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Objective:To screen the incidence of proteinuria in rural areas of Shanxi province and construct a risk prediction model of proteinuria based on machine learning algorithm.Methods:It was a cross-sectional investigation study. The residents ≥30 years old in rural areas of Shanxi province from April to November 2019 were screened by multi-stage stratified sampling method, and data from questionnaire surveys, physical examinations, and laboratory examinations were collected. Urine albumin/creatinine ratio ≥30 mg/g was defined as proteinuria, and the incidence of proteinuria was calculated. Subjects were divided into proteinuria group and non-proteinuria group. The machine learning binary classification model of proteinuria and non-proteinuria was constructed based on the stackable integrated logistic regression algorithm (SE-LR), logistic regression, support vector machine, decision tree, random forest and extreme gradient lift algorithms, respectively. The area under the receiver operating characteristic curve, accuracy, recall, and F1 weights were used to evaluate the predictive efficiency of the comparison models. Finally, the importance of the predictive features of the model with the best overall performance was ranked.Results:There were 8 869 rural residents included in the study, aged (58.59±9.49) years old, with 3 872 males (43.66%) and 4 997 females (56.34%). The prevalence of proteinuria in rural areas of Shanxi province was 13.49% (1 196/8 869). Blood pressure, pulse, body mass index, waist circumference, proportion of obesity or overweight, proportion of hypertension, proportion of moderate to severe salt intake, glycosylated hemoglobin, uric pH value, urinary specific gravity, proportion of positive urinary occult blood, proportion of positive urinary glucose, proportion of positive urinary ketone body, proportion of urinary red blood cell count ≥5/μl, proportion of urinary white blood cell count ≥10/μl and urinary α1 microglobulin in the proteinuria group were all higher than those in the non-proteinuria group (all P<0.05). The proportions of lack of exercise and drinking history in the proteinuria group were lower than those in non-proteinuria group (both P<0.05). The overall performance of SE-LR model was the best, with the area under the curve (0.736, 95% CI 0.719-0.746) slightly lower than that of the logistic regression model (0.745, 95% CI 0.680-0.762), and the highest accuracy (0.844), recall rate (0.621) and F1 weighting value (0.801). In the SE-LR model, the orders of importance of the top 10 features were urinary α1- microglobulin, urinary occult blood, urinary sugar, uric acid basicity, smoking history,overweight or obesity, body mass index, total cholesterol, glycosylated hemoglobin and hypertension. Conclusions:The prevalence of proteinuria is high in rural areas of Shanxi province. The risk prediction model of proteinuria established by machine learning algorithm can predict the risk of proteinuria and identify its risk factors, which can provide a scientific basis for disease prevention, intervention, and treatment in the community and clinic to a certain extent.
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Objective:To investigate the protective function and mechanism of β-hydroxybutyrate (β-HOB) on cisplatin (CP)-induced nephrotoxicity.Methods:C57BL/6 male mice aged 10 weeks were randomly divided into the following three groups: control group (no special treatment), β- HOB+CP group (mice received intraperitoneal injection of 20 mmol/kg β-HOB for 10 days), CP group (received intraperitoneal injection of normal saline for 10 days). CP group and β-HOB+CP group were given once cisplatin (20 mg/kg) intraperitoneal injection on the 8th day in the experiment. On the 10th day, all the mice were sacrificed. Renal pathology was evaluated by HE staining; blood samples were collected for blood urea nitrogen (BUN) and serum creatinine (Scr) measurement; immunohistochemistry staining was performed to detect the protein level of Caspase3, Cleaved-caspase3, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in renal tissues; Western blotting was used to detect the relative expression levels of p-MAPK/MAPK and p-NF-κB/NF-κB. In vitro experiment, HK-2 cells were set into three groups: control group, CP group, β-HOB+CP group, and β-HOB+CP+Sappanone A (Sap, MAPK-p38 activator) group. The expression levels of p-MAPK, p-NF-κB, Caspase3 and Cleaved-caspase3 were tested by cell immunofluorescence. The cell apoptosis and mitochondrial membrane potential (MMP) were examined by flow cytometry. DNA damage was detected by TUNEL staining. Results:In vivo experiments, the renal pathological injury score, BUN and Scr in CP group were significantly higher than those in control group (all P<0.05), while renal pathological injury score, BUN and Scr in β-HOB+CP group were lower than those in CP group (all P<0.05). The protein expression levels of p-MAPK, p-NF-κB, Caspase3 and Cleaved-caspase3 in CP group were higher than those in control group, while these indexes in β-HOB+CP group were lower than those in CP group (all P<0.05). In vitro experiments, compared with CP group, the MMP was higher in β-HOB+CP group; the ratio of cell apoptosis, the expression of Caspase3, Cleaved-caspase3, p-MAPK and p-NF-κB, and the number of TUNEL staining positive cells were significantly lower (all P<0.05). Compared with β-HOB+CP group, the MMP in β-HOB+CP+Sap group was lower; the ratio of cell apoptosis, the expression of Caspase3 and Cleaved-caspase3, and the number of TUNEL staining positive cells were significantly higher (all P<0.05). Conclusions:β-HOB can alleviate the acute renal injury induced by cisplatin, which may be related to the reduction of apoptosis and inhibition of MAPK/NF-κB pathway.
