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OBJECTIVE@#To explore the role of transforming growth factor-β1/integrin-linked kinase/fibroblast-specific protein 1 (TGF- β1/ILK/FSP1) signaling pathway in cyclosporine A (CsA)-induced renal tubular epithelial cell transdifferentiation.@*METHODS@#Rat renal tubular epithelial NRK-52E cells were induced with 1 mg/L CsA, treated with TGF-β1 inhibitor (SB431542, 10 μmol/L), or transfected with the ILK-RNAi lentiviral expression vector (ILKshRNA) or a negative control vector before CsA induction. The expressions of TGF-β1, ILK and FSP-1 mRNAs and proteins in the cells were detected using real-time PCR and Western blotting. The positive cells for α-SMA expression were detected by immunohistochemistry.@*RESULTS@#Compared with the blank control cells, the cells treated with CsA showed significantly increased levels of TGF-β1, ILK and FSP-1 mRNAs and proteins ( < 0.05). The expressions of TGF-β1, ILK and FSP-1 were significantly lower in TGF-β1 inhibitor group than in CsA group ( < 0.05). The levels of ILK and FSP-1 were significantly decreased after shRNA-mediated ILK silencing ( < 0.05). The number of positive cells for -SMA was significantly lower in cells treated with SB431542 and in cells with ILK silencing than in the cells treated with CsA alone ( < 0.05).@*CONCLUSIONS@#The activation of TGF-β1/ILK/FSP-1 signaling pathway is an important mechanism for CsA-induced transdifferentiation in rat renal tubular epithelial cells. ILK participates in CsA-induced epithelialmesenchymal transition of renal tubular epithelial cells.
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Animals , Rats , Calcium-Binding Proteins , Cells, Cultured , Cyclosporine , Epithelial Cells , Epithelial-Mesenchymal Transition , Protein Serine-Threonine Kinases , Signal Transduction , Transforming Growth Factor beta1ABSTRACT
Objective:To investigate the effect of specific inhibition of transforming growth factor-β1 (TGF-β1) with SB-431542 on the Smad2/3 and integrin-linked kinase (ILK) signaling molecules in tubule interstitial fibrosis(TIF)-induced cyclosporine A(CsA) in mouse.Methods:50 BALB/c mice were randomly divided into 5 groups (10 mice per group):the CsA model group (CMG),the interventional model group (IMG),the solvent control group (SCG),the low-salt control group (LCG),and the normal control group (NCG).The model mouse was established with low-sodium diet and intragastric administration of cyclosporine A,which was dissolved in olive oil at a dose of 60 mg/(kg·d).After 4 weeks,a specific inhibitor of TGF-β1 (SB-431542)was administered intraperitoneally with 10 mg/(kg·2 d) for 10 days (every other days).Mice were sacrificed at day 38.Serum creatinine (Scr) was measured,hydroxyp roline (Hyp)level and morphological changes of renal tissue were analyzed,expression levels of TGF-β1,P-Smad 2/3 and ILK were respectively detected by immunohistochemistry or Western blot,mRNA levels of TGF-β1,Smad 2/3 and ILK were respectively detected real-time polymerase chain reaction (RT-PCR).Results:Compared with three control groups (NCG,LCG and SCG),mice weight was decreased significantly,Scr level was increased significantly in two modeling groups (CMG and IMG) (P<0.01),and these changes in CMG were more obvious than those of IMG (P<0.05).Different levels of tubulointerstitial injury,interstitial infiltration of inflammatory cells and blue collagen staining in two modeling groups were observed,and particularly evident in CMG.TGF-β1,P-Smad2/3 and ILK immunostaining were mainly expressed in tubulointerstitium.The TGF-β1,P-Smad2/3 and ILK mRNA and immunostaining levels in two modeling groups were significantly increased as compared with three control groups (P<0.01),but their levels in IMG were significantly lower than those of CMG (P<0.05).The level of Hyp in renal tissue was positively correlated with Scr,TGF-β1,Smad2/3 and ILK (r=0.860,0.711,0.776,0.676,P<0.01).Conclusion:The activation of the TGF-β1/Smads signaling pathway plays an important role in the development of chronic CsA-induced TIF.The activation of ILK is closely correlated with the development of TIF,and may be used as a downstream factor of TGF-β1/Smads signaling pathway in regulating CsA-induced TIF.
