Selective protein degradation by the ubiquitin 26S proteasome pathway has emerged as a key regulatory mechanism in a wide variety of cellular processes.The ubiquitin/26S proteosome pathway mainly consists of ubiquitin activating enzyme(E1),ubiquitin conjugating enzyme(E2),ubiquitin protein ligase(E3),and 26S proteasome.In an ATP-dependent reaction,uibquitin(Ub) is conjugated to E1,the activated Ub is then transferred to an E2.Finally,the Ub-E2 intermediate delivers the Ub to the target protein by E3 recognition.Polyubiquinated proteins are eventually degraded by the 26S proteasome.In plants,regulated protein degradation by /26S proteasome pathway contributes significantly to development by affecting a wide range of progress,including hormone signaling,photomorphogenesis,self-incompatibility and cell cycle.The recent progress towards understanding the role of the Ub/26S proteasome pathway during plant development was reviewed.

OBJECTIVE:To evaluate the bioequivalence of the domestic pidotimod granules with the imported pidotimod syrup as control.METHODS:20 healthy male volunteers were treated with a single dose(800 mg)of pidotimod granules(test formulation)or pidotimod syrup(reference formulation)by a randomized crossover design,with plasma concentrations of pidotimod determined by HPLC and pharmacokinetic parameters of pidotimod computed,and the bioequivalence between two formulations was evaluated using DAS2.0 program.RESULTS:The pharmacokinetic parameters of the reference formation vs.the test formulation of pidotimod were expressed as follows:t1/2(2.70?0.80)h vs.(2.62?0.84)h;Cmax(4.04?0.59)?g?mL-1 vs.(3.87 ?0.66)?g?mL-1;tmax(2.28?0.44)h vs.(2.13 ?0.43)h;AUC0～14(22.11?4.20)mg?h?L-1 vs.(23.00?4.25)mg?h?L-1;AUC0～∞(22.85?4.42)mg?h?L-1 vs.(23.83?4.52)mg?h?L-1.The relative bioequivalence of the test formulation as against the control was(106.08?22.05)%.CONCLUSION:The pidotimod granules and pidotimod syrup are bioequivalent.

Objective This study was designed to predict the main targets of Alzheimer’s disease (AD) in Achyranthis Bidentatae Radix based on network pharmacology and molecular docking methods, and to explore its “multi-component, multi-target, and multi- pathway” mechanism. Methods According to the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the library of chemical constituents of Achyranthis Bidentatae Radix was established by referring to Chinese and foreign literature reports and collecting targets for treating AD in DrugBank. The Discovery Studio 3.5 software was used to carry out molecular docking, virtual screening of the chemical composition set of Achyranthis Bidentatae Radix combined with AD target, and KEGG database was used to enrich and analyze the key target of virtual screening. The active compounds of Achyranthis Bidentatae Radix with anti-AD activities were yielded to Discovery Studio 3.5 software and molecular docking to predict the poteneial proteins and carry out related KEGG pathways notation separately. Finally, the network of “active compound-target proteins-pathway” was built and analyzed using the Cytoscape 3.2.1 software. Results The 58 active compounds were selected from Achyranthis Bidentatae Radix, of which were mostly small alkanes, esters, and carboxylic acids followed by flavonoids and terpenoids. These active ingredients may regulate 36 potential target proteins such as CaMK-IIα, CaMK-IIβ, CaMK-IIγ, Akt1, and TNF-α to play a role in the pathogenesis of AD. The results also suggested that 12 signaling pathways were involved in the pathogenesis of AD, such as MAPK signaling pathway, Wnt signaling pathways and so on. Conclusion This research method initially revealed that the active ingredients of flavonoids and glycosides in Achyranthis Bidentatae Radix are the material basis for the treatment of AD. Its mechanism of action involved anti-inflammatory, anti-apoptosis and so on.

