirect contact co-culture manner, there were no significant differences of CD8 + T cell-induced HEK293 cell death, perforin, or granzyme B levels between no stimulation and IL-37 stimulation (all P>0.05). IFN-γ and TNF-α levels in the supernatants were reduced in response to IL-37 stimulation [(23.56±6.24) ng/L vs. (32.56±9.90) ng/L, t=2.550, P=0.019; (1.41±0.31) μg/L vs. (2.10±0.44) μg/L, t=4.011, P<0.001]. Conclusion:IL-37 level is reduced in DKD patients.Exogenous IL-37 suppresses the cytotoxicity of CD8 + T cells in DKD patients.
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Objective:To retrieve, evaluate and integrate the best evidence of blood glucose management in hemodialysis patients with end-stage diabetic kidney disease, so as to provide a basis for clinical evidence-based nursing practice.Methods:BMJ Best Clinical Practice, Cochrane, OVID, Scopus, UpToDate, CNKI, Wanfang Database, Medical Pulse database, and other guideline networks and professional association websites and databases were searched for blood glucose management in hemodialysis patients with end-stage diabetic kidney disease. The search time limit was from the establishment of the database to May 10, 2023.Results:A total of 14 articles were included, including 1 clinical decision, 5 guidelines, 6 systematic reviews, 1 randomized controlled trial, and 1 expert consensus. The best evidences for blood glucose management in hemodialysis patients were summarized, including 8 aspects of pre-dialysis assessment, pre-dialysis blood glucose management, blood glucose management during dialysis, blood glucose management during dialysis interval, diet and nutrition, exercise management, lifestyle intervention and health education, with 25 pieces of evidence.Conclusions:This study summarizes the best evidence of blood glucose management in hemodialysis patients with end-stage diabetic kidney disease, and provides evidence-based basis for clinical practice for medical staff.
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Objective:To investigate the efficacy and safety of atorvastatin combined with indobufen in the treatment of elderly patients with diabetic kidney disease (DKD) complicated with large atheromatous ischemic stroke (LAA-IS) during convalescence.Methods:The clinical data of 102 elderly patients with DKD complicated with LAA-IS during convalescence from September 2018 to April 2022 in Baoding Second Central Hospital were retrospectively analyzed. Among them, 51 patients were treated with atorvastatin combined with indobufen (observation group), 51 patients were treated with atorvastatin combined with aspirin (control group), and both groups were treated continuously for 6 months. The prethrombotic state indexes, neurological function and quality of daily life, carotid artery ultrasound indexes, renal fibrosis indexes before treatment and after treatment were compared between two group. The prethrombotic state indexes included arachidonic acid (AA) and adenosine diphosphate (ADP) induction platelet aggregation rate, fibrinogen (FIB), protein C; the National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the neurological function, and the modified Barthel index (MBI) was used to evaluate the quality of daily life; carotid artery ultrasound indexes included carotid artery intima-media thickness (IMT) and maximum plaque area; the renal fibrosis indexes included transforming growth factor-β 1 (TGF-β 1), matrix metalloproteinase-9 (MMP-9), hyaluronic acid and platelet derived growth factor-BB (PDGF-BB). The adverse reactions were recorded. Results:There were no statistical differences in the all indexes before treatment between two groups ( P>0.05). In two groups, compared before treatment, the AA induction platelet aggregation rate, ADP induction platelet aggregation rate, FIB, NIHSS score, IMT and maximum plaque area after treatment were significantly lower, the protein C and MBI score were significantly higher, and there were statistical differences ( P<0.01); but there were no statistical differences after treatment between two groups ( P>0.05). The TGF-β 1, MMP-9, hyaluronic acid and PDGF-BB after treatment in two groups were significantly lower than before treatment, and the indexes in observation group were significantly lower than those in control group: (39.46 ± 6.89) μg/L vs. (45.04 ± 8.20) μg/L, (278.46 ± 49.39) μg/L vs. (327.30 ± 57.28) μg/L, (102.37 ± 20.62) μg/L vs. (116.84 ± 24.97) μg/L vs. (25.26 ± 4.45) μg/L vs. (28.13 ± 5.08) μg/L, with statistically significant differences( P<0.01). The incidence of adverse reactions in observation group was significantly lower than that in control group: 7.84% (4/51) vs. 23.53% (12/51), and there was statistical difference ( P<0.05). Conclusions:Compared with atorvastatin combined with aspirin, atorvastatin combined with indobufen in elderly patients with DKD complicated with LAA-IS during convalescence has the same effect in improving the related indicators of prethrombotic state, reducing neurological function deficit, improving the ability of daily living, and reversing carotid atherosclerosis. However, atorvastatin combined with indobufen can further protect renal function with higher safety.