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Objective To study the application of remifentanil combined with sevoflurane or propofol in the anesthesia of patients with intracranial tumors.Methods From January 2015 to December 2015,60 patients with intracranial tumor surgery in our hospital were selected as the research object in this study.They were randomly divided into A group and B group,each group had a total of 30 cases.Patients in group A were treated with remifentanil combined with sevoflurane anesthesia,and B group was treated with remifentanil and propofol anesthesia.Comparative analysis of A group and B group of patients with clinical indicators.Results During the operation,two groups of patients with end tidal carbon dioxide partial pressure and pulse oxygen saturation score.Two groups of patients in the immediate intubation heart rate and blood pressure were significantly lower than before anesthesia,A group reduced the degree of greater,with statistical difference(P<0.05).In group A,30 min and 1H were significantly higher than those in group B after anesthesia,and the difference was statistically significant(P<0.05).The anesthesia time of A group was(187.3±22.7)min,and the extubation time was(22.1±8.2)min.The anesthesia time of B group was(181.4±19.1)min,and the extubation time was(10.2±5.3)min.As a result,B group of patients with anesthesia time and extubation time were significantly less than the A group,and with statistical difference(P<0.05).Conclusion Remifentanil Combined with propofol and sevoflurane anesthesia in patients with intracranial tumors compared to two kinds of methods can effectively stabilize the patient's life signs,but remifentanil and propofol recovery time is fast,contribute to the balance of cerebral oxygen supply and consumption in a certain extent,with the further promotion and application of clinical significance.
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Hepatorenal syndrome (HRS) is a serious complication of the end-stage liver disease. The overall treatment outcome of HRS is not satisfactory, with a short survival time and a poor prognosis. Currently, renal replacement therapy is one of the main non-transplantation therapeutic methods, but its clinical effect remains controversial. This review summarizes the research on HRS and advances in the clinical effect of renal replacement therapy for HRS, and points out that renal replacement therapy is not suitable as the conventional therapy for HRS, but it can be applied as the pre-transplantation transitional treatment for patients with a plan for liver transplantation, as well as the short-term treatment for non-transplantation patients who do not respond to vasoconstrictors.
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Objective The present study was to investigate the feasibility of use of high resolution magnetic reso?nance vessel wall imaging(HR-VWI)in evaluation of intracranial aneurysms. Methods We prospectively collected data from patients who had intracranial aneurysms and received HR-VWI scan before surgical treatment or conservative treatment. Aneurysms were divided into ruptured group (n=12) and unruptured group (n=88). Aneurysm site, size, neck, aspect ratio(AR), daughter sac and aneurysmal wall enhancement scale were analyzed in both groups. Univariate and multivariate Logistic regression were performed to evaluate the risk factors of aneurysm rupture. Subgroup analysis was also performed to study symptomatic and asymptomatic unruptured aneurysms. Results Aneurysm size(t=2.187,P=0.031),AR(t=3.164,P=0.002),incidence of daughter sac(P=0.012) and aneurysmal wall enhancement scale(P<0.001)were higher in ruptured aneurysm group. Multivariate Logistic regression showed that aneurysmal wall enhance?ment scale was the only independent risk factor of ruptured aneurysms(P=0.002). Subgroup analysis showed aneurysm wall enhancement scale(P<0.001) and AR(t=3.939,P<0.001) were higher in symptomatic unruptured aneurysms. Conclusion Aneurysm wall enhancement on HR-VWI is more frequently seen in ruptured aneurysms and symptomatic unruptured aneurysms. Histological study is needed for better understanding of the mechanism of aneurysm wall enhance?ment.
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Objective There are different degrees of angiogenesis in the tissues and organs of the patient with diabetic chron -ic vascular disease , and it is somehow difficult to observe angiogenesis .This study was to construct an experimental model of angiogen-esis in the diabetic rat in vivo. Methods Twelve SD rats were equally randomized into a normal control and a diabetes mellitus ( DM) group, the DM model constructed by intraperitoneal injection of streptozotocin .At 8 weeks after modeling , matrigel was planted under the abdominal skin of the control and model rats and removed 2 weeks later .Then the structure of the new vessels was observed by HE staining and the expressions of aminopeptidase P (JG12) and alpha-smooth muscle actin (α-SMA) detected by immunohisto-chemistry and immunofluorescence . Results Compared with the control rats , the DM models showed significant increases in the blood glucose level ([6.15 ±3.02] vs [35.08 ±6.92] mmol/L), 24-hour urine volume ([5.33 ±1.53] vs [105.00 ±20.82] mL), and 24-hour urinary protein level ([7.78 ±2.12] vs [47.70 ±9.63] mg/24 h) (P<0.01).The matrigel plug was white and transparent in the controls but red with a visible tiny vessel-like structures in the model rats .The vessel-like structures were found oc-casionally in the matrigel plug of the control animals but in large numbers with many erythrocytes in that of the DM models .In compari-son with the normal controls , the model rats exhibited significantly upregulated expressions of JG12 (7.76 ±1.85 vs 27.36 ±3.75, P<0.01) and α-SMA (10.22 ±2.64 vs 36.85 ±4.28, P<0.01) in the matrigel plug , and a vessel-like reticular distribution was ob-served. Conclusion Hyperglycemia may induce angiogenesis in the matrigel plug .The DM rat model of subcutaneous matrigel angio-genesis may contribute to the study of angiogenesis in diabetes .