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Objective:To explore the mechanism of highly expressed primary cilia in tibial growth plate chondrocytes accelerating chondrocytes differentiation in young rats with chronic renal failure (CRF).Methods:Forty male 4-week-old SD rats weighing (98±3) g were randomly divided into control group (intragastric administration with distilled water, n=20) and CRF group (intragastric administration with adenine suspension 150 mg·kg -1·d -1, n=20). All the young rats were sacrificed after continuous gavage for 6 weeks. The length of the growth plate was measured with histological sections. Immunofluorescence (IF) was used to detect the expression rate of primary cilia and the level of β-catenin, the key protein of Wnt/β-catenin signaling pathway in tibial growth plate chondrocytes. Chondrocytes isolated from growth plate in two groups were cultured in vitro to P3 generation, and the expression rate of primary cilia in chondrocytes, the levels of Indian hedgehog (IHH) and glycogen synthase kinase 3β (GSK3β) were detected by IF. Co-immunoprecipitation was used to detect the relationship between IHH and GSK3β. Results:Compared with the control group, the relative length of the growth plate was shorter in histological sections [(0.51±0.11) vs (1.00±0.08), t=16.11, P<0.001], the expression rate of primary cilia was higher [(26.3±5.5)% vs (7.6±1.9)%, t=14.37, P<0.001], and the level of β-catenin increased [(7.1±2.0) scores vs (3.6±1.0) scores, t=7.10, P<0.001] in CRF group. In vitro, the expression rate of primary cilia was higher in CRF group chondrocytes [(31.4±8.2)% vs (12.5±3.1)%, t=9.64, P<0.001] than that in control group. The level of IHH in CRF group increased than that in control group [(1 360±270) vs (310±84), t=16.61, P<0.001]. There was no significant difference in GSK3β level of chondrocytes between the two groups [(850±195) vs (780±140), t=1.30, P=0.200]. There was a direct interaction between IHH and GSK3β in CRF group chondrocytes. Conclusions:The expression levels of primary cilia and related protein IHH increase in tibial growth plate chondrocytes of CRF young rats. The IHH protein plays a direct interaction with GSK3β protein, Wnt/β-catenin signaling pathway antagonist, which leads to the activation of Wnt/β-catenin signaling pathway and final accelerated differentiation of chondrocytes. The rapid differentiation of chondrocytes causes the closing trend of growth plate.
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Objective To observe the expression of parathyroid hormone - related peptide (PTHrp) receptor in tibial growth plate and its effects on tibial extension in chronic renal insufficiency rats. Methods Two-week-old male Sprague-Dawley rats were randomly divided into sham group, model group and enalapril group, each with 20 rats. In model group and enalapril group rats had chronic renal insufficiency induced by left ureteral obstruction, and rats were respectively given saline and enalapril by gavage after the operation. In sham group, left ureter was only exposed without ligation, and rats were given saline. The urine was collected 4 weeks after the operation and the total protein content was measured. Then all rats were killed. The concentrations of PTHrp, creatinine and urea nitrogen in intracardiac blood were detected. HE staining and Masson staining were performed on the left kidney to observe pathological changes of glomeruli and renal tubules. The total length of bilateral tibia was measured. The number of columnar cells in the growth plate proliferative zone was measured by safranin O staining and the expression of PTHrp receptor in the growth plate was detected by immunohistochemistry. Results The 24 h urine total protein, creatinine and urea nitrogen in model group were higher than those in sham group (all P＜0.05), while these 3 renal functional parameters in enalapril group were lower than those in model group (all P＜0.05). In model group and enalapril group rats had higher blood concentrations of PTHrp than that in sham group (all P＜0.05), but blood PTHrp in enalapril group was lower than that in model group (P＜0.05). HE staining and Masson staining showed that in the model group rats had severe tubular dilation, inflammatory cell infiltration and the tissue fibrosis, while in enalapril group renal tubules slightly dilated and had a few inflammatory cell infiltration and tissue fibrosis. Compared with those in the sham group, in model group the tibia length, the chondrocyte number of column structure in the growth plate proliferative zone and the PTHrp receptor decreased (all P＜0.05). But in enalapril group those indexes increased than model group (all P＜0.05). Conclusions Chronic renal insufficiency rats had increased PTHrp concentration in the blood but decreased PTHrp receptors expression in tibial growth plate, which lead to their limited tibial extension.