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Objective:To investigate the effect of roxadustat combined with levocarnitine in the treatment of renal anemia in hemodialysis patients with diabetic kidney disease (DKD), and its effects on iron metabolism, microinflammation status and microvascular complications.Methods:The clinical data of 89 hemodialysis renal anemia patients with DKD from January 2020 to October 2021 in Beijing Geriatric Hospital were retrospectively analyzed. Among them, 44 patients (control group)were treated with recombinant human erythropoietin and levocarnitine for renal anemia, and 45 patients (study group) were treated with recombinant human erythropoietin, levocarnitine and roxadustat for renal anemia. Both groups were treated for 3 months. The efficacy was compared between two groups. The laboratory indexes were measured before treatment and after 1, 3 months of treatment, including anemia related indexes such as hemoglobin, red blood cell count and mean corpuscular volume (MCV); iron metabolism indexes such as serum iron, ferritin and transferrin saturation (TSAT); inflammatory indexes such as interleukin-8 (IL-8), C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α). The adverse reactions were recorded. The patients were followed up for 1 year after treatment, the incidence of diabetic microvascular complications, including diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR), was recorded.Results:The total effective rate in study group was significantly higher than that in control group: 93.33% (42/45) vs. 77.27% (34/44), and there was statistical difference ( χ2 = 4.60, P<0.05). There were no statistical differences in the laboratory indexes before treatment between two groups ( P<0.05); the hemoglobin, red blood cell count, MCV, serum iron, ferritin and TSAT after 1 and 3 months of treatment in study group were significantly higher than those in control group, the IL-8, CRP and TNF-α were significantly lower than those in control group, and there were statistical differences ( P<0.01 or <0.05). There was no significant difference in the incidence of adverse reactions between two groups ( P>0.05). After 1 year follow-up, 2 cases were lost in study group and 3 cases in the control group. The incidence of DR and DPN in study group were significantly lower than those in control group: 0 vs. 14.63% (6/41) and 2.33% (1/43) vs. 19.51% (8/41), and there were statistical differences ( χ2 = 4.75 and 4.81, P<0.05). Conclusions:Roxadustat combined with levocarnitine in the treatment of renal anemia in hemodialysis patients with DKD is reliable and safe, and can effectively relieve anemia symptoms, improve iron metabolism, reduce inflammatory response, and reduce the risk of diabetic microvascular complications.
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ABSTRACT Purpose: To assess the effect of Amorphophallus campanulatus tuber (Ac) extract in the protection of diabetic nephropathy in streptozotocin (STZ) induced diabetic nephropathy (DN) rat model. Methods: Diabetes was induced with STZ (60 mg/kg, i.p.), and DN was confirmed after six weeks of STZ administration with the estimation of kidney function test. Further rats were treated with Ac 250 and 500 mg/kg p.o. for next four week. Oxidative stress and level of inflammatory cytokines were estimated in the kidney tissue of DN rats. Histopathology of kidney tissue was performed using hematoxylin and eosin staining. Results: There was improvement in the body weight of Ac treated groups than DN group of rats. Blood glucose level was observed to be reduced in Ac treated groups than DN group on 42nd and 70th day of protocol. Treatment with Ac ameliorated the altered level of kidney function tests (creatinine and BUN), enzymes of liver function (aspartate aminotransferase and alanine aminotransferase), and lipid profile in the serum of DN rats. Oxidative stress parameters (malondialdehyde and reactive oxygen species enhances and reduction in the level of glutathione and superoxide dismutase) and inflammatory cytokines such as interleukin-6, tumour necrosis factor-α, and monocyte chemoattractant protein-1 reduces in the tissue of Ac treated group than DN group. Treatment with Ac also attenuates the altered histopathological changes in the kidney tissue of DN rats. Conclusions: The report suggests that Ac protects renal injury in DN rats by regulating inflammatory cytokines and oxidative stress.