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OBJECTIVE@#To evaluate the early predictive and diagnostic significance of the acute kidney injury (AKI) associated biomarkers for patients in the intensive care unit (ICU). @*METHODS@#From January to June, 2014, relevant clinical data of participants were collected upon admission to the intensive care unit (ICU) in Affiliated Hospital of Zunyi Medical College. Levels of serum cystatin C (sCys C), neutrophil gelatinase-associated lipocalin (sNGAL), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1), interleukin-18 (uIL-18), and N-acetyl-beta-D-glucosaminidase (uNAG) were detected by enzyme linked immune sorbent assay (ELISA), and compared between AKI and non-AKI patients. Diagnostic significance of these biomarkers was evaluated by a receiver operating characteristic (ROC) curve and the area under the ROC curve. @*RESULTS@#A total of 176 patients were enrolled in this study. Among them, 71 patients were diagnosed as AKI, in which 57 patients hospitalized with AKI and 14 developed AKI after 24 h hospitalization. The renal replacement therapy ratio was increased with the progress of clinical stage for AKI. AKI mortality rate was 18.8% (46.5% of the total number of deaths). The levels of sCys C, sNGAL, uNGAL, and uIL-18 in AKI patients were increased compared with those in the non-AKI patients (P<0.05). With the progress of AKI, sCys C, and uNGAL levels were also elevated. In 14 patients who suffered from AKI 24 h after hospitalization, the average levels of sCys C, uNGAL, uIL-18, and uKIM-1 were significantly increased (P<0.05). Sensitivity and specificity of the uNGAL, sCys C, and uIL-18 in AKI diagnosis were 97.2%, 76.1%, 54.9% and 93.3 %, 96.2%, 78.1%, respectively. The areas under the ROC curve of uNGAL, sCys C, and uIL-18 were 0.99, 0.90, and 0.69, respectively. @*CONCLUSION@#uNGAL, sCys C and uIL-18 can be used to predict and diagnose AKI, and to evaluate the AKI clinical stage.
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Humans , Acetylglucosaminidase , Urine , Acute Kidney Injury , Blood , Diagnosis , Urine , Acute-Phase Proteins , Urine , Biomarkers , Blood , Urine , Case-Control Studies , Cystatin C , Blood , Enzyme-Linked Immunosorbent Assay , Hepatitis A Virus Cellular Receptor 1 , Intensive Care Units , Interleukin-18 , Urine , Lipocalin-2 , Lipocalins , Blood , Urine , Membrane Glycoproteins , Urine , Proto-Oncogene Proteins , Blood , Urine , ROC Curve , Receptors, Virus , Sensitivity and SpecificityABSTRACT
Totally, 125 elderly inpatients with aspiration pneumonia (AP) were enrolled from departments of respiratory medicine and neurology at Zhongnan Hospital, Wuhan during June 2005 to October 2009 for analysis. Results showed that listlessness was manifested in 70 cases (56%), primary neurological illness in 80 cases (64%), 57 of them (46%) complicated with respiratory failure and 26 died with case-fatality of 21%. Main pathogen for them was Gram-negative bacillus, accounting for 57% of the total. Two kinds or more of antibiotics had ever been administered in 98 cases (78%), with an average length of antibiotics use for 28 days, ranging from one day to 128 days. Nasal feeding was instituted for those with choking over their feeding and coughing, and their inspired feeding was aspirated from the trachea or bronchi and lavished with bronchoscopy, with 38 cases by tracheal intubation, 26 by tracheotomy and 42 with artificial ventilation. Their average duration of hospital stay spanned 28 days with an average cost of 25 000 RMB yuan per capita, significantly higher than that for those with common pneumonia. In conclusion, clinical features of these elderly patients with AP were not so typical, most of them manifest severe, with lots of medical cost and bad prognosis.