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Objective To observe the changes of irisin in patients before and after hemodialysis (HD),as well as the differentiation of irisin change in patients with diabetes mellitus and protein energy waste.Methods Clinical parameters of patients on maintenance hemodialysis (MHD)in Shanxi People's Hospital from September 2016 to November 2016 were collected.A total of 33 cases were enrolled——14 cases of diabetic MHD group and 19 cases of non-diabetic MHD group as divided according to etiology.Based on the presence of protein energy waste,patients were also grouped into 17 cases with and 16 cases without protein waste.Before and after HD,the non parametric test was used to compare the changes of irisin in each group.Results After HD,the irisin value of 33patients with ERSD decreased,with the difference being statistically significant [0.666(0.218,1.365) ng/L vs 0.977(0.202,1.820) ng/L,P=0.01].The difference was not statistically significant in the diabetes MHD group;statistically significant in the non diabetes group [0.666(0.178,1.351) ng/L vs 0.913(0.100,1.497) ng/L,P ＜ 0.05];and not statistically significant in the protein energy group.The irisin of diabetic MHD group and non-diabetic MHD group were compared after HD:the difference was not statistically significant.Conclusions After HD,plasma irisin levels were reduced in patients with end-stage renal disease.Diabetes and protein wasting effects are not important for irisin at HD.
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Chronic hepatitis C virus ( HCV) infection has been reported in association with several extrahepatic complications, among which mixed cryoglobulinemia is the most documented. Clinical manifestations of HCV related cryoglobulinemia include skin lesions, glomerulonephritis, peripheral neuropathy, and widespread vasculitis.The therapy may be directed to eradicate HCV infections, suppress B-cell clonal expansion and cryoglobulin production, and ameliorate symptoms.This paper reviews the research progress on pathogenesis, clinical manifestations, diagnosis and treatment of HCV related cryoglobulinemia.
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Objective To investigate the medical and pharmaceutical knowledge of patients with chronic diseases and analyse the influence factors of rational administration in patients ,to provid data to support the establishment of pharmaceutical service mode . Methods 386 cases of patients with chronic diseases were asked to finish the questionnaires for the medical and pharmaceutical knowledge ,and factors affecting the rational drug were analyzed by single factor and multiple factors Logistic regression analysis . Results Among the 386 patients ,cardiovascular and celebralvascular disease ratio was the highest(53 .3% ) ,followed by respiratory system diseases(13 .8% ) and the musculoskeletal system diseases (11 .50% );The averaged score of 386 patients was 1 .76 ± 0 .78 , medication knowledge was at a general level;single factor analysis results showed that there was significant difference(P<0 .05) between rational drug-use and abuse of drugs among patients in number ,form of payment ,marital status ,income ,education level , taking drug knowledge lectures ,combined treatment .Multivariate Logistic regression analysis showed that education level ,partici-pation in lectures ,drug combination ,disease species had a significant impact on the rational drug use among patients with chronic disease(P<0 .05) .Conclusion The pharmaceutical knowledge that patients with chronic disease mastered is unsatisfactory ;and unreasonable behavior of medication is common scence .Education level ,participation in lectures ,drug combination ,the number of diseases have great influence on the rational use of drugs in patients with chronic diseases .A kind of effective pharmaceutical service mode should be established for patients with chronic diseases by clinical pharmacists .This is a very meaningful work for rational ad-ministration .
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Acute kidney injury (AKI), associated with significant morbidity and mortality, is widely known to involve epithelial apoptosis, excessive inflammation, and fibrosis in response to ischemia or reperfusion injury, which results in either chronic pathological changes or death. Therefore, it is imperative that investigations are conducted in order to find effective, early diagnoses, and therapeutic targets needed to help prevent and treat AKI. However, the mechanisms modulating the pathogenesis of AKI still remain largely undetermined. MicroRNAs (miRNAs), small non-coding RNA molecules, play an important role in several fundamental biological and pathological processes by a post transcriptional regulatory function of gene expression. MicroRNA-21 (miR-21) is a recently identified, typical miRNA that is functional as a regulator known to be involved in apoptosis as well as inflammatory and fibrotic signaling pathways in AKI. As a result, miR-21 is now considered a novel biomarker when diagnosing and treating AKI. This article reviews the correlative literature and research progress regarding the roles of miR-21 in AKI.
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Animals , Humans , Acute Kidney Injury , Diagnosis , Drug Therapy , Genetics , Pathology , Apoptosis , Biomarkers , Metabolism , MicroRNAs , Genetics , Metabolism , Molecular Targeted TherapyABSTRACT
Objective Proteomics changes from the proteserum which isolated from the rat model of renal ischemia/reperfusion(I/R) injury are detected and investigated by the matrix-assisted UV laser desorption ionization time of flight mass sperctra (MALDI-TOF MS). Methods After the establishment of rat renal ischemia-reperfusion model,the serum samples which we selected respectively in 6,12,24 hours after reperfusion in each group were detected by MALDI-TOF MS analysis. And the peptide fingerprint which existed differences in each group were analyzed to identify.SPSS13.0 software was used to the analysis the data. At the same time,we used Mascot Search to determine their nature in protein database. Results ①the serum which was analyzed by IMAC-Cu bead was detected and had statistically significant peptide fingerprint in the m/z 2481 Da.②the results obtained from peptide mass fingerprint (PMF) were analyzed by Mascot search program for protein identification. We identified it as rat fibrinogen fragment.Conclusion Fibrinogen in kidney ischemia/reperfusion (I/R) injury plays an important role.