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Objective:To explore the differential expression profile of miRN in the development of diabetes nephropathy (DN), and further explore the mechanism of miR-126-5p involved in high glucose induced injury of renal tubular epithelial cells.Methods:Firstly, we downloaded existing chip data from the Gene Expression Integrated Database (GEO) and used GEO2R, miRanda, gene ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to mine differential miRNAs. Subsequently, a high glucose induced HK-2 cell injury model was used and divided into three groups: high glucose model group, si-HOTAIR group, and si HOTAIR+ miR-126-5p inhibitor group. The three groups of cells were sequentially transfected with siRNA-NC, siRNA-HOTAIR, and siRNA-HOTAIR+ miR-126-5p mimic, and cultured in a medium containing 60 mmol/L glucose. Flow cytometry was used to detect changes in apoptosis levels in each group, while cell counting kit-8 (CCK-8) was used to detect changes in cell proliferation.Results:Through data mining analysis using GEO, it was found that compared to ordinary mice, DN mice had 74 upregulated miRNAs and 80 downregulated miRNAs in their kidney tissue. Enrichment analysis results showed that miRNAs could target signaling pathways such as Wnt, PKG, MAPK, and Rap1, and miR-126-5p was significantly downregulated. In the high glucose induced HK-2 cell injury model, the experimental results showed that the inhibitory effect on cell proliferation activity was more significant at a high glucose concentration of 60 mmol/L ( P<0.05); High glucose stimulation significantly reduced the expression of miR-126-5p ( P<0.05). The results of flow cytometry showed that compared with the high glucose model group, the apoptosis rate of the si-HOTAIR group significantly decreased ( P<0.05), while the apoptosis rate of the si-HOTAIR+ miR-126-5p inhibitor group significantly increased ( P<0.05). The CCK-8 experiment showed that compared with the high glucose model group, the cell viability of the si-HOTAIR group significantly increased ( P<0.05); The cell viability of the si-HOTAIR+ miR-126-5p inhibitor group was inhibited ( P<0.05). Conclusions:miR-126-5p can inhibit high glucose induced apoptosis in HK-2 cells and protect them.
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Objective:To explore the correlation between glycated hemoglobin variability index (HGI) and carotid artery plaque in patients with type 2 diabetic kidney disease (DKD).Methods:This cross-sectional study included 620 DKD patients admitted to the Department of Endocrinology in the First Affiliated Hospital of Nanjing Medical University from June 2019 to June 2022. Basic demographic and laboratory data, including age, disease duration, body mass index (BMI), blood pressure, fasting blood glucose (FBG), glycated hemoglobin (HbA 1c), lipid profile, and urinary albumin excretion rate (UAER), were collected for all participants. A linear regression equation was developed based on FPG and HbA 1c to calculate the HGI level of each patient. The patients were divided into low HGI group, medium HGI group, and high HGI group based on the tertiles of HGI. The detection rate of carotid artery plaque in the three HGI groups was analyzed. The patients were further divided into the non-plaque group (254 cases) and plaque group (366 cases) based on the presence or absence of carotid artery plaque. Binary logistic regression analysis was used to identify the risk factors for carotid artery plaque in DKD patients. Results:Among the DKD patients, the detection rate of carotid artery plaque was 59%. Compared with the non-plaque group, the patients in the plaque group had older age (60.52 years, t=-7.71), longer disease duration (10 years, Z=-4.17), higher systolic blood pressure (141.9 mmHg, t=-3.29), higher HbA 1c (9.2%, Z=-2.17), higher HGI (-0.20%, Z=-3.43), higher urea nitrogen (6.87 μmol/L, Z=-3.96), higher creatinine (77 mmol/L, Z=-4.05), and higher UAER (234.25 mg/24 h, Z=-5.59) (all P<0.05). The detection rate of carotid artery plaque in the low HGI group, medium HGI group and high HGI group was 50.5%, 57.9% and 68.5%, respectively, with a statistically significant difference among the three groups (χ 2=14.15, P=0.001). Age, UAER, and HGI were identified as risk factors for carotid artery plaque ( OR=1.051, 2.775 and 1.474, all P<0.05). The risk of carotid artery plaque in the high HGI group was 2.142 times of that in the low HGI group. After adjusting for confounding factors such as age, gender, disease duration, BMI, blood pressure, lipid profile and UAER, the risk of carotid artery plaque in the high HGI group was 2.558 times of that in the low HGI group. Conclusion:HGI is significantly elevated in DKD patients with carotid artery plaque, and the detection rate of carotid artery plaque increases with HGI level. Elevated HGI is an independent risk factor for carotid artery plaque in DKD patients.