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Fifty-six patients diagnosed as early stage lung cancer by spiral CT scan,underwent CTguided percutaneous transthoracic biopsy with a successful rate of 100%.Forty nice cases were confirmed pathologically including adenocarcinoma in 30 cases,squamous carcinoma in 14,alveolar cell carcinoma in 2 and small cell lung cancer in 3.Three cases were diagnosed as chronic inflammatory lesion,2 cases as tuberculosis and the diagnosis was not confirmed in 2 cases.The results suggest that CT-guided percutaneous transthoracic biopsy is an effective diagnostic measure for patients with stage Ⅰ-Ⅱ lung cancer.
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OBJECTIVE:To study the effects of Salvionolic acids dialyzate on anaphylatoxin,C-reactive protein(CRP),interleukin-6(IL-6)and tumor necrosis factor-?(TNF-?)in peripheral blood of patients with maintenance hemodialysis(MHD)and to discuss whether the Salvionolic acids dialyzate could improve the blood-membrane biocompatibility.METHODS:Thirty-six patients undergoing MHD for at least half a year were randomly divided into 3 groups:control group(conventional hemodialysis,n=12),low-dose group(dialysate with salvionolic acids 40 mg?L-1,n=12)and high-dose group(dialysate with Salvionolic acids 80 mg?L-1,n=12).Dialyzer of the polysulfone membranes was firstly used in all patients.Patients' blood sampling was scheduled before dialysis,30 minutes after dialysis and at the end of dialysis(5 minutes before withdrawal of dialyzer)for measurement of serum levels of complement(C3a,C5a),CRP,IL-6 and TNF-? using enzyme linked immunosorbent assay(ELISA).RESULTS:As compared with before dialysis,the levels of C3a and C5a in both control group and low-dose group were evidently increased at 30 minutes,while the difference in high-dose group was nonsignificant.No significant differences of IL-6 and TNF-? were found between pre-dialysis and post-dialysis in three groups.As compared with before dialysis,the concentration of CRP in control and low-dose groups obviously increased but decreased obviously in high-dose group after dialysis.CONCLUSION:The production of C3a,C5a and CRP in the process of hemodialysis could be inhibited by a certain dose of Salvionolic acids dialyzate,which can improve the biocompatibility of the dialysis-membrane to some degree,but can't improve the levels of IL-6 and TNF-? after single-time dialysis.
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Objective To explore the role and significance of vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)in peritubular angiogenesis of diabetic kidney.Methods diabetic rats were induced by Streptozotocin.The expressions of VEGF and Ang-2 in renal tissue of rats were detected by immunohisochemistry.VEGF and Ang-2 mRNA in kidney was also detected by RT-PCR,and quantified by computerimage analysis.Results From 2-week to 24-week,VEGF mRNA level in diabetic renal upregulated continuously compared with control group,with peak level at 16 and 20 weeks.VEGF immunostaining in diabetic renal tubuli increased apparently compared with control group.Ang-2 mRNA in diabetic renal was only detected at 16 and 20 weeks.Ang-2-expressing peritubular microvessel in diabetic renal cortex was found by immunohistochemistry from 12 -week to 24-week with peak level at 16 week.No detecable Ang-2 mRNA and immunostaining were found in control renal.The changes correlated VEGF with Ang-2 in diabetic renal after 12 weeks.Conclusion There are the formation of Ang-2-staining peritubular microvessels in diabetic renal cortex in middle and later stages.VEGF and Ang-2 take part in angiogenesis in diabetic renal.
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Objective To investigate the effect of hemodialysis(HD) on the endothelial cells of the patients with end-stage renal disease(ESRD). Methods The study population consisted of 30 patients with undergoing first hemodialysis treatment and 20 healthy individuals from March to November of 2003.The number of circulating endothelial cells(CEC) and the concentration of von Willebrand factor(vWF) were measured in HD patients at predialysis,1h during HD,2h during HD,and the end of HD.CEC and vWF were observed in healthy subjects. Results CEC and vWF were increased in HD patients compared with healthy individuals,and elevated continuously during HD.Increased CEC and vWF were correlated significantly with duration of HD. Conclusion Endothelial cell dysfunction exists in the patients with ESRD.HD procedures may cause endothelial cell damage.