Objective To investigate the role of vascular endothelial growth factor (VEGF)in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease (COPD). Methods Thirty patients with stable bronchial asthma (asthma group), 28 patients with stable COPD (COPD group), and 24 healthy subjects (control group) were studied. Lung function, inflammatory cell differentials in sputum and the level of VEGF in induced sputum were determined by induced sputum method and ELISA method respectively. Results The levels of eosinophils in induced sputum in asthma group were 0.9 (0.4-1.4) × 109/L, significantly higher than those in COPD greup[0.1 (0-0.2)×109/L], and control group[0.0(0-0.1) × 109/L] (P < 0.05). The levels of neutrophils in COPD group were 2.3 (1.8-2.8) × 109/L, significantly higher than those in asthma group [1.1 (0.2-1.9) × 109/L], and control group [1.0(0.8-1.2) × 109/L] (P < 0.05). The levels of VEGF in asthma group, COPD group and control group were (2.3 ± 0.5), (0.3 ± 0.1), (0.9 ± 0.2) μg/L, respectively, and significant difference was showed between each group (P < 0.05). The VEGF level in induced sputum was positively correlated with the number of eosinophils in induced sputum in asthma group (γ = 0.62,P < 0.05), and was negatively correlated with FEV<,1>% (γ =-0.56, P < 0.05). The VEGF level in induced sputum was positively correlated with FEV1% in COPD group (γ = 0.43, P < 0.05), and was not correlated with the number of neutrophils in induced sputum (γ = 0.21, P > 0.05). Conclusions The concentration of VEGF in induced sputum increases in patients with bronchial asthma. VEGF may take part in the airway inflammatory development of asthma. The concentration of VEGF in induced sputum decreases in patients with COPD. VEGF may take part in the incidence of COPD.

Adrenal Glands ; Female ; Hematopoiesis, Extramedullary ; Humans ; Spherocytosis, Hereditary ; complications ; Young Adult

To investigate the invasive ability of the residual tumor cells after immunotherapy and explore the feasible approach suppressing the invasion, mice were inoculated with B16 cells, and then treated by gene therapy with p4-1BBL/psPD-1 or IFN-gamma. The production and activities of MMP-9 and MMP-2 in residual tumor tissues were analyzed with gelatin zymography 1 day and 7 days after the termination of the immunotherapy. The production of MMP-9 and MMP-2 by B16 cells treated with IFN-gamma was also analyzed. IFN-gamma-treated B16 cells were inoculated to mice via subcutaneous injection. The invasion of tumor to muscular tissue was analyzed. Gene therapy with CH50 was used to suppress the invasive growth of tumor. The results showed that the expression and the activities of MMP-9 and MMP-2 were significantly increased 7 days after the end of immunotherapy. The response of tumor cells to ECM molecules was intensified after the removal of IFN-gamma, resulting in significant increase of both the production and activities of MMP-9 and MMP-2, and the increased invasion of tumor. Gene therapy with CH50 effectively suppressed the invasive growth of tumor. It is concluded that the termination of immunotherapy may result in a higher metastatic potential of residual tumor cells. Suppressing tumor invasion by suitable treatment will improve the efficacy of immunotherapy.

Objective To design a post-peripheral intervention observation form that uses the timepoint and observation project as the framework of contents,and to evaluated its clinical application effect.Methods Non-concurrent patients were used to make a control study.By using the convenient sampling method,101 patients,who received peripheral interventional therapy during the period from June 1,2014 to December 31,2014,were collected and used as the control group;routine nursing care was adopted and the results were documented.A total of 102 patients,who received peripheral interventional therapy during the period from January 1,2015 to June 30,2015,were used as the intervention group,for whom routine nursing care was carried out and self-designed post-peripheral intervention observation form was employed to record the nursing observation.The results of the two groups were statistically analyzed.After using the form,every month 10 patients,5 visiting physicians and 5 responsible nurses were asked to make an evaluation of nursing quality satisfaction.Results The incidence of main postoperative complications in the intervention group was lower than that in the control group,the chi-square test showed that the difference between the two groups was statistically significant (P＜0.05).The average hospitalization days and the mean medical expense of the intervention group were lower than those of the control group,the chi-square test indicated that the difference between the two groups was statistically significant (P＜0.05).After using this form,the nursing quality satisfaction of patients and visiting physicians was improved,the self-rating satisfaction assessed by responsible nurses was also improved,the chi-square test revealed that the difference between the two groups was statistically significant (P＜0.05).Conclusion All the evaluation indexes of the patients in the intervention group are better than those of the patients in the control group,indicating that this observation form is reasonably designed,meets the specialty characteristics,heightening the dynamic observation for patients after peripheral intervention,strengthens the effectiveness of monitoring postoperative complications,and is helpful for the implementation of the observation after peripheral intervention.Therefore,this observation form is worth promoting use.