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Objective:To investigate the intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) among patients with type 2 diabetes mellitus (T2DM).Methods:A diagnostic test. In this prospective study, patients with T2DM who underwent both IVIM-DWI and renal biopsy at the First Medical Center of Chinese PLA General Hospital between October 2017 and September 2021 were consecutively enrolled. IVIM-DWI parameters including perfusion fraction (f), pure diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were measured in the renal cortex, medulla, and parenchyma. Patients were divided into the DN group and NDRD group based on the renal biopsy results. IVIM-DWI parameters, clinical information, and diabetes-related biochemical indicators between the two groups were compared using Student′s t-test or Mann-Whitney U test. The correlation of IVIM-DWI parameters with diabetic nephropathy histological scores were analyzed using Spearman′s correlation analyzes. The diagnostic efficiency of IVIM-DWI parameters for distinguishing between DN and NDRD were assessed using the receiver operating characteristic (ROC) curves. Results:A total of 27 DN patients and 23 NDRD patients were included in this study. The DN group comprised 19 male and 8 female patients, with an average age of 52±9 years. The NDRD group comprised 16 male and 7 female patients, with an average age of 49±10 years. The DN group had a higher D* value in the renal cortex and a lower f value in the renal medulla than the NDRD group (9.84×10 -3 mm 2/s vs. 7.35×10 -3 mm 2/s, Z=-3.65; 41.01% vs. 46.74%, Z=-2.29; all P<0.05). The renal medulla D* value was negatively correlated with DN grades, interstitial lesion score, and interstitial fibrosis and tubular atrophy (IFTA) score ( r=-0.571, -0.409, -0.409; all P<0.05) while the renal cortex f value was positively correlated with vascular sclerosis score ( r=0.413, P=0.032). The renal cortex D* value had the highest area under the curve (AUC) for discriminating between the DN and NDRD groups (AUC=0.802, sensitivity 91.3%, specificity 55.6%). Conclusion:IVIM-derived renal cortex D* value can be used non-invasively to differentiate DN from NDRD in patients with T2DM that can potentially facilitate individualized treatment planning for diabetic patients.
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Objective:To investigate the changes of podocyte circadian rhythm in the high-glucose environment and diabetic nephropathy (DN) mouse model and the protective effect of melatonin on podocyte injury in DN.Methods:Primary podocytes were cultured in vitro and divided into 3 groups: control group, high glucose (30 mmol/L) group and high glucose (30 mmol/L) treated with melatonin (0.1 mmol/L or 0.5 mmol/L) group. The podocytes were collected every 4 hours for 24 hours, synchronized with dexamethasone (100 nmol/L) for 2 hours, which was recorded as zeitgeber time 0 point. Male C57BL/6J mice aged 6-8 weeks and weighing about 20 g were randomly (randomized block) assigned to three groups: control group, DN (high-fat diet+streptozotocin 120 mg/kg intravenously injected) group, and DN (high-fat diet+streptozotocin 120 mg/kg intravenously) treated with melatonin (20 mg/kg intragastric treatment) group (melatonin group). Real-time quantitative PCR was used to detect the mRNA levels of rhythm genes in podocytes. Western blotting was used to detect the protein expression levels of circadian clock genes (Clock and Bmal1), podocyte marker proteins (Nephrin, Synaptopodin, WT1, and Desmin) and autophagy-related proteins (Beclin1, LC3Ⅱ/Ⅰ and P62). Immunofluorescence staining was used to detect the protein expression level of WT1, and immunohistochemistry was used to analyze the protein expression levels of P62 and cleaved-caspase-3 in renal tissues of mice. The pathological changes of renal glomerulus were observed under electron microscope. Results:(1) Dexamethasone reseted the expression and rhythmic oscillation of circadian clock genes in podocytes. The circadian rhythmic oscillations of Clock and Ck1e mRNA in the high glucose group were flattened compared to the control group, and the circadian rhythmic oscillations in Clock and Ck1e mRNA expression were partial recovery in high glucose treated with melatonin group (all P<0.05). (2) Compared with the control group, the protein expression levels of Nephrin, Synaptopodin and WT1 were lower while Desmin was higher in the high glucose group (all P<0.05). The protein expression levels of Nephrin, Synaptopodin and WT1 were higher and the protein expression level of Desmin was lower in the high glucose treated with melatonin (0.5 mmol/L) group compared with the high glucose group (all P<0.05). (3) The invivo experimental results showed that compared with the DN group, melatonin group had higher protein expression levels of glomerular Nephrin and WT1, and lower urinary albumin/creatinine ratio, width of foot process and thickness of glomerular basement membrane (all P<0.05). The protein expression levels of Beclin1 and LC3Ⅱ/Ⅰ in the DN group were lower than those in the control group, and the protein expression level of P62 was higher than that in the control group (all P<0.05). Compared with the DN group, the protein expression levels of Beclin1 and LC3Ⅱ/Ⅰ in the melatonin group were significantly higher, and the protein expression level of P62 was lower (all P<0.05). Conclusions:Melatonin can partially restore the circadian rhythm of clock genes in high-glucose environment, improve autophagy and alleviate injury in podocytes.
