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.

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

This study was aimed to collect relevant provisions of bulging disease medical records in the Ming and Qing dynasties to excavate the syndrome differentiation, drug law and medication frequency analysis. A database was established to analyze relevant provisions. The results showed that the syndromes of liver stagnation and spleen deficiency, dampness-heat accumulation, spleen-yang deficiency are the most common type. The mainly used drugs are from the category to eliminate dampness and water, and to tonify the deficiency. The top three used drugs are poria, atractylodes, and dried citrus peel. It was concluded that medications used in the Ming and Qing dynasties were mainly targeted to the disordered zangfu-organ, which was mainly about the spleen and the stomach. The syn-drome differentiation is the mixture of deficiency and excess. And deficiency is the main part. The medication should combine tonification and reducing. And tonification should be paid attention to. The syndrome differentiation and treatment should be coordinated and the primary and secondary aspect should be identified. These rules provide ref-erence effect for the clinical practice and scientific research of bulging disease treatment.

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 evaluate the effectiveness of noninvasive positive pressure ventilation(NPPV) as a weaning strategy in patients with acute respiratory failure after failure to wean from invasive positive pressure ventilation(IPPV). Method A prospective randomized and controlled clinical trial of weaning of IPPV was carried out in patients mechanically ventilated in mode of IPPV for more than 48 hours with failure in a spontaneous breathing trial(SBT: PSV 6 cmH_2O). Patients with contraindications to NPPV were excluded. After failure the SBT, patients were randomly divided(random number) in two groups. Patients in NPPV group were extubated after being ventilated with high pressure support for 30 minutes and then placed on NPPV. Patients in IPPV group were weaned following conventional procedure. Arterial blood gases, maximal inspiratory pressure, respiratory rate,tidal volume, rapid shallow breathing index, heart rate, arterial blood pressure, and peripheral oxygen saturation were measured before and after failing the SBT. The rate of complications, including pneumonia and tracheotomy duration mechanical ventilation, days of hospital stay and outcome were observed. Findings of the two groups were vompared using the Student t test and the chi-square test. Results The percentage of complications in the NPPV group was lower(22.9% versus 72.2%, P <0.01) ,with lower incidences of pneumonia(6.1%,36.1%; P <0.01) and tracheotomy. Compared between the two groups, days of ICU stay( 14.16(3.45) d vs. 22.57( 7.71 ) d; P <0.01) and total days of mechanical ventilation(14.88±3.76 days vs. 20.68± 2.79 days, P <0.01) of NPPV group are shorter than IPPV group. Conclusions NPPV is a good alternative to the mechanically venti-lated patients who fail in initial weaning attempts. The key to successful NPPV weaning is the proper selection of weaning candidates and using NPPV as soon as possible after extubation.

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.

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.

Objective:Since malignant fibrous histiocytoma (MFH) may be taken as an undifferentia-ted pleomorphic sarcoma (UPS), this study was conducted to reassess 33 previously diagnosed MFH cases in the past 10 years based on the latest WHO concept. And then to search for the clinicopathological features, probably tumorigenesis, and the line of differentiation of the remaining MFH/UPS cases.Methods: Thirty-three cases in tissue microarray were studied by immunohistochemistry with panels of neurogenic, myogenic, and lipogenic antibodies. Three expertise pathologists reevaluated the slides separately. Results: Among the 33 cases, 17 cases (51.5%) of MFH had their diagnoses changed, including 5 leiomyosarcomas, 3 malignant peripheral nerve sheath tumors, 1 fibrosarcoma, 1 inflammatory myofibrosarcoma, 1 giant cell tumor and 1 angiomatoid fibrous histiocytoma. The remaining 16 cases (48.5%) were finally diagnosed as MFH/UPS, among which patients were mainly old adults (median age: 63 years; range: 38 to 76 years). The median tumor size was 6.0 cm (range: 3.0 to 14.0 cm), 8 cases (50%) located in lower limb and 5 cases (31.3%) located in thigh. These tumors had marked cytological and nuclear pleomorphism. Immunohistochemistry showed that Vimentin was strongly positive in all 16 MFH/UPS (100%), Muscle-specific actin was variously positive in 8 cases (50%) and 1 case focally expressed Desmin. Eleven cases (68.8%) variously expressed CD68 (KP1) and 7 cases (43.8%) expressed CD68 (PG-M1), which were much higher than leiomyosarcoma, malignant peripheral nerve sheath tumor and liposarcoma with significant difference. Moreover, Ki67 expression rates were from 10% to 100%, including 14 cases more than 50% and 11 cases more than 70%. However, only 2 cases (12.5%) showed P53 positive. Conclusion: MFH/UPS often show marked histological pleomorphism, and the diagnosis must be made by exclusion of other definitive sarcomas, especially myogenic and neurogenic sarcoma. Only Vimentin was always expressed in MFH/UPS, while some of the tumors were positive for myogenic antigen and CD68. It was suggested that MFH/UPS might arise from primary mesenchymal cells, and some cases exhibited fibroblastic and/or myofibroblastic features. In addition, histiocytic phenotypic marker did have more expression in MFH/UPS than in other sarcomas. MFH/UPS still had certain clinicopathological characteristics.