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OBJECTIVEï¼To elucidate the mechanism by which Huoxue Jiedu Huayu recipe (, HJHR) regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction (UUO) rats and the mechanism by which it reduces of renal fibrosis. METHODS: Male Wistar rats were randomly divided into 4 groups: the sham group, UUO group (180 d of left ureter ligation), UUO plus eplerenone (EPL) group, and UUO plus HJHR group. After 180 d of oral drug administration, blood and contralateral kidneys were collected for analysis. Angiogenesis- and fibrosis-related indexes were detected. RESULTS: HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels of α-smooth muscle actin (α-SMA), vimentin and collagen I. Moreover, these treatments could reduce the expression of vascular endothelial growth factor-A (VEGFA) by inhibiting the infiltration of macrophages. Furthermore, HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production, which inhibited angiogenesis. Finally, the coexpressions of CD34, CD105 and α-SMA were decreased in the HJHR and EPL groups, indicating that endothelial-to-mesenchymal transition was inhibited. CONCLUSIONS: These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFA-induced angiogenesis, encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.
Assuntos
Medicamentos de Ervas Chinesas , Fibrose , Rim , Macrófagos , Ratos Wistar , Obstrução Ureteral , Fator A de Crescimento do Endotélio Vascular , Animais , Masculino , Obstrução Ureteral/metabolismo , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/genética , Ratos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Rim/efeitos dos fármacos , Rim/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Nefropatias/etiologia , Nefropatias/genética , AngiogêneseRESUMO
The dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies hold great potential for cancer therapy. In this study, we found that WSB1, which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples, is a direct target gene of c-Myc, and can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and transactivated c-Myc. Of interest, the effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.
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Objective ToexploretheclinicalvalueofMSCTcombinedwithultrasonographyinthediagnosisofacuteappendicitis. Methods 238patientswithsuspiciousappendicitisunderwentMSCTandultrasonographybeforesurgery.Allpatientsweredivided intoappendicitisgroupandnormalappendixgroupaccordingtoCTappearances.TheefficacyofMSCTcombinedwithultrasoundin diagnosingappendicitiswasanalyzedbycomparisonofsurgicalpathologicalfindings.Results Therewere220casesinappendicitis group,whichhad165casesofappendicitisconfirmedbypathology,and55casesofnormalappendix.Therewere18casesinnormal group,2caseswereconfirmedappendicitisbypathology,and16caseswerenormalappendix.Theoveralldiagnosticperformancesof theCTscanwere98.8%ofsensitivity,22.5%ofspecificity,82.5%ofpositivepredictivevalue,88.9%ofnegativepredictivevalue, and76.1%ofaccuracy.TheperformancesofMSCTcombinedwithultrasonographywere90.4%ofsensitivity,93.0%ofspecificity, 96.8%ofpositivepredictivevalue,80.5%ofnegativepredictivevalue,and91.2%ofaccuracy.Thedifferencewasstatisticallysignificant indiagnosisperformancesbeforeandafterMSCTcombinedwithultrasonography (P<0.001).Conclusion MSCTcombinedwith ultrasonographyexaminationcouldimprovethediagnosticaccuracyofappendicitis,andmayreducethenegativerateofappendectomy.
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Objective To quantify any therapeutic effect of cyclic movement training combined with functional electrical stimulation for improving lower limb motor function and ability in the activities of daily life after stroke.Methods Seventy stroke survivors were randomly divided into a control group and an experimental group,each of 35.Both groups were given conventional rehabilitation,including cyclic training,but the experimental group was additionally provided with functional electrical stimulation of the quadriceps,hamstrings,anterior tibialis and gastrocnemius at the affected side.Before and after four weeks of treatment the Fugl-Meyer lower limb (FMA-L) and balance (FMA-B) assessments were performed and a modified Barthel index (MBI) was assigned to each subject to quantify functioning.Results Before the treatment,no significant differences were observed between the two groups in any of the measurements.But after four weeks of treatment the average FMA-L,FMA-B and MBI scores of the experimental group were all significantly better than before the treatment and significantly better than the control group's averages.Conclusion Cyclic movement training combined with functional electrical stimulation can improve the lower limb motor function of stroke survivors and their ability in the activities of daily life.
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Objective To quantify any therapeutic effect of cyclic movement training combined with functional electrical stimulation for improving lower limb motor function and ability in the activities of daily life after stroke.Methods Seventy stroke survivors were randomly divided into a control group and an experimental group,each of 35.Both groups were given conventional rehabilitation,including cyclic training,but the experimental group was additionally provided with functional electrical stimulation of the quadriceps,hamstrings,anterior tibialis and gastrocnemius at the affected side.Before and after four weeks of treatment the Fugl-Meyer lower limb (FMA-L) and balance (FMA-B) assessments were performed and a modified Barthel index (MBI) was assigned to each subject to quantify functioning.Results Before the treatment,no significant differences were observed between the two groups in any of the measurements.But after four weeks of treatment the average FMA-L,FMA-B and MBI scores of the experimental group were all significantly better than before the treatment and significantly better than the control group's averages.Conclusion Cyclic movement training combined with functional electrical stimulation can improve the lower limb motor function of stroke survivors and their ability in the activities of daily life.
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Objective To compare the differences in the practical operation of exercise therapy courses for rehabilitation major students between workshop teaching method and traditional teaching method, and to explore the teaching model and process of workshop teaching method. Methods We im-plemented traditional teaching method in 94 rehabilitation major students in grade 2012 from Xuzhou Medical University, while 96 students in grade 2013 were taught by workshop method, which is based on specific cases, combined with multi-angle evaluation methods and various treatment protocols, with the opti-mal therapeutic method carried out after learning different practical operations and comparing their indica-tions. Then we conducted course satisfaction survey and skills operation evaluation on students from both grades after the course, and the t test was performed with the use of SPSS 19.0. Results The survey showed that the satisfaction score was significantly higher in grade 2013 students with workshop teaching method (79.07±10.49), compared with that in grade 2012 students with traditional teaching method (72.59±13.56), and the difference was statistically significant (P<0.05); as for the skills operation evaluation, the average score was significantly higher in students from 2013 grade (95.04±2.98), compared with that in students from 2012 grade (92.33±1.97), and the difference was statistically significant (P<0.05). Conclusions The work-shop teaching method can significantly improve students' satisfaction for the practical course of exercise therapy while improving their operation abilities.
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Objective To investigate the relationship between Helicobacter pylori (HP) infection and the development of chronic urticaria.Methods Published case-control studies which concerned HP infection related chronic urticaria were searched in Wanfang,CNKI,CQVIP Chinese databanks and PubMed.Meta-analysis was applied to analyze the pooled odds ratio (OR) and 95% confidence interval (CI).Results 37 studies which comprised 2 909 cases of chronic urticaria and 1 873 persons served as controls were enrolled.When compared with the controls,HP infection significantly increased the risk of chronic urticaria development with a pooled OR of 3.20 (95%CI:2.31-4.43).Results from Meta-regression analyses showed that the distribution of residential areas and detection method being used were potential influential factors.Conclusion HP infection seemed to be associated with an increased risk of developing the chronic urticaria.