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Objective:To explore the relationship between urinary exosomal microRNA (exo-miR) - 155 in patients with type 2 diabetes mellitus (T2DM) and the onset and severity of diabetic kidney disease (DKD).Methods:From January to May 2019, 5 patients with T2DM normoalbuminuria and 5 patients with type 2 DKD were recruited from the Department of Endocrinology and Metabolism of Chongming Hospital of Shanghai Health Medical College as a microRNA screening cohort. Urine samples were collected to extract urinary exosomes, and the urine exo-miR spectrum was detected and analyzed using the miRCURY LNA array. From June 2019 to October 2022, 351 patients with T2DM who met the enrollment criteria and were matched by age and sex were included in the validation cohort in the Department of Endocrinology and Metabolism of the hospital. Patients were divided into 3 groups according to urinary albumin/creatinine ratio (UACR): normoalbuminuria group (UACR<30 mg/g, n=143), microalbuminuria group (30 mg/g≤UACR≤300 mg/g, n=171) and macroalbuminuria group (UACR>300 mg/g, n=37). According to DKD diagnostic guidelines, microalbuminuria group and macroalbuminuria group were classified into DKD group. Real-time fluorescence quantitative PCR was used to detect the expression level of exo-miR-155 in urine. Results:The results of transmission electron microscopy, nanoparticle tracking analysis, and Western blotting showed that the extraction of exosome vesicles was successful. In the screening cohort, according to the screening criteria of P<0.05 and fold changes (FC)>1.5, 226 differentially expressed miRNAs were identified from the urinary exosomes of the DKD group compared to the T2DM group. Among them, miR-155 ranged highest (FC=32.75, P<0.001). In the validation cohort, compared with the normoalbuminuria group [0.76 (0.55, 0.95)], the macroalbuminuria group [1.84 (1.18, 2.42)] had the most significant increase in urinary exo-miR-155 level ( Z=-7.411, P<0.001), followed by the microalbuminuria group [0.86 (0.69, 1.25)] ( Z=-4.092, P<0.001), and the urinary exo-miR-155 level in the macroalbuminuria group was significantly higher than that in the microalbuminuria group ( Z=-5.841, P<0.001). The correlation analysis showed that urinary exo-miR-155 level was positively correlated with UACR ( r s=0.329, P<0.001) and negatively correlated with estimated glomerular filtration rate ( r s=-0.249, P=0.015). The results of receiver operating characteristic curve analysis showed that the area under the curve of urinary exo-miR-155 level predicted DKD progression in T2DM patients was 0.892 (95% CI 0.859-0.925), corresponding cutoff value was 0.982, and the sensitivity and specificity were 71.9% and 87.7%, respectively. Multivariate logistic regression analysis showed that urinary exo-miR-155≥0.982 was an independent risk factor for progression to DKD in T2DM patients ( OR=3.310, 95% CI 1.981-5.530, P<0.001). Conclusion:The expression level of urinary exo-miR-155 is increased in T2DM patients with microalbuminuria and macroalbuminuria, which is related to the degree of albuminuria, and can be used as a predictive marker to identify potential DKD.