Objective: To investigate the relationship between blood pressure, blood glucose or blood lipids and patients with cerebral infarction (CI) or intracerebral hemorrhage (ICH) in diff erent age or gender. Methods: hT e case-control study consecutively recruited patients with if rst-ever-in-a-lifetime CI (n=358) and ICH (n=230) and community-acquired pneumonia (n=165) as controls between January 2010 and December 2013 at the Second Xiangya Hospital of Central South University. hT epatients with CI or ICH were divided into the young group, the middle-aged group and the older group, and the risk factors were compared between the 3 groups. hTe patients with CI or ICH were respectively further divided into the male group and the female group. hTe blood pressure, glucose and lipids were measured. Results: Data from logistic regression models showed that CI was closely associated with high blood pressure, hypertension, diabetes mellitus (DM) or fasting plasma glucose (FPG) (P<0.05), and ICH was closely related to high blood pressure, hypertension, low density lipoprotein-cholesterol (LDL-C), FPG, serum creatinine (SCr) or alcohol drinking (P<0.05); hypertension was the main risk factor for stroke. hTe odds ratios for the young, the middle-aged and older group were 10.43, 4.74 and 7.39 respectively (P<0.05). Systolic blood pressure (OR=28.74) was the important risk factor for the young stroke, and the OR is 2.81 for the middle-aged stroke. Diastolic blood pressure (OR=2.96) and DM (OR=6.25) were the risk factor for the middle-aged stroke. LDL-C (OR=2.87) was a risk factor for the older stroke; the mean levels of diastolic blood pressure in males were signiifcantly increased compared with that in females with CI, while the mean levels of TC, HDL-C or LDL-C in females were signiifcantly higher than that in males with ICH (P<0.05). Conclusion: Hypertension, systolic blood pressure in particular, is the most common risk factor for young stroke patients. DM and hypertension are the risk factors for the middle-aged patients, while hypertension, DM, LDL-C and alcohol consuming are the risk factors for the aged patients.

Objective To investigate the clinical,neuroradiologic characteristics and possible causes in 3 patients with combined developmental venous anomalies (DVAs) and cerebral cavernous malformations (CCM).Methods The clinical examination,magnetic resonance imaging (MRI) T1-weighted (T1 WI),T2-weighted (T2WI),susceptibility-weighted imaging (SWI) or T2 fast field echo (T2 FFE),contrast-enhanced MRI at 1.5 T field strength and digital substrate angiography were performed in 3 patients.Results Three patients presented with the seizure,vertigo,and dizziness respectively.MRI findings of reticulated “popcorn like” lesion with complete hemosiden rim showed typical sign of CCM.DSA,contrast-enhanced MRI and MRI-SWI revealed the caput medusae of the medullary veins and collected veins which was drained into subcortical and deep venous system,which indicated DVAs in 3 patients.The angulated medullary veins and collected veins in approaching distal zone of CCM were observed.Conclusion DVAs can be combined with CCM.The angulated medullary veins and collected veins combined with CCM in same territory reveals that the angioarchitectural factors is a key factor in pathogenesis of cavernous malformation.

Objective:To explore the histogenesis and differentiation of dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP). Methods: Clinical information and microscopic characteristics of 26 cases of DF and 26 cases of DFSP were investigated. The immunohistochemical study was performed on microarray sections by a panel of antibodies including FactorⅩⅢa, HLA-DR, CD34, CD14, S-100, MSA, and Ki67. Probe was labeled by in vitro transcription. The mRNA expression levels of TGF-? and bFGF were investigated by in situ hybridization. Results: All cases showed positive for Factor ⅩⅢa,HLA-DR and CD34 to different extent. The medians of positive rates in DF were FactorⅩⅢa 90%, HLA-DR 70%, and CD34 5%, and in DFSP were FactorⅩⅢa 10%, HLA-DR 5%, and CD34 80%. CD14 was positive in 3 cases of DF and 1 case of DFSP. S-100 was positive in 6 cases of DFSP and 2 cases of DF. MSA was positive in 5 cases of DFSP and 3 cases of DF. In all cases, positive rate of Ki67 was less than 5%. The mRNA expression levels of TGF-? was elevated in DF in comparison with DFSP. Conclusion: Both DF and DFSP can differentiate to dendritic cells (DC) in different degree. Considering the character of microscopic features and immunohistochemical phenotype, cells of DF are much similar to mature DC, while those of DFSP much similar to immature dermal reserve cell (DRC). The differences of cell differentiation between DF and DFSP result in different prognosis. DF is a benign tumor, while DFSP a low grade malignant tumor. The different expression of FactorⅩⅢa and CD34 may be helpful to differential diagnosis of DF and DFSP.