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Objective:To analyze the medication and compatibility law of TCM compound patents in the treatment of diabetic nephropathy (DN) based on data mining method; To provide basis for research and development of new drug in clinic.Methods:TCM compound patents for DN treatment were retrieved from national patent platform. Excel 2019 was used to conduct statistical analysis on drug frequency, property and taste and meridian. SPSS Modeler 18.0 and SPSS Statistic 26.0 were used for drug association rules and clustering analysis. The complex network of co-occurrence of core drugs was constructed with Cytoscape 3.9.0, and the potential of the correlation between new prescriptions and drugs was demonstrated.Results:A total of 261 TCM compound patents were included, including 438 kinds of Chinese materia medica. High-frequency drugs included Astragali Radix, Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma, Lycii Fructus, etc. Drug categories were mainly deficiency tonic drugs. The properties and tastes were mainly cold and sweet, and the meridians were mainly liver and kidney meridians. The commonly used medicinal pair was Ganoderma-Rehmannine Radix. The commonly used triple medicinal combination was Notoginseng Radix et Rhizoma-Angelicae Sinensis Radix-Ganoderma. There were 7 groups of clustering medicines, including Notoginseng Radix et Rhizoma, Ganoderma, Angelicae Sinensis Radix, Euryales Semen, Rehmanniae Radix and Lycii Fructus. There were 5 groups of potential medicines, including Campsis Flos-Caulis Tinosporae Sinensis-Kalopanacis Radix-Fimbristylis Rigiduta Nees-Padicularisdis Dissectae Radix -Korshinsk Peashrub-Alismatis Fructus-Cynanchi Wallichii Radix. The core new prescriptions for treating DN were obtained through topological attribute analysis and screening.Conclusions:The national TCM compounds patents treatment for DN is based on the pathogenesis of this disease, which is characterized by deficiency in nature and excess in superficiality. It often uses methods such as tonifying qi and spleen, nourishing yin and tonifying kidney, promoting blood circulation and resolving blood stasis to improve clinical efficacy, providing ideas for the development of new drugs.
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Objective:To investigate the protective effect and possible mechanism of Tangshenbao on renal damage in diabetic nephropathy (DN) rats.Methods:Totally 36 SPF male SD rats were randomly divided into normal group ( n=6) and model group ( n=30). The DN rat model was prepared by single high-dose intraperitoneal injection of STZ. According to the random number table method, the rats were divided into model group, irbesartan group and Tangshenbao low-, medium- and high-dosage groups, with 6 rats in each group. Drug intervention lasted for 8 weeks. The general condition and body weight of rats in each group were recorded. The blood glucose, kidney index, 24 h urine protein (24 h UTP), SCr and BUN levels were detected. The pathological morphology of renal tissue was observed by PAS staining and transmission electron microscopy. The mRNA and protein expressions of Ets-1, TGF-β1, Smad2 and Smad3 in renal tissue were detected by real-time fluorescence quantitative PCR and Western blot. Results:Compared with model group, the body weight of Tangshenbao low, medium and high dose groups and irbesartan group significantly increased ( P<0.01). The kidney index decreased ( P<0.05 or P<0.01). The contents of 24 hUTP, BUN and SCr significantly decreased ( P<0.05 or P<0.01). Glomerular volume was significantly reduced ( P<0.05 or P<0.01), the mRNA expressions of Ets-1 (1.59 ± 0.06, 1.47 ± 0.04, 1.31 ± 0.03, 1.39 ± 0.03 vs. 1.64 ± 0.04), TGF-β1 (1.65 ± 0.05, 1.59 ± 0.03, 1.38 ± 0.05, 1.49 ± 0.04 vs. 1.77 ± 0.08), Smad2 (1.48 ± 0.05,1.39 ± 0.05, 1.22 ± 0.03, 1.31 ± 0.04 vs. 1.54 ± 0.05), Smad3 (1.57 ± 0.04, 1.48 ± 0.03, 1.28 ± 0.03, 1.39 ± 0.02 vs. 1.64 ± 0.05) in renal tissue of rats significantly decreased ( P<0.05 or P<0.01), the protein expressions of Ets-1 (1.33 ± 0.32, 1.16 ± 0.38, 0.77 ± 0.06, 0.84 ± 0.06 vs. 1.97 ± 0.43), TGF-β1 ( 1.35 ± 0.14, 1.24 ± 0.22, 0.94 ± 0.13, 1.07 ± 0.06 vs. 1.63 ± 0.20), Smad2 (1.24 ± 0.26, 1.14 ± 0.31, 0.77 ± 0.28, 0.85 ± 0.19 vs. 1.72 ± 0.34) and Smad3 (1.29 ± 0.14, 1.19 ± 0.21, 0.85 ± 0.39, 0.90 ± 0.37 vs. 1.76 ± 0.21) decreased ( P<0.05 or P<0.01). Conclusion:Tangshenbao can improve renal damage in DN rats, and its mechanism may be related to the inhibition of Ets-1 expression and TGF-β1/Smads signaling pathway.
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Objective:To analyze the law of TCM syndrome differentiation and treatment for type 2 diabetic kidney disease (T2DKD) stage Ⅳ based on literature research.Methods:Literature on type 2 diabetic kidney disease stage Ⅳ was retrieved from CNKI, WanFang data, VIP and SinoMed database. The retrieval time was from the establishment of the databases to December 31, 2020. Data screening was conducted based on the inclusion and exclusion criteria prior to data entry in Microsoft Office Excel 365. Data mining and statistical analysis were performed by SPSS Statistics 23.0 and SPSS Modeler 18.1.Results:A total of 110 articles with 3 969 T2DKD stage Ⅳ cases, 111 prescriptions and 206 kinds of Chinese materia medica were included. Kidney and spleen were the main location of T2DKD stage Ⅳ. T2DKD stage Ⅳ based on TCM deficiency in nature syndrome was mainly based on qi and yin deficiency, and the most common excess in superficiality syndrome was blood stasis. The prescriptions commonly used included Liuwei Dihuang Decoction, Zhenwu Decoction, Buyang Huanwu Decoction, and Shenqi Dihuang Decoction etc. The classification of medication efficacy with the highest frequency was qi-tonifying herb, followed by blood-activating and stasis-resolving herb. Among them, Astragali Radix was the core Chinese materia medica in the prescription. The results of association rule obtained 54 association rules. Conclusions:The disease characteristics of T2DKD stage Ⅳ is simultaneous occurrence of deficiency and excess syndromes. The deficiency in nature is mainly characterized by deficiency of qi and yin, deficiency of spleen and kidney, deficiency of spleen-kidney yang, and excess in superficiality is mainly characterized by blood stasis, dampness and toxin. Tonifying qi and nourishing yin, activating blood circulation and dredging collaterals are the basic treatment methods, while strengthening spleen and kidney, dampness and detoxification should be emphasized. Astragali Radix, Angelicae Sinensis Radix, Salviae Miltiorrhizae Radix et Rhizoma, Poria, Dioscoreae Rhizoma, Corni Fructus, Rhei Radix et Rhizoma and Alismatis Rhizoma were the basic Chinese materia medica in this period, which reflects the idea of "treating qi, blood and water together".
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Objective:To explore the construction of a Logistic prediction model and countermeasures for type 2 diabetic nephropathy based on clinical data.Methods:The patients with type 2 diabetic nephropathy admitted to Shijiazhuang Second Hospital from September 2019 to September 2021 (study group) were selected and the patients were selected according to a 1∶1 ratio using individual matching (control group), each group with 200 patients. Single and multiple factors analysis were used to analyze the factors influencing type 2 diabetic nephropathy, and Logistic regression equation models were developed to verify their predictive value.Results:Logistic regression equation model showed that the course of type 2 diabetes, glycosylated hemoglobin (HbA 1c), fasting plasma glucose (FPG), homocysteine (Hcy), urinary microalbumin, and serum creatinine (Scr) were high risk factors for type 2 diabetic nephropathy ( P<0.05). The results of Logistic regression model evaluation showed that the model was established with statistical significance, and the coefficients of the regression equations had statistically significant differences. The Hosmer-Lemeshow goodness-of-fit test showed that the model fitting effect was good. Logistic regression model was used to statistically analyzed the data set, and the receiver operating characteristic (ROC) curve of type 2 diabetic nephropathy was drawn, the area under the curve was 0.949(95% CI 0.922 - 0.968), the prediction sensitivity was 81.50%, the specificity was 95.50%, the calibration curve showed that the predicted results was in good agreement with the observed results. Conclusions:The independent predictors of type 2 diabetic nephropathy involve HbA 1c, FPG, Hcy, urinary microalbumin. The Logistic prediction model based on these predictors has reliable predictive value and can help guide clinical diagnosis and treatment.
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Objective:To investigate and analyze the risk factors of pulmonary infection in hemodialysis patients with diabetes nephropathy (DN), and explore the effect of different antibiotic application methods on the efficacy of DN patients with pulmonary infection.Methods:337 inpatients with DN who were admitted to Lishui Central Hospital from August 2021 to April 2022 were selected as the study subjects, and the proportion of pathogenic bacteria in patients with pulmonary infection caused by hemodialysis was analyzed, and the influencing factors of pulmonary infection were analyzed by single factor and multiple factor logistic regression models. DN patients with pulmonary infection were treated with single or multiple antibiotics, and their curative effects were analyzed and compared.Results:Among 337 hospitalized patients with DN in this study, the rate of pulmonary infection caused by hemodialysis was 24.04%(81/337). 87 strains of pathogenic bacteria were cultivated, and the main pathogens of the infected individuals were Klebsiella pneumoniae (36.78%, 32/87), Staphylococcus aureus (17.24%, 15/87), and Acinetobacter baumannii (16.09%, 14/87). The results of univariate analysis showed that patient age, dialysis time, hospital stay, hemoglobin, postprandial blood glucose, malnutrition (blood albumin level<35 g/L), renal function, and volume load were the influencing factors for pulmonary infection in DN patients undergoing hemodialysis (all P<0.05). Multivariate logistic regression model analysis showed that dialysis time, hemoglobin, postprandial, blood glucose malnutrition, renal function, and volume load were risk factors for pulmonary infection caused by hemodialysis (all P<0.05). After treatment, the levels of white blood cells, neutrophils, and hypersensitive reactive protein in patients with pulmonary infection were significantly reduced compared to before treatment (all P<0.05). The effective rate of multi antibiotic therapy (97.44%, 38/39) was higher than that of single antibiotic therapy (80.95%, 34/42) (χ 2=5.563, P=0.018). Conclusions:There are many independent risk factors for pulmonary infection during hemodialysis in DN patients. The infection rate should be reduced through adequate dialysis, blood glucose control, nutrition supplementation, anemia correction and other measures, and the infected can be treated timely with antibiotics according to the situation.
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Objective:To investigate the correlation between serum remnant cholesterol(RC)and diabetic kidney disease(DKD)in elderly patients with type 2 diabetes mellitus(T2DM).Methods:The elderly patients with T2DM who were hospitalized in the Department of Geriatrics of the Second Xiangya Hospital of Central South University from January 2021 to March 2022 were selected and divided into simple diabetes group(410 cases)and DKD group(433 cases). The general clinical data and laboratory data were collected and the RC level was calculated.Spearman rank correlation was used to analyze the correlation between RC level and metabolic indicators.Logistic regression was used to analyze the correlation between serum RC level and the risk of DKD.Results:Compared with the simple diabetes group, patients in the DKD group had older age, longer duration of diabetes, higher levels of systolic blood pressure(SBP), fasting C-peptide, triglyceride(TG), uric acid(UA), serum creatinine, urinary albumin/creatinine ratio(UACR)and RC, and lower levels of albumin, high-density lipoprotein cholesterol(HDL-C)and estimated glomerular filtration rate(eGFR)( P<0.05 for all). Spearman rank correlation analysis showed that serum RC level was positively correlated with body mass index(BMI)( r=0.069, P=0.046), fasting blood glucose( r=0.099, P=0.004), glycosylated hemoglobin(HbA1c)( r=0.075, P=0.031), fasting C-peptide( r=0.177, P<0.001), TG( r=0.632, P<0.001), total cholesterol(TC)( r=0.306, P<0.001), low density lipoprotein cholesterol(LDL-C)( r=0.243, P<0.001), UA( r=0.128, P<0.001), serum creatinine( r=0.086, P=0.013)and UACR( r=0.147, P<0.001), and was negatively correlated with HDL-C( r=-0.271, P<0.001)and eGFR( r=-0.148, P<0.001). Logistic regression analysis showed that high serum RC level was a risk factor for DKD(Q1 as reference; Q2: OR=2.439, 95% CI: 0.836-7.113, P=0.103; Q3: OR=3.999, 95% CI: 1.187-13.478, P=0.025). Conclusions:High serum RC level is closely related to DKD in elderly patients with T2DM, and is a risk factor for DKD.